Suggest Sex Differences Research Articles

Sex and gender differences in cognitive resilience to aging and Alzheimer's disease.

Sex and gender-biological and social constructs-significantly impact the prevalence of protective and risk factors, influencing the burden of Alzheimer's disease (AD; amyloid beta and tau) and other pathologies (e.g., cerebrovascular disease) which ultimately shape cognitive trajectories. Understanding the interplay of these factors is central to understanding resilienceand resistance mechanismsexplaining maintained cognitive function andreduced pathology accumulation in aging and AD.In this narrative review, the ADDRESS! Special Interest Group (Alzheimer's Association) adopted a multidisciplinary approach to provide the foundations and recommendations for future research into sex- and gender-specific drivers of resilience, including a sex/gender-oriented review of risk factors, genetics, AD and non-AD pathologies, brain structure and function, and animal research.We urge the field to adopt a sex/gender-aware approach to resilience to advance our understanding of the intricate interplay of biological and social determinants and consider sex/gender-specific resilience throughout disease stages. HIGHLIGHTS: Sex differences in resilience to cognitive decline vary by age and cognitive status. Initial evidence supports sex-specific distinctions in brain pathology. Findings suggest sex differences in the impact of pathology on cognition. There is a sex-specific change in resilience in the transition to clinical stages. Gender and sex factors warrant study: modifiable, immune, inflammatory, and vascular.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.

Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes. Islets from T2D donors exhibited similar sex differences in sex chromosomes differentially expressed genes (DEGs), but also exhibited sex differences in autosomal genes. Comparing β cells from T2D vs. ND donors, gene enrichment of female β cells showed suppression in mitochondrial respiration, while male β cells exhibited suppressed insulin secretion. Thus, although sex differences in gene accessibility and expression of ND β cells predominantly affect sex chromosomes, the transition to T2D reveals sex differences in autosomes highlighting mitochondrial failure in females.

Impact of sex on clinical outcome in early Multiple Sclerosis

BackgroundPrevious evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS. MethodsUtilizing prospective cohort data, we assessed the impact of biological sex on time-to-relapse, disability progression (Expanded Disability Status Scale [EDSS]), extremity function (Nine-Hole Peg Test, Timed-25-food walk test), cognition (Paced Auditory Serial Addition Test, Symbol Digit Modalities Test), quality-of-life (Hamburg Quality of Life Questionnaire in Multiple Sclerosis, Short-Form-36), fatigue (Fatigue Severity Scale, Fatigue Scale for Motor and Cognitive functions), and depression (Beck Depression Inventory-II) in clinically isolated syndrome (CIS) or RRMS patients. Inclusion was within 12 months of symptom onset. Linear, negative binomial, mixed, and Cox models estimated male vs. female effects at the four-year follow-up including baseline-to-follow-up course. ResultsWe included 149 patients (65.1 % female). Eighty-five completed four-year follow-up. No sex differences in time-to-relapse emerged (HR = 0.91;95 %CI = 0.53–1.58). Males had no increased risk of EDSS worsening (OR = 0.75;95 %CI = 0.21–2.35) compared to females. Similarly, minor/no sex differences emerged in other outcomes. ConclusionsFour years after first manifestation, neither disease activity (disability progression and relapse rate) nor patient-reported outcomes showed sex-related disparities in this early-MS-cohort. ClinicalTrials.gov Identifier: NCT01371071

13-Week Repeated Oral Toxicity and Toxicokinetic Studies of Rabeprazole Sodium and Sodium Bicarbonate Combination in Dogs.

The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20mg/kg of rabeprazole sodium only, and 800mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively.

Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.

