Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders.

Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations.

Methods: A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests.

Structure-Guided Discovery of -Hexahydro-pyrido-oxazinones as Reversible, Drug-like Monoacylglycerol Lipase Inhibitors.

Monoacylglycerol lipase (MAGL) is a key enzyme involved in the metabolism of the endogenous signaling ligand 2-arachidonoylglycerol, a neuroprotective endocannabinoid intimately linked to central nervous system (CNS) disorders associated with neuroinflammation. In the quest for novel MAGL inhibitors, a focused screening approach on a Roche library subset provided a reversible benzoxazinone hit exhibiting high ligand efficiency. The subsequent design of the three-dimensional -hexahydro-pyrido-oxazinone (-HHPO) moiety as benzoxazinone replacement enabled the combination of high MAGL potency with favorable ADME properties.

Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders.

Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations.

Methods: A sample of WTC-exposed-FDNY responders ( = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests.

Replication studies in the Netherlands: Lessons learned and recommendations for funders, publishers and editors, and universities.

Drawing on our experiences conducting replications we describe the lessons we learned about replication studies and formulate recommendations for researchers, policy makers, and funders about the role of replication in science and how it should be supported and funded. We first identify a variety of benefits of doing replication studies. Next, we argue that it is often necessary to improve aspects of the original study, even if that means deviating from the original protocol.

Fluorescent Reporter Systems to Investigate Chromatin Effector Proteins in Living Cells.

Epigenetic research faces the challenge of the high complexity and tight regulation in chromatin modification networks. Although many isolated mechanisms of chromatin-mediated gene regulation have been described, solid approaches for the comprehensive analysis of specific processes as parts of the bigger epigenome network are missing. In order to expand the toolbox of methods by a system that will help to capture and describe the complexity of transcriptional regulation, we describe here a robust protocol for the generation of stable reporter systems for transcriptional activity and summarize their applications.

Accuracy of controlled attenuation parameter measurement for the detection of steatosis in autoimmune liver diseases.

Background & Aims: Concurrent fatty liver disease represents an emerging challenge in the care of individuals with autoimmune liver diseases (AILD). Therefore, we aimed to validate the ultrasound-based method of controlled-attenuation parameter (CAP) as a non-invasive tool to detect hepatic steatosis in individuals with AILD.

Methods: The diagnostic performance of CAP to determine biopsy-proven hepatic steatosis (>5%) was assessed in individuals with AILD (autoimmune hepatitis [AIH], primary biliary cholangitis [PBC], primary biliary cholangitis [PSC], or variant syndromes) who underwent liver biopsy at the University Medical Center Hamburg-Eppendorf between 2015-2020 by calculating the area under the receiver operating characteristic (AUROC) curves.

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English.

An Exploratory Qualitative Analysis of Explanations for COVID-19-Related Racial Disparities Among St. Louis Residents: "I Don't Really Pay Attention to the Racial Stuff Very Much".

Introduction: Public health explanations for the disproportionate share of COVID-19-related illness and death among the Black population often differ from lay explanations, which can affect the public's support for policies that address these disparities. This qualitative exploratory study examined the explanatory frameworks for COVID-19-related racial disparities in St. Louis among 54 St.

Trusted sources for COVID-19 testing and vaccination: lessons for future health communication.

Background: Promoting COVID-19 vaccination (both the primary series and boosters) remains a priority among healthcare professionals and requires understanding the various sources people trust for acquiring COVID-19 information.

Method: From October 2021 to May 2022, we interviewed 150 people who called 2-1-1 helplines in Connecticut and North Carolina about their COVID-19 testing and vaccination experiences in order to (1) better understand where people obtain trusted COVID-19 health information and (2) identify how public health professionals can share emergency health information in the future. We used a mixed methods approach in which semi-structured qualitative interviews and survey data were collected in parallel and analyzed separately.

Transcatheter Valve Replacement in Patients with Aortic Valve Stenosis: An Overview of Systematic Reviews and Meta-Analysis with Different Populations.

Background: Randomized controlled trials (RCTs) and observational studies have compared the efficacy and safety of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis.

Objectives: Compare TAVR and SAVR in patients with different surgical risks, population characteristics, and different transcatheter prosthetic valves.

Methods: An overview of systematic reviews (SRs) was conducted following a structured protocol.

Dopaminergic and norepinephrinergic modulation of endogenous event-related potentials: A systematic review and meta-analysis.

Event-related potentials (ERPs) represent the cortical processing of sensory, motor or cognitive functions invoked by particular events or stimuli. A current theory posits that the catecholaminergic neurotransmitters dopamine (DA) and norepinephrine (NE) modulate a number of endogenous ERPs during various cognitive processes. This manuscript aims to evaluate a leading neurotransmitter hypothesis with a systematic overview and meta-analysis of pharmacologic DA and NE manipulation of specific ERPs in healthy subjects during executive function.

Delay in desmopressin therapy: Disaster in waiting.

What Is Known And Objective: Central diabetes insipidus (DI) is a complex disease that requires firm adherence to desmopressin therapy. There is little information on the onset of hypernatremia after withdrawal of desmopressin.

