Carotid plaque offsets sex-related differences in cardiovascular risk of young hypertensive patients.

BACKGROUND: Women have a lower risk for cardiovascular (CV) disease compared to men. Whether this difference is influenced by the presence of hypertension-mediated organ damage is unknown. OBJECTIVE: To assess whether the presence of carotid plaque (CP) impacts the sex difference in risk for CV events in treated hypertensive patients. METHODS: From the Campania Salute Network Registry 2419 women and men <51 years of age with treated hypertension and free from prevalent CV disease were included. The presence of CP was identified by Doppler ultrasound (intima-media thickness≥1.5 mm). The primary outcome was a composite of fatal and non-fatal stroke or myocardial infarction, sudden death, TIA, myocardial revascularization, de novo angina, and atrial fibrillation. RESULTS: Among patients without CP at baseline (n = 1807), women were older, with higher systolic blood pressure, serum cholesterol level and prevalence of LVH but lower serum triglycerides and eGFR, compared to men (all p < 0.001). Among patients with CP (n = 612), women were older, used higher number of antihypertensive drugs, had higher serum cholesterol level and prevalence of left ventricular hypertrophy (LVH), but had lower serum triglycerides and eGFR compared to men (all p < 0.001). During follow-up, women without CP had a lower risk for CV disease than men (hazard ratio, HR, 0.51, 95 % confidence intervals, CI, 0.27-0.99, p = 0.04) after accounting for cardiovascular risk factors, LVH, and antihypertensive treatment. In contrast, among patients with CP, women had similar risk for CV disease compared with men (HR 1.3, 95 % CI, 0.59-2.9, p = 0.48). CONCLUSIONS: Our findings suggest that the presence of CP in young patients with treated hypertension offsets the CV disease protection in women. TRIAL REGISTRATION: NCT02211365.

Sex-specific effects on elements of the social brain neural network in Wistar rats from perinatal exposure to FireMaster 550 or its components.

Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2000 µg, 1000 µg, and 1000 µg oral to the dam respectively (absolute and not by bodyweight)) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional behaviors of relevance to neurodevelopmental disorders.

Masticatory Function, Sex, and Risk of Dementia Among Older Adults: A Population-Based Cohort Study.

BACKGROUND: A decline in masticatory function may indicate brain dysfunction related to dementia, but the relationship between masticatory function and dementia risk remains unclear. This study aimed to investigate whether masticatory function is associated with the risk of cognitive decline and dementia. METHODS: Data were obtained from the nationwide prospective cohort study of randomly sampled community-dwelling Koreans aged ≥ 60 years. The 5,064 non-demented participants, whose number of chewing cycles per bite was assessed by clinical interview, were followed for 8 years with biennial assessments of cognitive performance and clinical diagnoses of all-cause dementia and Alzheimer's disease (AD). Structural brain magnetic resonance imaging was collected from a subset of cohort participants and their spouses for imaging analyses. RESULTS: Males who chewed ≥ 30 cycles/bite had faster decline in global cognition and memory function and were at higher risk for incident all-cause dementia (hazard ratio [HR], 2.91; 95% confidence interval [CI], 1.18-7.18) and AD (HR, 3.22; 95% CI, 1.14-9.11) compared to males with less than 10 cycles/bite. Additionally, increased chewing cycles in males were associated with reduced brain volume, particularly in regions involved in compensatory cognitive control of mastication. There was no significant association between chewing cycles and the risk of dementia or brain volume in females. CONCLUSION: Older men who frequently chew their meals could be considered a notable population at risk for dementia who should be carefully assessed for their cognitive trajectories.

Gender differences between smoking and the risk of hip fracture.

