Large Sex Differences Research Articles

National gender equality and sex differences in Machiavellianism across countries

Machiavellianism is characterized by a focus on self-interest and a desire to achieve personal goals at any cost. Research consistently found that, on average, men score higher on Machiavellianism than women. However, the factors contributing to this sex difference remain unclear. The present research examined whether sex differences in Machiavellianism vary across countries and whether national levels of gender inequality are related to these differences. We analyzed Machiavellianism scores of 56,936 adults across 48 countries. We operationalized gender inequality at national level using two indices (the Gender Inequality Index and the Global Gender Gap Index) and assessed Machiavellianism at the individual level using the MACH-IV scale. Multilevel modeling indicated that men scored higher in Machiavellianism than women, with a larger sex difference in countries with higher levels of gender equality, irrespective of the gender inequality index used. This pattern emerged because women’s MACH-IV scores decreased as national gender equality increased, whereas men’s scores remained stable. We discuss the relevance of these findings for the literature on sex differences in personality and gender equality paradox.

Individual differences in proprioceptive reorientation: a study on body characteristics and Posturography

ABSTRACT Spatial reorientation guided by the proprioceptive information derived from walking on a slanted floor has revealed large individual and sex differences. Here we addressed the role of body characteristics and measures of stability and balance-related sensory function from computerized dynamic posturography. Blindfolded participants walked in a slanted arena and had to identify the uphill direction (Perceptual task) and use the slope to remember the location of a target object (Memory task). Male participants performed better in the Perceptual task. In the Memory task, heavier participants made smaller errors, suggesting that body mass may influence how we navigate in the environment.

Sex and mental health are related to subcortical brain microstructure

Some mental health problems such as depression and anxiety are more common in females, while others such as autism and attention deficit/hyperactivity (AD/H) are more common in males. However, the neurobiological origins of these sex differences are poorly understood. Animal studies have shown substantial sex differences in neuronal and glial cell structure, while human brain imaging studies have shown only small differences, which largely reflect overall body and brain size. Advanced diffusion MRI techniques can be used to examine intracellular, extracellular, and free water signal contributions and provide unique insights into microscopic cellular structure. However, the extent to which sex differences exist in these metrics of subcortical gray matter structures implicated in psychiatric disorders is not known. Here, we show large sex-related differences in microstructure in subcortical regions, including the hippocampus, thalamus, and nucleus accumbens in a large sample of young adults. Unlike conventional T1-weighted structural imaging, large sex differences remained after adjustment for age and brain volume. Further, diffusion metrics in the thalamus and amygdala were associated with depression, anxiety, AD/H, and antisocial personality problems. Diffusion MRI may provide mechanistic insights into the origin of sex differences in behavior and mental health over the life course and help to bridge the gap between findings from experimental, epidemiological, and clinical mental health research.

The association between 2D:4D digit ratio and sex-typed play in children with and without siblings

The 2D:4D digit ratio is commonly used as a surrogate possibly reflecting prenatal testosterone levels. Indirect evidence comes from studies investigating the association between 2D:4D and human characteristics that likely relate to prenatal testosterone. In children, sex-typed play reveals large sex differences early in development and an influence of prenatal testosterone is likely. Findings on the association between 2D:4D and children’s sex-typed play are heterogeneous and other influences on the development of sex-typed play have been suggested, most of all social influences like siblings, their sex and birth order. The current study examined the association between right and left 2D:4D, a proposed surrogate for prenatal testosterone exposure, which was assessed in right and left hands of N = 505 6-month-old children, and sex-typed play behavior, which was evaluated 3.5 years later using the Pre-School Activities Inventory (PSAI), and the influence of siblings. To capture differential effects of siblings’ sex and birth order, dummy-coded variables were used reflecting having no siblings as well as older or younger sisters or brothers. Multiple regression models were used to investigate the association between PSAI scores and sex, right and left 2D:4D, being a singleton as well as having an older or younger sister or brother. It was shown that sex and having an older brother were significant predictors for sex-typed play. Effects were further disentangled by conducting separate regression analyses in boys and girls. In boys, a significant association between PSAI scores and having an older brother was revealed, in girls, no significant associations were found. Results are discussed highlighting the non-significant association between 2D:4D and children’s sex-typed play, which weakens the applicability of 2D:4D as a surrogate reflecting influences of prenatal T. Further, the importance of social factors like siblings on children’s sex-typed play is discussed.

