Stroke Incidence in Patients With Hypertension According to Cardiorespiratory Fitness.

BACKGROUND: Hypertension and physical inactivity are risk factors for stroke. The effect of cardiorespiratory fitness (CRF) on stroke risk in patients with hypertension has not been assessed. We evaluated stroke incidence in patients with hypertension according to CRF and changes in CRF. METHODS: We included 483 379 patients with hypertension (mean age±SD; 59.4±9.0 years) and no evidence of unstable cardiovascular disease as indicated by a standardized exercise treadmill test. Patients were assigned to 5 age- and sex-specific CRF categories based on peak metabolic equivalents achieved at the initial exercise treadmill test and in 4 categories based on metabolic equivalent changes over time (n=110 576). Multivariable Cox models, adjusted for age, and comorbidities were used to estimate hazard ratios and 95% CIs for stroke risk. RESULTS: During a median follow-up of 10.6 (interquartile range, 6.6-14.6) years, 15 925 patients developed stroke with an average yearly rate of 3.1 events/1000 person-years. Stroke risk declined progressively with higher CRF and was 55% lower for the High-fit individuals (hazard ratio, 0.45 [95% CI, 0.42-0.48]) compared with the Least-fit. Similar associations were observed across the race, sex, and age spectra. Poor CRF was the strongest predictor of stroke risk of all comorbidities studied (hazard ratio, 2.24 [95% CI, 2.10-2.40]). Changes in CRF reflected inverse and proportional changes in stroke risk. CONCLUSIONS: Poor CRF carried a greater risk than any of the cardiac risk factors in patients with hypertension, regardless of age, race, or sex. The lower stroke risk associated with improved CRF suggests that increasing physical activity, even later in life, may reduce stroke risk.

Self-administered mindfulness interventions reduce stress in a large, randomized controlled multi-site study.

Mindfulness witnessed a substantial popularity surge in the past decade, especially as digitally self-administered interventions became available at relatively low costs. Yet, it is uncertain whether they effectively help reduce stress. In a preregistered (OSF https://doi.org/10.17605/OSF.IO/UF4JZ ; retrospective registration at ClinicalTrials.gov NCT06308744 ) multi-site study (nsites = 37, nparticipants = 2,239, 70.4% women, Mage = 22.4, s.d.age = 10.1, all fluent English speakers), we experimentally tested whether four single, standalone mindfulness exercises effectively reduced stress, using Bayesian mixed-effects models. All exercises proved to be more efficacious than the active control. We observed a mean difference of 0.27 (d = -0.56; 95% confidence interval, -0.43 to -0.69) between the control condition (M = 1.95, s.d. = 0.50) and the condition with the largest stress reduction (body scan: M = 1.68, s.d. = 0.46). Our findings suggest that mindfulness may be beneficial for reducing self-reported short-term stress for English speakers from higher-income countries.

FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice increased their responding for liquid protein rewards, but not carbohydrate, fat, or sweet rewards. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation of dopamine neurons as compared to casein in control-fed mice, while casein produced a larger response in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data demonstrate that FGF21 acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

More People, More Active, More Often for Heart Health - Taking Action on Physical Activity.

Physical inactivity is a leading contributor to increased cardiovascular morbidity and mortality. Almost 500 million new cases of preventable noncommunicable diseases (NCDs) will occur globally between 2020 and 2030 due to physical inactivity, costing just over US$300 billion, or around US$ 27 billion annually (WHO 2022). Active adults can achieve a reduction of up to 35% in risk of death from cardiovascular disease. Physical activity also helps in moderating cardiovascular disease risk factors such as high blood pressure, unhealthy weight and type 2 diabetes. For people with cardiovascular disease, hypertension, type 2 diabetes and many cancers, physical activity is an established and evidence-based part of treatment and management. For children and young people, physical activity affords important health benefits. Physical activity can also achieve important cross-sector goals. Increased walking and cycling can reduce journeys by vehicles, air pollution, and traffic congestion and contribute to increased safety and liveability in cities.

Limitations of the 2015-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for emergency bariatric operations.

