Sex Differences in Cortical Thickness and Neuropsychiatric Symptom Burden Based on APOE4 Homozygosity in Alzheimer's Disease.

Sex differences in patterns of cortical thickness and neuropsychiatric symptom (NPS) burden were examined among individuals with Alzheimer's disease (AD) and two copies (homozygote carriers) of the e4 allele of the apolipoprotein gene (APOE). A total of 752 participants with a clinical etiologic diagnosis of AD were selected from the National Alzheimer's Coordinating Center (NACC) database. Bayesian multilevel regression was used to examine both the within- and between-sex differences in gray-matter cortical thickness and total NPS burden associated with APOE homozygosity. Female homozygote carriers displayed a high probability of having reduced cortical thickness primarily in medial-lateral temporal regions and a greater burden of NPS, relative to both non-homozygous females and homozygous males. These findings support the notion that APOE4 status affects cortical thickness and symptom burden in men and women with AD differentially, with females showing more pronounced effects in brain areas known to be vulnerable in early AD. Future investigations should attempt to elucidate the proposed pattern of decline longitudinally.

Doublecortin-immunoreactive neurons in the piriform cortex are sensitive to the long lasting effects of early life stress.

The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.

Is Degradation in the Eye of the Beholder (or the Researcher)?

When people raise concerns about pornography, they most often are focused on whether pornography increases violence toward women and/or whether it degrades women. While a substantial amount of cross-cultural data suggests that there is no direct link between adult consumption and violence, the question of whether pornography is inherently degrading to women lacks clear answers. As does the question of whether behaviors in pornography that are commonly labeled as degrading are perceived that way when they take place outside pornography. To answer this question about the inherent nature of degradation, we need a better definition and understanding of what particular behaviors people consider to be degrading and whether their perception of what is degrading is influenced by the circumstance or the people involved in a non-pornography setting. To examine this, 496 individuals (247 females, 249 males) were asked to indicate their perceptions of various sexual behaviors when engaged in by males and females toward male and female partners. Results suggest that while some particular sexual behaviors are broadly viewed as degrading (e.g., watersports), perceptions of degradation for other behaviors seem to be influenced by who is doing what to whom. In this sense, the perception of degradation exists in the eye of beholder and is often not defined by the particular sexual act. Future studies of degradation should take into account the context as well as the players involved.

Psoriasis localization patterns in the Swiss Psoriasis Registry (SDNTT) over 11 years: an analysis by sex and age.

Real-world data on anatomically localized psoriasis and its response to systemic therapy across different age-groups and sexes is limited. This study aimed to evaluate the severity and distribution of psoriasis over time in female and male patients receiving systemic therapies, categorized by age within the Swiss psoriasis registry (SDNTT). Patient-data was obtained over 11 years through the SDNTT. The localized Psoriasis Area and Severity Index (locPASI) of the head, trunk, upper and lower extremities was analyzed over two years following the start of systemic non-/biologic treatment. A total of 316 female and 517 male patients were analyzed. Male patients had a higher baseline locPASI for legs, trunk and arms (p < 0.001), but not for the head (p = 0.961). The locPASI for the head in younger female patients (18-40 years) had a higher score than those aged 55 + (p = 0.022) and after two years, middle aged (41-54) showed a lower score compared to younger patients (p = 0.045). Younger male patients revealed a lower score after two years of therapy in the leg- and arm-area compared to older (p = 0.018 and p = 0.048, respectively). Female patients on non-biologics had a fast initial response, converging with male patients' scores over 24 months. Over 75% locPASI reduction was observed for female head-area (81.4%), male trunk (82.7%) and legs (76.1%). Absolute locPASI ≤ 2 was achieved 3-6 months for all locations with interleukin (IL)-17, IL-12/23 and IL-23-inhibitors, except for the legs of male patients on anti-IL-17 and female patients on anti-IL-12/23 and -IL-23. After two years, male patients did not achieve a locPASI ≤ 2 for any biologic-treatment in the legs, nor for the arms on anti-TNF-α. Significant disparities in localized PASI were observed between female and male patients. The age, sex and severity of distinct localizations should be considered to optimize treatment goals.

First manifestation of cardiovascular disease according to age and sex in a Mediterranean country.

