The Effect of Direct Oral Anticoagulants on Outcomes After Urgent or Emergent Cardiac Surgery.

OBJECTIVE: To determine the safety of performing urgent or emergent cardiac surgery within 5 days of a patient taking a direct oral anticoagulant (DOAC). DESIGN: A multicenter retrospective registry study. SETTING: Thirty-three hospitals in a quality collaborative from 2017 to 2019. PARTICIPANTS: Patients were included if they underwent urgent or emergent coronary artery bypass grafting (CABG). Patients were excluded if they received any anticoagulant or antiplatelet agent besides DOACs, heparin, or aspirin. INTERVENTIONS: Patients were stratified based upon the receipt of a DOAC within 5 days of their surgery. Patient cohorts included DOAC within 2 days, DOAC within 3-to-5 days, and no anticoagulation. Data were unavailable on the specific DOAC agent taken prior to admission. MEASUREMENTS AND MAIN RESULTS: There were 7,201 patients included, with 94 on DOACs. Intraoperative blood transfusion was required in 23.9% of patients on no anticoagulant, 26.2% on a DOAC within 3-to-5 days of surgery (odds ratio [OR] 0.98; 95% CI 0.46-2.11), and 30.3% on a DOAC within 2 days (OR 0.99; 95% CI 0.37-2.67). Five or more intraoperative blood products were required in 4.4% on no anticoagulant, 1.7% on DOAC within 3-to-5 days (OR 0.33; 95% CI 0.04-2.71), and 6.1% on DOAC within 2 days (OR 0.47; 95% CI 0.06-4.05). No difference in mortality was observed among the 3 groups (2.9% v 3.3% v 3.0%; p = 0.67). CONCLUSIONS: For urgent or emergent CABGs, no significant differences in minor bleeding, major bleeding, or mortality were observed in patients taking a DOAC within 5 days of surgery. This study was hypothesis-generating for performing urgent or emergent surgery sooner than 5 days after holding DOACs.

A new class of homoserine lactone quorum-sensing signals.

Quorum sensing is a term used to describe cell-to-cell communication that allows cell-density-dependent gene expression. Many bacteria use acyl-homoserine lactone (acyl-HSL) synthases to generate fatty acyl-HSL quorum-sensing signals, which function with signal receptors to control expression of specific genes. The fatty acyl group is derived from fatty acid biosynthesis and provides signal specificity, but the variety of signals is limited. Here we show that the photosynthetic bacterium Rhodopseudomonas palustris uses an acyl-HSL synthase to produce p-coumaroyl-HSL by using environmental p-coumaric acid rather than fatty acids from cellular pools. The bacterium has a signal receptor with homology to fatty acyl-HSL receptors that responds to p-coumaroyl-HSL to regulate global gene expression. We also found that p-coumaroyl-HSL is made by other bacteria including Bradyrhizobium sp. and Silicibacter pomeroyi. This discovery extends the range of possibilities for acyl-HSL quorum sensing and raises fundamental questions about quorum sensing within the context of environmental signalling.

Beyond Structure-Function: Getting at Sustainability within Biomimicry Pedagogy.

Biomimicry practice and pedagogy unify biology and design for problem solving inspired by nature. Pedagogy that supports biomimicry practice can facilitate the development of novel solutions to address societal needs and challenges. Even though biomimicry affords the possibility to address sustainability, its current practice does not necessarily lead to doing so, which can result in exploitation of nature and increased unsustainability. Recognition of this risk exists but is not yet widespread in biomimicry pedagogy, and few structured methodologies are available to support learner's efforts towards sustainability. The difficulties associated with incorporating sustainability within biomimicry are numerous and varied. In this report, we contribute to an understanding of incorporating sustainability in teaching and learning. We describe a pedagogical framing and conceptual scaffolding developed and used to bring sustainability into a biomimicry course for design- and biology-minded engineering students that integrates available biomimicry and design language, tools, and methods. We scaffold consideration of structure-function and conditions conducive to life separately, and then unify these perspectives in a way that is accessible to students. This approach centralizes sustainability in biomimicry practice and asks students to consider the ethics of design practice and responsibility to the natural world. We are encouraged by student outcomes, observing clear signs of creative systemic thinking and higher-level learning from nature. Based on pre- and post-design sprint results, students significantly shifted away from a narrower structure-function practice towards addressing conditions conducive to life. We propose that biomimicry educators and facilitators make a commitment to always include a sustainability approach within their pedagogy or explicitly acknowledge their delivery does not provide for it.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

