Screening for depression: a systematic review and meta-analysis.
The Canadian Task Force on Preventive Health Care has a guideline on screening for depression among adults 18 years of age or older at average or high risk for depression. To provide evidence for an update of this guideline, we evaluated the literature on the effectiveness of screening for depression in adults. For the period 1994 to May 23, 2012, we searched the following electronic databases: MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews. Randomized controlled trials, observational studies and systematic reviews with evidence for the benefits or harms of screening for depression were eligible for inclusion. We performed screening for relevance, extraction of data, analysis of risk of bias and quality assessments in duplicate. We used the generic inverse variance method to conduct a meta-analysis. To determine confidence in the effect, we analyzed the results according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Five quasi-experimental studies (before-after design with a nonrandomized control group) met the inclusion criteria for this review. These studies reported on the effect of community-based screening for depression, with follow-up on the risk of suicide completion, for older residents in regions of rural Japan with high suicide rates. Meta-analysis showed that the screening program had a protective effect on the overall incidence of suicide completion (ratio of rate ratios [RRR] 0.50, 95% confidence interval [CI], 0.32-0.78). When sex was considered, the RRR indicated a significantly lower rate of suicide among women (RRR 0.37, 95% CI 0.21-0.66) but not among men (RRR 0.67, 95% CI 0.35-1.27). The overall GRADE rating applied to this evidence indicated very low quality. No studies addressing the harms of screening for depression met the inclusion criteria for the review. There is very limited research evidence allowing conclusions about the effectiveness of screening for depression in either average-risk or high-risk populations.


Curative embolization with Onyx of dural arteriovenous fistulas with cortical venous drainage.
Dural fistulas with cortical venous drainage often present with hemorrhage or neurologic deficit, and prompt treatment is indicated. Occlusion of the draining vein by endovascular techniques or surgical disconnection is considered curative. We present our first endovascular experience with use of Onyx via the arterial route in these aggressive fistulas. Between October 2008 and October 2009, 8 consecutive patients with a dural fistula with exclusive cortical venous drainage were treated with Onyx. Three patients presented with hemorrhage; 3, with hemianopsia; 1 with bruit; and 1 after incomplete coil occlusion of a benign sigmoid sinus dural fistula. Fistula location was the sigmoid sinus segment in 4, the occipital area in 2, the cavernous sinus in 1, and the torcula in 1. In all 8 patients, it was possible to occlude the proximal venous site of the fistula with Onyx via arterial feeders, resulting in complete cure in all. In 6 patients, a prolonged (17- to 29-minute) single middle meningeal artery injection was sufficient to occlude the venous site of the fistula with retrograde occlusion of other arterial feeders; in the other 2 patients, 2 injections in supplying arteries were needed. Follow-up angiograms after 6-12 weeks confirmed lasting complete occlusion of the fistulas. All patients were clinically cured, there were no complications. In this small series, curative embolization of dural fistulas with exclusive cortical venous drainage by using Onyx via the arterial route was possible in all patients.


Examining the longitudinal nature of depressive symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC).
Depression during adolescence is associated with a number of negative outcomes in later life. Research has examined the longitudinal nature of adolescent depression in order to identify patterns of depressive mood, the early antecedents and later consequences. However, rich longitudinal data is needed to better address these questions. The Avon Longitudinal Study of Parents and Children (ALSPAC) is an intergenerational birth cohort with nine repeated assessments of depressive symptoms throughout late childhood, adolescence and young adulthood. Depressive symptoms are measured using the Short Mood and Feelings Questionnaire (SMFQ). Many studies have used ALSPAC to examine the longitudinal nature of depressive symptoms in combination with the wealth of early life exposure and later outcome data. This data note provides a summary of the SMFQ data, where the data are stored in ALSPAC, the characteristics and distribution of the SMFQ, and highlights some considerations for researchers wanting to use the SMFQ data in ALSPAC.


A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.
Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.


Multilevel analysis in road safety research.
Hierarchical structures in road safety data are receiving increasing attention in the literature and multilevel (ML) models are proposed for appropriately handling the resulting dependences among the observations. However, so far no empirical synthesis exists of the actual added value of ML modelling techniques as compared to other modelling approaches. This paper summarizes the statistical and conceptual background and motivations for multilevel analyses in road safety research. It then provides a review of several ML analyses applied to aggregate and disaggregate (accident) data. In each case, the relevance of ML modelling techniques is assessed by examining whether ML model formulations (i) allow improving the fit of the model to the data, (ii) allow identifying and explaining random variation at specific levels of the hierarchy considered, and (iii) yield different (more correct) conclusions than single-level model formulations with respect to the significance of the parameter estimates. The evidence reviewed offers different conclusions depending on whether the analysis concerns aggregate data or disaggregate data. In the first case, the application of ML analysis techniques appears straightforward and relevant. The studies based on disaggregate accident data, on the other hand, offer mixed findings: computational problems can be encountered, and ML applications are not systematically necessary. The general recommendation concerning disaggregate accident data is to proceed to a preliminary investigation of the necessity of ML analyses and of the additional information to be expected from their application.


Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial.
Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.


Catalytically inactive carbonic anhydrase-related proteins enhance transport of lactate by MCT1.
Carbonic anhydrases (CA) catalyze the reversible hydration of CO2 to protons and bicarbonate and thereby play a fundamental role in the epithelial acid/base transport mechanisms serving fluid secretion and absorption for whole-body acid/base regulation. The three carbonic anhydrase-related proteins (CARPs) VIII, X, and XI, however, are catalytically inactive. Previous work has shown that some CA isoforms noncatalytically enhance lactate transport through various monocarboxylate transporters (MCT). Therefore, we examined whether the catalytically inactive CARPs play a role in lactate transport. Here, we report that CARP VIII, X, and XI enhance transport activity of the MCT MCT1 when coexpressed in Xenopus oocytes, as evidenced by the rate of rise in intracellular H+ concentration detected using ion-sensitive microelectrodes. Based on previous studies, we suggest that CARPs may function as a 'proton antenna' for MCT1, to drive proton-coupled lactate transport across the cell membrane.


Investigation of differences between nanosecond electropulse and electrohydraulic methods of lithotripsy: a comparative in vitro study of efficacy.
To compare the effectiveness of novel nanosecond electropulse lithotripsy with standard electrohydraulic lithotripsy to demonstrate and authenticate their differences because both modalities appear to be similar. An in vitro fragmentation study was conducted using cuboid BegoStone phantoms, which mimic hard and soft stones, based on an established model. Three different stone sizes were used in the testing having volumes of 100, 256, and 320 mm(3). A nanosecond electropulse lithotripter (NEPL) and an electrohydraulic lithotripter (EHL) were operated using a range of probe sizes at comparable energy settings and pulse rates with the objective of obtaining a stone fragment <2 mm. To compare the efficacy of these two lithotripters, the number of pulses needed for stone phantom fragmentation was recorded according to probe size and energy setting, which were then converted into units of cumulative energy. The results clearly demonstrated that, for all operating modes and stone phantom types, the NEPL device needs much less cumulative energy and thus fewer pulses and consequently less time to achieve stone fragmentation than the EHL device. The disparity in the results is explained by the dissimilar mechanisms at work in the compared lithotripters during destruction of the stone. The electropulse stone disintegration mechanism transfers energy directly into the stone because of discharge penetration into a solid body. This contrasts with the electrohydraulic mechanism in EHL in which energy is transferred through the liquid medium, which also creates a damaging shockwave. The findings demonstrate that, for all operating modes and stone types, the NEPL device needs much less cumulative energy and thus fewer pulses for stone fragmentation than the EHL device. The disparity in the results is explained by the dissimilar mechanisms at work in the compared lithotripters during destruction of the stone.


Changes in joint laxity occurring during pregnancy.
We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies.


Temporal and micro-spatial heterogeneity in the distribution of Anopheles vectors of malaria along the Kenyan coast.
The distribution of anopheline mosquitoes is determined by temporally dynamic environmental and human-associated variables, operating over a range of spatial scales. Macro-spatial short-term trends are driven predominantly by prior (lagged) seasonal changes in climate, which regulate the abundance of suitable aquatic larval habitats. Micro-spatial distribution is determined by the location of these habitats, proximity and abundance of available human bloodmeals and prevailing micro-climatic conditions. The challenge of analysing--in a single coherent statistical framework--the lagged and distributed effect of seasonal climate changes simultaneously with the effects of an underlying hierarchy of spatial factors has hitherto not been addressed. Data on Anopheles gambiae sensu stricto and A. funestus collected from households in Kilifi district, Kenya, were analysed using polynomial distributed lag generalized linear mixed models (PDL GLMMs). Anopheline density was positively and significantly associated with amount of rainfall between 4 to 47 days, negatively and significantly associated with maximum daily temperature between 5 and 35 days, and positively and significantly associated with maximum daily temperature between 29 and 48 days in the past (depending on Anopheles species). Multiple-occupancy households harboured greater mosquito numbers than single-occupancy households. A significant degree of mosquito clustering within households was identified. The PDL GLMMs developed here represent a generalizable framework for analysing hierarchically-structured data in combination with explanatory variables which elicit lagged effects. The framework is a valuable tool for facilitating detailed understanding of determinants of the spatio-temporal distribution of Anopheles. Such understanding facilitates delivery of targeted, cost-effective and, in certain circumstances, preventative antivectorial interventions against malaria.


