Sex Interaction Research Articles

Irisin Levels in Cerebrospinal Fluid Correlate with Biomarkers and Clinical Dementia Scores in Alzheimer Disease.

Irisin, released by muscles during exercise, was recently identified as a neuroprotective factor in mouse models of Alzheimer disease (AD). In a cohort of AD patients, we studied cerebrospinal fluid (CSF) and plasma irisin levels, sex interactions, and correlations with disease biomarkers. Correlations between CSF and plasma irisin levels and AD biomarkers (amyloid β 1-42, hyperphosphorylated tau, and total tau [t-tau]) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) were analyzed in a cohort of patients with Alzheimer dementia (n = 82), mild cognitive impairment (n = 44), and subjective memory complaint (n = 20) biologically characterized according to the recent amyloid/tau/neurodegeneration classification. CSF irisin was reduced in Alzheimer dementia patients (p < 0.0001), with lower levels in female patients. Moreover, CSF irisin correlated positively with Aβ42 in both female (r = 0.379, p < 0.001) and male (r = 0.262, p < 0.05) patients, and negatively with CDR-SOB (r = -0.234, p < 0.05) only in female patients. A negative trend was also observed between CSF irisin and t-tau levels in all patients (r = -0.144, p = 0.082) and in the female subgroup (r = -0.189, p = 0.084). The results highlight the relationship between irisin and biomarkers of AD pathology, especially in females. Our findings also offer perspectives toward the use of irisin as a marker of the AD continuum. ANN NEUROL 2024;96:61-73.

Ethnic minority underachievement in UK higher education: an analysis of nationally representative data provides little support for the intersectionality thesis

ABSTRACT This study evaluated the intersectionality thesis, which suggests that the interaction of ethnicity, sex, and socioeconomic status significantly affects achievement in UK higher education. The study used a sample of 135,699 students from the Graduate Outcomes survey for the 2018/19 cohort, the last to leave higher education before the COVID-19 pandemic. Conditioning on a rich set of background characteristics, results from a series of regressions indicated that some interactions are statistically significant predictors of obtaining a good degree. However, the estimated size of these interaction effects, as estimated using marginal effects, appeared to be negligible. Robustness checks included consideration of selection on observables using Inverse Probability Weighted Regression Adjustment (IPWRA), which confirmed the main results’ robustness. Overall, the findings suggest that the data do not support the intersectionality thesis and that markers of disadvantage, when combined, do not have an effect on educational outcomes that is over and above that of the single factors in isolation. These results could have implications for recent policies introduced in England to close ethnic achievement gaps in higher education by 2038. However, the findings should be treated with some caution due to the ethnic categories used in the analysis and the potential bias from omitted and unobserved variables that may lead to an underestimation of ethnic penalties.

Sex differences in the association between social jetlag and hazardous alcohol consumption in Korean workers: A nationwide cross-sectional study

BackgroundSocial jetlag, the misalignment between biological and social rhythms, can lead to adverse health outcomes. This study explored the association between social jetlag and hazardous alcohol consumption, as well as the sex differences in this association. MethodsThis study included a nationally representative sample of Korean workers consisting of 11,462 individuals (5479 women). Social jetlag was calculated as the difference in the mid-point between sleep onset and offset on free days and workdays. Hazardous alcohol consumption was determined using the Alcohol Use Disorder Identification Test–Consumption (range 0–12), with a cutoff of ≥6 for men, ≥5 for women, and ≥3 for those aged ≥65. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs). ResultsAmong men, 599 out of 5983 individuals (10.0 %) had ≥120 min of social jetlag. Among women, 550 out of 5479 individuals (10.0 %) had ≥120 min of social jetlag. The prevalence of hazardous alcohol use was 56.2 % for men and 27.3 % for women. In the regression analysis, there was a significant sex interaction, where social jetlag ≥120 min was associated with hazardous alcohol consumption in female workers (OR: 1.52, 95 % CI: 1.18–1.96), but not in male workers (OR: 1.04, 95 % CI: 0.84–1.29). ConclusionHigh social jetlag was associated with an increased likelihood of hazardous alcohol consumption among women. Our findings underscore the importance of considering sex differences in future research and policy interventions regarding social jetlag and its associated behavior outcomes.

Does work after retirement affect health-related quality of life: Evidence from a propensity score matching study in China.

