Leg Cycling Efficiency is Unaltered in Healthy Aging Regardless of Sex, or Training Status.

Muscular efficiency during exercise has been used to interrogate aspects of human muscle energetics, including mitochondrial coupling and biomechanical efficiencies. Typically, assessments of muscular efficiency have involved graded exercises. Results of previous studies have been interpreted to indicate a decline in exercise efficiency with aging owing to decreased mitochondrial function. However, discrepancies in variables such as exercise stage duration, cycling cadence, and treadmill walking mechanics may have affected interpretations of results. Furthermore, recent data from our lab examining the ATP to oxygen ratio (P:O) in mitochondrial preparations isolated from NIA mouse skeletal muscle showed no change with aging. Thus, we hypothesized that Delta Efficiency (∆€) during steady-rate cycling exercise would not be altered in older healthy subjects compared to young counterparts regardless of biological sex or training status. Young (21-35 years) and older (60-80 years) men (n=21) and women (n=20) underwent continual, progressive leg cycle ergometer tests pedaling at 60 RPM for 3 stages (35, 60, 85 W) lasting 4 minutes. ∆€ was calculated as: (∆ Work Accomplished/∆ Energy Expended). Overall, cycling efficiencies were not significantly different in older compared to young subjects. Similarly, trained subjects did not exhibit significantly different exercise efficiency compared to untrained. Moreover, there were no differences between men and women. Hence, our results obtained on healthy young and older subjects are interpreted to mean that previous reports of decreased efficiency in older individuals were attributable to metabolic or biomechanical comorbidities, not aging per se.

Early U.S. Heart Transplant Experience With Normothermic Regional Perfusion Following Donation After Circulatory Death.

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

Revisiting Differences in Fourth-Year Orthopaedic Away Rotation Opportunities and Fees Among Allopathic and Osteopathic Medical Students.

Introduction: Fourth-year away rotations are an important modifiable variable proven to increase students' opportunities to match into orthopaedic surgery. The purpose of this study was to determine differences in away rotation eligibility requirements and cost of rotation between allopathic and osteopathic students during the 2023 application cycle. Eligibility requirements and fees were then compared with the 2021 application cycle. Methods: A cross-sectional study was performed during the 2023 application cycle of all nonmilitary, Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery residency programs (n = 194). Each program's website, affiliated school of medicine's website, visiting student application service portal, and Residency Explorer tool were searched for eligibility criteria, associated rotation fees, and other rotation requirements. Two-sample Z tests for proportions were utilized to compare differences in programs with differing requirements for students based on academic degree type. Data were compared statistically with previously reported data from the 2021 application cycle. Results: In 2023, there were more programs that restricted osteopathic medical students from away rotations than programs that restricted allopathic medical students (12/194, 6.2% vs. 0/194, 0.0%; p < 0.001). All 12 programs were formerly ACGME-accredited before the integration into a single accreditation system. There was a decrease in the number of programs restricting osteopathic medical students from away rotations compared with the 2021 application cycle (18/194, 9.3% vs. 12/194, 6.2%; p = 0.254). Fees associated with away rotations ranged from $25 to $4,000 for both allopathic and osteopathic students. The number of programs that charged osteopathic medical students higher rotation fees than programs that charged allopathic students when compared with the 2021 application cycles decreased (1/194, 0.5% vs. 5/194, 2.6%; p = 0.049). Conclusions: While some programs continue to have away rotation eligibility requirements that prohibit osteopathic medical students from rotating, only one residency program currently charges osteopathic medical students a higher fee to rotate than allopathic medical students.

Cost Analysis of Routine Histopathologic Evaluation of Specimens Following Total Ankle Arthroplasty.

