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Introduction: Rapid response teams (RRTs) have been shown to reduce cardiopulmonary arrests outside the intensive care unit (ICU). Yet the utility of RRTs remains in question, as most large studies have failed to demonstrate a significant reduction in hospital-wide mortality after RRT implementation.Methods: A cohort design with historical controls was used to determine the effect on hospital-wide mortality of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely promoted as a key trigger for activation. All nonprisoner patients admitted to a tertiary referral public teaching hospital from 2003 through 2008 were included. In total, 77, 021 admissions before RRT implementation (2003 through 2005) and 79, 013 admissions after RRT implementation (2006 through 2008) were evaluated. The a priori primary outcome was unadjusted hospital-wide mortality. A Poisson regression model was then used to adjust for hospital-wide mortality trends over time. Secondary outcomes defined a priori were unadjusted out-of-ICU mortality and out-of-ICU cardiopulmonary-arrest codes.Results: In total, 855 inpatient RRTs (10.8 per 1, 000 hospital-wide discharges) were activated during the 3-year postintervention period. Forty-seven percent of RRTs were activated for reasons of clinical judgment. Hospital-wide mortality decreased from 15.50 to 13.74 deaths per 1, 000 discharges after RRT implementation (relative risk, 0.887; 95% confidence interval (CI), 0.817 to 0.963; P = 0.004). After adjusting for inpatient mortality trends over time, the reduction in hospital-wide mortality remained statistically significant (relative risk, 0.825; 95% CI, 0.694 to 0.981; P = 0.029). Out-of-ICU mortality decreased from 7.08 to 4.61 deaths per 1, 000 discharges (relative risk, 0.651; 95% CI, 0.570 to 0.743; P < 0.001). Out-of-ICU cardiopulmonary-arrest codes decreased from 3.28 to 1.62 codes per 1, 000 discharges (relative risk, 0.493; 95% CI, 0.399 to 0.610; P < 0.001).Conclusions: Implementation of an RRT in which clinical judgment, in addition to vital-signs criteria, was widely cited as a rationale for activation, was associated with a significant reduction in hospital-wide mortality, out-of-ICU mortality, and out-of-ICU cardiopulmonary-arrest codes. The frequent use of clinical judgment as a criterion for RRT activation was associated with high RRT utilization. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the X chromosome gene PIGA lead to phosphatidylinositol glycan class A congenital disorder of glycosylation (PIGA-CDG), an ultra-rare CDG typically presenting with seizures, hypotonia, and neurodevelopmental delay. We identified two brothers (probands) with PIGA-CDG, presenting with epilepsy and mild developmental delay. Both probands carry PIGA c.395C>G (p.Ser132Cys), an ultra-rare variant predicted to be damaging. Strikingly, the maternal grandfather and a great uncle also carry the same PIGA variant, but neither presents with symptoms associated with PIGA-CDG. We hypothesized that genetic modifiers might contribute to this reduced penetrance. Using whole-genome sequencing and pedigree analysis, we identified possible susceptibility variants found in the probands and not in the carriers and possible protective variants found in the carriers and not in the probands. Candidate genetic modifier variants included heterozygous, damaging variants in three genes involved directly in glycosylphosphatidylinositol (GPI)-anchor biosynthesis and additional variants in other glycosylation pathways or encoding GPI-anchored proteins. Using a Drosophila eye-based model, we tested modifiers identified through genome sequencing. Loss of CNTN2, a predicted protective modifier that encodes a GPI-anchored protein responsible for neuron/glial interactions, rescues loss of PIGA in the eye-based model, as we predict in the family. Further testing found that the loss of CNTN2 also rescues PIGA-CDG-specific phenotypes, including seizures and climbing defects in Drosophila neurological models of PIGA-CDG. Using pedigree information, genome sequencing, and in vivo testing, we identified CNTN2 as a strong candidate modifier that could explain the incomplete penetrance in this family. Identifying and studying rare disease modifier genes in families may lead to therapeutic targets., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: Health research that significantly impacts global clinical practice and policy is often published in high-impact factor (IF) medical journals. These outlets play a pivotal role in the worldwide dissemination of novel medical knowledge. However, researchers identifying as women and those affiliated with institutions in low- and middle-income countries (LMICs) have been largely under-represented in high-IF journals across multiple fields of medicine. To evaluate disparities in gender and geographical representation among authors who have published in any of five top general medical journals, we conducted scientometric analyses using a large-scale dataset extracted from the New England Journal of Medicine , Journal of the American Medical Association , The BMJ , The Lancet and Nature Medicine ., Methods: Author metadata from all articles published in the selected journals between 2007 and 2022 were collected using the DimensionsAI platform. The Genderize.io Application Programming Interface was then used to infer each author's likely gender based on their extracted first name. The World Bank country classification was used to map countries associated with researcher affiliations to the LMIC or the high-income country (HIC) category. We characterised the overall gender and country income category