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BACKGROUND: Both the risk of developing heart disease and the course of the disease are determined in particular by comorbidities. In this context, gout has recently been identified as an important factor in influencing the development of cardiovascular events such as heart failure or coronary artery disease. METHODS: This retrospective cohort study compared the incidence of angina pectoris (AP) (ICD-10: I20), myocardial infarction (MI) (ICD-10: I21, I22), chronic coronary heart disease (CHD) (ICD-10: I25), atrial fibrillation (AF), and heart failure (HF) as a function of gout in Germany in a large collective of 66,000 gout patients in comparison to 66,000 individuals without gout between using propensity score matching (1:1) from January 2005 to December 2020. RESULTS: Within 10 years after the index date, AP was diagnosed in 5.2% of gout and 2.9% of non-gout patients (p < 0.001), MI in 3.1% of gout and 2.2% of non-gout patients (p < 0.001), CHD in 16.5% of gout and 11.8% of non-gout patients, AF in 12.6% of gout and 8.4% of non-gout patients (p < 0.001), and HF in 14.7% of gout and 8.5% of non-gout patients (p < 0.001). For all diagnoses except CHD, the association was stronger in male than in female patients. CONCLUSION: The relationship shown between gout and cardiovascular disease indicates that gout could be one of a series of inflammatory conditions that increase the risk of cardiac disease. The association we have shown between gout and all major cardiac diseases suggests that there is a risk modifier, the treatment of which could help prevent these diseases. Further research is needed to determine whether treating gout can effectively reduce this risk.

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BACKGROUND: Since diet is generally recognized as an important factor directly modulating the gut microbiome, it is also considered a potential environmental triggering factor for the pathogenesis and onset of inflammatory bowel disease (IBD). While the habitual and sex-related dietary behavior of the general population has been the subject of extensive study and reporting, data on IBD patients' dietary behavior and especially its sex-related differences are underrepresented. However, as diet is an important factor in the course of IBD, we hypothesized that men and women with IBD have a different dietary profile than the general population. METHODS: We performed a cohort analysis of a monocentric, cross-sectional study and compared the sex-related dietary behavior of 82 IBD patients (n = 40 women) to a sex- and age-matched cohort of the general German population [n = 328 (n = 160 women)]. Further on, disease-related quality of life and fecal calprotectin were correlated to the IBD patients' dietary behavior. RESULTS: While sex-related dietary behavior was frequently of statistical difference in the general population within the IBD cohort, only minor numerical differences were observed between the sexes, which were rarely statistically significant. However, correlation analyses of disease-related quality of life (IBDQ) and diet revealed significant differences in male IBD patients but not in female IBD patients (p = 0.007; r = 0.409 for energy intake (kJ/d); p = 0.003, r = 0.449 for adherence to Mediterranean diet). CONCLUSION: The dietary behavior of IBD patients showed more similarity between the sexes than the general German population. Distinct sex-related trends and differences in correlation with disease parameters demonstrated a significant difference for an adaptive dietary behavior, especially in IBD men.

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Background: Sex-specific differences in left ventricular (LV) geometry might help in developing tailored strategies for hypertension management. Objectives: The purpose of the study was to evaluate sex-related differences in LV geometry at baseline and over time in hypertension. Methods: From a prospective registry, we included hypertensives without prevalent cardiovascular disease, incident myocardial infarction, chronic kidney disease > stage III, and with normal LV ejection fraction. LV mass index >115 g/m2 in males and >95 g/m2 in females, identified LV hypertrophy (LVH). Relative wall thickness ≥0.43 defined LV concentric geometry. LVH in presence of concentric geometry was defined as concentric LVH, whereas relative wall thickness <0.43 was categorized as eccentric. Concentric geometry, or LVH, identified LV remodeling. Results: Six thousand four hundred twenty-seven patients (age 53 ± 11 years, 43% females) were included. At baseline, females showed lower prevalence of normal geometric pattern and higher prevalence of LVH than males (50% vs 72%, P < 0.001; 47% vs 23%, P < 0.001, respectively), with a higher prevalence of eccentric LVH (40% vs 18%, P < 0.001). Female sex was independently associated with LV remodeling (OR: 2.36; 95% CI: 2.12-2.62; P < 0.001). At long-term follow-up (mean 6.1 years, IQR: 2.8-8.6 years), prevalence of LV remodeling increased in both sexes, although a normal LV geometry remained less frequent in females than males (43% vs 67%, P < 0.001), with differences persisting in eccentric (41% vs 21%, P < 0.001) and concentric LVH (11% vs 5%, P < 0.001). Conclusions: We found sex-related differences in LV geometry among hypertensives. Females have higher risk of LV remodeling at baseline compared with males, with differences persisting at long-term follow-up.

