Extended spectrum β-lactamase-and AmpC β-lactamase-producing Enterobacterales associated with urinary tract infections in the New Zealand community: A case-control study.

(c) The Author/sOBJECTIVES: To assess whether having a pet in the home is a risk factor for community-acquired urinary tract infections associated with extended spectrum β-lactamase (ESBL)- or AmpC β-lactamase (ACBL)- producing Enterobacterales. METHODS: An unmatched case-control study was conducted between August 2015 and September 2017. Cases (n=141) were people with community-acquired urinary tract infection (UTI) caused by ESBL- or ACBL- producing Enterobacterales. Controls (n=525) were recruited from the community. A telephone questionnaire on pet ownership, and other factors was administered, and associations were assessed using logistic regression. RESULTS: Pet ownership was not associated with ESBL- or ACBL-producing Enterobacterales related human UTIs. A positive association was observed for recent antimicrobial treatment, travel to Asia in the previous year, and a doctor's visit in the previous six months. Among isolates with an ESBL-/ACBL-producing phenotype 126/134 (94%) were Escherichia coli, with sequence type (ST) 131 being the most common (47/126). CONCLUSIONS: Companion animals in the home were not found to be associated with ESBL- or ACBL-producing Enterobacterales related community-acquired UTI in New Zealand. Risk factors included overseas travel, recent antibiotic use, and doctor visits.Published onlin

Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

BACKGROUND: Untreated human immunodeficiency virus (HIV) disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. METHODS: A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. RESULTS: Overall 64 participants were recruited - 20 HIV uninfected (HIV-), 30 HIV infected ART naïve (HIV+N) and 14 HIV-infected ART treated (HIV+T). ART treatment had been taken for a median of 33 months (Range 12-60 months). Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008); reduced memory B cells (27 vs. 51 cells/μl p = 0.0008). The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02). In the HIV+N group we did not find an association between CD4 count and B cell numbers. CONCLUSIONS: HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study

Social marketing and healthy eating : Findings from young people in Greece

This document is the Accepted Manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s12208-013-0112-xGreece has high rates of obesity and non-communicable diseases owing to poor dietary choices. This research provides lessons for social marketing to tackle the severe nutrition-related problems in this country by obtaining insight into the eating behaviour of young adults aged 18–23. Also, the main behavioural theories used to inform the research are critically discussed. The research was conducted in Athens. Nine focus groups with young adults from eight educational institutions were conducted and fifty-nine participants’ views towards eating habits, healthy eating and the factors that affect their food choices were explored. The study found that the participants adopted unhealthier nutritional habits after enrolment. Motivations for healthy eating were good health, appearance and psychological consequences, while barriers included lack of time, fast-food availability and taste, peer pressure, lack of knowledge and lack of family support. Participants reported lack of supportive environments when deciding on food choices. Based on the findings, recommendations about the development of the basic 4Ps of the marketing mix, as well as of a fifth P, for Policy are proposedPeer reviewe

Pyrimidine biosynthesis is not an essential function for trypanosoma brucei bloodstream forms

<p>Background: African trypanosomes are capable of both pyrimidine biosynthesis and salvage of preformed pyrimidines from the host, but it is unknown whether either process is essential to the parasite.</p> <p>Methodology/Principal Findings: Pyrimidine requirements for growth were investigated using strictly pyrimidine-free media, with or without single added pyrimidine sources. Growth rates of wild-type bloodstream form Trypanosoma brucei brucei were unchanged in pyrimidine-free medium. The essentiality of the de novo pyrimidine biosynthesis pathway was studied by knocking out the PYR6-5 locus that produces a fusion product of orotate phosphoribosyltransferase (OPRT) and Orotidine Monophosphate Decarboxylase (OMPDCase). The pyrimidine auxotroph was dependent on a suitable extracellular pyrimidine source. Pyrimidine starvation was rapidly lethal and non-reversible, causing incomplete DNA content in new cells. The phenotype could be rescued by addition of uracil; supplementation with uridine, 2′deoxyuridine, and cytidine allowed a diminished growth rate and density. PYR6-5−/− trypanosomes were more sensitive to pyrimidine antimetabolites and displayed increased uracil transport rates and uridine phosphorylase activity. Pyrimidine auxotrophs were able to infect mice although the infection developed much more slowly than infection with the parental, prototrophic trypanosome line.</p> <p>Conclusions/Significance: Pyrimidine salvage was not an essential function for bloodstream T. b. brucei. However, trypanosomes lacking de novo pyrimidine biosynthesis are completely dependent on an extracellular pyrimidine source, strongly preferring uracil, and display reduced infectivity. As T. brucei are able to salvage sufficient pyrimidines from the host environment, the pyrimidine biosynthesis pathway is not a viable drug target, although any interruption of pyrimidine supply was lethal.</p&gt

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

Sequencing and association analysis of the type 1 diabetes - linked region on chromosome 10p12-q11

Background: In an effort to locate susceptibility genes for type I diabetes (TID) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with TID. Results: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with TID. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex TID families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05-0.0026), located near the PAPDI gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the TID families. We also tested 13 polymorphisms in the PAPDI gene and in five other loci in 1,612 TID patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPDI showed nominal evidence of association in both TID families and in the case-control sample (P = 0.037 and 0.03, respectively). Conclusion: We conclude that polymorphisms in the CREM and SDFI genes have no major effect on TID. The weak TID association that we detected in the association scan near the PAPDI gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region