BACKGROUND: Routine histopathologic examination of orthopaedic surgical specimens is a standard practice at many institutions. Previous studies have demonstrated that this practice seldom altered patient management for several orthopaedic procedures. As a result, the value of such practices has come into question. The purpose of this study is to determine the cost-effectiveness of routine histopathologic analysis of specimens obtained during total ankle arthroplasty (TAA). METHODS: A retrospective analysis was performed of patients who underwent uncomplicated primary TAA at a large, academic, health system between January 2015 and December 2021. The postoperative histopathologic diagnoses were compared with the respective patient's preoperative clinical and intraoperative diagnoses. The prevalence of concordant, discrepant, and discordant diagnoses was determined. Cost-effectiveness analysis was conducted to assess the financial implications of obtaining routine specimens for histopathologic examination for TAA. RESULTS: A total of 85 TAAs were identified in 85 individual patients and were included in the present study. A total of 172 specimens were sent for routine histopathologic review. On histopathologic analysis, a final diagnosis was confirmed in 82 (96.5%) of the total specimens reviewed. A discrepant diagnosis was discovered in 3 (3.5%; 2 cases of gout/pseudogout and 1 case of osteonecrosis) cases and 0 (0%) discordant diagnoses were discovered, corresponding to positive and negative predictive values of 97% and 100%, respectively The total estimate of costs incurred for the routine analysis of all specimens included in the study was between $12 299.20 and 17 846.00. The estimated cost to establish each discrepant diagnosis ranged between $4099.73 and $5948.67, and the cost for a discordant diagnosis was unable to be established. CONCLUSION: Routine histopathologic analysis of specimens obtained during TAA rarely revealed a discordant diagnosis and resulted in no alterations to patients' plan of care. Furthermore, the additional costs of routine histopathologic examination are significant. As such, it is recommended that such interventions in TAA should be performed on a per-case basis at the operating surgeon's discretion.

Delayed and Diminished Postprandial Lactate Shuttling in Healthy Older Men and Women.

Lactate, a product of glycolysis, is formed under aerobic conditions. Extensive work has shown lactate flux in young and exercising humans; however, the effect of age is not known. We tested the hypothesis that postprandial lactate shuttling (PLS) would be diminished in older adults. We used [3-13C]lactate and [6,6-2H]-glucose tracers, an OGTT, and arterialized blood sampling to determine postprandial lactate rates of appearance (Ra), disappearance (Rd), and oxidation (Rox) in 15 young (28.1 ± 1.4 yr) and 13 older (70.6 ± 2.4 yr) healthy men and women. In young participants fasting blood [lactate] [¼ 0.5 mM] rose after the glucose challenge, peaked at 15 min, dipped to a nadir at 30 min, and rose again peaking at 60 min [¼ 1.0mM]. Initial responses in lactate Ra of older participants were delayed and diminished until 90 minutes rising by 0.83 mg·kg-1·min-1. Lactate Rox was higher throughout the entire trial in young participants by a difference of approximately 0.5 mg·kg-1·min-1. Initial peaks in lactate Ra and concentration in all volunteers demonstrated presence of an enteric PLS following an OGTT. Notably, in the systemic, but not enteric PLS phase, lactate Ra correlated highly with glucose Rd (r2 = 0.92). Correspondence of second peaks in lactate Ra and concentration and glucose Rd show dependence of lactate Ra on glucose Rd. While results show both enteric and systemic PLS phases in young and older study cohorts, metabolic responses were delayed and diminished in healthy older individuals.

Primary Team Versus Local Recovery in Liver Transplantation in the Modern Era: A National Analysis of the United Network for Organ Sharing Database.

