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17624643 | Vitamin D deficiency has been recently associated with the metabolic syndrome. However, it is not known whether this possible association of vitamin D deficiency with the metabolic syndrome is still present at very high degrees of obesity, as in morbidly obese patients.
Transversal, observational study that included 73 consecutive morbidly obese patients (body mass index 40 kg/m(2)). In every patient, anthropometric variables were recorded, fasting blood was assayed for 25-hydroxyvitamin D concentrations, lipid profiles, glucose and insulin levels, and insulin resistance was estimated by homeostasis model assessment.
Vitamin D deficiency was present in 37 of the 73 patients (50.7%). As defined by revised Adult Treatment Panel III criteria, 46 of the 73 obese patients (63%) had the metabolic syndrome. Vitamin D deficiency was more prevalent in morbidly obese patients presenting with the metabolic syndrome, compared with those who did not achieve the criteria for this syndrome (60.9% vs. 33.3% respectively, P = 0.023). When serum concentrations of 25-hydroxyvitamin D were categorized in tertiles, there was an association of the prevalence of the metabolic syndrome with the former (P = 0.038). Serum high-density lipoprotein cholesterol concentrations were lower (37.0+/-7.8 mg/dl vs. 44.9+/-8.7 mg/dl, P = 0.003), and triglycerides levels were higher (163.3+/-81.5 mg/dl vs. 95.1+/-24.2 mg/dl, P = 0.001) in the vitamin D-deficient group. | Is vitamin D deficiency associated with the metabolic syndrome in morbid obesity? | Yes. Vitamin D deficiency is associated with the metabolic syndrome in morbidly obese patients. | PASS | pubmedQA | 1 |
20810157 | Nasal polyps often are associated with asthma. The phenotype of these patients is unknown.
To identify the mucosal factors associated with asthma comorbidity, we analyzed the inflammatory patterns of nasal polyps.
Nasal polyps from 70 Belgian patients, 34% with asthma, were analyzed for type of inflammation, T-cell cytokines, and IgE antibodies to Staphylococcus aureus enterotoxins. The same investigations were repeated in 93 Chinese patients with polyps, a group with a low asthma comorbidity rate (8%).
In Belgian patients with polyps, 54% of samples showed eosinophilic inflammation. A classification tree evaluation identified IL-5 as the main positive determinant. Enterotoxin IgE in tissue (37%) was associated with significantly increased total IgE and eosinophil cationic protein concentrations. Expression of enterotoxin IgE, total IgE at greater than 1,442 kU/L, and eosinophil cationic protein at greater than 17,109 μg/L in samples with a total IgE concentration of greater than 246 kU/L significantly predicted asthma (odds ratio, 5.8-13). Only 7.5% of the samples from Chinese patients with polyps showed eosinophilic inflammation. IL-5 was confirmed as a positive determinant of eosinophilic inflammation, and enterotoxin IgE in tissue (17% of patients) was associated with significantly increased total IgE and eosinophil cationic protein concentrations. The expression of IL-5 or total IgE at greater than 790 kU/L in samples with an IL-5 concentration of greater than 194 pg/mL significantly predicted comorbid asthma (odds ratio, 17.2-96). | Is presence of IL-5 protein and IgE antibodies to staphylococcal enterotoxins in nasal polyps associated with comorbid asthma? | Yes. Mucosal inflammation in nasal polyps orchestrated by T(H)2 cytokines and amplified by S aureus enterotoxins is characterized by an increased eosinophilic inflammation and formation of IgE antibodies. This phenotype is associated with comorbid asthma in white and Asian patients with nasal polyps. | PASS | pubmedQA | 1 |
18616665 | Initiation of alcohol consumption during adolescence is high, which usually begins with consumption of highly concentrated sweetened alcoholic beverages in adolescent humans. Enhanced voluntary ethanol (EtOH) intake has been observed previously in adolescent relative to adult rats under continuous access conditions using sweetened EtOH solutions. The present set of experiments investigated patterns of voluntary EtOH intake in adolescent and adult rats using sweetened EtOH solutions in a limited access paradigm.
Rats were trained with modified sucrose-substitution protocols that ended at either 5% sucrose-20% EtOH (5S/20E) (Exp. 1) or 5% sucrose-10% EtOH (5S/10E) (Exp. 2).
Voluntary EtOH consumption differences between the 2 age groups were apparent at higher (i.e., 10 and 20%), but not lower (i.e., 2 and 5%) EtOH concentrations. Adolescent rats consumed more EtOH on a g/kg basis only at 20% EtOH (Exp. 1). Adolescent rats voluntarily consumed more EtOH than adults when maintained at 5S/10E (Exp. 2). To assess whether these age-related differences in voluntary EtOH intake were concentration dependent, rats were trained with 5S/20E and subsequently trained with decreasing EtOH concentrations (i.e., 5S/10E and 5S/5E). Adolescents consumed more EtOH when initially presented with the 5S/10E and 5S/20E EtOH concentrations, and subsequently at the lower 5S/5E EtOH concentration (Exp. 3). There were no differences in preference for the sucrose-only solution, however adolescents tended to consume more sucrose at the 5S sucrose concentration (Exp. 4). Given that adolescents consumed more EtOH at the 5S/10E and 5S/20E, but not at the 5S/5E EtOH concentrations, preference for sucrose does not solely explain the age differences in voluntary EtOH intake observed. | Does voluntary ethanol consumption differ in adolescent and adult male rats using a modified sucrose-fading paradigm? | Yes. Overall, results replicate previous work, demonstrating adolescent rats consume more EtOH relative to adults. However, the present results were observed using sweetened EtOH solutions in a limited access paradigm. The present modified sucrose-substitution paradigm may serve as a valid model of human adolescent drinking behavior. | PASS | pubmedQA | 1 |
22349088 | We evaluated whether the addition of carotid intima media thickness and plaque (CIMT-P), and a single nucleotide polymorphism on chromosome 9p21 (9p21) together improve coronary heart disease (CHD) risk prediction in the ARIC study.
Ten year CHD risk was estimated using the ARIC coronary risk score (ACRS) alone and in combination with CIMT-P and 9p21 individually and together in White participants (n=9338). Area under the receiver operating characteristic curve (AUC), model calibration, net reclassification index (NRI), integrated discrimination index (IDI) and number of individuals reclassified were estimated.
The AUC of the ACRS, ACRS+9p21, ACRS+CIMT-P and ACRS+CIMT-P+9p21 models were 0.748, 0.751, 0.763 and 0.766 respectively. The percentage of individuals reclassified, model calibration, NRI and IDI improved when CIMT-P and 9p21 were added to the ACRS only model (see manuscript). | Is the 9p21 genetic variant additive to carotid intima media thickness and plaque in improving coronary heart disease risk prediction in white participants of the Atherosclerosis Risk in Communities ( ARIC ) Study? | Yes. Addition of 9p21 allele information to CIMT-P minimally improves CHD risk prediction in whites in the ARIC study. | PASS | pubmedQA | 1 |
11509232 | During Drosophila embryogenesis, Jun kinase (JNK) signaling has been shown to play a key role in regulating the morphogenetic process of dorsal closure, which also serves as a model for epithelial sheet fusion during wound repair. During dorsal closure the JNK signaling cascade in the dorsal-most (leading edge) cells of the epidermis activates the AP-1 transcription factor comprised of DJUN and DFOS that, in turn, upregulates the expression of the dpp gene. DPP is a secreted morphogen that signals lateral epidermal cells to elongate along the dorsoventral axis. The leading edge cells contact the peripheral cells of a monolayer extraembryonic epithelium, the amnioserosa, which lies on the dorsal side of the embryo. Focal complexes are present at the dorsal-most membrane of the leading edge cells, where they contact the amnioserosa.
We show that the JNK signaling cascade is initially active in both the amnioserosa and the leading edge of the epidermis. JNK signaling is downregulated in the amnioserosa, but not in the leading edge, prior to dorsal closure. The subcellular localization of DFOS and DJUN is responsive to JNK signaling in the amnioserosa: JNK activation results in nuclear localization of DFOS and DJUN; the downregulation of JNK signaling results in the relocalization of DFOS and DJUN to the cytoplasm. The HINDSIGHT (HNT) Zn-finger protein and the PUCKERED (PUC) JNK phosphatase are essential for downregulation of the JNK cascade in the amnioserosa. Persistent JNK activity in the amnioserosa leads to defective focal complexes in the adjacent leading edge cells and to the failure of dorsal closure. | Is downregulation of Jun kinase signaling in the amnioserosa essential for dorsal closure of the Drosophila embryo? | Yes. Focal complexes are assembled at the boundary between high and low JNK activity. In the absence of focal complexes, miscommunication between the amnioserosa and the leading edge may lead to a premature "stop" signal that halts dorsalward migration of the leading edge. Spatial and temporal regulation of the JNK signaling cascade may be a general mechanism that controls tissue remodeling during morphogenesis and wound healing. | PASS | pubmedQA | 1 |
19674198 | Skin cancers are the most frequent malignancies in organ transplant recipients (OTRs). Squamous cell carcinomas (SCCs) occur 65-250 times more frequently in OTRs and tend to be aggressive in behavior. Because matrix metalloproteinases (MMPs) have a central role in tumorigenesis and invasion, we investigated the epithelial and stromal MMP and tissue inhibitor of MMP (TIMP) expression profile in SCCs of immunosuppressed (IS) compared with immunocompetent (IC) patients to determine if differences could explain the more aggressive behavior of SCCs in OTRs.
Matched pairs from 20 SCCs of IS and IC patients were studied using immunohistochemistry for MMP-1, MMP-7, MMP-8, MMP-9, MMP-13 and MMP-26 and TIMP-1 and TIMP-3.
Among all MMPs studied, only staining for MMP-26 was significantly more intense in cancer cells of the post-transplant group compared with the IC group (p = 0.01), whereas MMP-9 expression was more abundant in stromal macrophages surrounding SCCs of IC patients (p = 0.02). MMP-26 expression in cancer cells (p = 0.04) and that of MMP-9 in neutrophils (p = 0.005) were more abundant in SCCs of patients using cyclosporine. | Is matrix metalloproteinase-26 present more frequently in squamous cell carcinomas of immunosuppressed compared with immunocompetent patients? | Yes. We conclude that MMP-26 and MMP-9 may contribute to the more aggressive behavior of SCCs in OTRs. | PASS | pubmedQA | 1 |
17615154 | To investigate the bactericidal activity of antiviral and anticancer nucleoside analogues against a variety of pathogenic bacteria and characterize the activating enzymes, deoxyribonucleoside kinases (dNKs).
Several FDA-approved nucleoside analogue drugs were screened for their potential bactericidal activity against several clinical bacterial isolates and type strains. We identified and subcloned the genes coding for putative deoxyribonucleoside kinases in Escherichia coli, Pasteurella multocida, Salmonella enterica, Yersinia enterocolitica, Bacillus cereus, Clostridium perfringens and Listeria monocytogenes. These genes were tested for their ability to increase the susceptibility of a dNK-deficient E. coli strain to various analogues. We overexpressed, purified and characterized the substrate specificity and kinetic properties of the recombinant enzymes from S. enterica and B. cereus.
The tested Gram-negative bacteria were susceptible to 3'-azido-3'-deoxythymidine (AZT) in the concentration range 0.032-31.6 microM except for a single E. coli isolate and two Pseudomonas aeruginosa isolates which were resistant to the tested AZT concentrations. Purified recombinant S. enterica thymidine kinase phosphorylated AZT efficiently with a Km of 73.3 microM and k(cat)/Km of 6.6 x 10(4) s(-1) M(-1) and is the activator of this drug in vivo. 2',2'-Difluoro-2'-deoxycytidine (gemcitabine) was a potent antibiotic against Gram-positive bacteria in the concentration range between 0.001 and 1.0 microM. The B. cereus deoxyadenosine kinase had a Km for gemcitabine of 33.5 microM and k(cat)/Km of 5.1 x 10(3) s(-1) M(-1) and activates gemcitabine in vivo. S. enterica and B. cereus are now amongst the first bacteria with a completely characterized set of dNK enzymes. | Are nucleoside analogues activated by bacterial deoxyribonucleoside kinases in a species-specific manner? | Yes. Bacterial dNKs efficiently activate nucleoside analogues in a species-specific manner. Therefore, nucleoside analogues have a potential to be employed as antibiotics in the fight against emerging multiresistant bacteria. | PASS | pubmedQA | 1 |
20712895 | The zebrafish has been suggested as a model system for studying human diseases that affect nervous system function and motor output. However, few of the ion channels that control neuronal activity in zebrafish have been characterized. Here, we have identified zebrafish orthologs of voltage-dependent Kv3 (KCNC) K+ channels. Kv3 channels have specialized gating properties that facilitate high-frequency, repetitive firing in fast-spiking neurons. Mutations in human Kv3.3 cause spinocerebellar ataxia type 13 (SCA13), an autosomal dominant genetic disease that exists in distinct neurodevelopmental and neurodegenerative forms. To assess the potential usefulness of the zebrafish as a model system for SCA13, we have characterized the functional properties of zebrafish Kv3.3 channels with and without mutations analogous to those that cause SCA13.
The zebrafish genome (release Zv8) contains six Kv3 family members including two Kv3.1 genes (kcnc1a and kcnc1b), one Kv3.2 gene (kcnc2), two Kv3.3 genes (kcnc3a and kcnc3b), and one Kv3.4 gene (kcnc4). Both Kv3.3 genes are expressed during early development. Zebrafish Kv3.3 channels exhibit strong functional and structural homology with mammalian Kv3.3 channels. Zebrafish Kv3.3 activates over a depolarized voltage range and deactivates rapidly. An amino-terminal extension mediates fast, N-type inactivation. The kcnc3a gene is alternatively spliced, generating variant carboxyl-terminal sequences. The R335H mutation in the S4 transmembrane segment, analogous to the SCA13 mutation R420H, eliminates functional expression. When co-expressed with wild type, R335H subunits suppress Kv3.3 activity by a dominant negative mechanism. The F363L mutation in the S5 transmembrane segment, analogous to the SCA13 mutation F448L, alters channel gating. F363L shifts the voltage range for activation in the hyperpolarized direction and dramatically slows deactivation. | Are functional effects of spinocerebellar ataxia type 13 mutations conserved in zebrafish Kv3.3 channels? | Yes. The functional properties of zebrafish Kv3.3 channels are consistent with a role in facilitating fast, repetitive firing of action potentials in neurons. The functional effects of SCA13 mutations are well conserved between human and zebrafish Kv3.3 channels. The high degree of homology between human and zebrafish Kv3.3 channels suggests that the zebrafish will be a useful model system for studying pathogenic mechanisms in SCA13. | PASS | pubmedQA | 1 |
20846423 | Within the European Union the use of growth promoting agents in animal production is prohibited. Illegal use of natural prohormones like dehydroepiandrosterone (DHEA) is hard to prove since prohormones are strongly metabolized in vivo. In the present study, we investigated the feasibility of a novel effect-based approach for monitoring abuse of DHEA. Changes in gene expression profiles were studied in livers of bull calves treated orally (PO) or intramuscularly (IM) with 1000 mg DHEA versus two control groups, using bovine 44K DNA microarrays. In contrast to controlled genomics studies, this work involved bovines purchased at the local market on three different occasions with ages ranging from 6 to 14 months, thereby reflecting the real life inter-animal variability due to differences in age, individual physiology, season and diet.
As determined by principal component analysis (PCA), large differences in liver gene expression profiles were observed between treated and control animals as well as between the two control groups. When comparing the gene expression profiles of PO and IM treated animals to that of all control animals, the number of significantly regulated genes (p-value <0.05 and a fold change >1.5) was 23 and 37 respectively. For IM and PO treated calves, gene sets were generated of genes that were significantly regulated compared to one control group and validated versus the other control group using Gene Set Enrichment Analysis (GSEA). This cross validation, showed that 6 out of the 8 gene sets were significantly enriched in DHEA treated animals when compared to an 'independent' control group. | Do feasibility of a liver transcriptomics approach to assess bovine treatment with the prohormone dehydroepiandrosterone ( DHEA )? | Yes. This study showed that identification and application of genomic biomarkers for screening of (pro)hormone abuse in livestock production is substantially hampered by biological variation. On the other hand, it is demonstrated that comparison of pre-defined gene sets versus the whole genome expression profile of an animal allows to distinguish DHEA treatment effects from variations in gene expression due to inherent biological variation. Therefore, DNA-microarray expression profiling together with statistical tools like GSEA represent a promising approach to screen for (pro)hormone abuse in livestock production. However, a better insight in the genomic variability of the control population is a prerequisite in order to define growth promoter specific gene sets that can be used as robust biomarkers in daily practice. | PASS | pubmedQA | 1 |
27142280 | Postural control requires numerous inputs interacting across multiple temporospatial scales. This organization, evidenced by the "complexity" contained within standing postural sway fluctuations, enables diverse system functionality. Age-related reduction of foot-sole somatosensation reduces standing postural sway complexity and diminishes the functionality of the postural control system. Sub-sensory vibrations applied to the foot soles reduce the speed and magnitude of sway and improve mobility in older adults. We thus hypothesized that these vibration-induced improvements to the functionality of the postural control system are associated with an increase in the standing postural sway complexity.
Twelve healthy older adults aged 74 ± 8 years completed three visits to test the effects of foot sole vibrations at 0 % (i.e., no vibration), 70 and 85 % of the sensory threshold. Postural sway was assessed during eyes-open and eyes-closed standing. The complexity of sway time-series was quantified using multiscale entropy. The timed up-and-go (TUG) was completed to assess mobility.
When standing without vibration, participants with lower foot sole vibratory thresholds (better sensation) had greater mediolateral (ML) sway complexity (r (2) = 0.49, p < 0.001), and those with greater ML sway complexity had faster TUG times (better mobility) (r (2) = 0.38, p < 0.001). Foot sole vibrations at 70 and 85 % of sensory threshold increased ML sway complexity during eyes-open and eyes-closed standing (p < 0.0001). Importantly, these vibration-induced increases in complexity correlated with improvements in the TUG test of mobility (r (2) = 0.15 ~ 0.42, p < 0.001 ~ 0.03). | Does sub-sensory vibratory noise augment the physiologic complexity of postural control in older adults? | Yes. Sub-sensory foot sole vibrations augment the postural control system functionality and such beneficial effects are reflected in an increase in the physiologic complexity of standing postural sway dynamics. | PASS | pubmedQA | 1 |
12028447 | In proteinuric nephropathies with increasingly severe defects of the glomerular filtering barrier, interstitial fibrogenesis is a major effector of scarring. An early event in this process is the peritubular accumulation of myofibroblasts that express alpha-smooth muscle actin (alpha-SMA) and contribute to abnormal matrix production. Common trigger factors are poorly understood. Enhanced protein trafficking may play a role by up-regulating inflammatory and fibrogenic genes in proximal tubular cells.
