Broussardlutz7316

From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. We also identified Leishmania major threonyl-tRNA synthetase (ThrRS) inhibitors from the same library. We discuss why chemotherapies targeting multiple aaRSs should be less prone to the evolution of resistance than monotherapeutic or synergistic combination chemotherapies targeting only one aaRS.Various species of the intestinal microbiota have been associated with the development of colorectal cancer (CRC)1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in CRC. Our study describes a distinct mutational signature in CRC and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.In January 2018, the Wisconsin Department of Health Services, Division of Public Health (DPH), received a report of a culture-confirmed case of Legionnaires' disease. The patient, who was immunocompromised, had died at a local hospital 10 days after being admitted. DPH and an infection preventionist from the hospital investigated to determine the source of the infection and prevent additional cases. Because the case was suspected to be nosocomial, health care facility water samples were tested for Legionella. When these samples were negative, water sources in the patient's home were tested. These tested positive for Legionella pneumophila, and the bacteria remained after an attempt to remediate. The patient and home isolates were identified as L. pneumophila serogroup 3, sequence type 93, by whole-genome multilocus sequence typing. A second resident of the home did not become ill. This case highlights the potential for immunocompromised persons and others at risk for Legionnaires' disease to be exposed to Legionella through home water systems containing the bacteria and demonstrates the difficulty of home remediation. This case also illustrates the role of lower respiratory tract specimens in the identification of less common Legionella infections (e.g., L. pneumophila serogroup 3) and confirmation of the infection source.An outbreak of coronavirus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (SARS-CoV-2) began in Wuhan, Hubei Province, China in December 2019, and has spread throughout China and to 31 other countries and territories, including the United States (1). As of February 23, 2020, there were 76,936 reported cases in mainland China and 1,875 cases in locations outside mainland China (1). There have been 2,462 associated deaths worldwide; no deaths have been reported in the United States. Fourteen cases have been diagnosed in the United States, and an additional 39 cases have occurred among repatriated persons from high-risk settings, for a current total of 53 cases within the United States. This report summarizes the aggressive measures (2,3) that CDC, state and local health departments, multiple other federal agencies, and other partners are implementing to slow and try to contain transmission of COVID-19 in the United States. These measures require the identification of cases and contacts of persons will rapidly incorporate new knowledge into guidance for action by CDC, state and local health departments, health care providers, and communities.Lung cancer is the leading cause of cancer death in the United States; 148,869 lung cancer-associated deaths occurred in 2016 (1). Mortality might be reduced by identifying lung cancer at an early stage when treatment can be more effective (2). In 2013, the U.S. Preventive Services Task Force (USPSTF) recommended annual screening for lung cancer with low-dose computed tomography (CT) for adults aged 55-80 years who have a 30 pack-year* smoking history and currently smoke or have quit within the past 15 years (2).† This was a Grade B recommendation, which required health insurance plans to cover lung cancer screening as a preventive service.§ To assess the prevalence of lung cancer screening by state, CDC used Behavioral Risk Factor Surveillance System (BRFSS) data¶ collected in 2017 by 10 states.** Overall, 12.7% adults aged 55-80 years met the USPSTF criteria for lung cancer screening. Among those meeting USPSTF criteria, 12.5% reported they had received a CT scan to check for lung cancer in the last 12 months. Efforts to educate health care providers and provide decision support tools might increase recommended lung cancer screening.PURPOSE Medically-focused journal clubs have been used as an educational tool for over 100 years with research indicating that they improve knowledge, reading behaviour, and critical appraisal skills. However, it is not known how widespread their use is among Australian medical schools, nor the opinions of medical education leaders as to their value. METHODS A nationwide cross-sectional study was performed on academic leaders from every Australian medical school. Individuals were asked to complete a survey detailing their attitudes towards journal clubs using single or multiple answer questions, Likert scales, and ranked data. They were asked whether students at their institutions were able to partake in journal clubs, and if so, details of their implementation. click here RESULTS At least one response was collected from 18 of 19 Australian medical schools. This represented 60 responses of a possible 147 (40.8%), the vast majority of whom were heads of clinical schools, 36 (60.0%). The prevalence of journal clubs among medical institutions was high, with 15 of 18 (83.