Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution.

Direct comparisons of human and non-human primate brains can reveal molecular pathways underlying remarkable specializations of the human brain. However, chimpanzee tissue is inaccessible during neocortical neurogenesis when differences in brain size first appear. To identify human-specific features of cortical development, we leveraged recent innovations that permit generating pluripotent stem cell-derived cerebral organoids from chimpanzee. Despite metabolic differences, organoid models preserve gene regulatory networks related to primary cell types and developmental processes. We further identified 261 differentially expressed genes in human compared to both chimpanzee organoids and macaque cortex, enriched for recent gene duplications, and including multiple regulators of PI3K-AKT-mTOR signaling. We observed increased activation of this pathway in human radial glia, dependent on two receptors upregulated specifically in human: INSR and ITGB8. Our findings establish a platform for systematic analysis of molecular changes contributing to human brain development and evolution.

Gamma-glutamyl transferase and cardiovascular events in patients with congenital heart disease.

INTRODUCTION: Serum gamma-glutamyl transferase activity (GGT) seems to predict cardiovascular events in different populations. However, no data exist on patients with congenital heart disease (CHD). METHODS: Observational, analytic, prospective cohort study design involving CHD patients and a control population to determine the effect of GGT levels on survival. RESULTS: A total of 589 CHD patients (58% males, 29 ± 14 years old) and 2745 matched control patients were followed up. A total of 69 (12%) CHD patients had a major acute cardiovascular event (MACE) during the follow-up time (6.1 [0.7-10.4] years). Patients with CHD and a GGT >60 U/L were significantly older, more hypertensive and dyslipidemic, had a worse NYHA functional class and a greater anatomical complexity than CHD patients with a GGT ≤60 U/L. The binary logistic regression analysis showed that age, a great CHD anatomical complexity, and having atrial fibrillation/flutter were the predictive factors of higher GGT levels (>60 U/L). The Kaplan-Meier analysis showed that patients with CHD and a GGT concentration above 60 UL showed the lowest probability of survival compared to that of CHD with GGT ≤60 U/L and controls irrespective of their GGT concentrations (p < .001). Similarly, the multivariable Cox regression analysis found an independent association between higher GGT levels (>60 U/L) and a worse prognosis (HR 2.44 [1.34-4.44], p = .003) among patients with CHD. CONCLUSION: Patients with CHD showed significant higher GGT levels than patients in the control group having those with higher GGT concentrations (>60 U/L) the worst survival.

Validation of a Social Networks and Support Measurement Tool for Use in International Aging Research: The International Mobility in Aging Study.

The purpose of this study was to develop and validate a new instrument to assess social networks and social support (IMIAS-SNSS) for different types of social ties in an international sample of older adults. The study sample included n = 1995 community dwelling older people aged between 65 and 74 years from the baseline of the longitudinal International Mobility in Aging Study (IMIAS). In order to measure social networks for each type of social tie, participants were asked about the number of contacts, the number of contacts they see at least once a month or have a very good relationship with, or speak with at least once a month. For social support, participants had to rate the level of social support provided by the four types of contacts for five Likert scale items. Confirmatory Factor Analysis was conducted to determine the goodness of fit of the measurement models. Satisfactory goodness-of-fit indices confirmed the satisfactory factorial structure of the IMIAS-SNSS instrument. Reliability coefficients were 0.80, 0.81, 0.85, and 0.88 for friends, children, family, and partner models, respectively. The models were confirmed by CFA for each type of social tie. Moreover, IMIAS-SNSS detected gender differences in the older adult populations of IMIAS. These results provide evidence supporting that IMIAS-SNSS is a psychometrically sound instrument and of its validity and reliability for international populations of older adults.

Fear of falling and its association with life-space mobility of older adults: a cross-sectional analysis using data from five international sites.

