Enhancing Flow Mediated Dilation Analysis by Optimizing an Open-Source Software with Automated Edge Detection.

Flow mediated dilation (FMD) is a common measure of endothelial function and an indicator of vascular health. Automated software methods exist to improve the speed and accuracy of FMD analysis. Compared to commercial software, open-source software offers similar capabilities at a much lower cost while allowing for increased customization specific to users' needs. We introduced modifications to an existing open-source software, FloWave.us to better meet FMD analysis needs. The purpose of this study was to compare the repeatability and reliability of the modified FloWave.us software to the original software and to manual measurements. To assess these outcomes, Duplex ultrasound imaging data from the popliteal artery in older adults were analyzed. The average percent FMD for the modified software was 6.98±3.68% and 7.27±3.81% for Observer 1 and 2 respectively, compared to 9.17±4.91% and 10.70±4.47% with manual measurements and 5.07±31.79% with the original software for Observer 1. The modified software and manual methods demonstrated higher intra-observer intraclass correlation coefficients (ICCs) for repeated measures for baseline diameter, peak diameter, and percent FMD compared to the original software. For percent FMD, the inter-observer ICC was 0.593 for manual measurements and 0.723 for the modified software. With the modified method an average of 97.7±2.4% of FMD videos frames were read, compared to only 17.9±15.0% frames read with the original method when analyzed by the same observer. Overall, this work further establishes open-source software as a robust and viable tool for FMD analysis and demonstrates improved reliability compared to the original software.

The dementia care study (D-CARE): Recruitment strategies and demographic characteristics of participants in a pragmatic randomized trial of dementia care.

INTRODUCTION: Pragmatic research studies that include diverse dyads of persons living with dementia (PLWD) and their family caregivers are rare. METHODS: Community-dwelling dyads were recruited for a pragmatic clinical trial evaluating three approaches to dementia care. Four clinical trial sites used shared and site-specific recruitment strategies to enroll health system patients. RESULTS: Electronic health record (EHR) queries of patients with a diagnosis of dementia and engagement of their clinicians were the main recruitment strategies. A total of 2176 dyads were enrolled, with 80% recruited after the onset of the pandemic. PLWD had a mean age of 80.6 years (SD 8.5), 58.4% were women, and 8.8% were Hispanic/Latino, and 11.9% were Black/African American. Caregivers were mostly children of the PLWD (46.5%) or spouses/partners (45.2%), 75.8% were women, 9.4% were Hispanic/Latino, and 11.6% were Black/African American. DISCUSSION: Health systems can successfully enroll diverse dyads in a pragmatic clinical trial.

Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease: JACC Scientific Statement.

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel gerotherapeutic approaches, some of which are already used in management of CVD, and explore their potential to transform care and management of CVD. The geroscience paradigm is gaining traction broadly in medical specialties, with potential to mitigate premature aging, reduce health care disparities, and improve population healthspan.

Postabsorptive muscle protein synthesis is higher in outpatients as compared to inpatients.

Several factors affect muscle protein synthesis (MPS) in the postabsorptive state. Extreme physical inactivity (e.g., bedrest) may reduce basal MPS, whereas walking may augment basal MPS. We hypothesized that outpatients would have a higher postabsorptive MPS than inpatients. To test this hypothesis, we conducted a retrospective analysis. We compared 152 outpatient participants who arrived at the research site the morning of the MPS assessment with 350 Inpatient participants who had an overnight stay in the hospital unit before the MPS assessment the following morning. We used stable isotopic methods and collected vastus lateralis biopsies ∼2 to 3 h apart to assess mixed MPS. MPS was ∼12% higher (P < 0.05) for outpatients than inpatients. Within a subset of participants, we discovered that after instruction to limit activity, outpatients (n = 13) took 800 to 900 steps in the morning to arrive at the unit, seven times more steps than inpatients (n = 12). We concluded that an overnight stay in the hospital as an inpatient is characterized by reduced morning activity and causes a slight but significant reduction in MPS compared with participants studied as outpatients. Researchers should be aware of physical activity status when designing and interpreting MPS results.NEW & NOTEWORTHY The postabsorptive muscle protein synthesis rate is lower in the morning after an overnight inpatient hospital stay compared with an outpatient visit. Although only a minimal amount of steps was conducted by outpatients (∼900), this was enough to increase postabsorptive muscle protein synthesis rate.

