Understanding Of Sex Differences Research Articles

Sex Differences in Moderate-to-Severe Traumatic Brain Injury Randomized Controlled Trials.

Understanding sex differences among persons with moderate-to-severe traumatic brain injury (TBI) is critical to addressing the unique needs of both males and females from acute care through to rehabilitation. Epidemiological studies suggest that 7 of every 10 persons with moderate-to-severe TBI are male, with females representing about 30%-33%. To examine the proportion of female and male individuals included in randomized controlled trials (RCTs) of interventions for moderate-to-severe TBI. A systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up to and including December 2022 using MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO databases. Studies were included if they met the following criteria: (1) human participants with a mean age ≥18 years, (2) ≥50% of the sample had moderate-to-severe TBI and (3) the study design was a RCT. Data extracted included author, year, country, sample size, number of female/male participants and time post-injury. 595 RCTs met the criteria for inclusion, published between 1978 and 2022, totaling 86,662 participants. The average proportion of female participants was 23.14%, and the percentage increased a small but significant amount over time. There was a significantly lower percentage of female participants in RCTs initiated in the acute phase (≤ 1 month) when compared with RCTs conducted in the chronic phase (≥ 6 months) post-injury (p < 0.001). Female participants are underrepresented in RCTs of moderate-to-severe TBI. Addressing this underrepresentation is critical to establish effective treatments for all persons with TBI.

Sex Differences in Physiological Responses to a National Collegiate Athletic Association Division I Soccer Season.

McFadden, BA, Walker, AJ, Cintineo, HP, Bozzini, BN, Sanders, DJ, Chandler, AJ, and Arent, SM. Sex differences in physiological responses to a National Collegiate Athletic Association Division I soccer season. J Strength Cond Res 38(11): 1891-1899, 2024-Identifying physiological changes that occur in response to workload demands can help to elucidate athlete management and recovery strategies. The purpose of this study was to compare the physical and physiological demands between men and women throughout the course of a collegiate soccer season. Men ( N = 23) and women ( N = 26) soccer players participated in blood draws before preseason (T1) and every 4 weeks thereafter (T2-T4). Workload was determined at all practices and games via heart rate and global positioning satellite monitoring systems. Repeated measures multivariate analysis of variance and linear mixed models were used to assess workload and biomarker responses throughout the season ( p < 0.05). Both teams experienced the highest workloads during the first 4 weeks of the season ( p < 0.05), which was followed by several biomarker perturbations. Sex-by-Time interactions were observed for total cortisol, growth hormone, insulin-like growth factor-1, thyroxine, thyroid-stimulating hormone, vitamin D, and omega 3 fatty acid index ( p < 0.05). Additional Sex effects were observed for free and total testosterone, estrogen, prolactin, sex-hormone binding globulin, creatine kinase, and iron levels ( p < 0.05). Women soccer players experienced further Time effects for free cortisol, iron, ferritin, and percent transferrin saturation ( p < 0.05). Male soccer players experienced additional Time effects for total testosterone, estrogen, creatine kinase, interleukin-6, triiodothyronine, and ferritin ( p < 0.05). Despite similar patterns of change in workloads, differential fluctuations in physiological markers were observed between the sexes. Understanding sex differences in response to comparable workloads may enhance exercise prescriptions for better athlete management plans. Additional strategies to increase iron may be warranted in female athletes.

Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents.