Biological sex affects the pathogenesis of type 2 and type 1 diabetes (T2D, T1D) including the development of β cell failure observed more often in males. The mechanisms that drive sex differences in β cell failure is unknown. Studying sex differences in islet regulation and function represent a unique avenue to understand the sex-specific heterogeneity in β cell failure in diabetes. Here, we examined sex and race differences in human pancreatic islets from up to 52 donors with and without T2D (including 37 donors from the Human Pancreas Analysis Program [HPAP] dataset) using an orthogonal series of experiments including single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), dynamic hormone secretion, and bioenergetics. In cultured islets from nondiabetic (ND) donors, in the absence of the in vivo hormonal environment, sex differences in islet cell type gene accessibility and expression predominantly involved sex chromosomes. Of particular interest were sex differences in the X-linked KDM6A and Y-linked KDM5D chromatin remodelers in female and male islet cells respectively. Islets from T2D donors exhibited similar sex differences in differentially expressed genes (DEGs) from sex chromosomes. However, in contrast to islets from ND donors, islets from T2D donors exhibited major sex differences in DEGs from autosomes. Comparing β cells from T2D and ND donors revealed that females had more DEGs from autosomes compared to male β cells. Gene set enrichment analysis of female β cell DEGs showed a suppression of oxidative phosphorylation and electron transport chain pathways, while male β cell had suppressed insulin secretion pathways. Thus, although sex-specific differences in gene accessibility and expression of cultured ND human islets predominantly affect sex chromosome genes, major differences in autosomal gene expression between sexes appear during the transition to T2D and which highlight mitochondrial failure in female β cells.

Childhood maltreatment and risk of metabolic dysfunction-associated steatotic liver disease – Evidence of sex-specific associations in the general population

Background and aimsChildhood maltreatment (CM) is linked to self-reported liver disease in adulthood. However, specific diagnostic entities, e.g., metabolic dysfunction-associated steatotic liver disease (MASLD) as the most frequent chronic liver disease, and sex-differences have previously not been considered. MethodsCross-sectional analyses were conducted in 4188 adults from a population-based cohort in Northeastern Germany after excluding individuals with excessive alcohol consumption, cirrhosis, or chronic viral hepatitis. CM-exposure was assessed using the Childhood Trauma Questionnaire (CTQ). Liver-related outcomes included serologic liver enzymes, fibrosis-4 score (FIB-4) and, in 1863 subjects who underwent magnetic resonance imaging examination, liver fat content. Sex-stratified linear regression and logistic regression models predicting liver-related outcomes and risk for MASLD, respectively, from overall CTQ scores were adjusted for age, school education, alcohol consumption, and waist circumference. Exploratory analyses investigated effects of CTQ-subscales on liver-related outcomes and risk for MASLD. ResultsIn both sexes, overall CM-exposure was associated with higher levels of serum aspartate aminotransferase and FIB-4 score. In men, effects were mainly driven by physical abuse, and in women by emotional neglect. Only in men, overall CM-exposure (β = 0.70, 95%-CI 0.26–1.13, p = 0.002) and four CTQ-subscales were associated with greater liver fat content, and physical abuse (aOR = 1.22, 95%-CI 1.02–1.46, p = 0.034) and physical neglect (aOR = 1.25, 95%-CI 1.04–1.49, p = 0.015) were associated with higher risk for MASLD. ConclusionsThese results suggest sex differences in the association between CM and objective serum and imaging markers of MASLD in adulthood. For men especially, a history of CM-exposure may increase risk of developing MASLD in adulthood.

Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status.

Guanylate cyclase C (GC-C) has been detected in the rodent brain in neurons of the cerebral cortex, amygdala, midbrain, hypothalamus, and cerebellum. In this study we determined GC-C protein expression in Brodmann areas (BA) 9, BA10, BA11, and BA32 of the human prefrontal cortex involved in regulation of feeding behavior, as well as in the cerebellar cortex, arcuate nucleus of hypothalamus and substantia nigra in brain samples of human 21 male and 13 female brains by ELISA with postmortem delay < 24 h. GC-C was found in all tested brain areas and it was expressed in neurons of the third cortical layer of BA9. The regulation of GC-C expression by feeding was found in male BA11 and BA10-M, where GC-C expression was in negative correlation to the volume of stomach content during autopsy. In female BA11 there was no correlation detected, while in BA10-M there was even positive correlation. This suggests sex differences in GC-C expression regulation in BA11 and BA10-M. The amount of GC-C was higher in female BA9 only when the death occurred shortly after a meal, while expression of GC-C was higher in BA10-O only when the stomach was empty. The expression of GC-C in female hypothalamus was lower when compared to male hypothalamus only when the stomach was full, suggesting possibly lower satiety effects of GC-C agonists in women. These results point toward the possible role of GC-C in regulation of feeding behavior. Since, this is first study of GC-C regulation and its possible function in prefrontal cortex, to determine exact role of GC-C in different region of prefrontal cortex, especially in humans, need further studies.

