Harnessing health information technology to promote equitable care for patients with limited English proficiency and complex care needs.

BACKGROUND: Patients with language barriers encounter healthcare disparities, which may be alleviated by leveraging interpreter skills to reduce cultural, language, and literacy barriers through improved bidirectional communication. Evidence supports the use of in-person interpreters, especially for interactions involving patients with complex care needs. Unfortunately, due to interpreter shortages and clinician underuse of interpreters, patients with language barriers frequently do not get the language services they need or are entitled to. Health information technologies (HIT), including artificial intelligence (AI), have the potential to streamline processes, prompt clinicians to utilize in-person interpreters, and support prioritization. METHODS: From May 1, 2023, to June 21, 2024, a single-center stepped wedge cluster randomized trial will be conducted within 35 units of Saint Marys Hospital & Methodist Hospital at Mayo Clinic in Rochester, Minnesota. The units include medical, surgical, trauma, and mixed ICUs and hospital floors that admit acute medical and surgical care patients as well as the emergency department (ED). The transitions between study phases will be initiated at 60-day intervals resulting in a 12-month study period. Units in the control group will receive standard care and rely on clinician initiative to request interpreter services. In the intervention group, the study team will generate a daily list of adult inpatients with language barriers, order the list based on their complexity scores (from highest to lowest), and share it with interpreter services, who will send a secure chat message to the bedside nurse. This engagement will be triggered by a predictive machine-learning algorithm based on a palliative care score, supplemented by other predictors of complexity including length of stay and level of care as well as procedures, events, and clinical notes. DISCUSSION: This pragmatic clinical trial approach will integrate a predictive machine-learning algorithm into a workflow process and evaluate the effectiveness of the intervention. We will compare the use of in-person interpreters and time to first interpreter use between the control and intervention groups. TRIAL REGISTRATION: NCT05860777. May 16, 2023.

Childhood Sexual Abuse and Compulsive Sexual Behavior Among Men Who Have Sex with Men Newly Diagnosed with HIV.

Childhood sexual abuse (CSA) continues to be a public health challenge. The prevalence of experiencing CSA is higher among men who have sex with men (MSM) than the general population. CSA has been linked to compulsive sexual behavior (CSB) among varying populations but has not been examined among MSM who were newly diagnosed with HIV. Therefore, the aims of this study were to assess the direct association between CSA and CSB among newly diagnosed MSM living with HIV, and to identify the potential mediating roles of depressive symptoms and emotion regulation in the association between CSA and CSB. The study was a secondary data analysis using data obtained from 2012 to 2017 from two community HIV clinics in New York City (n = 202). CSA was operationalized with questions asking about sexual abuse during childhood/adolescence. CSB was measured using the 13-item Compulsive Sexual Behavior Inventory (CSBI). Depressive symptoms were measured using the 20-item Centers for Epidemiologic Studies Depression (CES-D) scale and emotion regulation was measured using a 36-item Difficulties in Emotion Regulation Scale (DERS). Path analysis was conducted to determine the mediating role of depressive symptoms and emotion regulation in the association between CSA and CSB. There was a statistically significant association between CSA and CSB (ß = 0.160; p = 0.019). There were statistically significant indirect associations between CSA, depressive symptoms, emotion regulation, and CSB (depressive symptoms ß = 0.0.071; p = 0.010; DERS: ß = 0.080; p = 0.006). Depressive symptoms were also correlated with emotion regulation (r = 0.596; p < 0.001). The relationship between CSA and CSB was significantly mediated by depressive symptoms and emotion regulation. Trauma-informed interventions addressing depressive symptoms and difficulties in emotion regulation may help to reduce CSB among MSM living with HIV.

Antibody modulation of B cell responses-Incorporating positive and negative feedback.

Antibodies are powerful modulators of ongoing and future B cell responses. While the concept of antibody feedback has been appreciated for over a century, the topic has seen a surge in interest due to the evidence that the broadening of antibody responses to SARS-CoV-2 after a third mRNA vaccination is a consequence of antibody feedback. Moreover, the discovery that slow antigen delivery can lead to more robust humoral immunity has put a spotlight on the capacity for early antibodies to augment B cell responses. Here, we review the mechanisms whereby antibody feedback shapes B cell responses, integrating findings in humans and in mouse models. We consider the major influence of epitope masking and the diverse actions of complement and Fc receptors and provide a framework for conceptualizing the ways antigen-specific antibodies may influence B cell responses to any form of antigen, in conditions as diverse as infectious disease, autoimmunity, and cancer.

