Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated Escherichia coli ST131 Clone.

UNLABELLED: Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three (m6)A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for (m6)A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. IMPORTANCE: DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone

Triphasic Computed Tomography Enterography with Polyethylene Glycol to Detect Renal Cell Carcinoma Metastases to the Small Bowel

Enteroclysis was first used to diagnose small bowel obstruction in 1996. However, nasojejunal intubation required during enteroclysis causes discomfort to the patient. Triphasic computed tomography (CT) enterography, a noninvasive procedure that does not require intubation, was found to be an efficient method to diagnose small bowel lesions. We describe our experience of using triphasic CT enterography with polyethylene glycol (PEG) for diagnosing renal cell carcinoma (RCC) metastases to the small intestine. RCC can metastasize to many organs and can cause variable clinical presentations. We report the case of a 56-year-old man with RCC who had psoas muscle involvement and lung metastasis. The patient presented with melena and intermittent abdominal pain. Two conventional CT and small bowel series examinations had shown no obstructive lesion in the small intestine. However, triphasic CT enterography with PEG detected two enhanced masses suggestive of small bowel metastasis. The patient underwent laparotomy and segmental resection of the jejunum with primary anastomosis. Histologic examination was compatible with RCC. This is the first report where RCC metastasis to the small bowel was diagnosed using triphasic CT enterography. Our study emphasizes the importance of triphasic CT enterography in cases of obscure gastrointestinal bleeding, especially in patients suspected of having small bowel metastasis

Immunity-targeted approaches to the management of chronic and recurrent upper respiratory tract disorders in children

BACKGROUND: Upper respiratory tract infections (URTIs), including rhinitis, nasopharyngitis, tonsillitis and otitis media (OM), comprise of 88% of total respiratory infections, especially in children. Therefore effective prevention and treatment of RTIs remain a high priority worldwide. Preclinical and clinical data highlight the rationale for the use and effectiveness of immunity-targeted approaches, including targeted immunisations and non-specific immunomodulation in the prevention and management of recurrent upper RTIs. OBJECTIVE OF REVIEW: The idea of this review was to summarise the current evidence and address key questions concerning the use of conservative and immunity-targeted approaches to recurrent and chronic URTIs, with a focus on the paediatric population. SEARCH STRATEGY/EVALUATION METHOD: Literature searches were conducted in March 2017 and updated in September 2017 using: Academic Search Complete; CENTRAL; Health Source: Nursing/Academic Edition; MEDLINE; clinicaltrials.gov; and Cochrane databases. In total, 84 articles were retrieved and reviewed. Two independent researchers focused on primary and secondary endpoints in systematic reviews, meta-analyses and randomised, controlled trials, using immunity-directed strategies as the control group or within a subpopulation of larger studies. Existing guidelines and interventional/observational studies on novel applications were also included. RESULTS: Children are particularly susceptible to RTIs due to the relative immaturity of their immune systems, as well as other potential predisposing factors such as day care attendance and/or toxic environmental factors (eg increased pathogenic microbial exposure and air pollutants). Recurrent URTIs can affect otherwise healthy children, leading to clinical sequelae and complications, including the development of chronic conditions or the need for surgery. Available pre-clinical and clinical data highlight the rationale for the use and effectiveness of immunity-targeted approaches, including targeted immunisations (flu and pneumococcal vaccines) and non-specific immunomodulation (bacterial lysates), in the prevention and management of recurrent croup, tonsillitis, otitis media, recurrent acute rhinosinusitis and chronic rhinosinusitis. CONCLUSIONS: In this review, we summarise the current evidence and provide data demonstrating that some immunity-targeted strategies, including vaccination and immunomodulation, have proved effective in the treatment and prevention of recurrent and chronic URTIs in children.info:eu-repo/semantics/publishedVersio

Knowledge, attitudes and practice of breast cancer screening among female health workers in a Nigerian urban city

<p>Abstract</p> <p>Background</p> <p>Late presentation has been observed as the hallmark of breast cancer in Nigerian women and an earlier onset has been reported in this population. This study was designed to assess the awareness of female health workers about risk factors and screening methods for early detection of breast cancer.</p> <p>Methods</p> <p>A cross-sectional descriptive study was carried out among female health workers in the two major government health institutions in Benin City, Edo State capital in Nigeria.</p> <p>Data analysis was by SPSS version 10 and test of significance was done with differences considered significant at p < 0.05.</p> <p>Results</p> <p>Three hundred and ninety-three (393) female health workers out of five hundred and five eligible subjects completed and returned the questionnaires, giving a response rate of 77.8%. One hundred and two (26%) were Doctors, two hundred and fifty-four (64.6%) Nurses, and thirty-seven (9.4%) were Radiographers, Laboratory Scientists and Pharmacists. A high proportion of our respondents had very poor knowledge about risk factors for breast cancer (55%). The awareness of mammography as a diagnostic method was very high (80.7%), but an extremely low knowledge of mammography as a screening method was found. Mammography practice of only 3.1% was found among those above 40 years of age who qualify for routine annual screening. Relatively low knowledge (45.5%) about Breast Self Examination (BSE) as a screening method was found.</p> <p>Conclusion</p> <p>These female health workers who are expected to act as role models and educate the public had poor knowledge of risk factors for breast cancer and practice of breast cancer screening. There is very urgent need for regular update courses for health workers concerning breast cancer education including screening methods.</p