Sex Differences in T Cell Migration from the Spleen to the Kidney in Mice at Baseline and in Response to Angiotensin II Infusion

Decades of research has indicated that T cells contribute to the development of hypertension and target organ damage. There is a critical role of spleen-derived T cells in angiotensin II-mediated hypertension and kidney damage in mice. Splenectomy abolished sex differences in the development of hypertension in spontaneously hypertensive rats, suggesting sex differences in the spleen-kidney immune axis. It is well-appreciated that immune cells migrate from different tissues to infiltrate organs. However, whether there are sex differences in T cell migration from the spleen to the kidney remained unexplored. Thus, we hypothesized that male mice would show higher immune cell migration from the spleen to the kidney at baseline and in response to angiotensin II infusion when compared to female mice. To quantify T cell migration in male and female mice, we utilized Kikume Green-Red (KikGR) transgenic mice that ubiquitously express the kikume green protein in all cells throughout the body, and this protein can be stably photoconverted to kikume red with exposure to 405 nm blue light. We specifically photoconverted mouse spleens with 10-minute exposure to blue light and infused angiotensin II via mini-pump implantation (490 ng/kg*min) in half of the photoconverted mice. After 3 days post-photoconversion, all mice were sacrificed, and both kidneys were removed for analysis via spectral flow cytometry to determine spleen-derived infiltrating immune cells (CD45+, KikRed+ cells) as well as spleen-derived T cells (CD45+, KikRed+, CD3+) in the kidney. There were no differences in the immune cell profiles found between left and right kidneys within each sex (p = 0.8 [male kidneys] and 0.8292 [female kidneys], n = 6-10 kidneys per group). At baseline, we found significantly increased spleen-derived immune cells in the kidneys of male compared to female mice (P = 0.0173, n = 3-5 per group). In addition, sex was a significant factor in spleen-derived T cell percentages within the kidney (Two-Way ANOVA, P = 0.029, n = 3-5 mice). In response to 3 days of angiotensin II infusion, spleen-derived immune cells were significantly higher in the kidneys of males compared to females (P = 0.0499, n = 3-5 mice). We conclude that there is reduced immune cell migration to the kidney from the spleen at baseline and in response to angiotensin II infusion in female mice, which may contribute to the lower blood pressure and kidney damage observed in female mice. NIH TL1 DK139566 to LNB, NIH R01 DK134562 to JSP. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Low Testosterone Accelerates Age-Associated Declines in Kidney Function Assessed via Estimated Glomerular Filtration Rate in Men

