Quantitative Assessment of Morphological Changes in Lipid Droplets and Lipid-Mito Interactions with Aging in Brown Adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LD) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. Particularly, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Analysis showed reductions in LD volume, area, and perimeter in aged samples compared to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for mitochondria interacting with LD lipids. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology and mitochondrial functionality, metabolism, and bioactivity in aged BAT.

Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting.

BACKGROUND AND AIMS: A cardiovascular disease polygenic risk score (CVD-PRS) can stratify individuals into different categories of cardiovascular risk, but whether the addition of a CVD-PRS to clinical risk scores improves the identification of individuals at increased risk in a real-world clinical setting is unknown. METHODS: The Genetics and the Vascular Health Check Study (GENVASC) was embedded within the UK National Health Service Health Check (NHSHC) programme which invites individuals between 40-74 years of age without known CVD to attend an assessment in a UK general practice where CVD risk factors are measured and a CVD risk score (QRISK2) is calculated. Between 2012-2020, 44,141 individuals (55.7% females, 15.8% non-white) who attended an NHSHC in 147 participating practices across two counties in England were recruited and followed. When 195 individuals (cases) had suffered a major CVD event (CVD death, myocardial infarction or acute coronary syndrome, coronary revascularisation, stroke), 396 propensity-matched controls with a similar risk profile were identified, and a nested case-control genetic study undertaken to see if the addition of a CVD-PRS to QRISK2 in the form of an integrated risk tool (IRT) combined with QRISK2 would have identified more individuals at the time of their NHSHC as at high risk (QRISK2 10-year CVD risk of ≥10%), compared with QRISK2 alone. RESULTS: The distribution of the standardised CVD-PRS was significantly different in cases compared with controls (cases mean score .32; controls, -.18, P = 8.28×10-9). QRISK2 identified 61.5% (95% confidence interval [CI]: 54.3%-68.4%) of individuals who subsequently developed a major CVD event as being at high risk at their NHSHC, while the combination of QRISK2 and IRT identified 68.7% (95% CI: 61.7%-75.2%), a relative increase of 11.7% (P = 1×10-4). The odds ratio (OR) of being up-classified was 2.41 (95% CI: 1.03-5.64, P = .031) for cases compared with controls. In individuals aged 40-54 years, QRISK2 identified 26.0% (95% CI: 16.5%-37.6%) of those who developed a major CVD event, while the combination of QRISK2 and IRT identified 38.4% (95% CI: 27.2%-50.5%), indicating a stronger relative increase of 47.7% in the younger age group (P = .001). The combination of QRISK2 and IRT increased the proportion of additional cases identified similarly in women as in men, and in non-white ethnicities compared with white ethnicity. The findings were similar when the CVD-PRS was added to the atherosclerotic cardiovascular disease pooled cohort equations (ASCVD-PCE) or SCORE2 clinical scores. CONCLUSIONS: In a clinical setting, the addition of genetic information to clinical risk assessment significantly improved the identification of individuals who went on to have a major CVD event as being at high risk, especially among younger individuals. The findings provide important real-world evidence of the potential value of implementing a CVD-PRS into health systems.

A review of undergraduate research programs aimed at underrepresented students.

It is well-understood that the science, technology, engineering, and mathematics (STEM) fields have unique challenges that discourage recruiting and retaining underrepresented minorities. Research programs aimed at undergraduates have arisen as a critical mechanism for fostering innovation and addressing the challenges faced by underrepresented minorities. Here, we review various undergraduate research programs designed to provide exposure to undergraduates, with a focus on underrepresented minorities in STEM disciplines. We provide insight into selected programs' objectives, key features, potential limitations, and outcomes. We also offer recommendations for future improvements of each research program, particularly in the context of mentorship. These programs range from broad-reaching initiatives (e.g., Leadership Alliance) to more specific programs targeting underrepresented students. By offering a nuanced understanding of each program's structure, we seek to provide a brief overview of the landscape of diversity-focused STEM initiatives and a guide on how to run a research program effectively.