Background: Cardiovascular (CV) diseases are the most common cause of death worldwide. This study aimed to investigate the incidence and type of first CV event in a broad cohort of Spaniards, focusing on age and sex differences. Methods: This was a retrospective study using the SIDIAP database. Subjects aged 30-89 years in 2010 were included. Individuals with prevalent CV disease or atrial fibrillation were excluded. Subjects were followed until the occurrence of a CV event, death, or the study end (December 2016). CV outcomes (coronary heart disease [CHD], cerebrovascular or peripheral artery disease and heart failure [HF]) during follow-up were analyzed. Clinical, anthropometrical, and laboratory data were retrieved from clinical records. Results: Overall, 3,769,563 at-risk individuals (51.2 ± 15.2 years) were followed for a median of 7 years. The cumulative incidence of a first CV event was 6.66% (men vs. women, 7.48% vs. 5.90%), with the highest incidence (25.97%) among individuals >75 years. HF (29%) and CHD (28.8%) were the most common first events overall; in men it was CHD (33.6%), while in women it was HF and cerebrovascular disease (37.4% and 27.4%). In younger age groups, CHD was more prevalent, with HF in older age groups. Baseline CV risks factors conferred more risk in younger ages and differed between men and women. Conclusions: The incidence and type of the first CV event in this Mediterranean region were significantly influenced by age and sex. This information is relevant for tailoring primary prevention strategies including the treatment of risk factors.

Sex differences in the orofacial antinociceptive effect of metformin and the role of transient receptor potential channels.

Metformin is classified as a biguanide and is used in the treatment of type 2 diabetes. It is used worldwide and has been investigated in drug repositioning. The present study aims to investigate whether there is sexual dimorphism in the orofacial antinociceptive effect of metformin and the participation of TRP channels. Acute nociceptive behavior was induced by administering cinnamaldehyde or capsaicin to the upper lip. Nociceptive behavior was assessed through orofacial rubbing, and the effects of pre-treatment with metformin (125 or 250 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint. The chronic pain model involved infraorbital nerve transection (IONX) was evaluated using Von Frey electronic filaments. Trpv1 gene expression was analyzed in the nerve ganglion. Docking experiments were performed. Metformin, but not the vehicle, produced antinociception (p < 0.0001) in all acute nociceptive behaviors in both sexes, and these effects were attenuated by the TRPV1 antagonist capsazepine and the TRPA1 antagonist HC-030031. In IONX with better (**p < 0.01, ****p < 0.0001 vs. control) results in females. TRPV1 gene expression was observed in the metformin treated group (*p < 0.05 vs. control). Docking experiments revealed that metformin may interact with TRPV1 and TRPA1 channels. Metformin promotes orofacial antinociception in both sexes in acute pain and is more effective in chronic pain in females than in males, through the modulation of TRPV1 and TRPA1 channels. These preclinical findings suggest a potential repositioning of metformin as an analgesic agent in acute and chronic orofacial pain states.

Impact of gender, posture and phase on back and lower extremity moments and muscle excitation during lifting task: a cross-sectional study.

Purpose: The aim of this work was to investigate and compare back and lower extremity joint moments and muscle excitation during stoop and squat postures by incorporating gender-based differences and analyzing lifting phases. Methods: 18 healthy adults (9 males and 9 females; age: 24.44 ± 4.96 years, body mass: 66.00 ± 12.10 kg, height: 170.11 ± 9.20 cm, lean body mass: 48.46 ± 7.66 kg) lifted an object 30% of their lean body mass using squat and stoop postures. Marker-based motion capture, force plate, and surface electromyography were synchronously used to acquire joint moments and muscle excitation. A 3-way mixed model analysis was performed to determine the effect of gender, posture, and phase on internal joint moments and muscle excitation of the lower back and extremities. Results: Significant differences were observed in the interaction of lifting posture and phase on lower extremity moments and excitation of rectus femoris and medial gastrocnemius. Individual effects of posture were significant for peak internal joint moments of the lower extremities only. Anterior lower extremity muscles showed significantly increased excitation during squat, whereas medial gastrocnemius was higher in stoop. Joint moments and muscle excitations were all higher during the lifting than the bending phase. Gender differences were found only in the peak lumbosacral sagittal plane moment and rectus femoris muscle excitation. Conclusions: The study identified significant variations in the joint moments and muscle excitation in lifting, influenced by gender, posture, and phase, highlighting its complex nature. Overall interactions were lacking, however individual effects were evident, necessitating larger future studies.

