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1.
J Biomech ; 134: 111002, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35202964

ABSTRACT

Whether muscle properties gradually change with age and how muscle properties are affected by sex remain unclear. In this study, we investigated the influence of age and sex on the biomechanical and viscoelastic properties of arm muscles in middle-aged and older adults. In this cross-sectional study, 80 healthy participants were divided by sex (male and female), and each sex group, by 10-year age ranges (40-49, 50-59, 60-69, and 70-79 years). Muscle properties, including tone, stiffness, elasticity, and mechanical stress relaxation time, were measured with the MyotonPRO. Our results showed that the muscle tone and elasticity of the deltoid and flexor carpi radialis, and the muscle tone of the flexor carpi ulnaris, were significantly greater in men than in women, whereas the stress relaxation time of the triceps was significantly greater in women than in men. Significantly greater muscle stiffness in the biceps brachii was found in the participants over 50 years old. Less muscle elasticity was found in the deltoid, triceps, and flexor carpi ulnaris in those over 70 years old. In conclusion, age and sex have considerable impacts on upper-limb muscle properties in middle-aged and older adults, which should be taken into consideration when planning health promotion projects.


Subject(s)
Sex Characteristics , Upper Extremity , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Muscle, Skeletal/physiology , Pilot Projects
2.
PLoS One ; 17(5): e0266816, 2022.
Article in English | MEDLINE | ID: mdl-35511905

ABSTRACT

OBJECTIVE: Knowledge is needed on the total disease burden across the sexes in inflammatory arthritis (IA). We aimed to compare disease burden, including a broad range of health aspects, across men and women with IA treated with tumor necrosis factor inhibitors (TNFi). METHODS: Adult outpatients with IA (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis) were included as part of standard care. Patient-reported outcomes, disease activity, TNFi trough levels, calprotectin, Work Productivity and Activity Impairment, comorbidities and cardiovascular risk profile were assessed. Unadjusted comparisons across sexes were done with independent t-test, Mann-Whitney U-test and X2-test and adjusted analyses with General Linear Models and logistic/ordinal logistic regression. RESULTS: A total of 305 IA patients were included (167 men, 138 women). A significantly lower proportion of women (45%) than men (59%) were in remission according to disease-specific composite scores (p = 0.02). Women had significantly worse scores on pain, joint pain, fatigue, enthesitis, Health Assessment Questionnaire and Short Form (SF)-36 vitality and social functioning (all p≤0.04). Both sexes had worse SF-36 scale scores than the general population. Women reported more absenteeism (work time missed) and activity impairment. TNFi trough levels, neutralizing antibodies and calprotectin were similar across sexes. A similar total number of comorbidities was seen. Self-reported hypothyroidism was more frequent in women. Men had higher 10-year calculated risk of fatal cardiovascular events. CONCLUSION: Important differences in disease burden between men and women were seen. More attention to sex differences in the follow-up of IA patients is warranted.


Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/epidemiology , Cost of Illness , Female , Humans , Leukocyte L1 Antigen Complex , Male , Sex Characteristics , Treatment Outcome , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor-alpha
3.
J Am Heart Assoc ; 11(9): e024149, 2022 May 03.
Article in English | MEDLINE | ID: mdl-35492000

