Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of... Show moreHealthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the patient. It is therefore essential to take aging into consideration when investigating immune cells and their responses in atherosclerosis studies. This thesis describes research exploring the impact of aging on the immunological landscape in atherosclerotic cardiovascular disease using single-cell profiling. Through the use of a highly translational aging mouse model of atherosclerosis, we characterized inflammation in the plaques of young versus old mice. We discovered new cell types (T and B cells) not present in young mice with atherosclerosis. These cells secrete a variety of inflammatory factors that may contribute to the disease process and exacerbate arteriosclerosis. While the aged B cell is more prevalent in female mice, the aged T cell is more abundant in male mice. We then also found these aged cells in the blood and plaques of cardiovascular disease patients. These aged cell types could be interesting targets for future treatments against progression of atherosclerotic cardiovascular disease. Show less
Smit, V.; Mol, J. de; Bernabé Kleijn, M.N.A.B.; Depuydt, M.A.C.; Winther, M.P.J. de, Bot, I.; Kuiper, J.; Foks, A.C. 2024
Atherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall,... Show moreAtherosclerosis, the main underlying pathology of cardiovascular disease, is a chronic inflammatory disease characterized by lipid accumulation and immune cell responses in the vascular wall, resulting in plaque formation. It is well-known that atherosclerosis prevalence and manifestation vary by sex. However, sexual dimorphism in the immune landscape of atherosclerotic plaques has up to date not been studied at high-resolution. In this study, we investigated sex-specific differences in atherosclerosis development and the immunological landscape of aortas at single-cell level in aged Ldlr-/- mice.We compared plaque morphology between aged male and female chow diet-fed Ldlr-/- mice (22 months old) with histological analysis. Using single-cell RNA-sequencing and flow cytometry on CD45+ immune cells from aortas of aged Ldlr-/- mice, we explored the immune landscape in the atherosclerotic environment in males and females.We show that plaque volume is comparable in aged male and female mice, and that plaques in aged female mice contain more collagen and cholesterol crystals, but less necrotic core and macrophage content compared to males. We reveal increased immune cell infiltration in female aortas and found that expression of pro-atherogenic markers and inflammatory signaling pathways was enriched in plaque immune cells of female mice. Particularly, female aortas show enhanced activation of B cells (Egr1, Cd83, Cd180), including age-associated B cells, in addition to an increased M1/M2 macrophage ratio, where Il1b+ M1-like macrophages display a more pro-inflammatory phenotype (Nlrp3, Cxcl2, Mmp9) compared to males. In contrast, increased numbers of age-associated Gzmk+CD8+ T cells, dendritic cells, and Trem2+ macrophages were observed in male aortas.Altogether, our findings highlight that sex is a variable that contributes to immunological differences in the atherosclerotic plaque environment in mice and provide valuable insights for further preclinical studies into the impact of sex on the pathophysiology of atherosclerosis. Show less
Cardiovascular diseases (CVD) are the leading mortality cause. Its largest underlying issue is atherosclerosis: arterial narrowing due to the buildup of cholesterol, lipids, and immune cells. High... Show moreCardiovascular diseases (CVD) are the leading mortality cause. Its largest underlying issue is atherosclerosis: arterial narrowing due to the buildup of cholesterol, lipids, and immune cells. High blood pressure and cholesterol levels are well-known risk factors. Despite the effectiveness of currently-available medication to improve these factors, a considerable residual risk remains, indicating the importance of other risk factors, such as age and sex. Women have a lower risk of developing CVD than men at a young age, which reverses at older age. CVD are also more common among night shift workers. The research described in this thesis used mouse models to provide new insight in the interplay between sex, age, and disturbances in day and night rhythms in atherosclerosis development, and emphasize the importance of including both men and women in scientific studies. Brown fat is one of the tissues adversely affected by disturbances in day and night rhythms and aging, and the ANGPTL4 protein was identified as an important regulator of brown fat. Inhibiting ANGPTL4 production selectively in liver cells appears a safe and promising therapeutic strategy to combat atherosclerosis. The findings also imply that time-restricted eating could be an effective tool in lowering CVD risk in shift workers. Show less