BACKGROUND: The implementation of acuity circles (AC) in 2020 and the COVID-19 pandemic increased the use of local surgeons to recover livers for transplant; however, the impact on liver transplant (LT) outcomes is unknown. METHODS: Deceased donor adult LT recipients from the UNOS database were identified.  Recipients were grouped by donor surgeon: local versus primary recovery.  Patient and graft survival as well as trends in local recovery in the 2 years pre-AC and post-AC were assessed. RESULTS: The utilization of local recovery in LT increased from 22.3% to 37.9% post-AC (p < 0.01).  LTs with local recovery had longer cold ischemia times (6.5 h [5.4-7.8] vs. 5.3 h [4.4-6.5], p < 0.01) and traveled further (210 miles [89-373] vs. 73 miles [11-196], p < 0.01) than those using primary recovery. Multivariate analyses revealed no differences in patient or graft survival between local and primary recovery, and between OPO and local surgeon. There was no difference in survival when comparing simultaneous liver-kidney, donation after circulatory death, MELD ≥ 30, or redo-LT by recovery team.  Recovery and utilization rates were also noted to be higher post-AC (51.4% vs. 48.6% pre-AC, p < 0.01) as well as when OPO surgeons recovered the allografts (72.5% vs. 66.0%, p < 0.01). CONCLUSION: Nearly 40% of LTs are performed using local recovery, and utilization rates and trends continue to change with changing organ-sharing paradigms such as AC.  This practice appears safe with outcomes similar to recovery by the primary team in appropriately selected recipients and may lead to increased access and the ability to transplant more livers.

Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. OBJECTIVES: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. RESULTS: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. CONCLUSIONS: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Detection of Psychological Dysfunction and Suicide Risk Among Postpartum Women.

Prevalence rates of perinatal mood disorders range from 5 to 25%. Furthermore, suicide is a leading cause of death in postpartum women. Various factors have been associated with an increased risk of suicide in postpartum women, including co-occurring mental health disorders, lack of mental health care, and substance use. It is important for mental health screening and psychological assessment used within OB-GYN clinics to be current with regard to postpartum mood dysfunction and suicide risk assessment. We collected data from a sample of 78 postpartum women (0-6-month post-delivery), focusing specifically on patterns of emotional/internalizing dysfunction, using three different screening measures as predictors. Contrary to hypotheses, our sample did not produce significant elevations on target criterion scales of the Minnesota multiphasic personality inventory-3 (MMPI-3). Although the multidimensional behavioral health screen (MBHS) was better at differentially capturing MMPI-3 elevations when compared to the Edinburgh postnatal depression scale (EDPS) and patient health questionnaire-9 (PHQ-9), two of the three comparisons were not statistically significant. Statistical analyses were challenged by our extremely low base rate for elevated suicide risk. Despite this, the MBHS performed better than the EPDS and PHQ-9 at accurately capturing elevated suicide risk.

Tranexamic Acid Administration Does Not Alter Inflammation After Traumatic Brain Injury, Regardless of Timing.

INTRODUCTION: Tranexamic acid (TXA) administered early after traumatic brain injury (TBI) can decrease morbidity and mortality. The purpose of this study is to determine if the timing of TXA administration after TBI affects postinjury inflammatory markers or phosphorylated tau (p-tau) levels within the hippocampus. METHODS: Male mice (9-11 wk) were split into six groups based on injury and timing of TXA administration (n = 5 per group): Sham, TBI-only, 100 mg/kg TXA-only, TBI + TXA 10 min, TBI + TXA 1 h, and TBI + TXA 6 h. Moderate concussive TBI was induced via weight drop. Serum and brain homogenates were collected at 6 and 24 h postinjury and analyzed for 14 inflammatory cytokines via multiplex enzyme-linked immunosorbent assay. Serum was analyzed for glial fibrillary acidic protein levels. Additional cohorts were survived to 30 d for hippocampal p-tau quantification using immunohistochemistry. RESULTS: Serum levels of interleukin (IL) 1ß (IL-1ß), IL-3, IL-12, IL-17, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and regulated on activation, normal T-cell expressed and secreted were elevated in TBI mice compared to sham mice at 24 h. Levels of IL-1ß and monocyte chemoattractant protein-1 were lower in 6-h TXA-treated mice than 1-h TXA-treated mice following TBI. IL-12 and macrophage inflammatory protein-1α levels were decreased in 6-h TXA-treated mice compared to 10-min TXA-treated mice. Administration of TXA at 10 min and 6 h but not 1 h postTBI reduced serum glial fibrillary acidic protein levels compared to TBI-only mice. Hippocampal p-tau accumulation was increased after TBI but not reduced by TXA administration. CONCLUSIONS: Our results demonstrate that neither early nor delayed administration of TXA conveyed significant systemic or cerebral benefit in cytokine levels following TBI. Further research should be conducted to assess blood brain barrier integrity and neurobehavioral recovery following TXA administration postTBI.

