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Abstract Over the last decades, air pollution emissions have decreased substantially; however, inequities in air pollution persist. We evaluate county-level racial/ethnic and socioeconomic disparities in emissions changes from six air pollution source sectors (industry [SO2], energy [SO2, NOx], agriculture [NH3], commercial [NOx], residential [particulate organic carbon], and on-road transportation [NOx]) in the contiguous United States during the 40 years following the Clean Air Act (CAA) enactment (1970-2010). We calculate relative emission changes and examine the differential changes given county demographics using hierarchical nested models. The results show racial/ethnic disparities, particularly in the industry and energy generation source sectors. We also find that median family income is a driver of variation in relative emissions changes in all sectors—counties with median family income >$75 K vs. less generally experience larger relative declines in industry, energy, transportation, residential, and commercial-related emissions. Emissions from most air pollution source sectors have, on a national level, decreased following the United States CAA. In this work, we show that the relative reductions in emissions varied across racial/ethnic and socioeconomic groups.

Summary: Seven healthy, physically active men (n = 3) and women (n = 4) (30.7 ± 7.5 years, 172.7 ± 8.7 cm, 70.4 ± 11.6 kg, 23.6 ± 4.1 kg/m2, 49.2 ± 8.4 mL/kg/min) supplemented for 14 days with a placebo (PLA) or 1 × 1010 CFU doses of the probiotic Veillonella atypica FB0054 (FitBiomics, New York, NY). Participants had safety panels, hemodynamics, lactate, and anaerobic capacity assessed. Stool samples were collected to evaluate for metagenomic and metabolomic changes. Exhaustion times were not different between groups, whereas anaerobic capacity tended to shorten with PLA (61.14 ± 72.04 s; 95% CI: −5.49, 127.77 s, p = 0.066) with no change with VA (13.29 ± 100.13 s, 95% CI: −79.32, 105.89 s, p = 0.738). No changes in lactate, hemodynamics, or bacterial community changes were observed, whereas 14 metabolites exhibited differential expression patterns with VA supplementation. In conclusion, VA maintained exercise performance that tended to decline in PLA. Supplementation was well tolerated with no changes in safety markers or reported adverse events.

Conformational heterogeneity is key to understand how macromolecular function and structure converge. Here, the authors propose an algorithm designed to estimate structural landscapes directly from Cryo-EM particle images.

ObjectiveTo examine the efficacy of supplementing with a multi-strain probiotic (MSP) on changes associated with mood, anxiety, and neurotransmitter levels.MethodIn a randomized, double-blind, placebo-controlled fashion, 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented with a single capsule of MSP (a total daily dose of 4 × 109 live cells comprised of a 1 × 109 live cells dose from each of the following strains: Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04, Probiotical S.p.A., Novara, Italy) or a maltodextrin placebo (PLA). After 0, 2, 4, and 6 weeks of supplementation and 3 weeks after ceasing supplementation, study participants completed the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), and Leiden Index of Depression Sensitivity (LEIDS-R) questionnaires and had plasma concentrations of cortisol, dopamine, serotonin, and C-reactive protein determined.ResultsBDI, STAI, and total LEIDS-R scores were reduced from baseline (p 0.05) were reported in PLA. When compared to PLA, MSP scores for state anxiety, trait anxiety, and LEIDS-R (hopeless, aggression, rumination, and total score) were significantly lower (p 0.05) in plasma dopamine, C-reactive protein, or cortisol concentrations were observed between groups.ConclusionMSP supplementation resulted in widespread improvements in several questionnaires evaluating mood, anxiety, and depression in young, healthy men and women. MSP supplementation increased serotonin increased after 6 weeks of MSP supplementation with no change in dopamine, C-reactive protein, or cortisol.Clinical trial registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05343533, NCT05343533.

AMPA glutamate receptors, mediate the majority of excitatory signaling in the brain. Here the authors show how the auxiliary subunit TARP-γ8 shapes gating kinetics, ion conductance and rectification properties of the heteromeric GluA1/2 AMPA receptor.