ABSTRACT

Background The association between female sex and poor outcomes following surgery for type A acute aortic dissection has been reported; however, sex-related differences in clinical features and in-hospital outcomes of type B acute aortic dissection, including classic aortic dissection and intramural hematoma, remain to be elucidated. Methods and Results We studied 2372 patients with type B acute aortic dissection who were enrolled in the Tokyo Acute Aortic Super-Network Registry. There were fewer and older women than men (median age [interquartile range]: 76 years [66-84 years], n=695 versus 68 years [57-77 years], n=1677; P<0.001). Women presented to the aortic centers later than men. Women had a higher proportion of intramural hematoma (63.7% versus 53.7%, P<0.001), were medically managed more frequently (90.9% versus 86.3%, P=0.002), and had less end-organ malperfusion (2.4% versus 5.7%, P<0.001) and higher in-hospital mortality (5.3% versus 2.7%, P=0.002) than men. In multivariable analysis, age (per year, odds ratio [OR], 1.06 [95% CI, 1.03-1.08]; P<0.001), hyperlipidemia (OR, 2.09 [95% CI, 1.13-3.88]; P=0.019), painlessness (OR, 2.59 [95% CI, 1.14-5.89]; P=0.023), shock/hypotension (OR, 2.93 [95% CI, 1.21-7.11]; P=0.017), non-intramural hematoma (OR, 2.31 [95% CI, 1.32-4.05]; P=0.004), aortic rupture (OR, 26.6 [95% CI, 14.1-50.0]; P<0.001), and end-organ malperfusion (OR, 4.61 [95% CI, 2.11-10.1]; P<0.001) were associated with higher in-hospital mortality, but was not female sex (OR, 1.67 [95% CI, 0.96-2.91]; P=0.072). Conclusions Women affected with type B acute aortic dissection were older and had more intramural hematoma, a lower incidence of end-organ malperfusion, and higher in-hospital mortality than men. However, female sex was not associated with in-hospital mortality after multivariable adjustment.


Subject(s)
Aneurysm, Dissecting , Hospitals , Aged , Aneurysm, Dissecting/surgery , Female , Hematoma/epidemiology , Humans , Male , Registries , Sex Characteristics
4.
J Forensic Odontostomatol ; 1(40): 53-64, 2022 Apr 30.
Article in English | MEDLINE | ID: mdl-35499537

ABSTRACT

Sex determination is one of the primary concerns of forensic science. The cranial bones, pelvis, and mandible have been used for determining the sex of specimens. Because the mandible is robust and sexually dimorphic, studies have evaluated its metric and morphological traits. This study was designed as a retrospective study involving cone beam computed tomography (CBCT) images to assess sexual dimorphism of the mandible in the Turkish population. Total sample group consisted of 176 bimaxillary CBCT scans (71 males and 102 females; ages 19-67 years). Sixteen mandibular parameters were measured using two different software programmes. Measurements were recorded in various planes of three-dimensional (3D) reconstructions of the scans. All parameters aside from SIMaCD were found to be statistically significant. The highest diagnostic accuracy rate was associated with IMaF, and the overall accuracy rate of the fourteen parameters was found to be 80%.


Subject(s)
Sex Determination by Skeleton , Spiral Cone-Beam Computed Tomography , Adult , Aged , Female , Forensic Anthropology , Humans , Imaging, Three-Dimensional , Male , Mandible/diagnostic imaging , Middle Aged , Retrospective Studies , Sex Characteristics , Sex Determination by Skeleton/methods , Young Adult
5.
Front Endocrinol (Lausanne) ; 13: 837852, 2022.
Article in English | MEDLINE | ID: mdl-35527998

ABSTRACT

Background: The sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors. Methods: Data were obtained from the China Health and Retirement Longitudinal Study. Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used. Results: The relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors. Conclusions: Postmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.


Subject(s)
Menarche , Sex Characteristics , Aged , Female , Humans , Longitudinal Studies , Male , Memory Disorders/epidemiology , Memory Disorders/etiology , Menopause , Reproduction
6.
JAMA Netw Open ; 5(5): e2211336, 2022 May 02.
Article in English | MEDLINE | ID: mdl-35536576

