Neural Control of Sexually Dimorphic Social Behavior: Connecting Development to Adulthood.

Rapid advances in the neural control of social behavior highlight the role of interconnected nodes engaged in differential information processing to generate behavior. Many innate social behaviors are essential to reproductive fitness and therefore fundamentally different in males and females. Programming these differences occurs early in development in mammals, following gonadal differentiation and copious androgen production by the fetal testis during a critical period. Early-life programming of social behavior and its adult manifestation are separate but yoked processes, yet how they are linked is unknown. This review seeks to highlight that gap by identifying four core mechanisms (epigenetics, cell death, circuit formation, and adult hormonal modulation) that could connect developmental changes to the adult behaviors of mating and aggression. We further propose that a unique social behavior, adolescent play, bridges the preweaning to the postpubertal brain by engaging the same neural networks underpinning adult reproductive and aggressive behaviors.

Microglia phagocytosis mediates the volume and function of the rat sexually dimorphic nucleus of the preoptic area.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in mammalian brain and is singular for its presence across a wide range of species from rodents to ungulates to man. This small collection of Nissl-dense neurons is reliably larger in volume in males. Despite its notoriety and intense interrogation, both the mechanism establishing the sex difference and the functional role of the SDN have remained elusive. Convergent evidence from rodent studies led to the conclusion that testicular androgens aromatized to estrogens are neuroprotective in males and that higher apoptosis (naturally occurring cell death) in females determines their smaller SDN. In several species, including humans, a smaller SDN correlates with a preference for mating with males. We report here that this volume difference is dependent upon a participatory role of phagocytic microglia which engulf more neurons in the female SDN and assure their destruction. Selectively blocking microglia phagocytosis temporarily spared neurons from apoptotic death and increased SDN volume in females without hormone treatment. Increasing the number of neurons in the SDN in neonatal females resulted in loss of preference for male odors in adulthood, an effect paralleled by dampened excitation of SDN neurons as evidenced by reduced immediate early gene (IEG) expression when exposed to male urine. Thus, the mechanism establishing a sex difference in SDN volume includes an essential role for microglia, and SDN function as a regulator of sexual partner preference is confirmed.

Distinct action signals by subregions in nucleus accumbens during STOP-change performance.

Nucleus accumbens (NAc) is thought to contribute to motivated behavior by signaling the value of reward-predicting cues and the delivery of anticipated reward. NAc is subdivided into core and shell, with each region containing different populations of neurons that increase or decrease firing to rewarding events. While there are various and numerous theories of functions pertaining to these subregions and cell types, most are in the context of reward processing, with fewer considering that NAc might serve functions related to action selection more generally. We recorded from single neurons in NAc as rats of both sexes performed a STOP-change task that is commonly used to study motor control and impulsivity. In this task, rats respond quickly to a spatial cue on 80% of trials (GO) and must stop and redirect planned movement on 20% of trials (STOP). We found that the activity of reward-excited neurons signaled accurate response direction on GO, but not STOP trials, and that these neurons exhibited higher pre-cue firing after correct trials resulting in stronger firing during correct GO trials and errant STOP trials, while reward-inhibited neurons significantly represented response direction on STOP trials at the time of the instrumental response. Finally, the proportion of reward-excited to reward-inhibited neurons and the strength of pre-cue firing decreased as the electrode traversed NAc. We conclude that reward-excited cells (more common in core) promote proactive action selection, while reward-inhibited cells (more common in shell) contribute to accurate responding on STOP trials that require reactive suppression and redirection of behavior.Significant Statement The ability to appropriately adapt behavior is an important part of human cognition, and one that is disrupted by many neuropsychiatric disorders. Here we recorded from neurons in the nucleus accumbens (NAc) as rats performed a cognitive control task and found cell type- and subregion-specific firing patterns. Core and reward-excited cells track trial outcome history, proactively driving behavior to the first cue-a strategy that is appropriate for most trials. Conversely, shell and reward-inhibited neurons signal accurate response direction on trials requiring redirection of behavior. Together, these data suggest that NAc neuronal populations differentially contribute to action selection.