The remnant kidney model in rats was used to (1) analyze interactions between activated proximal tubular cells, peritubular cells expressing the myofibroblast marker, and inflammatory cells at time intervals (days 7, 14, and 30) after surgery, and (2) evaluate the effects of angiotensin-converting enzyme inhibitor (ACEi) on protein trafficking, fibrogenic signaling, and alpha-SMA expression.
Abnormal uptake of ultrafiltered proteins by proximal tubular cells (IgG staining) occurred at an early stage (day 7) and was subsequently associated with macrophage and alpha-SMA+ cell accumulation into the peritubular interstitium. alpha-SMA+ cells clustered with macrophages into the interstitium. These changes were associated with appearance of transforming growth factor-beta1 (TGF-beta1) mRNA in proximal tubular cells and in the infiltrating cells with time. At day 30, focal alpha-SMA staining also was found in the tubular cells and in peritubular endothelial cells on semithin ultracryosections. ACEi prevented both proteinuria and abnormal protein accumulation in tubular cells, as well as the inflammatory and fibrogenic reaction with peritubular alpha-SMA expression. | Do proximal tubular cells promote fibrogenesis by TGF-beta1-mediated induction of peritubular myofibroblasts? | Yes. Profibrogenic signaling from both proximal tubular cells on challenge with filtered protein and inflammatory cells is implicated as a key candidate trigger of progressive tubulointerstitial injury. | PASS | pubmedQA | 1 |
16530322 | Current staging for renal cancer (RC) does not directly rely on tumor size. We examined the increment in accuracy related to inclusion of pathologically determined tumor size in prediction of nodal metastases (N+), distant metastases (M+), and cancer-specific survival (CSS).
Partial or radical nephrectomy was performed in 2245 patients with clear cell histology. Pathologic stages were T1a in 566, T1b in 490, T2 in 303, T3 in 831, and T4 in 55 patients. Tumor size was 0.5-25 cm (mean, 6.8). Multivariate models relied on 1997 and 2002 TNM variables and addressed N+, M+ disease, and CCS. Their accuracy was compared according to either the presence or absence of tumor size.
In all univariate and multivariate models, tumor size was a statistically significant predictor of all outcomes (p< or =0.001). In all multivariate models, tumor size added between 3.7% and 0.8% to predictive accuracy of either 1997 or 2002 TNM categories. | Does tumor size improve the accuracy of TNM predictions in patients with renal cancer? | Yes. Tumor size represents a highly significant, multivariate, and informative predictor of RC outcomes and may warrant inclusion in future TNM revisions. | PASS | pubmedQA | 1 |
24763164 | CENTRAL, Medline, Embase, Web of Science, LILACS and BBO databases, the Brazilian database of thesis and dissertations (Banco de Teses CAPES), a Brazilian register of ethically approved projects involving human beings (SISNEP) and two registers of ongoing trials (Current Controlled Trials and Clinical-Trials.gov). Reference lists were also scanned for relevant papers. Study authors were contacted for additional information.
Individual or cluster-randomised or quasi-randomised controlled trials conducted in children under seven were included.
Study selection and data abstraction were conducted by two reviewers independently. Risk of bias assessment was undertaken using the Cochrane Collaboration tool. Meta-analyses of prevented fractions (PF) were performed to assess the effect of fluoride toothpaste on the dmft and dmfs. Meta-analyses were also performed to obtain a pooled relative risk (RR) to assess the effect of fluoride toothpastes on the proportion of children developing caries.
Eight studies were included. When standard F toothpastes were compared to placebo or no intervention, significant caries reduction at surface (PF = 31%; 95% CI 18-43; 2644 participants in five studies), tooth (PF = 16%; 95% CI 8-25; 2555 participants in one study) and individual (RR = 0.86; 95% CI 0.81-0.93; 2806 participants in two studies) level were observed. Low F toothpastes were effective only at surface level (PF = 40%; 95% CI 5-75; 561 participants in two studies). | Does limited evidence suggest standard fluoride toothpaste reduces caries potential in preschool children? | Yes. Standard F toothpastes are effective in reducing dental caries in the primary teeth of preschool children and thus their use should be recommended to this age group. | PASS | pubmedQA | 1 |
11164124 | To characterize the distribution of errors in self-reported sodium and potassium dietary intakes relative to more objective urine measures among participants receiving lifestyle interventions.
We analyzed longitudinal data from 900 individuals with hypertension who had been enrolled in a randomized controlled clinical trial to establish whether usual care or three lifestyle interventions (weight loss, sodium reduction, and combined weight loss and sodium reduction) could effectively substitute for phamacotherapy. Repeated standardized 24-hour diet recalls and 24-hour urine collections were collected over up to three years of follow-up to estimate sodium and potassium intakes. By contrasting self-reported and urine-based sodium and potassium data collected before and during interventions, we examined the relative impact of intervention assignment on estimated intakes, repeatability, and multivariate measurement error.
Relative to urine-based measures, mean self-reported sodium intakes were biased about 10% lower among participants assigned to combined weight loss and sodium reduction, but were unaffected by the other interventions. The repeatability of self-report measures increased slightly with time, particularly among participants assigned to sodium interventions. Errors in self-reported sodium and potassium intakes were correlated before the start of the intervention, but became uncorrelated among individuals assigned to sodium restriction interventions. | Do lifestyle interventions influence relative errors in self-reported diet intake of sodium and potassium? | Yes. Lifestyle interventions may influence not only diet intake, but also the measurement of diet intake. | PASS | pubmedQA | 1 |
22590653 | Blood vessels in tumors express higher level of aminopeptidase N (APN) than normal tissues. Evidence suggests that the CNGRC motif is an APN ligand which targets tumor vasculature. Increased expression of APN in tumor vascular endothelium, therefore, offers an opportunity for targeted delivery of NGR peptide-linked drugs to tumors.
To determine whether an additional cyclic CNGRC sequence could improve endothelial cell homing and antitumor effect, human plasminogen kringle 5 (hPK5) was modified genetically to introduce a CNGRC motif (NGR-hPK5) and was subsequently expressed in yeast. The biological activity of NGR-hPK5 was assessed and compared with that of wild-type hPK5, in vitro and in vivo. NGR-hPK5 showed more potent antiangiogenic activity than wild-type hPK5: the former had a stronger inhibitory effect on proliferation, migration and cord formation of vascular endothelial cells, and produced a stronger antiangiogenic response in the CAM assay. To evaluate the tumor-targeting ability, both wild-type hPK5 and NGR-hPK5 were (99 m)Tc-labeled, for tracking biodistribution in the in vivo tumor model. By planar imaging and biodistribution analyses of major organs, NGR-hPK5 was found localized to tumor tissues at a higher level than wild-type hPK5 (approximately 3-fold). Finally, the effects of wild-type hPK5 and NGR-modified hPK5 on tumor growth were investigated in two tumor model systems. NGR modification improved tumor localization and, as a consequence, effectively inhibited the growth of mouse Lewis lung carcinoma (LLC) and human colorectal adenocarcinoma (Colo 205) cells in tumor-bearing mice. | Does modification of cyclic NGR tumor neovasculature-homing motif sequence to human plasminogen kringle 5 improve inhibition of tumor growth? | Yes. These studies indicated that the addition of an APN targeting peptide NGR sequence could improve the ability of hPK5 to inhibit angiogenesis and tumor growth. | PASS | pubmedQA | 1 |
11546720 | Ischemic preconditioning protects the heart against subsequent prolonged ischemia by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. Thiopentone blocks K(ATP) channels in isolated cells. Therefore, we investigated the effects of thiopentone on ischemic preconditioning.
Isolated rat hearts (n=56) were subjected to 30 min of global no-flow ischemia, followed by 60 min of reperfusion. Thirteen hearts underwent the protocol without intervention (control, CON) and in 11 hearts (preconditioning, PC), ischemic preconditioning was elicited by two five-minute periods of ischemia. In three additional groups, hearts received 1 (Thio 1, n=11), 10 (Thio 10, n=11) or 100 microg x mL(-1) (Thio 100, n=10) thiopentone for five minutes before preconditioning. Left ventricular (LV) developed pressure and creatine kinase (CK) release were measured as variables of myocardial performance and cellular injury, respectively.
Recovery of LV developed pressure was improved by ischemic preconditioning (after 60 min of reperfusion, mean +/- SD: PC, 40 +/- 19% of baseline) compared with the control group (5 +/- 6%, P <0.01) and this improvement of myocardial function was not altered by administration of thiopentone (Thio 1, 37 +/- 15%; Thio 10, 36 +/- 16%; Thio 100, 38 +/- 16%, P=0.87-0.99 vs PC). Total CK release over 60 min of reperfusion was reduced by preconditioning (PC, 202 +/- 82 U x g(-1) dry weight) compared with controls (CON, 383 +/- 147 U x g(-1), P <0.01) and this reduction was not affected by thiopentone (Thio 1, 213 +/- 69 U x g(-1); Thio 10, 211 +/- 98 U x g(-1); Thio 100, 258 +/- 128 U x g(-1), P=0.62-1.0 vs PC). | Does thiopentone block ischemic preconditioning in the isolated rat heart? | No. These results indicate that thiopentone does not block the cardioprotective effects of ischemic preconditioning in an isolated rat heart preparation. | PASS | pubmedQA | 1 |
26477894 | To answer questions on the essential components (services, operations and resources) of a person-centered aged care home (iHome) using computer simulation.
iHome was developed with AnyLogic software using extant study data obtained from 60 Australian aged care homes, 900+ clients and 700+ aged care staff. Bayesian analysis of simulated trial data will determine the influence of different iHome characteristics on care service quality and client outcomes. Interim results: A person-centered aged care home (socio-cultural context) and care/lifestyle services (interactional environment) can produce positive outcomes for aged care clients (subjective experiences) in the simulated environment. | Does computer modeling with randomized-controlled trial data inform the development of person-centered aged care homes? | Yes. Further testing will define essential characteristics of a person-centered care home. | PASS | pubmedQA | 1 |
25589556 | High-density lipoprotein (HDL) is a heterogeneous population of particles. Differences in the capacities of HDL subfractions to remove cellular cholesterol may explain variable correlations between HDL-cholesterol and cardiovascular risk and inform future targets for HDL-related therapies. The ATP binding cassette transporter A1 (ABCA1) facilitates cholesterol efflux to lipid-free apolipoprotein A-I, but the majority of apolipoprotein A-I in the circulation is transported in a lipidated state and ABCA1-dependent efflux to individual HDL subfractions has not been systematically studied.
Our aims were to determine which HDL particle subfractions are most efficient in mediating cellular cholesterol efflux from foam cell macrophages and to identify the cellular cholesterol transporters involved in this process.
We used reconstituted HDL particles of defined size and composition, isolated subfractions of human plasma HDL, cell lines stably expressing ABCA1 or ABCG1, and both mouse and human macrophages in which ABCA1 or ABCG1 expression was deleted. We show that ABCA1 is the major mediator of macrophage cholesterol efflux to HDL, demonstrating most marked efficiency with small, dense HDL subfractions (HDL3b and HDL3c). ABCG1 has a lesser role in cholesterol efflux and a negligible role in efflux to HDL3b and HDL3c subfractions. | Is hDL particle size a critical determinant of ABCA1-mediated macrophage cellular cholesterol export? | Yes. Small, dense HDL subfractions are the most efficient mediators of cholesterol efflux, and ABCA1 mediates cholesterol efflux to small dense HDL and to lipid-free apolipoprotein A-I. HDL-directed therapies should target increasing the concentrations or the cholesterol efflux capacity of small, dense HDL species in vivo. | PASS | pubmedQA | 1 |
10632523 | Chemokines are chemotactic cytokines that stimulate recruitment of leukocytes. Monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and RANTES (regulated on activation, normal T cell expressed, and secreted) are 3 well-characterized CC-chemokines that regulate mononuclear cell recruitment. The recruitment of inflammatory cells is of particular importance in the oral cavity because of the likelihood that cells will be challenged with bacteria either during acute infection or following surgical procedures. Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans are putative periodontal pathogens that may be harbored in subgingival and supragingival plaque. The capacity of the host to respond to these bacteria by the elaboration of chemoattractants may represent an important defense mechanism.
In the present study, we examined CC-chemokine production by human mononuclear cells and bone-derived cells in response to P. gingivalis, A. actinomycetemcomitans and lipopolysaccharides (LPS) stimulation in vitro. The chemokines produced were measured by ELISA.
The results demonstrate that P. gingivalis and A. actinomycetemcomitans induce high levels of MIP-1alpha in mononuclear cells. P. gingivalis and A. actinomycetemcomitans stimulated high levels of MCP-1 in bone-derived cells and induced moderate levels of RANTES production in both mononuclear and osteoblastic cells. In mononuclear cells, LPS induced high levels of MIP-1alpha and RANTES and moderate levels of MCP-1; in osteoblasts LPS only induced MCP-1. | Do periodontal pathogens stimulate CC-chemokine production by mononuclear and bone-derived cells? | Yes. The capacity of bacteria to induce a given chemokine depends upon the cell type stimulated. That different cell types would exhibit differences in the CC-chemokines produced under the same stimulus provides a mechanism to explain tissue-specific recruitment of leukocytes. | PASS | pubmedQA | 1 |
27539026 | The use of electronic devices emitting blue light during evening hours has been associated with sleep disturbances in humans, possibly due to the blue light-mediated suppression of the sleep-promoting hormone melatonin. However, experimental results have been mixed. The present study therefore sought to investigate if reading on a self-luminous tablet during evening hours would alter sleepiness, melatonin secretion, nocturnal sleep, as well as electroencephalographic power spectral density during early slow-wave sleep.
Following a constant bright light exposure over 6.5 hours (~569 lux), 14 participants (six females) read a novel either on a tablet or as physical book for two hours (21:00-23:00). Evening concentrations of saliva melatonin were repeatedly measured. Sleep (23:15-07:15) was recorded by polysomnography. Sleepiness was assessed before and after nocturnal sleep. About one week later, experiments were repeated; participants who had read the novel on a tablet in the first experimental session continued reading the same novel in the physical book, and vice versa.
There were no differences in sleep parameters and pre-sleep saliva melatonin levels between the tablet reading and physical book reading conditions. | Does two hours of evening reading on a self-luminous tablet vs. reading a physical book alter sleep after daytime bright light exposure? | No. Bright light exposure during daytime has previously been shown to abolish the inhibitory effects of evening light stimulus on melatonin secretion. Our results could therefore suggest that exposure to bright light during the day - as in the present study - may help combat sleep disturbances associated with the evening use of electronic devices emitting blue light. However, this needs to be validated by future studies with larger sample populations. | PASS | pubmedQA | 1 |
12567340 | Arthroscopic anterior cruciate ligament (ACL) reconstruction of the knee is a painful procedure requiring intensive postoperative pain management. This prospective study investigates analgesic quality after a femoral block as compared with intra-articular injection of local anesthetic.
Eighty patients scheduled for elective ACL repair under general anesthesia were included in our study. Upon completion of surgery, the patients were randomly assigned into 1 of 2 groups: femoral group (n = 40) received a femoral block with 20 mL 1% ropivacaine; intra-articular group (n = 40) received 20 mL 1% ropivacaine injected intra-articularly. During the first 24 hours after surgery, all patients received 2 g propacetamol and 100 mg ketoprofen, intravenously. Additional postoperative analgesia was available with parenteral morphine if required. Analgesic duration was defined as the time from end of surgery to the first requirement for a supplemental analgesic. Data collection included patient demographics, visual analog scale (VAS) scores, analgesic duration, and morphine use. Analysis of variance (ANOVA) test was used to compare the 2 groups.
VAS score in the recovery room and during rehabilitation was higher in the intra-articular group than in the femoral group (P <.001). Morphine use was lower in the femoral group than in the intra-articular group (P <.001). Similarly, analgesic duration was longer in the femoral group than the intra-articular group (P <.0001). | Does femoral block provide superior analgesia compared with intra-articular ropivacaine after anterior cruciate ligament reconstruction? | Yes. Compared with intra-articular injection of local anesthetic, femoral nerve block (FNB) provides better analgesia and allows a significant morphine-sparing effect after ACL repair. | PASS | pubmedQA | 1 |
27555146 | Postoperative cognitive dysfunction (POCD) is a well-known complication after cardiac surgery and may cause permanent disabilities with severe consequences for quality of life. The objectives of this study were, first, to estimate the frequency of POCD after on-pump cardiac surgery in patients randomized to remifentanil- or sufentanil-based anesthesia and, second, to evaluate the association between POCD and quality of recovery and perioperative hemodynamics, respectively.
Randomized study.
Postoperative cardiac recovery unit, University Hospital.
Sixty patients with ischemic heart disease scheduled for elective coronary artery bypass grafting ± aortic valve replacement.
Randomized to either remifentanil or sufentanil anesthesia as basis opioid. Postoperative pain management consisted of morphine in both groups.
Cognitive functioning evaluated preoperatively and on the 1st, 4th, and 30th postoperative day using the cognitive test from the Palo Alto Veterans Affairs Hospital. Perioperative invasive hemodynamics and the quality of recovery was evaluated by means of invasive measurements and an intensive care unit discharge score.
No difference between opioids in POCD at any time. A negative correlation was found between preoperative cognitive function and POCD on the first postoperative day (r=-0.47; P=.0002). The fraction of patients with POCD on the first postoperative day was statistically greater in patients with more than 15minutes of Svo2 <60 (P=.037; χ(2) test). Among patients with postoperative ventilation time exceeding 300minutes, more patients had POCD on postoperative day 4 (P=.002). | Is ultrashort acting remifentanil superior to long-acting sufentanil in preserving cognitive function-a randomized study? | No. We could not demonstrate differences in POCD between remifentanil and sufentanil based anaesthesia, but in general, the fraction of patients with POCD seemed smaller than previously reported. We found an association between POCD and both perioperative low Svo2 and postoperative ventilation time, underlining the importance of perioperative stable hemodynamics and possible fast-track protocols with short ventilation times to attenuate POCD. | PASS | pubmedQA | 1 |
23726316 | To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task).
Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring (n = 38) were imaged by positron emission tomography with the DAT ligand [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT).