Multi-Modal Venous ThromboembolicProphylaxis Aids in Risk Reduction Following Splenectomy in Female and Male Mice.

INTRODUCTION: Splenectomy (SPLN) is associated with elevated risk of venous thromboembolic (VTE) disease. Enoxaparin (ENX) is a low-molecular-weight heparin agent used in VTE chemoprophylaxis. Early aspirin administration ameliorates postSPLN platelet hyperaggregability in male mice. Previous literature has excluded female mice, citing potential effects of estrogen on platelet count and activation as a reason. We hypothesized that multimodal therapy using aspirin and ENX would mitigate postoperative platelet aggregability in mice across sexes. METHODS: Murine models of SPLN included both male and female mice. Treatment groups included placebo gavage, sham laparotomy, SPLN alone, SPLN and aspirin, SPLN and ENX, and SPLN with aspirin and ENX (n = 5 per group). Chemoprophylaxis dosing was initiated before SPLN. Mice were euthanized on post-operative day (POD) 1 or 3; platelet counts were obtained and blood samples were analyzed via electrical impedance aggregometry. RESULTS: Females on POD 3 following SPLN demonstrated increased platelet count compared to female mice with no treatment intervention. Male and female mice demonstrated increased adenosine diphosphate (ADP)-induced platelet aggregability on POD 3 following SPLN compared to the placebo group. Treatment with aspirin and ENX decreased this post-SPLN platelet hyperaggregability in both sexes. Females demonstrated significantly higher ADP-mediated platelet aggregability in placebo, SPLN, and SPLN with aspirin and ENX when compared to males of identical treatment groups on POD 3. CONCLUSIONS: Platelet hyperaggregability following SPLN is mediated primarily by ADP in both males and females, but higher relative aggregability is demonstrated in females. Early administration of dual-agent VTE chemoprophylaxis utilizing aspirin and ENX mitigates this hyperaggregability and may aid in VTE risk reduction across sexes.

The role of metaphor in the corporate political strategies of health harming industries: Comparing the concept of balance in the gambling and opioid industry discourses.

Scholars have identified notable similarities between the political strategies employed by health-harming industries. This includes similarities in the narratives employed by industry actors seeking to oppose public health regulations that threaten their commercial interests. This study seeks to examine the use of a specific concept - the balance metaphor - in the policy discourses of two health-harming industries. Namely, the pharmaceutical industry implicated in the prescription opioid crisis in the US, and the UK gambling industry, whose products and practices are associated with a serious, but largely neglected, series of harms. We first review research on metaphors, demonstrating how this provides additional theoretically-informed concepts with which to understand how industry discourse circumscribes the terrain of policy debates in ways amenable to commercial interests. Building from these insights, we conducted a rhetorical analysis, examining how the concept of balance is employed by different actors in distinct contexts to shape understandings of the social and policy problems associated with gambling and opioid products and to promote industry-favourable regulatory responses to these. This brings a micro-level of analysis to supplement previous meso- and macro-level scholarship in this space. We use our findings to argue that the depoliticization of the policy process and objectivization of the policy space - in ways that obscure its contingent and political nature - through discourses of balance is itself an arch political act. Examining the metaphors used in policy debates and their functions provides important insights that can be used to inform the construction of counter-narratives to industry-favourable discourses, including the creative use of novel metaphors in the service of public health goals.

External Validation of Predictors of Mortality in Polytrauma Patients.