Why and How to Account for Sex and Gender in Brain and Behavioral Research.

Long overlooked in neuroscience research, sex and gender are increasingly included as key variables potentially impacting all levels of neurobehavioral analysis. Still, many neuroscientists do not understand the difference between the terms "sex" and "gender," the complexity and nuance of each, or how to best include them as variables in research designs. This TechSights article outlines rationales for considering the influence of sex and gender across taxa, and provides technical guidance for strengthening the rigor and reproducibility of such analyses. This guidance includes the use of appropriate statistical methods for comparing groups as well as controls for key covariates of sex (e.g., total intracranial volume) and gender (e.g., income, caregiver stress, bias). We also recommend approaches for interpreting and communicating sex- and gender-related findings about the brain, which have often been misconstrued by neuroscientists and the lay public alike.

Cardiovascular Health in Black and Latino Adults With Type 2 Diabetes.

BACKGROUND: The incidence of type 2 diabetes (T2DM) among U.S. adults has been rising annually, with a higher incidence rate in Black and Hispanic adults than in Whites. The American Heart Association (AHA) has defined cardiovascular health according to the achievement of seven health behaviors (smoking, body mass index [BMI], physical activity, diet) and health factors (total cholesterol, blood pressure, fasting glucose). Optimal cardiovascular health has been associated with a lower risk of cardiovascular disease, and awareness of this risk may influence healthy behaviors. OBJECTIVES: This study aimed to assess cardiovascular health in a sample of Black and Hispanic adults (age: 18-40 years) with T2DM and explore the barriers and facilitators to diabetes self-management and cardiovascular health. METHODS: This was an explanatory sequential mixed-method design. The study staff recruited adults with T2DM for the quantitative data followed by qualitative interviews with a subsample of participants using maximum variation sampling. The seven indices of cardiovascular health as defined by the AHA's "Life's Simple 7" were assessed: health behaviors (smoking, BMI, physical activity, diet) and health factors (total cholesterol, blood pressure, A1C). Qualitative interviews were conducted to explore their results as well as the effects of the pandemic on diabetes self-management. Qualitative and quantitative data were integrated into the final analysis phase. RESULTS: The majority of the sample was female, with 63% identifying as Black and 47% as Hispanic. The factor with the lowest achievement of ideal levels was BMI, followed by a healthy diet. Less than half achieved ideal levels of blood pressure or physical activity. Themes that emerged from the qualitative data included the impact of social support, the effects of the pandemic on their lives, and educating themselves about T2DM. DISCUSSION: Achievement of ideal cardiovascular health factors varied, but the achievement of several health factors may be interrelated. Intervening on even one factor while providing social support may improve other areas of cardiovascular health in this population.

Implementing a Clinical Decision Support Tool to Improve Physical Activity.

BACKGROUND: Currently, only about half of U.S. adults achieve current physical activity guidelines. Routine physical activity is not regularly assessed, nor are patients routinely counseled by their healthcare provider on achieving recommended levels. The three-question physical activity vital sign (PAVS) was developed to assess physical activity duration and intensity and identify adults not meeting physical activity guidelines. Clinical decision support provided via a best practice advisory in an electronic health record (EHR) system can be triggered as a prompt, reminding healthcare providers to implement the best practice intervention when appropriate. Remote patient monitoring of physical activity can provide objective data in the EHR. OBJECTIVES: This study aimed to evaluate the feasibility and clinical utility of embedding the PAVS and a triggered best practice advisor into the EHR in an ambulatory preventive cardiology practice setting to alert providers to patients reporting low physical activity and prompt healthcare providers to counsel these patients as needed. METHODS: Three components based in the EHR were integrated for the purpose of this study: Patients completed the PAVS through their electronic patient portal prior to an office visit, a best practice advisory was created to prompt providers to counsel patients who reported low levels of physical activity, and remote patient monitoring via Fitbit synced to the EHR provided objective physical activity data. The intervention was pilot-tested in the Epic EHR for 1 year (July 1, 2021 to June 30, 2022). Qualitative feedback on the intervention from both providers and patients was obtained at the completion of the study. RESULTS: Monthly assessments of the use of the PAVS and best practice advisory and remote patient monitoring were completed. Patients' completion of the PAVS varied from 35% to 48% per month. The best practice advisory was signed by providers between 2% and 65% and was acknowledged by 2%-22% per month. The majority (58%) of patients were able to sync a Fitbit device to their EHR for remote monitoring. DISCUSSION: Although uptake of each component needs improvement, this pilot demonstrated the feasibility of incorporating a physical activity promotion intervention into the EHR. Qualitative feedback provided guidance for future implementation.

