Survival after lung transplantation for cystic fibrosis in Sweden†.

Eur J Cardiothorac Surg. 2017 Mar 01;51(3):571-576

Authors: Gilljam M, Nyström U, Dellgren G, Skog I, Hansson L

Abstract
OBJECTIVES: In Sweden, lung transplantation has been performed in patients with end-stage lung disease since 1990. We assessed survival after lung transplantation for cystic fibrosis (CF) with focus on early mortality and outcome for patients infected with certain multiresistant bacteria, considered a relative contraindication for lung transplantation.
METHODS: Review of CF and transplant databases and patient charts. The Kaplan-Meier method and log-rank test were used for survival analysis and group comparison.
RESULTS: From November 1991 to December 2014, 115 transplantations were performed in 106 CF patients (9 retransplantations): 3 heart-lung, 106 double lung-, 1 double lobar- and 5 single lung transplantations, constituting 13% (115/909) of all lung-transplant procedures performed in Sweden. The mean age at surgery was 31 (SD 10, range 10-61) years and there were 48% females. Overall 1-year survival after lung transplantation for CF was 86.4%, 5-year survival was 73.7% and 10-year survival was 62.4%. The mean and median survival after transplantation were 13.1 (95% confidence interval (CI): 11-15.3) and 14.6 (95% CI: 9.3-19.8) years, respectively, and there was no significant difference for gender or transplant centre. Extracorporeal membrane oxygenation was used as a bridge to transplantation in 11 cases and five patients received reconditioned lungs. Vascular and infectious complications contributed to eight deaths within the first three postoperative months. The mean survival for 14 patients infected pretransplant with Mycobacterium abscessus or Burkholderia cepacia complex was 8.8 (95% CI: 6.1-11.6) years compared to 13.2 (95% CI: 10.9-15.8) years for patients negative for these bacteria. Nineteen patients (14% of all listed), of whom three were listed for retransplantation, died while waiting a median time of 94 days (range 4 days-2.5 years) after listing.
CONCLUSION: Survival after lung transplantation in Sweden is good, also for patients with pretransplant infection with M. abscessus or B. cepacia complex, and comparable to international data.

PMID: 28364441 [PubMed - in process]

Burkholderia cepacia complex in cystic fibrosis in the post-epidemic period: multilocus sequence typing-based approach.

Folia Microbiol (Praha). 2017 Mar 31;:

Authors: Fila L, Dřevínek P

Abstract
Cystic fibrosis (CF) patients in the Czech Republic suffered in the late 1990s from an epidemic with ST32 strain of Burkholderia cepacia complex (Bcc). Cohort segregation of Bcc and of ST32 positive patients was introduced in 1999 and 2002, respectively. We performed a study to evaluate the molecular epidemiology of Bcc infection after implementation of these infection control measures. Patients attending the Prague CF adult Centre from 2000 to 2015 were included in the present study. Demographic data and microbial statuses were collected from patient records. All Bcc isolates were analyzed using multilocus sequence typing (MLST). The prevalences of epidemic strain ST32 and of other Bcc strains were calculated. Ninety out of 227 CF patients were infected with Bcc during the study period. The prevalence of ST32 cases significantly decreased from 46.5% in 2000-2001 to 10.4% in 2014-2015 (P < 0.001) due to occurrence of only one new case in 2003, as well as to the death of 72% of ST32-infected patients. Conversely, there was a significant increase in prevalence of other Bcc strains, which rose from 0 to 14.9% (P = 0.015) and of transient infections. A micro-epidemic of infection with ST630 strain was observed in 2014 in lung transplant patients hospitalized in intensive care unit. The prevalence of epidemic strain ST32 decreased, whereas that of non-clonal strains of Bcc increased. Routine use of MLST allowed early detection of new and potentially epidemic strains.

PMID: 28364392 [PubMed - as supplied by publisher]

Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics.

J Am Soc Mass Spectrom. 2017 Mar 31;:

Authors: Zang X, Pérez JJ, Jones CM, Monge ME, McCarty NA, Stecenko AA, Fernández FM

Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted. EBC was chosen as the noninvasive surrogate for airway sampling over expectorated sputum as EBC can be collected in all CF subjects regardless of age and lung disease severity. When using pooled EBC collected from a healthy control, ESI detected the most metabolites, APCI a log order less, and TM-DART the least. TM-DART-TWIMS-TOF MS was used to profile metabolites in EBC samples from five healthy controls and four CF patients, finding that a panel of three discriminant EBC metabolites, some of which had been previously detected by other methods, differentiated these two classes with excellent cross-validated accuracy. Graphical Abstract ᅟ.