Besides trading, the Dutch East India Company (VOC) and its Western Indian counterpart (WIC) also sought to expand their dominant position by establishing and managing colonies. Central to this... Show moreBesides trading, the Dutch East India Company (VOC) and its Western Indian counterpart (WIC) also sought to expand their dominant position by establishing and managing colonies. Central to this strategy was to stimulate an orderly, self-producing colonial population, with a European elite at the top and a sharp distinction between free citizens and people in slavery. The reality was less orderly, however: in disparate colonial settlements such as Batavia, Cochin, Ceylon, Elmina, Suriname, Curaçao and Berbice, people from different backgrounds, religions, and social positions encountered one another and formed relationships – formal and informal, coercive and consensual – which could either challenge or reinforce the social divisions on which colonial hierarchies rested. Regulating Relations, focusing on the abovementioned settlements in the eighteenth century, investigates how norms around marriage, family, and sexuality formed in this complex world: how did colonial authorities attempt to regulate the intimate relations of populations under their control, and how did men and women of various backgrounds give shape to these norms through their own behavior and use of institutions? Show less
The influence of sex on preoperative expectations and their fulfillment following total hip and knee arthroplasty (THA/TKA) remains unexplored. We investigated differences between men and women in... Show moreThe influence of sex on preoperative expectations and their fulfillment following total hip and knee arthroplasty (THA/TKA) remains unexplored. We investigated differences between men and women in perceived preoperative expectations on the outcome of THA/TKA and their fulfillment 1 year postoperatively. We performed a cohort study. Expectations were collected preoperatively and 1 year postoperatively using the Hospital for Special Surgery Hip/Knee Replacement Expectations Surveys (HSS-HRES/KRES; not applicable = 0, applicable: back to normal = 1, much = 2/moderate = 3/slight improvement = 4). Fulfillment of expectations was calculated by subtracting preoperative from postoperative scores (score < 0:unfulfilled; score >= 0:fulfilled). We included patients with "applicable" expectations. Chi-square and ordinal regression were used to compare expectations and fulfillment regarding sex. 2333 THA (62% women) and 2398 TKA (65% women) patients were included. 77% of THA and 76% of TKA patients completed the HSS-HRES/HSS-KRES both preoperatively and 1 year postoperatively. Men more often perceived items as "applicable", with differences in 9/20 (HSS-HRES) and 9/19 (HSS-KRES) preoperative items and, respectively, 12/20 (HSS-HRES) and 10/19 (HSS-KRES) postoperative items. The largest differences (> 10%) were found in sexual activity and working ability. 16/20 (HSS-HRES) and 14/19 (HSS-KRES) items showed an increased probability of having higher preoperative expectations of >= 10%, in favor of men. In all items, 60% of the respondents indicated that their expectation was fulfilled. Differences were observed in 16/20 (HSS-HRES) and 6/19 (HSS-KRES) items in favor of men. Sex differences were present in expectations and fulfillment, with higher applicability of items, preoperative expectations and fulfillment in men, especially on items related to functional activities. Trial registration: Trial-ID NTR3348. Show less
Background: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has... Show moreBackground: Recent data showed poor long-term survival in patients with moderate AS. Although sex differences in left ventricular (LV) remodeling and outcome are well described in severe AS, it has not been evaluated in moderate AS. Methods: In this retrospective, multicenter study, patients with a first diagnosis of moderate AS diagnosed between 2001 and 2019 were identified. Clinical and echocardiographic parameters were recorded at baseline and compared between men and women. Patients were followed up for the primary endpoint of all-cause mortality with censoring at the time of aortic valve replacement. Results: A total of 1895 patients with moderate AS (age 73 +/- 10 years, 52% male) were included. Women showed more concentric hypertrophy and had more pronounced LV diastolic dysfunction than men. During a median follow-up of 34 (13-60) months, 682 (36%) deaths occurred. Men showed significantly higher mortality rates at 3 -and 5-year follow-up (30% and 48%, respectively) than women (26% and 39%, respectively) (p = 0.011). On multivariable analysis, male sex remained independently associated with mortality (hazard ratio 1.209; 95% CI: 1.024-1.428; p = 0.025). LV remodeling (according to LV mass index) was associated with worse outcomes (hazard ratio 1.003; CI: 1.001-1.005; p = 0.006), but no association was observed between the interaction of LV mass index and sex with outcomes. Conclusions: LV remodeling patterns are different between men and women having moderate AS. Male sex is associated with worse outcomes in patients with medically treated moderate AS. Further studies investigating the management of moderate AS in a sex-specific manner are needed. Show less