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PURPOSE: Pressure cycling technology (PCT) coupled with data-independent sequential window acquisition of all theoretical mass spectra (SWATH-MS) can be a powerful tool for identifying and quantifying biomarkers (e.g., proteins) in complex biological samples. Mouse models are frequently used in brain studies, including those focusing on different neurodevelopmental and psychiatric disorders. More and more pieces of evidence have suggested that sex-related differences in the brain impact the rates, clinical manifestations, and therapy outcomes of these disorders. However, sex-based differences in the proteomic profiles of mouse cerebella have not been widely investigated. EXPERIMENTAL DESIGN: In this pilot study, we evaluate the applicability of coupling PCT sample preparation with microLC-SWATH-MS analysis to map and identify differences in the proteomes of two female and two male mice cerebellum samples. RESULTS: We identified and quantified 174 proteins in mice cerebella. A comparison of the proteomic profiles revealed that the levels of 11 proteins in the female and male mice cerebella varied significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Although this study utilizes a small sample, our results indicate that the studied male and female mice cerebella possessed differing proteome compositions, mainly with respect to energy metabolism processes.

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The comorbidity between cocaine use disorder (CUD) and trauma/stressor-related disorders suggests a connection between neurophysiological changes induced by stress and those that lead to cocaine use. Due to the unexpected and sometimes uncontrollable nature and timing of stressful life events, their capacity to induce drug use poses a significant challenge for the administration of cocaine relapse therapy. This study aims to investigate the impact of chronic stress applied prior to cocaine acquisition on the development of cocaine-seeking behavior after different periods of drug abstinence in male and female rats. Rats were exposed to five days of inescapable footshocks (chronic stress) before undergoing extended access cocaine self-administration. Different groups then underwent forced abstinence periods of 1, 15, or 30 days before cue- and cocaine-induced seeking tests. Results showed that, after 30 days of abstinence, stressed females exhibited higher cue-induced, but not cocaine-induced seeking, compared to female controls and to males. In contrast, at 30 days, stressed males showed higher cocaine-, but not cue-induced seeking, versus controls. Such sex-dependent alterations in motivation and drug effects following prolonged abstinence highlight the importance of considering sex-specific differences in stress-related addiction research. Ongoing work should evaluate other stressors and self-administration models to elucidate neurophysiological and hormonal mechanisms underlying the incubation of cocaine craving. Identifying shared pathways between chronic stress and addiction could offer novel strategies for treating trauma/stress-related substance use disorders in a sex-specific manner.

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Alzheimer's disease (AD) is the most common form of dementia and characterized by extracellular amyloid-ß (Aß) plaques, intracellular neurofibrillary tau tangles and neurodegeneration. Over 80 % of AD patients also exhibit cerebral amyloid angiopathy (CAA). CAA is a cerebrovascular disease caused by deposition of Aß in the walls of cerebral blood vessels leading to vessel damage and impairment of normal blood flow. To date, different studies suggest that platelet function, including activation, adhesion and aggregation, is altered in AD due to vascular Aß deposition. For example, the transgenic AD model mice APP23 mice that exhibit CAA and parenchymal Aß plaques, show pre-activated platelets in the blood circulation and increased platelet integrin activation leading to a pro-thrombotic phenotype in these mice late stages of AD. However, it is still an open question whether or not platelets exhibit changes in their activation profile before they are exposed to vascular Aß deposits. Therefore, the present study examined platelets from middle-aged transgenic APP23 mice at the age of 8-10 months. At this age, APP23 mice show amyloid plaques in the brain parenchyma but not in the vasculature. Our analyses show that these APP23 mice have unaltered platelet numbers and size, and unaltered surface expression of glycoproteins. However, the number of dense granules in transgenic platelets was increased while the release was unaltered. Male, but not female APP23 mice, exhibited reduced platelet activation after stimulation of the thrombin receptor PAR4 and decreased thrombus stability on collagen under flow conditions ex vivo compared to control mice. In an arterial thrombosis model in vivo, male APP23 mice showed attenuated occlusion of the injured artery compared to controls. These findings provide clear evidence for early changes in platelet activation and thrombus formation in male mice before development of overt CAA. Furthermore, reduced platelet activation and thrombus formation suggest sex-specific differences in platelet physiology in AD that has to be considered in future studies of platelets and their role in AD.

