The finer details? The predictability of life outcomes from Big Five domains, facets, and nuances.
Associations between personality traits and life outcomes are usually studied using the Big Five domains and, occasionally, their facets. But recent research suggests these associations may be driven by the items (reflecting personality nuances) chosen to measure these traits. Using a large dataset (N = 6126), we examined associations with 53 self-reported outcomes using domains, facets and items (markers for nuances), training and validating models in different sample partitions. Facets better predicted outcomes than domains (on average, 18.0% versus 16.6% of variance explained), but items provided the most accurate predictions (on average 20.9%). Removing domain and facet variance from items had no effect on their predictive validity, suggesting that outcome-related information was often in items' unique variances (i.e., nuance-specific). Item-based prediction also showed the highest discriminant validity. These observations, replicating previous findings, suggest that personality traits' valid associations with outcomes are often driven by narrow personality nuances.


Diagnosis of cardiac tamponade by echocardiography: changes in mitral valve motion and ventricular dimensions, with special reference to paradoxical pulse.
The echocardiographic findings in three patients who presented with pericardial effusion and cardiac tamponade are described. Cyclic respiratory changes affected the diastolic movement of the anterior mitral leaflet, viz., during inspiration its anterior excursion decreased in amplitude and the E-F slope diminished. This inspiratory alteration in mitral valve motion was accompanied by an increase in right ventricular dimensions and a reciprocal decrease in left ventricular dimensions. Pericardial paracentesis confirmed the presence of effusion and relieved cardiac tamponade in all the patients. Repeat echocardiography, performed in two of the patients immediately after the pericardial tap, showed that the E-F slope had become steeper and that phasic respiratory variations in the diastolic motion of the anterior mitral leaflet were no longer present. The compatibility of our observations with the theories which endeavor to explain the mechanism of the paradoxical pulse in pericardial effusion with cardiac tamponade is discussed. We suggest that the abnormalities in anterior mitral leaflet motion defined by echocardiography constitute a useful addition to the study of patients with suspected cardiac tamponade resulting from pericardial effusion.


Variation in the Viral Hepatitis and HIV Policies and Practices of Methadone Maintenance Programs.
Patients prescribed methadone maintenance treatment (MMT) demonstrate elevated prevalence of hepatitis B virus (HBV), hepatitis C virus, and HIV. Government agencies recommend testing for these infections in MMT programs, but uptake is limited. We audited infection-related policies and practices of all 14 MMT programs in Philadelphia, Pennsylvania, in 2015. Results were tabulated and compared with the results from a 2010 audit of 10 of 12 MMT programs. The audit focused on which patients are tested, timing and frequency, specific tests ordered, vaccination, and communication of test results. Written policies were nonspecific, offering little guidance on appropriate testing. The principal change in policy between 2010 and 2015 involved adding clearer guidance for communication of results to patients. In 2010 and 2015, all MMT programs tested new patients for hepatitis C virus antibodies, although retesting of existing patients varied. HBV testing increased from 2010 to 2015, though it was not uniform, with 5 programs testing for HBV surface antibodies and 10 programs testing for HBV surface antigens. Six programs assessed hepatitis vaccination status, but only 1 administered vaccines. In 2010, city-sponsored HIV antibody testing was available at all MMT programs. Without this program in 2015, few MMT programs conducted HIV testing. Despite limited hepatitis and HIV screening in MMT programs nationally, this study shows that testing can be incorporated into routine procedures. MMT programs are positioned to play an integral role in the identification of patients with chronic infections, but additional guidance and resources are required to maximize their impact.


Talking about overweight and obesity in rural Australian general practice.
As many patients' sole point of contact with the health care system, primary health care physicians (general practitioners [GPs] in Australia) are often positioned as key players in responding to rates of overweight and obesity in dominant public discourse. However, research from Western industrialised countries suggests that GPs may not be prepared for, or confident in, having conversations about overweight and obesity with patients. Little attention has been given to this topic in Australia, particularly in the context of rural health. The aim of this study was to understand how GPs in two rural settings in Victoria, Australia talk about overweight and obesity with patients. Working from a multidisciplinary perspective, a qualitative study design was adopted, and semi-structured interviews were conducted with seven GPs and seven GP patients living in two rural communities between January and April, 2016. Data was coded manually and thematic analysis was used to explore the data. The findings of this study support the argument that, in contrast to dominant messages within public health discourses, GPs may not be best placed to act as the primary actors in responding to overweight and obesity as they are constructed in epidemiological terms. In fact, the perspectives of GP study participants suggest that to do so would compromise important dimensions of general medical practice that make it simultaneously a human practice. Instead, more balanced, holistic approaches to discussing and responding to overweight and obesity with patients could be taken up in local, interdisciplinary collaborations between different health professionals and patients, which utilise broader social supports. Focussing on long-term, incremental programs that consider the whole person within their particular socio-cultural environment would be a productive means of working with the complexities of overweight and obesity. However, structural level changes are required to ensure such initiatives are sustainable in rural practice.


Identification of Actinobacillus actinomycetemcomitans: polymerase chain reaction amplification of lktA-specific sequences.
Actinobacillus actinomycetemcomitans has been strongly implicated in the etiology of localized juvenile periodontitis. Techniques used in the identification of this periodontal pathogen include cultural, biochemical, immunological and DNA hybridization analysis. In this study, we report the use of polymerase chain reaction (PCR) to amplify unique sequences of A. actinomycetemcomitans. Specific oligonucleotide primers LKT2 and LKT3 were designed to hybridize to the A. actinomycetemcomitans lktA gene, which encodes leukotoxin, a putative A. actinomycetemcomitans virulence factor. The LKT2 and LKT3 primers amplified lktA-specific sequences from all 12 A. actinomycetemcomitans strains tested. In another set of experiments, 13 other bacterial species, most of which are normal residents of the oral cavity, were tested with these primers. These PCR amplifications also contained 2 additional primers, RRN4 and RRN5, which served as positive controls; RRN4 and RRN5 were designed to amplify specific sequences of eubacterial 16S ribosomal DNA (rDNA). PCR amplifications of all bacterial species tested, including A. actinomycetemcomitans, yielded 16S rDNA-specific DNA fragments. Furthermore, each bacterial species tested, with the exception of A. actinomycetemcomitans, failed to amplify lktA sequences. The LKT and RRN primers were used in further PCR experiments to detect A. actinomycetemcomitans directly from gingival fluid samples. The results clearly demonstrate the simplicity, rapidity, specificity and accuracy of the LKT primers in the identification of A. actinomycetemcomitans.


Characterization of Drosophila telomeric retroelement TAHRE: transcription, transpositions, and RNAi-based regulation of expression.
Telomeres in Drosophila are maintained by transpositions of specialized telomeric retroelements HeT-A and TART rather than by the telomerase activity adding short DNA repeats to chromosome ends in other eukaryotes. A novel element TAHRE was previously found in the telomeric regions of the genome of Drosophila melanogaster stock sequenced by the Genome Project. Comparative genomic analysis confirmed by Southern analysis and in situ hybridization of polytene chromosomes reveals conserved TAHRE elements in the genomes of melanogaster subgroup species. Spontaneous attachment of TAHRE retroelement to the broken end of terminally deleted chromosome allows us to consider TAHRE as the third retrotransposon family involved in telomere maintenance in Drosophila. The abundance of TAHRE transcripts in ovaries is strongly upregulated owing to mutations in the RNA interference genes spn-E, aub, piwi, and vasa locus. spn-E mutations eliminate TAHRE-specific short RNAs in the ovaries. These data suggest that TAHRE is a conservative element involved along with HeT-A and TART in telomere maintenance and a target of the RNAi-based system in the Drosophila germ line. This study reveals similar distribution of TAHRE and HeT-A transcripts, which accumulate in the oocyte, whereas TART transcripts localize in nurse cells. Taking into account a common pattern of HeT-A and TAHRE expression, one may consider TAHRE as a source of reverse transcriptase enzymatic activity for HeT-A transpositions in ovaries.


Distal anterior cerebral artery mirror aneurysms and middle cerebral artery aneurysms.
A 52-year-old woman presented with bilateral distal anterior cerebral artery (ACA) mirror aneurysms, in addition to two right middle cerebral artery (MCA) aneurysms. The left distal ACA and right MCA aneurysms were clipped through right interhemispheric and right pterional craniotomies. The right distal ACA aneurysm was thrombosed. Distal ACA aneurysms tend to be multiple, but mirror aneurysms are rare, especially in the absence of congenital vascular anomaly. Single stage unilateral craniotomy is recommended for surgical treatment.


Recovery patterns of shoulder subluxation after stroke: a six-month follow-up study.
Poststroke shoulder subluxation is a common complication that is thought to be irreversible without intervention. This study explores the natural recovery patterns of shoulder subluxation 6 months after stroke onset. Ten first-stroke survivors were evaluated in a free-standing rehabilitation hospital within 6 weeks of stroke onset and were reevaluated 6 months thereafter. Shoulder subluxation was measured in terms of glenohumeral asymmetries between affected and unaffected shoulders using anteroposterior radiographs before and after fitting of an appropriate support. Main outcome measures included shoulder subluxation asymmetries, range of motion, pain, and motor function as measured by the Fugl-Meyer Motor Function Assessment. Decreases in vertical asymmetry 6 months after initial evaluation were correlated with significant motor recovery (r =.7382, p =.018) and were associated with increases in the range of motion of shoulder abduction (r =.7167, p =.020). However, changes in vertical asymmetries were not correlated with changes in shoulder flexion (r =.3744, p =.286) or external rotation (r =.2155, p =.578) range of motion or with changes in shoulder pain (r = -.5189, p =.124). Six-month vertical asymmetries were correlated only with 6-month shoulder abduction range of motion (r =.6408, p =.046). Reductions in shoulder subluxation may occur spontaneously only when significant motor recovery of the affected upper limb occurs.