Results showed that prenatal stress yielded an overall increase of 15% in [(18)F]FECNT binding in the striatum (p = .016), 17% greater binding in the putamen (p = .012), and 13% greater binding in the head of the caudate (p = .028) relative to animals not exposed to prenatal stress. Striatal [(18)F]FECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on [(18)F]FECNT binding. | Does prenatal stress induce increased striatal dopamine transporter binding in adult nonhuman primates? | Yes. Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children. | PASS | pubmedQA | 1 |
16159818 | The purpose of this research was to investigate the in vivo morphofunctional changes induced in the radial artery (RA) by its use as coronary artery bypass conduit by comparing the morphological features and vasoreactivity of the native RA versus the coronary RA graft in the same patient.
Ten years after surgery, 10 patients were submitted to intravascular ultrasound examination of the RA graft of the controlateral (in situ) RA and of the internal thoracic artery (ITA) graft and to vasoactive challenges with acetylcholine and serotonin. Quantitative angiographic assessment showed that the mean diameter of the RA coronary grafts was significantly larger than that of the in situ RA and of the ITA (2.89+/-0.40 mm RA grafts, 2.14+/-0.52 mm in situ RA, 2.25+/-0.53 mm ITA grafts; P<0.001). The in situ RA demonstrated a typical muscular architecture, whereas RA coronary grafts showed a clear reduction of the thickness of the medial layer and had a less well-defined muscular component of the media with interposition of elastic tissue. Serotonin endovascular infusion elicited a strong spastic reaction in in situ RAs; the same challenge induced only moderate constriction in RA and ITA coronary grafts. | Does implantation in coronary circulation induce morphofunctional transformation of radial grafts from muscular to elastomuscular? | Yes. Implantation in the coronary circulation leads to major anatomic and vasoreactive modifications of the RAs that tend to lose the morphofunctional features of a muscular conduit and assume those of an elastomuscular artery, such as the ITA. | PASS | pubmedQA | 1 |
26068301 | This study investigates the effect of spectral loudness summation (SLS) in the electrical domain as perceived by cochlear implant (CI) users. Analogous to SLS in the acoustical domain, SLS was defined as the effect of electrode separation at a fixed overall stimulation rate.
Categorical loudness scaling (CLS) was conducted at three overall stimulation rates using single-electrode stimuli and multi-electrode stimuli presented interleaved on two or four electrodes. The specific loudness of the pulses in the multi-electrode stimuli were equalized based on single-electrode measurements at the same overall stimulation rate. At a fixed overall stimulation rate and a fixed loudness perception, SLS was calculated as the difference in mean current between single-electrode and multi-electrode stimuli.
Ten postlingually deafened adult CI users.
The amount of SLS varied between subjects and between the number and location of the stimulated electrodes in the multi-electrode configuration. SLS was significantly higher than 0 for a subset of the subjects. | Do spectral loudness summation for electrical stimulation in cochlear implant users? | Yes. For a subpopulation of CI users, loudness models should account for nonlinear interactions between electrodes (in the perceptual domain). Similarly, SLS should be accounted for when using CLS outcomes for fitting purposes, at least in a subpopulation of CI users. | PASS | pubmedQA | 1 |
20333792 | To investigate the efficacy of short-term peg-interferon (PEG-IFN) monotherapy for chronic hepatitis C patients who achieved an immediate virological response.
Defining an "immediate virological response (IVR)" as the loss of serum hepatitis C virus (HCV) RNA 7 d after the first administration of PEG-IFN alpha, we conducted a 12-wk course of PEG-IFN alpha2a monotherapy without the addition of ribavirin for 38 patients who had low pretreatment HCV RNA load and exhibited IVR. The patients included 21 men and 17 women, whose ages ranged from 22 to 77 years (mean +/- SD: 52.0 +/- 17.8 years). There were 4 patients with HCV genotype 1b, 23 patients with genotype 2a and 4 patients with genotype 2b. HCV genotype was not determined for the remaining 7 patients. Patients were categorized into a sustained virological response (SVR) group, if serum HCV RNA remained negative for 24 wk after the end of treatment, or into a relapse group.
Based on the intention-to-treat analysis, 35 patients (92.1%) achieved SVR. One patient (2.6%) relapsed with serum HCV RNA 12 wk after the end of treatment. Two patients (5.3%) withdrew from the study during the 24-wk follow-up period. With regard to the HCV RNA genotype, the SVR rates were 100% (4/4) for genotype 1b, 95.7% (22/23) for genotype 2a and 100% (4/4) for genotype 2b. The SVR rate in 7 patients, whose HCV RNA genotypes were not determined, was 71.4% (5/7). | Does immediate virological response predict the success of short-term peg-interferon monotherapy for chronic hepatitis C? | Yes. Short-term PEG-IFN alpha2a monotherapy is highly effective for chronic hepatitis C patients who have low pretreatment HCV RNA load and exhibit IVR. | PASS | pubmedQA | 1 |
24798308 | The current standard of care for burns requiring operative treatment consists of early burn excision and autologous split-thickness skin grafting. However, in large burns, sufficient donor sites may not be available to achieve total coverage, necessitating temporary coverage with allogeneic human cadaver skin grafts or synthetic skin substitutes. A previous study from this laboratory demonstrated that skin grafts from alpha-1,3 galactosyltransferase knockout (GalT-KO) miniature swine enjoyed survival comparable to that of allogeneic skin grafts in baboons.
In the present study, we have evaluated the immune response against sequential GalT-KO and allogeneic skin grafts to determine whether such serial grafts could extend the period of temporary wound coverage before definitive grafting with autologous skin.
We report that rejection of primary GalT-KO skin grafts led to an anti-xenogeneic humoral response with no evidence for sensitization to alloantigens nor acceleration of rejection of allogeneic skin grafts. Similarly, presensitization with allogeneic skin did not lead to accelerated rejection of xenogeneic skin. | Does lack of cross-sensitization between α-1,3-galactosyltransferase knockout porcine and allogeneic skin grafts permit serial grafting? | Yes. These data suggest that GalT-KO skin grafts could provide an early first-line treatment in the management of severe burns that would not preclude subsequent use of allografts, and that serial grafting of GalT-KO skin and allogeneic skin could potentially be used to provide an extended period of temporary burn wound coverage. | PASS | pubmedQA | 1 |
26276306 | The experience of social defeat may increase the risk of developing psychotic symptoms and psychotic disorders. We studied the relationship between social defeat and paranoid appraisal in people at high risk for psychosis in an experimental social environment created using Virtual Reality (VR).
We recruited UHR (N=64) participants and healthy volunteers (N=43). Regression analysis was used to investigate which baseline measures predicted paranoid appraisals during the VR experience.
At baseline, UHR subjects reported significantly higher levels of social defeat than controls (OR=.957, (CI) .941-.973, p<.000). Following exposure to the VR social environment, the UHR group reported significantly more paranoid appraisals than the controls (p<.000). Within the UHR sample, paranoid appraisals were predicted by the level of social defeat at baseline, as well as by the severity of positive psychotic and disorganised symptoms. | Does social defeat predict paranoid appraisals in people at high risk for psychosis? | Yes. In people who are at high risk of psychosis, a history of social defeat is associated with an increased likelihood of making paranoid appraisals of social interactions. This is consistent with the notion that social defeat increases the risk of developing psychosis. | PASS | pubmedQA | 1 |
19738375 | Our aim was to investigate the relationship between the number of stroke physicians (SPs) and management of intravenous thrombolysis using recombinant tissue plasminogen activator (IV rt-PA) in Japan.
Questionnaires about the infrastructure of acute-stroke care were sent to 1,466 hospitals that treated acute-stroke patients in September 2007. The responses were categorized as follows: (1) established or ineligible for IV rt-PA before September 2007, and discontinued or starting IV rt-PA from October 2007 to September 2008; (2) total number of SPs in those hospitals; (3) infrastructures according to acute-stroke treatment. Components related to discontinuing or starting IV rt-PA were analyzed.
Responses were received from 1,025 hospitals. Of these, 950 hospitals were continuing administration to acute-stroke patients, but 75 had discontinued administration. Before September 2007, 466 hospitals had already established administration of IV rt-PA (rt-PA hospitals) after government approval of IV rt-PA (non-rt-PA hospitals). From October 2007 to September 2008, 45 of 466 rt-PA hospitals (9.7%) discontinued IV rt-PA, while 29 of 479 (6.1%) non-rt-PA hospitals started. Less than 3 SPs were present in 73.9% of the 45 discontinued IV rt-PA hospitals and 37.9% of the 29 starting hospitals. In multivariate analysis, discontinuing IV rt-PA was inversely associated with > or =3 SPs (odds ratio = 0.37; 95% confidence interval = 0.15-0.87; p = 0.023). Factors associated with starting IV rt-PA were > or =3 SPs (OR = 6.19; 95% CI = 2.01-19.08; p = 0.002). | Is the number of stroke physicians the key to preparing IV rt-PA? | Yes. The number of SPs available may contribute to the management of rt-PA hospitals. | PASS | pubmedQA | 1 |
18067970 | To examine phenotypes of age-related macular degeneration (AMD) patients with the complement factor H (CFH) variant (Y402H, C allele at rs1061170).
Clinic-based case series study.
The data set contained a total of 956 unrelated cases of AMD.
Age-related macular degeneration phenotypes of 796 carriers of the CFH Y402H variant were compared with the AMD phenotypes of 160 noncarriers.
Presence or absence of 34 phenotypic features.
Of the 34 features analyzed, only peripheral reticular pigmentary change (PRPC) was associated with this CFH variant (P = 0.0006). The proportion of AMD cases with PRPC correlated with the number of CFH risk C alleles in a dose-response fashion. | Is peripheral reticular pigmentary change associated with complement factor H polymorphism ( Y402H ) in age-related macular degeneration? | Yes. The CFH Y402H polymorphism is associated with PRPC, suggesting that AMD changes are not limited to the macula. Current AMD grading methods assess only the macula and should consider incorporating peripheral retinal changes. Phenotypes that suggest a high-risk genotype may prove valuable for diagnostic, therapeutic, and research purposes. | PASS | pubmedQA | 1 |
16261403 | In the adjuvant setting, taxanes modestly improve clinical outcome and survival. The goal of the present study was to define the efficacy of neoadjuvant docetaxel in treatment-naïve large, locally advanced breast cancers and to better understand docetaxel's mechanism of action by evaluating biomarker modulation in response to treatment.
Fifty-one patients were enrolled. Patients received four cycles of docetaxel (100 mg/m2 q3weeks) followed by surgery and four cycles of doxorubicin and cyclophosphamide (60/600 mg/m2 q3weeks). Radiation and hormonal therapy were given if clinically indicated. Clinical responses were assessed at completion of neoadjuvant docetaxel. Pathological responses were considered complete (pCR) if no tumor cells were identified in the surgical specimen or near complete (npCR) if only occasional scattered tumor cells were seen. Proliferation (Ki-67) and apoptosis (cleaved caspase-3) were measured by IHC in tissue obtained at baseline and at surgery.
The median tumor size was 9 cm (range 4-30 cm). Objective response rate was 75% with clinical complete response in 27%, partial response in 48%, and stable disease in 25% of the patients. pCR/npCR was reported in 20% of patients. With a median follow up of 28 months, 98 and 78% of the patients were alive at 12 and 24 months, respectively. Overall survival at 24 months was significantly better in patients who achieved a clinical response, 85 versus 51%, p = 0.008, but pCR/npCR was not a significant predictor of outcome. Apoptosis was induced in clinical responders (p = 0.002), while the proliferation index did not change significantly. In patients who had no clinical response to docetaxel, neither apoptosis nor proliferation changed significantly. | Does clinical response to neoadjuvant docetaxel predict improved outcome in patients with large locally advanced breast cancers? | Yes. Neoadjuvant single agent docetaxel is effective in treating patients with large locally advanced breast cancer and clinical response is associated with improved survival. Docetaxel acts therapeutically by inducing apoptosis and this can be used as a marker of response. | PASS | pubmedQA | 1 |
12371978 | The clinical relevance of distinguishing two types of glomerulonephritis (GN) with non-amyloid organized immunoglobulin (Ig) deposits-fibrillary GN (FGN) and immunotactoid (microtubular) GN (IT/MTGN)-on the basis of ultrastructural organization, is debated.
Twenty-three patients with organized glomerular Ig deposits were classified into two groups based on the fibrillar or microtubular ultrastructural appearance of the deposits. Kidney biopsy samples were studied by immunofluorescence microscopy, using anti-light chain conjugates (all cases) and anti-IgG subclass conjugates (13 patients). In each group, we studied clinicopathological features, associated monoclonal gammapathy (detected by immunoelectrophoresis and/or immunoblot) or B-cell lymphoproliferative disease, effects of chemotherapy and long-term renal outcome.
In 14 IT/MTGN and 9 FGN patients, clinical symptoms [hypertension, nephrotic syndrome (NS) and hematuria] and the mean diameters of the substructures were similar. In 13 IT/MTGN patients, glomerular (IgG1, 2 or 3) deposits were monotypic (kappa, 7 cases; lambda, 6 cases). Glomerular deposits were associated with a monoclonal Ig of the same isotype in eight patients, detected in the serum (5 cases), and/or in the cytoplasm of lymphocytes (4 cases), and with lymphoproliferative disease in seven patients. The ultrastructural features of monoclonal Ig inclusions in lymphocytes were similar to those of glomerular microtubular deposits. In contrast, none of the FGN patients presented lymphoplasmocytic proliferation or paraproteinemia. Glomerular Ig deposits were polyclonal in eight cases and contained IgG4 in all three cases studied. Although patient and renal survival did not differ significantly between the two groups, chemotherapy led to remission of NS in ten IT/MTGN patients, with parallel improvement in hematological parameters. | Are fibrillary glomerulonephritis and immunotactoid ( microtubular ) glomerulopathy associated with distinct immunologic features? | Yes. The identification of ultrastructural patterns in these nephropathies is important. GN with organized microtubular monoclonal deposits (GOMMID) probably accounts for a large proportion of immunotactoid (microtubular) GN cases. | PASS | pubmedQA | 1 |
24449823 | TGF-β promotes tumor invasion and metastasis by inducing an epithelial-mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA malat1 (metastasis associated lung adenocarcinoma transcript 1) is a critical regulator of the metastasis phenotype of lung cancer cells.
We, therefore, investigated whether TGF-β regulates malat1 expression to promote tumor metastasis of bladder cancer. The expression levels of malat1 and EMT markers were assayed in specimens of bladder cancer. The role of malat1 in regulating bladder cancer metastasis was evaluated in cell and animal models.
TGF-β induces malat1 expression and EMT in bladder cancer cells. malat1 overexpression is significantly correlated with poor survival in patients with bladder cancer. malat1 and E-cadherin expression is negatively correlated in vitro and in vivo. malat1 knockdown inhibits TGF-β-induced EMT. malat1 is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of malat1 or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that malat1 or suz12 knockdown inhibits tumor metastasis in animal models. | Does tGF-β-induced upregulation of malat1 promote bladder cancer metastasis by associating with suz12? | Yes. These data suggest that malat1 is an important mediator of TGF-β-induced EMT, and suggest that malat1 inhibition may represent a promising therapeutic option for suppressing bladder cancer progression. | PASS | pubmedQA | 1 |
25481622 | Hunger enhances sensitivity to reward, yet individuals with anorexia nervosa (AN) are not motivated to eat when starved. This study investigated brain response to rewards during hunger and satiated states to examine whether diminished response to reward could underlie food restriction in AN.
Using a delay discounting monetary decision task known to discriminate brain regions contributing to processing of immediate rewards and cognitive control important for decision making regarding future rewards, we compared 23 women remitted from AN (RAN group; to reduce the confounding effects of starvation) with 17 healthy comparison women (CW group). Monetary rewards were used because the rewarding value of food may be confounded by anxiety in AN.
Interactions of Group (RAN, CW) × Visit (hunger, satiety) revealed that, for the CW group, hunger significantly increased activation in reward salience circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during processing of immediate reward, whereas satiety increased activation in cognitive control circuitry (ventrolateral prefrontal cortex, insula) during decision making. In contrast, brain response in reward and cognitive neurocircuitry did not differ during hunger and satiety in the RAN group. A main effect of group revealed elevated response in the middle frontal gyrus for the RAN group compared with the CW group. | Does hunger motivate reward in women remitted from anorexia nervosa? | No. Women remitted from AN failed to increase activation of reward valuation circuitry when hungry and showed elevated response in cognitive control circuitry independent of metabolic state. Decreased sensitivity to the motivational drive of hunger may explain the ability of individuals with AN to restrict food when emaciated. Difficulties in valuating emotional salience may contribute to inabilities to appreciate the risks inherent in this disorder. | PASS | pubmedQA | 1 |
15922431 | To determine whether use of the digital rectal examination (DRE) results in decreased participation in prostate cancer (PCa) screening, which, in turn, would result in lower detection. Population-based PCa screening includes prostate-specific antigen (PSA) measurement with or without a DRE. PSA and DRE screening provide greater sensitivity than PSA alone; however, the increased participation rate resulting from PSA-alone screening may result in a greater detection rate.
We performed a survey of 13,580 healthy men undergoing PSA-only population-based screening. In addition to the basic demographic information, the survey asked whether the participant would still be willing to participate in the screening if it included a DRE. We modeled the willingness to participate to assess the effect of PSA screening versus PSA and DRE screening on the basis of previously published data and our results.