ABSTRACT: Herd-level diagnosis of paratuberculosis using a pool-milk ELISA (pool size: n ≤ 50) is a novel, economical, and convenient method to identify blood serological Mycobacterium avium ssp. paratuberculosis (MAP) antibody–positive herds. To date, the diagnostic performance of the pool-milk ELISA has been described only under laboratory conditions where herd prevalence was simulated by the preparation of milk pools consisting of milk samples of cows with a known MAP status determined by fecal culture. In our observational study, test performance under field conditions was studied using pooled milk and individual blood samples. A total of 486 herds within the MAP prevalence reduction program of Lower Saxony, from which pooled milk and individual blood ELISA results were available, were assigned to this study. Data were analyzed for the period between January 1 and December 31, 2018, the first year after herd testing became obligatory in this federal state of Germany. To evaluate whether pooled milk samples reliably distinguish between herds with a MAP-apparent blood serological within-herd prevalence (MAP-Ab-WHPapp) ≥5% and herds with a MAP-Ab-WHPapp

Summary: The emergence of SARS-CoV-2 variants necessitates rational assessment of their impact on the recognition and neutralization of the virus by the host cell. We present a comparative analysis of the interactions of Alpha, Beta, Gamma, and Delta variants with cognate molecules (ACE2 and/or furin), neutralizing nanobodies (Nbs), and monoclonal antibodies (mAbs) using in silico methods, in addition to Nb-binding assays. Our study elucidates the molecular origin of the ability of Beta and Delta variants to evade selected antibodies, such as REGN10933, LY-CoV555, B38, C105, or H11-H4, while being insensitive to others including REGN10987. Experiments confirm that nanobody Nb20 retains neutralizing activity against the Delta variant. The substitutions T478K and L452R in the Delta variant enhance associations with ACE2, whereas P681R promotes recognition by proteases, thus facilitating viral entry. The Ab-specific responses of variants highlight how full-atomic structure and dynamics analyses are required for assessing the response to newly emerging variants.

Recent years have seen several hybrid simulation methods for exploring the conformational space of proteins and their complexes or assemblies. These methods often combine fast analytical approaches with computationally expensive full atomic molecular dynamics (MD) simulations with the goal of rapidly sampling large and cooperative conformational changes at full atomic resolution. We present here a systematic comparison of the utility and limits of four such hybrid methods that have been introduced in recent years: MD with excited normal modes (MDeNM), collective modes-driven MD (CoMD), and elastic network model (ENM)-based generation, clustering, and relaxation of conformations (ClustENM) as well as its updated version integrated with MD simulations (ClustENMD). We analyzed the predicted conformational spaces using each of these four hybrid methods, applied to four well-studied proteins, triosephosphate isomerase (TIM), 3-phosphoglycerate kinase (PGK), HIV-1 protease (PR) and HIV-1 reverse transcriptase (RT), which provide extensive ensembles of experimental structures for benchmarking and comparing the methods. We show that a rigorous multi-faceted comparison and multiple metrics are necessary to properly assess the differences between conformational ensembles and provide an optimal protocol for achieving good agreement with experimental data. While all four hybrid methods perform well in general, being especially useful as computationally efficient methods that retain atomic resolution, the systematic analysis of the same systems by these four hybrid methods highlights the strengths and limitations of the methods and provides guidance for parameters and protocols to be adopted in future studies.

In this study, we report the impact of structural 4H-SiC epitaxial defects on the electrical characteristics and blocking capabilities of SiC power devices. The detection and classification of the various crystal defects existing in 4H-SiC epitaxial layers and substrates was carried out with a commercial inspection tool using an optical microscope with a photoluminescence channel (PL). After the fabrication of dedicated test structures, devices that contain a single crystal defect were selected and electrically tested in reverse bias mode. Photon emission microscopy was performed to enable the localization of the leakage current spots within the devices. Thus, a direct correlation of the various crystal defects with the reduced blocking capability mechanism was made. This evaluation helps to set directions and build a strategy towards the reduction of critical defects in order to improve the performance of SiC devices for high power applications.