Case report: Interstitial pneumonitis after initiation of lamotrigine.
The second-generation anticonvulsant lamotrigine is widely used in the psychiatric field as a mood stabilizer or antidepressant augmentation therapy. Although particularly older anticonvulsants are known for their potential to cause hypersensitivity syndromes, newer antiepileptic drugs do hold a certain risk as well. Presenting a case of a 32-year-old male inpatient of African ethnicity suffering from a primary severe depressive episode in the course of a recurrent major depressive disorder, we report the occurrence of a rapid-onset drug-induced pneumonitis. Herewith, the interstitial pneumonitis occurred after the initiation of 25 mg lamotrigine as an augmentation therapy. Except for the clear temporal correlation between the administration of lamotrigine and the onset of pneumonitis, we did not reveal any further potentially causal diagnostic hints. Importantly, no relevant genetic variations of metabolizing enzymes or drug interactions resulting in lamotrigine overdosage as a potential cause of toxicity were identified. Our experience with a potentially life-threatening adverse drug reaction shortly after the initiation of the largely well-tolerated lamotrigine suggests a potential side effect under the second-generation anticonvulsant although similar adverse events are deemed to be very rare.


Grading the Severity of Damage to the Perijunctional Actomyosin Ring and Zonula Occludens-1 of the Corneal Endothelium by Ensemble Learning Methods.
Purpose: In many epithelia, including the corneal endothelium, intracellular/extracellular stresses break down the perijunctional actomyosin ring (PAMR) and zonula occludens-1 (ZO-1) at the apical junctions. This study aims to grade the severity of damage to PAMR and ZO-1 through machine learning. Methods: Immunocytochemical images of PAMR and ZO-1 were drawn from recent studies on the corneal endothelium subjected to hypothermia and oxidative stress. The images were analyzed for their morphological (e.g., Hu moments) and textural features (based on gray-level co-occurrence matrix [GLCM] and Gabor filters). The extracted features were ranked by SHapley analysis and analysis of variance. Then top features were used to grade the severity of damage using a suite of ensemble classifiers, including random forest, bagging classifier (BC), AdaBoost, extreme gradient boosting, and stacking classifier. Results: A partial set of features from GLCM, along with Hu moments and the number of hexagons, enabled the classification of damage to PAMR into Control, Mild, Moderate, and Severe with the area under the receiver operating characteristics curve (AUC) = 0.92 and F1 score = 0.77 with BC. In contrast, a bank of Gabor filters provided a partial set of features that could be combined with Hu moments, branch length, and sharpness for the classification of ZO-1 images into four levels with AUC = 0.95 and F1 score of 0.8 with BC. Conclusions: We have developed a workflow that enables the stratification of damage to PAMR and ZO-1. The approach can be applied to similar data during drug discovery or pathophysiological studies of epithelia.


Cytokine-induced NK-like T cells: from bench to bedside.
Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations.


Collagen/chitosan porous scaffolds with improved biostability for skin tissue engineering.
Porous scaffolds for skin tissue engineering were fabricated by freeze-drying the mixture of collagen and chitosan solutions. Glutaraldehyde (GA) was used to treat the scaffolds to improve their biostability. Confocal laser scanning microscopy observation confirmed the even distribution of these two constituent materials in the scaffold. The GA concentrations have a slight effect on the cross-section morphology and the swelling ratios of the cross-linked scaffolds. The collagenase digestion test proved that the presence of chitosan can obviously improve the biostability of the collagen/chitosan scaffold under the GA treatment, where chitosan might function as a cross-linking bridge. A detail investigation found that a steady increase of the biostability of the collagen/chitosan scaffold was achieved when GA concentration was lower than 0.1%, then was less influenced at a still higher GA concentration up to 0.25%. In vitro culture of human dermal fibroblasts proved that the GA-treated scaffold could retain the original good cytocompatibility of collagen to effectively accelerate cell infiltration and proliferation. In vivo animal tests further revealed that the scaffold could sufficiently support and accelerate the fibroblasts infiltration from the surrounding tissue. Immunohistochemistry analysis of the scaffold embedded for 28 days indicated that the biodegradation of the 0.25% GA-treated scaffold is a long-term process. All these results suggest that collagen/chitosan scaffold cross-linked by GA is a potential candidate for dermal equivalent with enhanced biostability and good biocompatibility.


Failure to Improve the Oxygenation Index Is a Useful Predictor of Therapy Failure in Acute Respiratory Distress Syndrome Clinical Trials.
Acute respiratory distress syndrome trials powered for mortality require significant resources, limiting the number of evaluable therapies. Validation of intermediate endpoints would enhance the feasibility of testing novel acute respiratory distress syndrome therapies in pilot studies and potentially reduce the frequency of failed large clinical trials. We sought to determine whether a change in the oxygenation index over the first 7 days of acute respiratory distress syndrome could discriminate between therapies likely or unlikely to show benefit in larger clinical trials. A derivation cohort from three acute respiratory distress syndrome studies was used to estimate the 7-day change in oxygenation index. Receiver operating characteristic curves were used to calculate optimal thresholds and predictability of the change in oxygenation index for 28-day mortality and ventilator-free days. The thresholds were then validated in two cohorts. Then, for each individual acute respiratory distress syndrome study, the threshold 7-day oxygenation index change was tested as an outcome measure and compared with mortality and ventilator-free days as reported in the original study. Medical ICUs. Acute respiratory distress syndrome patients. Various. Change in oxygenation index, 28-day mortality, and ventilator-free days. In the derivation cohort, the mean 7-day oxygenation index improved by 4.2 (± 11.7) in 28-day survivors compared with an increase of 2.4 (± 11.6) in 28-day nonsurvivors (p < 0.001). The mean 7-day oxygenation index decreased by 5.9 (± 8.4) in patients with more than 14 ventilator-free days, compared with a decrease of 1.9 (± 12.4) among those with less than 14 ventilator-free days (p = 0.001). The optimal 7-day oxygenation index threshold for predicting mortality was an increase of 1.71 and for predicting less than 14 ventilator-free days, a decrease of 2.34. When used as a surrogate endpoint, the optimal 7-day oxygenation index change closely approximated mortality and ventilator-free day outcomes in three Acute Respiratory Distress Syndrome Network studies used for the derivation cohort and a distinct study used for validation. The change in oxygenation index was a poor predictor of individual patient outcome. Failure to meet a threshold improvement in the oxygenation index over the first 7 days of therapy can be used to identify therapies unlikely to succeed in subsequent trials powered for mortality and ventilator-free days. By reducing trial time and costs, use of the 7-day oxygenation index change as an intermediate endpoint could increase the number of clinical trials of promising therapies for acute respiratory distress syndrome and reduce the number of large-scale trials of therapies unlikely to be of benefit.


The roles of Lewis acidic additives in organotransition metal catalysis.
We describe recent examples of prominent reactions in organic synthesis that involve transition metal and Lewis acid cocatalysts. Introducing Lewis acid additives to transition metal catalysis can enable new reactivity or improve activity and selectivity of an existing process. Several studies are highlighted to illustrate the possible roles of Lewis acids in catalytic mechanisms. The uses of Lewis acid additives in bond-breaking catalysis (C-C activation, C-H activation, and hydrogenolysis reactions) and bond-forming catalysis (Au-catalysed alkyne functionalisation, Pd-catalysed C-C and C-N bond formation) are reviewed.


Anatomical Origins of Radial Artery Perforators Evaluated Using Color Doppler Ultrasonography.
Background The radial artery perforator (RAP) flap has been widely used for covering hand and forearm defects, and real-time accurate perforator mapping is important in planning and elevating the perforator flap. The origins of perforators, especially the superficial and ulnar perforators, arising from the radial artery are very important in the elevation of the RAP flap. Recently, color Doppler ultrasonography (US) using a higher frequency transducer has been developed for high-quality detection of lower flow in smaller vessels. This study aimed to identify the anatomical locations and origins of perforators arising from the radial artery using color Doppler US in healthy volunteers. Methods Twenty forearms of 10 volunteers were examined. Results In total, 120 perforators arising from the radial artery were identified 15 cm proximal to the distal wrist crease, with an average of six perforators per forearm. More than half the perforators (n = 72, 60%) were located within 50 mm proximal to the distal wrist crease. Regarding the perforator origins in the axial view, 40 perforators (33%) were located in the radial aspect of the radial artery, 47 (39%) in the ulnar aspect, 15 (13%) in the superficial aspect, and 18 (15%) in the deep aspect. In total, 62 (52%) perforators were located in the superficial and ulnar areas, which are important in nourishing and elevating the RAP flap. Conclusion We are the first to evaluate RAP using color Doppler US. This noninvasive, convenient, and real-time technique could be useful for preoperative planning and reliably elevating the RAP flaps.


Dysphagia in Perry Syndrome: Pharyngeal Pressure in Two Cases.
To investigate the impact of dysphagia in Perry syndrome (PS), an autosomal dominant parkinsonism caused by mutation of DCTN1, which is associated with hypoventilation, depression, and weight loss. We used tongue pressure measurements and manofluorography to investigate swallowing function in 2 patients with PS. Case 1, a 60-year-old male showing parkinsonism, and case 2, a 49-year-old male admitted with pneumonia, were diagnosed as having PS based on the DCTN1 gene analysis. Case 1 showed a pharyngeal retention of the bolus on videofluorography (VF) and a few swallows were required for its passage into the esophagus. However, tongue pressure and manometry were within the normal range. This patient could eat a normal diet under supervision. Case 2 required artificial ventilation and tube feeding on admission. The VF image showed a slow transfer of the bolus, delayed swallow reflex, and pharyngeal retention of the bolus that required several swallows for its passage into the esophagus. The tongue pressure was within the normal range, but manometry showed a significant decrease in pressure at the hypopharynx and upper esophageal sphincter. The oral intake of the patients was limited to 2 cups of jelly per day. The investigation of swallowing dysfunction of 2 cases of PS showed that maintaining pharyngeal pressure within the normal range was very important for oral feeding success and prognosis.