Nutritional Interventions: Dietary Protein Needs and Influences on Skeletal Muscle of Older Adults.

BACKGROUND: This narrative review describes foundational and emerging evidence of how dietary protein intakes may influence muscle-related attributes of older adults. METHODS: PubMed was used to identify pertinent research. RESULTS: Among medically stable older adults, protein intakes below the recommended dietary allowance (RDA) (0.8 g/kg body weight [BW]/d) exacerbate age-related reductions in muscle size, quality, and function. Dietary patterns with total protein intakes at or moderately above the RDA, including one or preferably more meals containing sufficient dietary protein to maximize protein anabolism, promote muscle size and function. Some observational studies suggest protein intakes from 1.0 to 1.6 g/kg BW/d may promote greater muscle strength and function more so than muscle size. Experimental findings from randomized controlled feeding trials indicate protein intakes greater than the RDA (averaging ~1.3 g/kg BW/d) do not influence indices of lean body mass or muscle and physical functions with non-stressed conditions, but positively influence changes in lean body mass with purposeful catabolic (energy restriction) or anabolic (resistance exercise training) stressors. Among older adults with diagnosed medical conditions or acute illness, specialized protein or amino acid supplements that stimulate muscle protein synthesis and improve protein nutritional status may attenuate the loss of muscle mass and function and improve survival of malnourished patients. Observational studies favor animal versus plant protein sources for sarcopenia-related parameters. CONCLUSIONS: Quantity, quality, and patterning of dietary protein consumed by older adults with varied metabolic states, and hormonal and health status influence the nutritional needs and therapeutic use of protein to support muscle size and function.

Optimizing the Design of Clinical Trials to Evaluate the Efficacy of Function-Promoting Therapies.

BACKGROUND: Several candidate molecules that may have application in treating physical limitations associated with aging and chronic diseases are in development. Challenges in the framing of indications, eligibility criteria, and endpoints and the lack of regulatory guidance have hindered the development of function-promoting therapies. METHODS: Experts from academia, pharmaceutical industry, National Institutes of Health (NIH), and Food and Drug Administration (FDA) discussed optimization of trial design including the framing of indications, eligibility criteria, and endpoints. RESULTS: Mobility disability associated with aging and chronic diseases is an attractive indication because it is recognized by geriatricians as a common condition associated with adverse outcomes, and it can be ascertained reliably. Other conditions associated with functional limitation in older adults include hospitalization for acute illnesses, cancer cachexia, and fall injuries. Efforts are underway to harmonize definitions of sarcopenia and frailty. Eligibility criteria should reconcile the goals of selecting participants with the condition and ensuring generalizability and ease of recruitment. An accurate measure of muscle mass (eg, D3 creatine dilution) could be a good biomarker in early-phase trials. Performance-based and patient-reported measures of physical function are needed to demonstrate whether treatment improves how a person lives, functions, or feels. Multicomponent functional training that integrates training in balance, stability, strength, and functional tasks with cognitive and behavioral strategies may be needed to translate drug-induced muscle mass gains into functional improvements. CONCLUSIONS: Collaborations among academic investigators, NIH, FDA, pharmaceutical industry, patients, and professional societies are needed to conduct well-designed trials of function-promoting pharmacological agents with and without multicomponent functional training.

Skeletal Muscle Bioenergetics in Critical Limb Ischemia and Diabetes.

INTRODUCTION: Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus (T2DM) is a major risk factor for PAD development and progression to CLI and may also independently be related to mitochondrial dysfunction. We set out to determine the effect of T2DM in the relationship between CLI and muscle mitochondrial respiratory capacity and coupling control. METHODS: We studied CLI patients undergoing revascularization procedures or amputation, and non-CLI patients with or without T2DM of similar age. Mitochondrial respiratory capacity and function were determined in lower limb permeabilized myofibers by high-resolution respirometry. RESULTS: Fourteen CLI patients (65 ± 10y) were stratified into CLI patients with (n = 8) or without (n = 6) T2DM and were compared to non-CLI patients with (n = 18; 69 ± 5y) or without (n = 19; 71 ± 6y) T2DM. Presence of CLI but not T2DM had a marked impact on all mitochondrial respiratory states in skeletal muscle, adjusted for the effects of sex. Leak respiration (State 2, P < 0.025 and State 4o, P < 0.01), phosphorylating respiration (P < 0.001), and maximal respiration in the uncoupled state (P < 0.001), were all suppressed in CLI patients, independent of T2DM. T2DM had no significant effect on mitochondrial respiratory capacity and function in adults without CLI. CONCLUSIONS: Skeletal muscle mitochondrial respiratory capacity was blunted by ∼35% in patients with CLI. T2DM was not associated with muscle oxidative capacity and did not moderate the relationship between muscle mitochondrial respiratory capacity and CLI.

