Spatiotemporal and multi-isotope assessment of metal sedimentation in the Great Lakes.

This study investigates spatiotemporal dynamics in metal sedimentation in the North American Great Lakes and their underlying biogeochemical controls. Bulk geochemical and isotope analyses of n = 72 surface and core sediment samples show that metal (Cu, Zn, Pb) concentrations and their isotopic compositions vary spatially across oligotrophic to mesotrophic settings, with intra-lake heterogeneity being similar or higher than inter-lake (basin-scale) variability. Concentrations of Cu, Zn, and Pb in sediments from Lake Huron and Lake Erie vary from 5 to 73 mg/kg, 18-580 mg/kg, and 5-168 mg/kg, respectively, but metal enrichment factors were small (<2) across the surface- and core sediments. The isotopic signatures of surface sediment Cu (δ65Cu between -1.19‰ and +0.96‰), Zn (δ66Zn between -0.09‰ and +0.41‰) and Pb (206/207Pb from 1.200 to 1.263) indicate predominantly lithogenic metal sourcing. In addition, temporal trends in sediment cores from Lake Huron and Lake Erie show uniform metal concentrations, minor enrichment, and Zn and Pb isotopic signatures suggestive of negligible in-lake biogeochemical fractionation. In contrast, Cu isotopic signatures and correlation to chlorophyll and macronutrient levels suggest more differentiation from source variability and/or redox-dependent fractionation, likely related to biological scavenging. Our results are used to derive baseline metal sedimentation fluxes and will help optimize water quality management and strategies for reducing metal loads and enrichment in the Great Lakes and beyond.

Protein N-glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease.

BACKGROUND: Diabetes is expected to directly impact renal glycosylation, yet to date, there has not been a comprehensive evaluation of alterations in N-glycan composition in the glomeruli of patients with diabetic kidney disease (DKD). METHODS: We used untargeted mass spectrometry imaging to identify N-glycan structures in healthy and sclerotic glomeruli in FFPE sections from needle biopsies of five patients with DKD and three healthy kidney samples. Regional proteomics was performed on glomeruli from additional biopsies from the same patients to compare the abundances of enzymes involved in glycosylation. Secondary analysis of single nuclei transcriptomics (snRNAseq) data was used to inform on transcript levels of glycosylation machinery in different cell types and states. RESULTS: We detected 120 N-glycans, and among them identified twelve of these protein post-translated modifications that were significantly increased in glomeruli. All glomeruli-specific N-glycans contained an N-acetyllactosamine (LacNAc) epitope. Five N-glycan structures were highly discriminant between sclerotic and healthy glomeruli. Sclerotic glomeruli had an additional set of glycans lacking fucose linked to their core, and they did not show tetra-antennary structures that are common in healthy glomeruli. Orthogonal omics analyses revealed lower protein abundance and lower gene expression involved in synthesizing fucosylated and branched N-glycans in sclerotic podocytes. In snRNAseq and regional proteomics analyses, we observed that genes and/or proteins involved in sialylation and LacNAc synthesis were also downregulated in DKD glomeruli, but this alteration remained undetectable by our spatial N-glycomics assay. CONCLUSIONS: Integrative spatial glycomics, proteomics, and transcriptomics revealed protein N-glycosylation characteristic of sclerotic glomeruli in DKD.

Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation.

Endothelial cells (ECs) in the descending aorta are exposed to high laminar shear stress, and this supports an anti-inflammatory phenotype. High laminar shear stress also induces flow-aligned cell elongation and front-rear polarity, but whether these are required for the anti-inflammatory phenotype is unclear. Here, we showed that Caveolin-1-rich microdomains polarize to the downstream end of ECs that are exposed to continuous high laminar flow. These microdomains were characterized by high membrane rigidity, filamentous actin (F-actin), and raft-associated lipids. Transient receptor potential vanilloid-type 4 (TRPV4) ion channels were ubiquitously expressed on the plasma membrane but mediated localized Ca2+ entry only at these microdomains where they physically interacted with clustered Caveolin-1. These focal Ca2+ bursts activated endothelial nitric oxide synthase (eNOS) within the confines of these domains. Importantly, we found that signaling at these domains required both cell body elongation and sustained flow. Finally, TRPV4 signaling at these domains was necessary and sufficient to suppress inflammatory gene expression, and exogenous activation of TRPV4 channels ameliorated the inflammatory response to stimuli both in vitro and in vivo. Our work revealed a polarized mechanosensitive signaling hub in arterial ECs that dampens inflammatory gene expression and promotes cell resilience.

Willingness to use PrEP among PrEP naïve men who have sex with men: a meta-analysis.