Understanding sex differences in the adolescent brain is crucial, as these differences are linked to neurological and psychiatric conditions that vary between males and females. Predicting sex from adolescent brain data may offer valuable insights into how these variations shape neurodevelopment. Recently, attention has shifted toward exploring socially-identified gender, distinct from sex assigned at birth, recognizing its additional explanatory power. This study evaluates whether resting-state functional connectivity (rsFC) or cortical thickness more effectively predicts sex and sex/gender alignment (the congruence between sex and gender) and investigates their interrelationship in preadolescents. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we employed machine learning to predict both sex (assigned at birth) and sex/gender alignment from rsFC and cortical thickness. rsFC predicted sex with significantly higher accuracy (86%) than cortical thickness (75%) and combining both did not improve the rsFC model's accuracy. Brain regions most effective in predicting sex belonged to association (default mode, dorsal attention, and parietal memory) and visual (visual and medial visual) networks. The rsFC sex classifier trained on sex/gender aligned youth was significantly more effective in classifying unseen youth with sex/gender alignment than in classifying unseen youth with sex/gender unalignment. In females, the degree to which their brains' rsFC matched a sex profile (female or male), was positively associated with the degree of sex/gender alignment. Lastly, neither rsFC nor cortical thickness predicted sex/gender alignment. These findings highlight rsFC's predictive power in capturing the relationship between sex and gender and the complexity of the interplay between sex, gender, and the brain's functional connectivity and neuroanatomy.

Evaluating the role of sex-related structure-function differences on airway aerosol transport and deposition.

Several experimental studies have found that females have higher particle deposition in the airways than males. This has implications for the delivery of aerosolized therapeutics and for understanding sex differences in respiratory system response to environmental exposures. This study evaluates several factors that potentially contribute to sex differences in particle deposition, using scale-specific structure-function models of one-dimensional (1-D) ventilation distribution, particle transport, and deposition. The impact of gravity, inhalation flow rate, and dead space are evaluated in 12 structure-based models (7 females; 5 males). Females were found to have significantly higher total, bronchial, and alveolar deposition than males across a particle size range from 0.01 to 10 μm. Results suggest that higher deposition fraction in females is due to higher alveolar deposition for smaller particle sizes and higher bronchial deposition for larger particles. Females had higher alveolar deposition in the lower lobes and slightly lower particle concentration in the left upper lobe. Males were found to be more sensitive to changes due to gravity, showing greater reduction in bronchial deposition fraction. Males were also more sensitive to change in inhalation flow rate and to scaling of dead space due to the larger male baseline airway size. Predictions of sex differences in particle deposition-that are consistent with the literature-suggest that sex-based characteristics of lung and airway size interacting with particle size gives rise to differences in regional deposition.NEW & NOTEWORTHY Sex differences in airway tract particle deposition are analyzed using computational models that account for scale-specific structure and function. We show that sex-related differences in lung and airway size can explain experimental observations of increased deposition fraction in females, with females tending toward enhanced fine particle deposition in the alveolar airways and enhanced bronchial deposition for larger particles.

Sex differences in transradial access failure in ST segment elevation myocardial infarction.

Transradial access (TRA) is now the default access site for PPCI, but technically is a more challenging approach mostly due to anatomic challenges connected to the RA. To assess the differences according to sex in radial artery (RA) access site characteristics during primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI). All 5092 consecutive STEMI patients from our center in the period from March 2011 until December 2017 were examined. The right proximal radial was the "intention-to-treat" access in all patients. Preprocedural RA angiography was performed in all patients. Clinical and procedure characteristics, type of radial anatomy variants, need to use another arterial access sites (the primary endpoint for this study), and procedure time were analyzed by sex. Using logistic regression, we selected predictors of radial crossover. Access site bleeding complications and vascular complications were also recorded. The STEMI population in this period included 1326 females and 3766 male patients. Females were older (65 ± 11 years) than males (59 ± 11 years, p < 0.0001). Among standard risk factors, hypertension and diabetes mellitus were more common in women and smoking less common. RA anomalies were more frequent in the females (8.8% vs. 6.5%, p < 0.0001), with complex RA loop and tortuous RA twice as frequent in women. Failure of TRA access as the initially chosen site occurred in 4.6% (61) of females versus 2.5% (97) of male STEMI patients (p = 0.0003). The most common subsequent access site was right ulnar access in both groups (57 and 61% respectively). Access site bleeding complications were more common in women 4.4% versus 3.2%, mirrored in hematomas with EASY score III to V. Clinical RA spasm (RAS) was significantly more frequent in females (5.7% vs. 2.2%, p < 0.0001). Multiple regression analysis identified 5 independent predictors for TRA access crossover: previous TRA, anomalous RA, RAS, along with female sex and diabetes. Female sex is a significant predictor of more complex TRA in STEMI. Understanding sex differences and predictors for TRA crossover will strengthen the use of different procedural modalities that can help in preserving a successful wrist access in female STEMI patients.