Considerations When Designing and Implementing Pragmatic Clinical Trials That Include Older Hispanics.

Introduction: Pragmatic clinical trials (PCTs) are designed to connect researchers with clinicians to assess the real-world effectiveness and feasibility of interventions, treatments, or health care delivery strategies in routine practice. Within PCTs larger, more representative sampling is possible to improve the external validity of the research. Older adults from underrepresented groups can benefit from PCTs given their historically lower engagement in clinical research. The current article focuses on older Hispanic adults with Alzheimer disease and related dementias (ADRDs). Older Hispanic adults represent 19% of the US population and have a higher prevalence of ADRDs than Whites. We provide data from 2 PCTs about the recruitment of older Hispanics with ADRDs and discuss unique challenges associated with conducting PCTs and propose strategies to overcome challenges. Data and Methods: The first PCT outlined is the Patient Priorities Care for Hispanics with Dementia (PPC-HD) trial. PPC-HD is testing the feasibility of implementing a culturally adapted version of the Patient Priorities Care approach for older Hispanic adults with multiple chronic conditions and dementia. The second PCT is the Dementia Care (D-CARE) Study, which is a multisite pragmatic study comparing the effectiveness of a health care system-based approach and a community-based approach to dementia care to usual care in patients with ADRDs and their family caregivers. Lessons Learned and Recommendations for Future Studies: The lessons learned are summarized according to the various stakeholders that need to work together to effectively recruit diverse participants for PCTs: individuals, health care systems, research teams, and communities. Individual-level considerations include communication, priorities, and flexibility. Health care system-level considerations are grounded in 4 principles of Community-Based Participatory Research and include collaboration/partnership, available resources, priorities of the health care system, and sustainability. Research team-level considerations include team members, intentionality, and communication. Community-level considerations highlight the importance of partnerships, community members, and appropriate incentives. Discussion: PCTs provide a unique and potentially impactful opportunity to test interventions in real-world settings that must be culturally appropriate to reach underrepresented groups. Collectively, considering variables at multiple levels to address the needs of older adults with ADRDs is crucial, and the examples and suggestions provided in this report are a foundation for future research.

Effect of the STRIDE fall injury prevention intervention on falls, fall injuries, and health-related quality of life.

BACKGROUND: Falls are common in older adults and can lead to severe injuries. The Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) trial cluster-randomized 86 primary care practices across 10 health systems to a multifactorial intervention to prevent fall injuries, delivered by registered nurses trained as falls care managers, or enhanced usual care. STRIDE enrolled 5451 community-dwelling older adults age ≥70 at increased fall injury risk. METHODS: We assessed fall-related outcomes via telephone interviews of participants (or proxies) every 4 months. At baseline, 12 and 24 months, we assessed health-related quality of life (HRQOL) using the EQ-5D-5L and EQ-VAS. We used Poisson models to assess intervention effects on falls, fall-related fractures, fall injuries leading to hospital admission, and fall injuries leading to medical attention. We used hierarchical longitudinal linear models to assess HRQOL. RESULTS: For recurrent event models, intervention versus control incidence rate ratios were 0.97 (95% confidence interval [CI], 0.93-1.00; p = 0.048) for falls, 0.93 (95% CI, 0.80-1.08; p = 0.337) for self-reported fractures, 0.89 (95% CI, 0.73-1.07; p = 0.205) for adjudicated fractures, 0.91 (95% CI, 0.77-1.07; p = 0.263) for falls leading to hospital admission, and 0.97 (95% CI, 0.89-1.06; p = 0.477) for falls leading to medical attention. Similar effect sizes (non-significant) were obtained for dichotomous outcomes (e.g., participants with ≥1 events). The difference in least square mean change over time in EQ-5D-5L (intervention minus control) was 0.009 (95% CI, -0.002 to 0.019; p = 0.106) at 12 months and 0.005 (95% CI, -0.006 to 0.015; p = 0.384) at 24 months. CONCLUSIONS: Across a standard set of outcomes typically reported in fall prevention studies, we observed modest improvements, one of which was statistically significant. Future work should focus on patient-, practice-, and organization-level operational strategies to increase the real-world effectiveness of interventions, and improving the ability to detect small but potentially meaningful clinical effects. CLINICALTRIALS: gov identifier: NCT02475850.