The Importance of Social Support in the Management of Hypertension in Brazil.

BACKGROUND: The prevalence of hypertension (HTN) is high in Brazil, and control rates are low. Little is known about the factors that contribute to HTN control from a family-based perspective. OBJECTIVES: Guided by the family management style framework, specific aims were to (1) describe the prevalence of adequate blood pressure (BP) control in individuals cared for the Family Health Strategy, (2) identify facilitators and barriers to HTN management, and (3) identify individual contextual sociocultural influences (sociocultural context and social and Family Health Strategy support), definition of the situation, and management behaviors that help or interfere with individual functioning (BP control in the individual with HTN). METHODS: This descriptive, cross-sectional study included 213 individuals with HTN randomly selected from 3 Family Health Strategy units from July 2016 until July 2017. RESULTS: Most of the individuals were female (n = 139, 65.3%), retired (n = 129, 60.5%), and White (n = 129, 60.2%) and had less than a high school education (n = 123, 57.6%). Family income (n = 166, 77.8%) was less than 5500 reals (US $1117/month). Mean (SD) systolic BP was 137.1 (±24.1) mm Hg, and mean (SD) diastolic BP was 83.8 (±18.6) mm Hg, with 47.9% (n = 102) having uncontrolled BP. In the multivariate logistic model, only high levels of perceived social support were significantly associated (odds ratio, 3.29; 95% confidence interval, 1.44-7.5; P = .005) with controlled BP. CONCLUSIONS: Social support is strongly associated with BP control. Optimizing support may play an important role in BP control and preventing HTN-related complications.

Patient-related decisional regret: An evolutionary concept analysis.

BACKGROUND: Health-related decision-making is a complex process given the variability of treatment options, conflicting treatment plans, time constraints and variable outcomes. This complexity may result in patients experiencing decisional regret following decision-making. Nonetheless, literature on decisional regret in the healthcare context indicates inconsistent characterization and operationalization of this concept. AIM(S): To conceptually define the phenomenon of decisional regret and synthesize the state of science on patients' experiences with decisional regret. DESIGN: A concept analysis. METHODS: Rodgers' evolutionary method guided the conceptualization of this review. An interdisciplinary literature search was conducted from 2003 until 2023 using five databases, PubMed, CINAHL, Embase, PsycINFO and Web of Science. The search informed how the concept manifested across health-related literature. We used PRISMA-ScR checklist to guide the reporting of this review. RESULTS: Based on the analysis of 25 included articles, a conceptual definition of decisional regret was proposed. Three defining attributes underscored the negative cognitive-emotional nature of this concept, post-decisional experience relating to the decision-making process, treatment option and/or treatment outcome and an immediate or delayed occurrence. Antecedents preceding decisional regret comprised initial psychological or emotional status, sociodemographic determinants, impaired decision-making process, role regret, conflicting treatment plans and adverse treatment outcomes. Consequences of this concept included positive and negative outcomes influencing quality of life, health expectations, patient-provider relationship and healthcare experience appraisal. A conceptual model was developed to summarize the concept's characteristics. CONCLUSION: The current knowledge on decisional regret is expected to evolve with further exploration of this concept, particularly for the temporal dimension of regret experience. This review identified research, clinical and policy gaps informing our nursing recommendations for the concept's evolution. NO PATIENT OR PUBLIC CONTRIBUTION: This concept analysis examines existing literature and does not require patient-related data collection. The methodological approach does not necessitate collaboration with the public.

