Although fomites or contaminated surfaces have been considered as transmission routes, the role of environmental contamination by human parainfluenza virus type 3 (hPIV-3) in healthcare settings is ...not established.
To describe an hPIV-3 nosocomial outbreak and the results of environmental sampling to elucidate the source of nosocomial transmission and the role of environmental contamination.
During an hPIV-3 outbreak between May and June 2016, environmental surfaces in contact with clustered patients were swabbed and respiratory specimens used from infected patients and epidemiologically unlinked controls. The epidemiologic relatedness of hPIV-3 strains was investigated by sequencing of the haemagglutinin–neuraminidase and fusion protein genes.
Of 19 hPIV-3-infected patients, eight were haematopoietic stem cell recipients and one was a healthcare worker. In addition, four had upper and 12 had lower respiratory tract infections. Of the 19 patients, six (32%) were community-onset infections (symptom onset within <7 days of hospitalization) and 13 (68%) were hospital-onset infections (≥7 days of hospitalization). Phylogenetic analysis identified two major clusters: five patients, and three patients plus one healthcare worker. Therefore, seven (37%) were classified as nosocomial transmissions. hPIV-3 was detected in 21 (43%) of 49 environmental swabs up to 12 days after negative respiratory polymerase chain reaction conversion.
At least one-third of a peak season nosocomial hPIV-3 outbreak originated from nosocomial transmission, with multiple importations of hPIV-3 from the community, providing experimental evidence for extensive environmental hPIV-3 contamination. Direct contact with the contaminated surfaces and fomites or indirect transmission from infected healthcare workers could be responsible for nosocomial transmission.
No randomized controlled trials have evaluated the comparative outcomes of cefazolin versus nafcillin for methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia.
A prospective observational ...cohort study including all S. aureus bacteraemia was conducted at 10 hospitals. Patients (≥15 years) with MSSA bacteraemia who received cefazolin or nafcillin as definitive antibiotics were included. The rates of treatment failure (premature discontinuation of antibiotics because of adverse effects, switching of antibiotics because of clinical failure, all-cause mortality within 1 month, or recurrence) were compared between the cefazolin and nafcillin groups. Propensity score matching analyses were performed to balance the factors influencing the selection of antibiotics.
Among the 242 included cases, the bones and joints (36.8%) were the most common sites of infection and 60.7% of the patients had sepsis. The overall treatment failure rate was 43.8% (106/242). All-cause mortality within 1 month was 6.2% (15/242). After propensity score matching, the treatment failure rate of cefazolin was lower than that of nafcillin (30.4% (24/79) vs. 49.4% (39/79), p 0.015) because of a higher rate of discontinuation caused by adverse events. When the data were limited to patients with sepsis, the treatment failure rates of both groups were not significantly different. Approximately 22% (24/110) of MSSA isolates exhibited a cefazolin-inoculum effect (CIE) that had significant impact on the failure rate and mortality of the cefazolin group.
Cefazolin might be recommended as an adequate and better-tolerated treatment for MSSA bacteraemia in the absence of CIE.
With 7 figures and 6 tables ABSTRACT: Garlic is widely consumed for its culinary and medical benefits. Six hundred and thirteen accessions of garlic and its relatives with diverse origin were ...evaluated for genetic diversity at eight recently novel simple sequence repeat loci in this study. A total of 113 alleles were detected, the average allelic richness was 14.1 alleles per locus. Using a heuristic approach, a core set of 95 accessions was successfully developed, which showed 100% coverage of alleles with minimum redundancy. The model-based structure analysis here revealed the presence of four subpopulations in the selected core set, which was basically consistent with clustering based on the genetic distance. The analysis of molecular variance based on this core set showed that between-population component of genetic variance is <15.6% in contrast to 84.4% for the within population component. Overall FST value was 0.1560, indicating a moderate differentiation among the four groups. These results will provide an effective aid for future allele mining, association genetics, mapping and cloning gene(s), germplasm conservation, and improvement programs.
Circulating tumor DNA (ctDNA) has emerged as a tumor-specific biomarker for the early detection of various cancers. To date, several techniques have been devised to enrich the extremely small amounts ...of ctDNA present in plasma, but they are still insufficient for cancer diagnosis, especially at the early stage. Here, we developed a novel method, CUT (CRISPR-mediated, Ultrasensitive detection of Target DNA)-PCR, which uses CRISPR endonucleases to enrich and detect the extremely small amounts of tumor DNA fragments among the much more abundant wild-type DNA fragments by specifically eliminating the wild-type sequences. We computed that by using various orthologonal CRISPR endonucleases such as SpCas9 and FnCpf1, the CUT-PCR method would be applicable to 80% of known cancer-linked substitution mutations registered in the COSMIC database. We further verified that CUT-PCR together with targeted deep sequencing enables detection of a broad range of oncogenes with high sensitivity (<0.01%) and accuracy, which is superior to conventional targeted deep sequencing. In the end, we successfully applied CUT-PCR to detect sequences with oncogenic mutations in the ctDNA of colorectal cancer patients' blood, suggesting that our technique could be adopted for diagnosing various types of cancer at early stages.