V-110.3: Understanding sex differences in relative cancer survival in kidney transplant recipients: A bi-national study, 1980-2019

V-110.3: Understanding sex differences in relative cancer survival in kidney transplant recipients: A bi-national study, 1980-2019

Is Being Single Ok? Analysis of College Students' Conditions of Being Single from a Gender Perspective

&lt;p&gt;基於發展階段的任務與社會文化期待，大學生面對高唱「脫單」、「脫魯」的氛圍，往往面臨是否進入戀愛關係的壓力。本研究從性別觀點探討單身大學生面對單身的認知、態度、情緒及其性別差異，以及人際互動與社會文化因素如何影響個人心理的性別差異。本研究採主位觀點自編問卷，進行網路調查，參與者為1,157位單身大學生。單身過去被視為失敗的象徵，本研究顯示，現今大學生對於單身的想法已較為多元，因素分析及多元迴歸的結果顯示，除了單身焦慮情緒及歸咎於己外，還出現享受單身的因素，且存在性別差異。平行中介分析結果顯示，單身男大生的單身焦慮高於單身女大生，也較容易將單身歸咎於己，這些性別差異被「受同儕影響而感到形單影隻」的人際互動因素完全中介。單身女大生較單身男大生更能享受單身，此性別差異被人際互動和社會文化因素部分中介，部分是因為單身女大生較不會受同儕影響感到形單影隻，部分是因為較未感受到社會文化的單身烙印。本研究顯示，在人際網絡與社會文化構築的壓力網下，單身女大生較能從傳統性別規範中解放出來。最後，本研究針對正向單身論述、男性情感教育、父母及同儕的影響提出建議；並討論未來採取量化和質性研究的方向，期能促進單身者的心理健康。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;Romantic relationships are regarded as a milestone in college students’ developmental stage. Additionally, society and college culture demand that they leave their single status. College students visiting counseling centers commonly talk about romantic relationship problems. In response to college culture that emphasizes engagement in romantic relationships, college students are frequently troubled by the stress of being single when failing to meet this social and cultural expectation. However, research on singlehood has been neglected. This study explored college students’ emotions, attitudes, and cognitions regarding their singlehood and examined sex differences in these psychological states. The effects of interpersonal interactions and sociocultural factors on individual psychological states and sex differences were also examined. A questionnaire was developed from an emic perspective, and the items were adapted from articles posted on the Dcard forum regarding experiences of single college students. Exploratory factor analysis was applied to these items at three levels, that is, individual psychological state, interpersonal interactions, and social culture. The questionnaire was administered online to 1,157 single college students. While singlehood was marked as a symbol of failure, exploratory factor analysis revealed that college students had diverse thoughts about singlehood, ranging from enjoyment to anxiety. To understand sex differences in individual psychological states, multiple regression analyses were conducted, with anxiety about being single, enjoyment of a single life, and attribution of single status to personal traits respectively as dependent variables, and sexual orientation and grade level as covariates. We hypothesized that sex differences in individual psychological states are mediated by interpersonal interactions and sociocultural factors. The results of the parallel mediation analysis are consistent with this hypothesis. Sex differences in individual psychological states are mediated by interpersonal and sociocultural factors. The results showed that male students are more anxious about being single and more likely to attribute singlehood to personal traits than female students. By contrast, female students were more able to enjoy their single lives than male students. Specifically, controlling for sexual orientation and grade level, the sex differences in anxiety about being single and attribution of single status to personal traits were fully accounted for by the interpersonal interaction factor &amp;quot;&amp;quot;a sense of loneliness due to peer pressure.&amp;quot;&amp;quot; The sex differences in enjoyment of single life were partially accounted for by the interpersonal interaction factor &amp;quot;&amp;quot;a sense of loneliness due to peer pressure&amp;quot;&amp;quot; and sociocultural factor &amp;quot;&amp;quot;social stigma about singlehood.&amp;quot;&amp;quot; This study shows that single female college students are better able to liberate themselves from the pressure of interpersonal networks and sociocultural factors. In conclusion, single male college students are more anxious about their single status and are more likely to make internal attributions because of the pressure caused by interpersonal networks, whereas single female college students are more able to free themselves from peer pressure and social stigma, therefore, enjoying their single lives. Based on the results, we propose suggestions for positive discourse on being single, providing relationship education and counseling for male students, and analyzing the effect of parents and peers on college students’ perspectives on being single. This study explored college students’ perspectives on being single and the impact of individual, interpersonal, and societal factors. To measure the psychological state of a single person, reliable and valid inventories, such as single anxiety, need to be developed. Additionally, qualitative research may provide a deeper contextual understanding of single individuals. Further quantitative and qualitative research is needed to gain insight into the promotion of the well-being of a rising single population.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Association Between Obesity and Risk of Total and Obesity-Related Cancer in People With Incident Cardiovascular Disease.

Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow-up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist-to-hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity-cancer association was estimated using Fine-Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person-years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity-related cancers. Specifically, women with CVD and obesity had increased obesity-related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17-2.31]). No significant associations were found in men, even after excluding prostate cancer. This study suggests that obesity is linked to higher obesity-related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Understanding sex differences in extinction retention: Pre-extinction stress and sex hormone status

Difficulties in fear regulation can sometimes result in maladaptive fear responses. To better understand how to improve fear regulation, it is important to determine how known factors, such as sex hormone status and stress, might interact to influence fear memory. Research has shown that women with high estradiol levels (mid-cycle) and men exhibit better extinction retention compared to women with low estradiol levels (women in the early follicular cycle or using oral contraceptives). Stress has also been demonstrated to affect both the learning and retention of extinction. Despite documented interactions between stress and sex hormones, their combined effects have not been thoroughly studied. This study aims to examine the impact of stress as a function of sex hormone status on extinction learning and retention.A total of 168 non-clinical participants were studied, including men (n = 46), women using oral contraceptives (n = 38), women in the early follicular phase (n = 40), and women in mid-cycle (n = 44). On Day 1, fear acquisition training was performed. On day 2, prior to extinction training, half of the participants were exposed to a psychosocial stressor, while the other half performed a non-stressful control task. On day 3, extinction retention was tested. Fear was quantified using skin conductance responses, while stress hormones were quantified through saliva samples.Exposure to stress prior to extinction training did not affect extinction learning, regardless of sex hormone status. In contrast, pre-extinction stress exposure had different effects on extinction retention depending on hormone status. Stressed men showed impairment in extinction retention compared to controls, while the experimental condition had no effect on naturally cycling women. Regardless of stress exposure, early follicular women exhibited a deficit in fear regulation, while mid-cycle women showed effective fear regulation. Among women using oral contraceptives, the stress group demonstrated better extinction retention compared to the control group.These results demonstrate the importance of considering sex hormone status and stress exposure during extinction learning, as both components may modulate extinction retention. These results could help identifying hormonal conditions that may enhance the effectiveness of extinction-based psychological therapies used in the treatment of fear-related disorders.

