Hepatitis C virus infection and Parkinson's disease: insights from a joint sex-stratified BioOptimatics meta-analysis.

Hepatitis C virus (HCV) infection poses a significant public health challenge and often leads to long-term health complications and even death. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a proposed viral etiology. HCV infection and PD have been previously suggested to be related. This work aimed to identify potential biomarkers and pathways that may play a role in the joint development of PD and HCV infection. Using BioOptimatics-bioinformatics driven by mathematical global optimization-, 22 publicly available microarray and RNAseq datasets for both diseases were analyzed, focusing on sex-specific differences. Our results revealed that 19 genes, including MT1H, MYOM2, and RPL18, exhibited significant changes in expression in both diseases. Pathway and network analyses stratified by sex indicated that these gene expression changes were enriched in processes related to immune response regulation in females and immune cell activation in males. These findings suggest a potential link between HCV infection and PD, highlighting the importance of further investigation into the underlying mechanisms and potential therapeutic targets involved.

A parallel investigation of trauma exposure, maladaptive appraisals and posttraumatic stress reactions in two groups of trauma-exposed adolescents.

Background: Maladaptive appraisals, such as thoughts about experiencing a permanent and disturbing change and about being a fragile person in a scary world, are associated with posttraumatic stress reactions (PTSR) for trauma-exposed children and adolescents. Less is known about what puts young people at risk for developing such appraisals, and the differential relationship between the types of appraisals and PTSR.Objective: The primary aim was to examine the role of age, gender and exposure to potentially traumatizing events (PTEs) for the levels of maladaptive appraisals. The secondary aim was to investigate the association between the levels of maladaptive appraisals (appraisals of a permanent change and appraisals about a scary world) and PTSR.Methods: We investigated these aims in two samples: survivors after the terror attack at Utøya island in Norway in 2011 (N = 165, mean age 17.65, SD = 1.19) and adolescents referred to treatment after mainly interpersonal trauma (N = 152, mean age 15.08, SD = 2.18). The aims were investigated using linear regression and partial correlation.Results: In the terror-exposed sample, female gender was significantly associated with higher levels of scary-world appraisals, witnessing or learning that someone close were exposed to physical violence was significantly associated with more permanent-change appraisals, and a higher number of PTEs was significantly associated with higher levels of both types of appraisals. For the clinical sample, we found no significant associations between exposure to PTEs, gender, age, and the level of maladaptive appraisals. Both types of maladaptive appraisals were highly associated with PTSR in both samples, and there was no significant difference in the strength of the associations between the types of appraisals and PTSR.Conclusions: The results have implications for identifying adolescents at risk for developing harmful maladaptive appraisals. Both scary-world appraisals and permanent-change appraisals were strongly associated with PTSR in both groups of trauma-exposed adolescents.

Factors associated with elevated levels of maladaptive appraisals, and associations between maladaptive appraisals and posttraumatic stress reactions were investigated in two samples of trauma-exposed adolescents.Both appraisals about experiencing a permanent and disturbing change and appraisals about being a fragile person in a scary world were significantly associated with posttraumatic stress reactions.Exposure to a higher number of potentially traumatizing events (PTEs), being female, and witnessing or learning that someone close was exposed to physical violence were significantly associated with a higher level of maladaptive appraisals among terror-exposed adolescents.

Facial soft tissue characteristics of patients with different types of malocclusion.

BACKGROUND: This study aimed to investigate the facial soft tissue characteristics of patients with different types of malocclusion. METHODS: The 3dMD scanning data of patients with malocclusion admitted to our hospital from January 2018 to April 2022 were analyzed retrospectively. Forty-seven patients with Class I malocclusion, 43 patients with Class II malocclusion and 44 patients with Class III malocclusion were selected. All patients underwent 3dMD scans prior to orthodontic treatment. Then the differences in the 3D morphological parameters of the facial soft tissues were compared between different sexes and different types of malocclusion. Spearman's correlation was further used to analyze the correlation between each parameter and the classification of malocclusion. RESULTS: In the Class I group and Class II group, there were no significant differences in the 3D morphometric parameters of malocclusion patients of different sexes (P > 0.05). There were significant differences between Al (R)-AL (L), Ac (R)-Ac (L), Prn-Ac (L), n-Prn-Sn, and Al (R)-Al (L)/Ac (L)-Ah (L) values among the three groups of patients. Spearman correlation analysis showed that Ac (R)-Ac (L) and Al (R)-Al (L)/Ac (R)-Ac (L) were correlated with the type of malocclusion. CONCLUSION: Differences in facial soft tissues exist in patients with Class I, II, and III malocclusion. 3dMD technique may be helpful in developing an effective treatment plan prior to orthodontic treatment.