Given the potential worsening clinical severity of 2009 pandemic influenza A (H1N1) virus (pH1N1) infection from spring to fall 2009, we conducted a clinical case series among patients hospitalized with pH1N1 infection from September through October 2009. A case patient was defined as a hospitalized person who had test results positive for pH1N1 virus by real-time reverse-transcription polymerase chain reaction. Among 255 hospitalized patients, 34% were admitted to an intensive care unit and 8% died. Thirty-four percent of patients were children <18 years of age, 8% were adults ≥ 65 years of age, and 67% had an underlying medical condition. Chest radiographs obtained at hospital admission that had findings that were consistent with pneumonia were noted in 103 (46%) of 255 patients. Among 255 hospitalized patients, 208 (82%) received neuraminidase inhibitors, but only 47% had treatment started ≤ 2 days after illness onset. Overall, characteristics of hospitalized patients with pH1N1 infection in fall 2009 were similar to characteristics of patients hospitalized with pH1N1 infection in spring 2009, which suggests that clinical severity did not change substantially over this period.

Defining health activism: from MADD to mad activists: health activism in the 20th century.

Health Activism in the 20th Century: A History of Medicine Symposium at Yale University School of Medicine in October 2010 highlighted a variety of issues concerning the social history of medicine, including race, gender, sexual orientation, and disability. A watershed moment in a burgeoning interdisciplinary field, this symposium could pave the way for extensive future discourse.

Production of hydrogen gas from light and the inorganic electron donor thiosulfate by Rhodopseudomonas palustris.

A challenge for photobiological production of hydrogen gas (H(2)) as a potential biofuel is to find suitable electron-donating feedstocks. Here, we examined the inorganic compound thiosulfate as a possible electron donor for nitrogenase-catalyzed H(2) production by the purple nonsulfur phototrophic bacterium (PNSB) Rhodopseudomonas palustris. Thiosulfate is an intermediate of microbial sulfur metabolism in nature and is also generated in industrial processes. We found that R. palustris grew photoautotrophically with thiosulfate and bicarbonate and produced H(2) when nitrogen gas was the sole nitrogen source (nitrogen-fixing conditions). In addition, illuminated nongrowing R. palustris cells converted about 80% of available electrons from thiosulfate to H(2). H(2) production with acetate and succinate as electron donors was less efficient (40 to 60%), partly because nongrowing cells excreted the intermediary metabolite α-ketoglutarate into the culture medium. The fixABCX operon (RPA4602 to RPA4605) encoding a predicted electron-transfer complex is necessary for growth using thiosulfate under nitrogen-fixing conditions and may serve as a point of engineering to control rates of H(2) production. The possibility to use thiosulfate expands the range of electron-donating compounds for H(2) production by PNSBs beyond biomass-based electron donors.

Open-source institutional guideline recommendations during the COVID-19 pandemic.

PURPOSE: The global coronavirus disease 2019 (COVID-19) pandemic and the search for ways in which to provide the best available care have created unprecedented times in terms of rapidly evolving reports of available treatment options. The primary objective of our analysis was to categorize online, open-source guidance to determine how US institutions approached their recommendations for management of patients with COVID-19 in the early weeks of the pandemic. METHODS: A search for open-source, online institutional guidelines for the treatment of COVID-19 was conducted using predefined criteria. The search was limited to the United States and conducted from April 12 through 14, 2020, and again on April 22, 2020. Searches were conducted at 2 points in time in order to identify changes in treatment recommendations due to evolving literature or institutional experience. Treatment recommendations, including guidance on antiviral therapy, corticosteroid and interleukin-6 inhibitor use, and nutritional supplementation were compared. RESULTS: Of the 105 institutions that met initial screening criteria, 14 institutions (13.3%) had online COVID-19 guidance available. Supportive care and clinical trial enrollment were the primary recommendations in all evaluated guidance. Recommendations to consider antimicrobial and adjunctive therapy varied. Eighty-six percent of guidelines contained recommendations for use, or consideration of use, of hydroxychloroquine. Guidance from 2 institutions mentioned use of hydroxychloroquine and azithromycin in combination. Of the 13 institutions listing hydroxychloroquine dosing recommendations, 62% recommended maintenance dosing of 200 mg twice daily. Infectious diseases or other specialty consultation was required by 89% of institutions using interleukin-6 inhibitors for COVID-19 management. CONCLUSION: Overall, the analysis revealed variability in treatment or supplemental pharmacologic therapy for the management of COVID-19.