The impact of NHS charging regulations on healthcare access and utilisation among migrants in England: a systematic review.

BACKGROUND: The NHS Charges to Overseas Visitors Regulations 2015 outline when healthcare costs should be recuperated from overseas visitors in England. National and global stakeholders have expressed concerns that charging may exacerbate health inequalities and undermine public health efforts especially among vulnerable migrant groups. This review aims to systematically describe the evidence regarding the impact of NHS charging regulations on healthcare access and utilisation and health outcomes for migrants in England. METHODS: A systematic search of scientific databases and grey literature sources was performed. Quantitative and qualitative studies, case studies and grey literature published between 1 January 2014 and 1 April 2021 were included. Screening, data extraction and quality appraisal were carried out in accordance with PRISMA guidelines. RESULTS: From the 1,459 identified studies, 10 were selected for inclusion. 6 were qualitative, 3 were mixed methods and 1 was quantitative. The evidence is lacking but suggests that fears of charging and data sharing can deter some migrants from accessing healthcare. There is also evidence to suggest a lack of knowledge of the charging regulations among patients and healthcare professionals is contributing to this deterrence. CONCLUSIONS: Further independent research supported by strengthening of data collection is required to better understand the effects of charging on healthcare and health outcomes among vulnerable migrants. Our findings support improved training and communication about NHS Charging Regulations for patients and professionals.

Time, Technology, Social Support, and Cardiovascular Health of Emerging Adults With Type 1 Diabetes.

BACKGROUND: Emerging adults with Type 1 diabetes (T1DM) face an increased risk of cardiovascular disease; however, there are both barriers and facilitators to achieving ideal cardiovascular health in this stage of their lives. OBJECTIVES: The aim of this study was to qualitatively explore the barriers and facilitators of achieving ideal levels of cardiovascular health in a sample of emerging adults with T1DM ages 18-26 years. METHODS: A sequential mixed-methods design was used to explore achievement of ideal cardiovascular health using the seven factors defined by the American Heart Association (smoking status, body mass index, physical activity, healthy diet, total cholesterol, blood pressure, and hemoglobin A1C [substituted for fasting blood glucose]). We assessed the frequency of achieving ideal levels of each cardiovascular health factor. Using Pender's health promotion model as a framework, qualitative interviews explored the barriers and facilitators of achieving ideal levels of each factor of cardiovascular health. RESULTS: The sample was mostly female. Their age range was 18-26 years, with a diabetes duration between 1 and 20 years. The three factors that had the lowest achievement were a healthy diet, physical activity at recommended levels, and hemoglobin A1C of <7%. Participants described lack of time as a barrier to eating healthy, being physically active, and maintaining in-range blood glucose levels. Facilitators included the use of technology in helping to achieve in-range blood glucose and social support from family, friends, and healthcare providers in maintaining several healthy habits. DISCUSSION: These qualitative data provide insight into how emerging adults attempt to manage their T1DM and cardiovascular health. Healthcare providers have an important role in supporting these patients in establishing ideal cardiovascular health at an early age.

The Impact of an Electronic Best Practice Advisory on Patients' Physical Activity and Cardiovascular Risk Profile.

