Lentils based pasta affect satiation, satiety and food intake in healthy volunteers.

Plant-based diets represent a valid strategy to improve human health and increase food sustainability. The availability of legume-based products, a good source of proteins and fibers, could help consumers to promote healthy dietary patterns. The aim of this study was to examine the impact of different legume-based pastas on energy intake and appetite in healthy volunteers. Four ad libitum (protocol 1) and iso-caloric pre-load meals (protocol 2) were tested using a randomized repeated measure design. The test meals consisted of lentils pasta (LP), chickpeas pasta (CP); durum wheat pasta (DWP) and gluten free pasta (GFP), served with tomato sauce. Protocol 1: the ad libitum lunch meal was consumed then EI registered. Protocol 2: subjective appetite was assessed by visual analogue scale before and after the pre-load meal for 2 h until an ad libitum buffet was served to assess EI. Twenty (age: 39.2 ± 8.41 years; BMI: 23.4 ± 3.4 kg/m2) and 40 (age: 42.6 ± 8.7 years; BMI: 23.8 ± 4.2 kg/m2) healthy subjects were respectively recruited for each protocol. ANCOVA analysis showed an overall effect of meals and sex on EI within meal and at the subsequent meal, resulting in a lower EI after LP compared to DWP (p < 0.05). Appetite sensations were significantly influenced solely after the pre-load meal, where repeated measures ANCOVA showed increased post-prandial satiety after LP and CP (p < 0.05) compared to DWP in females, whereas a reduction in desire to eat and higher fullness was found following LP compared to the other meals in both sexes (p < 0.05). Overall, lentil-based pasta seemed to acutely affect EI both within and at the subsequent meal, especially in females. Consumption of legume-based pasta might enhance legume intake by modulating appetite feelings and increasing food sustainability. However, further studies are needed to support these results in the long-term and considering different target populations.

Sex-specific associations between levels of high-sensitivity C-reactive protein and severity of depression: retrospective cross-sectional analysis of inpatients in China.

BACKGROUND: We aimed to clarify the controversial relationship between levels of high-sensitivity C-reactive protein (hs-CRP) and severity of depression in men and women. METHODS: Medical records were retrospectively analyzed for 1,236 inpatients at our medical center who were diagnosed with depression at discharge between January 2018 and August 2022. Depression severity was assessed during hospitalization using the 24-item Hamilton Depression Rating Scale. Potential associations between severity scores and hs-CRP levels were explored using multivariate linear regression as well as smooth curve fitting to detect non-linear patterns. RESULTS: In male patients, hs-CRP levels between 2.00 mg/L and 10.00 mg/L showed a non-linear association with depression severity overall (fully adjusted ß = 1.69, 95% CI 0.65 to 2.72), as well as with severity of specific symptoms such as hopelessness, sluggishness, and cognitive disturbance. In female patients, hs-CRP levels showed a linear association with severity of cognitive disturbance (fully adjusted ß = 0.07, 95% CI 0.01 to 0.12). These results remained significant after adjusting for age, body mass index, diabetes, hypertension, history of drinking, history of smoking, and estradiol levels. DISCUSSION: Levels of hs-CRP show sex-specific associations with depression severity, particularly levels between 2.00 and 10.00 mg/L in men. These findings may help develop personalized anti-inflammatory treatments for depression, particularly for men with hs-CRP levels of 2.00-10.00 mg/L.

