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Context-dependent behavioral plasticity adjustments bothersome collection of sperm qualities in squid.
Meanwhile, obviously positive correlations between protein expression of PTHrP and RANKL and bone resorption degree were discovered.Conclusions and significance The increased protein expression of PTHrP and RANKL in cholesteatoma epithelium, and their associations with the degree of bone resorption, revealing that PTHrP might promote bone resorption process in middle ear cholesteatoma through RANKL signaling pathway.Introduction With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.Areas covered This review is based on a literature search using PubMed and Embase including all published manuscripts and presentations concerning imeglimin. Supplementary information was retrieved from the manufacturer's official webpage. Preclinical and clinical data are summarized with a focus on mechanisms of action as well as clinical efficacy and safety in T2D.Expert opinion Imeglimin's mode of action seems to be improved mitochondrial function in pancreatic beta cells leading to improved insulin secretion and lowering of plasma glucose levels. In clinical trials of up to 24 weeks, imeglimin in doses of 1,000-1,500 mg twice daily conferred modest reductions in glycates hemoglobin A1c of 6-11 mmol/mol (0.5-1.0%) (placebo-adjusted) as a monotherapy and 7 mmol/mol (0.6%) as an add-on therapy to metformin or sitagliptin in patients with T2D. Reported adverse effects were mainly gastrointestinal discomfort. The position of imeglimin among other pharmacotherapies in the treatment of T2D will be determined based on future studies more clearly outlining the safety and long-term cardiovascular effects.Abbreviations AUC area under the curve; BID twice daily; DPP-4 dipeptidyl peptidase 4; GLP-1R glucagon-like peptide-1 receptor; HbA1c glycated hemoglobin A1c; HFHSD high-fat high-sucrose diet; OAD oral antidiabetic; OD once daily; OGTT oral glucose tolerance test; PPAR-γ peroxisome proliferator-activated receptor gamma; PTP permeability transition pore; SGLT-2 sodium-glucose transport protein 2; STZ streptozotocin; T2D type 2 diabetes.Although many studies discussed evidence-based practice among general nurses, few studies were found by the researchers among intensive care unit nurses. Also, no study has been conducted to investigate the predictors of evidence-based practice among intensive care unit nurses in Jordan. Therefore, this study aims to identify the predictors of evidence-based practice among intensive care unit nurses in Jordan. A descriptive cross-sectional design was used to conveniently recruit 132 participants. Self-reported questionnaires were utilized including the Evidence-Based Practice Questionnaire and Evidence-Based Practice barrier scale. Participants' rate of evidence-based practice was 60% (M = 4.2/7), which was significantly correlated with their knowledge (r = 0.739, P less then .01) and attitudes (r = 0.564, P less then .01) of evidence-based practice. The results revealed a 2-predictor model that explained 62.2% of the variance in evidence-based practice among intensive care unit nurses. The 2 variables were attitude (β = 0.245) and knowledge (β = 0.563). The outcomes of this study added new information regarding the prediction of evidence-based practice among intensive care unit nurses. An educational program for nurses regarding this issue is crucial to improve their practice aiming at enhancing nursing care. Also, nursing schools should update their curricula to explain the importance of evidence-based practice and to enhance students' competencies in research utilization and statistical skills.A growing body of evidence suggests that age-related hearing loss is related to changes in older adults' memory. We test the hypothesis that the association is due to social disengagement following the onset of perceived hearing loss. At ages 65 (2004) and 72 years (2011), 3,986 participants from the Wisconsin Longitudinal Study (WLS) self-reported on hearing problems and several types of social engagement and completed three tests of memory. We estimated fixed effects regression models. Perceived hearing loss was related to significant decline in memory. Declines in frequency of in-person social contact were also associated with declining memory, but there was no evidence of a mechanism wherein reductions in social engagement explained the association between perceived hearing loss and memory decline. AZD1080 We conclude that self-reported hearing loss and social disengagement are likely independent risk factors for memory loss among older adults.RATIONALE Microdosing psychedelics - the practice of consuming small, sub-hallucinogenic doses of substances such as LSD or psilocybin - is gaining attention in popular media but remains poorly characterized. Contemporary studies of psychedelic microdosing have yet to report the basic psychiatric descriptors of psychedelic microdosers. OBJECTIVES To examine the practices and demographics of a population of psychedelic microdosers - including their psychiatric diagnoses, prescription medications, and recreational substance use patterns - to develop a foundation on which to conduct future clinical research. METHODS Participants (n = 909; Mage = 26.9, SD = 8.6; male = 83.2%; White/European = 79.1%) recruited primarily from the online forum Reddit completed an anonymous online survey. Respondents who reported using LSD, psilocybin, or both for microdosing were grouped and compared with non-microdosing