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Ultrarapid capillary electrophoresis method for the determination of reduced and oxidized glutathione in red blood cells. We describe a very rapid high-performance capillary electrophoresis method for the separation and quantification of reduced (GSH) and oxidized (GSSG) glutathione in red blood cells. Two procedures for sample preparation have been compared, Microcon-10 membrane filtration and acid precipitation. The separation is obtained in an uncoated capillary using a high ionic strength borate buffer at pH 7.8. The intra-assay coefficients of variation (CVs%) are 1.53 and 1.66 for GSH and GSSG, respectively. The run is shorter than 90 s and the migration time is highly reproducible both for GSH (CV% 0.22) and GSSG (CV% 0.17). When the filtration step is used only GSH is found, whereas both GSH and GSSG are detectable after acid precipitation, suggesting that GSSG revealed after acid treatment may be an artefact due to GSH oxidation. Because of its good analytical performance this method could be used for routine red blood cell glutathione measurement in healthy or pathological conditions.

Visuospatial updating of reaching targets in near and far space. The brain constructs multiple representations of near and far space but it is unclear which spatial mechanism guides reaching across eye movements in near space. Retinocentric reaching representations are known to exist in parietal cortex, but must be updated during eye movements, in order to remain accurate. In contrast, non-retinal (e.g. muscle-centered) reaching plans in motor cortex do not require updating, and so may provide a more stable encoding mechanism. To test between these, we employed a behavioral test. Subjects briefly foveated a target (located at various depths in near and far space) looked peripherally, then reached toward its remembered location. Surprisingly, subjects did not use the stable non-retinal reaching plan (compared to controls without eye movements). Instead, the intervening eye movements induced a systematic pattern of reaching errors for targets at all depths consistent with updating in a retinal frame. We conclude that a common eye-centered updating mechanism prevails in programming arm movements in both near and far space.

Rugate notch filter fabricated by atomic layer deposition. A Rugate notch filter is fabricated by atomic layer deposition. By regulating the thickness ratio of TiO2 and Al2O3 in a nanoscale layer, the refractive index is tailored between the refractive indices of the two materials. With the method of equivalent refractive index, the continuously variable refractive index of the designed Rugate filter is dispersed into several discrete ones, so that it can be realized by the refractive index tailoring. To coincide with the thickness, the nanoscale layer is iteratively deposited in the equivalent layer. The experimental reflectance matches the designed one well, and the average reflectance is 86.7% (510-590 nm).

Time while waiting: patients' experiences of scheduled surgery. Research on patients' experiences of wait time for scheduled surgery has centered predominantly on the relative tolerability of perceived wait time and impacts on quality of life. We explored patients' experiences of time while waiting for three types of surgery with varied wait times--hip or knee replacement, shoulder surgery, and cardiac surgery. Thirty-two patients were recruited by their surgeons. We asked participants about their perceptions of time while waiting in two separate interviews. Using interpretative phenomenological analysis (IPA), we discovered connections between participant suffering, meaningfulness of time, and agency over the waiting period and the lived duration of time experience. Our findings reveal that chronological duration is not necessarily the most relevant consideration in determining the quality of waiting experience. Those findings helped us create a conceptual framework for lived wait time. We suggest that clinicians and policy makers consider the complexity of wait time experience to enhance preoperative patient care.

Influence of assay conditions on ELISA determinations of anti-DNA antibodies. The influence of assay conditions on anti-DNA determinations by an enzyme-linked immunosorbent assay (ELISA) was investigated to evaluate the detection of various DNA antigenic specificities. Among 4 monoclonal anti-DNA antibodies of MRL-lpr/lpr strain origin, 2 showed higher titers in 100 mM NaCl-50 mM Tris, pH 7.5 (Tris-NaCl) than in phosphate-buffered saline (PBS). The determination of 'polyspecificity' for these monoclonal products also depended on the set of conditions used for assay with inhibitory activity of polynucleotides differing in the 2 buffers. The buffer effects were not confined to the monoclonal antibodies as increases in anti-DNA titers were demonstrated for certain SLE patient sera when assayed in Tris-NaCl rather than PBS; sera of MRL-lpr/lpr mice showed an opposite effect, however, with enhancement of anti-DNA activity by PBS. These results suggest that the representation of antigenic sites on DNA may be variably affected by the conditions of assay, altering quantitative and qualitative assessment of this important serological marker.

[Correlation Between Testosterone and Metabolic Index in Male Patients with Type 2 Diabetes Mellitus]. To determine the effect of testosterone on serum glucose,lipid,uric acid and insulin metabolism in male patients with type 2 diabetes mellitus. A total of 205 male patients with type 2 diabetes participated in this study. They were divided into two groups: those with normal testosterone (TT) (TT≥12 nmol/L,n=135) and those with low TT (TT<12 nmol/L,n=70). Their body mass,waist circumference (WC),body mass index (BMI),blood glucose, total cholesterol (TC), triglycerides (TG), serum uric acid (SUA),insulin,testosterone,luteinizing hormone (LH),follicle stimulating hormone (FSH),estradiol (E2),and sex hormone binding globulin (SHBG) were measured. The insulin resistance index (HOMA-IR) of the participants was calculated using a homeostasis model. Sex hormone levels were compared across the four groups divided by HOMA-IR and SUA in quartiles. The participants with low TT had higher age,SUA,BMI,WC,and HOMA-IR (P<0.05). TT and SHBG decreased with increased HOMA-IR index (P<0.05). TT,LH,FSH and SHBG decreased with increased SUA (P<0.05). The logistic regression model showed that SUA and BMI were predictors of hypogonadism. Male patients with type 2 diabetes who are prone to hypogonadism, are possibly related to increased SUA and obesity.

Determining the optimal method for proteinuria detection in chronic spinal cord injury. A retrospective analysis. The objective of this study is to determine whether dipstick protein analysis (DSP) or random urine protein:creatinine ratios (UPC) are accurate in predicting clinical proteinuria in the chronic spinal cord injury (SCI) population. A retrospective analysis was performed in 219 veterans with SCI, comparing DSP and 24-h urine protein excretion. Sensitivity, specificity, predictive values (PV) and receiver-operator characteristic (ROC) curves of DSP in predicting clinical proteinuria were calculated with and without correction for specific gravity (SG). A prospective study was also performed in 62 SCI patients, comparing the UPC and 24-h urines. Sensitivity, specificity, PV and ROC curves of UPC in predicting clinical proteinuria were calculated. Any level of positive DSP had high specificity, but low sensitivity, for detecting the presence of clinical proteinuria. ROC curves of DSP for identifying clinical proteinuria yielded area under the curve of 0.749 (95% confidence interval 0.699-0.794), and adjustment for SG did not significantly improve accuracy. A UPC of <0.3 was sensitive with a high negative PV for ruling out clinical proteinuria, whereas a ratio >0.8 was specific with a high positive PV. A UPC between 0.3-0.8 had an intermediate sensitivity and specificity. Urine collections of 24-h are still needed in the chronic SCI population for accurate detection of clinically significant proteinuria. DSP may not reliably detect low-grade clinical proteinuria, whereas a UPC below 0.3 may be used to rule out clinical range proteinuria.

Single-molecule junctions based on nitrile-terminated biphenyls: a promising new anchoring group. We present a combined experimental and theoretical study of the electronic transport through single-molecule junctions based on nitrile-terminated biphenyl derivatives. Using a scanning tunneling microscope-based break-junction technique, we show that the nitrile-terminated compounds give rise to well-defined peaks in the conductance histograms resulting from the high selectivity of the N-Au binding. Ab initio calculations have revealed that the transport takes place through the tail of the LUMO. Furthermore, we have found both theoretically and experimentally that the conductance of the molecular junctions is roughly proportional to the square of the cosine of the torsion angle between the two benzene rings of the biphenyl core, which demonstrates the robustness of this structure-conductance relationship.

Energetics of beta-oxidation. Reduction potentials of general fatty acyl-CoA dehydrogenase, electron transfer flavoprotein, and fatty acyl-CoA substrates. We have determined reduction potentials for porcine mitochondrial general fatty acyl-CoA dehydrogenase (GAD) and electron transfer flavoprotein (ETF) using an anaerobic spectroelectrochemical titration method. Computer simulation techniques were used to analyze the absorbance data. Nernst plots of the simulated data gave E'0, 7.1, quinone/semiquinone = -0.014 V and E'0, 7.1, semiquinone/hydroquinone = -0.036 V for ETF and E'0, 7.1, quinone/semiquinone = -0.155 V and E'0, 7.1, semiquinone/hydroquinone = -0.122 V for GAD. Using these techniques we have also determined a conditional reduction potential of -0.156 V for the chromophore producing fatty acyl-CoA substrate beta-2-furylpropionyl-CoA. From this value and our previous determination of the equilibrium constant for the transhydrogenation reaction between beta-2-furylpropionyl-CoA and the oxidized substrate crotonyl-CoA (Keq = 10.4), we have determined a reduction potential of -0.126 V for the butyryl-CoA/crotonyl-CoA couple. In light of the structural similarity between butyryl-CoA and octanoyl-CoA, the optimal substrate for GAD, the reduction potential for octanoyl-CoA should be similar to that for butyryl-CoA; i.e. fatty acyl-CoA substrates and GAD are essentially isopotential. The ability of octanoyl-CoA to reduce GAD quantitatively (Keq = 9.0) poses a dilemma in light of the nearly equal reduction potentials. We postulate that the stable charge-transfer complex formed between enzyme and optimal product is significantly lower in energy than enzyme and product and thus is responsible for pulling the reaction toward completion.

Opioid receptors regulate the extinction of Pavlovian fear conditioning. Rats received a single pairing of an auditory conditioned stimulus (CS) with a footshock unconditioned stimulus (US). The fear (freezing) that had accrued to the CS was then extinguished. Injection of naloxone prior to this extinction significantly impaired the development of extinction. This impairment was mediated by opioid receptors in the brain and was not observed when naloxone was injected after extinction training. Finally, an injection of naloxone on test failed to reinstate extinguished responding that had already accrued to the CS. These experiments show that opioid receptors regulate the development, but not the expression, of fear extinction and are discussed with reference to the roles of opioid receptors in US processing, memory, and appetitive motivation.

Proteome analysis of responses to ascochlorin in a human osteosarcoma cell line by 2-D gel electrophoresis and MALDI-TOF MS. Ascochlorin is a prenyl-phenol compound that was isolated from the fungus Ascochyta viciae. Ascochlorin reduces serum cholesterol and triglyceride levels, suppresses hypertension and tumor development, and ameliorates type I and II diabetes. Here, to better understand the mechanisms by which ascochlorin regulates physiological or pathological events and induces responses in the pharmacological treatment of cancer, we performed differential analysis of the proteome of the human osteosarcoma cells U2OS in response to ascochlorin. In addition, we established the first two-dimensional map of the U2OS proteome. The U2OS cell proteomes with and without treatment with ascochlorin were compared using two-dimensional electrophoresis, matrix-assisted laser desorption/ionization mass spectrometry and bioinformatics. The largest differences in expression were observed for the epidermal growth factor receptor (4-fold decrease), ribulose-5-phosphate-epimerase (13-fold decrease), ATP-dependent RNA helicase (8-fold decrease), and kelch-like ECH-associated protein 1 (6-fold decrease). The abundance of heterogeneous nuclear ribonucleoprotein L and minichromosome maintenance protein 7 increased 12- and 8.2-fold, respectively. In addition, Erk 2 was increased 3-fold in U2OS cells treated with ascochlorin. The expression of some selected proteins was confirmed by western blotting, zymography and RT-PCR analysis.

Changes in right ventricular longitudinal function: primary mitral and concomitant tricuspid valve repair. To evaluate the impact of concomitant tricuspid valve (TV) repair on the right ventricular (RV) function postoperatively and within the 6 months following degenerative mitral valve (MV) repair. The prospective study included 37 patients (mean age 57.32 ± 2.13 years) with severe MV regurgitation due to primary MV prolapse. Nineteen underwent successful MV repair (TV(-) group). Additional TV repair due to moderate-to-severe TV regurgitation was performed in 18 (TV(+) group). Two-dimensional (2D) speckle-tracking and tissue Doppler echocardiography was performed for all patients before surgery and 7 days and 6 months after surgery. Preoperative dimensions and indices of RV longitudinal function did not differ between the groups (right ventricle end-diastolic diameter (RVEDD) was 33.53 ± 0.94 mm vs. 34.67 ± 1.72 mm, tricuspid annular systolic motion (S') was 15.06 ± 0.85 cm/s vs. 16.0 ± 1.27 cm/s, tricuspid annular plane systolic excursion (TAPSE) was 24.02 ± 1.06 mm vs. 22.4 ± 1.36 mm, respectively; p>0.05). RVEDD decreased significantly and did not change within the follow-up in the TV(-) group. In the TV(+) group, RVEDD decreased early after surgery and more markedly six months later in comparison to the TV(-) group. Indices of RV systolic longitudinal function decreased early after surgery and had a tendency to increase after six months in both groups. Regional longitudinal strains of the lateral RV wall decreased early after surgery and improved within the six months in the TV(-) group and did not change significantly in the TV(+) group. Additional TV repair in degenerative MV repair more markedly reduces RV dimensions and does not have a negative impact on RV systolic function in comparison to an isolated MV repair although these conclusions are of limited value due to the lack of a control group.