Associations between urine specific gravity and race/ethnicity at the population level: Implications for hydration status categorization.

OBJECTIVE: We aimed to evaluate how urine specific gravity (USG) and rates of supposed hypohydration vary by race/ethnicity, and to examine how adjustment for several important factors impacts estimated USG. METHODS: Using the National Health and Nutrition Examination Survey, this cross-sectional study evaluated a total of 4195 (2098 female, 2097 male) Americans and categorized them as supposedly hypohydrated (USG≥1.020) or not using spot urine samples. USG and prevalence of supposed hypohydration were compared across racial/ethnic groups, separately by gender. The analyses considered the impact of urine creatinine, body composition, age, dietary nutrients, and physical activity. RESULTS: Differences in supposed hypohydration prevalence were observed by race/ethnicity in men (p = .030) and women (p < .001). In unadjusted models, Black women's USG (1.0189) was higher (p < .05) than all the other race/ethnicity groups' USG (1.0142-1.0171). In men, Blacks' USG (1.0197) was higher (p < .05) than the USG of Whites (1.0177) and other/multi-racial (1.0176) but not Mexican Americans (1.0196) or other Hispanics (1.0192). Adjustments for age, arm circumference, nutrients (protein, sodium, potassium, and moisture), and physical activity minimally influenced USG estimates. Further adjustment for urine creatinine lowered USG for Black women and men by 0.003 and 0.0023, respectively, with no notable lowering of USG in the other races/ethnicities. Supplemental analyses matching Whites and Blacks on age, moisture intake, and poverty-to-income ratio confirmed racial differences in urine creatinine and USG, though the effects were most pronounced in women. CONCLUSIONS: Using a USG≥1.020 to identify hypohydration in all races/ethnicities may be inappropriate due to, among other factors, differences in urinary creatinine.

RETRACTED: Skelton et al. Contribution of Host Immune Responses against Influenza D Virus Infection toward Secondary Bacterial Infection in a Mouse Model. Viruses 2019, 11, 994.

The Viruses Editorial Office retracts the article, "Contribution of Host Immune Responses Against Influenza D Virus Infection Toward Secondary Bacterial Infection in a Mouse Model" [...].

Effects of food bar chewing duration on the physiologic, metabolic, and perceptual responses to moderate-intensity running.

PURPOSE: Chewing duration can affect food particle size, gastric processing, and postprandial glycemia, but these effects have not been investigated with exercise. This study examined how the chewing duration of a food bar impacts glycemic and metabolic responses, gastrointestinal (GI) symptoms, psychological affect, and performance during endurance running. METHODS: This randomized, unblinded, crossover study had 15 males (35.2 ± 7.4 years, VO2peak: 56.1 ± 5.2 ml/kg/min) attend three laboratory visits. Visit 1 required a VO2peak test, 10 min familiarization run at 60% VO2peak, and familiarization time-to-exhaustion (TTE) test (10 min at 90% VO2peak, followed by TTE at 100% VO2peak). Visits 2 and 3 consisted of a 60 min run at 60% VO2peak, followed by TTE testing. Participants were fed 45 g of a bar (180 kcal, 4 g fat, 33 g carbohydrate, 3 g protein, 1 g fiber) in 9 g servings 30 min before running, and 27 g of bar in 9 g servings at three timepoints during the 60 min run. Participants consumed the servings in 20 (20CHEW) or 40 (40CHEW) masticatory cycles, at 1 chew/second. Outcomes included blood glucose, substrate use, GI symptoms, perceived exertion (RPE), overall feeling, and TTE. RESULTS: Post-prandial blood glucose, GI symptoms, and RPE increased over time, but there were no significant between-condition or condition-by-time effects. TTE showed no significant between-condition effect (20CHEW: 288 ± 133 s; 40CHEW: 335 ± 299 s; p = 0.240). Overall feeling demonstrated a time-by-condition effect (p = 0.006), suggesting possible better maintenance over time with 40CHEW. CONCLUSION: Cumulatively, the results suggest that extended chewing minimally impacts physiology, perceptions, and performance during 60 min moderate-intensity running.