This study aimed to measure the pooled estimate of willingness to use HIV pre-exposure prophylaxis (PrEP) (WTUP) among PrEP-naïve United States (U.S.)-based men who have sex with men (MSM). PubMed, Embase, Web of Science, CINAHL, and PsycINFO were searched. The search strategy contained the keyword willingness and interest and the MeSH terms for HIV and PrEP. Articles were included if they were published between January 2005 and May 2022, reported quantitative data on WTUP among PrEP-naïve US-based MSM, and were available as full text in English. Meta-analysis was conducted to assess the pooled effect size of WTUP prevalence using a random-effects model, heterogeneity in the pooled estimate was assessed, and subgroup analyzes were conducted. Fifteen studies were included based on the inclusion and exclusion criteria. Meta-analysis revealed a pooled prevalence proportion for WTUP of 0.58 (95% CI 0.54-0.61) (or 58 out of 100) among PrEP-naïve MSM. High inter-study heterogeneity (Q = 548.10, df = 19, p < 0.01, I2 = 96.53, τ2 = 0.09) was observed. Age of the study sample and region where the data were collected significantly moderated the pooled WTUP estimate. Age-appropriate PrEP related messaging and a focus on HIV priority areas of the U.S. would be important strategies to improve WTUP among MSM in the U.S. moving forward.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Pediatric Salivary Gland Pathology.

Benign and malignant salivary gland disorders are uncommon in the pediatric population; however, these can be frequently seen in pediatric otolaryngology or oral and maxillofacial surgery practices. The astute clinician should be aware of the clinical presentation, diagnosis, and management options for common inflammatory, infectious, benign, and malignant disorders of salivary glands.

Progress on priming HIV-1 immunity.

Four new studies inform on the multistep path to generate broadly active HIV-1 antibodies.

Spatial distribution of benthic taxonomic and functional diversity in the Yellow River Basin: From ecological processes to associated determinant factors.

One of the fundamental objectives in ecology is to investigate the ecological processes and associated factors governing the abundance and spatial distribution patterns of biodiversity. However, the reaction of biological communities to environmental degradation remains relatively unknown, even for ecologically crucial communities like macroinvertebrates in aquatic ecosystems. Here, we sampled 117 locations to quantify relative contributions of geographical and environmental factors, including water quality, land use, climate, and hydrological factors, to determine the absolute and relative compositions of macroinvertebrate communities and their spatial distribution in the Yellow River Basin (YRB), the sixth-longest river system on Earth. We assessed relative roles of species sorting and dispersal in determining macroinvertebrate community structure along YRB. Our results demonstrated that alpha and beta diversity indices showed an increase from the up- to low-reaches of YRB. The middle and low-reaches exhibited elevated species diversity and both regions exhibited relatively stable community compositions. The biodiversity of macroinvertebrates was influenced by a combination of geographical factors and environmental variables, with environmental factors predominantly serving as the principal determinants. Results of multiple linear regression and variance decomposition showed that the effect of environmental factors was approximately three times greater than that of spatial factors. These findings provide support for the hypothesis that species sorting, driven by environmental gradients, plays a significant role in shaping the community structure of macroinvertebrates in running water ecosystems at the basin scales. Moreover, the factors contributing to substantial shifts in biodiversity across different segments of YRB indicate that distinct river sections have been influenced by varying stressors, with downstream areas being more susceptible to the impacts of water pollution and urbanization resulting from human activities.

CO2 Response Screen in Grass Brachypodium Reveals Key Role of a MAP Kinase in CO2-Triggered Stomatal Closure.

Plants respond to increased CO2 concentrations through stomatal closure, which can contribute to increased water use efficiency. Grasses display faster stomatal responses than eudicots due to dumbbell-shaped guard cells flanked by subsidiary cells working in opposition. However, forward genetic screening for stomatal CO2 signal transduction mutants in grasses has yet to be reported. The grass model Brachypodium distachyon is closely related to agronomically important cereal crops, sharing largely collinear genomes. To gain insights into CO2 control mechanisms of stomatal movements in grasses, we developed an unbiased forward genetic screen with an EMS-mutagenized Brachypodium distachyon M5 generation population using infrared imaging to identify plants with altered leaf temperatures at elevated CO2. Among isolated mutants, a "chill1" mutant exhibited cooler leaf temperatures than wildtype Bd21-3 parent control plants after exposure to increased [CO2]. chill1 plants showed strongly impaired high CO2-induced stomatal closure despite retaining a robust abscisic acid-induced stomatal closing response. Through bulked segregant whole-genome-sequencing analyses followed by analyses of further backcrossed F4 generation plants and generation and characterization of sodium-azide and CRISPR-cas9 mutants, chill1 was mapped to a protein kinase, Mitogen-Activated Protein Kinase 5 (BdMPK5). The chill1 mutation impaired BdMPK5 protein-mediated CO2/HCO3- sensing together with the High Temperature 1 (HT1) Raf-like kinase in vitro. Furthermore, AlphaFold2-directed structural modeling predicted that the identified BdMPK5-D90N chill1 mutant residue is located at the interface of BdMPK5 with the BdHT1 Raf-like kinase. BdMPK5 is a key signaling component that mediates CO2-induced stomatal movements and is proposed to function as a component of the primary CO2 sensor in grasses.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

A Pilot Randomized Controlled Trial of Augmented Reality Just-in-Time Guidance for the Performance of Rugged Field Procedures.

