Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Ethnic variations in duration of untreated psychosis: report from the CRIS-FEP study

Objectives:  There is inconsistent evidence on the influence of ethnicity on duration of untreated psychosis (DUP). We investigated ethnic differences in DUP in a large epidemiological dataset of first episode psychosis patients in an inner city area of south London, UK. Methods:  We analysed data on 558 first episode psychosis patients at the South London and Maudsley NHS Trust, between 2010 and 2012. We performed multivariable logistic regression to estimate the odds of a short DUP (≤ 6 months) by ethnic group, controlling for confounders. Results:  There was no evidence that ethnicity is associated with duration of untreated psychosis. However, we found evidence that a short DUP was strongly associated with age, living circumstances, and pathways to care variables (involuntary admission, out of office hour contact, accident and emergency referral, criminal justice agency referral and family involvement in help-seeking). Conversely, a long DUP was associated with report of social isolation, living alone, being single and General Practitioner referral. Conclusion:  Our findings suggest that indicators of social isolation were associated with long DUP. Our data also show that pathways into care characteristics play significant role in DUP. Thus, the challenge of tackling the issue of timely access to EI under the new Access and Waiting Time standard for psychosis requires a multilevel approach, including joint working with communities, public awareness of psychosis, less restrictive referral pathways and adequate resourcing of early intervention for psychosis services. These will go a long way in addressing patients’ needs rather than be determined by service structures

Pathogens of Pathogens — Population Genetics of Viruses that Infect Mycobacteria

Mentor: Sarah C. R. Elgin From the Washington University Undergraduate Research Digest: WUURD, Volume 6, Issue 2, Spring 2011. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Isolation, Characterization, and Annotation of Mycobacteriophage Morgushi

Mentor: Sarah Elgin and Kathy Hafer From the Washington University Undergraduate Research Digest: WUURD, Volume 6, Issue 1, Fall 2010. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Co-editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Multistate Modeling of Clinical Trajectories and Outcomes in the ICU: A Proof-of-Concept Evaluation of Acute Kidney Injury Among Critically Ill Patients With COVID-19

IMPORTANCE:. Multistate models yield high-fidelity analyses of the dynamic state transition and temporal dimensions of a clinical condition’s natural history, offering superiority over aggregate modeling techniques for addressing these types of problems. OBJECTIVES:. To demonstrate the utility of these models in critical care, we examined acute kidney injury (AKI) development, progression, and outcomes in COVID-19 critical illness through multistate analyses. DESIGN, SETTING, AND PARTICIPANTS:. Retrospective cohort study at an urban tertiary-care academic hospital in the United States. All patients greater than or equal to 18 years in an ICU with COVID-19 in 2020, excluding patients with preexisting end-stage renal disease. MAIN OUTCOMES AND MEASURES:. Using electronic health record data, we determined AKI presence/stage in discrete 12-hour time windows and fit multistate models to determine longitudinal transitions and outcomes. RESULTS:. Of 367 encounters, 241 (66%) experienced AKI (maximal stages: 88 stage-1, 49 stage-2, 104 stage-3 AKI [51 received renal replacement therapy (RRT), 53 did not]). Patients receiving RRT overwhelmingly received invasive mechanical ventilation (IMV) (n = 60, 95%) compared with the AKI-without-RRT (n = 98, 53%) and no-AKI groups (n = 39, 32%; p < 0.001), with similar mortality patterns (RRT: n = 36, 57%; AKI: n = 74, 40%; non-AKI: n = 23, 19%; p < 0.001). After 24 hours in the ICU, almost half the cohort had AKI (44.9%; 95% CI, 41.6–48.2%). At 7 days after stage-1 AKI, 74.0% (63.6–84.4) were AKI-free or discharged. By contrast, fewer patients experiencing stage-3 AKI were recovered (30.0% [24.1–35.8%]) or discharged (7.9% [5.2–10.7%]) after 7 days. Early AKI occurred with similar frequency in patients receiving and not receiving IMV: after 24 hours in the ICU, 20.9% of patients (18.3–23.6%) had AKI and IMV, while 23.4% (20.6–26.2%) had AKI without IMV. CONCLUSIONS AND RELEVANCE:. In a multistate analysis of critically ill patients with COVID-19, AKI occurred early and heterogeneously in the course of critical illness. Multistate methods are useful and underused in ICU care delivery science as tools for understanding trajectories, prognoses, and resource needs

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotypes

Genomic analysis of a large set of phages infecting the common host Mycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotypes

Genomic analysis of a large set of phages infecting the common host Mycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode