Genomic characterization of the Yersinia genus

Comparative Yersinia genomics identifies features responsible for the colonization of specific host habitats and the horizontal transfer of virulence determinants

Rapid Identification of Genetic Modifications in Bacillus anthracis Using Whole Genome Draft Sequences Generated by 454 Pyrosequencing

Background The anthrax letter attacks of 2001 highlighted the need for rapid identification of biothreat agents not only for epidemiological surveillance of the intentional outbreak but also for implementing appropriate countermeasures, such as antibiotic treatment, in a timely manner to prevent further casualties. It is clear from the 2001 cases that survival may be markedly improved by administration of antimicrobial therapy during the early symptomatic phase of the illness; i.e., within 3 days of appearance of symptoms. Microbiological detection methods are feasible only for organisms that can be cultured in vitro and cannot detect all genetic modifications with the exception of antibiotic resistance. Currently available immuno or nucleic acid-based rapid detection assays utilize known, organism-specific proteins or genomic DNA signatures respectively. Hence, these assays lack the ability to detect novel natural variations or intentional genetic modifications that circumvent the targets of the detection assays or in the case of a biological attack using an antibiotic resistant or virulence enhanced Bacillus anthracis, to advise on therapeutic treatments. Methodology/Principal Findings We show here that the Roche 454-based pyrosequencing can generate whole genome draft sequences of deep and broad enough coverage of a bacterial genome in less than 24 hours. Furthermore, using the unfinished draft sequences, we demonstrate that unbiased identification of known as well as heretofore-unreported genetic modifications that include indels and single nucleotide polymorphisms conferring antibiotic and phage resistances is feasible within the next 12 hours. Conclusions/Significance Second generation sequencing technologies have paved the way for sequence-based rapid identification of both known and previously undocumented genetic modifications in cultured, conventional and newly emerging biothreat agents. Our findings have significant implications in the context of whole genome sequencing-based routine clinical diagnostics as well as epidemiological surveillance of natural disease outbreaks caused by bacterial and viral agents

Neurocognitive functioning in acute or early HIV infection

We examined neurocognitive functioning among persons with acute or early HIV infection (AEH) and hypothesized that the neurocognitive performance of AEH individuals would be intermediate between HIV seronegatives (HIV−) and those with chronic HIV infection. Comprehensive neurocognitive testing was accomplished with 39 AEH, 63 chronically HIV infected, and 38 HIV− participants. All AEH participants were HIV infected for less than 1 year. Average domain deficit scores were calculated in seven neurocognitive domains. HIV−, AEH, and chronically HIV infected groups were ranked from best (rank of 1) to worst (rank of 3) in each domain. All participants received detailed substance use, neuromedical, and psychiatric evaluations and HIV infected persons provided information on antiretroviral treatment and completed laboratory evaluations including plasma and CSF viral loads. A nonparametric test of ordered alternatives (Page test), and the appropriate nonparametric follow-up test, was used to evaluate level of neuropsychological (NP) functioning across and between groups. The median duration of infection for the AEH group was 16 weeks [interquartile range, IQR: 10.3–40.7] as compared to 4.9 years [2.8–11.1] in the chronic HIV group. A Page test using ranks of average scores in the seven neurocognitive domains showed a significant monotonic trend with the best neurocognitive functioning in the HIV− group (mean rank = 1.43), intermediate neurocognitive functioning in the AEH group (mean rank = 1.71), and the worst in the chronically HIV infected (mean rank = 2.86; L statistic = 94, p < 0.01); however, post-hoc testing comparing neurocognitive impairment of each group against each of the other groups showed that the chronically infected group was significantly different from both the HIV− and AEH groups on neurocognitive performance; the AEH group was statistically indistinguishable from the HIV− group. Regression models among HIV infected participants were unable to identify significant predictors of neurocognitive performance. Neurocognitive functioning was worst among persons with chronic HIV infection. Although a significant monotonic trend existed and patterns of the data suggest the AEH individuals may fall intermediate to HIV− and chronic participants, we were not able to statistically confirm this hypothesis