Extending working life is considered as an important initiative to respond to the population aging and pension payment dilemma. This study aimed to investigate whether work after retirement is related to improved health-related quality of life. We used two waves of data from the China Health and Retirement Longitudinal Study in 2011 and 2018. Work after retirement was ascertained based on self-reported retirement and work status, and health-related quality of life (HRQOL) was measured with the three-level EuroQol five-dimensions. The impact of work after retirement on HRQOL was analyzed using the propensity score matching with difference-in-difference approach. A total of 1043 retirees were included. The results showed that work after retirement was associated with significant improvement in HRQOL among retirees (β = 0.072, P < 0.001). Heterogeneity analyses did not show specificity on sex (P for sex interaction >0.05), but older-aged retirees seemed more sensitive to the benefits of work after retirement on HRQOL than their younger-aged counterparts (≥65 years: β = 0.167, P < 0.001 vs <65 years: β = -0.047, P > 0.05; P for age interaction = 0.010). Work after retirement shows a positive impact on HRQOL among community-dwelling adults in China. Policy-makers should take the health of retirees into account when implementing policies related to delayed retirement, and reduce health inequity. Geriatr Gerontol Int 2024; 24: 722-729.

The Intersection of a Child's Demographics and Household Socioeconomic Status in the Multimorbidity of Malaria, Anaemia, and Malnutrition among Children Aged 6-59 Months in Nigeria.

Multimorbidity of malaria, anemia, and malnutrition (MAMM) is a condition in which an individual has two or more of these health conditions, and is becoming an emergent public health concern in sub-Saharan African countries. The independent associations of a child's demographic variables and household socioeconomic (HSE) disparities with a child's health outcomes have been established in the literature. However, the effects of the intersection of these factors on MAMM, while accounting for other covariates, have not been studied. Therefore, this study aimed to determine how children's sex, age, and household socioeconomic status interact to explain the variations in MAMM among children aged 6-59 months in Nigeria. Data from the 2018 Nigeria Demographic and Health Survey and the 2018 National Human Development Report (NHDR) were used. This study included weighted samples of 10,184 children aged 6-59 months in Nigeria. A three-level multilevel mixed effect ordinal logistic regression model was used, such that individual characteristics at level 1 were nested in communities at level 2 and nested in states at level 3. Subsequently, predictive probability charts and average adjusted probability tables were used to interpret the intersectional effects. Five models were created in this scenario. Model 1 is the interaction between the child's sex and household wealth status; model 2 is the interaction between the child's sex and age; model 3 is the interaction between the child's age and household wealth status; model 4 has the three two-way interactions of the child's sex, age, and household wealth status; and model 5 includes model 4 and the three-way interactions between a child's sex, age, and household wealth quintiles; while accounting for other covariates in each of the models. The prevalence of children with a 'none of the three diseases' outcome was 17.3% (1767/10,184), while 34.4% (3499/10,184) had 'only one of the diseases', and 48.3% (4918/10,184) had 'two or more' MAMMs. However, in the multivariate analyses, model 3 was the best fit compared with other models, so the two-way interaction effects of a child's age and household wealth status are significant predictors in the model. Children aged 36-47 months living in the poorest households had a probability of 0.11, 0.18, and 0.32 of existing with MAMM above the probability of children of the same age who live in the middle class, more prosperous, and richest households, respectively, while all other covariates were held constant. Thus, the variation in the prevalence of MAMM in children of different ages differs depending on the household wealth quintile. In other words, in older children, the variations in MAMM become more evident between the richer and the poorer household quintiles. Therefore, it is recommended that policies that are geared toward economic redistribution will help bridge the disparities observed in the prevalence of multiple diseases among children aged 6-59 months in Nigeria.

Interactions Between Caregiving and Sex and the Antibody Response to COVID-19 Vaccination.

Antibody response to vaccination is a powerful paradigm for studying the effects of chronic stress on immune function. In the present study, we used this paradigm to examine the interaction between caregiving (as a type of chronic stress) and sex on the antibody response to a single dose of a COVID-19 vaccination; recent research has called for examination of sex differences on health outcomes among family caregivers. A three-way interaction between caregiving, sex, and psychological distress was also examined. COVID-19 antibody data were extracted from 165 caregivers (98 females) and 386 non-caregivers (244 females) from the UK's Understanding Society COVID-19 study. Relevant sociodemographics, health and lifestyle, and distress variables were gathered as potential covariates. In a 2 × 2 ANOVA, we found that the interaction between caregiving and sex was significant; male caregivers had a lower antibody response to the vaccine compared to female caregivers ( F (1,547), =24.82, p < .001, η2p = 0.043). Following adjustment, male caregivers had the lowest antibody response relative to all other groups. The three-way interaction model, controlling for covariates, was also significant ( R2 = 0.013, p = .049); the conditional effects for the three-way interaction revealed that male caregivers, compared to the other groups, had a lower antibody response at both low and medium levels of psychological distress. This study found evidence of a three-way interaction between caregiving, sex, and distress on antibody response. Male caregivers had poorer antibody response to a single shot of the COVID-19 vaccination than female caregivers and male and female non-caregivers, and this was evident at low and medium levels of distress. Our findings will be discussed in relation to the caregiver and sex interactions during the pandemic.