BACKGROUND: Regular physical activity (PA) is a component of cardiovascular health and is associated with a lower risk of cardiovascular disease (CVD). However, only about half of US adults achieved the current PA recommendations. OBJECTIVE: The study purpose was to implement PA counseling using a clinical decision support tool in a preventive cardiology clinic and to assess changes in CVD risk factors in a sample of patients enrolled over 12 weeks of PA monitoring. METHODS: This intervention, piloted for 1 year, had 3 components embedded in the electronic health record: assessment of patients' PA, an electronic prompt for providers to counsel patients reporting low PA, and patient monitoring using a Fitbit. Cardiovascular disease risk factors included PA (self-report and Fitbit), body mass index, blood pressure, lipids, and cardiorespiratory fitness assessed with the 6-minute walk test. Depression and quality of life were also assessed. Paired t tests assessed changes in CVD risk. RESULTS: The sample who enrolled in the remote patient monitoring (n = 59) were primarily female (51%), White adults (76%) with a mean age of 61.13 ± 11.6 years. Self-reported PA significantly improved over 12 weeks (P = .005), but not Fitbit steps (P = .07). There was a significant improvement in cardiorespiratory fitness (469 ± 108 vs 494 ± 132 m, P = .0034), and 23 participants (42%) improved at least 25 m, signifying a clinically meaningful improvement. Only 4 participants were lost to follow-up over 12 weeks of monitoring. CONCLUSIONS: Patients may need more frequent reminders to be active after an initial counseling session, perhaps getting automated messages based on their step counts syncing to their electronic health record.

Maternal-fetal transmission of delta-9-tetrahydrocannabinol (THC) and its metabolites following inhalation and injection exposure during pregnancy in rats.

Cannabis use during pregnancy has increased over the past few decades, with recent data indicating that, in youth and young adults especially, up to 22% of people report using cannabis during pregnancy. Animal models provide the ability to study prenatal cannabis exposure (PCE) with control over timing and dosage; however, these studies utilize both injection and inhalation approaches. While it is known that Δ9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis) can cross the placenta, examination of the transmission and concentration of THC and its metabolites from maternal blood into the placenta and fetal brain remains relatively unknown, and the influence of route of administration has never been examined. Pregnant female rats were exposed to either vaporized THC-dominant cannabis extract for pulmonary consumption or subcutaneous injection of THC repeatedly during the gestational period. Maternal blood, placenta, and fetal brains were collected following the final administration of THC for analysis of THC and its metabolites, as well as endocannabinoid concentrations, through mass spectrometry. Both routes of administration resulted in the transmission of THC and its metabolites in placenta and fetal brain. Repeated exposure to inhaled THC vapor resulted in fetal brain THC concentrations that were about 30% of those seen in maternal blood, whereas repeated injections resulted in roughly equivalent concentrations of THC in maternal blood and fetal brain. Neither inhalation nor injection of THC during pregnancy altered fetal brain endocannabinoid concentrations. Our data provide the first characterization of maternal-fetal transmission of THC and its metabolites following both vaporized delivery and injection routes of administration. These data are important to establish the maternal-fetal transmission in preclinical injection and inhalation models of PCE and may provide insight into predicting fetal exposure in human studies.

Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain.

The study of sex differences in the brain is a topic of neuroscientific study that has broad reaching implications for culture, society and biomedical science. Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field.

The immune cell profile of the developing rat brain.

Little is known about the peripheral immune cell (PIC) profile of the developing brain despite growing appreciation for these cells in the mature nervous system. To address this gap, the PIC profile, defined as which cells are present, where they are located, and for how long, was examined in the developing rat using spectral flow cytometry. Select regions of the rat brain (cerebellum, hippocampus, and hypothalamus) were examined at embryonic day 20, and postnatal days 0, 7 and 16. At their peak (E20), PICs were most abundant in the cerebellum, then the hippocampus and hypothalamus. Within the PIC pool, monocytes were most prevalent in all regions and time points, and shifted from being majority classical at E20 to non-classical by PN7. T cells increased over time, and shifted from majority cytotoxic to T-helper cells by PN7. This suggests the PIC profile transitions from reactive to adaptive and surveilling in the second postnatal week. NK cells and mast cells increased temporarily, and mast cells were restricted to the hippocampus and hypothalamus, suggesting they may play a specific role in the development of those regions. Mimicking a viral infection by administration of Poly I:C increased the influx of PICs into the neonatal brain, particularly of NK cells and in the case of males only, non-classical monocytes. This work provides a map for researchers as they study immune cell contributions to healthy and pathological brain development.

Exercise and Self-Management in Adults with Type 1 Diabetes.