The results of our study indicated that only 78% of men would participate in screening that included both DRE and PSA. Thus, 7800 men of a theoretical population of 10,000 would participate in a screening that included both DRE and PSA. The positive screen rate (PSA > or = 4.0 ng/mL and/or abnormal DRE) would then have been 2013, with 472 PCa cases and 1540 negative biopsies. In the PSA-alone arm, all 10,000 men would have agreed to participate, and the positive screen rate (PSA > or = 4.0 ng/mL) would have been 1480, with 499 PCa cases and 980 negative biopsies. The PSA-alone arm would thus have detected 27 more cancers and performed 560 fewer negative biopsies. | Is digital rectal examination barrier to population-based prostate cancer screening? | Yes. The results of our study have demonstrated that DRE is a significant barrier to participation in PCa screening. PSA plus DRE-based programs result in fewer cases of PCa detected, with a significant increase in negative biopsies. We, therefore, suggest that future mass screening efforts include only PSA determination and omit the DRE. | PASS | pubmedQA | 1 |
23929663 | Reactivity and titers of autoantibodies vary during the course of autoimmune hepatitis (AIH), and some autoantibodies have been associated with disease activity and adverse outcomes after treatment. The aim of this study was to assess the autoantibody behavior in AIH and its significance as predictors of biochemical and histological remission. A total of 117 patients with AIH (mean age 18.6 [4-69] years) were evaluated and tested for autoantibodies at disease onset and successively (mean 3.2 [2-6] times) after a mean follow-up evaluation of 70 [20-185] months. Antismooth muscle (ASMA), antiliver kidney microsome type 1 (anti-LKM1), antiliver cytosol type 1 (anti-LC1), antimitochondrial, antinuclear (ANA), and antiactin antibodies (AAA) were determined at disease onset and 379 other times during the follow-up evaluation through indirect immunofluorescence in rodent tissues, HEp-2 cells, and human fibroblasts. Anti-SLA/LP were assessed 45 times in the follow-up evaluation of 19 patients using enzyme-linked immunosorbent assay (ELISA). Upon admission, AIH types 1 and 2 were observed in 95 and 17 patients, respectively. Five subjects had AIH with anti-SLA/LP as the sole markers. Patients initially negative for AAA did not develop these antibodies thereafter. ANA were detected de novo in six and three subjects with AIH types 1 and 2, respectively. After treatment, only ASMA (>1:80) and AAA (>1:40) were significantly associated with biochemical (76.9% and 79.8%) and histological features (100% and 100%) of disease activity (P < 0.001). | Are antismooth muscle and antiactin antibodies indirect markers of histological and biochemical activity of autoimmune hepatitis? | Yes. With the exception of ANA, the autoantibody profile does not markedly vary in the course of AIH. The persistence of high titers of ASMA and/or AAA in patients with AIH is associated with disease activity. | PASS | pubmedQA | 1 |
23800339 | We addressed the question whether live-virus challenges could alter vaccine-induced antibody (Ab) responses in vaccinated rhesus macaques (RMs) that completely resisted repeated exposures to R5-tropic simian-human immunodeficiency viruses encoding heterologous HIV clade C envelopes (SHIV-Cs).
We examined the Ab responses in aviremic RMs that had been immunized with a multi-component protein vaccine (multimeric HIV-1 gp160, HIV-1 Tat and SIV Gag-Pol particles) and compared anti-Env plasma Ab titers before and after repeated live-virus exposures. Although no viremia was ever detected in these animals, they showed significant increases in anti-gp140 Ab titers after they had encountered live SHIVs. When we investigated the dynamics of anti-Env Ab titers during the immunization and challenge phases further, we detected the expected, vaccine-induced increases of Ab responses about two weeks after the last protein immunization. Remarkably, these titers kept rising during the repeated virus challenges, although no viremia resulted. In contrast, in vaccinated RMs that were not exposed to virus, anti-gp140 Ab titers declined after the peak seen two weeks after the last immunization. These data suggest boosting of pre-existing, vaccine-induced Ab responses as a consequence of repeated live-virus exposures. Next, we screened polyclonal plasma samples from two of the completely protected vaccinees by peptide phage display and designed a strategy that selects for recombinant phages recognized only by Abs present after - but not before - any SHIV challenge. With this "subtractive biopanning" approach, we isolated V3 mimotopes that were only recognized after the animals had been exposed to live virus. By detailed epitope mapping of such anti-V3 Ab responses, we showed that the challenges not only boosted pre-existing binding and neutralizing Ab titers, but also induced Abs targeting neo-antigens presented by the heterologous challenge virus. | Does live-virus exposure of vaccine-protected macaques alter the anti-HIV-1 antibody repertoire in the absence of viremia? | Yes. Anti-Env Ab responses induced by recombinant protein vaccination were altered by the multiple, live SHIV challenges in vaccinees that had no detectable viral loads. These data may have implications for the interpretation of "vaccine only" responses in clinical vaccine trials. | PASS | pubmedQA | 1 |
9672182 | Identification of the risk factors of multicentric hepatocarcinogenesis is important for the clinical management of hepatocellular carcinoma. We investigated hyperplastic foci in non-cancerous liver parenchyma, and clarified their pathological features and clinical significance.
Hyperplastic foci were defined as hypercellular areas, which architecturally and cytologically resembled early hepatocellular carcinoma or adenomatous hyperplasia but did not form macroscopically detectable nodules. Surgically resected livers from 155 patients with hepatocellular carcinoma were examined histopathologically and immunohistochemically.
Hyperplastic foci were found in 26 of 155 patients (16.8%). All the patients with hyperplastic foci had chronic liver diseases, and the incidence did not differ between those with chronic hepatitis and those with liver cirrhosis. Six of 92 (6.5%) patients with single primary hepatocellular carcinoma nodules, 8 of 42 (19.0%) with two nodules, and 12 of 21 (57.0%) with more than three nodules had hyperplastic foci. The incidence of hyperplastic foci showed a significant positive correlation with the multiplicity of hepatocellular carcinoma nodules. Immunohistochemically, hyperplastic foci were masses of proliferative hepatocytes similar to adenomatous hyperplasia and early hepatocellular carcinoma. | Do hyperplastic foci reflect the risk of multicentric development of human hepatocellular carcinoma? | Yes. Hyperplastic foci reflect the risk of multicentric hepatocarcinogenesis. Our results suggest strongly that hyperplastic foci are precursors of adenomatous hyperplasia or hepatocellular carcinoma. | PASS | pubmedQA | 1 |
20014210 | Current guidelines for the use of implantable cardioverter-defibrillators (ICDs) are broad and significantly increase the cost of caring for patients with heart failure. In an effort to identify the specific subset of patients who benefit from this therapy, the predictive value of numerous echocardiographic parameters have been studied. Severe diastolic dysfunction has been shown to predict adverse events in a group of patients who received an ICD for secondary prevention, but has not been tested in those who receive ICDs for primary prevention.
We tested the hypothesis that a restrictive mitral inflow pattern on echocardiography will predict the risk of appropriate therapy in this patient population.
This retrospective study identified 145 consecutive patients who met primary prevention criteria for ICD implantation and had an echo performed no more than 1 year prior to receiving the ICD. A restrictive pattern was defined as a mitral inflow E/A > 2 or a deceleration time < 150 ms.
A restrictive pattern was present in 69 patients (40.7% of the group). Appropriate ICD therapy occurred in 8 (11.5%) subjects with a restrictive pattern and 14 (18.4%) with a nonrestrictive pattern over 680 days of average follow-up (P = not significant). Cox regression analysis showed the presence of a restrictive pattern was not helpful in predicting time to first ICD therapy. | Does a restrictive inflow pattern predict implantable cardioverter-defibrillator therapy in primary prevention? | No. In a population of patients who received ICDs for primary prevention, echocardiographic findings of severe diastolic dysfunction were not helpful in targeting the use of ICDs to those at highest risk. | PASS | pubmedQA | 1 |
9586902 | The clinical impact of endogenous cytokines supplied with deterministic properties in the generation of either T helper (Th)1 -type or Th2-type immune response was investigated in patients with ovarian cancer. Whereas interleukin (IL)- 12 initiates the differentiation of naive Th0 cells toward Th1 phenotype, IL-4 and IL-10 mediate the development of Th2-type immunity.
Cytokines were determined before treatment by means of enzyme-linked immunosorbent assay (ELISA) in ascites fluid and serum of 76 patients with ovarian cancer. Cytokine levels were compared with each other and with standard clinicopathologic parameters. A stepwise logistic regression was calculated to rule out interdependence in the associations of the various variables. Survival analyses were performed with the Kaplan-Meier method and differences in survival were examined according to Mantel and Breslow. Cox proportional hazards analysis was used to identify independent prognostic factors.
Whereas IL-10 and IL-12 were detectable in all ascites-fluid samples, IL-4 was measurable in only 43% of the specimens. With the exception of neopterin, macrophage colony-stimulating factor (M-CSF), and IL-4, determined cytokine levels were significantly elevated in ascites fluid compared with serum (P < .01). In univariate analyses, high ascitic-fluid concentrations of either neopterin, tumor necrosis factor-alpha (TNF-alpha), or IL-12 were associated with poor disease-free (P < .005) and overall (P < .01) survival. Multivariate Cox regression analysis showed ascitic-fluid IL-12 levels to be the only immunologic variable that retained independent prognostic significance (P < .03 for disease-free and P < .01 for overall survival), together with residual disease, Fédération Internationale de Gynécologie et d'Obstétrique (FIGO)-stage, and patient age. | Is ascitic interleukin-12 an independent prognostic factor in ovarian cancer? | Yes. In ovarian cancer, high ascitic-fluid IL-12 levels, which may indicate a local Th1-generated immune response, are associated with disease progression. | PASS | pubmedQA | 1 |
19328471 | To examine the effect of transforming growth factor (TGF) beta3 on immortalized myometrial and leiomyoma cell lines cloned from primary cell cultures of surgical specimens, and to determine whether such treatment alters myometrial cell extracellular matrix (ECM) expression.
Laboratory study.
University hospital.
Immortalized myometrial and leiomyoma cells from patients with symptomatic leiomyomata.
Tissue culture, followed by cellular, RNA, and protein analysis.
Cell proliferation, alteration in ECM component expression.
Immortalized leiomyoma and myometrial cells demonstrate increased mRNA and protein production of the ECM proteins, collagen 1A1 (15.0-fold), fibronectin 1 (2.93 fold), and connective tissue growth factor (9.40-fold) with exogenous TGF-beta3 stimulation. Notably, the expression of collagen 1A1, fibronectin 1, and connective tissue growth factor in myometrial cells increase to similar expression levels as those found in leiomyoma cells. In addition, TGF-beta3 decreased production of genes involved in matrix resorption, including matrix metalloproteinase 2 (0.65-fold) and -11 (0.68-fold). | Do myometrial cells undergo fibrotic transformation under the influence of transforming growth factor beta-3? | Yes. TGF-beta3 induced a molecular phenotype in myometrial cells that was similar to leiomyoma cells, with elevated production of ECM-related genes and decreased production of ECM degradation-related genes. | PASS | pubmedQA | 1 |
12704355 | This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period.
This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis.
This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point.
Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. | Is fexofenadine efficacious and safe in children ( aged 6-11 years ) with seasonal allergic rhinitis? | Yes. The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis. | PASS | pubmedQA | 1 |
27647397 | To study the intratumor heterogeneity of esophageal squamous cell carcinoma (ESCC).
We used whole-exome sequencing and array-based comparative genomic hybridization to profile mutations and changes in copy number from 11 regions within 2 cases of ESCC and from the metastatic lymph nodes.
The numbers of somatic single nuclear polymorphisms (SNPs) in 4 regions within the tumors in case 1 and case 2 were 93±17 and 124±28, respectively. The majority of SNPs were non synonymous mutations, synonymous mutations, nonsense mutations and splicing junction mutations. The average indels in the 4 tumor regions of case 1 and case 2 were 40±6 and 51±3, respectively. These small indels mainly occurred in exonic (frame-shift and non-frame-shift), untranslational regions of genes and splicing junction regions. All regions from a tumor exhibitedo bvious heterogeneity, and mutational similarity of all four regions within a tumor was less than 25%. Furthermore, gene copy number alteration (gain or loss) varied among multiple regions of a tumor, and the similarity of gene copy number was less than 20%. Phylogenetic analysis of the somatic mutation frequency suggests that multiple, genomic heterogeneous clones co-exist within a primary ESCC, and metastatic subclones may evolve from the primary non-metastatic parental clone. These results indicated that a single-region sampling can not reflect the architecture of the genomic landscape of mutations in ESCC tumors. | Does [ Multiregion sequencing reveal intratumor heterogeneity in esophageal squamous cell carcinoma ]? | Yes. Sequence analysis of whole genome exon in multiple regions can provide strong evidence for genomic heterogeneity in esophageal squamous cell carcinoma. | PASS | pubmedQA | 1 |
15297829 | The cause of the coagulopathy seen with supraceliac aortic cross-clamping (SC AXC) is unclear. SC AXC for 30 minutes results in both clotting factor consumption and activation of fibrinolytic pathways. This study was undertaken to define the hemostatic alterations that occur with longer intervals of SC AXC.
Seven pigs underwent SC AXC for 60 minutes. Five pigs that underwent infrarenal aortic cross-clamping (IR AXC) for 60 minutes and 11 pigs that underwent SC AXC for 30 minutes served as controls. No heparin was used. Blood samples were drawn at baseline, 5 minutes before release of the aortic clamp, and 5, 30, and 60 minutes after unclamping. Prothrombin time, partial thromboplastin time, platelet count, and fibrinogen concentration were measured as basic tests of hemostatic function. Thrombin-antithrombin complexes were used to detect the presence of intravascular thrombosis. Fibrinolytic pathway activation was assessed with levels of tissue plasminogen activator antigen and tissue plasminogen activator activity, plasminogen activator inhibitor-1 activity, and alpha2-antiplasmin activity. Statistical analysis was performed with the Student t test and repeated measures of analysis of variance.
Prothrombin time, partial thromboplastin time, and platelet count did not differ between groups at any time. Fibrinogen concentration decreased 5 minutes (P =.005) and 30 minutes (P =.006) after unclamping in both SC AXC groups, but did not change in the IR AXC group. Thrombin-antithrombin complexes increased in both SC AXC groups, but were not significantly greater than in the IR AXC group. SC AXC for both 30 and 60 minutes produced a significant increase in tissue plasminogen activator antigen during clamping and 5 minutes after clamping. This increase persisted for 30 and 60 minutes after clamp release in the 60-minute SC AXC group. Tissue plasminogen activator activity, however, increased only in the 60-min SC AXC group during clamping (P =.02), and 5 minutes (P =.05) and 30 minutes (P =.06) after unclamping, compared with both control groups. | Is activation of fibrinolytic pathways associated with duration of supraceliac aortic cross-clamping? | Yes. Thirty and 60 minutes of SC AXC results in similar degrees of intravascular thrombosis and fibrinogen depletion. Although SC AXC for both 30 and 60 minutes leads to activation of fibrinolytic pathways, only 60 minutes of SC AXC actually induces a fibrinolytic state. Fibrinolysis appears to be an important component of the coagulopathy associated with SC AXC, and is related to the duration of aortic clamping. | PASS | pubmedQA | 1 |
18725048 | Sepsis, endotoxin tolerance, and heat shock (HS) all display down-regulation of innate immunity. We hypothesize that HS factor 1 (HSF-1) induces competitive inhibition of nuclear factor-kappaB (NF-kappaB)-induced signal transduction in both endotoxin tolerance and HS.
We compared endotoxin tolerance and HS in RAW 264.7 cells. We transfected cells with an HS protein 70 (HSP70) plasmid to test whether HSP70 is the mediator of HS-induced NF-kappaB inhibition. We studied the effects of endotoxin stimulation and HS, both separately and together, on "wild-type" cells, cells transfected with the HSP70 plasmid, and cells transfected with vehicle.
Heat shock protein 70 plasmid-transfected cells had increased HSP70 expression and demonstrated decreased nitric oxide (NO) release and inducible NO synthase messenger RNA expression in response to endotoxin compared with wild-type and empty plasmid-transfected cells. Heat shock completely abolished subsequent NO and inducible NO synthase messenger RNA expression in wild-type cells. Heat shock factor 1 reached maximum expression 60 to 90 minutes after HS. Heat shock protein 70-transfected cells still displayed endotoxin-induced NF-kappaB nuclear binding, whereas endotoxin tolerance, HS, and exposure to HSF-1, but not exposure to an unrelated promoter, inhibited NF-kappaB nuclear binding. | Does heat shock factor 1 inhibit nuclear factor-kappaB nuclear binding activity during endotoxin tolerance and heat shock? | Yes. Endotoxin tolerance and HS appear to share a common immune suppressive effect, possibly through HSF-1-mediated competitive inhibition of NF-kappaB nuclear binding. | PASS | pubmedQA | 1 |
25930174 | Haemophilia A is an X-linked recessive bleeding disorder that primarily affects males. Emerging data support evidence for increased bleeding in female haemophilia A carriers despite factor VIII activity within the normal range.
Data regarding the effect of increased bleeding on health-related quality of life (HR-QOL) in haemophilia A carriers is sparse. We tested the hypothesis that haemophilia A carriers have reduced HR-QOL related to bleeding symptoms.
We conducted a cross-sectional study at Vanderbilt University. Case subjects were obligate or genetically verified haemophilia A carriers age 18-60 years. Control subjects were mothers of children with cancer who receive care at the Vanderbilt paediatric haematology-oncology clinic. Trained interviewers administered the Rand 36-Item Health Survey 1.0, a validated questionnaire evaluating eight health concepts that may affect HR-QOL, to each study participant. Mann-Whitney U-tests were used to compare median scores for the eight health domains between the case and control groups.
Forty-two haemophilia A carriers and 36 control subjects were included in analyses. Haemophilia A carriers had significantly lower median scores for the domains of 'Pain' (73.75 vs. 90; P = 0.02) and 'General health' (75 vs. 85; P = 0.01) compared to control subjects. | Do haemophilia A carriers experience reduced health-related quality of life? | Yes. Haemophilia A carriers in our study demonstrated significantly lower median scores on the Rand 36-item Health Survey 1.0 in the domains of 'Pain' and 'General Health' compared to women in the control group. Our findings highlight the need for further investigation of the effect of bleeding on HR-QOL in this population. | PASS | pubmedQA | 1 |
26747087 | Histone deacetylase (HDAC) inhibitors are widely used in clinical investigation as novel drug targets. For example, panobinostat and vorinostat have been used to treat patients with melanoma. However, HDAC inhibitors are small-molecule compounds without a specific target, and their mechanism of action is unclear. Therefore, it is necessary to investigate which HDACs are required for the proliferation and metastasis of melanoma cells.
We used overexpression and knocking down lentivirus to clarify the influence of HDAC5 and HDAC6 in melanoma development. Also, we introduced stable HDAC5 or HDAC6 knockdown cells into null mice and found that the knockdown cells were unable to form solid tumors. Finally, we tested HDAC5 and HDAC6 expression and sub-location in clinical melanoma tissues and tumor adjacent tissues.
In this study, and found that HDAC5 and HDAC6 were highly expressed in melanoma cells but exhibited low expression levels in normal skin cells. Furthermore, we knocked down HDAC5 or HDAC6 in A375 cells and demonstrated that both HDAC5 and HDAC6 contributed to the proliferation and metastasis of melanoma cells. | Are both HDAC5 and HDAC6 required for the proliferation and metastasis of melanoma cells? | Yes. This study demonstrated both HDAC5 and HDAC6 were required for melanoma cell proliferation and metastasis through different signaling pathways. | PASS | pubmedQA | 1 |
24868224 | Identification of poor prognostic factors in papillary thyroid carcinoma (PTC) patients is important for the patients' care and follow-up. We can sometimes see small tumor clusters without desmoplasia and no evidence of lymphatic emboli around the main tumor mass of PTC. We termed this form of tumor clustering, 'tumor sprouting,' and determined whether these tumors correlate with lymphovascular invasion, lymph node metastasis, and recurrence.