Earthworm Coelomocyte Internalization of MoS2 Nanosheets: Multiplexed Imaging, Molecular Profiling, and Computational Modeling.
Fully understanding the cellular uptake and intracellular localization of MoS2 nanosheets (NSMoS2) is a prerequisite for their safe applications. Here, we characterized the uptake profile of NSMoS2 by functional coelomocytes of the earthworm Eisenia fetida. Considering that vacancy engineering is widely applied to enhance the NSMoS2 performance, we assessed the potential role of such atomic vacancies in regulating cellular uptake processes. Coelomocyte internalization and lysosomal accumulation of NSMoS2 were tracked by fluorescent labeling imaging. Cellular uptake inhibitors, proteomics, and transcriptomics helped to mechanistically distinguish vacancy-mediated endocytosis pathways. Specifically, Mo ions activated transmembrane transporter and ion-binding pathways, entering the coelomocyte through assisted diffusion. Unlike molybdate, pristine NSMoS2 (P-NSMoS2) induced protein polymerization and upregulated gene expression related to actin filament binding, which phenotypically initiated actin-mediated endocytosis. Conversely, vacancy-rich NSMoS2 (V-NSMoS2) were internalized by coelomocytes through a vesicle-mediated and energy-dependent pathway. Mechanistically, atomic vacancies inhibited mitochondrial transport gene expression and likely induced membrane stress, significantly enhancing endocytosis (20.3%, p < 0.001). Molecular dynamics modeling revealed structural and conformational damage of cytoskeletal protein caused by P-NSMoS2, as well as the rapid response of transport protein to V-NSMoS2. These findings demonstrate that earthworm functional coelomocytes can accumulate NSMoS2 and directly mediate cytotoxicity and that atomic vacancies can alter the endocytic pathway and enhance cellular uptake by reprogramming protein response and gene expression patterns. This study provides an important mechanistic understanding of the ecological risks of NSMoS2.


Trends in Diet Quality by Race/Ethnicity among Adults in the United States for 2011-2018.
This study aimed to investigate time trends in diet quality and the consumption of major food groups and nutrients by race/ethnicity among adults in the United States. Dietary data from 19,192 adults aged ≥ 20 years from four National Health and Nutrition Survey (NHANES) cycles (2011-2018) were included. The Healthy Eating Index (HEI) 2015 scores (range: 0-100; higher scores indicate better diet quality) and dietary consumption of food groups and nutrients were estimated for each cycle. Linear regression was used to test trends. For the overall population, the estimated overall HEI-2015 scores significantly decreased (p for trend = 0.011). However, decreases were observed in the estimated consumption of added sugars and total carbohydrates, while the estimated consumption of soy products and polyunsaturated fatty acids was significantly increased. A significant decrease in overall HEI-2015 score was observed in the non-Hispanic white group, but not in other racial/ethnic groups. Decreases in added sugar intake were found in the non-Hispanic black and Hispanic groups; sodium intake significantly decreased in the non-Hispanic Asian group. From 2011 to 2018, there was a decrease in estimated overall diet quality in US adults; however, there were improvements in certain nutrients and dietary components. Nevertheless, disparities in diet quality exist among racial/ethnic groups.


Development and validation of a model to predict 5-year risk of death without ESRD among older adults with CKD.
CKD is associated with mortality. Accurate prediction tools for mortality may guide clinical decision-making, particularly among elderly persons with CKD. A prediction equation was developed for 5-year risk of mortality among participants with CKD in the Cardiovascular Health Study. Sixteen candidate predictor variables were explored, which included demographics, physical examination measures, comorbidity, medication use, and kidney function measures (eGFR calculated from serum creatinine and the CKD Epidemiology Collaboration equation and the urine albumin-to-creatinine ratio). Models were developed using Cox regression and evaluated using c statistics. A final parsimonious model was externally validated in an independent cohort of community-living elders with CKD in the Health, Aging, and Body Composition Study. The development cohort included 828 participants who had a mean age of 80 (±5.6) years and an eGFR of 47 (±11) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-51) mg/g. The validation cohort included 789 participants who had a mean age of 74 (±2.8) years and an eGFR of 50 (±9) ml/min per 1.73 m(2), and median albumin-to-creatinine ratio of 13 (interquartile range 6-42) mg/g. The final model for 5-year mortality risk included age, sex, race, eGFR, urine albumin-to-creatinine ratio, smoking, diabetes mellitus, and history of heart failure and stroke (c statistic=0.72; 95% confidence interval, 0.68 to 0.74). When a point-based system was assigned for each of nine variables in the equation, the estimated risk of death within 5 years ranged from 3.8% among participants with the lowest scores to 83.6% among participants with nine points. The model performed fair in external validation (c statistic=0.69; 95% confidence interval, 0.64 to 0.74). A simple prediction tool using nine readily available clinical variables can assist in predicting 5-year mortality risk in elderly patients with CKD, which may be useful in counseling patients and guiding clinical decision making.


The role of psychopathology and suicidal intention in predicting suicide risk: a longitudinal study.
In this study, we describe psychological symptoms, any relationship with suicidal intention in a sample of subjects recently attempting suicide and the predictive value of this association in later completed suicide. An assessment was made of 467 suicidological consultations carried out by the Suicidology Unit of the Department of Neurology and Psychiatry, University of Padua, on 421 patients admitted to hospital following attempted suicide in the 5-year period 1990-1994. Suicidal intention was appraised by the Intent Score Scale (ISS). Suicide mortality was assessed after a mean follow-up period of 3.5 years. Psychiatric evaluation was completely negative in only 8% of cases. The most commonly identified symptom was depressed mood (79% of cases, 22% severe depression), followed by anxiety (43% of cases, 32% severe anxiety). From the study, it emerged that psychopathology seemed to influence suicidal intent, where this was characterized by severe depression. Anxiety and other symptoms appeared to have a secondary role. Assessments of suicidal intent showed that intention heightened as the number of symptoms increased. The symptom 'anxiety' did not prove to have a significant bearing on assessment of the seriousness of suicidal intention, whereas severely depressed mood did. The total number of subsequent suicide victims was 5.5%. During consultation relating to the index parasuicide, these subjects did not manifest a discriminate psychopathological profile (the only distinguishing characteristic was anxiety, which was less frequently identified in suicide victims), but did present a more positive personal and family psychiatric history. In subjects who had recently attempted suicide, the psychopathological profile appeared to be related to suicidal intent, where this was characterized by severe depression. Anxiety and other symptoms seemed to have a secondary role. Nonetheless, both total scores and subscores should be taken into consideration when assessing suicidal intention through the ISS. The psychopathological profile and ISS score following attempted suicide do not appear to permit prediction, in the medium to long term, of subsequent completed suicide.


Affordable Personalized, Immersive VR Motor Rehabilitation System with Full Body Tracking.
During the last decade, we have experienced fast development of virtual reality technology combined with various sensors and applications in different fields. The devices and applications are more easily accessible for the broader public. In this article, we describe a feasibility study of an affordable personalized, immersive VR motor rehabilitation system with full body tracking. While virtual reality rehabilitation is a relatively new field, several applications were already proven more effective than traditional rehabilitation programs. The applied methods utilize VR headset HTC Vive and HTC trackers together witch inverse kinematics algorithms to provide full body tracking. For that, we provide a framework for individual body calibration. The main result of the study is a developed virtual environment with guided rehabilitation scenarios based on personalized body calibration. We have proven that this approach can be used in personalized rehabilitation programs.


Incorporation of soy milk lipid into protein coagulum by addition of calcium chloride.
Lipid holding in tofu (soybean curd) has such stability that it is not released even when it is cooked. The lipid in soy milk is incorporated into the tofu with coagulation of proteins on processing by the addition of a calcium salt. In this study, the incorporation of lipid into the coagulum was examined from the association with protein. The lipid in soy milk was obtained as the floating fraction by centrifugation. The floating fraction decreased by the addition of calcium chloride prior to forming a protein coagulum. When half of the protein coagulated, all of the floating fraction became inseparable. The protein in soy milk, then, was separated into particulate and soluble fractions by centrifugation. The decrease of the floating fraction with added calcium chloride was parallel to the coagulation of the particulate protein. The association of the floating fraction and the soluble protein occurred after the new particles formed from the soluble proteins. These results indicated that the lipid incorporation took place by the conjugation of the lipid and protein particles.


Can young infants add and subtract?
Three experiments (N = 68), using Wynn's procedure, tested 5-month-old infants' looking time reactions to correct and incorrect results of simple addition and subtraction transformations. The aim was to investigate both the robustness and the parameters of infants' arithmetic competence. Experiments 1 and 2 (N = 44) were replications of Wynn's first two experiments in which infants were shown addition (1 + 1 = 1 or 2) and subtraction (2 - 1 = 1 or 2) requiring imprecise calculation. Experiment 3 (N = 24) was a subtraction counterpart (3 - 1 = 1 or 2) to Wynn's third experiment requiring precise calculation of addition (1 + 1 = 2 or 3). Unlike Wynn, we found no systematic evidence of either imprecise or precise adding and subtracting in young infants. Our results, together with the mix of both positive and negative findings from other studies of infant arithmetic, suggest that infants' reactions to displays of adding and subtracting are variable and, therefore, that infants' numerical competencies are not robust. This conclusion is consistent with previous findings indicating that simple adding and subtracting develops gradually and continuously throughout infancy and early childhood.


