Project description:Calcium-sensing receptors (CaSR) are integral to regulation of systemic Ca(2+) homeostasis. Altered expression levels or mutations in CaSR cause Ca(2+) handling diseases. CaSR is regulated by both endogenous allosteric modulators and allosteric drugs, including the first Food and Drug Administration-approved allosteric agonist, Cinacalcet HCl (Sensipar®). Recent studies suggest that allosteric modulators not only alter function of plasma membrane-localized CaSR, but regulate CaSR stability at the endoplasmic reticulum. This brief review summarizes our current understanding of the role of membrane-permeant allosteric agonists in cotranslational stabilization of CaSR, and highlights additional, indirect, signalling-dependent role(s) for membrane-impermeant allosteric drugs. Overall, these studies suggest that allosteric drugs act at multiple cellular organelles to control receptor abundance and hence function, and that drug hydrophobicity can bias the relative contributions of plasma membrane and intracellular organelles to CaSR abundance and signalling.
Project description:Light is a powerful stimulus regulating many aspects of plant development and phenotypic plasticity. Plants sense light through the action of specialized photoreceptor protein families that absorb different wavelengths and intensities of light. Recent discoveries in the area of photobiology have uncovered photoreversible changes in nuclear organization correlated with transcriptional regulation patterns that lead to de-etiolation and photoacclimation. Novel signalling components bridging photoreceptor activation with chromatin remodelling and regulation of gene expression have been discovered. Moreover, coregulated gene loci have been shown to relocate to the nuclear periphery in response to light. The study of photoinduced changes in nuclear architecture is a flourishing area leading to major discoveries that will allow us to better understand how highly conserved mechanisms underlying genomic reprogramming are triggered by environmental and endogenous stimuli. This review aims to discuss fundamental and innovative reports demonstrating how light triggers changes in chromatin and nuclear architecture during photomorphogenesis.
Project description:ObjectiveTo identify factors contributing to changes on quality, productivity, and safety outcomes during a large commercial electronic health record (EHR) implementation and to guide future research.MethodsWe conducted a mixed-methods study assessing the impact of a commercial EHR implementation. The method consisted of a quantitative longitudinal evaluation followed by qualitative semi-structured, in-depth interviews with clinical employees from the same implementation. Fourteen interviews were recorded and transcribed. Three authors independently coded interview narratives and via consensus identified factors contributing to changes on 15 outcomes of quality, productivity, and safety.ResultsWe identified 14 factors that potentially affected the outcomes previously monitored. Our findings demonstrate that several factors related to the implementation (e.g., incomplete data migration), partially related (e.g., intentional decrease in volume of work), and not related (e.g., health insurance changes) may affect outcomes in different ways.DiscussionThis is the first study to investigate factors contributing to changes on a broad set of quality, productivity, and safety outcomes during an EHR implementation guided by the results of a large longitudinal evaluation. The diversity of factors identified indicates that the need for organizational adaptation to take full advantage of new technologies is as important for health care as it is for other services sectors.ConclusionsWe recommend continuous identification and monitoring of these factors in future evaluations to hopefully increase our understanding of the full impact of health information technology interventions.
Project description:Cryptococcus neoformans is the pathogen responsible for cryptococcal pneumonia and meningitis, mainly affecting patients with suppressed immune systems. We have previously revealed the mechanism of anticryptococcal action of synthetic antimicrobial peptides (SAMPs). In this study, computational and experimental analyses provide new insights into the mechanisms of action of SAMPs. Computational analysis revealed that peptides interacted with the PHO36 membrane receptor of C. neoformans. Additionally, ROS (reactive oxygen species) overproduction, the enzymes of ROS metabolism, interference in the ergosterol biosynthesis pathway, and decoupling of cytochrome c mitochondrial membrane were evaluated. Three of four peptides were able to interact with the PHO36 receptor, altering its function and leading to ROS overproduction. SAMPs-treated C. neoformans cells showed a decrease in scavenger enzyme activity, supporting ROS accumulation. In the presence of ascorbic acid, an antioxidant agent, SAMPs did not induce ROS accumulation in C. neoformans cells. Interestingly, two SAMPs maintained inhibitory activity and membrane pore formation in C. neoformans cells by a ROS-independent mechanism. Yet, the ergosterol biosynthesis and lactate dehydrogenase activity were affected by SAMPs. In addition, we noticed decoupling of Cyt c from the mitochondria, which led to apoptosis events in the cryptococcal cells. The results presented herein suggest multiple mechanisms imposed by SAMPs against C. neoformans interfering in the development of resistance, thus revealing the potential of SAMPs in treating infections caused by C. neoformans.
