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.

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.

Absolute Lymphocyte Count after BCMA CAR-T Therapy is a Predictor of Response and Outcomes in Relapsed Multiple Myeloma.

BCMA-targeting CAR-T cells used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (RR) disease, and CAR-T cell expansion post-infusion has been shown to inform depth and duration of response, but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 relapsed MM patients treated with the BCMA-targeting agents cilta-cel and ide-cel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and duration of response (DoR). Patients with ALCmax >1.0 x103/uL had a superior PFS (30.5 versus 6 months, p <0.001) compared to those ≤1.0x103/uL, while patients with ALCmax ≤0.5 x103/uL represent a high-risk group with early disease progression and short PFS (HR 3.4, 95 CI: 2 -5.8, P <0.001). In multivariate analysis, ALCmax >1.0 x103/uL and non-paraskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for ISS staging, age, CAR-T product, high-risk cytogenetics and number of previous lines. Moreover, our flow cytometry data suggests that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in RRMM patients.

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.

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.

Passing on the Zzz's: Adolescent sleep attitudes are associated with sleep behaviors and parental prioritization of sleep.

OBJECTIVES: The purpose of this study is to examine adolescent attitudes about the importance of sleep and how they relate to adolescent sleep behaviors and parent sleep attitudes. METHODS: Participants included families with adolescents aged 10-17years and a parent (N = 170 dyads) who completed a virtual assessment. Adolescents reported on their sleep impairment and sleep hygiene behaviors, and all participants completed a newly developed scale to assess attitudes toward the importance of prioritizing sleep over other activities/responsibilities. RESULTS: Results suggest that older adolescents reported more negative sleep attitudes, and adolescents reported more negative sleep attitudes compared to adult/parent participants. More negative sleep attitudes were associated with poorer sleep hygiene behaviors. Parent sleep attitudes significantly predicted their adolescent's sleep attitudes, even after adjusting for family income, education, and adolescent age and sex. CONCLUSIONS: This is the first study to our knowledge to quantitatively examine adolescent sleep attitudes. Findings suggest that sleep attitudes are important for adolescent sleep, and may develop within the family system via parental socialization. Future research and implications for intervention are discussed.

Do Women and Minority Orthopaedic Residents Report Experiencing Worse Well-being and More Mistreatment Than Their Peers?