AngioSuite: an accurate method to calculate aneurysm volumes and packing densities.
AngioSuite was developed to allow the easy and accurate calculation of cerebral aneurysm volumes and packing densities. The present study was undertaken to validate its accuracy. Mathematical models and software were created to facilitate more complex aneurysm volume calculations than previously described three-dimensional geometric models. 20 phantom aneurysm clay models were created and analyzed (length, width, depth and volume) using angiographic mathematical modeling (AngioSuite), geometric modeling (AngioCalc) and three-dimensional volume reconstructions from the vendor's Leonardo workstation (Siemens). The mean volumes of all phantoms analyzed by the AngioSuite system differed from true volumes by an average of 2.2%. Mean volumes of all phantoms analyzed by the AngioCalc system differed from true volumes by an average of 11.3%. Mean volumes obtained from the Leonardo workstation windowed for best appearance differed by an average of 5.18%. The AngioSuite software system provides an accurate means of calculating aneurysm volumes. Typical packing densities (40% or less) are thus accurate within ±1%. Angiographic mathematical modeling with AngioSuite is more accurate than geometric modeling and three-dimensional volume reconstructions windowed for best appearance (Leonardo).


Profiling of Parkin-binding partners using tandem affinity purification.
Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting approximately 1-2% of the general population over age 60. It is characterized by a rather selective loss of dopaminergic neurons in the substantia nigra and the presence of α-synuclein-enriched Lewy body inclusions. Mutations in the Parkin gene (PARK2) are the major cause of autosomal recessive early-onset parkinsonism. The Parkin protein is an E3 ubiquitin ligase with various cellular functions, including the induction of mitophagy upon mitochondrial depolarizaton, but the full repertoire of Parkin-binding proteins remains poorly defined. Here we employed tandem affinity purification interaction screens with subsequent mass spectrometry to profile binding partners of Parkin. Using this approach for two different cell types (HEK293T and SH-SY5Y neuronal cells), we identified a total of 203 candidate Parkin-binding proteins. For the candidate proteins and the proteins known to cause heritable forms of parkinsonism, protein-protein interaction data were derived from public databases, and the associated biological processes and pathways were analyzed and compared. Functional similarity between the candidates and the proteins involved in monogenic parkinsonism was investigated, and additional confirmatory evidence was obtained using published genetic interaction data from Drosophila melanogaster. Based on the results of the different analyses, a prioritization score was assigned to each candidate Parkin-binding protein. Two of the top ranking candidates were tested by co-immunoprecipitation, and interaction to Parkin was confirmed for one of them. New candidates for involvement in cell death processes, protein folding, the fission/fusion machinery, and the mitophagy pathway were identified, which provide a resource for further elucidating Parkin function.


[Streptomyces globisporus 1912 mutants highly sensitive to ultraviolet radiation, their antibiotic activity and reparation ability].
Twenty five mutants defective in biosynthesis of antitumor antibiotic landomycin E and 22 mutants with higher level biosynthesis of this antibiotic were obtained after nitrosoguanidine mutagenic treatment of wild strain of Streptomyces globisporus 1912 spores. Six of them (5 mutants of LndE and 1 mutant of LndE+) were found to carry uvs-mutation responsible for high level UV-sensitivity. Uvs-mutants 1912-11 and 1912-16 were highly sensitive to the action of nitrous acid, hydrogen peroxide and methyl-methane-sulfonate.


The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.
To examine the role of androgens on birth weight in genetic models of altered androgen signalling. Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.


New serotypes of Treponema hyodysenteriae.
Three isolates of pathogenic Treponema hyodysenteriae, B8044, B6933, and Ack 300/8, were serotyped by double immunodiffusion using lipopolysaccharide antigen and rabbit antiserum. The precipitation reactions of these three isolates were then compared with precipitin reactions from the reference strains of serotypes 1 through 4. The data indicated that B8044, B6933, and Ack 300/8 share antigenic determinants with either serotype 1 or 2 or both. However, when the cross-reacting antibodies were removed by adsorption, all reactions were found to be monospecific. Based on these results, three new serotypes of pathogenic T. hyodysenteriae are proposed: B8044 serotype 5, B6933 serotype 6, and Ack 300/8 serotype 7.


Effects of exercise on amino acid metabolism in patients with chronic obstructive pulmonary disease.
Depletion of fat-free mass (FFM) significantly contributes to decreased skeletal muscle weakness and impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). FFM wasting suggests disturbances in intermediary metabolism, confirmed by data showing profound alterations in the skeletal muscle amino acid (AA) status in COPD at rest. To unravel whether there is a role for AAs in the mechanisms for skeletal muscle dysfunction in COPD, basic knowledge of AA metabolism in the muscle during exercise is important. We examined the effects of 20 min of exercise on AA metabolism in 14 patients with COPD and eight control subjects. Arterialized venous blood and a quadriceps femoris muscle biopsy were obtained before and immediately after exercise. FFM was not significantly different between the groups. In COPD, a significant reduction of most muscle AAs was present postexercise, whereas several plasma AAs were increased (p < 0.05). Consequently, sum AAs was reduced in muscle (20%; p < 0.01) and increased in plasma (16%, p < 0.05), suggesting an enhanced AA release from muscle in COPD during exercise. In the COPD group, the increase in plasma alanine and glutamine was even higher postexercise (61%, p < 0.01 and 21%, p < 0.01, respectively), suggesting enhanced nitrogen efflux. This study shows that exercise alters amino acid (intermediary) metabolism in patients with COPD and independent of the presence of FFM wasting.


Effects of prostaglandin E1 on platelet attenuation of oxidant-induced edema in isolated rabbit lungs.
Numerous studies suggest that platelets may contribute to preservation of normal endothelial cell permeability in models of lung injury. We have previously shown that washed human platelets prevent xanthine oxidase-induced edema in the isolated perfused lung and that protective mechanisms depend on the platelet glutathione redox cycle. It is uncertain, however, whether platelets preserve endothelial function by reducing toxic oxygen metabolites or by aggregating and releasing endothelial cell supportive factors-an activity that may require the glutathione redox cycle. In this study, we present data demonstrating that platelet prevention of oxidant lung injury occurs independent of platelet aggregation and release. Isolated rabbit lungs perfused with a cell-free medium were instilled with purine (2 mmol/L) and xanthine oxidase (0.003 U/ml) to generate oxidant lung edema. The infusion of washed human platelets (1 x 10(10) cells) prevented lung edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, and lung histology. Incubation of platelets with prostaglandin E1 (PGE1), a potent inhibitor of platelet aggregation and release, did not inhibit platelet attenuation of lung edema. Additionally, with the instillation of PGE1 into the perfusate to further inhibit platelet aggregation, no prevention of lung protection by PGE1-treated platelets was seen when these results were compared with those from studies in which lungs were infused with xanthine oxidase and PGE1. Aggregometry studies documented that the inhibitory effect of PGE1 on platelet aggregation persisted for up to 60 minutes, which was the duration of the isolated lung protocol. We conclude that platelet aggregation and release of platelet factors is not required for platelet attenuation of oxidant lung edema.


The νSaα Specific Lipoprotein Like Cluster (lpl) of S. aureus USA300 Contributes to Immune Stimulation and Invasion in Human Cells.
All Staphylococcus aureus genomes contain a genomic island, which is termed νSaα and characterized by two clusters of tandem repeat sequences, i.e. the exotoxin (set) and 'lipoprotein-like' genes (lpl). Based on their structural similarities the νSaα islands have been classified as type I to IV. The genomes of highly pathogenic and particularly epidemic S. aureus strains (USA300, N315, Mu50, NCTC8325, Newman, COL, JH1 or JH9) belonging to the clonal complexes CC5 and CC8 bear a type I νSaα island. Since the contribution of the lpl gene cluster encoded in the νSaα island to virulence is unclear to date, we deleted the entire lpl gene cluster in S. aureus USA300. The results showed that the mutant was deficient in the stimulation of pro-inflammatory cytokines in human monocytes, macrophages and keratinocytes. Purified lipoprotein Lpl1 was further shown to elicit a TLR2-dependent response. Furthermore, heterologous expression of the USA300 lpl cluster in other S. aureus strains enhanced their immune stimulatory activity. Most importantly, the lpl cluster contributed to invasion of S. aureus into human keratinocytes and mouse skin and the non-invasive S. carnosus expressing the lpl gene cluster became invasive. Additionally, in a murine kidney abscess model the bacterial burden in the kidneys was higher in wild type than in mutant mice. In this infection model the lpl cluster, thus, contributes to virulence. The present report is one of the first studies addressing the role of the νSaα encoded lpl gene cluster in staphylococcal virulence. The finding that the lpl gene cluster contributes to internalization into non-professional antigen presenting cells such as keratinocytes highlights the lpl as a new cell surface component that triggers host cell invasion by S. aureus. Increased invasion in murine skin and an increased bacterial burden in a murine kidney abscess model suggest that the lpl gene cluster serves as an important virulence factor.


Neuroendocrine regulation of seasonal gonadotrophin and prolactin rhythms: lessons from the Soay ram model.
Marked seasonality, responsiveness to photoperiod, diurnal behaviour, large body size, long lifespan and adaptability in captivity are characteristics that make the Soay ram a useful model for neuroendocrine research. Adult rams are routinely housed indoors under artificial lighting of alternating 16 week periods of long and short days to entrain the seasonal cycles in reproduction, growth and metabolism. The long-term cycles in individuals are monitored directly (measurements of testis diameter, androgen-dependent skin coloration, food intake, pelage moult, locomotor activity) and retrospectively (measurements of reproductive and metabolic hormone concentrations in peripheral blood). A wide spectrum of experimental procedures, including serial blood and cerebrospinal fluid (CSF) sampling with hormone or drug treatments, tissue biopsy, stereotaxic cerebral implantation and surgical lesions, not feasible in smaller species, are used to investigate the multiple interactive neuroendocrine systems regulating seasonality. The results from a recent experiment in which rams received a lesion of the caudal arcuate nucleus (caudal ARCX) or hypothalamo-pituitary disconnection (HPD) are presented to demonstrate the fidelity of long-term data derived from the Soay ram model. The results support the view that the melatonin signal that encodes photoperiod acts within the mediobasal hypothalamus to time the gonadotrophin/gonadal cycle, but acts directly within the pituitary gland to time the prolactin/pelage cycle.


Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.
Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1) is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression). Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06) in schizophrenia and bipolar disorder. In bipolar disorder, RAI-1-positive astrocytes in gray matter showed a significantly increased intensity and compound value. Thus, a significant increase in the parameters measured was found in schizophrenia, bipolar disorder, and major depression. Our study shows a significant increase in expression of RAI-1 in the brains from patients with schizophrenia, bipolar disorder, or major depression. The increased expression might reflect altered signaling pathways, like that for retinoic acid. The underlying mechanisms leading to the increased expression and its functional consequences are so far unknown, and remain to be investigated in future studies.


The association of intensive care with utilization and costs of outpatient healthcare services and quality of life.
Little is known about outpatient health services use following critical illness and intensive care. We examined the association of intensive care with outpatient consultations and quality of life in a population-based sample. Cross-sectional analysis of data from 6,686 participants of the Study of Health in Pomerania (SHIP), which consists of two independent population-based cohorts. Statistical modeling was done using Poisson regression, negative binomial and generalized linear models for consultations, and a fractional response model for quality of life (EQ-5D-3L index value), with results expressed as prevalence ratios (PR) or percent change (PC). Entropy balancing was used to adjust for observed confounding. ICU treatment in the previous year was reported by 139 of 6,686 (2,1%) participants, and was associated with a higher probability (PR 1.05 [CI:1.03;1.07]), number (PC +58.0% [CI:22.8;103.2]) and costs (PC +64.1% [CI:32.0;103.9]) of annual outpatient consultations, as well as with a higher number of medications (PC +37.8% [CI:17.7;61.5]). Participants with ICU treatment were more likely to visit a specialist (PR 1.13 [CI:1.09; 1.16]), specifically internal medicine (PR 1.67 [CI:1.45;1.92]), surgery (PR 2.42 [CI:1.92;3.05]), psychiatry (PR 2.25 [CI:1.30;3.90]), and orthopedics (PR 1.54 [CI:1.11;2.14]). There was no significant effect regarding general practitioner consultations. ICU treatment was also associated with lower health-related quality of life (EQ-5D index value: PC -13.7% [CI:-27.0;-0.3]). Furthermore, quality of life was inversely associated with outpatient consultations in the previous month, more so for participants with ICU treatment. Our findings suggest that ICU treatment is associated with an increased utilization of outpatient specialist services, higher medication intake, and impaired quality of life.


Demographic and genetic connectivity: the role and consequences of reproduction, dispersal and recruitment in seagrasses.
Accurate estimation of connectivity among populations is fundamental for determining the drivers of population resilience, genetic diversity, adaptation and speciation. However the separation and quantification of contemporary versus historical connectivity remains a major challenge. This review focuses on marine angiosperms, seagrasses, that are fundamental to the health and productivity of temperate and tropical coastal marine environments globally. Our objective is to understand better the role of sexual reproduction and recruitment in influencing demographic and genetic connectivity among seagrass populations through an integrated multidisciplinary assessment of our present ecological, genetic, and demographic understanding, with hydrodynamic modelling of transport. We investigate (i) the demographic consequences of sexual reproduction, dispersal and recruitment in seagrasses, (ii) contemporary transport of seagrass pollen, fruits and seed, and vegetative fragments with a focus on hydrodynamic and particle transport models, and (iii) contemporary genetic connectivity among seagrass meadows as inferred through the application of genetic markers. New approaches are reviewed, followed by a summary outlining future directions for research: integrating seascape genetic approaches; incorporating hydrodynamic modelling for dispersal of pollen, seeds and vegetative fragments; integrating studies across broader geographic ranges; and incorporating non-equilibrium modelling. These approaches will lead to a more integrated understanding of the role of contemporary dispersal and recruitment in the persistence and evolution of seagrasses.


Cystic recurrence of vestibular schwannoma post-radiosurgery: an institutional experience.
Stereotactic radiosurgery effectively controls vestibular schwannoma (VS). However, in certain cases, microsurgical resection may be necessary for post-radiosurgery tumour progression. The characteristics and microsurgical challenges of uncommon cystic recurrences post-radiosurgery are rarely addressed. We retrospectively analysed 24 consecutive patients who underwent microsurgical intervention for recurrent VS post-radiosurgery by the senior author. Tumour recurrence post-radiosurgery occurred as solid growth in 19 patients (79%), while 5 patients (21%) developed large brainstem-compressing cysts. The median time interval for tumour recurrence post-radiosurgery was similar between cystic and non-cystic recurrent VS (30 vs. 25 months; p=0.08). Cystic recurrences occurred in primarily cystic VS in 3 patients, and new cysts developed in 2 patients with primarily solid VS. Intra-operatively, tumours were firm in 18 cases (75%) and strongly adhered to surrounding structures in 14 cases (58%). All cystic cases underwent cyst decompression, while complete resection of solid tumour components was avoided due to neurovascular adherence. At a mean follow-up of 42±39 months, 12 patients (50%) showed contrast-enhancing tumour residuals in follow-up imaging, including all cystic recurrent cases. Tumour residuals remained stable without requiring further intervention, except for one patient revealing malignant tumour transformation. House-Brackmann grade I/II was preserved in 15 patients (62%). Three patients (13%) developed new facial palsy, and two patients (8%) improved to House-Brackmann grade II. Cystic recurrences had a significantly higher frequency of tumour residuals compared to solid recurrences (100% vs. 37%; p=0.01) but similar rates of facial palsy (60% vs. 32%; p=0.24) CONCLUSIONS: Cyst development in VS post-radiosurgery is more common in primary cystic lesions but can also occur in rare cases of primary solid VS. Symptomatic cysts require microsurgical decompression. However, complete resection of the solid tumour component is not crucial for long-term tumour control and should be avoided if it risks neurological function in this delicate area.


Phlebotomus sergenti (Parrot, 1917) identified as Leishmania killicki host in Ghardaïa, south Algeria.
Since 2005, an outbreak of human cutaneous leishmaniasis (CL) in Ghardaïa, south Algeria, was studied and one output of these investigations was the identification of two Leishmania species, Leishmania major and Leishmania killicki, as the CL causative agents. In the present study, we were curious to focus on sand fly fauna present in this area and detection of Leishmania-positive sand fly females. Sand flies (3717) were collected during two seasons using sticky papers and CDC light traps in urban, rural and sylvatic sites. Twelve Phlebotomus species were identified. Phlebotomus papatasi was dominant in the urban site while Phlebotomus sergenti and Phlebotomus riouxi/chabaudi were dominant in the sylvatic site. Out of 74 P. sergenti females captured by CDC light traps in the sylvatic site populated by Ghardaïas' Gundi (Massoutiera mzabi), three ones were hosting Leishmania promastigotes. PCR-RFLP and sequencing of seven single-copy coding DNA sequences identified the promastigotes as L. killicki. Furthermore, laboratory experiments revealed that L. killicki isolate sampled from a CL patient inhabiting the studied region develop well in P. sergenti females. Our findings strongly suggest that the human cutaneous leishmaniases caused by L. killicki is a zoonotic disease with P. sergenti sand flies acting as hosts and vectors and gundi rodents as reservoirs.


COVID-19 surveillance systems in African countries.
Background: Surveillance forms the basis for response to disease outbreaks, including COVID-19. Herein, we identified the COVID-19 surveillance systems and the associated challenges in 13 African countries. Methods: We conducted a comprehensive narrative review of peer-reviewed literature published between January 2020 and April 2021 in PubMed, Medline, PubMed Central, and Google Scholar using predetermined search terms. Relevant studies from the search and other data sources on COVID-19 surveillance strategies and associated challenges in 13 African countries (Mauritius, Algeria, Nigeria, Angola, Cote d'Ivoire, the Democratic Republic of the Congo, Ghana, Ethiopia, South Africa, Kenya, Zambia, Tanzania, and Uganda) were identified and reviewed. Results: Our findings revealed that the selected African countries have ramped up COVID-19 surveillance ranging from immediate case notification, virological surveillance, hospital-based surveillance to mortality surveillance among others. Despite this, there exist variations in the level of implementation of the surveillance systems across countries. Integrated Disease Surveillance and Response (IDSR) strategy is also being leveraged in some African countries, but the implementation across countries remains uneven. Our study also revealed various challenges facing surveillance which included shortage of skilled human resources resulting in poor data management, weak health systems, complexities of ethical considerations, diagnostic insufficiency, the burden of co-epidemic surveillance, and geographical barriers, among others. Conclusion: With the variations in the level of implementation of COVID-19 surveillance strategies seen across countries, it is pertinent to ensure proper coordination of the surveillance activities in the African countries and address all the challenges facing COVID-19 surveillance using tailored strategies.