Background: fear of falling (FOF) is a major health concern among community-dwelling older adults that could restrict mobility. Objective: to examine the association of FOF with life-space mobility (i.e. the spatial area a person moves through in daily life) of community-dwelling older adults from five diverse sites. Methods: in total, 1,841 older adults (65-74 years) were recruited from Kingston, Canada; Saint-Hyacinthe, Canada; Tirana, Albania; Manizales, Colombia and Natal, Brazil. FOF was assessed using the Fall Efficacy Scale-International (FES-I total score), and the life space was quantified using the Life-Space Assessment (LSA), a scale that runs from 0 (minimum life space) to 120 (maximum life space). Results: the overall average LSA total score was 68.7 (SD: 21.2). Multiple-linear regression analysis demonstrated a significant relationship of FOF with life-space mobility, even after adjusting for functional, clinical and sociodemographic confounders (B = -0.15, 95% confidence interval (CI) -0.26 to -0.04). The FOF × site interaction term was significant with a stronger linear relationship found in the Canadian sites and Tirana compared with the South American sites. After adjusting for all confounders, the association between FOF with LSA remained significant at Kingston (B = -0.32, 95% CI -0.62 to -0.01), Saint-Hyacinthe (B = -0.81, 95% CI -1.31 to -0.32) and Tirana (B = -0.57, 95% CI -0.89 to -0.24). Conclusion: FOF is an important psychological factor that is associated with reduction in life space of older adults in different social and cultural contexts, and the strength of this association is site specific. Addressing FOF among older adults would help improve their mobility in local communities, which in turn would improve social participation and health-related quality of life.

Relationships between community social capital and injury in Canadian adolescents: a multilevel analysis.

BACKGROUND: Characteristics of social environments are potential risk factors for adolescent injury. Impacts of social capital on the occurrence of such injuries have rarely been explored. METHODS: General health questionnaires were completed by 8910 youth aged 14 years and older as part of the 2010 Canadian Health Behaviour in School-Aged Children study. These were supplemented with community-level data from the 2006 Canada Census of Population. Multilevel logistic regression models with random intercepts were fit to examine associations of interest. The reliability and validity of variables used in this analysis had been established in past studies, or in new analyses that employed factor analysis. RESULTS: Between school differences explained 2% of the variance in the occurrence of injuries. After adjustment for all confounders, community social capital did not have any impact on the occurrence of injuries in boys: OR: 1.01, 95% CI 0.80 to 1.29. However, living in areas with low social capital was associated with lower occurrence of injuries in girls (OR 0.78, 95% CI 0.63 to 0.96). Other factors that were significantly related to injuries in both genders were younger age, engagement in more risky behaviours, and negative behavioural influences from peers. CONCLUSIONS: After simultaneously taking into account the influence of community-level and individual-level factors, community levels of social capital remained a relatively strong predictor of injury among girls but not boys. Such gender effects provide important clues into the social aetiology of youth injury.

Early life adversity and C-reactive protein in diverse populations of older adults: a cross-sectional analysis from the International Mobility in Aging Study (IMIAS).

BACKGROUND: Recent studies suggest potential associations between childhood adversity and chronic inflammation at older ages. Our aim is to compare associations between childhood health, social and economic adversity and high sensitivity C-reactive protein (hsCRP) in populations of older adults living in different countries. METHODS: We used the 2012 baseline data (n = 1340) from the International Mobility in Aging Study (IMIAS) of community-dwelling people aged 65-74 years in Natal (Brazil), Manizales (Colombia) and Canada (Kingston, Ontario; Saint-Hyacinthe, Quebec). Multiple linear and Poisson regressions with robust covariance were fitted to examine the associations between early life health, social, and economic adversity and hsCRP, controlling for age, sex, financial strain, marital status, physical activity, smoking and chronic conditions both in the Canadian and in the Latin American samples. RESULTS: Participants from Canadian cities have less adverse childhood conditions and better childhood self-reported health. Inflammation was lower in the Canadian cities than in Manizales and Natal. Significant associations were found between hsCRP and childhood social adversity in the Canadian but not in the Latin American samples. Among Canadian older adults, the fully-adjusted mean hsCRP was 2.2 (95% CI 1.7; 2.8) among those with none or one childhood social adversity compared with 2.8 (95% CI 2.1; 3.8) for those with two or more childhood social adversities (p = 0.053). Similarly, the prevalence of hsCRP > 3 mg/dL was 40% higher among those with higher childhood social adversity but after adjustment by health behaviors and chronic conditions the association was attenuated. No associations were observed between hsCRP and childhood poor health or childhood economic adversity. CONCLUSIONS: Inflammation was higher in older participants living in the Latin American cities compared with their Canadian counterparts. Childhood social adversity, not childhood economic adversity or poor health during childhood, was an independent predictor of chronic inflammation in old age in the Canadian sample. Selective survival could possibly explain the lack of association between social adversity and hsCRP in the Latin American samples.

