Restoration of LAMP2A expression in old mice leads to changes in the T cell compartment that support improved immune function.

Chaperone-mediated autophagy (CMA) is a selective form of autophagy that contributes to the maintenance of cellular homeostasis. CMA activity declines with age in most tissues and systems, including the immune system, due to a reduction in levels of lysosome-associated membrane protein type 2A (LAMP2A), an essential CMA component. In this study, we show that overexpressing a copy of hLAMP2A within T cells since middle-age can prevent some of their age-associated loss of function. Our data support the idea that preserving LAMP2A expression with age through genetic means leads to enhanced proliferative responses, decreased number of regulatory T cell populations, and down-regulated expression of inhibitory receptors by T cells. During aging, elevated numbers of these immunosuppressive T cell populations significantly contribute to the age-associated downregulation of T cell responses. Using comparative proteomics, we confirm that preservation of CMA activity in old mice prevents age-related changes in both the resting and the activated T cell proteome. We also explore the effect of using first-in-class small molecule activators of CMA and demonstrate improved T cell response upon their administration to old mice. We conclude that sustaining CMA activity constitutes a potentially viable therapeutic approach to improving T cell function with age.

The impact of cavaletti height on dogs' walking speed and its implications for ground reaction forces.

Objective: The objective of this study was to investigate the effects of cavaletti pole height on temporospatial (TPS) and ground reaction force (GRF) variables as compared to a walking gait in healthy dogs. Animals: A total of 25 client-owned dogs were included in this study. Procedures: This study used client-owned dogs to explore the effects of cavaletti pole height on TPS and GRF variables. Dogs were first walked over a validated pressure-sensitive walkway (PSW) and then walked over the PSW over which six cavaletti poles were set. Cavaletti pole height was initially set at 2 inches and then increased incrementally to 4 inches, 6 inches, and 8 inches. TPS and GRF variables were obtained for all dogs walking across a PSW without cavaletti poles and at each cavaletti height. TPS variables were then compared to those obtained at a normal walking gait. Results: Increasing cavaletti height resulted in significant decreases in walking gait velocity and the number of gait cycles per minute. Conversely, significant increases in gait cycle duration (duration of one complete cycle of gait, which includes the time from the initial contact of one paw to the subsequent contact of the same paw) and gait time (duration to walk the total distance on the PSW) were noted. Increases in stance time, normalized maximum force, and normalized vertical impulse were observed. Conclusion and clinical relevance: Cavaletti height does influence TPS variables in healthy dogs at a walking gait. The effects were most notable with regard to velocity. Due to the lack of consistent velocity for all cavaletti heights, no conclusions can be drawn regarding the effect of cavaletti height on ground reaction forces. Further investigation is needed to elucidate whether it is the velocity, cavaletti height, or combination of both that impacts ground reaction force variables. When selecting cavaletti pole heights for a therapeutic exercise program, an increase in cavaletti height results in a slower walking gait.

Solutions and insights for agricultural monitoring, reporting, and verification (MRV) from three consecutive issuances of soil carbon credits.

