Multisystem Toxicity in Cancer: Lessons from NASA's Countermeasures Program.

Astronauts and cancer patients are subject to similar multisystem physiological toxicities. Over the past sixty years, NASA developed a state-of-the-art countermeasures program (CMP) to characterize and mitigate the physiological consequences of spaceflight. Here, we propose a NASA-modeled CMP to elucidate and abrogate physiological toxicities in patients with cancer.

Implementing personalized pathways for cancer follow-up care in the United States: Proceedings from an American Cancer Society-American Society of Clinical Oncology summit.

A new approach to cancer follow-up care is necessary to meet the needs of cancer survivors while dealing with increasing volume and provider shortages, knowledge gaps, and costs to both health care systems and patients. An approach that triages patients to personalized follow-up care pathways, depending on the type(s) and level(s) of resources needed for patients' long-term care, is in use in the United Kingdom and other countries and has been shown to meet patients' needs, more efficiently use the health care system, and reduce costs. Recognizing that testing and implementing a similar personalized approach to cancer follow-up care in the United States will require a multipronged strategy, the American Cancer Society and the American Society of Clinical Oncology convened a summit in January 2018 to identify the needed steps to move this work from concept to implementation. The summit identified 4 key strategies going forward: 1) developing a candidate model (or models) of care delivery; 2) building the case for implementation by conducting studies modeling the effects of personalized pathways of follow-up care on patient outcomes, workforce and health care resources, and utilization and costs; 3) creating consensus-based guidelines to guide the delivery of personalized care pathways; and 4) identifying and filling research gaps to develop and implement needed care changes. While these national strategies are pursued, oncology and primary care providers can lay the groundwork for implementation by assessing their patients' risk of recurrence and the chronic and late effects of cancer as well as other health care needs and resources available for care and by considering triaging patients accordingly, referring patients to appropriate specialized survivorship clinics as these are developed, helping to support patients who are capable of self-managing their health, setting expectations with patients from diagnosis onward for the need for follow-up in primary care and/or a survivorship clinic, and improving coordination of care between oncology and primary care.

Effects of exercise therapy on chemotherapy delivery and response in primary breast cancer: A secondary analysis of a randomized trial.

BACKGROUND: Whether structured exercise therapy improves chemotherapy delivery, tolerability, and tumor response is unclear. METHODS: This was a secondary analysis of a phase 2 trial investigating exercise therapy (n = 72) versus usual care (n = 72) in patients with primary breast cancer. Exercise therapy comprised individualized treadmill walking three times weekly for 20-50 minutes per session at 55%-100% of pretreatment exercise capacity. Chemotherapy delivery was assessed according to the relative dose intensity (RDI), tolerability was assessed according to patient-reported outcomes and blood laboratory values, and response was assessed based on the pathologic complete response rate in patients who received neoadjuvant chemotherapy. RESULTS: In the exercise therapy group, 51 patients (71%) reached 100% RDI (median, 100%; interquartile range, 100%-100%) compared with 41 patients (57%) in the usual care group (median, 100%; interquartile range, 95%-100%; p = .08). Tolerability was similar in both groups; the rates of grade 3 or higher neutropenia and anemia were 22% versus 39% and 7% versus 10% in the exercise and usual care groups, respectively. In patients who received anthracyclines (n = 104), 41 (77%) had 100% chemotherapy RDI in the exercise therapy group versus 29 (57%) in the usual care group (p = .026). In the neoadjuvant chemotherapy subgroup (n = 51 tumors), the postneoadjuvant therapy (yp) pathologic complete response (ypT0ypN0) rate was 27% (95% confidence interval, 12%-50%) in the exercise therapy group compared with 28% (95% confidence interval, 13%-47%) in the usual care group (p > .9). CONCLUSIONS: In patients with primary breast cancer, exercise therapy was associated with improved delivery of anthracycline-based chemotherapy. Although exercise therapy was not significantly associated with tumor response, effects varied by tumor subtype (trial registration: Clinicaltrials.gov identifier NCT01943695).

CREBBP histone acetyltransferase domain mutations predict response to mTOR inhibition in relapsed/refractory follicular lymphoma.