The duration of orthodontic treatment. Characteristics of the patient, the treatment plan, and the practitioner's office were examined to evaluate causes for variation in the duration of orthodontic treatment. From six offices 118 patients were evaluated. All patients were treated in a single phase with fixed appliances. Appliances were worn for an average of 23.1 months. The mean duration for offices ranged from 19.4 to 27.9 months. Thirty-eight percent of the patients had extractions, and 32% wore headgear. Fifty percent of the variation in treatment duration among patients was explained by a five-step multiple regression equation. The variables entering this equation were (1) number of extracted premolars, (2) number of broken appointments, (3) pretreatment mandibular plane angle, (4) pretreatment ANB angle, and (5) pretreatment Salzmann Index. Observations within each office suggested that the time spent by individual clinicians in detailed finishing, which would not be detected by measures such as the Salzmann Index, was an important source of unexplained variation in treatment duration.

Older adults encode--but do not always use--perceptual details: intentional versus unintentional effects of detail on memory judgments. Investigations of memory deficits in older individuals have concentrated on their increased likelihood of forgetting events or details of events that were actually encountered (errors of omission). However, mounting evidence demonstrates that normal cognitive aging also is associated with an increased propensity for errors of commission--shown in false alarms or false recognition. The present study examined the origins of this age difference. Older and younger adults each performed three types of memory tasks in which details of encountered items might influence performance. Although older adults showed greater false recognition of related lures on a standard (identical) old/new episodic recognition task, older and younger adults showed parallel effects of detail on repetition priming and meaning-based episodic recognition (decreased priming and decreased meaning-based recognition for different relative to same exemplars). The results suggest that the older adults encoded details but used them less effectively than the younger adults in the recognition context requiring their deliberate, controlled use.

[Verotoxin production and adhesion genes of E. coli isolates from commercial poultry and psittacines: detection by PCR]. A total of 101 E. coli isolates from commercial poultry, companion psittacine birds and psittacine faecal samples were tested by the PCR technique for the presence of genes coding for verotoxin (slt I and slt II) production and adhesion to intestinal cells (eaeA gene). The O 157:H 7 strain EDL 933 served as positive control. Verotoxin production was assessed in Vero cell cultures. One E. coli isolate showed both alpha-haemolysis and enterohaemolysis (haemolysin production) but no gene for verotoxin production. All other isolates were negative for slt I, slt II and eaeA genes.

Potential role of interleukin-1 as the trigger for diffuse intravascular coagulation in acute nonlymphoblastic leukemia. Abnormalities of coagulation are common in patients with acute nonlymphoblastic leukemia, although the mechanisms involved are unclear, except in a few cases. To investigate the pathogenesis of this coagulopathy, suspensions of purified leukemic cells were prepared and tested for procoagulant activity. Neither the leukemic cells nor their supernatants directly accelerated the clotting of plasma. Since the leukemic cells did not possess direct procoagulant activity, their ability or inability to elaborate a mediator of cellular coagulant properties, interleukin-1, was studied. Leukemic cells from patients with coagulopathy elaborated interleukin-1, and addition of phytohemagglutinin increased interleukin-1 release. In contrast, no interleukin-1 was released, before or after stimulation with phytohemagglutinin, from leukemic cells from patients without coagulopathy. Leukemic cells from another group of patients with abnormalities of coagulation released interleukin-1 only after phytohemagglutinin treatment. In terms of the coagulation mechanism, interleukin-1 containing supernatants from leukemic cell cultures induced the procoagulant receptor tissue factor, a co-factor in the initiation of coagulation, on the endothelial cell surface. There was coordinate suppression of the anticoagulant endothelial cell receptor thrombomodulin, a co-factor for the antithrombotic protein C pathway. Antibody to interleukin-1 prevented these changes in cellular coagulant properties. Taken together, these changes result in a shift in the balance of endothelial cell coagulant properties to an activated state in which mechanisms promoting procoagulant reactions on the vessel surface predominate. Synthesis and release of the mediator interleukin-1 by leukemic cells thus defines a new mechanism through which malignant cells can potentially activate the coagulation mechanism.

Venous Doppler velocimetry in relationship to central venous pressure and heart rate during hypoxia in the ovine fetus. Characteristic changes in ductus venosus (DV) blood velocity and pulsations in the umbilical vein (UV) have been described during imminent fetal asphyxia. The aim of this study was to examine fetal venous blood velocity in relationship to pressure gradient across the DV during hypoxia in a fetal lamb preparation. In general anesthesia, a cesarean section was performed on seven pregnant ewes, the fetus was exteriorized and put into a heated waterbath with uninterrupted umbilical circulation. Pressure measurements in the UV and inferior vena cava (IVC) were performed with the catheter tips on both sides of the DV. Fetal hypoxemia was induced by giving the ewe 12% oxygen in inhaling air. Pressure across the DV and Doppler velocimetry were repeatedly measured during hypoxemia. Blood velocity was recorded in the DV and UV by Doppler ultrasound. Before hypoxia the median pressure gradient across the DV was in systole 1 mmHg and 0.31 mmHg in end-diastole and during hypoxemia 1.5 mmHg and zero, respectively. The pressure difference across the DV was constant during hypoxemia irrespective of the presence of umbilical venous pulsations or heart rate. IVC-pressure was greatly influenced by fetal heart rate (FHR). A small but linear fall in systolic IVC pressure was seen with increasing FHR. In end-diastole the IVC pressure changed in a parabolic fashion, with increasing pressure during brady- and tachycardia. Pulsations in the UV also showed a parabolic relationship to FHR and central venous pressure. DV end-systolic and end-diastolic blood velocity changed during hypoxemia in direct relationship to FHR and central venous pressure, but without direct relationship to fetal blood gases. The pressure gradient across the DV is constant during hypoxemia. Changes in central and umbilical venous pressure are directly related to FHR. Umbilical venous and DV blood velocity changed in direct relationship to FHR and central venous pressure.

[Insulin receptor function in subjects with above-normal body weight]. The insulin receptor binding ability was studied in 26 persons with above normal body mass (15 women and 11 men), mean age 44.15 +/- 10.1 years without family history of diabetes mellitus. According to the degree of obesity they were classified into 3 groups. In the persons with I-II degree of obesity parallel with the strongly reduced number of insulin receptors (total and the high affinity) an increase of the receptors affinity appears as a compensatory mechanism which ensures appropriate insulin receptor binding. In the persons with III-IV degree of obesity the number of insulin receptors is strongly reduced but the receptor affinity does not differ from that of the controls with normal body mass. The receptor changes in the persons with excessive obesity are similar to those found by the authors in patients with newly discovered non-insulin dependent diabetes mellitus. This allows the suggestion that these persons are in a potential risk of developing diabetes mellitus.

[Cardiac arrest following blunt chest injury. Emergency thoracotomy without ifs or buts?]. In German-speaking countries, most serious thoracic injuries are attributable to the impact of blunt force; they are the second most frequent result of injury after head injury in polytrauma patients with multiple injuries. Almost one in every three polytraumatized patients with significant chest injury develops acute lung failure, and one in every four, acute circulatory failure. The acute circulatory arrest following serious chest injury involves a high mortality rate, and in most cases it reflects a tension pneumothorax, cardiac tamponade, or hemorrhagic shock resulting from injury to the heart or one of the large vessels close to it. Brisk drainage of tension pneumothorax and adequate volume restoration are therefore particularly important in resuscitation of multiply traumatized patients, as are rapid resuscitative thoracotomy to allow direct heart massage, drainage of pericardial tamponade, and control of hemorrhage. However the probability of survival described in the literature is very low for patients sustaining severe chest trauma with acute cardiac arrest. The case report presented here describes a female polytrauma patient who suffered an acute cardiac arrest following cardiac tamponade after admission in the emergency department and who survived without neurological deficits after an emergency thoracotomy. Selections from the topical literature can help the treating physician in the emergency department in making decisions on whether an emergency thoracotomy is indicated after a blunt chest injury and on the procedure itself.

Distribution and abundance of uncultured heterotrophic flagellates in the world oceans. Heterotrophic flagellates play fundamental roles in marine ecosystems as picoplankton grazers. This recognized importance contrasts with our ignorance of the taxonomic composition of this functional group, which remains mostly unidentified by microscopical and culturing approaches. Recent molecular marine surveys based on 18S rDNA genes have retrieved many sequences unrelated to cultured organisms and marine stramenopiles were among the first reported uncultured eukaryotes. However, little is known about the organisms corresponding to these sequences. Here we determine the abundance of several marine stramenopile lineages in surface marine waters using molecular probes and fluorescent in situ hybridization. We show that these protists are free-living bacterivorous heterotrophic flagellates. They were widely distributed, occurring in the five world oceans, and accounted for a significant fraction (up to 35%) of heterotrophic flagellates in diverse geographic regions. A single group, MAST-4, represented 9% of cells within this functional assemblage, with the intriguing exception of polar waters where it was absent. MAST-4 cells likely contribute substantially to picoplankton grazing and nutrient re-mineralization in vast areas of the oceans and represent a key eukaryotic group in marine food webs.

Anxiolytic-like effects in rats produced by ventral pallidal injection of both N- and C-terminal fragments of substance P. Prior studies have shown that the neurokinin substance P (SP) has anxiolytic-like effects when administered into the nucleus basalis (NB) area of the rat ventral pallidum. The present work was performed to examine whether the anxiolytic effects of SP in the nucleus basalis can be assigned its amino (N)- or carboxy (C)-terminal moiety. Using the elevated plus-maze model of anxiety in combination with unilateral injection of N-terminal SP(1-7) or C-terminal SP(7-11) into the NB region, we found that the treatment with either SP-fragment increased the number of entries into and time spent on the open arms as well as excursions into the end of the open arms, indicative of an anxiolytic-like profile. Furthermore, the effective doses of SP(1-7) (0.67 ng) and SP(7-11) (0.45 ng) were equimolar to the dosage of the whole SP molecule (1 ng), which was effective to reduce anxiety. Thus, the results support earlier findings that ventral pallidal injection of SP has anxiolytic-like effects and provide new evidence that fragments of SP, representing the N- and C-terminal domain of the peptide can reduce fear-parameters at a concentration similar to that of the parent peptide.

Lipidation increases antiviral activities of coronavirus fusion-inhibiting peptides. Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies. Cholesterol or palmitate adducts increased antiviral potencies up to 1000-fold. Antiviral effects were evident after S proteolytic cleavage, implying that lipid conjugates affixed the peptides at sites of protease-triggered fusion activation. Unlike lipid-free peptides, the lipopeptides suppressed CoV S protein-directed virus entry taking place within endosomes. Cell imaging revealed intracellular peptide aggregates, consistent with their endocytosis into compartments where CoV entry takes place. These findings suggest that lipidations localize antiviral peptides to protease-rich sites of CoV fusion, thereby protecting cells from diverse CoVs.

Quality and price--impact on patient satisfaction. The purpose of this paper is to synthesize existing quality-measurement models and applies them to healthcare by combining a Nordic service-quality with an American service performance model. Results are based on a questionnaire survey of 1,298 respondents. Service quality dimensions were derived and related to satisfaction by employing a multinomial logistic model, which allows prediction and service improvement. Qualitative and empirical evidence indicates that customer satisfaction and service quality are multi-dimensional constructs, whose quality components, together with convenience and cost, influence the customer's overall satisfaction. The proposed model identifies important quality and satisfaction issues. It also enables transitions between different responses in different studies to be compared.

Selective zirconium dioxide-based enrichment of phosphorylated peptides for mass spectrometric analysis. Due to the dynamic nature and low stoichiometry of protein phosphorylation, enrichment of phosphorylated peptides from proteolytic mixtures is often necessary prior to their characterization by mass spectrometry. Several phosphopeptide isolation strategies have been presented in the literature, including immobilized metal ion affinity chromatography. However, that technique suffers from poor selectivity and reproducibility. Recently, titanium dioxide-based columns have been successfully employed for phosphopeptide enrichment by several research groups. Here, we present, to our knowledge, the first demonstration of the utility of zirconium dioxide microtips for phosphopeptide isolation prior to mass spectrometric analysis. These microtips display similar overall performance as TiO2 microtips. However, more selective isolation of singly phosphorylated peptides was observed with ZrO2 compared to TiO2 whereas TiO2 preferentially enriched multiply phosphorylated peptides. Thus, these two chromatographic materials possess complementary properties. For alpha- and beta-casein, Glu-C digestion provided no evident advantage compared to trypsin digestion when combined with TiO2 or ZrO2 phosphopeptide enrichment.