Regenerative agricultural practice adoption on conventionally managed fields has gained momentum as a climate mitigation strategy, given the ability of these practices to sequester carbon or reduce greenhouse gas emissions. However, the geospatial and temporal variability of the impact of specific practices, such as cover cropping or no-till, pose challenges for scalable quantification of emissions reduction and deploying incentives to drive increased adoption. To quantify impact while accounting for variability and uncertainty at scale, Indigo Ag created a monitoring, reporting, and verification (MRV) pipeline to produce agricultural soil carbon credits produced at large scales (hundreds of thousands of hectares). The pipeline ingests field data from enrolled farmers, checks data quality, uses hybrid soil sampling and biogeochemical modeling to produce estimates of emissions reduction and uncertainty, and then applies deductions based on calculated uncertainty and leakage to quantify total project-wide carbon credits and monitor for durability of carbon. The implementation of a carbon project (CAR1459) from 2018 to 2022 on 553,743 ha of U.S. cropland utilizing the pipeline is estimated to have reduced emissions by 398,408.5 tCO2e, amounting to 296,662 tCO2e of soil carbon credits after uncertainty deductions. This paper explores the effect sizes associated with specific regenerative practice changes across the project domain. Cover cropping consistently resulted in a net positive climate impact and reduced emissions by 1.29 tCO2e per hectare per year, on average. Introduction of no-till was more common in the project, but it had a lower average emissions reduction of 0.38 tCO2e per hectare per year. Effect sizes for no-till vary spatiotemporally and are typically low in the first several years after adoption but increase in subsequent years. Agricultural carbon programs that capture and incentivize the nuance of outcomes of practices rather than the implementation of practices, can promote adoption of the right management practice to be deployed on the right field for maximum environmental benefit.

Low-Resource Hospital Days for Children Following New Tracheostomy.

BACKGROUND AND OBJECTIVES: Children with new tracheostomy and invasive mechanical ventilation (IMV) require transitional care involving caregiver education and nursing support. To better understand hospital resource use during this transition, our study aimed to: (1) define and characterize low-resource days (LRDs) for this population and (2) identify factors associated with LRD occurrence. METHODS: This retrospective cohort analysis included children ≤21 years with new tracheostomy and IMV dependence admitted to an ICU from 2017 to 2022 using the Pediatric Health Information System database. A LRD was defined as a post tracheostomy day that accrued nonroom charges <10% of each patient's accrued nonroom charges on postoperative day 1. Factors associated with LRDs were analyzed using negative binomial regression. RESULTS: Among 4048 children, median post tracheostomy stay was 69 days (interquartile range 34-127.5). LRDs were common: 38.6% and 16.4% experienced ≥1 and ≥7 LRDs, respectively. Younger age at tracheostomy (0-7 days rate ratio [RR] 2.42 [1.67-3.51]; 8-28 days RR 1.8 (1.2-2.69) versus 29-365 days; Asian race (RR 1.5 [1.04-2.16]); early tracheostomy (0-7 days RR 1.56 [1.2-2.04]), and longer post tracheostomy hospitalizations (31-60 days RR 1.85 [1.44-2.36]; 61-90 days RR 2.14 [1.58-2.91]; >90 days RR 2.21 [1.71-2.86]) were associated with more LRDs. CONCLUSIONS: Approximately 1 in 6 children experienced ≥7 LRDs. Younger age, early tracheostomy, Asian race, and longer hospital stays were associated with increased risk of LRDs. Understanding the postacute phase, including bed utilization, serves as an archetype to explore care models for children with IMV dependence.

Hepatic veno-occlusive disease with asparaginase products: a review of cases reported to the FDA adverse event reporting system and published in the literature.

Multiple asparaginase products have been approved by the United States (US) Food and Drug Administration (FDA) for the treatment of acute lymphoblastic leukemia in pediatric and adult patients. Hepatic veno-occlusive disease (VOD) is a potentially life-threatening disorder resulting from damage to the liver sinusoidal endothelial cells. To evaluate this safety concern with asparaginase (i.e. Asparlas, Oncaspar, Rylaze, and Erwinaze) use, we performed a postmarketing review of hepatic VOD reports retrieved from the FDA Adverse Event Reporting System database and literature with these four products. We identified 55 cases of hepatic VOD following exposure to asparaginase products. The median time to onset of hepatic VOD from the first dose of asparaginase was 18 days (interquartile range 13-24 days). Notably, 80% (44/55) of cases reported grades 3-5 VOD per the Common Terminology Criteria for Adverse Events. Although patients received asparaginase with standard chemotherapeutic agents known to induce VOD, case-level data indicates that asparaginase products may have contributed to hepatic VOD. Asparaginase products are associated with hepatotoxicity and thrombosis, suggesting a plausible mechanism for asparaginase-induced hepatic VOD. Based on the totality of data, including temporality and biologic plausibility, we determined hepatic VOD to be a class effect with asparaginase products. These data contributed to the addition of hepatic VOD to the hepatoxicity warning in the US Prescribing Information for asparaginase class products.