A hybrid demultiplexing strategy that improves performance and robustness of cell hashing.

Cell hashing, a nucleotide barcode-based method that allows users to pool multiple samples and demultiplex in downstream analysis, has gained widespread popularity in single-cell sequencing due to its compatibility, simplicity, and cost-effectiveness. Despite these advantages, the performance of this method remains unsatisfactory under certain circumstances, especially in experiments that have imbalanced sample sizes or use many hashtag antibodies. Here, we introduce a hybrid demultiplexing strategy that increases accuracy and cell recovery in multi-sample single-cell experiments. This approach correlates the results of cell hashing and genetic variant clustering, enabling precise and efficient cell identity determination without additional experimental costs or efforts. In addition, we developed HTOreader, a demultiplexing tool for cell hashing that improves the accuracy of cut-off calling by avoiding the dominance of negative signals in experiments with many hashtags or imbalanced sample sizes. When compared to existing methods using real-world datasets, this hybrid approach and HTOreader consistently generate reliable results with increased accuracy and cell recovery.

Considerations for Quality Control Monitoring of Machine Learning Models in Clinical Practice.

Integrating machine learning (ML) models into clinical practice presents a challenge of maintaining their efficacy over time. While existing literature offers valuable strategies for detecting declining model performance, there is a need to document the broader challenges and solutions associated with the real-world development and integration of model monitoring solutions. This work details the development and use of a platform for monitoring the performance of a production-level ML model operating in Mayo Clinic. In this paper, we aimed to provide a series of considerations and guidelines necessary for integrating such a platform into a team's technical infrastructure and workflow. We have documented our experiences with this integration process, discussed the broader challenges encountered with real-world implementation and maintenance, and included the source code for the platform. Our monitoring platform was built as an R shiny application, developed and implemented over the course of 6 months. The platform has been used and maintained for 2 years and is still in use as of July 2023. The considerations necessary for the implementation of the monitoring platform center around 4 pillars: feasibility (what resources can be used for platform development?); design (through what statistics or models will the model be monitored, and how will these results be efficiently displayed to the end user?); implementation (how will this platform be built, and where will it exist within the IT ecosystem?); and policy (based on monitoring feedback, when and what actions will be taken to fix problems, and how will these problems be translated to clinical staff?). While much of the literature surrounding ML performance monitoring emphasizes methodological approaches for capturing changes in performance, there remains a battery of other challenges and considerations that must be addressed for successful real-world implementation.

Lack of memory recall in human CD4 T cells elicited by the first encounter with SARS-CoV-2.

The studies reported here focus on the impact of pre-existing CD4 T cell immunity on the first encounter with SARS-CoV-2. They leverage PBMC samples from plasma donors collected after a first SARS-CoV-2 infection, prior to vaccine availability and compared to samples collected prior to the emergence of SARS-CoV-2. Analysis of CD4 T cell specificity across the entire SARS-CoV-2 proteome revealed that the recognition of SARS-CoV-2-derived epitopes by CD4 memory cells prior to the pandemic are enriched for reactivity toward non-structural proteins conserved across endemic CoV strains. However, CD4 T cells after primary infection with SARS-CoV-2 focus on epitopes from structural proteins. We observed little evidence for preferential recall to epitopes conserved between SARS-CoV-2 and seasonal CoV, a finding confirmed through use of selectively curated conserved and SARS-unique peptides. Our data suggest that SARS-CoV-2 CD4 T cells elicited by the first infection are primarily established from the naive CD4 T cell pool.

Nucleosome-binding by TP53, TP63, and TP73 is determined by the composition, accessibility, and helical orientation of their binding sites.

