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Targeted protein degradation (TPD) is a recent strategy, utilizing the cell's proteostasis machinery to deplete specific proteins. This represents a paradigm shift in early drug discovery, away from occupancy-driven to event-driven mechanisms.Recent efforts have focused on the development of proteolysis-targeting chimeras (PROTACs). These heterobifunctional molecules combine a target-specific binding moiety linked to an E3 ligase ligand and trigger selective ubiquitination of the target protein, marking it for proteasomal degradation. While these molecules can be highly efficacious, they generally have unfavorable physicochemical properties due to their large size.In contrast, smaller molecules that induce degradation could represent an attractive, simple option to overcoming the limitations of both traditional modulators and PROTACs. These molecules may have a range of mechanisms recruitment of an E3 ligase (molecular glues), introduction of hydrophobic areas, or inducing local unfolding, each of which triggers degradation.We recently completed a high-throughput screen of 111,000 compounds in a cellular HiBiT assay in an effort to identify such molecules. Preliminary analysis indicates that we have been able to identify alternative small-molecule degraders. We highlight methods for triage, characterization, selectivity, and mode of action. In summary, we believe that these types of small-molecule degraders, which may possibly have more acceptable physicochemical properties than the inherently larger heterobifunctional molecules, are an exciting approach for inducing TPD, and we illustrate that a general screening approach can be successful in identifying useful start points for developing such molecules.Residents who are terminally ill often experience transfers to the emergency department resulting in hospitalizations, which may be potentially avoidable with treatment in the nursing home. This qualitative study explored the perspectives of 15 residents, 10 family members, and 20 nursing home staff regarding end-of-life care and the circumstances prompting resident transfers. Data analysis of participant interviews conducted January to May 2019 in a South Florida nursing home identified four themes related to transfer to the hospital time left to live, when aggressive treatments would be unavailing, not knowing what the nursing home can do, and transfer decisions are situation-dependent. Study findings underscore the importance of increasing resident and family awareness of treatments available in the nursing home and person-centered advance care planning discussions. Further research should explore the reasons for residents' and family members' choice of aggressive therapies and their goals for care at the end of life.Child sexual abuse (CSA) is a terrible type of maltreatment that occurs in all countries and social statuses, but due to the shame and taboo that it creates, it is still riddled with myths and false beliefs that make it difficult for the population and the authorities to adequately determine its prevalence. The objective of this work was to explore what Mexican women know about CSA. The participants were Mexican women (N = 499) who filled out a questionnaire comprising ten items referring to truths and myths about CSA, indicating their degree of agreement with them on a Likert scale. The results showed that although Mexican women have quite adequate knowledge about CSA, they still hold wrong beliefs about the child's feelings toward the abuser or the child victim becoming an adult abuser. Likewise, differences were found in the myths and truths about CSA held by women under 40 and over 40 years of age.Traumatic brain injury (TBI) is a leading cause of death and disability, especially in young persons, and constitutes a major socioeconomic burden worldwide. It is regarded as the leading cause of mortality and morbidity in previously healthy young persons. Most of the mechanisms underpinning the development of secondary brain injury are consequences of disruption of the complex relationship between the cells and proteins constituting the neurovascular unit or a direct result of loss of integrity of the tight junctions (TJ) in the blood-brain barrier (BBB). A number of changes have been described in the BBB after TBI, including loss of TJ proteins, pericyte loss and migration, and altered expressions of water channel proteins at astrocyte end-feet processes. There is a growing research interest in identifying optimal biological and radiological biomarkers of severity of BBB dysfunction and its effects on outcomes after TBI. This review explores the microscopic changes occurring at the neurovascular unit, after TBI, and current radiological adjuncts for its evaluation in pre-clinical and clinical practice.The role of science popularization remains relatively under-explored in research on contemporary public acceptance of evolution. In this study, we analyse national survey data to interrogate the role Britain's best-known celebrity scientists David Attenborough, Brian Cox, Richard Dawkins and Stephen Hawking may have played in changing public views of evolution, as well as the role of two creationists Ken Ham and Harun Yahya. We investigate how well known these public figures are, what their views of religion are perceived to be and, drawing on social identity theory, whether they exert different effects on attitudinal change to evolution among different religious and non-religious publics. Binary logistic regression analysis shows that among Muslim and Pentecostal Christian publics, those familiar with Dawkins as both a scientist and as someone who holds negative views of religion are more likely to have become less accepting of evolution. Conversely, among non-religious publics, Dawkins was the only celebrity scientist associated with higher odds of becoming more accepting of evolution. We suggest that engaging certain religious audiences with the science of evolutionary biology may be more effective when their religious identities are not threatened.Inappropriate healthcare waste management (HCWM) may lead to health hazards through the release of toxic and infectious agents into the environment. This study aimed to assess the appropriateness of a Health Action Model (HAM) operationalized in a training intervention to promote behavioral intent towards HCWM practice among hospital staff. This was a quasi-experimental intervention study of 128 hospital staff attending a training intervention in Sabzevar Hospital, Iran. Four training intervention was carried out using potential constructs of the HAM model to compare the quality of HCWM process and behavioral intent of hospital staff before and after a training session. A questionnaire based on HAM and multiple statistical analyses were used to assess the effectiveness of the training intervention. learn more The average age of the eligible participants was 35.05 ± 9.4 years. A majority of the participant was married (88%), nursing staff (54%) and possessed a bachelor's degree (66%) or diploma (18%). After the intervention, a significant change (p  less then  0.
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