A Photography-based, Social Media Walking Intervention Targeting Autonomous Motivations for Physical Activity: Semistructured Interviews With Older Women.

BACKGROUND: Older adult women are at risk for negative health outcomes that engaging in sustained physical activity can help prevent. However, promoting long-term maintenance of physical activity in this population has proven to be a challenge. Increasing autonomous motivations (ie, intrinsic, integrated, and identified regulations) for physical activity may facilitate enduring behavior change. Digitally delivered games for health that take a celebratory technology approach, that is, using technology to create new ways to experience valued behaviors and express valued beliefs, may be a useful way to target autonomous motivations for physical activity. Formative research with the target population is needed to design compelling intervention content. OBJECTIVE: The objective of this study is to investigate older adult women's reactions to and thoughts about a photography-based, social media walking game targeting autonomous motivations for physical activity. METHODS: During an individual semistructured interview, a moderator solicited feedback from 20 older adult women (age range 65-74 years) as part of formative research to develop a social media game featuring weekly walking challenges. The challenges were designed to target autonomous motivations for physical activity. Interviews were audio-recorded and transcribed verbatim. Two reviewers conducted thematic content analysis on interview transcripts. RESULTS: We identified 3 overarching themes in qualitative data analysis. These reflected the playful experiences, value, and acceptability associated with the intervention challenges. Generally, participants understood what the challenges were asking them to do, proffered appropriate example responses, and indicated that the challenges would be enjoyable. Participants reported that the intervention content afforded many and varied playful experiences (eg, competition, discovery, exploration, expression, fellowship, humor, nurture, sensation). Further, participants indicated that the intervention increased their motivation for physical activity, occasioned meaningful shifts in perspective, increased their knowledge of various topics of interest, provided an opportunity to create valued connection with others, and provided health-related benefits. Participants suggested the intervention emphasize local history, nature, and cultural events. CONCLUSIONS: The photography-based, social media walking game with relatively simple game mechanics was well received and judged to be apt to bring about a wide variety of emotive experiences. A clear, geographically specific identity emerged as a key driver of interest for intervention content. Taking a celebratory technology approach holds promise for targeting autonomous motivations for physical activity in older adult women.

Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.

Activating transcription factor 4 (ATF4) is a multifunctional transcription regulatory protein in the basic leucine zipper superfamily. ATF4 can be expressed in most if not all mammalian cell types, and it can participate in a variety of cellular responses to specific environmental stresses, intracellular derangements, or growth factors. Because ATF4 is involved in a wide range of biological processes, its roles in human health and disease are not yet fully understood. Much of our current knowledge about ATF4 comes from investigations in cultured cell models, where ATF4 was originally characterized and where further investigations continue to provide new insights. ATF4 is also an increasingly prominent topic of in vivo investigations in fully differentiated mammalian cell types, where our current understanding of ATF4 is less complete. Here, we review some important high-level concepts and questions concerning the basic biology of ATF4. We then discuss current knowledge and emerging questions about the in vivo role of ATF4 in one fully differentiated cell type, mammalian skeletal muscle fibers.

Improvements in sleep quality and fatigue are associated with improvements in functional recovery following hospitalization in older adults.