OBJECTIVE: This study aimed to estimate the relation between cigarette smoking and hip fracture in men compared with women using a meta-analytic approach. METHODS: On March 1, 2024, prospective cohort studies were searched from PubMed, Embase and Cochrane library systems. The gender difference in the relationship between smoking and hip fracture risk was evaluated by random effect model. RESULTS: Eleven prospective cohort studies involving data from 2,689,620 individuals were selected for meta-analysis. The ratio of relative risk (RRR) of hip fractures in current smokers was significantly higher in men than in women (RRR: 1.10; 95%CI: 1.00 - 1.20; P = 0.047), while no evidence of sex differences in former smoking and hip fracture risk (RRR: 0.98; 95%CI: 0.88 - 1.10; P = 0.759). CONCLUSIONS: The male-to-female RRR of hip fractures increased in current smokers, whereas no sex difference was found in the relationship between former smoking and the risk of hip fractures.

Sex differences in symptoms following the administration of BNT162b2 mRNA COVID-19 vaccine in children below 5 years of age in Germany (CoVacU5): a retrospective cohort study.

BACKGROUND: Sex differences exist not only in the efficacy but also in adverse event rates of many vaccines. Here we compared the safety of BNT162b2 vaccine administered off-label in female and male children younger than 5 years in Germany. METHODS: This is a retrospective cohort study, in which we performed a post-hoc analysis of a dataset collected through an authentication-based survey of individuals having registered children aged 0-<5 years for vaccination against SARS-CoV-2 in six private practices and/or two lay person-initiated vaccination campaigns. We analyzed the safety profiles of the first 3 doses of 3-10 µg BNT162b2. Primary outcome was comparison in frequencies of 4 common post-vaccination symptom categories such as local, general, musculoskeletal symptoms and fever. Data were analyzed according to sex in bivariate analyses and regression models adjusting for age, weight, and dosage. Interaction between sex and BNT162b2 dosage was assessed. An active-comparator analysis was applied to compare post-vaccination symptoms after BNT162b2 versus non-SARS-CoV-2 vaccines. RESULTS: The dataset for the present analysis consisted of 7801 participants including 3842 females (49%) and 3977 males (51%) with an age of 3 years (median, interquartile: 2 years). Among individuals receiving 3 µg BNT162b2, no sex differences were noted, but after a first dose of 5-10 µg BNT162b2, local injection-site symptoms were more prevalent in girls compared to boys. In logistic regression, female sex was associated with higher odds of local symptoms, odds ratio (OR) of 1.33 (95% confidence interval [CI]: 1.15-1.55, p < 0.05) and general symptoms with OR 1.21 (95% CI: 1.01-1.44, p < 0.05). Following non-BNT162b2 childhood vaccinations, female sex was associated with a lower odds of post-vaccination musculoskeletal symptoms (OR: 0.29, 95% CI: 0.11-0.82, p < 0.05). An active comparator analysis between BNT162b2 and non-SARS-CoV-2 vaccinations revealed that female sex positively influenced the association between BNT162b2 vaccine type and musculoskeletal symptoms. CONCLUSIONS: Sex differences exist in post-vaccination symptoms after BNT162b2 administration even in young children. These are of importance for the conception of approval studies, for post-vaccination monitoring and for future vaccination strategies (German Clinical Trials Register ID: DRKS00028759).

For many childhood vaccines, the immune responses are different between the sexes. For the COVID-19 vaccine BNT162b2, the symptoms occurring after vaccination in children have not sufficiently been investigated. In this study, we performed an analysis of a dataset of retrospectively collected information on symptoms occurring after vaccinations with BNT162b2 and regular childhood vaccines in 7801 children under the age of 5 years in Germany, with a focus on the sex differences. Among the four categories assessed, local injection-site and general symptoms were more frequent in girls compared to boys. In contrast, following the administration of other childhood vaccines, the caregivers more frequently reported muscle-related symptoms in boys than in girls. In conclusion, sex differences exist in symptoms occurring after vaccinations even in young children, which is important to consider for future studies evaluating vaccine safety.

Sex differences in human pre-gastrulation embryos.

