Metabolic Acidosis after Sodium Thiosulfate Infusion and the Role of Hydrogen Sulfide

Sodium thiosulfate (STS), first-line treatment for calcific uremic arteriolopathy, causes a mild asymptomatic acidosis in many patients. However, severe, life-threatening acidosis out of proportion with the expected acid load of STS may occur, potentially due to metabolism of STS to hydrogen sulfide

Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

The ciliate Tetrahymena thermophila is a model organism for molecular and cellular biology. Like other ciliates, this species has separate germline and soma functions that are embodied by distinct nuclei within a single cell. The germline-like micronucleus (MIC) has its genome held in reserve for sexual reproduction. The soma-like macronucleus (MAC), which possesses a genome processed from that of the MIC, is the center of gene expression and does not directly contribute DNA to sexual progeny. We report here the shotgun sequencing, assembly, and analysis of the MAC genome of T. thermophila, which is approximately 104 Mb in length and composed of approximately 225 chromosomes. Overall, the gene set is robust, with more than 27,000 predicted protein-coding genes, 15,000 of which have strong matches to genes in other organisms. The functional diversity encoded by these genes is substantial and reflects the complexity of processes required for a free-living, predatory, single-celled organism. This is highlighted by the abundance of lineage-specific duplications of genes with predicted roles in sensing and responding to environmental conditions (e.g., kinases), using diverse resources (e.g., proteases and transporters), and generating structural complexity (e.g., kinesins and dyneins). In contrast to the other lineages of alveolates (apicomplexans and dinoflagellates), no compelling evidence could be found for plastid-derived genes in the genome. UGA, the only T. thermophila stop codon, is used in some genes to encode selenocysteine, thus making this organism the first known with the potential to translate all 64 codons in nuclear genes into amino acids. We present genomic evidence supporting the hypothesis that the excision of DNA from the MIC to generate the MAC specifically targets foreign DNA as a form of genome self-defense. The combination of the genome sequence, the functional diversity encoded therein, and the presence of some pathways missing from other model organisms makes T. thermophila an ideal model for functional genomic studies to address biological, biomedical, and biotechnological questions of fundamental importance

The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Achieving educational mission and vision with an educational scorecard

Abstract Background Achieving an academic section’s educational mission and vision is difficult, particularly when individual faculty contributions may be self-directed and uncoordinated. Balanced scorecards have been used in other environments; however, a process for developing one focusing on the educational mission of an academic medical section has not previously been described. We aimed to develop and use an educational scorecard to help our academic clinical section achieve its educational mission and vision. Methods Six medical educators participated in a task force that developed, implemented, and evaluated an educational scorecard that incorporates four domains of educational value and six stakeholder perspectives. A modified Delphi process using 14 experts built expert consensus on the most valuable metrics. The task force then developed performance targets for each metric. Results Review of the scorecard at the sectional level resulted in both sectional and individual strategies which lead to a more balanced educational impact, including service structure changes and increased mentorship. Our section has used the scorecard and metrics to evaluate performance since 2014. Conclusion An educational scorecard is a feasible way for academic groups to communicate educational goals, engage faculty, and provide objective information with which to base strategic decisions affecting their educational mission

Does What We Write Matter? Determining the Features of High- and Low-Quality Summative Written Comments of Students on the Internal Medicine Clerkship Using Pile-Sort and Consensus Analysis: A Mixed-Methods Study

Background: Written comments by medical student supervisors provide written foundation for grade narratives and deans\u27 letters and play an important role in student\u27s professional development. Written comments are widely used but little has been published about the quality of written comments. We hypothesized that medical students share an understanding of qualities inherent to a high-quality and a low-quality narrative comment and we aimed to determine the features that define high-and low-quality comments. Methods: Using the well-established anthropological pile-sort method, medical students sorted written comments into \u27helpful\u27 and \u27unhelpful\u27 piles, then were interviewed to determine how they evaluated comments. We used multidimensional scaling and cluster analysis to analyze data, revealing how written comments were sorted across student participants. We calculated the degree of shared knowledge to determine the level of internal validity in the data. We transcribed and coded data elicited during the structured interview to contextualize the student\u27s answers. Length of comment was compared using one-way analysis of variance; valence and frequency comments were thought of as helpful were analyzed by chi-square. Results: Analysis of written comments revealed four distinct clusters. Cluster A comments reinforced good behaviors or gave constructive criticism for how changes could be made. Cluster B comments exhorted students to continue non-specific behaviors already exhibited. Cluster C comments used grading rubric terms without giving student-specific examples. Cluster D comments used sentence fragments lacking verbs and punctuation. Student data exhibited a strong fit to the consensus model, demonstrating that medical students share a robust model of attributes of helpful and unhelpful comments. There was no correlation between valence of comment and perceived helpfulness. Conclusions: Students find comments demonstrating knowledge of the student and providing specific examples of appropriate behavior to be reinforced or inappropriate behavior to be eliminated helpful, and comments that are non-actionable and non-specific to be least helpful. Our research and analysis allow us to make recommendations helpful for faculty development around written feedback