Study objectives: Poor sleep quality, a frequent problem in older adults, has been shown to be associated with reduced physical function and wellbeing. However, little is known about the relationship between sleep quality and the recovery of physical function following hospitalization. Thus, we conducted this study to examine the association between sleep quality and functional recovery after an acute hospitalization in community dwelling older adults. Methods: Older adult patients (N = 23, mean age = 74 ± 9 years) were recruited during an acute hospitalization (average length of stay 3.9 days) with a cardiovascular (56%), pulmonary (22%), or metabolic (13%) admission diagnosis. Objective physical function was measured using the Short Physical Performance Battery (SPPB) and self-reported function was assessed with Katz Index of Independence in Activities of Daily Living (ADL) and Lawton Instrumental Activities of Daily Living Scale (IADL). Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) global score and Iowa Fatigue Score (IFS). Testing was performed prior to discharge (baseline) and 4-weeks post-discharge (follow-up). Results: Regression models showed PSQI Subjective Sleep Quality change scores from baseline to 4-week follow-up predicted a change in ADL (ß = -0.22); PSQI Use of Sleep Medications change scores predicted a change in SPPB Total (ß = 1.62) and SPPB Chair Stand (ß = 0.63); IFS change scores predicted SPPB Total (ß = -0.16) and SPPB Chair Stand performance (ß = -0.07) change scores. Conclusions: For older adults, changes in sleep medication use, daytime dysfunction, and fatigue were associated with improvements in functional recovery (including physical performance and independence) from acute hospitalization to 4-week follow-up. These results suggest that interventions focused on improving sleep quality, daytime consequences, and fatigue might help enhance physical functioning following hospitalization. Clinical trial registration: ClinicalTrials.gov, identifier: NCT02203656.

Dietary Intake Patterns of Community-Dwelling Older Adults After Acute Hospitalization.

BACKGROUND: Malnutrition and sarcopenia are a growing concern in community-dwelling older adults. Hospitalization increases the risk of malnutrition and leads to a decline in functional and nutritional status at discharge. Persistent malnutrition after hospital discharge may worsen posthospital outcomes, including readmissions. The aim of this study was to determine dietary intakes and nutrient distribution patterns of community-dwelling older adults after acute hospitalization. METHOD: Participants (65 years and older, n = 85) were enrolled during acute hospitalization and dietary 24-hour recalls were collected weekly for 1 month postdischarge. Analysis included change in dietary intake over recovery timeframe; daily intake of energy, protein, fruit, vegetables, and fluids; comparison of intake to recommendations; distribution of energy and protein across mealtimes; and analysis of most common food choices. RESULTS: Most participants did not meet current recommendations for energy, fruit, vegetables, or fluids. Average protein consumption was significantly higher than the current recommendation of 0.8 g/kg/d; however, only 55% of participants met this goal and less than 18% met the 1.2 g/kg/d proposed optimal protein intake for older adults. The protein distribution throughout the day was skewed and no one met the 0.4 g/meal protein recommendation at all meals. CONCLUSIONS: Our findings indicate that community-dwelling older adults did not meet their nutritional needs during recovery after hospitalization. These data highlight the need for better nutritional evaluation and support of geriatric patients recovering from hospitalization.

Efficacy of Liposomal Melatonin in sleep EEG in Childhood: A Double Blind Case Control Study.

Electroencephalography (EEG) is pivotal in the clinical assessment of epilepsy, and sleep is known to improve the diagnostic yield of its recording. Sleep-EEG recording is generally reached by either partial deprivation or by administration of sleep-inducing agents, although it is still not achieved in a considerable percentage of patients. We conducted a double-blind placebo-controlled study, involving a hundred patients between 1 and 6 years old, randomized into two groups: Group 1 received liposomal melatonin (melatosome) whereas Group 2 received a placebo. Sleep latency (SL), defined as the time span between the onset of a well-established posterior dominant rhythm, considered as a frequency of 3 to 4 Hz, increasing to 4-5 Hz by the age of 6 months, to 5-7 Hz by 12 months, and finally to 8 Hz by 3 years, and the first EEG sleep figures detected, were measured for each patient. A significant difference in SL was observed (10.8 ± 5 vs. 18.1 ± 13.4 min, p-value = 0.002). Within each group, no differences in sleep latency were detected between genders. Furthermore, no difference in EEG abnormality detection was observed between the two groups. Our study confirmed the efficacy and safety of melatonin administration in sleep induction. Nonetheless, liposomal melatonin presents a greater bioavailability, ensuring a faster effect and allowing lower dosages. Such results, never before reported in the literature, suggest that the routine employment of melatonin might improve clinical practice in neurophysiology, reducing unsuccessful recordings.

Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review.

Exercise intolerance (EI) is the primary manifestation of chronic heart failure with preserved ejection fraction (HFpEF), the most common form of heart failure among older individuals. The recent recognition that HFpEF is likely a systemic, multiorgan disorder that shares characteristics with other common, difficult-to-treat, aging-related disorders suggests that novel insights may be gained from combining knowledge and concepts from aging and cardiovascular disease disciplines. This state-of-the-art review is based on the outcomes of a National Institute of Aging-sponsored working group meeting on aging and EI in HFpEF. We discuss aging-related and extracardiac contributors to EI in HFpEF and provide the rationale for a transdisciplinary, "gero-centric" approach to advance our understanding of EI in HFpEF and identify promising new therapeutic targets. We also provide a framework for prioritizing future research, including developing a uniform, comprehensive approach to phenotypic characterization of HFpEF, elucidating key geroscience targets for treatment, and conducting proof-of-concept trials to modify these targets.

Effect of the lysosomotropic agent chloroquine on mTORC1 activation and protein synthesis in human skeletal muscle.

BACKGROUND: Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine-a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction. METHODS: mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine (CHQ, n = 7) or serving as controls (CON, n = 7; no chloroquine). Additionally, differentiated C2C12 cells were used to assess mTORC1 signaling and myotube protein synthesis (MyPS) in the presence and absence of leucine and the lysosomotropic agent chloroquine. RESULTS: mTORC1, S6K1, 4E-BP1 and rpS6 phosphorylation increased in both CON and CHQ 1 h post EAA ingestion (P < 0.05). MPS increased similarly in both groups (CON, P = 0.06; CHQ, P < 0.05). In contrast, in C2C12 cells, 1 mM leucine increased mTORC1 and S6K1 phosphorylation (P < 0.05), which was inhibited by 2 mg/ml chloroquine. Chloroquine (2 mg/ml) was sufficient to disrupt mTORC1 signaling, and MyPS. CONCLUSIONS: Chloroquine did not inhibit amino acid-induced activation of mTORC1 signaling and skeletal MPS in humans as it does in C2C12 muscle cells. Therefore, different in vivo experimental approaches are required for confirming the precise role of the lysosome and amino acid sensing in human skeletal muscle. Trial registration NCT00891696. Registered 29 April 2009.

Intranasal Oxytocin Improves Lean Muscle Mass and Lowers LDL Cholesterol in Older Adults with Sarcopenic Obesity: A Pilot Randomized Controlled Trial.

OBJECTIVES: Obesity is associated with sarcopenia in older adults, and weight loss can lead to further muscle mass loss. Oxytocin decreases with age, and animal studies suggest that oxytocin administration has trophic effects on skeletal muscle cells and reduces adiposity. We conducted a clinical trial to examine the safety and preliminary efficacy of intranasal oxytocin for older adults with sarcopenic obesity. DESIGN: A double-blind, placebo-controlled randomized controlled trial of intranasal oxytocin (24 IU 4 times per day) for 8 weeks. SETTING AND PARTICIPANTS: Twenty-one older (67.5 ± 5.4 years), obese (30-43 kg/m2), sedentary (<2 strenuous exercise per week) adults with slow gait speed (<1 m/s, proxy measure of sarcopenia) were recruited. MEASURES: Generalized estimating equations were used to evaluate the effect of oxytocin on safety/tolerability of oxytocin administration and whole body muscle and fat mass. RESULTS: At baseline, body mass index (BMI) was 36.8 ± 3.6 kg/m2, fat mass 46.09 ± 6.99 kg, lean mass 50.98 ± 11.77 kg, fasting plasma glucose (FPG) 92.0 ± 8.9 mg/dL, hemoglobin A1c (HbA1c) 5.7% ± 0.4%, low density lipoprotein (LDL) 111.3 ± 41.5 mg/dL, high-density lipoprotein (HDL) 47.85 ± 10.96 mg/dL, and triglycerides 140.55 ± 83.50 mg/dL. Oxytocin administration was well tolerated without any significant adverse events. Oxytocin led to a significant increase of 2.25 kg in whole body lean mass compared with placebo (P < .01) with a trend toward decreasing fat mass, and a significantly reduced plasma LDL cholesterol by -19.3 mg/dL (P = .023) compared against placebo. There were no significant changes in BMI, appetite scores, glycemia, plasma HDL, triglycerides, or depressive symptoms. CONCLUSIONS AND IMPLICATIONS: This proof-of-concept study indicates that oxytocin may be useful for the treatment of sarcopenic obesity in older adults. Oxytocin administration may also provide additional cardiovascular benefits.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.