Sex- and age-specific differences in the use of antiarrhythmic therapies among atrial fibrillation patients: a nationwide cohort study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) patients frequently require active rhythm control therapy to maintain sinus rhythm and reduce symptom burden. Our study assessed whether antiarrhythmic therapies (AATs) are used disproportionately between men and women after new-onset AF. METHODS: The nationwide Finnish anticoagulation in atrial fibrillation (FinACAF) registry-based linkage study covers all patients with new-onset AF in Finland during 2007-2018. Study outcomes included initiation of AATs in the form of antiarrhythmic drugs (AAD), cardioversion, or catheter ablation. RESULTS: The study population constituted of 229 565 patients (50% females). Women were older than men (76.6 ± 11.8 vs. 68.9 ± 13.4 years) and had higher prevalence of hypertension or hyperthyroidism, but lower prevalence of vascular disease, diabetes, renal disease, and cardiomyopathies than men. Overall, 17.6% of women and 25.1% of men were treated with any AAT. Women were treated with AADs more often than men in all age groups (adjusted subdistribution hazard ratio (aSHR) 1.223, 95%-CI 1.187-1.261). Cardioversions were also performed less often on women than on men aged <65 years (aSHR 0.722, 95%-CI 0.695-0.749), more often in patients ≥75 years (aSHR 1.166, 95%-CI 1.108-1.227), while no difference between the sexes existed in patients aged 65-74 years. Ablations were performed less often in women aged <65 years (aSHR 0.908, 95%-CI 0.826-0.998) and ≥75 years (aSHR 0.521, 95%-CI 0.354-0.766), whereas there was no difference in patients aged 65-74 years. CONCLUSION: Women used more AAD than men in all age groups but underwent fewer cardioversion and ablation procedures when aged <65 years.

Sex- and dose-dependent catalase increase and its clinical impact in a benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease.

BACKGROUND: Sex differences in Alzheimer's disease (AD) are gaining increasing attention. Previously research has shown that sodium benzoate treatment can improve cognitive function in AD patients, particularly in the female patients; and 1000 mg/day of benzoate appears more efficacious than lower doses. Catalase is a crucial endogenous antioxidant; and deficiency of catalase is regarded to be related to the pathogenesis of AD. The current study aimed to explore the role of sex and benzoate dose in the change of catalase activity among benzoate-treated AD patients. METHODS: This secondary analysis used data from a double-blind trial, in which 149 CE patients were randomized to receive placebo or one of three benzoate doses (500, 750, or 1000 mg/day) and measured with Alzheimer's disease assessment scale-cognitive subscale. Plasma catalase was assayed before and after treatment. RESULTS: Benzoate treatment, particularly at 1000 mg/day, increased catalase among female patients, but not among male. The increases in the catalase activity among the benzoate-treated women were correlated with their cognitive improvements. In addition, higher baseline catalase activity was associated with more cognitive improvement after benzoate treatment among both female and male patients. CONCLUSIONS: Supporting the oxidative stress theory and sex difference in AD, the finding suggest that sex (female) and benzoate dose co-determine catalase increase in benzoate-treated AD patients and the catalase increment contributes to cognitive improvement of benzoate-treated women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03752463.

Sex differences in pathogenesis and treatment of dyslipidemia in patients with type 2 diabetes and steatotic liver disease.

Previously published studies have shown that women with type 2 diabetes have a higher risk of atherosclerotic cardiovascular disease than men with type 2 diabetes. The exact reason for this is not yet known. The association between metabolic dysfunction-associated steatotic liver disease and type 2 diabetes appears to be bidirectional, meaning that the onset of one may increase the risk of the onset and progression of the other. Dyslipidemia is common in both diseases. Our aim was therefore to investigate whether there is a sex difference in the pathogenesis and management of dyslipidemia in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction. While the majority of published studies to date have found no difference between men and women in statin treatment, some studies have shown reduced effectiveness in women compared to men. Statin treatment is under-prescribed for both type 2 diabetics and patients with dysfunction-associated steatotic liver disease. No sex differences were found for ezetimibe treatment. However, to the best of our knowledge, no such study was found for fibrate treatment. Conflicting results on the efficacy of newer cholesterol-lowering PCSK9 inhibitors have been reported in women and men. Results from two real-world studies suggest that up-titration of statin dose improves the efficacy of PCSK9 inhibitors in women. Bempedoic acid treatment has been shown to be effective and safe in patients with type 2 diabetes and more effective in lipid lowering in women compared to men, based on phase 3 results published to date. Further research is needed to clarify whether the sex difference in dyslipidemia management shown in some studies plays a role in the risk of ASCVD in patients with type 2 diabetes and steatotic liver disease with metabolic dysfunction.

Associations of ocular anterior segment structures with sex and age: the Yamagata study (Funagata).