Sex differences in neural responses to emotional facial expressions are associated with lifetime depression and mania risk

IntroductionNo studies systematically examined sex differences in neural mechanisms underlying depression and mania/hypomania risk. Method80 females and 35 males, n = 115(age21.6±1.90) were scanned using 3TfMRI during an implicit emotional-faces task. We examined neural activation to all emotional faces versus baseline, using an anatomical region-of-interest mask comprising regions supporting emotion and salience processing. Sex was a covariate. Extracted parameter estimates(FWE < 0.05,k > 15), age, IQ and their sex interactions were independent variables(IV) in two penalized regression models: dependent variable either MOODS-SR-lifetime, depressive or manic domain score as measures of mania and depression risk. Subsequent Poisson regression models included the non-zero variables identified in the penalized regression models. We tested each model in 2 independent samples. Test sample-I,n = 108(21.6 ± 2.09 years,males/females = 33/75); Test sample-II,n = 93(23.7 ± 2.9 years,males/females = 31/62). ResultsPoisson regression models yielded significant relationships with depression and mania risk: Positive correlations were found between right fusiform activity and depression(beta = 0.610) and mania(beta = 0.690) risk. There was a significant interaction between sex and right fusiform activity(beta = −0.609) related to depression risk, where females had a positive relationship than; and a significant interaction(beta = 0.743) between sex and left precuneus activity related to mania risk, with a more negative relationship in females than males. All findings were replicated in the test samples(qs < 0.05,FDR). LimitationsNo longitudinal follow-up. ConclusionGreater visual attention to emotional faces might underlie greater depression and mania risk, and confer greater vulnerability to depression in females, because of heightened visual attention to emotional faces. Females have a more negative relationship between mania risk and left precuneus activity, suggesting heightened empathy might be associated with reduced mania/hypomania risk in females more than males.

Sex affects transcriptional associations with schizophrenia across the dorsolateral prefrontal cortex, hippocampus, and caudate nucleus

Schizophrenia is a complex neuropsychiatric disorder with sexually dimorphic features, including differential symptomatology, drug responsiveness, and male incidence rate. Prior large-scale transcriptome analyses for sex differences in schizophrenia have focused on the prefrontal cortex. Analyzing BrainSeq Consortium data (caudate nucleus: n = 399, dorsolateral prefrontal cortex: n = 377, and hippocampus: n = 394), we identified 831 unique genes that exhibit sex differences across brain regions, enriched for immune-related pathways. We observed X-chromosome dosage reduction in the hippocampus of male individuals with schizophrenia. Our sex interaction model revealed 148 junctions dysregulated in a sex-specific manner in schizophrenia. Sex-specific schizophrenia analysis identified dozens of differentially expressed genes, notably enriched in immune-related pathways. Finally, our sex-interacting expression quantitative trait loci analysis revealed 704 unique genes, nine associated with schizophrenia risk. These findings emphasize the importance of sex-informed analysis of sexually dimorphic traits, inform personalized therapeutic strategies in schizophrenia, and highlight the need for increased female samples for schizophrenia analyses.

Early life exposure to mercury and relationships with telomere length and mitochondrial DNA content in European children

BackgroundTelomere length (TL) and mitochondrial function expressed as mitochondrial DNA copy number (mtDNAcn) are biomarkers of aging and oxidative stress and inflammation, respectively. Methylmercury (MeHg), a common pollutant in fish, induces oxidative stress. We hypothesized that elevated oxidative stress from exposure to MeHg decreases mtDNAcn and shortens TL. MethodsStudy participants are 6–11-year-old children from the HELIX multi-center birth cohort study, comprising six European countries. Prenatal and postnatal total mercury (THg) concentrations were measured in blood samples, TL and mtDNAcn were determined in child DNA. Covariates and confounders were obtained by questionnaires. Robust regression models were run, considering sociodemographic and lifestyle covariates, as well as fish consumption. Sex, ethnicity, and fish consumption interaction models were also run. ResultsWe found longer TL with higher pre- and postnatal THg blood concentrations, even at low-level THg exposure according to the RfD proposed by the US EPA. The prenatal association showed a significant linear relationship with a 3.46 % increase in TL for each unit increased THg. The postnatal association followed an inverted U-shaped marginal non-linear relationship with 1.38 % an increase in TL for each unit increased THg until reaching a cut-point at 0.96 μg/L blood THg, from which TL attrition was observed. Higher pre- and postnatal blood THg concentrations were consistently related to longer TL among cohorts and no modification effect of fish consumption nor children's sex was observed. No association between THg exposure and mtDNAcn was found. DiscussionWe found evidence that THg is associated with TL but the associations seem to be time- and concentration-dependent. Further studies are needed to clarify the mechanism behind the telomere changes of THg and related health effects.