Early maternal age at first birth is associated with chronic diseases and poor physical performance in older age: cross-sectional analysis from the International Mobility in Aging Study.

BACKGROUND: Early maternal age at first birth and elevated parity may have long-term consequences for the health of women as they age. Both are known risk factors for obstetrical complications with lifelong associated morbidities. They may also be related to diabetes and cardiovascular disease development. METHODS: We examine the relationship between early maternal age at first birth, defined as ≤18 years of age, multiparity (>2 births), and poor physical performance (Short Physical Performance Battery≤8) in community samples of women between 65 and 74 years of age from Canada, Albania, Colombia, and Brazil (N=1040). Data were collected in 2012 to provide a baseline assessment for a longitudinal cohort called the International Mobility in Aging Study. We used logistic regression and general linear models to analyse the data. RESULTS: Early maternal age at first birth is significantly associated with diabetes, chronic lung disease, high blood pressure, and poor physical performance in women at older ages. Parity was not independently associated with chronic conditions and physical performance in older age. After adjustment for study site, age, education, childhood economic adversity and lifetime births, women who gave birth at a young age had 1.75 (95% CI: 1.17-2.64) the odds of poor SPPB compared to women who gave birth>18 years of age. Adjustment for chronic diseases attenuated the association between early first birth and physical performance. Results were weaker in Colombia and Brazil, than Canada and Albania. CONCLUSIONS: This study provides evidence that adolescent childbirth may increase the risk of developing chronic diseases and physical limitations in older age. Results likely reflect both the biological and social consequences of early childbearing and if the observed relationship is causal, it reinforces the importance of providing contraception and sex education to young women, as the consequences of early pregnancy may be life-long.

Life-Space Assessment scale to assess mobility: validation in Latin American older women and men.

BACKGROUND: The Life-Space Assessment (LSA) instrument of the University of Alabama and Birmingham study is a useful and innovative measure of mobility in older populations. The purpose of this article was to assess the reliability, construct and convergent validity of the LSA in Latin American older populations. METHODS: In a cross-sectional study, a total of 150 women and 150 men, aged 65-74 years, were recruited from seniors' community centers in Manizales, Colombia and Natal, Brazil. The LSA questionnaire summarizes where people travel (5 levels from room to places outside of town), how often and any assistance needed. Four LSA variables were obtained according to the maximum life space achieved and the level of independence. As correlates of LSA, education, perception of income sufficiency, depression, cognitive function, and functional measures (objective and subjectively measured) were explored. The possible modifying effect of the city on correlates of LSA was examined. RESULTS: Reliability for the composite LSA score was substantial (ICC = 0.70; 95 % CI 0.49-0.83) in Manizales. Average levels of LSA scores were higher in those with better functional performance and those who reported less mobility difficulties. Low levels of education, insufficient income, depressive symptoms, and low scores of cognitive function were all significantly related to lower LSA scores. Women in both cities were more likely to be restricted to their neighborhood and had lower LSA scores. CONCLUSION: This study provides evidence for the validity of LSA in two Latin American populations. Our results suggest that LSA is a good measure of mobility that reflects the interplay of physical functioning with gender and the social and physical environment.

Cortisol profile and depressive symptoms in older adults residing in Brazil and in Canada.