Berg, B. van den; Hijma, H.J.; Koopmans, I.; Doll, R.J.; Zuiker, R.G.J.A.; Groeneveld, G.J.; Buitenweg, J.R. 2022
Sleep deprivation has been shown to increase pain intensity and decrease pain thresholds in healthy subjects. In chronic pain patients, sleep impairment often worsens the perceived pain intensity.... Show moreSleep deprivation has been shown to increase pain intensity and decrease pain thresholds in healthy subjects. In chronic pain patients, sleep impairment often worsens the perceived pain intensity. This increased pain perception is the result of altered nociceptive processing. We recently developed a method to quantify and monitor altered nociceptive processing by simultaneous tracking of psychophysical detection thresholds and recording of evoked cortical potentials during intra-epidermal electric stimulation. In this study, we assessed the sensitivity of nociceptive detection thresholds and evoked potentials to altered nociceptive processing after sleep deprivation in an exploratory study with 24 healthy male and 24 healthy female subjects. In each subject, we tracked nociceptive detection thresholds and recorded central evoked potentials in response to 180 single- and 180 double-pulse intra-epidermal electric stimuli. Results showed that the detection thresholds for single- and double-pulse stimuli and the average central evoked potential for single-pulse stimuli were significantly decreased after sleep deprivation. When analyzed separated by sex, these effects were only significant in the male population. Multivariate analysis showed that the decrease of central evoked potential was associated with a decrease of task-related evoked activity. Measurement repetition led to a decrease of the detection threshold to double-pulse stimuli in the mixed and the female population, but did not significantly affect any other outcome measures. These results suggest that simultaneous tracking of psychophysical detection thresholds and evoked potentials is a useful method to observe altered nociceptive processing after sleep deprivation, but is also sensitive to sex differences and measurement repetition. Show less
MaassenVanDenBrink, A.; Terwindt, G.M.; Cohen, J.M.; Barash, S.; Campos, V.R.; Galic, M.; ... ; Karppa, M. 2021
Background Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages.... Show moreBackground Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2 Delta a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18-45 years and > 45 years) and sex.Methods In the FOCUS study, eligible participants were randomized (1:1:1) to 12 weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18-45 and > 45 years) and sex subgroups.Results The modified intention-to-treat population (received >= 1 dose of study drug and had >= 10 days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18-45 years, n = 373; > 45 years, n = 464; male, n = 138; female, n = 699). Consistent reductions in monthly average number of migraine days during 12 weeks were observed, regardless of age (18-45 years: quarterly fremanezumab, - 4.1 days; monthly fremanezumab, - 4.7 days; placebo, - 0.9 days; P < 0.001; > 45 years: quarterly fremanezumab, - 3.6 days; monthly fremanezumab, - 3.7 days; placebo, - 0.3 days; P < 0.001) and sex (male: quarterly fremanezumab, - 4.1 days; monthly fremanezumab, - 4.6 days; placebo, - 0.3 days; P < 0.001; female: quarterly fremanezumab, - 3.6 days; monthly fremanezumab, - 3.9 days; placebo, - 0.6 days; P < 0.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups.Conclusions These results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex. Show less
Namazi, F.; Bijl, P. van der; Vo, N.M.; Wijngaarden, S.E. van; Marsan, N.A.; Delgado, V.; Bax, J.J. 2021
Aims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of... Show moreAims Secondary mitral regurgitation (MR) is more frequent in men than in women. However, little is known about differences in prognosis between men and women with secondary MR. The objective of this study is to investigate the sex distribution of secondary MR and the prognostic differences between sexes.Methods Patients with significant secondary MR, of both ischaemic and non-ischaemic aetiologies, were identified through the departmental electronic patient files and retrospectively analysed. The primary endpoint was all-cause mortality.Results A total of 698 patients (mean age 66 +/- 11 years) with significant secondary MR were included: 471 (67%) men and 227 (33%) women. Ischaemic heart failure was significantly more common in men (61%), whereas