We analyzed a total of 204 cases of papillary thyroid macrocarcinoma. Number, size and distance from the main tumor of the tumor sprouting were observed and analyzed with clinicopathologic characteristics.
Tumor sprouting was observed in 101 patients. Presence of tumor sprouting was significantly associated with positive resection margin (p=.002), lymphovascular invasion (p=.001), lymph node metastasis (p<.001), and recurrence (p=.004). Univariate analysis of recurrence-free survival revealed that tumor multiplicity (p=.037), positive resection margin (p=.007), lymphovascular invasion (p=.004), lymph node metastasis (p<.001), and tumor sprouting (p=.004) were poor prognostic factors. In multivariate analysis, positive resection margin was an independent poor prognostic factor of recurrence. | Is tumor sprouting in papillary thyroid carcinoma correlated with lymph node metastasis and recurrence? | Yes. In conclusion, tumor sprouting is significantly correlated with lymph node metastasis and recurrence. Evaluation of tumor sprouting in PTC patients could be helpful in predicting tumor recurrence or lymph node metastasis. | PASS | pubmedQA | 1 |
22576962 | The development of osteoarthritis (OA) may be caused by activation of hypertrophic differentiation of articular chondrocytes. Healthy articular cartilage is highly resistant to hypertrophic differentiation, in contrast to other hyaline cartilage subtypes, such as growth plate cartilage. The purpose of this study was to elucidate the molecular mechanism responsible for the difference in the propensity of human articular cartilage and growth plate cartilage to undergo hypertrophic differentiation.
Whole-genome gene-expression microarray analysis of healthy human growth plate and articular cartilage derived from the same adolescent donors was performed. Candidate genes, which were enriched in the articular cartilage, were validated at the messenger RNA (mRNA) and protein levels and examined for their potential to inhibit hypertrophic differentiation in two models. In addition, we studied a possible genetic association with OA.
Pathway analysis demonstrated decreased Wnt signaling in articular cartilage as compared to growth plate cartilage. This was at least partly due to increased expression of the bone morphogenetic protein and Wnt antagonists Gremlin 1, Frizzled-related protein (FRP), and Dkk-1 at the mRNA and protein levels in articular cartilage. Supplementation of these proteins diminished terminal hypertrophic differentiation without affecting chondrogenesis in long-bone explant cultures and chondrogenically differentiating human mesenchymal stem cells. Additionally, we found that single-nucleotide polymorphism rs12593365, which is located in a genomic control region of GREM1, was significantly associated with a 20% reduced risk of radiographic hip OA in 2 population-based cohorts. | Are gremlin 1 , frizzled-related protein , and Dkk-1 key regulators of human articular cartilage homeostasis? | Yes. Taken together, our study identified Gremlin 1, FRP, and Dkk-1 as natural brakes on hypertrophic differentiation in articular cartilage. As hypertrophic differentiation of articular cartilage may contribute to the development of OA, our findings may open new avenues for therapeutic intervention. | PASS | pubmedQA | 1 |
10210641 | The primary barrier to clinical application of in utero hematopoietic stem cell (HSC) transplantation is limited donor cell engraftment. We hypothesized that limited engraftment was due to competition between host and donor cells for available niches. We reasoned that increased engraftment might be achieved by performing multiple transplants separated by brief intervals to allow time for formation of new niches. To test this we performed multiple transplants in a congenic combination to avoid confounding immunologic effects.
C57Pep3B (H2Kb, CD45.1) mice were used as donors of adult bone marrow and C57Bl/6 (H2Kb, CD45.2) mice were used as 14-day-gestation fetal recipients. All fetuses were injected intraperitoneally with 1 x 10(6) mononuclear cells. Boosted neonates were injected at Days 2, 4, and 7 of life with 5 x 10(6) cells. All animals were analyzed for donor cell engraftment by dual-color flow cytometry using CD45 and CD45.1 antigens. Results are reported as the mean +/- SD. Statistical analysis was performed using the two-tailed Student t test with P < 0.05 considered significant.
Postnatally boosted animals demonstrated significantly elevated levels of donor cell engraftment (3.30 +/- 0.8%; n = 8; P < 0.00001) when compared to the control animals (0.69 +/- 0.5%; n = 9) as determined by peripheral blood analysis at 6 weeks of age. This elevated level of engraftment was stable long term. | Do postnatal booster injections increase engraftment after in utero stem cell transplantation? | Yes. Our results demonstrate a significant increase in donor cell engraftment with postnatal booster injections after in utero transplantation. This supports the hypothesis that a limited number of niches may be a major component of the barrier to engraftment. It also suggests that postnatal booster injections may be a viable therapeutic strategy for improving donor cell engraftment after in utero HSC transplantation. | PASS | pubmedQA | 1 |
26683568 | The objective of the present study was to evaluate the relationship between clinical outcome and time of day of surgery and experience level of the surgeon. Secondly, we examined the relationship between the length of hospital stay and the time of day of surgery.
This retrospective cross-sectional cohort design study included patients treated with intramedullary nailing at Aalborg University Hospital from 1998 to 2008 after tibial shaft fractures (N = 294). At follow-up, the participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS). Age, sex, complications, length of hospital stay, start time of surgery, and education level of surgeons were recorded.
The long-term analysis of the KOOS assessment shows no significant association between time of day of surgery and the level of surgeon experience. There was no difference in complication rates between time of day of surgery and the level of surgeon experience. The secondary outcome analysis showed an estimated increased risk of 25 % (p = 0.001), for a longer length of hospital stay when operated by a trainee at night-hours compared to day-hours, and an estimated increased risk of 17 % (p = 0.002) for longer length of stay, when operated at day-hours by a trauma surgeon compared to a trainee. | Is the long-term outcome after treatment for patients with tibial fracture treated with intramedullary nailing influenced by time of day of surgery and surgeon experience? | No. Complication rates and KOOS outcome after surgery with intramedullary nailing were not influenced by time of day of surgery and experience level of the surgeon. The lengths of hospital stay increase significantly when surgery is performed at night by trainee surgeons, but not when performed by trauma surgeons. | PASS | pubmedQA | 1 |
8466068 | Severe hyperkalemia is a serious problem during orthotopic liver transplantation. The effectiveness of insulin in decreasing serum potassium concentration during the anhepatic stage of orthotopic liver transplantation was investigated.
Forty patients with serum potassium concentrations greater than 4.0 mM/L at the onset of the anhepatic stage were randomized into two groups. Control group patients (n = 20) received no treatment, and treatment group patients (n = 20) received an intravenous bolus of regular insulin (20 u) 10 min into the anhepatic stage, followed by a glucose infusion (500 ml 5% dextrose in water) over 15 min.
In the control group, the potassium concentration did not change, whereas in the treatment group, it decreased from 4.70 +/- 0.54 to 4.18 +/- 0.63 mM/L (mean +/- SD) within 15 min and to 3.57 +/- 0.55 mM/L 60 min after therapy. The potassium concentration was less in the treatment group than in the control group within 30 min of treatment (3.97 +/- 0.52 vs. 4.49 +/- 0.43 mM/L, respectively; P < 0.05). The potassium concentration increased similarly 30 s after graft reperfusion in both groups of patients, but was less in the treatment group (5.91 +/- 1.63 vs. 7.37 +/- 1.67 mM/L, respectively; P < 0.05). The potassium concentration returned to prereperfusion levels within 5 min after graft reperfusion. | Does insulin decrease the serum potassium concentration during the anhepatic stage of liver transplantation? | Yes. In patients undergoing orthotopic liver transplantation, the administration of insulin rapidly decreases serum potassium concentration, even in the absence of the liver, suggesting an important contribution by extrahepatic tissues in the insulin-stimulated uptake of potassium. | PASS | pubmedQA | 1 |
15572021 | Many patients with coronary heart disease (CHD) are not managed adequately, and we often fail to reach treatment targets.
To investigate if knowledge of risk factors for CHD, measured by a questionnaire, would show any relation to advice to compliance to lifestyle changes to attain treatment goals and adherence to drug therapy.
Men and women <71 years who had had a cardiac event were screened consecutively (509) from the medical records. Responders (392) were interviewed, examined and received a questionnaire. Three hundred and forty-seven patients answered the questionnaire regarding their general knowledge of risk factors for CHD, compliance to lifestyle changes to attain treatment goals and adherence to drug therapy.
There were statistically significant correlations between general knowledge about risk factors for CHD and compliance to certain lifestyle changes: weight, physical activity, stress management, diet, attainment of lipid level goals and the likelihood of taking prescribed blood pressure-lowering drugs. General knowledge of risk factors had no correlation to blood glucose or blood pressure levels nor on smoking habits or treatment patterns for prescribed lipid- and blood glucose-lowering drugs. | Does better knowledge improve adherence to lifestyle changes and medication in patients with coronary heart disease? | Yes. Knowledge correlates to patient behaviour with respect to some risk factors, which should be recognised in preventive programs. | PASS | pubmedQA | 1 |
11724198 | To identify the indicators nurses employ in deciding to test healthy full-term newborns for total serum bilirubin in the absence of a written protocol.
Secondary analysis of data available on 130 mother-newborn pairs and informal interviews of 30 postpartum unit nurses.
Two university teaching hospitals.
All tested newborns and a 33% random sample of remaining newborns from a control group data set created during a previous study and a convenience sample of postpartum nurses from all shifts.
Outcome data were obtained from a review of records. Background data were obtained from a review of records and questionnaires. Nurse data were obtained through a modified form of participant observation.
Ninety-one percent of newborns tested for bilirubin were tested unnecessarily. In logistic regression analyses, variables predictive of nurse-driven total serum bilirubin testing were presence of jaundice, odds ratio (OR) = 31.95 (95% confidence interval, 6.71, 152.03), and feeding frequency, OR = 0.28 (0.11, 0.72). Identifying both presence and location of jaundice simultaneously did not significantly predict testing, OR = 1.82 (0.66, 5.04). Fifty-three percent of nurses who were interviewed identified both the presence of jaundice and feeding as indicators to consider for testing. | Do indicators nurses employ in deciding to test for hyperbilirubinemia? | Yes. Newborns are overtested for bilirubin. Indicators used by nurses in deciding to test a healthy newborn for total serum bilirubin are the presence of jaundice and feeding frequency. Nurses who assess feeding frequency are less likely to order bilirubin testing. | PASS | pubmedQA | 1 |
26814527 | Under the trimodal distribution, most trauma deaths occur within the first hour. Determination of cause of death without autopsy review is inaccurate. The goal of this study is to determine cause of death, in hourly intervals, in trauma patients who died in the first 24 h, as determined by autopsy.
Trauma deaths that occurred within 24 h at a Level I trauma center were reviewed over a six-year period ending December 2005. Timing of death was separated into 0-1, 1-3, 3-6, 6-12 and 12-24 h intervals. Cause of death was determined by clinical course and AIS scores, and was confirmed by autopsy results.
Overall, 9,388 trauma patients were admitted, of which 185 deaths occurred within 24 h, with 167 available autopsies. Blunt and penetrating were the injury mechanisms in 122 (73%) and 45 (27%) patients, respectively. Of 167 deaths, 73 (43.7%) occurred within the first hour. Brain injury, when compared to other body areas, was the most likely cause of death in all hourly intervals, but hemorrhage was as or more important than brain injury as the cause of death during the first 3 h and up to 6 h. No deaths were attributable to hemorrhage after 12 h. | Is hemorrhage More Prevalent than Brain Injury in Early Trauma Deaths : The Golden Six Hours? | Yes. The temporal distribution of the cause of death varies in the first 24 h after admission. Hemorrhage should not be overlooked as the cause of death, even after survival beyond 1 h. Understanding the temporal relationship of causes of early death can aid in the targeting of management and surgical training to optimize patient outcome. | PASS | pubmedQA | 1 |
26670667 | Mesenchymal stem cells (MSCs) have been widely applied to treat various inflammatory diseases. Inflammatory cytokines can induce both apoptosis and autophagy in MSCs. However, whether autophagy plays a pro- or con-apoptosis effect on MSCs in an inflammatory microenvironment has not been clarified.
We inhibited autophagy by constructing MSCs with lentivirus containing small hairpin RNA to knockdown Beclin-1 and applied these MSCs to a model of sepsis to evaluate therapeutic effect of MSCs.
Here we show that inhibition of autophagy in MSCs increases the survival rate of septic mice more than control MSCs, and autophagy promotes apoptosis of MSCs during application to septic mice. Further study demonstrated that autophagy aggravated tumor necrosis factor alpha plus interferon gamma-induced apoptosis of MSCs. Mechanically, autophagy inhibits the expression of the pro-survival gene Bcl-2 via suppressing reactive oxygen species/mitogen-activated protein kinase 1/3 pathway. | Does autophagy promote apoptosis of mesenchymal stem cells under inflammatory microenvironment? | Yes. Our findings indicate that an inflammatory microenvironment-induced autophagy promotes apoptosis of MSCs. Therefore, modulation of autophagy in MSCs would provide a novel approach to improve MSC survival during immunotherapy. | PASS | pubmedQA | 1 |
15839968 | Following anterior resection of the rectum it is common to defunction the anastomosis with an ileostomy. Prior to closure of this, a contrast study is usually performed to check for healing. Several patients at our institution have not undergone a contrast study prior to closure. The present study aimed to compare outcome in this group with patients who had undergone contrast radiology.
A retrospective review of patients undergoing anterior resection with an ileostomy was performed. We only included those patients who had a straight colorectal/coloanal anastomosis that could be examined clinically and had a smooth postoperative course with no evidence of pelvic sepsis.
Fifty-nine patients fulfilled the criteria for the study. Thirty-five patients had a contrast study. These showed two leaks and five strictures. The anastomosis was 0-7 cm from the anal verge in 31 patients (16 contrast studies). It was above 7 cm in 28 patients (19 contrast studies). No patient had pelvic sepsis after ileostomy reversal. | Is ileostomy closure without contrast study safe in selected patients? | Yes. In patients with an ileostomy following anterior resection, with a clinically examinable anastomosis and a smooth postoperative course, a radiological examination of the anastomosis prior to ileostomy closure appears unnecessary. | PASS | pubmedQA | 1 |
20731863 | Local adaptation to divergent environmental conditions can promote population genetic differentiation even in the absence of geographic barriers and hence, lead to speciation. Perturbations by catastrophic events, however, can distort such parapatric ecological speciation processes. Here, we asked whether an exceptionally strong flood led to homogenization of gene pools among locally adapted populations of the Atlantic molly (Poecilia mexicana, Poeciliidae) in the Cueva del Azufre system in southern Mexico, where two strong environmental selection factors (darkness within caves and/or presence of toxic H2S in sulfidic springs) drive the diversification of P. mexicana. Nine nuclear microsatellites as well as heritable female life history traits (both as a proxy for quantitative genetics and for trait divergence) were used as markers to compare genetic differentiation, genetic diversity, and especially population mixing (immigration and emigration) before and after the flood.
Habitat type (i.e., non-sulfidic surface, sulfidic surface, or sulfidic cave), but not geographic distance was the major predictor of genetic differentiation. Before and after the flood, each habitat type harbored a genetically distinct population. Only a weak signal of individual dislocation among ecologically divergent habitat types was uncovered (with the exception of slightly increased dislocation from the Cueva del Azufre into the sulfidic creek, El Azufre). By contrast, several lines of evidence are indicative of increased flood-induced dislocation within the same habitat type, e.g., between different cave chambers of the Cueva del Azufre. | Do locally adapted fish populations maintain small-scale genetic differentiation despite perturbation by a catastrophic flood event? | Yes. The virtual absence of individual dislocation among ecologically different habitat types indicates strong natural selection against migrants. Thus, our current study exemplifies that ecological speciation in this and other systems, in which extreme environmental factors drive speciation, may be little affected by temporary perturbations, as adaptations to physico-chemical stressors may directly affect the survival probability in divergent habitat types. | PASS | pubmedQA | 1 |
20602543 | Elevated neutrophil to lymphocyte ratio (NLR) is linked with worse survival in many malignancies, whereas its association with pancreatic cancer (PC) remains unclear.
We retrospectively reviewed 95 patients with locally advanced or metastatic PC receiving gemcitabine-based chemotherapy. The prognostic value of NLR was evaluated.
Elevated pretreatment NLR (> 5) was observed in 16 out of 89 eligible patients, which was identified as an independent prognostic factor for overall survival (OS). The median OS for patients with elevated and normal NLR were 2.4 months and 7.7 months, respectively (p < 0.001). | Does elevated neutrophil to lymphocyte ratio predict survival in advanced pancreatic cancer? | Yes. Elevated NLR is a predictor of shorter survival in patients with advanced PC. | PASS | pubmedQA | 1 |
12665491 | Increased expression of the beta2 integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions.
Expression of CD11b (alpha-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R=0.42, P<0.01) and the 8B2 increase (R=0.55, P<0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss. | Is stent-induced expression and activation of the leukocyte integrin Mac-1 associated with neointimal thickening and restenosis? | Yes. Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis. | PASS | pubmedQA | 1 |
17932889 | The purpose of this study was to determine the effectiveness and vascular response of a pimecrolimus drug eluting stent and a combination (pimecrolimus + paclitaxel) stent as compared with bare metal controls in the porcine coronary model.
In the first phase of the study, cobalt chromium stents were loaded with an erodible polymer and either a slow release or a fast release formulation of pimecrolimus. Thirty stents (metal, n = 10; pimecrolimus slow, n = 10; pimecrolimus fast, n = 10) were implanted in the coronary arteries of 10 pigs. At 30 days, neointimal proliferation and inflammation were both significantly less in the pimecrolimus fast release group as compared with the bare metal controls. Endothelialization was complete and equal in all three groups of stents. In the second phase of the study, stents were loaded with an erodible polymer with alternating reservoirs of paclitaxel and pimecrolimus. Twenty stents (8 control stents and 12 dual stents) were implanted in the coronary arteries of seven pigs. At 30 days, neointimal proliferation was significantly less in the dual drug group as compared with the bare metal controls. Endothelialization was complete in both groups of stents, suggesting complete healing of the arteries. | Do pimecrolimus and dual pimecrolimus-paclitaxel eluting stents decrease neointimal proliferation in a porcine model? | Yes. In a 30-day porcine stent model, pimecrolimus inhibits neointimal proliferation as compared with bare metal stents. Also, the proof of concept of a dual drug eluting stent was established showing both safety and efficacy. | PASS | pubmedQA | 1 |
25886616 | The transcription factor Ecotropic Virus Integration site 1 (EVI1) regulates cellular proliferation, differentiation, and apoptosis, and its overexpression contributes to an aggressive course of disease in myeloid leukemias and other malignancies. Notwithstanding, knowledge about the target genes mediating its biological and pathological functions remains limited. We therefore aimed to identify and characterize novel EVI1 target genes in human myeloid cells.