Evaluation of the membrane lipid selectivity of the pea defensin Psd1. Psd1, a 46 amino acid residues defensin isolated from the pea Pisum sativum seeds, exhibits anti-fungal activity by a poorly understood mechanism of action. In this work, the interaction of Psd1 with biomembrane model systems of different lipid compositions was assessed by fluorescence spectroscopy. Partition studies showed a marked lipid selectivity of this antimicrobial peptide (AMP) toward lipid membranes containing ergosterol (the main sterol in fungal membranes) or specific glycosphingolipid components, with partition coefficients (K(p)) reaching uncommonly high values of 10(6). By the opposite, Psd1 does not partition to cholesterol-enriched lipid bilayers, such as mammalian cell membranes. The Psd1 mutants His36Lys and Gly12Glu present a membrane affinity loss relative to the wild type. Fluorescence quenching data obtained using acrylamide and membrane probes further clarify the mechanism of action of this peptide at the molecular level, pointing out the potential therapeutic use of Psd1 as a natural antimycotic agent.

The utility of the additive EuroSCORE, RIFLE and AKIN staging scores in the prediction and diagnosis of acute kidney injury after cardiac surgery. Acute kidney injury (AKI) following cardiac surgery is a complication associated with high rates of morbidity and mortality. We compared staging systems for the diagnosis of AKI after cardiac surgery, and assessed pre-operative factors predictive of post-operative AKI. Clinical data, surgical risk scores, procedure and clinical outcome were obtained on all 4,651 patients undergoing cardiac surgery to the Royal Infirmary of Edinburgh between April 2006 and March 2011, of whom 4,572 had sufficient measurements of creatinine before and after surgery to permit inclusion and analysis. The presence of AKI was assessed using the AKIN and RIFLE criteria. By AKIN criteria, 12.4% of the studied population developed AKI versus 6.5% by RIFLE criteria. Any post-operation AKI was associated with increased mortality from 2.2 to 13.5% (relative risk 7.0, p < 0.001), and increased inpatient stay from a median of 7 (IQR 4) to 9 (IQR 11) days (p < 0.05). Patients identified by AKIN, but not RIFLE, had a mean peak creatinine rise of 34% from baseline and had a significantly lower mortality compared to RIFLE-'Risk' AKI (mortality 6.1 vs. 9.7%; p < 0.05). Pre-operative creatinine, diabetes, NYHA Class IV dyspnoea and EuroSCORE-1 (a surgical risk score) all predicted subsequent AKI on multivariate analysis. EuroSCORE-1 outperformed any single demographic factor in predicting post-operative AKI risk, equating to an 8% increase in relative risk for each additional point. AKI after cardiac surgery is associated with delayed discharge and high mortality rates. The AKIN and RIFLE criteria identify patients at a range of AKI severity levels suitable for trial recruitment. The utility of EuroSCORE as a risk stratification tool to identify high AKI-risk subjects for prospective intervention merits further study.

[Effect of schistosomiasis control projects in Hexi Reservoir on Oncomelania snail control]. To evaluate the effect of schistosomiasis control projects in Hexi Reservoir on Oncomelania hupensis snail control. The canal hardening + main water system widening + the overflow dam project, the concrete slope protection, the banking and reclamation + concrete slope protection project, the environment reform project, and the comprehensive treatment were implemented in the tail area, the hydro-fluctuation belt, the rainwater harvesting zoon of the upstream area, the dam area, and the downstream area of the reservoir, respectively. The changes of the snail situation were investigated before and after the construction of the reservoir, and the snail control effects of the schistosomiasis control projects in different parts of the reservoir were analyzed. There were no Oncomelania snails found 3 years in the bottom area, dam area, hydro-fluctuation belt, tail region and downstream of the dam after the construction and storage of the reservoir and the implementation of the schistosomiasis control projects. In the rainwater harvesting zoon of the upstream area, the density of living snails decreased from 0.620 4 snails/0.1 m2 in 2009 to 0.113 2 snails/0.1 m2 in 2013, but the snail area still remained. The schistosomiasis control projects in Hexi Reservoir have effectively prevented the diffusion of Oncomelania snails from the rainwater harvesting zone of the upstream area to the dam area, and they are effective in the snail control.

Evaluation of therapy response in children with untreated malignant lymphomas using technetium-99m-sestamibi. The aim of this study was to investigate the relationship between 99mTc-sestamibi accumulation in tumors and response to chemotherapy in children with untreated malignant lymphomas. Twenty-four children with malignant lymphoma (16 with Hodgkin's disease and 8 with non-Hodgkin's lymphoma) were studied with 201Tl and then with 99mTc-sestamibi scintigraphy before any therapeutic intervention. Visual and quantitative interpretation of 201Tl and 99mTc-sestamibi scans were performed. Visual uptake scores > or = 2+ were considered positive studies for 201Tl and 99mTc-sestamibi scintigraphy. Remission rates were evaluated at the end of induction therapy; patients were then followed clinically for 1-2 yr. All 17 patients who had positive 99mTc-sestamibi scans subsequently had a complete response to chemotherapy; all seven patients who had negative 99mTc-sestamibi scans subsequently had partial or no response to chemotherapy, irrespective of the lymphoma type. The mean tumor-to-background ratios of patients with complete response and with partial or no response were 1.395 +/- 0.2 and 1.031 +/- 0.05 (p = 0.0002), respectively. Thallium-201 scintigraphy results were not related to the response to chemotherapy. Technetium-99m-sestamibi scintigraphy can provide information predicting the response to chemotherapy in patients with malignant lymphoma.

Expression and regulation of retinoid-inducible gene 1 (RIG1) in breast cancer. Retinoid-inducible gene I (RIG1) is a growth regulator protein that exhibits activities to suppress cellular growth and induce cellular differentiation and apoptosis. This study analyzed the expression and regulation of RIG1 in breast cancer cells in vitro and in vivo. Expression of RIG1 RNA in breast cancer tissues was analyzed using RNA in situ hybridization. Regulation of RIG1 expression by 17beta-estradiol (E2) was analyzed by semi-quantitative reverse transcription polymerase chain reaction. RIG1 expression in 47 breast cancer tissues was detected mostly in the cytoplasm and in some nuclei. Levels of both cytoplasmic and nuclear RIG1 mRNA were significantly lower in 20 estrogen receptor-positive (ER+) than in 27 ER-negative (ER-) tissues (p < 0.05), in 20 progesterone receptor-positive (PR+) than in 27 PR-negative (PR-) tissues (p < 0.01), and in 14 ER+/PR+ than in 21 ER-/PR-tissues (p < 0.05). Basal levels of RIG1 and ER mRNA were inversely related between ER+ (MCF-7 WS8 and ZR75-1) and ER- (ZR-75-30) breast cancer cells. E2 (1 nM) treatment for two days suppressed RIG1 mRNA levels in MCF-7 WS8 and ZR-75-1 cells, but not in the ER- ZR-75-30 cells. The E2-mediated down-regulation of RIG1 expression was time- and concentration-dependent in ZR-75-1 cells. The negative association between RIG1 and ER expression in breast cancer tissues and down-regulation of RIG1 by E2 in breast cancer cells in vitro suggest that RIG1 expression is negatively regulated by E2 through activation of the ER in ER+ breast cancer cells.

Outcome after accidental food bolus-induced esophageal perforation. Food bolus-induced esophageal perforation is much more seldom than iatrogenic and emetic esophageal rupture. We present results from a non-operative treatment approach as well as long-term functional outcome. Medical records of 10 consecutive patients with food bolus-induced esophageal perforation from October 2007 to May 2015 were retrospectively registered in a database. Six patients developed perforation related to endoscopic removal of impacted food, and four during esophageal passage of bone, meat or bread. Treatment was sealing the perforation by stenting (n = 7) with (n = 4) or without (n = 3) chest tube drainage, chest tube drainage (n = 1), observation (n = 1) and gastroesophageal resection (n = 1) because of concomitant emesis of gastric effluent. After median 51 months nine patients reported about dysphagia, fatigue and health-related quality of life. Ten patients aged median 62.5 years (range 30-85) stayed in our hospital for 12 days (5-68 days). There was no treatment-related mortality. Nine patients were alive 63 months (18-126) after perforation. Five needed restenting (leakage, migration, impacted stent), two had drainage of a mediastinal abscess, one patient developed a transient esophagobronchial fistula. Dysphagia score was 0 (0-1). One patient developed dysphagia for some solid food. Scores for fatigue and HRQoL was similar to a Norwegian reference population. Treatment mainly with a non-operative approach occurred without mortality. Complications were handled by restenting and abscess drainage. Functional result for dysphagia was excellent. Interesting results on fatigue and HRQoL must be interpreted with caution because of a limited patient material.

Hormone replacement therapy in women treated for gynaecological malignancy. Can we prescribe hormone replacement therapy (HRT) safely for women, with postmenopausal complaints who were treated for a gynaecological malignancy? Only three retrospective studies have investigated this issue in endometrial cancer patients. No recurrences or deaths occurred in these treated groups. However, the physician introduced bias through the selection of favourable groups. At present, combined estrogen and progestogen therapy is probably not contra-indicated in endometrial cancer stage I and probably also not in stage II, although so far there is only circumstantial evidence. Squamous cell cancers of the cervix, vulva, and vagina are unlikely to be influenced by HRT. In the only study available of women with ovarian cancer, < or = 50 years, estrogen replacement therapy did not have a negative influence on (disease-free) survival. According to the data currently available, no evidence exists that HRT adversely influences survival and overall survival after treatment for ovarian cancer. In general, adenocarcinomas of the cervix and leiomyosarcomas of the uterus may be managed such as the adenocarcinomas of the uterus. During the last 25 years, HRT has been shown to substantially reduce the risk of cardiovascular diseases, osteoporotic fractures and colon carcinoma. On the other hand there is a significant increase of the risk in breast cancer with prolonged use of > 5 years. Re-evaluation of the current view that HRT should no be given to women treated for a gynaecological malignancy is strongly warranted after evaluating the advantages and the disadvantages of HRT use in each individual patient. Long-term HRT in women treated for a gynaecological cancer must be based on the medical history of the individual patient (and her family).

The comprehensive care rounds: facilitating multidisciplinary communication among caregivers of complex patients in the neonatal intensive care unit. Care of the very sick infant can be complicated by extraneous factors that challenge the cohesiveness of the health care team. Chaos results from low levels of professional agreement and certainty about outcomes and manifests in stress and miscommunication among care providers. This milieu is fertile ground for errors of commission and omission. Effective communication and collaboration are recognized as essential for reducing medical errors in such stressful environments. This article describes a multidisciplinary conference, the Comprehensive Care Rounds, at a neonatal intensive care unit of a Magnet-recognized midwestern pediatric hospital. The Comprehensive Care Round provides a forum for open communication among team members and builds on the hospital's efforts at systems approach to developing a culture of safety and quality.

Human papillomavirus type spectrum in normal skin of individuals with or without a history of frequent sun exposure. Cutaneous human papillomavirus (HPV) has been widely detected in healthy skin. Previous studies have found that UV radiation can activate several HPV types, and a possible role for cutaneous HPV in the development of non-melanoma skin cancer has been suggested. This study investigated the prevalence and type-spectrum of cutaneous HPV in relation to UV radiation by studying forehead skin swab samples from 50 healthy males frequently exposed to the sun and 50 healthy males who were not frequently exposed to the sun. A questionnaire including ethnic background of the participants, history of cancers and a self-assessment of sun-exposure was also conducted and analysed. PCR with the FAP primer pair was carried out to detect HPV DNA in samples. HPV prevalence was higher in individuals who spent more time outdoors and in individuals with a history of skin cancers (P=0.044 and P=0.04, respectively). Furthermore, individuals wearing sunglasses as a means of sun protection had a lower prevalence of HPV (P=0.018). Interestingly, HPV-76 was only detected in the group without frequent sun-exposure (P=0.001). These results suggest that increased UV radiation exposure may be a factor leading to a difference in prevalence of cutaneous HPV types.

Adequacy of pediatric triage. To assess the adequacy of the pediatric triage system in an acute care general hospital. All children younger than 14 years of age who presented with a primary medical condition to the accident and emergency department (ED) during January to March 2009 were recruited. Suitability of the triage system was assessed according to the vital parameters taken and the priority code assigned. Triage workload was assessed from the number of children presenting to ED and the timing of presentation. Of 2269 children presenting to ED, 1617 (71.3%) were younger than 5 years, and 883 (38.9%) were younger than 2 years. Only 0.26% (6/2269) had four vital parameters crucial for priority assignment measured, and 19.3% (437/2269) had at least one parameter measured. A priority code was assigned to 10% (225/2269). Our study revealed inadequacies in the pediatric triage system. A simple and objective triage system that is based on the measurement of crucial vital parameters and on prompt recognition of warning signs and symptoms to correctly identify high-risk groups has been introduced to ensure appropriate and effective triage of sick children.

