Sex-specific Variation Research Articles

Syndemic vulnerability in Dutch urban cities: investigating health disparities and intersectionality

Abstract Background Syndemics, the clustering of health and social issues, disproportionately affect marginalized communities. While prior research indicates sex-specific variations in syndemic vulnerability, current research often overlooks other sociodemographic characteristics and their interaction. An intersectionality-informed syndemic approach could offer more insights into the mechanisms in syndemic suffering, providing a deeper understanding and identifying groups most affected by structural inequalities. Methods Our study focused on adult residents in Leiden and The Hague, the Netherlands, registered at different general practices. Using existing routine health data linked with Central Bureau for Statistics information, we included adults who were registered with a general practitioner in 2018 and 2019, had a minimum of two registered health conditions documented by their general practitioner, lived in Leiden or The Hague, and were at least 18 years old in 2018. Results A total of 43340 adults were included for analyses. Distinct health condition clusters were observed within sex and age groups. Women experiences a broader range of health issues, often characterized by mental and psychosomatic symptoms like mood/anxiety disorders and abdominal complaints. Conversely, men exhibited a higher prevalence of specific physical conditions, including hypertension, diabetes, and cardiovascular diseases. Conclusions The findings align with previous research, suggesting the importance of further exploration into the role of intersectionality in syndemics. Currently, we are investigating the foundations of these disparities, including interaction analyses and Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA). Using MAIHDA, we will examine the relationship between intersectionality and syndemic vulnerability, quantifying intersecting factors (sex, ethnicity, SES) and exploring their impact at individual and group levels. Key messages • Understanding intersectionality in health disparities is crucial for addressing syndemic vulnerabilities. • Tailored interventions informed by intersectionality may promote equitable health outcomes.

Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Limited studies assess reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs). 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR} was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females >50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement (Kappa = 0.48, 95% confidence interval: 0.46-0.51) and positive correlation (r = 0.51; p<0.0001) between ALP and GGT was observed. For ALP and GGT, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and >50 years, respectively. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and >50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Manufacturer RIs agreed well with the IRIs for most subsets, but differed for ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females >50 years. Further investigation of the impact of preselecting patient populations on IRIs and a direct RI study on select patient subsets is worth investigation.

Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments.

Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis. Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis. There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts. This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.

Adenosine Metabolism Pathway Alterations in Frontal Cortical Neurons in Schizophrenia.

Schizophrenia is a neuropsychiatric illness characterized by altered neurotransmission, in which adenosine, a modulator of glutamate and dopamine, plays a critical role that is relatively unexplored in the human brain. In the present study, postmortem human brain tissue from the anterior cingulate cortex (ACC) of individuals with schizophrenia (n = 20) and sex- and age-matched control subjects without psychiatric illness (n = 20) was obtained from the Bronx-Mount Sinai NIH Brain and Tissue Repository. Enriched populations of ACC pyramidal neurons were isolated using laser microdissection (LMD). The mRNA expression levels of six key adenosine pathway components-adenosine kinase (ADK), equilibrative nucleoside transporters 1 and 2 (ENT1 and ENT2), ectonucleoside triphosphate diphosphohydrolases 1 and 3 (ENTPD1 and ENTPD3), and ecto-5'-nucleotidase (NT5E)-were quantified using real-time PCR (qPCR) in neurons from these individuals. No significant mRNA expression differences were observed between the schizophrenia and control groups (p > 0.05). However, a significant sex difference was found in ADK mRNA expression, with higher levels in male compared with female subjects (Mann-Whitney U = 86; p < 0.05), a finding significantly driven by disease (t(17) = 3.289; p < 0.05). Correlation analyses also demonstrated significant associations (n = 12) between the expression of several adenosine pathway components (p < 0.05). In our dementia severity analysis, ENTPD1 mRNA expression was significantly higher in males in the "mild" clinical dementia rating (CDR) bin compared with males in the "none" CDR bin (F(2, 13) = 5.212; p < 0.05). Lastly, antipsychotic analysis revealed no significant impact on the expression of adenosine pathway components between medicated and non-medicated schizophrenia subjects (p > 0.05). The observed sex-specific variations and inter-component correlations highlight the value of investigating sex differences in disease and contribute to the molecular basis of schizophrenia's pathology.

