Methicillin Resistant Staphylococcus aureus Contamination of Hands and Mobile Phones of Health Care Workers in a Health Care Setting: A Silent Threat

Background: The extensive use of mobile phones in the hospital among health care workers (HCWs) can lead to infectious agents being transferred from one patient to another and thus serve as a vehicle in the transmission of nosocomial pathogens. Objectives: This study aimed to investigate the prevalence of Methicillin Resistant Staphylococcus auerus (MRSA) contamination of mobile phones and hands of HCWs in Gandaki Medical College and Teaching Hospital. Methods: The present study was hospital and laboratory based cross-sectional study, carried out from April, 2017 to December, 2017. A total of 100 mobile phone swab and 100 hand swab samples of HCWs were collected and cultured directly on MacConkey agar, blood agar, and mannitol salt agar after 24 hrs of enrichment. All the isolated organisms including MRSA were identified using standard microbiological techniques and subjected to antibiotic susceptibility testing using disc diffusion technique. Results: Among the Gram positive isolates, frequency distribution from mobile phones showed the highest prevalence of coagulase negative Staphylococci (CONS) (34.69%), followed by Staphylococcus aureus (20.41%), Bacillus spp (15.31%), Micrococci spp (11.23%), however considerable number of Diptheroides (8.16%), Enterococci (6.12%) and Streptococcus pneumoniae (4.08%). Siimilarly from hand swabs CONS (39.62%), followed by S. aureus (26.42%), Bacillus spp (10.38%), Micrococci (11.32%), Enterococci (6.60%) and Diptheroids (5.66%) were isolated. The frequency of MRSA was 20%, 25% among mobile phones and hands of HCWs respectively. Drugs like Vancomycin, Amikacin, Clindamycin and Gentamycin were found quite effective against S. aureus in the present study and would be better options for the management of such infections. Conclusions: Mobile phones and hands of HCWs were the potential source of nosocomial infections including multidrug-resistant pathogens like methicillin-resistant S. aureus

Development of a chemical probe against NUDT15

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues

Body composition, gastrointestinal, and reproductive differences between broiler breeders fed using everyday or skip-a-day rearing programs

ABSTRACT: Broiler breeder feed restriction practices have intensified as broiler feed efficiency has been improved. Skip-a-day (SAD) rearing regimen has controlled breeder growth, although this practice has become questionable for the modern breeder. We compared everyday (ED) and SAD programs and evaluated their impact on pullet growth performance, body composition, gastrointestinal tract development, and reproduction. At d 0, Ross 708 (Aviagen) pullet chicks (n = 1,778) were randomly assigned to 7 floor pens. Three pens were fed using the ED and 4 pens with SAD program through wk 21 using a chain-feeder system. ED and SAD grower diets were formulated to be isonutritious, with the only difference that ED diets had more crude fiber. Pullets (n = 44 per pen) were moved to 16 hen pens by treatment at wk 21 with 3 YP males (Aviagen) in each pen. All birds were fed common laying diets. In addition to BW data, sampled pullets and hens were scanned using dual energy X-ray absorptiometry (DEXA) to obtain body bone density and composition. Hen performance and hatchery metrics were recorded through wk 60. ED birds were heavier with similar nutrient intake from wk 10 to 45 (P ≤ 0.013). Pullet uniformity was unaffected by feeding method (P ≥ 0.443). SAD pullets had less body fat at wk 19 (P = 0.034) compared to ED pullets, likely as a metabolic consequence of intermittent feeding. SAD birds had lower bone density at wk 7, 15, and 19 (P ≤ 0.026). At 4 wk of age, SAD pullets had less intestinal villi goblet cells compared to ED pullets (P ≤ 0.050), possibly explained by the effect that feed removal has on cell migration rates. Overall egg-specific gravity (P = 0.057) and hatch of fertile % (P = 0.088) tended to be higher in eggs from ED hens. Altogether, ED feeding increased young pullet intestinal goblet cells and increased both bone density and body fat at wk 19. ED program improved pullet feed conversion (2.6% less feed) and increased eggshell quality and hatch of fertile

Development of a chemical probe against NUDT15

The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6 thio d GTP, thereby dictating the clinical response of this standard of care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15 dependent chemotherapeutics. Lead compound TH1760 demonstrated low nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6 thioguanine through enhanced accumulation of 6 thio d GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenue