Sex-specific Differences Research Articles

Self-regulated analgesia in males but not females is mediated by endogenous opioids.

Converging lines of preclinical and clinical research indicate that females, in stark contrast to males, display an increased prevalence of chronic pain. Females also demonstrate weaker analgesic efficacy in response to opioid therapies when compared with males. These sex-specific differences may be driven by dimorphic endogenous opioidergic responses. In rodent models, analgesia exhibited in males but not females was reversed by inhibiting endogenous opioidergic reception. In humans, the sex-specific endogenous system(s) supporting the direct attenuation of evoked pain has not been identified. To determine whether opioidergic blockade reverses self-regulated analgesia in males as compared to females, the present study combined two operationally analogous clinical trials (n = 98; 51 females and 47 males). In a double-blinded, counterbalanced study involving healthy (n = 39) and chronic low back pain (n = 59) populations, a high-dose naloxone (μ-, κ-, δ-opioid antagonist) vs. placebo-saline cross-over design (15 mg/kg bolus +0.1 mg/kg/h) tested the hypothesis that endogenous opioids mediate analgesia in males but not females. An 11-point visual analog scale (VAS) (0 = no pain; 10 = worst pain imaginable) evaluated pain ratings in response to noxious heat stimulation (49 °C; calf). After baseline pain testing, participants were randomized to a validated four-session mindfulness meditation or sham mindfulness meditation training intervention. Participants practiced their respective meditation during noxious heat, intravenous high-dose naloxone, and placebo saline, respectively. In males and females, meditation significantly lowered evoked pain during saline infusion. Intravenous naloxone inhibited analgesia in males, but pain relief was well preserved in females. The present findings indicate that endogenous opioids mediate self-regulated analgesia in males but not females and underscore the need to establish sex-specific pain therapeutics.

Examining the effects of the HIV-1 protein Tat and morphine on antiretroviral accumulation and distribution within the brain.

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro-acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co-exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV-1 Tat transgenic mouse model by using infrared-matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI MSI). Morphine exposure uniquely decreased antiretroviral concentrations in anterior cerebral (primary motor and somatosensory) cortices, corpus collosum (anterior forceps), caudoputamen, nucleus accumbens, and posterior regions including the hippocampus, corpus callosum (main body), cerebral cortex (somatosensory and auditory cortices), thalamus, and hypothalamus. Interestingly, male mice experienced greater morphine-associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in antiretroviral concentrations were linked with inflammation in astroglia, assessed through the measurement of astroglial activation using glial fibrillary acidic protein (GFAP) as a marker. Alterations in antiretroviral concentrations co-registering with areas of astroglial activation exhibited sex-specific treatment differences. This study highlights the intricate interplay between HIV, opioids, and antiretroviral drugs within the CNS, elucidating distinct regional and sex variations in responsiveness. Our findings emphasize the identification of vulnerabilities within the neural landscape and underscore the necessity of carefully monitoring opioid use to maintain the efficacy of antiretroviral therapies.

192 Sex Specific Differences in Emergency Department Patient Mortality Predictors and Documentation of End-of-Life Goals of Treatment

192 Sex Specific Differences in Emergency Department Patient Mortality Predictors and Documentation of End-of-Life Goals of Treatment

Normative Profile of Retinal Nerve Fiber Layer Thickness and Lamina Cribrosa-Related Parameters in a Healthy Non-Glaucoma Cynomolgus Monkey Colony.

The purpose of this study was to investigate the normal range of ophthalmic parameters and the correlations between systematic and ocular parameters and retinal nerve fiber layer (RNFL) thickness among a healthy non-glaucoma cynomolgus monkey colony. All included monkeys were given detailed ophthalmic examinations, including anterior and posterior segments. Furthermore, univariate and multivariate linear regression models were conducted to estimate the relationship between systemic and ophthalmic parameters and global RNFL thickness. A total of 349 non-glaucoma monkeys (18.69 ± 2.88 years old) were collected. The global RNFL thickness was 94.61 ± 10.13 µm, and sex-specific differences existed in all sectors. The decreasing trend of RNFL is as follows: inferotemporal, superotemporal, inferonasal, superonasal, temporal, and nasal. For lamina cribrosa (LC)-related parameters, cup depth (P < 0.01), LC thickness (P = 0.014), and Bruch's membrane opening (BMO) - minimum rim width 2 (P = 0.002) were greater in the male group. However, LC depth (P = 0.02), anterior laminar insertion depth-1 (P = 0.009), and mean anterior laminar insertion depth (P = 0.029) of female monkeys were greater than those of male monkeys. In multivariate linear regression, only older age was significantly related to reduced global RNFL thickness (P < 0.001). Our findings suggest the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkeys and humans. Therefore, the impact of this difference on outcomes should be fully considered in laboratory animal studies. Our findings are also significant in terms of developing a normative optical coherence tomography (OCT) database in nonhuman primates (NHPs). We found that the differences in RNFL thickness distribution and sex between non-glaucoma cynomolgus monkey colonies and humans should be thoroughly taken into account in laboratory animal studies.

Sex Differences in Risk Factors for Generalized Anxiety Disorder in Korean Adolescents.

This study aimed to examine sex differences in the risk factors associated with generalized anxiety disorder (GAD) among Korean adolescents to provide insights for drafting more effective prevention strategies. Data from 51845 middle and high school students in the 18th Korea Youth Risk Behavior Web-based Survey were analyzed. GAD was assessed using the 7-item Generalized Anxiety Disorder tool, and factors such as grade, academic performance, economic status, living arrangements, smoking, drinking, sexual experience, and physical activity were included. The prevalence of GAD and its association with these factors were compared between male and female students using chi-square tests and logistic regression. Odds ratios were compared statistically to identify sex-specific differences. GAD prevalence was higher among girls (42.1%) than boys (30.1%). Both sexes showed increased GAD risk with lower academic performance, lower economic status, smoking, drinking, and sexual experience. Boys living apart from their families had a higher GAD risk, but this was not significant for girls. Additionally, smoking and drinking were associated with a higher increase in GAD risk in girls than in boys. This study underscores the importance of considering sex differences in the prevention of GAD among adolescents. Tailored sex-specific interventions are crucial for effective prevention and management of GAD in Korean adolescents.

When the Going Gets Tough, the Females Get Going: Sex-Specific Physiological Responses to Simultaneous Exposure to Hypoxia and Marine Heatwave Events in a Ubiquitous Copepod.

The existence of sex-specific differences in phenotypic traits is widely recognized. Yet they are often ignored in studies looking at the impact of global changes on marine organisms, particularly within the context of combined drivers that are known to elicit complex interactions. We tested sex-specific physiological responses of the cosmopolitan and ecologically important marine copepod Acartia tonsa exposed to combined hypoxia and marine heatwave (MHW) conditions, both of which individually strongly affect marine ectotherms. Females and males were acutely exposed for 5 days to a combination of either control (18°C) or a high temperature mimicking a MHW (25°C), and normoxia (100% O2 sat.) or mild hypoxia (35% O2 sat.). Life-history traits, as well as sex-specific survival and physiological traits, were measured. Females had overall higher thermal tolerance levels and responded differently than males when exposed to the combined global change drivers investigated. Females also showed lower metabolic thermal sensitivity when compared to males. Additionally, the MHW exerted a dominant effect on the traits investigated, causing a lower survival and higher metabolic rate at 25°C. However, egg production rates appeared unaffected by hypoxia and MHW conditions. Our results showed that MHWs could strongly affect copepods' survival, that combined exposure to hypoxia and MHW exerted an interactive effect only on CTmax, and that sex-specific vulnerability to these global change drivers could have major implications for population dynamics. Our results highlight the importance of considering the differences in the responses of females and males to rapid environmental changes to improve the implementation of climate-smart conservation approaches.

