Tau mutation S356T in the three repeat isoform leads to microtubule dysfunction and promotes prion-like seeded aggregation

Tauopathies are a group of neurodegenerative diseases, which include frontotemporal dementia (FTD) and Alzheimer’s disease (AD), broadly defined by the development of tau brain aggregates. Both missense and splicing tau mutations can directly cause early onset FTD. Tau protein is a microtubule-associated protein that stabilizes and regulates microtubules, but this function can be disrupted in disease states. One contributing factor is the balance of different tau isoforms, which can be categorized into either three repeat (3R) or four repeat (4R) isoforms based on the number of microtubule-binding repeats that are expressed. Imbalance of 3R and 4R isoforms in either direction can cause FTD and neurodegeneration. There is also increasing evidence that 3R tauopathies such as Pick’s disease form tau aggregates predominantly comprised of 3R isoforms and these can present differently from 4R and mixed 3R/4R tauopathies. In this study, multiple mutations in 3R tau were assessed for MT binding properties and prion-like aggregation propensity. Different missense tau mutations showed varying effects on MT binding depending on molecular location and properties. Of the mutations that were surveyed, S356T tau is uniquely capable of prion-like seeded aggregation and forms extensive Thioflavin positive aggregates. This unique prion-like tau strain will be useful to model 3R tau aggregation and will contribute to the understanding of diverse presentations of different tauopathies

Mapping of Dietary Interventions Beneficial in the Prevention of Secondary Health Conditions in Spinal Cord Injured Population: A Systematic Review.

OBJECTIVES Individuals with spinal cord injury are at risk of secondary health conditions (SHC) that develop as a consequence of autonomic dysfunction, prolonged oxidative stress and inflammation, and physical inactivity coupled with inadequate energy and nutritional intake. SHC can be debilitating and even life-threatening, and its prevention remains one of the major challenges in the continuum of medical care of aging SCI population. An unhealthy diet is a major driver of inflammation, oxidative stress, and unfavourable metabolic status and may be a practical preventive target to tackle increased SHC risk post-injury. AIMS To provide a catalogue of dietary interventions beneficial in prevention of SHC among individuals with SCI by conducting a systematic review of the literature on dietary interventions and dietary supplementation in promoting health and well-being after the injury. In addition, we aimed to provide a summary of observational studies exploring the association between habitual diet (macro- and micronutrients intake and dietary patterns) and health patterns following the injury. METHOD This review was registered at PROSPERO (University of York) with registration number CRD42022373773. Four medical databases (EMBASE.com, MEDLINE [Ovid], Cochrane CENTRAL, and Web of Science Core Collection) and Google Scholar were searched from inception until 11th July 2022. Studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. Based on strength of the study design and risk of bias assessment (using the NIH tool), we classified studies from Level 1 (most reliable studies) to Level 4 (least reliable studies). RESULTS Of 12,313 unique citations, 47 articles (based on 43 original studies) comprising 32 interventional (22 RCTs, 3 NRCT, and 7 pre-post studies) and 11 observational studies (2 cohort studies, 2 case-control, 1 post-intervention follow-up study, and 6 cross-sectional studies) were included in the present systematic review. Twenty studies (46.5%) were classified as Level 1 or 2, indicating high/moderate methodological quality. Based on those studies, dietary strategies including high protein diet, intermittent fasting, balanced diet in combination with physical conditioning and electrical stimulation, and dietary supplementation including alpha-lipoic acid, creatine, vitamin D, and cranberry-derived supplements and probiotics were mapped as the most promising in prevention of SHC among individuals with SCI. CONCLUSIONS To develop timely and effective preventive strategies targeting major SHC (e.g., cardiometabolic diseases, urinary tract infections) in SCI, further research is warranted to confirm the effectiveness of dietary strategies/interventions identified through the current systematic review of the literature

Self-diffusion in granular gases

The coefficient of self-diffusion for a homogeneously cooling granular gas changes significantly if the impact-velocity dependence of the restitution coefficient $\epsilon$ is taken into account. For the case of a constant $\epsilon$ the particles spread logarithmically slow with time, whereas the velocity dependent coefficient yields a power law time-dependence. The impact of the difference in these time dependences on the properties of a freely cooling granular gas is discussed.Comment: 6 pages, no figure

