Evolved changes in phenotype across skeletal muscles in deer mice native to high altitude.

The cold and hypoxic conditions at high altitude necessitate high metabolic O2 demands to support thermogenesis while hypoxia reduces O2 availability. Skeletal muscles play key roles in thermogenesis, but our appreciation of muscle plasticity and adaptation at high altitude has been hindered by past emphasis on only a small number of muscles. We examined this issue in deer mice (Peromyscus maniculatus). Mice derived from both high-altitude and low-altitude populations were born and raised in captivity and then acclimated as adults to normoxia or hypobaric hypoxia (12 kPa O2 for 6-8 wk). Maximal activities of citrate synthase (CS), cytochrome c oxidase (COX), ß-hydroxyacyl-CoA dehydrogenase (HOAD), hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) were measured in 20 muscles involved in shivering, locomotion, body posture, ventilation, and mastication. Principal components analysis revealed an overall difference in muscle phenotype between populations but no effect of hypoxia acclimation. High-altitude mice had greater activities of mitochondrial enzymes and/or lower activities of PK or LDH across many (but not all) respiratory, limb, core and mastication muscles compared with low-altitude mice. In contrast, chronic hypoxia had very few effects across muscles. Further examination of CS in the gastrocnemius showed that population differences in enzyme activity stemmed from differences in protein abundance and mRNA expression but not from population differences in CS amino acid sequence. Overall, our results suggest that evolved increases in oxidative capacity across many skeletal muscles, at least partially driven by differences in transcriptional regulation, may contribute to high-altitude adaptation in deer mice.NEW & NOTEWORTHY Most previous studies of muscle plasticity and adaptation in high-altitude environments have focused on a very limited number of skeletal muscles. Comparing high-altitude versus low-altitude populations of deer mice, we show that a large number of muscles involved in shivering, locomotion, body posture, ventilation, and mastication exhibit greater mitochondrial enzyme activities in the high-altitude population. Therefore, evolved increases in mitochondrial oxidative capacity across skeletal muscles contribute to high-altitude adaptation.

Thermoregulatory trade-offs underlie the effects of warming summer temperatures on deer mice.

Climate warming could challenge the ability of endotherms to thermoregulate and maintain normal body temperature (Tb), but the effects of warming summer temperatures on activity and thermoregulatory physiology in many small mammals remain poorly understood. We examined this issue in deer mice (Peromyscus maniculatus), an active nocturnal species. Mice were exposed in the lab to simulated seasonal warming, in which an environmentally realistic diel cycle of ambient temperature (Ta) was gradually warmed from spring conditions to summer conditions (controls were maintained in spring conditions). Activity (voluntary wheel running) and Tb (implanted bio-loggers) were measured throughout, and indices of thermoregulatory physiology (thermoneutral zone, thermogenic capacity) were assessed after exposure. In control mice, activity was almost entirely restricted to the night-time, and Tb fluctuated ∼1.7°C between daytime lows and night-time highs. Activity, body mass and food consumption were reduced and water consumption was increased in later stages of summer warming. This was accompanied by strong Tb dysregulation that culminated in a complete reversal of the diel pattern of Tb variation, with Tb reaching extreme highs (∼40°C) during daytime heat but extreme lows (∼34°C) at cooler night-time temperatures. Summer warming was also associated with reduced ability to generate body heat, as reflected by decreased thermogenic capacity and decreased mass and uncoupling protein (UCP1) content of brown adipose tissue. Our findings suggest that thermoregulatory trade-offs associated with daytime heat exposure can affect Tb and activity at cooler night-time temperatures, impacting the ability of nocturnal mammals to perform behaviours important for fitness in the wild.

Increasing the Rate of Venous Thromboembolism Chemoprophylaxis Administration Using the Electronic Medical Record.

Introduction: Venous thromboembolism (VTE) remains a leading cause of preventable harm among hospitalized patients. Pharmacologic VTE prophylaxis reduces the rate of in-hospital VTE by 60%, but medication administration is often missed for various reasons. Electronic medical record (EMR) prompts may be a useful tool to decrease withholding of critical VTE chemoprophylaxis medications. Methods: In August 2021, an EMR prompt was implemented at a tertiary referral academic medical center mandating nursing staff to contact a provider for approval before withholding VTE chemoprophylaxis. A pre-intervention group from August 2020 to August 2021 was compared to a post-intervention group from August 2021 to August 2022. Rates of VTE chemoprophylaxis withholding were compared between the groups with a P < .01 considered significant. Results: A total of 16,395 patients prescribed VTE chemoprophylaxis were reviewed, with 13,395 (81.7%) receiving low molecular weight heparin. Of the 16,395 patients included, 10,701 (65.3%) were medical and 5694 (34.7%) were surgical. Patients in the pre-intervention cohort (n = 8803) and post-intervention cohort (n = 7592) were similar in hospital length of stay and duration of DVT prophylaxis. In the post-intervention group, the frequency of surgical patients with at least one missed dose had increased by 4.2% (P = .002), with the trauma and acute care surgery (TACS) show an increase of 6.6% (P < .001). However, the frequency of medical patients and non-TACS patients with missed doses decreased by 3.1% (P = .002) and 1.0% (<.001), respectively. Conclusions: EMR prompts appear to be a low-cost intervention that increases the rate of VTE prophylaxis administration among medical and elective surgery patients.