Sex-specific effects of birth weight on longitudinal behavioural outcomes in children and adolescents: findings from the raine study.

Previous cross-sectional studies suggest that birth weight (BW) is associated with aggression-, social- and attention problems differently in boys and girls. We sought to test if these differences could be confirmed in a longitudinal study. The 1989 Raine Study provided prospectively collected data on perinatal variables and repeated child behaviour checklist assessments from ages 5 to 17. Linear mixed effects models provided crude and adjusted relationships between BW and childhood behaviour at a conservative significance threshold using prenatal maternal covariables in adjusted models. Sensitivity analyses included an age10 teacher assessment. Data on behaviour, BW and sex, was available in 2269 participants. Male sex was associated with increased aggression problems at lower BW compared to females in the crude model (Interaction B: -0.436, 98.3%CI: [-0.844, -0.0253]), but not the adjusted model (Interaction B: -0.310, 98.3%CI: [-0.742, 0.140]). Male sex was associated with increased attention problems at lower BW compared to females in both the crude model (Interaction B: -0.334, 98.3%CI: [-0.530, -0.137]) and the adjusted model (Interaction B: -0.274, 98.3%CI: [-0.507, -0.0432]). Male sex was associated with increased social problems at lower BW compared to females in both the crude model (Interaction B: -0.164, 98.3%CI: [-0.283, -0.0441]) and the adjusted model (Interaction B: -0.148, 98.3%CI: [-0.285, -0.00734]). Using repeated measures from ages 5-17 we were able to show a crude and adjusted male vulnerability to lower BW in the development of attention problems and social problems. We did not find a BW x sex interaction for the development of aggressive behaviour.

Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males.

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

Abstract PO2-10-03: Clinical characteristics and survival trends of male breast cancer in the United States: A propensity score matched analysis

Abstract Introduction Male breast cancer (MBC) is extremely rare and represents less than 1% of breast cancer (BC). There are limited studies investigating clinical outcomes of MBC. Although the survival of female breast cancer (FBC) has increased over the years; there is a substantial knowledge gap regarding survival trends of MBC. Given the rarity of MBC, recommendations on the treatment of MBC are scarce and mainly extrapolated from the data from FBC. We aim to analyze the clinical characteristics and annual trend in the survival of MBC compared to FBC. Methods We queried the National Cancer Database for BC patients (pts) diagnosed during 2004-2020. The demographic, clinicopathological and treatment characteristics were summarized by sex. An inverse-propensity weighted cox regression model was used to assess the association between sex and overall survival. Propensity weights were based on age, race, insurance, T, N, M-stages, subtype, grade, chemotherapy (CT), radiation (RT), hormone therapy (HT), and time to definitive treatment. To compare survival trends over time, year of diagnosis and its interaction with sex were included in the model. All analyses were performed at a significance level of 0.05. Results A total of 24, 055 MBC and 2,532,470 FBC pts were identified. MBC pts were older (mean age: 65.6 vs 61.4 years), Blacks (12.8 vs 11.2%) and had more government insurance (55.7% vs 45.8%) compared to FBC (all p&amp;lt; 0.001). Compared with FBC, more MBC pts had stage IV (7% vs 4.7%), fewer pts had stage I (33.4% vs 44.8%), more pts had larger tumors (cT4: 6% vs 3.7%), and node positive disease (18.5% vs 15.5%) (all p&amp;lt; 0.001). MBC were more likely estrogen (ER) (88.5% vs 78.5%) and progesterone receptor (PR) (79.6% vs 68%) positive and less likely HER2 receptor positive (7.9% vs 9.3%) or triple negative (2.8% vs 7.6%) compared to FBC (all p &amp;lt; 0.001). Male pts with BC received less CT (38.7% vs 41.2%), RT (32% vs 52.6%), HT (59.8% vs 62.5%) compared to females with BC (p &amp;lt; 0.001). The overall survival (OS) rates were lower in MBC compared to FBC (5-year: 73% vs 83%; 10-year: 54% vs 70%, p &amp;lt; 0.001). In the propensity weighted cox-regression model, males had higher mortality compared to females with BC (HR 2.8, 95% CI 2.88 - 2.9, p &amp;lt; 0.001). This difference in OS was observed in TNBC (HR 1.2, 95% CI 1.21 - 1.24) and HER2+ (HR 2, 95% CI 1.9 - 2.0), but not in ER/PR+ HER2- BC (HR 0.78, 95% CI 0.78 - 0.79), all p &amp;lt; 0.001. The 5-year and 10-year OS of early-stage MBC and advanced MBC was lower compared to FBC (Early-stage:- 5-year: 77% vs 86%, 10-year: 57% vs 72%, HR 2.9, 95% CI 2.9-2.92; Advanced: 5-year: 23% vs 28%, 10-year: 8% vs 13%, HR 1.14, 95% CI 1.14 – 1.2, both p &amp;lt; 0.001) The 5-year OS rates increased steadily for FBC from 2004-2015; however, the survival rates were not improved for MBC (Table 1) (p-value for interaction of sex and year of diagnosis was 0.02). Conclusion MBC pts have higher mortality rates and poor clinical outcomes compared to FBC pts. We demonstrate that the survival of MBC pts has not improved over the last decade, even after adjusting for clinicopathological and treatment characteristics. These findings suggest the need to investigate personalized treatment interventions for male breast cancer pts, especially given the disparate trends in survival among male and female BC over a period of time. Table 1: Survival trend by sex - overall BC cohort Citation Format: Arya Mariam Roy, Anthony George, Archit Patel, Malak Alharbi, Kristopher Attwood, Shipra Gandhi. Clinical characteristics and survival trends of male breast cancer in the United States: A propensity score matched analysis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-10-03.