Healthy women show more experimentally induced central sensitization compared with men.

Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. In 66 subjects (33 women), a thermal CS induction protocol was applied to the dorsum of one foot and a sham protocol to the other. Spatial extent [cm 2 ] of secondary mechanical hyperalgesia (SMH) and dynamic mechanical allodynia were assessed as subjective CS proxy measures, relying on verbal feedback. Changes in nociceptive withdrawal reflex magnitude (NWR-M) and response rate (NWR-RR) recorded through surface electromyography at the biceps and rectus femoris muscles were used as objective CS proxies. The effect of the CS induction protocol on SMH was higher in women than in men (effect size 2.11 vs 1.68). Nociceptive withdrawal reflex magnitude results were statistically meaningful for women (effect size 0.31-0.36) but not for men (effect size 0.12-0.29). Differences between men and women were not meaningful. Nociceptive withdrawal reflex response rate at the rectus femoris increased in women after CS induction and was statistically different from NWR-RR in men (median differences of 13.7 and 8.4% for 120 and 140% reflex threshold current). The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.

Inter-individual, hemispheric and sex variability of brain activations during numerosity processing

Numerosity perception is a fundamental and innate cognitive function shared by both humans and many animal species. Previous research has primarily focused on exploring the spatial and functional consistency of neural activations that were associated with the processing of numerosity information. However, the inter-individual variability of brain activations of numerosity perception remains unclear. In the present study, with a large-sample functional magnetic resonance imaging (fMRI) dataset (n = 460), we aimed to localize the functional regions related to numerosity perceptions and explore the inter-individual, hemispheric, and sex differences within these brain regions. Fifteen subject-specific activated regions, including the anterior intraparietal sulcus (aIPS), posterior intraparietal sulcus (pIPS), insula, inferior frontal gyrus (IFG), inferior temporal gyrus (ITG), premotor area (PM), middle occipital gyrus (MOG) and anterior cingulate cortex (ACC), were delineated in each individual and then used to create a functional probabilistic atlas to quantify individual variability in brain activations of numerosity processing. Though the activation percentages of most regions were higher than 60%, the intersections of most regions across individuals were considerably lower, falling below 50%, indicating substantial variations in brain activations related to numerosity processing among individuals. Furthermore, significant hemispheric and sex differences in activation location, extent, and magnitude were also found in these regions. Most activated regions in the right hemisphere had larger activation volumes and activation magnitudes, and were located more lateral and anterior than their counterparts in the left hemisphere. In addition, in most of these regions, males displayed stronger activations than females. Our findings demonstrate large inter-individual, hemispheric, and sex differences in brain activations related to numerosity processing, and our probabilistic atlas can serve as a robust functional and spatial reference for mapping the numerosity-related neural networks.

Sex-biased genome-editing effects of CRISPR-Cas9 across cancer cells dependent on p53 status

The CRISPR-Cas9 system has emerged as the dominant technology for gene editing and clinical applications. One major concern is its off-target effect after the introduction of exogenous CRISPR-Cas9 into cells. Several previous studies have investigated either Cas9 alone or CRISPR-Cas9 interactions with p53. Here, we reanalyzed previously reported data of p53-associated Cas9 activities and observed large significant sex differences between p53-wildtype and p53-mutant cells. To expand the impact of this finding, we further examined all protein-coding genes for sex-specific dependencies in a large-scale CRISPR-Cas9 screening dataset from the DepMap project. We highlighted the p53-dependent sex bias of gene knockouts (including MYC, PIK3CA, KAT2B, KDM4E, SUV39H1, FANCB, TLR7, and APC2) across cancer types and potential mechanisms (mediated by transcriptional factors, including SOX9, FOXO4, LEF1, and RYBP) underlying this phenomenon. Our results suggest that the p53-dependent sex bias may need to be considered in future clinical applications of CRISPR-Cas9, especially in cancer.