ABSTRACT

Importance: Sex differences in aortic surgery outcomes are commonly reported. However, data on ruptured abdominal aortic aneurysm (rAAA) repair outcomes in women vs men are limited. Objective: To assess differences in perioperative and long-term mortality following rAAA repair in women vs men. Design, Setting, and Participants: A multicenter, retrospective cohort study was conducted using the Vascular Quality Initiative database, which prospectively captures information on patients who undergo vascular surgery across 796 academic and community hospitals in North America. All patients who underwent endovascular or open rAAA repair between January 1, 2003, and December 31, 2019, were included. Outcomes were assessed up to January 1, 2020. Exposures: Patient sex. Main Outcomes and Measures: Demographic, clinical, and procedural characteristics were recorded, and differences between women vs men were assessed using independent t test and χ2 test. The primary outcomes were in-hospital and 8-year mortality. Associations between sex and outcomes were analyzed using univariable and multivariable logistic regression and Cox proportional hazards regression analysis. Results: A total of 1160 (21.9%) women and 4148 (78.1%) men underwent rAAA repair during the study period. There was a similar proportion of endovascular repairs in women and men (654 [56.4%] vs 2386 [57.5%]). Women were older (mean [SD] age, 75.8 [9.3] vs 71.7 [9.6] years), more likely to have chronic kidney disease (718 [61.9%] vs 2184 [52.7%]), and presented with ruptured aneurysms of smaller diameters (mean [SD] 68 [18.2] vs 78 [30.2] mm). In-hospital mortality was higher in women (34.4% vs 26.6%; odds ratio, 1.44; 95% CI, 1.25-1.66), which persisted after adjusting for demographic, clinical, and procedural characteristics (adjusted odds ratio, 1.36; 95% CI, 1.12-1.66; P = .002). Eight-year survival was lower in women (36.7% vs 49.5%; hazard ratio, 1.25; 95% CI, 1.04-1.50; P = .02), which persisted when stratified by endovascular and open repair. This survival difference existed in both the US and Canada. Variables associated with long-term mortality in women included older age and chronic kidney disease. Conclusions and Relevance: Women who underwent rAAA repair had higher perioperative and 8-year mortality rates following both endovascular and open repair compared with men. Older age and higher rates of chronic kidney disease in women were associated with higher mortality rates. These findings suggest that future studies should assess the reasons for these disparities and whether opportunities exist to improve AAA care for women.


Subject(s)
Aortic Aneurysm, Abdominal , Aortic Rupture , Endovascular Procedures , Renal Insufficiency, Chronic , Aged , Aortic Aneurysm, Abdominal/surgery , Aortic Rupture/epidemiology , Aortic Rupture/surgery , Female , Humans , Male , Retrospective Studies , Sex Characteristics
7.
F1000Res ; 11: 5, 2022.
Article in English | MEDLINE | ID: mdl-35514606

ABSTRACT

Background: This review aims to investigate the association of sex with the risk of multiple COVID-19 health outcomes, ranging from infection to death. Methods: Pubmed and Embase were searched through September 2020. We considered studies reporting sex and coronavirus disease 2019 (COVID-19) outcomes. Qualitative and quantitative data were extracted using standardised electronic data extraction forms with the assessment of Newcastle Ottawa Scale for risk of bias. Pooled trends in infection, hospitalization, severity, intensive care unit (ICU) admission and death rate were calculated separately for men and women and subsequently random-effects meta-analyses on relative risks (RR) for sex was performed. Results: Of 10,160 titles, 229 studies comprising 10,417,452 patients were included in the analyses. Methodological quality of the included studies was high (6.9 out of 9). Men had a higher risk for infection with COVID-19 than women (RR = 1.14, 95%CI: 1.07 to 1.21). When infected, they also had a higher risk for hospitalization (RR = 1.33, 95%CI: 1.27 to 1.41), higher risk for severe COVID-19 (RR = 1.22, 95%CI: 1.17 to 1.27), higher need for Intensive Care (RR = 1.41, 95%CI: 1.28 to 1.55), and higher risk of death (RR = 1.35, 95%CI: 1.28 to 1.43). Within the period studied, the RR for infection and severity increased for men compared to women, while the RR for mortality decreased for men compared to women. Conclusions: Meta-analyses on 229 studies comprising over 10 million patients showed that men have a higher risk for COVID-19 infection, hospitalization, disease severity, ICU admission and death. The relative risks of infection, disease severity and death for men versus women showed temporal trends with lower relative risks for infection and severity of disease and higher relative risk for death at the beginning of the pandemic compared to the end of our inclusion period. PROSPERO registration: CRD42020180085 (20/04/2020).


