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Telotristat ethyl reverses myxomatous changes in mice mitral valves
Get PDFRationale: Myxomatous mitral valve degeneration is a common pathological manifestation of mitral valve regurgitation, with or without valvular prolapse. In addition to similarities between naturally occurring and serotonergic valve degeneration, an increasing body of evidence has recently suggested that serotonin signaling is a regulator of degenerative valvulopathies. Studies have found that serotonin can be synthesized locally by valvular cells and serotonin receptors in turn may be activated to promote signaling. Recently, telotristat ethyl (TE) has been introduced as a treatment for carcinoid disease, by selectively inhibiting tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis. TE provides a unique tool to test inhibition of serotonin synthesis in vivo, without impacting brain serotonin, to further confirm the role of local serotonin synthesis on heart valves.
Objective: To confirm the link between serotonin and myxomatous valvular disease in vivo.
Methods and results: A hypertension-induced myxomatous mitral valve disease mouse model was employed to test the effect of TE on valvular degeneration. Circulating serotonin and local serotonin in valve tissues were tested by enzyme immunoassay and immunohistochemistry, respectively. TE was administrated in two modes: (1) parallel with angiotensin II (A2); (2) post A2 treatment. Myxomatous changes were successfully recapitulated in hypertensive mice, as determined by ECM remodeling, myofibroblast transformation, and serotonin signaling activation. These changes were at least partially reversed upon TE administration.
Conclusion: This study provides the first evidence of TE as a potential therapeutic for myxomatous mitral disease, either used to prevent or reverse myxomatous degeneration
Confirming Multiplex RT-qPCR Use in COVID-19 with Next-Generation Sequencing: Strategies for Epidemiological Advantage
Get PDFRapid identification and tracking of emerging SARS-CoV-2 variants are critical for understanding the transmission dynamics and developing strategies for interrupting the transmission chain. Next-Generation Sequencing (NGS) is an exceptional tool for whole-genome analysis and deciphering new mutations. The technique has been instrumental in identifying the variants of concern (VOC) and tracking this pandemic. However, NGS is complex and expensive for large-scale adoption, and epidemiological monitoring with NGS alone could be unattainable in limited-resource settings. In this study, we explored the application of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based detection of the variant identified by NGS. We analyzed a total of 78 deidentified samples that screened positive for SARS-CoV-2 from two timeframes, August 2020 and July 2021. All 78 samples were classified into WHO lineages by whole-genome sequencing and then compared with two commercially available RT-qPCR assays for spike protein mutation(s). The data showed good concordance between RT-qPCR and NGS analysis for specific SARS-CoV-2 lineages and characteristic mutations. RT-qPCR assays are quick and cost-effective and thus can be implemented in synergy with NGS for screening NGS-identified mutations of SARS-CoV-2 for clinical and epidemiological interest. Strategic use of NGS and RT-qPCR can offer several COVID-19 epidemiological advantages
Age- and sex-based differences in the moral intuitions of American early adolescents
Get PDFThis study sought to explore the validity of a latent-factor model of moral intuition development during early adolescence. The 3-Factor Character Foundations Survey (CFS-3) was used to assess the moral intuitions of early adolescents (n = 850, mean = 12.4 years old, SD = 0.96) under a moral foundations theory framework. Confirmatory factor analysis supported the psychometric validity of the three latent factor constructs (autonomy, loyalty and empathy), and partial metric invariance was established to allow for the comparison of latent factor means between four age- and sex-based groups coinciding with averages for pubertal onset. Results support prior findings of greater latent factor means for females in all three factors when compared with males in the 11–12-year-old age group. Additionally, 13–14-year-old females exhibited lower latent factor means in autonomy and loyalty factors when compared with 11–12-year-old females. This resulted in 13–14-year-old females remaining higher in empathy and autonomy but showing no difference in loyalty when compared with 13–14-year-old males. The results are interpreted through the lens of attachment theory, socio-cultural influence and certain limitations of the survey instrument itself. Suggestions for future studies are proposed
Enhanced numeracy skills following team-based learning in United States pharmacy students: a longitudinal cohort study
Get PDFPurpose: The literature suggests that the ability to numerate cannot be fully understood without accounting for the social context in which mathematical activity is represented. Team-based learning (TBL) is an andragogical approach with theoretical links to sociocultural and community-of-practice learning. This study aimed to quantitatively explore the impact of TBL instruction on numeracy development in 2 cohorts of pharmacy students and identify the impact of TBL instruction on numeracy development from a social perspective for healthcare education.
Methods: Two cohorts of students were administered the Health Science Reasoning Test-Numeracy (HSRT-N) before beginning pharmacy school. Two years after using TBL as the primary method of instruction, both comprehensive and domain data from the HSRT-N were analyzed.
Results: In total, 163 pharmacy student scores met the inclusion criteria. The students’ numeracy skills measured by HSRT-N improved after 2 years of TBL instruction.
