Found Sex Differences Research Articles

Sex differences of fall-risk-increasing drugs in the middle-aged and elderly: a descriptive, cross-sectional study of FDA adverse event reporting system

It’s well known that sex is a risk factor for the occurrence of adverse events (AEs), most of which have found sex differences. Real-world data studies on the sex differences of fall-risk-increasing drugs (FRIDs) are few and far between, with most small-scale retrospective studies based on FRID classes. To establish a list of FRIDs and describe their sex differences, we used preferred terms from the Medical Dictionary for Regulatory Activities to search for AEs in the FDA Adverse Event Reporting System (FAERS), and then perform disproportionality analyses and female/male ratio analyses. During January 2004 to March 2023, 101,746 fall-related AEs were reported in FAERS from patients aged 50 to 100, with 68,492 (67.3%) females and 32,547 (32.0%) males. We found 261 signals for females while 284 for males. For females, the top 3 signals with the highest reporting odds ratio (ROR) were anethole trithione, clopenthixol, nikethamide (ROR: 388.88, 212.10, 113.94), while the top 3 signals with the highest lower limit of information component (IC025) were nikethamide, anethole trithione, benzbromarone (IC025: 3.91, 3.15, 2.49). For males, the top 3 signals with the highest ROR were fluprednidene acetate, potassium hydroxide, ketazolam (ROR: 216.86, 108.43, 108.43), while the top 3 signals with the highest IC025 were clomethiazole, piribedil, melperone (IC025: 3.31, 3.24, 2.99). Moreover, among the 119 shared signals found between males and females, 33 were positively correlated with falls in females and 38 with falls in males. Signals showing significant sex differences were mainly concentrated on agents of the immune, nervous, musculo-skeletal, and cardiovascular systems. We offered a series of FRIDs and suggested their sex differences in falls through the FAERS. In the future, it is essential to balance the inclusion of women and men, and analyse sex-stratified for FRIDs.

Sex-specific topological structure associated with dementia via latent space estimation.

We investigate sex-specific topological structures associated with typical Alzheimer's disease (AD) dementia using a novel state-of-the-art latent space estimation technique. This study applies a probabilistic approach for latent space estimation that extends current multiplex network modeling approaches and captures the higher-order dependence in functional connectomes by preserving transitivity and modularity structures. We find sex differences in network topology with females showing more default mode network (DMN)-centered hyperactivity and males showing more limbic system (LS)-centered hyperactivity, while both show DMN-centered hypoactivity. We find that centrality plays an important role in dementia-related dysfunction with stronger association between connectivity changes and regional centrality in females than in males. The study contributes to the current literature by providing a more comprehensive picture of dementia-related neurodegeneration linking centrality, network segregation, and DMN-centered changes in functional connectomes, and how these components of neurodegeneration differ between the sexes. We find evidence supporting the active role network topology plays in neurodegeneration with an imbalance between the excitatory and inhibitory mechanisms that can lead to whole-brain destabilization in dementia patients. We find sex-based differences in network topology with females showing more default mode network (DMN)-centered hyperactivity, males showing more limbic system (LS)-centered hyperactivity, while both show DMN-centered hypoactivity. We find that brain region centrality plays an important role in dementia-related dysfunction with a stronger association between connectivity changes and regional centrality in females than in males. Females, compared to males, tend to exhibit stronger dementia-related changes in regions that are the central actors of the brain networks. Taken together, this research uniquely contributes to the current literature by providing a more comprehensive picture of dementia-related neurodegeneration linking centrality, network segregation, and DMN-centered changes in functional connectomes, and how these components of neurodegeneration differ between the sexes.

Sex Differences in Colonoscopy Indications and Findings: Results from a Large Multicenter Database.