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

GC-MS Analysis of Residues Reveals Nicotine in Two Late Prehistoric Pipes from CA-ALA-554

Three pipes were recovered during excavations at CA-ALA-554. Ethnographically, Native Californians smoked a range of plants, the most common of which is tobacco, in pipes. In order to determine the specific uses of these pipes, we extracted organic residues from the pipes and identified compounds using Gas Chromatography-Mass Spectrometry. Results show that the pipes have strong nicotine signatures, indicating they were used to smoke tobacco. Biomarkers for other plants are not present. Although tobacco use was introduced to California in ancient times, the precise date is unknown. The presence of nicotine in these pipes has implications for the timing of when tobacco entered California, and for indigenous horticultural practices

Mental Health Risk Factors Related to COVID-19 among Canadian Public Safety Professionals

Public safety personnel (PSP) are known to experience difficult and demanding occupational environments, an environment that has been complicated by the COVID-19 pandemic. Firefighters, paramedics, and public safety communicators were among the front-line workers that continued to serve the public throughout the course of the pandemic. The present study considered the potential impacts of the COVID-19 pandemic on self-reported symptoms of mental health challenges in Canadian firefighters, paramedics, and public safety communicators. Participants were firefighters (n = 123), paramedics (n = 246), and public safety communicators (n = 48), who completed an online survey, including demographics, questions related to COVID-19 exposure and worry, the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Social Interaction Phobia Scale, and the Posttraumatic Stress Disorder Checklist-5. Results revealed that risk factors for increased mental health symptom reporting were paramedic occupation, self-identified female, younger in age, COVID-19 personal contact, requirement to self-isolate, and self-perception of COVID-19 contraction (without confirmation through testing). The COVID-19 pandemic should be considered a risk factor for increased mental health symptom reporting in PSP

Leveraging web-based prediction calculators to set patient expectations for elective spine surgery: a qualitative study to inform implementation

Abstract Background Prediction calculators can help set outcomes expectations following orthopaedic surgery, however effective implementation strategies for these tools are unknown. This study evaluated provider and patient perspectives on clinical implementation of web-based prediction calculators developed using national prospective spine surgery registry data from the Quality Outcomes Database. Methods We conducted semi-structured interviews in two health systems, Vanderbilt University Medical Center (VUMC) and Duke University Health System (DUHS) of orthopedic and neurosurgery health care providers (VUMC: n = 19; DUHS: n = 6), health care administrators (VUMC: n = 9; DUHS: n = 9), and patients undergoing elective spine surgery (VUMC: n = 16). Qualitative template analysis was used to analyze interview data, with a focus on end-user perspectives regarding clinical implementation of web-based prediction tools. Results Health care providers, administrators and patients overwhelmingly supported the use of the calculators to help set realistic expectations for surgical outcomes. Some clinicians had questions about the validity and applicability of the calculators in their patient population. A consensus was that the calculators needed seamless integration into clinical workflows, but there was little agreement on best methods for selecting which patients to complete the calculators, timing, and mode of completion. Many interviewees expressed concerns that calculator results could influence payers, or expose risk of liability. Few patients expressed concerns over additional survey burden if they understood that the information would directly inform their care. Conclusions Interviewees had a largely positive opinion of the calculators, believing they could aid in discussions about expectations for pain and functional recovery after spine surgery. No single implementation strategy is likely to be successful, and strategies vary, even within the same healthcare system. Patients should be well-informed of how responses will be used to deliver better care, and concerns over how the calculators could impact payment and liability should be addressed prior to use. Future research is necessary to determine whether use of calculators improves management and outcomes for people seeking a surgical consult for spine pain

Molecular Characterization of a Variant of Bacillus anthracis-Specific Phage AP50 with Improved Bacteriolytic Activity▿ †

The genome sequence of a Bacillus anthracis-specific clear plaque mutant phage, AP50c, contains 31 open reading frames spanning 14,398 bp, has two mutations compared to wild-type AP50t, and has a colinear genome architecture highly similar to that of gram-positive Tectiviridae phages. Spontaneous AP50c-resistant B. anthracis mutants exhibit a mucoid colony phenotype