Human fetuses exhibit notable sex differences in growth rate and response to the intrauterine environment, yet their origins and underlying mechanisms remain uncertain. Here, we conduct a detailed investigation of sex differences in human pre-gastrulation embryos. The lower methylation and incomplete inactivation of the X chromosome in females, as well as the sex-specific cell-cell communication patterns, contribute to sex-differential transcription. Male trophectoderm is more inclined toward syncytiotrophoblast differentiation and exhibits a stronger hormone secretion capacity, while female trophectoderm tends to retain cytotrophoblast program with stronger mitochondrial function as well as higher vasculogenesis and immunotolerance signals. Male primitive endoderm initiates the anterior visceral endoderm transcriptional program earlier than females. The cell cycle activities of the epiblast and primitive endoderm are higher in males compared to females, while the situation is opposite in the trophectoderm. In conclusion, our study provides in-depth insights into the sex differences in human pre-gastrulation embryos and contributes to unraveling the origins of the sex differences in human fetal development.

Sex differences in contextual fear expression are associated with altered medial prefrontal cortex activity.

Understanding the neural basis of fear expression in rodents has implications for understanding pathological fear responses that characterize posttraumatic stress disorder. Even though posttraumatic stress disorder is more common in females, little is known about the neural circuit interactions supporting fear expression in female rodents. In this study, we were interested in determining whether neural activity associated with the expression of contextual fear differed between males and females within the projections from the medial prefrontal cortex to the ventrolateral periaqueductal gray, and in the medial prefrontal cortex in neurons that do not project to the periaqueductal gray. We infused a viral retrograde tracer into the ventrolateral periaqueductal gray in male and female rats and trained them in a contextual fear conditioning task. The following day rats were re-exposed to the conditioning context and were sacrificed shortly thereafter. Neural activity was measured using EGR1 immunofluorescence. The behavioral results showed that males exhibited higher levels of freezing during the context test than females. Male rats that underwent training and testing showed an increase in the proportion of viral infected cells that express EGR1 in the PL compared to rats that had only received context exposure. Trained female rats were not different than controls, however a direct comparison between sexes was not different. In cells not labeled by the tracer, males showed higher levels of fear-induced EGR1 expression in the prelimbic cortex than females. Conversely, females showed higher levels of EGR1 expression in the infralimbic cortex following testing as compared to males. These results suggest that sex differences in the expression of contextual fear may involve differences in the relative activity levels of the prelimbic and infralimbic cortex.

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 differences in clinical presentation, treatment response, and side effects of nutritional therapy among patients at nutritional risk A secondary analysis of the randomized clinical trial EFFORT.

BACKGROUND: Considering sex-specific factors has become an increasingly recognized area for research and practice. In the field of clinical nutrition, there is insufficient evidence regarding differences in clinical presentation, treatment response, and side effects of nutritional therapy among female and male patients. METHODS: This secondary analysis investigated differences among female and male patients at risk for malnutrition regarding initial presentation, clinical outcomes, and treatment response in patients included in the Effect of Early NutritionalSupporton Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial comparing individualized nutritional support to usual care. RESULTS: Of 2,028 patients included in the trial 964 were female and 1,064 were male. The nutritional history and clinical presentation of female patients was different: they consumed less food and had a greater loss of appetite than the male population. Male patients had higher risk for mortality at 180 days (27% compared to 19%, adjusted HR 1.35 [95%CI 1.12, 1.63]) and further adverse clinical outcomes. However, there was no difference in the effect of nutritional support on mortality among female and male patients (HR 0.76 [95%CI 0.45, 1.27] compared to 0.81 [95%CI 0.54, 1.21]; p for interaction =0.939). CONCLUSION: Results of this multicenter randomized trial suggest that multimorbid female inpatients, have a different clinical presentation and are more prone to loss of appetite and reduced daily dietary intake compared to male inpatients. Importantly, the favorable response to nutritional interventions was similar in both sexes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02517476.

Presbyopia, Dry Eye, and Retinal Thickness in the Middle-Aged Population: Focusing on Sex Differences.