Weight Loss Differentially Impacts Sex Hormones in Women and Men with Type 2 Diabetes: Look AHEAD Sex Hormone Study.

BACKGROUND: Despite sex differences in T2D, few studies have examined the role of sex hormones. We sought to assess the impact of weight loss, the cornerstone of T2D management, on sex hormone levels. METHODS: This was an ancillary study to the Look AHEAD (Action for Health In Diabetes) Study (n=850 postmenopausal females, n=890 males, with T2D and BMI ≥25 kg/m2). We measured total testosterone (T), estradiol (E2) and sex hormone binding globulin (SHBG) and calculated bioavailable T (bioT). We examined the effect of the intensive lifestyle intervention (ILI) on hormone changes, whether changes were mediated by waist circumference and sex differences in treatment effect. RESULTS: The baseline mean age was 60 years with a higher proportion of Black females (21%) vs. males (9%) and higher mean BMI in females vs. males (36.3 vs. 34.8 kg/m2). At year 1 in females, ILI decreased E2 by 15% and bioT by 13% and increased SHBG by 21%. At year 1 in males, ILI did not change E2 levels, but increased T by 14% and increased SHBG by 18%. The effect was attenuated over 4 years, there were statistically significant sex differences in treatment effect and change in waist circumference due to ILI at year 1 was a significant mediator of sex hormone changes. CONCLUSION: Weight loss in T2D resulted in sex hormone changes, which varied by sex and were mediated by changes in WC. Changes in sex hormone due to weight loss in T2D should be considered in the context of an individual's health risks, including cardiovascular, bone health, menopausal symptoms and cognition.

Sex differences in the clinical manifestations and treatment outcomes in a large cohort of spontaneous intracranial hypotension.

OBJECTIVE: To determine sex differences in clinical profiles and treatment outcomes in patients with spontaneous intracranial hypotension. BACKGROUND: Spontaneous intracranial hypotension is associated with considerable functional disability and potentially fatal complications, and it is uncertain whether males and females should be managed differently. METHODS: This was a cohort study of consecutive patients with spontaneous intracranial hypotension enrolled from a medical center. Medical records and imaging findings were reviewed. The outcome of treatment responses to epidural blood patches and risks of subdural hematoma were measured. RESULTS: In total, 442 patients with spontaneous intracranial hypotension (165 males, 277 females) were included in the analysis. Males were more likely to have a delayed (>30 days) initial presentation than females (32.1% [53/165] vs. 19.9% [55/277], p = 0.004), and males were less likely to have nausea (55.8% [92/165] vs. 67.1% [186/277], p = 0.016), vomiting (43.0% [71/165] vs. 54.2% [150/277], p = 0.024), photophobia (9.7% [16/165] vs. 17.0% [47/277], p = 0.034), and tinnitus (26.7% [44/165] vs. 39.7% [110/277], p = 0.005) compared with females despite comparable radiologic findings. Among the 374 patients treated with epidural blood patches, males were more likely to be nonresponders to the first epidural blood patch (58.0% [80/138] vs. 39.0% [92/236], OR = 2.2, 95% CI = 1.4-3.3, p < 0.001). Males were at a higher risk of having subdural hematoma (29.7% [49/165] vs. 10.8% [30/277], OR = 3.5, 95% CI = 2.1-5.8, p < 0.001). Among patients with subdural hematoma, males had greater thickness (12.8 ± 4.3 vs. 8.1 ± 5.9 mm, p < 0.001) and were more likely to receive surgical drainage (55.1% [27/49] vs. 10.0% [3/30], OR = 11.0, 95% CI = 3.0-41.3, p < 0.001) than females. CONCLUSION: In the present study, spontaneous intracranial hypotension in males was characterized by a delayed presentation, poorer response to the first epidural blood patch, and a higher risk of subdural hematoma. Caution should be exercised in the management of males with spontaneous intracranial hypotension. The generalizability of the findings needs to be further confirmed.

Vocal Fold Injury Produces Similar Biomechanical Outcomes in Male and Female Rabbits.

