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Does [ miR-497 suppress proliferation of human cervical carcinoma HeLa cells by targeting cyclin E1 ]?

To evaluate the effect of miR-497 on proliferation of human cervical carcinoma HeLa cells and target relationship between miR-497 and cyclin E1 (CCNE1). Pre-miR-497 sequences were synthesized and cloned into pcDNATM6.2-GW to construct recombinant plasmid pcDNATM6.2-GW-pre-miR-497 and identified by real-time quantitative PCR (qRT-PCR). In addition, sequences of the wild-type CCNE1 (WT-CCNE1) and mutant CCNE1 (MT-CCNE1) were respectively cloned into pmirGLO vectors. MTT assay was used to explore the impact of miR-497 on the proliferation of HeLa cells. Furthermore, the target effect of miR-497 on the CCNE1 was identified by dual-luciferase reporter assay system, qRT-PCR and Western blotting. The recombinant plasmids pcDNATM6.2-GW-pre-miR-497 and pmirGLO-WT-CCNE1, pmirGLO-MT-CCNE1 were successfully constructed, and the miR-497 expression level in HeLa cells transfected with pre-miR-497 was significantly higher than that in the neg-miR group (P<0.05). MTT assay showed that miR-497 could significantly inhibit the proliferation of HeLa cells (P<0.05). A remarkable reduction of luciferase activities of WT-CCNE1 reporter was observed in HeLa cells with pre-miR-497 transfection (P<0.01), and the mRNA and protein expression levels of CCNE1 were down-regulated in HeLa cells transfected with pre-miR-497 (P<0.05).

Over-expressed miR-497 in HeLa cells could suppress cell proliferation by targeting CCNE1.

Is rANTES promoter genotype associated with diabetic nephropathy in type 2 diabetic subjects?

To evaluate the effect of RANTES gene promoter polymorphism and RANTES receptor (CCR5 gene) promoter polymorphism on diabetic nephropathy in Japanese type 2 diabetic subjects. A total 616 Japanese subjects with type 2 diabetes were recruited. Polymorphisms of -28 C/G and -403 G/A in the RANTES gene promoter region, and of 59029 G/A in the CCR5 gene promoter region were detected by PCR-RFLP (restriction fragment length polymorphism). The association of these genotypes with nephropathy was analyzed. While the RANTES -403 genotype showed no association with nephropathy, the frequency of the -28G allele was significantly higher in the DN2 group (urinary albuminuria-to-creatinine ratio [ACR] >or=300 mg/g creatinine, serum creatinine <2.0 mg/dl) than in the DN0 (ACR <30 mg/g creatinine) and DN1 (ACR >or=30 mg/g creatinine and <300 mg/g creatinine) groups. The frequency of a RANTES -28G-positive genotype (C/G or G/G) was higher in the DN2 group than in the DN0 and DN1 groups (34% vs. 25 and 20%, P = 0.0268, chi(2) = 4.905), and the frequency of a CCR5 59029 A-positive genotype (G/A or A/A) was higher in the DN1 and DN2 groups than in the DN0 group (84 and 85% vs. 76%, P = 0.0123, chi(2) = 6.269). Discriminant analysis showed that the RANTES -28G-positive genotype and CCR5 59029A-positive genotype were independently associated with nephropathy. The percentage of macroalbuminuria was twofold higher in the subjects having -28G or 59029A and threefold higher in the subjects having -28G and 59029A than in the subjects without -28G and 59029A.

The RANTES promoter -28G genotype and CCR5 promoter 59029A genotype may be independent risk factors for diabetic nephropathy in patients with type 2 diabetes and may have an additive effect on nephropathy.

Can the inflammation markers of patients with high peritoneal permeability on continuous ambulatory peritoneal dialysis be reduced on nocturnal intermittent peritoneal dialysis?

Patients with high peritoneal permeability have the greatest degree of inflammation on continuous ambulatory peritoneal dialysis (CAPD), which may be associated with their higher mortality. Nocturnal intermittent peritoneal dialysis (NIPD; "dry day") may decrease inflammation by reducing the contact between dialysate and peritoneum and/or providing better fluid overload control. Therefore, the aims of this study were to determine and compare serum and dialysate concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) of patients with high or high-average peritoneal transport on CAPD, changed to NIPD, and ultimately to continuous cyclic peritoneal dialysis (CCPD). Crossover clinical trial in 11 randomly selected patients. All subjects had been on CAPD and were changed to NIPD, and ultimately to CCPD (6.4 +/- 3.1 months after initiation of study). All patients used glucose-based dialysate. Evaluations of clinical and biochemical parameters, dialysis adequacy, and serum and dialysis inflammation markers were performed at baseline on CAPD, 7 - 14 days after changing to NIPD, 7 - 14 days after switching to CCPD, and after 1 year of follow-up. All patients used only 1.5% glucose dialysate during evaluation days. CRP was determined by nephelometry, and IL-6 and TNF-alpha by ELISA. Seven patients were high transporters and 4 high average. Ultrafiltration increased (p<0.05) when patients changed from CAPD [0.38 L (-0.3 - 1.1 L)] to NIPD [2.64 L (0.7 - 4.7 L)]; it then decreased on CCPD [0.88 L (0.4 - 1.3 L) and at the end of study [0.65 L (0.3 - 1.0 L)]. This better fluid overload control was accompanied by decreased weight and systolic and diastolic blood pressure when patients changed from CAPD (89 +/- 13 kg, 160 +/- 23 and 97 +/-9 mmHg, respectively) to NIPD (86 +/- 17 kg, 145 +/- 14 and 86 +/- 9 mmHg, respectively), and increased weight and systolic and diastolic blood pressure on CCPD (85 +/- 15 kg, 143 +/-23 and 88 +/- 14 mmHg, respectively) and at the end of follow-up (87 +/- 16 kg, 155 +/- 24 and 89 +/- 12 mmHg, respectively). Median serum CRP decreased (p = 0.03), from 3.8 (1.6 - 8.5) mg/L on CAPD to 1.0 (0.4 - 4.4) mg/L on NIPD, but increased on CCPD [1.8 (1.3 - 21) mg/L]and at the end of the study [3.2 (0.3 - 8.2) mg/L]. Dialysate CRP decreased nonsignificantly, from 0.10 (0 - 0.5) mg/L on CAPD to 0 (0 - 0.03) mg/L on NIPD, to 0.01 (0 - 0.08) mg/L on CCPD, and to 0 (0 - 0) mg/L at final evaluation. Serum TNF-alpha concentration decreased, from 0.14 (0.04 - 0.6) pg/mL on CAPD to 0.01 (0 - 0.08) pg/mL on NIPD, and then increased to 0.06 (0 - 0.4) pg/mL on CCPD and to 0.11 (0 - 0.2) pg/mL at the end of the study; whereas dialysate TNF-alpha decreased, from 0.08 (0.03 - 0.2) pg/mL on CAPD to 0.04 (0 - 0.2) pg/mL on NIPD, and to 0 (0 - 0) pg/mL and 0 (0 - 0.05) pg/mL on CCPD and final evaluation respectively. Serum IL-6 decreased (p = 0.07), from 2.5 (2.0 - 4.2) pg/mL on CAPD to 1.0 (0.7 - 2.0) pg/mL on NIPD, and to 1.0 (0.8 - 2.9) pg/mL on CCPD and 1.0 (0.5 - 9.8) pg/mL at the end of the study; whereas dialysate levels remained similar on CAPD [8.0 (3.7 - 13) pg/mL]and NIPD [7.8 (5.1 - 23) pg/mL], and increased on CCPD [11.2 (9.5 - 19) pg/mL]and at final evaluation [11.2 (8.3 - 15) pg/mL].

NIPD significantly decreased serum CRP and displayed a trend to decrease TNF-alpha and IL-6 serum concentrations compared with CAPD; whereas CCPD tended to reverse these effects. These results did not appear to be due to decreased local peritoneal inflammation, but they could be associated with better control of fluid overload on NIPD. Thus, NIPD, as Long as the residual renal function allows it, may be useful in reducing the systemic inflammation of patients with high peritoneal membrane permeability.

Does interferon-alpha administration enhance CD8+ T cell activation in HIV infection?

Type I interferons play important roles in innate immune defense. In HIV infection, type I interferons may delay disease progression by inhibiting viral replication while at the same time accelerating disease progression by contributing to chronic immune activation. To investigate the effects of type I interferons in HIV-infection, we obtained cryopreserved peripheral blood mononuclear cell samples from 10 subjects who participated in AIDS Clinical Trials Group Study 5192, a trial investigating the activity of systemic administration of IFNα for twelve weeks to patients with untreated HIV infection. Using flow cytometry, we examined changes in cell cycle status and expression of activation antigens by circulating T cells and their maturation subsets before, during and after IFNα treatment. The proportion of CD38+HLA-DR+CD8+ T cells increased from a mean of 11.7% at baseline to 24.1% after twelve weeks of interferon treatment (p = 0.006). These frequencies dropped to an average of 20.1% six weeks after the end of treatment. In contrast to CD8+ T cells, the frequencies of activated CD4+ T cells did not change with administration of type I interferon (mean percentage of CD38+DR+ cells = 2.62% at baseline and 2.17% after 12 weeks of interferon therapy). As plasma HIV levels fell with interferon therapy, this was correlated with a "paradoxical" increase in CD8+ T cell activation (p<0.001).

Administration of type I interferon increased expression of the activation markers CD38 and HLA DR on CD8+ T cells but not on CD4+ T cells of HIV+ persons. These observations suggest that type I interferons may contribute to the high levels of CD8+ T cell activation that occur during HIV infection.

Do initial radiographs agree with crash site mechanism of injury in pelvic ring disruptions?

Direction of injury force inferred from pelvic radiographs may be used in trauma care to predict associated injuries and guide intervention. Our objective was to compare injury direction determined from anteroposterior (AP) pelvic radiographs with injury forces determined from crash site investigation. We studied all 28 subjects from the Crash Injury Research Engineering Network (CIREN) database who met inclusion criteria of pelvic ring disruption, single-event crash, restrained front-seat occupant, diagnostic-quality pelvic radiography, and complete crash investigation data. Assessment of diagnostic quality of pelvic radiography was made by 2 radiologists who were blinded to all other subject information. Crash site investigation data included principal direction of force (PDOF), crash magnitude, and passenger compartment intrusion. An orthopedic trauma surgeon and a fellowship-trained emergency radiologist independently assessed the pelvic radiographs to determine the injury PDOF and the Young-Burgess and Tile fracture classifications, with disputes resolved by an additional emergency radiologist. Agreement between injury forces and pelvic radiographs was assessed using the kappa statistic. The PDOF was anterior in 9 (32%) and lateral in 19 (68%) subjects. The readers agreed with the crash primary direction of force in 21 (75%) subjects (kappa=0.42). In subjects with lateral PDOF, agreement was 89% (17/19) compared to 44% for anterior PDOF (4/9). Interobserver agreement for the Young and Tile classification schemes was moderate (weighted kappa 0.44 and 0.54, respectively).

Crash site investigation and pelvic radiography may provide conflicting information about primary direction of injuring forces. Presumed anterior impact based on PDOF is not in consistent agreement with the pattern of injury evident on the AP pelvic radiograph.

Do national cross-sectional study of nonsteroidal anti-inflammatory drugs use highlights differences between parents and professionals and prompts safety concerns?

Controversy surrounding the safety of nonsteroidal anti-inflammatory drugs (NSAIDs) provides an opportunity to study parents' and healthcare professionals' differential use of over-the-counter drugs. In this national cross-sectional study, general practitioners, paediatricians and pharmacists were asked to include up to five consecutive febrile paediatric patients aged 1 month to 12 years. Parents and healthcare professionals completed questionnaires about the current fever episode. We studied the differential use of NSAIDs by parents and healthcare professionals notably in three clinical conditions with various estimated risk of NSAIDs complications: varicella, gastroenteritis and pharyngitis. The 1534 healthcare professionals prescribed 15% of the 6596 children with an NSAID, but 32% of the parents gave their child an NSAID. Generally, NSAID use was associated with older children, higher temperatures, pain due to otitis and the absence of a rash or gastroenteritis. The differential use of NSAIDs by parents and professionals was greater in conditions with high than low estimated risks of NSAID complications, with odds ratios ranging from to 9.0 to 2.9, respectively.

The differential use of NSAIDs by healthcare professionals and parents for clinical conditions with potential risks should prompt discussions about the safety of their over-the-counter status.

Does activation of a meiotic checkpoint during Drosophila oogenesis regulate the translation of Gurken through Chk2/Mnk?

During Drosophila oogenesis, unrepaired double-strand DNA breaks activate a mei-41-dependent meiotic checkpoint, which couples the progression through meiosis to specific developmental processes. This checkpoint affects the accumulation of Gurken protein, a transforming growth factor alpha-like signaling molecule, as well as the morphology of the oocyte nucleus. However, the components of this checkpoint in flies have not been completely elucidated. We show that a mutation in the Drosophila Chk2 homolog (DmChk2/Mnk) suppresses the defects in the translation of gurken mRNA and also the defects in oocyte nuclear morphology. We also found that DmChk2 is phosphorylated in a mei-41-dependent pathway. Analysis of the meiotic cell cycle progression shows that the Drosophila Chk2 homolog is not required during early meiotic prophase, as has been observed for Chk2 in C. elegans. We demonstrate that the activation of the meiotic checkpoint affects Dwee1 localization and is associated with DmChk2-dependent posttranslational modification of Dwee1. We suggest that Dwee1 has a role in the meiotic checkpoint that regulates the meiotic cell cycle, but not the translation of gurken mRNA. In addition, we found that p53 and mus304, the Drosophila ATR-IP homolog, are not required for the patterning defects caused by the meiotic DNA repair mutations.

DmChk2 is a transducer of the meiotic checkpoint in flies that is activated by unrepaired double-strand DNA breaks. Activation of DmChk2 in this specific checkpoint affects a cell cycle regulator as well as mRNA translation.

Do serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid?

The 180-kDa transmembrane hemidesmosomal protein (BPAG2) has been identified as an important autoantigen in bullous pemphigoid (BP). Using the NC16A domain as the antigenic target, a highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of autoantibodies to BP180 was developed. To investigate the correlation of clinical severity and ELISA indices in BP. Antibody titers in the sera from 20 patients were measured using BP180NC16a-ELISA, and an analysis of the correlation of ELISA indices with disease activity was performed. Serum was obtained from each patient with BP at least three times: before the initiation of treatment, during complete disease control just before the decrease in corticosteroid, and when the dosage of corticosteroid was successfully decreased to half the initial dose. Of the 20 patients, three showed recurrence at a later stage, caused by their decision to stop treatment; serum was obtained at the early stage of recurrence. ELISA indices were significantly decreased after successful therapy, although indirect immunofluorescence titers did not always show apparent correlations. Indices measured using BP180NC16a-ELISA were well correlated with disease activity. Three patients decided to stop taking their medication; subsequently (within 1-2 weeks), blisters recurred, and the levels of antibodies to BP180 increased to close to those before the initiation of treatment.

BP180 antibody titers showed a closer correlation than indirect immunofluorescence titers to disease activity. The titer of BP180 antibody may be a useful tool for the evaluation of disease activity and for the assessment of the effectiveness of treatments in BP.

Does secreted frizzled-related protein 1 loss contribute to tumor phenotype of clear cell renal cell carcinoma?

Incidence and mortality rates for renal cell carcinoma (RCC) have been rising for decades. Unfortunately, the molecular events that support RCC carcinogenesis remain poorly understood. In an effort to gain a better understanding of signaling events in clear cell RCC (cRCC), we investigated the antitumor activity of secreted frizzled-related protein 1 (sFRP1), a negative regulator of Wnt signaling. Genomic profiling of cRCC tumors and patient-matched normal tissues was done and confirmed using quantitative PCR and immunohistochemistry. Methylation-specific PCR was done on patient samples to evaluate the mechanism responsible for sFRP1 loss. sFRP1 expression was restored in cRCC cells and the effects on tumor phenotype were characterized. Genomic profiling, quantitative PCR, and immunohistochemistry indicated that loss of sFRP1 occurred in cRCC and papillary RCC patient tissues. Twelve Wnt-regulated genes were up-regulated in cRCC tissues, including c-myc and cyclin D1, potentiators of cell proliferation and survival. Methylation of the sFRP1 gene was one mechanism identified for attenuation of sFRP1 mRNA. Stable reexpression of sFRP1 in cRCC cells resulted in decreased expression of Wnt target genes, decreased growth in cell culture, inhibition of anchorage-independent growth, and decreased tumor growth in athymic nude mice.

To our knowledge, this is the first report to show that stable restoration of sFRP1 expression in cRCC cells attenuates the cRCC tumor phenotype. Our data support a role for sFRP1 as a tumor suppressor in cRCC and that perhaps loss of sFRP1 is an early, aberrant molecular event in renal cell carcinogenesis.

Do implicit Spoken Words and Motor Sequences Learning Are Impaired in Children with Specific Language Impairment?

This study aims to compare verbal and motor implicit sequence learning abilities in children with and without specific language impairment (SLI). Forty-eight children (24 control and 24 SLI) were administered the Serial Search Task (SST), which enables the simultaneous assessment of implicit spoken words and visuomotor sequences learning. Results showed that control children implicitly learned both the spoken words as well as the motor sequences. In contrast, children with SLI showed deficits in both types of learning. Moreover, correlational analyses revealed that SST performance was linked with grammatical abilities in control children but with lexical abilities in children with SLI.

Overall, this pattern of results supports the procedural deficit hypothesis and suggests that domain general implicit sequence learning is impaired in SLI.

Are paediatric medicines risk factors for dental caries and dental erosion?

To assess in vitro the cariogenic and erosive potentials of Brazilian liquid oral paediatric medicines. Twenty-three paediatric medicines available on the Brazilian market were evaluated. The sample consisted of antihistamines, antitussives, bronchodilators and mucolytics. Duplicates of each bottle were analyzed for sugar concentration using normal-phase- high-performance liquid chromatography (HPLC). Quantification of sugars and sorbitol was calculated using the peak heights of commercial standards as references. pH measurements were determined using a digital pH meter. Titratable acidity was assessed by diluting three aliquots of each medicine, and increments of 0.1N NaOH were titrated until neutrality was reached. Viscosity was determined using a viscosemeter. Sugars were detected in 56.5% of the medicines. Sucrose was identified in 10 medicines, with concentrations ranging from 11.36 g% to 85.99 g%. Glucose was detected in five medicines, with concentrations varying from 4.64 g% to 40.19 g%; fructose in six medicines, with concentrations ranging from 5.09 g% to 46.71 g%. Twelve medicines exhibited sorbitol, with values ranging from 5.39 g% to 46.09 g%. Most tested medicines were acidic, with pH values ranging between 2.6 and 5.7. Only two medicines (Fluimucil and Polaramine) presented pH 6.4 and 6.0, respectively. Titratable acidity mean values ranged between 0.28 and 16.33 mL. Viscosity values varied between 2.8 cP and 412.3 cP.