Background: Sex-based differences are common among diseases. We aimed to investigate the differences in colonoscopy indications and its findings between males and females. Methods: A large, multi-center, cross-sectional, retrospective study included all colonoscopies performed between 2016 and 2021 in seven endoscopy departments. The indications and findings of the procedures were compared between males and females. Results: A total of 151,411 (52.6%) women and 136,519 (47.4%) men were included, aged 56.54 ± 12.9 years and 56.59 ± 12.7. Cecal intubation was similar (95.6% vs 95.5%, p = 0.251). More females had excellent or good bowel preparation compared to males (71.4% vs 65.6%). Colonoscopy due to abdominal pain, constipation, diarrhea, and anemia was higher in females compared to males (15% vs 9.9%, 3.9% vs 2.2%, and 7.6% vs 4.9%, p < 0.001, respectively), while positive FOBT, rectal bleeding and post-polypectomy surveillance and screening were more common indications among males (9.5% vs 7.8%, 10.7% vs 7.8%, and 10.8% vs 7.1%, respectively). On colonoscopy, males were found to have significantly higher colorectal cancer and polyps (0.5% vs 0.4% and 35.1% vs 24.6%). Polyp detection rates were lower in females across all indications, whereas diverticulosis rates were higher in males. However, a clinically significant difference regarding diverticulosis was observed only in patients with anemia as the indication. Conclusions: Notable differences exist between males and females in terms of the indications and findings on colonoscopy. This highlights the need for identifying the factors contributing to these differences and the developing sex-specific approaches for the diagnosis and management of gastrointestinal diseases.

An Analysis of the Influence of a Patient's Sex on Quality of Life in Liver and Kidney Transplantation.

Renal and liver transplantation influences the quality of life of the patients who undergo these procedures. Therefore, the aim of the present study was to analyze possible differences in liver and kidney transplantation in relation to the patient's sex and to determine their impact on quality of life. An observational study was carried out with 147 patients with liver (n = 70) and kidney (n = 77) failure on the transplantation waiting list. The possible influence of sex on clinical, sociodemographic, and psychological aspects of the patients' quality of life before and 6 months after transplantation was analyzed. Questionnaires on health-related quality of life (SF-36), the perception of social and family support (EASP), and coping strategies (CEA), the depression and anxiety scale (HAD), and the Eysenck personality inventory (EPI) were used. A univariate analysis was performed according to sex using statistical tools including the Chi-square test, the t-test, and a univariate linear analysis of variance. In patients on the waiting list for liver transplantation, we found sex differences in terms of age (p = 0.040), time of evolution of end-stage liver disease (p = 0.013), etiology (p = 0.07), and associated complications, as well as in the consumption of tobacco and other psychotropic substances (p = 0.022), while patients on the waiting list for renal transplantation showed sex-related differences in terms of etiology (p = 0.012) and alcohol consumption (p = 0.005). The results showed significant sex-related differences in sociodemographic and psychological aspects, but no significant sex-related differences were observed in global quality of life in either of the two assessments in both groups. The findings suggest that improvement in quality of life after liver or kidney transplantation is not influenced by the patient's sex.

Physical exercise as a cognitive rehabilitation treatment after traumatic brain injury: Intensity- and sex-dependent effects

We investigated the effects of forced physical exercise (PE) intensity on cognitive dysfunction and histological changes associated with traumatic brain injury (TBI), in both male and female rats. Controlled cortical impact (CCI) produced similar short- and long-term memory deficits in both sexes, and these deficits were associated with reduced volume and neuronal loss in the hippocampus, but not with changes in neurogenesis. We found sex differences in the effects of intensity of forced PE on cognitive recovery: all PE intensities tested improved short-term memory in both sexes, but to a greater extent in females, while long-term memory benefits were intensity- and sex-dependent. Males benefited most from low-intensity PE, while females showed optimal results at moderate intensity. These optimal PE intensities increased the neurogenesis in both sexes. A neuroprotective effect of low-intensity PE was evident in males, but no effect was observed in females. These findings suggest an intensity- and sex-specific effect of PE post-TBI, emphasizing the need for tailored PE protocols based on sex to enhance therapeutic outcomes.

Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease

BackgroundSex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further.MethodsHere we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years.ResultsWe found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression.DiscussionIn our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.

Sex differences in physical functioning among older adults: cross-sectional results from the OUTDOOR ACTIVE study

BackgroundMaintaining good functional ability is a key component of healthy ageing and a basic requirement for carrying out activities of daily living, staying independent, and delaying admission to a nursing home. Even though women have a higher life expectancy and slower age-related muscle mass loss than men, they often show a higher prevalence of limitations in physical functioning. However, the reasons behind these sex differences are still unclear. Therefore, the aims of this study were to investigate sex differences among older adults regarding physical functioning and to study which factors are explaining these sex differences.MethodsCross-sectional data from participants of the OUTDOOR ACTIVE study residing in Bremen, Germany, aged 65 to 75 years, were included in the analyses. Physical functioning was assessed via a self-administered questionnaire using the SF-36 10-item Physical Functioning Scale. Social, lifestyle, and health-related factors were also assessed using the questionnaire. Physical activity was measured objectively using wrist-worn accelerometers over seven consecutive days. Descriptive analyses with absolute and relative frequencies, means and standard deviations, as well as T-tests and chi-square tests were carried out. To test for associations between sex, physical functioning, and several individual factors, linear regressions were performed.ResultsData of 2 141 participants (52.1% female) were included in the study. Women and men showed statistically significant differences in physical functioning, with men perceiving fewer limitations than women. On average, women had a physical functioning score of 81.4 ± 19.3 and men 86.7 ± 17.0. Linear regression showed a statistically significant negative association between physical functioning score and sex (β: -0.15, 95% CL: -0.19, -0.10). The association remained statistically significant when adding individual factors to the model. All factors together were only able to explain 51% of the physical functioning-sex association with health indicators and the presence of chronic diseases being the most influential factors.ConclusionsWe found sex differences in physical functioning, with older women having more limitations than older men. The results showed that health-related factors and chronic diseases played the biggest roles in the different physical functioning scores of women and men. These findings contribute to future longitudinal, more in-depth research.Trial registrationGerman Clinical Trials Register DRKS00015117 (Date of registration 17-07-2018).

Sex differences in chest electrical impedance tomography findings

Objective. Electrical impedance tomography (EIT) has been used to determine regional lung ventilation distribution in humans for decades, however, the effect of biological sex on the findings has hardly ever been examined. The aim of our study was to determine if the spatial distribution of ventilation assessed by EIT during quiet breathing was influenced by biological sex. Approach. 219 adults with no known acute or chronic lung disease were examined in sitting position with the EIT electrodes placed around the lower chest (6th intercostal space). EIT data were recorded at 33 images/s during quiet breathing for 60 s. Regional tidal impedance variation was calculated in all EIT image pixels and the spatial distribution of the values was determined using the established EIT measures of centre of ventilation in ventrodorsal (CoVvd) and right-to-left direction (CoVrl), the dorsal and right fraction of ventilation, and ventilation defect score. Main results. After exclusion of one subject due to insufficient electrode contact, 218 data sets were analysed (120 men, 98 women) (age: 53 ± 18 vs 50 ± 16 yr (p = 0.2607), body mass index: 26.4 ± 4.0 vs 26.4 ± 6.6 kg m−2 (p = 0.9158), mean ± SD). Highly significant differences in ventilation distribution were identified between men and women between the right and left chest sides (CoVrl: 47.0 ± 2.9 vs 48.8 ± 3.3% of chest diameter (p < 0.0001), right fraction of ventilation: 0.573 ± 0.067 vs 0.539 ± 0.071 (p = 0.0004)) and less significant in the ventrodorsal direction (CoVvd: 55.6 ± 4.2 vs 54.5 ± 3.6% of chest diameter (p = 0.0364), dorsal fraction of ventilation: 0.650 ± 0.121 vs 0.625 ± 0.104 (p = 0.1155)). Ventilation defect score higher than one was found in 42.5% of men but only in 16.6% of women. Significance. Biological sex needs to be considered when EIT findings acquired in upright subjects in a rather caudal examination plane are interpreted. Sex differences in chest anatomy and thoracoabdominal mechanics may explain the results.