A randomized multicenter study on ambulatory blood pressure and arterial stiffness in patients treated with valsartan/amlodipine or nifedipine GITS. In a pre-specified subgroup analysis of a 12-week randomized multicenter study, we investigated effects of valsartan/amlodipine 80/5 mg single-pill combination (n = 75) and nifedipine GITS 30 mg (n = 75) on ambulatory blood pressure (BP) and arterial stiffness assessed by brachial-ankle pulse wave velocity (PWV) in patients with uncontrolled hypertension. At week 12, the between-treatment mean differences in systolic/diastolic BP were smaller for 24-hour and daytime (-2.1/-1.7 and -2.0/-1.5 mm Hg, respectively, P ≥ 0.22) but greater (P < 0.01) for nighttime (-4.0/-2.8 mm Hg, P ≤ 0.09), especially in sustained uncontrolled hypertension (-5.0/-4.1 mm Hg, P ≤ 0.04) and non-dippers (-6.5/-3.7 mm Hg, P ≤ 0.07), in favor of valsartan/amlodipine. At week 12, PWV was significantly reduced from baseline by valsartan/amlodipine (n = 59, P < 0.0001) but not nifedipine (n = 59, P = 0.06). The changes in PWV were significantly associated with that in ambulatory systolic BP and pulse pressure in the nifedipine (P ≤ 0.0008) but not valsartan/amlodipine group (P ≥ 0.57), with a significant interaction (P ≤ 0.045). The valsartan/amlodipine combination was more efficacious than nifedipine GITS in lowering nighttime BP in sustained uncontrolled hypertension and non-dippers, and in lowering arterial stiffness independent of BP lowering.

Postnatal vascular growth in the neocortex of normal and protein-deprived rats. Morphometric studies. The postnatal vascular growth in the neocortical area 18 of normal and pre- and postnatally protein-deprived rats was examined. For control rats the specific length, the specific surface and the volume fraction of vessels increased rapidly between 7 and 20 days of age. Thereafter, only a minor increase was seen. In protein-deprived rats there was no increase in the specific length of vessels between 7 and 10 days of age and this variable was still reduced at 30 days of age compared to controls. This reduction was due to a decrease in the specific length of thin vessels (luminal diameter less than 8.25 mu) whereas the specific length of wider vessels was not affected by the protein deprivation. There were no significant differences in the specific surface or volume fraction of vessels between control and protein-deprived rats. These findings indicate an adaptive increase in luminal diameter of vessels in the protein deprived rats during postnatal development. At 90 days of age no significant differences between vascular variables of control and protein-deprived rats were seen.

"THINK" Before You Order: Multidisciplinary Initiative to Reduce Unnecessary Lab Testing. Inappropriate daily lab testing can have adverse effects on patients, including anemia, pain, and interruption of sleep. We implemented a student-led, multifaceted intervention featuring clinician education, publicity campaign, gamification, and system changes, including a novel nurse-driven protocol to reduce unnecessary daily lab testing in a teaching hospital. We applied a quasi-experimental interrupted time series design with a segmented regression analysis to estimate changes before and after our 14-month intervention with a comparison to a control surgical unit. There was an increasing trend in the baseline period, which was mitigated by the intervention (postintervention effect estimate -0.04 labs per patient day/month, p < .05), which was not seen in the control unit. Estimated cost savings was $94,269 ($6,734/month). A student-led, multidisciplinary campaign involving nurse-driven pathway, education, publicity, gamification, and system changes was effective in reducing daily lab testing.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials.

Effects of cannabinoid receptor ligands on LPS-induced pulmonary inflammation in mice. The effects of cannabinoid receptor agonists WIN 55,212-2, delta9-tetrahydrocannabinol (delta9-THC), arachidonoylethanolamide (anandamide) and palmitoylethanolamide on lipopolysaccharide (LPS) -induced bronchopulmonary inflammation in mice were investigated. WIN 55,212-2 and delta9-THC induced a concentration-dependent decrease in TNF-alpha level in the bronchoalveolar lavage fluid (BALF) (maximum inhibition 52.7% and 36.9% for intranasal doses of 750 nmol x kg(-1) and 2.65 mmol x kg(-1), respectively). This effect was accompanied by moderately reduced neutrophil recruitment. Palmitoylethanolamide (750 nmol x kg(-1)) diminished the level of TNF-alpha in BALF by 31.5% but had no effect on neutrophil recruitment. Anandamide (7.5-750 nmol x kg(-1)) did not influence the inflammatory process but TNF-alpha level and neutrophil recruitment were decreased by 28.0% and 62.0%, respectively, with 0.075 nmol x kg(-1). These results demonstrate that the cannabinoid receptor ligands inhibited LPS-induced pulmonary inflammation and suggest that this effect could be at least in part mediated by the cannabinoid CB2 receptor.

Total Synthesis and Structural Revision of Clavilactone D. A structural revision of clavilactone D, a potent inhibitor of protein tyrosine kinases, was achieved by total syntheses of two newly proposed structures. The syntheses relied on ring-opening/ring-closing metathesis, which transformed a cyclobutenecarboxylate into a γ-butenolide. The syntheses confirmed that the correct structure of clavilactone D has an amino group at C-3 instead of a hydroxy group at C-2 in the originally proposed structure.

Contamination and ecological risk assessment of toxic trace elements in the Xi River, an urban river of Shenyang city, China. The objectives of this study were to assess the enrichment, contamination, and ecological risk posed by toxic trace elements in the sediments of the Xi River in the industrialized city of Shenyang, China. Surface sediment and sediment core were collected; analyzed for toxic trace elements; and assessed with an index of geoaccumulation (Igeo), enrichment factor (EF) value, potential ecological risk factor (Er), ecological risk index (RI), and probable effect concentration quotient (PECQ). Elemental concentrations (milligram per kilogram) were 8.5-637.9 for As, 6.5-103.9 for Cd, 12.2-21.9 for Co, 90.6-516.0 for Cr, 258.1-1,791.5 for Cu, 2.6-19.0 for Hg, 70.5-174.5 for Ni, 126.9-1,405.8 for Pb, 3.7-260.0 for Sb, 38.4-100.4 for V, and 503-4,929 for Zn. The Igeo, EF, Er, and PECQ indices showed that the contamination of Cd and Hg was more serious than that of As, Cr, Cu, Ni, Pb, Sb, and Zn, whereas the presence of Co and V might be primarily from natural sources. The Igeo index for Cr and Ni might underestimate the degree of contamination, potentially as a result of high concentrations of these elements in the shale. The RI index was higher than 600, indicating a notably high ecological risk of sediment for the river. The average PECQ for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn ranged from 1.4 to 4.1 for surface sediment and from 5.2 to 9.6 in the sediment cores, indicating a high potential for an adverse biological effect. It was concluded that the sediment in the Xi River was severely contaminated and should be remediated as a hazardous material.

Mapping immune response profiles: the emerging scenario from helminth immunology. Metazoan parasites of mammals (helminths) belong to highly divergent animal groups and yet induce a stereotypical host response: Th2-type immunity. It has long been debated whether this response benefits the host or the parasite. We review the current literature and suggest that Th2 immunity is an evolutionarily appropriate response to metazoan invaders both in terms of controlling parasites and repairing the damage they inflict. However, successful parasites induce regulatory responses, which become superimposed with, and control, Th2 responses. Beyond helminth infection, this superimposition of response profiles may be the norm: both Th1 and Th2 responses coexist with regulatory responses or, on the contrary, with the inflammatory Th17 responses. Thus, typical responses to helminth infections may differ from Th2-dominated allergic reactions in featuring not only a stronger regulatory component but also a weaker Th17 component. The similarity of immune response profiles to phylogenetically distinct helminths probably arises from mammalian evolution having hard-wired diverse worm molecules, plus tissue-damage signals, to the beneficial Th2 response, and from the convergent evolution of different helminths to elicit regulatory responses. We speculate that initiation of both Th2 and regulatory responses involves combinatorial signaling, whereby TLR-mediated signals are modulated by signals from other innate receptors, including lectins.

Effective incorporation of spatial information in a mutual information based 3D-2D registration of a CT volume to X-ray images. This paper addresses the problem of estimating the 3D rigid pose of a CT volume of an object from its 2D X-ray projections. We use maximization of mutual information, an accurate similarity measure for multi-modal and mono-modal image registration tasks. However, it is known that the standard mutual information measure only takes intensity values into account without considering spatial information and its robustness is questionable. In this paper, instead of directly maximizing mutual information, we propose to use a variational approximation derived from the Kullback-Leibler bound. Spatial information is then incorporated into this variational approximation using a Markov random field model. The newly derived similarity measure has a least-squares form and can be effectively minimized by a multi-resolution Levenberg-Marquardt optimizer. Experimental results are presented on X-ray and CT datasets of a plastic phantom and a cadaveric spine segment.

Cystic Pleural Synovial Sarcoma. Fewer than 40 cases of primary pleural synovial sarcoma have been reported so far with only 3 cases of cystic synovial sarcoma including cases originating from sites other than the pleura. Here, we present an exceedingly rare case of cystic synovial sarcoma originating from the mediastinal side of the visceral pleura in a 25-year man presenting with hemoptysis. On contrast-enhanced computed tomography (CT), cystic synovial sarcoma and cystic thymoma were difficult to be distinguished due to mediastinal location. Histopathological examination showed spindled morphology of tumor cells with hypercellularity and nuclear atypia. As these features are associated with both monophasic fibrous synovial sarcoma and type Athymoma, immunohistochemistry was performed. Adiagnosis of synovial sarcoma was confirmed by detection of CD99 and EMAand negativity of other markers. Fluorescence in situhybridization (FISH) was not done. Surgical excision was done and followed by oncology referral.

Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides. Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-negative bacteria. In this study we also report the first identification of two component peptides in the complex polymyxin fermentation product colistin, a Thr2Ser isoform and an acyl group isomer. Both of these peptides, as well as a known component peptide, Leu7Ile, were similar to polymyxin E1 in potency, suggesting that conservative mutations in the colistin family are functionally inconsequential. In contrast, the acyclic analogs of all of these peptides were inactive, indicating that the characteristic lariat structure of the polymyxins is necessary for antimicrobial activity.

Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung. The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications.

A method for predicting maximal strength in collegiate women athletes. The purpose of this study was to develop a regression equation capable of accurately predicting a 1 repetition maximum bench press in collegiate women athletes. The findings of this study could benefit future women athletes by providing coaches and trainers with an easy method of determining maximum upper body strength in women athletes. Sixty-five University of Georgia NCAA Division 1 women athletes from 9 different sports were measured prior to the start of their season utilizing 2 repetition tests to fatigue (25 kg: REPS55; 31.8 kg: REPS70) and a 1 repetition maximum (1RM) bench press test in random order. Other independent variables that were used with a submaximal weight to predict 1RM were total body weight, lean body mass (LBM), height, and percent body fat. The variables of REPS70 and LBM were the best predictors of 1RM utilizing Pearson product correlations (r = 0.909, p = 0.000; r = 0.445, p = 0.000) and multiple regression results (R(2) = 0.834, p = 0.000) for this population. The results from this study indicate muscular endurance repetitions using an absolute weight of 31.8 kg in conjunction with LBM can be used to accurately predict 1RM bench press strength in collegiate women athletes.

Physical Activity, Decision-Making Abilities, and Eating Disturbances in Pre- and Postbariatric Surgery Patients. Physical activity (PA) is considered to have a beneficial influence on executive functioning, including decision-making. Enhanced decision-making after bariatric surgery may strengthen patients' ability to delay gratification, helping to establish appropriate eating behavior. The objectives of this study were to (1) compare a preoperative group with a postoperative group with regard to daily PA, decision-making, and eating disturbances; and (2) investigate the relationship between these variables. The study included 71 bariatric surgery candidates (78 % women, BMI [kg/m2] M = 46.9, SD = 6.0) and 73 postoperative patients (78 % women, BMI M = 32.0, SD = 4.1; 89 % Roux-en-Y gastric bypass, 11 % sleeve gastrectomy; months postoperative M = 8.2, SD = 3.5; total weight loss [%] M = 33.2, SD = 8.9) who completed SenseWear Pro2 activity monitoring. Decision-making was assessed using a computerized version of the Iowa Gambling Task and eating disorder psychopathology using the Eating Disorder Examination-Questionnaire. The number of patients who were classified as physically inactive was similarly high in the pre- and postoperative groups. No group differences emerged with regard to decision-making, but the postoperative group exhibited less eating disturbances than the preoperative group. No significant associations were found between PA, decision-making, and eating behavior. Patients after bariatric surgery were not more physically active than bariatric surgery candidates, which should be considered in care programs. Additionally, future research is needed to explore the possible link between PA, patients' decision-making abilities, and eating disturbances concerning dose-response questions.

Serological evidence of bluetongue in game animals in Botswana. Using the Agar Gel Precipitin technique the sera of 397 African buffalo (Syncerus caffer) and 90 sera of other common game species were examined for bluetongue antibodies. Of the adult buffalo 283 out of 325 (87 per cent) were positive. Buffalo calves were positive in 25 out of 72 cases (35 per cent). Positive reactions were also recorded in lechwe (Kobus leche), tsessebe (Damaliscus lunatus), red hartebeeste (Alcelaphus buselaphus), gemsbok (Oryx gazella), sable (Hippotragus niger) and impala (Aepyceros melampus).

[Enterococcal survival in forcemeat preserved in polymer films and in cutlets made from it]. The available data suggest that at 2 degrees and 5 degrees with a 12-day long storage in unpacked and in polymeric film packed forcemeat there occurs no propagation of the enterococci. At 22-24 degrees the multiplication of Str. faecalis var. liquefaciens proceeded similarly both in packed and unpacked forcemeat. When the temperature in the central part of the cutlets prepared from the enterococci-contaminated forcemeat reaches 7-80 degrees the bulk of the Str. faecalis var liquefaciens cells perishes, but even at 80 degrees there survive individual heat-resistant cells.

Prevalence of diabetes mellitus and impaired glucose tolerance in cystic fibrosis. The aim of this study was to evaluate the prevalence of impaired glucose tolerance or diabetes mellitus in 99 patients (53 M, 46 F; mean age 10.5 +/- 6.9 years), with cystic fibrosis. Glucose tolerance was evaluated in all patients without overt diabetes using the oral glucose tolerance test (OGTT). Six patients showed a pathological OGTT and 2 patients had insulin-requiring diabetes mellitus. The mean age of the patients with impaired glucose tolerance was significantly higher than that of the subjects with normal glucose metabolism (p less than 0.0001). Patients with overt diabetes mellitus were the oldest subjects in the study group.

Errors introduced in radioligand binding studies due to displaceable, cation dependent, [3H]prazosin binding to glass-fibre filters and glass surfaces. [3H]prazosin not only specifically and homogeneously labels alpha 1-adrenoceptors, but also binds to glass surfaces and non-linearly to the glass-fibre filters, commonly used in radioligand binding experiments. Binding to filters can be modulated by unlabeled alpha-adrenergic compounds and cations. If no correction is applied for displaceable filter binding, analysis of [3H]prazosin binding experiments leads to erroneous results. Analysis of [3H]prazosin saturation experiments on guinea-pig cerebral cortex membranes with correction for filter binding before the non-linear fit procedure indicated that [3H]prazosin labels a homogeneous population of alpha 1-adrenoceptors (Rtot: 8.33 fmol.mg-1 wet tissue) with a dissociation constant of 1.28 x 10(-10) M. However, analysis of the same data after correction for non-specific binding, (determined in parallel experiments by adding 10 microM phentolamine to the incubation medium) resulted in a best fit to a model in which [3H]prazosin labels two alpha 1-adrenoceptor subpopulations (R1: 15.0 fmol.mg-1 and R2: 14.6 fmol.mg-1 wet tissue) with dissociation constants of respectively 1.78 x 10(-10) and 5.63 x 10(-9) M. The discrepancy between the two methods of analysis is due to displacement of the radioligand from the filters by phentolamine. Prazosin and oxymetazoline are also able to displace filter-bound [3H]prazosin. The extent to which displaceable filter binding distorts the proper results depends on the actual magnitude of the error and also on the method of analysis.

Melioidosis in children: a retrospective study. Melioidosis, caused by Burkholderia pseudomallei, is endemic in Singapore and can present as localized or disseminated disease. Demographic data, clinical features, investigation results, treatments, and outcomes in patients aged <16 years diagnosed with melioidosis at KK Women's and Children's Hospital between January 2002 and January 2014 were retrospectively reviewed. Data for patients with primary skin disease and those with other organ involvement were compared. Seventeen children were diagnosed with melioidosis. Their median age was 12.5 years (range: 2-15 years). Nine (53%) patients presented with localized cutaneous melioidosis and five (29%) with localized lymphadenitis, pneumonia, or septic arthritis. The remaining three (18%) patients had melioidosis sepsis; two of these patients died from septic shock. Treatment included an initial 1-2 weeks of IV antibiotics followed by 3-6 months of oral combination antibiotics. All cases of localized cutaneous disease resolved completely with no recurrences. Three (60%) of the five patients with localized involvement of other organ systems achieved complete resolution of disease, and the remaining two were lost from follow-up. Although uncommon, melioidosis can occur in children living in endemic regions. Patients with localized skin disease have good outcomes with no recurrences. Systemic disease can be fatal, especially in the presence of underlying immunodeficiency. Diagnosis requires a high index of suspicion, and treatment requires prolonged combination antibiotic therapy.

Duration of antibacterial effectiveness of gentamicin ear drops in external otitis. The recommendation of Anderson and Steele, for the use of ear drops four times a day, has not been changed since 1948. In order to re-evaluate the frequency of using ear drops, we examined the duration of the effectiveness of the antibacterial activity of gentamicin ear drops in external otitis. Seventeen patients (25 ears) with external otitis were studied. We took 18 samples from each ear at 0, 1, 2, 3, 6, 8, 10, 12 and 14 hours and measured the concentration of gentamicin on the wick and in the ear canal. We found that the concentration of gentamicin began to decrease only after 12 hours and a more significant decrease was detected after 14 hours of treatment. We have shown that the antibiotic used on the wick is effective for 12 hours. In conclusion, we recommend using ear drops twice a day on a wick as routine therapy for external otitis.

Diagnosis and management of dental injuries in children. Approximately half of children sustain some type of dental injury. Management of injuries to the anterior teeth of preschool children is directed toward minimizing potential damage to the developing permanent teeth; therefore, heroic measures to save primary teeth are not indicated. Crown fractures in the permanent dentition, even those exposing the dental pulp, can be successfully treated hours after an injury. Prompt referral for dental treatment is advisable. Displacement injuries to permanent teeth constitute genuine dental emergencies in which the prognosis is directly related to the timeliness of treatment. Avulsed permanent teeth should be immediately reimplanted by any capable person. If that is impossible, the teeth should be placed in cold milk and the child referred for immediate treatment by a dentist. Mouthguards prevent dental injuries but are not widely used outside of a few organized sports. Efforts should continue to promote mouthguard use in all contact sports.

Immune interactions at the maternal-fetal interface. Models of murine allogeneic pregnancy have established that maternal T cells recognize fetal alloantigens and are normally suppressed or deleted. While the precise cellular interactions and mechanisms involved in maternal lymphocyte tolerance are not yet clear, the identity of some of the critical factors are beginning to be uncovered. Signals that have been shown in mice to have an obligatory role in immunological survival of the semiallogeneic fetus include, but are probably not limited to, indoleamine-2,3-dioxygenase and the newly discovered B7 family protein, B7-H1. Whether these proteins have intersecting functions is unknown, but it is possible that both are involved in the control of maternal T regulatory cells, which are also strictly required for successful allogeneic pregnancy in mice. Additional factors that are involved include trophoblast and/or maternally derived FasL, and in humans, class Ib HLA molecules. The potency of these mechanisms in protecting the fetal allograft is underscored by the scarcity of knockout and transgenic models in which pregnancy is immunologically compromised. Here, the current understanding of mechanisms of specific suppression of maternal lymphocytes is reviewed.

Synthesis of Bimetal Fe and Cu Altered TUD-1: A Mesoporous Catalyst for Phenol Hydroxylation Reaction. Fe and Cu ions incorporated (Si/Cu = 50, Si/Fe = 50 and Si/Cu + Fe = 50) amorphous, wormhole structured mesoporous catalysts (CuTUD-1, FeTUD-1 and FeCuTUD-1) (TUD-1-Technische Universiteit Delft) have been synthesized hydrothermally using low cost, non-surfactant template triethanolamine (TEA). Physicochemical properties of the catalysts were made using X-ray diffraction (XRD), Nitrogen sorption, FT-IR, DRS UV Visible, FT Raman, SEM, TEM and TG-DTG techniques. The results showed that the materials possess mesoporous, foam type morphology, surface area 485-634 m2/g, pore size 4.8-6.8 nm, pore volume 0.67-0.83 cm3/g and metal ions (Cu2+ and Fe3+) coordinative environment. The highly dispersed Cu2+ and Fe3+ active sites are observed in FeCuTUD-1 catalyst. Also, the synthesized catalysts are tested in the oxidation of phenol with hydrogen peroxide (H2O2) oxidant. Further, reaction parameters such as time, temperature, and catalyst were also investigated.

[2]Rotaxanes with palladium(II)-NHC stoppers. Bridge cleavage reactions of the dimeric monocarbene complex [PdBr(2)((i)Pr(2)-bimy)](2) can be effectively used to end-cap pyridine containing pseudorotaxanes affording stable [2]rotaxanes.

Diverse impacts of aging on insulin resistance in lean and obese women with polycystic ovary syndrome: evidence from 1345 women with the syndrome. Polycystic ovary syndrome (PCOS) represents a moving spectrum of hormonal to metabolic abnormalities, as women with the syndrome are aging. Hormonal abnormalities, anovulation, and hyperandrogenic signs were predominant during the early years of PCOS and fade away with the years. Metabolic abnormalities and insulin resistance (IR) remain throughout the PCOS life cycle; however, it is unclear as to how they change, as women with the syndrome are aging. To evaluate the changes in IR and its associations with clinical, biochemical, hormonal, and ultrasound findings in a large cohort of women with PCOS and controls, as they are aging. A cross-sectional study was carried out to evaluate the diverse impacts of aging on IR. An outpatient clinic was chosen for the study. A total of 1345 women with PCOS (Rotterdam criteria) and 302 controls of Caucasian origin and Greek ethnicity comprised the study group. The impact of age on IR, as calculated using homeostasis model assessment of IR (HOMA-IR) index, and several PCOS characteristics were evaluated. In PCOS, age (-0.045±0.008) was negatively, and BMI positively (0.18±0.007) associated with HOMA-IR (R(2)=0.36). When data were stratified with regard to the BMI status, a negative association of age with HOMA-IR was found in lean, normal, and overweight patients (r: -0.266, -0.233, -0.192, P<0.001), which was neutralized in obese patients (r: -0.009, P: NS). Free androgen index and BMI were positively associated with HOMA-IR in all age quartiles. When mean HOMA-IR values were plotted according to BMI subgroups at different age quartiles, a significant gradual decrease in HOMA-IR was observed in normal (P<0.001) and overweight (P: 0.004), but not obese, women (P: 0.202) across age quartiles. Aging increases IR in obese but not in lean and overweight women with PCOS. As BMI and androgens are positively associated with HOMA-IR and androgens decline through time, it appears that if women with PCOS do not become obese they may exhibit a better metabolic profile during their reproductive years.

Effects of fluid restriction on measures of circulatory efficacy in adults with septic shock. The haemodynamic consequences of fluid resuscitation in septic shock have not been fully elucidated. Therefore, we assessed circulatory effects in the first 24 h of restriction of resuscitation fluid as compared to standard care in intensive care unit (ICU) patients with septic shock. This was a post-hoc analysis of the multicentre CLASSIC randomised trial in which patients with septic shock, who had received the initial fluid resuscitation, were randomised to a protocol restricting resuscitation fluid or a standard care protocol in nine ICUs. The highest plasma lactate, highest dose of noradrenaline, and the urinary output were recorded in five time frames in the first 24 h after randomisation. We used multiple linear mixed effects models to compare the two groups. We included all 151 randomised patients; the cumulated fluid resuscitation volume in the first 24 h after randomisation was median 500 ml (Interquartile range (IQR) 0-1500) and 1250 ml (500-2500) in the fluid restriction group and standard care group, respectively. The estimated differences in the fluid restriction group vs. the standard care group were 0.1 mM (95% confidence interval -0.7 to 0.9; P = 0.86) for lactate, 0.01 μg/kg/min (-0.02 to 0.05; P = 0.48) for dose of noradrenaline, and -0.1 ml/kg/h (-0.3 to 0.2; P = 0.70) for urinary output during the first 24 h after randomisation. We observed no indications of worsening of measures of circulatory efficacy in the first 24 h of restriction of resuscitation fluid as compared with standard care in adults with septic shock who had received initial resuscitation.

Angiotensin-converting enzyme as a potential target for treatment of Alzheimer's disease: inhibition or activation? The accumulation of the amyloid beta-protein (Abeta), the main constituent of the 'amyloid plaque', is widely considered to be the key pathological event in Alzheimer's disease (AD). In particular, the accumulation of Abeta42 is the central event triggering neurodegeneration. Reduction of Abeta is now a major therapeutic strategy. However, only a few patients show evidence of increased Abeta production. Thus, defects in proteases that degrade Abeta could underlie some or many cases of familial and sporadic AD. Among the Abeta degrading enzymes, namely, neprilysin (NEP), insulin-degrading enzyme (IDE), endothelin-converting enzyme (ECE) and angiotensin-converting enzyme (ACE), ACE is the most commonly targeted enzyme by inhibitors in elderly populations because it plays a central role in the regulation of blood pressure and hypertension. Genetic, pathological and biochemical studies have associated ACE with AD. This review discusses genetic, molecular and clinical studies that might help explain the relationship between ACE, hypertension, Abeta degradation and AD.

Human stem-progenitor cells from neonatal cord blood have greater hematopoietic expansion capacity than those from mobilized adult blood. In this study we compared the hematopoietic capacity of CD34+ cell preparations from neonatal cord blood (CB) vs adult mobilized peripheral blood (PBSC) before and after ex vivo culture. CD34+ cell preparations purified from CB or PBSC were cultured in serum-free medium containing FKT: FLT-3 ligand (FL), KIT ligand (KL), and thrombopoietin (TPO). After 1-4 weeks ex vivo culture, CB CD34+ cell preparations had greatly increased numbers of total cells, CD34+ cells, and colony-forming cells (CFC). In contrast, ex vivo-cultured PBSC CD34+ cell preparations generated far less in vitro assessed hematopoietic capacity. Nonobese diabetic severe combined immunodeficient mouse (NOD/SCID) engrafting potential (SEP) was maintained in ex vivo-cultured CB CD34+ cell preparations, whereas ex vivo-cultured PBSC lost SEP. CB CD34+ cells continued to proliferate throughout 3 weeks ex vivo, whereas after 1 week, no additional cell divisions were detected in PBSC CD34+ cells. After 3 weeks in culture, the average CB CD34+ cell had divided more than 5 times, as compared to only 2 times for the average PBSC CD34+ cell. CB CD34+ cell preparations generated massively increased in vitro assessed hematopoietic capacity and maintained SEP during 1- to 4-week ex vivo cultures. In contrast, ex vivo-cultured PBSC CD34+ cell preparations generated far less in vitro assessed hematopoietic capacity and decreased SEP. The differences in the in vitro proliferative indices of membrane dye-labeled CD34+ cells from CB vs PBSC correlated with these functional differences.