non-ischaemic heart failure was more prevalent in women (63%). Women had significantly smaller left ventricular (LV) volumes when compared with men and more preserved LV systolic function when assessed with LV global longitudinal strain (GLS; 8.5 +/- 4.1% vs. 7.5 +/- 3.6%; P = 0.004). Women more often underwent surgical mitral valve repair (34%) when compared with men (26%), although no differences were observed for transcatheter mitral valve repair. During a median follow-up of 57 [interquartile range 29-110] months, 373 (53%) patients died. Women showed significantly lower mortality rates at 1-, 2- and 5-year follow-up (9%, 16% and 33% vs. 10%, 20% and 42%) when compared with men (P = 0.001).Conclusions Significant secondary MR is more frequently observed in men as compared with women and is associated with worse prognosis. Show less
Giustozzi, M.; Valerio, L.; Agnelli, G.; Becattini, C.; Fronk, E.M.; Klok, F.A.; ... ; Barco, S. 2021
Introduction: Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation,... Show moreIntroduction: Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors.Methods: PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes.Results: Of 3,455 patients with acute VTE, 1,623 (47%) were women. The mean age at the time of VTE was 61 (SD 18) in women, 60 (SD 15) in men. The distribution of provoking risk factors was similar between sexes, despite a tendency for higher frequency of minor and major transient risk factors in women, and cancer or unprovoked VTE in men. At 12-month follow-up, VTE recurrence was reported in 74 (6.5%) women and 80 (6.4%) men (absolute risk difference-0.1%, 95% CI-1.9%; +2.1%). In patients with unprovoked VTE, the VTE recurrence rate was 38/612 (6.2%) in women and 53/798 (6.6%) in men (absolute risk difference-0.4, 95% CI-3.0; +2.1%). Multivariable Cox regressions confirmed the absence of sex differences. Quality of life and treatment satisfaction scores one year after VTE were lower in women than in men irrespective of the provoking risk factors (p<0.001 for both scores).Conclusions: Despite differences in the provoking risk factors for VTE, women and men had a similar rate VTE recurrence at one year. After acute VTE, women had lower quality of life and treatment satisfaction scores. Show less
Ritter, R. de; Sep, S.J.S.; Kallen, C.J.H. van der; Greevenbroek, M.M.J. van; Jong, M. de; Vos, R.C.; ... ; Stehouwer, C.D.A. 2021
Background Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal... Show moreBackground Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. Methods In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. Results Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 mu m (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 mu m (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. Conclusions Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications. Show less
Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to... Show moreLong-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 +/- 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (beta -1.3 +/- 0.4%; p < 0.001), with no other significant differences. When stratifying patients by 55 years age threshold, fibro-fatty PAV remained higher in men in both age groups (p < 0.05) whilst women younger than 55 years demonstrated more regression of fibrous (beta -0.8 +/- 0.3% per year; p = 0.002) and non-calcified PAV (beta -0.7 +/- 0.3% per year; p = 0.027). In a low-to-intermediate risk population of stable CAD patients, no significant sex differences in total PAV increase over time were observed. Fibro-fatty PAV was lower in women at any age and women under 55 years demonstrated significantly greater reduction in fibrous and non-calcified PAV over time compared to age-matched men. (ClinicalTrials.gov number, NCT04448691.) Show less
Ghariq, M.; Thijs, R.D.; Bek, L.M.; Zwet, E.W. van; Benditt, D.G.; Dijk, J.G. van 2020
Purpose Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods We retrospectively studied TTT outcomes in suspected... Show morePurpose Vasovagal syncope (VVS) affects more women than men. We determined whether this sex ratio affects tilt table test (TTT) results. Methods We retrospectively studied TTT outcomes in suspected VVS. TTT consisted of supine rest, a maximum 20 min of head-up tilt without and, if nitroglycerin was needed, a further maximum 20 min after nitroglycerin administration. TTT was terminated if VVS occurred. We used binary logistic regression for the entire TTT and for each phase, with VVS as outcome and age and sex as predictors. Results TTT provoked vasovagal (pre)syncope in 494 out of 766 tests (64%). The proportion of men and women who fainted during the entire TTT did not differ significantly between the sexes (p = 0.13, corrected for age). A lower proportion of women than men had VVS in the phase without nitroglycerin (odds ratio 0.54; 95% confidence interval 0.37-0.79;p = 0.002, corrected for age), whereas a higher proportion of women than men fainted after nitroglycerin (odds ratio 1.58; 95% confidence interval 1.13-2.21;p = 0.008, corrected for age). These sex differences remained significant after correction for a history of orthostatic versus emotional triggers. The effect of sex on TTT outcome was closely associated with differences of blood pressure change upon tilt-up (lower in men in both TTT phases: without nitroglycerinp = 0.003; with nitroglycerinp = 0.05), but not with heart rate changes. Conclusion Men were more susceptible to induction of VVS without nitroglycerin and women after it. The unexpected findings may be due to sex-specific pathophysiological differences. Show less