Purpose: Risk factors for presbyopia have not been fully determined although previous studies suggested presbyopia was associate with age, dry eye, and retinal ganglion cell complex thickness (GCC). We accessed these signs and common ocular symptoms in the middle-aged population focusing on sex differences when women have drastic hormonal change. Methods: This cohort study consecutively enrolled 2743 patients aged 36-45 years (n=1000), 46-55 years (n=1000), and 56-65 years (n=743). All underwent ocular surface tests and had near add power and GCC measured. Common ocular symptoms were asked using questionnaire. Results: Among female participants, visual symptoms (eye strain and photophobia) were more prevalent in the age group 46-55, whereas non-visual symptoms (dryness, irritation, and pain) were not. We identified symptomatic presbyopia (near add power ≥ 1.5D) in 14.4%, 73.8%, and 97.8%, positive corneal staining in 29.1%, 23.8%, and 23.9%, and a mean GCC of 98.2 µm, 105.3 µm, and 89.6 µm in the age groups 36-45, 46-55, and 56-65, respectively. Mean tear break-up time were 3.3, 3.5, and 3.3 seconds, respectively. Results indicated a large progression of presbyopia (P<0.01) from the period of 36-45 years onward and significantly increased GCC (P<0.01) in women of age group 46-55. No notable tendency was observed in symptoms and GCC for male participants. Conclusion: Visual symptoms in women were worse between 46 and 55 years than before or after these ages. The increase of symptomatic presbyopia and GCC may be contributing to visual symptoms in addition to menopausal transition symptoms in this age group.

Relationship Between Neurodevelopmental Areas and Difficulties in Emotional-Behavioural Variables in Children With Typical Development Under 2 Years of Age: Sex Differences.

The aim of this study was to examine the relationship between neurodevelopmental areas and possible difficulties in emotional-behavioural variables, and to determine if sex moderated this relationship. A community sample of 231 boys and girls with typical development and with a mean age of 19.84 months was evaluated, using the Bayley-III and CBCL 1.5-5 scales. The main results confirmed: (1) better linguistic abilities in girls in both language areas (receptive communication and expressive communication), finding more evidence according to the Bayesian analysis in expressive communication; (2) in the emotional-behavioural area girls had higher scores in withdrawal; (3) significant negative correlations of low magnitude were found between the Bayley and CBCL scales, particularly in the areas of language and cognitive and internalising and externalising problems; (4) children with low cognitive abilities and those with poor receptive communication showed more inter and externalising difficulties; (5) no significant predictive value or moderating effect of sex was found, (6) the number of participants who simultaneously manifested significant deficits in both domains (neurodevelopmental and emotional-behavioural) was very reduced. Future research should corroborate these results and the characteristics of the relationship found at these early ages. Detecting the population at risk in the first two years of life would enable the implementation of interventions aimed at improving neurodevelopmental deficits and emotional-behavioural problems. Thus, identification of deficits in one domain should lead to evaluation of the other.

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Introduction: Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. Materials and Methods: Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. Results: Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. Conclusions: This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.

Proteomic analysis reveals key differences in pro-stromal corneal tissue between highly myopic males and females.

Background and purpose: Nowadays, myopia has become a highly prevalent disease globally, especially in East Asia. Epidemiological studies have found that there may be sex differences in the occurrence and progression of myopia, with females having a higher incidence of myopia and higher risk of myopia progression. The purpose of this study was to explore the sex differences in myopic cornea using corneal stroma removed by small incision lenticule extraction (SMILE) surgery. Methods: The corneal stroma of females with high myopia (FH) and males with high myopia (MH) were subjected to proteomic assays. Proteomic-related data were statistically analyzed using software such as MaxQuan, KAAS, Proteome Discovery, etc. The total number of proteins in the cornea and the proteins specifically expressed in the two groups were counted, and the differentially expressed proteins in the two groups were identified by expression fold change >2 and p-value <0.05, and volcano plots were constructed, and functional enrichment analysis, subcellular organelle analysis, and molecular interaction were implemented. Results: Ten samples from each group were analyzed. Twenty-seven proteins were down-regulated and 27 proteins were up-regulated in the FH group, of which 23 proteins were up-regulated in the range of 2-10-fold and 4 proteins were up-regulated in the range of >10-fold. Comparative proteomic analysis of the cornea of male and female patients with high myopia revealed that the expression of corneal extracellular matrix and collagen I, III, V, and VIII-associated proteins were increased in the cornea of female patients, and the transforming growth factor-ß (TGF-ß)/Smad pathway was an important pathway obtained by functional analysis. Conclusion: Comparative proteomic analysis of cornea from male and female patients with high myopia revealed increased expression of proteins related to extracellular matrix and collagen I, III, V, and VIII in female patients, and the TGF-ß/Smad pathway was an important pathway obtained from the functional analysis, suggesting that extracellular matrix remodeling and collagen fiber synthesis may be more active in the cornea of female patients.

