Inter- and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic.

The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances.

Data-driven methods distort optimal cutoffs and accuracy estimates of depression screening tools: a simulation study using individual participant data.

Objective: To evaluate, across multiple sample sizes, the degree that data-driven methods result in (1) optimal cutoffs different from population optimal cutoff and (2) bias in accuracy estimates.

Study Design And Setting: A total of 1,000 samples of sample size 100, 200, 500 and 1,000 each were randomly drawn to simulate studies of different sample sizes from a database (n = 13,255) synthesized to assess Edinburgh Postnatal Depression Scale (EPDS) screening accuracy. Optimal cutoffs were selected by maximizing Youden's J (sensitivity+specificity-1).

Correction: Piras, A.M., et al. Antibacterial, Antibiofilm, and Antiadhesive Properties of Different Quaternized Chitosan Derivatives. 2019, , 6297.

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Case fatality and recurrent tuberculosis among patients managed in the private sector: A cohort study in Patna, India.

Background: A key component of the WHO End TB Strategy is quality of care, for which case fatality is a critical marker. Half of India's nearly 3 million TB patients are treated in the highly unregulated private sector, yet little is known about the outcomes of these patients. Using a retrospective cohort design, we estimated the case fatality ratio (CFR) and rate of recurrent TB among patients managed in the private healthcare sector in Patna, India.

Effectiveness and cost-effectiveness of a health systems intervention for latent tuberculosis infection management (ACT4): a cluster-randomised trial.

Background: Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases.

Methods: ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care).

Genetic and clinical aspects of paediatric pheochromocytomas and paragangliomas.

Objective: Few and conflicting reports have characterized the genetics of paediatric pheochromocytomas and paragangliomas (PPGLs). This study aimed to investigate the clinical and genetic features of Brazilian children with PPGL.

Patients And Methods: This study included 25 children (52% girls) with PPGL.

A novel approach for the isolation and long-term expansion of pure satellite cells based on ice-cold treatment.

Satellite cells (SCs) are muscle stem cells capable of regenerating injured muscle. The study of their functional potential depends on the availability of methods for the isolation and expansion of pure SCs with preserved myogenic properties after serial passages in vitro. Here, we describe the ice-cold treatment (ICT) method, which is a simple, economical, and efficient method for the isolation and in vitro expansion of highly pure mouse and human SCs.

Changes in digestive cancer diagnosis during the SARS-CoV-2 pandemic in Italy: A nationwide survey.

Background: The SARS-CoV-2 pandemic has had a huge impact on healthcare systems, resulting in many routine diagnostic procedures either being halted or postponed.

Aims: To evaluate whether the diagnoses of colorectal, gastric and pancreatic cancers have been impacted by the SARS-CoV-2 pandemic in Italy.

Methods: A survey designed to collect the number of histologically-proven diagnoses of the three cancers in gastroenterology services across Italy from January 1 to October 31 in 2017-2020.

Phenotypic Characterization and Brain Structure Analysis of Calcium Channel Subunit αδ-2 Mutant (Ducky) and αδ Double Knockout Mice.

Auxiliary αδ subunits of voltage-gated calcium channels modulate channel trafficking, current properties, and synapse formation. Three of the four isoforms (αδ-1, αδ-2, and αδ-3) are abundantly expressed in the brain; however, of the available knockout models, only αδ-2 knockout or mutant mice display an obvious abnormal neurological phenotype. Thus, we hypothesize that the neuronal αδ isoforms may have partially specific as well as redundant functions.

Real-World Outcomes of Patients With Advanced Non-small Cell Lung Cancer Treated With Anti-PD1 Therapy on the Basis of PD-L1 Results in EBUS-TBNA vs Histological Specimens.

Background: Programmed death-ligand 1 (PD-L1) testing is feasible in most specimens acquired using endobronchial ultrasound-guided needle aspiration (EBUS-TBNA).

Research Question: Are the outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI) on the basis of PD-L1 expression in EBUS-TBNA samples significantly different from those of patients who are treated on the basis of PD-L1 expression in histological samples?

Study Design And Methods: Patients treated with pembrolizumab or nivolumab between June 2016 and 2019 were included. Patient characteristics, PD-L1 expression, line of treatment, response (Response Evaluation Criteria in Solid Tumors [RECIST] criteria), and vital status (May 14, 2020) were recorded.

Comparison of different scoring methods based on latent variable models of the PHQ-9: an individual participant data meta-analysis.

Background: Previous research on the depression scale of the Patient Health Questionnaire (PHQ-9) has found that different latent factor models have maximized empirical measures of goodness-of-fit. The clinical relevance of these differences is unclear. We aimed to investigate whether depression screening accuracy may be improved by employing latent factor model-based scoring rather than sum scores.

Failed Eradication Therapy of New-Onset Pseudomonas aeruginosa Infections in Children With Cystic Fibrosis Is Associated With Bacterial Resistance to Neutrophil Functions.

Background: Antibiotics, such as inhaled tobramycin, are used to eradicate new-onset Pseudomonas aeruginosa (PA) infections in patients with cystic fibrosis (CF) but frequently fail due to reasons poorly understood. We hypothesized that PA isolates' resistance to neutrophil antibacterial functions was associated with failed eradication in patients harboring those strains.

Methods: We analyzed all PA isolates from a cohort of 39 CF children with new-onset PA infections undergoing tobramycin eradication therapy, where 30 patients had eradicated and 9 patients had persistent infection.

Aryl hydrocarbon receptor deficiency causes the development of chronic obstructive pulmonary disease through the integration of multiple pathogenic mechanisms.