Subject(s)
COVID-19 , COVID-19/epidemiology , Female , Hospitalization , Humans , Intensive Care Units , Male , SARS-CoV-2 , Sex Characteristics
8.
PLoS One ; 17(5): e0268249, 2022.
Article in English | MEDLINE | ID: mdl-35522611

ABSTRACT

BACKGROUND: Sex differences in post-stroke cognitive decline have not been systematically evaluated in a nationally representative cohort. We use a quasi-experimental design to investigate sex differences in rate of post-stroke cognitive decline. METHODS: Utilizing the event study design, we use the Health and Retirement Study (HRS) data (1996-2016) to evaluate the differences (percentage points [95% Confidence interval]) in the rate of change in cognitive function, measured using the modified version of the Telephone Interview for Cognitive Status (TICS-m) score, before and after incident stroke, and among patients with and without incident stroke. We estimated this event study model for the overall study population and separately fit the same model for male and female participants. RESULTS: Of 25,872 HRS participants included in our study, 14,459 (55.9%) were females with an overall mean age (SD) of 61.2 (9.3) years. Overall, 2,911 (11.3%) participants reported experiencing incident stroke. Participants with incident stroke (vs. no stroke) had lower baseline TICS-m score (15.6 vs. 16.1). Among participants with incident stroke, the mean pre-stroke TICS-m score was higher than the mean post-stroke TICS-m score (14.9 vs. 12.7). Event study revealed a significant short-term acceleration of cognitive decline for the overall population (4.2 [1.7-6.6] percentage points, p value = 0.001) and among female participants (5.0 [1.7-8.3] percentage points, p value = 0.003). We, however, found no evidence of long-term acceleration of cognitive decline after stroke. Moreover, among males, incident stroke was not associated with significant changes in rate of post-stroke cognitive decline. CONCLUSION: Females, in contrast to males, experience post-stroke cognitive deficits, particularly during early post-stroke period. Identifying the sex-specific stroke characteristics contributing to differences in post stroke cognitive decline may inform future strategies for reducing the burden of post-stroke cognitive impairment and dementia.


Subject(s)
Cognitive Dysfunction , Stroke , Cognition , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Sex Characteristics , Stroke/complications , Stroke/epidemiology , Stroke/psychology
9.
Proc Biol Sci ; 289(1974): 20212540, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35506220

ABSTRACT

Body size mediates life history, physiology and inter- and intra-specific interactions. Within species, sexes frequently differ in size, reflecting divergent selective pressures and/or constraints. Both sexual selection and differences in environmentally mediated reproductive constraints can drive sexual size dimorphism, but empirically testing causes of dimorphism is challenging. Manakins (Pipridae), a family of Neotropical birds comprising approximately 50 species, exhibit a broad range of size dimorphism from male- to female-biased and are distributed across gradients of precipitation and elevation. Males perform courtship displays ranging from simple hops to complex aerobatic manoeuvres. We tested associations between sexual size dimorphism and (a) agility and (b) environment, analysing morphological, behavioural and environmental data for 22 manakin species in a phylogenetic framework. Sexual dimorphism in mass was most strongly related to agility, with males being lighter than females in species performing more aerial display behaviours. However, wing and tarsus length dimorphism were more strongly associated with environmental variables, suggesting that different sources of selection act on different aspects of body size. These results highlight the strength of sexual selection in shaping morphology-even atypical patterns of dimorphism-while demonstrating the importance of constraints and ecological consequences of body size evolution.


Subject(s)
Dancing , Passeriformes , Animals , Body Size , Female , Male , Phylogeny , Sex Characteristics
10.
J Exp Med ; 219(6)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35510951

ABSTRACT

Sexual dimorphism in the composition and function of the human immune system has important clinical implications, as males and females differ in their susceptibility to infectious diseases, cancers, and especially systemic autoimmune rheumatic diseases. Both sex hormones and the X chromosome, which bears a number of immune-related genes, play critical roles in establishing the molecular basis for the observed sex differences in immune function and dysfunction. Here, we review our current understanding of sex differences in immune composition and function in health and disease, with a specific focus on the contribution of the X chromosome to the striking female bias of three autoimmune rheumatic diseases.


