A false-carrier state for the c.579G>A mutation in the NCF1 gene in Ashkenazi Jews

BACKGROUND: Mutations in the NCF1 gene that encodes p47phox, a subunit of the NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi CGD patients with this mutation have never been described. METHODS: We used Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis, and measured NADPH oxidase activity and p47phox expression. RESULTS: In an Ashkenazi couple expecting a baby, both parents were found to be heterozygotes for this mutation, as was the fetus. However, segregation analysis in the extended family was consistent with the fetus inheriting both carrier alleles from the parents. MLPA indicated four complete NCF1 genes in the fetus and three in each parent. Gene sequencing confirmed these results. Analysis of fetal leucocytes obtained by cordocentesis revealed substantial oxidase activity with three different assays, which was confirmed after birth. In six additional Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with three complete NCF1 genes of which one was mutated (like the parents), and one individual with in addition a fusion gene of NCF1 with a pseudogene. CONCLUSION: These results point to the existence of a 'false-carrier' state in Ashkenazi Jews and have wide implications regarding pre-pregnancy screening in this and other population groups

Paracetamol biodegradation by activated sludge and photocatalysis and its removal by a micelle–clay complex, activated charcoal, and reverse osmosis membranes

<p>Kinetic studies on the stability of the pain killer paracetamol in Al-Quds activated sludge demonstrated that paracetamol underwent biodegradation within less than one month to furnish <i>p</i>-aminophenol in high yields. Characterizations of bacteria contained in Al-Quds sludge were accomplished. It was found that <i>Pseudomonas aeruginosa</i> is the bacterium most responsible for the biodegradation of paracetamol to <i>p</i>-aminophenol and hydroquinone. Batch adsorptions of paracetamol and its biodegradation product (<i>p</i>-aminophenol) by activated charcoal and a composite micelle (octadecyltrimethylammonium)–clay (montmorillonite) were determined at 25°C. Adsorption was adequately described by a Langmuir isotherm, and indicated better efficiency of removal by the micelle–clay complex. The ability of bench top reverse osmosis (RO) plant as well as advanced membrane pilot plant to remove paracetamol was also studied at different water matrixes to test the effect of organic matter composition. The results showed that at least 90% rejection was obtained by both plants. In addition, removal of paracetamol from RO brine was investigated by using photocatalytic processes; optimal conditions were found to be acidic or basic pH, in which paracetamol degraded in less than 5 min. Toxicity studies indicated that the effluent and brine were not toxic except for using extra low energy membrane which displayed a half maximal inhibitory concentration (IC-50) value of 80%.</p

Italian Society for the Study of Diabetes (SID)/Italian Endocrinological Society (SIE) guidelines on the treatment of hyperglycemia in Cushing's syndrome and acromegaly

none5noHyperglycemia is a common feature associated with states of increased growth hormone secretion and glucocorticoid levels. AIMS: The purpose of these guidelines is to assist clinicians and other health care providers to take evidence-based therapeutic decisions for the treatment of hyperglycemia in patients with growth hormone and corticosteroid excess. METHODOLOGY: Both the SID and SIE appointed members to represent each society and to collaborate in Guidelines writing. Members were chosen for their specific knowledge in the field. Each member agreed to produce--and regularly update--conflicts of interest. The Authors of these guidelines prepared their contributions following the recommendations for the development of Guidelines, using the standard classes of recommendation shown below. All members of the writing committee provided editing and systematic review of each part of the manuscript, and discussed the grading of evidence. Consensus was guided by a systematic review of all available trials and by interactive discussionsopenBaroni, M.G.; Giorgino, F.; Pezzino, V.; Scaroni, C.; Avogaro, ABaroni, M. G.; Giorgino, FRANCESCO LIBERO; Pezzino, V.; Scaroni, Carla; Avogaro, Angel