The p53 family of transcription factors plays key roles in driving development and combating cancer by regulating gene expression. TP53, TP63, and TP73-the three members of the p53 family-regulate gene expression by binding to their DNA binding sites, many of which are situated within nucleosomes. To thoroughly examine the nucleosome-binding abilities of the p53 family, we used Pioneer-seq, a technique that assesses a transcription factor's binding affinity to its DNA binding sites at all possible positions within the nucleosome core particle. Using Pioneer-seq, we analyzed the binding affinity of TP53, TP63, and TP73 to 10 p53-family binding sites across the nucleosome core particle. We found that the affinity of TP53, TP63, and TP73 for nucleosomes was largely determined by the positioning of p53-family binding sites within nucleosomes; p53-family members bind strongly to the more accessible edges of nucleosomes but weakly to the less accessible centers of nucleosomes. We also found that the DNA-helical orientation of p53-family binding sites within nucleosomal DNA impacted the nucleosome-binding affinity of p53-family members. The composition of their binding sites also impacted each p53-family member's nucleosome-binding affinities only when the binding site was located in an accessible location. Taken together, our results show that the accessibility, composition, and helical orientation of p53-family binding sites collectively determine the nucleosome-binding affinities of TP53, TP63, and TP73. These findings help explain the rules underlying p53-family-nucleosome binding and thus provide requisite insight into how we may better control gene-expression changes involved in development and tumor suppression.

Revolutionizing Postoperative Ileus Monitoring: Exploring GRU-D's Real-Time Capabilities and Cross-Hospital Transferability.

Background: Postoperative ileus (POI) after colorectal surgery leads to increased morbidity, costs, and hospital stays. Identifying POI risk for early intervention is important for improving surgical outcomes especially given the increasing trend towards early discharge after surgery. While existing studies have assessed POI risk with regression models, the role of deep learning's remains unexplored. Methods: We assessed the performance and transferability (brutal force/instance/parameter transfer) of Gated Recurrent Unit with Decay (GRU-D), a longitudinal deep learning architecture, for real-time risk assessment of POI among 7,349 colorectal surgeries performed across three hospital sites operated by Mayo Clinic with two electronic health records (EHR) systems. The results were compared with atemporal models on a panel of benchmark metrics. Results: GRU-D exhibits robust transferability across different EHR systems and hospital sites, showing enhanced performance by integrating new measurements, even amid the extreme sparsity of real-world longitudinal data. On average, for labs, vitals, and assisted living status, 72.2%, 26.9%, and 49.3% respectively lack measurements within 24 hours after surgery. Over the follow-up period with 4-hour intervals, 98.7%, 84%, and 95.8% of data points are missing, respectively. A maximum of 5% decrease in AUROC was observed in brutal-force transfer between different EHR systems with non-overlapping surgery date frames. Multi-source instance transfer witnessed the best performance, with a maximum of 2.6% improvement in AUROC over local learning. The significant benefit, however, lies in the reduction of variance (a maximum of 86% decrease). The GRU-D model's performance mainly depends on the prediction task's difficulty, especially the case prevalence rate. Whereas the impact of training data and transfer strategy is less crucial, underscoring the challenge of effectively leveraging transfer learning for rare outcomes. While atemporal Logit models show notably superior performance at certain pre-surgical points, their performance fluctuate significantly and generally underperform GRU-D in post-surgical hours. Conclusion: GRU-D demonstrated robust transferability across EHR systems and hospital sites with highly sparse real-world EHR data. Further research on built-in explainability for meaningful intervention would be highly valuable for its integration into clinical practice.

Differences in urine creatinine and osmolality between black and white Americans after accounting for age, moisture intake, urine volume, and socioeconomic status.

Urine osmolality is used throughout research to determine hydration levels. Prior studies have found black individuals to have elevated urine creatinine and osmolality, but it remains unclear which factors explain these findings. This cross-sectional, observational study sought to understand the relationship of self-reported race to urine creatinine and urine osmolality after accounting for age, socioeconomic status, and fluid intake. Data from 1,386 participants of the 2009-2012 National Health and Nutrition Examination Survey were utilized. Age, poverty-to-income ratio (PIR), urine flow rate (UFR), fluid intake, estimated lean body mass (LBM), urine creatinine, and urine osmolality were measured. In a sex-specific manner, black and white participants were matched on age, dietary moisture, UFR, and PIR. Urine creatinine was greater in black men (171 mg/dL) than white men (150 mg/dL) and greater in black women (147 mg/dL) than white women (108 mg/dL) (p < .001). Similarly, urine osmolality was greater in black women than white women (723 vs. 656 mOsm/kg, p = .001), but no difference was observed between white and black men (737 vs. 731 mOsm/kg, p = .417). Estimated LBM was greater in black men (61.8 kg) and women (45.5 kg) than in white men (58.9 kg) and women (42.2 kg) (p≤.001). The strongest correlate of urine osmolality in all race-sex groups was urine creatinine (Spearman ρ = .68-.75). These results affirm that individuals identifying as black produce higher urine creatinine concentrations and, in women, higher urine osmolality after matching for age, fluid intake, and socioeconomic status. The findings suggest caution when comparing urine hydration markers between racial groups.