OBJECTIVE: Sex differences in response to trauma and physiologic stressors have been identified in numerous organ systems but have not yet been defined in the larynx. The objective of this study was to develop an endoscopic vocal fold injury model in rabbits and to compare structural and functional outcomes between male and female subjects. STUDY DESIGN: Basic science study. METHODS: Two male and two female rabbits underwent unilateral endoscopic cordectomy. Animals were intubated with a size 3-0 neonatal endotracheal tube, and laryngoscopy was performed with a 4 mm Hopkins rod telescope. While visualizing, a 2 mm cupped forceps grasped and resected the mid-membranous portion of the right true vocal fold. Larynges were then harvested after 8weeks. Excised larynx phonation with high-speed videography and kymography was used to assess vibrational quality. Tissue elastic (Young's) modulus was measured by indentation. RESULTS: Injured larynges phonated with fundamental frequencies between 237-415 Hz. In both males and females, the scarred vocal fold exhibited an increased Young's modulus compared to the contralateral nonoperated vocal fold. There were no notable differences in glottal closure pattern or vocal fold oscillation symmetry between sexes. CONCLUSION: We have demonstrated a model for vocal fold scarring in rabbits. Vibrational and structural outcomes were similar between the examined male and female larynges.

Differences between sexes in STEMI treatment and outcomes with contemporary primary PCI.

BACKGROUND: Historically, differences in timely reperfusion and outcomes have been described in females who suffer ST-segment elevation myocardial infarction (STEMI). However, there have been improvements in the treatment of STEMI patients with contemporary Percutaneous Coronary Intervention (PCI) strategies. METHODS: Comparisons between sexes were performed on STEMI patients treated with primary PCI over a 4-year period (January 1, 2017-December 31, 2020) from the Queensland Cardiac Outcomes Registry. Primary outcomes were 30-day and 1-year cardiovascular mortality. Secondary outcomes were STEMI performance measures. The total and direct effects of gender on mortality outcomes were estimated using logistic and multinomial logistic regression models. RESULTS: Overall, 2747 (76% male) were included. Females were on average older (65.9 vs. 61.9 years; p < 0.001), had longer total ischemic time (69 min vs. 52 min; p < 0.001) and less achievement of STEMI performance targets (<90 min) (50% vs. 58%; p < 0.001). There was no evidence for a total (odds ratio [OR] 1.3 (95% confidence interval [CI]: 0.8-2.2; p = 0.35) or direct (adjusted OR 1.2 (95% CI: 0.7-2.1; p = 0.58) effect of female sex on 30-day mortality. One-year mortality was higher in females (6.9% vs. 4.4%; p = 0.014) with total effect estimates consistent with increased risk of cardiovascular mortality (Incidence rate ratio [IRR]: 1.5; 95% CI: 1.0-2.3; p = 0.059) and noncardiovascular mortality (IRR: 2.1; 95% CI: 0.9-4.7; p = 0.077) in females. However, direct (adjusted) effect estimates of cardiovascular mortality (IRR: 1.0; 95% CI: 0.6-1.6; p = 0.94) indicated sex differences were explained by confounders and mediators. CONCLUSION: Small sex differences in STEMI performance measures still exist; however, with contemporary primary PCI strategies, sex is not associated with cardiovascular mortality at 30 days or 1 year.

Sex-Differences in Post-Procedural Pain Experiences After Thermal Liver Ablations for Liver Tumors: A Retrospective Study.