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Obesity, primarily characterized by excessive fat accumulation, is a multifactorial chronic disease with an increasing global prevalence. Despite the well-documented epidemiology and significant advances in understanding its pathophysiology and clinical implications, the impact of sex is typically overlooked in obesity research. Worldwide, women have a higher likelihood to become obese compared to men. Although women are offered weight loss interventions more often and at earlier stages than men, they are more vulnerable to psychopathology. Men, on the other hand, are less likely to pursue weight loss intervention and are more susceptible to the metabolic implications of obesity. In this narrative review, we comprehensively explored sex- and gender-specific differences in the development of obesity, focusing on a variety of biological variables, such as body composition, fat distribution and energy partitioning, the impact of sex steroid hormones and gut microbiota diversity, chromosomal and genetic variables, and behavioural and sociocultural variables influencing obesity development in men and women. Sex differences in obesity-related comorbidities and varying effectiveness of different weight loss interventions are also extensively discussed.

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Background: In many conditions characterised by septal hypertrophy, females have been shown to have worse outcomes compared to males. In clinical practice and research, similar cutoff points for septal hypertrophy are still used for both sexes. Here, we explore the association between different cutoff points for septal hypertrophy and survival in relation to sex. Methods and results: We performed a retrospective analysis of consecutive patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral centre. A total of 70,965 individuals were included. Over a mean follow-up period of 59.1 ± 37 months, 9631 (25 %) males and 8429 (26 %) females died. When the same cutoff point for septal hypertrophy was used for both sexes, females had worse prognosis than males. The impact of septal hypotrophy on survival became statistically significant at a lower threshold in females compared to males: 11.1 mm (HR 1.13, CI 95 %:1.03-1.23, p = 0.01) vs 13.1 mm (HR 1.21, CI 95 %: 1.12-1.32, p < 0.001). However, when indexed wall thickness was used, the cutoff points were 6 mm/body surface area (BSA) (HR 1.08, CI 95 %: 1-1.18, p = 0.04) and 6.2 mm/BSA (HR 1.07, CI 95 %: 1-1.15, p = 0.05) for females and males, respectively. Conclusions: Septal hypertrophy is associated with increased mortality at a lower threshold in females than in males. This may account for the worse prognosis reported in females in many conditions characterised by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females.

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There is growing evidence of sex-related differences in the epidemiology and pathophysiology of cardiovascular diseases. This is the first systematic review and meta-analysis that aimed to highlight the sex-specific differences in the clinical features and outcomes of acute myocarditis. Electronic searches were performed on Scopus, Embase, and PubMed from inception up to June 2023 to identify studies comparing the clinical features and outcomes of acute myocarditis in males and females. Both qualitative and quantitative summaries were conducted. In this systematic review and meta-analysis of 11 studies involving 34,791 patients presenting with acute myocarditis. Male patients, who comprised 69.8% of the entire pooled population, presented at a markedly younger age (mean difference: -8.99 years; 95% CI: -13.60, -4.38; p=0.0001). They also had significantly lower rates of hypertension, diabetes mellitus, and coronary artery disease compared to female patients (p<0.01). Male patients were more likely to present with ST elevation (RR: 2.57 [1.38, 4.79]; p=0.003) and higher C-reactive protein levels (RR: 3.04 [2.75, 3.34]; p<0.00001) compared to female patients. This review underscores the crucial sex-specific evaluation in acute myocarditis, necessitating tailored approaches in assessment and diagnostic evaluation, and emphasizing the need for additional research in this domain.

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PURPOSE: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by persistent fatigue and decreased daily activity following physical and/or cognitive exertion. While ME/CFS affects both sexes, there is a higher prevalence in women. However, studies evaluating this sex-related bias are limited. METHODS: Circulating steroid hormones, including mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone), were measured in plasma samples using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Samples were obtained from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17). RESULTS: After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were significantly different between HC, ME/CFSmm, and ME/CFSsa. Comparing two independent groups, we found that female ME/CFSsa had higher levels of 11-deoxycortisol (vs. HC and ME/CFSmm) and 17α-hydroxyprogesterone (vs. HC). In addition, female ME/CFSmm showed a significant increase in progesterone levels compared to HC. In contrast, our study found that male ME/CFSmm had lower circulating levels of cortisol and corticosterone, while progesterone levels were elevated compared to HC. In addition to these univariate analyses, our correlational and multivariate approaches identified differential associations between our study groups. Also, using two-component partial least squares discriminant analysis (PLS-DA), we were able to discriminate ME/CFS from HC with an accuracy of 0.712 and 0.846 for females and males, respectively. CONCLUSION: Our findings suggest the potential value of including steroid hormones in future studies aimed at improving stratification in ME/CFS. Additionally, our results provide new perspectives to explore the clinical relevance of these differences within specific patient subgroups.