BACKGROUND: Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. METHODS: The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. RESULTS: Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. CONCLUSIONS: Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.

Global-scale massive feature extraction from monthly hydroclimatic time series: Statistical characterizations, spatial patterns and hydrological similarity.

Hydroclimatic time series analysis focuses on a few feature types (e.g., autocorrelations, trends, extremes), which describe a small portion of the entire information content of the observations. Aiming to exploit a larger part of the available information and, thus, to deliver more reliable results (e.g., in hydroclimatic time series clustering contexts), here we approach hydroclimatic time series analysis differently, i.e., by performing massive feature extraction. In this respect, we develop a big data framework for hydroclimatic variable behaviour characterization. This framework relies on approximately 60 diverse features and is completely automatic (in the sense that it does not depend on the hydroclimatic process at hand). We apply the new framework to characterize mean monthly temperature, total monthly precipitation and mean monthly river flow. The applications are conducted at the global scale by exploiting 40-year-long time series originating from over 13 000 stations. We extract interpretable knowledge on seasonality, trends, autocorrelation, long-range dependence and entropy, and on feature types that are met less frequently. We further compare the examined hydroclimatic variable types in terms of this knowledge and, identify patterns related to the spatial variability of the features. For this latter purpose, we also propose and exploit a hydroclimatic time series clustering methodology. This new methodology is based on Breiman's random forests. The descriptive and exploratory insights gained by the global-scale applications prove the usefulness of the adopted feature compilation in hydroclimatic contexts. Moreover, the spatially coherent patterns characterizing the clusters delivered by the new methodology build confidence in its future exploitation. Given this spatial coherence and the scale-independent nature of the delivered feature values (which makes them particularly useful in forecasting and simulation contexts), we believe that this methodology could also be beneficial within regionalization frameworks, in which knowledge on hydrological similarity is exploited in technical and operative terms.

Effect of a Multifactorial Fall Injury Prevention Intervention on Patient Well-Being: The STRIDE Study.

BACKGROUND/OBJECTIVES: In the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) study, a multifactorial intervention was associated with a nonsignificant 8% reduction in time to first serious fall injury but a significant 10% reduction in time to first self-reported fall injury relative to enhanced usual care. The effect of the intervention on other outcomes important to patients has not yet been reported. We aimed to evaluate the effect of the intervention on patient well-being including concern about falling, anxiety, depression, physical function, and disability. DESIGN: Pragmatic cluster-randomized trial of 5,451 community-living persons at high risk for serious fall injuries. SETTING: A total of 86 primary care practices within 10 U.S. healthcare systems. PARTICIPANTS: A random subsample of 743 persons aged 75 and older. MEASUREMENTS: The well-being measures, assessed at baseline, 12 months, and 24 months, included a modified version of the Fall Efficacy Scale, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety and depression scales, and Late-Life Function and Disability Instrument. RESULTS: Participants in the intervention (n = 384) and control groups (n = 359) were comparable in age: mean (standard deviation) of 81.9 (4.7) versus 81.8 (5.0) years. Mean scores were similar between groups at 12 and 24 months for concern about falling, physical function, and disability, whereas the intervention group's mean scores on anxiety and depression were .7 points lower (i.e., better) at 12 months and .6 to .8 points lower at 24 months. For each of these outcomes, differences between the groups' adjusted least square mean changes from baseline to 12 and 24 months, respectively, were quantitatively small. The overall difference in means between groups over 2 years was statistically significant only for depression, favoring the intervention: -1.19 (99% confidence interval, -2.36 to -.02), with 3.5 points representing a minimally important difference. CONCLUSIONS: STRIDE's multifactorial intervention to reduce fall injuries was not associated with clinically meaningful improvements in patient well-being.