Many paediatric medicines showed high sugar concentration, pH values below the critical value and high titratable acidity values, all of which increase the medicines' cariogenic and erosive potentials.

Do microsatellite markers for the New Zealand endemic Myosotis pygmaea species group ( Boraginaceae ) amplify across species?

Microsatellite loci were developed as polymorphic markers for the New Zealand endemic Myosotis pygmaea species group (Boraginaceae) for use in species delimitation and population and conservation genetic studies. Illumina MiSeq sequencing was performed on genomic DNA from seedlings of M. drucei. From trimmed paired-end sequences >400 bp, 484 microsatellite loci were identified. Twelve of 48 microsatellite loci tested were found to be polymorphic and consistently scorable when screened on 53 individuals from four populations representing the geographic range of M. drucei. They also amplify in all other species in the M. pygmaea species group, i.e., M. antarctica, M. brevis, M. glauca, and M. pygmaea, as well as 18 other Myosotis species.

These 12 polymorphic microsatellite markers establish an important resource for research and conservation of the M. pygmaea species group and potentially other Southern Hemisphere Myosotis.

Does contour plot assessment of existing meta-analyses confirm robust association of statin use and acute kidney injury risk?

Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure.

The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question.

Does the molecular staging in pelvic lymph nodes improve the detection of relevant prostate cancer metastases?

To assess the course of cancer-free survival and thus determine how reliably reverse transcriptase-polymerase chain reaction (RT-PCR) can detect prostate-specific antigen (PSA)-expressing cells, as patients with untreated lymph node-positive prostate cancer tend to have a poor prognosis, whereas those treated with radical prostatectomy (RP) and immediate adjuvant hormonal therapy show excellent local disease control and a disease-free survival comparable with that of patients with negative lymph nodes, but the detection of micrometastatic disease in pelvic lymph nodes remains a major challenge. Quantitative RT-PCR was used to detect PSA mRNA expression in total RNA of 457 pelvic lymph nodes from 70 patients who had RP (53 patients) or laparoscopic lymphadenectomy (17) at our clinic in 1999/2000. For this purpose, alternate sections of lymph node tissue were either snap-frozen for later RNA isolation or examined by standard histopathological methods. Clinicopathological data, adjuvant treatments and follow-up data were recorded for all patients. After January 2006 (6-year observation period), 13 patients had no follow-up data, while 27 had biochemical (PSA) recurrence or other evidence of clinical progression (two died from prostate cancer), and 30 had no signs of recurrence. Compared to the 'reference' standard (histopathology), the PCR method had a sensitivity of 83% and a specificity of 66%. The method had a positive predictive value of 52% and a negative predictive value of 57%.

Considered alone, pelvic lymph node PSA RT-PCR does not predict the clinical course better than a histopathological assessment of lymph nodes. However, it also identifies some patients with negative histology who later show progression. When added to the pathological classification, PSA RT-PCR improves the detection rate of primary lymphatic dissemination.

Does western blot quantification of aggrecan fragments in human synovial fluid indicate differences in fragment patterns between joint diseases?

To develop a Western blot method for quantification of multiple aggrecan fragments in human synovial fluids (SFs). SF aggrecan fragments were prepared from knee healthy (reference), knee injury and arthritis subjects by CsCl gradient centrifugations collecting D1 fractions. Samples were analyzed by Western blot, using antibodies against the N-terminal epitope ARGS and the G3 domain, and fragments were quantified using a digital luminescence image analyzer. The method had a coefficients of variation of 10-30%, and a high correlation (r(S)=0.86) with a corresponding enzyme-linked immunosorbent assay (ELISA). The SFs from reference, knee injured and arthritic subjects contained two major ARGS fragments, ARGS-SELE and ARGS-CS1, and three major G3 fragments (GRGT-G3, GLGS-G3 and AGEG-G3). Compared to the reference, the acute arthritis and acute joint injury groups had a 30-fold elevated concentration of ARGS fragments, and both groups had a higher proportion of the aggrecan in joint fluid as ARGS fragments compared to the other groups. The reference and chronic injury groups had an excess of ARGS-CS1 fragments over ARGS-SELE fragments, while subjects with acute arthritis or osteoarthritis had a more even distribution between these fragments.

We have developed a novel Western blot quantification method for quantification of SF aggrecan fragments which can differentiate fragments of different sizes sharing the same epitope. The anti-ARGS and anti-G3 quantitative Western blots provided information important for a better understanding of the proteolytic pathways in aggrecan breakdown, information that discriminates between different joint diseases, and may aid in identification of new biomarkers.

Does moderate physical exercise protect myenteric metabolically more active neurons in mice infected with Trypanosoma cruzi?

Trypanosoma cruzi causes neuronal myenteric depopulation compromising intestinal function. The purpose of this study was to evaluate the influence of moderate physical exercise on NADH diaphorase (NADH-d)-positive neurons in the myenteric plexus and intestinal wall of the colon in mice infected with T. cruzi. Forty 30-day-old male Swiss mice were divided into the following groups: trained infected (TI), sedentary infected (SI), trained control (TC), and sedentary control. The TC and TI groups were subjected to a moderate physical exercise program on a treadmill for 8 weeks. Three days after finishing physical exercise, the TI and SI groups were intraperitoneally inoculated with 1,300 blood trypomastigotes of the Y strain of Trypanosoma cruzi. Parasitemia was evaluated from days 4 to 61 after inoculation. On day 75 of infection, myenteric neurons in the colon were quantified (NADH-d), and inflammatory foci were counted. Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) levels were evaluated in plasma. The results were compared using analysis of variance and the Kruskal-Wallis test at a 5 % significance level. Moderate physical exercise reduced the parasite peak on day 8 of infection (p = 0.0132) and total parasitemia (p = 0.0307). It also prevented neuronal depopulation (p < 0.01), caused hypertrophy of these cells (p < 0.05), prevented the formation of inflammatory foci (p < 0.01), and increased the synthesis of TNF-α (p < 0.01) and TGF-β (p > 0.05).

These results reinforce the therapeutic benefits of moderate physical exercise for T. cruzi infection.

Does intervention study show outpatient cardiac rehabilitation to be economically at least as attractive as inpatient rehabilitation?

Since the late 1990 s, cost pressure has led to a growing interest in outpatient rehabilitation in Germany where predominantly inpatient rehabilitation has been provided. Taking into account the feasibility of a randomized design, the aim of this study was to compare outpatient and inpatient cardiac rehabilitation from a societal perspective. A comprehensive cohort design was applied. Costs during rehabilitation were measured using individual documentation of the rehabilitation centers. Economic end points were quality of life (EQ-5D), and total direct and indirect costs. A propensity score approach, integrated into a simultaneous regression framework for cost and effects, was used to control for selection bias. Bootstrap analysis was applied for assessing uncertainty in cost-effectiveness. A total of 163 patients were included in the study (112 inpatients, 51 outpatients). As randomization was chosen by only 2.5% of participants, the study had to be analyzed as an observational study. Direct costs during inpatient rehabilitation were significantly higher by 600 euro (+/-318; p < 0.001) compared to outpatient rehabilitation (2,016 euro +/- 354 euro vs. 1,416 euro +/- 315), while there was no significant difference in health-related quality of life. Over the 12-month follow-up period, adjusted costs difference in total cost was estimated at -2,895 euro (p = 0.102) and adjusted difference in effects at 0.018 quality-adjusted life years (QALYs) (n.s.) in favor of outpatient treatment.

The ratio of mean cost over mean effect difference (incremental cost-effectiveness ratio) indicates dominance of outpatient rehabilitation, but at a considerable statistical uncertainty. However, outpatient rehabilitation cannot be rejected from an economic perspective.

Do cervical length measured by transvaginal ultrasonography versus Bishop score to predict successful labour induction in term pregnancies?

To compare the value of transvaginal ultrasonographic measurement of the cervical length versus the Bishop score, prior to induction of labour, in predicting the mode of delivery within four days. This longitudinal study included 110 women (at term, singleton, vertex presentation) in whom induction of labour was performed at 37-42 weeks of gestation. Cervical length on transvaginal ultrasound and the Bishop score were assessed prior to induction according to standard protocol. Medical records were reviewed for relevant-- demographic and clinical data. Primary outcome criterion was successful vaginal delivery within 96 h. Univariate analyses and receiver operating characteristic (ROC) curves were used to examine differences between variables possibly predicting outcome. Of the 110 women 66 were nulliparous and 44 multiparous. Vaginal delivery within 96 h was successful in 48 (73%) nulliparous and in 40 (91%) multiparous women ( i.e. in 80% of the total population). The overall rate of caesarean delivery was 17%. THERE WAS A SIGNIFICANT DIFFERENCE BETWEEN NULLIPAROUS AND MULTIPAROUS WOMEN IN AGE, CERVICAL LENGTH (MEAN IN MM IN NULLIPAROUS WOMEN: 29.31, range: 5.00-56.00; in multiparous women: 37.04, range: 12.00-56.00), Bishop score and successful induction, but no significant difference between these subgroups in neonatal outcomes. Only the Bishop score in nulliparous women showed a significant relationship between this variable and predicting successful labour induction (area under the ROC curve 0.679; standard error 0.73; p < 0.05; 95% CI: 0.536-0.823). The best cut-off value for the Bishop score was 3, with a sensitivity of 56.3% and a specificity of 72.2%.

In this study group significant independent prediction of vaginal delivery within 96 h is provided by the Bishop score but only in nulliparous women. Transvaginal ultrasonographic measurement of cervical length is not a significant independent predictor of vaginal delivery within 96 h.

Does atorvastatin ameliorate sildenafil-induced penile erections in experimental diabetes by inhibiting diabetes-induced RhoA/Rho-kinase signaling hyperactivation?

One of the proposed mechanisms responsible for diabetes-related erectile dysfunction (ED) is overactivity of RhoA/ROCK signaling, as seen in experimental models of chemical diabetes. Because statins may interfere with RhoA/Rho-kinase (ROCK) signaling through the reduction of geranyl-geranyl pyrophosphate (GGPP), required for RhoA activation, we investigated whether atorvastatin ameliorated diabetes-related ED. Streptozotocin-induced (8 weeks) diabetic rats and alloxan-induced (8 weeks) diabetic rabbits received atorvastatin (5 mg/kg daily) for the last 2 weeks. In vitro contractility studies were conducted in the rabbit model. In the rat model, sildenafil effect on electrical stimulation (ES)-induced erection was investigated. Atorvastatin action was also analyzed using human fetal penile smooth muscle cells (hfPSMCs) exposed to low (5 mM), high (22 mM), and very high (40 mM) glucose. Atorvastatin effect on hyperglycemia-induced RhoA/ROCK signaling was evaluated using the ROCK inhibitor Y-27632 in both animal models and by analyzing functional effects downstream to RhoA activation in hfPSMCs. In both diabetic models, atorvastatin did not affect glycemia, lipid plasma levels, and the hypogonadal state. In diabetic rats, atorvastatin ameliorated the erectile response to the ES of the cavernous nerve and normalized sildenafil effect on erectile function, strongly decreased by diabetes. In penile tissue from diabetic animals, atorvastatin completely restored the diabetes-induced hypersensitivity to Y-27632 and prevented RhoA membrane translocation/activation. In hfPSMCs, high glucose significantly increased not only membrane RhoA expression, but also ROCK activity (increased phosphorylation of the ROCK substrate myosin phosphatase target subunit 1) and several RhoA-dependent functions such as proliferation, migration, and smooth muscle-related gene expression. Atorvastatin restored all the high-glucose-induced effects, an action specifically reverted by GGPP.

Atorvastatin improves diabetes-related ED and restores sildenafil responsiveness, most probably by inhibiting RhoA/ROCK signaling, which underlies several high-glucose-induced derangements in penile smooth muscle cell commitment.

Does kVLQT1 C-terminal missense mutation cause a forme fruste long-QT syndrome?

KVLQT1, the gene encoding the alpha-subunit of a cardiac potassium channel, is the most common cause of the dominant form of long-QT syndrome (LQT1-type), the Romano-Ward syndrome (RWS). The overall phenotype of RWS is characterized by a prolonged QT interval on the ECG and cardiac ventricular arrhythmias leading to recurrent syncopes and sudden death. However, there is considerable variability in the clinical presentation, and potential severity is often difficult to evaluate. To analyze the relationship between phenotypes and underlying defects in KVLQT1, we investigated mutations in this gene in 20 RWS families originating from France. By PCR-SSCP analysis, 16 missense mutations were identified in KVLQT1, 11 of them being novel. Fifteen mutations, localized in the transmembrane domains S2-S3, S4-S5, P, and S6, were associated with a high percentage of symptomatic carriers (55 of 95, or 58%) and sudden deaths (23 of 95, or 24%). In contrast, a missense mutation, Arg555Cys, identified in the C-terminal domain in 3 families, was associated with a significantly less pronounced QT prolongation (459+/-33 ms, n=41, versus 480+/-32 ms, n=70, P=.0012), and significantly lower percentages of symptomatic carriers (7 of 44, or 16%, P<.001) and sudden deaths (2 of 44, or 5%, P<.01). Most of the cardiac events occurring in these 3 families were triggered by drugs known to affect ventricular repolarization.

Our data show a wide KVLQT1 allelic heterogeneity among 20 families in which KVLQT1 causes RWS. We describe the first missense mutation in the C-terminal domain of KVLQT1, which is clearly associated with a fruste phenotype, which could be a favoring factor of acquired LQT syndrome.

Do hemophiliacs have a higher risk for dental caries than the general population?

The aim of this study was to examine if patients with hemophilia were at increased risk for dental decay as compared to the general population. Census sampling was used in this case-control study to recruit cases (patients with hemophilia) and a control group individuals recruited randomly from the general population, which were matched with cases based on gender, age and place of residence. Clinical examinations included dental health and salivary assessments (flow rate, buffer capacity, caries-associated bacteria) and a structured questionnaire which inquired about socioeconomic status and dental health-related behaviors. In the deciduous dentition, the overall caries experience (dmf) differed statistically significantly (P=0.003) between the hemophiliacs (2.6±2.6) and their matched healthy controls (6.1±2.5). Bivariate analyses did not reveal significant differences between cases and controls regarding salivary functions, except that higher bacteriological counts were found in healthy controls in deciduous dentitions than in patients with hemophilia (P=0.019). Children without hemophilia were from higher socioeconomic status families than hemophiliacs (P=0.004), but such differences were not found for adults (P=0.090). When compared to healthy adults, adult hemophiliacs had more gum bleeding at rest (P<0.001) as well as during their tooth brushing (P=0.007) and they also consumed more soft drinks than controls (P=0.025).

Better dental health was observed in children with hemophilia as compared to children without it. There were no differences in dental health between adult hemophiliacs and healthy controls from the general population. None of the linear multiple regression models confirmed hemophilia to be an additional caries risk when it was controlled for other caries determinants.

Hemi-cauda equina syndrome from herniated lumbar disc: a neurosurgical emergency?

We report experience with patients presenting with a specific combination of symptoms: unilateral sciatica, unilateral sensibility loss in the dermatomes S1 to S5 (hemi-saddle) and subjective micturation problems secondary to ruptured lumbar disc. Because of its similarities with a cauda equina syndrome, this combination of symptoms was thought to be a unilateral cauda equina syndrome and it was called hemi-cauda equina syndrome. Consequently, it was treated as an emergency. Ten patients were evaluated. They compromised 2.3% of all patients undergoing lumbar discectomy. Outcome is good with only 10% persisting minor neurologic deficit (sensibility loss in dermatomes S3 to S5). With the exception of urinary retention or incontinence, duration of symptoms and signs does not seem to influence outcome. Comparing signs, symptoms and radiographic findings with those of a cauda equina syndrome which were recently and thoroughly studied, they were found to be more severe in cases of cauda equina syndrome. Especially, the good outcome, (apparently unrelated to the duration of symptoms in cases of hemi-cauda equina syndrome) contrasted with the treatment results of cauda equina syndrome.

We defined the hemi-cauda equina syndrome from ruptured disc as a combination of unilateral leg pain, unilateral sensibility loss in dermatomes S1 to S5 and sphincter paralysis (proven urinary retention or incontinence). Motor deficit is not necessarily present. Emergency surgery is warranted. Patients presenting with micturation complaints other than urinary retention or incontinence do not suffer from a hemi-cauda equina syndrome.

Do positive Chlamydia trachomatis serology result in women seeking care for infertility is a negative prognosticator for intrauterine pregnancy?

There are no prior studies that assess the non-in vitro fertilization (IVF) pregnancy rates in chlamydia serology-positive versus serology-negative women. Therefore, we wanted to determine whether a positive Chlamydia trachomatis immunoglobulin G serology result predicts reduced clinical pregnancy rates without IVF. A prospective observational study was performed at a university-affiliated reproductive center. A total of 1279 new infertility patients seen at the Continuum Reproductive Center between January 2007 and June 2009 underwent C. trachomatis immunoglobulin G screening. Charts were later reviewed for hysterosalpingography, laparoscopy, treatment cycles, and ultrasound evidence of an intrauterine pregnancy. The main outcome measure was non-IVF cumulative pregnancy rates. Seventy (5.5%) of 1279 of the participants were found to have a positive chlamydia serology result. Serology-positive participants had significantly more tubal block on hysterosalpingography (37.5% vs. 10.1%, P = 0.001) and laparoscopically confirmed tubal damage (85.7% vs. 48.9%, P = 0.002). The percent of all participants who achieved an ultrasound documented clinical pregnancy, at our center, without IVF was significantly lower among Chlamydia-positive participants (10.0% versus 21.7%) in seronegative participants (P < 0.02). The hazard rate of non-IVF clinical pregnancy among chlamydia antibody testing-positive patients was 57% less than the rate of pregnancy among chlamydia antibody testing-negative patients (hazard ratio, 0.43; 95% confidence interval, 0.20-0.92). Both the per-cycle and the cumulative IVF pregnancy rates were equivalent in seropositive and in seronegative participants.

This is the first large study to report that a positive serology screening result is both predictive of tubal damage and a reduced cumulative pregnancy rate when excluding treatment with IVF.

Is apoptosis present in skeletal muscle of cachectic gastro-intestinal cancer patients?