Kidney function declines with increasing age and more than 50% of seniors over the age of 75 years are believed to have overt kidney disease. Data regarding declines in kidney function around the age of menopause in women are consistent with what would be expected of age alone, suggesting that the loss of estrogens do not contribute to declines in kidney function. In contrast, reports indicate that androgen deprivation therapy reduces estimated glomerular filtration rate (eGFR) and increases the risk of acute kidney injury, highlighting a possible influence of testosterone (T) on kidney function. The influence of age-related declines in T on declines in kidney function in otherwise healthy aging men has yet to be determine. PURPOSE: To determine the influence of low T on age-related declines in eGFR in men. Methods: Healthy young (YM; 18-40 years) and middle-aged/older (MA/O; 50-75 years) men participated. MA/O men were categorized as having either low (&lt;300 ng/dL) or normal (400-1000 ng/dL) T via a venous blood draw. Serum creatinine and blood urea nitrogen (BUN) were quantified and eGFR was calculated using the 2021 CKD-EPI creatinine equation. Differences in eGFR and BUN were examined using the Kruskal-Wallis test with Dunn’s multiple comparisons test in the case of a significant main effect. Results: 23 YM (age: 29±4 y, T: 508±60 ng/dL), 23 MA/O men with low T (age: 59±7 y, T: 267±44 ng/dL), and 58 MA/O men with normal T (age: 58±6 y, T: 480±72 ng/dL) participated. Serum creatinine was significantly higher in MA/O men with low T (1.05±0.12 mg/dL) compared to YM (0.95±0.14 mg/dL, p=0.043) and MA/O men with normal T (0.96±0.11 mg/d, p=0.019). There were no differences between YM and MA/O men with normal T (p=0.956). There were significant age-associated declines in eGFR (YM= 109.9±14.3 vs. MA/O men with normal T= 90.1±9.3 mL/min/1.73m2, p&lt;0.001) that were exaggerated in MA/O men with low T (82.6±10.4 mL/min/1.73m2, p=0.044 vs. MA/O men with normal T). BUN was significantly higher in MA/O men (normal T=17.2±3.4 mg/dL, low T=19.2 mg/dL) compared to YM (15.1±3.7 mg/dL, p=0.033 vs. normal T and p&lt;0.001 vs. low T), but there was no difference between MA/O men with normal or low T (p=0.110). CONCLUSIONS: These data suggest that age-associated declines in testosterone contribute to declines in kidney function in otherwise healthy men. These data contrast evidence in women suggesting that the loss of estrogen during the menopause transition does not accelerate kidney dysfunction, suggesting sex differences in the mechanisms of kidney dysfunction. This work was supported by NIH grants R01AG049762, K01HL164978, U54A062319, T32AG000279, the Colorado Clinical and Translational Sciences Institute UL1TR001082, Colorado Nutrition and Obesity Research Center P30DK048520, and the Eastern Colorado GRECC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex Differences in Obesity- and Aging-Mediated Increase of Body Weight and Blood Pressure

The rate of obesity is steadily increasing world-wide, and obesity may predispose to chronic kidney disease (CKD) via direct pathway or through its complications such as hypertension. Furthermore, incidence of CKD is affected by aging and obesity accelerates aging especially in association with its complications. Specifically, the relationship between obesity and aging in controlling CKD progression has not been well-defined. To address this gap in knowledge, we generated a diet-induced obesity mouse model of 52-58-week-old animals and started the characterization of the model by measuring body weight and blood pressure in male and female mice. We studied four groups of mice: first and second groups were male mice, fed 60% high-fat (HF) diet or 10% low-fat (LH) diet for 19 weeks. Third and fourth groups were female mice, fed HF or LF diet for the same number of weeks. A gain in body weight was measured in male mice on HF when compared to male mice on LF diet and was associated with a significant diet-dependent increase (about 30%) in blood pressure. The body weight gain in female mice was more pronounced than in male mice (62% female vs. 54% male). The blood pressure was higher in female mice than in age-matched male mice in control conditions and was not affected by the diet. These findings suggest sex differences in the increase of body weight and blood pressure mediated by diet-induced obesity in mice of 52-58 weeks of age. In summary, our mouse model mimics the phenotype seen in humans and its characterization is valuable to aid the understanding of the relationship of determinants that control the progression of kidney diseases. Des Moines University IOER Research &amp; Grant Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex Differences in Youth with Chronic Tic Disorder and Tourette Syndrome: Evaluation of Tic Severity, Psychological Profiles, and Quality of Life.

Background: Tourette syndrome (TS) and Chronic Tic Disorder (CT) are neurodevelopmental conditions involving motor and/or phonic tics. Youth with tics may encounter feelings of isolation, diminished self-esteem and quality of life, and academic difficulties. A growing body of scientific literature suggests sex differences in youth with tics, but findings have been mixed so far. Because symptom severity peaks around puberty, understanding sex differences in tic manifestations and associated symptoms during this critical period is essential. Therefore, we aimed to assess sex differences related to tic symptoms, action planning styles, quality of life, and externalizing/internalizing symptoms in youth with tics. Methods: Our sample consisted of 66 youths with tics (19 girls) aged 7-14 (mean = 10 years). Youths were assessed with clinical interviews, as well as self- and parent-reported inventories evaluating tic symptoms, psychological profiles, and quality of life. Results: While no differences in tic symptoms were found, girls exhibited lower functional inflexibility, reduced overall functional planning effectiveness, and higher impairment in the psychological well-being subscale than boys. Additionally, girls had reduced general life satisfaction and social self-esteem. Boys reported more explosive outbursts, higher levels of hyperactivity, and more difficulties with self-concept. Conclusions: Our analyses suggested differences in several manifestations associated with tics. This introduces new perspectives that refine our understanding of sex differences. A better understanding of sex differences in tic disorders may eventually improve outcomes for all individuals living with these conditions.