U937T_EVI1, a human myeloid cell line expressing EVI1 in a tetracycline regulable manner, was subjected to gene expression profiling. qRT-PCR was used to confirm the regulation of membrane-spanning-4-domains subfamily-A member-3 (MS4A3) by EVI1. Reporter constructs containing various parts of the MS4A3 upstream region were employed in luciferase assays, and binding of EVI1 to the MS4A3 promoter was investigated by chromatin immunoprecipitation. U937 derivative cell lines experimentally expressing EVI1 and/or MS4A3 were generated by retroviral transduction, and tested for their tumorigenicity by subcutaneous injection into severe combined immunodeficient mice.
Gene expression microarray analysis identified 27 unique genes that were up-regulated, and 29 unique genes that were down-regulated, in response to EVI1 induction in the human myeloid cell line U937T. The most strongly repressed gene was MS4A3, and its down-regulation by EVI1 was confirmed by qRT-PCR in additional, independent experimental model systems. MS4A3 mRNA levels were also negatively correlated with those of EVI1 in several published AML data sets. Reporter gene assays and chromatin immunoprecipitation showed that EVI1 regulated MS4A3 via direct binding to a promoter proximal region. Experimental re-expression of MS4A3 in an EVI1 overexpressing cell line counteracted the tumor promoting effect of EVI1 in a murine xenograft model by increasing the rate of apoptosis. | Does eVI1 promote tumor growth via transcriptional repression of MS4A3? | Yes. Our data reveal MS4A3 as a novel direct target of EVI1 in human myeloid cells, and show that its repression plays a role in EVI1 mediated tumor aggressiveness. | PASS | pubmedQA | 1 |
24836459 | Pathogenesis of early-onset preeclampsia (PE) is generally recognized by impaired trophoblast invasion of the myometrial arteries, which results in placental insufficiency. Recently, we reported that CDX1 is hypermethylated in the human preeclampsia placenta. However, whether CDX1 participates in trophoblast invasion has not been clearly elucidated.
We investigated the function of CDX1 in the extravillous trophoblast cell line HTR-8/SVneo using stable transfection of CDX1. Using a CDX1 stable transfected cell line, we determined the cell invasion using a QCM ECMatrix 24-well kit. The cell viability was detected using an MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. Quantitative RT-PCR and western blotting analyses were performed to examine the changes in the expression of downstream target genes and proteins. To disrupt PI3K/AKT signaling, we used the PI3K inhibitor perifosine.
Cell invasion assays demonstrated that CDX1 restricts trophoblast cell invasiveness. In contrast, quantification of cumulative cell numbers revealed that CDX1 did not affect cell proliferation. Western blotting analysis and quantitative real time PCR demonstrated that MMP-9 expression was reduced, whereas TIMP-1 expression was increased in CDX1-overexpressed cells. However, overexpression of CDX1 did not affect PI3K/AKT signaling in HTR-8/SVneo trophoblast cells. In contrast, CDX1 was regulated by the PI3K/AKT signaling pathway. | Does cDX1 restrict the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression? | Yes. Altogether, we found that in trophoblast cells, CDX1 reduced invasion independently of the PI3K/AKT signaling pathway. Furthermore, CDX1 functions in concert with PI3K/AKT signaling to regulate trophoblast invasion. We concluded that CDX1 restricts the invasion of HTR-8/SVneo trophoblast cells by inhibiting MMP-9 expression independently of the PI3K/AKT pathway. | PASS | pubmedQA | 1 |
20179671 | The growth and development of adipose tissue are thought to be associated with angiogenesis and extracellular matrix remodeling. As the composition of the herbal extract called Ob-X has been shown to have both anti-angiogenic and matrix metalloproteinase (MMP)-inhibiting activities, we hypothesized that growth of adipose tissue can be regulated by Ob-X.
The effects of Ob-X on angiogenesis and extracellular matrix remodeling were measured using in vitro and ex vivo assays. The effects of Ob-X on adipose tissue growth were investigated in nutritionally obese mice.
Ob-X inhibited angiogenesis in a dose-dependent manner in the human umbilical vein endothelial cell tube formation assay in vitro and the rat aortic ring assay ex vivo. Ob-X also suppressed MMP activity in vitro. Administration of Ob-X to high fat diet-induced obese mice produced significant reductions in body weight gain and adipose tissue mass compared with control. The mass of both visceral (VSC) and subcutaneous (SC) fat was reduced in Ob-X-treated mice. The size of adipocytes in VSC and SC adipose tissues was also significantly reduced in Ob-X-treated mice. Ob-X treatment decreased the blood vessel density and MMP activity in VSC adipose tissues of nutritionally obese mice. Ob-X reduced mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas it increased mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1 and TIMP-2) in SC and VSC adipose tissues of nutritionally obese mice. | Does the anti-angiogenic herbal composition Ob-X inhibit adipose tissue growth in obese mice? | Yes. Ob-X, which has anti-angiogenic and MMP-inhibitory activities, reduces adipose tissue mass in nutritionally induced obese mice, providing evidence that adipose tissue growth and development may be prevented by inhibiting angiogenesis. In addition, these data suggest that regulation of adipose tissue growth by inhibiting angiogenesis may alter the expression of genes involved in angiogenesis and the MMP system. | PASS | pubmedQA | 1 |
22238509 | The failure of cancer treatments is partly due to the enrichment of cancer stem-like cells (CSLCs) that are resistant to conventional chemotherapy. A novel micelle formulation of oxaliplatin (OXA) encapsulated in chitosan vesicle was developed. The authors postulate that micelle encapsulation of OXA would eliminate both CSLCs and bulk cancer cells in colorectal cancer (CRC).
In this study, using stearic acid-g-chitosan oligosaccharide (CSO-SA) polymeric micelles as a drug-delivery system, OXA-loaded CSO-SA micelles (CSO-SA/OXA) were prepared. Intracellular uptake of CSO-SA/OXA micelles was assessed by confocal microscope. The effects of free OXA, the empty carrier, and CSO-SA/OXA micelles were tested using human CRC cell lines in vitro and in vivo.
The micelles showed excellent internalization ability that increased OXA accumulation both in CRC cells and tissues. Furthermore, CSO-SA/OXA micelles could either increase the cytotoxicity of OXA against the bulk cancer cells or reverse chemoresistance of CSLC subpopulations in vitro. Intravenous administration of CSO-SA/OXA micelles effectively suppressed the tumor growth and reduced CD133+/CD24+ cell (putative CRC CSLC markers) compared with free OXA treatment, which caused CSLC enrichment in xenograft tumors (P < 0.05). | Do oxaliplatin-incorporated micelles eliminate both cancer stem-like and bulk cell populations in colorectal cancer? | Yes. The results of this study indicate that CSO-SA micelle as a drug-delivery carrier is effective for eradicating CSLCs and may act as a new option for CRC therapy. | PASS | pubmedQA | 1 |
24637128 | Olfactory dysfunction is considered to precede motor symptoms and early markers of Parkinson's disease (PD), while the relative time at which cardiovascular dysautonomia appears in PD is not well understood. To assess the appearance of cardiovascular dysautonomia in PD, we evaluated its relation to olfactory dysfunction in early-stage PD patients.
Twenty-three non-demented PD patients within 2 years from the onset of motor symptoms were enrolled. We evaluated olfactory dysfunction by the Odor Stick Identification Test for Japanese (OSIT-J) and analyzed its relationship to the results of other cardiovascular autonomic tests and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy.
There was a correlation between olfactory scores and increased blood pressure in both the norepinephrine (r = 0.75, p < 0.0001, n = 21) and dobutamine (r = 0.57, p = 0.0087, n = 20) infusion tests and cardiac MIBG uptake (r = 0.42, p = 0.049, n = 23). The fall in orthostatic blood pressure during the head-up tilt test was not correlated with the olfactory scores, but the Valsalva maneuver revealed that OSIT-J scores correlated with the pressure recovery time from phase III to the return of blood pressure to baseline (r = 0.54, p = 0.037, n = 15) and with the magnitude of blood pressure overshoot during phase IV (r = 0.67, p = 0.0016, n = 20). | Do hyposmia and cardiovascular dysautonomia correlatively appear in early-stage Parkinson 's disease? | Yes. Our results demonstrate that extensive components of the cardiovascular sympathetic system as well as the olfactory system are correlatively impaired in the early stage of PD, suggesting that degeneration of broad aspects of the cardiovascular sympathetic system occurs concurrently with olfactory system degeneration during the premotor phase of PD. | PASS | pubmedQA | 1 |
27287412 | The tumor microenvironment is composed of different types of stromal cells that represent a key component of tumor progression. Cancer-associated fibroblasts (CAFs) secrete several factors that promote tumorigenesis. The purpose of this study was to clarify the role of the interleukin-6 (IL-6) secreted from CAFs in the communication between CAFs and NSCLC cells that modulates chemoresistance.
We used standard NSCLC cell lines as well as NSCLC cells, lung normal fibroblasts, and CAFs obtained from specimens from patients with NSCLC to evaluate phenotypic changes. Immunohistochemical analysis was also utilized to examine the stromal changes in tumor specimens obtained from patients with NSCLC who had undergone chemotherapy.
IL-6 significantly increased transforming growth factor-β1-induced epithelial-to-mesenchymal transition (EMT) changes in cancer cells. Cisplatin treatment increased expression of transforming growth factor-β in cancer cells, and the conditioned media from cancer cells activated fibroblasts and increased their IL-6 production. Expression of IL-6 was increased in CAFs compared with in lung normal fibroblasts. The conditioned media from CAFs induced EMT and resistance to cisplatin in NSCLC cells through IL-6 signaling. Immunohistochemical analysis showed that stromal IL-6 expression was correlated with EMT changes in cancer cells as well as with a diffuse distribution of smooth muscle actin-stained fibroblasts. Univariate and multivariate analyses indicated that stromal IL-6 expression was an independent prognostic factor in patients with NSCLC. | Does iL-6 Secreted from Cancer-Associated Fibroblasts mediate Chemoresistance in NSCLC by Increasing Epithelial-Mesenchymal Transition Signaling? | Yes. IL-6 from CAFs enhanced EMT in NSCLC cells. IL-6 may contribute to maintenance of a paracrine loop that functions as part of the communication between CAFs and NSCLC cells, resulting in chemoresistance. | PASS | pubmedQA | 1 |
27585528 | The objective of this article was to qualify and test the recommendations of a national Danish report. We conducted an investigation on the readmittance rate as well as reasons for readmittance in a patient cohort defined through the process of internal audit at the Emergency Department at Zealand University Hospital, Køge, Denmark.
A retrospective, descriptive study of admitted patients in November 2014, including a total of 1,440 patients. Data and parameters were obtained from electronic patient records.
A total of 162 patients were readmitted within 30 days from their initial admission (11% of the cohort). Of this group, 139 (86%) readmittances were unpreventable or planned. Readmissions caused by missed diagnosis or insufficient treatment accounted for 8% and 6%, respectively. The median time until readmission in these cases were two and four and a half days, respectively. The median time to readmission for the unpreventable readmissions ranged from 13 to 18.5 days. | Are readmittance rates within seven days preferable in quality measuring of emergency departments? | Yes. In terms of patient safety, our data support a seven-day observation period for readmission rates when measuring or monitoring quality of care in emergency departments. | PASS | pubmedQA | 1 |
10801482 | The NF-kappaB family of dimeric transcription factors regulates the expression of several genes by binding to a variety of related DNA sequences. One of these dimers, p65(RelA), regulates a subclass of these targets. We have shown previously that p65 binds to the 5'-GGAA T TTTC-3' sequence asymmetrically. In that complex one subunit base specifically interacts with the preferred 5' half site and the other subunit binds non-specifically to the 3' half site.
Here we describe the crystal structures of two new p65-DNA complexes. One complex contains a pseudosymmetric 5'-GGAA T TTCC-3' DNA sequence taken from the enhancer of the gene encoding interleukin 8 (IL-8) and the other contains the asymmetric 5'-GGAA T TCCC-3' target DNA taken from the enhancer of the gene encoding type VII collagen. As expected, the global positioning of the dimer on both DNA targets is roughly symmetric, however, the hydrogen-bonding patterns at the protein-DNA interfaces differ significantly. One of the p65 monomers in complex with the asymmetric DNA binds to an extra base pair located immediately upstream of the 5'-GGAA-3' half site. We also show that p65 binds to these targets with almost equal affinity and that different residues have variable roles in binding different kappaB targets. | Does nF-kappaB p65 ( RelA ) homodimer used distinct mechanisms to recognize DNA targets? | Yes. Taken together, these structures reveal that p65 exhibits the unique capability to specifically bind DNA targets of variable lengths from four to ten base pairs. Also, the small protein segment Arg41-Ser42-Ala43 is at least partially responsible for flexibility in DNA-binding modes. | PASS | pubmedQA | 1 |
16565759 | To determine the differentiation of human limbal epithelial cells in tissue culture.
Epithelial cells from the human limbus (n = 29) were isolated and cultured in supplemental hormonal epithelial medium (SHEM) in the presence of mitomycin C-treated 3T3 feeder layer. Confluent cells were airlifted to form multiple layers. The expression of cytokeratin 3 (K3), cytokeratin 12 (K12), involucrin, connexin 43 (Cx43), proliferation cell nuclear antigen (PCNA) and p63 was studied in normal and airlifted cells by immunohistochemistry. Expression levels of K3 and K12 mRNA were examined by real-time polymerase chain reaction (PCR).
The colony-forming efficiency of primary cultured (P0) cells was about 19.35 +/- 6.46% (mean +/- SD, n = 7). Real-time PCR analysis showed that the transcription level of K3 and K12 in cultured cells was lower than in freshly isolated limbal cells or cells from central cornea (P <0.01). Few cells were positive for K3 in P0 or P1 cells [(1.99 +/- 1.27)% (n = 7, P0) and (3.96 +/- 1.35)% (n = 4, P1), P = 0.046]. More cells at all levels were found to stain positive for PCNA and p63 as compared to K3, K12 and involucrin. After air-lifting, cell sheets of 3 to 5 epithelial cell layers formed. Involucrin showed positive staining in suprabasal layers of the cell sheets while connexin 43 was only observed in the basal layer. Staining of K3 remained sparse. | Are human limbal progenitor cell characteristics maintained in tissue culture? | Yes. Human limbal cells isolated from cadaveric tissues were able to proliferate in vitro and exhibited a phenotype with characteristics similar to that of the limbal stem or progenitor cells. | PASS | pubmedQA | 1 |
15564772 | The human histamine H1 receptor is constitutively active and exhibits basal activation of nuclear factor-kappaB (NF-kappaB), an important modulator of allergic inflammation. Certain H1 antihistamines have recently been shown to inhibit basal NF-kappaB activity by stabilizing the H1 receptor in an inactive state, a phenomenon called 'inverse agonism'.
We evaluated the effect of the new H1 antihistamine, desloratadine, on basal and histamine-stimulated NF-kappaB activity and compared it with the activities of other H1 antihistamines.
Transiently transfected COS-7 cells co-expressing NF-kappaB-luciferase and the H1 receptor exhibited constitutive NF-kappaB activity. H1 antihistamines reduced basal NF-kappaB activity (rank order of potency: desloratadine > pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal NF-kappaB activity 8-fold, which was blocked by H1 antihistamines (rank order of potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine). Neither histamine nor antihistamines had any effect on NF-kappaB activity in the absence of the H1 receptor. | Does desloratadine inhibit constitutive and histamine-stimulated nuclear factor-kappaB activity consistent with inverse agonism at the histamine H1 Receptor? | Yes. Desloratadine, acting through the histamine H1 receptor, inhibited basal NF-kappaB activity and can thus be classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF-kappaB activity may help to explain previously reported inhibitory effects of desloratadine on allergic inflammatory mediators. | PASS | pubmedQA | 1 |
9672797 | Central serous chorioretinopathy is characterized on indocyanine green angiography by areas of transient choroidal hyperfluorescence. These findings are thought to be the consequence of altered permeability of the choroidal vessels.
The indocyanine green angiograms of 41 patients between 40 and 60 years of age, with central serous chorioretinopathy and of 120 patients above 64 years of age with occult choroidal neovascularization due to age-related macular degeneration were reviewed for the presence of transient indocyanine green leakage. Twelve eyes of 9 patients above 64 years of age with (1) fluorescein leakage of undetermined source corresponding with well-delineated zone(s) of retinal pigmentary changes and (2) transient indocyanine green hyperfluorescence are reported in detail.
Transient indocyanine green hyperfluorescence was seen in all eyes with central serous chorioretinopathy, either typical or chronic, and was seldom seen in occult choroidal neovascularization due to age-related macular degeneration. In the series of chronic serous chorioretinopathy in patients above 64 years of age, four classic choroidal neovascular membranes were found in 12 eyes. Most patients presented multizonal transient choroidal hyperfluorescence in both eyes on indocyanine green angiography. | Is indocyanine green angiography of value for the diagnosis of chronic central serous chorioretinopathy in elderly patients? | Yes. Transient choroidal hyperfluorescence is suggestive for chronic central serous chorioretinopathy in older patients presenting retinal pigmentary disease with fluorescein leakage of undetermined source. Chronic central serous chorioretinopathy is not uncommonly associated with classic choroidal neovascularization in the elderly. | PASS | pubmedQA | 1 |
27122334 | To investigate the effect of the decontaminants frequently used for phenol burn wounds.
The central part of the dorsal skin of adult male Sprague-Dawley rats were burned with 90% (W/V)phenol solution for 2 min, and water, 75% ethanol, polyethylene glycol 400 (PEG400), and Diphoterine were applied for decontamination for 15 min. The changes in wounds were observed, and the depth of skin burns at 24 hours after treatment and changes in six indicators of organ injuries, i.e., serum levels of total bilirubin (TBil), creatinine (Crea), alanine aminotransferase (ALT), alanine aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH), at 6 hours after treatment were compared.