A-093 Assessing Alkaline Phosphatase Reference Intervals Using Gamma-Glutamyl Transferase as a Surrogate for Normal Liver Function

Abstract Background There are limited published studies assessing reference intervals (RIs) for hepatic enzymes, particularly for alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT). In the US, ALP and GGT RIs were established on Roche assays using a European cohort of ≤ 450 patients that may not reflect population variance across practice settings. Further, age- and sex-specific variation in ALP and GGT may warrant tiered RIs, but evidence to justify this approach is limited. We aimed to evaluate the manufacturer’s RIs by comparing them to indirectly estimated RIs (IRIs) from routine clinical data. Methods 217,333 AST, ALT, ALP, and GGT results (Roche c702) performed between 1/1/2019-12/31/2022 on outpatients ≥21 years were extracted from the laboratory information system. The first ALP for each patient was identified, and the earliest AST, ALT, and GGT drawn within 7 days was included. This approach was repeated for GGT. Concordance and correlation were calculated using Weighted Cohen’s Kappa and Spearman’s rank correlation coefficient respectively. {refineR}, an algorithm for calculating IRIs, was applied to patients with “normal” liver function (defined as normal AST, ALT for all IRIs, plus normal GGT for ALP IRIs, and ALP for GGT IRIs). IRIs were estimated for all males, all females, females ≤50, and females &amp;gt;50 years and compared to the method specific manufacturer RI (ALP: 40-129 Units/L for males and 35-104 Units/L for females; GGT: 8-61 Units/L for males and 5-36 Units/L for females). Results Of the 71,783 outpatients, 54.9% were female, 74% self-identified as white and 19% as black. The median age was 58 (IQR: 43-68 years), the median ALP concentration was 77 (62-97 Units/L), and the median GGT concentration was 28 (17-57 Units/L). A moderate agreement between ALP and GGT was observed (Kappa = 0.48, 95% confidence interval: 0.46-0.51). A positive correlation between ALP and GGT was observed r = 0.51 (p&amp;lt;0.0001). For ALP, no significant differences were observed between the lower limit of the IRIs and the current RI. The upper limit of estimated IRIs was 132 [95% confidence interval: 117-147 Units/L] for patients with normal AST/ALT/GGT (n = 1596). For males, the sex-specific upper limit was 120 [101-140 Units/L] and for females, was 123 [110-136 Units/L]. Age stratified upper limits for females were 120 [101-140 Units/L], and 109 [97-121 Units/L] for ≤50 and &amp;gt;50 years, respectively. For GGT, no significant differences were observed for the lower limits. The upper limit for all patients with normal AST/ALT/ALP (n = 2,446) was 62 [55-70 Units/L]. For males, all females, females ≤50 and &amp;gt;50 years was 58 [46-69 Units/L], 40 [39-51 Units/L], 31 [23-39 Units/L], and 56 [41-71 Units/L]. Conclusions For the majority of patient subsets, the manufacturer RI agreed well with the IRIs. However, significant differences in IRIs were observed for the upper limit of ALP IRIs of all females with normal hepatobilliary function and in GGT for all females and females &amp;gt;50 years. Further investigation of the impact of preselecting patient populations on IRI estimation and a direct RI study on select patient subsets is worth investigation.

Allostatic load and cognitive recall among young adults: Racial, ethnic, and sex-specific variations

Abstract Introduction: While factors such as age and education have been associated with persistent differences in functional cognitive decline, they do not fully explain observed variations particularly those between different racial/ethnic and sex groups. The aim of this study was to explore the association between allostatic load (AL) and cognition in a racially diverse cohort of young adults. Methods: Utilizing Wave V of the National Longitudinal Study of Adolescent to Adult Health – a nationally representative, longitudinal survey of adults aged 34–44, this study utilized primary data from 10 immune, cardiovascular, and metabolic biomarkers to derive an AL Index. Cognition was previously recorded through word and number recall scores. Regression analysis evaluated the association between cognitive recall, AL, age, sex, and race/ethnicity. Results: Regression results indicated statistically higher AL scores among Blacks (IRR = 1.09, CI = 1.01, 1.19) compared to Whites and lower AL score among females compared to males (IRR = 0.76, CI = 0.72, 0.81). At zero AL, Blacks (IRR = 1.2399, CI = 1.2398, 1.24) and Other races (IRR = 1.4523, CI = 1.452, 1.4525) had higher recall while Hispanics (IRR = 0.808, CI = 0.8079, 0.8081) had lower recall compared to Whites. Relative to males, females had higher number recall (IRR = 1.1976, CI = 1.1976, 1.1977). However, at higher, positive levels of AL, Blacks (IRR = 0.9554, CI = 0.9553, 0.9554), Other races (IRR = 0.9479, CI = 0.9479, 0.9479) and females (IRR = 0.9655, CI = 0.9655, 0.9655) had significantly lower number recall than Whites and males respectively. Conclusions: Race and sex differences were observed in recall at different levels of AL. Findings demonstrate the need for further exploration of cognition in young adults across diverse populations that includes examination of AL.