PMID: 28364225 [PubMed - as supplied by publisher]

Logistic ex Vivo Lung Perfusion for Hyperimmunized Patients.

Ann Thorac Surg. 2016 Sep;102(3):e205-6

Authors: De Wolf J, Puyo P, Bonnette P, Roux A, Le Guen M, Parquin F, Chapelier A, Sage E

Abstract
Hyperimmunized patients have restricted access to lung transplantation because of the low rate of donor lung availability. Sensitization to human leukocyte antigen is associated with acute rejection, allograft dysfunction, and decreased survival. Prospective crossmatching could allow matching a lung graft with the recipient; however, such a strategy would increase graft ischemia, with a worse impact on the long-term results of lung transplantation. We used logistic ex vivo lung perfusion for 3 patients at the Foch Hospital while waiting for a negative result of the prospective crossmatching and then moved forward to lung transplantation. All patients are alive 3 years after bilateral lung transplantation.

PMID: 27549543 [PubMed - indexed for MEDLINE]

Direct monitoring of pulmonary disease treatment biomarkers using plasmonic gold nanorods with diffusion-sensitive OCT.

Nanoscale. 2017 Mar 30;:

Authors: Blackmon RL, Kreda SM, Sears PR, Chapman BS, Hill DB, Tracy JB, Ostrowski LE, Oldenburg AL

Abstract
The solid concentration of pulmonary mucus (wt%) is critical to respiratory health. In patients with respiratory disease, such as Cystic Fibrosis (CF) and Chronic Obstructive Pulmonary Disorder (COPD), mucus hydration is impaired, resulting in high wt%. Mucus with high wt% is a hallmark of pulmonary disease that leads to obstructed airways, inflammation, and infection. Methods to measure mucus hydration in situ and in real-time are needed for drug development and personalized therapy. We employed plasmonic gold nanorod (GNR) biosensors that intermittently collide with macromolecules comprising the mucus mesh as they self-diffuse, such that GNR translational diffusion (DT) is sensitive to wt%. GNRs are attractive candidates for bioprobes due to their anisotropic optical scattering that makes them easily distinguishable from native tissue using polarization-sensitive OCT. Using principles of heterodyne dynamic light scattering, we developed diffusion-sensitive optical coherence tomography (DS-OCT) to spatially-resolve changing DT in real-time. DS-OCT enables, for the first time, direct monitoring of changes in nanoparticle diffusion rates that are sensitive to nanoporosity with spatial and temporal resolutions of 4.7 μm and 0.2 s. DS-OCT therefore enables us to measure spatially-resolved changes in mucus wt% over time. In this study, we demonstrate the applicability of DS-OCT on well-differentiated primary human bronchial epithelial cells during a clinical mucus-hydrating therapy, hypertonic saline treatment (HST), to reveal, for the first time, mucus mixing, cellular secretions, and mucus hydration on the micrometer scale that translate to long-term therapeutic effects.

PMID: 28358158 [PubMed - as supplied by publisher]

Characterization and genome comparisons of three Achromobacter phages of the family Siphoviridae.

Arch Virol. 2017 Mar 29;:

Authors: Dreiseikelmann B, Bunk B, Spröer C, Rohde M, Nimtz M, Wittmann J

Abstract
In this study, we present the characterization and genomic data of three Achromobacter phages belonging to the family Siphoviridae. Phages 83-24, JWX and JWF were isolated from sewage samples in Paris and Braunschweig, respectively, and infect Achromobacter xylosoxidans, an emerging nosocomial pathogen in cystic fibrosis patients. Analysis of morphology and growth parameters revealed that phages 83-24 and JWX have similar properties, both have nearly the same head and tail measurements, and both have a burst size between 85 and 100 pfu/cell. In regard to morphological properties, JWF had a much longer and more flexible tail compared to other phages. The linear double-stranded DNAs of all three phages are terminally redundant and not circularly permutated. The complete nucleotide sequences consist of 81,541 bp for JWF, 49,714 bp for JWX and 48,216 bp for 83-24. Analysis of the genome sequences showed again that phages JWX and 83-24 are quite similar. Comparison to the GenBank database via BLASTN revealed partial similarities to Roseobacter phage RDJL phi1 and Burkholderia phage BcepGomr. In contrast, BLASTN analysis of the genome sequence of phage JWF revealed only few similarities to non-annotated prophage regions in different strains of Burkholderia and Mesorhizobium.