Adjusting vasopressin availability and formulation: A cost-savings initiative.

PURPOSE: The increase in vasopressin price has required many healthcare systems to consider cost-saving strategies. To combat rising medication costs, our institution changed formulations from 50 units/250 mL to 20 units/100 mL and removed vasopressin from automated dispensing cabinets (ADCs). METHODS: This retrospective review occurred at a 545-bed academic medical center with 97 adult intensive care unit beds. Adult patients receiving a continuous vasopressin infusion were included with no exclusion criteria. A 1-month period was assessed before and after changing the formulation (pre and post groups, respectively). Duplicate bags compounded by pharmacy and bedside teams were also assessed in the pre group. The primary outcome was the estimated annual cost savings due to formulation change with a secondary outcome of estimated annual cost savings due to removal of vasopressin from ADCs. Each 20-unit vial of vasopressin cost $183.21 (wholesale acquisition cost) at the time of the study. RESULTS: In the pre group, 39 patients requiring a vasopressin infusion were allocated an average of 2 bags each costing $1,099.26 per patient. In the post group, 41 patients required an average of 4 bags each costing $732.84 per patient. With respect to the primary outcome, a savings of $366.42 per patient and an average of 40 patients per month would lead to an annual cost savings of $175,881.60. Secondary outcome analysis identified 9 duplicate bags prepared in the pre group; therefore, removal of vasopressin from ADCs is estimated to provide additional cost savings of $59,360.04. The estimated annual cost savings from both initiatives is $235,241.64. CONCLUSION: Changing the vasopressin formulation and removing it from ADCs resulted in a significant cost savings to the health system.

Diagnostic accuracy and prognostic value of simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in cardiac sarcoidosis.

Aims: Cardiac death is the leading cause of mortality in patients with sarcoidosis, yet cardiac involvement often remains undetected. Cardiovascular magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) have been used to diagnose cardiac sarcoidosis (CS) yet never simultaneously in a cohort. This study sought to assess the diagnostic and prognostic utility of simultaneous hybrid cardiac PET/MR. Methods and results: Fifty-one consecutive patients with suspected CS (age 50 ± 13 years, 31 males) underwent simultaneous PET/MR following a high-fat/low-carbohydrate diet and 12-h fast. Blinded image analysis of FDG uptake and late gadolinium enhancement (LGE) was performed using the American Heart Association (AHA) 16-segment model. The sensitivity and specificity of PET/MR for diagnosing CS was estimated using the Japanese Ministry of Health and Welfare guidelines. The primary endpoint was a composite of death, aborted sudden cardiac death, sustained ventricular arrhythmia, complete heart block, and hospital admission with decompensated heart failure. The secondary endpoints were a fall in left ventricular ejection fraction (LVEF) >10%, non-sustained ventricular tachycardia and other cardiac-related hospital admission. The prevalence of CS was 65% (n = 33). The sensitivity of PET and CMR alone for detecting CS was 0.85 and 0.82, respectively. Hybrid PET/MR was superior for detecting CS with sensitivity, specificity, positive, and negative predictive values of 0.94, 0.44, 0.76, and 0.80, respectively. There was poor inter-modality agreement for the location of cardiac abnormalities (k = 0.02). Over the median follow-up of 2.2 years, there were 18 (35%) adverse events. Cardiac RV PET abnormalities and presence of LGE were independent predictors of adverse events. Abnormalities found on both PET and magnetic resonance imaging was the strongest predictor of major adverse cardiac events. Conclusion: Simultaneous PET/MR is an accurate method for diagnosing CS. FDG-PET and CMR combined offers complementary information on disease pathophysiology. The presence of LGE and FDG uptake on PET/MR identifies patients at higher risk of adverse events. PET and CMR should therefore be considered in the assessment of disease presence, stage, and prognosis in CS.

The development of social cognition in adolescence: An integrated perspective.

Social cognitive processes are critical in navigating complex social interactions and are associated with a network of brain areas termed the 'social brain'. Here, we describe the development of social cognition, and the structural and functional changes in the social brain during adolescence, a period of life characterised by extensive changes in social behaviour and environments. Neuroimaging and behavioural studies have demonstrated that the social brain and social cognition undergo significant development in human adolescence. Development of social cognition and the social brain are discussed in the context of developments in other neural systems, such as those implicated in motivational-affective and cognitive control processes. Successful transition to adulthood requires the rapid refinement and integration of these processes and many adolescent-typical behaviours, such as peer influence and sensitivity to social exclusion, involve dynamic interactions between these systems. Considering these interactions, and how they vary between individuals and across development, could increase our understanding of adolescent brain and behavioural development.

Josephine Letitia Denny Fairfield (1885-1978): pushing the boundaries of medicine.

Letitia Fairfield - doctor, lawyer, public health worker, feminist and war worker - was a woman of surprising contradictions. She displayed some eccentric tendencies that sometimes did not sit comfortably with her role as a medical professional; she was, for example, a believer in witchcraft and a convert to Roman Catholicism. However, she made great contributions to medicine throughout her active career and did so during a period in which female access to medical education was limited. Few of her female or male peers received such respect or oversaw such change. Despite pushing contemporary professional boundaries and reaching a level of seniority unusual for female doctors of her era, however, Letitia was, whether through choice or through convention, channelled into traditionally female areas of medicine. Thus, her medical success arguably was due not only to her motivation and capability but also because she represented no real competition to men.