Subject(s)
Autoimmune Diseases , Rheumatic Diseases , Female , Humans , Male , Sex Characteristics
11.
J Exp Med ; 219(6)2022 Jun 06.
Article in English | MEDLINE | ID: mdl-35510952

ABSTRACT

Reporting the distribution and inclusion of both males and females in immunology and infectious diseases research is improving, but rigorous analyses of differential outcomes between males and females, including mechanistic inquiries into the causes of sex differences, still lags behind.


Subject(s)
Communicable Diseases , Bias , Female , Humans , Male , Sex Characteristics , Sex Factors
12.
Future Cardiol ; 18(5): 355-357, 2022 05.
Article in English | MEDLINE | ID: mdl-35506472

ABSTRACT

Bibliography Dr Sanne Peters is an Associate Professor at The George Institute for Global Health and a Senior Lecturer at Imperial College London. She is also Associate Professor at the University Medical Center Utrecht. After completing her MSc in Epidemiology in 2009, she obtained a PhD in Epidemiology from Utrecht University in 2012. Her PhD focused on subclinical imaging measures of atherosclerosis as a means to identify people at high-risk for future cardiovascular disease. As part of her PhD training, she spent 6 months at The George Institute in Sydney. This is where she started her research on sex differences in cardiovascular disease. In 2013, she was awarded a postdoctoral fellowship, which enabled her to continue her work on sex differences at the University of Cambridge. In 2014, she was offered a position at the George Institute offices at the University of Oxford (now in collaboration with Imperial College London). In 2018, she relocated back to the Netherlands and was also appointed as Associate Professor in Utrecht.


Subject(s)
Cardiovascular Diseases , Cardiovascular Diseases/drug therapy , Female , Global Health , Humans , London , Male , Prescriptions , Sex Characteristics
13.
Thromb Res ; 214: 122-131, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35537232

ABSTRACT

BACKGROUND: Sex is an important factor associated with pulmonary embolism (PE) disease presentation and outcomes, which may be related to pathobiological, social, and treatment-based differences. We are seeking to illuminate sex differences in pulmonary embolism presentation, care, and outcomes using an international registry and a national US database of people 65 years and older, the age group in which the majority of these events occur. METHODS: The Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism (SERIOUS-PE) study has been designed to address knowledge gaps in this area. This study will use data from the Registro Informatizado Enfermedad TromboEmbolica (RIETE) registry and the US Medicare Fee-For-Service beneficiaries. RIETE is a large international registry of patients with venous thromboembolism with data collected on PE presentation, risk factors, co-morbidities, drug and interventional therapies, as well as 30-day and 1-year outcomes (including recurrent VTE, major bleeding, and mortality). Data from US Medicare Fee-For-Service beneficiaries will be used to understand the sex differences in PE hospitalizations, advanced therapies, and outcomes at 30-day and 1-year follow-up. Assessment of outcomes in both databases will be performed in unadjusted models, as well as those adjusted for demographics, co-morbidities, and treatments, to understand whether the potential sex differences in outcomes are related to differences in risk factors and co-morbidities, potential disparities in treatment, or a plausible biological difference in women versus men. Linear trends will be assessed over time. RESULTS: RIETE data from March 2001 through March 2021 include 33,462 elderly patients with PE, of whom 19,294 (57.7%) were women and 14,168 (42.3%) were men. In the Medicare Fee-For-Service database, between January 2001 and December 31, 2019, 1,030,247 patients were hospitalized with a principal discharge diagnosis of PE, of whom 599,816 (58.2%) were women and 430,431 (41.8%) were men. CONCLUSIONS: Findings from the SERIOUS-PE study will help address important knowledge gaps related to sex differences in presentation and risk factors, treatment patterns, and outcomes of older adults with PE. The results may guide changes in prognostic prediction rules based on sex-specific findings, identify sex-based disparities in care delivery that should be addressed by quality improvement, or uncover potential differences in response to available therapies that warrant testing in dedicated randomized trials.