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Aims Little is known about the association between habitual alcohol consumption and serum high-density lipoprotein cholesterol (HDL-C) in women. We aimed to investigate this association in middle-aged Japanese women in a community-based cohort study using conventional statistical analyses and explainable artificial intelligence (AI) analysis. Methods We retrospectively investigated the association between alcohol consumption and HDL-C after 10 years in 90,053 women aged 40-64 years whose drinking habits were generally consistent for 10 years. Results After 10 years, 11.3% and 17.9% of subjects had serum HDL-C decreased by ≥10 mg/dL and ≥10%, respectively. In unadjusted analysis, moderate-to-heavy alcohol consumption may both increase and decrease serum HDL-C levels after 10 years. After adjustment for potential confounding factors, moderate (23-45 g/day) and heavy (≥46 g/day) alcohol consumption were each significantly associated with decreases in HDL-C (OR (95% CI): 1.18 and 1.36 (1.11-1.26 and 1.21-1.53) for ≥10 mg/dL, 1.11 and 1.29 (1.05-1.17 and 1.17-1.43) for ≥10%), but not associated with an increase in HDL-C (0.96 and 0.98 (0.91-1.01 and 0.89-1.08) for ≥10 mg/dL, 0.97 and 0.96 (0.93-1.01 and 0.88-1.05) for ≥10%). Further analysis after adjustment for baseline serum HDL-C showed the same results. AI analysis showed that alcohol consumption was the 8th positive contributor to the decrease in HDL-C, following baseline high HDL-C (≥77 mg/dL), high low-density lipoprotein cholesterol (≥133 mg/dL), high body mass index (≥23.1 kg/m2), pharmacotherapy for dyslipidemia, high triglycerides (≥70 mg/dL), age 44-64 years, and smoking. Heavy alcohol consumption was a more positive contributor to decreased HDL-C than were other alcohol consumption levels. Conclusions Habitual moderate-to-heavy alcohol consumption may cause a significant decrease in serum HDL-C in middle-aged women, which may be modified by concomitant factors.

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Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.

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Heart failure affects over 2.6 million people in the United States. While women have better overall survival rates, they also suffer from higher morbidity as shown by higher rates of hospitalization and worse quality of life. Several anatomical differences in women's hearts affect both systolic and diastolic cardiac physiology. Despite these findings, women are significantly underrepresented in clinical trials, necessitating extrapolation of data from males. Because women have sex-specific etiologies of heart failure and unique manifestations in genetic-related cardiomyopathies, meaningful sex-related differences affect heart failure outcomes as well as access to and outcomes in advanced heart failure therapies in women. This review explores these gender-specific differences and potential solutions to balance care between women and men.

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The study presents data on the anti-inflammatory effects of a combination of sodium dichloroacetate and sodium valproate (DCA-VPA) on the expression of inflammation- and immune response-related genes in T lymphocytes of SARS-CoV-2 patients. The study aimed to assess the effects of DCA-VPA on the genes of cytokine activity, chemokine-mediated signaling, neutrophil chemotaxis, lymphocyte chemotaxis, T-cell chemotaxis, and regulation of T-cell proliferation pathways. The study included 21 patients with SARS-CoV-2 infection and pneumonia: 9 male patients with a mean age of 68.44 ± 15.32 years and 12 female patients with a mean age of 65.42 ± 15.74 years. They were hospitalized between December 2022 and March 2023. At the time of testing, over 90% of sequences analyzed in Lithuania were found to be of the omicron variant of SARS-CoV-2. The T lymphocytes from patients were treated with 5 mmol DCA and 2 mmol VPA for 24 h in vitro. The effect of the DCA-VPA treatment on gene expression in T lymphocytes was analyzed via gene sequencing. The study shows that DCA-VPA has significant anti-inflammatory effects and apparent sex-related differences. The effect is more potent in T cells from male patients with SARS-CoV-2 infection and pneumonia than in females.