Operant ethanol self-administration behaviors do not predict sex differences in continuous access home cage drinking

Understanding sex differences in disease prevalence is critical to public health, particularly in the context of alcohol use disorder (AUD). The goal of this study was to understand sex differences in ethanol drinking behavior and define the precise conditions under which sex differences emerge. Consistent with prior work, C57BL/6J females drank more than males under continuous access two-bottle choice conditions. However, using ethanol self-administration - where an operant response results in access to an ethanol sipper for a fixed time period - we found no sex differences in operant response rates or ethanol consumption (volume per body weight consumed, as well as lick behavior). This remained true across a wide range of parameters including acquisition, when the ethanol sipper access period was manipulated, and when the concentration of the ethanol available was scaled. The only sex differences observed were in total ethanol consumption, which was explained by differences in body weight between males and females, rather than by sex differences in motivation to drink. Using dimensionality reduction approaches, we found that drinking behavior in the operant context did not cluster by sex, but rather clustered by high and low drinking phenotypes. Interestingly, these high and low drinking phenotypes in the operant context showed no correlation with those same categorizations in the home cage context within the same animals. These data underscore the complexity of sex differences in ethanol consumption, highlighting the important role that drinking conditions/context plays in the expression of these differences.

Sex differences in discrimination behavior and orbitofrontal engagement during context-gated reward prediction.

Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here, we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+/DARK: X-/LIGHT: Y-/DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex (OFC) compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the OFC, and might have implications for our understanding of sex differences in psychiatric disorders.

Sex differences in discrimination behavior and orbitofrontal engagement during context-gated reward prediction

Animals, including humans, rely on contextual information to interpret ambiguous stimuli. Impaired context processing is a hallmark of several neuropsychiatric disorders, including schizophrenia, autism spectrum disorders, post-traumatic stress disorder, and addiction. While sex differences in the prevalence and manifestations of these disorders are well established, potential sex differences in context processing remain uncertain. Here, we examined sex differences in the contextual control over cue-evoked reward seeking and its neural correlates, in rats. Male and female rats were trained in a bidirectional occasion-setting preparation in which the validity of two auditory reward-predictive cues was informed by the presence, or absence, of a visual contextual feature (LIGHT: X+/DARK: X−/LIGHT: Y−/DARK: Y+). Females were significantly slower to acquire contextual control over cue-evoked reward seeking. However, once established, the contextual control over behavior was more robust in female rats; it showed less within-session variability (less influence of prior reward) and greater resistance to acute stress. This superior contextual control achieved by females was accompanied by an increased activation of the orbitofrontal cortex (OFC) compared to males. Critically, these behavioral and neural sex differences were specific to the contextual modulation process and not observed in simple, context-independent, reward prediction tasks. These results indicate a sex-biased trade-off between the speed of acquisition and the robustness of performance in the contextual modulation of cued reward seeking. The different distribution of sexes along the fast learning ↔ steady performance continuum might reflect different levels of engagement of the OFC, and might have implications for our understanding of sex differences in psychiatric disorders.

Sex differences in patient-reported outcomes and the association with clinical factors in axial spondyloarthritis patients treated with tumour necrosis factor inhibitors.

To investigate sex differences in patient-reported outcome measures (PROMs) among axSpA patients initiating their first TNFi and identify factors contributing to these disparities over the follow-up. Data were included from 15 EuroSpA registries and consisted of axSpA patients initiating their first TNFi, with ≥2 measurements for each analysed PROM (BASDAI and BASFI, scale 0-100) taken at any time point. Linear mixed models were employed to analyse sex differences in PROMs over 24 months and to evaluate how baseline characteristics were related to the observed sex differences. We analysed 13 102 (38% women) in the BASDAI analyses and 10 623 (38% women) in the BASFI analyses. At follow-up, mean sex differences in BASDAI increased from 4.3 units at baseline (95% CI, 3.5-5.1)-8.0 (7.2-8.8) at 6 months, and in BASFI from 2.2 (1.4-3.1)-4.6 (3.6-5.5), with consistently worse scores in women. Baseline characteristics could not substantially account for the observed sex differences over time; however, the magnitude of the sex differences was reduced by HLA-B27 positivity, longer disease duration, and increased CRP levels, but increased by TNFi initiation in later years and peripheral arthritis. In axSpA patients initiating their first TNFi, baseline sex differences in BASDAI and BASFI increased two-fold after 6 months of treatment and persisted thereafter, with worse scores in women. Several baseline characteristics moderated the sex differences, though none could fully account for them. These findings improve our understanding of sex differences and underscore their importance in axSpA.

Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0±6.7vs. 74.9±9.1 years, p=.06) with lower rates of comorbidities. While DRT was detected significantly later in women (173±267vs. 127±192 days, p=.01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p=.40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p=.24). Women were followed-up for a similar time as men (779±520vs. 908±687 days, p=.51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]:.68-4.37, p=.25) and no differences in stroke (HR:.83, 95%-CI:.30-2.32, p=.72) within 2 years after LAAC. Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

Sex differences in postconcussive symptom reporting in those with history of concussion: Findings from the federal interagency traumatic brain injury research (FITBIR) database

Objective: This study investigated influence of biological sex on postconcussive symptoms (PCS) following concussion using the Federal Interagency Traumatic Brain Injury Research (FITBIR) database. Method: All studies with publicly released data as of 4/7/21 that included both males and females, enough information to determine severity of injury consistent with concussion, a measure of PCS, and objective measures of neurocognitive functioning were used. This resulted in 6 studies with a total of 9890 participants (3206 females, 6684 males); 815 participants completed the Neurobehavioral Symptom Inventory (NSI), 471 completed the Rivermead Post-Concussion Symptoms Questionnaire (RPSQ), and 8604 completed the Sport Concussion Assessment Tool–3rd Edition (SCAT 3). Questionnaires were harmonized and the following symptom composite scores were computed: total score, somatic, cognitive, and affective. Data were analyzed using linear mixed-effects models. Results: Females endorsed higher total symptoms relative to males and that military personnel endorsed higher symptoms relative to civilians. Additionally, there was a small but significant interaction effect, such that female military personnel endorsed even higher symptoms than would be predicted by the main effects. Similar patterns were observed for somatic, cognitive, and affective symptom domains. Conclusions: Further understanding sex differences in PCS reporting is key to informing the most appropriate treatment options. Future work will need to examine whether sex differences in symptom reporting is due to sex differences in endorsement styles or genuine differences in symptom presentation, as well as the relationship between study population (e.g., military, civilian, sport) and sex on objective cognitive functioning and other functional outcomes.

Sex Differences in Energy Metabolism: A Female-Oriented Discussion.

The purpose of this review is to delineate aspects of energy metabolism at rest and during exercise that may be subject to sex differences and the potential underlying mechanisms involved. It focuses on distinct aspects of female physiology with an oriented discussion following the reproductive life stages of healthy, eumenorrheic females, including premenopausal time frames, pregnancy, perimenopause, and menopause. Finally, this review aims to address methodological challenges surrounding sexual dimorphism in energy metabolism investigations and confounding factors in this field. During resting conditions, females tend to have higher rates of non-oxidative free fatty acid clearance, which could contribute to lower respiratory exchange ratio measures. At the same time, carbohydrate energy metabolism findings are mixed. In general, females favor lipid energy metabolism during moderate-intensity exercise, while men favor carbohydrate energy metabolism. Factors such as age, dietary intake, genetics, and methodological decisions confound study findings, including properly identifying and reporting the menstrual cycle phase when female subjects are eumenorrheic. Pregnancy presents a unique shift in physiological systems, including energy metabolism, which can be observed at rest and during exercise. Changes in body composition and hormonal levels during the post-menopausal period directly impact energy metabolism, specifically lipid metabolism. This change in physiological state factors into the evidence showing a reduction in our understanding of sex differences in lipid metabolism during exercise in older adults. This review reveals a need for a focused understanding of female energy metabolism that could help exercise and nutrition professionals optimize female health and performance across the lifespan.

