The discovery and structural basis of two distinct state-dependent inhibitors of BamA.

BamA is the central component of the essential ß-barrel assembly machine (BAM), a conserved multi-subunit complex that dynamically inserts and folds ß-barrel proteins into the outer membrane of Gram-negative bacteria. Despite recent advances in our mechanistic and structural understanding of BamA, there are few potent and selective tool molecules that can bind to and modulate BamA activity. Here, we explored in vitro selection methods and different BamA/BAM protein formulations to discover peptide macrocycles that kill Escherichia coli by targeting extreme conformational states of BamA. Our studies show that Peptide Targeting BamA-1 (PTB1) targets an extracellular divalent cation-dependent binding site and locks BamA into a closed lateral gate conformation. By contrast, PTB2 targets a luminal binding site and traps BamA into an open lateral gate conformation. Our results will inform future antibiotic discovery efforts targeting BamA and provide a template to prospectively discover modulators of other dynamic integral membrane proteins.

Self-perceived middle-distance race pace is faster in advanced footwear technology spikes.

BACKGROUND: Quantifying the potential benefits of advanced footwear technology (AFT) track shoes (i.e., "spikes") in middle-distance events is challenging, because repeated maximal effort trials (as in sprinting) or aerobic running economy trials (as in long-distance running) are not feasible. METHODS: We introduce a novel approach to assess the benefits of AFT spikes, consisting of a series of 200-m runs at self-perceived middle-distance race pace with 10 min recovery, and conduct 4 experiments to evaluate its validity, sensitivity, reproducibility, and utility. RESULTS: In Experiment 1, participants ran 1.2% slower in spikes with 200 g added mass vs. control spikes, which is exactly equal to the known effects of shoe mass on running performance. In Experiment 2, participants ran significantly faster in AFT prototype spikes vs. traditional spikes. In Experiment 3, we compared 2 other AFT prototype spikes against traditional spikes on 3 separate days. Group-level results were consistent across days, but our data indicates that at least 2 separate sessions are needed to evaluate individual responses. In Experiment 4, participants ran significantly faster in 2 AFT spike models vs. traditional spikes (2.1% and 1.6%). Speed was similar between a third AFT spike model and the traditional spikes. These speed results were mirrored by changes in step length as participants took significantly longer steps in the 2 faster AFT spike models (2.3% and 1.9%), while step length was similar between the other spikes. CONCLUSION: Our novel, interval-based approach is a valid and reliable method for quantifying differences between spikes at middle-distance running intensity.

Chymase Activity in Plasma and Urine Extracellular Vesicles in Primary Hypertension.

BACKGROUND: Circulating extracellular vesicles (EVs) carry protected cargoes of nucleic acids, proteins, and metabolites. Here we identified and validated the surface proteins and enzymatic activity of chymase, angiotensin converting enzymes 1 (ACE) and 2 (ACE2), and neprilysin (NEP) in EVs isolated from the blood and urine of primary hypertensive patients. METHODS: Peripheral venous blood and spot urine from 34 hypertensive patients were processed to isolate plasma and urinary EVs. Immuno-gold labeling and transmission electron microscopy validated the presence of the exosomal marker protein CD63 on the surface of plasma and urinary EVs. Flow cytometry characterized plasma and urinary EVs for CD63, CD9, and CD81 surface markers. In addition, exosomal CD63, TSG101, and Alix were analyzed in urine by Western blotting. Urinary EVs did not express the endoplasmic reticulum protein calnexin and Golgi protein GM130. Chymase, ACE, ACE2, and NEP activities on 125I substrates ─ angiotensin-(1-12) [Ang-(1‒12)] and angiotensin II (Ang II) ─ [1 nmol/L each] were quantified by HPLC. Data were analyzed based on whether the patient's blood pressure was controlled (Group I: <140/80 mm Hg) or not controlled (Group II: ≥ 140/80 mm Hg). RESULTS: Chymase activity on Ang-(1‒12) was significantly higher in plasma and urinary EVs than in ACE, ACE2, and NEP. In addition, chymase activity in urine EVs was more than 3-fold higher than in plasma EVs. Chymase activity increased in plasma and urine EVs retrieved from Group II patients. No comparable differences were found in the enzymatic activities of ACE, ACE2, and NEP urinary EVs between Group I and Group II. CONCLUSION: These studies reveal a differential enzymatic activity of renin angiotensin system enzymes in plasma and urine EVs isolated from hypertensive patients. Demonstrating a comparatively high chymase enzymatic activity in EVs expands a previously documented finding of increased plasma Ang-(1‒12) in hypertensive patients.

