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ABSTRACT Medical modulation of sex hormone levels is a cornerstone of treatment for many conditions that impact well-being, including cancer, fertility/infertility, gender dysphoria, and chronic metabolic diseases such as diabetes and obesity. The microbial residents of the intestine, known as the microbiota, interact with sex hormones in the intestine, and there is correlative evidence that this interaction is bidirectional. Based on these published findings, we hypothesized that transgender individuals receiving exogenous testosterone as part of their gender-affirming medical treatment might undergo changes in their intestinal microbiome. To test this, we collected 26 stool samples from nine individuals before and up to 8 months after initiation of treatment with exogenous testosterone and subjected these samples to metagenomic analysis. While no species were significantly associated with the duration of testosterone therapy, pathways that generate glutamate increased in abundance, while those that consume glutamate decreased. Glutamate is a precursor of arginine, and testosterone is known to increase levels of arginine and its metabolites in the plasma. We hypothesize that testosterone increases the uptake of glutamate by enterocytes, thus decreasing access of the microbiota to this amino acid. While this pilot study establishes the impact of testosterone therapy on the intestinal microbiome, a more comprehensive study is necessary to establish the impact of testosterone-driven metagenomic shifts on the stool metatranscriptome, the stool metabolome, and the plasma metabolome.IMPORTANCEThe human intestine is inhabited by a large community of microbes known as the microbiome. Members of the microbiome consume the diet along with their human host. Thus, the metabolomes of the host and microbe are intricately linked. Testosterone alters the plasma metabolome. In particular, plasma levels of arginine and its metabolites and testosterone are positively correlated. To investigate the impact of exogenous testosterone on the microbiome, we analyzed the stool metagenomes of transgender individuals before and after the initiation of testosterone treatment. In this pilot project, we found a modest impact on the microbiome community structure but an increase in the abundance of metabolic pathways that generate glutamate and spare glutamate consumption. We propose that the host uses glutamate to generate arginine, decreasing the amount available for the microbiome.

Abstract The emergence of COVID-19 dramatically changed social behavior across societies and contexts. Here we study whether social norms also changed. Specifically, we study this question for cultural tightness (the degree to which societies generally have strong norms), specific social norms (e.g. stealing, hand washing), and norms about enforcement, using survey data from 30,431 respondents in 43 countries recorded before and in the early stages following the emergence of COVID-19. Using variation in disease intensity, we shed light on the mechanisms predicting changes in social norm measures. We find evidence that, after the emergence of the COVID-19 pandemic, hand washing norms increased while tightness and punishing frequency slightly decreased but observe no evidence for a robust change in most other norms. Thus, at least in the short term, our findings suggest that cultures are largely stable to pandemic threats except in those norms, hand washing in this case, that are perceived to be directly relevant to dealing with the collective threat.

Introduction: Helicopter emergency medical services (HEMS) are used in the United States and globally to respond to patients with critical illness and victims of traumatic injury. Relatively limited research has examined their role in responding to out-of-hospital cardiac arrests (OHCA) in the United States. In this study, we compared OHCA treated by HEMS units with cardiac arrests treated by ground ambulances. Methods: We queried a large national-level database of emergency medical services (EMS) activations in the United States (NEMSIS). Inclusion criteria were OHCA activations between January 1, 2022 and December 31, 2022 treated by either HEMS or ground ambulance. Key arrest data from both groups were then compared. Interfacility transfers and cardiac arrests after EMS arrival were excluded. Results: A total of 1,233 cardiac arrests treated by HEMS and 341,096 cardiac arrests treated by ground ambulances met inclusion criteria. Comparing the two groups, cardiac arrests with HEMS response were more likely to be male (66.7% vs. 62.8%, p