PMID: 28357512 [PubMed - as supplied by publisher]

New approach for cystic fibrosis diagnosis based on chloride/potassium ratio analyzed in non-invasively obtained skin-wipe sweat samples by capillary electrophoresis with contactless conductometric detection.

Anal Bioanal Chem. 2017 Mar 29;:

Authors: Ďurč P, Foret F, Pokojová E, Homola L, Skřičková J, Herout V, Dastych M, Vinohradská H, Kubáň P

Abstract
A new approach for sweat analysis used in cystic fibrosis (CF) diagnosis is proposed. It consists of a noninvasive skin-wipe sampling followed by analysis of target ions using capillary electrophoresis with contactless conductometric detection (C4D). The skin-wipe sampling consists of wiping a defined skin area with precleaned cotton swab moistened with 100 μL deionized water. The skin-wipe sample is then extracted for 3 min into 400 μL deionized water, and the extract is analyzed directly. The developed sampling method is cheap, simple, fast, and painless, and can replace the conventional pilocarpine-induced sweat chloride test commonly applied in CF diagnosis. The aqueous extract of the skin-wipe sample content is analyzed simultaneously by capillary electrophoresis with contactless conductometric detection using a double opposite end injection. A 20 mmol/L L-histidine/2-(N-morpholino)ethanesulfonic acid and 2 mmol/L 18-crown-6 at pH 6 electrolyte can separate all the major ions in less than 7 min. Skin-wipe sample extracts from 30 study participants-ten adult patients with CF (25-50 years old), ten pediatric patients with CF (1-15 years old), and ten healthy control individuals (1-18 years old)-were obtained and analyzed. From the analyzed ions in all samples, a significant difference between chloride and potassium concentrations was found in the CF patients and healthy controls. We propose the use of the Cl(-)/K(+) ratio rather than the absolute Cl(-) concentration and a cutoff value of 4 in skin-wipe sample extracts as an alternative to the conventional sweat chloride analysis. The proposed Cl(-)/K(+) ion ratio proved to be a more reliable indicator, is independent of the patient's age, and allows better differentiation between non-CF individuals and CF patients having intermediate values on the Cl(-) sweat test. Figure New approach for cystic fibrosis diagnosis based on skin-wipe sampling of forearm and analysis of ionic content (Cl(-)/K(+) ratio) in skin-wipe extracts by capillary electrophoresis with contactless conductometric detection.

PMID: 28357484 [PubMed - as supplied by publisher]

Effect of Anaerobiasis or Hypoxia on Pseudomonas aeruginosa Inhibition of Aspergillus fumigatus Biofilm.

Arch Microbiol. 2017 Mar 29;:

Authors: Anand R, Clemons KV, Stevens DA

Abstract
Pseudomonas aeruginosa (Pa) and Aspergillus fumigatus (Af) are the major bacterial and fungal pathogens in the airways of cystic fibrosis (CF) patients. This is likely related to their ability to form biofilms. Both microbes have been associated with CF disease progression. The interplay between these two pathogens has been studied under aerobic conditions, though accumulating data indicates that much of the CF airway is hypoxic or anaerobic. We studied the microbial interaction in these latter environments. Pa is an aggressor against Af forming biofilm or as established Af biofilm, whether Pa is cultivated in aerobic, hypoxic, or anaerobic conditions, or tested in aerobic or hypoxic conditions. Pa cells are generally more effective than planktonic or biofilm culture filtrates. Pa growth is less in anaerobic conditions, and filtrates less effective after anaerobic or hypoxic growth, or against hypoxic Af. These, and other comparisons shown, indicate that Pa would be less effective in such environments, as would be the case in a CF mucus plug. These observations would explain why Pa becomes established in CF airways before Af, and why Af may persist during disease progression.