BACKGROUND: The Metabolic and Bariatric Surgery Quality Improvement Project (MBSAQIP) is the largest bariatric surgery-specific clinical data set. OBJECTIVES: In 2020, the definition of emergency cases was altered to include only revisional or conversion cases and not primary cases. The aim of this study was to examine how this change affects the utility of the data set for emergency case tracking. SETTING: MBSAQIP database. METHODS: Emergency cases were extracted from available MBSAQIP data (2015-2021). A comparison of co-morbidity profiles was done, specifically before and after the recent change to how "emergency" is defined in the data set. RESULTS: Eleven thousand and twenty-nine of the 1,048,575 total cases were coded as "emergency cases." From 2015 to 2019, 10,574 emergency cases were performed (∼2115 cases/yr), markedly decreasing in 2020 and 2021 to 455 cases (∼228 cases/yr). Before 2020, the most common procedures were the unlisted procedure of the stomach (45.14%, n = 3101), gastric band removal (25.3%, n = 2676), and reduction of internal hernia (11.8%, n = 1244). Between 2020 and 2021, this distribution changed with Roux-en-Y gastric bypass (RYGB), the most common emergency procedure (29.23%, n = 133). As expected from the change that captured only revisional cases, the average operative length was greater between 2020 and 2021 (127.6 versus 86.5 min). CONCLUSIONS: Capturable emergency cases declined in 2020, a trend related to changing the definition of emergency as part of MBSAQIP standards. This change excludes data on internal hernia reduction and does not likely reflect a real change in the prevalence of emergency bariatric cases. Because capture for emergency cases has diminished, so has any prior utility of using MBSAQIP data for studying emergency cases.

Nucleated Red Blood Cell Counts Differentiate Cardiac from Respiratory Causes of Cyanosis at Birth.

Tissue hypoxia increases erythropoietin production and release of immature erythrocytes that can be measured using nucleated red blood cell counts (nRBC). We hypothesized that hypoxia due to congenital heart disease (CHD) is chronic and is better tolerated than hypoxia due to respiratory disease (RD), which is an acute stress in newborns leading to higher nRBC. This study assesses the utility of nRBC as a marker to differentiate hypoxia due to CHD vs RD in term neonates. This was a single-center, retrospective study of term neonates with cyanosis from 2015 to 2022. Neonates < 37 weeks of gestation, with hypoxic-ischemic encephalopathy, and those with other causes of cyanosis were excluded. The patients were divided into 2 groups: cyanotic CHD and cyanotic RD. Clinical and laboratory data done within 12 h and 24-36 h after birth were collected. Data are represented as median and Interquartile range. Of 189 patients with cyanosis, 80 had CHD and 109 had RD. The absolute nRBC count at ≤ 12 h of age was lower in the CHD (360 cells/mm3) compared to RD group (2340 cells/mm3) despite the CHD group having significantly lower baseline saturations. A value of 1070 cells/mm3 was highly sensitive and specific for differentiating CHD from RD. The positive predictive value for this cut-off value of 1070 cells/mm3 was 0.94 and the negative predictive value was 0.89. The absolute nRBC is a simple screening test and is available worldwide. A nRBC < 1070 cells/mm3 in cyanotic newborns should hasten the search for CHD etiology with the possible need for prostaglandin therapy.

Child Health Needs and the Pediatric Cardiology Workforce: 2020-2040.

This article evaluates the pediatric cardiology (PC) workforce and forecasts its future supply. Produced as part of a supplement in Pediatrics, this effort represents a collaboration among the American Board of Pediatrics Foundation, the University of North Carolina at Chapel Hill's Carolina Health Workforce Research Center, the Strategic Modeling and Analysis Ltd., and members of the pediatric subspecialty community. PC is a complex subspecialty including care from fetal life through adulthood and in practice settings that range from the outpatient clinic to procedural settings to the cardiac ICU. Complex subdisciplines include imaging, electrophysiology, heart failure, and interventional and critical care. Using American Board of Pediatrics data, US Census Bureau data, and data from the modeling project, projections were created to model the subspecialty workforce through 2040. Across all modeling scenarios considered, there is considerable projected growth in the supply of pediatric cardiologists by 2040. However, there is significant regional variation in the projected supply of trainees relative to demand in terms of local population growth, with evidence of a likely mismatch between areas surrounding training centers versus areas of greatest workforce need. In addition, this article highlights areas for future focus, including efforts to attract more residents to the subspecialty in general, particularly underrepresented minority members; increased support, more part-time career options, and improved academic career advancement for women in PC; and the development of better "real-time" workforce data to guide trainees and training programs in decisions regarding sub-subspecialty job availability.

Update to the 2016 American Heart Association cardiorespiratory fitness statement.