BACKGROUND: Despite the increased risk of attrition for women and minority residents during orthopaedic residency, there is currently a paucity of research examining the training environment of these residents. To address this, we examined how well-being constructs may differ for women or minority residents compared with their peers, and whether these residents report experiencing more mistreatment during residency. QUESTIONS/PURPOSES: (1) How does the psychologic wellbeing of women and minority residents compare with that of their peers regarding the constructs of burnout, lifestyle satisfaction, social belonging, and stereotype threat? (2) Do reported mistreatment experiences during residency differ among women and minority residents compared with their peers? (3) Is there a difference in the proportion of women and minority orthopaedic residents with thoughts of leaving residency compared with their peers? METHODS: Seventeen orthopaedic residency programs in the 91 programs comprising the Collaborative Orthopaedic Educational Research Group agreed to participate in the study. Program directors sent an anonymous one-time survey with two reminders to all orthopaedic residents at their respective institutions. The survey instrument comprised validated and previously used instruments with face validity designed to measure burnout, satisfaction, duty-hour violations, belonging, stereotype threat, mistreatment, and thoughts of leaving residency, in addition to demographic information. Forty-three percent (211 of 491) of residents responded to the survey. Race or ethnicity data were combined into "White" and "underrepresented in orthopaedics" (URiO), which included residents who self-identified as Asian, African American, Hispanic or Latino, Native American, or other, given that these groups are all underrepresented racial and ethnic groups in orthopaedics. The demographic makeup of our study, 81% men and 75% White, is roughly comparable to the current demographic makeup of orthopaedic residency programs, which is 82% men and 74% White. Data were analyzed using chi-square tests, Fisher exact tests, and t-tests as appropriate. For comparisons of Likert scale measures, we used an anchor-based approach to determining the minimum detectable change (MDC) and set the MDC as a 1-point difference on a 5-point scale and a 1.5-point difference on a 7-point scale. Stereotype threat is reported as the mean ▵ from the neutral response, and ▵ of 1.5 or greater was considered significant. RESULTS: Women residents were more likely than men to report experiencing emotional exhaustion (odds ratio 2.18 [95% confidence interval 1.1 to 4.5]; p = 0.03). Women reported experiencing stereotype threat regarding their identity as women surgeons (mean ▵ 1.5 ± 1.0). We did not identify a difference in men's and women's overall burnout (OR 1.4 [95% CI 0.7 to 3.0]; p = 0.3), lifestyle satisfaction across multiple domains, or sense of social belonging (men: 4.3, women 3.6; mean difference 0.7 [95% CI 0.4 to 0.9]; p < 0.001). We did not identify differences in overall burnout (OR 1.5 [95% CI 0.8 to 3.0]; p = 0.2), lifestyle satisfaction across multiple domains, sense of social belonging (White: 4.2, URiO: 3.9; mean difference 0.3 [95% CI 0.17 to 0.61]; p < 0.001), or stereotype threat (mean ▵ 0.8 ± 0.9) between White and URiO surgeons. Women were more likely than men to report experiencing mistreatment, with 84% (32 of 38) of women and 43% (70 of 164) of men reporting mistreatment at least a few times per year (OR 7.2 [95% CI 2.8 to 18.1]; p < 0.001). URiO residents were more likely than White residents to report experiencing mistreatment overall, with 65% (32 of 49) of URiO residents and 45% (66 of 148) of White residents reporting occurrences at least a few times per year (OR 2.3 [95% CI 1.2 to 4.6]; p = 0.01). Women were more likely than men to report experiencing gender discrimination (OR 52.6 [95% CI 18.9 to 146.1]; p < 0.001), discrimination based on pregnancy or childcare status (OR 4.3 [95% CI 1.4 to 12.8]; p = 0.005), and sexual harassment (OR 11.8 [95% CI 4.1 to 34.3]; p < 0.001). URiO residents were more likely than White residents to report experiencing racial discrimination (OR 7.8 [95% CI 3.4 to 18.2]; p < 0.001). More women than men had thoughts of leaving residency (OR 4.5 [95% CI 1.5 to 13.5]; p = 0.003), whereas URiO residents were not more likely to have thoughts of leaving than White residents (OR 2.2 [95% CI 0.7 to 6.6]; p = 0.1). CONCLUSION: Although we did not detect meaningful differences in some measures of well-being, we identified that women report experiencing more emotional exhaustion and report stereotype threat regarding their identity as women surgeons. Women and URiO residents report more mistreatment than their peers, and women have more thoughts of leaving residency than men. These findings raise concern about some aspects of the training environment for women and URiO residents that could contribute to attrition during training. CLINICAL RELEVANCE: Understanding how well-being and mistreatment affect underrepresented residents helps in developing strategies to better support women and URiO residents during training. We recommend that orthopaedic governing bodies consider gathering national data on resident well-being and mistreatment to identify specific issues and track data over time. Additionally, departments should examine their internal practices and organizational culture to address specific gaps in inclusivity, well-being, and mechanisms for resident support.

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.

Cellular Mass Response to Therapy Correlates With Clinical Response for a Range of Malignancies.

PURPOSE: Cancer patients with advanced-stage disease have poor prognosis, typically having limited options for efficacious treatment, and genomics-based therapy guidance continues to benefit only a fraction of patients. Next-generation ex vivo approaches, such as cell mass-based response testing (MRT), offer an alternative precision medicine approach for a broader population of patients with cancer, but validation of clinical feasibility and potential impact remain necessary. MATERIALS AND METHODS: We evaluated the clinical feasibility and accuracy of using live-cell MRT to predict patient drug sensitivity. Using a unified measurement workflow with a 48-hour result turnaround time, samples were subjected to MRT after treatment with a panel of drugs in vitro. After completion of therapeutic course, clinical response data were correlated with MRT-based predictions of outcome. Specimens were collected from 104 patients with solid (n = 69) and hematologic (n = 35) malignancies, using tissue formats including needle biopsies, malignant fluids, bone marrow aspirates, and blood samples. Of the 81 (78%) specimens qualified for MRT, 41 (51%) patients receiving physician-selected therapies had treatments matched to MRT. RESULTS: MRT demonstrated high concordance with clinical responses with an odds ratio (OR) of 14.80 (P = .0003 [95% CI, 2.83 to 102.9]). This performance held for both solid and hematologic malignances with ORs of 20.67 (P = .0128 [95% CI, 1.45 to 1,375.57]) and 8.20 (P = .045 [95% CI, 0.77 to 133.56]), respectively. Overall, these results had a predictive accuracy of 80% (P = .0026 [95% CI, 65 to 91]). CONCLUSION: MRT showed highly significant correlation with clinical response to therapy. Routine clinical use is technically feasible and broadly applicable to a wide range of samples and malignancy types, supporting the need for future validation studies.