PURPOSE: To investigate the associations of tomographic parameters in anterior segment optical coherence tomography (AS-OCT) with sex and age in a cohort study. STUDY DESIGN: A cohort design. MATERIALS AND METHODS: AS-OCT data from 391 Japanese participants aged ≥ 35 years were obtained using swept-source OCT. In the cornea, the keratometric power at the flat (Kf) and steep (Ks) meridians, maximum keratometric power (Kmax), keratometric cylinder, spherical power, regular astigmatism, asymmetry, higher-order irregularity (HOI) from the anterior and posterior surfaces, and the central and thinnest corneal thicknesses were evaluated. Also, anterior chamber depth (ACD), lens thickness, crystalline lens rise (CLR), and nasal and temporal angle opening distances at 500 µm from the scleral spur (AOD500) were assessed. Sex differences and age-related changes were analyzed. RESULTS: Women exhibited higher anterior Kf, Ks, and Kmax and lower posterior Kf, Ks, and Kmax than men. The ACD and nasal/temporal AOD500 were shorter in women than in men. The CLR was higher in women, whereas the lens thickness did not differ between the sexes, indicating a more anteriorly positioned lens in women. Age-related changes included increased anterior/posterior HOI, increased lens thickness and CLR resulting in decreased ACD and AOD500. CONCLUSION: This study reveals sex-related differences in corneal shape, anterior chamber conformation, and lens position, as well as age-related changes in tomographic parameters. ACD, CLR, nasal and temporal AOD500 showed significant sex differences in the 50-70 s, whereas lens thickness showed no difference.

Gender Differences in Variability in Intimate Relationship Satisfaction: A Secondary Analysis and Meta-Analysis.

There is a long-standing interest in gender differences in satisfaction in intimate relationships. Whereas prior research has focused on gender differences in central tendency (i.e., means), we conducted two studies - a secondary analysis of data from a probability sample of Australian married couples and a meta-analysis - to examine gender differences in variability (i.e., variances). We hypothesized that compared to males, females would demonstrate greater variability in intimate relationship satisfaction (i.e., greater female variability hypothesis), particularly at lower levels of relationship satisfaction. Results from a secondary analysis of data from 2,711 married couples in the Household, Income and Labour Dynamics in Australia (HILDA) survey and from a meta-analysis of 20 years of research (k = 171, N = 84,976), including independent samples from 33 countries, indicated that relative to males, females reported greater variability in relationship satisfaction. Obtained effect sizes (female-to-male variance ratios [VRs] of 1.42 for the HILDA sample and 1.19 for the meta-analysis) were larger than proposed cutoffs for meaningful group differences in variability. Analysis of tail ratios (ratios of the relative proportion of females divided by the relative proportion of males in the distributional tail regions) in the HILDA sample indicated that gender differences in variability were greater at lower (versus higher) levels of satisfaction. Findings support the greater female variability hypothesis and suggest that by focusing only on gender differences in means, the existing literature has underestimated gender differences in intimate relationship satisfaction.

Effects of passive smoking on cortical spreading depolarization in male and female mice.

BACKGROUND: Patients with migraine are typically advised to avoid passive smoking because it may aggravate headaches and other health conditions. However, there is insufficient high-quality evidence on the association between passive smoking and migraine, which warrants further investigation using animal models. Therefore, using a mouse model, we examined the effect of passive smoking on susceptibility to cortical spreading depolarization (CSD), the biological basis of migraine with aura. FINDINGS: Fifty C57BL/6 mice (25 males and 25 females) were exposed for one hour to cigarette smoke or room air. Subsequently, potassium chloride (KCl) was administered under isoflurane anesthesia to induce CSD, and the CSD threshold, frequency of induction, and propagation velocity were determined. The threshold to induce CSD (median [interquartile range (IQR)]) was significantly lower in female mice (adjusted p = 0.01) in the smoking group (0.05 [0.05, 0.088]) than in the sham group (0.125 [0.1, 0.15]); however, there was no significant difference in the male mice (adjusted p = 0.77). CSD frequency or propagation velocity did not differ significantly between the two groups for either sex. CONCLUSIONS: Female mice in the smoking group showed lower CSD threshold compared to the sham group, suggesting a potential sex-specific difference in the effect of smoking on the pathogenesis of CSD and migraine with aura. This finding may contribute to the understanding of migraine pathophysiology in association with passive smoking and sex difference.