Large sex differences in vulnerability to circulatory-system disease under current and future climate in Bucharest and its rural surroundings

Circulatory-system diseases (CSDs) are responsible for 50–60% of all deaths in Romania. Due to its continental climate, with cold winters and very warm summers, there is a strong temperature dependence of the CSD mortality. Additionally, within its capital Bucharest, the urban heat island (UHI) is expected to enhance (reduce) heat (cold)-related mortality. Using distributed lag non-linear models, we establish the relation between temperature and CSD mortality in Bucharest and its surroundings. A striking finding is the strong temperature-related response to high urban temperatures of women in comparison with men from the total CSDs mortality. In the present climate, estimates of the CSDs attributable fraction (AF) of mortality at high temperatures is about 66% higher in Bucharest than in its rural surroundings for men, while it is about 100% times higher for women. Additionally, the AF in urban areas is also significantly higher for elderly people, and for those with hypertensive and cerebrovascular diseases than in the rural surroundings. On the other hand, in rural areas, men but especially women are currently more vulnerable with respect to low temperatures than in the urban environment. In order to project future thermal-related mortality, we have used five bias-corrected climate projections from regional circulation models under two climate-change scenarios, RCP4.5 and RCP8.5. Analysis of the temperature-mortality associations for future climate reveals the strongest signal under the scenario RCP8.5 for women, elderly people as well as for groups with hypertensive and cerebrovascular diseases. The net AF increase is much larger in urban agglomeration for women (8.2 times higher than in rural surroundings) and elderly people (8.5 times higher than in rural surroundings). However, our estimates of thermal attributable mortality are most likely underestimated due to the poor representation of UHI and future demography.

The genetics of gaming: A longitudinal twin study.

Gaming is a popular past-time activity among children and adolescents, but it there is also a possible link to negative consequences such as psychological distress and lowered academic achievement. However, there are fundamental knowledge gaps remaining regarding central characteristics of gaming such as heritability, stability over time, and sex differences. We examined the genetic and environmental contribution to gaming behavior, including sex differences, continuity and change, in a longitudinal cohort of twins. This is the first longitudinal twin study on gaming, involving 32,006 twins in Sweden. Parents were asked about the twins' gaming at ages 9, 15 and 18. We used univariate and multivariate twin analyses to estimate the relative contribution of genetic and environmental influences at each time-point as well as across time. Sex-differences were also explored. The results showed large sex differences, where genetics explained more of the variance for boys (31.3%-62.5% depending on age) than for girls (19.4%-23.4%). Genetic factors explained an increasing amount of the variance for boys (31.3% at age 9, 62.5% at age 15 and 53.9% at age 18). Shared environmental factors explained a larger proportion of the variance among girls, which remained relatively stable over time (70.5% at age 9, 61.8% at age 15 and 60.5% at age 18). The results also indicated that most of the variance came from genetic and environmental sources specific to each age. Compared to many other behavioral phenotypes, such as gambling, gaming was relatively unstable with a large degree of genetic innovation. There were large sex differences in the contribution of genetic and environmental factors. This suggests that excessive gaming could be the result of age- and sex-specific genetic and environmental factors, and should be taken into account when mapping gaming behaviors, since these behaviors might be under continual etiological transformation.