[Visual complications of mitral leaflet prolapse (author's transl)]. Among ten patients with acute ischemic cerebral accident and mitral leaflet prolapse, two women presented with visual disturbances consistent with embolism in the ophthalmic or posterior cerebral circulation. These observations emphasize the importance of thorough cardiovascular assessment in all patients with acute cerebral or ocular ischemia, and we suggest that echocardiography should be part of routine investigation of such patients.

The role of oxidative stress in mechanisms of metal-induced carcinogenesis. Metals are necessary for the normal functioning of cells and the survival of organisms. However, exposure to higher than the physiological levels of several metals may lead to tumor development. Although the exact molecular mechanism(s) of metal-induced carcinogenesis is not clear, a vast body of evidence indicates that metal-induced generation of reactive oxygen species (ROS) may play a central role in this process. Two main pathways of ROS-induced effects are discussed in this chapter: (i) increased DNA damage induced either directly or indirectly by impeding DNA repair, and (ii) modulation of nuclear transcriptional factor activities, such as NF-kappaB and AP-1, through mitogen-activated protein kinases signal transduction mechanisms.

Melatonin premedication improves quality of recovery following bariatric surgery - a double blind placebo controlled prospective study. Melatonin has hypnotic, sedative, analgesic, anti-inflammatory, and antioxidant properties, and is a widely used sleep agent. Our aim was to evaluate the effect of melatonin premedication on postoperative recovery in patients undergoing bariatric surgery. University Hospital, Israel. Patients undergoing bariatric surgery were randomized to receive either 5 mg melatonin (M group) or placebo (P group) once on the night before surgery and again 2 hours before surgery. Quality of recovery was assessed using the QoR-15, a 15 item questionnaire on quality of recovery after surgery and anesthesia, regarding emotional state, physical comfort, psychological support, pain, and physical independence. A maximal score of 140 suggested good recovery (1 question was omitted due to irrelevance). The patients answered the questionnaire in the preanesthesia clinic, on admission to the operating room, and on the first postoperative day. A total of 44 patients completed the study. There was no statistical difference between M and P groups in the mean QoR-15 scores obtained before the surgery. Mean postoperative QoR-15 score was higher in the M group compared with the P group (118.3±12.9 versus 107.8±18.7, respectively; P<.01). Scores were also higher in the M group regarding pain (P<.05) and quality of sleep (P< .05). Use of melatonin premedication improved the quality of recovery 1 day after bariatric surgery as measured by the QoR-15, specifically the quality of sleep and pain levels. Melatonin may serve as a premedication, especially when other options, like benzodiazepines are not recommended.

CRISPR/Cas9-mediated somatic and germline gene correction to restore hemostasis in hemophilia B mice. Hemophilia B (HB) is an X-linked disorder caused by defects of F9 encoded coagulation factor IX, which is an ideal model for gene therapy. Most existing HB gene therapies are based on viral mediated gene supplementation, which could increase immunoreaction. In this study, CRISPR/Cas9 system was used for gene correction in an F9 mutant HB mouse model in both adult mice (in vivo) and in germline cells (ex vivo). In vivo, naked Cas9-sgRNA plasmid and donor DNA were delivered to HB mice livers to recover the mutation via hydrodynamic tail vein (HTV) injection. 62.5% of the HTV-treated mice showed a detectable gene correction (>1%) in the F9 alleles of hepatocytes, which was sufficient to remit the coagulation deficiency. Ex vivo, three different forms of Cas9 were microinjected into germline cells of HB mice to investigate their efficiency and safety in gene correction. Cas9 protein showed higher gene recovery rates, less embryo toxicity, and lower mosaic repair percentage, making it more suitable for germline gene therapy. Our study strongly supports that CRISPR/Cas9-mediated genome editing is feasible in gene therapy of genetic disorders.

[Minimum provider volumes in heart surgery]. The introduction of minimum provider volumes for certain medical procedures has been the subject of scientific investigation and political controversy for quite a while. The core of the discussion focuses on the hypothesis that minimum provider volumes could significantly improve operative results and cost efficiency. In Germany the Fifth Volume of Social Law (Sozialgesetzbuch V) set the legal stage for the implementation of minimum provider volumes. This article is a brief review on the experience with minimum provider volumes in cardiac surgery. The main focus is on coronary artery bypass surgery, as this happens to be the most frequently investigated procedure.

Lysozyme levels in tissues of iron-deficient rats. Fats were fed either diets sufficient (300 ppm) or insufficient (5 ppm) in iron for 10 weeks. The iron-deficient animals had lowered hemoglobin and hematocrit levels and higher levels of kidney lysozyme activity than did control animals. There were no significant changes in serum and spleen lysozyme activity levels.

Detection of mRNA for inhibin alpha- and beta A-subunits in bovine ovarian tissues and the effect of in vivo administration of GNRH. The aims of these studies were to determine which types of bovine ovarian tissue contain mRNA for inhibin/activin subunits and whether administration of GnRH influences concentration of these mRNAs. In experiment (exp.) one, cows in the luteal phase of the estrous cycle were given prostaglandin F2 alpha (PGF2 alpha) to induce luteal regression and injected after 40 hr with saline (n = 5) or 100 micrograms GnRH (n = 6). Ovaries were removed 6 hr later. In exp. two, unilaterally ovariectomized (OVX) heifers (n = 33) in the luteal phase of their estrous cycle were given PGF2 alpha to induce luteal regression. Twelve heifers were OVX without injection of GnRH at 24 (n = 6) or 40 hr (n = 6) after PGF2 alpha. The remaining heifers (n = 21) were given 100 micrograms GnRH at 40 hr after PGF2 alpha injection and OVX 8 (n = 4), 16 (n = 5), 24 (n = 6) or 48 (n = 6) hr after GnRH injection. Total cellular RNA was isolated from large follicles (exp. one and two), small-medium follicles and stromal tissue (SMS) and corpora lutea (CL; exp. one) tissues and analyzed by dot blot and Northern blot techniques by hybridizing with cDNA probes for human inhibin/activin alpha- and beta A-subunits. Large follicles were classified as steroidogenically active (EA) if follicular fluid (FF) concentration of estradiol-17 beta (E2) was greater than progesterone (P4), or if P4 and E2 concentrations in FF were greater than 100 ng/ml, and estrogen inactive (EI) if FF concentration of E2 and P4 did not satisfy these criteria. In exp. one, mRNA for the alpha-subunit was primarily expressed in EA follicles, and detectable in EI follicles, SMS, and CL while beta A-subunit mRNA was detected only in large EA follicles and a few SMS samples. The mRNA (x +/- SEM fmoles/mg DNA) for both subunits of inhibin/activin was higher (P < .05) in EA follicles from GnRH-treated cows (alpha = 210.2 +/- 38.6; beta A = 376.9 +/- 41.0) than in EA follicles from control cows (alpha = 102.5 +/- 28.6; beta A = 170.8 +/- 57.6). Concentration of mRNA for the alpha-subunit of inhibin in other ovarian tissues was not different (P > .10) between saline and GnRH treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

A daily process approach to coping. Linking theory, research, and practice. For decades, coping researchers have used between-person designs to address inherently within-person questions derived from theory and clinical practice. The authors describe recent developments in the use of within-person, process-oriented methods that examine individuals intensively over time. Ongoing studies of stress and alcohol consumption, the effects of depression on adaptational processes, and the temporal dynamics of coping with chronic pain demonstrate that by tracking rapidly fluctuating processes such as mood and coping close to their real-time occurrence, daily process designs offer unique insights into conceptually and clinically challenging questions. Such designs also provide new opportunities to examine the purported mechanisms of therapeutic interventions. Despite its demands on participants and investigators, daily process research offers fresh opportunities to link psychological theory, research, and practice.

[The functional therapy of condylar fractures: a kinesiographic follow-up]. Mandibular condylar fractures are frequent traumatic events which, if not properly treated, can develop dysfunctional and degenerative aspects. The treatment has the two goals of maintaining the correct mandibular movements and of sustaining the potential of condylar growth in young patients. The CMS (Computerized Mandibular Scanner) analysis showed the efficacy of functional therapy in condylar fractures.

Modeling relationships between catchment attributes and river water quality in southern catchments of the Caspian Sea. Increasing land utilization through diverse forms of human activities, such as agriculture, forestry, urban growth, and industrial development, has led to negative impacts on the water quality of rivers. To find out how catchment attributes, such as land use, hydrologic soil groups, and lithology, can affect water quality variables (Ca(2+), Mg(2+), Na(+), Cl(-), HCO 3 (-) , pH, TDS, EC, SAR), a spatio-statistical approach was applied to 23 catchments in southern basins of the Caspian Sea. All input data layers (digital maps of land use, soil, and lithology) were prepared using geographic information system (GIS) and spatial analysis. Relationships between water quality variables and catchment attributes were then examined by Spearman rank correlation tests and multiple linear regression. Stepwise approach-based multiple linear regressions were developed to examine the relationship between catchment attributes and water quality variables. The areas (%) of marl, tuff, or diorite, as well as those of good-quality rangeland and bare land had negative effects on all water quality variables, while those of basalt, forest land cover were found to contribute to improved river water quality. Moreover, lithological variables showed the greatest most potential for predicting the mean concentration values of water quality variables, and noting that measure of EC and TDS have inversely associated with area (%) of urban land use.

Assessment of Dermatophytosis Treatment Studies: Interpreting the Data. Antifungal therapy has recently enjoyed a resurgence of interest due to the introduction of a number of new formulations of topical drugs and novel molecules. This has led to a plethora of new publications on management of cutaneous fungal disease. This paper summarizes the various clinical trial factors which may affect the published data regarding how well antifungal drugs work. Understanding these parameters allows the healthcare provider to choose more rationally between available agents based upon an assessment of the evidence.

A one-step RT-PCR assay to detect and discriminate porcine reproductive and respiratory syndrome viruses in clinical specimens. Outbreaks of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) have led to large economic losses and, subsequently, have drawn great attention to its diagnosis and prevention. To facilitate rapid discrimination of HP-PRRSV from classical PRRSV (C-PRRSV), we developed a one-step RT-PCR assay. Primer specificities were evaluated with RNA extracted from 8 viral strains and our results revealed that the primers had a high specificity for PRRSV. The assay sensitivity was 25 copies/μL for both HP-PRRSV and C-PRRSV. A total of 929 serum samples were identified, of which 20.45% were HP-PRRSV-positive and 1.51% were C-PRRSV-positive, which was completely consistent with that of immunochromatochemistry and sequencing method. The proposed assay can detect the virus 2 days prior the onset of symptoms and it can be performed in 2h, thereby providing a rapid method to discriminate HP-PRRSV from C-PRRSV for the identification and prevention of PRRSV infections.

[Methodological problems in clinical and epidemiological research on ageing]. A lot of methological difficulties interfere with the design and the interpretation of data analysis in clinical and epidemiological research on diseases related to ageing. The first one is that normal and pathological ageing are often strongly related, with blurred limits. The selection bias is particularly frequent, related to numerous health care resources, to premature death, to deny or refusals. Data collection is also particularly difficult, due to memory problems related to ageing and prolonged lag time between exposure of a given factor and interview, or related to the disease of interest itself (in particular, dementia). Multiple confounding factors are frequent, due to polypathology and polymedication, also interference between biological, psychological and sociological factors. Another difficulty is related to the insidious evolution of many chronic pathologies related to ageing which interfere with the direction of the causality between factors and disease.

Kinetics of amino acid extraction by lactating mammary glands in control and sometribove-treated Holstein cows. Studies of mammary arteriovenous difference were conducted on multiparous lactating Holstein cows (n = 21) on d 35, 70, 105, and 126 of lactation to examine kinetic relationships between arterial concentration and mammary gland extraction of AA. Additionally, these cows were paired by previous lactational performance and assigned to bST-treated or control groups to examine the effect of bST treatment on AA concentration and extraction by lactating mammary glands. Treated cows were injected daily with 40 mg of recombinant bST from d 71 through 126 of lactation. Arterial concentrations of Asp, Ser, Asn, Gly, beta-aminoisobutyrate, and Met were increased. Concentrations of Val, Ile, Leu, Phe, Orn, and Lys were decreased in bST-treated cows compared with controls. Increased extractions of Asp and Met by mammary glands in treated versus control cows were correlated positively with treatment-induced changes in arterial concentrations of these AA. However, increased mammary extractions of Arg, cystathionine, Leu, and Lys by bST-treated compared with control cows were not correlated with bST-induced changes in arterial concentrations of these AA. Extractions of Asn, His, Thr, Arg, Tyr, Met, cystathionine, cystine, Ile, Phe, Orn, Glu, Gly, Tau, Cit, Leu, and Val were correlated linearly with arterial concentrations (r2 greater than .15) of each AA. Extractions of Asp, Glu, Ser, Asn, Gly, Gln, Tau, His, Cit, Thr, Pro, Tyr, Val, cystine, Ile, Leu, Trp, Orn, and Lys also were correlated with arteriovenous differences of Met.