Health-related lifestyles among Italian university students: A cross-sectional study.
to investigate lifestyle, health-related behaviours, and nutritional knowledge among a sample of Italian university students and to identify social determinants of - and barriers to - healthier lifestyles. cross-sectional observational study. students attending degree courses in health professions in a single university in Northern Italy (No. 1,495) were invited to participate in a structured web survey. a comprehensive, validated questionnaire was used. Questions regarded nutritional knowledge and habits, smoking habit, physical activity, self-efficacy, and barriers to change. Anthropometric and sociodemographic information was collected. Descriptive statistics were used to summarize results. With single and multiple regression models, differences between subgroups and ranked predictors of students' attitudes towards healthy behaviours were analysed. Statistical significance was set at p<0.05. a total of 554 subjects completed the survey (participation rate: 42%; completion rate: 88%). Students showed good nutritional knowledge (73%), but some deficiencies related to low fruit/high sweets consumption, and a lack of basic macronutrients information. Only 30% of the students led a very active lifestyle and physical inactivity was greatest among overweight/obese students. Sedentary lifestyle and unhealthy diet were mainly associated with modifiable risk factors, e.g., being overweight and smoking. this study provides evidence that health profession students have good knowledge, but their health-related lifestyle is a concern, especially given the role of prescribers that they will play. Structured programmes need to be developed to address the modifiable risk factors associated with detrimental behaviours manifest already during the university years.


Survival of patients with unresectable non-small cell lung cancer following 6,000 rad megavoltage radiotherapy.
One hundred and fifty-seven patients with histologically proven, locally advanced, unresectable or inoperable non-small cell lung cancer were treated in a uniform fashion with external-beam megavoltage radiotherapy. Patients received a continuous course of 6,000 rad in 7½ weeks (four fractions of 200 rad per fraction each week). The comparatively high, uncorrected one-year survival rate of 48.7 percent, and uncorrected two-year survival rate of 25.7 percent, would be expected following uniform treatment with a relatively high external-beam tumor dose. The five-year uncorrected actuarial survival rate of 2.7 percent demonstrates that although the median survival can be increased by the use of higher radiation doses and better delivery technique, the ultimate cure rate and prognosis for inoperable and unresectable non-small cell lung cancer remains poor with current equipment and methods of radiotherapy.


Acute effects and postactivation potentiation in the Special Judo Fitness Test.
The purpose of this study was to compare the acute short-term effects of (1) plyometric exercise, (2) combined strength and plyometric exercise (contrast), and (3) maximum strength performance in the Special Judo Fitness Test (SJFT). Eight male judo athletes (mean ± SD, age, 19 ± 1 years; body mass, 60.4 ± 5 kg; height, 168.3 ± 5.4 cm) took part in this study. Four different sessions were completed; each session had 1 type of intervention: (a) SJFT control, (b) plyometric exercises + SJFT, (c) maximum strength + SJFT, and (d) contrast + SJFT. The following variables were quantified: throws performed during series A, B, and C; total number of throws; heart rate immediately and 1 minute after the test; and test index. Significant differences were found in the number of throws during series A: the plyometric exercise (6.4 ± 0.5 throws) was superior (p < 0.05) to the control condition (5.6 ± 0.5 throws). Heart rate 1 minute after the SJFT was higher (p < 0.01) during the plyometric exercise (192 ± 8 bpm) than during the contrast exercise (184 ± 9 bpm). The contrast exercise (13.58 ± 0.72) resulted in better index values than the control (14.67 ± 1.30) and plyometric exercises (14.51 ± 0.54). Thus, this study suggests that contrast and plyometric exercises performed before the SJFT can result in improvements in the test index and anaerobic power of judo athletes, respectively.


Intrinsic and Synaptic Properties Shaping Diverse Behaviors of Neural Dynamics.
The majority of neurons in the neuronal system of the brain have a complex morphological structure, which diversifies the dynamics of neurons. In the granular layer of the cerebellum, there exists a unique cell type, the unipolar brush cell (UBC), that serves as an important relay cell for transferring information from outside mossy fibers to downstream granule cells. The distinguishing feature of the UBC is that it has a simple morphology, with only one short dendritic brush connected to its soma. Based on experimental evidence showing that UBCs exhibit a variety of dynamic behaviors, here we develop two simple models, one with a few detailed ion channels for simulation and the other one as a two-variable dynamical system for theoretical analysis, to characterize the intrinsic dynamics of UBCs. The reasonable values of the key channel parameters of the models can be determined by analysis of the stability of the resting membrane potential and the rebound firing properties of UBCs. Considered together with a large variety of synaptic dynamics installed on UBCs, we show that the simple-structured UBCs, as relay cells, can extend the range of dynamics and information from input mossy fibers to granule cells with low-frequency resonance and transfer stereotyped inputs to diverse amplitudes and phases of the output for downstream granule cells. These results suggest that neuronal computation, embedded within intrinsic ion channels and the diverse synaptic properties of single neurons without sophisticated morphology, can shape a large variety of dynamic behaviors to enhance the computational ability of local neuronal circuits.


Hypoxemia During Extreme Hyperleukocytosis: How Spurious?
Spurious hypoxemia has been described in case reports during extreme hyperleukocytosis and has led to recommendations for immediate cooling and analysis of arterial blood gases (ABGs). We sought to determine, in samples processed as recommended, the magnitude of spurious hypoxemia in acute leukemia subjects with hyperleukocytosis. A retrospective chart review was conducted of all subjects admitted between 2003 and July 2014 for acute leukemia, who presented with white blood cell (WBC) count > 50 × 10(9) cells/L and had ABGs performed. For each ABG, we collected PaO2 , SaO2 , simultaneous WBC count, and SpO2 when available. Bland and Altman analysis was used to assess the agreement between SpO2 and SaO2 . One-hundred forty-six samples (from 45 subjects) were included, of which 57 samples (from 18 subjects) had data available for Bland and Altman analysis. Mean (SpO2 - SaO2 ) was 2.5%, and 95% CI for limits of agreement between SpO2 and SaO2 was (-10.1,15.1)%. The mean (SpO2 - SaO2 ) was significantly higher for WBC count > 100 × 10(9)/L as compared with WBC count < 100 × 10(9)/L (3.8% vs 0.4%, P = .04), and the 95% CIs for limits of agreement were (-10.3,18)% versus (-7.9,8.6)%. SpO2 and SaO2 were poorly correlated (r(2) = 0.19), whereas the difference (SpO2 - SaO2 ) was fairly correlated with WBC count (r(2) = 0.44). Overall, 11 of 19 samples with WBC count > 150 × 10(9)/L had PaO2 < 55 mm Hg whereas SpO2 was > 94%, the proportion being 5 of 62 samples for WBC count < 150 × 10(9)/L (P < .001). Three subjects with WBC count > 150 × 10(9)/L exhibited large SpO2 to SaO2 differences (10-20%) before leukapheresis, which decreased to below 5% afterward. In subjects with acute leukemia and hyperleukocytosis, despite cooling and quickly analyzing the samples, we observed poor correlation and agreement between SpO2 and SaO2 , unacceptably low for WBC count > 100 × 10(9)/L. Our results suggest that current guidelines may not totally prevent the diagnosis of spurious hypoxemia.


Value and types of medicines returned by patients to sultan qaboos university hospital pharmacy, oman.
Frequent physician visits, improper therapeutic adherence and treatment modification after hospitalisation could result in unused medicine accumulating at home. This study aims to examine the value and types of medicines returned by patients at a tertiary care unit in Oman. All medicines voluntarily returned to Sultan Qaboos University Hospital main pharmacy between February and June 2003 were reviewed. The cost of these medicines and potential cost saving, if some were returned to the hospital distribution cycle, were computed. A method of determining by physical observation whether they can be recycled was developed based on institutional-based guidelines and criteria. Three hundred and eighty one patients returned their medicines (69% female). The patients returned a total of 1071 drugs (mean per patient 3.1 per month) corresponding to a total cost of Omani Rials (OR) 20,140 (mean per patient OR 10.6) (1 OR = 2.58 US dollar). Potential cost saving was OR 5,550 (mean per patient OR 2.9). Medicines of the cardiovascular group were returned in greatest number (24%) while anti-infective drugs had the highest share of the total cost (61%). The study identified values and types of medicines returned by patients at tertiary care unit in Oman. Medications used for cardiovascular and infectious diseases appeared as the most frequent and the most expensive returned medicines. It suggests that health care providers in Oman should devise health education programmes to improve proper utilization of medicine.


TRUE Gene Silencing: Screening of a Heptamer-type Small Guide RNA Library for Potential Cancer Therapeutic Agents.
TRUE gene silencing (termed after tRNase Z(L)-utilizing efficacious gene silencing) is one of the RNA-directed gene silencing technologies, which utilizes an artificial small guide RNA (sgRNA) to guide tRNA 3' processing endoribonuclease, tRNase Z(L), to recognize a target RNA. sgRNAs can be taken up by cells without any transfection reagents and can downregulate their target RNA levels and/or induce apoptosis in human cancer cells. We have screened an sgRNA library containing 156 heptamer-type sgRNAs for the effect on viability of human myeloma and leukemia cells, and found that 20 of them can efficiently induce apoptosis in at least one of the cancer cell lines. Here we present a protocol for screening of a heptamer-type sgRNA library for potential therapeutic drugs against blood cancers. The protocol includes how to construct the sgRNA library, how to assess the effect of each sgRNA on cell viability, and how to further evaluate the effective sgRNAs by flow cytometry. Around 2,000 hits would be expected to be obtained by screening the full-scale sgRNA library composed of 16,384 heptamers.


Stereological quantification of placental villus vascularization and its relation to umbilical artery Doppler flow in intrauterine growth restriction.
The aim of this study was to investigate the changes in the number of vessels within tertiary stem villi and intermediate/terminal villi which may be responsible for the abnormalities in placental vascular resistance and Doppler velocity index values in growth-restricted fetuses. The placentas of 20 cases with intrauterine growth restriction and 30 cases which were appropriate for gestational age were studied. The umbilical artery resistance index, pulsatility index and systolic to diastolic ratio were measured in each case. The vessels were quantified by a stereological method described previously and vascular surface density and the volume portion of the villi were calculated. The placentas of preterm and term cases with intrauterine growth restriction displayed significant reductions in the vascular surface density of stem and intermediate/terminal villi and volume portion of intermediate/terminal villi stroma when compared with gestation-matched normally grown cases (p<0.05). There was no significant correlation between Doppler index values of the umbilical artery and the stereological parameters of the intermediate/terminal and stem villi in the intrauterine growth restriction group (p>0.05). Some of the pregnancies with intrauterine growth restriction (six patients) with normal Doppler flow velocity waveforms had reduced vascularization in the placentas, and these pregnancies were found to have no perinatal complications. We conclude that,although the placental villi show reduced vascularization in pregnancies with intrauterine growth restriction, the Doppler indices may be normal and this normal flow pattern is related to reduced complication rate.


