Reinvestigation of aminoacyl-TRNA synthetase core complex by affinity purification-mass spectrometry reveals TARSL2 as a potential member of the complex

10.1371/journal.pone.0081734PLoS ONE812-POLN

Multidrug resistance, inappropriate empiric treatment and hospital mortality in Acinetobacter baumannii pneumonia and sepsis

Background: The relationship between multidrug resistance (MDR), inappropriate empiric therapy (IET), and mortality among patients with Acinetobacter baumannii (AB) remains unclear. We examined it using a large U.S. database. Methods: We conducted a retrospective cohort study using the Premier Research database (2009–2013) of 175 U.S. hospitals. We included all adult patients admitted with pneumonia or sepsis as their principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure, along with antibiotic administration within 2 days of admission. Only culture-confirmed infections were included. Resistance to at least three classes of antibiotics defined multidrug-resistant AB (MDR-AB). We used logistic regression to compute the adjusted relative risk ratio (RRR) of patients with MDR-AB receiving IET and IET’s impact on mortality. Results: Among 1423 patients with AB infection, 1171 (82.3 %) had MDR-AB. Those with MDR-AB were older (63.7 ± 15.4 vs. 61.0 ± 16.9 years, p = 0.014). Although chronic disease burden did not differ between groups, the MDR-AB group had higher illness severity than those in the non-MDR-AB group (intensive care unit 68.0 % vs. 59. 5 %, p < 0.001; mechanical ventilation 56.2 % vs. 42.1 %, p < 0.001). Patients with MDR-AB were more likely to receive IET than those in the non-MDR-AB group (76.2 % MDR-AB vs. 13.8 % non-MDR-AB, p < 0.001). In a regression model, MDR-AB strongly predicted receipt of IET (adjusted RRR 5.5, 95 % CI 4.0–7.7, p < 0.001). IET exposure was associated with higher hospital mortality (adjusted RRR 1.8, 95 % CI 1.4–2.3, p < 0.001). Conclusions: In this large U.S. database, the prevalence of MDR-AB among patients with AB infection was > 80 %. Harboring MDR-AB increased the risk of receiving IET more than fivefold, and IET nearly doubled hospital mortality

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy

<p>Abstract</p> <p>Background</p> <p>Small bowel adenocarcinomas (SBAs) are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening</p> <p>Case presentation</p> <p>A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ). Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma.</p> <p>Conclusion</p> <p>Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.</p

GeneXpert—A Game-Changer for Tuberculosis Control?

Carlton Evans considers whether the new tuberculosis diagnostic test, GeneXpert, is the solution for TB control that it's said to be

Prognostic significance of HER3 and HER4 protein expression in colorectal adenocarcinomas

BACKGROUND: Colorectal cancer remains a major cause of cancer mortality in the Western world. A limited number of studies has been conducted in respect of Her-3 and Her-4 expression and their correlation with clinical parameters and prognosis in colorectal carcinomas . In this study we sought to determine the pattern and the prognostic significance of HER-3 and HER-4 in colorectal adenocarcinoma. METHODS: We studied HER-3 and HER-4 protein expression in106 paraffin embedded specimens of primary colorectal tumors using immunohistochemistry. The pattern and protein expression levels of HER-3 and HER-4 were correlated with several clinical and pathological parameters. RESULTS: HER-3 staining displayed membranous and cytoplasmic expression pattern in 18 (17%) and 30 samples (28,3%), respectively. HER-4 membranous and cytoplasmic expression was found in 20 (18,9%) and 32 samples (30,2%), respectively. Specimens regarded as positive for HER-3 cytoplasmic expression were associated with moderate tumor grade (p = 0,032) and older median age (p = 0,010). Specimens regarded as positive for HER-4 membranous protein expression were associated with involved lymphnodes (p = 0,0003). Similar results were obtained when considering Her-3 and Her-4 protein expression irrespective of their cellular localization. There was no correlation between the expression of HER-3 and HER-4 and patients outcome. CONCLUSION: HER-4 membranous protein expression was found to predict for lymph nodes positivity in this cohort of patients with colorectal cancer.HER-4 expression status may identify tumors with aggressive biological behavior and increased metastatic potential

Slip-Sliding Away: Serial Changes and Homoplasy in Repeat Number in the Drosophila yakuba Homolog of Human Cancer Susceptibility Gene BRCA2

Several recent studies have examined the function and evolution of a Drosophila homolog to the human breast cancer susceptibility gene BRCA2, named dmbrca2. We previously identified what appeared to be a recent expansion in the RAD51-binding BRC-repeat array in the ancestor of Drosophila yakuba. In this study, we examine patterns of variation and evolution of the dmbrca2 BRC-repeat array within D. yakuba and its close relatives. We develop a model of how unequal crossing over may have produced the expanded form, but we also observe short repeat forms, typical of other species in the D. melanogaster group, segregating within D. yakuba and D. santomea. These short forms do not appear to be identical-by-descent, suggesting that the history of dmbrca2 in the D. melanogaster subgroup has involved repeat unit contractions resulting in homoplasious forms. We conclude that the evolutionary history of dmbrca2 in D. yakuba and perhaps in other Drosophila species may be more complicated than can be inferred from examination of the published single genome sequences per species

Audiologic monitoring of multi-drug resistant tuberculosis patients on aminoglycoside treatment with long term follow-up

<p>Abstract</p> <p>Background</p> <p>Multi-drug resistant tuberculosis has emerged as a significant problem with the resurfacing of tuberculosis and thus the need to use the second line drugs with the resultant increased incidence of adverse effects. We discuss the effect of second line aminoglycoside anti-tubercular drugs on the hearing status of MDR-TB patients.</p> <p>Methods</p> <p>Sixty four patients were put on second line aminoglycoside anti-TB drugs. These were divided into three groups: group I, 34 patients using amikacin, group II, 26 patients using kanamycin and group III, 4 patients using capreomycin.</p> <p>Results</p> <p>Of these, 18.75% of the patients developed sensorineural hearing loss involving higher frequencies while 6.25% had involvement of speech frequencies also. All patients were seen again approximately one year after aminoglycoside discontinuation and all hearing losses were permanent with no threshold improvement.</p> <p>Conclusion</p> <p>Aminoglycosides used in MDR-TB patients may result in irreversible hearing loss involving higher frequencies and can become a hearing handicap as speech frequencies are also involved in some of the patients thus underlining the need for regular audiologic evaluation in patients of MDR-TB during the treatment.</p