respondents using exploratory odds ratio testing on demographic variables, rates of psychiatric diagnoses, and past-year recreational substance use. RESULTS Of microdosers, most reported using LSD (59.3%; Mdose = 13 mcg, or 11.3% of one tab) or psilocybin (25.9%; Mdose = 0.3 g of dried psilocybin mushrooms) on a one-day-on, two-days-off schedule. Compared with non-microdosers, microdosers were significantly less likely to report a history of substance use disorders (SUDs; OR = 0.17 (95% CI 0.05-0.56)) or anxiety disorders (OR = 0.61 (95% CI 0.41-0.91)). Microdosers were also more likely to report recent recreational substance use compared with non-microdosers (OR = 5.2 (95% CI 2.7-10.8)). CONCLUSIONS Well-designed randomized controlled trials are needed to evaluate the safety and tolerability of this practice in clinical populations and to test claims about potential benefits.Right ventricular (RV) dysfunction is the main determinant of mortality in patients with pulmonary arterial hypertension (PAH) and while inflammation is pathogenic in PAH there is limited information on the role of RV inflammation in PAH. Sulforaphane (SFN), a potent Nrf2 activator, has significant anti-inflammatory effects and facilitates cardiac protection in preclinical diabetic models. Therefore, we hypothesized SFN might play a comparable role in reducing RV and pulmonary inflammation and injury in a murine PAH model. We induced PAH using SU5416 and 10% hypoxia (SuHx) for 4 weeks in male mice randomized to SFN at a daily dose of 0.5 mg/kg, 5 days per week for 4 weeks or to vehicle control. Transthoracic echocardiography was performed to characterize chamber specific ventricular function during PAH induction. At 4 weeks we measured RV pressure and relevant measures of histology, protein, and gene expression.SuHx induced progressive RV, but not LV, diastolic and systolic dysfunction and RV and pulmonary remodeling, fibrosis, and inflammation. SFN prevented SuHx-induced RV dysfunction and remodeling, reduced RV inflammation and fibrosis, upregulated Nrf2 expression and its downstream gene NQO1 and reduced the inflammatory mediator NLRP3. SFN also reduced SuHx induced pulmonary vascular remodeling, inflammation and fibrosis. SFN alone had no effect on the heart or lungs. Thus, SuHx-induced RV and pulmonary dysfunction, inflammation, and fibrosis can be attenuated or prevented by SFN supporting the rationale for further studies to investigate SFN and the role of Nrf2 and NLRP3 pathways in preclinical and clinical PAH studies.Due to remarkable surgical and medical advances over the past several decades, there are growing numbers of infants and children living with single ventricle congenital heart disease (SV), where there is only one functional cardiac pumping chamber. Nevertheless, cardiac dysfunction and ultimately heart failure is a common complication in the SV population and pharmacologic heart failure therapies have largely been ineffective in mitigating the need for heart transplantation. Given that there are several inherent risk factors for ventricular dysfunction in the setting of SV in addition to probable differences in molecular adaptations to heart failure between children and adults, it is perhaps not surprising that extrapolated adult heart failure medications have had limited benefit in children with SV heart failure. Further investigations into the molecular mechanisms involved in pediatric SV heart failure may assist with risk stratification as well as development of targeted, efficacious therapies specific to this patient population. In this review, we present a brief overview of SV anatomy and physiology, with a focus on patients with a single morphologic right ventricle requiring staged surgical palliation. Additionally, we discuss outcomes in the current era, risk factors associated with the progression to heart failure, present state of knowledge regarding molecular alterations in end-stage SV heart failure and current therapeutic interventions. Potential avenues for improving SV outcomes, including identification of biomarkers of heart failure progression, implications of personalized medicine and stem cell-derived therapies and applications of novel models of SV disease, are proposed as future directions.BACKGROUND Coordinated interactions within central and peripheral neural networks determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation in response to ischemia is a major contributor to sudden cardiac death. OBJECTIVE To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, and those specifically related to modulating sympathetic preganglionic (SPN) neural activity during cardiovascular stress. METHODS Adult, anesthetized Yorkshire pigs (n=10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,703 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload and transient occlusion of the left anterior descending (LAD) coronary artery. Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. RESULTS While some DH neurons responded solely to changes in preload/afterload (8.5±1.9%) or ischemic stress (10.5±3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2±4.7%) with ischemia sensitivity being one of the modalities (26.1±4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43±0.61 to 7.30 ±1.84%, p=0.04) and between SPN to DH neurons (1.32±0.78 to 7.24±1.84%, p=0.02). DH to SPN network correlations were reduced during great vessel occlusion. CONCLUSION Increased intra-segmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.
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