Advanced subject-specific neck musculoskeletal modeling unveils sex differences in muscle moment arm and cervical spine loading

Neck pain and injuries are growing healthcare burdens with women having a higher incidence rate and poorer treatment outcomes than males. A better understanding of sex differences in neck biomechanics, foundational for more targeted, effective prevention or treatment strategies, calls for more advanced subject-specific musculoskeletal modeling. Current neck musculoskeletal models are based on generic anatomy, lack subject specificity beyond anthropometric scaling, and are unable to accurately reproduce neck strengths exhibited in vivo without arbitrary muscle force scaling factors or residual torque actuators. In this work, subject-specific neck musculoskeletal models of 23 individuals (11 male, 12 female) were constructed by integrating multi-modality imaging and biomechanical measurements. Each model simulated maximal voluntary neck static exertions in three postures: neck flexion in a neutral posture, flexion in a 40° extended posture, and extension in a 40° flexed posture. Quantitative model validation showed close agreement between model-predicted muscle activation and EMG measurement. The models unveiled that (1) males have greater moment arms in one flexor muscle group and five extensor muscle groups, (2) females exhibited higher cervical spinal compression per unit exertion force in the flexed posture, and (3) the variability of compression force was much greater in females in all three exertions but most notably in the extension with a flexed “dropped head” position. These insights illuminated a plausible pathway from sex differences in neck biomechanics to sex disparities in the risk and prevalence of neck pain.

Understanding sex differences and the translational value of models of persistent substance use despite negative consequences

Persistent substance use despite negative consequences is a key facet of substance use disorder. The last decade has seen the preclinical field adopt the use of punishment to model adverse consequences associated with substance use. This has largely involved the pairing of drug use with either electric foot shock or quinine, a bitter tastant. Whilst at face value, these punishers may model aspects of the physical and psychological consequences of substance use, such models are yet to assist the development of approved medications for treatment. This review discusses progress made with animal models of punishment to understand the behavioral consequences of persistent substance use despite negative consequences. We highlight the importance of examining sex differences, especially when the behavioral response to punishment changes following drug exposure. Finally, we critique the translational value these models provide for the substance use disorder field.

Swimming training induced sex-specific differences in cardiac hypertrophy and blood levels of the renin-angiotensin system

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): FNS Background Exercise promotes physiological cardiac hypertrophy that is adaptive and reversible and influenced by age, genetics, sex, exercise intensity and type. The renin-angiotensin system (RAS) plays a crucial role in cardiovascular remodelling at both systemic and tissue levels. However, a significant gap exists in our understanding of sex differences in response to physical activity. Our objective is to characterise swimming-induced cardiac remodelling in female and male rats and RAS at both the cardiac tissue and systemic levels. Methods Male and female Lewis rats swam in a container filled with tap water at 32° C for 1 hour per day for 4 weeks or up to 8 weeks, respectively. Sedentary animals served as control. Echocardiography and immunostaining of RAS components, including angiotensin-converting enzyme 2 (ACE2) on cardiac sections' staining were performed. Cardiomyocyte (CM) size was measured. Cardiac RAS receptors were quantified with RT-PCR. Blood levels of Angiotensinogen, Angiotensins (Ang) were measured with Mass Spectrometry. Renin activity was calculated by the ratio Ang1/Angiotensinogen. Results After 4 weeks, an increase in ventricle diameter was shown in exercised male rats compared to the control. The cardiac hypertrophy was confirmed by increased heart/body weight (H/BW= 3x10-3±1.3x10-4vs2.5x10-3±3.10-5mg/g p&amp;lt;0.0001) and CM size (288±23 vs 198±1μm2 p=0.0028) associated with increased intra-CM immunostained ACE2 (AC2 area fraction: 38.5%±2.8%vs20%±5 p=0.0001). In females, ventricle diameter was unchanged, but wall thickness increased. Exercise was pursued for up to 8 weeks. At 6 and 8 weeks, echocardiography measurements remained similar as at 4 weeks. Hypertrophy was then confirmed by increased H/BW (3.2x10-3±1.7x10-4vs control:2.7x103 ±1.8x104mg/g p&amp;lt;0.0001) and CM size (335±47vs233±25μm2 p= 0.0019). An increased intra-CM-ACE2 was characterised by immunostaining (55.8%±6vs32.5%±6.6% p&amp;lt;0.0001) and confirmed by the increased ACE2 gene expression in cardiac tissue. At 4 weeks, the blood levels of RAS components were similar in trained and control males as well as renin activity. On contrary, exercised female rats showed increased blood levels of Angiotensinogen (4.2x10-4±7x10-5 vs 3x10-4±7x10-5au p=0.0288), Ang1 (2±1.9vs0.0±0.9au p=0.0151), Ang2 (1.2±1.5vs0.0±0.9au p=0.0204), and Ang1-7 (3.4±2.9vs 0.0±0.9au p=0.0058). The blood levels of these RAS compounds returned to the control levels after 6 and 8 weeks. In addition, a sex-distinct blood proteome was identified. Conclusion Our results showed a sex-distinct RAS regulation post-exercise and suggested a sex difference in the timing of adaptive responses at the system and cardiac tissue levels.