BACKGROUND AND AIM: How cortisol, a stress biological marker, differs according to depressive symptoms has mostly been examined in high-income countries. Including low- and middle-income countries in research on this matter would allow examining a wider range of exposure to adversity and improving the estimates of the associations between diurnal cortisol and depression. The aim of this study is to compare the profile of diurnal cortisol and depressive symptoms in 65- to 74-year-old residents of Santa Cruz (in an underdeveloped region, northeast Brazil, n = 64) and Saint-Bruno (a suburban area, QC, Canada, n = 60). METHODS: Home interviews included assessments of socioeconomic variables, health behaviors, depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D) and Cortisol Awakening Response (CAR: awakening, 30, 60 min afterward), and at 1500 hours and bedtime from saliva collected over 2 days. Mixed linear models were used to estimate the associations between diurnal cortisol and depressive symptoms. RESULTS: Santa Cruz residents had lower cortisol levels upon awakening (ß = -1.24, p = 0.04) and elevated bedtime levels (ß = 20.29, p < 0.001) indicating chronic stress compared to Saint-Bruno residents. Elevated depressive symptoms were associated with a blunted CAR (flatter slope, indicative of chronic stress) in Santa Cruz residents (ß = -0.19, p = 0.04), while greater diurnal cortisol levels (larger area under the curve), indicative of moderate stress, were observed in Saint-Bruno residents (ß = 1.96, p = 0.047). CONCLUSION: Adverse living conditions in this remote area of Brazil may lead to a state of chronic stress and a different relationship with elevated depressive symptoms from persons aging in a Canadian suburban area.

Diabetes self-management education (DSME) for older persons in Western countries: A scoping review.

Diabetes mellitus is a chronic metabolic health condition affecting millions globally. Diabetes is a growing concern among aging societies, with its prevalence increasing among those aged 65 and above. Enabling disease self-management via relevant education is part of high-quality care to improve health outcomes and minimize complications for individuals living with diabetes. Successful diabetes self-management education (DSME) programs usually require tailoring for the intended audience; however, there is limited literature about the preferences of older persons in Western countries concerning DSME. As such, a broad overview of DSME for older persons was an identified need. To map the available evidence on DSME for persons aged 65 years and older in Western countries, the JBI methodology for conducting and reporting scoping reviews was used. In this scoping review, we considered all studies about DSME for older persons with T1D and T2D in Western countries where lifestyles, risks, prevention, treatment of diabetes, and approaches to self-management and DSME are similar (e.g., North America, Western and Northern Europe and Australasia). Systematic keyword and subject heading searches were conducted in 10 databases (e.g., MEDLINE, JBI EBP) to identify relevant English language papers published from 2000 to 2022. Titles and abstracts were screened to select eligible papers for full-text reading. Full-text screening was done by four independent reviewers to select studies for the final analysis. The review identified 2,397 studies, of which 1,250 full texts were screened for eligibility. Of the final 44 papers included in the review, only one included participants' understanding of DSME. The education programs differed in their context, design, delivery mode, theoretical underpinnings, and duration. Type of research designs, outcome measures used to determine the effectiveness of DSME, and knowledge gaps were also detailed. Overall, most interventions were effective and improved clinical and behavioural outcomes. Many of the programs led to improvements in clinical outcomes and participants' quality of life; however, the content needs to be adapted to older persons according to their culture, different degrees of health literacy, preference of education (e.g., individualized or group), preference of setting, degree of frailty and independence, and comorbidities. Few studies included the voices of older persons in the design, implementation, and evaluation of DSME programs. Such experiential knowledge is vital in developing educational programs to ensure alignment with this population's preferred learning styles, literacy levels, culture, and needs-such an approach could manifest more substantive, sustained results.

"I Could Have Stood a Little More Education Rather than Just: 'Hey, you're Diabetic Man, Make the Best out of It'": Revisioning Diabetes Self-Management Education for Older Adults.