Mandibular morphology in schizophrenia patients compared with non-psychiatric controls using digital panoramic radiography: a retrospective cross-sectional study from Istanbul, Türkiye.

BACKGROUND: Schizophrenia is a chronic severe mental disorder characterized by impairment in cognition, emotion, perception, and other aspects of behavior. In light of the association of craniofacial dysmorphology with schizophrenia, mandibular morphology may provide clues about the role of neurodevelopment in the pathophysiology of schizophrenia. This retrospective cross-sectional study aimed to compare the mandibular morphology of patients with schizophrenia with controls using digital panoramic radiography (DPR). METHODS: 302 recorded diagnostic panoramic images obtained from 143 schizophrenia patients (98 males, 45 females), and 159 controls (73 males, 86 females), aged 18-45 years, were evaluated. Seven mandibular measurements consisting of ramus height, condylar height, gonial angle, antegonial angle, antegonial notch depth, ramal notch depth and bigonial width were measured from the DPRs in a double-blinded manner. Bivariate comparisons were carried out using the Independent t-test and Mann-Whitney U test. Logistic regression analysis was used for multivariate comparisons. RESULTS: Linear measurements were higher while angular measurements were lower in schizophrenia patients. Regression analyses indicated that female patients had greater ramus height (OR = 1.243; P = 0.001), condylar height (OR = 1.463; P = 0.048) and bigonial width (OR = 1.082; P < 0.001); male patients had greater ramus heights (OR = 1.216; P = 0.001) and bigonial width (OR = 1.076; P < 0.001) as well as lower antegonial angle (OR = 0.908; P = 0.012) compared to their respective controls. CONCLUSION: Quantitative differences in mandibular morphology in schizophrenia patients versus controls deserve attention and corroborate with the concept of abnormal neurodevelopment in schizophrenia.

Exploring the association between consultation themes and suicidal ideation: a gender-stratified analysis of Hangzhou Mental Health Hotline (2014-2023).

BACKGROUND: Suicide is a critical global public health issue that demands a better understanding of its complex causes and effective interventions. This study examines data from the Hangzhou Mental Health Hotline (2014-2023) to explore the relationship between consultation themes and suicidal ideation, with an emphasis on gender differences and how these associations changed during different phases of the COVID-19 pandemic. METHODS: This retrospective analysis covers 128,245 calls to the hotline over a decade. Chi-square tests identified differences in suicidal ideation across consultation themes and demographics. Multivariate logistic regression models were used to examine the relationship between specific themes and suicidal ideation, adjusting for confounders. The analysis was stratified by gender and pandemic phases to assess the interaction between gender and pandemic-related changes. RESULTS: The incidence of suicidal ideation was highest during the mid-pandemic phase (11.95%), compared to the pre-pandemic (7.68%) and post-pandemic phases (10.66%). Additionally, the rate was slightly higher among female callers (9.8%) than male callers (9.4%). Physical illness (OR = 4.70, 95% CI: 3.71-5.91) had the strongest association with suicidal ideation, followed by mental health issues (OR = 3.35, 95% CI: 3.03-3.70). Compared to male callers, female callers were more significantly affected by physical illness (OR = 6.86 vs. OR = 3.71, p < 0.001) and mental health issues (OR = 6.81 vs. OR = 2.11, p < 0.001). In the context of romantic relationship problems, female callers had a higher likelihood of suicidal ideation (OR = 4.13 vs. OR = 1.88, p < 0.001). Similarly, marital and family issues were more strongly associated with suicidal ideation in female callers (OR = 4.58 vs. OR = 1.21, p < 0.001). During the global COVID-19 pandemic, the association between suicidal ideation and consultation themes among male callers showed a sharp upward trend, which eased after the pandemic. In contrast, the association among female callers gradually accumulated and continued to worsen in the later stages of the pandemic. CONCLUSION: This study highlights the necessity of implementing gender-sensitive mental health interventions tailored to different gender groups during and after global crises such as the COVID-19 pandemic, to safeguard public mental health effectively.

Comparison of Causes of Mortality Between Hospitalized Unsheltered Homeless Patients and Non-Homeless Sex and Age-Matched Controls: A Retrospective Case-Control Study.