Optimising the diagnostic accuracy of First post-contrAst SubtracTed breast MRI (FAST MRI) through interpretation-training: a multicentre e-learning study, mapping the learning curve of NHS Breast Screening Programme (NHSBSP) mammogram readers using an enriched dataset.

BACKGROUND: Abbreviated breast MRI (FAST MRI) is being introduced into clinical practice to screen women with mammographically dense breasts or with a personal history of breast cancer. This study aimed to optimise diagnostic accuracy through the adaptation of interpretation-training. METHODS: A FAST MRI interpretation-training programme (short presentations and guided hands-on workstation teaching) was adapted to provide additional training during the assessment task (interpretation of an enriched dataset of 125 FAST MRI scans) by giving readers feedback about the true outcome of each scan immediately after each scan was interpreted (formative assessment). Reader interaction with the FAST MRI scans used developed software (RiViewer) that recorded reader opinions and reading times for each scan. The training programme was additionally adapted for remote e-learning delivery. STUDY DESIGN: Prospective, blinded interpretation of an enriched dataset by multiple readers. RESULTS: 43 mammogram readers completed the training, 22 who interpreted breast MRI in their clinical role (Group 1) and 21 who did not (Group 2). Overall sensitivity was 83% (95%CI 81-84%; 1994/2408), specificity 94% (95%CI 93-94%; 7806/8338), readers' agreement with the true outcome kappa = 0.75 (95%CI 0.74-0.77) and diagnostic odds ratio = 70.67 (95%CI 61.59-81.09). Group 1 readers showed similar sensitivity (84%) to Group 2 (82% p = 0.14), but slightly higher specificity (94% v. 93%, p = 0.001). Concordance with the ground truth increased significantly with the number of FAST MRI scans read through the formative assessment task (p = 0.002) but by differing amounts depending on whether or not a reader had previously attended FAST MRI training (interaction p = 0.02). Concordance with the ground truth was significantly associated with reading batch size (p = 0.02), tending to worsen when more than 50 scans were read per batch. Group 1 took a median of 56 seconds (range 8-47,466) to interpret each FAST MRI scan compared with 78 (14-22,830, p < 0.0001) for Group 2. CONCLUSIONS: Provision of immediate feedback to mammogram readers during the assessment test set reading task increased specificity for FAST MRI interpretation and achieved high diagnostic accuracy. Optimal reading-batch size for FAST MRI was 50 reads per batch. Trial registration (25/09/2019): ISRCTN16624917.

Follow-up after major traumatic injury: a survey of services in Australian and New Zealand public hospitals.

BACKGROUND: Increased survival from traumatic injury has led to a higher demand for follow-up care when patients are discharged from hospital. It is currently unclear how follow-up care following major trauma is provided to patients, and how, when, and to whom follow-up services are delivered. The aim of this study was to describe the current follow-up care provided to patients and their families who have experienced major traumatic injury in Australia and New Zealand (ANZ). METHODS: Informed by Donabedian's 'Evaluating the Quality of Medical Care' model and the Institute of Medicine's Six Domains of Healthcare Quality, a cross-sectional online survey was developed in conjunction with trauma experts. Their responses informed the final survey which was distributed to key personnel in 71 hospitals in Australia and New Zealand that (i) delivered trauma care to patients, (ii) provided data to the Australasian Trauma Registry, or (iii) were a Trauma Centre. RESULTS: Data were received from 38/71 (53.5%) hospitals. Most were Level 1 trauma centres (n = 23, 60.5%); 76% (n = 16) follow-up services were permanently funded. Follow-up services were led by a range of health professionals with over 60% (n = 19) identifying as trauma specialists. Patient inclusion criteria varied; only one service allowed self-referral (3.3%). Follow-up was within two weeks of acute care discharge in 53% (n = 16) of services. Care activities focused on physical health; psychosocial assessments were the least common. Most services provided care for adults and paediatric trauma (60.5%, n = 23); no service incorporated follow-up for family members. Evaluation of follow-up care was largely as part of a health service initiative; only three sites stated evaluation was specific to trauma follow-up. CONCLUSION: Follow-up care is provided by trauma specialists and predominantly focuses on the physical health of the patients affected by major traumatic injury. Variations exist in terms of patient selection, reason for follow-up and care activities delivered with gaps in the provision of psychosocial and family health services identified. Currently, evaluation of trauma follow-up care is limited, indicating a need for further development to ensure that the care delivered is safe, effective and beneficial to patients, families and healthcare organisations.