INTRODUCTION: Literature shows differences in pain experiences between sexes. The exact influence of thermal liver ablation on experienced pain is still not well-known. This study aims to investigate the maximum pain intensity at the recovery between men and women after percutaneous thermal liver ablation. METHODS: Patients treated with percutaneous thermal liver ablation (radiofrequency or microwave ablation) in Maastricht University Medical Center + between 2018 and 2022 for primary or secondary liver tumors were included retrospectively. Outcomes included maximum numerical rating scale (NRS, scale:0-10) score at the recovery room, prevalence of post-procedural pain (defined as NRS score ≥ 4), duration of anesthesia, length of stay at recovery, and complications. Regression analyses were adjusted for age, ASA-score, BMI, tumor type, maximum diameter of lesion, chronic pain in patients' history, and history of psychological disorder. RESULTS: 183 patients were included of which 123 men (67%). Results showed higher average maximum NRS scores in women patients compared to men (mean:3.88 versus 2.73), but not after adjustments (aß:0.75, 95%CI:-0.13-1.64). Women suffered more from acute post-procedural pain (59% versus 35%; aOR:2.50, 95%CI:1.16-5.39), and needed analgesics more often at the recovery room (aOR:2.43, 95%CI:1.07-5.48) compared to men. NRS score at recovery arrival did not significantly differ (aß:0.37, 95%CI:-0.48-1.22). No differences were seen in the length of stay at the recovery, duration of anesthesia, procedure time, and complication rate. Location of the tumor (subcapsular or deep), total tumors per patient, and distinction between primary and secondary tumors had no influence on the NRS. CONCLUSION: This retrospective single-center study shows higher post-procedural pain rates after thermal liver ablation in women, resulting in higher analgesics use at the recovery room. The results suggest considering higher dosage of analgesics during thermal liver ablation in women to reduce post-procedural pain. LEVEL OF EVIDENCE 3: Non-controlled retrospective cohort study.

Reprint of: Sex differences in appeal, reward, and sensory experience of E-cigarette flavors among adults who smoke cigarettes.

OBJECTIVE: Flavors enhance nicotine e-cigarette appeal by altering sensory experience. Females may be more sensitive to tobacco-associated cues and uniquely affected by flavor. The current study is an exploratory analysis to examine differences by sex on reward, appeal, and sensory experience of popular e-cigarette flavors. METHODS: Adults (N = 121) who use cigarettes (≥1 cigarette/day) were enrolled in a laboratory study in which they vaped four e-cigarette flavors (tobacco, cherry, menthol, vanilla; in separate lab sessions) in one of two freebase nicotine concentrations (6 mg/ml,18 mg/ml). Following exposures, participants rated e-cigarette reward using the Drug Effects Questionnaire (DEQ), flavor and overall e-cigarette appeal using Labeled Hedonic Scales (LHS), and intensity of flavor, irritation, coolness, fruitiness, and sweetness using Generalized Labeled Magnitude Scales (gLMS). Linear mixed models were conducted for outcomes to analyze effects of sex, flavor, and sex x flavor interaction. RESULTS: For DEQ ratings, there was a trend (p = .08) toward a sex x flavor interaction, in which menthol flavor produced more reward than other flavors for females, but not males. For LHS ratings, there was a significant sex x flavor interaction (p = .03) for overall e-cigarette experience with females but not males rating menthol higher than other flavors. All gLMS scales but irritation showed that females generally had greater differences between flavors compared to males (ps ≤ 0.03). CONCLUSION: Menthol in e-cigarettes may play an important role in mediating appeal and/or reward among females. This may be due in part to their ability to better detect sensory effects of e-cigarettes.

Sex-Based Differences in the Risk of Contrast-Induced Nephropathy and Clinical Outcomes in Patients Undergoing Coronary Angiography and/or Percutaneous Coronary Intervention.

Background: There is still controversial or limited evidence on whether sex differences exist in clinical characteristics, the risk of contrast-induced nephropathy (CIN), and other clinical outcomes of patients who received coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The aim of this study was to characterize the effect of sex on clinical characteristics and outcomes of patients undergoing CAG and/or PCI. Methods: A total of 3,340 consecutive patients undergoing CAG and/or PCI from May 2017 to December 2022 were assessed in this retrospective study. Subgroup analyses by sex were performed. Clinical characteristics, treatments, the risk of CIN, and other clinical outcomes, including in-hospital and follow-up, were compared between females and males. Results: Females undergoing CAG and/or PCI tended to have an advanced age (65.8 versus 63.3 years, p < 0.001), a higher burden of complications, and received PCI less frequently compared with males (43.2% versus 64.2%, p < 0.001). After adjustment, female sex was associated with a higher incidence of CIN [adjusted odds ratio (aOR) 1.47; 95% CI 1.08-2.01; p = 0.015] and a higher all-cause readmission rate (aOR 1.26; 95%CI 1.02-1.56; p = 0.031). Meanwhile, females undergoing CAG alone demonstrated a higher risk of severe arrhythmia compared with males after controlling for potential confounders (aOR 1.52; 95% CI 1.12-2.04; p = 0.006). Conclusion: Sex disparities exist in the clinical characteristics, treatments, the risk of CIN, and other clinical outcomes among patients undergoing CAG and/or PCI. Female sex was identified as an independent predictor of risk for CIN, all-cause readmission rate, and severe arrhythmia.