Sexually dimorphic effects of pexidartinib on nerve injury-induced neuropathic pain in mice.

It is well-established that spinal microglia and peripheral macrophages play critical roles in the etiology of neuropathic pain; however, growing evidence suggests sex differences in pain hypersensitivity owing to microglia and macrophages. Therefore, it is crucial to understand sex- and androgen-dependent characteristics of pain-related myeloid cells in mice with nerve injury-induced neuropathic pain. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony-stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL). Following PSL induction, healthy male and female mice and male gonadectomized (GDX) mice exhibited similar levels of spinal microglial activation, peripheral macrophage accumulation, and mechanical allodynia. Treatment with PLX3397 significantly suppressed mechanical allodynia in normal males; this was not observed in female and GDX male mice. Sex- and androgen-dependent differences in the PLX3397-mediated preventive effects were observed on spinal microglia and dorsal root ganglia (DRG) macrophages, as well as in expression patterns of pain-related inflammatory mediators in these cells. Conversely, no sex- or androgen-dependent differences were detected in sciatic nerve macrophages, and inhibition of peripheral CC-chemokine receptor 5 prevented neuropathic pain in both sexes. Collectively, these findings demonstrate the presence of considerable sex- and androgen-dependent differences in the etiology of neuropathic pain in spinal microglia and DRG macrophages but not in sciatic nerve macrophages. Given that the mechanisms of neuropathic pain may differ among experimental models and clinical conditions, accumulating several lines of evidence is crucial to comprehensively clarifying the sex-dependent regulatory mechanisms of pain.

Sex differences in prevalence and clinical correlates of internet addiction among Chinese adolescents with schizophrenia

BackgroundPatients with schizophrenia (SCZ) exhibit sex differences in various aspects, and patients with SCZ have a high prevalence of internet addiction (IA). However, sex differences in IA among patients with SCZ mostly remain unstudied, particularly in Chinese adolescent patients with SCZ. This study investigated sex differences in prevalence, risk factors, and clinical correlates of IA among Chinese adolescent patients with SCZ.MethodsA total of 706 adolescent patients with SCZ were enrolled in this study using a cross-sectional design and a convenience sampling method. Demographics and clinical data of the patients were collected using a standardized clinical assessment form. The Positive and Negative Syndrome Scale (PANSS) and the Young’s Internet Addiction Test were used to evaluate psychopathological symptoms and IA respectively.ResultsOverall, the prevalence of IA among Chinese adolescent patients with SCZ was 26.30% (95% CI: 23.09-29.60%). In Chinese adolescents with SCZ, there was a sex difference in the comorbidity of IA (males: 33.33% vs. females: 21.69%). Binary logistic regression analysis showed that IA was significantly predicted by good socioeconomic status in male and female patients with SCZ. City of living and PANSS total score were associated with IA in male patients with SCZ. In contrast, hospitalization rate and depression score were associated with IA in female patients with SCZ.ConclusionOur study suggests sex differences in clinical correlates of IA in Chinese adolescent patients with SCZ. An additional longitudinal study is required to confirm the findings of the present study.

Sex differences in treatment effect in neuroprotectant trials for acute ischemic stroke: A systematic review

BackgroundPre-clinical data suggest sex differences in mechanisms of cerebral ischemic injury. This might result in differential outcomes of putative neuroprotectants by sex, though little systematic data is available to assess this. MethodsWe performed a systematic review of multicenter randomized controlled trials published from January 1980–June 2022 enrolling >100 subjects and testing neuroprotectants in acute ischemic stroke (AIS). For each trial, reported treatment effect by sex was extracted. When published results by sex were not available, we contacted individual authors to attempt to retrieve these data. ResultsWe identified 59 publications reporting 64 trials that met inclusion criteria. Of these, data on treatment effect by sex were published for 14/64 trials. Unpublished data for an additional 5 trials were obtained from trial investigators (19/64, or 29.7%). Two trials (one testing uric acid and one dexborneol) reported treatment benefit in women but not men. Pooled analysis of six trials of tirilazad reported worse treatment outcomes in women and no effect in men. No clear difference was apparent in the other trials. ConclusionsMost trials did not report treatment effect by sex. Of those that did, there was little evidence of systematic sex differences in treatment response.