Ablation of Sam50 is associated with fragmentation and alterations in metabolism in murine and human myotubes.

The sorting and assembly machinery (SAM) Complex is responsible for assembling ß-barrel proteins in the mitochondrial membrane. Comprising three subunits, Sam35, Sam37, and Sam50, the SAM complex connects the inner and outer mitochondrial membranes by interacting with the mitochondrial contact site and cristae organizing system complex. Sam50, in particular, stabilizes the mitochondrial intermembrane space bridging (MIB) complex, which is crucial for protein transport, respiratory chain complex assembly, and regulation of cristae integrity. While the role of Sam50 in mitochondrial structure and metabolism in skeletal muscle remains unclear, this study aims to investigate its impact. Serial block-face-scanning electron microscopy and computer-assisted 3D renderings were employed to compare mitochondrial structure and networking in Sam50-deficient myotubes from mice and humans with wild-type (WT) myotubes. Furthermore, autophagosome 3D structure was assessed in human myotubes. Mitochondrial metabolic phenotypes were assessed using Gas Chromatography-Mass Spectrometry-based metabolomics to explore differential changes in WT and Sam50-deficient myotubes. The results revealed increased mitochondrial fragmentation and autophagosome formation in Sam50-deficient myotubes compared to controls. Metabolomic analysis indicated elevated metabolism of propanoate and several amino acids, including ß-Alanine, phenylalanine, and tyrosine, along with increased amino acid and fatty acid metabolism in Sam50-deficient myotubes. Furthermore, impairment of oxidative capacity was observed upon Sam50 ablation in both murine and human myotubes, as measured with the XF24 Seahorse Analyzer. Collectively, these findings support the critical role of Sam50 in establishing and maintaining mitochondrial integrity, cristae structure, and mitochondrial metabolism. By elucidating the impact of Sam50-deficiency, this study enhances our understanding of mitochondrial function in skeletal muscle.

Methods to Utilize Pulse Wave Velocity to Measure Alterations in Cerebral and Cardiovascular Parameters.

Alzheimer's Disease (AD) is a global health issue, affecting over 6 million in the United States, with that number expected to increase as the aging population grows. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. However, the study of cerebrovascular techniques for AD is still evolving. Here, we provide reproducible methods to measure impedance-based pulse wave velocity (PWV), a marker of arterial stiffness, in the systemic vascular (aortic PWV) and in the cerebral vascular (cerebral PWV) systems. Using aortic impedance and this relatively novel technique of cerebral impedance to comprehensively describe the systemic vascular and the cerebral vascular systems, we examined the sex-dependent differences in 5x transgenic mice (5XFAD) with AD under normal and high-fat diet, and in wild-type mice under a normal diet. Additionally, we validated our method for measuring cerebrovascular impedance in a model of induced stress in 5XFAD. Together, our results show that sex and diet differences in wildtype and 5XFAD mice account for very minimal differences in cerebral impedance. Interestingly, 5XFAD, and not wildtype, male mice on a chow diet show higher cerebral impedance, suggesting pathological differences. Opposingly, when we subjected 5XFAD mice to stress, we found that females showed elevated cerebral impedance. Using this validated method of measuring impedance-based aortic and cerebral PWV, future research may explore the effects of modifying factors including age, chronic diet, and acute stress, which may mediate cardiovascular risk in AD. New and Noteworthy: Here, we presented a new technique which is an application of the concept of aortic impedance to determining cerebral impedance. While aortic PWV is typically utilized to study aortic stiffness, we also developed a technique of cerebral PWV to study cerebral vascular stiffness. This method may be useful in improving the rigor of studies that seek to have a dual focus on cardiovascular and cerebral function.

Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure.

PURPOSE OF REVIEW: Hypertension is a principal risk factor for cardiovascular morbidity and mortality, with its severity exacerbated by high sodium intake, particularly in individuals with salt-sensitive blood pressure. However, the mechanisms underlying hypertension and salt sensitivity are only partly understood. Herein, we review potential interactions in hypertension pathophysiology involving the immune system, endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and proteostasis pathways; identify knowledge gaps; and discuss future directions. RECENT FINDINGS: Recent advancements by our research group and others reveal interactions within and between adaptive and innate immune responses in hypertension pathophysiology. The salt-immune-hypertension axis is further supported by the discovery of the role of dendritic cells in hypertension, marked by isolevuglandin (IsoLG) formation. Alongside these broadened understandings of immune-mediated salt sensitivity, the contributions of T cells to hypertension have been recently challenged by groups whose findings did not support increased resistance of Rag-1-deficient mice to Ang II infusion. Hypertension has also been linked to ER stress and the UPR. Notably, a holistic approach is needed because the UPR engages in crosstalk with autophagy, the ubiquitin proteasome, and other proteostasis pathways, that may all involve hypertension. There is a critical need for studies to establish cause and effect relationships between ER stress and the UPR in hypertension pathophysiology in humans and to determine whether the immune system and ER stress function mainly to exacerbate or initiate hypertension and target organ injury. This review of recent studies proposes new avenues for future research for targeted therapeutic interventions.

Patient-Led, Technology-Assisted Malnutrition Risk Screening in Hospital: A Feasibility Study.

Malnutrition risk screening is crucial to identify at-risk patients in hospitals; however, screening rates can be suboptimal. This study evaluated the feasibility, acceptability, and potential cost-effectiveness of patient-led, technology-assisted malnutrition risk screening. A prospective multi-methods study was conducted in a 750-bed public hospital in Australia. Patients were recruited from seven wards and asked to complete an electronic version of the Malnutrition Screening Tool (e-MST) on bedside computer screens. Data were collected on feasibility, acceptability, and cost. Feasibility data were compared to pre-determined criteria on recruitment (≥50% recruitment rate) and e-MST completion (≥75% completion rate). Quantitative acceptability (survey) data were analyzed descriptively. Patient interview data were analyzed thematically. The economic evaluation was from the perspective of the health service using a decision tree analytic model. Both feasibility criteria were met; the recruitment rate was 78% and all 121 participants (52% male, median age 59 [IQR 48-69] years) completed the e-MST. Patient acceptability was high. Patient-led e-MST was modeled to save $3.23 AUD per patient and yield 6.5 more true malnutrition cases (per 121 patients) with an incremental cost saving per additional malnutrition case of 0.50 AUD. Patient-led, technology-assisted malnutrition risk screening was found to be feasible, acceptable to patients, and cost-effective (higher malnutrition yield and less costly) compared to current practice at this hospital.

Strategies for inducing and validating zinc deficiency and zinc repletion.

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.NEW & NOTEWORTHY This methods paper details dietary approaches to alter zinc homeostasis in rodents and qualitative and quantitative methods to ensure the zinc status of experimental animals. The outlined accessible and cost-effective protocol will elevate scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of a multitude of health conditions and diseases.

Co-design of an intervention to improve patient participation in discharge medication communication.