Prevalence of complications and co-morbidities in males and females with obesity: Real-world insights from claims data analysis.

To comprehensively examine the range of co-morbidities among males and females with a diagnosis of obesity. This cross-sectional retrospective study used US commercial and Medicare claims data from Merative MarketScan Research Databases to identify adults (age ≥ 18 years) with a diagnosis of obesity with continuous insurance coverage from 2018 to 2020. Co-morbidities were tabulated based on coded diagnoses, and prevalences were calculated in males and females across age groups. Age-adjusted odds ratios (ORs) determined differences in co-morbidities between the sexes. Of an eligible sample of 6.9 million, we identified 2 028 273 individuals with at least one obesity-related International Classification of Diseases, 10th Revision, Clinical Modificationcode. The proportions of males and females with obesity were 43.0% versus 57.0%. The most prevalent co-morbidities among males and females were hypertension (62.8% vs. 52.2%), dyslipidaemia (63.3% vs. 50.3%) and depression and/or anxiety (D/A; 29.7% vs. 48.5%). The prevalence of D/A was high in the younger age group, but steadily decreased with age in both sexes; however, hypertension and dyslipidaemia continued to increase with age. The presence of diagnosis of hypertension and dyslipidaemia was 6-8 years earlier in males than in females. Females had higher odds than males for osteoarthritis (OR 1.33), depression (OR 2.22) or osteoporosis (OR 7.10); all P < .0001. Males with obesity received a diagnosis of cardiovascular risk factors at an earlier age than females, which may have contributed to the higher prevalence of coronary heart disease. Understanding sex-specific variations in co-morbidities across ages can support early screening and diagnosis of risk clusters for optimal obesity management.

Sex-Specific Imaging Biomarkers for Parkinson's Disease Diagnosis: A Machine Learning Analysis.

This study aimed to identify sex-specific imaging biomarkers for Parkinson's disease (PD) based on multiple MRI morphological features by using machine learning methods. Participants were categorized into female and male subgroups, and various structural morphological features were extracted. An ensemble Lasso (EnLasso) method was employed to identify a stable optimal feature subset for each sex-based subgroup. Eight typical classifiers were adopted to construct classification models for PD and HC, respectively, to validate whether models specific to sex subgroups could bolster the precision of PD identification. Finally, statistical analysis and correlation tests were carried out on significant brain region features to identify potential sex-specific imaging biomarkers. The best model (MLP) based on the female subgroup and male subgroup achieved average classification accuracy of 92.83% and 92.11%, respectively, which were better than that of the model based on the overall samples (86.88%) and the overall model incorporating gender factor (87.52%). In addition, the most discriminative feature of PD among males was the lh 6r (FD), but among females, it was the lh PreS (GI). The findings indicate that the sex-specific PD diagnosis model yields a significantly higher classification performance compared to previous models that included all participants. Additionally, the male subgroup exhibited a greater number of brain region changes than the female subgroup, suggesting sex-specific differences in PD risk markers. This study underscore the importance of stratifying data by sex and offer insights into sex-specific variations in PD phenotypes, which could aid in the development of precise and personalized diagnostic approaches in the early stages of the disease.

Sex-Specific Variation in Metabolic Responses to Diet.

Suboptimal nutrition is a leading cause of cardiometabolic disease and mortality. Biological sex is a variable that influences individual responses to dietary components and may modulate the impact of diet on metabolic health and disease risk. This review describes findings of studies reporting how biological sex may associate with or affect metabolic outcomes or disease risk in response to varying dietary macronutrient content, Mediterranean diet, Western diet, and medical very low-calorie diet. Although few dietary interventions have been specifically designed to identify sex-diet interactions, future studies improving understanding how sex influences dietary responses could inform precision nutrition interventions for disease prevention and management.

1501P Sex-specific variation in symptoms presentation: Experience of an outpatient clinic integrated model between radiotherapy and palliative care

1501P Sex-specific variation in symptoms presentation: Experience of an outpatient clinic integrated model between radiotherapy and palliative care

Lagging Brain Gene Expression Patterns of Drosophila melanogaster Young Adult Males Confound Comparisons Between Sexes.