Thyroid endocrine disruption effects of OBS in adult zebrafish and offspring after parental exposure at early life stage

As an alternative to perfluorooctane sulfonate, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been widely used and caused ubiquitous water pollution. However, its toxicity to aquatic organisms is still not well known. Therefore, in this study, parental zebrafish were exposed to OBS at environmentally relevant concentrations from ∼ 2 h post-fertilization to 21 days post-fertilization (dpf) in order to investigate the thyroid disrupting effects in F0 adults and F1 offspring. Histopathological changes, such as hyperplasia of thyroid follicular epithelia and colloidal depletion, were observed in F0 adults at 180 dpf. In F0 females, thyroxine (T4) levels were significantly reduced in 30 and 300 μg/L exposure groups, while triiodothyronine (T3) levels were significantly increased in 3 μg/L exposure group. For F0 males, significant increases of T4 and T3 levels were observed, revealing the sex-specific differences after the OBS exposure. The transcription levels of some key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were significantly disrupted, which induced the thyroid endocrine disruption effects in adult zebrafish even after a prolonged recovery period. For F1 offspring, the thyroid hormone (TH) homeostasis was also altered as T4 and T3 levels in embryos/larvae exhibited similar changes as F0 females. The transcription levels of some key genes related to the HPT axis were also significantly dysregulated, suggesting the transgenerational thyroid disrupting effects of OBS in F1 offspring. In addition, the decreased swirl-escape rate was observed in F1 larvae, which could be caused by disrupting gene expressions related to the central nervous system development and be associated with the TH dyshomeostasis. Therefore, parental OBS exposure at early life stage resulted in thyroid endocrine disruption effects in both F0 adult zebrafish and F1 offspring, and caused the developmental neurotoxicity in F1 larvae.

The IgLON family of cell adhesion molecules expressed in developing neural circuits ensure the proper functioning of the sensory system in mice

Deletions and malfunctions of the IgLON family of cell adhesion molecules are associated with anatomical, behavioral, and metabolic manifestations of neuropsychiatric disorders. We have previously shown that IgLON genes are expressed in sensory nuclei/pathways and that IgLON proteins modulate sensory processing. Here, we examined the expression of IgLON alternative promoter-specific isoforms during embryonic development and studied the sensory consequences of the anatomical changes when one of the IgLON genes, Negr1, is knocked out. At the embryonal age of E12.5 and E13.5, various IgLONs were distributed differentially and dynamically in the developing sensory areas within the central and peripheral nervous system, as well as in limbs and mammary glands. Sensory tests showed that Negr1 deficiency causes differences in vestibular function and temperature sensitivity in the knockout mice. Sex-specific differences were noted across olfaction, vestibular functioning, temperature regulation, and mechanical sensitivity. Our findings highlight the involvement of IgLON molecules during sensory circuit formation and suggest Negr1’s critical role in somatosensory processing.

Association of perfluoroalkyl substances (PFAS) with liver function biomarkers in the highly exposed population of the veneto region

IntroductionEpidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association. MethodsThe study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation. ResultsOne ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects. ConclusionOur findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators.

Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework

Background/Objectives: Plasma levels of 4β-hydroxycholesterol (4β-OHC), a CYP3A-specific metabolite of cholesterol, are elevated after administration of CYP3A inducers like rifampicin and carbamazepine. To simulate such plasma 4β-OHC increase, we developed a physiologically based pharmacokinetic (PBPK) model of cholesterol and 4β-OHC in the Simcyp PBPK Simulator (Version 23, Certara UK Ltd.) using a middle-out approach. Methods: Relevant physicochemical properties and metabolic pathway data for CYP3A and CYP27A1 was incorporated in the model. Results: The PBPK model recovered the observed baseline plasma 4β-OHC levels in Caucasian, Japanese, and Korean populations. The model also captured the higher baseline 4β-OHC levels in females compared to males, indicative of sex-specific differences in CYP3A abundance. More importantly, the model recapitulated the increased 4β-OHC plasma levels after multiple-dose rifampicin treatment in six independent studies, indicative of hepatic CYP3A induction. The verified model also captured the altered 4β-OHC levels in CYP3A4/5 polymorphic populations and with other CYP3A inducers. The model is limited by scant data on relative contributions of CYP3A and CYP27A1 pathways and does not account for regulatory mechanisms that control plasma cholesterol and 4β-OHC levels. Conclusion: This study provides a quantitative fit-for-purpose and framed-for-future modelling framework for an endogenous biomarker to evaluate the DDI risk with hepatic CYP3A induction.

