Pilot study assessing gut microbial diversity among sexual and gender minority young adults.

Evidence supports that people identifying as a sexual or gender minority (SGMs) experience minority-related stress resulting from discrimination or expectations of prejudice, and that this is associated with increased mental and physical health problems compared to cisgender heterosexuals. However, the biological mechanisms driving minority-related stress impacts remain unknown, including the role of the gut microbiome. Thus, the aim of this study was to determine the relationship between SGM status and gut microbiome health among young adults attending a 4-year university. To this end, a prospective pilot study was completed in the fall and spring semesters of 2021-22. Self-identified SGMs (N = 22) and cisgender-heterosexuals (CIS-HET, N = 43) completed in-person interviews to provide mental health data and demographic information. Nail and saliva samples were collected at the time of interview to quantify chronic and acute cortisol. Stool samples were collected within 48 hours of interview for microbiome analysis. Assessment of the gut microbiota identified a significant reduction in alpha diversity among the SGM group, even when adjusting for mental health outcome. SGM group showed trends for higher abundance of microbes in phylum Bacteroidetes and lower abundance of microbes in phyla Firmicutes, Actinobacteria, and Proteobacteria compared to the CIS-HET group. These findings support that the gut microbiome could be contributing to negative health effects among the SGM community.

Preliminary Validation of the Acute Care Mobility Assessment as a Measure of Hospital Mobility.

BACKGROUND: Despite heightened interest, measurement of hospital mobility remains challenging. Available assessment tools lack patient input regarding level and frequency of hospital mobility. The purpose of this study was to validate a brief self-reported mobility assessment to measure out-of-bed activity during hospitalization. METHODS: We recruited cognitively intact hospitalized adults (age ≥ 65 years) who walked prior to admission, to wear an accelerometer for 24 hours, and to complete the Acute Care Mobility Assessment (ACMA), a self-report of mobility that ranges from bed rest to walking off the hospital unit in the prior 24 hours. For each mobility level from sitting in a chair to walking off the unit, patients reported the frequency of the activity and the need for help from another person or equipment. Spearman correlation coefficients were calculated using several scoring algorithms to compare ACMA to accelerometer data. RESULTS: Fifty-one patients (mean age 74.3 [standard deviation 6.2] years, 63% female, 39% Black) had complete data. Steps taken in 24 hours ranged from 10 to 2 831. Correlation analyses identified strong associations between ACMA scores and total steps, and moderate correlations with total time walking using all algorithms. However, the unweighted frequency count using the 3 ambulation levels only (walking in room, in hall, and off ward) had the highest correlation with total steps (r = 0.84; p < .001) and total time walking (r = 0.66; p < .001). CONCLUSIONS: ACMA is a valid measure of mobility among cognitively intact hospitalized older adults. The ACMA may add value to our current armamentarium of tools by adding patient reports of hospital mobility.

National Norms for Hospitalizations Due to Ambulatory Care Sensitive Conditions among Adults in the US.

BACKGROUND: Ambulatory care sensitive conditions (ACSCs) are acute or chronic health issues that lead to potentially preventable hospitalizations when not treated in the outpatient primary care setting. OBJECTIVE: To describe national hospitalization rates due to ACSCs among adult inpatients in the US. DESIGN: A retrospective cross-sectional analysis of the 2018 US National Inpatient Sample (NIS) dataset from the Healthcare Cost and Utilization Project at the Agency of Healthcare Research and Quality was completed in the year 2022. PARTICIPANTS: Participants were adult inpatients from community hospitals in 48 states of the US and District of Columbia. MAIN MEASURES: ACSC admission rates were calculated using ICD-10 codes and the Purdy ACSC definition. The admission rates were weighted to the US inpatient population and stratified by age, sex, and race. KEY RESULTS: ACSC hospitalization rates varied considerably across age and average number of hospitalizations varied across sex and race. ACSC hospitalization rates increased with age, male sex, and Native American and Black race. The most common ACSCs were pneumonia, diabetes, and congestive heart failure. CONCLUSIONS: Previous studies have emphasized the importance of preventable hospitalizations, however, the national rates for ACSC hospitalizations across all ages in the US have not been reported. The national rates presented will facilitate comparisons to identify hospitals and health care systems with higher-than-expected rates of ACSC admissions that may suggest a need for improved primary care services.

National Norms for the Elixhauser and Charlson Comorbidity Indexes Among Hospitalized Adults.