Intimate Partner Violence and Breastfeeding Outcomes Among Canadian Women: An Exploratory Correlational Study.

PURPOSE: Human breastmilk is the optimal nutrition for infants; however, preliminary research suggests that women who experience intimate partner violence (IPV) are less likely to initiate and continue breastfeeding. Self-efficacy is a known facilitator to achieve positive breastfeeding outcomes. This study aimed to explore the relationship between experiencing IPV and breastfeeding duration, exclusivity, and self-efficacy for Canadian mothers, and to identify potential variables that influence breastfeeding decision-making among women with experiences of IPV. METHOD: This was a cross-sectional secondary analysis of surveys completed by 129 mothers with children under the age of 2 years from Ontario, Canada. Data were stratified according to those who had experienced IPV and those who had not. Breastfeeding outcomes assessed included breastfeeding self-efficacy and breastfeeding duration and exclusivity. Non-parametric tests and correlations were used to determine if relationships existed between IPV and breastfeeding outcomes. RESULTS: 72.3% (n = 94) of women in this sample breastfed their child(ren). Experiencing IPV was associated with lower breastfeeding self-efficacy scores (W = 768, p = 0.055) with a moderate effect size (r = 0.32 [95% 0.06,0.55]). This relationship was significant in the context of psychological abuse (W = 816.5, p = 0.015) with a small effect size (r = 0.22 [95% 0.03,0.41]). CONCLUSIONS: This study provides novel preliminary evidence suggesting that experiencing IPV of any type can negatively impact breastfeeding self-efficacy, with psychological abuse potentially being the most detrimental. Future research is required to build upon these findings.

The Association Between State-Level Prenatal Substance Use Policies and Rates of Maternal Mortality in the United States: A Legal Epidemiology Study.

Little research has explored relationships between prenatal substance use policies and rates of maternal mortality across all 50 states, despite evidence that prenatal substance use elevates risk of maternal death. This study, utilizing publicly available data, revealed that state-level mandated testing laws predicted maternal mortality after controlling for population characteristics.

Evolution of Medical Students' Interest in Orthopaedic Surgery Careers from Matriculation to Graduation.

Introduction: Little is known about risk factors for changes in students' interest in orthopaedics during medical school. We aimed to identify variables associated with diminished (vs. sustained) and emerging (vs. no) plans to become board certified in orthopaedic surgery. Methods: We conducted a retrospective national-cohort study of students who matriculated in US MD-granting medical schools in academic years 1993 to 1994 through 2000 to 2001. The outcome measure was the evolution of students' board-certification plans in orthopaedic surgery from matriculation to graduation using responses on the Association of American Medical Colleges' Matriculating Student Questionnaire and Graduation Questionnaire. Covariates included demographic, attitudinal, experiential, and career intention variables. Results: Of 53,560 graduates with complete data, 2,765 students reported diminished interest in becoming board certified in orthopaedics, 1,345 reported emerging interest, and 1,327 reported sustained interest. In multivariable logistic regression models, students who were female (adjusted odds ratio [aOR] 1.83, 95% confidence interval [CI] 1.43-2.34), Asian (aOR 1.46, 95% CI 1.18-1.82), reported greater importance of social responsibility (aOR 1.16, 95% CI 1.02-1.33) and prestige (aOR 1.20, 95% CI 1.10-1.30) in choosing a medicine career, and planned full-time university faculty careers (aOR 1.58, 95% CI 1.33-1.89) at graduation were independently more likely to have diminished (vs. sustained) interest. Students who participated in research and/or authorship electives (aOR 3.50, 95% CI 3.00-4.07) and who attended private institutions (aOR 1.23, 95% CI 1.10-1.39) were more likely to have emerging (vs. no) interest. Conclusions: Twice as many students lost interest than gained interest in orthopaedics during medical school, and the cohort of students interested in orthopaedics became less diverse over the course of medical school. Several risk factors amenable to change were identified. Interventions that target these risk factors are warranted to increase the diversity of the orthopaedic surgery workforce.