The Effect of Dietary Sodium and Potassium Consumption on Intestinal Permeability and its Relation to Blood Pressure, and Endothelial Function: A Pilot Study

High sodium (HS) diets can reduce endothelial function (EF) and increase blood pressure (BP) while high potassium (HK) diets are shown to counter this effect. Furthermore, HS diets have also been shown to lead to gut dysbiosis, which is related to increased intestinal permeability (IP). However, the effect of HS diets on IP and whether the addition of HK can attenuate potential HS-induced changes to IP is unknown. Hypotheses: We hypothesized IP would increase on a HS diet and be mitigated by HK and that a higher IP would be related to elevations in BP and lower EF. Methods: Eleven healthy participants (5W/6M, age 32±8 yrs, BMI 23±1, BP 105±6/66±7 mmHg) consumed three 10-day diets of differing sodium and potassium content in randomized order: low sodium (LS)/low potassium (LK) (50mmol/65mmol), HS/LK (300mmol/65mmol), and HS/HK (300mmol/120mmol). On day 9 of each intervention, they collected their urine and wore an ambulatory BP monitor for 24-hr. On day 10, brachial artery flow-mediated dilation (FMD) was measured. Blood was collected and lipopolysaccharide-binding protein (LBP), a biomarker of IP and bacterial translocation, was measured by ELISA. Mixed design ANOVAs assessed sex differences in LBP, FMD, and BPs between diets. Simple linear regressions assessed relations between variables. Results: Twenty-four-hr urinary sodium excretion was higher on both HS diets compared to LS/LK diet (both p&lt;0.01) and 24-hr urinary potassium excretion was higher on HS/HK compared to LS/LK and HS/LK diets (both p&lt;0.01). LBP was different between diets (p&lt;0.01), and there was a significant diet*sex interaction (p=0.02) where men had increased LBP compared to women on the HS/LK and HS/HK diets (both p&lt;0.01). FMD was not different between diets (p=0.13) although men had a lower FMD compared to women after each diet (sex: p&lt;0.01). Twenty-four-hr mean arterial pressure (MAP) was different between diets (p=0.047) as men demonstrated higher 24-hr MAP on the HS/LK diet compared to LS/LK diet (p=0.03) and lower MAP on the HS/HK diet compared to HS/LK diet (p=0.01). LBP was inversely related to FMD (r=-0.82, p&lt;.01) and positively related to MAP (r=0.72, p&lt;.01), 24-hr systolic BP (r=0.66, p=0.03), and 24-hr diastolic BP (r=0.66, p=0.03) on the HS/LK diet for all participants, but not the LS/LK or HS/HK diets. Conclusions: These pilot data suggest that HS diets may increase IP in men, and, in the context of a HS/LK diet, greater IP is associated with lower FMD and higher BP in all participants. NIH R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Comparison Of Transient ACE Inhibitor Vs. Angiotensin Receptor Blocker Treatment On Angiotensin II-Induced Oxidative Stress In The Heart Of Spontaneously Hypertensive Rats