Emphysema, a component of chronic obstructive pulmonary disease (COPD), is characterized by irreversible alveolar destruction that results in a progressive decline in lung function. This alveolar destruction is caused by cigarette smoke, the most important risk factor for COPD. Only 15%-20% of smokers develop COPD, suggesting that unknown factors contribute to disease pathogenesis.

Lack of information about umbilical cord blood banking leads to decreased donation rates among Brazilian pregnant women.

The donation of umbilical cord blood (UCB) to public banks is essential to increase the probability of finding compatible donors for hematopoietic stem cell transplants. Brazil is currently the third-largest country in number of registered bone marrow donors, but it is far behind in terms of UCB donation. Thus, this questionnaire-based study aimed to assess Brazilian pregnant women's awareness, knowledge, beliefs, and opinions about UCB banking in order to identify the causes of low donation rates.

Performance of Saliva, Oropharyngeal Swabs, and Nasal Swabs for SARS-CoV-2 Molecular Detection: a Systematic Review and Meta-analysis.

Nasopharyngeal (NP) swabs are considered the highest-yield sample for diagnostic testing for respiratory viruses, including SARS-CoV-2. The need to increase capacity for SARS-CoV-2 testing in a variety of settings, combined with shortages of sample collection supplies, have motivated a search for alternative sample types with high sensitivity. We systematically reviewed the literature to understand the performance of alternative sample types compared to NP swabs.

Genotoxicity and Immunotoxicity of Titanium Dioxide-Embedded Mesoporous Silica Nanoparticles (TiO@MSN) in Primary Peripheral Human Blood Mononuclear Cells (PBMC).

TiO nanoparticles (TiO NPs) are the nanomaterial most produced as an ultraviolet (UV) filter. However, TiO is a semiconductor and, in nanoparticle size, is a strong photocatalyst, raising concerns about photomutagenesis. Mesoporous silica nanoparticles (MSN) were synthetized incorporating TiO NPs (TiO@MSN) to develop a cosmetic UV filter.

Gastrointestinal disorders as immune-related adverse events.

Immune checkpoint inhibitors, such as cytotoxic T-lymphocyte antigen 4 inhibitors, programmed cell death 1 inhibitors and programmed cell death-ligand 1 inhibitors, have recently emerged as novel drugs in the anti-cancer therapy. Their use in different types of advanced cancer has shown good results and an increase in survival rates. However, immune-related adverse events (irAEs) are frequent and often require special care.

Genotype-Phenotype Correlations in Central Precocious Puberty Caused by MKRN3 Mutations.

Context: Loss-of-function mutations of makorin RING finger protein 3 (MKRN3) are the most common monogenic cause of familial central precocious puberty (CPP).

Objective: To describe the clinical and hormonal features of a large cohort of patients with CPP due to MKRN3 mutations and compare the characteristics of different types of genetic defects.

Methods: Multiethnic cohort of 716 patients with familial or idiopathic CPP screened for MKRN3 mutations using Sanger sequencing.

Shortening the Edinburgh postnatal depression scale using optimal test assembly methods: Development of the EPDS-Dep-5.

Aims: This study used a large database to develop a reliable and valid shortened form of the Edinburgh Postnatal Depression Scale (EPDS), a self-report questionnaire used for depression screening in pregnancy and postpartum, based on objective criteria.

Methods: Item responses from the 10-item EPDS were obtained from 5157 participants (765 major depression cases) from 22 primary screening accuracy studies that compared the EPDS to the Structured Clinical Interview for DSM (SCID). Unidimensionality of the EPDS latent construct was verified using confirmatory factor analysis, and an item response theory model was fit.

Chest x-ray analysis with deep learning-based software as a triage test for pulmonary tuberculosis: a prospective study of diagnostic accuracy for culture-confirmed disease.

Background: Deep learning-based radiological image analysis could facilitate use of chest x-rays as triage tests for pulmonary tuberculosis in resource-limited settings. We sought to determine whether commercially available chest x-ray analysis software meet WHO recommendations for minimal sensitivity and specificity as pulmonary tuberculosis triage tests.

Methods: We recruited symptomatic adults at the Indus Hospital, Karachi, Pakistan.

Evaluation of a home-based 7-day infection control strategy for healthcare workers following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2): A cohort study.

Objective: Evidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). In this study, we evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy.

Methods: HCWs advised by their infection control or occupational health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May and October 2020.

Diaphragm Morphology Assessed by Computed Tomography in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is associated with abnormal skeletal muscle morphology and function. To test the hypothesis that diaphragm muscle morphology assessed by computed tomography (CT) imaging would be associated with COPD severity, exacerbations, health status, and exercise capacity. The COPD Morphometry Study is a cross-sectional study that enrolled a clinical sample of smokers with COPD.

NEK1 Phosphorylation of YAP Promotes Its Stabilization and Transcriptional Output.

Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC); however, the mechanism and key players leading to this are not fully understood. While studying the role of tousled-like kinase 1 (TLK1) and never in mitosis gene A (NIMA)-related kinase 1 (NEK1) in a DNA damage response (DDR)-mediated cell cycle arrest in LNCaP cells treated with bicalutamide, we uncovered that overexpression of wt-NEK1 resulted in a rapid conversion to androgen-independent (AI) growth, analogous to what has been observed when YAP1 is overexpressed. We now report that overexpression of wt-NEK1 results in accumulation of YAP1, suggesting the existence of a TLK1>NEK1>YAP1 axis that leads to adaptation to AI growth.