PMID: 28357473 [PubMed - as supplied by publisher]

Concordance between upper and lower airway microbiota in infants with cystic fibrosis.

Eur Respir J. 2017 Mar;49(3):

Authors: Prevaes SM, de Steenhuijsen Piters WA, de Winter-de Groot KM, Janssens HM, Tramper-Stranders GA, Chu ML, Tiddens HA, van Westreenen M, van der Ent CK, Sanders EA, Bogaert D

Abstract
Nasopharyngeal and oropharyngeal samples are commonly used to direct therapy for lower respiratory tract infections in non-expectorating infants with cystic fibrosis (CF).We aimed to investigate the concordance between the bacterial community compositions of 25 sets of nasopharyngeal, oropharyngeal and bronchoalveolar lavage (BAL) samples from 17 infants with CF aged ∼5 months (n=13) and ∼12 months (n=12) using conventional culturing and 16S-rRNA sequencing.Clustering analyses demonstrated that BAL microbiota profiles were in general characterised by a mixture of oral and nasopharyngeal bacteria, including commensals like Streptococcus, Neisseria, Veillonella and Rothia spp. and potential pathogens like Staphylococcus aureus, Haemophilus influenzae and Moraxella spp. Within each individual, however, the degree of concordance differed between microbiota of both upper respiratory tract niches and the corresponding BAL.The inconsistent intra-individual concordance between microbiota of the upper and lower respiratory niches suggests that the lungs of infants with CF may have their own microbiome that seems seeded by, but is not identical to, the upper respiratory tract microbiome.

PMID: 28356374 [PubMed - in process]

Production and characterization of a PEGylated derivative of recombinant human deoxyribonuclease I for cystic fibrosis therapy.

Int J Pharm. 2017 Mar 26;:

Authors: Guichard MJ, Patil HP, Koussoroplis SJ, Wattiez R, Leal T, Vanbever R

Abstract
Recombinant human deoxyribonuclease I (rhDNase) is the mucolytic agent most widely used for the treatment of respiratory disease in cystic fibrosis. However, rhDNase is rapidly cleared from the lungs which implies a high dosing frequency and limited patient adherence. The aim of this study was to produce a long-acting PEGylated derivative of rhDNase presenting a preserved enzymatic activity. Site-specific PEGylation on the N-terminal (N-ter) leucine residue of rhDNase was achieved by reductive alkylation at acidic pH using linear 20kDa, linear 30kDa or two-arm 40kDa polyethylene glycol (PEG) propionaldehydes. Yields of mono-PEGylated products ranged between 45% and 61%. Conjugation to PEG fully preserved the secondary structure and the in vitro enzymatic activity of the native protein. These properties offer interesting perspectives for in vivo inhalation studies of the PEGylated enzyme.

PMID: 28356227 [PubMed - as supplied by publisher]

Archibald Percy Norman.

BMJ. 2017 Jan 19;356:j312

Authors: Watts G

PMID: 28104584 [PubMed - indexed for MEDLINE]

Defective postsecretory maturation of MUC5B mucin in cystic fibrosis airways.

JCI Insight. 2017 Mar 23;2(6):e89752

Authors: Abdullah LH, Evans JR, Wang TT, Ford AA, Makhov AM, Nguyen K, Coakley RD, Griffith JD, Davis CW, Ballard ST, Kesimer M

Abstract
In cystic fibrosis (CF), airway mucus becomes thick and viscous, and its clearance from the airways is impaired. The gel-forming mucins undergo an ordered "unpacking/maturation" process after granular release that requires an optimum postsecretory environment, including hydration and pH. We hypothesized that this unpacking process is compromised in the CF lung due to abnormal transepithelial fluid transport that reduces airway surface hydration and alters ionic composition. Using human tracheobronchial epithelial cells derived from non-CF and CF donors and mucus samples from human subjects and domestic pigs, we investigated the process of postsecretory mucin unfolding/maturation, how these processes are defective in CF airways, and the probable mechanism underlying defective unfolding. First, we found that mucins released into a normal lung environment transform from a compact granular form to a linear form. Second, we demonstrated that this maturation process is defective in the CF airway environment. Finally, we demonstrated that independent of HCO3(-) and pH levels, airway surface dehydration was the major determinant of this abnormal unfolding process. This defective unfolding/maturation process after granular release suggests that the CF extracellular environment is ion/water depleted and likely contributes to abnormal mucus properties in CF airways prior to infection and inflammation.

