Examine Sex Differences Research Articles

Comparing two MRI methods to assess fundamental sex differences in resting cerebral blood flow

Background: Cerebral blood flow (CBF) is a critical measurement for understanding healthy brain physiology prior to aging or neurologic diseases. Patterns of stroke and neurologic pathologies are often sex-specific. Therefore, it is important to understand basic sex differences in CBF, which are often associated with poor brain outcomes. Furthermore, prior literature examining sex differences in CBF is confounded by age, comorbidities, medications, lack of control of menstrual cycle and/or hormonal contraceptive use, and methodological discrepancies. The objective of this study was to compare two different magnetic resonance imaging (MRI) methods of quantifying CBF in young adults while controlling for the aforementioned confounding factors. We hypothesized that females would display higher CBF than males, and that there would be a high reliability between Arterial Spin Labeling (ASL) and 4D Flow MRI. Methods: 30 males and 26 females (23 ± 4yr) were studied on a single MRI (3T) visit. Subjects were fasted 8 hours and withheld caffeine, exercise, and NSAIDs for at least 24 hours. Females were not taking hormonal contraception and were studied on days 1-7 of the menstrual cycle. Microvascular CBF (mL/100g/min) was assessed via pseudo-continuous ASL (pcASL) while 4D Flow MRI acquired with Phase Contrast Vastly undersampled Isotropic Projection Reconstruction (PC VIPR) yielded macrovascular flow via the larger cerebral arteries, summing the internal carotid arteries and basilar artery for total CBF (mL/min). A T1-weighted MRI scan was used to provide brain volumes, allowing CBF from PC VIPR to be normalized and compared to ASL (mL/100g/min). The scans were taken consecutively, with subjects breathing normoxic gas while hemodynamics and end tidal CO2 were monitored. Regression analysis was used to determine reliability of two measures to test a sex difference in CBF. Results: Linear regression analysis demonstrated reliability between measurements of resting CBF via ASL and PC VIPR (p<0.001, R2=0.621). However, ASL measured significantly higher blood flows than PC VIPR in females (63.40 ± 8.55 vs. 56.47 ± 8.48 mL/100g/min, p<0.001) while male subjects had similar flows measured by both methods (45.75 ± 9.39 vs. 46.69 ± 8.19 mL/100g/min, p=0.464). Females displayed an increase in resting CBF compared to males, being 27.8% and 17.3% higher in the ASL and PC VIPR flow measurements (both p<0.001), respectively. Conclusions: These results demonstrate that ASL and PC VIPR CBF display a strong correlation, and that females have greater resting CBF compared to males that is detected by both MRI methods of quantification. However, ASL resulted in greater flow measurements in females, resulting in larger differences being observed (27.8% versus 17.3%). This discrepancy in CBF quantification warrants further investigation to determine the optimal mode of CBF measurement and comparison. Funding by NIH (HL150361). 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.

No sex differences in the cardiac responses during high altitude sojourn to 4300 m

Ascent to high altitude reduces oxygen availability and provokes compensatory cardiovascular responses. Females may exhibit attenuated hypoxic ventilatory responses compared to males, which could subsequently exaggerate the cardiovascular response to high altitude among females. The purpose of this study was to examine sex differences in cardiac responses during high altitude sojourn in young, healthy males and females. We hypothesized that females would exhibit a greater reduction in arterial oxygen saturation, and greater cardiac dysfunction compared to males. 17 healthy adults (8 males, 24±4 yrs, BMI 25.7±3.1 kg/m2; 9 females, 23±4 yrs, BMI 24.5±3.0 kg/m2) underwent cardiac assessment via echocardiography at 1400 m and after an 8-day ascent to 4300 m. Left ventricular (LV) systolic function was assessed via ejection fraction and fractional shortening. Diastolic function was assessed as the ratio between early and late mitral filling velocities (E:A ratio). The subendocardial viability ratio (SEVR) was derived from carotid tonometry, and carotid pressure waves were integrated with echocardiography derived measures of left ventricular ejection to estimate a left ventricular pressure-volume loop and calculate stroke work. Ascent from 1400 m to 4300 m resulted in reduced end-tidal CO2 (-Δ8±3 [males], -Δ8±2 mmHg [females], p<0.001), oxygen saturation (-Δ11±3 [males], -Δ11±5 % [females], p<0.001), and LV fractional shortening (-Δ7.9±7.5% [males] -Δ1.0±6.4 % [females], p=0.028) in both groups. Despite greater stroke work among males (p=0.002), high altitude-induced changes were not statistically different compared to females (+Δ35±184 [males], +Δ3±113 mL/mmHg [females]). Changes in LV ejection fraction (-Δ1.9±14.4 [males], -Δ1.5±18.7 % [females]) mitral E:A (-Δ0.33±0.53 [males], -Δ0.09±0.64 au [females]), and SEVR (-Δ0.06±0.33 [males], +Δ0.15±0.20 au [females]) from 1400 to 4300 m were not statistically different between sexes. Ascent from 1400 to 4300 m decreased end-tidal CO2, arterial oxygen saturation, and select metrics of LV systolic function (e.g., fractional shortening), but LV diastolic function, stroke work, and SEVR was preserved in both males and females. We observed no apparent sex differences in the effects of 8-day sojourn to 4300 m on arterial oxygen saturation, or cardiac systolic and diastolic function. Additional research is necessary to confirm these results in the context of longer-term altitude exposure and acclimatization, and in older populations (middle-aged and older adults). 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.

Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques

Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder. We performed slice electrophysiology recordings from BNST neurons in male and female monkeys following daily “open access” (22 h/day) to 4% ethanol and water for more than one year or control conditions. We found that BNST neurons from control females had reduced overall current density, hyperpolarization-activated depolarizing current (Ih), and inward rectification, as well as higher membrane resistance and greater synaptic glutamatergic release and excitatory drive, than those from control males, suggesting that female BNST neurons are more basally excited than those from males. Chronic alcohol drinking produced a shift in these measures in both sexes, decreasing current density, Ih, and inward rectification and increasing synaptic excitation. In addition, network activity-dependent synaptic inhibition was basally higher in BNST neurons of males than females, and alcohol exposure increased this in both sexes, a putative homeostatic mechanism to counter hyperexcitability. Altogether, these results suggest that the rhesus BNST is more basally excited in females than males and chronic alcohol drinking produces an overall increase in excitability and synaptic excitation. These results shed light on the mechanisms contributing to the female-biased susceptibility to neuropsychiatric diseases including co-expressed anxiety and alcohol use disorder.

Incongruence between Cardiorespiratory Fitness and Subjective Reports of Physical Activity in Multiple Sclerosis: A Focus on Sex Differences.

The link between moderate- to vigorous-intensity physical activity (MVPA) and cardiorespiratory fitness in individuals with multiple sclerosis (MS) remains unclear. This study examined the relationship between self-reported MVPA and objectively assessed cardiorespiratory fitness, emphasizing sex differences. 107 adults with MS (77 females), aged (mean ± standard deviation) 47.2 ± 10.2 years, were recruited from a local MS clinic. Fitness was measured as maximal oxygen uptake (V̇O2max) during a graded maximal exercise test using a recumbent stepper. MVPA (24-hour recall) was estimated as the duration of activities ≥ 3 MET (metabolic equivalent of task). MET-minutes were calculated by multiplying MET by duration. We explored sex differences in self-reported MVPA, cardiorespiratory fitness, and disability; examined sex differences in associations between these variables; and investigated whether MET-minutes of MVPA predicted V̇O2max in females and males. Mean V̇O2max was 24.79 mL·kg-1·min-1, indicating poor cardiorespiratory fitness levels, despite high levels of self-reported MVPA (mean = 412.5 MET-minutes). Fifty-three percent of males and 40% of females had V̇O2max levels below the 20th age- and sex-standardized population percentile, indicating poor cardiorespiratory fitness. There were statistically significant associations between MVPA and V̇O2max (Rho = 0.27, p = .01), as well as disability and V̇O2max (Rho = -0.35, p = .02), in females but not males. A regression model using sex, age, body mass, disability, and MVPA to estimate V̇O2max was valid in predicting V̇O2max values that were statistically equivalent to those measured in the laboratory in females but not males. However, the inclusion of MVPA did not add to the predictive value of this equation. Despite reporting high levels of MVPA, people with MS had poor cardiorespiratory fitness. MVPA, fitness, and disability were associated in females only, indicating that sex differences should be considered in fitness appraisal. Self-reported MVPA did not predict fitness, suggesting 24-hour recall may not be representative of true activity or fitness levels in persons with MS. Future work should examine sex differences in associations between MVPA and fitness using objective measures such as accelerometry.