Genome Sequence of Bacillus megaterium O1, a Saponin-Degrading Bacterium.

Bacillus megaterium strain O1 was isolated from a soapnut (Sapindus saponaria) surface and degrades Quillaja saponin as a sole carbon source. We report the draft genome sequence of B. megaterium O1, which has an estimated size of 5.1 Mb. Study of this isolate will provide insight into mechanisms of saponin degradation.

Changes in suicide methods in Quebec between 1987 and 2000: the possible impact of bill C-17 requiring safe storage of firearms.

This study presents the changes in the overall and firearm suicide rates for Québec (Canada) before and after Bill C-17, which was implemented to secure safe storage of firearms. It covers 20,009 suicide cases reported to the coroner's office. Interrupted time series analysis is used to compare suicide rates in the two periods. Firearm suicide rates have dropped among males and females, but the downward trends were not significant when compared to those prior to the law. Hanging suicide rates have risen considerably among men and women, but those upward trends did not increase significantly when compared with those preceding the law. The decline in suicide rates involving firearms has not resulted in a parallel decline in overall suicide rates. The analyses suggest that Bill C-17 neither improved the downward trend in firearm suicide, which had already begun before the enactment of the law, nor reduced the upward trend of the overall suicide rate. Correlation analyses between firearm suicide, hanging suicide, and the overall suicide rate suggest that firearm suicide is replaced by hanging suicide among males.

Genome Sequence of Pseudomonas putida Strain ASAD, an Acetylsalicylic Acid-Degrading Bacterium.

Pseudomonas putida strain ASAD was isolated from compost because of its ability to utilize aspirin (acetylsalicylic acid) as a carbon and energy source. We report the draft genome sequence of strain ASAD, with an estimated length of 6.9 Mb. Study of this isolate will provide insight into the aspirin biodegradation pathway.

SlpE is a calcium-dependent cytotoxic metalloprotease associated with clinical isolates of Serratia marcescens.

Serralysin-like proteases are found in a wide variety of bacteria. These metalloproteases are frequently implicated in virulence and are members of the widely conserved RTX-toxin family. We identified a serralysin-like protease in the genome of a clinical isolate of Serratia marcescens that is highly similar to the canonical serralysin protein, PrtS. This gene was named serralysin-like protease E, SlpE, and was found in the majority (67%) of tested clinical isolates, but was absent from most tested non-clinical isolates including the insect pathogen and reference S. marcescens strain Db11. Purified recombinant SlpE exhibited calcium-dependent protease activity similar to metalloproteases PrtS and SlpB. Induction of slpE in the low-protease-producing S. marcescens strain PIC3611 highly elevated extracellular protease activity, and extracellular secretion required the lipD type 1 secretion system gene. Transcription of slpE was highly reduced in an eepR transcription factor mutant. Mutation of the slpE gene in a highly proteolytic clinical isolate reduced its protease activity, and evidence suggests that SlpE confers cytotoxicity of S. marcescens to the A549 airway carcinoma cell line. Together, these data reveal SlpE to be an EepR-regulated cytotoxic metalloprotease associated with clinical isolates of an important opportunistic pathogen.

Loss of nicastrin elicits an apoptotic phenotype in mouse embryos.

Nicastrin is a member of the high molecular weight presenilin complex that plays a central role in gamma-secretase cleavage of numerous type-1 membrane-associated proteins required for cell signaling, proliferation and lineage development. We have generated a nicastrin-null mouse line by disruption of exon 3. Similar to previously described nicastrin-null mice, these animals demonstrate severe growth retardation, mortality beginning at embryonic age 10.5 days, and marked developmental abnormalities indicative of a severe Notch phenotype. Preceding their mortality, 10.5-day-old nicastrin-null embryos were found to also exhibit specific apoptosis within regions showing profound deformities, particularly in the developing heart and brain. This result suggests that complete disruption of presenilin complexes elicits programmed cell death, in addition to a Notch phenotype, which may contribute to the developmental abnormalities and embryonic mortality of nicastrin-null mice and possibly neurodegeneration in Alzheimer's disease.

Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration.

To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m(2), P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained.

Experimental and Computational Investigation of Biofilm Formation by Rhodopseudomonas palustris Growth under Two Metabolic Modes.

We examined biofilms formed by the metabolically versatile bacterium Rhodopseudomonas palustris grown via different metabolic modes. R. palustris was grown in flow cell chambers with identical medium conditions either in the presence or absence of light and oxygen. In the absence of oxygen and the presence of light, R. palustris grew and formed biofilms photoheterotrophically, and in the presence of oxygen and the absence of light, R. palustris grew and formed biofilms heterotrophically. We used confocal laser scanning microscopy and image analysis software to quantitatively analyze and compare R. palustris biofilm formation over time in these two metabolic modes. We describe quantifiable differences in structure between the biofilms formed by the bacterium grown heterotrophically and those grown photoheterotrophically. We developed a computational model to explore ways in which biotic and abiotic parameters could drive the observed biofilm architectures, as well as a random-forest machine-learning algorithm based on structural differences that was able to identify growth conditions from the confocal imaging of the biofilms with 87% accuracy. Insight into the structure of phototrophic biofilms and conditions that influence biofilm formation is relevant for understanding the generation of biofilm structures with different properties, and for optimizing applications with phototrophic bacteria growing in the biofilm state.

Draft Genome Sequence of Ralstonia sp. MD27, a Poly(3-Hydroxybutyrate)-Degrading Bacterium, Isolated from Compost.

Ralstonia sp. strain MD27, a novel biopolymer-degrading betaproteobacterium, was isolated from compost samples. This organism has been shown to utilize the biopolymer poly(3-hydroxybutyrate) [P(3HB)] as a carbon source for growth. We report the draft genome sequence of MD27 with an estimated total sequence length of 5.9 Mb.

The Impact of Hepatitis B Vaccination Status on the Risk of Diabetes, Implicating Diabetes Risk Reduction by Successful Vaccination.

BACKGROUND: The liver plays a key role in fuel metabolism. It is well established that liver disease is associated with an increased risk for diabetes mellitus. Hepatitis C virus infection has been known to increase the risk of diabetes. However, much less is known about the role of hepatitis B virus (HBV) infection in diabetes. We examined the association of diabetes based on the vaccination status for HBV. METHODS: In this cross-sectional study, we included adult subjects (≥20 y/o) with HBV serology available from the National Health and Nutrition Examination Survey 2005-2010. Diabetes was defined as established diabetes or fasting plasma glucose concentration ≥7.0 mmol/L, 2-hour plasma glucose concentration ≥11.1 mmol/L, or HbA1c ≥ 47.5 mmol/mol (6.5%). Vaccination was based on the reported history and immunization was determined by HBV serology. The odds ratio (OR) with 95% confidence intervals (95% CI) were calculated with consideration of the following covariates: age, gender, BMI, ethnic/racial group, current smoker, current alcohol consumption, family history of diabetes, poverty index, and education. RESULTS: This study included 15,316 subjects. Among them, 2,320 subjects was immunized based the HBV serology. Among 4,063 subjects who received HBV vaccination, successful vaccination was only noted in 39% of subjects. The HBV vaccination was not associated with diabetes (OR: 1.08, 95%CI: 0.96-1.23). Serology evidence of HBV immunization was associated with a reduced OR of diabetes (0.75, 95%CI: 0.62-0.90). Successful HBV vaccination was also associated with a reduced OR of diabetes (0.67, 95%CI: 0.52-0.84). CONCLUSIONS: Although our study shows the association of HBV vaccination with the reduced odds of diabetes by 33%, a prospective study is warranted to confirm and examine the impact of HBV vaccination in prevention of diabetes.

Association of insulin resistance with serum ferritin and aminotransferases-iron hypothesis.

