Ibrahimandreasen3994
This paper addresses the role of categories and dimensions in the classification of psychopathology. While psychopathology does not sort itself out neatly into natural categories, we do find rough, symptom-based groupings that, through refinement, become diagnostic categories. Given that these categories suffer from comorbidity, uncertain boundaries, and excessive "unspecified disorder" diagnoses, there has been a move toward refining the diagnoses with dimensional measures. The paper traces efforts both to improve the diagnostic categories with validators that allow at least partial validity and to introduce dimensional measures into the diagnostic manual. Drawing from the philosophical pragmatism of Charles Sanders Peirce, William James, and John Dewey, which emphasizes the practical, effect-sensitive consequences of a theory along with an emphasis on empirical evidence and the progressive, probabilistic character of knowledge, the paper argues that these efforts must be guided both by scientific validity and clinical utility.The BES1/BZR1 transcription factors regulate the expression of genes responsive to brassinosteroids and play pivotal roles in plant development, but their role in regulating kernel development in maize remains unclear. In this study, we found that ZmBES1/BZR1-5 positively regulates kernel size. Association analysis of candidate genes in 513 diverse maize inbred lines indicated that three SNPs related to ZmBES1/BZR1-5 were significantly associated with kernel width and whilst four SNPs were related to 100-kernel weight. Overexpression of ZmBES1/BZR1-5 in Arabidopsis and rice both significantly increased seed size and weight, and smaller kernels were produced in maize Mu transposon insertion and EMS mutants. The ZmBES1/BZR1-5 protein locates in the nucleus, contains bHLH and BAM domains, and shows no transcriptional activity as a monomer but forms a homodimer through the BAM domain. ChIP-sequencing analysis, and yeast one-hybrid and dual-luciferase assays demonstrated that the protein binds to the promoters of AP2/EREBP genes (Zm00001d010676 and Zm00001d032077) and inhibits their transcription. cDNA library screening showed that ZmBES1/BZR1-5 interacts with casein kinase II subunit β4 (ZmCKIIβ4) and ferredoxin 2 (ZmFdx2) in vitro and in vivo, respectively. Taken together, our study suggests that ZmBES1/BZR1-5 positively regulates kernel size, and provides new insights into understanding the mechanisms of kernel development in maize.Immediately before the release of DSM-5, a group of psychiatric thought leaders published the results of field tests of DSM-5 diagnostic criteria. They characterized the interrater reliability for diagnosing major depressive disorder by two trained mental health practitioners as of "questionable agreement." These field tests confirmed an open secret among psychiatrists that our current diagnostic criteria for diagnosing major depressive disorder are unreliable and neglect essential experiences of persons in depressive episodes. Alternative diagnostic criteria exist, but psychiatrists rarely encounter them, forestalling the discipline's epistemological crisis. In Alsadair MacIntyre's classic essay, such crises occur in science when a person encounters a rival schemata that is incompatible with their current schemata and subsequently constructs a narrative that allows them to reconstruct their own tradition. In search of rival schemata that are in conversation with their own tradition, psychiatric practitioners can utilize alternative diagnostic criteria like the Cultural Formulation Interview, embrace an epistemologically humble psychiatry, and attend to the narrative experience of a person experiencing a depressive episode.
The admission interview is regarded as one of the most significant moments in the process of applying to medical school, but there is limited empirical evidence that supports this claim. Previous analyses have offered what is largely anecdotal evidence of the interview's importance while also suggesting that there is ample opportunity for ethnic and gender bias to impact interview scores. We also asked what medical schools can learn from comparing the attributes of matriculants and those applicants who rejected offers of acceptance.
This study investigated the association between interview performance and admission committee decisions for applicants applying to the School of Medicine of the USU. The study cohort included all candidates who were invited for an on-site interview at the USU in 2014, 2015, and 2016 (n = 1825).