BACKGROUND: Comorbidity burden is commonly measured among hospitalized adults, yet the U.S. national norms for 2 commonly used comorbidity indexes have not yet been reported. Thus, this study reports U.S. national norms for both Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) among hospitalized adults based on age, biological sex, and race. METHODS: A retrospective observational cohort study using data from the Agency of Healthcare Research and Quality U.S. National Inpatient Sample database for 2017. Patient data were extracted from 7 159 694 inpatient adults, and analyses were focused on individuals older than 45 years, yielding 4 370 225 patients. International Classification of Diseases, 10th Edition, diagnostic codes were used to calculate CCI and ECI scores. These scores were then weighted for the U.S. national population. RESULTS: The weighted mean CCI was 1.22 (95% confidence interval [CI]: 1.22, 1.22), and the weighted mean ECI was 2.76 (95% CI: 2.76, 2.76). Both indexes had increasing average scores with increasing age, independent of sex and race (all p values < .001). CONCLUSION: For the first time, U.S. national norms for the CCI and ECI are reported for adult inpatients. The norms can serve as a reference tool for determining if clinical and research populations have greater or lesser comorbidity burden than typical hospitalized adults in the United States for their age, sex, and race.

A systematic review and meta-analysis: Assessment of hospital walking programs among older patients.

AIM: The aim of this study is to assess effect of hospital walking programs on outcomes for older inpatients and to characterize hospital walking dose reported across studies. DESIGN: A systematic review and meta-analysis examining impact of hospital walking and/or reported walking dose among medical-surgical inpatients. For inclusion, studies were observational or experimental, published in English, enrolled inpatients aged ≥ 65 yrs hospitalized for medical or surgical reasons. METHODS: Searches of PubMed, CINAHL, Embase, Scopus, NICHSR, OneSearch, ClinicalTrials.gov, and PsycINFO were completed in December 2020. Two reviewers screened sources, extracted data, and performed quality bias appraisal. RESULTS: Hospital walking dose was reported in 6 studies and commonly as steps/24 hr. Length of stay (LOS) was a common outcome reported. Difference in combined mean LOS between walking and control groups was -5.89 days. Heterogeneity across studies was considerable (I2  = 96%) suggesting poor precision of estimates. Additional, high-quality trials examining hospital walking and patient outcomes of older patients is needed.

An Analysis of Factors That Influence Students to Pursue Immunology.

One considers many factors before choosing a career path, such as interest, accessibility of resources, academic ability, and social network support. As employment around the world in science, technology, engineering, and math (STEM) disciplines continues to increase, there is a need to understand why students select specific majors in an effort to increase overall enrollment and retention of STEM majors. The purpose of this study was to elucidate how undergraduate and graduate students were introduced to immunology, a STEM discipline, and how these experiences influenced their desire to pursue immunology as a major. The findings from this study show that a majority of both immunology and nonimmunology majors were initially exposed to immunology through an educational experience compared with a personal experience. Our data also indicate that the timing of the experience is critical, such that an educational experience at an advanced academic level, for example, in college, or a personal experience as a teen or young adult correlated with the decision to pursue an immunology degree. Moreover, graduate students studying immunology report that having research experiences and/or an experience with a mentor positively influenced their decision to pursue immunology. Overall, the findings from this research highlight the type and timing of exposures that influence individuals to major in the field of immunology, and these data can be used in the future to increase the number of immunology graduates.

Development and evolution of a two-day intensive resident experience in geriatric medicine.

As the older adult population increases, the need to enhance medical education and training in Geriatric Medicine (GM) is essential. To enhance resident training, faculty at two southeastern universities developed a Resident Award Summit, a two-day active learning experience, designed to expose family and internal medicine residents to GM principles and the various career options available in GM.Over 10 years, 353 residents from 108 residency programs participated. Resident feedback indicated that attending the event had a positive impact on future practice (M = 4.65, SD = .58) and showed that the amount of GM training received was limited, with 83.5% and 70.2% ranking adequacy of medical student and resident training as limited, respectively.To impact practice, long-term change must occur. Experiences such as the Resident Award Summit allow GM faculty to educate and prepare residents though positive teaching experiences, providing residents with the skills needed to care for older adults in their communities.

Prevalence of Hospital-Associated Disability in Older Adults: A Meta-analysis.

