Cystic fibrosis in Turkey: First data from the national registry.
Related ArticlesCystic fibrosis in Turkey: First data from the national registry. Pediatr Pulmonol. 2019 Nov 11;: Authors: Dogru D, Çakır E, Şişmanlar T, Çobanoğlu N, Pekcan S, Cinel G, Yalçın E, Kiper N, Şen V, S Şen H, Ercan Ö, Keskin Ö, B Eltan S, Al Shadfan LM, Yazan H, Altıntaş DU, Şaşihüseyinoğlu Ş, Sapan N, Çekiç Ş, Çokuğraş H, A Kılınç A, R Gürsoy T, Aslan AT, Bingöl A, Başaran AE, Özdemir A, Köse M, Hangül M, Emiralioğlu N, Tuğcu G, Yüksel H, Yılmaz Ö, Orhan F, Gayretli Aydın ZG, Topal E, Tamay Z, Süleyman A, Can D, Bal CM, Çaltepe G, Özçelik U Abstract BACKGROUND: Cystic fibrosis (CF) care has been implemented in Turkey for a long time; however, there had been no patient registry. For this purpose, the Turkish National CF Registry was established. We present the first results of registry using data collected in 2017. METHODS: The data were collected using a data-entry software system, which was accessed from the internet. Demographic and annually recorded data consisted of 15 and 79 variables, respectively. RESULTS: There were 1170 patients registered from 23 centers; the estimated coverage rate was 30%. The median age at diagnosis was 1.7 years (median current age: 7.3 years); 51 (4.6%) patients were aged over 18 years. Among 293 patients who were under 3 years of age, 240 patients (81.9%) were diagnosed through newborn screening. Meconium ileus was detected in 65 (5.5%) patients. Genotyping was performed in 978 (87.4%) patients and 246 (25.2%) patients' mutations were unidentified. The most common mutation was deltaF508 with an allelic frequency of 28%, followed by N1303K (4.9%). The median FEV1% predicted was 86. Chronic colonization with Pseudomonas aeruginosa was seen in 245 patients. The most common complication was pseudo-Bartter syndrome in 120 patients. The median age of death was 13.5 years in a total of 15 patients. CONCLUSIONS: Low coverage rate, lack of genotyping, unidentified mutations, and missing data of lung functions are some of our greatest challenges. Including data of all centers and reducing missing data will provide more accurate data and help to improve the CF care in Turkey in the future.PMID: 31710166 [PubMed - as supplied by publisher]
A new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B.
Related ArticlesA new role for heat shock factor 27 in the pathophysiology of Clostridium difficile toxin B. Am J Physiol Gastrointest Liver Physiol. 2019 Nov 11;: Authors: Yanda MK, Guggino WB, Cebotaru L Abstract Clostridium difficile (CD) is a common pathogen that causes severe gastrointestinal inflammatory diarrhea in patients undergoing antibiotic therapy. Its virulence derives from two toxins, toxin CD, A & B (TcdA and TcdB) (10). Among the prime candidates for CD colonization are patients with cystic fibrosis (CF), who are routinely treated with antibiotics and frequently hospitalized. Indeed, ~50% of CF patients are colonized with virulent forms of CD but do not exhibit diarrhea (7, 9, 61). We found that TcdB has global effects on colonic cells, including reducing the steady-state levels of sodium proton exchange regulatory factors (NHERF), reducing the levels of heat shock protein Hsp27, and increasing the fraction of total Hsp27 bound to the cystic fibro-sis transmembrane regulator (CFTR). Also, since some mutations in CFTR seem to be protective, we asked whether CFTR is a target of TcdB. We show here that TcdB increases the maturation of CFTR and transiently increases its function. These combined effects promote increased surface expression of CFTR, resulting in a transient increase in Cl- secretion. This increase is followed by a precipitous decline in both CFTR-dependent Cl- secretion and transepithelial resistance (TER), suggesting a breakdown in the epithelial cells' tight junctions. We also found that overexpressing Hsp27 reverses some of the deleterious effects of TcdB, in particular preserving TER, and therefore likely the maintenance of barrier function. Thus, our data suggest that Hsp27 plays a role in the diarrhea generated by CD infection and is a potential therapeutic target for treating this diarrhea.PMID: 31709831 [PubMed - as supplied by publisher]
The environmental occurrence of Pseudomonas aeruginosa.