Background: Oxidative stress plays a crucial role in the pathogenesis of coronary artery disease. In cardiovascular research using murine models, the generation and maintenance of models with robust coronary arterial atherosclerosis has been challenging., Methods: We characterized a new mouse model in which the last 3 amino acids of the carboxyl terminus of the HDL (high-density lipoprotein) receptor (SR-B1 [scavenger receptor, class B, type 1]) were deleted in a low-density lipoprotein receptor knockout (LDLR -/- ) mouse model (SR-B1ΔCT/LDLR -/- ) fed an atherogenic diet. We also tested the therapeutic effects of an oxidative stress-targeted nanoparticle in atherogenic diet-fed SR-B1ΔCT/LDLR -/- mice., Results: The SR-B1ΔCT/LDLR -/- mice fed an atherogenic diet had occlusive coronary artery atherosclerosis, impaired cardiac function, and a dramatically lower survival rate, compared with LDLR -/- mice fed the same diet. As SR-B1ΔCT/LDLR -/- mice do not exhibit female infertility or low pup yield, they are far easier and less costly to use than the previously described SR-B1-based models of coronary artery disease. We found that treatment with the targeted nanoparticles improved the cardiac functions and corrected hematologic abnormalities caused by the atherogenic diet in SR-B1ΔCT/LDLR -/- mice but did not alter the distinctive plasma lipid levels., Conclusions: The SR-B1ΔCT/LDLR -/- mice developed diet-inducible, fatal atherosclerotic coronary artery disease, which could be ameliorated by targeted nanoparticle therapy. Our study provides new tools for the development of cardiovascular therapies., Competing Interests: None.

Context: Data dashboards have emerged as critical tools for surveillance and informing resource allocation. Despite their utility and popularity during COVID-19, there is a growing need to understand what tools and training are tailored to nonprofit community-based organizations that may partner with public health officials., Program: In June 2021, the Rhode Island Department of Health and Brown University partnered to create Project SIGNAL (Spatiotemporal Insights to Guide Nuanced Actions Locally), which utilizes spatiotemporal analytics to identify Rhode Island's largest disparities in COVID-19-related outcomes (eg, testing, diagnosis, vaccinations) at the neighborhood level. Results were hosted in an interactive online dashboard (signal-ri.org) designed using principles of the CDC Clear Communication Index. The target audience included a network of 15 geographic areas called Health Equity Zones, funded by the health department to provide critical grassroots public health programs to address social, health, and economic outcomes in their communities., Implementation: To disseminate the dashboard, a 6-hour virtual workshop series was created to train leaders to use the dashboard and increase their confidence in understanding common public health data terminology and concepts and better prepare attendees for rapid decision making during future public health emergencies., Evaluation: The Project SIGNAL dashboard was launched in August 2022 and has been accessed over 7500 times. A total of 84 community leaders were trained to use this dashboard, increasing their confidence in applying common public health metrics to make decisions about their COVID-19-related activities., Discussion: While several studies have outlined best practices for data dashboards, this is among the first to examine incorporating these practices into a spatiotemporal decision tool designed specifically for community organizations. Project SIGNAL demonstrates that by incorporating design best practices and pairing data dashboards with hands-on training, we can empower community leaders to utilize advanced spatiotemporal methods to identify health disparities and take localized action., Competing Interests: The authors have indicated that they have no potential conflicts of interest to disclose ., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 3D range-modulator (RM), optimized for a single energy and a specific target shape, is a promising and viable solution for the ultra-fast dose delivery in particle therapy. The aim of this work was to investigate the impact of potential beam and modulator misalignments on the dose distribution. Moreover, the FLUKA Monte Carlo model, capable of simulating 3D RMs, was adjusted and validated for the 250 MeV single-energy proton irradiation from a Varian ProBeam system. A 3D RM was designed for a cube target shape rotated 45° around two axes using a Varian-internal research version of the Eclipse treatment planning software, and the resulting dose distribution was simulated in a water phantom. Deviations from the ideal alignment were introduced, and the dose distributions from the modified simulations were compared to the original unmodified one. Finally, the FLUKA model and the workflow were validated with base-line data measurements and dose measurements of the manufactured modulator prototype at the HollandPTC facility in Delft. The adjusted FLUKA model, optimized particularly in the scope of a single-energy FLASH irradiation with a PMMA pre-absorber, demonstrated very good agreement with the measured dose distribution resulting from the 3D RM. Dose deviations resulting from modulator-beam axis misalignments depend on the specific 3D RM and its shape, pin aspect ratio, rotation angle, rotation point, etc. A minor modulator shift was found to be more relevant for the distal dose distribution than for the spread-out Bragg Peak (SOBP) homogeneity. On the other hand, a modulator tilt (rotation away from the beam axis) substantially affected not only the depth dose profile, transforming a flat SOBP into a broad, Gaussian-like distribution with increasing rotation angle, but also shifted the lateral dose distribution considerably. This work strives to increase awareness and highlight potential pitfalls as the 3D RM method progresses from a purely research concept to pre-clinical studies and human trials. Ensuring that gantry rotation and the combined weight of RM, PMMA, and aperture do not introduce alignment issues is critical. Given all the other range and positioning uncertainties, etc., not related to the modulator, the RM must be aligned with an accuracy below 1° in order to preserve a clinically acceptable total uncertainty budget. Careful consideration of critical parameters like the pin aspect ratio and possibly a novel robust modulator geometry optimization are potential additional strategies to mitigate the impact of positioning on the resulting dose. Finally, even the rotated cube 3D modulator with high aspect ratio pin structures (~80 mm height to 3 mm pin base width) was found to be relatively robust against a slight misalignment of 0.5° rotation or a 1.5 mm shift in one dimension perpendicular to the beam axis. Given a reliable positioning and QA concept, the additional uncertainties introduced by the 3D RM can be successfully managed adopting the concept into the clinical routine.