From mood to use: Using ecological momentary assessments to examine how anhedonia and depressed mood impact cannabis use in a depressed sample.

Anhedonia and depressed mood are two cardinal symptoms of major depressive disorder (MDD). Prior work has demonstrated that cannabis consumers often endorse anhedonia and depressed mood, which may contribute to greater cannabis use (CU) over time. However, it is unclear (1) how the unique influence of anhedonia and depressed mood affect CU and (2) how these symptoms predict CU over more proximal periods of time, including the next day or week (rather than proceeding weeks or months). The current study used data collected from ecological momentary assessment (EMA) in a sample with MDD (N = 55) and employed mixed effects models to detect and predict weekly and daily CU from anhedonia and depressed mood over 90 days. Results indicated that anhedonia and depressed mood were significantly associated with CU, yet varied at daily and weekly scales. Moreover, these associations varied in both strength and directionality. In weekly models, less anhedonia and greater depressed mood were associated with greater CU, and directionality of associations were reversed in the models looking at any CU (compared to none). Findings provide evidence that anhedonia and depressed mood demonstrate complex associations with CU and emphasize leveraging EMA-based studies to understand these associations with more fine-grained detail.

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in female mdx mice.

Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA-binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.

Co-Locating Obstetrics and Addiction Medicine Clinics to Improve Attendance in Services for Pregnant People with Opioid Use Disorder.

Objective: Pregnant people receiving treatment for opioid use disorders (OUD) are at significant risk of return to use during the postpartum period. Recently, practice groups and other national organizations have called for the co-location of addiction medicine and obstetric care to reduce the burden on pregnant and postpartum people with OUD associated with engaging in treatment. This paper examines the effectiveness of co-locating services in retaining pregnant people with OUD in care following childbirth. Methods: A records review of pregnant people receiving medication for OUD between 2012 and 2017 in stand-alone addiction medicine clinic (n = 23) and from 2017 to 2021 following the creation of an integrated addiction medicine-obstetric care clinic (n = 67) was conducted to compared rates of attendance in both obstetric and addiction medicine services. Results: Findings from this study suggest that individuals receiving services in a co-located clinic had significantly fewer missed appointments during the postpartum period relative to individuals who sought care at separate addiction medicine and obstetric care clinics. Conclusions: Results from this study support the potential for co-locating clinics to reduce barriers to accessing obstetric and addiction medicine services, as well as support continued attendance in care across a vulnerable period.

"Breaking through the Brokenness": An Arts-Based Qualitative Exploration of Pregnant Women's Experience of Intimate Partner Violence while Receiving Trauma- and Violence-Informed Antenatal Care.

Intimate partner violence (IPV) is a pervasive, worldwide public health concern. Risk of IPV may elevate during the perinatal period, increasing maternal and fetal health risks. Trauma- and violence-informed care shows promise among interventions addressing associated mental health sequelae. As a secondary analysis, the purpose of this study was to employ a qualitative arts-based exploration to better understand pregnant women's experiences of trauma and violence-informed perinatal care in the context of IPV. Using an arts-based qualitative methodology, different art forms were used to analyze, interpret, and report data, resulting in a layered exploration to represent phenomena. From this, four themes were reflected in four poetic pieces: Black Deep Corners, Triggering my Thoughts, Breaking through the Brokenness, and Now Perfectly Imperfect. Nine pieces of visual art were created reflecting these themes, creating a layered, embodied, artistic way to empathically explore and translate phenomena.