Reduced Risk of Cardiovascular Diseases after Bariatric Surgery Based on the New PREVENT Equations.

Background: We applied the novel Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations to evaluate cardiovascular-kidney-metabolic (CKM) health and estimated CVD risk, including heart failure (HF), after bariatric surgery. Methods: Among 7804 patients (20-79 years) undergoing bariatric surgery at Vanderbilt University Medical Center during 1999-2022, CVD risk factors at pre-surgery, 1-year, and 2-year post-surgery were extracted from electronic health records. The 10- and 30-year risks of total CVD, atherosclerotic CVD (ASCVD), coronary heart disease (CHD), stroke, and HF were estimated for patients without a history of CVD or its subtypes at each time point, using the social deprivation index-enhanced PREVENT equations. Paired t-tests or McNemar tests were used to compare pre- with post-surgery CKM health and CVD risk. Two-sample t-tests were used to compare CVD risk reduction between patient subgroups defined by age, sex, race, operation type, weight loss, and history of diabetes, hypertension, and dyslipidemia. Results: CKM health was significantly improved after surgery with lower systolic blood pressure, non-high-density-lipoprotein cholesterol (non-HDL), and diabetes prevalence, but higher HDL and estimated glomerular filtration rate (eGFR). The 10-year total CVD risk decreased from 6.51% at pre-surgery to 4.81% and 5.08% at 1- and 2-year post-surgery (relative reduction: 25.9% and 16.8%), respectively. Significant risk reductions were seen for all CVD subtypes (i.e., ASCVD, CHD, stroke, and HF), with the largest reduction for HF (relative reduction: 55.7% and 44.8% at 1- and 2-year post-surgery, respectively). Younger age, White race, >30% weight loss, diabetes history, and no dyslipidemia history were associated with greater HF risk reductions. Similar results were found for the 30-year risk estimates. Conclusions: Bariatric surgery significantly improves CKM health and reduces estimated CVD risk, particularly HF, by 45-56% within 1-2 years post-surgery. HF risk reduction may vary by patient's demographics, weight loss, and disease history, which warrants further research.

Self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults: unmeasured, unknown and unmanaged.

Background Effective management of hearing loss in adults is fundamental for communication, relationships, employment, and learning. This study examined the rates and management of self-reported hearing loss in urban Aboriginal and Torres Strait Islander adults. Methods A retrospective, observational study of Aboriginal and Torres Strait Islander people aged ≥15years who had annual health checks at an urban Aboriginal and Torres Strait Islander primary healthcare clinic in Inala, Queensland, was conducted to determine self-reported hearing loss rates by age and ethnic groups stratified by sex. A medical record audit of patients who self-reported hearing loss from January to June 2021 was performed to identify current management approaches, and the proportion of patients that were appropriately managed. Results Of the 1735 patients (average age 40.7years, range 15.0-88.5years, 900 [52.0%] women) who completed 3090 health checks between July 2018 and September 2021, 18.8% self-reported hearing loss. Rates did not differ between men and women. However, significant effects were noted for age, with rates increasing from 10.7% for patients aged 15-24years to 38.7% for those aged ≥65years. An audit of 73 patient medical records revealed that 39.7% of patients with self-reported hearing loss were referred to Ear, Nose and Throat/audiology or received other management. A total of 17.8% of patients owned hearing aids. Conclusions Only 40% of Aboriginal and Torres Strait Islander adults who self-reported hearing loss were referred for management. Significant changes to clinical management and government-funded referral options for hearing services are required to improve the management of self-reported hearing loss in this population.

Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review.

BACKGROUND: To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. METHODS: Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. RESULTS: Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 µmol/L for NMP and 129.9 µmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. CONCLUSIONS: Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

BACKGROUND: The benefit of antibiotic treatment of acute drops in FEV1 percent predicted (FEV1pp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant. METHODS: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEV1pp and return to 100% baseline FEV1pp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category. RESULTS: Overall, 16,495 PWCF had a decline: 16.5% were treated with IV antibiotics, 25.0% non-IV antibiotics, and 58.5% received no antibiotics. Antibiotic treatment was more likely for those with lower lung function, history of a positive PA culture, older age and larger FEV1 decline (p < 0.001). Treatment with IV antibiotics or oral/inhaled antibiotics was associated with a higher odds of recovery to baseline compared to no treatment across all levels of decline, including declines of 5%-10%. CONCLUSIONS: A large proportion of acute drops in FEV1pp continue to be untreated, especially in younger patients and those with higher baseline lung function. Acute drops as small as 5% predicted are less likely to be recovered if antibiotic treatment is not prescribed. These findings suggest the need for more aggressive antimicrobial treatment of acute drops in FEV1, including those of a magnitude previously believed to be associated with self-recovery.

Pilot-scale evaluation of cascade anaerobic digestion of mixed municipal wastewater treatment sludges.

This work assessed the performance of a pilot-scale cascade anaerobic digestion (AD) system when treating mixed municipal wastewater treatment sludges. The cascade system was compared with a conventional continuous stirred tank reactor (CSTR) digester (control) in terms of process performance, stability, and digestate quality. The results showed that the cascade system achieved higher volatile solids removal (VSR) efficiencies (28-48%) than that of the reference (25-41%) when operated at the same solids residence time (SRT) in the range of 11-15 days. When the SRT of the cascade system was reduced to 8 days the VSR (32-36%) was only slightly less than that of the reference digester that was operated at a 15-day SRT (39-43%). Specific hydrolysis rates in the first stage of the cascade system were 66-152% higher than those of the reference. Additionally, the cascade system exhibited relatively stable effluent concentrations of volatile fatty acids (VFAs: 100-120 mg/l), while the corresponding concentrations in the control effluent demonstrated greater fluctuations (100-160 mg/l). The cascade system's effluent pH and VFA/alkalinity ratios were consistently maintained within the optimal range. During a dynamic test when the feed total solids concentration was doubled, total VFA concentrations (85-120 mg/l) in the cascade system were noticeably less than those (100-170 mg/l) of the control, while the pH and VFA/alkalinity levels remained in a stable range. The cascade system achieved higher total solids (TS) content in the dewatered digestate (19.4-26.8%) than the control (17.4-22.1%), and E. coli log reductions (2.0-4.1 log MPN/g TS) were considerably higher (p < 0.05) than those in the control (1.3-2.9 log MPN/g TS). Overall, operating multiple CSTRs in cascade mode at typical SRTs and mixed sludge ratios enhanced the performance, stability digesters, and digestate quality of AD. PRACTITIONER POINTS: Enhanced digestion of mixed sludge digestion with cascade system. Increased hydrolysis rates in the cascade system compared to a reference CSTR. More stable conditions for methanogen growth at both steady and dynamic states. Improved dewaterability and E. coli reduction of digestate from the cascade system.

Forced Expiratory Volume in 1 Second Variability Predicts Lung Transplant or Mortality in People with Cystic Fibrosis in the United States.