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Context: Biological sex can play a role in the severity of certain diseases. Objective: Our objective was to evaluate whether sex-related differences affect the signs and symptoms of pheochromocytomas and paragangliomas (PPGLs) at presentation. Methods: We reviewed the records of patients with PPGLs at our center from 1995 to 2022. Results: Our study included 385 patients with PPGLs: 118 (30.6%) head and neck paragangliomas (HNPGLs), 58 (15.1%) thoracoabdominal paragangliomas (TAPGLs) and 209 (54.3%) pheochromocytomas (PHEOs). The cohort consisted of 234 (60.8%) women and 151 (39.2%) men. At diagnosis, more women than men presented with headaches (47.5% vs 32.4%; P = .007); however, more men presented with diabetes (21.1% vs 12.5%; P = .039). When subdivided by tumor location, headaches occurred more often in women with HNPGLs and TAPGLs (31.0% vs 11.4%; P = .0499 and 60.0% vs 21.7%; P = .0167). More men presented with diabetes among patients with PHEOs (28.2% vs 11.2%; P = .0038). In regard to nonsecretory PPGLs, women presented with a higher prevalence of headaches (46.9% vs 3.6%; P = .0002), diaphoresis (16.3% vs 0.0%; P = .0454), and palpitations (22.4% vs 0.0%; P = .0057). In patients with secretory tumors, women presented with more headaches (58.9% vs 42.7%; P = .0282) and men with more diabetes (29.3% vs 12.5%; P = .0035). Conclusion: In our cohort, more women presented with headaches across all tumor types and secretory statuses. More men presented with diabetes among patients with PHEOs and secretory tumors. In nonsecretory PPGLs, women had more adrenergic symptoms. These findings can be explained by differences in adrenergic receptor sensitivity, self-reported symptoms, and possibly other vasoactive peptides and sex-hormone status.

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BACKGROUND: The objective of the study is to analyse the regions, age and sex differences in the incidence of knee osteoarthritis (KOA). METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, years lived with disability (YLD), disability-adjusted life-years (DALYs) and risk factors. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age standardized rate (ASR) of KOA. Paired t-test, paired Wilcoxon signed-rank test and spearman correlation were performed to analyze the association of sex disparity in KOA and socio-demographic index (SDI). RESULTS: There were significant regional differences in the incidence of knee osteoarthritis. In 2019, South Korea had the highest incidence of knee osteoarthritis (474.85,95%UI:413.34-539.64) and Thailand had the highest increase in incidence of knee osteoarthritis (EAPC = 0.56, 95%CI = 0.54-0.58). Notably, higher incidence, YLD and DALYs of knee osteoarthritis were associated with areas with a high socio-demographic index (r = 0.336, p < 0.001; r = 0.324, p < 0.001; r = 0.324, p < 0.001). In terms of age differences, the greatest increase in the incidence of knee osteoarthritis was between the 35-39 and 40-44 age groups. (EAPC = 0.52, 95%CI = 0.40-0.63; 0.47, 95%CI = 0.36-0.58). In addition, there were significant sex differences in the disease burden of knee osteoarthritis (P < 0.001). CONCLUSIONS: The incidence of knee osteoarthritis is significantly different with regions, age and sex.

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Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the nociceptin opioid receptor (NOP) has been shown to block cocaine-induced locomotor sensitization in mice and rats, and also reverses this phenomenon when injected intracerebroventricularly in animals with an established sensitized response. In the present study, we determined whether small-molecule NOP agonists would recapitulate this effect after systemic administration. Male C57BL/6 mice treated with cocaine (15 mg/kg) on days 1-3 and showed locomotor sensitization to the same dose of cocaine on day 8 were injected with vehicle or one of the two NOP agonists (AT-202 and AT-524) (but not cocaine) on days 9-11. On day 15, locomotor sensitization was assessed after a cocaine challenge (15 mg/kg). Subchronic administration of the two NOP agonists to sensitized mice significantly decreased the sensitized response on day 15. In a separate experiment conducted in male and female mice lacking NOP and their wildtype littermates, AT-524 reversed sensitization in male wildtype but not in mice lacking NOP. Further, co-administration of the NOP agonist with cocaine for three days on days 16-18 prevented the development of locomotor sensitization from this cocaine treatment in wild-type but not in NOP knockout mice. However, none of these effects of the NOP agonist was observed in female mice. Together, these results suggest that subchronic repeated administration of small-molecule NOP agonists may reverse adaptive behavioral changes associated with repeated intermittent cocaine treatment in male but not female mice.