Individual energetics scale up to community coexistence: Movement, metabolism and biodiversity dynamics in fragmented landscapes.

Unravelling the intricate mechanisms that govern community coexistence remains a daunting challenge, particularly amidst ongoing environmental change. Individual physiology and metabolism are often studied to understand the response of individual animals to environmental change. However, this perspective is currently largely lacking in community ecology. We argue that the integration of individual metabolism into community theory can offer new insights into coexistence. We present the first individual-based metabolic community model for a terrestrial mammal community to simulate energy dynamics and home range behaviour in different environments. Using this model, we investigate how ecologically similar species coexist and maintain their energy balance under food competition. Only if individuals of different species are able to balance their incoming and outgoing energy over the long-term will they be able to coexist. After thoroughly testing and validating the model against real-world patterns such as of home range dynamics and field metabolic rates, we applied it as a case study to scenarios of habitat fragmentation - a widely discussed topic in biodiversity research. First, comparing single-species simulations with community simulations, we find that the effect of habitat fragmentation on populations is strongly context-dependent. While populations of species living alone in the landscape were mostly positively affected by fragmentation, the diversity of a community of species was highest under medium fragmentation scenarios. Under medium fragmentation, energy balance and reproductive investment were also most similar among species. We therefore suggest that similarity in energy balance among species promotes coexistence. We argue that energetics should be part of community ecology theory, as the relative energetic status and reproductive investment can reveal why and under what environmental conditions coexistence is likely to occur. As a result, landscapes can potentially be protected and designed to maximize coexistence. The metabolic community model presented here can be a promising tool to investigate other scenarios of environmental change or other species communities to further disentangle global change effects and preserve biodiversity.

Phase I and Randomized Phase II Study of Ruxolitinib With Frontline Neoadjuvant Therapy in Advanced Ovarian Cancer: An NRG Oncology Group Study.

PURPOSE: The interleukin-6/Janus kinase (JAK)/signal transducers and activators of transcription 3 axis is a reported driver of chemotherapy resistance. We hypothesized that adding the JAK1/2 inhibitor ruxolitinib to standard chemotherapy would be tolerable and improve progression-free survival (PFS) in patients with ovarian cancer in the upfront setting. MATERIALS AND METHODS: Patients with ovarian/fallopian tube/primary peritoneal carcinoma recommended for neoadjuvant chemotherapy were eligible. In phase I, treatment was initiated with dose-dense paclitaxel (P) 70 mg/m2 once daily on days 1, 8, and 15; carboplatin AUC 5 intravenously day 1; and ruxolitinib 15 mg orally (PO) twice a day, every 21 days (dose level 1). Interval debulking surgery (IDS) was required after cycle 3. Patients then received three additional cycles of chemotherapy/ruxolitinib, followed by maintenance ruxolitinib. In the randomized phase II, patients were randomly assigned to paclitaxel/carboplatin with or without ruxolitinib at 15 mg PO twice a day for three cycles, IDS, followed by another three cycles of chemotherapy/ruxolitinib, without further maintenance ruxolitinib. The primary phase II end point was PFS. RESULTS: Seventeen patients were enrolled in phase I. The maximum tolerated dose and recommended phase II dose were established to be dose level 1. One hundred thirty patients were enrolled in phase II with a median follow-up of 24 months. The regimen was well tolerated, with a trend toward higher grade 3 to 4 anemia (64% v 27%), grade 3 to 4 neutropenia (53% v 37%), and thromboembolic events (12.6% v 2.4%) in the experimental arm. In the randomized phase II, the median PFS in the reference arm was 11.6 versus 14.6 in the experimental, hazard ratio (HR) for PFS was 0.702 (log-rank P = .059). The overall survival HR was 0.785 (P = .24). CONCLUSION: Ruxolitinib 15 mg PO twice a day was well tolerated with acceptable toxicity in combination with paclitaxel/carboplatin chemotherapy. The primary end point of prolongation of PFS was achieved in the experimental arm, warranting further investigation.