Related ArticlesThe environmental occurrence of Pseudomonas aeruginosa. APMIS. 2019 Nov 10;: Authors: Crone S, Vives-Flórez M, Kvich L, Saunders AM, Malone M, Nicolaisen MH, Martínez-García E, Rojas-Acosta C, Catalina Gomez-Puerto M, Calum H, Whiteley M, Kolter R, Bjarnsholt T Abstract Pseudomonas aeruginosa is generally described as ubiquitous in natural settings, such as soil and water. However, because anecdotal observations and published reports have questioned whether or not this description is true, we undertook a rigorous study using three methods to investigate the occurrence of P. aeruginosa: we investigated environmental samples, analyzed 16S rRNA data, and undertook a systematic review and meta-analysis of published data. The environmental sample screening identified P. aeruginosa as significantly associated with hydrocarbon and pesticide contaminated environments and feces, as compared to uncontaminated environments in which its prevalence was relatively low. The 16S rRNA data analysis showed that P. aeruginosa sequences were present in all habitats but were most abundant in samples from human and animals. Similarly, the meta-analysis revealed that samples obtained from environments with intense human contact had a higher prevalence of P. aeruginosa compared to those with less human contact. Thus, we found a clear tendency of P. aeruginosa to be present in places closely linked with human activity. Although P. aeruginosa may be ubiquitous in nature, it is usually scarce in pristine environments. Thus, we suggest that P. aeruginosa should be described as a bacterium largely found in locations associated with human activity.PMID: 31709616 [PubMed - as supplied by publisher]
A rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens.
Related ArticlesA rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens. J Assist Reprod Genet. 2019 Nov 10;: Authors: Ge B, Zhang M, Wang R, Wang D, Li T, Li H, Wang B Abstract PURPOSE: Congenital aplasia of vas deferens (CAVD) is an atypical form of cystic fibrosis (CF) and causes obstructive azoospermia and male infertility. Compound heterozygous variants of CFTR are the main cause of CAVD. However, most evidence comes from genetic screening of sporadic cases and little is from pedigree analysis. In this study, we performed analysis in a Chinese pedigree with two CAVD patients in order to determine the genetic cause of this familial disorder. METHODS: In the present study, we performed whole-exome sequencing and co-segregation analysis in a Chinese pedigree involving two patients diagnosed with CAVD. RESULTS: We identified a rare frameshift variant (NM_000492.3: c.50dupT;p.S18Qfs*27) and a frequent CBAVD-causing variant (IVS9-TG13-5T) in both patients. The frameshift variant introduced a premature termination codon and was not found in any public databases or reported in the literature. Co-segregation analysis confirmed these two variants were in compound heterozygous state. The other male members, who harbored the frameshift variant and benign IVS9-7T allele, did not have any typical clinical manifestations of CF or CAVD. CONCLUSION: Our findings may broaden the mutation spectrum of CFTR in CAVD patients and provide more familial evidence that the combination of a mild variant and a severe variant in trans of CFTR can cause vas deferens malformation.PMID: 31709488 [PubMed - as supplied by publisher]
Serum amyloid A: A potential biomarker of lung disorders.
Related ArticlesSerum amyloid A: A potential biomarker of lung disorders. Respir Investig. 2019 Nov 07;: Authors: Vietri L, Fui A, Bergantini L, d'Alessandro M, Cameli P, Sestini P, Rottoli P, Bargagli E Abstract Serum amyloid A is an acute-phase protein with multiple immunological functions. Serum amyloid A is involved in lipid metabolism, inflammatory reactions, granuloma formation, and cancerogenesis. Additionally, serum amyloid A is involved in the pathogenesis of different autoimmune lung diseases. The levels of serum amyloid A has been evaluated in biological fluids of patients with different lung diseases, including autoimmune disorders, chronic obstructive pulmonary diseases, obstructive sleep apnea syndrome, sarcoidosis, asthma, lung cancer, and other lung disorders, such as idiopathic pulmonary fibrosis, tuberculosis, radiation pneumonitis, and cystic fibrosis. This review focuses on the cellular and molecular interactions of serum amyloid A in different lung diseases and suggests this acute-phase protein as a prognostic marker.PMID: 31708467 [PubMed - as supplied by publisher]