Objectives: Roofless individuals represent the most severe category of homelessness. Their clinical characteristics and mortality patterns in Central and Eastern Europe are little known. Methods: A single-center retrospective case-control study at the internal medicine department in Bratislava, Slovakia was conducted. 5694 mortality records from 2010 to 2023 were screened, and 141 (118 men, 23 women) roofless individuals were identified. Patients were sex- and age-matched, with 141 patients from the cohort of non-homeless deceased patients. Results: Compared to controls, roofless people had a higher incidence of immobility (p = 0.02) and hypothermia (p < 0.0001) at admission. 83% of the roofless people were men, and 59% of the roofless people died before reaching old age (60+). Homeless men died more often from infectious disease (p = 0.02), pneumonia being the most common one (60%). Men from the control group died more often from liver diseases (p = 0.03). There were no significant differences in the causes of mortality between women. Conclusion: These findings could help to reduce the invisibility of the issue of massive premature mortality amongst homeless populations and roofless individuals, in particular.

Predicting primal weight and primal yield in pork carcasses from a large-scale survey at major meat processing centers in Japan.

Pork primal weight and primal yield are important indicators for pig breeding, feeding management, commercial distribution systems, and meat processing. Here, we aimed to determine whether primal weight and primal yield could be predicted through non-destructive measurements of pork carcass traits. A total of 4397 carcasses (1958 gilts and 2439 barrows) from eight major meat processing centers were used, and the mean primal weight and primal yield were 56.0 kg and 73.9%, respectively. Significant sex differences were observed for all primal and carcass traits (P < 0.001), except for carcass weight. A maximum of 12 variables were examined, and primal weight was predicted with very high accuracy (R = 0.95, RMSE = 1.7, RPD = 3.0) using four variables. Primal yield was predicted with relatively good accuracy (R = 0.71, RMSE = 2.3, RPD = 1.4) using three variables, and these same variables were also effective for predicting primal weight. These prediction formulas were sufficiently accurate without accounting for the effect of sex. Overall, our results demonstrate that primal weight and primal yield can be accurately predicted using four variables, "carcass weight," "backfat thickness above M. gluteus medius," "spinous process length of 13th thoracic vertebra," and "length from 1st thoracic vertebra to backfat," without accounting for the effect of sex.

Sex Differences in Allergic Bronchopulmonary Aspergillosis and its Impact on Exacerbations.

The impact of sex on allergic bronchopulmonary aspergillosis (ABPA) outcomes remains uncertain. We retrospectively included ABPA subjects per the revised International Society for Human and Animal Mycology ABPA working group criteria over 13 years. We compared the clinical features, lung function, immunological tests, imaging, and ABPA exacerbation rates between men and women. Our primary objective was to assess whether women experience higher ABPA exacerbations than men. We included 731 ABPA subjects (mean age, 34.5 years; 49.5% women). Women with ABPA were older and had underlying asthma more frequently than men. There was no difference in lung function, immunological investigations, and imaging between men and women. ABPA exacerbations occurred in a slightly higher proportion of women than men (44.5% vs. 38.2%) but did not reach statistical significance (p = 0.09). We did not find a significant sex difference in ABPA exacerbation rates. Prospective studies should confirm our findings.

Prevalence and gender - specific analysis of a systemic sclerosis cohort in Latvia.

BACKGROUND: Systemic sclerosis (SSc) is considered by many to be one of the most severe autoimmune rheumatic diseases with lower prevalence observed in Northern Europe. No previous studies on the prevalence of SSc in Latvia have been conducted and the aim was to study the demographic and clinical data of patients with SSc in northeastern Europe country. METHODS: This study was conducted in two main Latvian hospitals for adults and includes patients with SSc who were consulted between 2016 and 2021. RESULTS: During the study period, 159 patients with SSc were consulted. The point prevalence on 1 January 2021 was 84.0 per million. Female to male ratio was 4.67:1, and highest gender ratio was observed in the age group 70-79-year (6.75:1). Antinuclear antibodies were present in 82.58% of patients, without gender difference. Centromere pattern was more frequently observed in females (40.19% vs. 19.04%), in contrast to speckled pattern (50.98% vs. 57.14%). At disease onset females tended to be younger (46.51 ± 13.52) than males (50.5 ± 16.64). Males had more diffuse cutaneous subtype, interstitial lung disease, pulmonary hypertension and esophageal dysmotility. More than half of patients received treatment with glucocorticoids at any point of the disease (68.31%), without gender difference. CONCLUSIONS: Systemic sclerosis is less common in Latvia than in other countries and regions. Due to its location, the data from Latvia are consistent with a north-south gradient in Europe. Gender ratio differences persisted in older age groups as well. Antinuclear antibodies presence did not differ between genders, but in female's centromere pattern was much more likely to be present. Males had more severe disease course, but in both genders more than half of patients received treatment with GCs at any point of the disease.