Background: Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke., Methods: We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with Ldlr knockout (designated SR-BI ∆CT/∆CT / Ldlr -/- ). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI ∆CT/∆CT / Ldlr -/- mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions., Results: SR-BI ∆CT/∆CT / Ldlr -/- mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI ∆CT/∆CT / Ldlr -/- mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI ∆CT/∆CT / Ldlr -/- mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions., Conclusions: WD-fed SR-BI ∆CT/∆CT / Ldlr -/- mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.

Background: In the context of polysubstance use and fentanyl detection in non-opioid drugs supplies (e.g., cocaine, methamphetamine), it is important to re-evaluate and expand our understanding of which populations are at high risk for fatal drug overdoses. The primary objective of this pilot study was to gather data from the ED to characterize the population presenting with drug overdose, including demographics, drug use patterns and comorbidities, to inform upstream overdose prevention efforts., Methods: A consecutive sample of ED patients undergoing treatment for non-fatal overdose were prospectively recruited for study participation at the time of ED visit. Participants reported history of substance use over the past six months, recent and lifetime overdose, and naloxone receipt and administration history., Results: A total of 76 eligible participants were enrolled over the course of seven months. Participants reported high rates of opioid (56%), stimulant (56%), and cannabis use (59%). Self-reported polysubstance use, defined as self-reported use of more than one substance, was 83%. Of enrolled participants, 64% reported at least one overdose and 39% reported three or more lifetime overdoses prior to their index overdose ED visit. Participants with no self-reported intentional opioid use (n = 32) in the past six months had fentanyl positive urine drug screen 84% of the time versus 89% in the overall study population (n = 74). Participants who did not report opioid use in the past six months were less likely to possess (34% vs. 55%) or to know how to acquire (50% vs. 74%) naloxone compared to participants with self-reported history of opioid use., Conclusion: This study demonstrated high rates of fentanyl exposure on toxicology testing at time of overdose across all participants including study participants without self-reported intentional opioid use. Data gathered in the ED at time of overdose can be used to inform upstream naloxone distribution and public health initiatives., Competing Interests: Declaration of competing interest Research reported in this publication is supported by the National Institute of General Medical Sciences of the NIH under grant number P20GM125507. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This data has been presented at the North American Conference of Clinical Toxicology in Montreal, Canada in September 2023., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: There are a limited number of pharmacologic therapies for coronary artery disease, and few rodent models of occlusive coronary atherosclerosis and consequent myocardial infarction with which one can rapidly test new therapeutic approaches. Here, we characterize a novel, fertile, and easy-to-use HDL receptor (SR-B1)-based model of atherogenic diet-inducible, fatal coronary atherosclerosis, the SR-B1ΔCT/LDLR KO mouse. Additionally, we test intramyocardial injection of Stromal Cell-Derived Factor-1 alpha (SDF-1α), a potent angiogenic cytokine, as a possible therapy to rescue cardiac function in this mouse., Methods: SR-B1ΔCT/LDLR KO mice were fed the Paigen diet or standard chow diet, and we determined the effects of the diets on cardiac function, histology, and survival. After two weeks of feeding either the Paigen diet (n = 24) or standard chow diet (n = 20), the mice received an intramyocardial injection of either SDF-1α or phosphate buffered saline (PBS). Cardiac function and angiogenesis were assessed two weeks later., Results: When six-week-old mice were fed the Paigen diet, they began to die as early as 19 days later and 50% had died by 38 days. None of the mice maintained on the standard chow diet died by day 72. Hearts from mice on the Paigen diet showed evidence of cardiomegaly, myocardial infarction, and occlusive coronary artery disease. For the five mice that survived until day 28 that underwent an intramyocardial injection of PBS on day 15, the average ejection fraction (EF) decreased significantly from day 14 (the day before injection, 52.1 ± 4.3%) to day 28 (13 days after the injection, 30.6 ± 6.8%) (paired t-test, n = 5, p = 0.0008). Of the 11 mice fed the Paigen diet and injected with SDF-1α on day 15, 8 (72.7%) survived to day 28. The average EF for these 8 mice increased significantly from 48.2 ± 7.2% on day 14 to63.6 ± 6.9% on day 28 (Paired t-test, n = 8, p = 0.003)., Conclusions: This new mouse model and treatment with the promising angiogenic cytokine SDF-1α may lead to new therapeutic approaches for ischemic heart disease., Competing Interests: Declaration of competing interest The authors 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients living with obesity continue to experience body image dissatisfaction following bariatric metabolic surgery. The underlying reasons are poorly understood but may be due to unmet expectations. Negative body image perception following metabolic surgery leads to poorer psychological and clinical outcomes. This study aims to establish the acceptability and feasibility of three-dimensional (3D) reconstruction and virtual reality (VR) as a method of providing psychological support to bariatric patients to improve body image satisfaction and interventional outcomes., Methods: Seven participants were recruited from the Imperial Weight Centre. 3D photographs were captured and processed to produce two 3D reconstructed images with 15% and 25% total weight loss. Participants were shown their images using VR and participated in peer group workshops., Results: Six participants were retained until the end of the study. Five out of six participants agreed the images provided them with a more accurate representation of their body changes and overall appearance following bariatric metabolic surgery. All participants strongly agreed with the group setting and felt VR facilitated discussions on body image. Overall, all participants felt that the use of VR and 3D reconstruction is beneficial in supporting patients to adjust to changes in their body image after bariatric metabolic surgery., Conclusions: This is the first study to explore and demonstrate that 3D reconstruction and VR is an acceptable and feasible method providing patients with a realistic expectation of how their body will change following significant weight loss, potentially improving body image satisfaction after surgery, as well as psychological and interventional outcomes., (© 2024. The Author(s).)