BackgroundProgressive difficulty in performing everyday functional activities is a key diagnostic feature of dementia syndromes. However, not much is known about the neural signature of functional decline, particularly during the very early stages of dementia. Early intervention before overt impairment is observed offers the best hope of reducing the burdens of Alzheimer disease (AD) and other dementias. However, to justify early intervention, those at risk need to be detected earlier and more accurately. The decline in complex daily function (CdF) such as managing medications has been reported to precede impairment in basic activities of daily living (eg, eating and dressing). ObjectiveOur goal is to establish the neural signature of decline in CdF during the preclinical dementia period. MethodsGait is central to many CdF and community-based activities. Hence, to elucidate the neural signature of CdF, we validated a novel electroencephalographic approach to measuring gait-related brain activation while participants perform complex gait-based functional tasks. We hypothesize that dementia-related pathology during the preclinical period activates a unique gait-related electroencephalographic (grEEG) pattern that predicts a subsequent decline in CdF. ResultsWe provide preliminary findings showing that older adults reporting CdF limitations can be characterized by a unique gait-related neural signature: weaker sensorimotor and stronger motor control activation. This subsample also had smaller brain volume and white matter hyperintensities in regions affected early by dementia and engaged in less physical exercise. We propose a prospective observational cohort study in cognitively unimpaired older adults with and without subclinical AD (plasma amyloid-β) and vascular (white matter hyperintensities) pathologies. We aim to (1) establish the unique grEEG activation as the neural signature and predictor of decline in CdF during the preclinical dementia period; (2) determine associations between dementia-related pathologies and incidence of the neural signature of CdF; and (3) establish associations between a dementia risk factor, physical inactivity, and the neural signature of CdF. ConclusionsBy establishing the clinical relevance and biological basis of the neural signature of CdF decline, we aim to improve prediction during the preclinical stages of ADs and other dementias. Our approach has important research and translational implications because grEEG protocols are relatively inexpensive and portable, and predicting CdF decline may have real-world benefits. International Registered Report Identifier (IRRID)DERR1-10.2196/56726

BackgroundPhysical activity is associated with improved health and function in older adults, yet most older adults are sedentary. Loneliness is associated with decreased physical activity at the cross-section, but longitudinal studies are scarce. We examined longitudinal associations between loneliness and physical activity—and whether they were modified by marital status and network size (the number of children, relatives, and friends a person interacts with at least once a month).MethodsWe analyzed data from 1,931 older adults without dementia at baseline from the Rush Memory and Aging Project with a mean follow-up of 4.8 years (mean age 79.6 ± 7.7, 74.9% women). Loneliness was assessed using the de Jong Gierveld Loneliness Scale. Physical activity was assessed as the frequency with which participants engaged in five categories of activities (e.g., walking, gardening, calisthenics, bicycling, and swimming). Linear mixed effects models examined associations between baseline loneliness and change in physical activity over time after adjusting for demographics, depressive symptoms, global cognition, disability, network size, marital status, social support, and social and cognitive activities. We assessed for effect modification by marital status and network size.ResultsAssociations between loneliness and physical activity differed by marital status. In widowed individuals, baseline loneliness was associated with a 0.06 h/week greater decrease in physical activity per year compared to those who were not lonely (p = 0.005, CI -0.1, 0.02)—which equaled a 150% decrease in physical activity per year. Loneliness did not predict a statistically significant decrease in physical activity in married or unmarried individuals.DiscussionLoneliness is associated with decreased physical activity in widowed older adults and should be considered in the design of interventions to prevent or slow the decline in physical activity and promote healthy aging.

BackgroundThe southern India state of Kerala has among the highest proportion of older adults in its population in the country. An increase in chronic age-related diseases such as dementia is expected in the older Kerala population. Identifying older individuals early in the course of cognitive decline offers the best hope of introducing preventive measures early and planning management. However, the epidemiology and pathogenesis of predementia syndromes at the early stages of cognitive decline in older adults are not well established in India. ObjectiveThe Kerala Einstein Study (KES) is a community-based cohort study that was established in 2008 and is based in the Kozhikode district in Kerala state. KES aims to establish risk factors and brain substrates of motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by the presence of slow gait and subjective cognitive concerns in individuals without dementia or disability. This protocol describes the study design and procedures for this KES project. MethodsKES is proposing to enroll a sample of 1000 adults ≥60 years old from urban and rural areas in the Kozhikode district of Kerala state: 200 recruited in the previous phase of KES and 800 new participants to be recruited in this project. MCR is the cognitive phenotype of primary interest. The associations between previously established risk factors for dementia as well as novel risk factors (apathy and traumatic brain injury) and MCR will be examined in KES. Risk factor profiles for MCR will be compared between urban and rural residents as well as with individuals who meet the criteria for mild cognitive impairment (MCI). Cognitive and physical function, medical history and medications, sociodemographic characteristics, lifestyle patterns, and activities of daily living will be evaluated. Participants will also undergo magnetic resonance imaging and electrocardiogram investigations. Longitudinal follow-up is planned in a subset of participants as a prelude to future longitudinal studies. ResultsKES (2R01AG039330-07) was funded by the US National Institutes of Health in September 2019 and received approval from the Indian Medical Council of Research to start the study in June 2021. We had recruited 433 new participants from urban and rural sites in Kozhikode as of May 2023: 41.1% (178/433) women, 67.7% (293/433) rural residents, and 13.4% (58/433) MCR cases. Enrollment is actively ongoing at all the KES recruitment sites. ConclusionsKES will provide new insights into risk factors and brain substrates associated with MCR in India and will help guide future development of regionally specific preventive interventions for dementia. International Registered Report Identifier (IRRID)DERR1-10.2196/49933