The Prevalence of Parkinson's Disease in Poland: Regional and Sex-Related Differences.

Given the growing evidence for an environmental contribution to the etiology of Parkinson's disease (PD), searching for local and regional differences in PD prevalence in multiple areas across the world may further clarify the role of environmental toxins. To provide local and regional prevalence estimates of PD in Poland. We analyzed the prevalence of PD and its trend over the last decade (2010 to 2019) based on data from the National Health Fund in Poland. We specifically examined sex differences in PD prevalence, as well as differences across Polish regions. During the above period, the prevalence of PD in Poland increased from 226 per 100,000 to 269 per 100,000 inhabitants. Unexpectedly, we found that PD was 1.2-times more common in women than men. The increase in prevalence over the past decade was different between both sexes: an increase from 250 to 283 per 100,000 for women (13.3% increase), and from 200 to 254 per 100,000 for men (27.1% increase). In addition, we observed differences in prevalence across different Polish regions, with some regions having up to 51% lower prevalence rates than others. The prevalence of PD in Poland is in line with previously reported prevalence rates across Europe. However, unlike the situation in most of the world, PD was more prevalent in women than men. We discuss several possible explanations as well as potential measures that might help to reduce the growth of PD.

Examining Sex Differences in Autism Heritability

Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. To estimate the sex-specific heritability of ASD. This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age. Data analysis occurred from August 2022 to November 2023. Models were fitted to estimate the relative variance in risk for ASD occurrence owing to sex-specific additive genetics, shared environmental effects, and a common residual term. The residual term conceptually captured other factors that promote individual behavioral variation (eg, maternal effects, de novo variants, rare genetic variants not additively inherited, or gene-environment interactions). Estimates were adjusted for differences in prevalence due to birth year and maternal and paternal age by sex. The sample included 1 047 649 individuals in 456 832 families (538 283 males [51.38%]; 509 366 females [48.62%]). Within the entire sample, 12 226 (1.17%) received a diagnosis of ASD, comprising 8128 (1.51%) males and 4098 (0.80%) females. ASD heritability was estimated at 87.0% (95% CI, 81.4%-92.6%) for males and 75.7% (95% CI, 68.4%-83.1%) for females with a difference in heritability estimated at 11.3% (95% CI, 1.0%-21.6%). There was no support for shared environmental contributions. These findings suggest that the degree of phenotypic variation attributable to genetic differences (heritability) differs between males and females, indicating that some of the underlying causes of the condition may differ between the 2 sexes. The skewed sex ratio in ASD may be partly explained by differences in genetic variance between the sexes.

Sex differences in pain catastrophizing and its relation to the transition from acute pain to chronic pain

Background and importanceDifferences exist between sexes in pain and pain-related outcomes, such as development of chronic pain. Previous studies suggested a higher risk for pain chronification in female patients. Furthermore, pain catastrophizing is an important risk factor for chronification of pain. However, it is unclear whether sex differences in catastrophic thinking could explain the sex differences in pain chronification.ObjectivesThe aim of this study was to examine sex differences in pain catastrophizing. Additionally, we investigated pain catastrophizing as a potential mediator of sex differences in the transition of acute to chronic pain.Design, settings and participantsAdults visiting one of the 15 participating emergency departments in the Netherlands with acute pain-related complaints. Subjects had to meet inclusion criteria and complete questionnaires about their health and pain.Outcomes measure and analysisThe outcomes in this prospective cohort study were pain catastrophizing (short form pain catastrophizing) and pain chronification at 90 days (Numeric Rating Scale ≥ 1). Data was analysed using univariate and multivariable logistic regression models. Finally, stratified regression analyses were conducted to assess whether differences in pain catastrophizing accounted for observed differences in pain chronification between sexes.Main resultsIn total 1,906 patients were included. Females catastrophized pain significantly more than males (p < 0.001). Multiple regression analyses suggested that pain catastrophizing is associated with pain chronification in both sexes.ConclusionsThis study reported differences between sexes in catastrophic cognitions in the development of chronic pain. This is possibly of clinical importance to identify high-risk patients and ensure an early intervention to prevent the transition from acute to chronic pain.