Patients can experience medication-related harm and hospital readmission because they do not understand or adhere to post-hospital medication instructions. Increasing patient medication literacy and, in turn, participation in medication conversations could be a solution. The purposes of this study were to co-design and test an intervention to enhance patient participation in hospital discharge medication communication. In terms of methods, co-design, a collaborative approach where stakeholders design solutions to problems, was used to develop a prototype medication communication intervention. First, our consumer and healthcare professional stakeholders generated intervention ideas. Next, inpatients, opinion leaders, and academic researchers collaborated to determine the most pertinent and feasible intervention ideas. Finally, the prototype intervention was shown to six intended end-users (i.e. hospital patients) who underwent usability interviews and completed the Theoretical Framework of Acceptability questionnaire. The final intervention comprised of a suite of three websites: (i) a medication search engine; (ii) resources to help patients manage their medications once home; and (iii) a question builder tool. The intervention has been tested with intended end-users and results of the Theoretical Framework of Acceptability questionnaire have shown that the intervention is acceptable. Identified usability issues have been addressed. In conclusion, this co-designed intervention provides patients with trustworthy resources that can help them to understand medication information and ask medication-related questions, thus promoting medication literacy and patient participation. In turn, this intervention could enhance patients' medication self-efficacy and healthcare utilization. Using a co-design approach ensured authentic consumer and other stakeholder engagement, while allowing opinion leaders and researchers to ensure that a feasible intervention was developed.

Strategies for Inducing and Validating Zinc Deficiency and Zinc Repletion.

Given the growing interest in the role of zinc in the onset and progression of diseases, there is a crucial demand for reliable methods to modulate zinc homeostasis. Using a dietary approach, we provide validated strategies to alter whole-body zinc in mice, applicable across species. For confirmation of zinc status, animal growth rates as well as plasma and urine zinc levels were evaluated. The accessible and cost-effective methodology outlined will increase scientific rigor, ensuring reproducibility in studies exploring the impact of zinc deficiency and repletion on the onset and progression of diseases.

Running a successful STEMM summer program: A week-by-week guide.

While some established undergraduate summer programs are effective across many institutions, these programs may only be available to some principal investigators or may not fully address the diverse needs of incoming undergraduates. This article outlines a 10-week science, technology, engineering, mathematics, and medicine (STEMM) education program designed to prepare undergraduate students for graduate school through a unique model incorporating mentoring dyads and triads, cultural exchanges, and diverse activities while emphasizing critical thinking, research skills, and cultural sensitivity. Specifically, we offer a straightforward and adaptable guide that we have used for mentoring undergraduate students in a laboratory focused on mitochondria and microscopy, but which may be customized for other disciplines. Key components include self-guided projects, journal clubs, various weekly activities such as mindfulness training and laboratory techniques, and a focus on individual and cultural expression. Beyond this unique format, this 10-week program also seeks to offer an intensive research program that emulates graduate-level experiences, offering an immersive environment for personal and professional development, which has led to numerous achievements for past students, including publications and award-winning posters.

Analysis and Optimization of Equitable US Cancer Clinical Trial Center Access by Travel Time.