Gender disparity regarding the impact of retirement on marital satisfaction: Evidence from a longitudinal study of older Korean adults.

To investigate the impact of retirement on marital satisfaction by gender on Koreans aged >45 years in a large, nationally representative cohort. Retirement status and marital satisfaction data of 5867 individuals were analysed. Marital dissatisfaction was defined as a satisfaction score reduction of more than 10 points versus the previous wave. Lagged generalised estimating equation (GEE) models adjusted for demographics (age, sex, education level and household income), health-related habits (smoking and drinking status) and comorbidities (obesity, hypertension, type 2 diabetes, and depression and frailty) were used to confirm the relationship between retirement and marital dissatisfaction. The final GEE model adjusted for covariates revealed sex-specific differences in marital satisfaction after retirement. Whereas male retirees reported higher satisfaction than non-retired men, female retiree responses revealed lower satisfaction than non-retired women. Furthermore, these trends were consistent regardless of the time elapsed after retirement. Marital satisfaction should be screened in women during the transition to retirement.

Investigating the impact of climate change on mental health among Libyan Arabs: a validation study of the Hogg Eco-Anxiety Scale

Anxiety, especially within the realm of eco-anxiety, has become an increasingly significant focus of research. In our exploration of eco-anxiety within the Arab Libyan population, we employed a cross-sectional approach and successfully validated the Hogg Eco-Anxiety Scale (HEAS-13). Across two separate subsamples, both Exploratory (n = 790) [M = 21.64 (SD = 3.51), % women = 86.8] and Confirmatory Factor Analysis (n = 829) [M = 22.24 (SD = 3.76), % women = 84.6] confirmed the validity of HEAS-13. This scale effectively captured four distinct dimensions of eco-anxiety: affective symptoms, rumination, behavioral symptoms, and anxiety regarding one’s negative impact on the planet. Moreover, the total HEAS-13 and its dimensions had good internal consistency coefficients, ranging from 0.65 to 0.82. The findings highlight significant correlations between eco-anxiety subscales, behavioral symptoms, and rumination, indicating distinct profiles of eco-anxiety. Additionally structural equation modelling analysis revealed that eco-anxiety dimensions serve as a significant predictor of various psychological symptoms, climate change perception and climate value, emphasizing the interconnectedness between eco-anxiety and psychological distress. Furthermore, Sex-specific differences in eco-anxiety and its associations with climate change perceptions are explored, suggesting heightened awareness and involvement among females. The results emphasize eco-anxiety as a quantifiable psychological phenomenon, demonstrably measured through our 13-item eco-anxiety scale and associated with the mental health outcomes.

Toxoplasma Gondii infection and cardiovascular mortality: sex-specific differences in a United States population-based cohort study

BackgroundAlthough Toxoplasma gondii (T. gondii) infection has been linked to cardiac injury, the extent to which it increases the risk of cardiovascular disease (CVD) mortality remains unclear. We aimed to assess the association between T. gondii infection and CVD mortality in the United States population.MethodsThis study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2014 to investigate the association between T. gondii infection and CVD mortality. The T. gondii infection status was determined by measuring serum T. gondii IgG antibody levels. CVD mortality outcomes were ascertained through linkage with the national mortality index records. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of T. gondii infection on CVD mortality.ResultsA total of 10,237 (Male, n = 5010; Female, n = 5227) individuals aged ≥ 20 years were included in the analysis, of which 1,632 were positive for T. gondii serum IgG antibodies. After a median follow-up of eight years, there were 312 deaths due to CVD. In multivariable-adjusted analyses, the risk of death from CVD was 40% higher in T. gondii-seropositive men compared with seronegative men (HR: 1.40; 95%CI: 1.02–1.93), but not in women (HR: 0.87; 95% CI: 0.57–1.34). These results remained consistent in further stratified and sensitivity analyses.ConclusionIn this large population-based cohort study, T. gondii infection was associated with an increased risk of CVD mortality in men, but not in women. Further studies are required to elucidate the underlying mechanisms and potential sex-specific differences in the effects of T. gondii infection on CVD mortality. Future investigations should focus on validating these results and exploring the potential implications for cardiovascular risk assessment and management.