Sex similarities and dopaminergic differences in interval timing.

Rodent behavioral studies have largely focused on male animals, which has limited the generalizability and conclusions of neuroscience research. Working with humans and rodents, we studied sex effects during interval timing that requires participants to estimate an interval of several seconds by making motor responses. Interval timing requires attention to the passage of time and working memory for temporal rules. We found no differences between human females and males in interval timing response times (timing accuracy) or the coefficient of variance of response times (timing precision). Consistent with prior work, we also found no differences between female and male rodents in timing accuracy or precision. In female rodents, there was no difference in interval timing between estrus and diestrus cycle stages. Because dopamine powerfully affects interval timing, we also examined sex differences with drugs targeting dopaminergic receptors. In both female and male rodents, interval timing was delayed after administration of sulpiride (D2-receptor antagonist), quinpirole (D2-receptor agonist), and SCH-23390 (D1-receptor antagonist). By contrast, after administration of SKF-81297 (D1-receptor agonist), interval timing shifted earlier only in male rodents. These data illuminate sex similarities and differences in interval timing. Our results have relevance for rodent models of both cognitive function and brain disease by increasing representation in behavioral neuroscience. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex differences in conditioned pain modulation effects and its associations with autonomic nervous system activities in healthy, younger individuals: a pilot study.

Sex differences in conditioned pain modulation (CPM) have not been sufficiently explored. This pilot study aimed to examine sex differences in CPM effects and associations between autonomic activities and CPM effects in healthy, younger individuals. University students were recruited from February to March 2021 and divided by sex. They remained seated for 10 minutes as a rest period, then immersed their right hands in cold water for 2 minutes as a cold period. The pressure pain threshold (PPT) was measured after each period, presenting the CPM index (%) using the formula: (PPTcold/PPTrest) × 100. Autonomic nervous system variables were calculated using the formula-(autonomic variablecold/autonomic variablerest) × 100-and suffixed by "index" such as low-frequency/high-frequency (LF/HF) index. Some psychological questionnaires were self-recorded. Sex differences in the CPM index were statistically compared, and a simple linear regression analysis between the CPM and autonomic indices was conducted. Thirty-two participants were analyzed (14 women and 18 men; aged 21.1 ± 0.6 and 20.9 ± 0.3 years, respectively). Conditioned pain modulation effects were not different at 127.0 ± 19.1% in women and 124.0 ± 18.7% in men. The LF/HF index, LF normalized unit (nu) index (LFnu), and HFnu index had significant predictor variables for the CPM index across overall samples. The LF/HF index and LFnu index were significant predictor variables for the CPM index for women but not for men. Conditioned pain modulation effects between groups seem to be similar. The LF/HF and LFnu indices in women were significant, indicating that descending pain modulations in women might be more associated with autonomic activities than those in men.

I want to play a game: Examining sex differences in the effects of pathological gaming, academic self-efficacy, and academic initiative on academic performance in adolescence

AbstractAlthough research has investigated the association between pathological gaming and academic performance in adolescence, the complexity of the relationship has not been thoroughly examined. This short longitudinal study aimed to investigate the interactions between pathological gaming, academic self-efficacy, academic initiative, and academic performance in an adolescent sample, focusing on sex differences. The participants (N = 2853; 50.1% boys) were students in the second and third years of upper secondary school. Their grade point average (GPA) at graduation the same year was obtained. The moderated mediation structural equation model results showed that academic self-efficacy, directly and indirectly through academic initiative, impacted later GPA. There was no direct effect of pathological gaming on academic initiative or GPA. However, academic self-efficacy moderated the impact of pathological gaming on GPA for boys. In other words, boys with increased pathological gaming tended to achieve poorer grades in school if they experienced a strong academic self-efficacy. This study contributes to the understanding of the complex interplay between sex, pathological gaming, academic self-efficacy, academic initiative, and academic performance. We suggest that future research examines confidence or other relevant factors as explanatory mechanisms in the relationships between pathological gaming, academic self-efficacy, and GPA, particularly in male samples.