Kong, W.K.F.; Bax, J.J.; Michelena, H.I.; Delgado, V. 2020
Bicuspid aortic valve (BAV), the most frequent congenital heart disease, is characterized by an uneven distribution between sexes. BAV is three to four times more frequent in men than in women... Show moreBicuspid aortic valve (BAV), the most frequent congenital heart disease, is characterized by an uneven distribution between sexes. BAV is three to four times more frequent in men than in women which could be associated with a reduced dosage of X chromosome genes. In addition, BAV has a multifactorial inheritance, low penetrance and variable phenotypes that may lead to different form of valve degeneration and dysfunction over time as well as different incidence of aortic valve and vascular complications between men and women.Definition of the phenotype is the first step in the evaluation of patients with BAV. Among the various phenotypes, BAV with a fusion raphe between the left and the right coronary cusp is the most frequent phenotype observed in men and women. It has been hypothesized that the valve and vascular related complications vary according to the BAV phenotype and this could explain differences in the clinical outcomes of men versus women. However, the evidence on the distribution of the various BAV phenotypes between sexes in not consistent and while some series have described differences between male and female, others have not confirmed those findings.In terms of valvular complications, women present more frequently with aortic stenosis while aortic regurgitation is more frequently diagnosed in men. Furthermore, endocarditis is more frequently reported in men as compared to women. In terms of vascular complications, men show larger diameters of the various parts of the aortic root and ascending aorta and more frequently present complications in terms of aortic aneurysm and dissection as compared to women. Although there are no survival differences between men and women with BAV, compared to the general population some large series have shown that women have worse prognosis. The present review article summarizes the differences between men and women in terms of BAV phenotype, type and incidence of aortic valve and vascular complications that will determine the differences in clinical outcomes. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Hof, M.V. van 't; Ester, W.A.; Serdarevic, F.; Berckelaer-Onnes, I. van; Hillegers, M.H.J.; Tiemeier, H.; ... ; Jansen, P.W. 2020
Children with Autism Spectrum Disorder (ASD) often exhibit problematic eating behaviors, an observation mostly based on male dominated, clinical ASD study samples. It is, however, important to... Show moreChildren with Autism Spectrum Disorder (ASD) often exhibit problematic eating behaviors, an observation mostly based on male dominated, clinical ASD study samples. It is, however, important to evaluate both children with an ASD diagnosis and children with subclinical autistic traits as both often experience difficulties. Moreover, considering the suggestion of a possible girl-specific ASD phenotype, there is a need to determine whether autistic traits are related with problematic eating behaviors in girls as well. This study explores the sex-specific association between autism (both autistic traits and diagnosed ASD) and eating behavior in middle childhood in Generation R, a prospective population-based cohort from fetal life onwards. We collected parental reports of autistic traits at six years (Social Responsiveness Scale) and of eating behavior at ten years (Children's Eating Behaviour Questionnaire). In this cohort of 3559 children, autistic traits at six years were associated with more Picky Eating, Emotional Eating and Food Responsiveness in later childhood (e.g. adjusted B for Picky Eating = 0.07; 95% CI: 0.03, 0.11). Stratified analyses showed that in girls, autistic traits were associated with more Emotional Overeating and Emotional Undereating (e.g. adjusted B for Emotional Undereating= 0.12; 95% CI: 0.04, 0.20), while no associations were found for boys. Results comparing children with and without an ASD diagnosis in the cohort largely confirm these associations (e.g. in girls, adjusted B for Emotional Undereating = 0.72; 95% CI: 0.01, 1.42). Our results point to a sex-specific association between autism and eating behavior in middle childhood. Also, our study is the first study to show that autistic traits are associated with emotionally based eating problems in girls and possibly represent part of a girl-specific ASD phenotype. Show less