Resumo Este estudo investiga as dimensões do uso de dispositivos tecnológicos, entre eles a Inteligência Artificial (IA), em processos de Recrutamento e Seleção (R&S) sob a perspectiva de recrutadores de empresas do setor farmacêutico instaladas no estado de São Paulo. Para isso, foi realizada uma pesquisa qualitativa, por meio de um roteiro semiestruturado, com 12 entrevistados com experiência em R&S antes e depois do advento da tecnologia. Foram observados os benefícios, as tendências e resistências com relação ao uso de tecnologia e IA nos processos de R&S. Como benefício, tem-se o papel da tecnologia e IA na desburocratização da área de Recursos Humanos (RH), de modo a tornar seu foco mais estratégico e consultivo, na medida em que reduz tempo e custo na triagem de currículos e seleção de candidatos. Como tendência, verificou-se que a pandemia trouxe uma quebra de paradigma no uso de tecnologias no processo de R&S, a qual deverá ser utilizada, seja de forma integral ou parcial, em uma maior amplitude de vagas. Dentre as resistências ao seu uso, tem-se o ceticismo acerca da assertividade na seleção do candidato por meio da tecnologia e IA, devido à redução do contato humano. Foram abordadas, ainda, as questões ambíguas acerca das implicações do uso de tecnologia e IA na diversidade dos negócios. Sugestões para futuras pesquisas e limitações da pesquisa também foram apresentadas.

Objectives Happiness has been shown to influence many health-related outcomes in older adults. Identifying correlates and brain substrates of happiness across countries and cultures is an important goal, as the global older adult population continues to increase. Methods We used univariate and multiple regression to examine associations between happiness and several demographic, health, and lifestyle variables in 665 older adults (39% female) from Kerala, India. We also used Bayesian regression to examine associations between cortical thickness and happiness in a subsample of 188 participants that completed MRI scanning. Results Happiness was significantly associated with several variables. In our multiple regression model, which included all significant univariate predictors, self-rated health, depression, anxiety, apathy, social network size, social network diversity, and social support significantly predicted happiness. Demographic indicators (age, sex, education, marital status, residence, and employment status/type), cognitive impairment, comorbidities, and leisure activities were not significantly associated with happiness in the multiple regression model. Cortical thickness in several brain regions was positively associated with happiness scores, including frontal, temporal, parietal, occipital, and cingulate regions. Discussion Understanding the key correlates is critical for identifying both modifiable factors that can be targeted in well-being interventions and fixed characteristics that identify those at-risk for reduced happiness. The widespread pattern of brain regions associated with happiness is consistent with the multifactorial nature of happiness and, given that the regions identified do not overlap with those vulnerable to cortical thinning, can help explain why subjective well-being, unlike other cognitive functions, is largely resistant to age-related decline. [ABSTRACT FROM AUTHOR]

Identification of novel, non-invasive, non-cognitive based markers of Alzheimer’s disease (AD) and related dementias are a global priority. Growing evidence suggests that Alzheimer’s pathology manifests in sensory association areas well before appearing in neural regions involved in higher-order cognitive functions, such as memory. Previous investigations have not comprehensively examined the interplay of sensory, cognitive, and motor dysfunction with relation to AD progression. The ability to successfully integrate multisensory information across multiple sensory modalities is a vital aspect of everyday functioning and mobility. Our research suggests that multisensory integration, specifically visual-somatosensory integration (VSI), could be used as a novel marker for preclinical AD given previously reported associations with important motor (balance, gait, and falls) and cognitive (attention) outcomes in aging. While the adverse effect of dementia and cognitive impairment on the relationship between multisensory functioning and motor outcomes has been highlighted, the underlying functional and neuroanatomical networks are still unknown. In what follows we detail the protocol for our study, named The VSI Study, which is strategically designed to determine whether preclinical AD is associated with neural disruptions in subcortical and cortical areas that concurrently modulate multisensory, cognitive, and motor functions resulting in mobility decline. In this longitudinal observational study, a total of 208 community-dwelling older adults with and without preclinical AD will be recruited and monitored yearly. Our experimental design affords assessment of multisensory integration as a new behavioral marker for preclinical AD; identification of functional neural networks involved in the intersection of sensory, motor, and cognitive functioning; and determination of the impact of early AD on future mobility declines, including incident falls. Results of The VSI Study will guide future development of innovative multisensory-based interventions aimed at preventing disability and optimizing independence in pathological aging.