Sex Differences in Response Inhibition–Related Neural Predictors of Posttraumatic Stress Disorder in Civilians With Recent Trauma

BackgroundFemales are more likely to develop posttraumatic stress disorder (PTSD) than males. Impaired inhibition has been identified as a mechanism for PTSD development, but studies on potential sex differences in this neurobiological mechanism and how it relates to PTSD severity and progression are relatively rare. Here, we examined sex differences in neural activation during response inhibition and PTSD following recent trauma. MethodsParticipants (n = 205, 138 female sex assigned at birth) were recruited from emergency departments within 72 hours of a traumatic event. PTSD symptoms were assessed 2 weeks and 6 months posttrauma. A Go/NoGo task was performed 2 weeks posttrauma in a 3T magnetic resonance imaging scanner to measure neural activity during response inhibition in the ventromedial prefrontal cortex, right inferior frontal gyrus, and bilateral hippocampus. General linear models were used to examine the interaction effect of sex on the relationship between our regions of interest and the whole brain, PTSD symptoms at 6 months, and symptom progression between 2 weeks and 6 months. ResultsLower response inhibition–related ventromedial prefrontal cortex activation 2 weeks posttrauma predicted more PTSD symptoms at 6 months in females but not in males, while greater response inhibition–related right inferior frontal gyrus activation predicted lower PTSD symptom progression in males but not females. Whole-brain interaction effects were observed in the medial temporal gyrus and left precentral gyrus. ConclusionsThere are sex differences in the relationship between inhibition-related brain activation and PTSD symptom severity and progression. These findings suggest that sex differences should be assessed in future PTSD studies and reveal potential targets for sex-specific interventions.

Sex Differences in Recreational Fear

In this article I examine sex differences related to recreational fear, including theory on the evolved fear system, morbid curiosity, and disgust sensitivity. I use an evolutionary framework to argue that recreational fear can appeal specifically to women, with a focus on media preferences. Through an analysis of the true crime podcast My Favorite Murder and the slasher movie Halloween, I argue that both examples are popular with women, because they provide recreational fear in a way that aligns with women’s fears, curiosity, and threshold for disgust. They are relatively less scary than many other forms of frightening media. They also center around the fear of hostile conspecifics, which is common for women to experience. Because of this, they appeal to women’s morbid curiosity towards dangerous people and their motives. Lastly, they are careful to avoid excessive disgusting stimuli that could discourage a female audience from engaging.

Abstract P290: Telephone Lifestyle Coaching - Sex Differences in Referrals and Enrollment During National Implementation

Objectives: Telephone Lifestyle Coaching (TLC) is an evidence-based program providing individualized telephone coaching and self-management support to Veterans working on personalized, healthy living SMART goals. Given the flexibility of telephone support, we explored sex differences in TLC referrals and enrollment. We focus on sex to identify potential opportunities with virtual/telephone prevention programs in VA. Methods: Since March 2019, 44 VA sites have implemented TLC nationwide. Under VA’s QUERI rapid response evaluation program, we examined sex differences in referrals and enrollment with logistic regression controlling for demographics, mental and physical health, prior participation in a VA Whole Health Program and VA’s MOVE! Weight Management Program, and site-level clustering. The sample included all Veterans with at least one primary care visit one year prior to starting TLC. Results: As of 12/31/22, a total of 11,719 Veterans had at least one TLC referral, with 9,514 enrolled (82%), totaling 122,233 encounters. For both referrals and enrollment, mean age was 54, with 33% female, 29% Black, 7% Hispanic, and 34% with rural residence. In adjusted models, female Veterans had increased odds of being referred (OR=2.40, CI:1.89-3.05) and enrolling (OR=1.27, CI:1.13-1.42) compared to male Veterans. Odds of referral were higher for younger Veterans (OR=0.98, CI:0.97-0.98), those with depression (OR=1.62, CI:1.46-1.81), PTSD (OR=1.45, CI:1.21-1.73), overweight/obesity (OR=2.38, CI:1.58-3.57), at least one cardiovascular (CV) risk (OR=1.94, CI:1.63-2.30), and prior participation in Whole Health (OR=2.46, CI:1.74-3.51) or MOVE! (OR=6.40; CI:4.02-10.19). Similar associations with enrollment were observed, except Veterans with depression had decreased odds of enrollment (OR=0.84, CI:0.750.93), and effects for PTSD and CV risks were not significant. Conclusions: TLC demonstrated success in reach and engagement of female Veterans at rates above their national proportions in VA care. Referrals targeted weight and CV risk consistent with Veteran clinical needs. Our findings suggest that prior participation with MOVE! and Whole Health may facilitate engagement. Mental health diagnoses were not a barrier to referral, but depression status may reduce patient participation. Impact: TLC and virtual modalities of lifestyle coaching may have broader application for reaching and engaging female Veterans, as well as Veterans with mental health and CV risks who can benefit from health behavior change to optimize care.