Abstract 82: Sex Differences In Recurrent Stroke: Twenty-Year Trends From A Population-Based Study

The growing number of stroke survivors in the US, especially among women, makes understanding sex-specific trends in recurrent strokes crucial. Yet, such data are rare. We estimated 20-year sex-specific trends in recurrence in a population-based stroke study. Methods: We included first-ever ischemic strokes (IS) ascertained between January 1, 2000 and December 31, 2019 from the Brain Attack Surveillance in Corpus Christi (BASIC) Project in South Texas. Time to recurrence was calculated from first-ever IS to recurrence, death, or December 31, 2019, whichever came first. We estimated the cumulative incidence function (CIF) of recurrence by a multivariable Fine-Gray subdistribution hazard model, which accounted for the competing risk of death. An interaction term between calendar year and sex was used to generate 1-year and 5-year sex-specific trends in risks of recurrence between 2000-2019 from the fitted CIF. Results: Among the 5,752 IS (median age 69, 49.9% women), 786 (13.7%) had recurrences over a median of 7.6 years of follow-up and 2,653 (46.1%) died over a median of 3.7 years of follow-up. Women had significantly higher adjusted 1-year and 5-year risks of recurrence than men in 2000 (Figure). One-year and 5-year risk of recurrence declined in both sexes over time but women experienced larger declines such that the risks were similar between both sexes around 2009 but higher among men after that. The largest sex difference in recurrence was in the 5-year risk in 2000 with women having 5.0% (1.5%-8.4%) higher risk. Conclusions: The welcoming trends in recurrent strokes suggest successful secondary stroke prevention, especially in women, where greater declines were noted.

Integrated analyses reveal evolutionarily conserved and specific injury response genes in dorsal root ganglion

Rodent dorsal root ganglion (DRG) is widely used for studying axonal injury. Extensive studies have explored genome-wide profiles on rodent DRGs under peripheral nerve insults. However, systematic integration and exploration of these data still be limited. Herein, we re-analyzed 21 RNA-seq datasets and presented a web-based resource (DRGProfile). We identified 53 evolutionarily conserved injury response genes, including well-known injury genes (Atf3, Npy and Gal) and less-studied transcriptional factors (Arid5a, Csrnp1, Zfp367). Notably, we identified species-preference injury response candidates (e.g. Gpr151, Lipn, Anxa10 in mice; Crisp3, Csrp3, Vip, Hamp in rats). Temporal profile analysis reveals expression patterns of genes related to pre-regenerative and regenerating states. Finally, we found a large sex difference in response to sciatic nerve injury, and identified four male-specific markers (Uty, Eif2s3y, Kdm5d, Ddx3y) expressed in DRG. Our study provides a comprehensive integrated landscape for expression change in DRG upon injury which will greatly contribute to the neuroscience community.

Sickness absence and disability pension in white-collar workers in the trade and retail industry

Abstract Background Very little is known about sickness absence among white-collars workers in the trade and retail industry, despite being a large and important group on the labour market. The aim was to investigate future sickness absence (SA) and disability pension (DP) in a cohort of privately employed white-collar employees in the trade and retail industry. Methods A prospective population-based cohort study of all 192,077 such white-collar workers (44% women) in Sweden in 2012, using linked microdata from three nationwide registers covering 2012-2016. Prevalence and mean number of SA and/or DP net days/year in general and by diagnoses categories were calculated for all and also stratified by sex. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) between sociodemographic and work-related factors and future SA/DP. Results The proportion who had SA and/or DP was higher in women (10-13%, depending on year) than men (4-6%) each year. Each studied year, women had more mean SA/DP net days than men in the entire cohort, however, among those who had SA and/or DP, there were no gender differences regarding the mean number of net days. The mean number of SA/DP net days increased for both women and men each year, especially SA due to mental diagnoses. SA in 2012 was the strongest factor associated with SA/DP in 2016 (OR women 3.28, 95% CI 3.09-3.47; men 4.10, 95% CI 3.76-4.48). Work-related factors were only weakly or insignificantly associated with future SA/DP. The ORs for most factors were stronger for men than for women. Conclusions More knowledge about the mechanisms behind these results are needed. Some SA/DP measures showed large sex-differences, others not - it is important to use different measures to show the complexity of these phenomena. Several factors were more strongly associated with SA/DP among men than among women, indicating that there are other factors of importance for women. Key messages