AIM: To investigate the relationship of iron indices with diabetes mellitus (DM) in those without hemochromatosis. METHODS: This cross-sectional study examined data collected during the Third National Health and Nutrition Examination Survey (NHANES III). Only those who fasted properly and were not anemic with transferrin saturation < 45% were included (n = 6849). Insulin sensitivity and beta cell function were calculated from fasting glucose and insulin concentrations. Indices of iron metabolism were examined in the presence or absence of DM. We examined the relationship of insulin sensitivity and beta cell function with serum ferritin concentration. The influence of C-reactive protein and liver enzymes was also investigated. RESULTS: Serum ferritin concentration was significantly higher in diabetic subjects (P = 0.0001 to < 0.000001). The difference remained significant after adjustment for age, body mass index, alcohol consumption, and mineral/iron supplement (P = 0.03 to < 0.000001). In those who did not take insulin, serum ferritin concentration was negatively associated with insulin sensitivity (P = 0.05 to 0.00001), but not with beta cell function. The alanine aminotransferase was correlated with serum ferritin concentration (P = 0.02 to < 0.000001) but not with insulin sensitivity, suggesting the role of the liver in iron-associated insulin resistance. CONCLUSION: As most of diabetes is type 2 diabetes and insulin resistance is a cardinal feature of type 2 diabetes, disordered iron metabolism could play a role in the pathogenesis of insulin resistance and type 2 diabetes through its effect on liver function.

Clinical implication of fasting and post-challenged plasma glucose in diagnosis of diabetes mellitus.

Fasting plasma glucose (FPG) is the preferred test in diagnosis of diabetes mellitus (DM) to 2-h post-challenged plasma glucose (2hPG). There is little information available on the comparison between FPG and 2hPG diagnostic criteria. This study included adult participants (≥18 years old) of the NHANES 2005-2010 with FPG, 2hPG, and BMI measured. Subjects with established DM were excluded. The sensitivity of FPG and 2hPG diagnostic criteria was compared as the main outcome measure. Among 5,782 subjects, 476 subjects (8.23 %) were diagnosed with DM by either FPG, 2hPG, or both criteria. Among the subjects meeting the criterion of FPG, those with 2hPG <200 mg/dL were younger (57 ± 16 vs. 61 ± 15 years old, P < 0.05, mean ± STD) and less obese (30.81 ± 7.89 vs. 32.71 ± 6.68 kg/m(2), P < 0.05) as compared to those with 2hPG ≥200 mg/dL. Among the subjects meeting the criterion of 2hPG, those with FPG <126 mg/dL were more female (55.41 vs. 39.88 %, P < 0.0002), less obese (29.24 ± 5.83 vs. 32.71 ± 6.68 kg/m(2), P < 0.000001), lower diastolic blood pressure (67 ± 12 vs. 71 ± 14 mmHg, P < 0.02), and less family history of DM (36.35 vs. 48.47 %, P < 0.02) as compared to those with FPG ≥126 mg/dL. The sensitivity of diagnosis of DM was only 41.37 % for FPG criterion, while it was 66.53 % for 2hPG criterion. Thus, compared to 2hPG criterion, FPG criterion had a lower sensitivity detecting new cases of DM. The use of FPG criterion would more likely result in underdiagnosing DM, especially in female and less obese subjects, as compared to the use of 2hPG criterion.

Differential display analysis of presenilin 1-deficient mouse brains.

Missense mutations in presenilin 1 (PS1) gene are the most common cause of early onset familial Alzheimer's disease (FAD). AD pathogenic PS1 mutations result in elevated gamma-secretase cleavage of APP and diminished S3-site cleavage of Notch. We have previously described a PS1-hypomorphic mouse line that could survive postnatally with markedly reduced gamma-secretase cleavage of APP and S3-site cleavage of Notch, resulting in a Notch developmental phenotype similar to PS1-null mice. This model was exploited to identify genes whose expression is altered due to the loss of PS1. A global gene expression study by differential display was performed on whole brains of PS1-hypomorphic mice and their wild type siblings. In total, more than 16,000 bands corresponding to cDNAs were compared between the mutant and wild-type brains. This analysis identified 19 cDNAs showing significantly altered expression resulting from PS1 deficiency. Four of the identified cDNAs corresponded to genes that could be associated with AD or presenilin function. Hypoxia inducible factor 1a (Hif1a), NPRAP (delta-catenin) and cell division cycle 10 (CDC10) showed significantly reduced expression in the PS1-hypomorphic compared to wild-type brains, whereas expression of nucleoside diphosphate kinase sub-unit A (NDPK-A) was markedly elevated in the respective brains. Clarification of the possible role of these genes in AD and the basis for their differential expression induced by PS1-deficiency may provide insight into the disease, presenilin function and consequences of its loss, as well as possible deleterious effects of AD therapeutics aimed at inhibiting PS1.