Project description:BackgroundMental health problems cover a wide spectrum. Depression and anxiety disorders are the most frequent mental health problem in the general population and in elite athletes. The aim of the present study was to assess the prevalence of symptoms of depression, generalised anxiety disorder and eating disorders in professional dancers, to compare the results between genders and to the general population and to analyse potential determinants.MethodsDuring a pre-season health screening, professional dancers of six German companies answered a comprehensive questionnaire on personal and dancer-specific characteristics, medical history and the Patient Health Questionnaire (PHQ-9), Generalised Anxiety Disorder Questionnaire (GAD-7) and Eating-Disorder-Examination-Questionnaire (EDE-QS).ResultsA total of 82 (55.8%) female and 65 (44.2%) male dancers answered the questionnaire. One in five (20.8%) dancers had at least moderate symptoms of either depression, generalised anxiety disorder or eating disorders. The prevalence of at least moderate symptoms of depression was 11.1% in female and 6.4% in male dancers, of generalised anxiety disorder 16.0% in female and 6.4% in male dancers and of eating disorders 14.8% in female and 6.1% in male dancers. Compared to the general population of the same gender and similar age, the prevalence of at least moderate symptoms of generalised anxiety disorder was significantly higher in both genders. About one in four dancers (26.9%) reported a subjective need for support from a psychotherapist at the time of the screening. The PHQ-9, GAD-7 and EDE-QS sum scores were not related to the size or type of the companies, the age or rank of the dancers, but the PHQ-9 and GAD-7 sum score were significantly related to severity of musculoskeletal pain in the past seven days and to chronic or recurrent symptoms of low mood and generalised anxiety.ConclusionThe prevalence of symptoms of depression, generalised anxiety and eating disorders was high in professional dancers. Routine screening and low-threshold interventions to improve mental health of professional dancers are recommended.
Project description:In this study, we investigated whether background information of a visual charity appeal can influence people's motivation to donate and the hypothetical amount donated. Specifically, participants were presented with a charity appeal to help a local hospital respond to the Coronavirus Disease-19 (COVID-19) emergency depicting a man sitting on a bed in a hospital room. The number of visual details (i.e., medical equipment) depicted in the background was manipulated according to three conditions: (1) "High information" condition (i.e., a room full of medical equipment), (2) "low information" condition (i.e., room with few pieces of medical equipment), and (3) "no information" condition (i.e., non-contextual background). We investigated whether the number of visual background details would have increased the tangibility of the cause measured as the hospital's adequate preparedness to deal with the COVID-19 emergency and severity of the patient's medical conditions. We also investigated whether increased tangibility, elicited by a higher amount of background information, would heighten participants' perceived impact of their donation and warm glow, which in turn would have led to increased motivation to donate and the amount donated. We found no significant direct effect of condition on the donated amount. However, path models revealed that more background information positively influenced participants' motivation to donate and the amount donated indirectly through increased tangibility, impact, and warm glow. Finally, we showed that a higher risk perception of COVID-19 was associated with higher donations. Results are discussed in line with relevant literature.