Hypothalamic-Pituitary-Adrenal Axis Dysfunction Elevates SUDEP Risk in a Sex-Specific Manner.

Epilepsy is often comorbid with psychiatric illnesses, including anxiety and depression. Despite the high incidence of psychiatric comorbidities in people with epilepsy, few studies address the underlying mechanisms. Stress can trigger epilepsy and depression. Evidence from human and animal studies supports that hypothalamic-pituitary-adrenal (HPA) axis dysfunction may contribute to both disorders and their comorbidity ( Kanner, 2003). Here, we investigate if HPA axis dysfunction may influence epilepsy outcomes and psychiatric comorbidities. We generated a novel mouse model (Kcc2/Crh KO mice) lacking the K+/Cl- cotransporter, KCC2, in corticotropin-releasing hormone (CRH) neurons, which exhibit stress- and seizure-induced HPA axis hyperactivation ( Melon et al., 2018). We used the Kcc2/Crh KO mice to examine the impact on epilepsy outcomes, including seizure frequency/burden, comorbid behavioral deficits, and sudden unexpected death in epilepsy (SUDEP) risk. We found sex differences in HPA axis dysfunction's effect on chronically epileptic KCC2/Crh KO mice seizure burden, vulnerability to comorbid behavioral deficits, and SUDEP. Suppressing HPA axis hyperexcitability in this model using pharmacological or chemogenetic approaches decreased SUDEP incidence, suggesting that HPA axis dysfunction may contribute to SUDEP. Altered neuroendocrine markers were present in SUDEP cases compared with people with epilepsy or individuals without epilepsy. Together, these findings implicate HPA axis dysfunction in the pathophysiological mechanisms contributing to psychiatric comorbidities in epilepsy and SUDEP.

Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast-Scan Cyclic Voltammetry: Effects of Social Housing and Repeated Stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation-induced (ES; 60 Hz) DA release was recorded in the NAc of single- or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than that in males. Finally, DA release following ES of the medial forebrain bundle at 60 Hz was studied over 4 weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, and sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.

Exploring the correlation and synchronicity between environmental factors and occupant thermal response in dynamic outdoor cabin environments

To improve the cabin thermal environment and explore advanced automotive air-conditioning control methods, it is essential to understand the key factors affecting occupant thermal response as well as the synchronicity of the thermal response to environmental changes in outdoor conditions. Given the current gaps in research, this study conducted outdoor experiments in summer to analyze the correlation and synchronicity between the cabin thermal environment and occupant thermal sensation as well as facial skin temperature. Results showed that, during the cooling phases of experiments with high initial cabin air temperatures, occupant thermal sensation improved significantly within 7 min. After 15 min, facial skin temperature and thermal sensation reached quasi-steady states. Thermal sensation was primarily influenced by air temperature, followed by solar radiation, and exhibited significant synchronicity with changes in these factors. When the air temperature stabilized at around 26 °C, every 200 W/m2 of solar radiation exposure increased the thermal sensation unit during the 40-min experiment period. Cheek and nose skin temperatures were significantly correlated with air temperature and solar radiation, and were sensitive to environmental changes, synchronizing with changes in air temperature and relative humidity. Further analysis showed the feasibility of using cheek and nose skin temperatures to characterize the occupant thermal sensation in a cabin. Additionally, this study found sex differences in the occupant thermal response in a cabin. The results provide insight into the key optimization parameters for comfort-oriented cabin thermal environment design and offer support for future air conditioning control in cabins based on thermal imaging.

Nut-cracking success and efficiency in two wild capuchin monkey populations.