Previous studies of our research group have shown that apoptosis is present in skeletal muscle of tumour-bearing animals subject to cachexia. For this reason we decided to investigate the apoptosis in skeletal muscle of cancer patients. In the present study, muscle biopsies from weight-losing patients with upper gastro-intestinal cancer showed a significant increase in muscle DNA fragmentation (three-fold), as compared with control subjects. The increase in DNA laddering was associated with an increase in poly(ADP-ribose) polymerase (PARP) cleavage (four-fold) as measured by western blotting. These two events indicate the presence of muscle apoptosis. These changes were associated with a decrease in MyoD protein content, suggesting important alterations in skeletal muscle physiology.

The results presented therefore confirm that apoptosis is also present in human subjects undergoing cancer cachexia.

Is susceptibility of Escherichia coli to the toxic L-proline analogue L-selenaproline dependent on two L-cystine transport systems?

L-Selenaproline (L-selenazolidine-4-carboxylic acid) is a toxic analogue of L-proline that inhibits the growth of the urinary tract pathogen Escherichia coli in both laboratory culture media and normal human urine. The aim of this study was to identify the transport systems involved in its uptake. Deletion mutants from the Keio collection were tested for their susceptibility to L-selenaproline (SCA) and L-selenocystine (SeCys) on minimal salts agar medium. All single-gene mutants were sensitive to both compounds, but double mutants with deletions in fliY and ydjN or in yecS and ydjN were resistant to SCA and SeCys. The YdjN transporter active in strain JW1905 (ΔfliY::kan yecC(+) yecS(+) ydjN(+)) was inhibited by both SCA and SeCys, but the FliY YecS YecC ABC transporter system active in strain JW1718 (fliY(+) yecC(+) yecS(+) ΔydjN::kan) was best inhibited by these compounds in the presence of dithiothreitol.

L-selenaproline and L-selenocystine are accumulated by both the FliY YecC YecS and the YdjN L-cystine transporter systems in E. coli.

Is sputum club cell protein concentration associated with pulmonary exacerbation in cystic fibrosis?

Cystic fibrosis (CF) patients exhibit a progressive decline in lung function accelerated by intermittent pulmonary exacerbations. There are urgent needs for clinically relevant biomarkers to aid in the diagnosis and management of a CF pulmonary exacerbation, in addition to providing insight into its pathophysiology. Club cell secretory protein (CCSP) is produced by bronchial epithelial cells, known to have anti-inflammatory properties and may play a role in CF pulmonary exacerbations. Our objective was to measure sputum CCSP concentration during hospitalizations for CF pulmonary exacerbation and during quarterly outpatient clinic visits for 2 years. We explored the correlations between CCSP concentration, lung function and markers of inflammation and infection. In this prospective, longitudinal cohort study, expectorated sputum, blood and lung function data were collected from 45 CF patients during 68 hospitalizations for pulmonary exacerbation and 193 clinic visits. Sputum CCSP concentration was measured and sputum and blood were assayed with a panel of inflammatory cytokines. We used a repeated measures model to compare log transformed sputum CCSP concentrations across multiple time points and to correlate those concentrations with related clinical variables. Our population had a mean age of 29 (16-58 years), and a median FEV(1) %predicted of 60% (18-105%). Sputum CCSP concentration was significantly lower in the initial, interim and final exacerbation samples (p=0.0021, p=0.0005 and p=0.0274, respectively) compared to outpatient visits. Sputum CCSP concentration was negatively associated with sputum neutrophil elastase concentration (p=0.0373). Patients with Pseudomonas aeruginosa mucoid had a significantly lower sputum CCSP concentration (p=0.0129).

Sputum CCSP concentration is associated with CF pulmonary exacerbation.

Surgical Treatment of Adolescent Acetabular Dysplasia With a Periacetabular Osteotomy: Does Obesity Increase the Risk of Complications?

The Bernese periacetabular osteotomy (PAO) is frequently used to treat symptomatic acetabular dysplasia in the adolescent age group. Despite encouraging results, factors predictive of the development of postoperative complications remain poorly understood. The purpose of this study was to investigate whether obesity is a risk factor for complications following PAO in adolescents. A retrospective cohort study design was used to collect data from 3 different institutions. Children and adolescents (below 19 y of age) who underwent PAO and were followed for minimum of 12 months were included. Obesity was defined as a body mass index ≥95 percentile. The modified Clavien-Dindo classification was used to grade complications. A logistic regression analysis was used to identify factors related to the development of a complication that required treatment outside of routine postoperative care (complication grades II to V). Changes in radiographic parameters including Tönnis acetabular roof angle, anterior center-edge angle, and lateral center-edge angle among obese versus nonobese subjects were also evaluated. The mean age at surgery among the 84 adolescents included in the study was 16.5 years (range, 12 to 19 y). A total of 11% of the population was considered obese. Obesity (P=0.0047) was the only variable significantly associated with the development of a complication. After controlling for study site, the odds of an obese subject developing a complication were 10 [95% confidence interval (CI), 1.89-59.8] times the odds of a nonobese subject developing a complication. There was no difference in the magnitude of change in anterior center-edge angle (P=0.1251), lateral center-edge angle (P=0.9774), or Tönnis (P=0.5770) angular correction that was achieved among the obese versus nonobese subjects following surgery.

The Bernese PAO allows for adequate radiographic correction of acetabular dysplasia among obese and nonobese adolescents. However, the hip preservation surgeon should be aware of the higher risk of complications among obese adolescents undergoing PAO for the treatment of symptomatic acetabular dysplasia.

Does exogenous H2S modulate mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state?

Vascular smooth muscle cell (VSMC) proliferation in response to hyperglycemia is an important process in the development of arterial vessel hyperplasia. The shape change of mitochondria is dynamic and closely related to fission and fusion. Hydrogen sulfide (H2S) was confirmed to have anti-oxidative, anti-inflammatory and anti-proliferative effects. However, little it is known about its effects on mitochondrial morphology induced by hyperglycemia. The aim of the study is to demonstrate that H2S inhibits VSMC proliferation through regulating mitochondrial fission. We observe lower H2S levels as well as higher proliferative protein expression levels for proliferative cell nuclear antigen (PCNA) and cyclin D1 and higher mitochondrial fusion-fission protein expression levels for dynamin-related protein 1 (Drp 1) in human kidney arteries and in db/db mouse aorta. Exogenous H2S (100 μM NaHS) inhibits vascular smooth muscle cells of human pulmonary aorta(HPASMC) proliferation and migration in response to high glucose using the BrdU and scratch wound repair assays, decreases proliferative protein (PCNA and cyclin D1) expression, and reduces ROS production in the cytoplasm and mitochondria. When HPASMCs proliferate with a high glucose treatment, the mitochondria become small spheres with a short rod-shaped structure, whereas NaHS, a mitochondrial division inhibitor and siDrp prevent VSMC proliferation and maintain mitochondria as stationary and randomly dispersed with fixed structures.

Exogenous H2S aids in inhibiting mitochondrial fragmentation and affects proliferation in db/db mice and HPASMCs by decreasing Drp 1 expression.

Does inhibition of nitric oxide synthesis reduce infarct size by an adenosine-dependent mechanism?

Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart. We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 mumol/L NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% (P < .05 versus control). This effect was abolished by pretreatment with 75.5 mumol/L 8-p-sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 mumol/L per 100 g of heart (control) to a peak of 24.0 mumol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 mumol/g dry wt; L-NAME, 5.5 mumol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 mumol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 mumol/g dry wt.

Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent.

Does basal blood flow in complex regional pain syndrome necessarily indicate vasoconstrictor nerve activity?

To quantitatively investigate simultaneous skin blood flow and sweating in a patient with complex regional pain syndrome. Using one probe, skin blood flow and sweating were measured on the affected and non-affected sides at baseline and after activation of sympathetic system in a 47-year-old woman with complex regional pain syndrome type I of the left hand. Basal sweating, sympathetic sweat response, basal blood flow, sympathetic flow response, and attrition rate of blood flow (the ratio of sympathetic flow response to basal blood flow) of the affected side were greater than those on the non-affected side.

Although sympathetic nerve activity (sympathetic flow response) appeared greater on one side, basal blood flow was also greater on that side. These contradictory results suggest that some factor or factors increase basal blood flow despite a higher sympathetic nerve tone on the side. Comparing basal blood flow on one side to the contralateral side does not necessarily indicate lesser vasoconstrictor nerve activity on that side. Advantages of simultaneous measurement of skin blood flow and sweating with a single probe may make the method useful.

Does instant Typing be Essential to Detect Transmission of Extended-Spectrum Beta-Lactamase-Producing Klebsiella Species?

Infections with multidrug-resistant (MDR) microorganisms are an increasing threat to hospitalized patients. Although rapid typing of MDR microorganisms is required to apply targeted prevention measures, technical barriers often prevent this. We aimed to assess whether extended-spectrum beta-lactamase (ESBL)-producing Klebsiella species are transmitted between patients and whether routine, rapid typing is needed. For 43 months, the clonality of all ESBL-producing Klebsiella isolates from patients admitted to Erasmus MC University Medical Center in Rotterdam, the Netherlands was assessed with Raman spectroscopy. A cluster was defined as n ≥ 2 patients who had identical isolates. Primary patients were the first patients in each cluster. Secondary patients were those identified with an isolate clonally related to the isolate of the primary patient. Isolates from 132 patients were analyzed. We identified 17 clusters, with 17 primary and 56 secondary patients. Fifty-nine patients had a unique isolate. Patients (n = 15) in four out of the 17 clusters were epidemiologically related. Ten of these 15 patients developed an infection.

Clonal outbreaks of ESBL-producing Klebsiella species were detected in our hospital. Theoretically, after Raman spectroscopy had detected a cluster of n ≥ 2, six infections in secondary patients could have been prevented. These findings demonstrate that spread of ESBL-producing Klebsiella species occurs, even in a non-outbreak setting, and underscore the need for routine rapid typing of these MDR bacteria.

Do [ The influence of L-arginine on the angiogenesis in burn wounds in diabetic rats ]?

To investigate the possible mechanism of L-arginine supplementation on the angiogenesis of burn wounds in diabetic rats. One hundred male Sprague-Dawley (SD) rats were used in the study and were randomly divided into A (scalding control, n = 25), B (scalding of the rats with diabetes, n = 25), C (L-glycine control, n = 25) and D (L-arginine supplementation, n = 25) groups. Diabetes was produced by intra-peritoneal injection of streptozotocin (STZ) in B, C and D groups. The rats in C and D groups were gavaged with L-glycine and L-arginine in dose of 200 mg.kg(-1).d(-1), respectively. The glucose content of the back skin tissue was determined for five rats in each group eight weeks after STZ administration. Deep partial thickness scalding of 20% TBSA was engendered on the back in the other 80 rats. The wound area, wound healing rate, and microvascular density with CD34 immunohistochemistry staining were determined on 3rd, 7th, 14th, and 21st post scalding days (PSDs), In addition, the amount of nitric oxide (NO) released from the wound tissue and the tissue contents of vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) from wound were determined at the above time points. Compared to those in group B, the wound healing rate in group D increased significantly since the 7th PSD [(44.10 +/- 3.50)%, P < 0.05], and the wound MVD value was increased significantly at all postburn time points. Furthermore, the levels of VEGF, NO and TGF-beta1 in the wound tissue was also increased significantly, while the glucose content in the cutaneous tissue was decreased to (1.380 +/- 0.120) mg/g.

L-arginine supplementation could be beneficial to the angiogenesis in the burn wound of the rats with diabetes, as well as to wound healing by increasing the synthesis and the release of VEGF, NO and TGF-beta1 from burn wound and by decreasing the glucose content in the cutaneous tissue of diabetic rats.

Are multiple CT scans required for planning curative radiotherapy in lung tumors of the lower lobe?

Lung tumors located in the lower lobe are the most mobile. Multiple computed tomographic (CT) scans, which had been performed for radiotherapy planning, were analyzed to determine the minimal number of required scans. Six spiral CT scans (3 rapid and 3 slow) from 7 such patients were coregistered. Reproducibility of target volumes was defined as the ratio between the overlapping and encompassing volume (COM/SUM) from scans derived using one technique. Volumetric and dosimetric analyses were performed. Slow CT scans generated larger and more reproducible target volumes than rapid planning scans, with a mean COM/SUM ratio of 71.9 +/- 8.7% and 58.0 +/- 12.7%, respectively. When only a single slow CT scan was used for planning, the addition of a symmetrical 3D margin of 5 mm ensured 99% coverage of the "optimal" target volume, which was derived from summation of target volumes from all six scans.

Planning target volumes (PTVs) derived from a single slow CT scan plus a 5-mm margin covered the "optimal" PTVs generated from six scans. Although these "slow PTVs" were larger, the increase in V(20) (the volume of lung tissue receiving a dose>or = 20 Gy) was limited. This indicates that only two CT scans, i.e., a full rapid scan of the entire thorax and a limited slow scan, are necessary for treatment planning in peripheral lung cancers.

Is low expression of microRNA-143 related to degenerative scoliosis possibly by regulation of cyclooxygenase-2 expression?

This study is to determine if expression level of microRNA-143 (miR-143) and cyclooxygenase-2 (COX-2) are related to the occurrence and development of degenerative scoliosis. A total of 30 patients with degenerative scoliosis, 30 patients with adolescent idiopathic scoliosis were enrolled in this study. For control, 30 patients with spinal burst fractures were also enrolled in this study. Real-time PCR and western blotting was performed to measure the expression levels of COX-2 in intervertebral disc tissues, peripheral blood and cerebrospinal. Expression levels of miR-143 in intervertebral disc tissues, peripheral blood and cerebrospinal were detected by real-time PCR. The expression levels of COX-2 were increased in intervertebral disc tissues, peripheral blood and cerebrospinal of patients with degenerative scoliosis when compared with those of patients with adolescent idiopathic scoliosis and spinal burst fractures (P < 0.05). However, the expression levels of miR-143 were decreased in intervertebral disc tissues, peripheral blood and cerebrospinal of patients with degenerative scoliosis when compared with those of patients with adolescent idiopathic scoliosis and spinal burst fractures (P < 0.05).

COX-2 is highly expressed whereas miR-143 is lowly expressed in patients with degenerative scoliosis. Decreased expression of miR-143 may be related to the aggravation of degenerative scoliosis by regulation of COX-2.

Does ras induce experimental lung metastasis through up-regulation of RbAp46 to suppress RECK promoter activity?

Mutant Ras plays multiple functions in tumorigenesis including tumor formation and metastasis. Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a metastasis inhibitor gene, suppresses matrix metalloproteinase (MMP) activity in the metastatic cascade. Clarifying the relationship between Ras and RECK and understanding the underlying molecular mechanism may lead to the development of better treatment for Ras-related tumors. Suppression subtractive hybridization PCR (SSH PCR) was conducted to identify Ha-ras (val12) up-regulated genes in bladder cancer cells. Stable cell lines of human breast cancer (MCF-7-ras) and mouse NIH3T3 fibroblasts (7-4) harboring the inducible Ha-ras (val12) oncogene, which could be induced by isopropylthio-β-D-galactoside (IPTG), were used to clarify the relationship between Ras and the up-regulated genes. Chromatin immunoprecipitation (ChIP) assay, DNA affinity precipitation assay (DAPA) and RECK reporter gene assay were utilized to confirm the complex formation and binding with promoters. Retinoblastoma binding protein-7 (RbAp46) was identified and confirmed as a Ha-ras (val12) up-regulated gene. RbAp46 could bind with histone deacetylase (HDAC1) and Sp1, followed by binding to RECK promoter at the Sp1 site resulting in repression of RECK expression. High expression of Ras protein accompanied with high RbAp46 and low RECK expression were detected in 75% (3/4) of the clinical bladder cancer tumor tissues compared to the adjacent normal parts. Ras induced RbAp46 expression increases invasion of the bladder cancer T24 cells and MMP-9 activity was increased, which was confirmed by specific lentiviral shRNAs inhibitors against Ras and RbAp46. Similarly, knockdown of RbAp46 expression in the stable NIH3T3 cells "7-4" by shRNA decreased Ras-related lung metastasis using a xenograft nude mice model.

We confirmed that RbAp46 is a Ha-ras (val12) up-regulated gene and binds with HDAC1 and Sp1. Furthermore, RbAp46 binds to the RECK promoter at the Sp1 site via recruitment by Sp1. RECK is subsequently activated, leading to increased MMP9 activity, which may lead to increased metastasis in vivo. Our findings of Ras upregulation of RbAp46 may lead to revealing a novel mechanism of Ras-related tumor cell metastasis.

Is response to methadone maintenance treatment associated with the MYOCD and GRM6 genes?

There is increasing interest in the pharmacogenetic basis for explaining differences between patients in treatment outcome among methadone-treated subjects. Most studies have focused on genetic polymorphisms related to methadone pharmacokinetics and, to a lesser extent, those genes implicated in the pharmacodynamics of methadone. This study aimed to investigate the associations between response to methadone maintenance treatment (MMT) and polymorphisms in genes coding for the OPRM1 opioid receptor, the metabotropic glutamate receptors GRM6 and GRM8, the nuclear receptor NR4A2, the photolyase enzyme cryptochrome 1 (CRY1), and the transcription factor myocardin (MYOCD), which have previously been associated with the risk of opioid dependence disorder. The study used an association, case-control design, conducted in the setting of an MMT program in a drug abuse outpatient center in Barcelona, Spain. We recruited 169 opioid-dependent patients (diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders [4th Edition] criteria) receiving MMT. The inclusion criteria included Caucasian ethnicity, being enrolled in MMT for at least 6 months, and receiving a stable methadone dose for the previous 2 months. The exclusion criteria included language-related barriers, severe cognitive impairment, or any medical disorder that would interfere with the research assessments. Single nucleotide polymorphism (SNP) variants in several candidate genes and regions were genotyped: MYOCD (rs1714984), GRM8 (rs1034576), CRY1 (rs1861591), GRM6 (rs953741), OPRM1 (rs1074287), NR4A2 (rs1405735), and the intergenic variants rs965972 (1q31.2) and rs1867898 (2q21.2). MMT response status was assessed by the number of opioid-positive controls detected by random urinalysis in the previous 2 months. We used the chi-squared test and p-value for the allele frequencies of the eight SNPs in responders versus nonresponders, and multivariate logistic regression analyses to examine associations between genotypes in the responder and ronresponder groups under codominant, dominant, and recessive models of inheritance. A final sample of 116 opioid-dependent patients were included and classified as methadone responders (n = 83) and nonresponders (n = 33), according to illicit opioid use detection in random urinalysis. The responders and nonresponders showed similar demographic and clinical characteristics. All SNPs were in Hardy-Weinberg equilibrium. Subjects carrying the AA genotype at rs1861591 (CRY1; Chr 12: 105941056 G>A) had a higher risk of being nonresponders (odds ratio [OR] = 2.99; 95% CI 1.14, 7.85; p = 0.035), although this difference disappeared with multiple testing corrections. Patients carrying the A allele at rs1714984 (MYOCD; Chr 17: 12558425 G>A) had an increased risk of being nonresponders only if they were also carriers of the AG genotype at rs953741 (GRM6; Chr5: 178262451 A>G) [OR = 10.83; 95% CI 2.52, 46.66; p = 0.006].