Sucrose homeostasis: Mechanisms and opportunity in crop yield improvement.

Sugar homeostasis is a critical feature of biological systems. In humans, raised and dysregulated blood sugar is a serious health issue. In plants, directed changes in sucrose homeostasis and allocation represent opportunities in crop improvement. Plant tissue sucrose varies more than blood glucose and is found at higher concentrations (cytosol and phloem ca. 100 mM v 3.9-6.9 mM for blood glucose). Tissue sucrose varies with developmental stage and environment, but cytosol and phloem exhibit tight sucrose control. Sucrose homeostasis is a consequence of the integration of photosynthesis, synthesis of storage end-products such as starch, transport of sucrose to sinks and sink metabolism. Trehalose 6-phosphate (T6P)-SnRK1 and TOR play central, still emerging roles in regulating and coordinating these processes. Overall, tissue sucrose levels are more strongly related to growth than to photosynthesis. As a key sucrose signal, T6P regulates sucrose levels, transport and metabolic pathways to coordinate source and sink at a whole plant level. Emerging evidence shows that T6P interacts with meristems. With careful targeting, T6P manipulation through exploiting natural variation, chemical intervention and genetic modification is delivering benefits for crop yields. Regulation of cereal grain set, filling and retention may be the most strategically important aspect of sucrose allocation and homeostasis for food security.

Twelve tips for using the Understanding by Design® curriculum planning framework.

BACKGROUND: Health professions faculty engaged in curriculum planning or redesign can struggle with developing courses or programs that align desired learner outcomes, such as competencies to be applied in a clinical setting, with assessment and instruction. AIMS: Our medical school implemented the Understanding by Design (UbD) framework to achieve alignment of outcomes, assessments and teaching during the renewal of our four-year curriculum. This article shares our strategies and practices for implementing UbD with teams of faculty curriculum developers. DESCRIPTION: The UbD framework is a 'backward' approach to curriculum development that begins by identifying learner outcomes, followed by the development of assessments that demonstrate achievement of competencies and concludes with the design of active learning experiences. UbD emphasizes the development of deep understandings that learners can transfer to novel contexts. CONCLUSIONS: We found UbD to be a flexible, adaptable approach that aligns program and course-level outcomes with learner-centred instruction and principles of competency-based medical education and assessment.

Hypothermic oxygenated perfusion (HOPE) safely and effectively extends acceptable donor heart preservation times: Results of the Australian and New Zealand trial.

BACKGROUND: Cold static storage preservation of donor hearts for periods longer than 4 hours increases the risk of primary graft dysfunction (PGD). The aim of the study was to determine if hypothermic oxygenated perfusion (HOPE) could safely prolong the preservation time of donor hearts. METHODS: We conducted a nonrandomized, single arm, multicenter investigation of the effect of HOPE using the XVIVO Heart Preservation System on donor hearts with a projected preservation time of 6 to 8 hours on 30-day recipient survival and allograft function post-transplant. Each center completed 1 or 2 short preservation time followed by long preservation time cases. PGD was classified as occurring in the first 24 hours after transplantation or secondary graft dysfunction (SGD) occurring at any time with a clearly defined cause. Trial survival was compared with a comparator group based on data from the International Society of Heart and Lung Transplantation (ISHLT) Registry. RESULTS: We performed heart transplants using 7 short and 29 long preservation time donor hearts placed on the HOPE system. The mean preservation time for the long preservation time cases was 414 minutes, the longest being 8 hours and 47 minutes. There was 100% survival at 30 days. One long preservation time recipient developed PGD, and 1 developed SGD. One short preservation time patient developed SGD. Thirty day survival was superior to the ISHLT comparator group despite substantially longer preservation times in the trial patients. CONCLUSIONS: HOPE provides effective preservation out to preservation times of nearly 9 hours allowing retrieval from remote geographic locations.

Overestimation of Balance Ability Among Older Adults at Risk for Falls.