Plasma Biomarkers of Alzheimer's Disease and Neurodegeneration According to Sociodemographic Characteristics and Chronic Health Conditions.

Ultrasensitive assays have been developed which enable biomarkers of Alzheimer's disease pathology and neurodegeneration to be measured in blood. These biomarkers can aid in diagnosis, and have been used to predict risk of cognitive decline and Alzheimer's disease. The ease and cost-effectiveness of blood collections means that these biomarkers could be applied more broadly in population-based screening, however it is critical to first understand what other factors could affect blood biomarker levels. The aim of this review was to determine the extent that sociodemographic, lifestyle and health factors have been associated with blood biomarkers of Alzheimer's disease and neuropathology. Of the 32 studies included in this review, all but one measured biomarker levels in plasma, and age and sex were the most commonly investigated factors. The most consistent significant findings were a positive association between age and neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), and females had higher GFAP than men. Apolipoprotein ε4 allele carriers had lower Aß42 and Aß42/40 ratio. Body mass index was negatively associated with GFAP and NfL, and chronic kidney disease with higher levels of all biomarkers. Too few studies have investigated other chronic health conditions and this requires further investigation. Given the potential for plasma biomarkers to enhance Alzheimer's disease diagnosis in primary care, it is important to understand how to interpret the biomarkers in light of factors that physiologically impact blood biomarker levels. This information will be critical for the establishment of reference ranges and thus the correct interpretation of these biomarkers in clinical screening.

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.

Gender-specific correlations between remnant cholesterol and severe abdominal aortic calcification in American adults.

Background: Remnant cholesterol (RC) predicts cardiovascular risk and is associated with a range of diseases, including asthma, hypertension, depression, periodontitis, and alcoholic fatty liver disease. However, its correlation with abdominal aortic calcification (AAC) has not been reported. Methods: Using a cross-sectional approach, this study examined data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cycle. Multiple logistic regression, generalized summation models, and subgroup analyses were used in examining the correlation between RC and the prevalence of severe AAC. Results: The mean age of participants in this study was 57.70 ± 11.73 years, with 142 individuals (9.67%) suffering from severe AAC. The median RC was 0.52 mmol/L (Q1-Q3, 0.36-0.75 mmol/L). Among female participants, a significant positive correlation was observed between RC and severe AAC (per natural log [RC] increment: 2.14; 95% CI, 1.07-4.27). Smooth curve fitting and threshold effect analysis revealed a saturation effect at an RC level of 0.57 mmol/L. Conversely, in male participants, no significant correlation was found between RC and the prevalence of severe AAC (per natural log [RC] increment: 0.88; 95% CI, 0.43-1.78). Our findings suggest a significant interaction between gender and RC in relation to severe AAC (P for interaction = 0.0042). Conclusions: Higher RC levels were significantly associated with an increased prevalence of severe AAC in women.

Epidemiology of Alcohol-Associated Liver Disease Including Increasing Burden in Young Adults and Females Especially Since Covid-19 Pandemic.

Alcohol-associated liver disease (ALD) was already on the rise globally when the advent of coronavirus disease 2019 further accelerated this trend. ALD has emerged as the leading cause for liver transplantation in the United States. The pandemic has not only intensified the prevalence of ALD but has also highlighted significant disparities in its impact, particularly, among young adults and women. This review aims to dissect the complex landscape of ALD, focusing on gender, race, and emerging risk factors in the context of the current global health crisis.

Serosurvey and associated risk factors for bovine viral diarrhea virus infection in cattle in Egypt.

Bovine viral diarrhea virus (BVDV), is widely spread, poses a considerable risk of infection in the majority of dairy farms, causing respiratory, gastrointestinal, and reproductive problems. The aim of this study was to determine the seroprevalence and the risk variables associated with the seroprevalence of BVDV infection in cattle in four Egyptian governorates. A total of 680 blood samples were collected from cattle and examined for the presence of antibodies against BVDV using indirect ELISA (iELISA). Reproductive and management factors were considered, and epidemiological surveys were conducted. The total seroprevalence of BVDV in cattle was 18.24% (124/680) and it was significantly higher in females 19.66% (116/590), cattle older than 8 years 22.14% (62/280), dairy animals 22.65% (94/514), introduction of new animals to herd 21.39% (89/416), breeding with artificial insemination 28.46% (74/260), animals with history of abortion 28.76% (49/357), or during lactation stage 23% (89/387). The present findings suggest that BVD is prevalent in Egyptian dairy cattle and has an impact on farm productivity and production. Therefore, older, lactating, and aborted animals should also be identified for the disease, pose a risk of infection, and be handled appropriately.