A positive association was observed between response to methadone and two variants in the genes MYOCD and GRM6. A pharmacogenetic epistatic effect between SNPs in MYOCD and GRM6 appears to modulate inter-individual variations in MMT response.

Does treadmill gait training improve baroreflex sensitivity in Parkinson 's disease?

Partial weight supported treadmill gait training (PWSTT) is widely used in rehabilitation of gait in patient with Parkinson’s Diseases (PD). However, its effect on blood pressure variability (BPV) and baroreflex sensitivity (BRS) in PD has not been studied. To evaluate the effect of conventional and treadmill gait training on BPV components and BRS. Sixty patients with idiopathic PD were randomized into three groups. Twenty patients in control group were on only stable medication, 20 patients in conventional gait training (CGT) group (Stable medication with CGT) and 20 patients in PWSTT group (Stable medication with 20 % PWSTT). The CGT and PWSTT sessions were given for 30 min per day, 4 days per week, for 4 weeks (16 sessions). Groups were evaluated in their best ‘ON’ states. The beat-to-beat finger blood pressure (BP) was recorded for 10 min using a Finometer instrument (Finapres Medical Systems, The Netherlands). BPV and BRS results were derived from artifact-free 5-min segments using Nevrocard software. BRS showed a significant group with time interaction (F = 6.930; p = 0.003). Post-hoc analysis revealed that PWSTT group showed significant improvement in BRS (p < 0.001) after 4 weeks of training. No significant differences found in BPV parameters; systolic BP, diastolic BP, co-variance of systolic BP and low frequency component of systolic BP.

Four weeks of PWSTT significantly improves BRS in patients with PD. It can be considered as a non-invasive method of influencing BRS for prevention of orthostatic BP fall in patients with PD.

Is the adapted Radimer/Cornell questionnaire valid to measure food insecurity of urban households in Tehran, Iran?

To assess the validity of the adapted Radimer/Cornell questionnaire to measure food insecurity in low-income urban households in Tehran, the capital of Iran. The Radimer/Cornell questionnaire was modified and used to assess the applicability, validity and reliability of such a measure in a culturally different context of urban households in Tehran. Factor analysis and Cronbach's alpha were used to assess validity and reliability, respectively. Socio-economic characteristics and food consumption frequency of the household were used to assess the criterion validity of the questionnaire. District 20 of Tehran. A sample of 250 Iranian nuclear households with at least one child aged 1-18 years and a non-pregnant, non-lactating woman of reproductive age, selected through a multistage random sampling method. Three scales, labelled as household, individual and child hunger, were extracted through factor analysis using varimax rotation. Internal consistency of the scales was 0.897, 0.820 and 0.796, respectively. Individual insecurity and child hunger were inversely correlated with monthly per capita income, father's education, mother's education and father's occupational status, and positively correlated with household size, as expected. However, household insecurity did not follow the same pattern. Consumption frequency of fruits, vegetables, dairy, red meat and rice declined as food insecurity status worsened, while bread and potato consumption increased.

The results show that a modified version of the Radimer/Cornell questionnaire is a valid and reliable instrument to measure household food insecurity in a culturally different context. However, further modifications seem necessary to measure food insecurity at household level. Results lend support to the utility and applicability of experience-based measures in varying cultural communities.

Does cysteamine prevent the development of lens opacity in a rat model of selenite-induced cataract?

The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model. Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined. In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats.

Cysteamine suppresses cataract formation induced by selenite in rats, suggesting that cysteamine can be used as a pharmaceutical intervention to prevent or delay cataract formation.

Is local nasal immunotherapy with extract in powder form effective and safe in grass pollen rhinitis : a double-blind study?

Local nasal immunotherapy has been studied, by means of an extract in powder form, in patients with allergic rhinitis caused by grass pollen. Thirty-two patients allergic to grass were studied for 37 weeks in a double-blind controlled trial. Subjects were selected on the basis of a positive history, skin test result, RAST finding, and result of intranasal challenge to grass pollen. Two 16-patient groups were randomly assigned to active or placebo treatment. The treatment lasted 26 weeks (14 for the build-up phase, 12 for the maintenance period). No significant differences were observed in nasal symptoms during the treatment. During the pollen season the mean weekly symptom and medication scores were significantly lower in the treated group, compared with the control group, even considering each allergic symptom separately. Moreover, only in the treated group was a significant increase of specific nasal threshold to grass pollen observed after treatment.

This study indicates that local nasal immunotherapy with allergen in powder form can be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety in grass-allergic rhinitis.

Does adherent-invasive Escherichia coli exacerbate Antibiotic-associated Intestinal Dysbiosis and Neutrophil Extracellular Trap Activation?

Antibiotic-associated disruption of the gut microbiota is a known risk factor for Crohn's disease. This chronic inflammatory disorder results from aberrant host immune responses to subsets of the gut microbiota, and is characterized by intense neutrophil recruitment to the lamina propria, surface and crypt epithelium. Importantly, adherent-invasive Escherichia coli (AIEC) is abundant in ileal biopsies, highlighting a possible etiological role. In this study, we investigated the impact of antibiotics and AIEC challenge on murine intestinal dysbiosis and neutrophil extracellular trap activation, which is a critical component of the neutrophil antimicrobial repertoire. Male C57BL/6 mice were administered vancomycin and gentamicin (once daily, 3 days), and subsequently challenged with AIEC strain LF82 (once daily, 2 days). Perturbation of the gut microbiota was monitored using a combination of molecular and phylogenetic analyses. The impact of commensal and dysbiotic gut bacterial communities on neutrophil extracellular trap mobilization and intestinal redox balance was also quantified. Exposure of neutrophils to murine commensal gut microbial communities activated neutrophil extracellular trap formation. The capacity of neutrophils to cast these web-like structures was exacerbated following antibiotic and AIEC-associated intestinal dysbiosis, highlighting the possible overgrowth of immune-activating intestinal pathobionts. Intestinal dysbiosis was associated with an elevated capacity of the cultivated gut bacteria to produce reactive oxygen species in vitro, and increased colonic oxidative stress in vivo.

Together, these data provide new insights into the detrimental effects of antibiotics on the gut microbiota, with clinically relevant implications for intestinal dysbiosis on neutrophil function and intestinal redox balance.

Does ketamine stereoselectively affect vasorelaxation mediated by ATP-sensitive K ( + ) channels in the rat aorta?

The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K(+) channel opener in the isolated rat aorta. Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to an ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor sodium nitroprusside (10(-10) to 10(-5) M) was obtained. Glibenclamide (10(-5) M), S(+) ketamine (10(-4) M), or ketamine racemate (10(-5) to 10(-4) M) was applied 15 min before addition of phenylephrine. Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M) in the aorta with or without endothelium. Ketamine racemate (3 x 10(-5) to 10(-4) M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium.

In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K(+) channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation ATP-sensitive K(+) channels in the conduit artery.

Is it safe the reversal of a diverting stoma during adjuvant chemotherapy in elderly rectal cancer patients?

The aim of this study was to investigate the clinical outcomes between 2 groups of elderly rectal cancer patients according to the time duration after which their diverting stoma can be reversed. We recruited 124 patients who were ≥65 years old and had undergone diverting stoma after rectal cancer surgery. In Group 1, the reversal of the stoma was predominantly performed after the sixth adjuvant chemotherapy. In Group 2, the reversal was predominantly performed after the third adjuvant chemotherapy. The mean duration for which patients had a stoma was 28.6 ± 9.9 weeks in Group 1 and 17.1 ± 7.4 weeks in Group 2. The interval between stoma formation and stoma formation-related complications was slightly longer in Group 1 than in Group 2 (13.5 ± 9.7 vs. 8.0 ± 4.9 weeks, p = 0.075). There were 16 stoma-related complications in Group 1 (23.2%) and 10 in Group 2 (18.2%) (p = 0.516). There were 6 stoma closure-related complications in Group 1 (8.8%) and 6 in Group 2 (10.9%) (p = 0.766). This study shows that stoma closure during adjuvant chemotherapy is no more harmful than stoma closure after termination of adjuvant chemotherapy.

It may be possible to limit the duration of diverting stoma following rectal cancer surgery, even if patients are elderly and undergoing adjuvant chemotherapy.

Does loss of function of NaPiIIa cause nephrocalcinosis and possibly kidney insufficiency?

Inherited metabolic disorders associated with nephrocalcinosis are rare conditions. The aim of this study was to identify the genetic cause of an Israeli-Arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency. Clinical and biochemical data of the proband and family members were obtained from both previous and recent medical charts. Genomic DNA was isolated from peripheral blood cells. The coding sequence and splice sites of candidate genes (CYP24A1, CYP27B1, FGF23, KLOTHO, SLC34A3 and SLC34A1) were sequenced directly. Functional studies were performed in Xenopus laevis oocytes and in transfected opossum kidney (OK) cells. Our patient was identified as having nephrocalcinosis in utero, and at the age of 16.5 years, he had kidney insufficiency but no bone disease. Genetic analysis revealed a novel homozygous missense mutation, Arg215Gln, in SLC34A1, which encodes the renal sodium phosphate cotransporter NaPiIIa. Functional studies of the Arg215Gln mutant revealed reduced transport activity in Xenopus laevis oocytes and increased intracellular cytoplasmic accumulation in OK cells.

Our findings show that dysfunction of the human NaPiIIa causes severe renal calcification that may eventually lead to reduced kidney function, rather than complications of phosphate loss.

Public Interest in Medical Research Participation: Does It Matter if Patients or Community Members Have Helped Design the Study?

We determined national levels of public participation in medical research study design. We compared public interest in medical research participation (MRP) in studies overall, versus studies explicitly designed with public involvement. Cross-sectional household survey of US population in June 2013. Descriptive statistics estimated participation in medical research study design. Chi-square test compared levels of interest in MRP if respondent knew patients or community members helped design the study. Of 2,048 respondents (participation rate 60%), 5% knew someone who had helped design a medical research study. There was no association between having known someone or personal participation in study design and willingness to engage in MRP. Although the overall proportion of respondents who would consider MRP initially (51%) was similar to the proportion who would consider MRP with community member involvement in study design (49%), the changes in respondents' views across the different scenarios were significantly greater than what would have been expected by chance.

We found similar levels of interest in MRP whether or not the public is involved in medical research study design. This finding may indicate that public involvement in study design, like community-based participatory research, may not affect overall rates of MRP.

Is [ CD5 expression an adverse prognostic factor in diffuse large B-cell lymphoma ]?

To analyze CD5 expression in diffuse large B cell lymphoma (DLBCL) and to explore its relationship with the clinicopathological characteristics. The clinical data from 160 DLBCL patients who were treated in First Bethune Hospital of Jilin University from January 2001 to December 2010 were retrospectively analyzed. Immunohistochemical staining (SP method) for CD5, CD10, bcl-6 and MUM-1 was performed on the paraffin-embedded tissue. The relationship between CD5 expression and the clinicopathological characteristics was evaluated by Chi-square test. Survival analysis adopted Kaplan-Meier analysis and Log-rank test. In the patients aged 60 years or older, the incidence of CD5(+) lymphoma (12/17) was significantly higher than that of CD5(-) ones (39.9%, 57/143); two or more extranodal involvements in CD5(+) patients (11/17) were more commonly found than that of CD5(-)patients (31.5%, 45/143); DLBCL-related death in CD5(+) patients (13/17) was higher than that of CD5(-) patients (37.1%, 53/143). Survival analysis showed that the overall survival (OS) and the event-free survival (EFS) of CD5(+) patients were significantly lower than those of CD5(-) patients. In the condition of different GCB type, different therapy and low IPI (0 ∼ 2), the OS of CD5(+) DLBCL patients was significantly lower than that of CD5(-) patients, while in the condition of high IPI (3 ∼ 5), the OS of CD5(+) and CD5(-) DLBCL patient had no obvious difference.

CD5 expression is an adverse prognostic factor in DLBCL and it has more prognostic value in the condition of low IPI (0 ∼ 2).

Does peritoneovenous shunting restore atrial natriuretic factor responsiveness in refractory hepatic ascites?

Sodium retention in cirrhosis has been attributed to an imbalance between vasoconstrictive, antinatriuretic forces such as the renin aldosterone angiotensin system and the sympathetic nervous system, and vasodilatory, natriuretic agents such as atrial natriuretic factor (ANF). Patients with diuretic resistant refractory ascites may require peritoneovenous shunting (PVS) to control ascites. To study the factors responsible for the improvement in sodium homeostasis post-PVS, we compared the response to ANF infusion before and 1 month after PVS in 6 patients with massive ascites. Before PVS, sodium excretion at baseline and in response to ANF infusion was blunted but became more normal post-PVS. ANF infusion post-PVS induced a significant increase in the glomerular filtration rate and filtration fraction and also in distal delivery of sodium. ANF's distal effect of increasing the fractional excretion of distally delivered sodium was present pre-PVS and was not significantly increased post-PVS. Changes in sodium handling were accompanied by a significant decrease in antinatriuretic forces (baseline aldosterone, 2079 +/- 507 vs. 647 +/- 17 nmol/L; P < 0.04) post-PVS.

The improvement in sodium homeostasis and response to ANF infusion post-PVS appears to be associated with the decrease in antinatriuretic forces with the loss of massive refractory ascites. Thus, PVS restores the balance toward ANF responsiveness.

Is lipopolysaccharide ( LPS ) induction of nitric oxide synthase-2 and cyclooxygenase-2 impaired in fructose overloaded rats?

Fructose (F) overload in rats induces metabolic dysfunctions that resemble the human metabolic syndrome. In this paper, we aimed to investigate the response of F overload rats to lipopolysaccharide (LPS) challenge in terms of nitric oxide (NO) production and prostanoids (PR) release. NO blood steady-state concentration was monitored through the detection of nitrosyl-hemoglobin complexes (NO-Hb) by electronic spin resonance. Production of 6-keto PGF(1)α, PGE(2), PGF(2)α and TXB(2) was measured in aorta and mesenteric beds by HPLC. Western blot analysis was used to examine the changes in the expression levels of NOS-2 and COX-2 in aorta. Our results showed that increases in NO circulating steady-state concentration and PR production by aorta and mesenteric beds 6h after LPS administration were significantly attenuated in F overload rats with respect to control animals. Oxidative stress parameters were equally affected in the presence or absence of the F treatment. Aorta protein levels of NOS-2 and COX-2, two enzymes inducible by LPS, were significantly lower in F overload rats with respect to control rats at the end of the treatment (-39% and -61% for NOS-2 and COX-2 respectively).

These results suggest that the metabolic alterations established by 15 weeks of F overload should affect the response to LPS challenge due to an attenuation in the induction of NOS-2 and COX-2. This effect would be one of the components contributing to abnormalities in the course of the inflammatory response in other conditions associated to insulin resistance, such as diabetes.

Does assessment of Cotinine reveal a Dose-Dependent Effect of Smoking Exposure on Long-term Outcomes After Renal Transplantation?

Smoking is a risk factor for poor late outcomes in renal transplant recipients (RTR). Smoking exposure can be assessed by self-report and cotinine measurements. We investigated whether use of cotinine as a biomarker for smoking exposure can serve as an alternative for self-report and to compare associations of smoking exposure by self-report and cotinine with outcomes in RTR and assess dose dependency. Renal transplant recipients were classified as never, former, light (≤10 cigarettes/day), and heavy smokers (>10 cigarettes/day) according to self-report and analogous categories for urine and plasma cotinine. First, we assessed agreement of self-reported smoking exposure with smoking exposure according urine and plasma cotinine. Second, we compared the associations with graft failure and mortality. Of 603 RTR (age 51.5 ± 12.1 years, 55% men), 36.0% RTR were never, 42.3% former, 10.6% light, and 11.1% heavy smokers according to self-report. The majority (98.6%) of never smokers had nondetectable cotinine. However, 14 and 13 RTR reporting no active smoking had respective urine or plasma cotinine consistent with active smoking. Cotinine-based measurements were dose-dependently associated with mortality and graft failure.

Plasma and urine cotinine can serve as an alternative to self-report and were dose-dependently associated with poor late outcomes in RTR.

Does proteomic Profiling reveal Adaptive Responses to Surgical Myocardial Ischemia-Reperfusion in Hibernating Arctic Ground Squirrels Compared to Rats?

Hibernation is an adaptation to extreme environments known to provide organ protection against ischemia-reperfusion (I/R) injury. An unbiased systems approach was utilized to investigate hibernation-induced changes that are characteristic of the hibernator cardioprotective phenotype, by comparing the myocardial proteome of winter hibernating arctic ground squirrels (AGS), summer active AGS, and rats subjected to I/R, and further correlating with targeted metabolic changes. In a well-defined rodent model of I/R by deep hypothermic circulatory arrest followed by 3 or 24 h of reperfusion or sham, myocardial protein abundance in AGS (hibernating summer active) and rats (n = 4 to 5/group) was quantified by label-free proteomics (n = 4 to 5/group) and correlated with metabolic changes. Compared to rats, hibernating AGS displayed markedly reduced plasma levels of troponin I, myocardial apoptosis, and left ventricular contractile dysfunction. Of the 1,320 rat and 1,478 AGS proteins identified, 545 were differentially expressed between hibernating AGS and rat hearts (47% up-regulated and 53% down-regulated). Gene ontology analysis revealed down-regulation in hibernating AGS hearts of most proteins involved in mitochondrial energy transduction, including electron transport chain complexes, acetyl CoA biosynthesis, Krebs cycle, glycolysis, and ketogenesis. Conversely, fatty acid oxidation enzymes and sirtuin-3 were up-regulated in hibernating AGS, with preserved peroxisome proliferator-activated receptor-α activity and reduced tissue levels of acylcarnitines and ceramides after I/R.

Natural cardioprotective adaptations in hibernators involve extensive metabolic remodeling, featuring increased expression of fatty acid metabolic proteins and reduced levels of toxic lipid metabolites. Robust up-regulation of sirtuin-3 suggests that posttranslational modifications may underlie organ protection in hibernating mammals.