Craniopharyngioma Clinical Status Scale: a standardized metric of preoperative function and posttreatment outcome.
Controversy persists concerning the optimal treatment of craniopharyngiomas in children, and no standard outcome metric exists for comparison across treatment modalities, nor is there one that adequately reflects the multisystem dysfunction that may arise. The authors retrospectively analyzed the records of 86 consecutive children who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. Excluding 3 perioperative deaths and 3 patients with inadequate follow-up, 80 children (34 girls and 46 boys; mean age 9.56 years; mean follow-up 9.6 years) composed the study group (53 primary and 27 previously treated/recurrent tumors). Building on existing classification schemes proposed by De Vile for hypothalamic dysfunction and Wen for overall functional outcome, the authors devised a more nuanced classification system (Craniopharyngioma Clinical Status Scale [CCSS]) that assesses outcome across 5 axes, including neurological examination, visual status, pituitary function, hypothalamic dysfunction, and educational/occupational status at last follow-up (there is a 4-tiered grading scale in each domain, with increasing values reflecting greater dysfunction). There was a significant increase in pituitary dysfunction following treatment-consistent with the high rates of diabetes insipidus and hypopituitarism common to the surgical management of craniopharyngiomas-and less dramatic deterioration in hypothalamic function or cognitive domains. Significant improvement in vision was also demonstrated, with no significant overall change in neurological status. Preoperative CCSS scores predicted postoperative outcome better than clinical characteristics like patient age, sex, tumor size, and the location or presence of hydrocephalus. Preoperative CCSS scores predicted outcome with higher accuracy than clinical or imaging characteristics. In lieu of randomized trials, the CCSS may provide a useful outcome assessment tool for comparison across treatment paradigms and surgical approaches. Long-term follow-up is critical to the analysis of outcomes of craniopharyngioma treatment, given the often-delayed sequelae of all therapies and the high recurrence rates of these tumors.


Origin of evolution versus origin of life: a shift of paradigm.
The question of the primordial ancestor must be approached through the search for the origin of evolution, not through the search for the origin of life. There is a major issue with the concept of life because it is impossible to define, thus is not a scientific but a metaphysical concept. On the contrary, evolution may be defined by as few as three conditions. These do not necessarily involve biopolymers. However, such an approach must give clues to explain the emergence of distinct lineages to allow Darwinian natural selection. A plausible solution exists within an autotrophic lipidic vesicle-based model that is presented. The model requires the existence of hydrothermal sites such as the Lost City Hydrothermal Field leading to specific constraints. For this reason Mars and Europa may be questioned as possible cradles of evolution. If we replace the search for the origin of life by the one for the origin of evolution our priority first is to find a consensus on the minimal conditions that would allow evolution to emerge and persist anywhere in the universe.


Purification and characterization of type 1 fimbriae of Salmonella typhi.
Type 1 fimbriae have been purified from a Salmonella typhi strain of clinical origin. Purified fimbriae retained their ability to bind to erythrocytes in a mannose-inhibitable fashion and, in doing so, behaved preferentially as a monovalent adhesin. SDS-PAGE analysis of the fimbrial preparation showed the presence of a 20-kDa major polypeptide component (fimbrillin) and of additional larger polypeptides present in smaller amounts. The amino-terminal sequence of fimbrillin was determined and turned out to be very similar but not identical to that of type 1 fimbrillins of other Salmonella serovars. A Western blot analysis of the purified fimbrial preparation using an antiserum raised against native fimbriae suggested that fimbrial proteins did not carry any major sequential epitope and that, in native fimbriae, conformational epitopes, possibly generated between different subunits, might provide for the major immunogenic epitopes. Analysis of different S. typhi clinical isolates using the anti-fimbrial antiserum showed an overall immunological similarity of these structures within this serovar.


Pharmacology of flibanserin.
Flibanserin has preferential affinity for serotonin 5-HT(1A), dopamine D(4k), and serotonin 5-HT(2A) receptors. In vitro and in microiontophoresis, flibanserin behaves as a 5-HT(1A) agonist, a very weak partial agonist on dopamine D(4) receptors, and a 5-HT(2A) antagonist. In vivo flibanserin binds equally to 5-HT(1A) and 5-HT(2A) receptors. However, under higher levels of brain 5-HT (i.e., under stress), flibanserin may occupy 5-HT(2A) receptors in higher proportion than 5-HT(1A) receptors. The effects of flibanserin on adenylyl cyclase are different from those of buspirone and 8-OH-DPAT, two other purported 5-HT(1A) receptor agonists. Flibanserin reduces neuronal firing rate in cells of the dorsal raphe, hippocampus, and cortex with the CA1 region being the most sensitive in the brain. Flibanserin-induced reduction in firing rate in the cortex seems to be mediated through stimulation of postsynaptic 5-HT(1A) receptors, whereas the reduction of the number of active cells seems to be mediated through dopamine D(4) receptor stimulation. Flibanserin quickly desensitizes somatic 5-HT autoreceptors in the dorsal raphe and enhances tonic activation of postsynaptic 5-HT(1A) receptors in the CA3 region. Flibanserin preferentially reduces synthesis and extracellular levels of 5-HT in the cortex, where it enhances extracellular levels of NE and DA. Flibanserin displays antidepressant-like activity in most animal models sensitive to antidepressants. Such activity, however, seems qualitatively different from that exerted by other antidepressants. Flibanserin seems to act via direct or indirect stimulation of 5-HT(1A), DA, and opioid receptors in those animal models. Flibanserin does not display consistent effects in animal models of anxiety and seems to exert potential antipsychotic effects. Flibanserin may induce some sedation but does not induce observable toxic effects at pharmacologically relevant doses.


FDG PET/CT imaging features and clinical utility in COVID-19.
To determine the imaging findings and potential clinical utility of FDG PET/CT in patients with laboratory-confirmed COVID-19. We performed a single institution retrospective review of patients diagnosed with COVID-19 using real time reverse transcription-polymerase chain reaction (RT-PCR) who underwent FDG PET/CT for routine cancer care between March 1, 2020 to April 30, 2020, during the height of the pandemic in New York City, New York, United States. PET/CT scans were retrospectively reviewed for imaging findings suspicious for COVID-19. For positive scans, PET and CT findings were recorded, including location, FDG avidity (SUVmax) and CT morphology. Patient demographics and COVID-19 specific clinical data were collected and analyzed with respect to PET/CT scan positivity, lung SUVmax, and time interval between PET/CT and RT-PCR. Thirty-one patients (21 males and 10 females, mean age 57 years ± 16) were evaluated. Thirteen of 31 patients had positive PET/CT scans, yielding a detection rate of 41.9%. Patients with positive scans had significantly higher rates of symptomatic COVID-19 infection (77% vs 28%, p = 0.01) and hospitalizations (46% vs. 0%, p = 0.002) compared to patients with negative scans. Eleven of 13 patients (84.6%) with positive scans had FDG-avid lung findings, with mean lung SUVmax of 5.36. Six of 13 patients (46.2%) had extrapulmonary findings of FDG-avid thoracic lymph nodes. The detection rate was significantly lower when the scan was performed before RT-PCR versus after RT-PCR (18.8% (n = 3/16) vs. 66.7% (n = 10/15), p = 0.009). Lung SUVmax was not associated with COVID-19 symptoms, severity, or disease course. FDG PET/CT has limited sensitivity for detecting COVID-19 infection. However, a positive PET scan is associated with higher risk of symptomatic infection and hospitalizations, which may be helpful in predicting disease severity.


Roles of Runx2 in Skeletal Development.
Runx2 is the most upstream transcription factor essential for osteoblast differentiation. It regulates the expression of Sp7, the protein of which is a crucial transcription factor for osteoblast differentiation, as well as that of bone matrix genes including Spp1, Ibsp, and Bglap2. Runx2 is also required for chondrocyte maturation, and Runx3 has a redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the expression of Col10a1, Spp1, Ibsp, and Mmp13 in chondrocytes. It also inhibits chondrocytes from acquiring the phenotypes of permanent cartilage chondrocytes. It regulates chondrocyte proliferation through the regulation of Ihh expression. Runx2 enhances osteoclastogenesis by regulating Rankl. Cbfb, which is a co-transcription factor for Runx family proteins, plays an important role in skeletal development by stabilizing Runx family proteins. In Cbfb isoforms, Cbfb1 is more potent than Cbfb2 in Runx2-dependent transcriptional regulation; however, the expression level of Cbfb2 is three-fold higher than that of Cbfb1, demonstrating the requirement of Cbfb2 in skeletal development. The expression of Runx2 in osteoblasts is regulated by a 343-bp enhancer located upstream of the P1 promoter. This enhancer is activated by an enhanceosome composed of Dlx5/6, Mef2, Tcf7, Ctnnb1, Sox5/6, Smad1, and Sp7. Thus, Runx2 is a multifunctional transcription factor that is essential for skeletal development, and Cbfb regulates skeletal development by modulating the stability and transcriptional activity of Runx family proteins.


Bilateral primary adrenal diffuse large B cell lymphoma without adrenal insufficiency: A case report and review of the literature.
Primary adrenal lymphoma (PAL) is an infrequent malignant tumor, occurring in the bilateral adrenal glands as a mass in the majority of cases. The current study presents a case of bilateral primary adrenal diffuse large B cell lymphoma in a 52-year-old female patient, who presented with abdominal pain in the left lumbar region for ~2 weeks. Abdominal ultrasound examination and computed tomography scanning revealed a mass of 132×119×101 mm on the left adrenal gland and a mass of 53×27 mm on the right adrenal gland. A percutaneous biopsy was performed and histopathological examination further confirmed this lesion as diffuse large B cell lymphoma. The present study highlights the importance of early diagnosis of PAL, and performs a literature review of the subject.