Humans are chronically exposed to furan, a potent liver toxicant and carcinogen that occurs in a variety of heat-processed foods. Assessment of human exposure based on the furan content in foods is, however, subject to some uncertainty due to the high volatility of furan. Biomarker monitoring is thus considered an alternative or complementary approach to furan exposure assessment. Previous work suggested that urinary furan metabolites derived from the reaction of cis-2-butene-1,4-dial (BDA), the reactive intermediate of furan, with glutathione (GSH) or amino acids may serve as potential biomarkers of furan exposure. However, some metabolites were also reported to occur in urine of untreated animals, indicating either background contamination via animal feed or endogenous sources, which may limit their suitability as biomarkers of exposure. The overall aim of the present study was to accurately establish the correlation between external dose and concentration of furan metabolites in urine over time and to discriminate against endogenous formation and furan intake via feed. To this end, the furan metabolites GSH-BDA (N-[4-carboxy-4-(3-mercapto-1H-pyrrol-1-yl)-1-oxobutyl]-L-cysteinylglycine), NAcLys-BDA (R-2-(acetylamino)-6-(2,5-dihydro-2-oxo-1H-pyrrol-1-yl)-1-hexanoic acid), NAcCys-BDA-NAcLys (N-acetyl-S-[1-[5-(acetylamino)-5-carboxypentyl]-1H-pyrrol-3-yl]-L-cysteine) and NAcCys-BDA-NAcLys sulfoxide (N-acetyl-S-[1-[5-(acetylamino)-5-carboxypentyl]-1H-pyrrol-3-yl]-L-cysteine sulfoxide) were simultaneously analyzed by stable isotope dilution ESI-LC-MS/MS as unlabeled and [ 13 C 4 ]-furan dependent metabolites following oral administration of a single oral dose of isotopically labelled [ 13 C 4 ]-furan (0.1, 1, 10, 100 and 1000 µg/kg bw) to male and female F344/DuCrl rats. Although a linear correlation between urinary excretion of [ 13 C 4 ]-furan-dependent metabolites was observed, analysis of unlabeled NAcLys-BDA, NAcCys-BDA-NAcLys and NAcCys-BDA-NAcLys sulfoxide revealed substantial, fairly constant urinary background levels throughout the course of the study. Analysis of furan in animal feed excluded feed as a source for these background levels. GSH-BDA was identified as the only furan metabolite without background occurrence, suggesting that it may present a specific biomarker to monitor external furan exposure. Studies in humans are now needed to establish if analysis of urinary GSH-BDA may provide reliable exposure estimates., (© 2024. The Author(s).)

Background: In the last three decades, much effort has been invested in measuring and improving the quality of diabetes care. We assessed the association between adherence to diabetes quality indicators and all-cause mortality in the primary care setting., Methods: A nationwide, population-based, historical cohort study of all people aged 45-80 with pharmacologically-treated diabetes in 2005 (n = 222,235). Data on annual performance of quality indicators (including indicators for metabolic risk factor management and glycemic control) and vital status were retrieved from electronic medical records of the four Israeli health maintenance organizations. Cox proportional hazards and time-dependent models were used to estimate hazard ratios (HRs) for mortality by degree of adherence to quality indicators., Results: During 2,000,052 person-years of follow-up, 35.8% of participants died. An inverse dose-response association between the degree of adherence and mortality was shown for most of the quality indicators. Participants who were not tested for proteinuria or did not visit an ophthalmologist during the first-5-years of follow-up had HRs of 2.60 (95%CI:2.49-2.69) and 2.09 (95%CI:2.01-2.16), respectively, compared with those who were fully adherent. In time-dependent analyses, not measuring