Despite the clinical and molecular heterogeneity of follicular lymphoma (FL), there remains a lack of biomarker-directed therapeutic approaches in routine clinical practice, with the notable exception of the EZH2 inhibitor tazemetostat in EZH2-mutant FL. Here we examined whether gene mutation status predicts response to clinical mTOR inhibitors (mTORi) in FL, by performing targeted mutational profiling of biopsies from 21 relapsed/refractory FL patients treated with mTORi everolimus or temsirolimus within clinical trials. We observed an enrichment of mutations within the catalytic histone acetyltransferase (HAT) domain of CREBBP in mTORi-responders, and describe distinct transcriptional characteristics and co-occurring mutations of FL harbouring these mutations; reinforcing the growing appreciation of CREBBPHAT mutation as a key biological determinant and its promise as a therapeutic biomarker in FL.

Leveraging Spaceflight to Advance Cardiovascular Research on Earth.

The direct (eg, radiation, microgravity) and indirect (eg, lifestyle perturbations) effects of spaceflight extend across multiple systems resulting in whole-organism cardiovascular deconditioning. For over 50 years, National Aeronautics and Space Administration has continually enhanced a countermeasures program designed to characterize and offset the adverse cardiovascular consequences of spaceflight. In this review, we provide a historical overview of research evaluating the effects of spaceflight on cardiovascular health in astronauts and outline mechanisms underpinning spaceflight-related cardiovascular alterations. We also discuss how spaceflight could be leveraged for aging, industry, and model systems such as human induced pluripotent stem cell-derived cardiomyocytes, organoid, and organ-on-a-chip technologies. Finally, we outline the increasing opportunities for scientists and clinicians to engage in cardiovascular research in space and on Earth.

Feasibility and acceptability of a parent-child intervention to improve step count in childhood cancer survivors exposed to cardiotoxic therapy: The STEP UP for FAMILIES Study.

BACKGROUND: Late morbidity after childhood cancer may be mitigated by healthy lifestyle behaviors. We piloted a game-based, parent-child digital intervention to increase activity in sedentary survivors. METHODS: Survivors aged 10-16 treated with cardiotoxic therapy and not meeting US physical activity guidelines were enrolled in a single-arm study with a parent. Following a 14-day run-in, participants chose a prespecified step goal and wore an accelerometer daily for 24 weeks (12-week game-based intervention; 12-week follow-up). Participants completed the Acceptability of Intervention Measure (AIM) at 24 weeks; a subset of dyads completed qualitative interviews. RESULTS: Among 129 eligible survivors, 27 enrolled (20.9% participation rate) with a parent. Four dyads were removed during the 14-day run-in period due to noncompliance. Among the 23 dyads who continued to the study, the tracker was worn for 95% of days during the 12-week intervention (95% confidence interval [CI]: 94-96) and 81% during the 12-week follow-up (95% CI: 79-82). Overall, the prespecified step goal was met for 64% (95% CI: 63-66) of days during the intervention and 37% (95% CI: 35-38) during the follow-up. At the end of study, 17/23 dyads responded to AIM; 82% of survivors and 94% of parents reported the intervention as acceptable. During qualitative interviews (n = 5), dyads noted that they liked the accountability of the "buddy system," but would have liked more personalized goal-setting. CONCLUSIONS: Despite high ratings of acceptability among participants, difficulties with sustained adherence and retention were encountered in this parent-child gamification intervention. Alternate, tailored designs should be considered in the future.

Developing a typology of interventions to support doctors' mental health and wellbeing.

BACKGROUND: The problem of mental ill-health in doctors is complex, accentuated by the COVID-19 pandemic, and impacts on healthcare provision and broader organisational performance. There are many interventions to address the problem but currently no systematic way to categorise them, which makes it hard to describe and compare interventions. As a result, implementation tends to be unfocussed and fall short of the standards developed for implementing complex healthcare interventions. This study aims to develop: 1) a conceptual typology of workplace mental health and wellbeing interventions and 2) a mapping tool to apply the typology within research and practice. METHODS: Typology development was based on iterative cycles of analysis of published and in-practice interventions, incorporation of relevant theories and frameworks, and team and stakeholder group discussions. RESULTS: The newly developed typology and mapping tool enable interventions to be conceptualised and/or mapped into different categories, for example whether they are designed to be largely preventative (by either improving the workplace or increasing personal resources) or to resolve problems after they have arisen. Interventions may be mapped across more than one category to reflect the nuance and complexity in many mental health and wellbeing interventions. Mapping of interventions indicated that most publications have not clarified their underlying assumptions about what causes outcomes or the theoretical basis for the intervention. CONCLUSION: The conceptual typology and mapping tool aims to raise the quality of future research and promote clear thinking about the nature and purpose of interventions, In doing so it aims to support future research and practice in planning interventions to improve the mental health and wellbeing of doctors.