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.

Comparison of clinical, hormonal, pathological and treatment outcomes of ectopic Cushing's syndrome by sex: results of a multicenter study.

OBJECTIVE: To compare clinical and hormonal data, neuroendocrine neoplasia (NEN) localization, treatment, and survival outcomes in ectopic Cushing's syndrome (ECS) by sex. METHODS: Eleven experienced centers from our country participated in this retrospective study. The clinical and hormonal features, tumor imaging, pathological results, treatment modalities, and disease courses of the patients were evaluated. RESULTS: 28 female and 26 male patients with ECS were compared. The mean age at diagnosis, clinical characteristics, and hormonal evaluation results were similar. However, insulin-requiring diabetes mellitus (p = 0.04) and osteoporosis with fractures were more common in males (p = 0.03). While more patients with increased DHEA-S levels than the upper limit of normal were found to be higher in females, central hypothyroidism were higher in males (p = 0.02). At the diagnosis, 36 NENs (68% of females and 69% of males) were localized. Small cell lung carcinoma was higher in males (p = 0.02), and the frequency of other NENs was not different. Curative surgery was performed on 61% of females and 46% of males. Tumor size, Ki-67 labeling index, positive ACTH immunostaining, local lymph node and distant metastasis rates were similar in both sexes. In the follow-up, the tumor became visible in 7 of 10 females and 4 of 8 males after medical treatment and/or bilateral adrenalectomy. The remission rates (65% of females, 62% of males) and NEN-related death rates (14% of females, 30% of males) were similar. CONCLUSION: While ECS has a similar disease course in many aspects in males and females, hyperglycemia and osteoporosis are more severe in males.

Chronic nasal inflammation early in life induces transient and long-term dysbiosis of gut microbiota in mice.

The gut microbiota begins to colonize the host body following birth, develops during the suckling period and changes to the adult type after weaning. The early gut microbiota during the suckling period is thought to have profound effects on the host physiology throughout life but it is still unclear whether early dysbiosis is retained lifelong. Our previous study indicated that chronic nasal inflammation induces dysbiosis of gut microbiota in adult mice. In the present study, we addressed the question as to whether early exposure to chronic nasal inflammation induces dysbiosis, and if so, whether the dysbiosis is retained until adulthood and the sex differences in this effect. Male and female mice received repeated intranasal administration of lipopolysaccharide (LPS) or saline twice a week from P7 to P24 and were weaned at P24. The cecal contents were obtained for 16S rRNA analysis at 2 time points: at 4 weeks (wks), just after weaning, and at maturation to adulthood at 10 wks. The body weight did not differ between saline- and LPS-treated mice till around weaning, suggesting that the mothers' milk was given similarly to all mice. At 4 wks, the beta diversity was significantly different between saline- and LPS-treated male and female mice and the composition of the gut microbiota changed in LPS-treated mice. The abundance of phylum Bacteroidota tended to decrease and that of Firmicutes increased in LPS-treated male mice, while the abundance of Deferribacterota increased in LPS-treated female mice. At 10 wks, the beta diversity was not different between saline- and LPS-treated mice, but the abundance of family Lachnospiraceae significantly decreased in LPS-treated male and female mice by LEfSe analysis. Together, chronic nasal inflammation early in life caused transient and long-term dysbiosis of gut microbiota, which may contribute to the onset and progress of metabolic and neuropsychiatric disorders.

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.

Neonatal limited bedding and nesting experience may lead to a sex-dependent increase in panic-like defensive behaviours in adult mice.

In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO2 (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg-1 i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg-1 i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.

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.