Objective: This study examined alignment of subjective balance confidence with Stopping Elderly Accidents, Deaths and Injuries (STEADI) fall risk. Methods: Cross-sectional analysis of 155 community-dwelling adults (60 + y/o) from 2016 to 2018 who completed a STEADI fall assessment. Descriptive statistics, Chi-Square analysis, and biserial point correlations were applied. Results: Adults who overestimate balance confidence, 55.6% (n = 50) reported a fall in the past year, 62.2% (n = 56) were worried about falling, 48.9% (n = 44) felt unsteady when standing/walking, and 70.0% (n = 63) had a score of ≥4 on the Stay Independent Questionnaire (SIQ). Physical performance for these adults were mean TUG score 10.9s (SD = 3.4), mean 30 second chair stands 10.8 (SD = 3.5), and mean 4-stage balance score 3.1 (SD = .76). Discussion: Older adults are more likely to overestimate their subjective balance confidence. Individuals are equally likely to have reported a fall in the past year if they were "at fall risk," regardless of their subjective balance confidence.

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction.

BACKGROUND: Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. OBJECTIVES: To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID+ equids and aged and young PPID- controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID+ equids and aged PPID- equids. STUDY DESIGN: Case-control study: five PPID+ equids and six aged and four young PPID- control horses. METHODS: PPID status was based on clinical signs and necropsy examination of the pituitary gland (PG). The lumbar vertebral column, right front third metacarpus (MC3), left hind third metatarsus (MT3), and PG were removed after euthanasia. BMD was determined by quantitative computed tomography of regions of interest (ROI) in each bone and biomechanical testing was performed on the fourth lumbar vertebral body. Serum concentrations of parathormone (PTH), ionised Ca++ , 25-hydroxyvitamin D, and osteocalcin (OC) were also measured. Data were analysed using one-way ANOVA and correlation analyses. RESULTS: BMD of trabecular and cortical regions of interest (ROI) of the third, fourth (L4), and fifth lumbar vertebrae were significantly lower in PPID+ equids as compared with aged (p < 0. 001) and young (p < 0.01) PPID- controls. In contrast, no differences were found in BMD of trabecular or cortical ROIs of MC3 and MT3 between groups. No differences were detected in force at fracture, displacement at fracture, Young's modulus or strain of L4 between PPID+ and aged PPID- horses. No differences were found in serum PTH, ionised Ca++ , 25-hydroxyvitamin D, or OC concentrations between groups. MAIN LIMITATIONS: Limited number of equids studied and variation in test results. CONCLUSIONS: BMD of nonweight bearing bones can be decreased with PPID and could increase risk of developing pathological fractures.

Sleep loss and emotion: A systematic review and meta-analysis of over 50 years of experimental research.

In a largely sleep-deprived society, quantifying the effects of sleep loss on emotion is critical for promoting psychological health. This preregistered systematic review and meta-analysis quantified the effects of various forms of sleep loss on multiple aspects of emotional experiences. Eligible studies used experimental reductions of sleep via total sleep deprivation, partial sleep restriction, or sleep fragmentation in healthy populations to examine effects on positive affect, negative affect, general mood disturbances, emotional reactivity, anxiety symptoms, and/or depressive symptoms. In total, 1,338 effect sizes across 154 studies were included (N = 5,717; participant age range = 7-79 years). Random effects models were conducted, and all forms of sleep loss resulted in reduced positive affect (standardized mean difference [SMD] = -0.27 to -1.14), increased anxiety symptoms (SMD = 0.57-0.63), and blunted arousal in response to emotional stimuli (SMD = -0.20 to -0.53). Findings for negative affect, reports of emotional valence in response to emotional stimuli, and depressive symptoms were mixed and depended on the type of sleep loss. Nonlinear effects for the amount of sleep loss as well as differences based on the stage of sleep restricted (i.e., rapid eye movement sleep or slow-wave sleep) were also detected. This study represents the most comprehensive quantitative synthesis of experimental sleep and emotion research to date and provides strong evidence that periods of extended wakefulness, shortened sleep duration, and/or nighttime awakenings adversely influence human emotional functioning. Findings provide an integrative foundation for future research on sleep and emotion and elucidate the precise ways that inadequate sleep may impact our daytime emotional lives. (PsycInfo Database Record (c) 2024 APA, all rights reserved).