Timing of exercise therapy when initiating adjuvant chemotherapy for breast cancer: a randomized trial.

AIMS: The most appropriate timing of exercise therapy to improve cardiorespiratory fitness (CRF) among patients initiating chemotherapy is not known. The effects of exercise therapy administered during, following, or during and following chemotherapy were examined in patients with breast cancer. METHODS AND RESULTS: Using a parallel-group randomized trial design, 158 inactive women with breast cancer initiating (neo)adjuvant chemotherapy were allocated to receive (1:1 ratio): usual care or one of three exercise regimens-concurrent (during chemotherapy only), sequential (after chemotherapy only), or concurrent and sequential (continuous) (n = 39/40 per group). Exercise consisted of treadmill walking three sessions/week, 20-50 min at 55%-100% of peak oxygen consumption (VO2peak) for ≈16 (concurrent, sequential) or ≈32 (continuous) consecutive weeks. VO2peak was evaluated at baseline (pre-treatment), immediately post-chemotherapy, and ≈16 weeks after chemotherapy. In intention-to-treat analysis, there was no difference in the primary endpoint of VO2peak change between concurrent exercise and usual care during chemotherapy vs. VO2peak change between sequential exercise and usual care after chemotherapy [overall difference, -0.88 mL O2·kg-1·min-1; 95% confidence interval (CI): -3.36, 1.59, P = 0.48]. In secondary analysis, continuous exercise, approximately equal to twice the length of the other regimens, was well-tolerated and the only strategy associated with significant improvements in VO2peak from baseline to post-intervention (1.74 mL O2·kg-1·min-1, P < 0.001). CONCLUSION: There was no statistical difference in CRF improvement between concurrent vs. sequential exercise therapy relative to usual care in women with primary breast cancer. The promising tolerability and CRF benefit of ≈32 weeks of continuous exercise therapy warrant further evaluation in larger trials.

Literacy and signing deaf students: a multi-national scoping review.

Many literature reviews or other types of reviews (e.g., meta-analyses, scoping reviews) in deaf education research are focused upon primarily or exclusively research that is performed in U.S. contexts or English-speaking contexts only. However, research that is conducted in non-English-speaking, non-U.S. settings that may be more likely to be multilingual, has value for our understanding of how deaf students using multiple languages may develop literacy skills. The objective of this review was to explore the literature on literacy development with deaf learners conducted outside of English-speaking contexts that has been published in English, Portuguese, or Spanish. We identified 13 English-language articles, 9 Portuguese-language articles, and 0 Spanish articles that met inclusion criteria. From these articles, we glean important insights into the reading process, including the teaching of subskills of reading, writing instruction, early literacy experiences, and the potential relationship between signed languages and literacy. We also note the need for multiple, converging sources of evidence and the value of an asset-driven approach to understanding deaf learners.

Exercise Associated with Cognitive Function in Older Men with Prostate Cancer Undergoing Androgen Deprivation Therapy.

BACKGROUND: To examine associations between exercise and cognitive function in older men undergoing hormone therapy for prostate cancer. METHOD: Men ≥ 65 years old with prostate cancer, currently undergoing androgen deprivation therapy for ≥ 6 months (n = 50), completed the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and standard neuropsychological tests. Pearson's correlations and linear regressions were used to examine associations between exercise and cognitive performance. RESULTS: Exercise was significantly positively correlated with performance on tests of memory, attention, and executive function. Linear regressions showed that when controlling for age and education, exercise remained a significant predictor of attention and executive function performance (p < 0.05), and showed moderate, but statistically non-significant effects on memory performance (p < 0.10). CONCLUSION: Greater exercise is associated with better functioning in multiple cognitive domains in men with prostate cancer undergoing hormone therapy, providing proof-of-concept evidence that exercise may be a feasible intervention to limit cognitive dysfunction in prostate cancer patients.