INTRODUCTION: The Parkland Trauma Index of Mortality (PTIM) is an integrated, machine learning 72-h mortality prediction model that automatically extracts and analyzes demographic, laboratory, and physiological data in polytrauma patients. We hypothesized that this validated model would perform equally as well at another level 1 trauma center. METHODS: A retrospective cohort study was performed including ∼5000 adult level 1 trauma activation patients from January 2022 to September 2023. Demographics, physiologic and laboratory values were collected. First, a test set of models using PTIM clinical variables (CVs) was used as external validation, named PTIM+. Then, multiple novel mortality prediction models were developed considering all CVs designated as the Cincinnati Trauma Index of Mortality (CTIM). The statistical performance of the models was then compared. RESULTS: PTIM CVs were found to have similar predictive performance within the PTIM + external validation model. The highest correlating CVs used in CTIM overlapped considerably with those of the PTIM, and performance was comparable between models. Specifically, for prediction of mortality within 48 h (CTIM versus PTIM): positive prediction value was 35.6% versus 32.5%, negative prediction value was 99.6% versus 99.3%, sensitivity was 81.0% versus 82.5%, specificity was 97.3% versus 93.6%, and area under the curve was 0.98 versus 0.94. CONCLUSIONS: This external cohort study suggests that the variables initially identified via PTIM retain their predictive ability and are accessible in a different level 1 trauma center. This work shows that a trauma center may be able to operationalize an effective predictive model without undertaking a repeated time and resource intensive process of full variable selection.

Exploring the link between dystrophic microglia and the spread of Alzheimer's neuropathology.

Genetics and other data modalities indicate that microglia play a critical role in Alzheimer's disease (AD) progression, but details of microglia's disease-driving influence are poorly understood. Microglial cells can be parsed into subtypes based on their histologic appearance. One microglia subtype, termed dystrophic microglia, is characterised structurally by fragmented processes and cytoplasmic decay, and their presence has been associated with ageing and neurodegeneration. Recent studies suggest that the interaction between tau proteins and amyloid-ß might induce dystrophic changes in microglia, potentially linking amyloid-ß and tau pathologies to their effects on these microglia. We developed a study of human brains to test the hypothesis that dystrophic microglia are involved in AD progression. We speculated that if their presence is unique to AD neuropathologic change (ADNC), they would be substantially more common in ADNC than in neurodegenerative diseases characterised by other proteinopathies, e.g., α-synuclein or TDP-43 pathology. Our analyses used histologically stained sections from five human brain regions of 64 individuals across six disease states, from healthy controls to advanced AD stages, including comparative conditions such as Lewy Body Disease (LBD) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). Using stereological sampling and digital pathology, we assessed ramified, hypertrophic, and dystrophic microglia populations. We found a significant increase in dystrophic microglia in areas early affected by ADNC, suggesting a disease-specific role in neuropathology. Mediation analysis and structural equation modelling suggest dystrophic microglia may impact the regional spread of ADNC. In the mediation model, tau was found to be the initiating factor leading to the development of dystrophic microglia, which then was associated with the spread of amyloid-ß and tau. These results suggest that a loss of microglia's protective role could contribute to the spread of ADNC and indicate that further research into preserving microglial function may be warranted.

Interpersonal Violence-Related Trauma Among South African Children.

INTRODUCTION: Injuries account for a major portion of disability-adjusted life years in children globally, and low-and middle-income countries are disproportionally affected. While injuries due to motor vehicle collisions and self-harm have been well-characterized in pediatric populations in South Africa, injuries related to interpersonal violence (IPV) are less understood. Our study aims to characterize patterns of injury, management, and outcomes for pediatric patients presenting with IPV-related injuries in a South African trauma center. METHODS: We performed a retrospective review of trauma patients ≤18 y of age presenting to the Pietermaritzburg Metropolitan Trauma Service in Gray's Hospital in South Africa from 2012 to 2022, comparing those with injuries resulting from IPV to those with non-IPV injuries. Patients' and injury pattern characteristics and outcomes were descriptively analyzed. RESULTS: Out of 2155 trauma admissions, 500 (23.2%) had IPV-related injuries. Among patients with IPV-related injuries, the median age was 16.0 y. 407 (81.4%) patients were male. 271 (54.2%) patients experienced blunt trauma, 221 (44.2%) had penetrating trauma, and 3 (0.6%) suffered both. The most common weapons were knives (21.6%), stones (11.2%), and firearms (11.0%). The most commonly injured regions were the head (56.4%), abdomen (20.8%), and thorax (19.2%). 19.6% underwent surgical intervention, and 14.4% were referred out for subspecialty care. 1.4% patients died, and 1.2% returned to Pietermaritzburg Metropolitan Trauma Service within 30 d of discharge. CONCLUSIONS: IPV patients are a distinctive subgroup of pediatric trauma patients with different demographics, patterns of injury, and clinical needs. Further research is needed to better understand the unique needs of this neglected population.