Importance: Racially minoritized and socioeconomically disadvantaged populations are currently underrepresented in clinical trials. Data-driven, quantitative analyses and strategies are required to help address this inequity. Objective: To systematically analyze the geographical distribution of self-identified racial and socioeconomic demographics within commuting distance to cancer clinical trial centers and other hospitals in the US. Design, Setting, and Participants: This longitudinal quantitative study used data from the US Census 2020 Decennial and American community survey (which collects data from all US residents), OpenStreetMap, National Cancer Institute-designated Cancer Centers list, Nature Index of Cancer Research Health Institutions, National Trial registry, and National Homeland Infrastructure Foundation-Level Data. Statistical analyses were performed on data collected between 2006 and 2020. Main Outcomes and Measures: Population distributions of socioeconomic deprivation indices and self-identified race within 30-, 60-, and 120-minute 1-way driving commute times from US cancer trial sites. Map overlay of high deprivation index and high diversity areas with existing hospitals, existing major cancer trial centers, and commuting distance to the closest cancer trial center. Results: The 78 major US cancer trial centers that are involved in 94% of all US cancer trials and included in this study were found to be located in areas with socioeconomically more affluent populations with higher proportions of self-identified White individuals (+10.1% unpaired mean difference; 95% CI, +6.8% to +13.7%) compared with the national average. The top 10th percentile of all US hospitals has catchment populations with a range of absolute sum difference from 2.4% to 35% from one-third each of Asian/multiracial/other (Asian alone, American Indian or Alaska Native alone, Native Hawaiian or Other Pacific Islander alone, some other race alone, population of 2 or more races), Black or African American, and White populations. Currently available data are sufficient to identify diverse census tracks within preset commuting times (30, 60, or 120 minutes) from all hospitals in the US (N = 7623). Maps are presented for each US city above 500 000 inhabitants, which display all prospective hospitals and major cancer trial sites within commutable distance to racially diverse and socioeconomically disadvantaged populations. Conclusion and Relevance: This study identified biases in the sociodemographics of populations living within commuting distance to US-based cancer trial sites and enables the determination of more equitably commutable prospective satellite hospital sites that could be mobilized for enhanced racial and socioeconomic representation in clinical trials. The maps generated in this work may inform the design of future clinical trials or investigations in enrollment and retention strategies for clinical trials; however, other recruitment barriers still need to be addressed to ensure racial and socioeconomic demographics within the geographical vicinity of a clinical site can translate to equitable trial participant representation.

The impact of COVID-19 on emergency department presentations for mental health disorders in Queensland, Australia: A time series analysis.

BACKGROUND: The COVID-19 pandemic has been associated with detrimental effects on mental health and psychological well-being. Although multiple studies have shown decreases in mental health-related Emergency Department (ED) presentations early in the COVID-19 pandemic, the medium-term effects on mental health-related ED presentations have remained less clear. This study aimed to evaluate the effect of the pandemic on mental health ED presentations by comparing observed presentation numbers to predictions from pre-pandemic data. METHODS: This retrospective cohort study tallied weekly ED presentations associated with mental health disorders from a state-wide minimum dataset. Three time periods were identified: Pre-Pandemic (January 1, 2018-March 8, 2020), Statewide Lockdown (March 9, 2020-June 28, 2020), and Restrictions Easing (June 29, 2020-June 27, 2021). Time series analysis was used to generate weekly presentation forecasts using pre-pandemic data. Observed presentation numbers were compared to these forecasts. RESULTS: Weekly presentation numbers were lower than predicted in 11 out of 16 weeks in the Statewide Lockdown period and 52 out of 52 weeks in the Restrictions Easing period. The largest decrease was seen for anxiety disorders (Statewide Lockdown: 76.8% of forecast; Restrictions Easing: 36.4% of forecast), while an increase was seen in presentations for eating disorders (Statewide Lockdown: 139.5% of forecast; Restrictions Easing: 194.4% of forecast). CONCLUSIONS: Overall weekly mental health-related presentations across Queensland public EDs were lower than expected for the first 16 months of the COVID-19 pandemic. These findings underline the limitations of emergency department provision of mental health care and the importance of alternate care modalities in the pandemic context.

Considerations for developing mitochondrial transplantation techniques for individualized medicine.

Tweetable abstract Mitochondrial transplantation has been used to treat various diseases associated with mitochondrial dysfunction. Here, we highlight the considerations in quality control mechanisms that should be considered in the context of mitochondrial transplantation.

End-of-life decision-making in the emergency department and intensive care unit: Health professionals' perspectives on and knowledge of the law in Queensland.