Evidence-based strategies for the characterisation of human drug and chemical glucuronidation in vitro and UDP-glucuronosyltransferase reaction phenotyping.
Enzymes of the UDP-glucuronosyltransferase (UGT) superfamily contribute to the elimination of drugs from almost all therapeutic classes. Awareness of the importance of glucuronidation as a drug clearance mechanism along with increased knowledge of the enzymology of drug and chemical metabolism has stimulated interest in the development and application of approaches for the characterisation of human drug glucuronidation in vitro, in particular reaction phenotyping (the fractional contribution of the individual UGT enzymes responsible for the glucuronidation of a given drug), assessment of metabolic stability, and UGT enzyme inhibition by drugs and other xenobiotics. In turn, this has permitted the implementation of in vitro - in vivo extrapolation approaches for the prediction of drug metabolic clearance, intestinal availability, and drug-drug interaction liability, all of which are of considerable importance in pre-clinical drug development. Indeed, regulatory agencies (FDA and EMA) require UGT reaction phenotyping for new chemical entities if glucuronidation accounts for ≥25% of total metabolism. In vitro studies are most commonly performed with recombinant UGT enzymes and human liver microsomes (HLM) as the enzyme sources. Despite the widespread use of in vitro approaches for the characterisation of drug and chemical glucuronidation by HLM and recombinant enzymes, evidence-based guidelines relating to experimental approaches are lacking. Here we present evidence-based strategies for the characterisation of drug and chemical glucuronidation in vitro, and for UGT reaction phenotyping. We anticipate that the strategies will inform practice, encourage development of standardised experimental procedures where feasible, and guide ongoing research in the field.


The impact of Internet-based specific activities on the perceptions of Internet addiction, quality of life, and excessive usage: A cross-sectional study.
Recent research has examined the context in which preference for specific online activities arises, leading researchers to suggest that excessive Internet users are engaged in specific activities rather than 'generalized' Internet use. The present study aimed to partially replicate and expand these findings by addressing four research questions regarding (i) participants' preferred online activities, (i) possible expected changes in online behavior in light of hypothetical scenarios, (iii) perceived quality of life when access to Internet was not possible, and (iv) how participants with self-diagnosed Internet addiction relate to intensity and frequency of Internet use. A cross-sectional design was adopted using convenience and snowball sampling to recruit participants. A total of 1057 Internet users with ages ranging from 16 to 70 years (Mage = 30 years, SD = 10.84) were recruited online via several English-speaking online forums. Most participants indicated that their preferred activities were (i) accessing general information and news, (ii) social networking, and (iii) using e-mail and/or online chatting. Participants also reported that there would be a significant decrease of their Internet use if access to their preferred activities was restricted. The study also found that 51% of the total sample perceived themselves as being addicted to the Internet, while 14.1% reported that without the Internet their life would be improved. The context in which the Internet is used appears to determine the intensity and the lengths that individuals will go to use this tool. The implications of these findings are further discussed.


[Comparison of two commercial DNA extraction kits and PCR master mixes for the detection of Brucella from blood samples and blood culture bottles].
The diagnosis of human brucellosis requires culture or serological tests for the conformation of the clinical findings. Isolation of the bacteria is used as a gold standard, however it is time consuming and processing of positive cultures has a potential risk for laboratory acquired human brucellosis. Polymerase chain reaction (PCR) based methods have offered new approaches for early diagnosis of brucellosis and reduce the risk of laboratory acquired human brucellosis. A major limitation of the PCR method is the difficulty to remove the inhibitors in specimens. The aim of this study was to determine the performance of two DNA extraction kits by using two separate PCR master mixes and to determine appropriate "extraction kit - PCR master mix" combination for the diagnosis of Brucella from whole blood samples and blood culture bottles. Two commercial DNA extraction kits, NORGEN Blood DNA isolation kit (Norgen) and Thermo Scientific GeneJet Whole blood genomic DNA purification kit (Thermo Fisher Scientific, USA) and two PCR master mixes, QuantiTect multiplex PCR (QuentiTect, Qiager, Almanya) and Ampliqon Multiplex TEMPase (Amliqon, Denmark) were assessed on 30 simulated blood samples with known concentrations (102-104 cfu/ml) of Brucella melitensis ATCC 23456 strain and 10 blood culture bottles that gave positive signal. By using different combinations of extraction kits and PCR master mixes, a total of 160 different multiplex real-time PCR (Rt-PCR) trials were performed with probes and primers specific to Brucella spp., B.melitensis, and the internal control glyceraldehyde-3-phosphate dehydrogenase (GAPDH). All the 120 Rt-PCR trials performed on the DNA samples extracted from blood samples gave positive results with GAPDH probe/primers. The rate of positive PCR results for Brucella spp. was 96.7% for the combination of Norgen-QuantiTect, 93.3% for Thermo-Ampliqon, 93.3% for Thermo-QuantiTect, and 86.7% for Norgen-Ampliqon. The frequency of positive B.melitensis results for these combinations were 96.7%, 93.3%, 56.7% and 90%, respectively. In the samples with the bacterial density of 102 cfu/ml, Brucella spp. detection rates were 80% for Thermo-Ampliqon and Norgen-Ampliqon, and 90% for Thermo-QuantiTect and Norgen-QuantiTect; and for B.melitensis positivite rates were 90%, 70%, 20%, and 90%, respectively. Rt-PCR assays with the DNA samples extracted from blood culture bottles using Norgen isolation kit yielded 80% positivite result. However, the frequency of PCR positivite results was only 20% in the DNA samples extracted by Thermo DNA extraction kit. PCR result for GAPDH gene was also negative in 80% of the samples extracted by Thermo kit. Our results revealed that for the removal of inhibitors and detection of even low number of Brucella spp./B.melitensis in blood samples and blood culture bottles, NORGEN Blood DNA isolation kit can be used with a combination of QuantiTect multiplex PCR or Ampliqon Multiplex TEMPase.


Dispersive liquid-liquid microextraction of Cd, Hg and Pb from medicines prior to ICP OES determination according to the United States Pharmacopeia.
A simple, sensitive and matrix-effect free analytical method for simultaneous determination of Cd, Hg and Pb in drug samples (i.e., commercial dosage tablets) by inductively coupled plasma optical emission spectrometry (ICP OES) has been developed. According to the United States Pharmacopeia (USP) Chapter 232, those metals are considered elemental impurities from class 1 and they must be assessed in pharmaceutical production as well as in quality control evaluation. In order to increase the sensitivity of the analysis, dispersive liquid-liquid microextraction (DLLME) was performed and seven factors affecting analyte extraction were optimized by multivariate analysis. A microvolume of analyte enriched phase was directly introduced into the plasma using a multi-nebulizer, providing a high enrichment factor. When compared to conventional ICP OES analysis, DLLME improves the limit of quantitation (LOQ) values on average 40-fold for all analytes. Consequently, LOQ values were significantly lower than their permissible daily exposure limits for oral drugs. Accuracy was evaluated by addition and recovery experiments following USP recommendations in eight commercial drug samples. Recovery and RSD values were within the range of 90-108% and 1-9%, respectively.


A Conformance Test Suite for Arden Syntax Compilers and Interpreters.
The Arden Syntax for Medical Logic Modules is a standardized and well-established programming language to represent medical knowledge. To test the compliance level of existing compilers and interpreters no public test suite exists. This paper presents the research to transform the specification into a set of unit tests, represented in JUnit. It further reports on the utilization of the test suite testing four different Arden Syntax processors. The presented and compared results reveal the status conformance of the tested processors. How test driven development of Arden Syntax processors can help increasing the compliance with the standard is described with two examples. In the end some considerations how an open source test suite can improve the development and distribution of the Arden Syntax are presented.


The Antecedent of Organizational Outcomes Is Psychological Capital.
Psychological capital (PsyCap), which provides a new outlook on the fields of human resources and organizational behavior, is the entirety of positive and improvable features of an individual. An employee's PsyCap can be positively or negatively affected by a social worker's perceptions and beliefs. The purpose of this study was to assess the impact of PsyCap on the job satisfaction and organizational commitment of health care personnel. Data collection was performed through a survey of 501 health care personnel at a public university hospital in Turkey. Structural equation modeling (path analysis) was conducted to test the hypotheses. As a result of the analyses, it was determined that PsyCap positively affects job satisfaction and organizational commitment. In addition, subdimensions of PsyCap-optimism and hope-positively affected job satisfaction, whereas optimism had a positive effect on organizational commitment.


Rat preprocarboxypeptidase A: cDNA sequence and preliminary characterization of the gene.
Rat carboxypeptidase A cDNA clones have been isolated from a cDNA library prepared from pancreatic mRNA. An almost complete mRNA sequence has been deduced that predicts a polypeptide having 78% amino acid sequence homology with bovine carboxypeptidase A. The amino acid sequence of the activation and signal peptides of the carboxypeptidase A precursor were inferred from the nucleotide sequence. The cDNA was used as a probe to identify DNA fragments containing carboxypeptidase A sequences in a bacteriophage lambda library of rat genomic DNA. Heteroduplexes revealed that the DNA coding sequence occupies 5.5 kilobases and is interrupted by nine intervening sequences. The nucleotide sequence of the 5' end of the gene and the adjacent flanking region provides information on the site of initiation of transcription and the putative control regions. There is no evident relationship between the localization of intervening sequences in the gene and functional/structural domains of the protein.