Unable to find a pet food to recommend, I set up a business to make one. While working in small animal practice, vet John Burns developed an interest in holistic pet health and eventually became a pet food manufacturer.

Deployable membranes designed from folding tree leaves. A simple model of deploying tree leaves is assembled in different arrangements to produce polygonal foldable membranes for use as deployable structures. One family of folding patterns exhibits a small strain mechanism, which is investigated. Variations on the basic arrangements can be used to fold membranes with a discretized curvature.

Induction of proliferation or transformation of neuroretina cells by the mil and myc viral oncogenes. The genome of the avian retrovirus MH2 contains, in addition to the v-myc oncogene shared with three other avian retroviruses (MC29, CMII and OK-10), a second cell-derived oncogene, v-mil (refs 1-3). Like the three other viruses, which contain only v-myc, MH2 induces mainly liver and kidney carcinomas in fowl and transforms fibroblasts and macrophages in vitro. However, MH2 and MC29 differ in their biological properties when assayed on cultures of chicken embryo neuroretina (NR) cells. Indeed, NR cells, which normally do not multiply in vitro, are induced to proliferate and become transformed upon infection with MH2, whereas infection with MC29 has no apparent effect on these cells. To analyse the functions of the two oncogenes of MH2, we isolated spontaneous and in vitro-constructed mutants of this virus and investigated their effects on NR cell multiplication and transformation. We report here that expression of v-mil is sufficient to induce NR cell proliferation, although it does not result in cell transformation. In addition, viruses expressing only the v-myc oncogene fail to induce any detectable change in NR cells. However, cooperation of the two oncogenes is required to achieve transformation of NR cells by MH2.

The Potential of Frog Skin Peptides for Anti-Infective Therapies: the Case of Esculentin-1a(1-21)NH2. Antimicrobial peptides (AMPs) are key effectors of the innate immunity and represent promising molecules for the development of new antibacterial drugs. However, to achieve this goal, some problems need to be overcome: (i) the cytotoxic effects at high concentrations; (ii) the poor biostability and (iii) the difficulty in reaching the target site. Frog skin is one of the richest natural storehouses of AMPs and over the years, many peptides have been isolated from it, characterized and classified into several families encompassing temporins, brevinins, nigrocins and esculentins. In this review, we summarized how the isolation/characterization of peptides belonging to the esculentin-1 family drove us to the design of an analogue, i.e. esculentin-1a(1-21)NH2, with a powerful antimicrobial action and immunomodulatory properties. The peptide had a wide spectrum of activity, especially against the opportunistic Gram-negative bacterium Pseudomonas aeruginosa. We described the structural features and the in vitro/in vivo biological characterization of this peptide as well as the strategies used to improve its biological properties. Among them: (i) the design of a diastereomer carrying D-amino acids in order to reduce the peptide's cytotoxicity and improve its half-life; (ii) the covalent conjugation of the peptide to gold nanoparticles or its encapsulation into poly(lactide- co-glycolide) nanoparticles; and (iii) the peptide immobilization to biomedical devices (such as silicon hydrogel contact lenses) to obtain an antibacterial surface able to reduce microbial growth and attachment. Summing up the best results obtained so far, this review traces all the steps that led these frog-skin AMPsto the direction of peptide-based drugs for clinical use.

Is there a need for a national medical ethics committee. To answer the question posed the terms of reference of local ethical committees as well as a few from overseas were reviewed. It was noted that these committees were established by various professional bodies and functioned independently. Guidelines for ethical practice and conduct were made available to the profession with compliance left to the individual doctor. Amongst the many ethical issues of concern both to the public and the profession was that of self regulation. It is being suggested that these concerns be addressed rather then set up a national body.

Effects of filler composition and surface treatment on the characteristics of opaque resin composites. The effects of filler composition and surface treatment of titanium dioxide (TiO2) on the shear bond strength to noble metal and mechanical properties of opaque dental resin composites were assessed. A series of fillers for resin composites were prepared with untreated TiO2 or treated silica/alumina-coated TiO2 with silane coupling agent; these fillers were replaced with silanized SiO2 in increasing amounts. Each of various powder compositions were mixed with the liquid and applied to the surface of a silver-palladium-copper-gold (Ag-Pd-Cu-Au) alloy and light cured. A light-activated resin-veneering composite material was placed on top with the use of a brass ring mold and light cured. Specimens were stored at 37 degrees C in water for a period of 24 h. Additionally some specimens were thermocycled at 4 degrees C and 60 degrees C in water baths for 1 min each for 5000 cycles before shear mode testing was performed. Light-activated opaque resin composites containing filler with specific filler compositions of 50 wt% of untreated TiO2-50 wt% of silanized SiO2 (untreated TiO2(50)) and 40 wt% of untreated TiO2-60 wt% of silanized SiO2 (untreated TiO2(40)) showed higher shear bond strengths to the Ag-Pd-Cu-Au alloy than any other specific compositions when no thermocycling was involved. Surface treatment of TiO2 filler and TiO2(50)- and TiO2(40)-opaque resin composites prepared thereof showed significantly higher shear bond strengths than untreated TiO2(50)- and TiO2(40)-opaque resin composites when subjected to thermocycling. Surface-treated opaque resin composite had significantly higher compressive and flexural strength than untreated opaque resin composite after immersion in water for 1 month. Scanning electron microscopy of the fractured opaque resin composite surface showed an interface failure between TiO2 and the matrix resin for untreated composite, and cohesive failure within the resin for surface-treated composite. Surface-treated TiO2(50) and TiO2(40) may be clinically useful as the filler for light-activated opaque dental resin composites.

Epidemiology & antibiograms of Vibrio cholerae isolates from a tertiary care hospital in Chandigarh, north India. Cholera is endemic in Chandigarh and its surrounding areas. This retrospective study was undertaken over a period of nine years (January 1999-December 2007) from a tertiary care hospital in north India to understand the changing epidemiology aspects and antibiotic resistance patterns in Vibrio cholerae isolates. A total of 277 isolates of V. cholerae were included in the study. V. cholerae was identified by standard microbiological procedures. Antibiotic sensitivity testing was performed by disc diffusion method and isolates phage typed. All the isolates were identified as V. cholerae O1 biotype El Tor serotype Ogawa; phage 27 was the predominant type. Men were more commonly affected with maximum number in the age group 0-5 yr. Majority of the isolates were resistant to furazolidone but sensitive to gentamicin and cefotaxime. Resistance pattern to amoxycillin was variable. Three isolates were found to be resistant to ciprofloxacin. All the patients presented during June-October coinciding with the monsoon season and a majority were from suburbs. The emergence of resistance amongst V. cholerae especially towards ciprofloxacin may significantly influence the control strategies in future outbreaks. Phage 27 remained the predominant type in all the years. Continuous surveillance with regard to drug resistance, early detection and a strong regional commitment may help contain the disease.

Lowered DHCR7 activity measured by ergosterol conversion in multiple cell types in Smith-Lemli-Opitz syndrome. Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of cholesterol metabolism characterized by multiple congenital anomalies and mental retardation. SLOS results from mutations in 7-dehydrocholesterol Delta7 reductase (DHCR7), the gene encoding the final enzyme involved in cholesterol biosynthesis. The resulting cholesterol deficiency and excessive 7- and 8-dehydrocholesterol (7-DHC, 8-DHC) in plasma and tissues are almost always diagnostic for SLOS. We measured DHCR7 activity in fibroblasts, amniocytes, and chorionic villi from controls, heterozygotes, and SLOS subjects. The enzyme activity (expressed as percent conversion of substrate) was significantly lower in untransformed fibroblasts from SLOS subjects (4.47%+/-0.72) compared to untransformed fibroblasts from heterozygotes (26.6%+/-4.6, p<0.01) or controls (50.6%+/-5.3, p<0.001). We also measured plasma cholesterol and 7-DHC, determined the severity score and identified DHCR7 mutations for most of the subjects. There was no significant correlation of enzyme activity with severity score, plasma cholesterol level, plasma 7-DHC level, or the 7-DHC:cholesterol ratio. We conclude that even though enzyme activity as measured by the ergosterol assay may not correlate with severity, this assay has the potential to distinguish SLOS cells from carrier or unaffected cells in a variety of cell types, and should prove useful in confirming a diagnosis in atypical cases where sterol levels are equivocal. Additionally, it may be important to measure residual enzyme activity in SLOS subjects being considered for a trial of statins, as this treatment could theoretically be detrimental in subjects with little or no DHCR7 activity. Finally, the data suggest a threshold enzyme activity of 8% conversion, below which disease occurs.

Evolution of the structures and stabilities of boron-doped lithium cluster cations: ab initio and DFT studies. The lowest-energy structures and stabilities of the BLi(n)+ (n = 1-7) cluster cations are reported using the B3LYP, MP2, and CCSD(T) methods with the 6-311 + G(d) basis set. The first three-dimensional ground state in BLi(n)+ occurs for BLi5+ and the impurity, B atom, is seen to be trapped in an Li cage from BLi5+ onwards. Significant changes occur for BLi(n)+ (n = 2-4) when compared with their corresponding neutral clusters. However, there is very little change between the geometries of neutral and charged clusters for BLi6+ and BLi7+. The evolution of the binding energies, vertical and adiabatic electron affinities, and dissociation enthalpies with the size of BLi(n)+, show an especial stability for BLi6+ among BLi(n)+ cluster cations. The unique stability of the 8-valence electron BLi6+ can be understood from the cluster electronic shell model (CSM).

Asymmetric Catalysis Using Aromatic Aldehydes as Chiral α-Alkoxyalkyl Anions. We have developed a new umpolung strategy for catalytically forming a chiral α-alkoxyalkyl anion from an aromatic aldehyde for use in asymmetric synthesis. The reaction between aromatic aldehydes and aryl or allyl electrophiles with a silylboronate utilizing a chiral copper-N-heterocyclic carbene catalyst and a palladium-bisphosphine catalyst in a synergistic manner occurred with high enantioselectivities to deliver the three-component coupling products, chiral silyl-protected secondary alcohol derivatives. Our method features the catalytic generation of enantioenriched chiral α-alkoxyalkylcopper(I) intermediates from aldehydes and their subsequent palladium-catalyzed stereospecific cross-coupling.

Synbiotic effect of various prebiotics on in vitro activities of probiotic lactobacilli. In the present study, five Lactobacillus strains were evaluated for their viability in presence of different prebiotics viz. inulin, oligofructose, lactulose, raftilose, and honey. The viability of lactobacilli was observed before and after 5 weeks of refrigerated storage. The doubling time varied from 5.2 hrs to 9.6 hrs. The lowest doubling time was for Lactobacillus plantarum M5 followed by L. plantarum Ch1 with inulin. Viability of lactobacilli was greatest with inulin. The growth and viability in presence of prebiotics were found to be strain-specific. Hence, it could be concluded that the addition of prebiotics have a significant effect on probiotics, and hence, a combination of suitable Lactobacillus strain(s) with a specific prebiotic could be a viable probiotic-based functional food approach in administering the beneficial bacteria in-vivo.

Variable-temperature study of the heme-reorientation process in equine myoglobin. The redistribution of the initially-formed myoglobin heme-insertion isomers from the initially formed 50/50 mixture to the equilibrium ratio of 90/10 has long been assumed to occur by one of two mechanisms, both of which require the rupture of the heme iron-protein bond (La Mar, G.N., Toi, H. and Krishnamoorthi, K. (1984) J. Am. Chem. Soc. 106, 6395-6401). In this study we compared the use of nuclear magnetic resonance and optical spectroscopic techniques as methods for studying the reorientation of heme within myoglobin. We found that kinetics determinations of the heme insertion isomer redistribution process in Mb by optical spectroscopy are quantitatively compatible with the results obtained by nuclear magnetic resonance spectroscopy. A variable-temperature analysis for horse myoglobin using the optical method at pH 8.4 +/- 0.1 yielded the following activation energy parameters: delta H++ = 31 kcal/mol, delta S++ = 34 cal/mol per K, and delta G++21 degrees C = 21 kcal/mol. The value of delta G++ expected for complete dissociation of the heme from myoglobin can be estimated, from its dissociation constant and insertion rate, to be on the order of 23-27 kcal/mol under the same conditions as our determination. Therefore, although the mechanism for heme reorientation in Mb is likely non-dissociative, it has an activation energy which is not far from the lower bound expected for a complete-dissociation/recombination mechanism. Our measured entropy of activation is not especially large, perhaps owing to a large contribution by the solvent.