Subject(s)
Pulmonary Embolism , Venous Thromboembolism , Aged , Female , Humans , Male , Medicare , Pharmaceutical Preparations , Pulmonary Embolism/diagnosis , Registries , Risk Factors , Sex Characteristics , United States , Venous Thromboembolism/etiology
14.
Cardiovasc Diabetol ; 21(1): 65, 2022 May 03.
Article in English | MEDLINE | ID: mdl-35505344

ABSTRACT

BACKGROUND: We examined trends in incidence (2001-2019), clinical characteristics, and in-hospital outcomes following major and minor lower extremity amputations (LEAs) among type 1 diabetes mellitus (T1DM) patients in Spain and attempted to identify sex differences. METHODS: Retrospective cohort study using data from the Spanish National Hospital Discharge Database. We estimated the incidence of the LEA procedure stratified by type of LEA. Joinpoint regression was used to estimate incidence trends, and logistic regression was used to estimate factors associated with in-hospital mortality (IHM). RESULTS: LEA was coded in 6011 patients with T1DM (66.4% minor and 33.6% major). The incidence of minor LEA decreased by 9.55% per year from 2001 to 2009 and then increased by 1.50% per year, although not significantly, through 2019. The incidence of major LEA decreased by 13.39% per year from 2001 to 2010 and then remained stable through 2019. However, incidence increased in men (26.53% per year), although not significantly, from 2017 to 2019. The adjusted incidence of minor and major LEA was higher in men than in women (IRR 3.01 [95% CI 2.64-3.36] and IRR 1.85 [95% CI 1.31-2.38], respectively). Over the entire period, for those who underwent a minor LEA, the IHM was 1.58% (2.28% for females and 1.36% for males; p = 0.045) and for a major LEA the IHM was 8.57% (10.52% for females and 7.59% for males; p = 0.025). IHM after minor and major LEA increased with age and the presence of comorbid conditions such as peripheral arterial disease, ischemic heart disease or chronic kidney disease. Female sex was associated with a higher IHM after major LEA (OR 1.37 [95% CI 1.01-1.84]). CONCLUSIONS: Our data show a decrease in incidence rates for minor and major LEA in men and women with T1DM and a slight, albeit insignificant, increase in major LEA in men with T1DM in the last two years of the study. The incidence of minor and major LEA was higher in men than in women. Female sex is a predictor of IHM in patients with T1DM following major LEA.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Amputation/adverse effects , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/surgery , Diabetes Mellitus, Type 2/epidemiology , Female , Hospital Mortality , Humans , Incidence , Lower Extremity/surgery , Male , Retrospective Studies , Sex Characteristics , Spain/epidemiology
15.
Biol Sex Differ ; 13(1): 19, 2022 May 03.
Article in English | MEDLINE | ID: mdl-35505436

ABSTRACT

Sex and age associated differences in the tumor immune microenvironment of non-muscle invasive bladder (NMIBC) cancer and associated clinical outcomes are emerging indicators of treatment outcomes. The incidence of urothelial carcinoma of the bladder is four times higher in males than females; however, females tend to present with a more aggressive disease, a poorer response to immunotherapy and suffer worse clinical outcomes. Recent findings have demonstrated sex differences in the tumor immune microenvironment of non-muscle invasive and muscle invasive bladder cancer and associated clinical outcomes. However, a significant gap in knowledge remains with respect to the current pre-clinical modeling approaches to more precisely recapitulate these differences towards improved therapeutic design. Given the similarities in mucosal immune physiology between humans and mice, we evaluated the sex and age-related immune alterations in healthy murine bladders. Bulk-RNA sequencing and multiplex immunofluorescence-based spatial immune profiling of healthy murine bladders from male and female mice of age groups spanning young to old showed a highly altered immune landscape that exhibited sex and age associated differences, particularly in the context of B cell mediated responses. Spatial profiling of healthy bladders, using markers specific to macrophages, T cells, B cells, activated dendritic cells, high endothelial venules, myeloid cells and the PD-L1 immune checkpoint showed sex and age associated differences. Bladders from healthy older female mice also showed a higher presence of tertiary lymphoid structures (TLSs) compared to both young female and male equivalents. Spatial immune profiling of N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) carcinogen exposed male and female bladders from young and old mice revealed a similar frequency of TLS formation, sex differences in the bladder immune microenvironment and, age associated differences in latency of tumor induction. These findings support the incorporation of sex and age as factors in pre-clinical modeling of bladder cancer and will potentially advance the field of immunotherapeutic drug development to improve clinical outcomes.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Aging , Animals , Butylhydroxybutylnitrosamine/adverse effects , Carcinogens , Female , Humans , Male , Mice , Sex Characteristics , Tumor Microenvironment , Urinary Bladder/pathology , Urinary Bladder Neoplasms/chemically induced , Urinary Bladder Neoplasms/pathology
16.
PLoS One ; 17(5): e0267904, 2022.
Article in English | MEDLINE | ID: mdl-35507560