Appearance of Meningioma on 99mTc-HMPAO SPECT: Correlation with MRI.
On brain perfusion SPECT, a primary brain lesion presents as a localized defect that corresponds to the mass lesion. (99m)Tc-HMPAO images generally show a focal defect in the region of abnormality, whether containing necrotic tissue, recurrent tumor, or both. Further characterization with MR imaging is needed to confirm the diagnosis, as demonstrated in this case report.


Multiple comparisons of repeated measured response: issues of assessment of prolongation of QT interval in thorough QT trials.
The primary objective of a thorough QT clinical trial is to demonstrate the lack of QT prolongation induced by the test treatment. The ICH E14 guidance defined drug-induced prolongation of QT interval as evidenced by an upper bound of the 95% one-sided confidence interval around the mean effect on QTc of 10 ms. Furthermore, it defined a negative thorough QT/QTc study as one in which the upper bound of the 95% one-sided confidence interval for the largest time-matched mean effect of the drug on the QTc interval excludes 10 ms. Conventionally, this objective is tested with the intersection-union test by testing the mean difference between the test treatment and placebo of QTc changes from baseline at each of the matched time points. The multiple-comparison nature of the test leads to higher false positive rate when comparisons are made repeatedly at multiple time points. Many approaches have been proposed in the last 5 years in order to improve the efficiency of the test. In this article, we survey and discuss some of the approaches.


[Association between chronic diseases and possible sarcopenia in middle-aged and older Chinese men: A prospective cohort study].
To investigate the association between chronic diseases and the risk of possible sarcopenia among middle-aged and older Chinese males. This prospective cohort study included the data collected from the China Health and Retirement Longitudinal Study on 4 878 males aged over 45 years without possible sarcopenia as the baseline population in 2011 and 2013, and all were followed up until 2015. Possible sarcopenia was determined by measuring the grip strength and the time of five successive sit-ups. The Cox proportional risk model was used to analyze the relationship of the type and number of chronic diseases with the risk of possible sarcopenia in males. The risk of possible sarcopenia in the middle-aged and older men with prostatic disease, cognitive impairment or depression was increased by 16% (HR = 1.16, 95% CI: 1.01-1.33), 23% (HR = 1.23, 95% CI: 1.10-1.38) and 12% (HR = 1.12, 95% CI: 1.01-1.24), respectively. The risk in those with one, two or three or more chronic diseases was raised by 22% (HR = 1.22, 95% CI: 1.04-1.42), 20% (HR = 1.20, 95% CI: 1.02-1.42) and 46% (HR = 1.46, 95% CI: 1.25-1.71), respectively, compared with those without chronic diseases, and it was increased in a dose-dependent manner (P < 0.01) Conclusion: Prostatic disease, cognitive impairment and depression increase the risk of possible sarcopenia in middle-aged and older Chinese males, and the risk rises with the increased number of chronic comorbidities.


Anatomical variation at the sapheno-femoral junction.
The aim of this study was to assess the anatomical variations of the sapheno-femoral junction (SFJ) and the incidence of these variations. Between April 2005 and March 2010, 2552 limbs of 1563 patients with complaints of varicose veins underwent ultrasonography. Ultrasonography was used to identify the anatomical variations of the SFJ, especially the relationship to the femoral artery. Variations were seen in six limbs (0.24%) at the SFJ. The most common anatomical variation was the great saphenous vein crossing posterior to the common femoral artery, which was present in three limbs. It is important to investigate the anomalies of the SFJ using preoperative duplex ultrasound, although the incidence of such anomalies is lower than that of the sapheno-popliteal junction. An anomaly of the SFJ always should be taken into consideration in order to minimize surgical complications of varicose veins. (English translation of Jpn J Phlebol 2012; 23: 25-29).


Biochemical and immunological characterization of polyproteins coded for by the McDonough, Gardner-Arnstein, and Snyder-Theilen strains of feline sarcoma virus.
The McDonough (SM), Gardner-Arnstein (GA), and Snyder-Theilen (ST) strains of feline sarcoma virus (FeSV) code for high-molecular-weight polyproteins that contain varying amounts of the amino-terminal region of the FeLV gag gene-coded precursor protein and a polypeptide(s) of an as yet undetermined nature. The SM-FeSV primary translational product is a 180,000-dalton polyprotein which is immediately processed into a highly unstable 60,000-dalton molecule containing the p15-p12-p30 fragment of the FeLV gag gene-coded precursor protein and a 120,000-dalton FeSV-specific polypeptide. The GA- and ST-FeSV genomes code for polyproteins of 95,000 and 85,000 daltons, respectively, which in addition to the amino-terminal moiety (p15-12 and a portion of p30) of the FeLV gag gene-coded precursor protein also contain FeSV-specific polypeptides. However, the GA- and ST-FeSV polyproteins appear to be relatively stable molecules (half-lives of around 16 h) and are not significantly processed into smaller polypeptides. Immunological and biochemical analysis of each of the above FeSV translational products revealed that the sarcoma-specific regions of the GA- and ST-FeSV polyproteins are antigenically cross-reactive and exhibit common methionine-containing peptides. These findings favor the concept that these sarcoma-specific polypeptides are coded for by the similar subsets of cellular sequences incorporated into the GA- and ST-FeSV genomes during the generation of these transforming agents.


Cryo-EM structures and functional properties of CALHM channels of the human placenta.
The transport of substances across the placenta is essential for the development of the fetus. Here, we were interested in the role of channels of the calcium homeostasis modulator (CALHM) family in the human placenta. By transcript analysis, we found the paralogs CALHM2, 4, and 6 to be highly expressed in this organ and upregulated during trophoblast differentiation. Based on electrophysiology, we observed that activation of these paralogs differs from the voltage- and calcium-gated channel CALHM1. Cryo-EM structures of CALHM4 display decameric and undecameric assemblies with large cylindrical pore, while in CALHM6 a conformational change has converted the pore shape into a conus that narrows at the intracellular side, thus describing distinct functional states of the channel. The pore geometry alters the distribution of lipids, which occupy the cylindrical pore of CALHM4 in a bilayer-like arrangement whereas they have redistributed in the conical pore of CALHM6 with potential functional consequences.


Molecular products from the thermal degradation of glutamic acid.
The thermal behavior of glutamic acid was investigated in N2 and 4% O2 in N2 under flow reactor conditions at a constant residence time of 0.2 s, within a total pyrolysis time of 3 min at 1 atm. The identification of the main pyrolysis products has been reported. Accordingly, the principal products for pyrolysis in order of decreasing abundance were succinimide, pyrrole, acetonitrile, and 2-pyrrolidone. For oxidative pyrolysis, the main products were succinimide, propiolactone, ethanol, and hydrogen cyanide. Whereas benzene, toluene, and a few low molecular weight hydrocarbons (propene, propane, 1-butene, and 2-butene) were detected during pyrolysis, no polycyclic aromatic hydrocarbons (PAHs) were detected. Oxidative pyrolysis yielded low molecular weight hydrocarbon products in trace amounts. The mechanistic channels describing the formation of the major product succinimide have been explored. The detection of succinimide (major product) and maleimide (minor product) from the thermal decomposition of glutamic acid has been reported for the first time in this study. Toxicological implications of some reaction products (HCN, acetonitrile, and acyrolnitrile), which are believed to form during heat treatment of food, tobacco burning, and drug processing, have been discussed in relation to the thermal degradation of glutamic acid.


The safety and probable therapeutic effect of routine use of antibiotics and simultaneously treating bleeding gastric varices by using endoscopic cyanoacrylate injection and concomitant esophageal varices with banding ligation: a pilot study.
Gastroesophageal varices are the most common type of gastric varices. Although endoscopic injection of N-butyl-2-cyanoacrylate is the current treatment of choice for acute gastric variceal bleeding, whether the concomitant esophageal varices should be ligated simultaneously with the first treatment session is currently not known. The aim of this study was to evaluate the safety and probable therapeutic effect of simultaneous cyanoacrylate injection for bleeding gastric varices obliteration (GVO) and endoscopic band ligation (EBL) for concomitant esophageal varices in combination with routine antibiotics (simultaneous group), and to compare our results with historical results in which the patients underwent GVO first and then EBL for concomitant esophageal varices (separate group). A single-center pilot study. A tertiary referral center. Patients with liver cirrhosis and gastroesophageal varices, who presented with acute gastric varices bleeding. Simultaneous treatment in the form of GVO and EBL for concomitant esophageal varices in combination with routine antibiotics. Rebleeding and mortality within the first year of index bleeding. Twenty patients in the simultaneous group and 67 patients in the separate group were included in the study. The 2 groups had similar baseline characteristics. The hemostasis of active bleeding was 100% in both groups (7/7 vs 20/20). The 1-year rebleeding rate was 10% (2/20) in the simultaneous group and 37.31% (25/67) in the separate group (P = .041). Kaplan-Meier analysis showed higher probability of remaining free of rebleeding in the simultaneous group (88.5% vs 61.1%; P = .044). Multivariate analysis indicated that treatment method (separate group) and high model for end-stage liver disease score (> or = 13) were independent risk factors of rebleeding in 1 year. The treatment failure, complications, 1-year mortality, and survival were similar in both groups. Simultaneous endoscopic treatment for gastric varices bleeding and concomitant esophageal varices is a safe and effective procedure in combination with antibiotic prophylaxis for patients with cirrhosis. The 1-year mortality rate was similar between the 2 groups. The results need further validation.


Sodium hydroxide treatment effectively inhibits PrPCWD replication in farm soil.
Chronic wasting disease (CWD) agents are shed into biological samples, facilitating their horizontal transmission between cervid species. Once prions enter the environment, binding of PrPCWD by soil particles may maintain them near the soil surface, posing a challenge for decontamination. A 2 N sodium hydroxide (NaOH) or 2% sodium hypochlorite (NaClO) solution is traditionally recommended for prion decontamination of equipment and surfaces. Using protein misfolding cyclic amplification with beads and a bioassay with TgElk mice, we compared the effects of these disinfectants in CWD-contaminated soil for 1 or 16 h to those of controls of known infectious titres. Our results suggest that 2 N NaOH in a 1/5 farm soil volume provides a large decrease (>102-fold) in prion infectivity.