Water Oxidation Catalysts for Artificial Photosynthesis. Water oxidation is the primary reaction of both natural and artificial photosynthesis. Developing active and robust water oxidation catalysts (WOCs) is the key to constructing efficient artificial photosynthesis systems, but it is still facing enormous challenges in both fundamental and applied aspects. Here, the recent developments in molecular catalysts and heterogeneous nanoparticle catalysts are reviewed with special emphasis on biomimetic catalysts and the integration of WOCs into artificial photosystems. The highly efficient artificial photosynthesis depends largely on active WOCs integrated into light harvesting materials via rational interface engineering based on in-depth understanding of charge dynamics and the reaction mechanism.

Hypoxia-induced cell death and changes in hypoxia-inducible factor-1 activity in PC12 cells upon exposure to nerve growth factor. The transcription factor hypoxia-inducible factor-1 (HIF-1) strongly contributes to the expression of adaptive genes under hypoxic conditions. In addition, HIF-1 has been implicated in the regulation of delayed neuronal cell death. Suspension-grown and adherent PC12 cells treated with NGF were used as an experimental model for studying the relationship between hypoxia-induced cell death and activation of HIF-1. Cell damage was assessed by flow cytometry of double-stained (Annexin V and propidiumiodide) cells, and by analysis of the overall death parameters LDH and mitochondrial dehydrogenase. In parallel, cells were transfected with a control and a three-hypoxia-responsive-elements (HRE)-containing vector and HIF-1-driven luciferase activity was determined. Exposure of NGF-treated PC12 cells to hypoxia resulted in a higher cell death rate when compared to untreated controls. PC12 cells exposed for 2 days to NGF exhibited a decrease of HIF-1 activity up to a factor of ten. This decrease may contribute to the enhanced hypoxia-induced cell death via reduced expression of HIF-1alpha-regulated genes responsible for adaptation to hypoxia, like those for glucose transport proteins and enzymes of the glycolytic chain. The decrease in HIF-1 activity and the increase in hypoxia sensitivity may suggest that NGF act as an hierarchically organized signaling molecule.

Gait cycle finite element comparison of rotating-platform total knee designs. Functional load transmission and kinematic performance were compared for standard versus posterior-stabilized versions of a rotating-platform total knee implant, over a standardized loading cycle, using three-dimensional contact finite element analysis. These two design variants differ primarily in terms of the latter's polyethylene insert having a cam that engages with the femoral component during appreciable flexion, thereby inducing femoral component rollback. The finite element model, previously validated experimentally, afforded direct comparisons of anterior lift-off of the insert from the tibial tray, of bearing mobility (insert rotation about the pivot post), of femoral rollback, and of metal-on-polyethylene contact stresses at the bearing and backside surfaces of the insert. Both design variants generally performed comparably, exhibiting an internal and external rotation range of approximately 5 degrees, approximately 1.5 mm peak lift-off at the anterior aspect of the insert, and approximately 15 mm of posterior rollback, the respective maxima for both designs occurring at approximately the same instants in the gait cycle. However, the posterior-stabilized design had slightly more rollback, and slightly less anterior lift-off and rotation, than did the standard rotating-platform design. Peak polyethylene stresses occurred on the backside of the insert near the posterior edge of the medial compartment, the magnitude being approximately 18% higher for the posterior-stabilized design (21 MPa) than for the standard design.

Second primary cancer in irradiated stage I testicular seminoma. The incidence of second primary cancer (SPC) was determined in 64 irradiated stage I testicular seminoma patients, treated and followed at the Northern Israel Oncology Center from 1968 to 1988. Seven (11%) patients developed a total of eight second cancers. The cumulative risk for developing second primary cancer at ten, 15 and 20 years following the diagnosis of seminoma was 2.5%, 5.1% and 8.9%, respectively. Two patients developed SPC within the radiation field (urinary bladder, sigmoid colon) and four patients outside the radiation field (bronchogenic cancer, thymoma, malignant melanoma, thyroid cancer). In two patients, who developed lung cancer and testicular seminoma, respectively, scatter dose from the main radiation field could not be excluded as one of the factors contributing to the SPC. Three patients died as a direct result of their SPC. It is concluded that there is a low, but significant risk of solid SPC among patients apparently cured of early stage seminoma. It will be important in future surveillance studies of stage I seminoma to assess the risk of SPC in the non-irradiated patients.

Potentiation of enkephalin action by peptidase inhibitors in rat locus ceruleus in vitro. Intracellular recordings were made from locus ceruleus (LC) neurons in slices of rat pons. It has been shown previously that opioids inhibit firing and hyperpolarize LC neurons by activating mu-opioid receptors. Concentration-response curves were constructed by measuring the hyperpolarization, or outward current at -60 mV, caused by various opioid agonists added to the superfusing solution. Peptidase inhibitors (kelatorphan, bestatin and thiorphan) each increased the potency of Met-enkephalin, Leu-enkephalin and metorphamide but had no effect of their own on the LC neurons. Kelatorphan (20 microM) produced a 7-fold shift to the left of the Met-enkephalin dose-response curve. Higher concentrations produced no further shift. Thiorphan (3 microM) and bestatin (20 microM) each had a smaller potentiating effect on the Met-enkephalin hyperpolarization. The effects of Tyr-D-Ala-Gly-MePhe-Gly-ol and noradrenaline were not potentiated by these peptidase inhibitors. Electrical stimulation produced an inhibitory synaptic potential that was prolonged by cocaine (10 microM) and blocked by the alpha-2 adrenoceptor antagonist idazoxan (1 microM). After addition of idazoxan, hyperpolarizing synaptic potentials could be evoked even in the presence of kelatorphan (20 microM). These results indicate that peptide metabolism in the intact brain slice can account for a substantial decrease in the sensitivity of LC neurons to exogenously applied opioid peptides; even after peptidase inhibition, no evidence could be obtained for hyperpolarizing synaptic potentials due to the release of endogenous opioids.

[The role of echocardiography and venous ultrasonography in the diagnosis of acute pulmonary thromboembolism]. Patients with pulmonary embolism (PE) are undergoing echocardiography and venous ultrasonography with increasing frequency. Echocardiography is ideal because it is readily available and is useful for the differential diagnosis in hemodynamically unstable patients. Although predominantly employed to characterize RV pressure overload, echocardiography may detect right heart thrombus or may provide alternative diagnosis. Echocardiography also is useful in assessing the prognosis of patients as well as their response to therapy. Right ventricular hypokinesis, a patent foramen ovale, and right heart thrombus are markers identifying patients at risk for death. PE and deep vein thrombosis are different clinical manifestations of a common disease entity. Venous ultrasonography may reduce pulmonary angiography in patients with non-diagnostic lung scan.

Structure analysis of small proteins by electron microscopy: valinomycin, bacitracin and low molecular weight cell growth stimulators. Dark field electron microscopy was combined with optical filtering to study at high resolution the structure of the cyclopeptide antibiotics, bacitracin and valinomycin, and two proteins of unknown structure, LMW-CSA N and B, low molecular weight granulocyte colony stimulating activity isolated from medium conditioned with normal or leukemic leukocytes. For bacitracin and valinomycin the images faithfully represented the known structural features at a resolution of 0.5 nm or better, depicting a two-ring structure for bacitracin, as well as the position of the potassium ion in valinomycin. Both proteins of unknown structrue had at least one cyclic peptide portion. LMW-CSA N had a size of 2.0 nm, LMW-CSA B of 2.4 nm. A potential site of the calcium ionophoric activity in the latter protein was found to be in the larger of the two ring portions constituting the molecule.

Heart rate variability in atrial fibrillation: The balance between sympathetic and parasympathetic nervous system. Atrial fibrillation (AF) is the commonest abnormal heart rhythm with significant related morbidity and mortality. Several pathophysiologic mechanisms have been advocated to explain the onset of AF. There has been increasing evidence that abnormalities of the autonomic nervous system (ANS) that includes sympathetic, parasympathetic and intrinsic neural network are involved in the pathogenesis of AF. This review will consider the anatomical and pathophysiological concepts of the cardiac neuronal network and discuss how it can be investigated. Relevant articles for this review were selected primarily from Ovid Medline and Embase databases (see appendix). We searched for key terms "atrial fibrillation," "AF," "autonomic dysfunction," "autonomic nervous system," "heart rate variability" and "HRV" to gather relevant studies. Duplicate papers were excluded. Heart is richly innervated by autonomic nerves. Both sympathetic and parasympathetic systems interact in developing AF along with cardiac ganglionated plexi (GP). Thus autonomic dysfunction is present in AF. There are methods including selective ablation that reduce autonomic innervation and show to reduce the incidence of spontaneous or induced atrial arrhythmias. Heart rate variability (HRV) is a useful tool to assess sympathetic and parasympathetic influences on disease states. HRV can be improved following intervention and is thus a useful application in assessing autonomic dysfunction in patients with AF. ANS plays a crucial role in the development, propagation and complexity of AF. Assessment of the autonomic involvement in the propagation of AF may help in explaining why certain patients with AF do not benefit from cardioversion or ablation.

[Clinical recommendations for diagnosis, treatment and monitoring of patients with colorectal cancer]. Colorectal cancer is the third most common malignant tumour in males and the fourth most common malignancy in women in the Republic of Croatia. It is usually manifested as stool forming disorders, feeling that bowel does not empty completely, finding blood in the stool, weight loss and fatigue. In-time diagnosis, confirmed by pathohistological findings, is cornerstone of successful treatment. The decision about treatment is made based on clinical assessment of disease stage and other risk factors, after completion of the diagnostic process. Depending on that, treatment options include surgery, the application of systemic therapy (chemotherapy, immunotherapy) and radiotherapy. The following text presents the clinical guidelines in order to standardize procedures and criteria for the diagnosis, management, treatment and monitoring of patients with colorectal cancer in the Republic of Croatia.

Sewing needle: a rare cause of intra-cardiac foreign body in a 3-year-old child. Sewing needles are rare causes of penetrating cardiac injury. Suicidal attempt, accidental penetration, domestic violence, and child abuse are likely causes for such injury. 1 Owing to their sharp nature, needles can rapidly migrate through the tissues. Fatalities are due to cardiac tamponade, infection, peripheral embolism, and valve dysfunction.

Dysregulation of urinary miR-21 and miR-200b associated with interstitial fibrosis and tubular atrophy (IFTA) in renal transplant recipients. microRNAs (miRNAs) are endogenous gene expression regulators that are involved in renal function and physiopathology, making them potential biomarkers in the realm of transplantation. Here, we aimed to evaluate urinary miRNA expression levels and assess their possible values in the prospective evaluation of renal allograft function. The expression levels of four miRNAs involved in renal fibrosis were quantified in urine cell pellets of 47 kidney recipients (with stable allograft function (SGF) and biopsy proven interstitial fibrosis and tubular atrophy; IFTA) and 15 healthy controls by real-time quantitative-PCR (RT-qPCR). The hierarchical clustering and receiver operating characteristic (ROC) analysis of miRNAs were performed in the study groups. Significant differences were observed in the urinary expression of miR-21 (P<0.001), miR-142-3p (P<0.001), and miR-200b (P=0.021) between IFTA and controls. The hierarchical clustering of miRNA expression clustered most of the SGF and IFTA patients in separated groups. Estimated GFR was significantly correlated with urinary levels of miR-21 (r=0.585, P=0.003) and miR-200 (r=-0.447, P=0.033). ROC analysis confirmed the ability of urinary miR-21 and miR-200b to discriminate the IFTA recipients with an area under the ROC curve of ≥0.81 (P<0.001) and high sensitivity and specificity. Taken together, our findings indicated that the aberrant urinary miR-21 and miR-200b expression levels were accompanied with renal allograft dysfunction and IFTA. Therefore, they can be considered as potential diagnostic biomarkers for renal allograft monitoring.

In vitro neutralization of hepatitis B virus by monoclonal antibodies against the viral surface antigen. In vitro HBV infection and neutralization were assayed using an anti-preS1 murine monoclonal antibody (1B3) and anti-preS2 (H69K) and anti-S (CS131A) murine-human chimeric antibodies. The 1B3 (IgG1) and H69K (IgG1) was constructed previously and the CS131A was constructed for this study by expressing stably the chimeric heavy and light chains in Chinese hamster ovary cells and purifying from the culture supernatant. Previous study showed that the H69K and CS131A recognize known virus-neutralizing epitopes, while the 1B3 does not. For the assays, adult human hepatocyte primary culture was infected with the adr or ayw subtype of HBV, and the infectivity and subsequent replication was confirmed both by measuring the kinetics of HB-sAg secretion by the infected cells and detecting the intermediate replicative form of HBV DNA in the cells. Next, the hepatocytes were infected with the adr or ayw subtype of the virus that had been preincubated with various concentrations of each of the antibodies and the neutralization of HBV was analyzed. The results showed that the anti-preS2 and anti-S chimeric antibodies exhibited neutralizing activity against both the adr and ayw subtypes of the virus, with approximately 1,000 and 2,000 times higher specific activity than polyclonal hepatitis B immune globulin, respectively, but the anti-preS1 antibody scarcely neutralized the infection. The neutralizing activities of the antibodies were consistent with their epitope specificity and antigenbinding affinity, suggesting that this neutralization assay is specific. The in vitro neutralization assay will be useful for evaluating the neutralizing activity of anti-HBV antibodies before in vivo testing in chimpanzees.