Genistein mitigates diet-induced obesity and metabolic dysfunctions in gonadectomized mice with some sex-differential effects.

Background: Obesity is associated with insulin resistance (IR) and metabolic dysfunction-associated steatotic liver disease (MASLD). Genistein, an isoflavone, is a promising natural compound for preventing and treating obesity and metabolic dysfunctions. We aimed to investigate the sex-specific protective effects of genistein on obesity, IR, and MASLD in a murine model of sex hormone deprivation with diet-induced obesity (DIO), mimicking postmenopausal women or aging men with metabolic syndrome. Methods: Gonadectomized and sham-operated C57BL/6NJcl mice were fed a high-fat high-sucrose diet for 4 weeks to induce obesity (7 mice per group). In gonadectomized mice, genistein (16 mg/kg/day) or vehicle (7.5% dimethyl sulfoxide) was orally administered for 45 days. We assessed glucose homeostasis parameters, hepatic histopathology, and hepatic gene expression to investigate the effects of gonadectomy and genistein treatment. Results: Gonadectomy exacerbated adiposity in both sexes. Ovariectomy diminished the protective effects of female gonadal hormones on the homeostatic model assessment for insulin resistance (HOMA-IR), serum alanine transaminase levels, hepatic steatosis score, and the expression of hepatic genes associated with MASLD progression and IR, such as Fasn, Srebf1, Saa1, Cd36, Col1a1, Pck1, and Ppargc1a. Genistein treatment in gonadectomized mice significantly reduced body weight gain and the hepatic steatosis score in both sexes. However, genistein treatment significantly attenuated HOMA-IR and the expression of the hepatic genes only in female mice. Conclusion: Genistein treatment mitigates DIO-related MASLD in both male and female gonadectomized mice. Regarding hepatic gene expression associated with MASLD and IR, the beneficial effect of genistein was significantly evident only in female mice. This study suggests a potential alternative application of genistein in individuals with obesity and sex hormone deprivation, yet pending clinical trials.

Sex differences in functional and structural alterations of hippocampus region in chronic pain: a DTI and resting-state fMRI study.

Introduction: It is well known that there are significant differences in the prevalence of chronic pain between males and females. Human and animal imaging studies have shown that chronic pain profoundly alters the structure and function of brain regions. However, there is limited research on the sex-specific mechanisms underlying the brain plasticity and adaptive changes associated with chronic pain. In this article, we conducted a multimodal study to evaluate how nerve injury-induced chronic pain affects the brain. Methods: Male and female Sprague-Dawley (SD) rats with spared nerve injury (SNI) model underwent resting-state functional magnetic resonance imaging (rs-fMRI) (male sham group: n = 18; male SNI group: n = 18; female sham group: n = 20; female SNI group: n = 18) and magnetic resonance diffusion tensor imaging (DTI) (male sham group: n = 23; male SNI group: n = 21; female sham group: n = 20; female SNI group: n = 21) scanning. ICA method, Fractional amplitude of low-frequency fluctuations (fALFF), immunofluorescence staining, and graph theory analysis was utilized to extract the rs-fMRI changes of brain regions of each group. Results: Using SNI model, which promotes long-lasting mechanical allodynia, we found that neuropathic pain deeply modified the intrinsic organization of the brain functional network in male and female rats (main effect of operation: F = 298.449, P < 0.001). 64 independent components (ICs) in the brain were divided and assigned to 16 systems. In male rats, we observed significant alterations in the microstructure of the hippocampal cornu ammonis 1 and cornu ammonis 2 (CA1/CA2) region, as indicated by increased mean diffusivity (MD) (CA1_L: P = 0.02; CA1_R: P = 0.031; CA2_L: P = 0.035; CA2_R: P = 0.015) and radial diffusivity (RD) (CA1_L: P = 0.028; CA1_R: P = 0.033; CA2_L: P = 0.037; CA2_R: P = 0.038) values, along with enhanced activating transcription factor 3 (ATF3) expression. Conversely, in female rats, we found significant increases in the fractional amplitude of low frequency fluctuations (fALFF) value within the hippocampal dentate gyrus (DG) (F = 5.419, P = 0.023), accompanied by elevated c-Fos signal (F = 6.269, P = 0.031). Furthermore, graph theory analysis revealed notable differences in the small-world network of the hippocampal system in female rats, characterized by reduced small-world attributes and increased inter-nodal transmission efficiency. Discussion: Our study indicates sex differences in structural and functional alterations in the hippocampal system in rats under chronic pain conditions. The results suggest that the hippocampus system plays an important role in the different mechanisms of chronic pain in different sexes. These findings provide reliable insights to explore the complex mechanisms underlying sex differences in chronic pain.