Bijl, P. van der; Abou, R.; Goedemans, L.; Gersh, B.J.; Holmes, D.R.; Marsan, N.A.; ... ; Bax, J.J. 2020
Aims Left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) worsens outcome. The effect of sex on LV post-infarct remodelling is unknown. We therefore... Show moreAims Left ventricular (LV) remodelling after ST-segment elevation myocardial infarction (STEMI) worsens outcome. The effect of sex on LV post-infarct remodelling is unknown. We therefore investigated the sex distribution and long-term prognosis of LV post-infarct remodelling after STEMI in the contemporary era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy.Methods and results Data were obtained from an ongoing primary PCI STEMI registry. LV remodelling was defined as >= 20% increase in LV end-diastolic volume at either 3, 6, or 12 months post-infarct, and LV remodelling impact on outcome was evaluated with a log-rank test. A total population of 1995 STEMI patients were analysed (mean age 60 +/- 12 years): 1527 (77%) men and 468 (23%) women. The mean age of male patients was 60 +/- 11 versus 63 +/- 13 years for women (P < 0.001). A total of 953 (48%) patients experienced LV remodelling in the first 12 months of follow-up, and it was equally frequent amongst men (n = 729, 48%) and women (n = 224, 48%). After a median follow-up of 94 (interquartile range 69-119) months, 225 patients died: 171 (11%) men and 54 (12%) women. No survival difference was seen between remodellers and non-remodellers in the male (P = 0.113) and female (P = 0.920) groups.Conclusion LV post-infarct remodelling incidence, as well as long-term survival of LV remodellers and non-remodellers, was similar in men and women who were treated with primary PCI and optimal pharmacotherapy post-STEMI. Show less
The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune... Show moreThe incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-α, interleukin (IL)-6, IL-12, IL-1β, IL-1RA, and IL-10, but not for interferon-γ. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial. Show less
The incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune... Show moreThe incidence of bacterial infections and sepsis, as well as the mortality risk from sepsis, is sex specific. These clinical findings have been attributed to sex differences in immune responsiveness. The aim of the present study was to investigate sex differences in monocyte-derived cytokine production response upon stimulation with the gram-negative stimulus lipopolysaccharide (LPS) using cytokine data from 15 study populations. Individual data on ex vivo cytokine production response upon stimulation with LPS in whole blood were available for 4,020 subjects originating from these 15 study populations, either from the general population or from patient populations with specific diseases. Men had a stronger cytokine production response than women to LPS for tumour necrosis factor-alpha, interleukin (IL)-6, IL-12, IL-1 beta, IL-1RA, and IL-10, but not for interferon-gamma. The granulocyte-macrophage colony-stimulating factor production response was lower in men than in women. These sex differences were independent of chronological age. As men had higher monocyte concentrations, we normalized the cytokine production responses for monocyte concentration. After normalization, the sex differences in cytokine production response to LPS disappeared, except for IL-10, for which the production response was lower in men than in women. A sex-based approach to interpreting immune responsiveness is crucial. Show less
The gender difference in the prevalence of depression is well-documented, poorly understood and multifactorial. Considering that gender differences exist in the expression of emotions, we... Show moreThe gender difference in the prevalence of depression is well-documented, poorly understood and multifactorial. Considering that gender differences exist in the expression of emotions, we hypothesized that ambivalence over the expression of sadness and anger contributes to the difference in depression scores between men and women. Questionnaires on depressive symptoms and ambivalence regarding sadness and anger expression were completed by 550 respondents (66.9% women, average age 27.8years). Women reported more depressive symptoms and were more ambivalent over the expression of both sadness and anger than men. Ambivalence over sadness andto a lesser extentanger mediated the relationship between gender and depressive symptoms. We conclude that ambivalence over emotion expression may partly explain why depression occurs more frequently in women than men. Show less