Skeletal Muscle Mitochondrial Function and Mitochondria-related Protein Expression in Men and Women During Acute Exercise-Heat Stress and Acclimation

INTRODUCTION: Military personnel can exhibit improved performance and reduced physiological strain in hot environments with the induction of heat adaptations. Mild heat exposure at 40°C heat serves therapeutic purposes, enhancing metabolic flexibility, and promoting positive muscle adaptations. Research indicates that heat acclimation (HA) leads to increased mitochondrial biogenesis and reduced reactive oxygen species in skeletal muscle, improving thermal tolerance. However, understanding sex differences in mitochondrial function and related protein expression affected by heat acclimation remain limited. Therefore, this study aimed to explore mitochondrial respiration and the expression of mitochondria-related proteins to better understand the impact of heat stress on mitochondrial adaptations in skeletal muscle in both males and females. METHODS: Healthy men (M:n = 7, 22±2yo, VO2max 52.86±2.35ml·kg−1·min−1) and women (F:n = 7, 24±1yo, VO2max 45.97±2.57 ml·kg−1·min−1) participated in a 5-day heat acclimation (HA) at 40°C and 40% relative humidity. Before and after HA, participants completed a heat tolerance test (HTT) measuring time to reach a rectal temperature of 39.5°C or volitional failure. Biopsies from the vastus lateralis were taken immediately post-HTT for musculoskeletal analysis. Mitochondrial respiratory function was assessed using Oroboros O2K, employing high-resolution respirometry. Paired sample t-tests were used to determine statistical significance between groups (p&lt;0.05). Proteomics data were mined for Gene Ontology (GO) terms related to mitochondrial function (STRING V.12.0) (adjusted p&lt;0.05). RESULTS: Both men and women exhibited significant enhancements in complex I-mediated respiration and complex I+II maximal coupled respiration after HA (PRE-HA: M:P=0.009, P=0.026; F:P=0.016, P=0.011). No sex differences in mitochondria respiration were observed before or after HA. Before HA, skeletal muscle from women showed higher expression in 4 proteins (ND61, NDUFB1, COX1, ATP5MF) associated with 9 GO terms related to mitochondrial function compared to men. However, after HA, men exhibited higher expression in 14 proteins (MTX2, APOOL, DNAJC11, TIMM13, NDUFAB1, DNAJC11, MAVS, CHCHD4, NDUFAF4, ATP5PF, NDUFAS, UQCRH, SSBP1, ND3) associated with 21 mitochondria-related GO terms compared to women. CONCLUSION: Acclimation to heat stress is associated with positive mitochondrial adaptation in both men and women. Although enhancements in mitochondrial respiratory function in both men and women after HA, there were different skeletal muscle responses between men and women regarding the regulation of mitochondria-related proteins after a bout of exercise-heat stress. Funding: DoD BA200299. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.