After phenol burns, the Diphoterine group had a significantly better effect and significantly lower degrees of skin and organ injuries compared with the water group (P<0.05). The effect of decontamination and degrees of skin and organ injuries were similar between the 75% ethanol group and the PEG400 group, and both groups had a better effect of decontamination compared with the water group; the 75% ethanol group had significantly lower serum levels of CK and LDH than the water group (P<0.05). Among these four groups, the water group had the worst effect, the deepest wounds, and the most severe organ injuries. | Do [ Selection of decontaminants for experimental phenol burn wounds ]? | Yes. After phenol burns, early decontamination with water has a poor effect, while Diphoterine can reduce the depth of phenol burns and the degrees of injuries of vital organs, and has a good effect of decontamination. | PASS | pubmedQA | 1 |
22545885 | To report a systematic review and meta-regression of the association between the threshold for intervention in patients with isolated type II endoleak after endovascular aneurysm repair (EVAR) and the fate of the aneurysm sac.
Medline, trial registries, conference proceedings, and article reference lists were searched to identify case series reporting sac outcomes following a specific treatment threshold for isolated type II endoleak. Articles were classified by the threshold for intervention as conservative, selective (intervention for >5-mm sac expansion or persistent type II endoleak >6 months), or aggressive (any type II endoleak or persistent for >3 months) and sac outcomes were extracted for review. Standard meta-regression to estimate the pooled odds ratios (OR), presented with the 95% confidence interval (CI), was performed to identify whether an aggressive, selective, or conservative threshold for intervention was associated with sac expansion or sac regression.
Ten series were analyzed that reported the outcomes of isolated type II endoleak in 231 patients; of these, 56 patients were treated at an aggressive threshold, 104 at a selective threshold, and 71 at a conservative threshold. The majority (194/231, 84.0%) demonstrated either stable or shrinking sacs during follow-up. No ruptures occurred. Meta-regression demonstrated no evidence that any strategy, compared to using a conservative approach, reduced sac expansion (aggressive estimated OR 0.70, 95% CI 0.15 to 3.31, p = 0.60; selective estimated OR 1.72, 95% CI 0.49 to 6.00, p = 0.34) or improved sac regression (aggressive estimated OR 0.55, 95% CI 0.02 to 16.94, p = 0.69; selective estimated OR 5.54, 95% CI 0.39 to 79.21, p = 0.17). | Is current evidence insufficient to define an optimal threshold for intervention in isolated type II endoleak after endovascular aneurysm repair? | Yes. There is inadequate information to support any one threshold for intervention. The rarity of rupture and sac expansion confirms the predominantly benign nature of isolated type II endoleak. In the absence of statistical support for a uniform approach to this problem, patient and physician preference remain key. Prospective data are still needed to investigate whether an optimum management algorithm can be devised. | PASS | pubmedQA | 1 |
27249091 | To examine the potential differential impact of childhood trauma, according to the age at the time of exposure, on the psychopathological profile of patients with early psychosis treated in a specialized 3-year program during the early phase of the disease.
196 subjects with early psychosis aged 18-35 years were followed up prospectively over 36 months of treatment between 2004 and 2010. Patients who had faced at least 1 experience of abuse (physical, sexual, or emotional) or neglect (physical or emotional) were classified according to age at the time of the first exposure (early trauma: before 12 years of age; late trauma: from age 12 through 16 years) and then compared with unexposed patients (nontrauma). The level of symptoms was assessed using the Positive and Negative Syndrome Scale, the Young Mania Rating Scale, and the Montgomery-Asberg Depression Rating Scale.
Exposure to 1 or more forms of trauma before 16 years of age was present in 31.63% of patients. Comparisons over the 3 years of treatment with the nontrauma patients revealed that (1) patients with early trauma showed consistently higher levels of positive (P = .006), depressive (P = .001), manic (P = .006), and negative (P = .029) symptoms and (2) patients with late trauma showed only more negative symptoms (P = .029). | Does age at the time of exposure to trauma modulate the psychopathological profile in patients with early psychosis? | Yes. These results suggest that the age at the time of exposure to trauma has a modulating effect on symptoms in patients with early psychosis. Various biological and psychological hypotheses can be proposed to explain this observation, and they need to be investigated in an experimental setting in order to develop therapeutic avenues. | PASS | pubmedQA | 1 |
25375979 | TNF-α generates inflammatory responses and insulin resistance, lipolysis, and protein breakdown. It is unclear whether these changes depend on intact hypothalamo-pituitary stress hormone responses to trigger the release of cortisol and growth hormone.
To define differential effects of TNF-α on glucose, protein, and lipid metabolism in hypopituitary patients (without intact hypothalamo-pituitary axis) and healthy controls.
Randomized, placebo controlled, single-blinded. Setting, Participants, and Intervention: We studied eight hypopituitary (HP) patients and eight matched control subjects [control volunteers (CTR)] twice during 4-h basal and 2-h hyperinsulinemic clamp conditions with isotope dilution during infusion of saline or TNF-α(12 ng/kg/h) for 6 h.
Phenylalanine, urea, palmitate, and glucose fluxes and fat biopsies in basal and clamp periods.
TNF-α infusion significantly increased cortisol and GH levels in CTR but not in HP. TNF-α increased phenylalanine fluxes in both groups, with the increase being significantly greater in CTR, and raised urea flux by 40 % in CTR without any alteration in HP. Endogenous glucose production (EGP) was elevated in CTR compared to HP after TNF-α administration, whereas insulin sensitivity remained similarly unaffected in both groups. TNF-α increased whole body palmitate fluxes and decreased palmitate specific activity in CTR, but not in HP without statistical difference between groups. We did not detect significant effects TNF-α on lipase expression or regulation in fat. | Is intact pituitary function decisive for the catabolic response to TNF-α : studies of protein , glucose and fatty acid metabolism in hypopituitary and healthy subjects? | Yes. TNF-α increased both urea and amino acid fluxes and EGP significantly more in CTR compared to HP, suggesting that increases in endogenous cortisol and GH release are significant components of the metabolic response to TNF-α. | PASS | pubmedQA | 1 |
22095239 | There is substantial evidence that mitochondrial dysfunction is linked to insulin resistance and is present in several tissues relevant to the pathogenesis of type 2 diabetes. Here, we examined whether common variation in genes involved in oxidative phosphorylation (OxPhos) contributes to type 2 diabetes susceptibility or influences diabetes-related metabolic traits.
OxPhos gene variants (n = 10) that had been nominally associated (p < 0.01) with type 2 diabetes in a recent genome-wide meta-analysis (n = 10,108) were selected for follow-up in 3,599 type 2 diabetic and 4,956 glucose-tolerant Danish individuals. A meta-analysis of these variants was performed in 11,729 type 2 diabetic patients and 43,943 non-diabetic individuals. The impact on OGTT-derived metabolic traits was evaluated in 5,869 treatment-naive individuals from the Danish Inter99 study.
The minor alleles of COX10 rs9915302 (p = 0.02) and COX5B rs1466100 (p = 0.005) showed nominal association with type 2 diabetes in our Danish cohort. However, in the meta-analysis, none of the investigated variants showed a robust association with type 2 diabetes after correction for multiple testing. Among the alleles potentially associated with type 2 diabetes, none negatively influenced surrogate markers of insulin sensitivity in non-diabetic participants, while the minor alleles of UQCRC1 rs2228561 and COX10 rs10521253 showed a weak (p < 0.01 to p < 0.05) negative influence on indices of glucose-stimulated insulin secretion. | Is common variation in oxidative phosphorylation genes a major cause of insulin resistance or type 2 diabetes? | No. We cannot rule out the possibility that common variants in or near OxPhos genes may influence beta cell function in non-diabetic individuals. However, our quantitative trait studies and a sufficiently large meta-analysis indicate that common variation in proximity to the examined OxPhos genes is not a major cause of insulin resistance or type 2 diabetes. | PASS | pubmedQA | 1 |
11271094 | To describe patients admitted to intensive care unit (ICU) for hypothermia, evaluate prognostic factors, and test the hypothesis that patients found indoors have a worse outcome.
Retrospective clinical investigation in a medical ICU.
Eighty-one consecutive patients admitted to ICU, with a body temperature of 35 degrees C or lower and rewarmed passively or with minimally invasive techniques, over a 17-year period.
Patients were analyzed by age, gender, and causes of hypothermia and split into two groups (indoors and outdoors), according to the location where hypothermia occurred. Prognostic factors were determined by univariate method and stepwise logistic regression. The major complications were acute renal failure (43 %), aspiration pneumonia (22 %), rhabdomyolysis (22 %), and acute respiratory distress syndrome (12%). Principal comorbidities in the outdoor patients (21%) were alcohol and drug intoxication, and those in the indoor patients (79 %) were sepsis and neuropsychiatric disorders. Stepwise logistic regression identified two variables predictive of death: illness severity at admission (SAPS II > or = 40) and the location where hypothermia occurred (indoors versus outdoors). | Is hypothermia with indoor occurrence associated with a worse outcome? | Yes. With equivalent body temperature, patients found indoors were more severely affected and died more frequently than those found outdoors. | PASS | pubmedQA | 1 |
19247169 | An in vitro biomechanical study of halo-vest and odontoid screw fixation of Type II dens fracture.
The objective were to determine upper cervical spine instability due to simulated dens fracture and investigate stability provided by the halo-vest and odontoid screw, applied individually and combined.
Previous studies have evaluated posterior fixation techniques for stabilizing dens fracture. No previous biomechanical study has investigated the halo-vest and odontoid screw for stabilizing dens fracture.
A biofidelic skull-neck-thorax model was used with 5 osteoligamentous whole cervical spine specimens. Three-dimensional flexibility tests were performed on the specimens while intact, following simulated dens fracture, and following application of the halo-vest alone, odontoid screw alone, and halo-vest and screw combined. Average total neutral zone and total ranges of motion at C0/1 and C1/2 were computed for each experimental condition and statistically compared with physiologic motion limits, obtained from the intact flexibility test. Significance was set at P < 0.05 with a trend toward significance at P < 0.1.
Type II dens fracture caused trends toward increased sagittal neutral zone and lateral bending range of motion at C1/2. Spinal motions with the dens screw alone could not be differentiated from physiologic limits. Significant reductions in motion were observed at C0/1 and C1/2 in flexion-extension and axial rotation due to the halo-vest, applied individually or combined with the dens screw. At C1/2, the halo-vest combined with the dens screw generally allowed the smallest average percentages of intact motion: 3% in axial rotation, 17% in flexion-extension, and 18% in lateral bending. | Do biomechanics of halo-vest and dens screw fixation for type II odontoid fracture? | Yes. The present reduction in C1/2 motion observed, due to the halo-vest and dens screw combined is similar to previously reported immobilization provided by the polyaxial screw/rod system and transarticular screw fixation combined with wiring. The present biomechanical data may be useful to clinicians when choosing an appropriate treatment for those with Type II dens fracture. | PASS | pubmedQA | 1 |
26248649 | miRNA expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. In this study, miRNA expression profiles were determined in clear cell renal cell carcinomas (ccRCC) and in matched normal kidney tissues by using a miRNA microarray platform which covers a total of 851 human miRNAs. Differential expression of 74 miRNAs were identified between ccRCC specimens and their matched adjacent noncancerous tissues, of which 30 were significantly upregulated in ccRCCs, and the other 44 were downregulated (fold change ≥ 2, P < 0.05). Interestingly, miR-200c was commonly downregulated in ccRCC specimens and ccRCC cell lines with significant functional consequences. Growth curve and FACS assay indicated that overexpression of miR-200c suppressed cell growth and induced cell-cycle arrest at G0-G1 phases in SN12-PM6 and 786-O cells. Furthermore, miR-200c could suppress in vivo tumor growth of SN12-PM6 cells in mice. Bioinformatics exposed cyclin-dependent kinase 2 (CDK2) as a potential target of miR-200c, which was validated using a luciferase reporter assay. Mechanistic investigations revealed that miR-200c was directly responsible for suppressing the expression of CDK2 in ccRCC cell lines and xenografts. Taken together, miR-200c plays an antioncogenic role in ccRCC, through controlling cell growth and cell-cycle progression by downregulating the G1-S regulator CDK2. | Does miR-200c Targets CDK2 and suppress Tumorigenesis in Renal Cell Carcinoma? | Yes. miR-200c exerts its novel antioncogenic function in renal cell carcinoma by controlling CDK2-dependent cell growth and cell-cycle progression. | PASS | pubmedQA | 1 |
17082491 | The mechanisms responsible for maintaining the differentiated phenotype of adult vascular smooth muscle cells (VSMCs) are incompletely understood. Reactive oxygen species (ROS) have been implicated in VSMC differentiation, but the responsible sources are unknown. In this study, we investigated the role of Nox1 and Nox4-derived ROS in this process.
Primary VSMCs were used to study the relationship between Nox homologues and differentiation markers such as smooth muscle alpha-actin (SM alpha-actin), smooth muscle myosin heavy chain (SM-MHC), heavy caldesmon, and calponin. We found that Nox4 and differentiation marker genes were downregulated from passage 1 to passage 6 to 12, whereas Nox1 was gradually upregulated. Nox4 co-localized with SM alpha-actin-based stress fibers in differentiated VSMC, and moved into focal adhesions in de-differentiated cells. siRNA against nox4 reduced NADPH-driven superoxide production in serum-deprived VSMCs and downregulated SM-alpha actin, SM-MHC, and calponin, as well as SM-alpha actin stress fibers. Nox1 depletion did not decrease these parameters. | Is nox4 required for maintenance of the differentiated vascular smooth muscle cell phenotype? | Yes. Nox4-derived ROS are critical to the maintenance of the differentiated phenotype of VSMCs. These findings highlight the importance of identifying the specific source of ROS involved in particular cellular functions when designing therapeutic interventions. | PASS | pubmedQA | 1 |
19460157 | Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers.
Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept.
We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values 58 to 72%; negative predictive values 63 to 78%). | Do blood autoantibody and cytokine profiles predict response to anti-tumor necrosis factor therapy in rheumatoid arthritis? | Yes. We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients. | PASS | pubmedQA | 1 |
15897483 | To evaluate the relationship between fasting plasma concentrations of ghrelin and gastric emptying in obese individuals compared with lean subjects.
We included 20 obese patients (9 men and 11 women, BMI > 30 kg/m2) and 16 nonobese control subjects (7 men and 9 women, BMI < or = 25 kg/m2). Gastric emptying of solids (egg sandwich labeled with radionuclide) was measured at 120 minutes with (99m)Tc-single photon emission computed tomography imaging. Ghrelin and leptin were analyzed by radioimmunoassay and ELISA methods, respectively.
The gastric half-emptying time was similar in obese men and women (67.8 +/- 14.79 vs. 66.6 +/- 13.56 minutes) but significantly shorter (p < 0.001) than in the control population (men: 88.09 +/- 11.72 minutes; women: 97.25 +/- 10.31 minutes). Ghrelin levels were significantly lower in obese subjects (131.37 +/- 47.67 vs. 306.3 +/- 45.52 pg/mL; p < 0.0001 in men and 162.13 +/- 32.95 vs. 272.8 +/- 47.77 pg/mL; p < 0.0001 in women). A negative correlation between gastric emptying and fasting ghrelin levels was observed only in lean subjects (y = -0.2391x + 157.9; R2 = 0.95). Also, in the lean group, ghrelin was the only significant independent determinant of gastric emptying, explaining 98% of the variance (adjusted R2) in a multiple regression analysis. | Does ghrelin influence gastric emptying in obese subjects? | No. This report shows that, in humans, gastric emptying is faster in obese subjects than in lean controls and that, whereas ghrelin is the best determinant of gastric kinetics in healthy controls, this action is lost in obesity. | PASS | pubmedQA | 1 |
23193908 | We assessed the likelihood of arytenoid dislocation during intubation through the application of controlled force.
Six cadaveric human larynges were mounted in an apparatus for simulating forcible collision with the arytenoid complexes. An endotracheal tube tip probe (ETTP) was used to push one arytenoid complex, and a non-slip probe (NSP) was tested on the other. Increasing pressure was applied until the probes either slipped or reached 5 kg of force. Dissection was then performed to assess the integrity of the cricoarytenoid ligament. The forces obtained by pushing an endotracheal tube against an electronic balance were measured to estimate the maximal possible intubating force.
None of the ETTP or NSP trials disrupted the cricoarytenoid joint ligaments, and the joint never appeared to be dislocated. The mean maximal forces were 1.8 kg for the ETTP (after which, slippage consistently occurred) and 4.7 kg for the NSP. The mean maximal forces from an endotracheal tube pushed against a scale were 1.5 kg (without stylet) and 4.6 kg (with stylet). | Does high-force simulated intubation fail to dislocate cricoarytenoid joint in ex vivo human larynges? | Yes. Arytenoid dislocation did not happen, and gross disruption of the joint capsule or ligament did not occur, even when the testing approximated the maximum force achievable under extreme conditions. Endotracheal tube insertion thus seems unlikely to cause arytenoid dislocation. | PASS | pubmedQA | 1 |
12359973 | Alterations in microvascular function have been hypothesized as a possible mechanism explaining the negative association of weight at birth with blood pressure and insulin resistance in adult life. However, these variables are closely associated, so that it has been difficult to establish whether microvascular dysfunction is a cause or a consequence of increased blood pressure or insulin resistance.
Cohort study.
VU University Medical Center, Amsterdam, The Netherlands.
Twenty-one prepubertal healthy children showing a wide range in birth weight.
Birth weight data were obtained from hospital records. Blood pressure was measured with an ambulatory 24-h blood pressure monitor, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Microvascular function (i.e. capillary recruitment during post-occlusive reactive hyperaemia and endothelium (in)dependent vasodilatation of the skin) was evaluated by videomicroscopy and iontophoresis of acetylcholine and sodium nitroprusside.
Birth weight was positively and significantly associated with capillary recruitment [slope, 22%/kg birth weight; 95% confidence interval (CI), 0.1-43; 0.05]. Birth weight was not associated with insulin sensitivity and systolic blood pressure (slope, -0.11 mg/kg per min per pmol/l; 95% CI, -2.4 to 2.2; = 0.9; and slope, 1.4 mmHg; 95% CI, -5.0 to 7.7/kg birth weight; = 0.7, respectively). The association between low birth weight and impaired capillary recruitment was not affected by adjustment for blood pressure and insulin sensitivity. Birth weight was not associated with endothelium-(in)dependent vasodilatation. | Is the association between birth weight and capillary recruitment independent of blood pressure and insulin sensitivity : a study in prepubertal children? | Yes. These results suggest that the association between birth weight and capillary recruitment is independent of blood pressure and insulin sensitivity. These findings are consistent with the hypothesis that an impaired capillary recruitment plays a mechanistic role in the association of birth weight with blood pressure and insulin resistance in adult life. | PASS | pubmedQA | 1 |
25058883 | The aim of this study was to investigate the risk factors for acute kidney injury (AKI) in patients with acute pancreatitis (AP).