LDL-cholesterol, blood pressure, HbA1c, or HbA1c>9% were similarly associated with mortality (HRs ≈1.5). The association of uncontrolled blood pressure with mortality was modified by age, with increased mortality shown for those with controlled blood pressure at older ages (≥65 years)., Conclusions: Longitudinal adherence to diabetes quality indicators is associated with reduced all-cause mortality. Primary care professionals need to be supported by health care systems to perform quality indicators., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdel-Rahman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Angler Saddleback pig is an endangered local breed originating from Germany. The breed is said to have low demands in terms of husbandry and feeding, and an excellent meat quality. To date, there is a lack of more recent scientific investigations of the breed. Therefore, 58 Angler Saddleback pigs were fattened in two consecutive trials whereby performance, carcass quality and meat quality were assessed. At an average age of 324 days, the pigs reached an average final live weight of 143 kg, an intramuscular fat (IMF) content of 2.6%, a lean meat percentage of 47% and a backfat thickness of 38 mm. A significant influence of the independent variables "breeder" and "age at the end of fattening" on the majority of target variables was found. Furthermore, IMF as well as pH value 45 minutes post mortem was significantly influenced by sex. These results give a current overview of the phenotypic characteristics of this endangered breed. It is shown that the slower growing Angler Saddleback breed may need alternative marketing concepts for its meat and meat products. Additionally, further research is necessary to clarify the reasons for the high phenotypic variation within this breed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Olschewsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plasmalogen is a specific glycerophospholipid present in both animal and bacterial organisms. It plays a crucial function in eukaryotic cellular processes and is closely related to several human diseases, including neurological disorders and cancers. Nonetheless, the precise biological role of plasmalogen in bacteria is not well understood. In this study, we identified SMU_438c as the enzyme responsible for plasmalogen production in Streptococcus mutans under anaerobic conditions. The heterologous expression of SMU_438c in a plasmalogen-negative strain, Streptococcus sanguinis , resulted in the production of plasmalogen, indicating that this enzyme is sufficient for plasmalogen production. Additionally, the plasmalogen-deficient S. mutans exhibited significantly lower acid tolerance and diminished its colonization in Drosophila flies compared to the wild-type strain and complemented strain. In summary, our data suggest that plasmalogen plays a vital role in bacterial stress tolerance and in vivo colonization., Importance: This study sheds light on the biological role of plasmalogen, a specific glycerophospholipid, in bacteria, particularly in Streptococcus mutans . Plasmalogens are known for their significant roles in eukaryotic cells and have been linked to human diseases like neurological disorders and cancers. The enzyme SMU_438c, identified as essential for plasmalogen production under anaerobic conditions, was crucial for acid tolerance and in vivo colonization in Drosophila by S. mutans , underscoring its importance in bacterial stress response and colonization. These findings bridge the knowledge gap in bacterial physiology, highlighting plasmalogen's role in microbial survival and offering potential insights into microbial pathogenesis and host-microbe interactions., Competing Interests: The authors declare no conflict of interest.