Preliminary findings from the Dynamics of the Immune Responses to Repeat Influenza Vaccination Exposures (DRIVE I) Study: a Randomized Controlled Trial.

Background: Studies have reported that repeated annual vaccination may influence the effectiveness of the influenza vaccination in the current season. The mechanisms underlying these differences are unclear but might include "focusing" of the adaptive immune response to older strains. Methods: We established a 5-year randomized placebo-controlled trial of repeated influenza vaccination (Flublok, Sanofi Pasteur) in adults 18-45 years of age. Participants were randomized equally between five groups, with planned annual receipt of vaccination (V) or saline placebo (P) as follows: P-P-P-P-V, P-P-P-V-V, P-P-V-V-V, P-V-V-V-V, or V-V-V-VV. Serum samples were collected each year just before vaccination and after 30 and 182 days. A subset of sera were tested by hemagglutination inhibition assays, focus reduction neutralization tests and enzyme-linked immunosorbent assays against vaccine strains. Results: From 23 October 2020 through 11 March 2021 we enrolled and randomized 447 adults. We selected sera from 95 participants at five timepoints from the first two study years for testing. Among vaccinated individuals, antibody titers increased between days 0 and 30 against each of the vaccine strains, with substantial increases for first-time vaccinees and smaller increases for repeat vaccinees, who had higher pre-vaccination titers in year 2. There were statistically significant reductions in the proportion of participants achieving a four-fold greater rise in antibody titer for the repeat vaccinees for A(H1N1), B/Victoria and B/Yamagata, but not for influenza A(H3N2). There were no statistically significant differences between groups in geometric mean titers at day 30 or the proportions of participants with antibody titers ≥40 at day 30 for any of the vaccine strains. Conclusions: In the first two years, repeat vaccinees and first-time vaccinees had similar post-vaccination geometric mean titers to all four vaccine strains, indicative of similar levels of clinical protection. The vaccine strains of A(H1N1) and A(H3N2) were updated in year 2, providing an opportunity to explore antigenic distances between those strains in humans in subsequent years.

Reframing reentry: Understanding how reentry programming affects the well-being and quality of life of returning citizens.

This study examined the experiences returning citizens (RCs) have in participating in different reentry programs and how these experiences may lead to improved well-being and quality of life (QOL). We conducted 14 semi-structured interviews with RCs participating in employment-oriented reentry programs. The interviews focused on participants' reentry programming experience and areas affecting their well-being (e.g., housing, education, financial stability). QOL was enhanced for RCs when they were able to access stable housing, develop supportive relationships, have a job that permitted them the resources needed to live independently, and increase their perceptions of self-efficacy and social capital. While reentry programs maintain a focus on employment for RCs, housing, healthy relationships, and opportunities for increasing self-efficacy and social capital are tied to well-being and QOL among RCs. Reentry programs have the potential to influence a variety of factors at multiple levels that shape well-being and QOL, and in turn employment and recidivism, among RCs.

Epitopes recognition of SARS-CoV-2 nucleocapsid RNA binding domain by human monoclonal antibodies.

Coronavirus nucleocapsid protein (NP) of SARS-CoV-2 plays a central role in many functions important for virus proliferation including packaging and protecting genomic RNA. The protein shares sequence, structure, and architecture with nucleocapsid proteins from betacoronaviruses. The N-terminal domain (NPRBD) binds RNA and the C-terminal domain is responsible for dimerization. After infection, NP is highly expressed and triggers robust host immune response. The anti-NP antibodies are not protective and not neutralizing but can effectively detect viral proliferation soon after infection. Two structures of SARS-CoV-2 NPRBD were determined providing a continuous model from residue 48 to 173, including RNA binding region and key epitopes. Five structures of NPRBD complexes with human mAbs were isolated using an antigen-bait sorting. Complexes revealed a distinct complement-determining regions and unique sets of epitope recognition. This may assist in the early detection of pathogens and designing peptide-based vaccines. Mutations that significantly increase viral load were mapped on developed, full length NP model, likely impacting interactions with host proteins and viral RNA.