Patients with AP were retrospectively divided into AKI group and non-AKI group. To investigate the risk factors for AKI, logistic regression analysis was performed with demography, etiologies, and comorbidities. Mortalities of patients with different body mass indexes were compared.
There were 43 patients with AKI and 202 patients without AKI. The risk factor for AKI in AP was hypertriglyceridemia (odds ratio, 2.964; 95% confidence interval, 1.485-5.915; P = 0.007). Forty-two patients developed AKI within the first 48 hours. The mortalities of normal weight, overweight, and obese groups in patients with AKI were 16.7%, 17.4%, and 62.5%, respectively. All the 4 patients who died in the non-AKI group were of normal weight. | Is hypertriglyceridemia a risk factor for acute kidney injury in the early phase of acute pancreatitis? | Yes. Hypertriglyceridemia is an independent risk factor for AKI in the early phase of AP. Obesity does not increase mortality of patients without AKI. We hypothesize that the role of pancreatic enzymes on triglyceride accumulated in renal may be an explanation for AKI in the early phase of AP. | PASS | pubmedQA | 1 |
21346095 | To examine the relationship between different measures of testosterone and estradiol (E(2)), muscle mass, muscle strength, and physical performance; and to test whether the association of sex hormone level with muscle strength and physical performance was independent of muscle mass.
A cross-sectional survey on 1489 community-dwelling men older than 64 years of age. Serum levels of testosterone and E(2) were measured by mass spectrometry, and sex hormone-binding globulin (SHBG) levels were measured by immunoradioassay. Muscle mass was examined by dual-energy X-ray absorptiometry and physical performance was assessed by hand-grip strength, gait speed, step length and chair-stand test.
Appendicular skeletal mass (ASM) was positively associated with total testosterone (TT; P<0.001), free testosterone (FT; P<0.001), and total E(2) (P<0.001) but not with free E(2) (P=0.102). After adjustment for age, serum SHBG and relative ASM, both TT and FT were significantly associated with grip strength, narrow-walk speed and the composite neuromuscular score. Higher total E(2), but not free E(2) was associated with lower grip strength (P<0.05) after adjustment for age, FT, SHBG and relative ASM. | Is testosterone but not estradiol level positively related to muscle strength and physical performance independent of muscle mass : a cross-sectional study in 1489 older men? | Yes. Testosterone level was related to both muscle mass, strength and physical performance. Total E(2) level, though related to muscle mass positively, affected muscle strength adversely in older men. | PASS | pubmedQA | 1 |
23088972 | We investigated the relationship between the distribution of the eNOS4a/b polymorphism and the clinical features of superficial bladder cancer.
This study included 201 healthy controls with a mean ± SD age of 62.35 ± 7.96 years and 123 patients with a mean age of 64.03 ± 11.00 years diagnosed with histopathologically confirmed superficial bladder cancer. The eNOS4a/b polymorphism genotype (aa, bb or ab) was identified by polymerase chain reaction. Blood glutathione and plasma malondialdehyde levels were measured by spectrophotometry as an indicator of oxidative stress. We estimated total plasma levels of nitric oxide metabolites using a colorimetric assay kit.
There were no significant differences in age or body mass index between patients and controls. Malondialdehyde and nitric oxide metabolite levels were statistically significantly increased (p = 0.000 and 0.024, respectively) and glutathione levels were decreased (p = 0.000) in patients with superficial bladder cancer. The bb genotype of the eNOS4a/b polymorphism is the most frequent one in the Turkish population and the aa genotype was significantly more common in patients with superficial bladder cancer (p = 0.000). Also, the aa plus ab genotype was significantly more common in patients with high grade tumors (p = 0.013) and in those with more progression to muscle invasive disease (p = 0.000). This genotype was also a significant independent risk factor for recurrence after adjusting for smoking status, stage, grade and the presence of carcinoma in situ on logistic regression analyses (OR 3.095, 95% CI 1.21-7.86, p = 0.018). | Is nitric oxide synthase ( eNOS4a/b ) gene polymorphism associated with tumor recurrence and progression in superficial bladder cancer cases? | Yes. The current study suggests that a genotype containing the a allele of the eNOS4a/b polymorphism may be a risk factor for bladder cancer. Additionally, patients harboring the aa plus ab genotype are more likely to experience tumor recurrence and progression. | PASS | pubmedQA | 1 |
26962854 | microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.
HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.
miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size. | Does high-Density Lipoprotein-Associated miR-223 be Altered after Diet-Induced Weight Loss in Overweight and Obese Males? | Yes. HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss. | PASS | pubmedQA | 1 |
19751814 | The present study describes antispasmodic, antidiarrheal, bronchodilatory and tracheo-relaxant activities of Artemisia vulgaris to rationalize some of its traditional uses.
Crude extract of Artemisia vulgaris (Av.Cr) was studied in the isolated tissue preparations of rabbit jejunum and guinea-pig trachea, as well as in the in vivo castor oil-induced diarrhea and bronchodilatory techniques.
Av.Cr which tested positive for alkaloids, coumarins, flavonoids, saponins, sterols, tannins and terpenes caused concentration-dependent (0.03-10mg/mL) relaxation of jejunum spontaneous contractions. Av.Cr inhibited the carbachol (CCh, 1 microM) and K(+) (80 mM)-induced contractions in a pattern, similar to that of dicyclomine. Av.Cr shifted the Ca(2+) concentration-response curves to right, like that caused by verapamil and dicyclomine. Av.Cr produced rightward parallel shift in CCh-curves, followed by non-parallel shift at higher concentration with the suppression of the maximum response, similar to that caused by dicyclomine. It exhibited protective effect against castor oil-induced diarrhea and CCh-mediated bronchoconstriction in rodents. In trachea, Av.Cr relaxed the CCh (1 microM) and K(+) (80 mM)-induced contractions and shifted the CCh-curves to right. | Are antispasmodic and bronchodilator activities of Artemisia vulgaris mediated through dual blockade of muscarinic receptors and calcium influx? | Yes. These results indicate that Artemisia vulgaris exhibits combination of anticholinergic and Ca(2+) antagonist mechanisms, which provides pharmacological basis for its folkloric use in the hyperactive gut and airways disorders, such as abdominal colic, diarrhea and asthma. | PASS | pubmedQA | 1 |
16314597 | Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity, is a chronic, polysymptomatic condition that cannot be explained by an organic disease. Physical and psychological complaints are believed to be sustained by low levels of chemically unrelated substances in the environment. At present, it is unclear whether IEI is an environmental illness or a variant of somatoform disorders (SFD). This study examined whether IEI can be distinguished from SFD with respect to self-reported symptoms, trait anxiety, body-related cognitions, and symptom attributions.
We compared 54 subjects with IEI, 54 subjects with SFD but without IEI, and 44 subjects with neither IEI nor SFD on symptom scales, psychological questionnaires, and structured interviews for IEI, depression, anxiety, and SFD.
More than half of the IEI subjects met Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria of SFD. This group shared both symptoms and psychological features of somatization with the SFD group. IEI subjects who did not fulfill criteria for a specific SFD were less impaired by their chemical sensitivity but differed nevertheless from nonsomatoform controls by significantly higher symptom scores, higher trait anxiety, a focus on autonomic sensations, and more pronounced somatic symptom attributions. These psychological features were significantly associated with the burden of somatic symptoms in both SFD and IEI. Furthermore, self-reported allergy but not total immunoglobulin E correlated with symptom burden in the total sample. | Do evidence for overlap between idiopathic environmental intolerance and somatoform disorders? | Yes. The similarity of IEI and SFD regarding symptoms and psychological features of somatization support the hypothesis that IEI is a variant of SFD. | PASS | pubmedQA | 1 |
16368648 | Radiation therapy is one of the standard treatments for cervical cancer. Glucose regulated protein 94 (GRP94) is a molecular chaperone, which increases in amount after X-ray irradiation. This study examined the involvement of GRP94 in radio-resistance in human cervical cancer cells.
Seven human cervical carcinoma cell lines (HeLa, SKG-I, SKG-IIIb, QG-U, Caski, SiHa and C33A) were examined for basal levels of GRP94 protein by western blotting analysis. Sensitivity to X-ray irradiation of these cell lines was determined with a colony survival assay. The suppression of GRP94 expression was performed using specific small-interfering RNA (siRNA) in HeLa and Caski cells.
HeLa cells and QG-U cells, with higher basal levels of GRP94, exhibited a low sensitivity to X-ray cell killing. In HeLa cells, the sensitivity increased when protein GRP94 levels were reduced by specific siRNA transfection. However, a reduction in GRP94 protein had little effect on the X-ray sensitivity of Caski cells, which expressed low basal GRP94 protein levels but showed a low sensitivity to X-rays. | Is increased expression of GRP94 protein associated with decreased sensitivity to X-rays in cervical cancer cell lines? | Yes. High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer. | PASS | pubmedQA | 1 |
26274822 | The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis.
Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein.
Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. | Do simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro? | Yes. We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo protein synthesis, depending on whether the two factors induced alone or overlapping, and as such it is important for in vivo studies to take this into account. | PASS | pubmedQA | 1 |
25680823 | Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population.
We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors ≥ 18 years of age with a GCS<8 at hospital admission and treated with TTM at 32-34 °C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome.
416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p < 0.001) and a similar incidence of good functional outcome. | Are prophylactic antibiotics associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management? | Yes. Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome. | PASS | pubmedQA | 1 |
10918163 | Macrophage migration inhibitory factor (MIF) is known to be a proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a regulator of tumor growth. Although positive and negative effects of MIF on tumor cell growth have been reported, to the authors' knowledge the precise role of MIF in tumorigenesis remains unclear. In the current study the authors assessed expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient prognosis.
Immunohistochemical analysis was performed on tissue specimens surgically obtained from 74 patients with primary lung adenocarcinoma (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In addition, expression of MIF mRNA in the cancerous tissue was investigated using in situ hybridization. Patient prognosis was evaluated with regard to MIF expression levels and its distribution was analyzed with the Kaplan-Meier method.
MIF mRNA and MIF protein were observed in the bronchial epithelium, alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF mRNA and protein were observed at much higher levels than in the normal alveolar epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in all tumor specimens examined. MIF protein also was observed in the nuclei of tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei of tumor cells from 15 patients (20.3%). The patients without nuclear MIF expression had a worse prognosis compared with those patients with MIF expression in the nuclei (P = 0.04). | Does intracellular distribution of macrophage migration inhibitory factor predict the prognosis of patients with adenocarcinoma of the lung? | Yes. The results of the current study suggest that intracellular MIF distribution predicts patient prognosis in individuals with adenocarcinoma of the lung. | PASS | pubmedQA | 1 |
20872968 | To investigate the effect of oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24 on hepatocellular carcinoma (HCC) cell lines and normal liver cell line.
HCC cell lines (HepG2, Hep3B and MHCC97L) and normal liver cell line (L02) with a different p53 status were infected with SG600-IL24 and Ad.IL-24, respectively. Melanoma differentiation-associated (MDA)-7/interleukin (IL)-24 mRNA and protein expressions in infected cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting, respectively. Apoptosis of HCC cells and normal liver cells was detected by cytometric assay with Hoechst33258 staining. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to investigate proliferation of HCC cells and normal liver cells, and cell cycle was assayed by flow cytometry.
RT-PCR, ELISA and Western blotting showed that the exogenous MDA-7/IL-24 gene was highly expressed in cells infected with SG600-IL24. MTT indicated that SG600-IL24 could suppress the growth of HepG2, Hep3B, MHCC97L, with an inhibition rate of 75% ± 2.5%, 85% ± 2.0%, 72% ± 1.8%, respectively (P < 0.01), promote the apoptosis of HepG2, Hep3B, MHCC97L, with an apoptosis rate of 56.59% ± 4.0%, 78.36% ± 3.5%, 43.39% ± 2.5%, respectively (P < 0.01), and block the HCC cell lines in the G2/M phase with a blocking rate of 35.4% ± 4.2%, 47.3% ± 6.2%, 42% ± 5.0%, respectively (P < 0.01) but not the normal liver cell line in a p53-independent manner. | Does oncolytic adenovirus SG600-IL24 selectively kill hepatocellular carcinoma cell lines? | Yes. SG600-IL24 can selectively suppress the proliferation and apoptosis of HCC cell lines in vitro but not normal liver cell line L02 in a p53-independent manner. Compared with Ad.IL-24, SG600-IL24 can significantly enhance the antitumor activity in HCC cell lines. | PASS | pubmedQA | 1 |
25405654 | The rapid development of computer and internet technology has a strong influence over one's quality of education within different fields of study. To determine the potential benefits of introducing internet into medical school classes, a pilot study was conducted in three different Chinese medical schools.
Seven hundred and eight medical school undergraduates, 385 dental school students and 366 foreign students were randomly recruited to complete a self-administered questionnaire. The contents included personal information, current usage of computer and internet, and attitudes towards the computerised teaching methods. Two forum groups were created using instant message software and were randomly assigned to two classes, allowing students to freely ask or discuss questions with the help of their teachers in these two virtual classrooms.
All 1539 questionnaires were accepted and analysed. Although there were some differences between Chinese and foreign undergraduates, both group of students were highly proficient in internet usage and navigation. Overwhelmingly, 88.37% of the students owned a computer and frequently logged onto the internet. Most of them believed that the internet is a helpful adjunct to their studies and held positive attitudes towards computerised teaching. Compared to the classes that were not assigned internet forums, the two experimental classes performed significantly better on the examination. | Does virtual classroom help medical education for both Chinese and foreign students? | Yes. Our results suggest that computerised teaching methods have significant potential to assist in learning for both Chinese and foreign medical undergraduates. | PASS | pubmedQA | 1 |
20224364 | To investigate whether maximal sterile barrier precautions (MSBPs) during central venous catheter (CVC) insertion are truly effective in preventing catheter-related bloodstream infections (CRBSIs) in patients in general surgical units.
The reported effectiveness of MSBPs was based on the results of a single-center randomized controlled trial by Raad et al and the majority of the patients (99%) in the study were chemotherapy outpatients.
Between March 14, 2004 and December 28, 2006, the patients scheduled for CVC insertion in surgical units at 9 medical centers in Japan were randomly assigned to either an MSBP group (n = 211) or a standard sterile barrier precaution (SSBP) group (n = 213). This study was registered in the UMIN Clinical Trials Registry (registration ID number: UMIN000001400).
The median (range) duration of catheterization was 14 days (0-92 days) in the MSBP group and 14 days (0-112 days) in the SSBP group. There were 5 cases (2.4%) of CRBSI in the MSBP group and 6 cases (2.8%) in the SSBP group (relative risk, 0.84; 95% confidence interval, 0.26-2.7; P = 0.77). The rate of CRBSIs per 1000 catheter days was 1.5 in the MSBP group and 1.6 in the SSBP group. There were 8 cases (3.8%) of catheter-related infections in the MSBP group and 7 cases (3.3%) in the SSBP group (relative risk, 1.2; 95% confidence interval, 0.43-3.1; P = 0.78). The rate of catheter-related infection per 1000 catheter days was 2.4 in the MSBP group and 1.9 in the SSBP group. | Do maximal sterile barrier precautions reduce catheter-related bloodstream infections in general surgery units : a multi-institutional randomized controlled trial? | No. This study is larger in sample size than the one performed by Raad et al and could not demonstrate better prevention of CRBSIs by MSBP compared with SSBP. A large randomized controlled trial or at least a meta-analysis of any other studies in the literature is necessary to reach to a conclusion on this issue. | PASS | pubmedQA | 1 |
17335599 | Penile carcinoma is a common disease in northeast Brazil. This paper shows the results of the use of isolated gamma probe and discusses the incidence of false negative rates.
From July 2000 to September 2003, 27 newly diagnosed penile carcinoma patients (T1, T2, N0) were included in this prospective study. The isolated gamma probe technique uses the sodium phytate technetium as a tracer and inguinal scanning with probe and after identified the lymph node it is removed. Lymphadenectomies were performed for positive inguinal lymph nodes metastasis.
There were 27 patients (mean age 59.6). Follow up was 37 months. Patients from country were 72% and illiterate or semi-illiterate were 56.7%. The tumors were mostly located in the glans (81.4%). They were T1, 52 % and T2, 48 %. 81.4% of the patients underwent partial penectomy, and 18.6% underwent postectomy and excision with wide margins. In 48% of the patients, the highest radioactive count rate was located on the left side, while in 41% was located on the right side. Only one patient had a positive pathological lymph node metastasis at the moment of the surgery. Additionally 3 patients became inguinal lymph node positive at the follow up. This date yielded a sensibility rate of 25% and a false-negative rate of 42.8%. | Is the isolated gamma probe technique for sentinel node penile carcinoma detection unreliable? | Yes. Isolated gamma probe technique for sentinel node penile carcinoma has a very low sensibility and a high false negative rate. Therefore it is highly advisable the addition of others methods such as lymphoscintigraphy, vital blue, ultrasonography and so on. The isolated gamma probe technique for sentinel node penile carcinoma detection is unreliable. | PASS | pubmedQA | 1 |
9665051 | Preclinical atherosclerosis is associated with increased endothelial cell (EC) expression of leukocyte adhesion molecules (LAMs), which mediate monocyte adhesion during atherogenesis. Identification of cell-surface LAMs may uniquely allow assessment of endothelial function, but there are no in vivo methods for detecting LAMs. We tested a new microbubble designed to bind to and allow specific ultrasound detection of intercellular adhesion molecule-1 (ICAM-1).
A perfluorobutane gas-filled lipid-derived microsphere with monoclonal antibody to ICAM-1 covalently bound to the bubble shell was synthesized. Bubbles with either nonspecific IgG or no protein on the shell were synthesized as controls. Coverslips of cultured human coronary artery ECs were placed in a parallel-plate perfusion chamber and exposed to 1 of the 3 microbubble species, followed by perfusion with culture medium. Experiments were performed with either normal or interleukin-1beta-activated ECs overexpressing ICAM-1, and bubble adherence was quantified with epifluorescent videomicroscopy. There was limited adherence of control bubbles to normal or activated ECs, whereas a 40-fold increase in adhesion occurred when anti-ICAM-1-conjugated bubbles were exposed to activated ECs compared with normal ECs (8.1+/-3.5 versus 0.21+/-0.09 bubbles per cell, respectively, P<0.001). Although diminished, this difference persisted even after perfusion at higher wall shear rates. | Do microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells? | Yes. A gas-filled microbubble with anti-ICAM-1 antibody on its shell specifically binds to activated ECs overexpressing ICAM-1. Diagnostic ultrasound in conjunction with targeted contrast agents has the unique potential to characterize cell phenotype in vivo. | PASS | pubmedQA | 1 |