representation across the five medical journals. In addition, we computed article-level diversity metrics and contrasted their distributions across the journals., Results: We studied 151 536 authors across 49 764 articles published in five top medical journals, over a period spanning 15 years. On average, approximately one-third (33.1%) of the authors of a given paper were inferred to be women; this result was consistent across the journals we studied. Further, 86.6% of the teams were exclusively composed of HIC authors; in contrast, only 3.9% were exclusively composed of LMIC authors. The probability of serving as the first or last author was significantly higher if the author was inferred to be a man (18.1% vs 16.8%, p<0.01) or was affiliated with an institution in a HIC (16.9% vs 15.5%, p<0.01). Our primary finding reveals that having a diverse team promotes further diversity, within the same dimension (ie, gender or geography) and across dimensions. Notably, papers with at least one woman among the authors were more likely to also involve at least two LMIC authors (11.7% vs 10.4% in baseline, p<0.001; based on inferred gender); conversely, papers with at least one LMIC author were more likely to also involve at least two women (49.4% vs 37.6%, p<0.001; based on inferred gender)., Conclusion: We provide a scientometric framework to assess authorship diversity. Our research suggests that the inclusiveness of high-impact medical journals is limited in terms of both gender and geography. We advocate for medical journals to adopt policies and practices that promote greater diversity and collaborative research. In addition, our findings offer a first step towards understanding the composition of teams conducting medical research globally and an opportunity for individual authors to reflect on their own collaborative research practices and possibilities to cultivate more diverse partnerships in their work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Asphalt, widely used in infrastructure, emits complex chemical mixtures throughout its service life, posing significant risks to human health and the environment. This expanded understanding extends the concern from a construction-related hazard to a broader public health issue, especially affecting vulnerable populations like children who play on blacktop surfaces. Despite increased awareness, the specific mechanisms behind asphalt emissions, their impact on asphalt deterioration, and their effects on the human nervous system remain poorly understood. Our study addresses these knowledge gaps by examining the long-term health effects of asphalt emissions, focusing on neurological impacts. We investigate how environmental stressors and asphalt's chemical composition influence emission types and severity, using a combination of in vitro experiments, Drosophila melanogaster models, and advanced computational analyses. FTIR analysis reveals that as asphalt ages, emissions evolve from aliphatic to aromatic compounds, increasing toxicity. Our results demonstrate significant neurological damage from asphalt emissions, with effects worsening with age and being more pronounced in females, as shown in the Drosophila model, emphasizing the need for gender-specific health risk research. In vitro studies using 3T3L1 cells show that VOC exposure disrupts lipid droplet formation and metabolism, processes linked to neurodegenerative disorders. To mitigate emissions, our novel approach introduces wood-based biochar as a functional carbon to enhance intermolecular interactions within asphalt. GC-MS analysis indicates that biochar reduces VOC emissions by up to 76 %, while molecular dynamics (MD) simulations highlight biochar's effectiveness in hindering free-radical diffusion. Density functional theory (DFT) calculations confirm biochar's role, with adsorption energies of -20.4 kcal/mol, demonstrating strong and stable interactions that decelerate oxidative aging and mass loss. These findings offer a comprehensive understanding of emission mechanisms and propose a sustainable strategy to enhance asphalt durability while reducing environmental and health risks. This in turn provides evidence-based recommendations for the asphalt industry, emphasizing proactive measures toward long-term exposure mitigation. SYNOPSIS: Asphalt emits chemicals throughout its service life, posing neurological risks, especially to vulnerable groups, and needs emission mitigation., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elham H. Fini reports financial support was provided by National Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

To identify genes required for brain growth, we took an RNAi knockdown reverse genetic approach in Drosophila . One potential candidate isolated from this effort is the anti-lipogenic gene adipose ( adp ). Adp has an established role in the negative regulation of lipogenesis in the fat body of the fly and adipose tissue in mammals. While fat is key to proper development in general, adp has not been investigated during brain development. Here, we found that RNAi knockdown of adp in neuronal stem cells and neurons results in reduced brain lobe volume and sought to replicate this with a mutant fly. We generated a novel adp mutant that acts as a loss-of-function mutant based on buoyancy assay results. We found that despite a change in fat content in the body overall and a decrease in the number of larger (>5 µm) brain lipid droplets, there was no change in the brain lobe volume of mutant larvae. Overall, our work describes a novel adp mutant that can functionally replace the long-standing adp 60 mutant and shows that the adp gene has no obvious involvement in brain growth.