Dim light at night unmasks sex-specific differences in circadian and autonomic regulation of cardiovascular physiology

Shift work and artificial light at night disrupt the entrainment of endogenous circadian rhythms in physiology and behavior to the day-night cycle. We hypothesized that exposure to dim light at night (dLAN) disrupts feeding rhythms, leading to sex-specific changes in autonomic signaling and day-night heart rate and blood pressure rhythms. Compared to mice housed in 12-hour light/12-hour dark cycles, mice exposed to dLAN showed reduced amplitudes in day-night feeding, heart rate, and blood pressure rhythms. In female mice, dLAN reduced the amplitude of day-night cardiovascular rhythms by decreasing the relative sympathetic regulation at night, while in male mice, it did so by increasing the relative sympathetic regulation during the daytime. Time-restricted feeding to the dim light cycle reversed these autonomic changes in both sexes. We conclude that dLAN induces sex-specific changes in autonomic regulation of heart rate and blood pressure, and time-restricted feeding may represent a chronotherapeutic strategy to mitigate the cardiovascular impact of light at night.

Sex-dependent effects of acute stress and alcohol exposure during adolescence on mRNA expression of brain signaling systems involved in reward and stress responses in young adult rats

BackgroundAdolescent stress and alcohol exposure increase the risk of maladaptive behaviors and mental disorders in adulthood, with distinct sex-specific differences. Understanding the mechanisms underlying these early events is crucial for developing targeted prevention and treatment strategies.MethodsMale and female Wistar rats were exposed to acute restraint stress and intermittent alcohol during adolescence. We assessed lasting effects on plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, and mRNA expression of genes related to corticotropin releasing hormone (CRH), neuropeptide Y (NPY), corticoid, opioid, and arginine vasopressin systems in the amygdala and hypothalamus.ResultsThe main findings are as follows: (1) blood alcohol concentrations (BAC) increased after the final alcohol administration, but stressed males had lower BAC than non-stressed males; (2) Males gained significantly more weight than females; (3) Stressed females showed higher ACTH levels than non-stressed females, with no changes in males; (4) Stress increased CORT levels in males, while stressed, alcohol-treated females had lower CORT levels than non-stressed females; (5) CRH: Females had lower Crhr1 levels in the amygdala, while alcohol reduced Crhr2 levels in males but not females. Significant interactions among sex, stress, and alcohol were found in the hypothalamus, with distinct patterns between sexes; (6) NPY: In the amygdala, stress reduced Npy and Npy1r levels in males but increased them in females. Alcohol decreased Npy2r levels in males, with varied effects in females. Similar sex-specific patterns were observed in the hypothalamus; (7) Corticoid system: Stress and alcohol had complex, sex-dependent effects on Pomc, Nr3c1, and Nr3c2 in both brain regions; (8) Opioid receptors: Stress and alcohol blunted the elevated expression of Oprm1, Oprd1, and Oprk1 in the amygdala of males and the hypothalamus of females; (8) Vasopressin: Stress and alcohol interacted significantly to affect Avp and Avpr1a expression in the amygdala, with stronger effects in females. In the hypothalamus, alcohol increased Avp levels in females.ConclusionsThis study demonstrates that adolescent acute stress and alcohol exposure induce lasting, sex-specific alterations in systems involved in reward and stress responses. These findings emphasize the importance of considering sex differences in the prevention and management of HPA dysfunction and psychiatric disorders.