PURPOSE OF REVIEW: The purpose of this review paper is to examine the most recent evidence of exercise-related self-management in adults with type 1 diabetes (T1D). RECENT FINDINGS: This paper reviews the benefits and barriers to exercise, diabetes self-management education, the role of the healthcare provider in assessment and counseling, the use of technology, and concerns for special populations with T1D. Adults with T1D may not exercise at sufficient levels. Assessing current levels of exercise, counseling during a clinical visit, and the use of technology may improve exercise in this population.

Associations of insomnia symptoms with sociodemographic, clinical, and lifestyle factors in persons with HF: Health and retirement study.

Insomnia symptoms are very common in persons with heart failure (HF). However, many of the correlates and predictors of insomnia symptoms in this population remain unclear. The purpose of this study is to investigate the associations of sociodemographic, clinical, and lifestyle factors with insomnia symptoms in persons with HF. A theoretical framework was adapted from the neurocognitive model of chronic insomnia to guide the study. Data from the health and retirement study were used for the analysis. Parametric and nonparametric bivariate and multivariate analyses were conducted to investigate these associations. Age, depressive symptoms, comorbidity, dyspnea, pain, and smoking had significant bivariate associations with all insomnia symptoms. Race, Hispanic ethnicity, marital status, household income, poverty, and physical activity were associated with difficulty initiating sleep (DIS) and early morning awakening (EMA). Female sex, education, and alcohol consumption had a significant bivariate association with DIS. Sleep-disordered breathing and body mass index were significantly associated with EMA. Multivariate analysis suggested that depressive symptoms, comorbidity, dyspnea, and pain had independent associations with each insomnia symptom. Age explained DIS and difficulty maintaining sleep, and significant interaction effects between age and physical activity on DIS and EMA were revealed. Results suggest that insomnia symptoms are associated with several sociodemographic, clinical, and lifestyle factors. Age below 70 years, depressive symptoms, comorbidity, dyspnea, and pain might be considered as a phenotype to identify persons with HF who are at increased risk for insomnia symptoms.

The promises and pitfalls of sex difference research.

Funding agencies in North America and Europe are recognizing the importance of the integration of sex differences into basic and clinical research. Although these mandates are in place to improve our knowledge of health for both men and women, there have been a number of implementation issues that require vigilance on the part of funders and the research community. Here we discuss issues on simple inclusion of both sexes in studies to specialisation of sex differences with attention paid to statistics and the need for sex-specific treatments. We suggest differing mandates need to be considered regarding simple integration versus the need for studies in the specialisation of sex differences and/or the need for research that recognises the importance of male-specific or female-specific factors that influence subsequent health such as menstruation, menopause or pregnancy.

An Integrated Review of Hypertrophic Cardiomyopathy in Black Populations: Underrecognized and Understudied.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder globally, affecting 0.2% to 0.5% of individuals. Existing clinical HCM guidelines do not address diverse populations, specifically minority groups who often experience health disparities. OBJECTIVE: The aim of this study was to describe the state of the science of HCM in black populations. METHODS: This integrated review guided by Whittemore and Knafl's methodology included literature search of multiple databases, data evaluation, and analysis. Publications between 2000 and 2020 were included if they addressed HCM cardiac anatomic manifestations, disease course, symptoms, quality of life, or outcomes in black populations. RESULTS: Six articles met the inclusion criteria. Overall, blacks are underrepresented in HCM research. Certain HCM structural phenotypes are more commonly exhibited in blacks, and physiology drives HCM treatment. Sudden death events and all-cause mortality do not differ between blacks and whites with HCM. Fewer blacks with HCM undergo genetic testing than whites with HCM. The lack of diversity in general genomic databases has resulted in reclassification of several genetic variants identified as more common in blacks. CONCLUSIONS: Blacks are underrepresented in HCM research, even those focused on elucidating HCM manifestations, disease course, and outcomes in black populations. This may be due in part to HCM research that is largely generated from specialty centers that can require patients to navigate complex healthcare systems to reach expert HCM care. Longitudinal studies with large samples of blacks with HCM are necessary to elucidate how HCM affects this population.