Participation Rates Of Female And Male Runners Predict Marathon Performance

Males are ~11% faster than females in marathon running at the elite level, largely due to sex differences in physiology. This sex difference in performance, however, is often greater than 11% especially in older runners with lower proportion of female runners. PURPOSE: To determine whether the sex difference in marathon performance is predicted by the number of male to female runners and how this prediction changes among lower placed runners within an age group. METHODS: The number of male and female finishers within 10-year age groups (20 - 79 years) and the running times of the top 10 age group runners who competed in the Chicago marathon (1996-2018) and New York City (NYC) marathon (1980-2019) were retrieved from public databases. Univariate ANOVA and correlation analysis determined differences and associations between the ratios of male:female finishers and the sex difference in velocity. RESULTS: The ratio of male:female runners increased with older age groups (p < 0.001) and place of the runner from 1st to 10th place (p < 0.001) for both marathons. Males were faster than females across all age groups for the Chicago (17.4% ± 0.2%) and NYC marathon (18.8% ± 0.1%). The sex difference, however, was smallest for 1st placed runners and largest for the 10th placed for Chicago (14.8 ± 0.5% to 18.5 ± 0.4%) and NYC (15.9 ± 0.4% to 20.3 ± 0.3%). The ratio of the number of males:females was correlated with the sex difference in velocity (%) for Chicago (n = 2325, r2 = 0.28, p < 0.001) and NYC (n = 4223, r2 = 0.32, p < 0.001) in that fewer females relative to males indicated a larger sex difference in velocity. The strength of the associations progressively increased between 1st and 10th place. Combined for both marathons, the association for 1st place was r2 = 0.20 (p < 0.001, n = 709) and 10th place was r2 = 0.38 (p < 0.001, n = 614). Thus, the number of males:females explained 20% of the variance in the sex differences in velocity of 1st placed runners but 38% of the sex difference in 10th placed runners. CONCLUSION: Lower participation rates of females in the marathon potentially masks an accurate understanding of the contribution of physiological sex differences, especially in lower ranked and older runners. This data provides a window into the impact of the inequity of testing less females than males in studies of human performance.

Sex Differences In Marathon Performance Are Larger In The Past Decade Than Expected Physiologically

The sex difference in performance of marathon runners historically has been larger than explained by physiological differences, possibly reflecting lower participation of females (1). The number of female participants across all age groups has increased in recent decades, but it is unclear if the sex difference in performance has continued to diminish. PURPOSE: To determine the sex difference in performance in the New York City (NYC) marathon across age groups, and with the place of runner (1st-10th place), in the past decade and relative to earlier published data (1980-2010) (1). METHODS: Running times of the top 10 placed male and female finishers (5-year age groups) who competed in the NYC marathon (2009-2019) were retrieved from a public database (https://results.nyrr.org/races). Univariate ANOVA determined the sex difference in the mean running velocity; (% Δ males and females/males) across age groups and place. RESULTS: The sex difference in running velocity increased across age groups (p < 0.001). For 2015-2019, the 30-39-year olds had the smallest difference (12.9 ± 0.5%) and the 70-79 year olds the largest (22.9 ± 0.9%). Across all age groups, the sex difference in running velocity decreased across years from 22.0 ± 0.4% in 1980-84 to 16.1 ± 0.2% in 2005-2009 and plateaued for the subsequent decade. The largest drop was in the two older age groups (60-79 years, 36% to 21%) and the least for youngest (20-49 years, 18% to 12.5%). Across all age groups, the sex difference in running velocity for 1st placed runners was 15.9 ± 0.4 % and increased to 20.3 ± 0.3% for 10th (P < 0.001). The greatest increase in the sex difference (1st to 10th) was in the 70-79 age group (21.9 ± 1.5% to 31.6 ± 1.7%) and the least in the 40-49 age group (13.9 ± 0.6% to 17.8 ± 0.4%). CONCLUSION: The largest sex differences in marathon performance were within the older age groups and lower (slower)-placed runners. Across all age groups, the sex difference in performance plateaued in the past 15 years despite more female participants and the continued decrease in male:female participation ratios. These results also suggest that physiological and sociological factors that impact the sex difference in running velocity vary by age group. (1) Hunter SK, et al Med Sci Sports Exerc 45: 148-156, 2013.