Correction for partial volume averaging in the quantification of radiopaque nanomaterial-embedded resorbable polymers.

Resorbable inferior vena cava (IVC) filters require embedded contrast for image-guided placement and integrity monitoring. We calculated correction factors to account for partial volume averaging of thin nanoparticle (NP)-embedded materials, accounting for object and slice thicknesses, background signal, and nanoparticle concentration. We used phantoms containing polycaprolactone disks embedded with bismuth (Bi) or ytterbium (Yb): 0.4- to 1.2-mm-thick disks of 20 mg ml-1NPs (thickness phantom), 0.4-mm-thick disks of 0-20 mg ml-1NPs in 2 mg ml-1iodine (concentration phantom), and 20 mg ml-1NPs in 0.4-mm-thick disks in 0-10 mg ml-1iodine (background phantom). Phantoms were scanned on a dual-source CT with 80, 90, 100, and 150 kVp with tin filtration and reconstructed at 1.0- to 1.5-mm slice thickness with a 0.1-mm interval. Following scanning, disks were processed for inductively coupled plasma optical emission spectrometry (ICP-OES) to determine NP concentration. Mean and maximum CT numbers (HU) of all disks were measured over a 0.5-cm2area for each kVp. HU was converted to concentration using previously measured calibrations. Concentration measurements were corrected for partial volume averaging by subtracting residual slice background and extrapolating disk thickness to both nominal and measured slice sensitivity profiles (SSP, mm). Slice thickness to agreement (STTA, mm) was calculated by replacing the CT-derived concentrations with ICP-OES measurements and solving for thickness. Slice thickness correction factors improved agreement with ICP-OES for all measured data. Yb corrections resulted in lower STTA than Bi corrections in the concentration phantom (1.01 versus 1.31 STTA/SSP, where 1.0 is perfect agreement), phantoms with varying thickness (1.30 versus 1.87 STTA/SSP), and similar ratio in phantoms with varying background iodine concentration (1.34 versus 1.35 STTA/SSP). All measured concentrations correlated strongly with ICP-OES and all corrections for partial volume averaging increased agreement with ICP-OES concentration, demonstrating potential for monitoring the integrity of thin IVC resorbable filters with CT.

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

Tritrichomonas muris sensitizes the intestinal epithelium to doxorubicin-induced apoptosis.

Doxorubicin (DXR) is a widely used chemotherapy drug that can induce severe intestinal mucositis. While the influence of gut bacteria on DXR-induced damage has been documented, the role of eukaryotic commensals remains unexplored. We discovered Tritrichomonas muris ( Tmu ) in one of our mouse colonies exhibiting abnormal tuft cell hyperplasia, prompting an investigation into its impact on DXR-induced intestinal injury. Mice from Tmu -colonized and Tmu -excluded facilities were injected with DXR, and tissue morphology and gene expression were evaluated at acute injury (6 h) and peak regeneration (120 h) phases. Contrary to previous reports, DXR did not significantly alter villus height, crypt depth, or crypt density in any mice. However, we did observe apoptosis, measured by cleaved caspase 3 (CC3) staining, in intestinal crypts at 6 h post-DXR that was significantly higher in mice colonized by Tmu . Interestingly, while DXR did not alter the expression of active and facultative intestinal stem cell (ISC) marker genes in control mice, it significantly reduced their expression in Tmu + mice. Tmu , but not DXR, is also associated with increased inflammation and expression of the type 2 cytokines IL-5 and IL-13. However, pre-treatment of intestinal organoids with these cytokines is not sufficient to drive elevated DXR-induced apoptosis. These findings highlight the significant influence of commensal microbiota, particularly eukaryotic organisms like Tmu , on intestinal biology and response to chemotherapy, underscoring the complexity of gut microbiota interactions in drug-induced mucositis. NEW & NOTEWORTHY: Our study found that the eukaryotic commensal Tritrichomonas muris ( Tmu ) significantly increases DXR-induced intestinal apoptosis in mice, despite no changes in tissue morphology. Tmu also reduces intestinal stem cell gene expression post-DXR injury, and elevates inflammation and type 2 cytokine expression in the absence of injury. In vitro organoid assays suggest that type 2 cytokines alone are insufficient to promote increased DXR-associated apoptosis. These findings emphasize the complex role of gut microbiota in drug-induced intestinal damage.

