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Disparities in overall outcomes for atrial fibrillation (AF) across racial and ethnic groups have been demonstrated in prior studies. We aim to evaluate in-hospital outcomes and resource utilization across 3 racial/ethnic groups with AF using contemporary data. We identified patients admitted with AF in the National Inpatient Sample registry from 2015 to 2018. ICD-10-CM codes were used to identify variables of interest. The primary outcomes were in-hospital complications and resource utilization. There were 1,250,075 AF admissions. Our sample was made up of 85.49% White, 8.12% Black, and 6.38% Hispanic patients. Black patients were younger but had a higher burden of cardiovascular comorbidities including obesity, hypertension, and chronic kidney disease. Social determinants were also less favorable in Black patients, with a higher percentage of Medicaid insurance and a high proportion of patients being in the lowest percentile for household income. Total hospital charge was highest in Hispanic patients. Despite higher rates of gastrointestinal bleed, Black patients were least likely to undergo left atrial appendage occlusion device implantation. Black and Hispanic patients were less like to undergo catheter ablation therapy. Black race was an independent predictor of mortality, stroke, mechanical ventilation, acute kidney injury, hemodynamic shock, need for vasopressor, upper gastrointestinal bleed, need for blood transfusion, total hospital charges, and length of stay when compared to other groups. Disparities exist in the risk of AF, and its management among racial and ethnic groups. Health care costs and inpatient outcomes disproportionately impact minorities in the United States.Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI.The present study investigated the oral bioavailability of celecoxib when incorporated into solid lipid nanoparticles either dissolved or suspended. In vitro drug release in different media, in vivo performance, and in vitro-in vivo correlation were conducted. The results revealed that the compound was successfully encapsulated into the nanocarriers with good physicochemical properties for oral administration. The in vitro release profiles followed the Weibull model, with significant differences between the formulations containing the solubilized and the suspended compound. Furthermore, in vitro release data could be used to rank the observed in vivo bioavailability. The relative bioavailability of celecoxib from the solid lipid nanoparticles was 2.5- and 1.8-fold higher for the drug solubilized and suspended solid lipid nanoparticle formulation, respectively, when compared to the celecoxib reference. A significant difference was observed between the plasma concentration-time profiles and pharmacokinetic parameters for the three investigated formulations. Finally, this investigation displayed promising outcomes that both solubilized and suspended celecoxib in the lipid core of the solid lipid nanoparticles offers the potential to improve the compound's oral bioavailability and thereby reduce the dosing frequency.Cardiac fibrosis is a common irreversible pathological feature of diverse heart disorders. Uncontrolled cardiac fibrosis contributes to maladaptive cardiac remodeling and eventually heart failure. However, the molecular determinants of ischemic and non-ischemic pathological cardiac fibrosis remain largely unknown. Here, we investigated the role of Bruton's tyrosine kinase (BTK) in cardiac fibrosis and remodeling of mice under various pathological conditions. BTK expression was increased in myocardium of mice after pressure overload or myocardial infarction (MI). BTK was mainly located in cardiac fibroblasts of myocardium, and its expression in isolated cardiac fibroblasts was also upregulated following TGF-β treatment. The deficiency or pharmacological inhibition of BTK with the second-generation inhibitor Acalabrutinib attenuated cardiac fibrosis, preserved cardiac function and prevented adverse cardiac remodeling, which protected against heart failure in mice following pressure overload or MI. BTK deficiency or inhibitor treatment significantly decreased the expression of pro-fibrotic molecules in isolated cardiac fibroblasts and inhibited the transition of fibroblasts to myofibroblasts in response to diverse pathological stresses. BTK directly bound and phosphorylated TGF-β receptor Ⅰ (TβRⅠ) at tyrosine 182, and then promoted the activation of downstream SMAD-dependent or -independent TGF-β signaling, leading to the enhanced transition of fibroblasts to pro-fibrotic myofibroblasts and the excessive extracellular matrix gene expression. Our finding uncovers a driving role of BTK in cardiac fibrosis and dysfunction following pressure overload and MI stress, and highlights novel pathogenic mechanisms in ischemic and non-ischemic maladaptive cardiac remodeling, which presents as a promising target for the development of anti-fibrotic therapy.One challenge many marital couples face is that they experience discrepant levels of sexual desire for one another. Such discrepancies are particularly likely to arise in