Sex Differences in the Antidepressant and Neurocognitive Effects of Nonconvulsive Electrotherapy in Patients with Treatment-Refractory Depression.

The objective of this study was to examine sex differences in the antidepressant and neurocognitive effects of adjunctive nonconvulsive electrotherapy (NET) in patients with treatment-refractory depression (TRD), which has not yet been thoroughly investigated. The study enrolled 20 patients with TRD, comprising 11 males and 9 females, who underwent a series of 6 NET sessions. The 17-item Hamilton Depression Rating Scale (HAMD-17) was used to assess depressive symptoms, response, and remission at baseline and after the first, third, and sixth NET sessions. The Wisconsin Card Sorting Test (WCST) was used to assess neurocognitive function at baseline and after the sixth NET session. After completing 6 NET sessions, female patients experiencing TRD exhibited a higher inclination toward achieving an antidepressant response (77.8% vs. 45.5%, P = .197) and antidepressant remission (22.2% vs. 0%, P = .189) when compared to their male counterparts. No significant differences were observed in changes in the HAMD-17 and WCST subscale scores (all P > .05), including completing classification number, total error number, persistent error number, and random error number between males and females. Additionally, no significant correlations were observed between baseline WCST subscale scores and changes in HAMD-17 scores or endpoint scores, irrespective of sex (all P > .05). These pilot findings suggest that female patients with TRD exhibited increased rates of achieving antidepressant response and remission after undergoing NET. However, further studies should be conducted to confirm these findings.

Artificial intelligence based prediction model of in-hospital mortality among females with acute coronary syndrome: for the Jerusalem Platelets Thrombosis and Intervention in Cardiology (JUPITER-12) Study Group.

Despite ongoing efforts to minimize sex bias in diagnosis and treatment of acute coronary syndrome (ACS), data still shows outcomes differences between sexes including higher risk of all-cause mortality rate among females. Hence, the aim of the current study was to examine sex differences in ACS in-hospital mortality, and to implement artificial intelligence (AI) models for prediction of in-hospital mortality among females with ACS. All ACS patients admitted to a tertiary care center intensive cardiac care unit (ICCU) between July 2019 and July 2023 were prospectively enrolled. The primary outcome was in-hospital mortality. Three prediction algorithms, including gradient boosting classifier (GBC) random forest classifier (RFC), and logistic regression (LR) were used to develop and validate prediction models for in-hospital mortality among females with ACS, using only available features at presentation. A total of 2,346 ACS patients with a median age of 64 (IQR: 56-74) were included. Of them, 453 (19.3%) were female. Female patients had higher prevalence of NSTEMI (49.2% vs. 39.8%, p < 0.001), less urgent PCI (<2 h) rates (40.2% vs. 50.6%, p < 0.001), and more complications during admission (17.7% vs. 12.3%, p = 0.01). In-hospital mortality occurred in 58 (2.5%) patients [21/453 (5%) females vs. 37/1,893 (2%) males, HR = 2.28, 95% CI: 1.33-3.91, p = 0.003]. GBC algorithm outscored the RFC and LR models, with area under receiver operating characteristic curve (AUROC) of 0.91 with proposed working point of 83.3% sensitivity and 82.4% specificity, and area under precision recall curve (AUPRC) of 0.92. Analysis of feature importance indicated that older age, STEMI, and inflammatory markers were the most important contributing variables. Mortality and complications rates among females with ACS are significantly higher than in males. Machine learning algorithms for prediction of ACS outcomes among females can be used to help mitigate sex bias.

Network analysis to examine sex differences linked to emotional well-being in cardiovascular disease.