Project description:BackgroundThe Grasha-Riechmann teaching styles, which includes three didactic and two prescriptive styles, have been shown to help enhance learning within educational settings. Although an adaption of the Grasha-Riechmann style classification has enabled coaching styles to be identified for use as part of quality improvement (QI) initiatives, research has not examined the styles actually utilized by coaches within a QI initiative or how the styles change overtime when the coach is guiding an organization through change implementation. Interactions between coaches and HIV service organization (HSO) staff participating in a large implementation research experiment called the Substance Abuse Treatment to HIV care (SAT2HIV) Project were evaluated to begin building an evidence base to address this gap in implementation research.MethodsImplementation & Sustainment Facilitation (ISF) Strategy meetings (n = 137) between coaches and HSO staff were recorded and professionally transcribed. Thematic coding classifications were developed from the Grasha-Riechmann framework and applied to a purposively selected sample of transcripts (n = 66). Four coders independently coded transcripts using NVivo to facilitate text identification, organization, and retrieval for analysis. Coaching style use and changes across the three ISF phases were explored.ResultsFacilitator and formal authority were the two coaching styles predominately used. Facilitator sub-themes shifted from asking questions and providing support to supporting independent action over time. Coaches' use of formal authority sub-styles shifted notably across time from setting expectations or ensuring preparation to offering affirmation or feedback about changes that the HSO's were implementing. The use of the delegator or personal model coaching styles occurred infrequently.ConclusionsThe current research extends implementation research's understanding of coaching. More specifically, findings indicate it is feasible to use the Grasha-Riechmann framework to qualitatively identify coaching styles utilized in a facilitation-based implementation strategy. More importantly, results provide insights into how different coaching styles were utilized to implement an evidence-based practice. Further research is needed to examine how coaching styles differ by organization, impact implementation fidelity, and influence both implementation outcomes and client outcomes.Trial registrationClinicalTrials.gov NCT02495402 . Registered on July 6, 2015.
Project description:(1) Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began spreading across the globe in December and, as of 9 July 2020, had inflicted more than 550,000 deaths. Public health measures implemented to control the outbreak caused socio-economic havoc in many countries. The pandemic highlighted the quality of health care systems, responses of policymakers in harmony with the population, and socio-economic resilience factors. We suggest that different national strategies had an impact on mortality and case count. (2) Methods: We collected fatality data for 17 countries until 2 June 2020 from public data and associated these with implemented containment measures. (3) Results: The outcomes present the effectiveness of control mechanisms in mitigating the virus for selected countries and the UAE as a special case. Pre-existing conditions defined the needed public health strategies and fatality numbers. Other pre-existing conditions, such as temperature, humidity, median age, and low serum 25-hydroxyvitamin D (25(OH)D) concentrations played minor roles and may have had no direct impact on fatality rates. (4) Conclusions: Prevention, fast containment, adequate public health strategies, and importance of indoor environments were determining factors in mitigating the pandemic. Development of public health strategies adapted to pre-existing conditions for each country and community compliance with implemented policies ensure the successful control of pandemics.
Project description:There are few studies in literature reporting drawing as a strong trigger of praxis-induced focal seizures. The aim of the present case report was describing a case of focal epilepsy with praxis induced EEG activation, due to a cavernoma, in the left middle anterior temporal lobe by using a multimodal approach. We combined video-EEG, showing that drawing increased a sustained monomorphic delta activity localized on left anterior temporal region (F7-T1a), diffusing to the vertex (Fz) and the fronto-polar electrodes (F3), with DTI data, showing that the left uncinate fasciculus, connecting the temporal pole to the orbitofrontal cortex, significantly differed from controls. fMRI confirmed that drawing increased activation in these areas. The congruence between findings supports the role of the left uncinated fasciculus linking the temporal lobe to the orbitofrontal cortex in the present focal epilepsy mainly facilitated by drawing.
Project description:Many medical (and nonmedical) technologies are the fruit of years and even decades of work by dedicated members of startup companies and commitment of capital by their investors. The launching of a medical device venture is fraught with many risks, but the personal, societal, and potential financial rewards of developing therapies that improve the lives of others makes the risk and sacrifice worthwhile. The litany of risks and challenges can be daunting, and persistence is the key ingredient to every incremental iota of success achieved. This is a personal war story behind the launching of a medical device venture that developed an implanted seizure prediction system (NCT01043406). The intent is to share the experience so that others with interest in the field may learn from the experience and also decide whether such an endeavor is something that they want to undertake.