Role of the lymnaeid snail Pseudosuccinea columella in the transmission of the liver fluke Fasciola hepatica in Egypt.
Experimental infections of three Egyptian Pseudosuccinea columella populations with sympatric miracidia of Fasciola sp., coming from cattle- or sheep-collected eggs, were carried out to determine the capacity of this lymnaeid to support larval development of the parasite. Using microsatellite markers, the isolates of Egyptian miracidia were identified as Fasciola hepatica. Apart from being independent of snail origin, prevalences ranging from 60.4 to 75.5% in snails infected with five miracidia of F. hepatica were significantly higher than values of 30.4 to 42.2% in snails with bi-miracidial infections. The number of metacercariae ranged from 243 to 472 per cercarial-shedding snail and was independent of snail origin, parasite origin and miracidial dose used for infection. If P. columella was subjected to two successive bi-miracidial infections with F. hepatica, prevalence of infection was 63.3%, with a mean of 311 metacercariae per snail. These values were clearly greater than those already reported for Radix natalensis infected with the same parasite and the same protocol. Successful experimental infection of P. columella with F. hepatica suggests that this lymnaeid snail is an important intermediate host for the transmission of fascioliasis in Egypt.


Diclofenac in combination with opiate infusion after joint replacement surgery.
The effect of intramuscular diclofenac or placebo on analgesia obtained and on opiate and antiemetic requirements was observed in a randomised double-blind study of sixty patients receiving continuous intravenous papaveretum. Those patients receiving diclofenac required less papaveretum (P = 0.001) than those receiving placebo. They also had lower visual analogue pain scores (VAS) at four hours (P less than 0.05) and decreased requirement for antiemetics (P less than 0.02). No gastrointestinal complications were observed in either group and blood loss did not differ significantly between the two.


Reduced Access to Acute Hand Care and Potential Role of Telemedicine in Tennessee During the COVID Pandemic.
Previous studies have identified that there is limited, although expanding, access to acute hand care in Tennessee. Because of the rapid changes that occurred in health delivery and access during the coronavirus disease pandemic, we reassessed access to acute hand care, with particular interest in the utilization of telemedicine to assess if this increased access. We surveyed Tennessee hospitals listed by the Tennessee Hospital Association on their management of hand trauma and availability of telemedicine programs. Census data including population demographics such as race, age, income, and county size were merged with the survey data. Descriptive analysis was performed comparing the 2021 cohort with the historic 2018 cohort and between counties that had hand care versus counties that had no hand care. Survey response rate was 71.4% (n = 80 of 112). Telemedicine was used in 80% of the hospitals for other specialties but was not used for hand care. Overall, counties that offered hand trauma care reduced from 60% to 26% from 2018 to 2021 (P < 0.001). This change was associated with a significant reduction of acute hand care among counties that were classified micropolitan (from 56.3% to 6.7%, P < 0.01). Percentage of hand specialists on staff and 24/7 specialists availability remained low and were similar to the availability in 2018. There was a decrease of acute hand care access in Tennessee during the coronavirus disease pandemic despite widespread utilization of telemedicine for other specialty consults. Expansion of telemedicine in acute hand care, targeted to micropolitan areas, may help to reduce variability in access to care.


Orthopedically induced condylar growth in a patient with hemifacial microsomia.
Hemifacial microsomia is a congenital abnormality that causes three-dimensional facial asymmetry, affection of the dental occlusion, and failure of growth of the midface in the growing child. This report outlines orthopedically induced condylar growth in a patient with hemifacial microsomia. A 7-year-old girl with hemifacial microsomia, complete absence of the left mandibular condyle, and severe facial asymmetry was treated orthopedically in an early stage by means of a functional appliance. Functional therapy was instituted to stretch the deficient soft tissues to guide and promote skeletal growth and stimulate the affected areas. The treatment was completed with fixed appliances. The effect of the therapy was an excessive change in condylar growth in the affected side. Facial asymmetry was corrected and a symmetric mouth opening was established. The treatment of patients with hemifacial microsomia should be initiated early enough so that the stimulus could in some degree normalize the deficient tissues and induce bone apposition, and in some cases surgical intervention could be avoided.


AV-casNet: Fully Automatic Arteriole-Venule Segmentation and Differentiation in OCT Angiography.
Automatic segmentation and differentiation of retinal arteriole and venule (AV), defined as small blood vessels directly before and after the capillary plexus, are of great importance for the diagnosis of various eye diseases and systemic diseases, such as diabetic retinopathy, hypertension, and cardiovascular diseases. Optical coherence tomography angiography (OCTA) is a recent imaging modality that provides capillary-level blood flow information. However, OCTA does not have the colorimetric and geometric differences between AV as the fundus photography does. Various methods have been proposed to differentiate AV in OCTA, which typically needs the guidance of other imaging modalities. In this study, we propose a cascaded neural network to automatically segment and differentiate AV solely based on OCTA. A convolutional neural network (CNN) module is first applied to generate an initial segmentation, followed by a graph neural network (GNN) to improve the connectivity of the initial segmentation. Various CNN and GNN architectures are employed and compared. The proposed method is evaluated on multi-center clinical datasets, including 3 ×3 mm2 and 6 ×6 mm2 OCTA. The proposed method holds the potential to enrich OCTA image information for the diagnosis of various diseases.


A treatment algorithm for the management of cervical spine fractures and deformity in patients with ankylosing spondylitis.
Patients with ankylosing spondylitis (AS) who present with cervical spine fractures represent a unique challenge to spine surgeons. These injuries often result in neurological deficits that necessitate early and aggressive surgical management with posterior and/or anterior fixation. The authors introduce a clinical problem-solving algorithm to assist in the surgical management of instability and deformity in this exigent patient population. Thirteen patients with AS and fractures of the cervical spine were radiographically evaluated to determine if spinal realignment was obtainable with cervical manipulation or traction. Seven patients had flexible deformities that were stabilized with either anterior or posterior fixation only, and 6 patients had fixed deformities and required circumferential anterior-posterior instrumentation. All patients were observed for neurological outcome, radiographic evidence of bone fusion, and complications. With the use of the authors' treatment algorithm, all patients were able to achieve satisfactory spinal realignment and bone fusion; 92% of patients achieved postoperative stability or improvement in Nurick and modified Japanese Orthopaedic Association scale scores. One patient experienced neurological deterioration following surgery, and 1 patient died at an acute rehabilitative facility following discharge. Patients with AS are highly susceptible to extensive neurological injury and spinal deformity after sustaining cervical fractures from even minor traumatic forces. These injuries are uniquely complex in nature and require considerable scrutiny and aggressive surgical management to optimize spinal stability and functional outcomes. The authors' clinical problem-solving algorithm will assist spine surgeons in providing optimal care in this difficult population.


Charcoal reflectance reveals early holocene boreal deciduous forests burned at high intensities.
Wildfire size, frequency, and severity are increasing in the Alaskan boreal forest in response to climate warming. One of the potential impacts of this changing fire regime is the alteration of successional trajectories, from black spruce to mixed stands dominated by aspen, a vegetation composition not experienced since the early Holocene. Such changes in vegetation composition may consequently alter the intensity of fires, influencing fire feedbacks to the ecosystem. Paleorecords document past wildfire-vegetation dynamics and as such, are imperative for our understanding of how these ecosystems will respond to future climate warming. For the first time, we have used reflectance measurements of macroscopic charcoal particles (>180μm) from an Alaskan lake-sediment record to estimate ancient charring temperatures (termed pyrolysis intensity). We demonstrate that pyrolysis intensity increased markedly from an interval of birch tundra 11 ky ago (mean 1.52%Ro; 485°C), to the expansion of trees on the landscape ~10.5 ky ago, remaining high to the present (mean 3.54%Ro; 640°C) irrespective of stand composition. Despite differing flammabilities and adaptations to fire, the highest pyrolysis intensities derive from two intervals with distinct vegetation compositions. 1) the expansion of mixed aspen and spruce woodland at 10 cal. kyr BP, and 2) the establishment of black spruce, and the modern boreal forest at 4 cal. kyr BP. Based on our analysis, we infer that predicted expansion of deciduous trees into the boreal forest in the future could lead to high intensity, but low severity fires, potentially moderating future climate-fire feedbacks.


Association of serum phosphate and changes in serum phosphate with 28-day mortality in septic shock from MIMIC-IV database.
This study aimed to investigate the relationship between serum phosphate levels, changes in serum phosphate levels, and 28-day mortality in patients with septic shock. In this retrospective study, data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database between 2008 and 2019. Patients were divided into three groups according to the tertiles of serum phosphate levels. Kaplan-Meier curves and log-rank test analyses were used for survival analysis. Multivariate logistic regression, and restricted cubic spline (RCS) curve were used to explore the association between serum phosphate, delta serum phosphate levels and 28-day mortality. In total, 3296 patients with septic shock were included in the study, and the 28-day mortality was 30.0%. Serum phosphate levels were significantly higher in the non-survivor group than in the survivor group. The Kaplan-Meier curves showed significant differences among the three groups. Multivariate logistic regression analysis and the RCS curve showed that serum phosphate levels were independently and positively associated with the 28-day mortality of septic shock. Non-survivors had higher delta serum phosphate levels than survivors. Survival analysis showed that patients with higher delta serum phosphate levels had higher 28-day mortality. A non-linear relationship was detected between delta serum phosphate and 28-day mortality with a point of inflection at - 0.3 mg/dL. Serum phosphate levels were positively and independently associated with 28-day mortality in septic shock. Delta serum phosphate level was a high-risk factor for patients with septic shock.


Connections, Renewal, and Inspiration.
In her Presidential Address at the AOTA INSPIRE 2023 Annual Conference & Expo in Kansas City, Missouri, American Occupational Therapy Association (AOTA) President Alyson Stover shared her experiences traveling in 2022 to different state conferences and occupational therapy events. She described how the incredible people she met on her cross-country journey helped her to find "connections, renewal, and inspiration" and reinspired her passion for expanding her understanding of occupational therapy. During her address, Alyson Stover invited people who are a part of her cross-country occupational therapy community to share their own experiences with the conference audience.