Capuchins can employ several strategies to deal with environmental challenges, such as using stone tools to access encapsulated resources. Nut-cracking is customary in several capuchin populations and can be affected by ecological and cultural factors; however, data on success and efficiency are only known for two wild populations. In this work, using camera traps, we assessed palm nut-cracking success and efficiency in two newly studied wild bearded capuchin populations (Sapajus libidinosus) and compared them with other sites. We tested the hypothesis that the overall success and efficiency of nut-cracking would be similar between sites when processing similar resources, finding partial support for it. Although using hammerstones of different sizes, capuchins had a similar success frequency. However, efficiency (number of strikes to crack a nut) was different, with one population being more efficient. We also tested whether success and efficiency varied between sexes in adults. We predict adult males would be more successful and efficient when cracking hard nuts. We found no differences between the sexes in one site but found sex differences in the other, although also for the low-resistant nut, which was unexpected. Our data add to the knowledge of capuchin nut-cracking behaviour flexibility, variance and potential cultural traits.

Sex differences in the structure and function of the vasopressin system in the ventral pallidum are associated with the sex-specific regulation of social play behavior in juvenile rats

Vasopressin (AVP) regulates various social behaviors, often in sex-specific ways, including social play behavior, a rewarding behavior displayed primarily by juveniles. Here, we examined whether and how AVP acting in the brain's reward system regulates social play behavior in juvenile rats. Specifically, we focused on AVP signaling in the ventral pallidum (VP), a brain region that is a part of the reward system. First, we examined the organization of the VP-AVP system in juvenile rats and found sex differences, with higher density of both AVP-immunoreactive fibers and AVP V1a receptor (V1aR) binding in males compared to females while females show a greater number of V1aR-expressing cells compared to males. We further found that, in both sexes, V1aR-expressing cells co-express a GABA marker to a much greater extent (approx. 10 times) than a marker for glutamate. Next, we examined the functional involvement of V1aR-expressing VP cells in social play behavior. We found that exposure to social play enhanced the proportion of activated V1aR-expressing VP cells in males only. Finally, we showed that infusion of a specific V1aR antagonist into the VP increased social play behaviors in juvenile male rats while decreasing these behaviors in juvenile female rats. Overall, these findings reveal structural and functional sex differences in the AVP-V1aR system in the VP that are associated with the sex-specific regulation of social play behavior.

Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens.

Circadian rhythms are critical for human health and are highly conserved across species. Disruptions in these rhythms contribute to many diseases, including psychiatric disorders. Previous results suggest that circadian genes modulate behavior through specific cell types in the nucleus accumbens (NAc), particularly dopamine D1-expressing medium spiny neurons (MSNs). However, diurnal rhythms in transcript expression have not been investigated in NAc MSNs. In this study we identified and characterized rhythmic transcripts in D1- and D2-expressing neurons and compared rhythmicity results to homogenate as well as astrocyte samples taken from the NAc of male and female mice. We find that all cell types have transcripts with diurnal rhythms and that top rhythmic transcripts are largely core clock genes, which peak at approximately the same time of day in each cell type and sex. While clock-controlled rhythmic transcripts are enriched for protein regulation pathways across cell type, cell signaling and signal transduction related processes are most commonly enriched in MSNs. In contrast to core clock genes, these clock-controlled rhythmic transcripts tend to reach their peak in expression about 2-h later in females than males, suggesting diurnal rhythms in reward may be delayed in females. We also find sex differences in pathway enrichment for rhythmic transcripts peaking at different times of day. Protein folding and immune responses are enriched in transcripts that peak in the dark phase, while metabolic processes are primarily enriched in transcripts that peak in the light phase. Importantly, we also find that several classic markers used to categorize MSNs are rhythmic in the NAc. This is critical since the use of rhythmic markers could lead to over- or under-enrichment of targeted cell types depending on the time at which they are sampled. This study greatly expands our knowledge of how individual cell types contribute to rhythms in the NAc.