The Promise and Practicality of Addressing Sex as a Biological Variable and the Ovarian Cycle in Preclinical Epilepsy Research.

Seizures and epilepsy affect people of all sexes and genders. In the last several years, funding agency initiatives such as the U.S. National Institutes of Health policy on sex as a biological variable (SABV) have intended to encourage researchers to study both males and females from cell to tissue to organism and analyze and report the resulting data with sex as a factor. Preclinical epilepsy research, however, continues to be plagued by confusion regarding both the SABV policy and its implementation, reflecting similar beliefs in the larger neuroscience research community. This article aims to address some common misconceptions and provide practical tools and suggestions for preclinical epilepsy researchers in implementing SABV and analysis of the female ovarian cycle (estrous cycle in rodents) in their research programs, with a focus on studies using rodent models. Examples of recent publications in preclinical epilepsy research highlighting the value of incorporating SABV and information on the estrous cycle are included. The specifics of how best to address SABV and the estrous cycle can vary depending on the needs and goals of a particular research program, but an embrace of these physiological factors by the preclinical epilepsy research community promises to yield more rigorous research and improved treatment strategies for all people with epilepsy.

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.

Sex difference, proteostasis and mitochondrial function impact stroke-related sarcopenia-A systematic review and meta-analysis.

BACKGROUND: The prevalence of stroke-related sarcopenia has been noted; however, epidemiological data and interventions that increase or reduce the incidence of stroke-related sarcopenia remain lacking. METHODS: Studies on stroke-related sarcopenia were included in association or interventional analyses. All analyses were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two evaluators independently extracted the data. RESULTS: Female stroke patients had a higher preference for sarcopenia than male patients (pooled odds ratio [OR] = 0.670, 95 % CI 0.533-0.842, p = 0.001). Although stroke patients without drug use have improved skeletal muscle mass index (SMI) (MD = 0.272, 95 % CI 0.087-0.457, p = 0.004), handgrip strength (HGS) was not significantly altered (MD = -0.068, 95 % CI -0.221-0.076, p = 0.354). Stroke patients with nutrient interventions have improved SMI (MD = -0.354, 95 % CI -0.635- -0.073, p = 0.014) and HGS (MD = -0.394, 95 % CI -0.678- -0.111, p = 0.006); the synergistic effect of rehabilitation exercise has not been ruled out. Whether a sex difference exists in these interventions remains to be investigated. The underlying pathological mechanisms and potential therapeutic strategies for this disease are discussed. CONCLUSION: Sex difference, proteostasis, and mitochondrial function may impact the incidence of stroke-related sarcopenia. Understanding the underlying pathological mechanisms and potential therapeutic targets for this disease will provide new insights into disease treatment, prevention, and drug development.

Neuronal lipid droplets play a conserved and sex-biased role in maintaining whole-body energy homeostasis.

Lipids are essential for neuron development and physiology. Yet, the central hubs that coordinate lipid supply and demand in neurons remain unclear. Here, we combine invertebrate and vertebrate models to establish the presence and functional significance of neuronal lipid droplets (LD) in vivo. We find that LD are normally present in neurons in a non-uniform distribution across the brain, and demonstrate triglyceride metabolism enzymes and lipid droplet-associated proteins control neuronal LD formation through both canonical and recently-discovered pathways. Appropriate LD regulation in neurons has conserved and male-biased effects on whole-body energy homeostasis across flies and mice, specifically neurons that couple environmental cues with energy homeostasis. Mechanistically, LD-derived lipids support neuron function by providing phospholipids to sustain mitochondrial and endoplasmic reticulum homeostasis. Together, our work identifies a conserved role for LD as the organelle that coordinates lipid management in neurons, with implications for our understanding of mechanisms that preserve neuronal lipid homeostasis and function in health and disease.