Sex differences in survival outcomes of early-onset colorectal cancer

Colorectal cancer (CRC) is one of the most fatal cancers in the United States. Although the overall incidence and mortality rates are declining, an alarming rise in early-onset colorectal cancer (EOCRC), defined as CRC diagnosis in patients aged < 50 years, was previously reported. Our study focuses on analyzing sex-specific differences in survival among EOCRC patients and comparing sex-specific predictors of survival in both males and females in the United States. We retrieved and utilized data from the Surveillance, Epidemiology, and End Results (SEER) program. EOCRC patients, between the ages of 20 and 49, were exclusively included. We conducted thorough survival analyses using Kaplan–Meier curves, log-rank tests, Cox regression models, and propensity score matching to control for potential biases. Our study included 58,667 EOCRC patients (27,662 females, 31,005 males) diagnosed between 2000 and 2017. The baseline characteristics at the time of diagnosis were significantly heterogeneous between males and females. Males exhibited significantly worse overall survival (OS), cancer-specific survival (CSS), and noncancer-specific survival (NCSS) in comparison to females in both the general cohort, and the matched cohort. Predictors of survival outcomes generally followed a similar pattern in both sexes except for minor differences. In conclusion, we identified sex as an independent prognostic factor of EOCRC, suggesting disparities in survival between sexes. Further understanding of the epidemiological and genetic bases of these differences could facilitate targeted, personalized therapeutic approaches for EOCRC.

Sex- specific differences in suspected myocarditis presentations and outcomes

BackgroundSigns and symptoms of myocarditis may vary among men and women. ObjectivesThis study aimed to analyze sex-specific differences in the presentation and outcomes of patients with suspected myocarditis. MethodsPatients meeting clinical ESC criteria for suspected myocarditis were included from two tertiary centers between 2002 and 2021. Baseline characteristics, cardiac magnetic resonance (CMR), and outcomes (i.e. major adverse cardiovascular events (MACE), including all-cause death, ventricular tachycardia, hospitalization for heart failure, and recurrent myocarditis) in women and men were compared. Results776 consecutive patients (mean age 48 ± 16 years, 286 [36.9 %] women) were followed for a median of 3.7 years. Compared to men, women presented more often with severe dyspnea (NYHA III-IV: 25.9 % versus 19.2 % of men; p = 0.029), while chest pain was more frequent in men (39.8 % versus 32.2 % in women; p = 0.037). There was no difference in left ventricular ejection fraction at the time of presentation (women: 48.5 ± 15.4 % versus men: 48.6 ± 15.1 %;p = 0.954). Further, no sex-specific difference in the occurrence of MACE was noted; however, women were more often hospitalized for heart failure than men (women: 9.8 % versus men: 5.3 %, p = 0.018). Accordingly, female sex was independently associated with heart failure hospitalization in an adjusted model (HR: 2.31, 95 % CI:1.25–4.26; p = 0.007). The prognostic value of CMR markers was similar in both sex. ConclusionSignificant sex-specific differences in presentations and imaging findings are found in patients with suspected myocarditis. Female sex is associated with a twofold increase in the risk of heart failure hospitalization, which should be considered in risk stratification.

Mitochondrial dynamics and sex-specific responses in the developing rat hippocampus: Effect of perinatal asphyxia and mesenchymal stem cell Secretome treatment

AimsPerinatal asphyxia is one of the major causes of neonatal death at birth. Survivors can progress but often suffer from long-term sequelae. We aim to determine the effects of perinatal asphyxia on mitochondrial dynamics and whether mesenchymal stem cell secretome (MSC-S) treatment can alleviate the deleterious effects. Materials and methodsAnimals were subjected to 21 min of asphyxia at the time of delivery. MSC-S or vehicle was intranasally administered 2 h post-delivery. Mitochondrial mass (D-loop, qPCR), mitochondrial dynamics proteins (Drp1, Fis1 and OPA1, Western blot), mitochondrial dynamics (TOMM20, Immunofluorescence), as well as mitochondrial membrane potential (ΔΨm) (Safranin O) were evaluated at P1 and P7 in the hippocampus. Key findingsPerinatal asphyxia increased levels of mitochondrial dynamics proteins Drp1 and S-OPA1 at P1 and Fis1 at P7. Mitochondrial density and mass were decreased at P1. Perinatal asphyxia induced sex-specific differences, with increased L-OPA1 in females at P7 and increased mitochondria circularity. In males, asphyxia-exposed animals exhibited a reduced ΔΨm at P7. MSC-S treatment normalised levels of mitochondrial dynamics proteins involved in fission. SignificanceThis study provides novel insights into the effects of perinatal asphyxia on mitochondrial dynamics in the developing brain and on the therapeutic opportunities provided by mesenchymal stem cell secretome treatment. It also highlights on the relevance of considering sex as a biological variable in perinatal brain injury and therapy development. These findings contribute to the development of targeted, personalised therapies for infants affected by perinatal asphyxia.