Rationale: Declines in percent predicted forced expiratory volume in 1 second (ppFEV1) are an important marker of clinical progression of cystic fibrosis (CF). Objectives: We examined ppFEV1 variability in relation to a combined outcome of lung transplant or death. Methods: We estimated the association between ppFEV1 variability and the combined outcome of lung transplant or death. We included children aged 8 years and older with CF and two prior years of ppFEV1 data before baseline between 2005 and 2021. We defined ppFEV1 increased variability as any relative increase or decrease of at least 10% in ppFEV1 from a 2-year averaged baseline. A marginal structural Cox proportional hazards model was used. We examined a cumulative measure of ppFEV1 variability, defined as the cumulative proportion of visits with ppFEV1 variability at each visit. Kaplan-Meier survival curves were generated on the basis of quartiles of the cumulative distribution of ppFEV1 variability. Results: We included 9,706 patients with CF in our cohort. The median age at cohort entry was 8.3 (interquartile range, 8.2-8.4) years; 50% of patients were female; 94% were White; and the median baseline ppFEV1 was 94.4 (interquartile range, 81.6-106.1). The unadjusted hazard ratio for increased ppFEV1 variability on lung transplant/mortality was 4.13 (95% confidence interval, 3.48-4.90), and the weighted hazard ratio was 1.49 (95% confidence interval, 1.19-1.86). Survival curves stratified by quartile of cumulative variability demonstrated an increased hazard of lung transplant/mortality as the proportion of cumulative ppFEV1 variability increased. Conclusions: We found a strong association between ppFEV1 variability and lung transplant or mortality in a cohort of people with CF in the United States.

Oxidative Stress-Associated Male Infertility: Current Diagnostic and Therapeutic Approaches.

Infertility is a prevalent global issue affecting approximately 17.5% of adults, with sole male factor contributing to 20-30% of cases. Oxidative stress (OS) is a critical factor in male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants. This imbalance detrimentally affects sperm function and viability, ultimately impairing fertility. OS also triggers molecular changes in sperm, including DNA damage, lipid peroxidation, and alterations in protein expression, further compromising sperm functionality and potential fertilization. Diagnostic tools discussed in this review offer insights into OS markers, antioxidant levels, and intracellular ROS concentrations. By accurately assessing these parameters, clinicians can diagnose male infertility more effectively and thus tailor treatment plans to individual patients. Additionally, this review explores various treatment options for males with OS-associated infertility, such as empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. By addressing the root causes of male infertility and implementing targeted interventions, clinicians can optimize treatment outcomes and enhance the chances of conception for couples struggling with infertility.

Medicolegal death investigations on tribal lands-underrepresented or underserved?

Death investigation on tribal lands and of American Indian/Alaska Native (AIAN) people is complex and not well documented. An analysis of data from the 2018 Census of Medical Examiner and Coroner Offices (CMEC) provides a timely update on the extent of medicolegal death investigations (MDIs) on federal and state-recognized tribal lands. An estimated 150 MEC offices serve tribal lands, however, 44 % of these offices (i.e., 4 % of MEC offices) do not track cases from tribal lands separately. MEC offices with a population of 25,000 to 250,000 that serve tribal lands had more resources and access to information to perform MDIs than all other MEC offices. Analysis also indicates that the median number of unidentified human remains cases from MECs serving tribal lands is 6 times higher than that of jurisdictions not serving tribal lands. This analysis begins to elucidate gaps in the nation's understanding of MDI on tribal lands.

Active workstations: A literature review on workplace sitting.

The purpose of this paper is to further understand current literature on prolonged sitting, sitting posture and active sitting solutions. This paper is divided into three sections: The first section (Part I) is a comprehensive overview of the literature on how a static prolonged seated posture can affect: spinal health, trunk posture, contact pressure/discomfort development and vascular issues. The second section (Part II) reviews and qualitatively compares the four working postures recognized in ANSI/HFES 100-2007: reclined sitting, upright sitting, declined sitting and standing. The final section (Part III) is a summary of research on active chairs that revolves around the two types of movement patterns: 1- sustaining continual movement over a range of postures, occasionally reaching neutral lordosis, and 2- maintaining high frequency and duration of daily light contractile activity in the legs (or lower limbs).