Davunetide sex-dependently boosts memory in prodromal Alzheimer's disease.

BACKGROUND: The tauopathy inhibitor, davunetide shows sex-dependent efficacy in women suffering from progressive supranuclear palsy. Extending these findings to prodromal Alzheimer's disease, we submitted a double-blind, placebo-controlled, 12 weeks/16 weeks follow-up, davunetide clinical trial results in amnestic mild cognitive impairment (ClinicalTrials.gov ID NCT00422981), to a sex-dependent analysis. METHODS: One hundred forty-four individuals, separated into eight groups (1:2 placebo-and 2 doses, 5 mg davunetide/daily or 15 mg davunetide/twice-daily, with matching placebo intranasal volumes), were evaluated. RESULTS: Significant dose-dependent cognitive increases were observed in men compared to women with a test of delayed (12 ss) visual matching to the sample. In a test of semantic working memory and attention (digit span), women showed a significant low-dose placebo effect, ensuing in a high dose significant davunetide improvement, over the matched placebo. Correlating anxiety with cognition showed sex-opposing results, with women depicting significant anxiety correlations with delayed matching to sample. DISCUSSION: In conclusion, sex-specific prodromal Alzheimer's drug development is encouraged, with davunetide playing a lead initiative role.

Sex differences in DNA methylation variations according to ART conception-evidence from the Norwegian mother, father, and child cohort study.

Previous studies have shown cord-blood DNA methylation differences in newborns conceived using assisted reproductive technologies (ART) compared to those conceived naturally. However, whether these ART-related DNA methylation differences vary with children's sex is unknown. We hypothesize that the DNA methylation differences in cord blood between ART-conceived and naturally conceived newborns also varies by the sex of the child, with distinct patterns of differential methylation present in males and females. We investigated sex differences in cord-blood DNA methylation variation according to conception by ART using the Illumina MethylationEPIC platform, comparing 456 ART-conceived versus 507 naturally-conceived girls, and 503 ART-conceived and 473 naturally-conceived boys. We identified 37 differentially methylated CpGs according to ART-conception among girls, and 70 differentially methylated CpGs according to ART-conception among boys, when we used a 1% false discovery rate to account for multiple testing. Ten CpGs were differentially methylated according to conception by ART in both sexes. Among the genes that were associated with these CpGs, we found the BRCA1; NBR2 gene (two CpGs) was hypermethylated in girls while the APC2 (two CpGs) and NECAB3;ACTL10, (four CpGs) related to cellular signaling were hypomethylated in boys. These findings confirm the presence of sex-specific epigenetic differences, illustrating the nuanced impact of ART on the fetal epigenome. There is a need for further explorations into the implications for sex-specific developmental trajectories and health outcomes in ART-conceived children.

Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

Sex differences in the development of experimental diabetic retinopathy.

This study aimed to characterize the role of female sex in the pathogenesis of diabetic retinopathy. In the retinae of female Ins2Akita-diabetic mice (F-IA), ovariectomized female Ins2Akita-diabetic mice (F-IA/OVX), male Ins2Akita-diabetic mice (M-IA), and female STZ-diabetic mice (F-STZ), the formation of reactive metabolites and post-translational modifications, damage to the neurovascular unit, and expression of cellular stress response genes were analyzed. Compared to the male diabetic retina, the concentrations of the glycation adduct fructosyl-lysine, the Maillard product 3-deoxyglucosone, and the reactive metabolite methylglyoxal were significantly reduced in females. In females, there was also less evidence of diabetic damage to the neurovascular unit, as shown by decreased pericyte loss and reduced microglial activation. In the male diabetic retina, the expression of several members of the crystallin gene family (Cryab, Cryaa, Crybb2, Crybb1, and Cryba4) was increased. Clinical data from type 1 diabetic females showed that premenopausal women had a significantly lower prevalence of diabetic retinopathy compared to postmenopausal women stratified for disease duration and glycemic control. These data emphasize the importance of estradiol in protecting the diabetic retina and highlight the pathogenic relevance of sex in diabetic retinopathy.

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.