Conclusion: Numeracy was the most significantly improved HSRT-N domain in pharmacy students following two years of TBL instruction. Although a closer examination of numeracy development in TBL is warranted, initial data suggest that TBL instruction may be an adequate proxy for advancing numeracy in a cohort of pharmacy students. TBL may encourage a social practice of mathematics to improve pharmacy students’ ability to numerate critically
Asthma Education with Asthma Action Plan
Get PDFMSN capstone project in which pediatric asthma patients were given audio visits for the purpose of formulating asthma action plans
Impact of Self-Care Techniques on Nurse Burnout
Get PDFNurse burnout is a serious, widespread problem in the healthcare arena. Registered nurses need to understand the importance of self-care to prevent or alleviate nurse burnout. An Evidence-Based Practice Benchmark Study implements a relaxation room on a nursing unit to encourage and promote self-care among acute care nurses
From Bedside to the Bench—A Call for Novel Approaches to Prognostic Evaluation and Treatment of Empyema
Get PDFEmpyema, a severe complication of pneumonia, trauma, and surgery is characterized by fibrinopurulent effusions and loculations that can result in lung restriction and resistance to drainage. For decades, efforts have been focused on finding a universal treatment that could be applied to all patients with practice recommendations varying between intrapleural fibrinolytic therapy (IPFT) and surgical drainage. However, despite medical advances, the incidence of empyema has increased, suggesting a gap in our understanding of the pathophysiology of this disease and insufficient crosstalk between clinical practice and preclinical research, which slows the development of innovative, personalized therapies. The recent trend towards less invasive treatments in advanced stage empyema opens new opportunities for pharmacological interventions. Its remarkable efficacy in pediatric empyema makes IPFT the first line treatment. Unfortunately, treatment approaches used in pediatrics cannot be extrapolated to empyema in adults, where there is a high level of failure in IPFT when treating advanced stage disease. The risk of bleeding complications and lack of effective low dose IPFT for patients with contraindications to surgery (up to 30%) promote a debate regarding the choice of fibrinolysin, its dosage and schedule. These challenges, which together with a lack of point of care diagnostics to personalize treatment of empyema, contribute to high (up to 20%) mortality in empyema in adults and should be addressed preclinically using validated animal models. Modern preclinical studies are delivering innovative solutions for evaluation and treatment of empyema in clinical practice: low dose, targeted treatments, novel biomarkers to predict IPFT success or failure, novel delivery methods such as encapsulating fibrinolysin in echogenic liposomal carriers to increase the half-life of plasminogen activator. Translational research focused on understanding the pathophysiological mechanisms that control 1) the transition from acute to advanced stage, chronic empyema, and 2) differences in outcomes of IPFT between pediatric and adult patients, will identify new molecular targets in empyema. We believe that seamless bidirectional communication between those working at the bedside and the bench would result in novel personalized approaches to improve pharmacological treatment outcomes, thus widening the window for use of IPFT in adult patients with advanced stage empyema
Aryl Hydrocarbon Receptor Regulation of Induction of Inflammatory Mediators by Organic Dust Extract in Lung Epithelial Cells
Get PDFPrevious studies have indicated a link between respiratory symptoms and diseases and organic dust exposure in agricultural workers. The aryl hydrocarbon receptor (AhR), a transcription factor activated by a wide variety of exogenous and endogenous compounds, is known to be involved in the metabolism of toxic chemicals and recently in the modulation of immune and inflammatory responses. To better understand mechanisms of pathogenesis of respiratory symptoms and diseases, the role of AhR in the regulation of induction of inflammatory mediators by poultry organic dust extract in airway epithelial cells was studied. The role of AhR was studied by investigating the effects of organic dust extract on AhR nuclear translocation and the effects of AhR silencing on the organic dust extract induction of proinflammatory mediators IL-1, ICAM- 1, IL-6 and IL-8. Our studies showed that AhR translocation is increased by organic dust extract indicating AhR activation and AhR silencing inhibited induction of inflammatory mediators by organic dust extract. Collectively, our studies showed that AhR positively regulates induction of inflammatory mediators in airway epithelial cells by organic dust
Stochasticity among Victims of COVID-19 Pandemic
Get PDFThis article provides a thorough explanation of methods and theoretical concepts to detect infectivity of COVID-19. The concept of heterogeneity is discussed and its impacts on COVID-19 pandemics are explored. Observable heterogeneity is distinguished from non- observable heterogeneity. The data support the concepts of heterogeneity and the methods to extract and interpret the data evidence for the conclusions in this paper. Heterogeneity among the vulnerable to COVID-19 is a significant factor in the contagion of COVID-19, as demonstrated with incidence rates using data of a Diamond Princess cruise ship. Given the nature of the pandemic, its heterogeneity with different social norms, pre- and post-voyage quick testing procedures ought to become the new standard for cruise ship passengers and crew. With quick testing, identification of those infected and thus, not allowing to embark on a cruise or quarantine those disembarking, and other mitigation strategies, the popular cruise adventure could become norm for safe voyage. The novel method used in this article adds valuable insight in the modeling of disease and specifically, the COVID-19 virus