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Development and evaluation of a web-based breast cancer cultural competency course for primary healthcare providers

<p>Abstract</p> <p>Background</p> <p>To develop and evaluate a continuing medical education (CME) course aimed at improving healthcare provider knowledge about breast cancer health disparities and the importance of cross-cultural communication in provider-patient interactions about breast cancer screening.</p> <p>Methods</p> <p>An interactive web-based CME course was developed and contained information about breast cancer disparities, the role of culture in healthcare decision making, and demonstrated a model of cross-cultural communication. A single group pre-/post-test design was used to assess knowledge changes. Data on user satisfaction was also collected.</p> <p>Results</p> <p>In all, 132 participants registered for the CME with 103 completing both assessments. Differences between pre-/post-test show a significant increase in knowledge (70% vs. 94%; p < .001). Ninety-five percent of participants agreed that the web based training was an appropriate tool to train healthcare providers about cultural competency and health disparities.</p> <p>Conclusion</p> <p>There was an overall high level of satisfaction among all users. Users felt that learning objectives were met and the web-based format was appropriate and easy to use and suggests that web-based CME formats are an appropriate tool to teach cultural competency skills. However, more information is needed to understand how the CME impacted practice behaviors.</p

Constraints to Economic Development and Growth in the Middle East and North Africa

When comparing the speed and extent of economic development in different geographic regions of the world over the past 20 years, the under-average performance of Arab countries in general and Arab Mediterranean countries in particular is striking. This is despite an overall favorable geo-strategic situation at the crossroads of three continents, with excellent connections to sea and waterways and in direct proximity to the European Union, one of the world’s economic hubs. It is also despite the minor importance of negative factors such as a high-burden diseases or high levels of ethnic fractionalization. In this paper, I focus on identifying the most important constraints on Arab Mediterranean economic development. I use state-of-the-art econometric tools to quantify constraints that have been identified through economic theory and studies of the political economy characteristics of the region. The empirical results offer support for the central hypothesis that limited technological capacities and political economy structures are the primary constraints on economic development. With a view to international structural adjustment efforts, my findings imply that the limited success of the Euro-Mediterranean policy to stimulate the economic development of the Arab Mediterranean countries might be because structural adjustment efforts do not tackle—or at least do not sufficiently tackle— these constraints.Vergleicht man Geschwindigkeit und Umfang der wirtschaftlichen Entwicklung der verschiedenen Weltregionen in den vergangenen zwanzig Jahren, so fällt insbesondere das unterdurchschnittliche Abschneiden der arabischen Länder im Allgemeinen und der arabischen Mittlemeerländer im Besonderen ins Auge, und dies trotz einer insgesamt vorteilhaften geographischen Lage im Schnittpunkt dreier Kontinente mit exzellenten Anschlussmöglichkeiten an See- und Wasserwege, trotz der direkten Nachbarschaft zum Weltwirtschaftsdrehkreuz Europäische Union und trotz der relativ geringen Bedeutung wichtiger entwicklungshemmender Faktoren, beispielsweise ethnische Zersplitterung oder massive Ausbreitung von Krankheiten wie AIDS oder Malaria. In diesem Aufsatz wird versucht, von den unterschiedlichen Hemmfaktoren wirtschaftlicher Entwicklung, die in der wirtschaftstheoretischen Literatur und/oder in MENARegionalstudien diskutiert werden, diejenigen herauszuarbeiten, die wirtschaftliche Entwicklung am stärksten behindern oder möglicherweise stärker als andere. Dabei benutze ich modernste ökonometrische Verfahren, um den Einfluss der verschiedenen erklärenden Variablen zu quantifizieren. Die Ergebnisse stützen die Eingangshypothese, dass insbesondere mangelnde technologische Kapazitäten und Fähigkeiten sowie regionalspezifische politökonomische Strukturen die wirtschaftliche Entwicklung in den arabischen Mittelmeerländern behindern