Angiotensin II (Ang II) is a primary mediator of the renin angiotensin system (RAS) with strong profibrotic effects, mediated in part through increased levels of reactive oxygen species (ROS). We have previously shown that transient treatment with an Ang II converting enzyme inhibitor (ACEi) produces long-term protection against Ang II-induced fibrosis. Our goal was to compare the impact of prior transient AT1 receptor antagonist (ARB) vs. ACEi treatment on the oxidative stress response and fibrotic signaling profile in the left ventricle (LV) in response to Ang II. Male and female spontaneously hypertensive rats were initially treated with vehicle, ARB (losartan, 30mg/kg per day) or ACEi (enalapril, 30mg/kg per day) for two weeks. To assess long term protection of ARB and ACEi treatment, after two-weeks of washout, the rats then received Ang II (400ng/kg/day) for 2 additional weeks. Protein levels of pro-oxidant (NOX-2) and antioxidant (SOD1, SOD2) enzymes, fibrosis marker (LOX) in the left ventricle (LV) were measured by western blotting. Cardiac hypertrophy was evaluated by the LV mass/tibia Length (LV/TL) ratio. Data were analyzed by 2-way ANOVA. After a transient ARB treatment, Ang II promoted an increase in LV/TL in both male (+7%) and female (+9%) rats when compared to vehicle+Ang II (treatment effect, p&lt;0.009). Ang II had no effect on LV/TL in rats previously treated with ACEi or vehicle. In response to Ang II, male and female rats that were previously treated with ACEi showed a decrease in LOX expression (treatment effect, p=0.02) in both male (-21%) and female (-22%) rats. No changes were observed in LOX in response to Ang II after ARB treatment. In rats transiently treated with ARB or ACEi, the expression of NOX2 was reduced after Ang II infusion. In the ARB group the NOX2 was reduced 25% in male and 28% in female (treatment effect, P=0.003). Similarly, in the ACEi group, NOX2 was reduced 27% in male and 26% in female rats (treatment effect, p&lt;0.0001). Prior ACEi and ARB produced sex-selective changes in SOD1 expression following Ang II infusion. Specifically, following transient ARB treatment, Ang II increased SOD1 in females (24%), but not males (sex x ARB treatment interaction: p=0.0033). Similarly, prior treatment with ACEi produced sex-dependent effects, whereby AngII increased SOD1 in females (10%) and decreased expression in males (-8%, ACEi x sex interaction: p=0.043). Neither ARB, ACEi nor Ang II affected the expression of SOD2 Our data indicate a sex and treatment-specific response to Ang II following transient ARB or ACEi treatment. Both ARB and ACEi showed a long-term beneficial effect on oxidative stress. However, ARB appeared to sensitize males and females to a hypertrophy response to AngII. Future studies will evaluate this differential response observed in cardiac hypertrophy and the mechanisms leading to cardiac fibrosis. NHBL R01HL153112. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Prenatal transportation stress and sex influence the metabolomic profile of the liver of 28-day-old Brahman bulls and heifers

Prenatal transportation stress (PNS) reportedly induced differential DNA methylation of genes related to behavior, immune function, stress response, and metabolism in Brahman heifer and bull calves (doi:10.1093/jas/skz368). The objective of the present experiment was to conduct a metabolomics analysis of liver samples of 25-day-old beef calves to identify biochemicals and determine effects of PNS and sex classification. Mature Brahman cows artificially inseminated to the same Brahman sire were assigned to be either Control (n=35; not transported) or PNS (n=37; 2 h of transportation at 60, 80, 100, 120, and 140±5 d of gestation). Livers were obtained from 16 Control (8 bulls and 8 heifers) and 16 PNS (8 bulls and 8 heifers) calves that were humanely euthanized at 25±2 d of age. Liver samples (200 mg) were submitted to Metabolon, Inc. to identify metabolites by ultra-high-performance liquid chromatography/tandem high resolution/accurate mass spectrometry chromatography methods. An estimate of the false discovery rate was calculated and following log transformation, two-way ANOVA was used to identify significant interactions and biochemicals that differed significantly ( p ≤ 0.05). Principal component analysis (PCA) was also used to compare PNS and sex effects. A total of 851 biochemicals were identified and categorized; this report emphasizes energy pathways and lipid mediators of inflammation. PNS increased 45 metabolites and decreased 21 whereas 23 were increased and 30 decreased in bulls versus heifers. Significant interaction of PNS and sex was noted for 33 metabolites. Glucose did not differ due to PNS; however, it was increased in bulls versus heifers. Maltotriose and maltose were higher in PNS, and it was greater in heifers than bulls. Lactate was higher in bulls than heifers. Lipid mediators of inflammation were elevated in PNS calves. to our knowledge this is the first report on the liver metabolome of prenatally stressed calves. These observations suggest an influence of prenatal stress and sex on liver metabolomics within 1 month of age in cattle. USDA NIFA Award No. 2019-67015-29573. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Thermoregulatory Responses to Very Hot and Dry Heat Exposure: Interactions Between Age and Sex

