- The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage. [Journal Article]
- AMAppl Microbiol Biotechnol 2016 Oct 21
- Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholder...
Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.
- Dornase alfa for cystic fibrosis. [Journal Article]
- PRPaediatr Respir Rev 2016 Sep 15
- Vitamin D3 supplementation among adult patients with cystic fibrosis. [Journal Article]
- CNClin Nutr 2016 Oct 8
- CONCLUSIONS: This supplementation protocol is efficient and needs to be tested in other CF adult cohorts and correlated to potential health benefit measurements.
- Antimicrobial susceptibility of microorganisms isolated from sputum culture of patients with cystic fibrosis: Methicillin-resistant Staphylococcus aureus as a serious concern. [Journal Article]
- MPMicrob Pathog 2016 Sep 22; 100:201-204
- CONCLUSIONS: The prevalence of MRSA has been rising. Since its impact on clinical outcomes, optimal prevention and treatment strategies are unclear, further studies to expand the knowledge about the infection control strategies and MRSA treatment are highly recommended.
- Global initiative for meticillin-resistant Staphylococcus aureus pneumonia (GLIMP): an international, observational cohort study. [Journal Article]
- LILancet Infect Dis 2016 Sep 1
- CONCLUSIONS: This multicountry study shows low prevalence of MRSA pneumonia and specific MRSA risk factors among community-dwelling patients hospitalised with pneumonia.
- Detailed faecal fat analysis using Fourier transform infrared spectroscopy: Exploring the possibilities. [Journal Article]
- CBClin Biochem 2016; 49(16-17):1283-1287
- CONCLUSIONS: For the analysis of faecal material, FTIR provides unique information, difficult to obtain using other techniques. These findings offer perspectives for diet monitoring in patients with (non-)pancreatic malabsorption.
- CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis. [Journal Article]
- OOncotarget 2016 Oct 19
- While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) develop...
While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.
- Evaporimeter and Bubble-Imaging Measures of Sweat Gland Secretion Rates. [Journal Article]
- PlosPLoS One 2016; 11(10):e0165254
- Beta-adrenergically-stimulated sweat rates determined by evaporimetry or by sweat bubble imaging are useful for measuring CFTR function because they provide a near-linear readout across almost the fu...
Beta-adrenergically-stimulated sweat rates determined by evaporimetry or by sweat bubble imaging are useful for measuring CFTR function because they provide a near-linear readout across almost the full range of CFTR function. They differentiate cystic fibrosis (CF) subjects from CF carriers and carriers from controls. However, evaporimetry, unlike bubble imaging, appears to be unable to detect improved levels of CFTR function in G551D subjects taking the CFTR modulator ivacaftor. Here, we quantify the sensitivity of evaporimetry and bubble imaging methods for assessing low levels of CFTR-dependent sweat rates. To establish sensitivity, we did dose-ranging studies using intradermally injected [cAMP]i-elevating cocktails. We reduced isoproterenol/aminophylline levels while maintaining a high level of atropine to block muscarinic elevation of [Ca2+]i. We stimulated the same sets of glands for both assays and recorded responses for 20 min. In response to a 3-log dilution of the stimulating cocktail (0.1%), bubble responses were detected in 12/12 tests (100%), with 49% ± 3% of glands secreting to produce an aggregate volume of 598 nl across the 12, 20-min tests. This was ~5% of the response to full cocktail. Evaporimetry detected responses in 3/12 (25%) tests with an aggregate secretion volume of 175 nl. After stimulation with a still more dilute cocktail (0.03%), bubble imaging detected 15 ± 13% of glands secreting at a rate ~0.9% of the response to full cocktail, while zero responding was seen with evaporimetry. The bubble imaging method detected secretion down to aggregate rates of <0.2 nl/(cm2·min), or ~1/30th of the average basal transepithelial water loss (TEWL) in the test subject of 4 g/m2·hr or 6.7 nl/(cm2·min). The increased sensitivity of bubble imaging may be required to detect small but physiologically important increases in secretion rates produced by CFTR modulators.
- The Cost-Effectiveness of Palivizumab in Infants with Cystic Fibrosis in the Canadian Setting: A Decision Analysis Model. [Journal Article]
- HVHum Vaccin Immunother 2016 Oct 21; :0
- Background Children with cystic fibrosis (CF) are at higher risk of severe respiratory syncytial virus (RSV) infection, which can lead to a decline in lung function. A monoclonal antibody, palivizuma...
Background Children with cystic fibrosis (CF) are at higher risk of severe respiratory syncytial virus (RSV) infection, which can lead to a decline in lung function. A monoclonal antibody, palivizumab (PMB), effectively prevents RSV hospitalizations; however, the high cost of PMB, approximately C$10,000 per patient per RSV season, limits its widespread use. We assess the cost-effectiveness of PMB prophylaxis in CF children less than 2 years of age from the Canadian healthcare payer's perspective. Methods In 2014, a Markov cohort model of CF disease and infant RSV infections in the Canadian setting was developed based on literature data. Infants were treated with monthly PMB injections over the five-month RSV season. Lifetime health outcomes, quality-adjusted life years (QALYs) and 2013 $CAD costs, discounted at 5%, were estimated. Findings are summarized as incremental cost-effectiveness ratios (ICERs) and budget impact. Deterministic sensitivity analysis was conducted to assess parameter uncertainty. Results Implementation of a hypothetical Canadian RSV prophylaxis program resulted in ICERs of C$652,560 (all CF infants) and C$157,332 (high-risk CF infants) per QALY gained and an annual budget impact of C$1,400,000 (all CF infants) and C$285,000 (high-risk CF infants). The analysis was highly sensitive to the probability of severe RSV, the degree of lung deterioration following infection, and the cost of PMB. Conclusions Our results suggest PMB is not cost-effective in Canada by commonly used thresholds. However, given the rarity of CF and relatively small budget impact, consideration may be given for the selective use of PMB for immunoprophylaxis of RSV in high-risk CF infants on a case-by-case scenario basis.
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- Distal intestinal obstruction syndrome: a rare complication of cystic fibrosis in infants. [Journal Article]
- MPMinerva Pediatr 2016; 68(6):498-500