Psychosocial dimensions are essential to guarantee an optimal approach to improve emotional well-being in patients with cardiovascular disease (CVD). There is evidence of sex differences regarding these dimensions. Thus, the connections between them are crucial to implement personalized therapies. Network model analyses were conducted on data from 593 CVD patients. The models included scores from the Hospital Anxiety and Depression Scale (HADS), positive (PA) and negative affect (NA), positivity (PS), satisfaction of life (SLS), social support (SS), self-efficacy on emotion regulation (RESE), cardiac self-efficacy (CSE) and the Short Form-12 Health Survey. The main sex differences were found in: PA-PS (p = 0.03), SS-RESE (p = 0.04), for which the positive associations are stronger for men than for women and PA-RESE (p < 0.01) for which the positive association is stronger for women than for men. These nuances should be considered to implement tailored and integrative therapies for each CVD patient.

Characteristics, management, and outcomes in women and men with congestive heart failure in 40 countries at different economic levels: an analysis from the Global Congestive Heart Failure (G-CHF) registry

There is a paucity of data on the clinical characteristics, management, and outcomes of women compared with men with heart failure in low-income and middle-income countries compared with high-income countries. We examined sex differences in risk factors, clinical characteristics, and treatments, and prospectively assessed the risk of heart failure hospitalisation and mortality in patients with heart failure in 40 high-income, middle-income, and low-income countries. Participants aged 18 years or older with heart failure were enrolled from Dec 20, 2016, to Sept 9, 2020 in the prospective Global Congestive Heart Failure (G-CHF) study from 257 centres in 40 high-income, middle-income, and low-income countries. Participants were followed up until May 25, 2023. We recorded the demographic characteristics, medical history, and treatments of participants. We prospectively recorded data on heart failure hospitalisation and mortality by sex in the overall study, according to country economic status, and according to level of left ventricular ejection fraction (LVEF). 23 341 participants (9119 [39·1%] women and 14 222 [60·1%] men) were recruited and followed up for a mean of 2·6 years (SD 1·4). The mean age of women in the study was 62 years (SD 17) compared with 64 years (14) in men. Fewer women than men had an LVEF of 40% or lower (51·7% women vs 66·2% men). By contrast, more women than men had an LVEF of 50% or higher (33·2% women vs 18·6% men). Hypertensive heart failure was the most common aetiology in women (25·5% women vs 16·8% men), whereas ischaemic heart failure was the most common aetiology in men (45·6% men vs 26·6% women). Signs and symptoms of congestion were more common in women than men: 42·6% of women had a New York Heart Association functional class of III or IV compared with 37·9% of men. The use of heart failure medications and cardiac tests did not differ systematically between the sexes, although implantable cardioverter defibrillator (ICD) implantation was lower among women than men (8·7% women vs 17·2% men). The adjusted risk of heart failure hospitalisation was similar in women and men (women-to-men adjusted hazard ratio [HR] 0·99 [95% CI 0·92-1·05]). This pattern was consistent within groups of countries categorised by economic status, geographical region, and by LVEF level. However, women had a lower adjusted risk of mortality (women-to-men adjusted HR 0·79 [95% CI 0·75-0·84]) despite adjustments for prognostic factors-a pattern which was consistently observed across groups of countries irrespective of economic status, geography, and LVEF levels of patients. The underlying cause of heart failure and ejection fraction phenotype differ between women and men, as do the severity of symptoms. Heart failure treatments (except ICD use) were not consistently in favour of one sex. Paradoxically, while the rates of hospitalisations were similar among women and men, the risk of death was lower among women. These patterns were consistent regardless of the economic status of the countries. The higher mortality among men is unexplained and warrants further study. Bayer.

Sex differences in cognitive function trajectories and their determinants in older adults: Evidence from the Chinese longitudinal healthy longevity survey.