The ubiquitous inflammophilic oral pathobiont Fusobacterium nucleatum (Fn) is widely recognized for its strong association with inflammatory dysbiotic diseases and cancer. Fn is subdivided into four subspecies, which are historically considered functionally interchangeable in the oral cavity. To test this assumption, we analyzed patient-matched dental plaque and odontogenic abscess clinical specimens and examined whether an inflammatory environment selects for/against particular Fn subspecies. Dental plaque harbored a greater diversity of fusobacteria, with Fn. polymorphum dominating, whereas odontogenic abscesses were exceptionally biased for the largely uncharacterized organism Fn. animalis. Comparative genomic analyses revealed significant genotypic distinctions among Fn subspecies that correlate with their preferred ecological niches and support a taxonomic reassignment of each as a distinct Fusobacterium species. Despite originating as a low-abundance organism in dental plaque, Fn. animalis typically outcompetes other oral fusobacteria within the inflammatory abscess environment, which may explain its prevalence in other oral and extraoral diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Drug overdose persists as a leading cause of death in the United States, but resources to address it remain limited. As a result, health authorities must consider where to allocate scarce resources within their jurisdictions. Machine learning offers a strategy to identify areas with increased future overdose risk to proactively allocate overdose prevention resources. This modeling study is embedded in a randomized trial to measure the effect of proactive resource allocation on statewide overdose rates in Rhode Island (RI)., Methods: We used statewide data from RI from 2016 to 2020 to develop an ensemble machine learning model predicting neighborhood-level fatal overdose risk. Our ensemble model integrated gradient boosting machine and super learner base models in a moving window framework to make predictions in 6-month intervals. Our performance target, developed a priori with the RI Department of Health, was to identify the 20% of RI neighborhoods containing at least 40% of statewide overdose deaths, including at least one neighborhood per municipality. The model was validated after trial launch., Results: Our model selected priority neighborhoods capturing 40.2% of statewide overdose deaths during the test periods and 44.1% of statewide overdose deaths during validation periods. Our ensemble outperformed the base models during the test periods and performed comparably to the best-performing base model during the validation periods., Conclusions: We demonstrated the capacity for machine learning models to predict neighborhood-level fatal overdose risk to a degree of accuracy suitable for practitioners. Jurisdictions may consider predictive modeling as a tool to guide allocation of scarce resources., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)