Orthopaedic Surgery Attrition Before Board Certification: A National-Cohort Study of US MD Graduates in Orthopaedic Surgery Residency Programs.

Introduction: Little is known about attrition before American Board of Orthopaedic Surgery (ABOS) board certification for orthopaedic residents training in Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedics programs. This national-cohort study examined orthopaedic surgery attrition, associated risk factors, and specialties pursued by residents who left orthopaedics. Methods: From August 2022 through July 2023, we analyzed deidentified, individual-level data from the Association of American Medical Colleges for 129,860 US MD-granting medical-school matriculants in academic years 1993 to 1994 through 2000 to 2001. Graduates with records of training ≥1 year in orthopaedic surgery during GME and of board certification as of May 2020 were included. Retention was defined as being ABOS-certified; attrition was defined as being certified by another specialty board and not ABOS. We identified variables independently associated with attrition from orthopaedics using multivariable logistic regression analysis and reported adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Of 4,319 US medical-school graduates from 1997 to 2009 with ≥1 year of orthopaedic surgery GME, 4,085 (94.6%) obtained ABOS board certification (retention) and 234 did not (attrition). Women (OR 2.8, 95% CI 2.0-3.9), first-generation college graduates (OR 1.6, 95% CI 1.1-2.2), Asians (OR 1.9, 95% CI 1.4-2.7), and residents who placed greater importance on innovation/research in choosing medicine as a career (OR 1.4, 95% CI 1.1-1.7) and completed ≥1 year of research during GME (OR 2.4, 95% CI 1.7-3.5) were more likely to leave orthopaedics. Overall, 121 trainees who left orthopaedics selected surgical specialties for board certification, most commonly plastic surgery (n = 66) and general surgery (n = 45). Conclusions: The increased risk of attrition among women, Asians, first-generation college graduates, and trainees endorsing higher importance of innovation/research in choosing medicine and participating in research during GME raises concerns about the potential loss of underrepresented groups among orthopaedic surgeons and surgeon-scientists. Efforts to mitigate attrition among residents in high-risk groups are warranted.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Age differences in patterns of cannabis use among an online US sample of adults who consume cannabis frequently.

Background: Cannabis use is increasing among middle-aged and older US adults, populations that are particularly vulnerable to the adverse effects of cannabis. Risks for adverse effects differ by cannabis use patterns, which have become increasingly heterogeneous. Nevertheless, little is known about age differences in such patterns.Objective: To investigate age differences in cannabis use patterns, comparing younger (age 18-49), middle-aged (age 50-64), and older adults (age ≥65).Methods: A total of 4,151 US adults with past 7-day cannabis consumption completed an online survey (35.1% male; 60.1% female; 4.8% identified as "other"). Regression models examined age differences in cannabis use patterns.Results: Compared to younger adults, middle-aged and older adults were more likely to consume cannabis during evening hours (50-64: adjusted odds ratio [aOR] = 2.98, 95% CI 2.24-3.96; ≥65: aOR = 4.23, 95 CI 2.82-6.35); by only one method (50-64: aOR = 1.67, 95% CI 1.34-2.09; ≥65: aOR = 3.38, 95 CI 2.24-5.09); primarily by smoking as the only method (50-64: aOR = 1.52, 95% CI 1.29-1.78; ≥65: aOR = 2.12, 95 CI 1.64-2.74); but less likely to consume concentrated cannabis products (concentrates) with extremely high %THC (50-64: aOR = 0.71, 95% CI 0.54-0.93; ≥65: aOR = 0.30, 95 CI 0.16-0.55). Age differences in cannabis use patterns were also observed between middle-aged and older adults.Conclusion: Findings suggest that middle-aged and older adults may engage in less risky cannabis use patterns compared to younger groups (e.g. lower likelihood of consuming highly potent concentrates). However, findings also underscore the importance of recognizing risks unique to these older demographics, such as smoking-related health events. Consequently, prevention strategies targeting such use patterns are needed.