Sex-specific differences in alive hospital discharge following infrarenal abdominal aortic aneurysm repair.

A longer time to alive hospital discharge following infrarenal abdominal aortic aneurysm (AAA) repair is associated with reduced patient-satisfaction and increased length of stay, hospital-acquired deconditioning, infection and costs. This study investigated sex-specific differences in, and drivers of, the rate of alive hospital discharge. Examination of UK National Vascular Registry (UK NVR), 2014-2019 and Swedish National Patient Registry (SE NPR) elective AAA patients, 2010-2018, for endovascular (EVAR) or open (OAR) aneurysm repair. Cox models assessed sex-specific difference in rate of alive hospital discharge, adjusting for co-morbidity, anatomy, standard-of-care, post-operative complications, and year, with in-hospital death as the competing risk. 29,751 AAA repairs (UK NVR -EVAR 12518:1532; OAR 6803:837; SE NPR - EVAR 4234:792; OAR 2638:497, men:women) were assessed. For EVAR, the unadjusted rate of alive hospital discharge was ∼25% lower for women (UK NVR HR 0.75 [0.71-0.80], p<.001; SE NPR HR 0.75 [0.69-0.81], p<.001). Following adjustment the sex-specific hazard ratio narrowed but remained significant (UK NVR: HR 0.83 [0.79-0.88], p<.001; SE NPR HR 0.83 [0.76-0.89], p<.001). For OAR, the rate of alive hospital discharge was 23-27% lower for women (UK NVR HR 0.73 [0.67-0.78], p<.001; SE NPR HR 0.77 [0.70-0.85], p<.001). Following adjustment the sex-specific hazard ratio narrowed (UK NVR HR 0.82 [0.76-0.88], p<.001; SE NPR HR 0.79 [0.72-0.88], p<.001) but remained significant. Women have a 25% lower rate of alive discharge after aortic surgery, despite adjustment for pre/peri- and postoperative parameters. Efforts to increase rate of alive hospital discharge for women should be sought.

Sex-Based Differences in Lung Cancer Incidence: A Retrospective Analysis of Two Large US-Based Cancer Databases

Background/Objectives: Non-small cell lung cancer (NSCLC) has seen a relative rise in incidence among females versus males in recent years, although males still have a higher overall incidence. However, it is unclear whether this trend is consistent across all populations. Therefore, we retrospectively examined this relationship in two large high-risk clinical cohorts. Methods: First, we analyzed lung cancer incidence among individuals with a smoking history of over 40 pack-years in the National Lung Screening Trial (NLST). Then, we investigated the incidence of second primary NSCLC in patients who underwent lobectomy for previous stage I lung cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We performed both univariate and multivariable time-to-event analyses to investigate the relationship between sex and lung cancer incidence. Results: In the NLST cohort (n = 37,627), females had a higher risk of developing primary NSCLC than males (HR = 1.11 [1.007–1.222], p = 0.035) after adjusting for age and pack-year history. In the SEER cohort (n = 19,327), females again exhibited an increased risk of developing a second primary lung cancer (HR = 1.138 [1.02–1.269], p = 0.021), after adjusting for age, race, grade, and histology. Conclusions: Our analysis reveals that females have a modestly higher lung cancer incidence than males in high-risk populations. These findings underscore the importance of further researching the underlying cellular processes that may cause sex-specific differences in lung cancer incidence.