ABSTRACT

A 180-day experiment was conducted to evaluate the effects of density on sex differentiation, sexual dimorphism, cortisol level, and stress related gene expression. Yellow perch, Perca flavescens, with initial mean body weight of 0.03 ± 0.001 g were reared in three different stocking densities: 1, 2, and 4 fish/L, termed as low (LD), moderate (MD), and high (HD) density, respectively, in a flow-through tank system. Results showed no significant differences in sex ratio in all density groups compared to normal population 1:1, and sexual size dimorphism (SSD) appeared when male and female were as small as the mean size reaching 11.5 cm and 12.3 cm in total length (TL) or 13.2g and 16.9g in body weight (BW), respectively. This female-biased sexual growth dimorphism was more pronounced in LD, although it was observed across all density groups. A significantly higher condition factor (K) of females than males in the LD group, and significantly higher R values of LD and MD than HD with the length/weight (L/W) linear relationships in females, were observed. Parallelly, fish reared in LD showed significantly higher mean body weight than those in the MD and HD groups, but there were no significant differences between the MD and HD. Similar results were also observed in all the other parameters of weight gain, specific growth rate (SGR), condition factor (K), and survival. These findings suggested that high density not only affected growth itself, but also affected SSD, growth trajectory or body shape, and general wellbeing in fish, especially in females. There were no significant differences in gonadosomatic index (GSI) and viscerosomatic index (VSI) among all the density groups; however, the hepatosomatic index (HSI) of LD was significantly higher than MD and HD, suggesting high density affected liver reserves or functions. Physiologically, plasma cortisol level was significantly highest in the LD among all groups, followed by MD, and lowest in HD. At the molecular level, the expression of the 70-kDa heat shock protein (Hsp70), glutathione peroxidase (GPx), and superoxide dismutase (SOD) genes involved in cellular stress were significantly upregulated in the HD group. The most significantly downregulated expression of these genes was consistently observed in the MD when compared to the LD and HD groups. In conclusion, increasing density induced chronic stress in yellow perch without affecting sex differentiation, but negatively affected expression of stress-related genes and mobilization of liver reserve, resulting in poorer wellbeing and reduced SSD, growth, and survival.


Subject(s)
Perches , Animals , Body Weight , Female , Gene Expression , Hydrocortisone , Male , Perches/physiology , Sex Characteristics , Sex Differentiation/genetics
17.
Sci Rep ; 12(1): 7269, 2022 May 04.
Article in English | MEDLINE | ID: mdl-35508566