Validation of the Brazilian version of the Hip Outcome Score (HOS) questionnaire.
The Hip Outcome Score (HOS) was developed to evaluate physically active patients with hip disease but without severe degenerative change. A translation and cultural adaptation into Brazilian Portuguese was previously conducted. The aim of this study was to validate the Brazilian version of the HOS (HOS-Brazil) among a group of physically active patients with a diagnosis of femoroacetabular impingement (FAI) or greater trochanteric pain syndrome (GTPS). The following questionnaires were applied: the HOS-Brazil; the validated Brazilian versions of the Nonarthritic Hip Score (NAHS) and the 12-Item Short-Form Health Survey (SF-12). The psychometric properties analyzed with regard to the validation process were reliability and validity. Internal consistency and intra-rater test-retest reliabilities were analyzed using Cronbach's alpha and the intraclass correlation coefficient (ICC) statistical tests based on test-retest agreement. Construct and content validities were examined using Pearson's correlation coefficient. Content validity was also analyzed based on evidence of floor, ceiling, or both types of effects from the questionnaires. A total of 70 male and female patients were selected, aged between 19 and 70 years old. The internal consistency and intra-rater test-retest reliability values were high (Cronbach's α > 0.9; ICC > 0.9). The questionnaire showed acceptable convergent (r > 0.7) and divergent (r < 0.4) validities. No floor or ceiling effects were observed. The HOS-Brazil was validated. Additional studies are underway to evaluate its responsiveness.


Overcoming stiffness in stochastic simulation stemming from partial equilibrium: a multiscale Monte Carlo algorithm.
In this paper the problem of stiffness in stochastic simulation of singularly perturbed systems is discussed. Such stiffness arises often from partial equilibrium or quasi-steady-state type of conditions. A multiscale Monte Carlo method is discussed that first assesses whether partial equilibrium is established using a simple criterion. The exact stochastic simulation algorithm (SSA) is next employed to sample among fast reactions over short time intervals (microscopic time steps) in order to compute numerically the proper probability distribution function for sampling the slow reactions. Subsequently, the SSA is used to sample among slow reactions and advance the time by large (macroscopic) time steps. Numerical examples indicate that not only long times can be simulated but also fluctuations are properly captured and substantial computational savings result.


A pyroptosis-related gene signature for prognostic and immunological evaluation in breast cancer.
Pyroptosis exerts an undesirable impact on the clinical outcome of breast cancer. Since any single gene is insufficient to be an appropriate marker for pyroptosis, our aim is to develop a pyroptosis-related gene (PRG) signature to predict the survival status and immunological landscape for breast cancer patients. The information of breast cancer patients was retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the gene expressions of this signature in breast cancer. Its prognostic value was evaluated by univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, receiver operating characteristics (ROCs), univariate/multivariate analysis, and nomogram. Analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to explore its potential biological function in breast cancer. The potential correlation between this signature and tumor immunity was revealed based on single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms. A PRG signature containing GSDMC, GZMB, IL18, and TP63 was created in a TCGA training cohort and validated in two validation GEO cohorts GSE58812 and GSE37751. Compared with a human mammary epithelial cell line MCF-10A, the expression levels of GSDMC, GZMB and IL18 were upregulated, while TP63 was found with lower expression level in breast cancer cells SK-BR-3, BT-549, MCF-7, and MDA-MB-231 using RT-qPCR assay. Based on univariate and multivariate Cox models, ROC curve, nomogram as well as calibration curve, it was revealed that this signature with high-risk score could independently predict poor clinical outcomes in breast cancer. Enrichment analyses demonstrated that the involved mechanism was tightly linked to immune-related processes. SsGSEA, ESTIMATE and CIBERSORT algorithms further pointed out that the established model might exert an impact on immune cell abundance, immune cell types and immune-checkpoint markers. Furthermore, individuals with breast cancer responded differently to these therapeutic agents based on this signature. Our data suggested that this PRG signature with high risk was tightly associated with impaired immune function, possibly resulting in an unfavorable outcome for breast cancer patients.


Minimally Invasive Method for Correcting Reducible Cryptotia.
Various surgical methods have been used to treat cryptotia; however, there is a drawback of these methods in that they leave a permanent scar. The authors describe a 7-year-old child who missed the optimal corrective time for cryptotia. Minimally invasive surgery was planned as a 3rd alternative to external splinting or invasive surgery by taking advantage of 2 methods. Silly putty was prefabricated as an auricular sulcus retainer, and fixation sutures between the deep dermis and temporal fascia were placed through small incisions along the future auricular sulcus. Then the prefabricated auricular sulcus retainer was maintained for 2 months. After 6 months, the corrected ear shape remained stable with the inconspicuous scar. With minimally invasive correction, a successful treatment effect can be expected while minimizing scarring in patients who are not expected to have a therapeutic effect with a simple reduction.


The treatment of acne vulgaris with low dosage doxycycline.
Doxycycline hyclate 20 mg bid is an effective maintenance dosage in patients with inflammatory acne. Twelve subjects aged 14 to 36, both men and women, completed a 16-week study to demonstrate the effectiveness of submicrobial dosing of doxycycline hyclate. Seventeen subjects were screened, and three withdrew before receiving any medication. The subjects received doxycycline hyclate 100 mg daily for eight weeks. One subject withdrew due to unrelated side effects. Eleven subjects had a 50% reduction of lesions at eight weeks, which qualified them to enter the second eight-week phase of the study. This group received either doxycycline hyclate 20 mg bid or placebo. The six subjects receiving doxycycline hyclate 20 mg bid maintained their improvement, while the placebo group did not.


The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.
Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.


Solubilization of kainic acid binding sites from rat brain.
Kainic acid binding sites were solubilized from rat brain using a combination of Triton X-100 and digitonin. The highest percentage of solubilized binding sites (45%) was obtained by treating brain membranes with 1% Triton-X-100 and 0.2% digitonin in 0.5 M potassium phosphate containing 20% glycerol. The solubilized binding sites were stable and amenable to analysis by gel filtration and lectin affinity chromatography. Computer assisted analyses demonstrated that the solubilized sites displayed high- and low-affinity binding constants similar to the membrane-bound sites. Competition experiments further supported the pharmacological similarities of the solubilized and membrane-bound sites. Gel filtration chromatography of the solubilized binding site indicated that the detergent-bound complex had a Stokes radius of 82.7 A. The [3H]kainic acid binding site appears to be glycosylated based on its capability to bind to lectins. The lectin, wheatgerm agglutinin, proved to be a potentially useful tool for characterization because the solubilized binding sites were bound and eluted in relatively high yield.


Solubilisation of the benzodiazepine receptor from rat cerebellum by the detergent n-octylpentaoxyethylene.
The detergent n-octylpentaoxyethylene is one in the series of tenside detergents developed for membrane solubilisation. We have used this detergent to solubilise benzodiazepine receptors from rat cerebellum. The soluble receptor has an affinity (KD) for [3H]flunitrazepam of 1.8 nM +/- 0.2, which is not significantly different from that observed in synaptic membranes. Under optimal conditions (0.6% wt/vol), the number of soluble flunitrazepam binding sites (Bmax) of 0.35 pmol/mg protein suggests an apparent solubilisation of 40% of sites from the membrane. However, the absence of the characteristic facilitation of [3H]flunitrazepam binding by gamma-aminobutyric acid (GABA), cartazolate, and pentobarbital in this soluble receptor preparation suggests that such a preparation is unlikely to be a useful preparation for further studies on the molecular mechanisms underlying GABAA receptor function.


Control of Forelimb and Hindlimb Movements and Their Coordination during Quadrupedal Locomotion across Speeds in Adult Spinal Cats.
Coordinating the four limbs is critical for terrestrial mammalian locomotion. Thoracic spinal transection abolishes neural communication between the brain and spinal networks controlling hindlimb/leg movements. Several studies have shown that animal models of spinal transection (spinalization), such as mice, rats, cats, and dogs recover hindlimb locomotion with the forelimbs stationary or suspended. We know less on the ability to generate quadrupedal locomotion after spinal transection, however. We collected kinematic and electromyography data in four adult cats during quadrupedal locomotion at five treadmill speeds before (intact cats) and after low-thoracic spinal transection (spinal cats). We show that adult spinal cats performed quadrupedal treadmill locomotion and modulated their speed from 0.4 m/sec to 0.8 m/sec but required perineal stimulation. During quadrupedal locomotion, several compensatory strategies occurred, such as postural adjustments of the head and neck and the appearance of new coordination patterns between the forelimbs and hindlimbs, where the hindlimbs took more steps than the forelimbs. We also observed temporal changes, such as shorter forelimb cycle/swing durations and shorter hindlimb cycle/stance durations in the spinal state. Forelimb double support periods occupied a greater proportion of the cycle in the spinal state, and hindlimb stride length was shorter. Coordination between the forelimbs and hindlimbs was weakened and more variable in the spinal state. Changes in muscle activity reflected spatiotemporal changes in the locomotor pattern. Despite important changes in the pattern, our results indicate that biomechanical properties of the musculoskeletal system play an important role in quadrupedal locomotion and offset some of the loss in neural communication between networks controlling the forelimbs and hindlimbs after spinal transection.


Zygotic pioneer factor activity of Odd-paired/Zic is necessary for late function of the Drosophila segmentation network.
Because chromatin determines whether information encoded in DNA is accessible to transcription factors, dynamic chromatin states in development may constrain how gene regulatory networks impart embryonic pattern. To determine the interplay between chromatin states and regulatory network function, we performed ATAC-seq on Drosophila embryos during the establishment of the segmentation network, comparing wild-type and mutant embryos in which all graded maternal patterning inputs are eliminated. While during the period between zygotic genome activation and gastrulation many regions maintain stable accessibility, cis-regulatory modules (CRMs) within the network undergo extensive patterning-dependent changes in accessibility. A component of the network, Odd-paired (opa), is necessary for pioneering accessibility of late segmentation network CRMs. opa-driven changes in accessibility are accompanied by equivalent changes in gene expression. Interfering with the timing of opa activity impacts the proper patterning of expression. These results indicate that dynamic systems for chromatin regulation directly impact the reading of embryonic patterning information.