Extreme heat events can cause mass morbidity and mortality. Older adults are more susceptible to the adverse effects of heat. Additionally, sex is known to independently influence the physiological responses to heat stress. However, less is known regarding the interaction between age and sex on thermoregulation. Purpose: This study investigated differences in thermoregulatory responses between males and females in older and younger individuals exposed to a hot and dry environment with accompanying activities of daily living. Methods: Twenty older (70 ± 4 yrs) and twenty younger (29 ± 5 yrs) adults (10 males and 10 females per group) were exposed to 3-hours of ambient heating, replicating peak environmental conditions during the 2018 Los Angeles heat wave (47 °C, 15% relative humidity). Participants performed seven 5-minute periods of light exercise (≍3 METS; metabolic heat production: 2.99 ± 0.33 W/kg) dispersed throughout the heat exposure to simulate heat generation associated with activities of daily living. Participants ingested 3 mL/kg/hr of tap-temperature water throughout the trial. Core temperature, skin temperature, and heart rate changes were assessed from pre-post heat exposure. Whole-body sweat rate and forearm blood flow changes were indexed to changes in core temperature. Data were analyzed using a two-way ANOVA (Age x Sex) Results: Delta core temperature was greater in older individuals (males: 1.43 ± 0.47°C, females: 1.31 ± 0.39°C) than in younger (males: 0.83 ± 0.22°C, females: 0.53 ± 0.24°C, p&lt;0.001) but there was no difference between sex (p = 0.063) nor was there an interaction (p = 0.423). There was an interaction of age and sex on delta heart rate (p = 0.019). Older females (32 ± 9 bpm) had greater increases in heart rate than older males (18 ± 8 bpm), younger males (18 ± 6 bpm), and younger females (18 ± 12 bpm, p ≤ 0.009 for all comparisons). There was no effect of age (p = 0.529), sex (p = 0.670), or interaction (p = 0.422) on delta skin temperature. There was an interaction between age and sex for whole-body sweat loss (WBSL) indexed to changes in core temperature and body surface area (p = 0.009). Younger females (1688 ± 685 mL/m2/°C) had greater WBSL than older females (612 ± 211 mL/m2/°C, p &lt; 0.0001), older males (694 ± 327 mL/m2/°C, p &lt; 0.0001), and younger males (1038 ± 282 mL/m2/°C, p &lt; 0.0001). There was a main effect of sex (p = 0.003) and age (p &lt; 0.0001), but no interaction (p = 0.152) on delta forearm blood flow indexed to changes in core temperature (older males: 116 ± 67 mL/min/°C, older females: 194 ± 73 mL/min/°C, younger males: 263 ± 72 mL/min/°C, younger females: 468 ± 243 mL/min/°C). Conclusion: These data suggest that many thermoregulatory responses to heat stress are influenced by the interaction between age and sex. Supported by NIH R01AG069005 (CGC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Differential Acute Adipogenic Signaling Changes Following Neuromusculoskeletal Injuries