Clinical Prediction Rule for Patient Outcome after In-Hospital CPR: A New Model, Using Characteristics Present at Hospital Admission, to Identify Patients Unlikely to Benefit from CPR after In-Hospital Cardiac Arrest

BACKGROUND: Physicians and patients frequently overestimate likelihood of survival after in-hospital cardiopulmonary resuscitation. Discussions and decisions around resuscitation after in-hospital cardiopulmonary arrest often take place without adequate or accurate information. METHODS: We conducted a retrospective chart review of 470 instances of resuscitation after in-hospital cardiopulmonary arrest. Individuals were ran-domly assigned to a derivation cohort and a validation cohort. Logistic Regression and Linear Discriminant Analysis were used to perform multivariate analysis of the data. The resultant best performing rule was converted to a weighted integer tool, and thresholds of survival and nonsurvival were determined with an attempt to optimize sensitivity and specificity for survival. RESULTS: A 10-feature rule, using thresholds for survival and nonsurvival, was created; the sensitivity of the rule on the validation cohort was 42.7 % and specificity was 82.4%. In the Dartmouth Score (DS), the features of age (greater than 70 years of age), history of cancer, previous cardiovascular accident, and presence of coma, hypotension, abnormal PaO2, and abnormal bicarbonate were identified as the best predictors of nonsurvival. Angina, dementia, and chronic respiratory insufficiency were selected as protective features. CONCLUSIONS: Utilizing information easily obtainable on admission, our clinical prediction tool, the DS, provides physicians individualized informa-tion about their patients ’ probability of survival after in-hospital cardiopulmonary arrest. The DS may become a useful addition to medical expertise and clinical judgment in evaluating and communicating an individual’s probability of survival after in-hospital cardiopulmonary arrest after it is validated b

Identifying protective and risk factors for injurious falls in patients hospitalized for acute care: a retrospective case-control study

Abstract Background Admitted patients who fall and injure themselves during an acute hospitalization incur increased costs, morbidity, and mortality, but little research has been conducted on identifying inpatients at high risk to injure themselves in a fall. Falls risk assessment tools have been unsuccessful due to their low positive predictive value when applied broadly to entire hospital populations. We aimed to identify variables associated with the risk of or protection against injurious fall in the inpatient setting. We also aimed to test the variables in the ABCs mnemonic (Age > 85, Bones-orthopedic conditions, anti-Coagulation and recent surgery) for correlation with injurious fall. Methods We performed a retrospective case-control study at an academic tertiary care center comparing admitted patients with injurious fall to admitted patients without fall. We collected data on the demographics, medical and fall history, outcomes, and discharge disposition of injured fallers and control patients. We performed multivariate analysis of potential risk factors for injurious fall with logistic regression to calculate adjusted odds ratios. Results We identified 117 injured fallers and 320 controls. There were no differences in age, anti-coagulation use or fragility fractures between cases and controls. In multivariate analysis, recent surgery (OR 0.46, p = 0.003) was protective; joint replacement (OR 5.58, P = 0.002), psychotropic agents (OR 2.23, p = 0.001), the male sex (OR 2.08, p = 0.003) and history of fall (OR 2.08, p = 0.02) were significantly associated with injurious fall. Conclusion In this study, the variables in the ABCs parameters were among the variables not useful for identifying inpatients at risk of injuring themselves in a fall, while other non-ABCs variables demonstrated a significant association with injurious fall. Recent surgery was a protective factor, and practices around the care of surgical patients could be extrapolated to reduce the in-hospital fall rates