Chronic variable stress leads to sex specific gut microbiome alterations in mice

Stress has been implicated in the incidence and severity of psychiatric and gastrointestinal disorders. The immune system is capable of modulating the activity and composition of the gut following stress and vice versa. In this study we sought to examine the sequential relationship between immune signaling and microbiome composition occurring in male and female mice over time using a variable stress paradigm. Tissue was collected prior to, during, and after the stress paradigm from the same mice. Cytokines from plasma and brain were quantified using a multiplexed cytokine assay. Fecal samples were collected at the same timepoints and 16S rRNA amplicon sequencing was performed to determine the relative abundance of microbiota residing in the guts of stressed and control mice. We found sex differences in the response of the gut microbiota to stress following 28 days of chronic variable stress but not 6 days of sub-chronic variable stress. Immune activation was quantified in the nucleus accumbens immediately following Sub-chronic variable when alterations of gut composition had not yet occurred. In both sexes, 28 days of stress induced significant changes in the proportion of Erysipelotrichaceae and Lactobacillaceae, but in opposite directions for male and female mice. Alterations to the gut microbiome in both sexes were associated with changes in cytokines related to eosinophilic immune activity. Our use of an animal stress model reveals the immune mechanisms that may underly changes in gut microbiome composition during and after stress. This study reveals potential drug targets and microbiota of interest for the intervention of stress related conditions.

Sexual dimorphism and ecomorphology of the Berthold’s bush anole (Polychrus gutturosus) in Costa Rica

Abstract Morphological variation present within a species is the result of sexual or natural selection and determines the ecological relationships (i.e., ecomorphology) and the degree of sexual dimorphism. For most lizard species, either males or females are the larger sex, suggesting that selection operates differently on each sex. Thus, differences in morphology can determine the habitat use made by males and females. Here we use the Berthold’s bush anole (Polychrus gutturosus), a rare arboreal, diurnal lizard, to examine whether morphological and ecological measures differ among sexes and whether such potential differences emerge as a result of resource partitioning. We measured the morphology of wild individuals from one population and from preserved specimens collected in Costa Rica. We collected data on nine morphological measurements, nocturnal body and air temperatures, and sleeping perch height. We measured 45 wild individuals (22 males and 23 females) and 17 preserved specimens (6 males and 11 females). We found a female-biased body size, and male-biased tail length, head dimensions, and limb lengths. We also observed differences between males and females in body color and the size and shape of femoral pores, although these differences require quantification. We did not find sex differences in sleeping perch height or nocturnal body temperature. Our results demonstrate that resource partitioning does not explain differences among sexes, and that female-biased body size in P. gutturosus might reflect selection operating on increased fecundity.

Sex Differences in Alterations of Brain Functional Network in Tobacco Use Disorder.

Many studies have found sex differences in alterations of brain function in cigarette-smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette-smoking men and women from three perspectives: nodal and network efficiency and modular connections. Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed, and a two-way analysis of covariance with false discovery rate correction (q < 0.05) was performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular, and nodal levels. Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower intermodular connections between the visual and executive control and between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular, and nodal levels, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.

Pancreas agenesis and fetal growth: a semi-quantitative analysis.

Pancreas agenesis is a rare condition underlying a variant of permanent neonatal diabetes mellitus. Neonates with this condition are born small for gestational age, but less is known about which components of growth are impacted, the timing of the growth restriction and potential sex differences. Our objective was to assess in which periods in gestation complete pancreas agenesis restricts fetal growth and possible sex differences in susceptibility. Published cases (n=49) with pancreas agenesis providing relevant data (gestational age, fetal sex, birth weight, birth length, head circumference, placental weight) were identified by MEDLINE and secondary literature search covering the years 1950-January 2023. Semi-quantitative analysis of these case reports used centiles based on Intergrowth-21 reference charts. Neonates with pancreas agenesis were severely growth restricted, however, median centiles for birth weight, length and head circumference of those born before week 36 were significantly higher compared to those born from 36 weeks. Similar results were found when data were separated by before and from 38 weeks. Head circumference was less affected than birth weight or length. No sex differences were found. In conclusion, pancreas agenesis severely restricts fetal length and head circumference in addition to weight growth, with stronger effects evident from 36 weeks of gestation. In addition to the well-known effects of insulin on growth of fetal fat mass, the pronounced effect on birth length and head circumference indicates effects of insulin on fetal lean body growth as well. Lack of power may account for failure to find sex differences.