NICU Visitation Time and Adherence to Safe Sleep Practices Among Mothers of Very Preterm Infants.

BACKGROUND: Sleep-associated infant death is the leading cause of postneonatal mortality in the United States. Preterm infants are at higher risk for sleep-associated death, but maternal adherence to safe sleep practices is lower than for mothers of full-term infants. Data are lacking on whether maternal neonatal intensive care unit (NICU) visitation time impacts safe sleep compliance after hospital discharge. PURPOSE: For mothers of preterm infants, to investigate the association of time days per week spent in the NICU and adherence to safe sleep practices after discharge. METHODS: A prospective observational study of 109 mothers with infants born at less than 32 weeks from 4 Colorado NICUs who completed a survey at 6 weeks after discharge about infant sleep practices. Maternal time spent in the NICU was defined as the average number of days spent in the NICU per week of infant hospitalization, as documented in the electronic medical record. Multivariable logistic regression models assessed the relationship between time in the NICU and safe sleep adherence. Covariates included maternal/infant characteristics significant at P < .2 level in bivariate analysis. RESULTS: Predictors of compliance with all safe infant sleep practices included public/no insurance compared with private insurance (adjusted odds ratio [AOR] 0.29; 95% confidence interval [CI] 0.09-0.96), some college/associate-level education versus bachelor's degree (AOR 5.88; 95% CI 1.21-28.67), and depression/anxiety symptoms (AOR 0.37; 95% CI 0.14-0.97). NICU visitation days was not associated with adherence to safe sleep practices. IMPLICATIONS FOR PRACTICE AND RESEARCH: Maternal visitation days was not associated with adherence to safe infant sleep practices after discharge, highlighting the need to identify barriers and facilitators to engaging families about SUID risk-reducing behaviors.

Theoretical and Experimental Investigation of Functionalized Cyanopyridines Yield an Anolyte with an Extremely Low Reduction Potential for Nonaqueous Redox Flow Batteries.

Cyanopyridines and cyanophenylpyridines were investigated as anolytes for nonaqueous redox flow batteries (RFBs). The three isomers of cyanopyridine are reduced at potentials of -2.2 V or lower vs. ferrocene+/0 (Fc+/0 ), but the 3-CNPy⋅- radical anion forms a sigma-dimer that is re-oxidized at E≈-1.1 V, which would lead to poor voltaic efficiency in a RFB. Bulk electrochemical charge-discharge cycling of the cyanopyridines in acetonitrile and 0.50 M [NBu4 ][PF6 ] shows that 2-CNPy and 4-CNPy lose capacity quickly under these conditions, due to irreversible chemical reaction/decomposition of the radical anions. Density-functional theory (DFT) calculations indicated that adding a phenyl group to the cyanopyridines would, for some isomers, limit dimerization and improve the stability of the radical anions, while shifting their E1/2 only about +0.10 V relative to the parent cyanopyridines. Among the cyanophenylpyridines, 3-CN-6-PhPy and 3-CN-4-PhPy are the most promising as anolytes. They exhibit reversible reductions at E1/2 =-2.19 and -2.22 V vs. ferrocene+/0 , respectively, and retain about half of their capacity after 30 bulk charge-discharge cycles. An improved version of 3-CN-6-PhPy with three methyl groups (3-cyano-4-methyl-6-(3,5-dimethylphenyl)pyridine) has an extremely low reduction potential of -2.50 V vs. Fc+/0 (the lowest reported for a nonaqueous RFB anolyte) and loses only 0.21 % of capacity per cycle during charge-discharge cycling in acetonitrile.

Comparisons of Three Measures of Maternal Engagement Activities in the Neonatal Intensive Care Unit.