ABSTRACT

Fragile X Syndrome (FXS) is the most common heritable form of mental retardation and monogenic cause of autism spectrum disorder (ASD). FXS is due to a mutation in the X-linked FMR1 gene and is characterized by motor, cognitive and social alterations, mostly overlapping with ASD behavioral phenotypes. The severity of these symptoms and their timing may be exacerbated and/or advanced by environmental adversity interacting with the genetic mutation. We therefore tested the effects of the prenatal exposure to unpredictable chronic stress on the behavioral phenotype of juveniles of both sexes in the Fmr1 knock-out (KO) mouse model of FXS. Mice underwent behavioral tests at 7-8 weeks of age, that is, when most of the relevant behavioral alterations are absent or mild in Fmr1-KOs. Stress induced the early appearance of deficits in spontaneous alternation in KO male mice, without exacerbating the behavioral phenotype of mutant females. In males stress also altered social interaction and communication, but mostly in WT mice, while in females it induced effects on locomotion and communication in mice of both genotypes. Our data therefore highlight the sex-dependent relevance of early environmental stressors to interact with genetic factors to influence the appearance of selected FXS- and ASD-like phenotypes.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Fragile X Syndrome , Animals , Autism Spectrum Disorder/genetics , Disease Models, Animal , Female , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/genetics , Gene-Environment Interaction , Male , Mice , Mice, Knockout , Sex Characteristics
18.
J Evol Biol ; 35(5): 752-762, 2022 05.
Article in English | MEDLINE | ID: mdl-35470907

ABSTRACT

In species with marked sexual dimorphism, the classic prediction is that the sex which undergoes stronger intrasexual competition ages earlier or quicker. However, more recently, alternative hypotheses have been put forward, showing that this association can be disrupted. Here, we utilize a unique, longitudinal data set of a semi-captive population of Asian elephants (Elephas maximus), a species with marked male-biased intrasexual competition, with males being larger and having shorter lifespans, and investigate whether males show earlier and/or faster body mass ageing than females. We found evidence of sex-specific body mass ageing trajectories: adult males gained weight up to the age of 48 years old, followed by a decrease in body mass until natural death. In contrast, adult females gained body mass with age until a body mass decline in the last year of life. Our study shows sex-specific ageing patterns, with an earlier onset of body mass declines in males than females, which is consistent with the predictions of the classical theory of ageing.


Subject(s)
Elephants , Aging , Animals , Female , Longevity , Male , Reproduction , Sex Characteristics
19.
BMJ Open ; 12(4): e054661, 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35487710

ABSTRACT

OBJECTIVES: This study investigates the gender disparities in difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL) and explores its contributing factors among older adults in India. DESIGN: A cross-sectional study was conducted using country representative survey data. SETTING AND PARTICIPANTS: The present study uses the data from the Longitudinal Ageing Study in India, 2017-2018. Participants included 15 098 male and 16 366 female older adults aged 60 years and above in India. PRIMARY AND SECONDARY OUTCOME MEASURES: Difficulty in ADL and IADL were the outcome variables. Descriptive statistics and bivariate analysis were carried out to present the preliminary results. Multivariate decomposition analysis was used to identify the contributions of covariates that explain the group differences to average predictions. RESULTS: There was a significant gender differential in difficulty in ADL (difference: 4.6%; p value<0.001) and IADL (difference: 17.3%; p value<0.001). The multivariate analysis also shows significant gender inequality in difficulty in ADL (coefficient: 0.046; p value<0.001) and IADL (coefficient: 0.051; p value<0.001). The majority of the gender gap in difficulty in ADL was accounted by the male-female difference in levels of work status (18%), formal education (15% contribution), marital status (13%), physical activity (9%), health status (8%) and chronic morbidity prevalence (5%), respectively. Equivalently, the major contributors to the gender gap in difficulty in IADL were the level of formal education (28% contribution), marital status (10%), alcohol consumption (9%), health status (4% contribution) and chronic morbidity prevalence (2% contribution). CONCLUSION: Due to the rapidly increasing ageing population, early detection and prevention of disability or preservation of daily functioning for older adults and women in particular should be the highest priority for physicians and health decision-makers.


Subject(s)
Activities of Daily Living , Sex Characteristics , Aged , Aging , Cross-Sectional Studies , Female , Humans , India/epidemiology , Male , Multivariate Analysis
20.
Zootaxa ; 5120(3): 391-401, 2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35391161

ABSTRACT

A new species of the New World genus Trivialia Malloch from Peru is described and illustrated, along with discussion of unusual head morphology in Lauxaniidae. This new species represents an odd case where only a single known species in an otherwise non-dimorphic genus displays extreme sexual dimorphism.


Subject(s)
Diptera , Animals , Peru , Sex Characteristics
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