Calderonforrest7547

PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature. © 2020, MacKay et al.Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. selleck chemical They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins. © 2020, Hoffmann-Conaway et al.Clinical trials for acute conditions such as myocardial infarction and stroke pose challenges related to informed consent due to time limitations, stress, and severe illness. Consent processes should be sensitive to the context in which trials are conducted and to needs of patients and surrogate decision-makers. This manuscript describes a collaborative effort between ethicists, researchers, patients, and surrogates to develop patient-driven, patient-centered approaches to consent for clinical trials in acute myocardial infarction and stroke.Our group identified important ways in which existing consent processes and forms for clinical trials fail to meet patients' and surrogates' needs in the acute context. We collaborated to create model forms and consent processes that are substantially shorter and, hopefully, better-matched to patients' and surrogates' needs and expectations from the perspective of content, structure, and tone. These changes, however, challenge some common conventions regarding consent.Community engagement (CE) is gaining prominence in global health research. A number of ethical goals-spanning the instrumental, intrinsic, and transformative-have been ascribed to CE in global health research. This paper draws attention to an additional transformative value that CE is not typically linked to but that seems very relevant solidarity. Both are concerned with building relationships and connecting parties that are distant from one another. This paper first argues that furthering solidarity should be recognized as another ethical goal for CE in global health research. It contends that, over time, CE can build the bases of solidaristic relationships-moral imagination, recognition, understanding, empathy-between researchers and community members. Applying concepts from existing accounts of solidarity, the paper develops preliminary ideas about who should be engaged and how to advance solidarity. The proposed approach is compared to current CE practice in global health research. Finally, the paper briefly considers how solidaristic CE could affect how global health research is performed.Background A recent AAOMPT position paper was published that opposed the use of the term 'degenerative disc disease' (DDD), in large part because it appears to be a common age-related finding. While common, there are significant physiologic and biomechanical changes that occur as a result of discogenic degeneration, which are relevant to consider during the practice of manual therapy.Methods A narrative review provides an overview of these considerations, including a historical perspective of discogenic instability, the role of the disc as a pain generator, the basic science of a combined biomechanical and physiologic cycle of degeneration and subsequent discogenic instability, the influence of rotation on the degenerative segment, the implications of these factors for manual therapy practice, and a perspective on an evidence-based treatment approach to patients with concurrent low back pain and discogenic degeneration.Conclusions As we consider the role of imaging findings such as DDD, we pose the following question Do our manual interventions reflect the scientifically proven biomechanical aspects of DDD, or have we chosen to ignore the helpful science as we discard the harmful diagnostic label?School principals must rely on state statutes and district policies to navigate reports of school bullying. Investigating reports to determine the outcomes may vary depending upon the districts definition of bullying, the investigation process, and follow through to reporting the findings of the investigation to the involved children and youth's parents. However, investigating reports can be challenging due to the confusion of what constitutes bullying. This confusion can be especially troubling for parents who believe their child is being bullied. In order to understand principals' perspectives on bullying, two focus groups were conducted with nine urban school principals. Researchers examined principals' perceptions of how state- and district-level policies were used within their bully investigation practices. These principals suggest that a clear, specific district wide definition of bullying and step by step procedures to investigate reports, along with the state anti-bullying statute, provide a valuable guide for follow-through and back up in determining cases of school bullying.