In 2016 the American Heart Association published a scientific statement that summarized a large body of evidence concluding that cardiorespiratory fitness (CRF) was a powerful marker of cardiovascular disease (CVD) and CVD-mortality risk; its association with morbidity and mortality was independent of commonly obtained risk factors, and consequently, that it should be a routine measure in all health care settings. Since 2016 the interest in CRF as a prognostic for human health and performance has increased exponentially. This review will summarize a growing body of evidence that reinforces the notion that the assessment of CRF improves patient/client management. Feasible means of CRF assessment in health care settings is considered, and the expected response of CRF to exercise consistent with consensus recommendations is reviewed. The association between CRF and health care costs is also explored. The evidence reviewed will reinforce the conclusions drawn in 2016; that overwhelming evidence demands that CRF should be a routine assessment in all health care settings - a vital sign.

Construct validity evidence reporting practices for the Reading the Mind in the Eyes Test: A systematic scoping review.

The Reading the Mind in the Eyes Test (RMET) is one of the most influential measures of social cognitive ability, and it has been used extensively in clinical populations. However, questions have been raised about the validity of RMET scores. We conducted a systematic scoping review of the validity evidence reported in studies that administered the RMET (n = 1461; of which 804 included at least one clinical sample) with a focus on six key dimensions: internal consistency, test-retest reliability, factor structure, convergent validity, discriminant validity, and known group validity. Strikingly, 63% of these studies failed to provide validity evidence from any of these six categories. Moreover, when evidence was reported, it frequently failed to meet widely accepted validity standards. Overall, our results suggest a troubling conclusion: the validity of RMET scores (and the research findings based on them) are largely unsubstantiated and uninterpretable. More broadly, this project demonstrates how unaddressed measurement issues can undermine a voluminous psychological literature.

Does Aerobic Exercise Increase Skeletal Muscle Mass in Female and Male Adults?

INTRODUCTION: It is uncertain whether aerobic exercise in the form of walking contributes to the preservation or increase in total or regional skeletal muscle mass (SMM). PURPOSE: This study aimed to determine the effects of aerobic exercise on total and regional (upper body verses leg SMM) in male ( n = 105) and female ( n = 133) adults with overweight and obesity. METHODS: A retrospective analysis of data from four randomized controlled trials. Participants included those who completed the given trial (control, n = 63; intervention, n = 175) and with complete magnetic resonance imaging (MRI) measured adipose tissue and SMM pre- and postintervention. Macronutrient intake was assessed for a subsample of participants. Supervised exercise was performed by walking on a treadmill for durations ranging from 12 to 24 wk at intensities between 50% and 75% of V̇O 2peak . RESULTS: All MRI-measured adipose tissue depots were reduced, and cardiorespiratory fitness was increased by aerobic exercise compared with controls ( P < 0.001). Independent of baseline SMM, aerobic exercise was associated with a small reduction (estimated mean difference ± standard error) in whole-body SMM (-0.310 ± 0.150 kg, P = 0.039) and upper body SMM (-0.273 ± 0.121 kg, P = 0.025) compared with control. No between-group difference was observed for change in leg SMM ( P > 0.10). A negative association was observed between the relative change in body weight and change in total ( R2 = 0.37, P < 0.001), upper body ( R2 = 0.21, P < 0.001), and leg SMM ( R2 = 0.09, P = 0.701). The SMM-to-adipose tissue ratio increased in response to aerobic exercise and was positively associated with weight loss ( P < 0.001). Change in SMM was not associated with dietary protein intake ( P > 0.10). CONCLUSIONS: Aerobic exercise performed while walking preserves, but does not increase, SMM in exercising muscle of adults. SMM not directly targeted by aerobic exercise may not be maintained.

Invoking and identifying task-oriented interlocutor confusion in human-robot interaction.

Successful conversational interaction with a social robot requires not only an assessment of a user's contribution to an interaction, but also awareness of their emotional and attitudinal states as the interaction unfolds. To this end, our research aims to systematically trigger, but then interpret human behaviors to track different states of potential user confusion in interaction so that systems can be primed to adjust their policies in light of users entering confusion states. In this paper, we present a detailed human-robot interaction study to prompt, investigate, and eventually detect confusion states in users. The study itself employs a Wizard-of-Oz (WoZ) style design with a Pepper robot to prompt confusion states for task-oriented dialogues in a well-defined manner. The data collected from 81 participants includes audio and visual data, from both the robot's perspective and the environment, as well as participant survey data. From these data, we evaluated the correlations of induced confusion conditions with multimodal data, including eye gaze estimation, head pose estimation, facial emotion detection, silence duration time, and user speech analysis-including emotion and pitch analysis. Analysis shows significant differences of participants' behaviors in states of confusion based on these signals, as well as a strong correlation between confusion conditions and participants own self-reported confusion scores. The paper establishes strong correlations between confusion levels and these observable features, and lays the ground or a more complete social and affect oriented strategy for task-oriented human-robot interaction. The contributions of this paper include the methodology applied, dataset, and our systematic analysis.