Does rNA sequencing distinguish benign from malignant pancreatic lesions sampled by EUS-guided FNA?

EUS-guided FNA (EUS-FNA) is the primary method used to obtain pancreatic tissue for preoperative diagnosis. Accumulating evidence suggests diagnostic and prognostic information may be obtained by gene-expression profiling of these biopsy specimens. RNA sequencing (RNAseq) is a newer method of gene-expression profiling, but published data are scant on the use of this method on pancreas tissue obtained via EUS-FNA. The aim of this study was to determine whether RNAseq of EUS-FNA biopsy samples of undiagnosed pancreatic masses can reliably discriminate between benign and malignant tissue. In this prospective study, consenting adults presented to 2 tertiary care hospitals for EUS of suspected pancreatic mass. Tissue was submitted for RNAseq. The results were compared with cytologic diagnosis, surgical pathology diagnosis, or benign clinical follow-up of at least 1 year. Forty-eight patients with solid pancreatic mass lesions were enrolled. Nine samples were excluded because of inadequate RNA and 3 because of final pathologic diagnosis of neuroendocrine tumor. Data from the first 13 patients were used to construct a linear classifier, and this was tested on the final 23 patients (15 malignant and 8 benign lesions). RNAseq of EUS-FNA biopsy samples distinguishes ductal adenocarcinoma from benign pancreatic solid masses with a sensitivity of .87 (range, .58-.98) and specificity of .75 (range, .35-.96).

This proof-of-principle study suggests RNAseq of EUS-FNA samples can reliably detect adenocarcinoma and may provide a new method to evaluate more diagnostically challenging pancreatic lesions.

Does high-dose porcine hematopoietic cell transplantation combined with CD40 ligand blockade in baboons prevent an induced anti-pig humoral response?

In pig-to-primate organ transplantation, hyperacute rejection can be prevented, but the organ is rejected within days by acute vascular rejection, in which induced high-affinity anti-Gal alpha1-3Gal (alphaGal) IgG and possibly antibodies directed against new porcine (non-alphaGal) antigenic determinants are considered to play a major role. We have explored the role of an anti-CD40L monoclonal antibody in modifying the humoral response to porcine hematopoietic cells in baboons pretreated with a nonmyeloablative regimen. Porcine peripheral blood mobilized progenitor cells obtained by leukapheresis from both major histocompatibility complex-inbred miniature swine (n=7) and human decay-accelerating factor pigs (n=3) were transplanted into baboons. Group 1 baboons (n=3) underwent whole body (300 cGy) and thymic (700 cGy) irradiation, T cell depletion with ATG, complement depletion with cobra venom factor, short courses of cyclosporine, mycophenolate mofetil, porcine hematopoietic growth factors, and anti-alphaGal antibody depletion by immunoadsorption before transplantation of high doses (2-4 x 10(10)/cells/kg) of peripheral blood mobilized progenitor cells. In group 2 (n=5), cyclosporine was replaced by eight doses of anti-CD40L monoclonal antibodies over 14 days. The group 3 baboons (n=2) received the group 1 regimen plus 2 doses of anti-CD40L monoclonal antibodies (on days 0 and 2). In group 1, sensitization to alphaGal (with increases in IgM and IgG of 3- to 6-fold and 100-fold, respectively) and the development of antibodies to new non-alphaGal porcine antigens occurred within 20 days. In group 2, no sensitization to alphaGal or non-alphaGal determinants was seen, but alphaGal-reactive antibodies did return to their pre- peripheral blood mobilized progenitor cells transplant levels. In group 3, attenuated sensitization to alphaGal antigens was seen after cessation of cyclosporine and mycophenolate mofetil therapy at 30 days (IgM 4-fold, IgG 8-30-fold), but no antibodies developed against new porcine determinants. In no baboon did anti-CD40L monoclonal antibodies prevent sensitization to its own murine antigens.

We believe these studies are the first to consistently demonstrate prevention of a secondary humoral response after cell or organ transplantation in a pig-to-primate model. The development of sensitization to the murine elements of the anti-CD40L monoclonal antibodies suggests that nonresponsiveness to cell membrane-bound antigen (e.g., alphaGal) is a specific phenomenon and not a general manifestation of immunological unresponsiveness. T cell costimulatory blockade may facilitate induction of mixed hematopoietic chimerism and, consequently, of tolerance to pig organs and tissues.

Is the most frequent cause of 90-day unplanned hospital readmission following colorectal cancer resection chemotherapy complications?

NHS England deems 90-day readmission rates as a marker of quality of care. The causes of readmission have not been previously reported in the UK. The aim of this study was to examine the factors associated with 90-day readmission following colorectal cancer surgery at a hospital trust with a catchment population 1.2 million. A retrospective review was performed of all patients undergoing resection for colorectal cancer between January 2012 and December 2013. Unplanned readmission was defined as an emergency admission to the trust for any cause within 90 days of surgery. Readmission analyses were restricted to patients discharged from hospital within 28 days of resection. A total of 570 patients underwent surgery, of whom 522 were discharged within 28 days and are included for readmission analysis. The readmission rate was 24.3% (127 patients with a total of 163 episodes of hospital readmissions) within 90 days following surgery. The most frequent cause for readmission was complications related to adjuvant chemotherapy (18.4%) followed by wound-related complications (14.1%). Most patients presenting with wound-related complications were admitted within 60 days and patients with chemotherapy-related complications after 61 days; 13/127 (10.2%) patients who were readmitted underwent emergency surgery, and one patient died following readmission. Multivariate analysis demonstrated that comorbidity was the only independent risk factor.

Ninety-day readmissions include a high number of readmissions secondary to chemotherapy-related complications, whereas most surgical-related readmission present within 60 days.

Do reactive oxygen species-reducing strategies improve pulmonary arterial responses to nitric oxide in piglets with chronic hypoxia-induced pulmonary hypertension?

There are no effective treatments for chronic pulmonary hypertension in infants with cardiopulmonary disorders associated with hypoxia, such as those with chronic lung disease. These patients often have poor or inconsistent pulmonary dilator responses to inhaled nitric oxide (iNO) therapy for unknown reasons. One possible explanation for poor responsiveness to iNO is reduced NO bioavailability caused by interactions between reactive oxygen species (ROS) and NO. Our major aim was to determine if strategies to reduce ROS improve dilator responses to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), in resistance pulmonary arteries (PRAs) from a newborn piglet model of chronic pulmonary hypertension. The dilation to SNAP was significantly impaired in PRAs from piglets with chronic hypoxia-induced pulmonary hypertension. ROS scavengers, including cell-permeable and impermeable agents to degrade hydrogen peroxide (H(2)O(2)), improved dilation to SNAP in PRAs from chronically hypoxic piglets. Treatment with agents to inhibit nitric oxide synthase and NADPH oxidase, potential enzymatic sources of ROS, also improved dilation to SNAP in PRAs from hypoxic piglets. Our studies are the first to utilize a newborn model of chronic pulmonary hypertension to evaluate the impact of a number of potential therapeutic strategies for ROS removal on responses to exogenous NO in the vessels most relevant to the regulation of pulmonary vascular resistance (PRA).

Strategies aimed at reducing ROS merit further evaluation and consideration as therapeutic approaches to improve responses to iNO in infants with chronic pulmonary hypertension.

Does vector-mediated delivery of bcl-2 prevent degeneration of auditory hair cells and neurons after injury?

To test the hypothesis that bcl-2 prevents oxidative stress-induced apoptosis of auditory sensory cells in explants of the organ of Corti and dissociated cell cultures of the spiral ganglion. Organ of Corti explants and dissociated spiral ganglion cell cultures obtained from 3-day-old (P3) rats or adult spiral ganglion cell cultures from 28-day-old (P28) rats were transduced with vectors containing a human bcl-2 gene. Cultures were then exposed to neomycin, cisplatin or subjected to withdrawal of neurotrophin supplementation. Outcome measures included hair cell and neuron counts, mitochondrial membrane potential and a histological measure of apoptosis. Expression of bcl-2 in the organ of Corti explants and neuronal cell cultures provided a significant level of protection against cell death. Bcl-2 expression in the organ of Corti explants also protected mitochondria from loss of membrane potential and blocked an early step in the commitment of hair cells to apoptosis.

Expression of bcl-2 in cochlear tissues protects sensory cells from a variety of insults that have been demonstrated to damage the inner ear.

Does microRNA-10a influence Osteoblast Differentiation and Angiogenesis by Regulating β-Catenin Expression?

Elucidation of the molecular mechanisms governing osteoblast differentiation and angiogenesis are of great importance for improving the treatment of bone-related diseases. In this study, we examined the role of microRNA (miR)-10a in the differentiation of MC3T3-E1 cells and pro angiogenic activity of mouse umbilical vein endothelial cells (MUVECs). The murine pre-osteoblast cell line MC3T3-E1 and MUVECs were used in the experiment. After transfected with miR-10a mimics or inhibitors, with or without LiCl pretreatment, the miR-10a, ALP, Runx2, Osx, OC and Dlx5 expression were assessed by RT-PCR. MC3T3-E1 cells were cultured with BMP2 to differentiate into bone cells, osteogenic differentiation of MC3T3-E1 cells were detected by ALP and ARS staining. Cell viability were analyzed by MTT and the protein expression of β-catenin, LEF1, cyclinD1, MMP2, and VEGF were detected by Western blotting; VEGF and VE-cadherin release were assessed by ELISA, and the migration of MUVECs, as well as tube formation were also detected. MiR-10a expression was obviously down-regulated during osteogenic differentiation. Overexpression of miR-10a inhibited osteogenic differentiation of MC3T3-E1 cells, effectively decreasing MUVECs proliferation, migration, VEGF expression, VE-cadherin concentrations, and tube formation in vitro, whereas miR-10a silence enhanced those processes. Further mechanism assays demonstrated that overexpression of miR-10a reduced the β-catenin at both protein and transcription level, while pretreatment with Wnt signaling activator Licl partially attenuated the suppression effects of miR-10a overexpression on osteoblast differentiation and angiogenesis.

Our findings imply that miR-10a plays a suppressive role in osteoblast differentiation of MC3T3-E1 cells and pro angiogenic activity of MUVECs by regulating the β-catenin expression, representing a novel and potential therapeutic target for the treatment of bone regeneration-related diseases.

Is gender difference in adrenal sensitivity to ACTH abolished in type 2 diabetes?

Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis has been implicated in type 2 diabetes (T2D). The aim of this study was to investigate the impact of T2D and gender on the HPA axis. Synthetic ACTH (1 μg) was administered to 21 subjects with T2D (age 62 (54-70) years, 11 men/ten women, HbA1c 49±2 mmol/mol, treated with diet or oral antidiabetic drugs) and 38 controls (age 58 (41-67) years, 20 men/18 women). Fasting basal B-glucose, serum cortisol, insulin, IGF1 and IGFBP1 concentrations were measured, and sampling for all but IGF1 was repeated 30, 60, and 90 min after ACTH injection. Patients took 0.25 mg dexamethasone at 2200-2300 h and returned the next morning for the measurement of serum cortisol concentration. Cross-sectional study. Patients with T2D had similar fasting serum cortisol, IGF1 and IGFBP1 concentrations; however, serum cortisol concentration after administration of dexamethasone did not differ between the groups. Healthy women exhibited higher peak cortisol levels compared with healthy men (675±26 vs 582±21 nmol/l, P=0.014), while the peak levels were equally high in men and women with T2D, resulting in a higher peak level in men with T2D compared with healthy men (691±42 vs 582±21 nmol/l, P=0.024). Serum cortisol concentration after administration of dexamethasone did not differ between the groups, nor did IGF1 and IGFBP1. Some studies have previously indicated disturbed regulation of the hypothalamus-pituitary-adrenal (HPA) axis in subjects with type 2 diabetes (T2D); however, much remains unknown in this area. To the best of our knowledge, this is the first study to show that the gender difference in the adrenal response to ACTH (with greater reactivity in women) is abolished in T2D. While the clinical implications cannot be determined by this paper, it is known that gender differences exist in the pathogenesis and complications of T2D. Thus, our findings suggest that further research into gender differences in the HPA axis is warranted.

Gender differences in adrenal response to ACTH were abolished in T2D. Men with T2D had a higher peak cortisol compared with controls. Further studies are needed to elucidate the clinical implications.

Does pigmentation in African American skin decrease with skin aging?

Tristimulus colorimetry, which uses the Commission Internationale de l'Eclairage L*a*b* model to quantify color, has previously been used to analyze pigmentation and erythema in human skin; however, colorimetry of African American skin is not well characterized. We sought to analyze skin color patterns in African Americans and compare them with those of Caucasians. Colorimetry readings of the sun-protected buttock and sun-exposed back of forearm were taken from 40 Caucasian and 43 African American participants from March 2011 through August 2015. African American participants also completed a lifestyle questionnaire. Correlation coefficients, paired t tests, and multivariable linear regression analyses were used for statistical comparisons. Forearm skin was lighter in African Americans ages 65 years and older versus 18 to 30 years (P = .02) but darker in Caucasians ages 65 years or older versus 18 to 30 years (P = .03). In African Americans ages 18 to 30 years, the buttock was darker than the forearm (P < .001), whereas in Caucasians the buttock was lighter than the forearm (P < .001). A lighter forearm than buttock was correlated with supplement use, smoking (ages 18-30 years), and less recreational sun exposure (ages ≥65 years) in African Americans.

Our study was limited by the sample size and focal geographic source.

Is immunoreactive tumor necrosis factor-alpha elevated in maternal plasma but undetected in amniotic fluid in the second trimester?

We investigated the participation of the cellular arm of the immune system in adaptation to pregnancy by assessing plasma and amniotic fluid levels of the cytokine tumor necrosis factor-alpha. Fifty-five healthy pregnant women who underwent second-trimester genetic amniocentesis at a mean gestational age of 17.0 +/- 1.4 weeks composed study group A. Blood was drawn from each patient before amniocentesis, and an aliquot of amniotic fluid was obtained for this study. Twenty-one healthy patients at a mean gestational age of 35.5 +/- 4.8 weeks composed study group B, and blood was obtained from each patient at an outpatient prenatal visit. Twenty-two healthy, nonpregnant women of reproductive age composed the control group (C). All specimens were stored at -70 degrees C and collectively assayed for tumor necrosis factor-alpha by a specific enzyme-linked immunoassay. All patients in group A had a normal karyotype and all patients in groups A and B had uneventful pregnancies. Tumor necrosis factor-alpha was detected in the plasma of 43 of 55 (78.2%) patients in group A compared with 7 of 21 (33.3%) patients in group B (p < 0.001); tumor necrosis factor-alpha was not detected in any of the 22 women in group C. The median plasma tumor necrosis factor-alpha level for group A was 135 pg/ml (range 0 to 625 pg/ml) compared with 0 pg/ml (range 0 to 110 pg/ml) in group B (p < 0.001). Tumor necrosis factor-alpha was not detected in any of the amniotic fluid specimens studied.

Levels of tumor necrosis factor-alpha were elevated in the plasma but not detected in the amniotic fluid of normal pregnant patients in the second trimester. These findings suggest involvement of the cellular branch of the immune system and its products, the cytokines, in the normal adaptation of the mother to the fetal allograft, with a possible role in regulating trophoblast growth and invasion.

Is serum retinol binding protein 4 decreased in congenital generalized lipodystrophy : a case series?

Previous studies have suggested that Retinol Binding Protein 4 (RPB4), a protein produced by the adipose tissue, is associated with insulin resistance (IR). Congenital Generalized Lipodystrophy (CGL) is a rare disease characterized by IR and paucity of adipose tissue. Our objective was to determine RBP4 levels in patients with CGL. Six (6) patients with CGL and a healthy control group were selected to participate in the study. Anthropometric and biochemical variables were compared between groups. No difference was observed in RBP4 levels between the two groups (CGL 42.5 [12.5 - 127] vs. control 57.4 [15.9 - 165]; p = 0.78). On the other hand, leptin levels were significantly lower in CGL patients (CGL 0.65 [0.2 - 0.7] vs. control 10.9 [0.9 - 38.6]; p = 0.015). No correlation was found between RBP-4 and waist circunference (r = 0.18, p = 0.57), or BMI (r = 0.24, p = 0.45).

RBP4 is not decreased in CGL. These results suggest that adipose tissue may not be the main source of RBP4.

Do class II cytokine receptor ligands inhibit human vascular smooth muscle proliferation?

Vessel injury provokes the release of proinflammatory cytokines and growth factors that influence vascular smooth muscle cell (VSMC) proliferation and migration. Produced by T lymphocytes, interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) both have immunoregulatory functions and act on similar receptors, designated class II cytokine receptors. We hypothesized that the class II cytokine receptor participates in vascular remodeling by inhibiting VSMC proliferation. The purposes of this study were to determine the influence of class II cytokine receptor stimulation on (1) unstimulated, (2) cytokine-stimulated, and (3) growth factor-stimulated VSMC proliferation. Human aortic VSMCs were isolated and cultured. VSMCs were treated with IL-10 or IFN with or without tumor necrosis factor-alpha (TNF-alpha) or basic fibroblast growth factor (FGF). Proliferation was quantified by colormetric assay. Compared to control, both TNF and FGF stimulated concentration-dependent VSMC proliferation (P < .005). IL-10 and IFN alone had no effect on unstimulated cell growth. With TNF or FGF stimulation, both IL-10, at a dose as low as 10 fg/ml, and IFN, at a dose as low as 1.0 U/ml, inhibited cell growth (P < .001).

The class II cytokine receptor ligands, IL-10 and IFN, inhibit cytokine-(TNF) and growth factor-(FGF) induced VSMC proliferation. The class II cytokine receptor may provide a novel therapeutic target in regulating vessel wall remodeling after vascular injury.

Does tetracycline regulator expression alter the transcriptional program of mammalian cells?

Tetracycline regulated ectopic gene expression is a widely used tool to study gene function. However, the tetracycline regulator (tetR) itself has been reported to cause certain phenotypic changes in mammalian cells. We, therefore, asked whether human myeloid U937 cells expressing the tetR in an autoregulated manner would exhibit alterations in gene expression upon removal of tetracycline. Microarray analyses revealed that 172 and 774 unique genes were significantly differentially expressed by at least 2- or 1.5-fold, respectively, when tetR expressing U937 cells were maintained in media with or without the antibiotic.

These alterations in gene expression are likely to contribute to the phenotypic consequences of tetR expression. In addition, they need to be taken into consideration when using the tetR system for the identification of target genes of transcription factors or other genes of interest.