Consideration of absolute intensity when examining sex differences in blood pressure responses during static exercise.

Low-to-moderate intensity submaximal static contractions are commonly used to study the effects of biological sex on the cardiovascular responses to exercise. Under this paradigm, premenopausal females frequently demonstrate smaller blood pressure responses than age-matched males. These differences are preserved during post-exercise circulatory occlusion, implicating the muscle metaboreflex as an important driver of sex differences in the blood pressure response to static exercise. The mechanisms responsible for these differences are incompletely understood but often attributed to innate sex differences in skeletal muscle fibre type distribution, muscle metabolism, and/or sympathetic control of the circulation. However, one potential confounding factor is that the majority of studies use relative intensity exercise (e.g., 30% of maximal voluntary contraction), such that on average, females are completing static contractions at a lower absolute intensity. In this review, we summarize human evidence showing that sex differences in blood pressure responses to static exercise are attenuated or abolished when controlling for absolute intensity and muscle strength, either by statistical methods or strength-matching cohorts. We highlight evidence that the effect of higher absolute contraction intensity on blood pressure responses likely occurs through increased mechanical occlusion of skeletal muscle microvasculature, leading to greater activation of the muscle metaboreflex. These findings highlight an important need to account for absolute intensity when studying and interpreting sex differences in cardiovascular responses to exercise.

Sex-Specific Imaging Biomarkers for Parkinson's Disease Diagnosis: A Machine Learning Analysis.

This study aimed to identify sex-specific imaging biomarkers for Parkinson's disease (PD) based on multiple MRI morphological features by using machine learning methods. Participants were categorized into female and male subgroups, and various structural morphological features were extracted. An ensemble Lasso (EnLasso) method was employed to identify a stable optimal feature subset for each sex-based subgroup. Eight typical classifiers were adopted to construct classification models for PD and HC, respectively, to validate whether models specific to sex subgroups could bolster the precision of PD identification. Finally, statistical analysis and correlation tests were carried out on significant brain region features to identify potential sex-specific imaging biomarkers. The best model (MLP) based on the female subgroup and male subgroup achieved average classification accuracy of 92.83% and 92.11%, respectively, which were better than that of the model based on the overall samples (86.88%) and the overall model incorporating gender factor (87.52%). In addition, the most discriminative feature of PD among males was the lh 6r (FD), but among females, it was the lh PreS (GI). The findings indicate that the sex-specific PD diagnosis model yields a significantly higher classification performance compared to previous models that included all participants. Additionally, the male subgroup exhibited a greater number of brain region changes than the female subgroup, suggesting sex-specific differences in PD risk markers. This study underscore the importance of stratifying data by sex and offer insights into sex-specific variations in PD phenotypes, which could aid in the development of precise and personalized diagnostic approaches in the early stages of the disease.

Various modalities of resistance exercise promote similar acute cognitive improvements and hemodynamic increases in young, healthy adults.

The aim was to examine the effects of modalities of acute resistance exercise (RE) on cognition and hemodynamics including internal carotid artery (ICA) blood flow (BF). Twenty adults completed familiarization and experimental visits. One-repetition maximum (1RM) for bilateral leg extension was quantified, and baseline executive functioning was determined from three run-in visits. Subsequent visits included three randomized, volume-equated, acute exercise bouts of 30 %1RM+blood flow restriction (BFR), 30 %1RM, and 70 %1RM. Both 30 %1RM trials completed four sets of exercise (1 × 30, 3 × 15), and the 70 %1RM condition completed four sets of 8 repetitions. BFR was induced with 40 % of the pressure to occlude the femoral arteries. 11 min following each exercise, participants completed the Stroop and Shifting Attention Tests. Baseline and post-exercise values were used to calculate change scores. The resulting mean change scores were evaluated with mixed factorial ANOVAs. A p≤0.05 was considered significant. All measured outcome variables increased in response to exercise. The ANOVAs for cognitive scores indicated no significant (p>0.05) interactions. For cognitive flexibility and executive function index, there were main effects of Sex. Change scores of the females were significantly greater than the males for cognitive flexibility (7.6 ± 5.9 vs. -2.6 ± 8.4 au; p=0.007) and executive function index (7.4 ± 4.6 vs. -2.5 ± 6.5 au; p=0.001). For ICA BF, there was no significant interaction or any main effect. The females exhibited a smaller exercise-induced increase in blood pressure compared to the males (17.7 ± 5.9 vs. 11.0 ± 4.1 mmHg; p=0.010). Each RE modality yielded acute improvements in cognition, but only for females. There were no cognitive improvements related to BFR such that each RE bout yielded similar results.