Prognostic value of left ventricular mechanical dyssynchrony by phase analysis in patients with non-ischemic cardiomyopathy with ejection fraction 35-50% and QRS < 150 ms.
Left ventricular mechanical dyssynchrony (LVMD) by phase analysis of gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful tool for predicting response to cardiac resynchronization therapy and has prognostic value. While most of the studies were done on patients with ischemic cardiomyopathy or those with LV ejection fraction (EF) < 35%, there are little data on the prognostic value of LVMD in patients with non-ischemic cardiomyopathy (NICM), particularly those with mildly decreased systolic function and narrow or intermediate QRS duration. From the stress SPECT-MPI database at Cleveland Clinic, we identified 324 consecutive patients (mean age 62 ± 13 years, 62% male, 36% diabetics) with NICM, LVEF 35-50% (median [Q1,Q3] 45 [41,49]), and QRS < 150 ms (13% with QRS 120-149 ms). LVMD was determined from gated stress images and expressed as phase standard deviation (SD) and histogram BW (% R-R cycle). For easier graphical illustration, patients were divided into tertiles of LVMD. All-cause death was the primary endpoint and determined using the Social Security Death Index. Cox proportional hazard model was performed to determine the independent predictive value of LVMD, and next Cox models for incremental value. After a mean follow-up time of 1,689 days, 86 (26.5%) of patients died. These patients were older, had more diabetes, more use of diuretics, with wider QRS duration, and with a trend for higher phase SD and BW. After adjusting for age, hypertension, diabetes, aspirin, beta-blockers, diuretics, QRS, and EF, phase SD was an independent predictor of all-cause mortality with hazard ratio [95% CI] 1.97 [1.06,3.66] for the highest tertile, and added incremental prognostic value (P = .025). Similar findings were obtained using histogram BW. In patients with NICM, EF 35-50%, and QRS < 150 ms, increased LVMD on peak stress SPECT was an independent predictor of all-cause mortality. The utility and applicability of such findings in clinical practice need further evaluation in larger and prospective studies.


Dobbs v. Jackson Women's Health: Undermining Public Health, Facilitating Reproductive Coercion.
Dobbs v. Jackson Women's Health continues a trajectory of U.S. Supreme Court jurisprudence that undermines the normative foundation of public health - the idea that the state is obligated to provide a robust set of supports for healthcare services and the underlying social determinants of health. Dobbs furthers a longstanding ideology of individual responsibility in public health, neglecting collective responsibility for better health outcomes. Such an ideology on individual responsibility not only enables a shrinking of public health infrastructure for reproductive health, it facilitates the rise of reproductive coercion and a criminal legal response to pregnancy and abortion. This commentary situates Dobbs in the context of a long historical shift in public health that increasingly places burdens on individuals for their own reproductive health care, moving away from the possibility of a robust state public health infrastructure.


Effect of trimethoprim/sulfamethoxazole on thyroid function in dogs with pyoderma.
The effect of trimethoprim/sulfamethoxazole (T/SMX, 30 mg/kg, PO, q 12 h for 6 weeks) on thyroid function was evaluated in 21 dogs with pyoderma and normal baseline serum thyroxine concentrations. The population mean serum thyroxine concentration, but not the population mean serum triiodothyronine concentration, was significantly decreased at the end of treatment. After 6 weeks of treatment, the response in 3 dogs to thyrotropin administration was substantially reduced. Radionuclide thyroid imaging of 2 dogs after T/SMX treatment revealed higher-than-normal thyroid technetium 99m pertechnetate uptake, suggestive of an interference with iodide metabolism. Use of T/SMX may cause hypothyroidism, and inadequate thyroid function may be incorrectly diagnosed in dogs treated with this antimicrobial.


Beyond the peak flow meter: newer technologies for determining and documenting changes in lung function in the workplace.
There are many potential problems with the use of serial peak expiratory flow (PEF) measurement to investigate potential occupational asthma. Among these are inaccurate and incomplete recording of results. However, PEF meters will continue to be used because of their relatively low cost and the availability of improved graphing methods and computer-assisted interpretation (OASYS-2). New technologies that automatically record PEF values and the time at which the maneuver was performed have improved the reliability of serial PEF measurements. Further, new hand-held spirometers not only record the test time but also the FEV&inf1; and FEV&inf6;, in addition to PEF. Automated assessment of maneuver quality with immediate feedback to the worker may improve test quality. The storage of raw volume-time or flow-volume curves, not yet widely available, can be used by reviewers to evaluate the quality of the maneuver on which PEF and FEV&inf1; values are based-further improving the reliability of serial measurements. Mechanical stimulators and testing waveforms are available to thoroughly test these new devices and insure that they meet the minimum ATS requirements for monitoring devices.


A case of incontinentia pigmenti associated with multiorgan abnormalities.
Incontinentia pigmenti is a systemic disorder affecting the skin, teeth, eyes, nervous tissue, hair, nails, musculoskeletal system, and heart. We describe an 11-month-old girl with incontinentia pigmenti associated with a ventricular septal defect, left hemiatrophy, hemangiomas, an abnormal labial frenum, and spastic cerebral palsy manifested as left hemiplegia and developmental delay. We believe this patient illustrates that incontinentia pigmenti is a systemic disorder necessitating a multidisciplinary approach to management.


Early treatment with risperidone for subsyndromal delirium after on-pump cardiac surgery in the elderly: a randomized trial.
The aim of this randomized, parallel-arm trial was to study the effect of treating subsyndromal delirium with risperidone on the incidence of clinical delirium in elderly patients who underwent on-pump cardiac surgery. One hundred one patients aged 65 yr or older who experienced subsyndromal delirium after on-pump cardiac surgery were randomized using a computer-generated list to receive 0.5 mg risperidone (n = 51) or placebo (n = 50) every 12 h by mouth. Patients were assessed at 8 h by a blinded observer using the Intensive Care Delirium Screening Checklist, and those scoring more than 3 were evaluated by a blinded psychiatrist to confirm delirium. Patients in either group who experienced delirium were treated according to the same algorithm. Initially, risperidone was administered and if symptoms were not controlled, haloperidol was administered. The primary outcome was the proportion of patients who experienced delirium in either group. Seven (13.7%) patients in the risperidone group experienced delirium versus 17 (34%) in the placebo group (P = 0.031) Competing-risks regression analysis showed that failure to treat subsyndromal delirium with risperidone was an independent risk factor for delirium (subhazard ratio, 3.83; 95% CI, 1.63-8.98; P = 0.002). Two (3.9%) patients in the risperidone group experienced extrapyramidal manifestations versus one (2%) in the placebo group (P = 1.0). Administration of risperidone to elderly patients who experienced subsyndromal delirium after on-pump cardiac surgery was associated with significantly lower incidence of delirium. Larger studies are required to determine whether early administration of risperidone during the subsyndromal phase of delirium would influence the clinical course of such patients.


Femtosecond laser-assisted cataract surgery versus 2.2 mm clear corneal phacoemulsification.
Phacoemulsification is the surgical procedure of choice for cataract, providing excellent visual and safety outcomes. Femtosecond laser-assisted cataract surgery (FLACS) is an addition to the surgical armamentarium. The study aims to compare the outcomes of FLACS using LenSx™ (Alcon Inc., USA) to standard 2.2 mm clear corneal phacoemulsification. Prospective case-control, comparative, interventional study was conducted in a tertiary care center. In each group, 55 eyes of 55 patients underwent cataract surgery using either FLACS or conventional phacoemulsification (control group). The primary outcome variables, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), specular microscopy, pachymetry, mean absolute error (MAE), and anterior chamber depth (ACD) were compared between two groups at 4 weeks postoperatively. Intraoperative effective phaco time (EPT), postoperative circularity of the rhexis, capsular overlap over the edge of the intraocular lens (IOL), and decentration of the IOL were the secondary variables which were compared. No significant difference was found between the groups for UCVA, pachymetry, MAE, and ACD at 4 weeks postoperatively. The FLACS group had better BCVA (P = 0.0294). Circularity of capsulorrhexis (P = 0), circular overlap over the edge of IOL (P = 0), and centration of IOL (P = 0.002) at 4 weeks postoperatively were better in the FLACS group. EPT was lower in FLACS for similar grade of cataract (P = 0). Endothelial cell loss in FLACS group was 4.2% more (P = 0.032). FLACS is superior to conventional phaco in the circularity of rhexis, capsular overlap, and centration of the IOL and uses less EPT. However, conventional phacoemulsification is equivalent to FLACS in most other parameters.


Shone's complex with dextrocardia and situs inversus totalis: a case report.
Parachute mitral valve complex is an unusual congenital anomaly that has been described by Shone et al. It is characterized by a parachute deformity of the mitral valve associated with additional forms of left heart anomalies, such as aortic valvular stenosis and coarctation of the aorta. A 21-year-old female who was referred to our department because of progressive dyspnea on effort and at rest and minimal cyanosis is presented in this case report. On cardiac auscultation, the patient had a grade III/VI pansystolic murmur best heard at the lower left sternal border. The chest X-ray demonstrated dextrocardia and mild cardiomegaly. Echocardiographic evaluation revealed Shone's complex, including parachute mitral valve anomaly.


Allocation rules for global donors.
In recent years, donors such as the Bill and Melinda Gates Foundation have made an enormous contribution to the reduction of the global burden of disease. It has been argued that such donors should prioritise interventions based on their cost-effectiveness, that is to say, the ratio of costs to benefits. Against this, we argue that the donor should fund not the most cost-effective interventions, but rather interventions which are just cost-ineffective for the country, thus encouraging the country to contribute its own domestic resources to the fight against disease. We demonstrate that our proposed algorithm can be justified within the context of a model of the problem as a leader-follower game, in which a donor chooses to subsidise interventions which are implemented by a country. We argue that the decision rule we propose provides a basis for the allocation of aid money which is efficient, fair and sustainable.