OBJECTIVES: Hospital-associated disability (HAD), defined as loss of independence in activities of daily living (ADL) following acute hospitalization, is observed among older adults. The study objective is to determine overall prevalence of HAD among older adults hospitalized in acute care, and to assess the impact of study initiation year in moderation of prevalence. DESIGN: Meta-analysis of data collected from randomized trials, quasi-experimental, and prospective cohort studies. English-language searches to identify included studies were completed February 2018 and updated May 2018 of electronic databases and reference lists of studies and reviews. Included studies were human subjects investigations that measured ADL ≥2 time points before or during and after hospitalization and reported prevalence of ADL decline among older adults. SETTING: Acute care hospital units. PARTICIPANTS: Adults aged ≥65 years hospitalized in medical-surgical acute care; total sample size across all included studies was 7375. METHODS: Independence in ADL was assessed using the Katz Index of Independence in Activities of Daily Living and Barthel Index of Independence in Activities of Daily Living. RESULTS: Random effects meta-analysis across included studies identified combined prevalence of HAD as 30% (95% CI 24%, 33%; P < .001). The effect of study initiation year on the prevalence rate was minimal. A large amount of heterogeneity was observed between studies, which may be due in part to nonstandardized measurement of ADL impairment or other methodological differences. CONCLUSIONS AND IMPLICATIONS: Hospitalization in acute care poses a significant risk to functional independence of older adults, and this risk is unchanged despite shorter lengths of stay. The evidence supports the continued need for hospital-based programs that provide assessment of functional ability and identification of at-risk older adults in order to better treat and prevent HAD.

Hepatic Glucagon Receptor Signaling Enhances Insulin-Stimulated Glucose Disposal in Rodents.

Glucagon receptor (GCGR) agonists cause hyperglycemia but also weight loss. However, GCG-like peptide 1 receptor (GLP1R)/GCGR mixed agonists do not exhibit the diabetogenic effects often attributed to GCGR activity. Thus, we sought to investigate the effect of glucagon agonism on insulin action and glucose homeostasis. Acute GCGR agonism induced immediate hyperglycemia, followed by improved glucose tolerance and enhanced glucose-stimulated insulin secretion. Moreover, acute GCGR agonism improved insulin tolerance in a dose-dependent manner in both lean and obese mice. Improved insulin tolerance was independent of GLP1R, FGF21, and hepatic glycogenolysis. Moreover, we observed increased glucose infusion rate, disposal, uptake, and suppressed endogenous glucose production during euglycemic clamps. Mice treated with insulin and GCGR agonist had enhanced phosphorylation of hepatic AKT at Ser473; this effect was reproduced in isolated mouse primary hepatocytes and resulted in increased AKT kinase activity. These data reveal that GCGR agonism enhances glucose tolerance, in part, by augmenting insulin action, with implications for the use of GCGR agonism in therapeutic strategies for diabetes.

Trajectories of Community Mobility Recovery After Hospitalization in Older Adults.

OBJECTIVES: To identify trajectories of recovery of community mobility in acutely ill older adults using the University of Alabama at Birmingham Life-Space Assessment (LSA). DESIGN: Prospective observation cohort study. SETTING: Central Alabama, Birmingham Veterans Affairs Medical Center. PARTICIPANTS: Community-dwelling adults aged 65 and older hospitalized for nonsurgical medical reasons (N=173). MEASUREMENTS: We determined LSA scores for the month before and monthly for 6 months after hospitalization (composite scores ranging from 0-120, with 120 reflecting completely unrestricted mobility). RESULTS: In the month after hospitalization, 92 (53%) participants had a clinically significant decrease in life-space mobility, while 42 (24%) were unchanged, and 39 (23%) had an increase from the month preceding hospitalization. Of participants with a life-space decrease, the majority recovered their prehospitalization mobility status during 6 months of follow-up, whereas 34% did not recover. Participants whose life-space decreased were hospitalized significantly longer (P=.01) and, on average, had higher prehospital life-space scores (P=.01) than those who maintained or increased their life-space. CONCLUSION: A clinically significant loss of community mobility was common after hospitalization, but most participants recovered to prehospitalization mobility within 6 months of discharge. Research examining in-hospital and posthospitalization interventions to achieve faster recovery of community mobility is needed.

LDB1 Regulates Energy Homeostasis During Diet-Induced Obesity.

The broadly expressed transcriptional coregulator LDB1 is essential for ß-cell development and glucose homeostasis. However, it is unclear whether LDB1 has metabolic roles beyond the ß-cell, especially under metabolic stress. Global Ldb1 deletion results in early embryonic lethality; thus, we used global heterozygous Ldb1+/- and inducible ß-cell-specific Ldb1-deficient (Ldb1Δß-cell) mice. We assessed glucose and insulin tolerance, body composition, feeding, and energy expenditure during high-fat diet exposure. Brown adipose tissue (BAT) biology was evaluated by thermogenic gene expression and LDB1 chromatin immunoprecipitation analysis. We found that partial loss of Ldb1 does not impair the maintenance of glucose homeostasis; rather, we observed improved insulin sensitivity in these mice. Partial loss of Ldb1 also uncovered defects in energy expenditure in lean and diet-induced obese (DIO) mice. This decreased energy expenditure during DIO was associated with significantly altered BAT gene expression, specifically Cidea, Elovl3, Cox7a1, and Dio2. Remarkably, the observed changes in energy balance during DIO were absent in Ldb1Δß-cell mice, despite a similar reduction in plasma insulin, suggesting a role for LDB1 in BAT. Indeed, LDB1 is expressed in brown adipocytes and occupies a regulatory domain of Elovl3, a gene crucial to normal BAT function. We conclude that LDB1 regulates energy homeostasis, in part through transcriptional modulation of critical regulators in BAT function.