The Effects of Age and Height on Gait Smoothness in Adolescent Athletes.

(1) Background: Despite evidence of increased rates of sports injury during the years surrounding peak growth in adolescents, little is known regarding the relationship between adolescent growth and gait stability. The aim of this study was to gain a better understanding of how chronological age and height relate to gait stability in both male and female adolescents. (2) Methods: Participants (N = 67; females: n = 34, ages 8.7-15.9 years; males: n = 33, ages 10.0-16.7 years) completed two trials of treadmill walking at varying speeds: the preferred walking speed and 30% above and below. Trials were separated by a bout of fatiguing exercises. HarmonicRatios of the trunk, calculated from acceleration signals taken during walking, were used to quantify gait stability. Data were separated by sex and relationships between height and chronological age, and HarmonicRatios were assessed using multiple linear regression. (3) Results: Females' HarmonicRatios improved with chronological age both before and after fatigue. Males' HarmonicRatios increased with chronological age before fatigue; however, this effect was eliminated post-fatigue. Females' height was negatively associated with HarmonicRatios post-fatigue. Males' height was positively associated with HarmonicRatios pre-fatigue. (4) Conclusions: The study findings suggest sex differences in the effects of fatigue on gait stability during adolescence. In both sexes, HarmonicRatios increased with chronological age. These improvements were eliminated for males and altered for females with fatigue. The results of this study indicate the need for the reevaluation of sports progression based on chronological age in adolescents.

Do captive fish need cognitive enrichment? A test with a puzzle feeder in guppies

AbstractFor many mammalian and avian species, it has been proposed that cognitive enrichment, such as puzzle feeders, can improve welfare in captive conditions. A well‐established method to evaluate the need for cognitive enrichment is to observe the preference of the animal between freely available food and a puzzle feeder. We investigated this preference in a teleost fish, the guppy. In most of our experimental trials, guppies first chose the feeder with freely available food over the puzzle feeder, in contrast with what was observed in most other species. Nevertheless, the guppies' number of choices for the puzzle feeder was significantly greater than zero. Moreover, after consuming the freely available food, most of the guppies tackled the puzzle feeder. This pattern of results suggests that guppies displayed a certain interest in the puzzle feeder that was overshadowed by their strong attraction towards the free food. Interestingly, several measures of performance indicated that female guppies responded more positively towards the puzzle feeder as compared to the males, suggesting sex differences in the preference for cognitive enrichment. In conclusion, our study highlights the potential significance of cognitive enrichment for captive fish. Considering that the number of individual fish maintained in captivity exceeds by far that of any other vertebrate group, it is paramount to investigate cognitive enrichment in other teleost species.

Sex and ethnic differences in unrecognized myocardial infarctions: Observations on recognition and preventive therapies from the multiethnic population-based HELIUS cohort

BackgroundEpidemiological studies suggest sex differences in the prevalence and characteristics of unrecognized and recognized myocardial infarction (uMI, rMI). Despite increasingly diverse populations, observations are limited in multiethnic contexts. Gaining better understanding may inform policy makers and healthcare professionals on populations at risk of uMI who could benefit from preventive measures. MethodsWe used baseline data from the multiethnic population-based HELIUS cohort (2011–2015; Amsterdam, the Netherlands). Using logistic regressions, we studied sex differences in the prevalence and proportion of uMIs across ethnic groups. Next, we studied whether symptoms, clinical parameters, and sociocultural factors were associated with uMIs. Finally, we compared secondary preventive therapies in women and men with a uMI or rMI. We relied on pathological Q-waves on a resting electrocardiogram as the electrocardiographic signature for (past) MI. ResultsOverall, and in Turkish and Moroccan subgroups, the prevalence of uMIs was higher in men than women. The proportion of uMIs was similar in women (21.0%) and men (18.4%), yet varied by ethnicity. In women and men, symptoms (chest pain, dyspnea) and clinical parameters (hypertension, hypercholesterolemia), and in women also lower educational level and diabetes were associated with lower odds of uMIs. Women (0.0%) and men (3.6%) with uMI were unlikely to receive secondary preventive therapies compared to those with rMI (28.1–40.9%). ConclusionsThe prevalence of uMIs was higher in men than women, and sex differences in the proportion of uMIs varied somewhat across ethnic groups. People with uMIs did not receive adequate preventative medications, posing a risk for recurrent events.

