Variability of interobserver interpretation of selected helminth ova in the development of a training image set.

Background: Diagnosis of soil-transmitted helminthiasis and schistosomiasis for surveillance relies on microscopic detection of ova in Kato-Katz (KK) prepared slides. Artificial intelligence (AI)-based platforms for parasitic eggs may be developed using a robust image set with defined labels by reference microscopists. This study aimed to determine interobserver variability among reference microscopists in identifying parasite ova.

Reevaluating safety pharmacology respiratory studies within the ICH S7A core battery: A multi-company evaluation of preclinical utility and clinical translation.

Optimization of ICH safety guideline studies for inclusion into regulatory submissions is critical for resource conservation, animal use reduction, and efficient drug development. The ICH S7A guidance for Safety Pharmacology (SP) studies adopted in 2001 identified the core battery of studies to evaluate the acute safety of putative pharmaceutical molecules prior to First in Human (FIH) trials. To assess the utility of respiratory studies in predicting clinical AE's, seven pharmaceutical companies pooled preclinical and clinical respiratory findings.

YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle.

Few transcription factors have been examined for their direct roles in physically connecting enhancers and promoters. Here acute degradation of Yin Yang 1 (YY1) in erythroid cells revealed its requirement for the maintenance of numerous enhancer-promoter loops, but not compartments or domains. Despite its reported ability to interact with cohesin, the formation of YY1-dependent enhancer-promoter loops does not involve stalling of cohesin-mediated loop extrusion.

Scientific Review of the Proarrhythmic Risks of Oligonucleotide Therapeutics: Are Dedicated ICH S7B/E14 Studies Needed for Low-Risk Modalities?

Oligonucleotide therapeutics (ONTs) represent a new modality with unique pharmacological and chemical properties that modulate gene expression with a high degree of target specificity mediated by complementary Watson-Crick base pair hybridization. To date, the proarrhythmic assessment of ONTs has been influenced by International Conference on Harmonization (ICH) E14 and S7B guidance. To document current hERG/QTc evaluation practices, we reviewed US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Approval Packages (source: PharmaPendium.

Coping in adolescents: A mediator between stress and disordered eating.

Background: Adolescence is a developmental period that can place individuals at heightened risk of engaging in disordered eating patterns. Stress and coping have been included as etiological factors of eating pathology, yet the mechanism of this relationship in adolescent males and females remains understudied.

Aims: This study investigated the role of coping as a mediator in the stress-disordered eating relationship in a sample of adolescents.

Examining Shared Pathways for Eating Disorders and Obesity in a Community Sample of Adolescents: The REAL Study.

Several psychosocial models have been proposed to explain the etiology of eating disorders (EDs) and obesity separately despite research suggesting they should be conceptualized within a shared theoretical framework. The objective of the current study was to test an integrated comprehensive model consisting of a host of common risk and protective factors (socio-environmental, psychological, and behavioral) expected to explain both eating and weight disorders simultaneously in a large school-based sample of adolescents. Data were collected from 3,043 youth (60% female, 14.

The Mechanical Response and Tolerance of the Anteriorly-Tilted Human Pelvis Under Vertical Loading.

Military vehicle underbody blast (UBB) is the cause of many serious injuries in theatre today; however, the effects of these chaotic events on the human body are not well understood. The purpose of this research was to replicate UBB loading conditions on the human pelvis and investigate the resulting response in a controlled laboratory setting. In addition to better understanding the response of the human pelvis to high rate vertical loading, this test series also aimed to identify high rate injury thresholds.

Development of the Ottawa Disordered Eating Screen for Youth: The ODES-Y.

Objective: To develop a concise screening tool that allows for early identification of disordered eating in youth.

Study Design: In this 2-step classification accuracy study, questions for the Ottawa Disordered Eating Screen-Youth, a 2-question screening tool (index test), were conceptualized by clinician-scientists from tertiary care pediatric eating disorder and weight-related clinics, and was validated using retrospective data (2004-2010) from a community-based study, the Research on Eating and Adolescent Lifestyles (REAL) study.

Results: Analyses of contrast between the index test and the reference standard using data from 2892 (1714 females) students between grade 7 and grade 12 revealed classification statistics of 67.

Integration of cardiac energetics, function and histology from isolated rat hearts perfused with doxorubicin and doxorubicin-ol; a model for use in drug safety evaluations.

The isolated rat heart (Langendorff) assay combined with NMR spectroscopy and histology were used to elucidate functional, metabolic, and histological signs of cardiotoxicity resulting from acute exposure to clinically relevant concentrations of doxorubicin and its metabolite dox-ol. Doxorubicin blood concentrations and pharmacokinetic parameters were assessed following a clinically relevant dose of 2 mg/kg in order to select concentrations for isolated heart perfusions. Isolated rat hearts were exposed to 1 or 10 μM of doxorubicin or 0.

A 90-day oral toxicity study of glycolipids from Dacryopinax spathularia in Beagle dogs.

The subchronic toxicity of glycolipids from Dacryopinax spathularia (herein referred to as "AM-1") was studied in male and female Beagle dogs administered AM-1 by oral capsule at doses of 150, 500 or 1000 mg/kg/day for 90 days. AM-1 was well tolerated at all dosages and there were no test article-related effects on survival, clinical observations, neurological screening (functional observational battery) parameters, clinical pathology parameters, organ weights, macroscopic or microscopic evaluations. Test article-related changes were limited to minimal effects on food consumption and body weight changes in the 1000 mg/kg/day group females.

The Interplay Between Housing Stability and Child Separation: Implications for Practice and Policy.