Seizures affect a large proportion of the global population and occur due to abnormal neuronal activity in the brain. Unfortunately, widespread genetic and phenotypic heterogeneity contribute to insufficient treatment options. It is critical to identify the genetic underpinnings of how seizures occur to better understand seizure disorders and improve therapeutic development. We used the Drosophila model to identify that IGF-II mRNA Binding Protein (Imp) is linked to the onset of this phenotype. Specific reduction of Imp in neurons causes seizures after mechanical stimulation. Importantly, gross motor behavior is unaffected, showing Imp loss does not affect general neuronal activity. Developmental loss of Imp is sufficient to cause seizures in adults, thus Imp-modulated neuron development affects mature neuronal function. Since Imp is an RNA-binding protein, we sought to identify the mRNA target that Imp regulates in neurons to ensure proper neuronal activity after mechanical stress. We find that Imp protein binds Syndecan ( Sdc ) mRNA, and reduction of Sdc also causes mechanically-induced seizures. Expression of Sdc in Imp deficient neurons rescues seizure defects, showing that Sdc is sufficient to restore normal behavior after mechanical stress. We suggest that Imp protein binds Sdc mRNA in neurons, and this functional interaction is important for normal neuronal biology and animal behavior in a mechanically-induced seizure model. Since Imp and Sdc are conserved, our work highlights a neuronal specific pathway that might contribute to seizure disorder when mutated in humans.

Background: With an increasing demand for critical care expertise and limitations in intensivist availability, innovative staffing models, such as the utilization of advanced practice providers (APPs), have emerged., Objectives: The purpose of the study was to compare patient outcomes between APP and housestaff teams in the cardiac intensive care unit (CICU)., Methods: This retrospective study, spanning March 2022 to July 2023, compares patient characteristics and outcomes between two CICU teams embedded in the same CICU at a large urban academic hospital: one staffed by housestaff and the other by APPs (80% physician assistants, 20% nurse practitioners) who each had approximately 1 to 2 years of experience in the CICU. The primary outcome was CICU mortality. Multivariable Cox regression analyses and Kaplan-Meier curves were used to assess the primary outcome., Results: A total of 1,620 admissions were analyzed: 1,013 patients on the housestaff service and 607 patients on the APP service. There were no significant differences in patient demographics, admitting diagnoses, use of vasoactive medications, inotropes, or mechanical circulatory support. There was no difference in CICU mortality (8.4% vs 8.2%, adjusted hazard ratio 0.73; 95% CI: 0.51-1.05; P  = 0.10), in-hospital mortality (13.5% vs 13.8%, aHR 0.82; 95% CI: 0.62-1.08; P  = 0.17), or in-hospital length of stay between the housestaff and APP teams. Patients managed by the housestaff team had a lower CICU length of stay (2 days IQR: 1-4 days] vs 3 days [IQR: 1-5 days], P  = 0.047). Fellowship rotation scores (based on surveys completed by the cardiology fellows) of the CICU also improved after the implementation of the APP-based team (3.87 ± 0.14 before vs 4.61 ± 0.06 after, P  < 0.0001)., Conclusions: Our moderately sized study demonstrated no difference in CICU or in-hospital mortality between patients managed by a housestaff team versus those managed by an APP team., Competing Interests: Dr Bangalore serves on the advisory board of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, and Truvic. Dr Alviar serves as a consultant at Zoll Inc, Abbott, and Abiomed and receives research grants from Baxter Medical. Dr Katz has received research support (modest) from Abbott Corporation, Speaker Honoraria of Zoll Inc, and the member of the Data Safety & Monitoring Board of Abiomed Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background & Objectives: Cardiopulmonary resuscitation (CPR) is the key for surviving cardiac arrest. Recent recommendations propose that CPR can - and should -be taught to schoolchildren. This e-learning-based study analyzes whether face-to-face CPR training can be partly substituted with e-learning by measuring CPR knowledge and self-efficacy in trainees., Methods: In this cluster randomized-controlled prospective, students attending grades 5 to 7 of a German secondary school volunteered to participate and were randomly assigned to one of two groups with different methods for CPR training each: a traditional instructor-led group (control) where students received face-to-face teaching by a BLS instructor (45 min), and an e-learning group (intervention) where schoolchildren were able to accomplish their theoretical CPR training using an e-learning module (15 min). CPR knowledge and self-efficacy were measured and compared before (t0) and after (t1) the training using questionnaires. Face-to-face CPR training (45 min) on manikins proceeded in both groups hereafter. The formal hypothesis was that e-learning would result in better CPR knowledge., Results: Overall, 375 students participated; 33 of which had to be excluded. 