摘要： Peri-operative myocardial injury, detected by dynamic and elevated cardiac troponin (cTn) concentrations, is a common complication of noncardiac surgery that is strongly associated with 30-day mortality. Although active screening for peri-operative myocardial injury has been suggested in recent guidelines, clinical implementation remains tentative due to a lack of examples on how to tackle such an interdisciplinary project at a local level. Moreover, consensus on which assay and cTn cut-off values should be used has not yet been reached, and guidance on whom to screen is lacking. In this article, we aim to summarise local examples of successfully implemented cTn screening practices and review the current literature in order to provide information and suggestions for patient selection, organisation of a screening programme, caveats and a potential management pathway.

关键词： Bone marrow-derived macrophages   Microarray   M2   Micro-RNA   PP2C  

摘要： Background: Timely differentiation of monocytes into M2-like macrophages is important in the cardiac healing process after myocardial infarction (MI), but molecular mechanisms governing M2-like macrophage differentiation at the transcriptional level after MI have not been fully understood. Methods and Results: A time-series microarray analysis of mRNAs and microRNAs in macrophages isolated from the infarcted myocardium was performed to identify the microRNAs involved in regulating the process of differentiation to M2-like macrophages. Correlation analysis revealed 7 microRNAs showing negative correlations with the progression of polarity changes towards M2-like subsets. Next, correlation coefficients for the changes in expression of mRNAs and miRNAs over time were calculated for all combinations. As a result, miR-27a-5p was extracted as a possible regulator of the largest number of genes in the pathway for the M2-like polarization. By selecting mouse mRNAs and human mRNAs possessing target sequences of miR-27a-5p and showing expression patterns inversely correlated with that of miR-27a-5p, 8 potential targets of miR-27a-5p were identified, including Ppm1l. Using the mouse bone marrow-derived macrophages undergoing differentiation into M2-like subsets by interleukin 4 stimulation, we confirmed that miR-27a-5p suppressed M2-related genes by negatively regulating Ppm1l expression. Conclusions: Ppm1l and miR-27a-5p may be the key molecules regulating M2-like polarization, with miR-27a-5p inhibiting the M2-like polarization through downregulation of Ppm1l expression.

摘要： Women remain underrepresented within academic medicine despite past and present efforts to promote gender equity. The authors discuss how the COVID-19 pandemic could stymie progress toward gender parity within the biomedical workforce and limit the retention and advancement of women in science and medicine. Women faculty face distinct challenges as they navigate the impact of shelter-in-place and social distancing on work and home life. An unequal division of household labor and family care between men and women means women faculty are vulnerable to inequities that may develop in the workplace as they strive to maintain academic productivity and professional development without adequate assistance with domestic tasks and family care. Emerging data suggest that gender differences in academic productivity may be forthcoming as a direct result of the pandemic. Existing gender inequities in professional visibility, networking, and collaboration may be exacerbated as activities transition from in-person to virtual environments and create new barriers to advancement. Meanwhile, initiatives designed to promote gender equity within academic medicine may lose key funding due to the economic impact of COVID-19 on higher education. To ensure that the gender gap within academic medicine does not widen, the authors call upon academic leaders and the broader biomedical community to support women faculty through deliberate actions that promote gender equity, diversity, and inclusion. The authors provide several recommendations, including faculty needs assessments;review of gender bias within tenure-clock-extension offers;more opportunities for mentorship, sponsorship, and professional recognition;and financial commitments to support equity initiatives. Leadership for these efforts should be at the institutional and departmental levels, and leaders should ensure a gender balance on task forces and committees to avoid overburdening women faculty with additional service work. Togethe

摘要： Type 2 diabetes (T2D) has a strong genetic component. Most of the gene variants driving the pathogenesis of T2D seem to target pancreatic beta-cell function. To identify novel gene variants acting at early stage of the disease, we analyzed whole transcriptome data to identify differential expression (DE) and alternative exon splicing (AS) transcripts in pancreatic islets collected from two metabolically diverse mouse strains at 6 weeks of age after three weeks of high-fat-diet intervention. Our analysis revealed 1218 DE and 436 AS genes in islets from NZO/Hl vs C3HeB/FeJ. Whereas some of the revealed genes present well-established markers for beta-cell failure, such as Cd36 or Aldh1a3, we identified numerous DE/AS genes that have not been described in context with beta-cell function before. The gene Lgals2, previously associated with human T2D development, was DE as well as AS and localizes in a quantitative trait locus (QTL) for blood glucose on Chr.15 that we reported recently in our N-2(NZOxC3H) population. In addition, pathway enrichment analysis of DE and AS genes showed an overlap of only half of the revealed pathways, indicating that DE and AS in large parts influence different pathways in T2D development. PPARG and adipogenesis pathways, two well-established metabolic pathways, were overrepresented for both DE and AS genes, probably as an adaptive mechanism to cope for increased cellular stress. Our results provide guidance for the identification of novel T2D candidate genes and demonstrate the presence of numerous AS transcripts possibly involved in islet function and maintenance of glucose homeostasis.