Does a workflow task force affect emergency physician compliance for point-of-care ultrasound documentation and billing?

Emergency point-of-care ultrasound (POC u/s) is an example of a health information technology that improves patient care and time to correct diagnosis. POC u/s examinations should be documented, as they comprise an integral component of physician decision making. Incomplete documentation prevents coding, billing and physician group compensation for ultrasound-guided procedures and patient care. We aimed to assess the effect of directed education and personal feedback through a task force driven initiative to increase the number of POC u/s examinations documented and transferred to medical coders by emergency medicine physicians. Three months before a chosen go-live date, departmental leadership, the ultrasound division, and residents formed a task force. Barriers to documentation were identified through brain storming and email solicitation. The total number and application-specific POC u/s examinations performed and transferred to the healthcare record and medical coders were compared for the pre- and post-task force intervention periods. Chi square analysis was used to determine the difference between the number of POC u/s examinations reported before and after the intervention. A total of 1652 POC u/s examinations were reported during the study period. Successful reporting to the patient care chart and medical coders increased from 41 % pre-task force intervention to 63 % post-intervention (p value 0.000). The number of scans performed during the 3-month periods (pre-intervetion, post-intervention 0-3 months, post-intervention 3-6 months) was similar (521, 594 and 537). When analyzed by specific application, the majority showed a statistically significant increase in the percentage of examinations reported, including those most critical for patient care decision making: (EFAST (41 vs. 64 %), vascular access (26 vs. 61 %), and cardiac (43 vs. 72 %); and those most commonly performed: biliary (44 vs. 61 %) and pelvic (60 vs. 66 %). Of the POC u/s studies coded and reported for reimbursement, 15.9 % were billed before intervention and 32 % were billed after intervention (p value: 0.000).

The formation of a workflow solution task force positively affected emergency physician compliance with POC u/s documentation for coding and billing over a 6-month period. Further investigation should assess the long-term effect of the intervention and whether this translates into increased revenue to the department.

Is intense exercise training effective to restore the endothelial NO-dependent relaxation in STZ-diabetic rat aorta?

The aim of this study was to examine the effects of intense physical training on vascular function in streptozotocin-diabetic rats. We focused on the endothelium-dependent relaxation (EDR) induced by acetylcholine (ACh) and stable ADP adenosine-5'- O - (2-thiodiphosphate) (ADPβS). Control or diabetic male Wistar rats (n=44) were randomly assigned to sedentary or trained groups. The training program consisted in a regular period of running on a treadmill during 8 weeks (10° incline and up to 25 m/min, 60 min/day). The reactivity of isolated thoracic aorta rings of healthy, diabetic and/or trained has been tested. ACh and ADPβS-induced EDR were observed in phenylephrine (PE) pre-contracted vessels. As compared to sedentary control group, diabetic rats showed an increase in PE-induced contraction and a decrease in ACh and ADPβS-induced EDR (p<0.05). Moreover, there were no increase in ACh and ADPβS-induced EDR in diabetic rats. N-Nitro-L-Arginine Methyl Ester inhibited the nitric oxide synthase in diabetic and control rats, thereby resulting in a strong inhibition of the EDR induced by ACh and ADPβS (10-6 M).

Diabetes induced an endothelium dysfunction. Nevertheless, our intense physical training was not effective to restore the aorta endothelial function.

Does prostaglandin E ( 2 ) suppress CCL27 production through EP2 and EP3 receptors in human keratinocytes?

The chemokine CCL27 attracts skin-homing T cells. CCL27 production by keratinocytes is enhanced in skin lesions from patients with atopic dermatitis or psoriasis vulgaris. It is suggested that prostaglandin E(2) (PGE(2)) regulates skin inflammation. We examined the in vitro effects of PGE(2) on CCL27 production in human keratinocytes. Keratinocytes were incubated with TNF-alpha in the presence or absence of PGE(2) . CCL27 secretion and mRNA level were analyzed by means of ELISA and RT-PCR, respectively. Nuclear factor kappaB (NF-kappaB)-dependent transcriptional activity was analyzed by using luciferase assays. TNF-alpha increased CCL27 secretion and mRNA levels in parallel to NF-kappaB activity in keratinocytes. NF-kappaB p50 or p65 antisense oligonucleotides suppressed TNF-alpha-induced CCL27 production, indicating the requirement of NF-kappaB for CCL27 production. PGE(2) , EP2, or EP3 agonists reduced TNF-alpha-induced CCL27 secretion and mRNA levels in parallel to NF-kappaB activity and CCL2, CCL5, CXCL8, and CXCL10 mRNA levels. Either EP3-specific or dual EP1-EP2 antagonist partially blocked the inhibitory effects of PGE(2) on CCL27 production and NF-kappaB activity, and the addition of both completely abrogated the inhibition, whereas EP1 or EP4 antagonists were ineffective. Intracellular Ca(2+) chelator BAPTA/AM or cyclic adenosine monophosphate (cAMP)-dependent protein kinase inhibitor H-89 partially blocked the inhibitory effects of PGE(2) on CCL27 production and NF-kappaB activity, and the addition of both completely abrogated the inhibition. PGE(2) or EP3 agonist increased intracellular Ca(2+) concentrations. PGE(2) or EP2 agonist increased intracellular cAMP concentrations.

PGE(2) might suppress CCL27 production by inhibiting NF-kappaB activity through EP2-mediated cAMP and EP3-mediated Ca(2+) signals. PGE 2 might terminate T cell-mediated skin inflammation by inhibiting CCL27 production.

Does norepinephrine-induced hyperglycemia increase cortical lactate in brain-injured rats?

Hyperglycemia aggravates ischemic brain damage. Since catecholamines increase hepatic gluconeogenesis, resulting in hyperglycemia, we investigated whether norepinephrine and dopamine elevate arterial blood glucose, thereby increasing pericontusional cortical glucose and lactate concentrations and brain edema in brain-injured rats. Prospective, randomized, controlled animal study. Male Sprague Dawley rats. Physiological saline solution, norepinephrine, or dopamine were infused intravenously for 90 min beginning 4.5 h after inducing a focal cortical contusion. Blood glucose, lactate, and pericontusional cortical extracellular glucose and lactate were determined before, during and up to 60 min after the infusion period. Thereafter brains were removed to assess hemispheric water content. Continuous norepinephrine and dopamine infusion significantly increased pericontusional glucose concentrations, being mostly sustained by norepinephrine (NaCl: 1.3+/-0.2, dopamine: 2.7+/-0.2, norepinephrine: 4.8+/-1.1 mM). While arterial blood glucose was only significantly elevated in norepinephrine-treated rats from 8.6+/-0.6 to 12.6+/-1.6 mM, the extracellular to blood glucose ratio was significantly increased in dopamine- and norepinephrine-treated rats (0.28+/-0.01 and 0.38+/-0.05 vs. 0.17+/-0.01). Plasma and pericontusional lactate remained unchanged, and brain edema was similar in all groups.

Norepinephrine and dopamine significantly increased pericontusional glucose concentrations which did not elevate extracellular lactate and aggravate underlying posttraumatic edema formation. In addition to possibly increased facilitated endothelial glucose transport, the elevated extracellular to blood glucose ratio suggests a passive concentration- and pressure- dependent entry via a damaged blood-brain barrier. This might contribute to the observed reversible increase in extracellular glucose.

Nonalcoholic fatty liver disease across ethno-racial groups: do Asian-American adults represent a new at-risk population?

Nonalcoholic fatty liver disease (NAFLD) is increasingly common worldwide. We explored clinical, laboratory, and histological features of NAFLD as well as risk factors for histologically advanced disease among under-represented ethno-racial groups. Patient records from one NAFLD clinic in California from 1998-2008 were reviewed. Biopsies were graded using Brunt criteria by a hepatopathologist blinded to clinical data. We used multivariate logistic regression to assess associations between ethno-racial group and histological severity of NAFLD, while controlling for other factors. We identified 90 biopsy-proven cases of NAFLD. Mean age was 49 years (standard deviation [SD]= 11.6), and half were female. 52% of patients were Caucasian, 20% Latino-American, 18% Asian-American, and 10% Middle Eastern-American. There were significant differences among groups with respect to age, weight, body mass index (BMI), and grade of hepatic steatosis (all P<0.05). In multivariate analysis, older age was associated with severe (Brunt ≥ 2) inflammation (odds ratio [OR] 1.1, P = 0.002) and severe (Brunt ≥ 3) fibrosis (OR 1.2, P = 0.001), diabetes was associated with severe inflammation (OR 3.18, P = 0.07) and severe fibrosis (OR 8.81, P = 0.002), and increased BMI was associated with severe fibrosis (OR 2.43, P = 0.07). Additionally, compared to Caucasians, Asian-Americans showed a trend toward an association with severe (Brunt>2) steatosis (OR 3.83, P = 0.08) and severe inflammation (OR 5.42, P = 0.06).

The findings from this ethno-racially diverse clinic-based cohort are consistent with prior studies and also suggest that Asian-Americans may be at risk for advanced NAFLD. This may have implications for the prevention, evaluation, and treatment of patients with NAFLD that merit further study.

Does n-pentyl-nitrofurantoin induce apoptosis in HL-60 leukemia cell line by upregulating BAX and downregulating BCL-xL gene expression?

Nitrofurantoin is a nitroderivative antibiotic that has bactericidal activity against pathogens causing urinary tract infection. A few studies have reported that nitrofurantoin has cytotoxic activity against cancer cells; however, nitrofurans remain a poorly explored class of compounds with respect to their anticancer potential. The aim of this study was to investigate the anticancer effects of a nitrofurantoin derivative, n-pentyl-nitrofurantoin (NFP), on HL-60 leukemia cells. Cytotoxicity was assayed by the MTT assay. Cell morphology and phosphatidylserine externalization were visualized after Giemsa-May-Grunwald and annexin V staining, respectively. DNA content and mitochondrial depolarization were measured by flow cytometry. BAX and BCL-xL expression was examined by RT-PCR. NFP was 3.8-fold more cytotoxic against HL-60 leukemia cells than against normal cells. NFP reduced the number of viable cells 24h after the treatment with a concomitant increase in the number of apoptotic cells indicated by the externalization of phosphatidylserine, DNA fragmentation, and mitochondrial depolarization. The mRNA levels of BAX increased, whereas the mRNA levels of BCL-xL decreased.

The results indicate that NFP induces apoptosis in HL-60 cells by upregulating BAX and downregulating BCL-xL.

Does increased prosthetic weight affect gait speed and patient preference in dysvascular transfemoral amputees?

To determine if increased prosthetic weight affects gait speed in dysvascular transfemoral amputees and to see if there is any patient preference for lighter versus heavier prostheses. Randomized prospective double-blind crossover trial. Outpatient, tertiary care, amputee clinic in Ontario, Canada. A convenience sample of 10 subjects with unilateral transfemoral amputations because of peripheral vascular disease. All subjects were independent community ambulators over 50 years old. Seemingly identical weights of 150g (placebo weight), 770g, and 1625g were added to the prosthesis 14cm below the knee joint. Two-minute walk test (2MWT) and subject preference. The 2MWT results were not significantly influenced by weight added (mean, 53.4+/-28.4m, 55.1+/-28.9m, and 52.8+/-26.7m for 150g, 770g, and 1625g of added weight, respectively). Subject preference revealed that more than half preferred a weighted prosthesis over the "placebo" weight (5 subjects preferred 770g added, 4 subjects preferred 150g added, 1 preferred 1625g added).

Short-term intervention with increased prosthetic mass had no significant adverse affect on gait speed, and more than half of the subjects preferred an added mass condition.

Does osteopontin alter endothelial and valvular interstitial cell behaviour in calcific aortic valve stenosis through HMGB1 regulation?

Calcific aortic valve stenosis (CAVS) is an important clinical problem predominantly affecting elderly individuals. Studies suggest that the progression of CAVS is actively regulated with valve endothelial injury leading to inflammation, fibrosis and calcification. The aim of this study was to delineate the possible regulatory role of osteopontin (OPN) on high-mobility group box 1 (HMGB1) function and the associated inflammatory and fibrotic response in CAVS. Aortic valve leaflets were collected from CAVS patients undergoing aortic valve replacement (n = 40), and control aortic valve leaflets were obtained from heart transplant recipients (n = 15). Valves and plasma were analysed by quantitative real-time polymerase chain reaction (PCR), immunohistochemical staining and Western blot. Recombinant OPN or neutralizing OPN antibody was added to cultured endothelial and valvular interstitial cells (VICs), and cell proliferation scores and HMGB1 expression were assessed. CAVS valves had a decreased total percentage of VICs but increased numbers of infiltrating macrophages relative to control valves. RT-PCR studies showed higher expression of OPN, the inflammatory cytokine tumour necrosis factor-alpha as well as markers of fibrosis, tissue inhibitor of matrix metalloproteinase 1 and matrix metalloproteinase 2 in CAVS valves. Elevated expression of OPN was also observed in plasma of CAVS patients compared with controls. HMGB1 was detected in the secretory granules of cultured valve endothelial and VICs derived from CAVS valves. The addition of exogenous OPN inhibited the proliferation of cultured endothelial and VICs from CAVS valves and was associated with the extracellular expression of HMGB1, whereas neutralizing OPN had the opposite effect.

We conclude that altered OPN expression in CAVS affects cellular HMGB1 function inducing cytoplasmic translocation and secretion of HMGB1 in endothelial cells and VICs, thus indicating a regulatory role for OPN in the progression of CAVS through alteration of HMGB1 function.

Does signaling of ERBB receptor tyrosine kinases promote neuroblastoma growth in vitro and in vivo?

ERBB receptor tyrosine kinases can mediate proliferation, migration, adhesion, differentiation, and survival in many types of cells and play critical roles in many malignancies. Recent reports suggest a role for EGFR signaling in proliferation and survival of neuroblastoma, a common form of pediatric cancer that often has an extremely poor outcome. The authors examined ERBB family expression in neuroblastoma cell lines and patient samples by flow cytometry, western blot, and quantitative real time polymerase chain reaction (Q-PCR). Response to ERBB inhibition was assessed in vitro by cell-cycle analysis and western blot and in vivo by serial tumor-size measurements. A panel of neuroblastoma cell lines and primary patient tumors expressed EGFR, HER-3, and HER-4, with HER-2 in some tumors. HER-4 mRNA was expressed predominantly in cleavable isoforms. Whereas EGFR inhibition with erlotinib and pan-ERBB inhibition with CI-1033 inhibited EGF-induced phosphorylation of EGFR, AKT, and ERK1/2, only CI-1033 induced growth inhibition and dose-dependent apoptosis in vitro. Both CI-1033 and erlotinib treatment of neuroblastoma xenograft tumors resulted in decreased tumor growth in vivo, although CI-1033 was more effective. In vivo expression of EGFR was observed predominantly in vascular endothelial cells.

Pan-ERBB inhibition is required for ERBB-related neuroblastoma apoptosis in vitro, although EGFR contributes indirectly to tumor growth in vivo. Inhibition of EGFR in endothelial cells may be an important aspect of erlotinib's impact on neuroblastoma growth in vivo. Our results suggest that non-EGFR ERBB family members contribute directly to neuroblastoma growth and survival, and pan-ERBB inhibition represents a potential therapeutic target for treating neuroblastoma.

Does iL-6 potentiate tumor resistance to photodynamic therapy ( PDT )?

Photodynamic therapy (PDT) is an anticancer modality approved for the treatment of early disease and palliation of late stage disease. PDT of tumors results in the generation of an acute inflammatory response. The extent and duration of the inflammatory response is dependent upon the PDT regimen employed and is characterized by rapid induction of proinflammatory cytokines, such as IL-6, and activation and mobilization of innate immune cells. The importance of innate immune cells in long-term PDT control of tumor growth has been well defined. In contrast the role of IL-6 in long-term tumor control by PDT is unclear. Previous studies have shown that IL-6 can diminish or have no effect on PDT antitumor efficacy. In the current study we used mice deficient for IL-6, Il6(-/-) , to examine the role of IL-6 in activation of antitumor immunity and PDT efficacy by PDT regimens known to enhance antitumor immunity. Our studies have shown that elimination of IL-6 had no effect on innate cell mobilization into the treated tumor bed or tumor draining lymph node (TDLN) and did not affect primary antitumor T-cell activation by PDT. However, IL-6 does appear to negatively regulate the generation of antitumor immune memory and PDT efficacy against murine colon and mammary carcinoma models. The inhibition of PDT efficacy by IL-6 appears also to be related to regulation of Bax protein expression. Increased apoptosis was observed following treatment of tumors in Il6(-/-) mice 24 hours following PDT.

The development of PDT regimens that enhance antitumor immunity has led to proposals for the use of PDT as an adjuvant treatment. However, our results show that the potential for PDT induced expression of IL-6 to enhance tumor survival following PDT must be considered.

Do steroids reduce morbidity of tonsillectomy?

The study aims to reconcile conflicting published reports regarding the clinical efficacy of a single intraoperative dose of dexamethasone in reducing post-tonsillectomy morbidity. Systematic overview (meta-analysis). To critically evaluate the existing evidence, we performed a formal meta-analysis of eight double-blinded, randomized, placebo-controlled studies of dexamethasone in pediatric patients undergoing tonsillectomy or adenotonsillectomy. Reduction in postoperative emesis and pain, as well as early return to soft or solid diet, were studied as distinct end points. Children being given a single intraoperative dose of dexamethasone (dosing, 0.15-1.0 mg/kg; maximum dose, 8-25 mg) were two times less likely to vomit in the first 24 hours than children being given placebo (relative risk [RR] = 0.55; 95% confidence interval [CI], 0.41-0.74; P<.0001). Routine use in four children would be expected to result in one less patient having post-tonsillectomy emesis (risk difference [RD]= -0.24; 95% CI, -0.38 to -0.10; P = .0006). In addition, children being given dexamethasone were more likely to advance to a soft or solid diet on post-tonsillectomy day 1 (RR = 1.69; 95% CI, 1.02-2.79; P = .04) than those being given placebo. Because of missing data and varied outcome measures, pain could not be meaningfully analyzed as a distinct end point.

Given the frequency of tonsillectomy, relative safety and low cost of dexamethasone, and the reduction in postoperative morbidity, we recommend routine use of a single intravenous dose during pediatric tonsillectomy.

Is the balance between nitric oxide and superoxide altered in spontaneously hypertensive rats with endothelial dysfunction?