Sex Differences in Physiological Determinants of Performance in Elite Adolescent, Junior, and Senior Cross-Country Skiers.

To compare sex differences in physiological determinants of skiing performance in elite adolescent, junior, and senior cross-country skiers matched for within-age-group performance level. Eight male and 12 female adolescent (15 [1]y), 8 male and 7 female junior (18 [1]y), and 7 male and 6 female senior (28 [5]y) skiers participated. Gross efficiency was calculated during submaximal uphill treadmill roller skiing (approximately 84% of peak oxygen uptake [V˙O2peak]) using the G2 ski-skating technique. Distance covered, V˙O2peak, and maximal accumulated oxygen deficit were established from a 3-minute time-trial. Fifteen-second maximal skiing power was calculated from an incremental treadmill speed test. Finally, upper- and lower-body maximal strength tests were conducted. The 3-minute time-trial distance and maximal skiing power were, respectively, 23% and 15% (adolescent), 24% and 19% (junior), and 17% and 14% (senior) greater for men than women (all groups, P ≤ .01, effect size [ES] = 2.43-4.18; very large). V˙O2peak relative to body mass was 17% (adolescent, P = .002, ES = 1.66, large), 21% (junior, P < .01, ES = 2.60, very large), and 19% (senior, P < .01, ES = 2.35, very large) greater for men than women. The within-age-group sex differences in gross efficiency, relative accumulated oxygen deficit, and strength were not significant, with the exception of greater lower-body strength in male than female juniors (P = .01, ES = 1.26, large). The within-age-group sex difference in skiing performance is of similar magnitude for adolescent, junior, and senior skiers. This difference can likely be attributed to the large to very large sex difference in V˙O2peak within all age-groups.

Prevalence, frequency, intensity, and location of cigarette use among adolescents in China from 2013–14 to 2019: Findings from two repeated cross-sectional studies