The transcription factor ZNF469 regulates collagen production in liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) - characterized by excess accumulation of fat in the liver - now affects one third of the world's population. As NAFLD progresses, extracellular matrix components including collagen accumulate in the liver causing tissue fibrosis, a major determinant of disease severity and mortality. To identify transcriptional regulators of fibrosis, we computationally inferred the activity of transcription factors (TFs) relevant to fibrosis by profiling the matched transcriptomes and epigenomes of 108 human liver biopsies from a deeply-characterized cohort of patients spanning the full histopathologic spectrum of NAFLD. CRISPR-based genetic knockout of the top 100 TFs identified ZNF469 as a regulator of collagen expression in primary human hepatic stellate cells (HSCs). Gain- and loss-of-function studies established that ZNF469 regulates collagen genes and genes involved in matrix homeostasis through direct binding to gene bodies and regulatory elements. By integrating multiomic large-scale profiling of human biopsies with extensive experimental validation we demonstrate that ZNF469 is a transcriptional regulator of collagen in HSCs. Overall, these data nominate ZNF469 as a previously unrecognized determinant of NAFLD-associated liver fibrosis.

Potency-Enhanced Peptidomimetic VHL Ligands with Improved Oral Bioavailability.

The von Hippel-Lindau (VHL) protein plays a pivotal role in regulating the hypoxic stress response and has been extensively studied and utilized in the targeted protein degradation field, particularly in the context of bivalent degraders. In this study, we present a comprehensive peptidomimetic structure-activity relationship (SAR) approach, combined with cellular NanoBRET target engagement assays to enhance the existing VHL ligands. Through systematic modifications of the molecule, we identified the 1,2,3-triazole group as an optimal substitute of the left-hand side amide bond that yields 10-fold higher binding activity. Moreover, incorporating conformationally constrained alterations on the methylthiazole benzylamine moiety led to the development of highly potent VHL ligands with picomolar binding affinity and significantly improved oral bioavailability. We anticipate that our optimized VHL ligand, GNE7599, will serve as a valuable tool compound for investigating the VHL pathway and advancing the field of targeted protein degradation.

A histological and diceCT-derived 3D reconstruction of the avian visual thalamofugal pathway.

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system.

Dronedarone for the Treatment of Atrial Arrhythmias in Adults With Congenital Heart Disease.

BACKGROUND: Atrial tachyarrhythmias are common and difficult to treat in adults with congenital heart disease. Dronedarone has proven effective in patients without congenital heart disease, but data are limited about its use in adults with congenital heart disease of moderate to great complexity. METHODS: A single-center, retrospective chart review of 21 adults with congenital heart disease of moderate to great complexity who were treated with dronedarone for atrial tachyarrhythmias was performed. RESULTS: The median (IQR) age at dronedarone initiation was 35 (27.5-39) years. Eleven patients (52%) were male. Ten patients (48%) had New York Heart Association class I disease, 10 (48%) had class II disease, and 1 (5%) had class III disease. Ejection fraction at initiation was greater than 55% in 11 patients (52%), 35% to 55% in 9 patients (43%), and less than 35% in 1 patient (5%). Prior treatments included ß-blockers (71%), sotalol (38%), amiodarone (24%), digoxin (24%), and catheter ablation (38%). Rhythm control was complete in 5 patients (24%), partial in 6 (29%), and inadequate in 10 (48%). Two patients (10%) experienced adverse events, including nausea in 1 (5%) and cardiac arrest in 1 (5%), which occurred 48 months after initiation of treatment. There were no deaths during the follow-up period. The median (IQR) follow-up time for patients with complete or partial rhythm control was 20 (1-54) months. CONCLUSION: Dronedarone can be effective for adult patients with congenital heart disease and atrial arrhythmias for whom more established therapies have failed, and with close monitoring it can be safely tolerated.