Increases in oxidant stress, i.e. excessive production of superoxide anion (O2(.-)), have been reported in different models of hypertension. This study was designed to test the hypothesis that increased O2(.-) production, more than diminished nitric oxide (NO) generation, plays a critical role in endothelial dysfunction present in spontaneously hypertensive rats (SHR). The study was performed in 30-week-old normotensive Wistar-Kyoto rats (WKY) and SHR. In addition, 16-week-old SHR were treated with oral irbesartan (average dose 20 mg/kg per day) for 14 weeks (SHR-I). Aortic nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity was determined by use of chemiluminescence with lucigenin. Aortic constitutive nitric oxide synthase (cNOS) activity was determined by measuring the conversion of L-arginine to L-citrulline. Vascular responses to acetylcholine were determined by isometric tension studies. Whereas systolic blood pressure (SBP) was significantly increased in SHR compared with WKY, no differences were observed in SBP between SHR-I and WKY. In SHR compared with WKY, we found significantly greater NADH/NADPH-driven O2(.-) production, similar cNOS-mediated NO production and an impaired vasodilation in response to acetylcholine. Treated SHR had similar NADH/NADPH oxidase activity and significantly lower cNOS activity than the WKY group. Vasodilation in response to acetylcholine was improved in SHR-I.

These findings suggest that a diminished availability of NO secondary to an enhanced NADH/NADPH oxidase-dependent O2(.-) production may play a critical role in endothelial dysfunction of adult SHR.

Does the major facilitator superfamily transporter MdtM contribute to the intrinsic resistance of Escherichia coli to quaternary ammonium compounds?

Quaternary ammonium compounds (QACs) are used extensively as biocides and their misuse may be contributing to the development of bacterial resistance. Although the major intrinsic resistance to QACs of Gram-negative bacteria is mediated by the action of tripartite multidrug transporters of the resistance-nodulation-division family, we aimed to test if the promiscuity of the recently characterized major facilitator superfamily multidrug transporter, MdtM, from Escherichia coli enabled it also to function in the efflux of QACs. The ability of the major facilitator mdtM gene product, when overexpressed from multicopy plasmid, to protect E. coli cells from the toxic effects of a panel of seven QACs was determined using growth inhibition assays in liquid medium. Interaction between QACs and MdtM was studied by a combination of substrate binding assays using purified protein in detergent solution and transport assays using inverted vesicles. E. coli cells that overproduced MdtM were less susceptible to the cytotoxic effects of each of the QACs tested compared with cells that did not overproduce the transporter. Purified MdtM bound each QAC with micromolar affinity and the protein utilized the electrochemical proton gradient to transport QACs across the cytoplasmic membrane. Furthermore, the results suggested a functional interaction between MdtM and the tripartite resistance-nodulation-division family AcrAB-TolC efflux system.

The results support a hitherto unidentified capacity for a single-component multidrug transporter of the major facilitator superfamily, MdtM, to function in the efflux of a broad range of QACs and thus contribute to the intrinsic resistance of E. coli to these compounds.

Does pRL-3 promote gastric cancer migration and invasion through a NF-κB-HIF-1α-miR-210 axis?

Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues. In gastric cancer cells, PRL-3 upregulated miR-210 expression in a HIF-1α-dependent fashion under normoxia and hypoxia. In addition, PRL-3 activated NF-κB signaling and promoted HIF-1α expression through modulating phosphorylation of p65. NF-κB signaling, HIF-1α, and miR-210 partially contributed to PRL-3-induced migration and invasion. Furthermore, the levels of PRL-3, HIF-1α, and miR-210 transcripts inversely affected the overall survival of gastric cancer patients. Our work identified the existence of a PRL-3-NF-κB-HIF-1α-miR-210 axis, thus providing new insight into the role of PRL-3 in promoting gastric cancer invasiveness.

PRL-3 regulates microRNA in gastric cancer. PRL-3 elevates hsa-miR-210 by upregulating HIF-1α. PRL-3 activates a NF-κB-HIF-1α-miR-210 axis by enhancing the phosphorylation of p65. PRL-3 promotes cell migration and invasion via the NF-κB-HIF-1α-miR-210 axis. High levels of PRL-3 and miR-210 are related with poor OS in gastric cancer.

Does nurse-led education set out to improve patient concordance and prevent recurrence of leg ulcers?

This study evaluated the effects of a structured nurse-led education programme that aimed to improve patient concordance and prevent venous leg ulcer recurrence. The design was quasi-experimental. Subjects (average age: 80) had venous leg ulceration that had healed within the previous two years, and were cared for at home by a district nurse. Data were available on 49 patients with 97 legs, 72 of which had had venous leg ulcers. Patients were divided into two groups: a control group, which received 'usual' care, and experimental group, which was exposed to the education programme. Recurrence rates, the effects of the education on patient behaviour and the effect on recurrence of having both ankle movement and general mobility were measured over one year. Patients in the experimental group experienced significantly less recurrence over the year (log rank test = 8.28, p = 0.004). To control for differences in mobility and ankle movement in the control and experimental groups at baseline, simultaneous logistic regression analysis was undertaken. This revealed a significant advantage for patients in the experimental group (p = 0.035; OR = 4.45, 95% CI = 1.11-17.74), who spent more time with their legs elevated each day. This difference was sustained throughout the 52 weeks (f = 2.88, p = 0.015). Those who had both full ankle movement (> 60 degrees) and full mobility (without aid) had significantly less recurrence (p = 0.042). Education had no significant effect on the amount of time patients wore compression hosiery (f = 2.1).

A structured nurse-led patient concordance programme is effective in preventing venous leg ulcer recurrence and increasing the time patients spend with their legs elevated at heart level. Having both full ankle movement and full mobility reduces the risk of recurrence.

Do once-daily pantoprazole 40 mg and esomeprazole 40 mg have equivalent overall efficacy in relieving GERD-related symptoms?

To compare the efficacy of pantoprazole and esomeprazole for the treatment of gastro-oesophageal reflux disease- (GERD-) related symptoms. In this multicentre, randomized, double-blind study 217 patients [intention-to-treat (ITT) population] diagnosed with endoscopically proven GERD grade B/C received pantoprazole (40 mg once daily (o.d.), n = 112] or esomeprazole (40 mg o.d/, n = 105) for 4 weeks. Patients recorded GERD-related symptoms (daytime and night-time) using diaries (daily), and/or by telephone interviews (every third day) and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. The area under the time curve (AUC) for the sum score of GERD-related symptoms (symptom load of each patient during the treatment) and the time to reach adequate relief from GERD-related symptoms were calculated. Patients reported first adequate relief from daytime GERD-related symptoms after a mean of 3.7 (pantoprazole) and 5.9 days (esomeprazole) (P = 0.034); the values for the night-time were 1.7 and 3.5 days, respectively (P = 0.012, ITT). The AUCs for the single symptoms and the sum scores were comparable.

Treatment with pantoprazole resulted in significantly faster first-time relief from daytime and night-time GERD-related symptoms than esomeprazole. Pantoprazole and esomeprazole were similar with respect to reduction of load of GERD-related symptoms.

Do an oscillating/pulsating electric toothbrush versus a high-frequency electric toothbrush in the treatment of gingivitis?

The objective of this study was to compare the effect of an oscillating/pulsating power toothbrush (Oral-B ProfessionalCare 7000; PC 7000) and a high-frequency power toothbrush (Philips Sonicare Elite; SE) on the reversal of experimental gingivitis. The study had a randomised, examiner-blind, split-mouth design. After dental prophylaxis, subjects refrained from brushing mandibular teeth for 21 days to allow development of gingivitis. During a 4-week treatment phase, the right or left side of the mouth was brushed with either the PC 7000 or the SE toothbrush as randomly allocated. Plaque and gingivitis were assessed at baseline (Day 0), after 21 days of no oral hygiene, and after 1, 2 and 4 weeks of brushing twice daily. Gingival abrasion was assessed at Day 0 and after 1, 2 and 4 weeks of product use. Of 38 enrolled subjects, 35 provided evaluable data. The experimentally induced gingivitis (EIG) phase resulted in higher bleeding and plaque scores as compared to Day 0. During the treatment phase, plaque and bleeding scores were significantly lower with the PC 7000 than the SE toothbrush. After 4 weeks of use, the mean plaque scores changed from 2.78 (Day 21 of EIG phase) to 0.70 for the PC 7000 and from 2.67 (Day 21) to 0.88 for the SE. The mean bleeding scores changed from 1.86 (Day 21) to 1.24 for the PC 7000 and from 1.88 (Day 21) to 1.42 for the SE. No major differences were found between brushes with regard to gingival abrasion.

The oscillating/pulsating power toothbrush (Oral-B ProfessionalCare 7000) was more effective than the high-frequency power toothbrush (Philips Sonicare Elite) at plaque removal and improvement of gingival condition, with no greater potential for causing gingival abrasion.

Does automated 3D Volumetry of the Pulmonary Arteries based on Magnetic Resonance Angiography have Potential for Predicting Pulmonary Hypertension?

To demonstrate feasibility of automated 3D volumetry of central pulmonary arteries based on magnetic resonance angiography (MRA), to assess pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and to investigate the potential of the technique for predicting pulmonary hypertension. MRA of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls. 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries (MPA, RPA and LPA). Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA). For comparison, diameters were also manually measured on axial reconstructions and double oblique multiplanar reformations. Analyses were performed by two cardiovascular radiologists, and by one radiologist again after 6 months. Mean volumes of MPA, RPA and LPA for patients/controls were 5508 ± 1236/3438 ± 749, 3522 ± 934/1664 ± 468 and 3093 ± 692/1812 ± 474 μl/(cm length x m2 BSA) (all p<0.001). Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls (all p<0.001). Intra- and interobserver agreement were excellent for both volume and diameter measurements using 3D segmentation (intraclass correlation coefficients 0.971-0.999, p<0.001). Area under the curve for predicting pulmonary hypertension using volume was 0.998 (95% confidence interval 0.990-1.0, p<0.001), compared to 0.967 using manually measured MPA diameter (95% confidence interval 0.910-1.0, p<0.001).

Automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery volume may serve as a superior predictor for pulmonary hypertension compared to manual measurements on axial images but verification in a larger study population is warranted.

Is pPAR gamma an important transcription factor in 1 alpha,25-dihydroxyvitamin D3-induced involucrin expression?

1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25(OH)2D3), the active form of vitamin D, suppresses keratinocyte proliferation, promotes keratinocyte differentiation, and induces involucrin expression. Peroxisome proliferation-activated receptors (PPARs) are ligand-activated transcription factors. It has been reported that PPARs stimulate keratinocyte differentiation and regulate the expression of differentiation molecules. Keratinocytes treated with 1 alpha,25(OH)2D3 induced PPAR gamma, which was followed by increased involucrin expression. In this study, we investigated whether PPAR gamma is involved in the 1 alpha,25(OH)2D3-induced involucrin expression in human keratinocytes. Subconfluent keratinocytes were treated with 10(-7)M 1 alpha,25(OH)2D3 for the indicated times, and PPAR and involucrin mRNA expression were determined by real-time RT-PCR. The levels of PPARs, involucrin, p38, and phospho-p38 proteins were assayed by Western blotting, and the DNA binding activities of PPAR gamma and AP-1 were investigated by electrophoretic mobility shift assays (EMSA). To examine the role of PPAR gamma in 1 alpha,25(OH)2D3 responses, recombinant adenovirus carrying a dominant-negative form of PPAR gamma (Axdn-PPAR gamma) was constructed and transfected into keratinocytes. The p38 inhibitor SB203580 was added to the cultures to evaluate the involvement of p38 in involucrin expression. 1 alpha,25(OH)2D3 induced PPAR gamma expression and stimulated PPAR gamma activity. The introduction of dn-PPAR gamma inhibited the expression of involucrin mRNA and protein induced by 1 alpha,25(OH)2D3, and suppressed AP-1 DNA binding activity. 1 alpha,25(OH)2D3 also triggered the phosphorylation of p38, which contributes to involucrin induction. Moreover, dn-PPAR gamma prevented the 1 alpha,25(OH)2D3-induced phosphorylation of p38.

These results suggest that PPAR gamma regulates involucrin expression by controlling the AP-1 signal and p38 activation in 1 alpha,25(OH)2D3-induced keratinocyte differentiation.

Does normothermia during cardiopulmonary bypass increase neutrophil-endothelium interactions?

The use of warm blood cardioplegia is usually associated with that of warm cardiopulmonary bypass (CPB). Little is known, however, about the effect of temperature during bypass on neutrophil-endothelium interactions, which are currently considered a key component of the inflammatory response to CPB. Twenty-five patients operated on under CPB were studied. Core temperature during bypass was kept normothermic (33.5 degrees C to 37 degrees C) in 14 and lowered to 28 degrees C to 30 degrees C in the 11 remaining patients. The two groups were otherwise comparable. Arterial blood samples were collected before CPB and 30 minutes, 4 hours, and 24 hours thereafter. Samples were assayed for interleukin-1 receptor antagonist (IL-1ra), soluble intercellular adhesion molecule 1 (sICAM-1), and elastase, which are markers of cytokine production, cytokine-upregulated endothelial ligands for neutrophil adhesion molecules, and degranulation secondary to adhesion of neutrophils to endothelial cells, respectively. IL-1ra levels (mean +/- SEM) peaked 4 hours after bypass and were significantly higher in the warm group (87,926 +/- 24,067 versus 18,090 +/- 5798 mg/L, P<.02). Peak values of sICAM-1, which occurred 24 hours after bypass, were correspondingly higher in warm patients (414 +/- 74 versus 298 +/- 23 micrograms/L in cold patients). In keeping with these data, warm patients released significantly more elastase at both the 30-minute (703 +/- 101 versus 349 +/- 55 micrograms/L, P<.01) and 4-hour (627 +/- 116 versus 324 +/- 31 micrograms/L, P<.03) post-CPB study points.

Temperature profoundly affects neutrophil-endothelium interactions, which leads one to question the use of systemic normothermia in patients at higher risk of suffering from postbypass inflammation-mediated organ damage.

Does resting magnetocardiography predict 3-year mortality in patients presenting with acute chest pain without ST segment elevation?

Magnetocardiography (MCG) as a noninvasive, noncontact and risk-free diagnostic method predicts ischemic coronary artery disease (CAD) in patients with acute chest pain at admission with high accuracy. However, it remains unclear whether MCG findings can add prognostic information. A cohort of 402 consecutive patients presenting at the intensive care unit (ICU) with acute chest pain without ST segment elevation (NSTEMI) were included in a prospective registry. In order to prove the prognostic value of MCG a head-to-head comparison of the admission MCG, ECG, TnI, and ECHO tests was made. In 43 patients (10.7%) the MCG could not be analyzed due to insufficient signal-to-noise ratio. Complete follow-up over a period of up to 3 years was obtained in 355 out of the 359 patients (98.9%). Age at admission was 67.2 +/- 10.3 years, 59.7% males. In the group of patients with an abnormal MCG at admission, 43 out of 249 patients (17.3%) died in the follow-up period, while in the group of patients with a normal MCG at admission only 4 out of 106 patients died (3.77%). The relative risk was 4.58 (95% confidence intervals: 1.68-12.42). A multivariate regression analysis revealed the highest mortality risk for patients with diabetes mellitus and an abnormal MCG at admission (RR = 18.0; 95% CI: 2.49-133.3).

Resting MCG at hospital admission predicts 3-year mortality in patients presenting with acute chest pain without ST segment elevation in the ECG. MCG seems to be valuable in identifying chest pain patients at highest risk.

Does debio 0507 primarily form diaminocyclohexane-Pt-d ( GpG ) and -d ( ApG ) DNA adducts in HCT116 cells?

To characterize the cellular action mechanism of Debio 0507, we compared the major DNA adducts formed by Debio 0507- and oxaliplatin-treated HCT116 human colon carcinoma cells by a combination of inductively coupled plasma mass spectrometry (ICP-MS) and ultraperformance liquid chromatography mass spectrometry (UPLC-MS/MS). HCT116 cells were treated with IC(50) doses of Debio 0507 or oxaliplatin for 3 days. Total cellular Pt-DNA adducts were determined by ICP-MS. The DNA was digested, and the major Pt-DNA adducts formed by both drugs were characterized by UPLC/MS/MS essentially as described previously for cisplatin (Baskerville-Abraham et al. in Chem Res Toxicol 22:905-912, 2009). The Pt level/deoxynucleotide was 7.4/10(4) for DNA from Debio 0507-treated cells and 5.5/10(4) for oxaliplatin-treated cells following a 3-day treatment at the IC(50) for each drug. UPLC-MS/MS in the positive ion mode confirmed the major Pt-DNA adducts formed by both drugs were dach-Pt-d(GpG) (904.2 m/z → 610 m/z and 904.2 m/z → 459 m/z) and dach-Pt-d(ApG) (888.2 m/z → 594 m/z and 888.2 m/z → 459 m/z).

These data show that the major DNA adducts formed by Debio 0507 are the dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts and at equitoxic doses Debio 0507 and oxaliplatin form similar levels of dach-Pt-d(GpG) and dach-Pt-d(ApG) adducts. This suggests that the action mechanisms of Debio 0507 and oxaliplatin are similar at a cellular level.

Unintentional pediatric superwarfarin exposures: do we really need a prothrombin time?

To determine whether routine follow-up coagulation studies are useful in children with accidental exposures to rodenticides containing superwarfarin compounds. Retrospective review of poison center charts involving pediatric superwarfarin exposures occurring in two 2-year periods. An American Association of Poison Control Centers-certified regional poison control center with an annual call volume of 55 000 calls per year from a 2-state area with a combined population of 4 million people. Prothrombin times and/or international normalized ratios and reported clinical signs of excessive anticoagulation after exposure. Of 542 children in 4 years of data collection, follow-up prothrombin times and/or international normalized ratios measurements did not detect any significant coagulation abnormalities. No child developed bleeding complications. No child required or received antidotal treatment with vitamin K.

Normal preschool-aged children with unintentional acute exposures to superwarfarin rodenticides do not require any routine follow-up laboratory studies and do not require any medical intervention.

Does propofol attenuate oxidant-induced acute lung injury in an isolated perfused rabbit-lung model?

Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger. We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc). In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values.

Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.

Do naturally occurring level of mixed aflatoxins B and G stimulate toll-like receptor-4 in bovine mononuclear cells?