Sex-dependent regulation of retinal pigment epithelium and retinal function by Pgc-1α.

Age-related macular degeneration (AMD) is a major cause of blindness that affects people over 60. While aging is the prominent factor in AMD, studies have reported a higher prevalence of AMD in women compared to age-matched men. Higher levels of the innate immune response's effector proteins complement factor B and factor I were also found in females compared to males in intermediate AMD. However, the mechanisms underlying these differences remain elusive. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is a key regulator of mitochondrial biogenesis and metabolic pathways. Previously, we showed that Pgc-1α repression and high-fat diet induce drastic AMD-like phenotypes in mice. Our recent data revealed that Pgc-1α repression alone can also induce retinal pigment epithelium (RPE) and retinal dysfunction in mice, and its inhibition in vitro results in lipid droplet accumulation in human RPE. Whether sex is a contributing factor in these phenotypes remains to be elucidated. Using electroretinography, we demonstrate that sex could influence RPE function during aging independent of Pgc-1α in wild-type (WT) mice. We further show that Pgc-1α repression exacerbates RPE and retinal dysfunction in females compared to aged-match male mice. Gene expression analyses revealed that Pgc-1α differentially regulates genes related to antioxidant enzymes and mitochondrial dynamics in males and females. RPE flat mounts immunolabeled with TOMM20 and DRP1 indicated a sex-dependent role for Pgc-1α in regulating mitochondrial fission. Analyses of mitochondrial network morphology suggested sex-dependent effects of Pgc-1α repression on mitochondrial dynamics. Together, our study demonstrates that inhibition of Pgc-1α induces a sex-dependent decline in RPE and retinal function in mice. These observations on the sex-dependent regulation of RPE and retinal function could offer novel insights into targeted therapeutic approaches for age-related RPE and retinal degeneration.

Classifiers of anterior cruciate ligament status in female and male adolescents using return-to-activity criteria.

PURPOSE: A lack of standardization exists for functional tasks in return-to-activity (RTA) guidelines for adolescents with anterior cruciate ligament injury (ACLi). Identifying the variables that discern ACLi status among adolescents is a first step in the creation of such guidelines following surgical reconstruction. This study investigated the use of classification models to discern ACLi status of adolescents with and without injury using spatiotemporal variables from functional tasks typically used in RTA guidelines for adults. METHODS: Sixty-four adolescents with ACLi and 70 uninjured adolescents completed single-limb hops, lunges, squats, countermovement jumps and drop-vertical jumps. Jumping distances, heights, and depths were collected. Decision trees (DTs) were used to classify ACLi status and were evaluated using the F-measure (F1), kappa statistic (ĸ) and area under the precision-recall curve (PRC). Independent t tests and effect sizes were calculated for each important classifier of the DT models. RESULTS: A five-variable model classified ACLi status with an accuracy of 67.5% (F1 = 0.6842; ĸ = 0.350; PRC = 0.491) with sex as a classifier. Significant differences were found in three of the four spatiotemporal variables (p ≤ 0.002). Separate models then classified ACLi status in males and females with an accuracy of 53.3% (F1 = 0.5882; ĸ = 0.0541; PRC = 0.476) and 76.9% (F1 = 0.7692; ĸ = 0.541; PRC = 0.528), respectively, with significant differences for all variables (p ≤ 0.013). CONCLUSIONS: Among the DT models, females were better able to classify ACLi status compared to males, highlighting the importance of sex-specific rehabilitation guidelines for adolescents. LEVEL OF EVIDENCE: Level III.

Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism.