Simulated Soccer Game Protocols: A Systematic Review on Validated Protocols That Represent the Demands of the Game.
Brito, P, Costa, J, Figueiredo, P, and Brito, J. Simulated soccer game protocols: A systematic review on validated protocols that represent the demands of the game. J Strength Cond Res 38(1): 192-205, 2024-Several laboratory and field testing protocols have been developed attempting to simulate the activity pattern and physiological demands of soccer. In the present systematic review, we aimed to analyze and discuss the appropriateness, strengths, and limitations of soccer-specific simulated tests. A systematic review of the literature was conducted based on the PRISMA guidelines. Studies conducted in soccer, simulated soccer match tests, and validated simulation protocols performed on-the-field or on a treadmill were considered. No sex restriction was applied, and age >18 years (i.e., adults) was considered. At least 1 outcome measure (e.g., neuromuscular performance, external load, internal load, or psychometric state) of post-simulated-match test or protocol had to be reported. Within the 14 studies included, the average methodological quality of the included articles was 0.61 ± 0.09 (mean ± SD) of 1. Overall, 9 validated protocols were identified. In the protocols, only amateur, university, or semiprofessional soccer players were analyzed. Only one study evaluated female soccer players. None of the studies evaluated the effect on performance over the 2-3 days after the protocol. Accelerations and decelerations, and changes in direction typically present in a game have not been clearly described in any protocol. Future research should address this issue and validate soccer-specific protocols in women.


The Bacillus thuringiensis PlcR-regulated gene inhA2 is necessary, but not sufficient, for virulence.
We previously reported that Bacillus thuringiensis strain 407 Cry 32(-) secretes a zinc-requiring metalloprotease, InhA2, that is essential for virulence in orally infected insects. Analysis of the inhA2-lacZ transcriptional fusion showed that inhA2 expression is repressed in a PlcR(-) background. Using DNase I footprinting experiments, we demonstrated that PlcR activates inhA2 transcription directly by binding to a DNA sequence showing a one-residue mismatch with the previously reported PlcR box. It was previously reported that PlcR is essential for B. thuringiensis virulence in oral infection by contributing to the synergistic properties of the spores on the insecticidal activity of the Cry1C protein. We used complementation experiments to investigate whether the PlcR(-) phenotype was due to the absence of InhA2. The results indicated that overexpression of inhA2 in the (Delta)plcR strain did not restore the wild-type phenotype. However, virulence was fully restored in the (Delta)inhA2 complemented mutant. Thus, inhA2 is the first example of a PlcR-regulated gene found to be directly involved in virulence. However, it is not sufficient for pathogenicity when the other members of the PlcR regulon are lacking. This suggests that InhA2 may act in concert with other PlcR-regulated gene products to provide virulence.


Neural representation of a rhythm depends on its interval ratio.
Rhythm is determined solely by the relationship between the time intervals of a series of events. Psychological studies have proposed two types of rhythm representation depending on the interval ratio of the rhythm: metrical and nonmetrical representation for rhythms formed with small integer ratios and noninteger ratios, respectively. We used functional magnetic resonance imaging to test whether there are two neural representations of rhythm depending on the interval ratio. The subjects performed a short-term memory task for a seven-tone rhythm sequence, which was formed with 1:2:4, 1:2:3, or 1:2.5:3.5 ratios. The brain activities during the memory delay period were measured and compared with those during the retention of a control tone sequence, which had constant intertone intervals. The results showed two patterns of brain activations; the left premotor and parietal areas and right cerebellar anterior lobe were active for 1:2:4 and 1:2:3 rhythms, whereas the right prefrontal, premotor, and parietal areas together with the bilateral cerebellar posterior lobe were active for 1:2.5:3.5 rhythm. Analysis on individual subjects revealed that these activation patterns depended on the ratio of the rhythms that were produced by the subjects rather than the ratio of the presented rhythms, suggesting that the observed activations reflected the internal representation of rhythm. These results suggested that there are two neural representations for rhythm depending on the interval ratio, which correspond to metrical and nonmetrical representations.


Pig liver phosphomevalone kinase. 1. Purification and properties.
Pig liver phosphomevalonate kinase (EC 18.104.22.168) has been purified to homogeneity as shown by polyacrylamide gel electrophoresis. The molecular weight estimates range from 21,000 to 22,500. Each molecule is composed of one polypeptide chain. The presence of SH-containing reagents is essential for the preservation of enzymes activity at all steps in the purification. The enzyme shows absolute specificity for ATP and requires for activity a divalent metal cation, Mg2+ being most effective. The optimum pH for the enzyme ranges from 7.5 to over 9.5. Kinetics are hyperbolic for both substrates, showing a sequential mechanism; true Km values of 0.075 mM and 0.46 mM have been obtained for phosphomevalonate and ATP, respectively. Amino acid composition shows a high content of acid amino acids, one cysteine residue per molecule of enzyme, and the absence of methionine. The results obtained suggest that the enzyme plays no regulatory function in cholesterol biosynthesis in pig liver, although a variable enzyme content was detected in different livers.


Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection.
Trypanosoma cruzi causes Chagas disease, which is a neglected tropical disease that produces severe pathology and mortality. The mechanisms by which the parasite invades cells are not well elucidated. We recently reported that T. cruzi up-regulates the expression of thrombospondin-1 (TSP-1) to enhance the process of cellular invasion. Here we characterize a novel TSP-1 interaction with T. cruzi that enhances cellular infection. We show that labeled TSP-1 interacts specifically with the surface of T. cruzi trypomastigotes. We used TSP-1 to pull down interacting parasite surface proteins that were identified by mass spectrometry. We also show that full length TSP-1 and the N-terminal domain of TSP-1 (NTSP) interact with T. cruzi surface calreticulin (TcCRT) and other surface proteins. Pre-exposure of recombinant NTSP or TSP-1 to T. cruzi significantly enhances cellular infection of wild type mouse embryo fibroblasts (MEF) compared to the C-terminal domain of TSP-1, E3T3C1. In addition, blocking TcCRT with antibodies significantly inhibits the enhancement of cellular infection mediated by the TcCRT-TSP-1 interaction. Taken together, our findings indicate that TSP-1 interacts with TcCRT on the surface of T. cruzi through the NTSP domain and that this interaction enhances cellular infection. Thus surface TcCRT is a virulent factor that enhances the pathogenesis of T. cruzi infection through TSP-1, which is up-regulated by the parasite.


Anterior Sagittal Anorectoplasty: Our Experience.
Anterior sagittal anorectoplasty (ASARP) is accepted as one of the techniques for the repair of vestibular fistula (VF) and low-type anomalies, but some may have reservations. The aim of the study is to describe the technique, important features, and functional and cosmetic outcomes of ASARP for the treatment of anorectal malformation (ARM) in females. A prospective study was performed from 1992 to 2017. The study included 157 pediatric patients (aged 1-15 years) with diagnosis of ARMs with VF, perineal fistula (perineal ectopic anus), and rectovaginal fistula managed by ASARP. Most cases (36.94%) were 1-6 months' age group; 92.99% of patients (146) were having VF, 5.09% (8) perineal fistula, and 1.91% (3) rectovaginal fistula. Associated anomalies (37) were present in 19.75% (31) of patients. Primary ASARP was performed in 85.35% (134) of cases. The mean operative time was 105 (±15) min. Intraoperative complications were seen in 3.82% (6) of patients. Early postoperative complications were seen in 5.09% (8) of patients - wound infection (4), wound dehiscence (3), and retraction of the rectum (1). Late complications were seen in 12.73% (20) of cases. Overall, five patients developed anal stenosis, two responded to dilatation therapy, and three required anoplasty. The external appearance of the perineum after the 3rd month (postoperatively) was satisfactory in 95.54% (150); overall, 4.46% (7) of patients required the second procedure. Stooling pattern could be assessed in 80.25% (126) of patients at 3 years' age group. Only one had poor outcome with severe soiling (incontinence) and perineal excoriation that also had myelomeningocele. ASARP is an excellent procedure for VF as it results in optimal correction with minimal sphincteric damage, without additional complexity or difficulties. Primary ASARP is a quick and effective technique and does not require colostomy if performed after due preoperative gut preparation and by an experienced pediatric surgeon.


Synthesis, evaluation and QSAR studies of 16-(4 & 3,4-substituted) benzylidene androstene derivatives as anticancer agents.
In a systematic effort aimed at identifying new steroidal cytotoxic agents with potent antipoliferative activity against cancer cells and developing their QSAR models, series of 4-nitro, 4-isopropyl, 4-methoxy and 3,4-dimethoxy substituted benzylidene androst-5-ene derivatives were synthesized. The selected compounds were evaluated for antineoplastic activity against a panel of three human cell lines-breast, CNS and lungs at NCI, Bethesda, USA. The results presented herein reports that compounds 7, 9, 10, 15,16, 18, 20-25, 30, 32-36 and 44 have been found to be active anticancer agents. The QSAR of 20 compounds was performed separately for each cell line and best-fit QSAR models are developed. The QSAR models obtained have shown significant correlations (r(2) range: 0.9163 to 0.8164) and good predictive performance (q(2) range: 0.8499- 0.6320). The validation of models has also been performed using the test set of compounds 5, 15 and 44.