Greater understanding of how residential stability affects child separation and reunification among homeless families can guide both child welfare and homeless policy and practice. This article draws upon two longitudinal studies examining services and housing for homeless families and their relationship to family and housing stability. Both studies were conducted in the same state at roughly the same time with similar instruments.

Alternative stable states and the sustainability of forests, grasslands, and agriculture.

Endangered forest-grassland mosaics interspersed with expanding agriculture and silviculture occur across many parts of the world, including the southern Brazilian highlands. This natural mosaic ecosystem is thought to reflect alternative stable states driven by threshold responses of recruitment to fire and moisture regimes. The role of adaptive human behavior in such systems remains understudied, despite its pervasiveness and the fact that such ecosystems can exhibit complex dynamics.

Evaluation of WIAMan Technology Demonstrator Biofidelity Relative to Sub-Injurious PMHS Response in Simulated Under-body Blast Events.

Three laboratory simulated sub-injurious under-body blast (UBB) test conditions were conducted with whole-body Post Mortem Human Surrogates (PMHS) and the Warrior Assessment Injury Manikin (WIAMan) Technology Demonstrator (TD) to establish and assess UBB biofidelity of the WIAMan TD. Test conditions included a rigid floor and rigid seat with independently varied pulses. On the floor, peak velocities of 4 m/s and 6 m/s were applied with a 5 ms time to peak (TTP).

Attachment Style and Obesity: Disordered Eating Behaviors as a Mediator in a Community Sample of Canadian Youth.

Objective: Obesity and overweight are associated with many negative health outcomes. Attachment style has been implicated in the development of obesity in youth. The present study examined if disordered eating behaviors mediate the relationship between attachment style and body mass index (BMI) in a large community sample of Canadian youth.

Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake.

Fruits, nuts, legumes, and vegetables are rich sources of boron (B), an essential plant nutrient with chemopreventive properties. Blood boric acid (BA) levels reflect recent B intake, and men at the US mean intake have a reported non-fasting level of 10 μM. Treatment of DU-145 prostate cancer cells with physiological concentrations of BA inhibits cell proliferation without causing apoptosis and activates eukaryotic initiation factor 2 (eIF2α).

Serious engagement in sport and health benefits among Korean immigrants in the USA.

There is a dearth of information pertaining to ethnicity and serious leisure among immigrants. The purpose of our study was to explore the health benefits of serious engagement in sports among Korean immigrants who are part of club activities. Using semi-structured in-depth interviews, we identified three themes associated with the benefits of serious leisure: (a) coping with acculturative stress, (b) creating ethnic strength, and (c) personal benefits.

The impact of the TelEmergency program on rural emergency care: An implementation study.

Introduction Timely, appropriate intervention is key to improving outcomes in many emergent conditions. In rural areas, it is particularly challenging to assure quality, timely emergency care. The TelEmergency (TE) program, which utilizes a dual nurse practitioner and emergency medicine-trained, board-certified physician model, has the potential to improve access to quality emergency care in rural areas.

Comparative chemical genomics reveal that the spiroindolone antimalarial KAE609 (Cipargamin) is a P-type ATPase inhibitor.

The spiroindolones, a new class of antimalarial medicines discovered in a cellular screen, are rendered less active by mutations in a parasite P-type ATPase, PfATP4. We show here that S. cerevisiae also acquires mutations in a gene encoding a P-type ATPase (ScPMA1) after exposure to spiroindolones and that these mutations are sufficient for resistance.

Neurobehavioral and Cardiovascular Effects of Potassium Cyanide Administered Orally to Mice.

The Food and Drug Administration Animal Rule requires evaluation of cardiovascular and central nervous system (CNS) effects of new therapeutics. To characterize an adult and juvenile mouse model, neurobehavioral and cardiovascular effects and pathology of a single sublethal but toxic, 8 mg/kg, oral dose of potassium cyanide (KCN) for up to 41 days postdosing were investigated. This study describes the short- and long-term sensory, motor, cognitive, and behavioral changes associated with oral dosing of a sublethal but toxic dose of KCN utilizing functional observation battery and Tier II CNS testing in adult and juvenile mice of both sexes.

Selective sorting and destruction of mitochondrial membrane proteins in aged yeast.

Mitochondrial dysfunction is a hallmark of aging, and underlies the development of many diseases. Cells maintain mitochondrial homeostasis through a number of pathways that remodel the mitochondrial proteome or alter mitochondrial content during times of stress or metabolic adaptation. Here, using yeast as a model system, we identify a new mitochondrial degradation system that remodels the mitochondrial proteome of aged cells.

Examining the bidirectional relationship between physical activity, screen time, and symptoms of anxiety and depression over time during adolescence.

More physical activity (PA) and less screen time (ST) are positively associated with mental health in adolescents; however, research is limited by short-term designs and the exclusion of ST when examining PA. We examined: (a) changes in PA, ST, symptoms of depression, and symptoms of anxiety over four assessments spanning 11years, and (b) bidirectional relationships between initial PA, ST, and symptoms of depression and anxiety as predictors of change in each other during adolescence. Between 2006 and 2010, participants from Ottawa Canada (Time1; N=1160, Mean age=13.

Screen time is associated with depression and anxiety in Canadian youth.

Objective: This study examined the relationships between screen time and symptoms of depression and anxiety in a large community sample of Canadian youth.

Method: Participants were 2482 English-speaking grade 7 to 12 students. Cross-sectional data collected between 2006 and 2010 as part of the Research on Eating and Adolescent Lifestyles (REAL) study were used.