Seventeen percent of the variance of the outcome variables-admission committee decisions to accept, place on the alternate list, or reject an applicant-can be explained by consideringUSU and those who rejected offers of acceptance are small, indicating that the USU continues to build a class body that excels in both cognitive and noncognitive domains.
The various forms of mass spectrometry (MS) instrumentation have had a major impact on testing for analytes performed with clinical and forensic laboratories over the past decade. Improvements in MS instrumentation have led to the use of MS in many areas.
To highlight the value of MS testing, short reports are presented that are relevant to the following fields pain management, transplant medicine, clinical toxicology, designer drug testing, genetic metabolic disorders, nutrition, dietary exposure to heavy metals, herbals and supplements, forensic pathology, pharmacogenomics, homeland security, performance enhancing drugs and peptides, clinical microbiology, physician licensing, and environmental exposures. These reports are based on real patients. The "stories" have been altered to comply with privacy regulations.
Analysis of MS provides objective results that have an impact on many areas of medicine and society as a whole. Accurate analysis has an impact on guidance for medical practices.
The value of MS testing will continue to grow in the years to come.
The value of MS testing will continue to grow in the years to come.
Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)-the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported.
We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. find more We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis.
Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.
Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.
Nursing homes (NHs) care for 70% of Americans dying with dementia. Many consider deaths in NHs rather than hospitals as preferable for most of these residents. NH characteristics such as staff teamwork, communication, and other components of patient safety culture (PSC), together with state minimum NH nurse staffing requirements, may influence location of death. We examined associations between these variables and place of death (NH/hospital) among residents with dementia.
Cross-sectional study of 11,957 long-stay NH residents with dementia, age 65+, who died in NHs or hospitals shortly following discharge from one of 800 US NHs in 2017. Multivariable logistic regression systematically estimated effects of PSC on odds of in-hospital death among residents with dementia, controlling for resident, NH, county, and state characteristics. Logistic regressions also determined moderating effects of state minimum NH nurse staffing requirements on relationships between key PSC domains and location of death.
Residents with dementia in NHs with higher PSC scores in communication openness had lower odds of in-hospital death. This effect was stronger in NHs located in states with higher minimum NH nurse staffing requirements.
Promoting communication openness in NHs across nursing disciplines may help avoid unnecessary hospitalization at the end of life, and merits particular attention as NHs address nursing staff mix while adhering to state staffing requirements. Future research to better understand unintended consequences of staffing requirements is needed to improve end-of-life care in NHs.
Promoting communication openness in NHs across nursing disciplines may help avoid unnecessary hospitalization at the end of life, and merits particular attention as NHs address nursing staff mix while adhering to state staffing requirements. Future research to better understand unintended consequences of staffing requirements is needed to improve end-of-life care in NHs.Deregulation of MYC occurs in a broad range of human cancers and often predicts poor prognosis and resistance to therapy. However, directly targeting oncogenic MYC remains unsuccessful, and indirectly inhibiting MYC emerges as a promising approach. Checkpoint kinase 1 (CHK1) is a protein kinase that coordinates the G2/M cell cycle checkpoint and protects cancer cells from excessive replicative stress. Using c-MYC-mediated T-cell acute lymphoblastic leukemia (T-ALL) and N-MYC-driven neuroblastoma as model systems, we reveal that both c-MYC and N-MYC directly bind to the CHK1 locus and activate its transcription. CHIR-124, a selective CHK1 inhibitor, impairs cell viability and induces remarkable synergistic lethality with mTOR inhibitor rapamycin in MYC-overexpressing cells. Mechanistically, rapamycin inactivates carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD), the essential enzyme for the first three steps of de novo pyrimidine synthesis, and deteriorates CHIR-124-induced replicative stress. We further demonstrate that dual treatments impede T-ALL and neuroblastoma progression in vivo. These results suggest simultaneous targeting of CHK1 and mTOR as a novel and powerful co-treatment modality for MYC-mediated tumors.