Psychosocial Factors Associated with dizziness and chronic dizziness: a nationwide cross-sectional study.

Dizziness is a common symptom in adults, and chronic dizziness, such as persistent postural-perceptual dizziness, is also frequently reported and affects the quality of life of patients. This study aimed to identify psychosocial factors related to dizziness and chronic dizziness in a large-scale nationwide cohort. This population-based cross-sectional study used the database of the Eighth Korea National Health and Nutrition Examination Survey in 2020. Data from 4,147 adults over 40 years old were analyzed, and 1,102 adults who experienced dizziness were included in the dizziness cohort. Demographic data, medical conditions, comorbidities, functional status variables, nutritional variables and psychological variables were collected. The pattern of depressive symptoms according to the severity of dizziness was analyzed by network analysis. The prevalence rate of dizziness was 24.6% in the general population, and chronic dizziness (≥ 3 months) developed in 210 of 1,102 (17.1%) individuals who experienced dizziness. Multiple logistic regression analysis revealed that female sex, stress, and depression were associated with dizziness. Chronic dizziness was related to tympanic abnormalities, diabetes, short sleep duration, and higher levels of stress and depression. Psychomotor retardation/agitation was a central symptom of depression in patients with chronic dizziness. This study found sex differences in factors associated with dizziness and identified psychosocial factors linked to chronic dizziness. Focusing on somatic factors rather than depressive symptoms may benefit patients with chronic dizziness.

Brain growth until adolescence after a neonatal focal injury: sex related differences beyond lesion effect.

Early focal brain injuries lead to long-term disabilities with frequent cognitive impairments, suggesting global dysfunction beyond the lesion. While plasticity of the immature brain promotes better learning, outcome variability across individuals is multifactorial. Males are more vulnerable to early injuries and neurodevelopmental disorders than females, but long-term sex differences in brain growth after an early focal lesion have not been described yet. With this MRI longitudinal morphometry study of brain development after a Neonatal Arterial Ischemic Stroke (NAIS), we searched for differences between males and females in the trajectories of ipsi- and contralesional gray matter growth in childhood and adolescence, while accounting for lesion characteristics. We relied on a longitudinal cohort (AVCnn) of patients with unilateral NAIS who underwent clinical and MRI assessments at ages 7 and 16 were compared to age-matched controls. Non-lesioned volumes of gray matter (hemispheres, lobes, regions, deep structures, cerebellum) were extracted from segmented T1 MRI images at 7 (Patients: 23 M, 16 F; Controls: 17 M, 18 F) and 16 (Patients: 18 M, 11 F; Controls: 16 M, 15 F). These volumes were analyzed using a Linear Mixed Model accounting for age, sex, and lesion characteristics. Whole hemisphere volumes were reduced at both ages in patients compared to controls (gray matter volume: -16% in males, -10% in females). In ipsilesional hemisphere, cortical gray matter and thalamic volume losses (average -13%) mostly depended on lesion severity, suggesting diaschisis, with minimal effect of patient sex. In the contralesional hemisphere however, we consistently found sex differences in gray matter volumes, as only male volumes were smaller than in male controls (average -7.5%), mostly in territories mirroring the contralateral lesion. Females did not significantly deviate from the typical trajectories of female controls. Similar sex differences were found in both cerebellar hemispheres. These results suggest sex-dependent growth trajectories after an early brain lesion with a contralesional growth deficit in males only. The similarity of patterns at ages 7 and 16 suggests that puberty has little effect on these trajectories, and that most of the deviation in males occurs in early childhood, in line with the well-described perinatal vulnerability of the male brain, and with no compensation thereafter.