Objectives: Providing diabetes self-management education (DSME) in an evidence-based format that is accessible and tailored to the population needs is crucial for individuals living with diabetes mellitus. Our qualitative study explores the experiences of older adults living with diabetes while residing in a rural setting. Methods: Adults aged 65 or older and residing in a rural area of Ontario completed a photovoice activity and semi-structured interviews to illustrate their experience of living with diabetes and accessing DSME. Results: Fourteen participants (11 males; mean age = 74 years) completed the photovoice activity and interview. Four main themes were identified pertaining to learning about diabetes education, the depth and breadth of learning, applying knowledge to daily life, and engaging older adults in DSME. Discussion: Diabetes self-management education should account for older adults' preferences in learning about diabetes and self-management to promote access to evidence-based information, bolster knowledge and self-management efficacy, and improve disease control.

Diabetes self-management education for older adults in Western countries: a scoping review protocol.

OBJECTIVE: This scoping review will map the available evidence on diabetes self-management education programs for older adults in Western countries. INTRODUCTION: Self-management and education are crucial for controlling diabetes and its associated complications. The successful uptake of diabetes self-management education programs is not straightforward, and little is known about diabetes programs for older adults. Within this context, a broad overview of diabetes self-management education for older adults, considering all types of related evidence, is needed. INCLUSION CRITERIA: All studies in English concerning diabetes self-management education for older adults (aged 65 years and older) living with type 1 or 2 diabetes will be included. This review will not be specific to gender, sex, ethnicity, frailty, or other demographic variables. The review will be restricted to Western countries (North America, Western and Northern Europe, and Australasia), where approaches to diabetes self-management education will be similar. Studies including older adults with or without diabetes will not be considered unless they provide separate analyses for the 2 cohorts. METHODS: This scoping review will follow the JBI methodology for scoping reviews. We will conduct searches of electronic databases, including CINAHL, MEDLINE, and PubMed, from January 1, 2000, to the present to capture eligible articles. The review will consider all study designs, including quantitative, qualitative, mixed methods designs, as well as text and opinion papers, and systematic reviews that meet the inclusion criteria. After duplicates are removed, titles and abstracts will be screened independently by 2 reviewers, and the full texts will be reviewed. The screening criteria and data extraction protocol will be pilot-tested by the research team. The results will be summarized in tables accompanied by narrative text.

Machine learning dissection of human accelerated regions in primate neurodevelopment.

Using machine learning (ML), we interrogated the function of all human-chimpanzee variants in 2,645 human accelerated regions (HARs), finding 43% of HARs have variants with large opposing effects on chromatin state and 14% on neurodevelopmental enhancer activity. This pattern, consistent with compensatory evolution, was confirmed using massively parallel reporter assays in chimpanzee and human neural progenitor cells. The species-specific enhancer activity of HARs was accurately predicted from the presence and absence of transcription factor footprints in each species. Despite these striking cis effects, activity of a given HAR sequence was nearly identical in human and chimpanzee cells. This suggests that HARs did not evolve to compensate for changes in the trans environment but instead altered their ability to bind factors present in both species. Thus, ML prioritized variants with functional effects on human neurodevelopment and revealed an unexpected reason why HARs may have evolved so rapidly.

Early and surgical menopause associated with higher Framingham Risk Scores for cardiovascular disease in the Canadian Longitudinal Study on Aging.