Automated Identification of Modified Nucleosides during HRAM-LC-MS/MS using a Metabolomics ID Workflow with Neutral Loss Detection.

The role of post-transcriptional modification in biological processes has been an ongoing field of study for several decades. Improvements in liquid chromatography platforms and mass spectrometry instrumentation have resulted in the enhanced identification, characterization, and quantification of modified nucleosides in biological systems. One consequence of the rapid technological improvements in the analytical acquisition of modified nucleosides has been a dearth of robust data processing workflows for analyzing more than a handful of samples at a time. To improve the utility of LC-MS/MS for batch analyses of modified nucleosides, a workflow for automated nucleoside identification has been developed. We adapted the Thermo Fisher Scientific metabolomics identification software package, Compound Discoverer, to accurately identify modified nucleosides from batch LC-MS/MS acquisitions. Three points of identification are used: accurate mass from a monoisotopic mass list, spectral matching from a spectral library, and neutral loss identification. This workflow was applied to a batch (n = 24) of urinary nucleosides, resulting in the accurate identification and relative quantification of 16 known nucleosides in less than 1 h.

RING Program: The CFAR Diversity, Equity, and Inclusion Pathway Initiative.

BACKGROUND: Case Western Reserve University (CWRU)/University Hospitals Cleveland Medical Center in Cleveland, OH, and the University of Pittsburgh (Pitt) in Pittsburgh, PA, forged a strategic alliance to form the Rustbelt Center for AIDS Research. The Rustbelt Center for AIDS Research developed a National Institutes of Health-supported diversity, equity, and inclusion pathway initiative termed the "Rustbelt Investigators for the Next Generation (RING) Program" that provides research training experiences for Puerto Rican students that will help them pursue a biomedical research career in HIV. SETTING: The RING Program provides 10-week research training experiences in different disciplines of HIV/AIDS for under-represented minority undergraduate and masters students from 4 campuses (Río Piedras, Mayagüez, Humacao, and Cayey) at the University of Puerto Rico. Mentors are drawn from both CWRU and Pitt. RESULTS: The RING Program recently completed our first wave of recruitment. Recruitment sessions were either virtual or on site at the University of Puerto Rico campuses and included an overview presentation, a Q&A session, and in-person interviews. We interviewed 32 eligible applicants and accepted 10 into the program, of which 9 were female. Five students were matched with faculty at CWRU and 5 with faculty at Pitt. CONCLUSIONS: The RING Program is a comprehensive program in laboratory and implementation science that aims to enhance under-represented Hispanic undergraduate and masters students' passion for pursuing a biomedical research career in HIV.

m6A RNA methylation orchestrates transcriptional dormancy during paused pluripotency.

Embryos across metazoan lineages can enter reversible states of developmental pausing, or diapause, in response to adverse environmental conditions. The molecular mechanisms that underlie this remarkable dormant state remain largely unknown. Here we show that N6-methyladenosine (m6A) RNA methylation by Mettl3 is required for developmental pausing in mouse blastocysts and embryonic stem (ES) cells. Mettl3 enforces transcriptional dormancy through two interconnected mechanisms: (1) it promotes global mRNA destabilization and (2) it suppresses global nascent transcription by destabilizing the mRNA of the transcriptional amplifier and oncogene N-Myc, which we identify as a crucial anti-pausing factor. Knockdown of N-Myc rescues pausing in Mettl3-/- ES cells, and forced demethylation and stabilization of Mycn mRNA in paused wild-type ES cells largely recapitulates the transcriptional defects of Mettl3-/- ES cells. These findings uncover Mettl3 as a key orchestrator of the crosstalk between transcriptomic and epitranscriptomic regulation during developmental pausing, with implications for dormancy in adult stem cells and cancer.

Bariatric surgery alters mitochondrial function in gut mucosa.

BACKGROUND: The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. METHODS: Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. RESULTS: Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. CONCLUSION: Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.