Evaluation of benazepril in cats with heart disease in a prospective, randomized, blinded, placebo-controlled clinical trial

© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine. Background: Heart disease is an important cause of morbidity and mortality in cats, but there is limited evidence of the benefit of any medication. Hypothesis: The angiotensin-converting enzyme inhibitor benazepril would delay the time to treatment failure in cats with heart disease of various etiologies. Animals: One hundred fifty-one client-owned cats. Methods: Cats with heart disease, confirmed by echocardiography, with or without clinical signs of congestive heart failure, were recruited between 2002 and 2005 and randomized to benazepril or placebo in a prospective, multicenter, parallel-group, blinded clinical trial. Benazepril (0.5-1.0 mg/kg) or placebo was administered PO once daily for up to 2 years. The primary endpoint was treatment failure. Analyses were conducted separately for all-cause treatment failure (main analysis) and heart disease-related treatment failure (supportive analysis). Results: No benefit of benazepril versus placebo was detected for time to all-cause treatment failure (P =.42) or time to treatment failure related to heart disease (P =.21). Hazard ratios (95% confidence interval [CI]) from multivariate analysis for benazepril compared with placebo were 1.00 (0.57-1.74) for all-cause failure, and 0.99 (0.50-1.94) for forward selection and 0.93 (0.48-1.81) for bidirectional selection models for heart disease-related failure. There were no significant differences between groups over time after administration of the test articles in left atrium diameter, left ventricle wall thickness, quality of life scores, adverse events, or plasma biochemistry or hematology variables. Conclusions and Clinical Relevance: Benazepril was tolerated well in cats with heart disease, but no evidence of benefit was detected

Model construction of medical endoscope service evaluation system-based on the analysis of Delphi method

Background: Medical endoscope is widely used in clinical practice for the purpose of diagnosis and treatment, occupying around 5% of the medical device market. Evaluating the true service level of medical endoscope is essential and necessary to improve overall performance of medical diagnosis and treatment, and to maintain competitiveness of endoscope manufacturers, however, such a tool is not available in the market. This study develops an Evaluation Index System (EIS) to assess service level of medical endoscope, and to provide suggestions for improving the service level through the Delphi method. Methods: Firstly, the possible factors influencing the service level were identified from literature review. In parallel, the Delphi expert method questionnaire was designed and 25 experts were invited to conduct three rounds of questionnaire, to evaluate and rate the possible factors. Finally, we determined the weights associated with the factors, using the analytic hierarchy process (AHP) and percentage method, and developed the service level EIS. Results: The EIS consists of 3 first-level indicators, 24 s-level indicators and 68 third-level indicators. According to the weights computed using AHP, first-level indicators are ranked as post-sale (0.62), in-sale (0.25) and pre-sale (0.13). Through case verification, the medical endoscope brand Olympus had a total score of 4.17, Shanghai Aohua had a total score of 3.71, and Shanghai Chengyun had a total score of 3.28, which matches its market popularity and ranking in terms of market share. The results obtained from the EIS are consistent with the reality. Conclusions: The EIS established in this study is comprehensive, reliable and reasonable with strong practicality. The EIS can act as a tool for the endoscope users to evaluate potential products and make informed choices. It also provides a measurable basis for endoscope manufacturers and service providers to improve service quality

Prescription of medicines by medical students of Karachi, Pakistan: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Prescription of medicines by non-doctors is an issue with serious global implications. To our knowledge prescription of drugs by medical and non-medical students has not been studied before. We aimed to determine the practice and attitudes of drug prescription by medical students and: a) how non-medical students respond to this practice, b) How this compares with the attitudes and practices of non-medical students.</p> <p>Methods</p> <p>A cross-sectional study was conducted on a sample of 600 students randomly selected from 2 medical and 2 non-medical universities. Ethical requirements were ensured and data was collected using self administered questionnaires. The Chi square tests and logistic univariate regression analyses were performed using SPSS v 14 to identify associations and differences.</p> <p>Results</p> <p>A total of 572 forms were completed and the sample consisted of 295 medical students and 277 non-medical students with no significant difference in their demographic profile. Of the 295 medical students 163 (55.3%) had prescribed a medicine independently and most (48.5%) said that they did this 2–3 times a year. The commonest reasons for this were 'previous experience' (68.7%), 'problem too trivial' (34.4%) and 'we knew everything about the condition' (31.3%). One-third (33.6%) of the undergraduate medical students thought that it was alright to independently diagnose an illness while a vast majority (78.3%) thought that it was alright for them to prescribe medicines to others. Common prescriptions were pain-killers, antipyretics, antiallergics and antibiotics. Medical students who prescribed medicines were of lesser age (CI = 1.366–1.887) and more likely to belong to the 1^st(CI = 3.588–21.731), 2^nd(CI = 2.059– 10.869) or 3^rd(CI = 4.331–26.374) year of medical college. One-third (33.9%) of the non-medical students reported that a medical student had prescribed medicines to them and 21.3% said that they trusted medical students and would follow their advice blindly. Many students thought it alright for medical students to diagnose and treat illnesses. A similar proportion of non-medical students (58.5%) reported prescribing medicines to others.</p> <p>Conclusion</p> <p>Prescription of medicines by non-doctors is rampant and urgent corrective measures are warranted. We have highlighted areas for future research and intervention and have given a few recommendations.</p