mixed-sex relationships because, at least in long-term relationships, men tend to have higher levels of sexual desire for their partner than do women. But what underlies this sex difference? We used a dyadic study of 100 mixed-sex community-based newlywed spouses to investigate the role of biological, relational, cognitive, and emotional factors in explaining sex differences in dyadic sexual desire for a long-term partner. Consistent with predictions, wives on average reported lower daily sexual desire for their spouse than did husbands. Moreover, individual differences in men's and women's levels of circulating testosterone explained this sex difference whereas relational (marital satisfaction, commitment), cognitive (sex-role identification, stress, self-esteem), and emotional (mood, depressive symptoms) factors did not. These findings advance our knowledge of factors that influence dyadic sexual desire and may have practical implications for treating relationship distress in mixed-sex marriages.Opioid Use Disorder (OUD) is a chronic relapsing disorder that has severe negative impacts on the individual, the family, and the community at large. In 2021, opioids contributed to nearly 70% of all drug overdose deaths in the United States. This number of opioid related deaths coincides with a significant rise in the use of fentanyl, a synthetic opioid that is 150 times more potent than morphine. Furthermore, this overdose trend has spared no demographic and costs the nation an estimated $51.2 billion annually. Thus, it is imperative to better understand the underlying mechanisms of OUD in an effort to identify new treatment targets. [https://www.selleckchem.com/btk.html BTK screening] Using animal models, studies have shown that rats readily self-administer heroin and increase seeking following exposure to cues for drug, the drug itself, or stress. We have shown that treatment with the glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, can reduce heroin taking and seeking behavior in rats. Therefore, using our rodent model, we established a fentanyl self-administration paradigm to test whether acute treatment with the GLP-1R agonist also can reduce fentanyl seeking in fentanyl experienced rats. The results showed that rats readily self-administered fentanyl (2.5 ug/kg) intravenously, with marked individual differences in drug taking behavior. As with other drugs of abuse tested, rats exhibited high seeking behavior when challenged with a drug-related cue or, after a period of extinction, the drug itself. Here, acute treatment with the GLP-1R agonist, liraglutide (0.3 mg/kg s.c.), was found to attenuate both cue-induced fentanyl seeking and drug-induced reinstatement of fentanyl seeking with the same efficacy as the currently approved partial opioid agonist, buprenorphine. Taken together, these data suggest that a known satiety signal, GLP-1, may serve as an effective non-opioid alternative for the treatment of OUD.The objective of the current meta-analysis was to assess the effect size of the Late Positive Potential (LPP) to drug and emotional cues in substance users compared to controls. The secondary objective was to test for moderation by age, gender, years of use, use status, and substance type. Search was performed in August 2021 using PubMed. Inclusion criteria were substance use disorder/dependence or validated self-report, LPP means, healthy control comparison, non-acute drug study, data available, peer-reviewed journal, English, and human participants. Selection bias was tested through modified Egger's regression and exploratory 3-parameter selection model tests. Results (k = 11) indicated LPP to drug cues was larger in substance use compared to control group, with a large effect size (Hedges' g=1.66, 95%CI [0.64,2.67], p = 0.005). There were no overall differences for emotional cues. Though threats of selection bias were not severe, inclusion of more studies with larger sample sizes in future meta-analyses will allow more robust tests of publication bias and more accurate measures of effect size.A systematic review of investigations evaluating hemispheric asymmetries for emotions in primates was undertaken to individuate the most consistent lines of research allowing to check the hypothesis of a continuum in emotional lateralization across vertebrates. We reviewed studies on the lateralization of emotional expression (N = 31) and perception (N = 32) and of markers of emotional activation (N = 9), trying to distinguish those which had given respectively more consistent or more conflicting outcomes. Furthermore, we tried to identify the most strongly supported model of emotional lateralization. The most consistent results were obtained in studies investigating asymmetries in emotional expression at the facial level and in the perception of emotional facial expressions, whereas the most disappointing data were obtained in investigations evaluating possible neurophysiological markers of lateralized emotional activation. These results supported more the hypothesis of a continuity between humans and non-human primates than the more general hypothesis of a continuum between humans and all vertebrates.