OBJECTIVE: To investigate ED and intensive care unit healthcare professionals' perspectives and knowledge of the law that underpins end-of-life decision-making in Queensland, Australia. METHODS: An online survey with questions about perspectives, perceived, and actual, knowledge of the law was distributed by the professional organisations of medical practitioners, nurses and social workers who work in Queensland EDs and intensive care units. RESULTS: The survey responses of 126 healthcare professionals were included in the final analysis. Most respondents agreed that the law was relevant to end-of-life decision-making, but that clinician and family consensus mattered more than following the law. Generally, doctors' legal knowledge was higher than nurses'; however, there were significant gaps in the knowledge of all respondents about the operation of advance health directives in Queensland. CONCLUSIONS: The legal framework that supports end-of-life decision-making for adults who lack decision-making capacity has been in place for more than two decades. Despite frequently being involved in making or enacting these decisions, gaps in the legal knowledge of healthcare professionals who work in EDs and intensive care units in Queensland are evident. Further research to better understand how to improve knowledge and application of the law is warranted.

ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle.

Mitochondria and endoplasmic reticulum (ER) contact sites (MERCs) are protein- and lipid-enriched hubs that mediate interorganellar communication by contributing to the dynamic transfer of Ca2+, lipid, and other metabolites between these organelles. Defective MERCs are associated with cellular oxidative stress, neurodegenerative disease, and cardiac and skeletal muscle pathology via mechanisms that are poorly understood. We previously demonstrated that skeletal muscle-specific knockdown (KD) of the mitochondrial fusion mediator optic atrophy 1 (OPA1) induced ER stress and correlated with an induction of Mitofusin-2, a known MERC protein. In the present study, we tested the hypothesis that Opa1 downregulation in skeletal muscle cells alters MERC formation by evaluating multiple myocyte systems, including from mice and Drosophila, and in primary myotubes. Our results revealed that OPA1 deficiency induced tighter and more frequent MERCs in concert with a greater abundance of MERC proteins involved in calcium exchange. Additionally, loss of OPA1 increased the expression of activating transcription factor 4 (ATF4), an integrated stress response (ISR) pathway effector. Reducing Atf4 expression prevented the OPA1-loss-induced tightening of MERC structures. OPA1 reduction was associated with decreased mitochondrial and sarcoplasmic reticulum, a specialized form of ER, calcium, which was reversed following ATF4 repression. These data suggest that mitochondrial stress, induced by OPA1 deficiency, regulates skeletal muscle MERC formation in an ATF4-dependent manner.

Disparities in funding for Nobel Prize awards in medicine and physiology across nationalities, races, and gender.

Since 1901, the Nobel Prize in Physiology and Medicine has been awarded to numerous individuals for their outstanding contributions. This article presents a comprehensive analysis of the Nobel Prize recipients, focusing on gender, race, and nationality. We observe that an alarming disparity emerges when we examine the underrepresentation of Black scientists among Nobel laureates. Furthermore, trends in nationalities show how Americans make up the majority of Nobel Prize winners, while there is a noticeable lack of gender and racial minority winners of the Nobel Prize in Physiology and Medicine. Together, this highlights the importance of diversity and inclusion in scientific achievement. We offer suggestions and techniques, including funding opportunities and expanding nominators, to improve the gender, racial, and geographical diversity of Nobel Prizes.

A workshop to showcase the diversity of scientists to middle school students.

Identity matters in science, technology, engineering, mathematics, and medicine (STEMM) because it can affect an individual's long-term sense of belonging, which may in turn affect their persistence in STEMM. Early K-12 science classes often teach students about the foundational discoveries of the field, which have been predominately made, or at least published, by White men. This homogeneity can leave underrepresented individuals in STEMM feeling isolated, and underrepresented K-12 students may feel as though they cannot enter STEMM fields. This study aimed to examine these feelings of inclusivity in STEMM through an interactive workshop that asked middle schoolers to identify scientists from images of individuals with various racial and gender identities. We found that a plurality of students had a positive experience discussing diversity in science and recognizing underrepresented individuals as scientists.NEW & NOTEWORTHY We observed positive sentiments from middle school students following a workshop that showcased diversity in science. This workshop uniquely encourages students to recognize that physiologists and scientists today are much more diverse than textbooks typically demonstrate and can be adapted for middle schoolers, high schoolers, and college students.