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volitional micturition. Moreover, engaging this inhibitory function of CRH can ameliorate bladder hyperexcitability induced by cyclophosphamide in a model of cystitis. The data underscore CRH as a novel target for the treatment of voiding dysfunctions, which are highly prevalent disease processes in children and adults.The human brain extracts statistical regularities embedded in real-world scenes to sift through the complexity stemming from changing dynamics and entwined uncertainty along multiple perceptual dimensions (e.g., pitch, timbre, location). While there is evidence that sensory dynamics along different auditory dimensions are tracked independently by separate cortical networks, how these statistics are integrated to give rise to unified objects remains unknown, particularly in dynamic scenes that lack conspicuous coupling between features. Using tone sequences with stochastic regularities along spectral and spatial dimensions, this study examines behavioral and electrophysiological responses from human listeners (male and female) to changing statistics in auditory sequences and uses a computational model of predictive Bayesian inference to formulate multiple hypotheses for statistical integration across features. Neural responses reveal multiplexed brain responses reflecting both local statistics along individual over time. In the face of this complexity, the brain builds an internal representation of the external world by collecting statistics from the sensory input along multiple dimensions. Using a Bayesian predictive inference model, this work considers alternative hypotheses for how statistics are combined across sensory dimensions. Behavioral and neural responses from human listeners show the brain multiplexes two representations, where local statistics along each feature linearly affect neural responses, and global statistics nonlinearly combine statistical beliefs across dimensions to shape perception of stochastic auditory sequences.The expression of long noncoding RNAs is highly enriched in the human nervous system. However, the function of neuronal lncRNAs in the cytoplasm and their potential translation remains poorly understood. Here we performed Poly-Ribo-Seq to understand the interaction of lncRNAs with the translation machinery and the functional consequences during neuronal differentiation of human SH-SY5Y cells. We discovered 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, 58%-70% of which are associated with polysome translation complexes. Among these polysome-associated lncRNAs, we find 45 small ORFs to be actively translated, 17 specifically upon differentiation. Fifteen of 45 of the translated lncRNA-smORFs exhibit sequence conservation within Hominidea, suggesting they are under strong selective constraint in this clade. The profiling of publicly available data sets revealed that 8/45 of the translated lncRNAs are dynamically expressed during human brain development, and 22/45 are associated with cancers of the central nervous system. One translated lncRNA we discovered is LINC01116, which is induced upon differentiation and contains an 87 codon smORF exhibiting increased ribosome profiling signal upon differentiation. The resulting LINC01116 peptide localizes to neurites. Knockdown of LINC01116 results in a significant reduction of neurite length in differentiated cells, indicating it contributes to neuronal differentiation. Our findings indicate cytoplasmic lncRNAs interact with translation complexes, are a noncanonical source of novel peptides, and contribute to neuronal function and disease. Specifically, we demonstrate a novel functional role for LINC01116 during human neuronal differentiation.In biological systems, conformational changes and allosteric modulation play pivotal roles in regulating biological functions, such as the dynamic change of protein molecules, in response to binding or interacting with other factors such as pH, voltage, salt, light, or ligand. RNA can be manipulated and tuned with a level of simplicity that is characteristic of DNA or polymers, while displaying versatility in structure, diversity in function, and adaptability in a configuration similar to proteins. In the past, the work on the investigation of conformational change mainly focused on protein. The induced-fit and conformational capture in RNA have also been explored, such as in the study of riboswitches. Herein, we report the engineering of three-dimensional RNA nanocubes and demonstrated the operation and regulation for its configuration. We demonstrate the operation of reconfigurable RNA nanocubes whose shapes change precisely and reversibly in response to a specific trigger strand. The shape, size, and conformation can be regulated precisely and reversibly in response to the specific triggering signals. The shape and conformational conversion were observed by cryo-EM and gel electrophoresis, respectively. Harnessing the size, shape, conformation, and self-assembly capabilities of the RNA nanocube can provide a new potential use of this technology as nanocarriers for the treatment of various diseases.
Statin potentially improved outcome in patients with COVID-19. Patients who receive statin generally have a higher proportion of comorbidities than those who did not, which may introduce bias. In this meta-analysis, we aimed to investigate the association between statin use and mortality in patients with COVID-19 by pooling the adjusted effect estimates from propensity-score matching (PSM) matched studies or randomised controlled trials to reduce bias.
A systematic literature search using the PubMed, Scopus and Embase databases were performed up until 1 March 2021. Studies that were designed the study to assess statin and mortality using PSM with the addition of Inverse Probability Treatment Weighting or multivariable regression analysis on top of PSM-matched cohorts were included. The effect estimate was reported in term of relative risk (RR).