To examine sex differences in the cognitive trajectories of a nationally representative sample of older people living in China and to explore potential determinants of these trajectories. The study included 2230 women and 2171 men who were cognitively healthy and aged over 60 at the first observation from the Chinese Longitudinal Healthy Longevity Survey based on the 2008-2018 cohort. Cognitive function was measured using the Chinese version of the Mini-Mental State Examination (MMSE). Group-based trajectory modeling was used to identify potential heterogeneity of longitudinal changes over the 10years in each gender. Logistic regression was used to investigate associations between baseline characteristics (age, education, fertility history, sleep length, physical activity, and health status and behaviors) and trajectory classes. Three trajectories (labeled stable, slow decline, and rapid decline) were identified according to the changes in MMSE scores for both women and men. For the women, both the slow and rapid decline groups accounted for a larger proportion (14.7% and 11.0%, respectively) than the male decline groups (8.1% and 6.6%, respectively), and the women had a lower baseline MMSE score with a faster decline. In the multivariable logistic regression analyses, older age, less education, older age at first birth, poorer functional abilities, hearing impairment, and lower baseline MMSE scores were significantly associated with cognitive decline in both the female and male groups compared to the stable group. For the women, sleeping over 9h was also associated with a rapid cognitive decline trajectory, while current exercise and being overweight/obese were protective factors against cognitive decline. The women had an overall more serious cognitive decline than men. The potential determinants of cognitive decline identified in this study could be considered for developing specific intervention strategies aimed at promoting a healthy brain and preventing cognitive decline in different sexes, especially in low-income and developing countries.

Sex differences in response to cognitive behavioural therapy for insomnia: A chart review of 455 patients with chronic insomnia

BackgroundInsomnia is more prevalent in females, however studies examining sex differences in response to insomnia treatment are scarce. This study assessed sex-specific differences in cognitive behavioural therapy for insomnia (CBT-I)-related changes in insomnia symptoms in a large clinical cohort. MethodsA chart review was conducted of a clinical cohort (females n = 305, males n = 150) referred to a sleep clinic. Participants had a registered psychologist confirm diagnosis of chronic insomnia according to DSM-IV/V criteria and a Level 1 or 2 sleep study. Daily sleep diaries and questionnaires including the Insomnia Severity Index (ISI), Flinders Fatigue Scale (FFS), the Daytime Feelings and Functioning Scale (DFFS), and the Depression, Anxiety and Stress Scale-21 items (DASS), were administered at baseline, post-treatment, and three-month follow-up. Linear mixed models determined interactions between sex and timepoint on symptoms. ResultsMean (SD) age was 51.7 yrs (15.7, range = 18-90 yrs), and mean BMI was 26.3 kg/m2 (4.9), neither of which differed by sex. At pre-treatment, females demonstrated higher objective total sleep time (min) [343.5 (97.6) vs 323.8 min (92.1), p = 0.044], ISI [19.7 (4.2) vs 18.6 (4.4), p = 0.033], and FFS scores [19.2 (6.0) vs 16.9 (7.2), p = 0.003]. Compared to males, females experienced a greater reduction in FFS and DFFS scores and DASS depressive symptoms (p for interaction: 0.017, 0.043, 0.016 respectively) from baseline to follow-up. The greater reduction in depressive symptoms did not persist after controlling for age, BMI, and sleep apnea severity. Subjective total sleep time similarly increased across treatment for both males [baseline: 335.7 (15.1), post: 357.9 (15.5)] and females [baseline: 318.3 (10.4), post: 354.4 (10.7)], p for interaction: 0.22. ConclusionFemales and males experience similar, substantial benefits from CBT-I after accounting for comorbidities, suggesting the same treatment can resolve insomnia in both sexes.

Sex differences in body temperature and neural power spectra in response to repeated restraint stress

Repeated stress is associated with an increased risk of developing psychiatric illnesses such as post-traumatic stress disorder (PTSD), which is more common in women, yet the neurobiology behind this sex difference is unknown. Habituation to repeated stress is impaired in PTSD, and recent preclinical studies have shown that female rats do not habituate as fully as male rats to repeated stress, which leads to impairments in cognition and sleep. Further research should examine sex differences after repeated stress in other relevant measures, such as body temperature and neural activity. In this study, we analyzed core body temperature and EEG power spectra in adult male and female rats during restraint, as well as during sleep transitions following stress. We found that core body temperature of male rats habituated to repeated restraint more fully than female rats. Additionally, we found that females had a higher average beta band power than males on both days of restraint, indicating higher levels of arousal. Lastly, we observed that females had lower delta band power than males during sleep transitions on Day 1 of restraint, however, females demonstrated higher delta band power than males by Day 5 of restraint. This suggests that it may take females longer to initiate sleep recovery compared with males. These findings indicate that there are differences in the physiological and neural processes of males and females after repeated stress. Understanding the way that the stress response is regulated in both sexes can provide insight into individualized treatment for stress-related disorders.