Technology Access and Perceptions of Telehealth Services Among Young Adults Involved in the Court System.

PURPOSE: This study examined access to technology and telehealth among young adults (ages 18-24) who were court-involved and were recruited from an alternative sentencing program in New York City. METHODS: Using sequential mixed methods design, we examined demographic factors linked with access to technology and perceived usefulness of the Internet among n = 321 young adults who were court-involved (75% male, 65% African American, 35% Latinx). We then conducted in-depth interviews with 27 young adults to elicit first-person account of their access to, interest in, and experience with technology and telehealth. RESULTS: Although most participants had access to a phone with a data plan, a substantial proportion reported inconsistent access to the technology critical to telehealth. Certain young adults were more likely to lack consistent access to the technology needed for telehealth, including Black young adults, males, those with less than a high school diploma, those with a history of homelessness, and those who had difficulties paying for basic necessities. Qualitative interviews revealed that most had a strong self-efficacy using technology, while distrust of technology, inexperience with and skepticism of telehealth, low perceived need for care, and medical mistrust were common significant barriers in this underserved population. DISCUSSION: Findings underscored the critical need to address medical mistrust and increase access to and utilization of care among young adults who are court-involved. Results can inform the development and implementation of interventions designed to improve accessibility and acceptability of telehealth.

Limits of Ultra: Towards an Interdisciplinary Understanding of Ultra-Endurance Running Performance.

Ultra-endurance running (UER) poses extreme mental and physical challenges that present many barriers to completion, let alone performance. Despite these challenges, participation in UER events continues to increase. With the relative paucity of research into UER training and racing compared with traditional endurance running distance (e.g., marathon), it follows that there are sizable improvements still to be made in UER if the limitations of the sport are sufficiently understood. The purpose of this review is to summarise our current understanding of the major limitations in UER. We begin with an evolutionary perspective that provides the critical background for understanding how our capacities, abilities and limitations have come to be. Although we show that humans display evolutionary adaptations that may bestow an advantage for covering large distances on a daily basis, these often far exceed the levels of our ancestors, which exposes relative limitations. From that framework, we explore the physiological and psychological systems required for running UER events. In each system, the factors that limit performance are highlighted and some guidance for practitioners and future research are shared. Examined systems include thermoregulation, oxygen delivery and utilisation, running economy and biomechanics, fatigue, the digestive system, nutritional and psychological strategies. We show that minimising the cost of running, damage to lower limb tissue and muscle fatigability may become crucial in UER events. Maintaining a sustainable core body temperature is critical to performance, and an even pacing strategy, strategic heat acclimation and individually calculated hydration all contribute to sustained performance. Gastrointestinal issues affect almost every UER participant and can be due to a variety of factors. We present nutritional strategies for different event lengths and types, such as personalised and evidence-based approaches for varying types of carbohydrate, protein and fat intake in fluid or solid form, and how to avoid flavour fatigue. Psychology plays a vital role in UER performance, and we highlight the need to be able to cope with complex situations, and that specific long and short-term goal setting improves performance. Fatigue in UER is multi-factorial, both physical and mental, and the perceived effort or level of fatigue have a major impact on the ability to continue at a given pace. Understanding the complex interplay of these limitations will help prepare UER competitors for the different scenarios they are likely to face. Therefore, this review takes an interdisciplinary approach to synthesising and illuminating limitations in UER performance to assist practitioners and scientists in making informed decisions in practice and applicable research.

Biochemical and biophysical characterization of natural polyreactivity in antibodies.