SummaryBackgroundThe burden of disease caused by tobacco use is a grave public health concern in China. Preventing smoking initiation among adolescents will lower the prevalence of adult tobacco use later. Surveillance of tobacco use among adolescents helps set priorities in developing tobacco control policies. We aim to ascertain the prevalence and differences of cigarette use across sex, grade, and region among middle and high school students in 2019 and associated changes from 2013-14 to 2019 among middle school students.MethodsUsing a multistage stratified cluster-randomized sampling design with national and provincial representativeness, we conducted two school-based cross-sectional surveys in 2013–14 and in 2019. A total of 155 117 middle school students in grades 7–9 in 2013-14 and 288 192 middle and high school students in grades 7–12 in 2019 were interviewed. Self-reported experimental and current (past 30-day) cigarette use among middle school and high school students; frequent use (≥20 days in the past 30 days) and intensity (>20 cigarettes per day) of smoking among current cigarette users; and location of smoking among current cigarette users were investigated. All estimates were weighted based on the complex sampling design.FindingsThe 2013-14 survey (overall response rate: 98.1%) included 155 117 middle school students (47.1% girl). The 2019 survey (overall response rate: 98.7%) included 147 270 middle school students (46.5% girl), 106 432 academic high school students (50.8% girl) and 34 490 vocational high school students (43.8% girl). In 2019, the prevalence rate of experimental and current cigarette use was 12.9% and 3.9% for middle school students, 21.6% and 5.6% for academic high school students, and 30.3% and 14.7% for vocational high school students, respectively, with large sex and regional differences. The prevalences of smoking on 20 or more days and daily cigarette use in the past 30 days were higher in vocational high school (5.9%, 4.1%) than in academic high school (1.8%, 1.2%) and middle school (0.7%, 0.5%), and higher among boys than girls. The proportions of current cigarette users smoking more than 20 cigarettes per day in the past 30 days for girls were higher than for boys in academic high school. Students usually smoke at school and at home. Boys were more likely to use cigarettes in an internet cafe, while girls often smoked at social venues. From 2013-14 to 2019, the prevalences of experimental and current cigarette use declined by 5.0% and 2.0% (percentage points), respectively, among middle school students but increased by 1.4% and 0.5% (percentage points) among rural girls. Among current cigarette users in middle school students, the proportions of heavy cigarette use (>20 cigarettes per day) have increased by 1.8 percentage points, mainly among boys, by 2.2% (percentage points).InterpretationFrom 2013–14 to 2019, the prevalences of experimental and current cigarette use among middle school students decreased overall but increased among rural girls, while the intensity of cigarette use rose among boys. Cigarette use among Chinese adolescents differs across sex and regions, with higher rates among boys, in rural areas, and in the Western region (low socioeconomic status). Smoking is much more prevalent in vocational high schools than the other settings. Effective targeted tobacco control interventions among adolescents are urgently needed in China.FundingDr. Zhuo Chen is supported by National Natural Science Foundation (Grant#: 72174098) through the University of Nottingham Ningbo China.

Milieu effects on the Dark Triad traits and their sex differences in 49 countries

Most research on the development of personality traits like the Dark Triad (i.e., narcissism, Machiavellianism, and psychopathy) focuses on local effects like parenting style or attachment, but people live in a larger society that may set the stage for any local effects. Here we paired nation-level data on the traits from 49 nations with several milieu indicators (e.g., life expectancy, homicide rates) from three timepoints (and change among them) where the average participant (≈ 22yo) would have been a child (≈ 6yo), a pre-teen (≈ 11yo), and a teenager (≈ 16yo). Congruent with previous research, variance in narcissism was far more sensitive to variance in milieu conditions in general and across all three time points than variance in Machiavellianism or psychopathy. The milieu conditions differentiated the traits somewhat with income and education revealing negative correlations with narcissism, positive correlations with Machiavellianism, and null correlations with psychopathy. Sex differences in Machiavellianism and narcissism were correlated with homicide rates across the three timepoints. The evidence that changes in milieu conditions in ones' past predicts the traits was erratic, but larger sex differences in the traits were associated with decreased life expectancies and homicide rates between childhood and pre-teens.

Sex differences in lipopolysaccharide‐induced cytokine secretion in skeletal muscle