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OBJECTIVES: To investigate the association between habitual tea consumption and transitions between frailty states among older adults in China. DESIGN: A prospective cohort study based on the Chinese Longitudinal Healthy Longevity Study. SETTING AND PARTICIPANTS: A total of 23,720 older adults aged ≥65 years with complete data regarding frailty status and tea consumption were recruited. METHODS: The frequency and consistency of tea consumption were introduced to evaluate levels of tea consumption. The frailty index was used to define frailty status (frail and nonfrail). Frailty transition was classified into remaining nonfrail, improvement, worsening, and remaining frail groups. Logistic regression models were applied. RESULTS: The overall frailty prevalence at baseline was 19.1%, being lower among consistent daily tea drinkers (12.5%) and higher among non-tea drinkers (21.9%). Logistic regression analyses showed that the risk of frailty was significantly reduced among consistent daily tea drinkers after adjusting for all confounders [odds ratio (OR), 0.81; 95% CI, 0.67-0.98]. During the 3-year follow-up, improvement in frailty status was more common among consistent daily tea drinkers (50.9%) than non-tea drinkers (40.9%), and this trend was opposite in participants with worsened frailty status (consistent daily tea drinkers: 12.2%) vs non-tea drinkers: 19.2%). Further analysis showed that consistent daily tea drinkers were significantly associated with improvement in frailty status (OR, 3.24; 95% CI, 1.02-10.31) and remaining in a nonfrail state (OR, 1.35; 95% CI, 1.00-1.83). In addition, daily tea consumption was observed to be positively associated with remaining in a nonfrail state and inversely associated with worsened frailty status in men, but not in women. CONCLUSIONS AND IMPLICATIONS: Older people consuming tea daily tend to have an improved frailty status in the future. Men with daily tea consumption were less likely to have a worsened frailty status. Advocating for the traditional lifestyle of drinking tea could be a promising way to advance healthy aging for older adults.

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Pediatric mild traumatic brain injury (pmTBI) has received increased public attention over the past decade, especially for children who experience persistent post-concussive symptoms (PCS). Common methods for obtaining pediatric PCS rely on both self- and parental report, exhibit moderate test-retest reliability, and variable child-parent agreement, and may yield high false positives. The current study investigated the impact of age and biological sex on PCS reporting (Post-Concussion Symptom Inventory) in patients with pmTBI (n = 286) at retrospective, 1 week, 4 months, and 1 year post-injury time points, as well as reported symptoms in healthy controls (HC; n = 218) at equivalent assessment times. HC and their parents reported higher PCS for their retrospective rating relative to the other three other study visits. Child-parent agreement was highest for female adolescents, but only approached acceptable ranges (≥ 0.75) immediately post-injury. Poor-to-fair child/parental agreement was observed for most other study visits for pmTBI and at all visits for HC. Parents rated female adolescents as being more symptomatic than their male counterparts in spite of small (pmTBI) or no (HC) sex-related differences in self-reported ratings, suggestive of a potential cultural bias in parental ratings. Test-retest reliability for self-report was typically below acceptable ranges for both pmTBI and HC groups, with reliability decreasing for HC and increasing for pmTBI as a function of time between visits. Parental test-retest reliability was higher for females. Although continued research is needed, current results support the use of child self-report over parental ratings for estimating PCS burden. Results also highlight the perils of relying on symptom self-report for diagnostic and prognostic purposes.

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OBJECTIVES: The present study seeks to quantify changes in long bone cross-sectional properties in a colony of semi-free-ranging rhesus macaques and compare observed aging patterns to those of other primates, including humans. METHODS: Peripheral quantitative computed tomography was used to obtain midshaft cross sections of the femora, tibiae, humeri, and radii of 115 macaque specimens ranging from 7 to 31 years of age. Linear regressions of cross-sectional properties on age were analyzed. An analysis of covariance was conducted to quantify differences in rates of change between males and females. RESULTS: Results show that medullary area increases while cortical area decreases with age in both sexes. The polar section modulus and the polar strain-strength index, measuring torsional and bending strength, show no decline in most sections but decrease significantly with age in the hindlimb elements of female macaques. Volumetric bone mineral density (vBMD) also decreases with age in both male and female macaques; however, the cumulative change in vBMD over the adult lifespan is relatively small, equivalent to a less than 10% decrease in material strength. An analysis of covariance shows no differences between males and females in the rate of change of properties with age. DISCUSSION: Overall, this study shows that there are some similarities in the skeletal aging patterns of macaques and those of other primates, including humans, but also some differences, with greater losses of bone found in human females as a result of an extended post-reproductive period that is generally not found among wild or semi-wild macaques.

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