Many species, including fruit flies (Drosophila melanogaster), are sexually dimorphic. Phenotypic variation in morphology, physiology, and behavior can affect development, reproduction, health, and aging. Therefore, designating sex as a variable and sex-blocking should be considered when designing experiments. The brain regulates phenotypes throughout the lifespan by balancing survival and reproduction, and sex-specific development at each life stage is likely. Changes in morphology and physiology are governed by differential gene expression, a quantifiable molecular marker for age- and sex-specific variations. We assessed the fruit fly brain transcriptome at three adult ages for gene expression signatures of sex, age, and sex-by-age: 6698 genes were differentially expressed between sexes, with the most divergence at 3days. Between ages, 31.1% of 6084 differentially expressed genes (1890 genes) share similar expression patterns from 3 to 7days in females, and from 7 to 14days in males. Most of these genes (90.5%, 1712) were upregulated and enriched for chemical stimulus detection and/or cilium regulation. Our data highlight an important delay in male brain gene regulation compared to females. Because significant delays in expression could confound comparisons between sexes, studies of sexual dimorphism at phenotypically comparable life stages rather than chronological age should be more biologically relevant.

Iron Homeostasis-Related Parameters and Hepcidin/Ferritin Ratio: Emerging Sex-Specific Predictive Markers for Metabolic Syndrome.

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively (p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 (p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 (p = 0.015), and for men, it had an AUC of 0.792 (p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

Sex-specific differences in NAFLD development: effect of a high-sucrose diet on biochemical, histological, and genetic markers in C57bl/6N mice

ABSTRACT Sucrose intake is a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Individual characteristics such as sex, play arole in the biological variation of the disease, potentially related to genetic regulation. This research evaluated sex differences in biochemical, histopathological, and gene expression responses associated with NAFLD in C57bl/6N mice on a high sucrose diet. Female and male mice were assigned to control or high sucrose diets (50% sucrose solution) for 20 weeks. After sacrifice, blood and hepatic tissue were collected for analysis. Female mice revealed moderate-to-high NAFLD, whereas male mice showed mild-to-moderate NAFLD. Sex-specific variations were observed in Cd36 gene expression, an upregulation in females compared with the male group, and Adipor1 gene expression showed significant downregulation in the female group in response to high sucrose diet compared with the control group. These findings highlight the importance of considering gender disparities in the treatment and management of NAFLD.

Interpretable single-cell factor decomposition using sciRED.

Single-cell RNA sequencing (scRNA-seq) maps gene expression heterogeneity within a tissue. However, identifying biological signals in this data is challenging due to confounding technical factors, sparsity, and high dimensionality. Data factorization methods address this by separating and identifying signals in the data, such as gene expression programs, but the resulting factors must be manually interpreted. We developed Single-Cell Interpretable Residual Decomposition (sciRED) to improve the interpretation of scRNA-seq factor analysis. sciRED removes known confounding effects, uses rotations to improve factor interpretability, maps factors to known covariates, identifies unexplained factors that may capture hidden biological phenomena and determines the genes and biological processes represented by the resulting factors. We apply sciRED to multiple scRNA-seq datasets and identify sex-specific variation in a kidney map, discern strong and weak immune stimulation signals in a PBMC dataset, reduce ambient RNA contamination in a rat liver atlas to help identify strain variation, and reveal rare cell type signatures and anatomical zonation gene programs in a healthy human liver map. These demonstrate that sciRED is useful in characterizing diverse biological signals within scRNA-seq data.

Interpretable single-cell factor decomposition using sciRED.

Single-cell RNA sequencing (scRNA-seq) maps gene expression heterogeneity within a tissue. However, identifying biological signals in this data is challenging due to confounding technical factors, sparsity, and high dimensionality. Data factorization methods address this by separating and identifying signals in the data, such as gene expression programs, but the resulting factors must be manually interpreted. We developed Single-Cell Interpretable Residual Decomposition (sciRED) to improve the interpretation of scRNA-seq factor analysis. sciRED removes known confounding effects, uses rotations to improve factor interpretability, maps factors to known covariates, identifies unexplained factors that may capture hidden biological phenomena and determines the genes and biological processes represented by the resulting factors. We apply sciRED to multiple scRNA-seq datasets and identify sex-specific variation in a kidney map, discern strong and weak immune stimulation signals in a PBMC dataset, reduce ambient RNA contamination in a rat liver atlas to help identify strain variation, and reveal rare cell type signatures and anatomical zonation gene programs in a healthy human liver map. These demonstrate that sciRED is useful in characterizing diverse biological signals within scRNA-seq data.

Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids

Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of sex and Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related to testosterone and Adtrp mRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels. Adtrp deletion had minimal impact on both sexes' metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes, and the role of ADTRP is limited to adipose depots. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex-dependent regulation of human FAHFA metabolism.

Sex-Specific Variations in Glycated Hemoglobin Responses to Structured Exercise in Type 2 Diabetes: Healthcare Implications of Walking and Strength Training on Glycemic Control.

Type 2 diabetes mellitus (T2DM) affects one in ten individuals in the United States, with rates expected to rise significantly. This novel study aimed to evaluate the impact of a structured exercise program on glycated hemoglobin (HbA1c) levels among males and females with T2DM, and to compare the effects of different volumes of combined aerobic and resistance exercise. A total of 67 adult participants with T2DM were randomly assigned to two groups: Group 1 (exercise classes and walking sessions) and Group 2 (exercise classes only). After 10 weeks, 39 participants completed the intervention and 34 had complete HbA1c records. Results indicated a significant improvement in HbA1c levels overall, with males exhibiting a greater decrease compared to females. Minimal baseline differences were observed between the walking and non-walking groups and improvements in HbA1c were noted in both groups with no significant differences. These findings suggested potential sex-specific differences in response to structured exercise programs. The study highlighted the importance of tailored exercise interventions in healthcare while managing T2DM. Further research is necessary to optimize exercise prescriptions and evaluate long-term benefits, but the current evidence supports structured exercise as a valuable component of comprehensive diabetes care. This research underscores the need for personalized approaches in exercise regimens, contributing to the growing body of knowledge on sex-specific responses to T2DM interventions.

Sex-specific phosphorus acquisition strategies and cycling in dioecious Populus euphratica forests along a natural water availability gradient.

Soil phosphorus (P) availability affects plant growth and distribution. However, it is still unknown how sex-specific variation in functional traits affects plants' P acquisition and soil P transformation. On wet sites, female poplars had a greater specific root length (SRL), and a higher diversity of arbuscular mycorrhizal fungi (AMF) and phosphate-solubilizing bacteria (PSB). Male poplars living on wet sites increased the abundance of AMF and PSB communities and enhanced moderately labile and highly resistant organic P mineralisation via increased phosphatase activity. In contrast, on the dry site, the abundance and diversity of AMF and PSB communities increased in females, enhancing moderately labile and highly resistant organic P mineralisation via elevating phosphatase activities. Males maintained greater SRL and promoted Ca-P mobilisation via the release of root carboxylic acids and rhizosphere acidification on the dry site. The AMF community diversity followed a similar pattern as that of the PSB community when altering the P availability of different-sex plants. Our results indicated that organic P and Ca-P are the major sources of plant-available P in natural P. euphratica forests. Seasonal shifts and geographic locations affected the share of organic and inorganic P pools, and AMF and PSB diversities, ultimately altering sex-specific P acquisition strategies of plants.

Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood

ABSTRACT Objectives: Obesity is recognized for its adverse impact on brain health and related behaviors; however, the specific longitudinal effects of a high-fat diet (HFD) from juvenile stages of development through late adulthood remain poorly understood, particularly sex-specific outcomes. This study aimed to determine how prolonged exposure to HFD, commencing during periadolescence, would differentially predispose male and female mice to an elevated risk of dopaminergic dysregulation and associated behavioral deficits. Methods: One-month-old C57BL/6J male and female mice were subjected to either a control diet or an HFD for 5 and 9 months. Muscle strength, motor skills, sensorimotor integration, and anxiety-like behaviors were assessed at the end of the 5th and 8th months. Key dopaminergic molecules, including dopamine (DA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2), were quantified at the end of the 5th or 9th months. Results: Behaviorally, male mice exposed to HFD exhibited more pronounced alterations in sensorimotor integration, anxiety-like behavior, and muscle strength after the 5th month of dietary exposure. In contrast, female mice displayed most behavioral differences after the 8th month of HFD exposure. Physiologically, there were notable sex-specific variations in the dopaminergic pathway response to HFD. Male mice exposed to HFD exhibited elevated tissue levels of VMAT2 and DRD2, whereas female mice showed reduced levels of DRD2 and DAT compared to control groups. Discussion: These findings indicate a general trend of altered time course susceptibility in male mice to chronic HFD consumption compared to their female counterparts, with male mice impacted earlier than females.

Short-term response of primary human meniscus cells to simulated microgravity

BackgroundMechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events.MethodsIn this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture.ResultsRNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes.ConclusionThese findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.