In this Letter, the authors analyse the diversity order of the precoding-aided spatial modulation (PSM) system with receive antenna subset (RAS) selection. It is shown that when there are $N_{\rm ...T}$NT transmit antennas, $N_{\rm R}$NR receive antennas, and $N_{\rm S}$NS selected receive antennas, the achievable diversity order is given by $\left({N_{\rm T} - N_{\rm S} + 1} \right)\left({N_{\rm R} - N_{\rm S} + 1} \right)$NT−NS+1NR−NS+1, where the product gain of $\left({N_{\rm T} - N_{\rm S} + 1} \right)$NT−NS+1 is achieved by the zero-forcing precoding scheme and another of $\left({N_{\rm R} - N_{\rm S} + 1} \right)$NR−NS+1 can be attained by the optimal RAS selection algorithm.
Background
In the eighth edition of the AJCC staging system for differentiated thyroid carcinoma (DTC), minimal extrathyroidal extension (ETE) is no longer a determinant of T3 category. Instead, ...gross ETE invading only strap muscles has been designated as a new T3b category. The long‐term prognosis of patients with DTC and gross ETE invading only strap muscles was investigated.
Methods
This was a retrospective analysis of patients who underwent thyroidectomy between 1996 and 2005. Differences in cancer‐specific and recurrence‐free survival according to extent of ETE were assessed.
Results
A total of 3174 patients with DTC were included. No significant differences were observed in 10‐year cancer‐specific survival among patients with no ETE (98·6 per cent), microscopic ETE (98·3 per cent) and gross ETE invading only strap muscles (98·9 per cent) (P = 0·375). The 10‐year recurrence‐free survival rate for patients with gross ETE invading only strap muscles (89·2 per cent) was shorter than that for patients with no ETE (93·7 per cent; P = 0·016), but similar to that of patients with microscopic ETE (90·3 per cent). In univariable analysis, patients with gross ETE invading only strap muscles had a significantly higher risk of recurrence than those with no ETE (hazard ratio (HR) 1·67, 95 per cent c.i. 1·10 to 2·55; P = 0·017). In multivariable analysis, gross ETE invading only strap muscles was not an independent predictor of recurrence (HR 1·09, 0·71 to 1·69; P = 0·685).
Conclusion
Although gross ETE invading only strap muscles may provide prognostic information about long‐term recurrence, it does not affect mortality. The actual impact of gross ETE invading only strap muscles will be important in revising the staging system in the future.
None, for survival
Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen ...species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1β substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.
KRAS mutations in non-small-cell lung cancer (NSCLC) are associated with poor prognosis. Trametinib, a selective inhibitor of MEK1/MEK2, demonstrated similar efficacy to docetaxel in patients with ...advanced KRAS-mutant NSCLC, with median progression-free survival of 12 and 11 weeks, respectively. With moderate activity as a monotherapy, trametinib-based combination regimens may show improve efficacy.
KRAS mutations are detected in 25% of non-small-cell lung cancer (NSCLC) and no targeted therapies are approved for this subset population. Trametinib, a selective allosteric inhibitor of MEK1/MEK2, demonstrated preclinical and clinical activity in KRAS-mutant NSCLC. We report a phase II trial comparing trametinib with docetaxel in patients with advanced KRAS-mutant NSCLC.
Eligible patients with histologically confirmed KRAS-mutant NSCLC previously treated with one prior platinum-based chemotherapy were randomly assigned in a ratio of 2 : 1 to trametinib (2 mg orally once daily) or docetaxel (75 mg/m2 i.v. every 3 weeks). Crossover to the other arm after disease progression was allowed. Primary end point was progression-free survival (PFS). The study was prematurely terminated after the interim analysis of 92 PFS events, which showed the comparison of trametinib versus docetaxel for PFS crossed the futility boundary.
One hundred and twenty-nine patients with KRAS-mutant NSCLC were randomized; of which, 86 patients received trametinib and 43 received docetaxel. Median PFS was 12 weeks in the trametinib arm and 11 weeks in the docetaxel arm (hazard ratio HR 1.14; 95% CI 0.75–1.75; P = 0.5197). Median overall survival, while the data are immature, was 8 months in the trametinib arm and was not reached in the docetaxel arm (HR 0.97; 95% CI 0.52–1.83; P = 0.934). There were 10 (12%) partial responses (PRs) in the trametinib arm and 5 (12%) PRs in the docetaxel arm (P = 1.0000). The most frequent adverse events (AEs) in ≥20% of trametinib patients were rash, diarrhea, nausea, vomiting, and fatigue. The most frequent grade 3 treatment-related AEs in the trametinib arm were hypertension, rash, diarrhea, and asthenia.
Trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive NSCLC.
NCT01362296.
Removal of sulfonamide (SAs) and tetracycline (TAs) classes of antibiotic compound from deionized water and DOC water by powdered activated carbon (PAC) adsorption was evaluated in this study. ...According to the study results, TAs were more easily adsorbed than SAs although TAs were more hydrophilic than SAs. The phenolic compounds in TAs might be responsible for their high adsorption. Complex formation of TAs with metal and metal oxide on the surface of activated carbon might also contribute to higher adsorption. The hydrophobic effect was important for removal of SAs. More hydrophobic SAs were removed more easily. The carbon type was not important for adsorption of SAs and TAs. Coal based carbon and coconut based carbon showed similar removal efficiencies for these antibiotics. Dissolved organic materials interfered with adsorption of SAs and TAs. Organic interference was more significant for the antibiotic compound, which was more subject to the PAC adsorption. Self-decomposition of SAs and TAs occurred even after 1 day. TAs were more subject to self-decomposition than SAs. Depending on the antibiotic type, more than 60% of TA was removed through self-decomposition.
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