Case Summary: We present a case of an elderly woman with central DI whose serum sodium jumped from 141 to 171 mEq/L after 48-72 h of holding oral desmopressin.

The Collective Trust Game: An Online Group Adaptation of the Trust Game Based on the HoneyComb Paradigm.

The need to understand trust in groups holistically has led to a surge in new approaches to measuring collective trust. However, this construct is often not fully captured in its emergent qualities by the available research methods. In this paper, the Collective Trust Game (CTG) is presented, a computer-based, multi-agent trust game based on the HoneyComb paradigm, which enables researchers to assess the emergence of collective trust.

Cultivating the ideal obstetrical patient: How physicians-in-training describe pain associated with childbirth.

We explore the work labor pain does in cultivating obstetrics and gynecology (OB/GYN) resident physicians' conceptualization of the "ideal" obstetrical patient - replete with moral, pharmacological, classed, and racialized dimensions. Our data is derived from a single-site, qualitative study conducted at an urban academic OB/GYN residency program in the midwestern U.S.

Implementation and safety evaluation of autoverification for select low-risk, high-volume medications in the emergency department.

Purpose: Use of autoverification has decreased in many emergency departments (EDs) with the expansion of emergency medicine (EM) pharmacists. Few studies have evaluated ways to prioritize verification of medications. Here we describe a process to design, implement, and measure the safety of autoverification of low-risk, high-volume medications.

Predictors of excess body weight concurrently affecting mother-child pairs: a 6 year follow-up.

Background: We examined the predictors of excess body weight (EBW) concurrently affecting mother-child pairs after delivery during 6 years of follow-up.

Methods: Prospective cohort study conducted on 435 mother-child pairs. Data were collected at four time points: at birth in the maternity hospital; 1-2 years old, 4-5 years old and 6 years old at the participant's home.

Questioning Biomedicine's Privileging of Disease and Measurability.

Within biomedicine, the diagnosis of disease is often privileged over a patient's experience of illness. Yet up to 30% of primary care visits might be attributable to persistent illness without a diagnosed disease, including functional somatic syndromes like fibromyalgia and chronic fatigue syndrome. When clinicians are unable to diagnose disease or correlate symptoms with measurable changes in biomarkers, patients experiencing such an illness are at increased risk for suspicion, misplaced questioning, or having their motives misinterpreted through damaging social and cultural narratives about gender, race, ethnicity, socioeconomic status, or disability.

International spillover effects in the EU's textile supply chains: A global SDG assessment.

Successful implementation of the Sustainable Development Goals (SDGs) requires world countries to account for actions that inadvertently generate negative impacts on other countries. These actions/effects are called 'spillovers', and can hinder a country's SDG progress. In this work, we analyse negative social spillover effects, focussing specifically on the occupational health and safety aspects of workers in textile supply chains.

Association of ADIPOQ-rs2241766 and FTO-rs9939609 genetic variants with body mass index trajectory in women of reproductive age over 6 years of follow-up: the PREDI study.

Background: Interindividual variations in body mass index (BMI) can be partially explained by genetic differences. We aimed to examine the association of the ADIPOQ-rs2241766, LEP-rs7799039 and FTO-rs9939609 genetic variants with BMI trajectory in women of reproductive age over 6 years of follow-up.

Methods: This was a prospective study that used data from 435 women of the PREDI Study conducted in Brazil.

A functional LSD1 coregulator screen reveals a novel transcriptional regulatory cascade connecting R-loop homeostasis with epigenetic regulation.

The lysine specific demethylase 1 (LSD1) plays a pivotal role in cellular differentiation by regulating the expression of key developmental genes in concert with different coregulatory proteins. This process is impaired in different cancer types and incompletely understood. To comprehensively identify functional coregulators of LSD1, we established a novel tractable fluorescent reporter system to monitor LSD1 activity in living cells.

Mitigating ethical conflict and moral distress in the care of patients on ECMO: impact of an automatic ethics consultation protocol.

Aims: This study evaluates a protocol for early, routine ethics consultation (EC) for patients on extracorporeal membrane oxygenation (ECMO) to support decision-making in the context of clinical uncertainty with the aim of mitigating ethical conflict and moral distress.

Methods: We conducted a single-site qualitative analysis of EC documentation for all patients receiving ECMO support from 15 August 2018 to 15 May 2019 (n=68). Detailed analysis of 20 ethically complex cases with protracted ethics involvement identifies four key ethical domains: limits of prognostication, bridge to nowhere, burden of treatment and system-level concerns.

Cytokinin Signaling Downstream of the His-Asp Phosphorelay Network: Cytokinin-Regulated Genes and Their Functions.

The plant hormone cytokinin, existing in several molecular forms, is perceived by membrane-localized histidine kinases. The signal is transduced to transcription factors of the type-B response regulator family localized in the nucleus by a multi-step histidine-aspartate phosphorelay network employing histidine phosphotransmitters as shuttle proteins across the nuclear envelope. The type-B response regulators activate a number of primary response genes, some of which trigger in turn further signaling events and the expression of secondary response genes.