14 446 patients were included in the eight PSM-matched studies. Statin was associated with decreased mortality in patients with COVID-19 (RR 0.72 (0.55, 0.95), p=0.018; I
84.3%, p<0.001). Subgroup analysis in patients receiving statin in-hospital showed that it was associated with lower mortality (RR 0.71 (0.54, 0.94), p=0.030; I
64.1%, p<0.025). The association of statin and mortality was not significantly affected by age (coefficient -0.04, p=0.382), male gender (RR 0.96 (0.95, 1.02), p=0.456), diabetes (RR 1.02 (0.99, 1.04), p=0.271) and hypertension (RR 1.01 (0.97, 1.04), p=0.732) in this pooled analysis.
In this meta-analysis of PSM-matched cohorts with adjusted analysis, statin was shown to decrease the risk of mortality in patients with COVID-19.
CRD42021240137.
CRD42021240137.Herd immunity through vaccination is a key measure to control COVID-19 pandemic. However, vaccine hesitancy remains a public health threat, which is still common among healthcare workers (HCWs). This systematic review aimed to synthesise evidence on HCWs' attitudes towards COVID-19 vaccination and analyse associated factors to provide information for vaccine policy development and practice. We searched PubMed, Embase, ScienceDirect, Web of Science and three Chinese databases for literature published on 12 February 2021. Two researchers screened the literature independently, and 13 studies were included in the systematic review. see more Vaccine acceptance varied widely and ranged from 27.7% to 77.3%. HCWs had positive attitudes towards future COVID-19 vaccines, while vaccine hesitancy was still common. Demographic variables such as men, older age and physicians were positive predictive factors. Women and nurses had more vaccine hesitancy. Previous influenza vaccination and self-perceived risk were facilitators. Concerns for safety, efficacy and effectiveness and distrust of the government were barriers. Influences of direct (COVID-19) patient care towards vaccination intention were less conclusive. Tailored communication strategies were needed to increase the uptake rate of COVID-19 vaccines among HCWs. More importantly, more data and information on the safety and efficacy of vaccines should be provided with transparency.The COVID-19 pandemic has changed forever the way we do certain things. Although the race for a cure and vaccine has taken centre stage, traditional face-to-face medical education has slowly metamorphosised in the background to a virtual world with innumerable webinars, virtual tutorials and lectures in the World Wide Web. Despite this seemingly 'perfect' solution, there remains a hidden cost. Educators are forced to learn new skills to engage students as well as manipulate the electronic platform. Impact on learning for students, both undergraduate and postgraduate from a lack of social interactions, remains unknown. In this article, the authors share their experiences from different specialities about the pros and cons of virtual learning and teaching. Suggestions and practical tips are offered to enhance the learning experience. More emphasis may need to be placed on the creation of learning communities rather than lecture-based curricula. Hybrid curricula or conferences may become the future norm. As we slowly move out of lockdown into a changed world and new ways of doing things, lessons learnt can be harnessed for future hybrid models that can combine the best of technology and physical teaching to reduce worldwide inequalities.
Quality improvement and patient safety (QIPS) have been assigned a higher profile in CanMEDS 2015, CanMEDS-Family Medicine 2017 and new accreditation standards, prompting an initiative at Dalhousie University to create a vision for integrating QIPS into postgraduate medical education.
The purpose of this study is to describe the implementation of a QIPS strategy across residency education at Dalhousie University.
A QIPS task force was formed, and a literature review and needs assessment survey were completed. A needs assessment survey was distributed to all Dalhousie residency programme directors. 12 programme directors were interviewed individually to collect additional feedback. The results were used to develop a 'road map' of recommendations with a graduated timeline.
A task force report was released in February 2018. 46 recommendations were developed with a timeframe and responsible party identified for each. Implementation of the QIPS strategy is underway, and evaluation and challenges faced will be described.
We have developed a multiyear strategy that is available to provide guidance and support to all programmes in QIPS. The development and implementation of this QIPS framework may serve as a template for other institutions who seek to integrate these competencies into residency training.
We have developed a multiyear strategy that is available to provide guidance and support to all programmes in QIPS. The development and implementation of this QIPS framework may serve as a template for other institutions who seek to integrate these competencies into residency training.Dante Alighieri died in 1321; therefore, 2021 is the 700th anniversary of his death. His best known work is the Divine Comedy, which explores Dante's journey through the three realms of the underworld. Each realm is associated with three different sensations Inferno, bodily (pain); Purgatorio, acoustic (music); and Paradiso, visual (light). The progression of the painful experiences and the resolution through music and light mirror the modern understanding of pain and its management. Music has both direct and indirect benefits and can help with coping. Sunlight promotes well-being and self-awareness.
Website: https://www.selleckchem.com/TGF-beta.html
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