To become specialized binders, antibodies undergo a process called affinity maturation to maximize their binding affinity. Despite this process, some antibodies retain low-affinity binding to diverse epitopes in a phenomenon called polyreactivity. Here we seek to understand the molecular basis of this polyreactivity in antibodies. Our results highlight that polyreactive antigen-binding fragments (Fabs) bind their targets with low affinities, comparable to T cell receptor recognition of autologous classical major histocompatibility complex. Extensive mutagenic studies find no singular amino acid residue or biochemical property responsible for polyreactive interaction, suggesting that polyreactive antibodies use multiple strategies for engagement. Finally, our crystal structures and all-atom molecular dynamics simulations of polyreactive Fabs show increased rigidity compared to their monoreactive relatives, forming a neutral and accessible platform for diverse antigens to bind. Together, these data support a cooperative strategy of rigid neutrality in establishing the polyreactive status of an antibody molecule.

Effects of drinking water treatment residual amendments to biosolids on plant uptake of per- and polyfluoroalkyl substances.

Drinking water treatment residuals (DWTRs), solid by-products of drinking water treatment, are dominated by calcium (Ca), iron (Fe), or aluminum (Al), depending on the coagulant used. DWTRs are often landfilled, but current research is exploring options for beneficial reuse. Previous studies have shown that Al- and Fe-rich materials have potential to reduce the mobility of per- and polyfluoroalkyl substances (PFAS). Here, we investigated how amending biosolids with 5% wt/wt DWTRs affected plant bioavailable PFAS in two different simulated scenarios: (1) agricultural scenario with Solanum lycopersicum (tomato) grown in soil amended with an agronomically relevant rate of DWTR-amended biosolids (0.9% w/w, resulting in 0.045% w/w DWTR in the biosolids-amended soil) and (2) mine reclamation scenario examining PFAS uptake by Lolium perenne (perennial ryegrass) grown in soil that received DWTR-amended biosolids amendment at a rate consistent with the mine remediation (13% w/w, resulting in 0.65% w/w DWTR in the biosolids-amended soil). Amending biosolids with Ca-DWTR significantly reduced perfluorobutanoic acid (PFBA) uptake in ryegrass and perfluorohexanoic acid uptake in tomatoes, possibly due to DWTR-induced pH elevation, while Fe-DWTR amendment reduced PFBA bioaccumulation in ryegrass. The Al-DWTR did not induce a significant reduction in accumulated PFAS compared to controls. Although the reasons for this finding are unclear, the relatively low PFAS concentrations in the biosolids and relatively high Al content in the biosolids and soil may be partially responsible.

Trunk-to-leg-volume ratio is not associated with bone density or fracture risk in middle-aged adults: results from the National Health and Nutrition Examination Survey.

Unlike a high body mass index or waist circumference, a high trunk-to-leg-volume ratio does not associate with a lower risk of osteopenia/osteoporosis at the femoral neck. While elevated TLVR showed a suggestive association with a history of wrist fracture in women, additional research is needed to confirm this suggestion. PURPOSE: Body mass index (BMI) and waist circumference (WC) are commonly used to predict bone health, which is typically assessed via bone mineral density (BMD). Trunk-to-leg-volume ratio (TLVR), a relatively novel measure, predicts cardiometabolic outcomes, but its relationships with BMD and fracture remain unstudied. This study evaluated these anthropometric measures' associations with BMD and fracture in Americans aged 40-60 years. METHODS: Analyses of middle-aged adults from the 2013-2014 to 2017-2018 National Health and Nutrition Examination Survey were conducted. Whole-body, dual-energy X-ray absorptiometry was used to quantify TLVR as well as BMD at the lumbar spine, while a femur-specific scan was used to quantify femoral neck BMD. Fracture history was self-reported. Linear and logistic regression models were constructed with age, diabetes, smoking, race/ethnicity, education, and physical activity as confounding variables. RESULTS: TLVR was generally not associated with BMD, while WC and BMI showed positive associations with femoral neck BMD. Odds of osteopenia/osteoporosis at the femoral neck were ~ 65-80% lower among participants in the highest tertile of BMI and WC versus the lowest (p < 0.001). There were no statistically significant associations between anthropometric predictors and fracture. Women in tertiles 2 or 3 of TLVR (p = 0.097 and 0.079, respectively) did have 2.66 times the odds of wrist fracture than women in tertile 1, but this was not significant. CONCLUSION: As shown in previous research, BMI and WC show positive associations with femoral BMD. In contrast, the more novel anthropometric marker TLVR shows no association with femoral BMD, and no clear association with fracture.