Fibroblast growth factor 21 is required for beneficial effects of exercise during chronic high-fat feeding.

Exercise is an effective therapy against the metabolic syndrome. However, the molecular pathways underlying the advantageous effects of exercise are elusive. Glucagon receptor signaling is essential for exercise benefits, and recent evidence indicates that a downstream effector of glucagon, fibroblast growth factor 21 (FGF21), is implicated in this response. Therefore, we tested the hypothesis that FGF21 action is necessary in mediating metabolic effects of exercise. We utilized acute exhaustive treadmill exercise in Wistar rats to identify a putative, concomitant increase in plasma glucagon and FGF21 with the increase in glucose and lactate following exercise. To test the necessity of FGF21 action in the exercise response, we exposed FGF21 congenitally deficient mice (Fgf21(-/-)) and their wild-type (Wt) littermates to chronic high-fat (HF) feeding and inoperable (sedentary) or operable (exercise) voluntary running wheels. Physiological tests were performed to assess the role of FGF21 in the beneficial effect of exercise on glucose metabolism. Wt and Fgf21(-/-) littermates exhibited similar running behavior, and exercise was effective in suppressing weight and fat mass gain and dyslipidemia independently of genotype. However, exercise failed to positively affect hepatic triglyceride content and glucose tolerance in HF diet-fed Fgf21(-/-) mice. Furthermore, Fgf21(-/-) mice exhibited an impaired adaptation to exercise training, including reduced AMP-activated protein kinase activity in skeletal muscle. This study demonstrates that FGF21 action is necessary to achieve the full metabolic benefits of exercise during chronic HF feeding.

Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation.

OBJECTIVE: Melanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome. METHODS: Electrically evoked dopamine release was measured in slice preparations from sedentary wild-type and MC4R-deficient Mc4r (K314X) (HOM) rats. VWR was assessed in wild-type and HOM rats, and in MC4R-deficient loxTB (Mc4r) mice, wild-type mice body weight-matched to loxTB (Mc4r) mice, and wild-type mice with intracerebroventricular administration of the MC4R antagonist SHU9119. Mesolimbic dopamine system function (gene/protein expression) and metabolic parameters were examined in wheel-running and sedentary wild-type and HOM rats. RESULTS: Sedentary obese HOM rats had increased electrically evoked dopamine release in several ventral tegmental area (VTA) projection sites compared to wild-type controls. MC4R loss-of-function decreased VWR, and this was partially independent of body weight. HOM wheel-runners had attenuated markers of intracellular D1-type dopamine receptor signaling despite increased dopamine flux in the VTA. VWR increased and decreased ΔFosB levels in the nucleus accumbens (NAc) of wild-type and HOM runners, respectively. VWR improved metabolic parameters in wild-type wheel-runners. Finally, moderate voluntary exercise corrected many aspects of the metabolic syndrome in HOM runners. CONCLUSIONS: Central dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training.

Brown fat fuel use and regulation of energy homeostasis.

PURPOSE OF REVIEW: New evidence has recently supported the notion that brown adipose tissue (BAT) is present in adult humans and can play a prominent role in the regulation of body weight and metabolism. This has renewed the efforts to understand the physiologic mechanisms by which BAT is activated, which in turn could provide new therapeutic strategies for obesity and diabetes. RECENT FINDINGS: BAT mass and activity are positively correlated with measures of metabolic health in rodents and humans; however, the amount of functional BAT in adult humans is highly variable with less found in overweight and obese individuals. The impact of BAT in the uptake and utilization of circulating nutrients is systemic, with major effects on whole-body insulin sensitivity and glucose tolerance as illustrated by BAT transplantation in rodents. Furthermore, a host of physiologic conditions and novel peptides/hormones have been implicated in the activation of BAT thermogenesis and/or 'browning' of white adipocytes. SUMMARY: These new findings open the way for novel strategies aimed at increasing BAT mass and activity in obese humans as an important clinical goal in the midst of unprecedented high prevalence of obesity and associated metabolic disorders.