Notes

Treating commercial toxins using zero-valent iron- and zero-valent aluminium-activated persulfate: an incident research together with 3,5-dichlorophenol and 2,4-dichloroaniline.
Mutations in NDUFS4, which encodes an accessory subunit of mitochondrial oxidative phosphorylation (OXPHOS) complex I (CI), induce Leigh syndrome (LS). LS is a poorly understood pediatric disorder featuring brain-specific anomalies and early death. To study the LS pathomechanism, we here compared OXPHOS proteomes between various Ndufs4-/- mouse tissues. Ndufs4-/- animals displayed significantly lower CI subunit levels in brain/diaphragm relative to other tissues (liver/heart/kidney/skeletal muscle), whereas other OXPHOS subunit levels were not reduced. Absence of NDUFS4 induced near complete absence of the NDUFA12 accessory subunit, a 50% reduction in other CI subunit levels, and an increase in specific CI assembly factors. Among the latter, NDUFAF2 was most highly increased. Regarding NDUFS4, NDUFA12 and NDUFAF2, identical results were obtained in Ndufs4-/- mouse embryonic fibroblasts (MEFs) and NDUFS4-mutated LS patient cells. Ndufs4-/- MEFs contained active CI in situ but blue-native-PAGE highlighted that NDUFAF2 attached to an inactive CI subcomplex (CI-830) and inactive assemblies of higher MW. In NDUFA12-mutated LS patient cells, NDUFA12 absence did not reduce NDUFS4 levels but triggered NDUFAF2 association to active CI. BN-PAGE revealed no such association in LS patient fibroblasts with mutations in other CI subunit-encoding genes where NDUFAF2 was attached to CI-830 (NDUFS1, NDUFV1 mutation) or not detected (NDUFS7 mutation). Supported by enzymological and CI in silico structural analysis, we conclude that absence of NDUFS4 induces near complete absence of NDUFA12 but not vice versa, and that NDUFAF2 stabilizes active CI in Ndufs4-/- mice and LS patient cells, perhaps in concert with mitochondrial inner membrane lipids. INTRODUCTION Stomal recurrence is a troublesome complication after total laryngectomy Despite a large number of studies having been performed, there is still controversy about which risk factors are most significant for the development of stomal recurrence. OBJECTIVE The objective of the present meta-analysis was to analyze the potential factors leading to stomal recurrence after total laryngectomy. METHODS PubMed, Web of Science, Cochrane Library, and Ovid databases were systematically searched using multiple search terms. Eighteen studies with 6462 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. RESULTS The results showed that, tumor subsite (supraglottic vs. subglottic, RR=0.292, 95% CI 0.142-0.600, p=0.001; glottic vs. subglottic, RR=0.344, 95% CI 0.175-0.676, p=0.002), T stage (RR=0.461, 95% CI 0.286-0.742, p=0.001), preoperative tracheotomy (RR=1.959, 95% CI 1.500-2.558, p less then 0.001) were the high-risk factors associated with the development of stomal recurrence. CONCLUSION From the results of our study, tumor subsite, T stage and preoperative tracheotomy were the significant risk factors for stomal recurrence. Methodologically high-quality comparative investigations are needed for further evaluation. BACKGROUND Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p less then 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p less then 0.001). CONCLUSIONS The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms. BACKGROUND The increasing pulmonary diseases are reported to be affected by mixed infection of Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM). In this study, our objective was to assess the efficiency of mycobacterial culture plus DNA sequencing to detect the mixed infections with MTB and various NTM organisms. We also aimed to investigate how efficiently GeneXpert detected MTB in mixed infections with NTM in in vitro models. METHODS A serial of mixed infection samples was generated by combining suspensions of MTB and five NTM bacteria, respectively. The mixed suspensions were further detected with GeneXpert and liquid culture plus DNA sequencing. RESULTS Overall, the GeneXpert assay exhibited promising capability to identify the presence of MTB at different proportions ranging from 1% to 99%. For the liquid culture, the subsequent DNA sequencing only detected the presence of NTM bacteria in the mixed samples, which the proportion of NTM ranged from 1% to 99%, including M. intracellulare, M. kansasii, M. abscessus, and M. fortuitum. For M. selleck chemicals avium, DNA sequencing was able to identify the mixtures as M. avium infection in suspensions with no less than 10% M. avium bacteria, whereas only MTB was found in the other suspensions with less M. avium bacteria. CONCLUSIONS Our data demonstrate that the current diagnostic algorithm cannot yield a precise detection of mixed infections with MTB and NTM bacteria. The GeneXpert assay only identify MTB in the mixed samples, while the subculture plus DNA sequencing prefers to identify the NTM species with the higher growth rate. Further targeted molecular analysis by specific capture of multiple loci of mycobacterial species from specimens is urgently required to solve this diagnostic dilemma.
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