INTRODUCTIONPrevious work has demonstrated large sex differences in the response to sepsis when various components of immune signaling are knocked out of muscle fibers. Skeletal muscle is a heterogeneous organ that holds many phenotypes, including resident immune cells such as resident myeloid‐derived immune cells. Skeletal muscle fibers are functional contributors to the inflammatory pathway, however, the contribution of these fibers to secrete cytokines relative to resident myeloid cells remains unknown. In an effort to further characterize the homeostatic and immunologic basis by which skeletal muscle‐derived immune cells contribute to whole‐body homeostasis, we evaluated the cytokine secretory capability of solei ex vivo in response to lipopolysaccharide (LPS) exposure.METHODS75 C57BL/6 mice were divided into two groups based on genetic profile: 36 LysMCrexMyD88 knockout (K/O) mice (18 female, 23 male) and 39 wild‐type (W/T) mice (23 female, 16 male). The resident myeloid cells found within the skeletal muscle fibers of LysMCrexMyD88 K/O mice lack proper toll‐like receptor‐4 function. Following anesthetization under isoflurane, mouse hind limbs were placed in oxygenated (95% O2, 5% CO2) Krebs‐Ringer solution. Solei were promptly excised and studied ex vivo in oxygenated muscle baths containing 2 mL Krebs‐Ringer solution. Half of the female and male solei from the K/O and W/T groups were randomized to receive 1 µg/mL of LPS while the remaining half received no LPS (Vehicle). Half of the solei received 1 µg/mL of LPS while vehicles received no LPS. Three samples were obtained from the buffer over the 2‐hour time course: before treatment (T0), 60 min following treatment (T1), and 120 minutes following treatment (T2). Samples were stored at ‐80°C and later analyzed for 22 common innate immune cytokines using Luminex Multiplex Analysis.RESULTSOf the 22 cytokines assessed, 16 displayed significant secretory differences between sexes when measured across T1‐T0 and T2‐T1 overall.During T1‐T0, K/O males exhibited significant depression in secretory responsiveness with LPS treatment compared to females (IFN‐γ, p=0.03; IL‐6, p =0.009; IL‐12p70, p=0.019; IL‐15, p=0.019; IP‐10, p=0.037; KC, p=0.024; MIP‐1β, p=0.005; MIP‐2, p=0.002). During T2‐T1, K/O LPS‐treated males had significantly different secretory responses compared to females (↓G‐CSF, p=0.045; ↓Eotaxin, p=0.034; ↑IL‐1α, p=0.019; ↑IL12‐p40, p=0.038; ↑RANTES=0.018). W/T LPS‐treated males exhibited significant depression in secretory responsiveness compared to females during T1‐T0 (IL‐12p70, p=0.049; IP‐10, p=0.003; MCP‐1, p=0.021; MIP‐1α, p=0.034; TNFα, p=0.011). During T2‐T1, W/T LPS‐treated males displayed significant elevation in secretory responsiveness compared to females (MIP‐2, p=0.024; RANTES, p=0.006).CONCLUSIONSIn the initial response period (T1‐T0), both K/O and W/T LPS‐treated males secreted significantly fewer cytokines relative to K/O and W/T LPS‐treated females, respectively. In the secondary interval (T2‐T1), some cytokine responses were elevated in males compared to females. These results demonstrate significant variations in the processes by which male and female skeletal muscle fibers respond to inflammatory stimuli. This may help to elucidate recent sex differences found regarding the interference of the inflammatory signaling cascade within muscle fibers during sepsis.

Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges

Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.

Sex differences in global disability-adjusted life years due to ischemic stroke: findings from global burden of diseases study 2019

To investigate the sex differences in disability-adjusted life years (DALYs) due to ischemic stroke (IS) by year, location and age. We extracted sex-specific data on DALYs number, age-standardized DALYs rate (ASDR) and all-age DALYs rate of IS by year, location and age from the Global Burden of Diseases study 2019. The estimated annual percentage changes (EAPC) were calculated to evaluate the temporal trend of ASDR. For both sexes, although the ASDR of IS slightly decreased from 1990 to 2019, there has been an 60.3% increase in DALYs number worldwide. Sex difference in DALYs number (men minus women) decreased from − 2.83 million in 1990 to 0.14 million in 2019, while the men to women’s ASDR ratio slightly increased from 1.10 in 1990 to 1.21 in 2019. The sex differences in IS DALYs showed remarkable regional variation. The largest sex differences in DALYs number and ASDR were in China and Vietnam. Middle-aged men had a higher IS DALYs than their age-matched counterparts. High systolic blood pressure accounted for the highest DALYs number in 2019, but the top three attributable risk factors that had the greatest sex differences were tobacco, dietary risk, and alcohol use. Sex differences in IS DALYs varied by year, location and age, mostly attributed to the disproportion of cardiovascular risk factors between sexes. Considering the population growth and aging, it is necessary to monitor the sex difference in IS DALYs in different populations and thus provide evidence for local administration to improve current preventive and management strategies of IS.