As common contaminants of agricultural commodities, aflatoxins (AFs) are highly hazardous carcinogenic mycotoxins originating from very common fungi present in the environment. Their effect on bovine key immune-surveillance molecules is unclear. To determine the in vitro effects of naturally occurring level of AFs on toll-like receptor-4 (TLR4) and viability in bovine peripheral blood mononuclear cells (PBMCs) as a model system for immunotoxicity. Ten healthy dairy cows were selected as a source of PBMCs. The mRNA expression of TLR4 was quantitatively evaluated in PBMCs treated with a mix of 1.0, 0.5, 0.25 and 0.25 ng/ml of AFB1, AFB2, AFG1 and AFG2, respectively, and 10 ng/ml of the well-known TLR4 agonist lipopolysaccharide (LPS) for 0.5, 2, 5 and 18 hours. We also analyzed the viability of PBMCs exposed to AFs by means of the trypan blue exclusion method and the tetrazolium bromide assay. Compared with control PBMCs, transcription of TLR4 in AFs-treated PBMCs was significantly up-regulated at post-exposure hours (PEH) 2 and 5, but was unchanged at PEH 0.5 and 18. Unsurprisingly, much higher up-regulation of TLR4 transcript was observed in LPS-treated PBMCs at PEH 0.5, 2, 5 and 18. Conversely, the viability of post-AFs and/or LPS-exposed PBMCs revealed no significant changes.

Naturally occurring levels of AFs result in increased expression of TLR4 mRNA in bovine PBMCs.

Is preoperative Nutritional Status an Independent Predictor of 30-day Hospital Readmission After Elective Spine Surgery?

A retrospective cohort review. The aim of this study is to investigate whether preoperative malnutrition is an independent risk factor for unplanned 30-day readmission after elective spine surgery. Thirty-day hospital readmission rate is being used as a proxy for quality of care. Accordingly, hospitals and health systems are investing considerable resources into the identification of patients at risk of hospital readmission and designing interventions to reduce the rate of hospital readmissions. The medical records of 145 patients undergoing elective spine surgery at a major academic medical center were reviewed. Preoperative serum albumin level was assessed on all patients and used to quantify nutritional status. Albumin less than 3.5 g/dL was recognized malnourished. Patient demographics, comorbidities, and postoperative complication rates were collected. The association between preoperative serum albumin level and 30-day readmission rate was assessed via multivariate logistic regression analysis. Baseline characteristics were similar between both groups. Low albumin was found in 28% of patients in this study. Malnourished patients were more likely to experience a postoperative complication and a prolonged duration of hospital stay (3.80 vs. 8.67 days), P = 0.03. Overall, 14.48% of patients were readmitted within 30 days of discharge, with malnourished patients experiencing a three-fold increase in 30-day readmission rates (malnourished: 27.50% vs. nourished: 9.52%, P = 0.02). Binary logistic regression with and without propensity score adjustment for risk factors demonstrated that preoperative malnutrition (low serum albumin level) is an independent predictor of 30-day readmission after elective spine surgery (P = 0.01).

Pre-operative malnutrition is an independent risk factor for readmission within 30 days of discharge after elective spine surgery. Laboratory markers of nutrition can identify patients at risk of unplanned hospital readmission. This risk determination identifies a potentially modifiable risk factor for early readmission.

Is an expanded self-antigen peptidome carried by the human lymph as compared to the plasma?

The pre-nodal afferent lymph is the fluid which directly derives from the extracellular milieu from every parenchymal organ and, as it continues to circulate between the cells, it collects products deriving from the organ metabolism/catabolism. A comprehensive qualitative and quantitative investigation of the self-antigenic repertoire transported by the human lymph is still missing. A major difference between lymph and plasma could be visualized by FPLC and 2D gel in the amount of low molecular weight products corresponding to peptide fragments. Naturally processed peptides in normal pre-nodal human lymph were then fractionated by HPLC and characterized by multidimensional mass spectrometry. Analysis of more then 300 sequences identified self-peptides derived from both intracellular and extracellular proteins revealing the variety of catabolic products transported by human lymph. Quantitative analysis established that at least some of these peptides are present in the circulating lymph in nanomolar concentration.

The peptidome, generated by physiological tissue catabolism and transported by the pre-nodal lymph, is in addition to the self-peptidome generated in endosomal compartment. Unlike self antigen processed by local or nodal APC, which mostly produce epitopes constrained by the endosomal processing activity, self antigens present in the lymph could derived from a wider variety of processing pathways; including caspases, involved in cellular apoptosis, and ADAM and other metalloproteinases involved in surface receptor editing, cytokines processing and matrix remodeling. Altogether, expanding the tissue-specific self-repertoire available for the maintenance of immunological tolerance.

Is bilirubin level in the drainage fluid an early and independent predictor of clinically relevant bile leakage after hepatic resection?

Variations in the definition of bile leakage after hepatic resection have prevented the identification of risk factors for early diagnosis and efficient management. The International Study Group of Liver Surgery (ISGLS) definition standardizes reporting of this complication. It was our aim in the present study to prospectively validate the ISGLS definition of bile leakage after hepatic resection. Furthermore, we sought to identify early predictors of clinically relevant bile leakage. A total of 265 patients who underwent elective hepatic resection were enrolled prospectively. Bilirubin concentrations were determined in the serum and drainage fluid until postoperative day 5. Risk factors of Grade B/C bile leakage were assessed by the use of univariate and multivariate analyses. Grade A, B, and C bile leakage was diagnosed in 23 (8.7%), 38 (14.3%), and 11 (4.1%) patients, respectively. The definition as well as severity grading of bile leakage correlated with the duration of drainage and intensive care unit and hospital stay. Perioperative mortality was 0% for Grade A, 5.2% for Grade B, and 45.4% for Grade C bile leakage (P < .0001). Multivariate analysis confirmed bilirubin concentration in the drainage fluid ≥2.4 mg/dL on postoperative day 2 (odds ratio 11.88; 95% confidence interval 5.33-26.49; P < .0001) and anatomic resection (odds ratio 3.59; 95% CI 1.08-11.97; P = .04) as independent predictors of clinically relevant bile leakage.

The ISGLS definition and severity grading of bile leakage after hepatic resection is clinically meaningful. Bilirubin concentration in the drainage fluid on postoperative day 2 is a strong predictor of clinically relevant bile leakage.

Does intravascular ultrasound provide clinical benefits for percutaneous coronary intervention with bare-metal stent implantation?

The role of intravascular ultrasound (IVUS) in percutaneous coronary interventions (PCI) is still controversial despite several previously published meta-analyses. A meta-analysis to evaluate the controversial role of IVUS-guided PCI with bare-metal stenting was performed and a previous published meta-analysis was re-evaluated in order to clarify the discrepancy between results of these studies. A systematic review was performed by an electronic search of the PubMed, Embase and Web of Knowledge databases and by a manual search of reference lists for randomized controlled trials published until April 2011, with clinical outcomes and, at least, six months of clinical follow-up. A meta-analysis based on the intention to treat was performed with the selected studies. Five studies and 1,754 patients were included. There were no differences in death (OR = 1.86; 95% CI = 0.88-3.95; p = 0.10), non-fatal myocardial infarction (OR = 0.65; 95% CI = 0.27-1.58; p = 0.35) and major adverse cardiac events (OR = 0.74; 95% CI = 0.49-1.13; p = 0.16). An analysis of the previous published meta-analysis strongly suggested the presence of publication bias.

There is no evidence to recommend routine IVUS-guided PCI with bare-metal stent implantation. This may be explained by the paucity and heterogeneity of the studies published so far.

Are microRNAs miR-1 , miR-133a , miR-133b and miR-208 dysregulated in human myocardial infarction?

MicroRNAs (miRNAs) are noncoding single-stranded RNA molecules that regulate gene expression in physiological functions, development and disease. In recent studies, three miRNAs have been described as muscle or cardiac specific: miR-1, miR-133, and miR-208, being involved in heart development and disease; but there are limited data on their role in human myocardial infarction (MI). We therefore analyzed their expression in human MI. Autopsy samples of infarcted heart tissue from 50 patients with MI, 8 healthy trauma victims and 9 fetuses that died in utero were included. miRNAs miR-1, miR-133a/b and miR-208 were analyzed using quantitative real-time polymerase chain reaction. miR-208 was upregulated, whereas miR-1 and miR-133a were downregulated in MI compared to healthy adult and fetal hearts. All four tested miRNAs were downregulated in fetal hearts compared to healthy adult hearts.

Our study showed the involvement of muscle- and/or cardiac-specific miRNAs miR-1, miR-133a/b and miR-208 in human MI. The most significant finding was upregulation of miR-208 and downregulation of miR-1 and miR-133a in MI compared to healthy adult hearts. Some patterns of miRNA expression were similar in MI and fetal hearts, supporting the concept of cardiac gene reprogramming in the remodeling of the heart.

Does clodronate inhibit tumor angiogenesis in mouse models of ovarian cancer?

Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations. Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis. Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density.

Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer.

Is childhood adversity associated with left basal ganglia dysfunction during reward anticipation in adulthood?

Childhood adversity increases the risk of psychopathology, but the neurobiological mechanisms underlying this vulnerability are not well-understood. In animal models, early adversity is associated with dysfunction in basal ganglia regions involved in reward processing, but this relationship has not been established in humans. Functional magnetic resonance imaging was used to examine basal ganglia responses to: 1) cues signaling possible monetary rewards and losses; and 2) delivery of monetary gains and penalties, in 13 young adults who experienced maltreatment before age 14 years and 31 nonmaltreated control subjects. Relative to control subjects, individuals exposed to childhood adversity reported elevated symptoms of anhedonia and depression, rated reward cues less positively, and displayed a weaker response to reward cues in the left globus pallidus. There were no group differences in right hemisphere basal ganglia response to reward cues or in basal ganglia response to loss cues, no-incentive cues, gains, or penalties.

Results indicate that childhood adversity in humans is associated with blunted subjective responses to reward-predicting cues as well as dysfunction in left basal ganglia regions implicated in reward-related learning and motivation. This dysfunction might serve as a diathesis that contributes to the multiple negative outcomes and psychopathologies associated with childhood adversity. The findings suggest that interventions that target motivation and goal-directed action might be useful for reducing the negative consequences of childhood adversity.

Can particulate extraction from the ascending aorta reduce neurologic injury in cardiac surgery?

This study examined whether extraction of particulate emboli using intra-aortic filtration could decrease neurologic outcomes. Patients (N = 582) were enrolled in a prospective, controlled study and alternately assigned to the therapy arm (n = 304; intra-aortic filtration) or control arm (n = 278). Preoperative, procedural, and postoperative data were collected. Neurologic examinations included the National Institutes of Health Stroke Scale, Glasgow Coma Scale, and memory tests. Investigators administering neurologic tests were blinded to the study arm. By the use of logistic regression and propensity matching, composite neurologic outcomes (transient ischemic attack, stroke, delirium, coma, and memory deficit) were evaluated. Patients in the filter group experienced a lower incidence of adverse neurologic outcomes than patients in the control group (4.3% vs 11.9%) (P<.001). There were significantly less transient ischemic attacks (0% vs 1.4%), delirium (3.0% vs 6.5%), and memory deficit (1.3% vs 6.2%). There were fewer strokes in the filter group compared with the control group (0.7% vs 2.2%), although the sample size was too small for a significant finding. Both groups experienced 1 coma outcome. The use of a filter was associated with an adjusted odds ratio of 0.375, implying that a patient who does not receive a filter is 2.7 times more likely to experience an adverse neurologic event. Logistic modeling also demonstrated that there are increasing chances of poor neurologic outcome with increasing age. The model indicates that there may be an increasing protective benefit from the filter with increasing age, although the interaction was not significant.

The extraction of particulate emboli using intra-aortic filtration resulted in decreased neurologic outcomes.

Is minimally invasive esophagectomy safe and effective following neoadjuvant chemoradiation therapy?

Minimally invasive esophagectomy (MIE) is technically demanding, and implementation has been hindered by a steep learning curve. Despite widespread concern about the successful performance of this procedure following neoadjuvant chemoradiotherapy (NACR) treatment, we hypothesized that safe and effective MIE could be performed in this setting. We reviewed our prospective database of patients undergoing MIE for esophageal cancer at our institution between January 2008 and February 2010. We analyzed the association of NACR on perioperative outcomes and compared them with those patients undergoing MIE without NACR. NACR was used in ≥T2 or N+ tumors. A total of 61 consecutive patients underwent a planned MIE. A complete MIE or hybrid procedure was performed in 58 patients (95%), while 3 patients were unresectable. Median age was 67 years (range 38-85). Anastomoses were performed in the cervical region in 47 patients (81%) while 11 patients had an anastomosis in the right chest. Serious complications included: 3 cervical anastomotic leaks (5%), 2 thoracic duct leaks (4%), 12 pneumonias (21%), 10 atrial fibrillations (18%), and 1 death in a patient not undergoing NACR. NACR was used in 41 patients. There was no significant difference in estimated blood loss (EBL), complications, or negative pathologic margins in patients undergoing NACR with MIE vs. MIE alone (P=NS). Median number of lymph nodes excised and PostOp LOS was 15 and 11 in patients undergoing NACR compared with 13 and 9 in those undergoing MIE alone (P=NS).

MIE is safe following NACR. Excellent results can be achieved with this operation in patients with advanced tumors.

Does diethyldithiocarbamate ( DEDC ) impair neuronal recovery following sciatic nerve injury in rats?

Diethyldithiocarbamate (DEDC) is a substituted dithiocarbamate that is metabolically interconvertible with disulfiram (Ant-abuse). In recent years DEDC has received considerable attention because of its clinical applications and potential role in mediating both the toxic and therapeutic actions of disulfiram which is frequently used for alcohol aversion therapy. DEDC is known for its multiplicity of action that exerts both pro- and antioxidant effects. In rodents DEDC has been shown to produce neuroprotective as well as neurotoxic effects. The purpose of this study was to examine the effect of DEDC on neurological recovery following sciatic nerve crush injury (SNCI) in rats. Adult female Wistar rats were subjected to SNCI with a haemostat under deep anaesthesia. The animals were orally treated with DEDC at the doses of 250 mg/kg, 500 mg/kg and 750 mg/kg body weight 1 hr before SNCI and then once daily for 60 days. The animals were observed for sciatic functional index (walking deficit), electrophysiological and histological changes. Vitamin E level was measured to deter-mine antioxidant status of sciatic nerve. Crush injury to the sciatic nerve resulted in a significant impairment of functional response which gradually recovered over a period of 22 days. Treatment of animals with DEDC caused a significant delay in functional recovery which was accompanied by poor histo-logical and electrophysiological outcome. Prooxidant effect of DEDC is quite evident from a significant decrease in vitamin E levels in both injured and uninjured sciatic nerves.

Our results demonstrate that exposure to DEDC adversely affects recovery from peripheral nerve injury. The delay may to some extent be attributed to DEDC induced oxidative stress.

Does tNF-alpha antagonist therapy improve insulin sensitivity in non-diabetic ankylosing spondylitis patients?

Since insulin resistance can promote endothelial dysfunction, and anti-TNF-α treatment improves endothelial function in ankylosing spondylitis (AS) patients, in the present study we sought to assess whether an infusion of the anti-TNF-α monoclonal antibody-infliximab may improve insulin sensitivity in non-diabetic AS patients. We assessed a series of 30 non-diabetic patients with AS attending hospital outpatient clinics who fulfilled the modified New York diagnostic criteria for AS. In all cases, the drug was given as an intravenous infusion in a saline solution over 120 minutes. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately before (time 0) and after infliximab infusion (time 120). At the time of the study only 8 (26.7%) of the 30 patients fulfilled definitions for insulin resistance as HOMA index was in most cases less than 2.29. Nevertheless, a statistically significant reduction in the HOMA values was observed when results found at time 0 (mean±SD: 1.72±1.22) were compared with those observed immediately after infliximab infusion (1.18±0.94) (p<0.001). The reduction in HOMA values was more important in those patients with the higher values of HOMA before infliximab infusion. Also, a significant improvement of insulin sensitivity was observed in most patients when QUICKI values before (0.37±0.04) and after infusion (0.39±0.04) were compared (p=0.004).

The present study shows that non-diabetic patients with AS on treatment with infliximab experience a rapid improvement of insulin sensitivity following administration of this drug.

Is atrial fibrillation a risk factor for contrast-induced nephropathy in patients with ST-elevation myocardial infarction?

Contrast-induced nephropathy (CIN) is an iatrogenic problem in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Atrial fibrillation (AF) may also contribute to impaired kidney function. Several factors may contribute to the development of CIN. In patients with STEMI, concomitant AF is associated with higher in-hospital/follow-up mortality and morbidity. Therefore, we aimed to investigate the relationship between AF and CIN developments. In this study, 650 consecutive STEMI patients treated with PPCI were enrolled. Patients with AF at admission who did not achieve a sinus rhythm during 48h after hospitalization were defined as AF patients. CIN was defined by an increase in serum creatinine by>25% or 0.5mg/dL within 72h following contrast media exposure. Our patients were divided into two groups based on whether they had AF, and although warfarin usage was different, the other parameters were similar between the groups. When our patients were grouped according to CIN development [group 1: CIN (+), group 2: CIN (-)], creatinine levels prior to PPCI (p=0.020), estimated glomerular filtration rate (eGFR) prior to PPCI (p<0.001), left ventricular ejection fraction (LVEF) (p=0.011), AF (p<0.001), and warfarin usage (p=0.016) were different between the two groups. We also performed multivariate logistic regression analyses and found that AF [odds ratio (OR), 6.945; 95% confidence interval (CI), 2.789-17.293; p<0.001], eGFR (OR, 0.973; 95% CI, 0.957-0.989; p=0.001), and LVEF (OR, 0.963; 95% CI, 0.935-0.991; p=0.010) independently predicted CIN development in patients with STEMI.

The risk factors for CIN are multifactorial and identifying high-risk patients is the most important step for prevention. In addition to traditional risk factors, AF can contribute to CIN development in patients with STEMI.

Dialectical behavior therapy: is outpatient group psychotherapy an effective alternative to individual psychotherapy?

This study evaluates a 12-month-duration adapted outpatient group dialectical behavior therapy (DBT) program for patients with a borderline personality disorder in an unselected, comorbid population. If the results of this approach are comparable with the outcome rates of a standard DBT program, the group approach can have several advantages over individual treatment. One advantage is the possibility of treating more patients per therapist. A pre-post design was used to measure the effectiveness of an outpatient group DBT. Data from the Beck Depression Inventory II, the Symptom Checklist 90-Revised, the State-Trait Anger Inventory, the State and Trait Anxiety Inventory, of 34 female patients (mean age, 32.65 years) were collected before and after a treatment period of 1 year. Overall, a significant reduction (P<.05) of depressive symptoms, suicidal thoughts, anxiety, and anger was experienced by the patients.

This study is a first attempt in showing that DBT in an outpatient group setting can be effective in reducing psychiatric complaints and therefore has several advantages, such as the opportunity to treat more patients at once.