BACKGROUND: Whole-genome sequencing (WGS) analyses have found higher genetic burden in autistic females compared to males, supporting higher liability threshold in females. However, genomic evidence of sex differences has been limited to European ancestry to date and little is known about how genetic variation leads to autism-related traits within families across sex. METHODS: To address this gap, we present WGS data of Korean autism families (n = 2255) and a Korean general population sample (n = 2500), the largest WGS data of East Asian ancestry. We analyzed sex differences in genetic burden and compared with cohorts of European ancestry (n = 15,839). Further, with extensively collected family-wise Korean autism phenotype data (n = 3730), we investigated sex differences in phenotypic scores and gene-phenotype associations within family. RESULTS: We observed robust female enrichment of de novo protein-truncating variants in autistic individuals across cohorts. However, sex differences in polygenic burden varied across cohorts and we found that the differential proportion of comorbid intellectual disability and severe autism symptoms mainly drove these variations. In siblings, males of autistic females exhibited the most severe social communication deficits. Female siblings exhibited lower phenotypic severity despite the higher polygenic burden than male siblings. Mothers also showed higher tolerance for polygenic burden than fathers, supporting higher liability threshold in females. CONCLUSIONS: Our findings indicate that genetic liability in autism is both sex- and phenotype-dependent, expanding the current understanding of autism's genetic complexity. Our work further suggests that family-based assessments of sex differences can help unravel underlying sex-differential liability in autism.

Sex-Specific Adherence to the Mediterranean Diet in Obese Individuals.

Adherence to the Mediterranean diet (MedDiet) has long been associated with several health benefits, including a reduced risk of heart disease, diabetes, and obesity. The MedDiet is characterized by a high consumption of foods such as fruits, vegetables, whole grains, fish, and olive oil, along with a moderate intake of red meat and red wine with meals. Some studies report significant differences between men and women in susceptibility to obesity, with women at a higher prevalence of obesity than men. One unexplored aspect, however, concerns the sex difference in MedDiet adherence, which could be influenced by various factors, such as health perceptions, food preferences, and cultural influences. The aim of this study is to assess the effectiveness and impact of MedDiet adherence in men and women, with a focus on its influence on health and well-being, as well as its ability to promote sex equity in healthcare outcomes. Moreover, we aim to measure the overall health improvements in men and women participating in a MedDiet program, including changes in body composition and overall quality of life. This study highlights that the MedDiet is associated with more significant body weight loss in women, although their increase in MedDiet adherence was lower than in men. Trial registration: NCT01890070. Registered 24 June 2013.

Sex-specific in the association between depressive symptoms and risk of cognitive impairment in Chinese older adults.

BACKGROUND: Many studies have focused on the relationship between depressive symptoms and cognitive impairment, but gender differences in this relationship are unclear, especially among Chinese older adults. Therefore, this study explores whether there are gender differences between depressive symptoms and risk of cognitive impairment based on a survey of a Chinese older adult population. STUDY DESIGN: This is a cross-sectional study. METHOD: We screened 9678 older adults aged 65 to 105 from the 2018 CLHLS database. The 10-item Center for Epidemiological Studies Depression Scale (CESD-10) and Mini-Mental State Examination (MMSE) were utilized for measuring depressive symptoms and cognitive performance, respectively. Logistic regressions and restricted cubic spline were applied to investigate the relationship between depressive symptoms and cognitive impairment. RESULTS: Of the 9678 participants, 4719 (48.8 %) were men. The association between severe depressive symptoms and cognitive impairment was more pronounced in older men (male × severe depressive symptoms: OR = 2.71, 95%CI = 1.07-6.92, p = 0.037). Compared with no depressive symptoms, severe depressive symptoms were associated with an almost five times greater risk of cognitive impairment in men (OR = 4.84, 95 % CI = 2.26-10.40, p < 0.001, compared to OR = 2.25, 95 % CI = 1.27-3.96, p = 0.005 in women). Gender differences were demonstrated in the association of individual ten depressive symptoms with cognitive impairment: men who felt lonely were more likely to have cognitive impairment (OR = 1.24, 95 % CI = 1.06-1.47, p = 0.010), while women who slept poorly were more likely to have cognitive impairment (OR = 1.42, 95 % CI = 1.16-1.74, p = 0.001). CONCLUSION: Results indicate a stronger association between severe depressive symptoms and cognitive impairment among older Chinese males. Our study suggests that reducing loneliness can help prevent cognitive impairment in older men, and improving sleep quality can help improve cognitive function in older women.