Thymoquinone inhibits the migration of mouse neuroblastoma (Neuro-2a) cells by down-regulating MMP-2 and MMP-9.
Thymoquinone (TQ), an active component derived from the medial plant Nigella sativa, has been used for medical purposes for more than 2 000 years. Recent studies have reported that TQ blocked angiogenesis in animal model and reduced migration, adhesion, and invasion of glioblastoma cells. We have recently shown that TQ could exhibit a potent cytotoxic effect and induce apoptosis in mouse neuroblastoma (Neuro-2a) cells. In the present study, TQ treatment markedly decreased the adhesion and migration of Neuro-2a cells. TQ down-regulated MMP-2 and MMP-9 protein expression and mRNA levels and their activities. Furthermore, TQ significantly down-regulated the protein expression of transcription factor NF-κB (p65) but not significantly altered the expression of N-Myc. Taken together, our data indicated that TQ's inhibitory effect on the migration of Neuro-2a cells was mediated through the suppression of MMP-2 and MMP-9 expression, suggesting that TQ treatment can be a promising therapeutic strategy for human malignant neuroblastoma.


Limited evidence for common interannual trends in Baltic Sea summer phytoplankton biomass.
The Baltic Sea summer phytoplankton community plays an important role in biogeochemical cycling and in the transfer of energy through the food web via zooplankton. We aimed to improve the understanding of the degree to which large-scale versus local environmental dynamics regulate phytoplankton dynamics by analyzing time series at the Baltic Sea scale. We used dynamic factor analysis to study if there are common patterns of interannual variation that are shared ("common trends") among summer phytoplankton total and class-level biomass time series observed across Baltic Sea latitudinal gradients in salinity and temperature. We evaluated alternative hypotheses regarding common trends among summer phytoplankton biomass: Baltic Sea-wide common trends; common trends by geography (latitude and basin); common trends differing among functional groups (phytoplankton classes); or common trends driven by both geography and functional group. Our results indicated little support for a common trend in total summer phytoplankton biomass. At a finer resolution, classes had common trends that were most closely associated with the cryptophyte and cyanobacteria time series with patterns that differed between northern and southern sampling stations. These common trends were also very sensitive to two anomalous years (1990, 2008) of cryptophyte biomass. The Baltic Sea Index, a regional climate index, was correlated with two common class trends that shifted in mean state around the mid-1990s. The limited coherence in phytoplankton biomass variation over time despite known, large-scale, ecosystem shifts suggests that stochastic dynamics at local scales limits the ability to observe common trends at the scale of monitoring data collection.


Resolution of radiation necrosis with bevacizumab following radiation therapy for primary CNS lymphoma.
Radiation necrosis (RN) is a rare but serious adverse effect following treatment with radiation therapy. No standard of care exists for the management of RN, and efforts to prevent and treat RN are limited by a lack of insight into the pathomechanics and molecular drivers of RN. This case series describes the outcomes of treatment with bevacizumab (BV) in two primary CNS lymphoma (PCNSL) patients who developed symptomatic biopsy-proven RN after whole brain radiation (WBRT) with a stereotactic radiosurgery (SRS) boost. Patient 1 is a 52 year-old female with PCNSL treated with WBRT followed by an SRS boost. She developed symptomatic biopsy-proven RN, and initial treatment with tocopherol and pentoxifylline was unsuccessful. A 100% clinical and radiographic response was achieved with 4 cycles of BV. Patient 2, a 48 year-old male with PCNSL, presented with seizures and biopsy-proven RN after radiation therapy. Initial empiric treatment with tocopherol and pentoxifylline was unsuccessful. A 100% clinical and radiographic response was achieved with 3 cycles of BV. Monitoring for RN in patients with PCNSL treated with radiation therapy is warranted. BV is an efficacious treatment and a viable alternative to corticosteroids or surgical intervention.


Unveiling the triplet state of a 4-amino-7-nitrobenzofurazan derivative in cyclohexane.
The nitrobenzofurazan (NBD) moiety has gained tremendous popularity over the last decades due to its fluorogenic nature. Indeed, upon interaction with aliphatic amines, it generates a stable fluorescent adduct, which has been used for protein and lipid labeling. In fact the 4-amino substituted NBD belongs to the broad family of intramolecular charge transfer molecules, with the amino group acting as an electron donor upon photoexcitation, and the nitro group as an electron acceptor. Although the singlet excited state of 4-amino NBD derivatives has been abundantly studied, investigation of its triplet manifold is scarce and even the absence of intersystem crossing for this type of molecules has been suggested. However, intramolecular charge transfer molecules are known to undergo intersystem crossing and high phosphorescence quantum yields have been reported in a nonpolar solvent. In the present paper, we have investigated the photophysical and photochemical properties of N-hexyl-7-nitrobenzo[c][1,2,5]xadiazole-4-amine. We have shown the existence of a triplet state for this molecule in cyclohexane via nanosecond laser flash photolysis. Interestingly, deactivation of the triplet state leads to photoproducts formation, which are only present in the absence of oxygen.


[Interferon-alpha upregulates thymidine phosphorylase expression via JAK-STAT transcriptional activation and mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells].
To examine how the thymidine phosphorylase (TP) gene expression is upregulated by interferon-alpha (IFN-alpha) in human hepatocellular carcinoma SMMC-7721 cells. TP mRNA levels were determined by RT-PCR. Whether the JAK-STAT cascade mediates IFN-alpha-induced TP mRNA expression was studied by pretreatment with Janus Kinase (JAK) inhibitor, AG-490. Effects of IFN-alpha on TP mRNA stability were detected with additional actinomycin D. The expression of TP mRNA was induced by IFN-alpha in a dose- and time-dependent manner in SMMC-7721 (human hepatocellular carcinoma) cells. TP mRNA levels rose at 8 h, reached the peak value at 12 h, and remained at a high level up to 72 h in SMMC-7721 cells treated with IFN-alpha 10000 U/ml. IFN-alpha at a dose of 5000 or 10000 U/ml up-regulated TP expression about 3 fold compared with that of non-treated cells (P < 0.05). Induction of TP mRNA expression by IFN-alpha was significantly inhibited in SMMC-7721 cells by pretreatment with AG-490, in comparison with that treated with IFN-alpha alone. Pretreatment of SMMC-7721 cells with IFN-alpha 10000 U/ml for 24 h caused a substantial stabilization of TP mRNA, with a half-live of 35.8 h, compared with 8.5 hr in the control SMMC-7721 cells. IFN-alpha at certain doses upregulates TP mRNA expression via both JAK-STAT transcriptional activation and post-transcriptional mRNA stabilization in human hepatocellular carcinoma SMMC-7721 cells.


[Leiomyo-fibro-angiomatous hamartoma of the myocardium].
Casuistic report on an intramural hamartoma of the size of a walnut in the left ventricle consisting of fibrous connective tissue, vessels and smooth musculature which was found as secondary findings in the autopsy of a 76-year-old man. With the help of statistic material from literature is referred to the rarity of primary cardiac tumours. On the basis of other casuistic contributions of newer literature is referred to the clinical significance which cardiac tumors may have in adequate localisation as well as sufficient size.


Assisting medical students to conduct empathic conversations with patients from a sexual medicine clinic.
To describe an exercise, the structure and content of which assists medical students to conduct potentially embarrassing conversations concerning sexual health which require expression of empathy, to integrate previous learning, to identify their further learning needs, and to develop and test strategies to meet these needs. Students' role play, sequentially, speakers (patients) and listeners (clinical students) in a "carousel," in which all students are engaged at all times in a sequence of pairings which change at rapid intervals. Half way through the exercise, students reflect on the experience, identify difficulties and successes, and develop and share strategies for experimental use in the second half of the exercise. Qualitative comments from the written student evaluations are reported. The exercise provides a formative student centred approach to the integration and further development of previously learnt knowledge and skills of value for promoting sexual health education. It is useful for educators interested in promoting more open and informed learning about sexual health.


[A PhD completed. Positive effects for multidisciplinary orofacial treatment on tinnitus complaints].
Tinnitus can be influenced by somatosensory input from the temporomandibular area and is then called somatic tinnitus. However, not much research has been conducted on whether orofacial treatment can decrease tinnitus severity in patients with somatic tinnitus. Therefore, the purpose of this thesis was 1) to evaluate the effect of orofacial treatment on tinnitus complaints, 2) to investigate potential prognostic indicators for a positive treatment outcome after orofacial therapy, and 3) to explore to what extent a decrease in temporomandibular disorder contributes to a reduction in tinnitus severity. In this thesis, it was found that orofacial therapy can reduce tinnitus severity in 61% of the patients with temporomandibular-related somatic tinnitus. Specifically, young female patients with a shorter duration of their tinnitus have the best prognosis. The analysis showed that 35% of the decrease of the tinnitus severity can be explained by the reduction in temporomandibular disorder.


Tribochemical Behaviors of Onion-like Carbon Films as High-Performance Solid Lubricants with Variable Interfacial Nanostructures.
Onion-like carbon (OLC), spherical nanoparticles consisting of carbon shells, is capable of providing exceptional lubrication effects. Nevertheless, the underlying mechanism, especially the tribo-induced evolution of interfacial nanostructures and their correlation with the friction states, is not clear. In this work, OLC films with a thickness of ∼1 μm were synthesized by electrophoretic deposition on the mirror-polished stainless steel. The lubricity was evaluated by tailoring the sliding aspects including applied normal load, contact time, and counterface materials. It is found that the friction reduction level is highly dependent on the material transfer and transformation of the OLC surface and the physicochemical nature of the as-formed tribolayer in the contact areas. The subsurface of the OLC film always undergoes a deep amorphization transformation upon sliding. It is interesting to note that the tribolayer formed on the bare steel ball is mainly composed of highly ordered graphene-like nanoflakes derived from the sliding-induced degradation of OLC nanospheres. In comparison, the nanospherical carbon structure can be retained in the topmost subsurface of the tribolayer formed on the ceramic Si3N4 ball. Such a nanosphere-/amorphization-coupled interface is capable of providing a robust lubrication state under high contact stresses. The findings identify a new lubrication mechanism for the spherical carbon nanostructure, rendering them effective solid lubricants.