BACKGROUND: Mothers' engagement with their hospitalized preterm infant(s) is recognized as an important aspect of treatment in neonatal intensive care units (NICUs). However, no gold standard exists for measuring maternal engagement, and the various methods used to measure mothers' time have documented limitations. OBJECTIVES: This study sought to compare three measurement methods of maternal engagement (a five-item maternal cross-sectional survey, time use diaries, and electronic health records [EHRs]) to identify whether these methods capture consistent data and patterns in detected differences in measures of engagement. METHODS: Maternal engagement was defined as time spent visiting the infant in the NICU (presence), holding (blanket holding in the mother's arms or by kangaroo care [KC]), and caregiving (e.g., bathing and changing diapers). The survey estimating daily maternal engagement was administered in two Level III NICUs and one Level IV NICU at study enrollment, at least 2 weeks after admission. Mothers then completed the daily time use diaries until infant discharge. Data were also collected from participants' EHRs, charted by nursing staff. Wilcoxon signed-rank tests were used for pairwise analysis of the three measures for maternal engagement activities. RESULTS: A total of 146 participants had data across all three measurement types and were included in the analysis. In the Level III NICUs (n = 101), EHR data showed significantly more time spent with all engagement activities than the diary data. In the Level IV data, only differences in time holding were significant when comparing EHR data with survey data, with mothers reporting more time doing KC and less time blanket holding. Comparison of EHR data with diary data showed more time in all activities except KC. DISCUSSION: In most cases, time spent in engagement activities measured in the EHR was higher than in the surveys or time use diaries. Accuracy of measurements could not be determined because of limitations in data collection, and there is no gold standard for comparison. Nevertheless, findings contribute to ongoing efforts to develop the most valuable and accurate strategies for measuring maternal engagement-a significant predictor of maternal and infant health.

Are genetic counselors prepared to counsel active-duty service members? A survey of genetic counselors' self-efficacy, counseling techniques, and knowledge of military policy.

Given the expected rise in genomic sequencing projects within the US Military and the increased availability of genetic testing to the United States as a whole, current and prospective active-duty service members (SMs) may undergo genetic counseling services in the civilian sector for pre-test and post-test counseling. The overall goal of this study was to better understand genetic counselors' preparedness to address military-specific policies and psychosocial needs of patients from this underrepresented population. Members of the National Society of Genetic Counselors were asked to complete a four-part survey including demographic information, Likert scale questions to separately rate self-efficacy when working with civilians and SMs, case scenarios with multiple-choice options and open-ended responses to assess knowledge of military policy, and open-ended questions regarding psychosocial scenarios related to military service. Eighty-eight responses were analyzed using Microsoft Office Excel for the qualitive thematic analysis and SPSS/RStudio for the quantitative data. While over 75% (n = 69/88, SD = 0.48) of surveyed genetic counselors scored 4 of 4 on knowledge of military policy and reported similarly high levels of self-efficacy when working with SMs (mean = 26.77 out of 30, SD = 4.15) and the general population (mean = 27.99 out of 30, SD = 4.31), the qualitative data suggested an alternative perspective. Up to 57% (n = 50/88) of responses were scored as expressing low confidence concerning knowledge of military policy. One potential explanation for this uncertainty may be due to participants reporting that they never (69.32% (n = 61/88]) or are unsure if (12.50% (n = 11/88]) they received training related to providing counseling services to SMs. We suggest the establishment of educational initiatives for genetic counselors focusing on how to discuss genetic testing with SMs in relation to their health and safety, well-being, and potential employment implications.

Word-Level Instruction for Deaf and Hard-of-Hearing Students: An Observation Study.

Despite the fact that children's word reading and spelling skills are crucial for developing text-level comprehension and composition, little is known about what teachers do in classrooms to promote deaf and hard-of-hearing (DHH) students' learning of word reading and spelling. This observational study examined strategies teachers of DHH students used when teaching word reading and spelling to DHH students who used spoken English. One day of language arts instruction in 23 kindergartens through second-grade classrooms was observed. Teachers' word-level instruction was coded. Results indicated that teachers spent substantially more time on word-level instruction during decoding and encoding contexts than they did during text reading and writing contexts. In addition, differences were found in teachers' use of strategies depending on the instructional contexts. Teachers utilized phonological strategies considerably more frequently than any other strategy in their word-level instruction.

Effects of Exercise Therapy Dosing Schedule on Impaired Cardiorespiratory Fitness in Patients With Primary Breast Cancer: A Randomized Controlled Trial.