关键词： Gene expression   Organogenesis  

摘要： Analysis of RNA-seq datasets from seven organs across seven species generates an alternative splicing (AS) atlas and shows that AS events provide functional gene diversification through generation of tissue- and time-specific transcript isoforms. Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

关键词： Urinary tract infections   urine incontinence   older adults   incontinence pads   urine specimen collection method  

摘要： Objective: There is unmet need for an easy, noninvasive urine collection method to diagnose urinary tract infections (UTIs) in nursing home residents suffering from urinary incontinence or cognitive impairments. UTIs are highly prevalent in nursing home residents, and urine specimen collection can be difficult. The objective of this study was to assess if urine specimens collected from super-absorbing incontinence pads (adult diapers) are a reliable collection method for UTI diagnosis. Design: This was a paired noninferiority laboratory study, in which pairing refers to UTI diagnostics performed directly using clinical urine specimens (reference specimen) and indirectly using urine extracted from diapers (diaper specimen). Setting and participants: In this study, remnants of 250 clinical urine specimens were used to assess noninferiority in diagnosing UTIs, based on a 1-sided type I error of 2.5%, a power of 90%, and a non inferiority margin of 15%. Methods: Urine specimens were poured on super-absorbing disposable adult diapers and extracted after 3 hours, to use for dipstick urinalysis and bacterial culture. UTIs were defined as presence of leukocytes and a positive bacterial culture. Noninferiority was assessed by calculating a Wald-type test statistic. Results: Noninferiority was established for diagnosing UTIs in diaper specimens, and for each of its components (dipstick leukocyte detection and bacterial culture positivity). Positive bacterial cultures were found in 72 (29.0%) diaper specimens compared with 65 (26.2%) reference specimens (difference-2.8%, 97.5% CI-7.1% to 1.5%). Leukocytes were present in 162 (64.8%) diaper specimens, compared with 175 (70.0%) reference specimens (difference-5.7%, 97.5% CI:-10.6% to-0.7%). Conclusion and implications: Our results on diagnosing UTIs, by dipstick analysis and bacterial cultures, using super-absorbing adult diapers are promising. Before translation into clinical practice, further studies are needed to evaluate the

摘要： BACKGROUND Intra-operative hypotension is associated with adverse postoperative outcomes. A machine-learning-derived algorithm developed to predict hypotension based on arterial blood pressure (ABP) waveforms significantly reduced intra-operative hypotension. The algorithm calculates the likelihood of hypotension occurring within minutes, expressed as the Hypotension Prediction Index (HPI) which ranges from 0 to 100. Currently, HPI is only available for patients monitored with invasive ABP, which is restricted to high-risk procedures and patients. In this study, the performance of HPI, employing noninvasive continuous ABP measurements, is assessed. OBJECTIVES The first aim was to compare the performance of the HPI algorithm, using noninvasive versus invasive ABP measurements, at a mathematically optimal HPI alarm threshold (Youden index). The second aim was to assess the performance of the algorithm using a HPI alarm threshold of 85 that is currently used in clinical trials. Hypotension was defined as a mean arterial pressure (MAP) below 65 mmHg for at least 1 min. The predictive performance of the algorithm at different HPI alarm thresholds (75 and 95) was studied. DESIGN Observational cohort study. SETTING Tertiary academic medical centre. PATIENTS Five hundred and seven adult patients undergoing general surgery. RESULTS The performance of the algorithm with invasive and noninvasive ABP input was similar. A HPI alarm threshold of 85 showed a median [IQR] time from alarm to hypotension of 2.7 [1.0 to 7.0] min with a sensitivity of 92.7 (95% confidence interval [CI], 91.2 to 94.3), specificity of 87.6 (95% CI, 86.2 to 89.0), positive predictive value of 79.9 (95% CI, 77.7 to 82.1) and negative predictive value of 95.8 (95% CI, 94.9 to 96.7). A HPI alarm threshold of 75 provided a lower positive predictive value but a prolonged time from prediction to actual hypotension. CONCLUSION This study demonstrated that the algorithm can be employed using continuous noninvasiv

关键词： COVID-19   Chemical disinfectants   Virus inactivation   Ultraviolet light irradiation   Reactive oxygen species  

摘要： The coronavirus disease COVID-19 has spread throughout the world and has been declared as a pandemic by the World Health Organization on March 11th, 2020. The COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). One possible mode of virus transmission is through surfaces in the healthcare settings. This paper reviews currently used disinfection strategies to control SARS-CoV-2 at the healthcare facilities. Chemical disinfectants include hypochlorite, peroxymonosulfate, alcohols, quaternary ammonium compounds, and hydrogen peroxide. Advanced strategies include no-touch techniques such as engineered antimicrobial surfaces and automated room disinfection systems using hydrogen peroxide vapor or ultraviolet light.

关键词： Optimal Pricing   Price Discrimination   Pharmacoeconomics   Health Insurance   Health Care Financing   Deadweight Loss  

摘要： Pharmaceuticals are priced uniformly by convention, but vary in their degree of effectiveness for different disease indications. As more high-cost therapies have launched, the demand for alternative payment models (APMs) has been increasing in many advanced markets, despite their well-documented limitations and challenges to implementation. Among policy justifications for such contracts is the maximization of value given scarce resources. We show that while uniform pricing rules can handle variable effectiveness in efficient markets, market inefficiencies of other kinds create a role for different value-based pricing structures. We first present a stylized theoretical model of efficient interaction among drug manufacturers, payers, and beneficiaries. In this stylized setting, uniform pricing works well, even when treatment effects are variable. We then use this framework to define market failures that result in obstacles to uniform pricing. The market failures we identify include: (1) uncertainty of patient distribution, (2) asymmetric beliefs, (3) agency imperfection by payer, (4) agency imperfection by provider, and (5) patient behavior and treatment adherence. We then apply our insights to real-world examples of alternative payment models, and highlight challenges related to contract implementation.