LC–MS-based absolute metabolite quantification:Application to metabolic flux measurement in trypanosomes

Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite, Trypanosoma brucei. In the mammalian bloodstream, the trypanosome’s metabolism differs significantly from that of its host. For example, the parasite relies exclusively on glycolysis for energy source. Recently, computational and mathematical models of trypanosome metabolism have been generated to assist in understanding the parasite metabolism with the aim of facilitating drug development. Optimisation of these models requires quantitative information, including metabolite concentrations and/or metabolic fluxes that have been hitherto unavailable on a large scale. Here, we have implemented an LC–MS-based method that allows large scale quantification of metabolite levels by using U-13C-labelled E. coli extracts as internal standards. Known amounts of labelled E. coli extract were added into the parasite samples, as well as calibration standards, and used to obtain calibration curves enabling us to convert intensities into concentrations. This method allowed us to reliably quantify the changes of 43 intracellular metabolites and 32 extracellular metabolites in the medium over time. Based on the absolute quantification, we were able to compute consumption and production fluxes. These quantitative data can now be used to optimise computational models of parasite metabolism

Assessing the disease burden of Yi people by years of life lost in Shilin county of Yunnan province, China

<p>Abstract</p> <p>Background</p> <p>Years of Life Lost (YLL) is one of the methods used to estimate the duration of time lost due to premature death. While previous studies of disease burden have been reported using YLL, there have been no studies investigating YLL of Yi people in rural China. Yunnan Province ranks first in terms of Yi people in China. This paper uses YLL to estimate the disease burden of Yi people in Shilin county of Yunnan Province. This study aims to address the differentials about YLL between Yi people and Han people for providing useful information for health planning.</p> <p>Methods</p> <p>We applied the Global Burden of Disease (GBD) method created by WHO. YLL rate per 1,000 were calculated from medical death certificates in 2003 in Shilin Yi Nationality Autonomous County (Shilin county).</p> <p>Results</p> <p>The male had greater YLL rate per 1,000 than did the female almost in each age group. It demonstrated a higher premature mortality burden due to injuries in Shilin county. Among the top non-communicable diseases, respiratory diseases are the most common mortality burden. Yi people are still suffering from maternal conditions, with two times the burden rates of Han people. For Yi people, while malignant neoplasm was one of the least burden of disease for male, it was the greatest for female, which is the opposite to Han people.</p> <p>Conclusion</p> <p>Strategies of economic development should be reviewed to enhance the prevention and treatment of injuries, maternal conditions and respiratory diseases for Yi people.</p

Asymptomatic neurocognitive disorders in patients infected by HIV: fact or fiction?

Neurocognitive disorders are emerging as a possible complication in patients infected with HIV. Even if asymptomatic, neurocognitive abnormalities are frequently detected using a battery of tests. This supported the creation of asymptomatic neurocognitive impairment (ANI) as a new entity. In a recent article published in BMC Infectious Diseases, Magnus Gisslén and colleagues applied a statistical approach, concluding that there is an overestimation of the actual problem. In fact, about 20% of patients are classified as neurocognitively impaired without a clear impact on daily activities. In the present commentary, we discuss the clinical implications of their findings. Although a cautious approach would indicate a stricter follow-up of patients affected by this disorder, it is premature to consider it as a proper disease. Based on a review of the data in the current literature we conclude that it is urgent to conduct more studies to estimate the overall risk of progression of the asymptomatic neurocognitive impairment. Moreover, it is important to understand whether new biomarkers or neuroimaging tools can help to identify better the most at risk population

Effects of an irregular bedtime schedule on sleep quality, daytime sleepiness, and fatigue among university students in Taiwan

<p>Abstract</p> <p>Background</p> <p>An irregular bedtime schedule is a prevalent problem in young adults, and could be a factor detrimentally affecting sleep quality. The goal of the present study was to explore the association between an irregular bedtime schedule and sleep quality, daytime sleepiness, and fatigue among undergraduate students in Taiwan.</p> <p>Methods</p> <p>A total of 160 students underwent a semi-structured interview and completed a survey comprising 4 parts: Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and a rating of irregular bedtime frequency. Participants were grouped into 3 groups in terms of irregular bedtime frequency: low, intermediate, or high according to their 2-week sleep log. To screen for psychological disorders or distress that may have affected responses on the sleep assessment measures, the Chinese health questionnaire-12 (CHQ-12) was also administered.</p> <p>Results</p> <p>We found an increase in bedtime schedule irregularity to be significantly associated with a decrease in average sleep time per day (Spearman r = -0.22, p = 0.05). Multivariate regression analysis revealed that irregular bedtime frequency and average sleep time per day were correlated with PSQI scores, but not with ESS or FSS scores. A significant positive correlation between irregular bedtime frequency and PSQI scores was evident in the intermediate (partial r = 0.18, p = 0.02) and high (partial r = 0.15, p = 0.05) frequency groups as compared to low frequency group.</p> <p>Conclusion</p> <p>The results of our study suggest a high prevalence of both an irregular bedtime schedule and insufficient sleep among university students in Taiwan. Students with an irregular bedtime schedule may experience poor sleep quality. We suggest further research that explores the mechanisms involved in an irregular bedtime schedule and the effectiveness of interventions for improving this condition.</p