342 participants were included in statistical analysis (instructor-led group n  = 109; e-learning group n  = 233). The study was terminated early due to the Covid19 pandemic, and did not reach the required number of participants. Lacking statistical power, an analysis of the existing datasets failed to show superiority of e-learning vs. conventional training for CPR knowledge ( p  = 0.306). Both groups improved CPR knowledge ( p  < 0.001) and self-efficacy ( p  < 0.001) after CPR training and showed an equal, high level of satisfaction with their perceived training method (face-to-face: 4.1[4.0-4.2] vs. e-learning: 4.0[3.9-4.1]; p  = 0.153; maximum 5 points)., Conclusions: This study failed to demonstrate superiority for e-learning but was terminated early and hence underpowered. Further research is necessary to prove the efficiency of e-learning tools for CPR., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Wolfgang A. Wetsch, Nikolas Link, Niels Rahe-Meyer and Rico Dumcke have no conflicts of interest to declare regarding this manuscript. Jan Stock is Head of the L2R GmbH and Projekt Manager at the Hans Peter Esser GmbH. Bernd W. Böttiger is treasurer of the European Resuscitation Council (ERC), Founder of the ERC Research NET, Chairman of the German Resuscitation Council (GRC), Member of the „Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation (ILCOR), Member of the Executive Committee of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), Founder of the “Deutsche Stiftung Wiederbelebung”, Federal Medical Advisor of the German Red Cross (DRK), Member of the Advisory Board of the “Deutsche Herzstiftung”, Co-Editor of “Resuscitation”, Editor of the Journal “Notfall + Rettungsmedizin”, Co-Editor of the Brazilian Journal of Anesthesiology. He received fees for lectures from the following companies: Forum für medizinische Fortbildung (FomF), Baxalta Deutschland GmbH, ZOLL Medical Deutschland GmbH, C.R. Bard GmbH, GS Elektromedizinische Geräte G. Stemple GmbH, Novartis Pharma GmbH, Philips GmbH Market DACH, Bioscience Valuation BSV GmbH, Becton Dickinson GmbH, Fundacja Polski Instytut Evidence Based Medicine. Sabine Wingen is executive personal assistant of the executive board of the German Resuscitation Council (GRC)., (© 2024 The Author(s).)

Loss of function mutations in the X-linked PIGA gene lead to PIGA-CDG, an ultra-rare congenital disorder of glycosylation (CDG), typically presenting with seizures, hypotonia, and neurodevelopmental delay. We identified two brothers (probands) with PIGA-CDG, presenting with epilepsy and mild developmental delay. Both probands carry PIGA S132C , an ultra-rare variant predicted to be damaging. Strikingly, the maternal grandfather and a great-uncle also carry PIGA S132C , but neither presents with symptoms associated with PIGA-CDG. We hypothesized genetic modifiers may contribute to this reduced penetrance. Using whole genome sequencing and pedigree analysis, we identified possible susceptibility variants found in the probands and not in carriers and possible protective variants found in the carriers and not in the probands. Candidate variants included heterozygous, damaging variants in three genes also involved directly in GPI-anchor biosynthesis and a few genes involved in other glycosylation pathways or encoding GPI-anchored proteins. We functionally tested the predicted modifiers using a Drosophila eye-based model of PIGA-CDG. We found that loss of CNTN2 , a predicted protective modifier, rescues loss of PIGA in Drosophila eye-based model, like what we predict in the family. Further testing found that loss of CNTN2 also rescues patient-relevant phenotypes, including seizures and climbing defects in Drosophila neurological models of PIGA-CDG. By using pedigree information, genome sequencing, and in vivo testing, we identified CNTN2 as a strong candidate modifier that could explain the incomplete penetrance in this family. Identifying and studying rare disease modifier genes in human pedigrees may lead to pathways and targets that may be developed into therapies.

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused scorable phenotypes, such as overall lethality, gross morphological defects, reduced brain size and neuronal function defects. We further used this system to identify strain-dependent phenotypes that may have contributed to the increased pathogenesis associated with the outbreak of ZIKV in the Americas in 2015. Our work demonstrates the use of Drosophila as an efficient in vivo model to rapidly decipher how pathogens cause disease and lays the groundwork for further molecular study of ZIKV pathogenesis in flies., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. While adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of symptoms caused by this virus including microcephaly. In this study, we generated a toolkit to ectopically express Zika viral proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We use this toolkit to identify phenotypes and host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins cause scorable phenotypes, such as overall lethality, gross morphological defects, reduced brain size, and neuronal function defects. We further use this system to identify strain-dependent phenotypes that may contribute to the increased pathogenesis associated with the more recent outbreak of ZIKV in the Americas. Our work demonstrates Drosophila's use as an efficient in vivo model to rapidly decipher how pathogens cause disease and lays the groundwork for further molecular study of ZIKV pathogenesis in flies.