OBJECTIVE: In women, the risk of cardiovascular disease (CVD) is higher in the postmenopausal period. The effect that menopausal type, natural versus surgical, or the age at natural menopause has on CVD needs further investigation. To this end, we assessed the association between menopausal type and timing and the 10-year office-based Framingham Risk Score (FRS) in women from the Canadian Longitudinal Study on Aging. METHODS: We included women aged 45 to 85 years from the Canadian Longitudinal Study on Aging Comprehensive cohort of seven Canadian provinces who were menopausal at the time of recruitment and had no prior CVD. Poisson regressions were used to evaluate the association between menopausal characteristics and the FRS. Natural menopause was defined as the cessation of menstrual periods for at least 1 year in women with no history of hysterectomy. Surgical menopause was defined as hysterectomy with or without oophorectomy prior to natural menopause. As main covariates, we examined age, education, province of residency, and hormone therapy. RESULTS: A total of 10,090 women (8,200 natural menopausal and 1,890 surgical menopausal) were eligible for the study. In the multivariable model, surgical menopause was associated with a higher mean FRS compared with natural menopause (CVD risk 12.4% vs 10.8%, P < 0.001). Compared with women with age at natural menopause from 50 to 54 years (CVD risk 10.2%), natural menopause before age 40, 40 to 44, or 45 to 49 had a higher CVD risk (12.2%, 11.4%, and 10.6%, respectively, P < 0.001). CONCLUSIONS: Our study supports an association between menopausal type and timing on CVD risk prediction and highlights the need to be judicious about surgical menopause. Preventative interventions for CVD should be considered in surgical menopausal women and women with an age at natural menopause less than 45 years.

Video Summary:http://links.lww.com/MENO/A701 .

Adaptation and Pilot Evaluation of an Intervention Addressing the Sexual Health Needs of Gay Men Living with HIV Infection in Colombia.

Interventions addressing the sexual health need of HIV-positive men who have sex with men (MSM) in Latin America are scarce. We adapted and evaluated GPS, a group-based intervention led by peers, developed using the Information-Motivation-Behavioral (IMB) model and motivational interviewing (MI). We used McKleroy et al framework to culturally adapt GPS to MSM living with HIV infection in Colombia. Then, a one-armed pilot trial examined changes in depressive symptoms, loneliness, self-efficacy for engaging in sexual risk reduction behaviors, sexual sensation seeking and sexual compulsivity at pre-intervention, post-intervention, and 3-month follow-up. These results were complemented with semistructured interviews with participants 3 months after the intervention. GPS was identified to be culturally acceptable with few changes in materials and exercises. Facilitators showed high levels of adherence and fidelity to MI principles. Seven of 11 eligible participants finished the intervention; GPS positively influenced self-efficacy for condom negotiation, depressive symptoms, and condomless anal sex with partners of unknown HIV status. Exit interviews revealed that GPS was well-designed, relevant, facilitated discussion of sex in a nonjudgmental manner, and helped make positive changes in participants' sexual lives. These results provided preliminary evidence of an intervention to address sexual and mental health of MSM living with HIV in Latin America.

Application of the "syndemics" theory to explain unprotected sex and transactional sex: A crosssectional study in men who have sex with men (MSM), transgender women, and non-MSM in Colombia. / Aplicación de la teoría de la "sindemia" para entender el sexo sin protección y el sexo comercial: un estudio transversal en hombres que tienen sexo con hombres (HSH), mujeres transexuales y hombres que no tienen sexo con hombres en Colombia

INTRODUCTION: Men who have sex with men (MSM) and transgender women (TW) in Colombia are highly affected by HIV. To improve understanding of the role of HIV risk behaviors in HIV acquisition, we used the syndemic framework, a useful concept to inform prevention efforts. OBJECTIVE: To examine the effect of four psychosocial conditions, namely, forced sex, history of childhood sexual abuse, frequent alcohol use, and illicit drug use on unprotected sex and the synergistic effects ("syndemic" effects) of these conditions on HIV risk behavior. MATERIALS AND METHODS: We enrolled a total of 812 males (54.7% men who have sex with men, MSM; 7.3% transgender women, and 38% non-MSM). The participants were recruited from neighborhoods of low socioeconomic status through free HIV-counseling and -testing campaigns. We performed Poisson regression analysis to test the associations and interactions between the four psychosocial conditions and unprotected sex with regular, occasional, and transactional partners. To test the "syndemic" model, we assessed additive and multiplicative interactions. RESULTS: The prevalence of any psychosocial condition was 94.9% in transgender women, 60.1% in MSM, and 72.2% in non-MSM. A higher likelihood of transactional sex was associated in MSM (prevalence ratio (PR)=7.41, p<0.001) and non-MSM (PR=2.18, p< 0.001) with three or all four conditions compared to those with one condition. Additive interactions were present for all combinations of psychosocial problems on transactional sex n MSM. No cumulative effect or additive interaction was observed in transgender women. CONCLUSIONS: Our study highlights the need for bundled mental health programs addressing childhood sexual abuse, illicit drug use, and frequent alcohol use with other HIV prevention programs.

