Helicobacter pylori, one of the most common bacterial pathogens of humans, colonizes the gastric mucosa, where it appears to persist throughout the host's life unless the patient is treated. Colonization induces chronic gastric inflammation which can progress to a variety of diseases, ranging in severity from superficial gastritis and peptic ulcer to gastric cancer and mucosal-associated lymphoma. Strain-specific genetic diversity has been proposed to be involved in the organism's ability to cause different diseases or even be beneficial to the infected host and to participate in the lifelong chronicity of infection. Here we compare the complete genomic sequences of two unrelated H. pylori isolates. This is, to our knowledge, the first such genomic comparison. H. pylori was believed to exhibit a large degree of genomic and allelic diversity, but we find that the overall genomic organization, gene order and predicted proteomes (sets of proteins encoded by the genomes) of the two strains are quite similar. Between 6 to 7% of the genes are specific to each strain, with almost half of these genes being clustered in a single hypervariable region.

Sirolimus has antineoplastic effects and may reduce skin cancer rates in kidney transplant patients. This prospective, multicenter, randomized, open-label, controlled trial randomized 86 kidney transplant recipients (≥1 year posttransplant) with history of nonmelanoma skin cancer (NMSC) to continue calcineurin inhibitor (CNI) or convert to sirolimus. Patients were stratified by number of NMSC lesions (0-5, 6-20) in previous year. Primary end point was number of biopsy-confirmed new NMSC lesions per patient-year. Yearly NMSC rate was significantly lower with sirolimus (1.31 vs. 2.48 lesions/patient-year; p = 0.022). Squamous cell carcinoma occurred at a lower rate in the sirolimus versus CNI group (p = 0.038); basal cell carcinoma rate was similar in both. A lower proportion of patients receiving sirolimus developed new or recurrent NMSC (56.4% vs. 80.9%; p = 0.015) or new squamous cell carcinoma (41.0% vs. 70.2%; p = 0.006). No sirolimus patients and one CNI continuation patient experienced acute rejection. Incidence of treatment-emergent adverse events was similar between groups; however, discontinuation rates related to adverse events were significantly higher with sirolimus (46.2% vs. 0%; p < 0.001). In kidney transplant recipients with history of NMSC, conversion from CNI to sirolimus reduced rates of NMSC, without increasing acute rejection risk.

In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in Helicobacter pylori that confer resistance to clarithromycin (Cla r Antibiotic resistance is an increasing problem for the treatment of infectious diseases. Bacteria have evolved diverse mechanisms (pathways) of resistance to antimicrobial agents, including control of uptake and efflux of drugs, modification and detoxification of drugs, alteration and protection of the target sites, and acquisition of heterologous resistance genes from external sources. In Helicobacter pylori, the etiological agent of a wide range of gastric diseases, genetic determinants for resistance to several antibiotics, including clarithromycin, metronidazole, ciprofloxacin, and rifampin, have been determined. Remarkably, the known mechanisms of antibiotic resistance in H. pylori are all due to mutations in chromosomal genes. Clarithromycin resistance is associated with mutations in the 23S rRNA gene (22,25), which inhibit the binding of clarithromycin to the ribosome. Ciprofloxacin resistance is due to mutations in the gyrA gene, which encodes the A subunit of DNA gyrase (16), and rifampin resistance results from mutations in the rpoB gene, encoding the ␤ subunit of RNA polymerase (7). For metronidazole resistance, although several different mechanisms may exist, the predominant determinant has been shown to be the mutational inactivation of the rdxA gene that encodes an oxygen-insensitive NADPH nitroreductase (4, 9, 10, 13, 21).)The importance of de novo mutation in developing antibiotic resistance prompted us to ask how mutations occur in H. pylori (28). The first step in elucidating the mechanisms of mutagenesis is to define the background of frequency and specificity of spontaneous mutations. From the pioneering works of Luria and Delbruck (14) and recent developments in determining mutation rates of bacterial populations, it is known that determination of mutation rates is not simple (15,17), and determination of mutation spectra is particularly tedious. In this study we systematically examined the in vitro frequencies and spectra of spontaneous mutations in H. pylori that confer resistance to clarithromycin, metronidazole, amoxicillin, ciprofloxacin, and rifampin. MATERIALS AND METHODSH. pylori strains, growth medium, and antibiotics. H. pylori reference strains 26695, NCTC11639, and UA802 (26), as well as some isolates from University of Alberta Hospital, were used; all are susceptible to the antibiotics tested in this study. H. pylori strains were grown on BHI-YE broth (3.7% brain heart infusion with 0.3% yeast extract and 5% animal serum) or agar plates at 37°C under microaerobic conditions (5% CO 2 , 5% H 2 , and 90% N 2 ). Antibiotics used in this study include clarithromycin (Bayer), metronidazole (Sigma), ciprofloxacin (Bayer), rifampin (Sigma), and amoxicillin (Sigma).MIC test. H. pylori cells were grown for 2 days and suspended in sterile BHI-YE liquid medium, and the turbidity of the suspensions was adjusted to that...

Our study demonstrated real-world, direct effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia following introduction into a routine immunization program among adults aged ≥65 years, many of whom had immunocompromising and chronic medical conditions.

Exposure to disaster-related media may be a risk factor for mental distress, but this has not been examined in the context of the COVID-19 pandemic. This study assesses whether exposure to social and traditional media during the rise of the COVID-19 pandemic was associated with mental distress among U.S. adults. Methods: Data came from the Understanding America Study, conducted with a cross-sectional, nationally representative sample of adults who completed surveys online. Participants included 6,329 adults surveyed between March 10 and March 31, 2020. Regression analyses examined the associations of (1) self-reported average time spent on social media in a day (hours) and (2) number of traditional media sources (radio, TV, and newspaper) consulted to learn about COVID-19 with self-reported mental distress (4-item Patient Health Questionnaire). Data were analyzed in April 2020. Results: Participants responding at later survey dates reported more time spent on social media (b=0.02, 95% CI=0.01, 0.03), a greater number of traditional media sources consulted to learn about COVID-19 (b=0.01, 95% CI=0.01, 0.02), and greater mental distress (b=0.07, 95% CI=0.04, 0.09). Increased time spent on social media and consulting a greater number of traditional media sources to learn about COVID-19 were independently associated with increased mental distress, even after adjusting for potential confounders (social media: b=0.14, 95% CI=0.05, 0.23; traditional media: b=0.14, 95% CI=0.08, 0.20). Conclusions: Exposure to a greater number of traditional media sources and more hours on social media was modestly associated with mental distress during the rise of the COVID-19 pandemic in the U.S.

Considerable genomic microdiversity has been reported previously among Helicobacter pylori isolates. We have constructed genome maps of four unrelated H. pylori strains (NCTC11637, NCTC11639, UA802 and UA861) using pulsed-field gel electrophoresis (PFGE) with NotI and NruI, hybridization with extracted PFGE DNA fragments and probing with 17 gene probes. These strains of H. pylori were compared with a fifth unrelated H. pylori strain NCTC11638 mapped previously. Considerable diversity in gene arrangement was evident among the five H. pylori maps, and no consistent gene clustering was found. The association of only four genes, katA (catalase gene), vacA (vacuolating cytotoxin gene), hpaA (a putative adhesin gene), and pfr (bacterial ferritin gene) were generally conserved within approximately the same 25% of the genome; however, the order of these genes also varied. Our study demonstrates that macrodiversity, i.e. variability in gene order, in addition to microdiversity, is a characteristic of the H. pylori genome.

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