Dynamic sensing of localized corrosion at the metal/solution interface.
A Mach-Zehnder interferometer is employed to detect localized corrosion at the metal/solution interface in the potentiodynamic sweep of the iron electrode in solutions. During the electrochemical reactions, local variations of the electrolyte's refractive index, which correlate with the concentration of dissolved species, change the optical path length (OPL) of the object beam when the beam passes through the electrolyte. The distribution of the OPL difference was obtained to present the concentration change of the metal ions visually, which enable direct evidence of corrosion processes. The OPL difference distribution shows localized and general corrosion during the anodic dissolution of the iron electrode in solutions with and without chloride ions, respectively. This method provides an approach for dynamic detection of localized corrosion at the metal/solution interface.


Virulence & pathogenicity of Yersinia enterocolitica under different test systems.
Eight clinical isolates of Y. enterocolitica were tested for various pathogenicity and virulence markers. Seven of the eight strains gave positive results for Congo red magnesium oxalate (CRMOX) agar test and autoagglutination test at 37 degrees C. Seven strains bound crystal violet (CV) completely at 37 degrees C but not at 25 degrees C. One strain (Y1) bound CV partially. None of the strains showed pyrazinamidase activity indicating these strains to be virulent. Cells of all but one strains were aggregated by 1.8 M and 3.2M concentration of ammonium sulphate. A good correlation between these tests and virulence was observed.


Ca sensitivity and acetylcholine receptor currents of twitch and tonic snake muscle fibers.
Myofibrillar Ca sensitivity and single-channel acetylcholine receptor (AChR) currents were studied in garter snake (Thamnophis sirtalis sirtalis) costocutaneous muscle fibers. Nomarski optics were used to identify tonic and fast- and slow-twitch fibers. Measurements of tension generation were made using chemically skinned fibers. The maximum tensions of the three types of fibers were similar, and the fast- and slow-twitch fibers had similar Ca sensitivities. Compared with twitch fibers, tonic fibers had lower threshold Ca concentrations for tension generation and a larger range of Ca concentrations between threshold and maximum tension. The AChR channels were studied by enzymatically removing the nerve terminals and performing patch-clamp recordings on the exposed postsynaptic membrane. Twitch fibers had only one class of end-plate channel with a conductance of approximately 51 pS. Tonic fibers had two types of synaptic channels. One AChR channel in the tonic fibers resembled the type seen in twitch fibers. The other channel in tonic fibers had a smaller conductance of approximately 33 pS and resembled extrajunctional AChRs on denervated twitch fibers.


Relationship of polymorphisms of the Interleukin-1 gene cluster to occurrence and severity of rheumatoid arthritis.
Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). We investigated whether IotaL-1 gene locus polymorphisms are associated with susceptibility to or severity of RA. Genotyping for IL-1alpha, IL-1beta and IL-1Ra single nucleotide polymorphisms (SNPs) performed in a cross-sectional group of 312 consecutive RA patients (RA-group 1) and a cohort of 94 incident female RA patients (RA-group 2) revealed that the rare IL-1RN + 2017 C allele was significantly increased in RA compared to controls (n = 245). A retrospective analysis in RA-group 1 showed no significant associations between IL-1 genotypes and disease severity. A prospective study in RA-group 2 demonstrated that the extent of joint destruction over 12 years was higher in patients genotyped heterozygous for the IL-1 A + 4845, IL-1B + 3953 and IL-1RN + 5111 SNPs compared to homozygous wildtype patients, although differences did not reach statistical significance. These data indicate that the IL-1RN + 2017 polymorphism is associated with susceptibility to RA.


Assessing HTS performance using BioAssay Ontology: screening and analysis of a bacterial phospho-N-acetylmuramoyl-pentapeptide translocase campaign.
With the public availability of biochemical assays and screening data constantly increasing, new applications for data mining and method analysis are evolving in parallel. One example is BioAssay Ontology (BAO) for systematic classification of assays based on screening setup and metadata annotations. In this article we report a high-throughput screening (HTS) against phospho-N-acetylmuramoyl-pentapeptide translocase (MraY), an attractive antibacterial drug target involved in peptidoglycan synthesis. The screen resulted in novel chemistry identification using a fluorescence resonance energy transfer assay. To address a subset of the false positive hits, a frequent hitter analysis was performed using an approach in which MraY hits were compared with hits from similar assays, previously used for HTS. The MraY assay was annotated according to BAO and three internal reference assays, using a similar assay design and detection technology, were identified. Analyzing the assays retrospectively, it was clear that both MraY and the three reference assays all showed a high false positive rate in the primary HTS assays. In the case of MraY, false positives were efficiently identified by applying a method to correct for compound interference at the hit-confirmation stage. Frequent hitter analysis based on the three reference assays with similar assay method identified additional false actives in the primary MraY assay as frequent hitters. This article demonstrates how assays annotated using BAO terms can be used to identify closely related reference assays, and that analysis based on these assays clearly can provide useful data to influence assay design, technology, and screening strategy.


Turning a stroke into a TIA: curative thrombolysis with combined intravenous and intra-arterial tPA.
Intravenous tissue plasminogen activator (tPA) is standard treatment for eligible patients with acute ischemic stroke, but may be less effective for very severe strokes caused by proximal intracranial artery occlusions. We report the case of a woman with a devastating stroke who recovered completely following emergency revascularization of an occluded proximal middle cerebral artery using a novel treatment approach that combines both intravenous (i.v.) and intra-arterial (IA) tPA. This case illustrates the potential value of the combined i.v.-IA thrombolytic approach, which is an emerging investigational treatment strategy for selected patients with severe acute ischemic stroke.


[Ambulatory surgery of umbilical, epigastric and small incisional hernias: open preperitoneal flat mesh technique in local anaesthesia].
The dilemma whether to use the mesh or non mesh technique in the management of umbilical, epigastric and small incisional hernia is slowly fading away. The open preperitoneal "flat mesh" technique performed as ambulatory surgery may be one of the solutions. The aim of this retrospective study is to present the results of open preperitoneal "flat mesh" technique in the management of umbilical, epigastric and small incisional hernia within This study included 34 patients (11 of them with umbilical, 13 with epigastric and 8 of them with small incisional hernia) operated by one surgeon in the period January 2004-January 2006. The median operative time was 52 minutes for umbilical hernia's, 43 minutes for epgastric and 54 minutes for incisional hernia's. The ambulatory surgery was performed at 91% of patients. The median hospitalization was 4h for patients with umbilical hernia's, 3,7h for patients with epigastric and, 7,7h for patients with small incisional hernia. The follow up is 10,5 months. Apart of one superficial infection other complications were absent. The open preperitoneal "flat mesh" technique performed in local anesthesia as an ambulatory surgery provides good results in the management of umbilical, epigastric and small incisional hernia.


[Magnetic resonance imaging of the olfactory pathways in Kallmann de Morsier syndrome].
Kallmann syndrome is a disease clinically characterized by the association of hypogonadotrophic hypogonadism and anosmia or hyposmia. Most cases have been recorded among men. It is a genetic disorder with a specific gene location on the X chromosome. The cells that normally express luteinizing hormone-releasing hormone or LHRH fail to migrate the olfactory placode to the forebrain. The lateral projections of the olfactory placode also fail to induce development of the olfactory bulbs and tracts. The aim of this study was to compare the MRI appearance of the olfactory sulci, the olfactory bulbs and frontal lobe between groups. The first reference group was composed of 20 subjects and the second group of 18 patients suffering from Kallmann syndrome. For all studies we used a 1.5 T magnet system (Signa GE). We performed two sagittal and coronal T1-weighted sequences in spin echo (TR = 600 ms, TE = 12 ms) with interleaved 3 mm slices and a 14 cm field of view. In the first group, the two olfactory bulbs were always seen on coronal slices just behind the crista galli measuring 2 to 3.2 mm transversally. On sagittal slices, in 60% of the cases two bulbs were seen (3 mm laterally of the pituitary stalk) and in the other 40% only one bulb was seen. The length of the bulb has been measured between 6 and 11 mm. We noticed a plat frontal lobe in 85% of the cases. In the second group the olfactory bulbs were never visible among the 18 patients suffering from Kallmann syndrome. The hypoplasic sulci were hardly visible and their size was less or equal to 1 cm and the frontal lobe was triangular in 80% of the cases. One patient had hypoplasia of corpus callosum. MRI is helpful tool to demonstrate abnormalities of the olfactory system which are always present among patients suffering from Kallmann syndrome. MRI can also show, at the same time, a possible associated brain abnormality.


Aeromonas chitinase degrades chironomid egg masses.
Chironomids are freshwater insects that undergo a complete metamorphosis of four life stages. Chironomid egg masses can be degraded by Vibrio cholerae and some Aeromonas species. Egg mass degradation by V. cholerae requires haemagglutinin protease activity. Our aim was to identify the egg mass degrading (EMD) factor secreted by Aeromonas dhkanesis 3K1C15. Following the hypothesis that the EMD factor of A. dhkanesis is also a protease, secreted proteases were screened, but none of them proved to have the same properties as the EMD factor. Using conventional protein purification methods, we found that the active fraction included chitinases. We further confirmed chitin as a building block of the egg masses. Interestingly, by supplementing bacterial growth media with chitin, we observed unexpected EMD factor activity in Aeromonas isolates that initially were not able to degrade egg masses. Accordingly, we concluded that although strain 3K1C15 secretes chitinases constitutively, most Aeromonas strains secrete chitinases inductively. Induction of chitinases in nature presumably occurs when bacteria are attached to the egg mass habitat, in which chitin is abundant. Considering that chitinases are highly conserved across bacteria phyla, we assume that the role of this enzyme in the bacteria-insect interplay could be wider than is currently thought.