INTRODUCTION: Medical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care. STUDY OBJECTIVE: The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures. METHODS: Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables. RESULTS: Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02). CONCLUSIONS: This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.

Macroergonomic components of the patient work system shaping dyadic care management during adolescence: a case study of type 1 diabetes.

The role of the social, physical, and organisational environments in shaping how patients and their caregivers perform work remains largely unexplored in human factors/ergonomics literature. This study recruited 19 dyads consisting of a parent and their child with type 1 diabetes to be interviewed individually and analysed using a macroergonomic framework. Our findings aligned with the macroergonomic factors as presented in previous models, while highlighting the need to expand upon certain components to gain a more comprehensive representation of the patient work system as relevant to dyadic management. Examples of design efforts that should follow from these findings include expanding existing data sharing options to include information from the external environment and capitalising on the capabilities of artificial intelligence as a decision support system. Future research should focus on longitudinally assessing patient work systems throughout transition periods in addition to more explicitly exploring the roles of social network members.

Work performed by patients and their caregivers is shaped by the social, physical, and organisational contexts they are embedded within. This paper explored how adolescents with type 1 diabetes managed their health alongside their parents in the context of these macroergonomic factors. These findings have implications for research and design.

Contributions of white adipose tissue to energy requirements for female reproduction.

Body composition impacts female fertility and there are established relationships between adipose tissue and the reproductive system. Maintaining functional adipose tissue is vital for meeting the energetic demands during the reproductive process, from ovulation to delivery and lactation. White adipose tissue (WAT) shows plastic responses to daily physiology and secretes diverse adipokines that affect the hypothalamic-pituitary-ovarian axis, but many other interorgan interactions remain to be determined. This review summarizes the current state of research on the dialogue between WAT and the female reproductive system, focusing on the impact of this crosstalk on ovarian and endometrial factors essential for fecundity.

Foraging behaviour and habitat use during chick-rearing in the Australian endemic black-faced cormorant (Phalacrocorax fuscescens).

Despite its wide distribution, relatively little is known of the foraging ecology and habitat use of the black-faced cormorant (Phalacrocorax fuscescens), an Australian endemic seabird. Such information is urgently required in view of the rapid oceanic warming of south-eastern Australia, the stronghold of the species. The present study used a combination of opportunistically collected regurgitates and GPS/dive behaviour data loggers to investigate diet, foraging behaviour and habitat-use of black-faced cormorants during four chick-rearing periods (2020-2023) on Notch Island, northern Bass Strait. Observed prey species were almost exclusively benthic (95%), which is consistent with the predominantly benthic diving behaviour recorded. Males foraged at deeper depths than females (median depth males: 18 m; median depth females: 8 m), presumably due to a greater physiological diving capacity derived from their larger body size. This difference in dive depths was associated with sexual segregation of foraging locations, with females predominantly frequenting shallower areas closer to the coastline. These findings have strong implications for the management of the species, as impacts of environmental change may disproportionally affect the foraging range of one sex and, thereby, reproductive success.

Comparison of 3T MR arthrography and 3T MRI in intra-articular hip pathology: a cost-analysis.

BACKGROUND: MR arthrography (MRA) has previously been the radiological gold standard for investigating labral and chondral lesions of the hip joint. In recent years, 3T MRI has demonstrated comparable accuracy, being adopted as the first-line imaging investigation in many institutions. AIMS: We compare the associated increased cost and radiation dose of the fluoroscopic component of the MRA compared to MRI. METHODS: In this retrospective review over 2 years, 120 patients (mean age 27.3 years ± 13.2, range 8-67) underwent 3T MRA or non-contrast 3T MRI. Three musculoskeletal radiologists reported the data independently. Primary objectives included cost-comparison between each and radiation dose of the fluoroscopic component of the MRA. Secondary objectives included comparing detection of pathology involving the acetabular labrum, femoral cartilage, and acetabular cartilage. RESULTS: Then, 58 (48%) underwent 3T MRA and 62 (52%) patients underwent 3T MRI. The added cost of the fluoroscopic injection prior to MRA was €116.31/patient, equating to €7211.22 savings/year. MRA was associated with a small radiation dose of 0.003 mSv. CONCLUSIONS: Transitioning from 3T MRA to 3T MRI in the investigation of intra-articular hip pathology increases cost savings and reduces radiation dose.

Natural Killer Cell Dysfunction In Human Bladder Cancer Is Caused By Tissue-Specific Suppression of SLAMF6 Signaling.

NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors. Rather, TME-specific TGF-ß and metabolic perturbations such as hypoxia directly suppressed NK cell function. Specifically, an oxygen-dependent reduction in signaling through SLAMF6 was mechanistically responsible for poor NK cell function, as tumor-infiltrating NK cells cultured ex vivo under normoxic conditions exhibited complete restoration of function, while deletion of SLAMF6 abrogated NK cell cytolytic function even under normoxic conditions. Collectively, this work highlights the role of tissue-specific factors in dictating NK cell function, and implicates SLAMF6 signaling as a rational target for immuno-modulation to improve NK cell function in bladder cancer.