Introducción. Los hombres que tienen sexo con hombres (HSH), y las mujeres transgenero (MT) en Colombia continuan estando a mayor riesgo de VIH. Para entender como los comportamientos se asocian al VIH, se uso la teoria de la sindemia, la cual se ha considerado muy útil en el desarrollo de estrategias de prevención. Objetivo. Examinar el efecto de cuatro afecciones psicosociales, a saber: historia de sexo forzado, historia de abuso sexual infantil, consumo frecuente de alcohol y consumo de drogas ilícitas en las relaciones sexuales sin protección, así como los efectos sinérgicos (efectos "sindémicos") de estas afecciones sobre el comportamiento de riesgo para HIV. Materiales y métodos. Se hizo un estudio transversal que incluyó 812 participantes (hombres que tienen sexo con hombres, HSH: 54,7 %; mujeres transgénero: 7,3 % y hombres que no tenían sexo con otros hombres: 38 %). Los participantes se reclutaron en barrios de estratos socioeconómicos bajos a través de campañas gratuitas de asesoramiento y pruebas de HIV. Se hizo un análisis de regresión de Poisson para probar las asociaciones e interacciones entre las cuatro condiciones psicosociales y las relaciones sexuales sin protección con parejas regulares, ocasionales y comerciales. Para probar el modelo "sindémico" se evaluaron las interacciones aditivas y multiplicativas. Resultados. La prevalencia de cualquiera de las condiciones psicosociales fue de 94,9 % en mujeres transexuales, de 60,1 % en HSH y de 72,2 % en hombres que no tienen sexo con hombres. Se encontró una mayor probabilidad de tener sexo comercial en los HSH (razón de prevalencia (RP)=7,41, p<0,001) y en los que no tienen sexo con otros hombres (RP=2.18, p<0,001) con tres de las condiciones psicosociales, o con las cuatro, en comparación con aquellos con una sola condición. Las interacciones aditivas se registraron entre todas las combinaciones de problemas psicosociales con el sexo comercial en los HSH. No se observó un efecto acumulativo ni interacciones en mujeres transexuales. Conclusiones. El estudio resalta la necesidad de combinar programas de salud mental que aborden el abuso sexual infantil, el abuso de drogas y el consumo frecuente de alcohol con otros programas de prevención del HIV.

Direct analysis of brain phenotypes via neural blastocyst complementation.

We provide a protocol for generating forebrain structures in vivo from mouse embryonic stem cells (ESCs) via neural blastocyst complementation (NBC). We developed this protocol for studies of development and function of specific forebrain regions, including the cerebral cortex and hippocampus. We describe a complete workflow, from methods for modifying a given genomic locus in ESCs via CRISPR-Cas9-mediated editing to the generation of mouse chimeras with ESC-reconstituted forebrain regions that can be directly analyzed. The procedure begins with genetic editing of mouse ESCs via CRISPR-Cas9, which can be accomplished in ~4-8 weeks. We provide protocols to achieve fluorescent labeling of ESCs in ~2-3 weeks, which allows tracing of the injected, ESC-derived donor cells in chimeras generated via NBC. Once modified ESCs are ready, NBC chimeras are generated in ~3 weeks via injection of ESCs into genetically programmed blastocysts that are subsequently transferred into pseudo-pregnant fosters. Our in vivo brain organogenesis platform is efficient, allowing functional and systematic analysis of genes and other genomic factors in as little as 3 months, in the context of a whole organism.

Outer Radial Glia-like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma.

Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a reference framework of the developing and adult human brain. We find that multiple GSC subtypes exist within a single tumor. Within these GSCs, we identify an invasive cell population similar to outer radial glia (oRG), a fetal cell type that expands the stem cell niche in normal human cortex. Using live time-lapse imaging of primary resected tumors, we discover that tumor-derived oRG-like cells undergo characteristic mitotic somal translocation behavior previously only observed in human development, suggesting a reactivation of developmental programs. In addition, we show that PTPRZ1 mediates both mitotic somal translocation and glioblastoma tumor invasion. These data suggest that the presence of heterogeneous GSCs may underlie glioblastoma's rapid progression and invasion.

Explaining health differences between men and women in later life: a cross-city comparison in Latin America and the Caribbean.

This paper describes differences in health and functional status among older men and women and attempts to anchor the explanations for these differences within a lifecourse perspective. Seven health outcomes for men and women 60 years and older from seven Latin American and Caribbean cities are examined, using data from the 2000 SABE survey (Salud, Bienestar y Envejecimiento-n=10,587). Age-adjusted as well as city- and sex-specific prevalence was estimated for poor self-rated health, comorbidity, mobility limitations, cognitive impairment, depressive symptoms and disability in basic and instrumental activities of daily living. Logistic regressions were fitted to determine if the differences between men and women in each outcome could be explained by differential exposures in childhood (hunger, poverty), adulthood (education, occupation) and old age (income) and/or by differential vulnerability of men and women to these exposures. Sao Paulo, Santiago and Mexico, cities in countries with a high level of income inequalities, presented the highest prevalence of disability, functional limitations and poor physical health for both women and men. Women showed poorer health outcomes as compared with men for all health indicators and in all cities. Controlling for lifecourse exposures in childhood, adulthood and old age did not attenuate these differences. Women's unadjusted and adjusted odds of reporting poor self-rated health, cognitive impairment and basic activities of daily living disability were approximately 50% higher than for men, twice as high for number of comorbidities, depressive symptoms and instrumental activities of daily living disability, and almost three times as high for mobility limitations. Higher vulnerability to lifecourse exposures in women as compared with men was not found, meaning that lifecourse exposures have similar odds of poor health outcomes for men and women. A more integrated understanding of how sex and gender act together to influence health and function in old age needs consideration of additional biological and social factors.

Age at natural menopause and physical functioning in postmenopausal women: the Canadian Longitudinal Study on Aging.

OBJECTIVE: The aim of this study was to evaluate the association between categories of age at natural menopause (ANM) and gait speed (slowness) and grip strength (weakness), common measures of physical functioning in older women. METHODS: We analyzed data from the Canadian Longitudinal Study on Aging, which included participants from seven cities across Canada collected in 2012. The sample was restricted to women who reported to have entered menopause (N = 9,920). Women who had a hysterectomy before menopause were excluded since the age at which this surgical procedure was performed was not available. ANM was categorized into five groups: less than 40 (premature), 40 to 44 (early), 45 to 49, 50 to 54, and more than 54. We conducted linear regressions to assess the association between ANM and gait speed (m/s) and grip strength (kg) adjusting for participant age, education, body mass index, smoking, use of hormone therapy, height, and province of residence. RESULTS: Mean ANM was 49.8 (95% confidence interval [CI]: 49.7-50.0), with 3.8% of women having a premature menopause; the average gait speed was 0.98 m/s (standard deviation: 0.22), the average grip strength was 26.6 kg (standard deviation: 6.39). Compared to women with ANM of 50 to 54, women with premature menopause had 0.054 m/s (95% CI -0.083, -0.026) lower gait speed when adjusting for age and study site. In the fully adjusted model, the association was attenuated, 0.032 m/s (95% CI -0.060, -0.004). ANM was not associated with grip strength. CONCLUSION: Our study suggests that premature menopause (<40 years) may be associated with lower gait speed (slowness) among Canadian women. No association was observed between ANM and grip strength. Future studies should include a life course approach to evaluate whether social and biological pathways modify the association between age at menopause and physical function in populations from different contexts.