The effects of prenatal and postnatal high-dose vitamin B-12 supplementation on human milk vitamin B-12: a randomized, double-blind, placebo-controlled trial in Tanzania.

BACKGROUND: Vitamin B-12 status in human milk (HM) has critical implications for infant growth and development. Few studies have separately evaluated the effects of prenatal and postnatal maternal high-dose vitamin B-12 supplementation on HM vitamin B-12 concentration. OBJECTIVES: This randomized controlled trial aimed to assess the effects of prenatal and postnatal vitamin B-12 supplementation on HM vitamin B-12 at 6 wk and 7 mo postpartum. METHODS: Pregnant women were enrolled in Dar es Salaam, Tanzania, between 2001 and 2004. From recruitment (12-27 weeks of gestation) through 6 wk postpartum, participants were randomly assigned to daily oral multiple micronutrient supplementation or placebo. From 6 wk to 18 mo postpartum, a subset of participants was randomly assigned to a postnatal supplement or placebo. The supplement included 50 µg/d of vitamin B-12 and various other vitamins. HM vitamin B-12 concentrations were analyzed at 6 wk and 7 mo postpartum for 412 participants. RESULTS: The prevalence of HM vitamin B-12 of <310 pmol/L was 73.3% and 68.4% at 6 wk and 7 mo postpartum, respectively. Prenatal supplementation increased HM vitamin B-12 concentration (percent difference: 34.4; 95% CI: 17.0, 54.5; P < 0.001) at 6 wk; this effect was not present at 7 mo. Postnatal supplementation increased HM vitamin B-12 concentration (percent difference: 15.9; 95% CI: 1.91, 31.9; P = 0.025) at 7 mo. Effect modification between prenatal and postnatal supplementation on HM vitamin B-12 status at 7 mo was found, with the effects of prenatal and postnatal supplements more pronounced among those receiving control during the other period; the prenatal supplement had a greater effect with postnatal control, and the postnatal supplement had a greater effect with prenatal control. CONCLUSIONS: Prenatal maternal vitamin B-12 supplementation has benefits on short-term HM status, and postnatal maternal vitamin B-12 supplementation has benefits on long-term HM status. This trial was registered at clinicaltrials.gov as NCT00197548. https://clinicaltrials.gov/ct2/show/NCT00197548.

Resilience Across the Life Course for Women Experiencing Intimate Partner Violence.

This study employed a life course perspective to explore the resilience of Canadian women of various ages who had experienced intimate partner violence (IPV). Interpretive description was used to analyze 22 in-depth, semi-structured interview transcripts with women who ranged in age from >19 to 60+ years. Results revealed that developmental age affected service accessibility and effectiveness, historical age shaped abuse normalization, and social age presented barriers and facilitators to women's resilience. This study highlighted the central role of resilience for women of all ages who have experienced IPV and emphasized the need for accessible, effective, and supportive services.

Ever Expanding Morphologic Patterns of Mesonephric-like Adenocarcinomas of the Uterine Corpus: A Report of Two Tumors and a Brief Review of the Literature.

Mesonephric-like adenocarcinoma (MLA) of the endometrium shows a variety of morphologic appearances, including small glands, tubules with eosinophilic materials in the lumen, prominent papillary patterns, spindled cells, solid formations, and corded and hyalinized patterns. Unique morphology, characteristic immunohistochemical staining patterns, molecular alterations, and awareness of the pathologists make it possible to identify this tumor accurately. This report of two additional morphologic patterns, intestinal goblet cells mimicking intestinal-type mucinous carcinoma and squamous differentiation with spindle and epithelioid cells mimicking carcinosarcoma of the endometrium will expand the literature on MLA.