BACKGROUND: Current exercise guidelines for clinical populations recommend an exercise therapy (ET) prescription of fixed intensity (moderate), duration (40-50 minutes per session), and volume (120-160 min/wk). A critical overarching element of exercise programming that has received minimal attention is dose scheduling. We investigated the tolerability and efficacy of 2 exercise training dose regimens on cardiorespiratory fitness and patient-reported outcomes in patients with posttreatment primary breast cancer. METHODS: Using a parallel-group randomized trial, we randomly allocated 174 postmenopausal patients (2.8 years after adjuvant therapy) with impaired peak oxygen consumption (VO2peak) to 1 of 2 supervised exercise training interventions delivered with a standard linear (LET) (fixed dose intensity per session for 160 min/wk) or nonlinear (NLET) (variable dose intensity per session for ≈120 min/wk) schedule compared with a stretching attention control group for 16 consecutive weeks. Stretching was matched to exercise dosing arms on the basis of location, frequency, duration, and treatment length. The primary end point was change in VO2peak (mL O2·kg-1·min-1) from baseline to after intervention. Secondary end points were patient-reported outcomes, tolerability, and safety. RESULTS: No serious adverse events were observed. Mean attendance was 64%, 75%, and 80% for attention control, LET, and NLET, respectively. In intention-to-treat analysis, VO2peak increased 0.6±1.7 mL O2·kg-1·min-1 (P=0.05) and 0.8±1.8 mL O2·kg-1·min-1 (P=0.07) in LET and NLET, respectively, compared with attention control. Change in VO2peak ranged from -2.7 to 4.1 mL O2·kg-1·min-1 and from -3.6 to 5.1 mL O2·kg-1·min-1 in LET and NLET, respectively. Approximately 40% of patients in both exercise dosing regimens were classified as VO2peak responders (ie, Δ ≥1.32 mL O2·kg-1·min-1). NLET improved all patient-reported outcomes compared with attention control. CONCLUSIONS: Short-term exercise training, independently of dosing schedule, is associated with modest improvements in cardiorespiratory fitness in patients previously treated for early-stage breast cancer. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01186367.

Vitamin D Receptor Activation in Liver Macrophages Protects Against Hepatic Endoplasmic Reticulum Stress in Mice.

BACKGROUND AND AIMS: Hepatic endoplasmic reticulum (ER) stress, whether triggered by intrinsic or extrinsic factors, can be resolved by the unfolded protein response (UPR). Sustained UPR activation leads to cell death and inflammatory response and contributes to liver disease progression. Hepatic tissue macrophages are key players in orchestrating liver inflammation, and ER stress can enhance macrophage activation. However, it is not well defined how the interplay between ER stress and inflammation is regulated during hepatic stress response. APPROACH AND RESULTS: Here we demonstrate that vitamin D receptor (VDR) activation mitigates hepatic ER stress response, whereas VDR knockout mice undergo persistent UPR activation and apoptosis in response to chemical ER stress inducer. Moreover, VDR deficiency promotes hepatic macrophage infiltration and increases gene expression and systematic levels of proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor α. VDR expression is induced in hepatic macrophages by ER stress, and VDR plays a dual regulatory role in macrophages by protecting against ER stress and promoting anti-inflammatory polarization. Co-culture with VDR-activated bone marrow-derived macrophages suppresses UPR target genes in primary hepatocytes treated with ER stress inducers. Thus, the immunomodulatory functions of VDR in macrophages are critical in hepatic ER stress resolution in mice. CONCLUSIONS: VDR signaling in macrophages regulates a shift between proinflammatory and anti-inflammatory activation during ER stress-induced inflammation to promote hepatic ER stress resolution.

Vitamin D Receptor Activation in Liver Macrophages Ameliorates Hepatic Inflammation, Steatosis, and Insulin Resistance in Mice.