Following traumatic injury, neuromusculoskeletal tissue undergoes extensive plastic modification. Changes can be observed at the local and systemic levels and can involve tissue function, signaling, and local composition. Currently there is limited understanding of early adipogenic changes following some traumatic injuries, which is needed to understand the long-term lack of functional muscle recovery. The objective of this project was to examine plasticity after injury, namely systemic and local adipogenic signaling and fat droplet deposition following volumetric muscle loss (VML) and denervation injuries. We hypothesized there would be differential changes in local and systemic adipogenic signaling, specifically changes in fat droplet accumulation following neuromusculoskeletal injuries. Adult C57B1/6J mice (n=36; 6 male, 6 female/group): posterior compartment VML, tibial nerve denervation, and naïve control. Both injury models target plantarflexor muscles. Mice were euthanized 72-hrs post-injury. In vivo muscle function was assessed, and gastrocnemius, liver, and serum were saved for analysis. Whole gastrocnemius muscles from a subset (n=4/group) were saved for histology, and five standardized sections were systematically obtained 1.5mm apart; muscle sections were stained with H&amp;E and Oil-Red-O to evaluate total fiber number and fat droplet accumulation, respectively. Data were analyzed by two- and three-way ANOVA with Tukey’s HSD post hoc. Maximal torque declined ~81 and 98% following VML and denervation injury, respectively (main effect p&lt;0.001), and VML-injured muscle was more fatigable than injury naïve (main effect p=0.001). Following denervation, liver insulin-like growth factor 1 (IGF-1) was increased ~52% compared to other groups, and was most pronounced in males (main effect injury p&lt;0.001; sex p=0.021). VML injury resulted in a 4-fold higher muscle IGF-1 regardless of sex (interaction p=0.021), and greater muscle interleukin-6 (IL-6), which was more pronounced in females (main effect injury p=0.001; sex p=0.049). Platelet-derived factor growth receptor (PDFGRα) expression was diminished following VML injury in both sexes (interaction p=0.016); suggesting a decrease in fibro-adipogenic progenitors (FAPs) and an alternative origin responsible for increases in IGF-1 and IL-6 rather than FAPs. Serum leptin concentrations were blunted following both VML- and denervation-injury (main effect p=0.002), which may illicit alterations in the regenerative process, specifically the maintenance of muscle quality. Serum IGF-1 and IL-6 concentrations were not affected by injury (p≥0.164). Histological analysis revealed a significant decrease in total fiber number across the middle three sections of the VML-injured muscle (i.e., the section initially injured) compared to other groups (p≤0.034). Findings provide a foundation for characterizing adipocyte development in the muscle remaining after injury and identify therapeutic targets for rehabilitative and nutritional approaches to address contractile and metabolic impairments following injury. Future work should elucidate the time course of adipogenic signaling following these injuries, with particular interest in their relationship to changes in metabolic and contractile impairments. R01-AR078903 (JAC &amp; SMG); University of Minnesota UROP (BAC). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect of the Brain Learning Strategy on the Development of Science Processes in the life Sciences Subject for Tenth Grade Students

This study aimed to reveal the effect of the brain learning strategy on the development of science processes in the life sciences subject for tenth grade students at Latin Patriarchate School- Fuhais, The sample was distributed into two groups; group (A) comprises the experimental group who learnt using the brain learning strategy, and group (B) comprises the control group who learnt using the conventional strategy, each of which consisted of (24) female and male students. To achieve the objectives of the study; a teacher’s guide was created outlining the activities for the educational strategy, and a scale of Science Process was created as an assessment tool. The scale was applied in the first semester (2021) and statistical methods: unilateral and binary analysis of variance were used to answer the study questions. The results showed statistically significant difference in favor of the experimental group positively without any significant difference due to the interaction of sex and teaching strategy. Based on the study's results, several recommendations were given, including the use of brain-based learning strategies to improve sciences processes skills in teaching life sciences.

Investigating sex differences and age of onset in emotion regulation, executive functioning, and cannabis use in adolescents and young adults

BackgroundYoung adults have historically high levels of cannabis use at a time which coincides with emotional and cognitive development. Age of regular onset of cannabis use and sex at birth are hypothesized to influence the relationship between cannabis use and cognition. Here we investigated past 6-month cannabis use in relation to emotional and executive functioning. We further considered age of onset and sex in subgroup analyses.MethodYoung adults (N = 225; ages 16–22) completed a substance use interview and cognitive battery, including the Emotional Word-Emotional Face Stroop and NIH toolbox executive functioning tasks. Linear regressions examined relationships between past 6-month cannabis use episodes and performance. Subgroup analyses investigated whether age of onset or sex impacted relationships.ResultsAfter correcting for multiple comparisons, greater past 6-month cannabis use episodes were related to poorer Emotional Stroop Congruent Accuracy (p = .0004, FDR-p = .002) and List Sorting Working Memory (p = .02, FDR-p = .10) performance. Younger age of regular use onset marginally related to lower Emotional Stroop Congruent Accuracy performance (p = .03, FDR-p = .13). There were no cannabis use by sex interactions on cognition.ConclusionsConsistent with prior findings, results suggest small reductions in cannabis-related performance in processing speed during emotional Stroop and working memory tasks. Age of onset was modestly related to Stroop performance, but not sex. Longitudinal studies which detail patterns of cannabis and other substance use are needed to better assess brain-behavior relationships and other factors (e.g., age of onset of regular use, sex) which could influence cannabis-related impairments in cognitive functioning.

Neighborhood disadvantage is associated with working memory and hippocampal volumes among older adults

ABSTRACT It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance (p < .01) and lower hippocampal volumes (p < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.