Ending "domestic helicopter research".

"Helicopter research" refers to a practice where researchers from wealthier countries conduct studies in lower-income countries with little involvement of local researchers or community members. This practice also occurs domestically. In this Commentary, we outline strategies to curb domestic helicopter research and to foster equity-centered collaborations.

Framework to Quantify Uncertainty in Microplastic Concentrations in Wastewaters and Sludges Incorporating Analytical Recovery Information into Data Analysis.

Wastewater treatment plants (WWTPs) serve a pivotal role in transferring microplastics (MPs) from wastewater to sludge streams, thereby exerting a significant influence on their release into the environment and establishing wastewater and biosolids as vectors for MP transport and delivery. Hence, an accurate understanding of the fate and transport of MPs in WWTPs is vital. Enumeration is commonly used to estimate concentrations of MPs in performance evaluations of treatment processes, and risk assessment also typically involves MP enumeration. However, achieving high accuracy in concentration estimates is challenging due to inherent uncertainty in the analytical workflow to collect and process samples and count MPs. Here, sources of random error in MP enumeration in wastewater and other matrices were investigated using a modeling approach that addresses the sources of error associated with each step of the analysis. In particular, losses are reflected in data analysis rather than merely being measured as a validation step for MP extraction methods. A model for addressing uncertainty in the enumeration of microorganisms in water was adapted to include key assumptions relevant to the enumeration of MPs in wastewater. Critically, analytical recovery, the capacity to successfully enumerate particles considering losses and counting error, may be variable among MPs due to differences in size, shape, and type (differential analytical recovery) in addition to random variability between samples (nonconstant analytical recovery). Accordingly, differential analytical recovery among the categories of MPs was added to the existing model. This model was illustratively applied to estimate MP concentrations from simulated data and quantify uncertainty in the resulting estimates. Increasing the number of replicates, counting categories of MPs separately, and accounting for both differential and nonconstant analytical recovery improved the accuracy of MP enumeration. This work contributes to developing guidelines for analytical procedures quantifying MPs in diverse types of samples and provides a framework for enhanced interpretation of enumeration data, thereby facilitating the collection of more accurate and reliable MP data in environmental studies.

Sex- and operation-dependent effects on 5-year weight loss results of bariatric surgery.

BACKGROUND: Weight loss response after bariatric surgery is highly variable, and several demographic factors are associated with differential responses to surgery. Preclinical studies demonstrate numerous sex-specific responses to bariatric surgery, but whether these responses are also operation dependent is unknown. OBJECTIVE: To examine sex-specific weight loss outcomes up to 5 years after laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). SETTING: Single center, university, United States. METHODS: Retrospective, observational cohort study including RYGB (n = 5057) and vertical SG (n = 2041) patients from a single, academic health center. Percentage total weight loss (TWL) over time was examined with generalized linear mixed models to determine the main and interaction effects of surgery type on weight loss by sex. RESULTS: TWL demonstrated a strong sex-by-procedure interaction, with women having a significant advantage with RYGB compared with SG (adjusted difference at 5 yr: 8.0% [95% CI: 7.5-8.5]; P < .001). Men also experienced greater TWL over time with RYGB or SG, but the difference was less and clinically insignificant (adjusted difference at 5 yr: 2.9% [2.0-3.8]; P < .001; P interaction between sex and procedure type = .0001). Overall, women had greater TWL than men, and RYGB patients had greater TWL than SG patients (adjusted difference at 5 yr: 3.1% [2.4-3.2] and 6.9% [6.5-7.3], respectively; both P < .0001). Patients with diabetes lost less weight compared with those without (adjusted difference at 5 yr: 3.0% [2.7-3.2]; P < .0001). CONCLUSIONS: Weight loss after bariatric surgery is sex- and procedure-dependent. There is an association suggesting a clinically insignificant difference in weight loss between RYGB and SG among male patients at both the 2- and 5-year postsurgery time points.