Impact of early risk factors on schizophrenia risk and age of diagnosis: A Danish population-based register study.

While several risk factors for schizophrenia have been identified, their individual impacts are rather small. The relative independent and cumulative impacts of multiple risk factors on disease risk and age of onset warrant further investigation. We conducted a register-based case-control study including all individuals receiving a schizophrenia spectrum disorder in Denmark from 1973 to 2018 (N=29,142), and a healthy control sample matched 5:1 on age, sex, and parental socioeconomic status (N=136,387). Register data included parental history of psychiatric illness, birth weight, gestational age, season of birth, population density of birthplace, immigration, paternal age, and Apgar scores. Data were analysed using logistic regression and machine learning. Parental history of psychiatric illness (OR=2.32 [95%CI 2.21-2.43]), high paternal age (OR=1.30 [1.16-1.45]), and low birth weight (OR=1.28 [1.16-1.41]) increased the odds of belonging to the patient group. In contrast, being a second-generation immigrant (OR=0.65 [0.61-0.69]) and high population density of the birthplace (OR=0.92 [0.89-0.96]) decreased the odds. The findings were supported by a decision tree analysis where parental history, paternal age, and birth weight contributed most to diagnostic classification (ACCtest=0.69, AUCtest=0.59, p<0.001). Twenty percent of patients were child-onset cases. Here, female sex (OR=1.82 [1.69-1.97]) and parental psychiatric illness (OR=1.62 [1.49-1.77]) increased the odds of receiving the diagnosis <18years. Multiple early factors contribute independently to a higher psychosis risk, suggesting cumulative effects leading to symptom onset. Routine assessments of the most influential risk factors could be incorporated into clinical practise. Being female increased the risk of diagnosis during childhood, suggesting sex differences in the developmental trajectories of the disorder.

Adenosine Receptor mRNA Expression in Frontal Cortical Neurons in Schizophrenia.

Schizophrenia is a devastating neuropsychiatric disorder associated with the dysregulation of glutamate and dopamine neurotransmitter systems. The adenosine system is an important neuroregulatory system in the brain that modulates glutamate and dopamine signaling via the ubiquitously expressed adenosine receptors; however, adenosine A1 and A2A receptor (A1R and A2AR) mRNA expression is poorly understood in specific cell subtypes in the frontal cortical brain regions implicated in this disorder. In this study, we assayed A1R and A2AR mRNA expression via qPCR in enriched populations of pyramidal neurons, which were isolated from postmortem anterior cingulate cortex (ACC) tissue from schizophrenia (n = 20) and control (n = 20) subjects using laser microdissection (LMD). A1R expression was significantly increased in female schizophrenia subjects compared to female control subjects (t(13) = -4.008, p = 0.001). A1R expression was also significantly decreased in female control subjects compared to male control subjects, suggesting sex differences in basal A1R expression (t(17) = 2.137, p = 0.047). A significant, positive association was found between dementia severity (clinical dementia rating (CDR) scores) and A2AR mRNA expression (Spearman's r = 0.424, p = 0.009). A2AR mRNA expression was significantly increased in unmedicated schizophrenia subjects, suggesting that A2AR expression may be normalized by chronic antipsychotic treatment (F(1,14) = 9.259, p = 0.009). Together, these results provide novel insights into the neuronal expression of adenosine receptors in the ACC in schizophrenia and suggest that receptor expression changes may be sex-dependent and associated with cognitive decline in these subjects.