BACKGROUND AND AIMS: Obesity-induced chronic inflammation is a key component in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Increased secretion of proinflammatory cytokines by macrophages in metabolic tissues promotes disease progression. In the diet-induced obesity (DIO) mouse model, activation of liver resident macrophages, or Kupffer cells (KCs), drives inflammatory responses, which recruits circulating macrophages and promotes fatty liver development, and ultimately contributes to impaired hepatic insulin sensitivity. Hepatic macrophages express the highest level of vitamin D receptors (VDRs) among nonparenchymal cells, whereas VDR expression is very low in hepatocytes. VDR activation exerts anti-inflammatory effects in immune cells. APPROACH AND RESULTS: Here we found that VDR activation exhibits strong anti-inflammatory effects in mouse hepatic macrophages, including those isolated from DIO livers, and mice with genetic loss of Vdr developed spontaneous hepatic inflammation at 6 months of age. Under the chronic inflammation conditions of the DIO model, VDR activation by the vitamin D analog calcipotriol reduced liver inflammation and hepatic steatosis, significantly improving insulin sensitivity. The hyperinsulinemic euglycemic clamp revealed that VDR activation greatly increased the glucose infusion rate, while hepatic glucose production was remarkably decreased. Glucose uptake in muscle and adipose did not show similar effects, suggesting that improved hepatic insulin sensitivity is the primary contributor to the beneficial effects of VDR activation. Finally, specifically ablating liver macrophages by treatment with clodronate liposomes largely abolished the beneficial metabolic effects of calcipotriol, confirming that VDR activation in liver macrophages is required for the antidiabetic effect. CONCLUSIONS: Activation of liver macrophage VDRs by vitamin D ligands ameliorates liver inflammation, steatosis and insulin resistance. Our results suggest therapeutic paradigms for treatment of NAFLD and type 2 diabetes mellitus.

Promoting cultural awareness, professionalism, and communication skills in medicine through anatomy: The Deaf culture session.

The anatomy curriculum is a place where professionalism can be learned and practiced, including training in cultural competence and communication skills for working with diverse populations. One population that has received little attention in terms of medical education are d/Deaf and hard of hearing (d/DHH) patients, although there is much evidence to support health care disparities in this population. Several major contributing factors include differing views of deafness between medical professionals and those who are culturally Deaf, a lack of understanding of Deaf culture and American Sign Language (ASL) by medical professionals, a lack of educational resources in ASL, and poor experiences in health care. To address this need, a Deaf Culture Applied Anatomy session was incorporated into the first-year curriculum at Morehouse School of Medicine while medical students were studying anatomy of the ear and hearing. Panelists, who were culturally Deaf, hard of hearing, and hearing children of deaf adults, shared their experiences in healthcare, including challenges they faced with communication and care. Surveys were provided to students before and after the panel session. Surveys indicated a lack of knowledge prior to this session, while also demonstrating that this 90-min session improved students' understanding of effective communication with future patients and issues related to deafness. Qualitative feedback also suggested that the students found the session to be personally and professionally beneficial. Implementing the Deaf Culture session was an effective means for introducing students to Deaf culture and working with d/DHH patients.

Evaluation of a delirium awareness podcast for undergraduate nursing students in Northern Ireland: a pre-/post-test study.

BACKGROUND: Delirium is a common disorder affecting several people in primary, secondary, and tertiary settings. The condition is frequently under-diagnosed leading to long-lasting physical and cognitive impairment or premature death. Despite this, there has been limited research on the impact of innovative approaches to delirium education amongst undergraduate nursing students. The aim of this study was to evaluate the effect of a delirium awareness podcast on undergraduate nursing student knowledge and confidence related to the condition in Northern Ireland. METHODS: The intervention was a 60-min delirium awareness podcast, available throughout May 2020, to a convenience sample of year one undergraduate nursing students (n = 320) completing a BSc Honours Nursing degree programme in a Northern Ireland University. The podcast focused on how nursing students could effectively recognise, manage, and prevent delirium. Participants had a period of 4 weeks to listen to the podcast and complete the pre and post questionnaires. The questionnaires were comprised of a 35-item true-false Delirium Knowledge Questionnaire (DKQ), a 3-item questionnaire about professional confidence and a 7-item questionnaire evaluating the use of podcasting as an approach to promote knowledge and confidence about delirium. Data were analysed using paired t-tests and descriptive statistics. RESULTS: Students improved across all three core areas in the post-test questionnaire, demonstrating improvements in knowledge about symptoms of delirium (7.78% increase), causes and risk factors of delirium (13.34% increase) and management of delirium (12.81% increase). In relation to perceived confidence, students reported a 46.50% increase in confidence related to recognition of delirium, a 48.32% increase in relation to delirium management and a 50.71% increase their ability to communicate about delirium. Both questionnaires were statistically significant (P < 0.001). The final questionnaire illustrated that nursing students positively evaluated the use of podcast for promoting their knowledge and confidence about delirium and 96.32% of nursing students believed that the podcast met their learning needs about delirium. CONCLUSIONS: A 60-min podcast on delirium improved first year student nurse knowledge about delirium. Nursing students also expressed that this approach to delirium education was effective in their learning about the condition.