Sex differences in the roles of nicotine use and puberty on youth C-reactive protein levels: Effects above and beyond adversity.

Inflammation likely mediates associations between nicotine use and negative health outcomes. Sex differences have been observed in nicotine use-inflammation links, and physiological processes during puberty might allow for these differences to arise. In this cross-sectional study of 498 youth (ages 8-13, 52% girls, 77% with history of child maltreatment (CM) investigation), sex-differentiated associations between self-reported nicotine use and high-sensitivity C-reactive protein (hs-CRP) were explored. Additionally, self-reported pubertal stage was investigated as a moderator of such nicotine use-hs-CRP links. Hierarchical generalized estimating equation models were adjusted for a wide range of adversity effects: CM investigation history derived from state records, self- and caregiver-report of traumatic life events, adversity-related demographic risk factors (i.e., identification with historically marginalized racial and ethnic groups, household income), and other characteristics that may influence the variables of interest (e.g., medication use, age, body mass index). Nicotine use had a negative main effect on hs-CRP among boys (ß = -0.50, p = 0.02), and pubertal stage did not moderate this association (ß = 0.06, p = 0.71). In contrast, pubertal stage moderated the association between nicotine use and hs-CRP among girls (ß = 0.48, p = 0.02) such that a positive association between nicotine use and hs-CRP levels was stronger at more advanced pubertal stages (ß = 0.45, SE = 0.21, 95% CI [0.03, 0.87]). Findings suggest that puberty may influence the effect of nicotine on inflammation in sex-differentiated ways and have implications for timing of prevention and treatment efforts geared toward reducing nicotine use and subsequent inflammation-related health risk among youth.

Liver adrenoceptor alpha-1b plays a key role in energy and glucose homeostasis in female mice.

The liver plays a major role in glucose and lipid homeostasis and acts as a key organ in the pathophysiology of metabolic diseases. Intriguingly, increased sympathetic nervous system (SNS) activity to the liver has been associated with the development and progression of type 2 diabetes and obesity. However, the precise mechanisms by which the SNS regulates hepatic metabolism remain to be defined. While liver alpha1-adrenoceptors were suggested to play a role in glucose homeostasis, the specific subtypes involved are unknown mainly because of the limitations of pharmacological tools. Here we generated and validated a novel mouse model allowing tissue-specific deletion of alpha-1b adrenoceptor (Adra1b) in hepatocytes to investigate the role of liver ADRA1B in energy and glucose metabolism. We found that selective deletion of Adra1b in mouse liver has limited metabolic impact in lean mice. However, loss of Adra1bin hepatocytes exacerbated diet-induced obesity, insulin resistance and glucose intolerance in female, but not male mice. In obese females, this was accompanied by reduced hepatic gluconeogenic capacity and reprogramming of gonadal adipose tissue with hyperleptinemia. Our data highlight sex-dependent mechanisms by which the SNS regulates energy and glucose homeostasis through liver ADRA1B.

Insights into Uromodulin and Blood Pressure.

PURPOSE OF REVIEW: We review the role of uromodulin, a protein exclusively expressed in the kidney, in blood pressure regulation and hypertension. RECENT FINDINGS: The last few years have seen a shift of focus from genetic association to mendelian randomisation and uromodulin-salt interaction studies, thus confirming the causal role of uromodulin in blood pressure regulation and hypertension. This work has been complemented by phenome-wide association studies in a wider range of ethnicities. Important recent molecular work elucidated uromodulin trafficking and secretion and provided more insights into the pathophysiological roles of circulating and urinary uromodulin. Uromodulin has a causal role in blood pressure regulation and hypertensin. Recent studies show utility of the uromodulin as a biomarker and a possible precision medicine application based on genetically determined differential responses to loop diuretics.