Examining Retention Sentiments and Attrition Among Active Duty Army Medical Officers.

INTRODUCTION: Providing quality care and maintaining exceptional medical providers are important priorities for military medicine. The present study examines the association between retention sentiments and voluntary separation from army service among Army Medical Corps and Nurse Corps Officers. Retention sentiments are derived from the Department of the Army Career Engagement Survey, a voluntary survey that Active Duty Soldiers complete annually. MATERIALS AND METHODS: The sample included active Army officers in the Medical Corps (n = 1198) and Nurse Corps (n = 1016) who completed the Department of the Army Career Engagement Survey between May 06, 2020 and November 02, 2023, passed the embedded attention check, and said their responses could be used for research purposes. The most frequently cited "Extremely Important" reasons to leave the army were identified within each sample. Binomial logistic regression was used to examine the likelihood of separating from army service based on the top five reasons to leave the Army as identified on the Department of the Army Career Engagement Survey. This study was determined by Exempt Human Subjects Research. RESULTS: An examination of the factors most frequently endorsed as an "Extremely Important" reason to leave the Army revealed that "Effects of deployments on Family or personal relationships" and "Impact of military service on my Family's well-being" were among the five most cited "Extremely Important" reasons to leave the army within both the Medical Corps and the Nurse Corps samples. When examined together (i.e., summed), the Composite Leave Score was associated with a significantly greater odds of separating from army service in each sample. Specifically, each additional top five "Extremely Important" leave reason identified was associated with a 38% greater odds of separating from army service within the Medical Corps and 50% greater odds of separating from army service within the Nurse Corps. CONCLUSIONS: The current study highlights unique retention concerns among army medical providers in the Medical Corps and Nurse Corps. Additionally, this study ties medical provider sentiments to subsequent voluntary separation from the army. These findings can help army senior leaders evaluate, draft, and revise policy aimed at increasing retention among army medical providers, and increasing access to quality healthcare for service members and their families.

Establishing species boundaries in Bornean geckos.

Species delimitation using mitochondrial DNA (mtDNA) remains an important and accessible approach for discovering and delimiting species. However, delimiting species with a single locus (e.g. DNA barcoding) is biased towards overestimating species diversity. The highly diverse gecko genus Cyrtodactylus is one such group where delimitation using mtDNA remains the paradigm. In this study, we use genomic data to test putative species boundaries established using mtDNA within three recognized species of Cyrtodactylus on the island of Borneo. We predict that multi-locus genomic data will estimate fewer species than mtDNA, which could have important ramifications for the species diversity within the genus. We aim to (i) investigate the correspondence between species delimitations using mtDNA and genomic data, (ii) infer species trees for each target species, and (iii) quantify gene flow and identify migration patterns to assess population connectivity. We find that species diversity is overestimated and that species boundaries differ between mtDNA and nuclear data. This underscores the value of using genomic data to reassess mtDNA-based species delimitations for taxa lacking clear species boundaries. We expect the number of recognized species within Cyrtodactylus to continue increasing, but, when possible, genomic data should be included to inform more accurate species boundaries.