PMID: 28352653 [PubMed - in process]

Commentary on "Autogenic Drainage in Children With Cystic Fibrosis".

Pediatr Phys Ther. 2017 Apr;29(2):117

Authors: Swisher AK, von Berg K

PMID: 28350763 [PubMed - in process]

SERS detection of the biomarker hydrogen cyanide from Pseudomonas aeruginosa cultures isolated from cystic fibrosis patients.

Sci Rep. 2017 Mar 28;7:45264

Authors: Lauridsen RK, Sommer LM, Johansen HK, Rindzevicius T, Molin S, Jelsbak L, Engelsen SB, Boisen A

Abstract
Pseudomonas aeruginosa is the primary cause of chronic airway infections in cystic fibrosis (CF) patients. Persistent infections are seen from the first P. aeruginosa culture in about 75% of young CF patients, and it is important to discover new ways to detect P. aeruginosa at an earlier stage. The P. aeruginosa biomarker hydrogen cyanide (HCN) contains a triple bond, which is utilized in this study because of the resulting characteristic C≡N peak at 2135 cm(-1) in a Raman spectrum. The Raman signal was enhanced by surface-enhanced Raman spectroscopy (SERS) on a Au-coated SERS substrate. After long-term infection, a mutation in the patho-adaptive lasR gene can alter the expression of HCN, which is why it is sometimes not possible to detect HCN in the breath of chronically infected patients. Four P. aeruginosa reference strains and 12 clinical P. aeruginosa strains isolated from CF children were evaluated, and HCN was clearly detected from overnight cultures of all wild type-like isolates and half of the later isolates from the same patients. The clinical impact could be that P. aeruginosa infections could be detected at an earlier stage, because daily breath sampling with an immediate output could be possible with a point-of-care SERS device.

PMID: 28349938 [PubMed - in process]

Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.

Cochrane Database Syst Rev. 2017 Mar 27;3:CD002009

Authors: Smyth AR, Bhatt J, Nevitt SJ

Abstract
BACKGROUND: People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review.
OBJECTIVES: To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis.
SEARCH METHODS: We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 24 June 2016.
SELECTION CRITERIA: All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS: The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies.
MAIN RESULTS: Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was no significant difference between treatment groups in: forced expiratory volume in one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48, moderate quality evidence); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16, low quality evidence); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13, low quality evidence); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42, low quality evidence); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96, moderate quality evidence). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08, moderate quality evidence), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33, moderate quality evidence). The included trials did not report antibiotic resistance patterns or quality of life.
AUTHORS' CONCLUSIONS: Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.

PMID: 28349527 [PubMed - as supplied by publisher]

Response to 'Refined analyses suggest that recombination is a minor source of genomic diversity in Pseudomonas aeruginosa chronic cystic fibrosis infections' by ).

Microb Genom. 2016 Mar;2(3):e000054

Authors: Darch SE, McNally A, Corander J, Diggle SP

PMID: 28348849 [PubMed - in process]

Refined analyses suggest that recombination is a minor source of genomic diversity in Pseudomonas aeruginosa chronic cystic fibrosis infections.

Microb Genom. 2016 Mar;2(3):e000051

Authors: Williams D, Paterson S, Brockhurst MA, Winstanley C

Abstract
Chronic bacterial airway infections in people with cystic fibrosis (CF) are often caused by Pseudomonas aeruginosa, typically showing high phenotypic diversity amongst co-isolates from the same sputum sample. Whilst adaptive evolution during chronic infections has been reported, the genetic mechanisms underlying the observed rapid within-population diversification are not well understood. Two recent conflicting reports described very high and low rates of homologous recombination in two closely related P. aeruginosa populations from the lungs of different chronically infected CF patients. To investigate the underlying cause of these contrasting observations, we combined the short read datasets from both studies and applied a new comparative analysis. We inferred low rates of recombination in both populations. The discrepancy in the findings of the two previous studies can be explained by differences in the application of variant calling techniques. Two novel algorithms were developed that filter false-positive variants. The first algorithm filters variants on the basis of ambiguity within duplications in the reference genome. The second omits probable false-positive variants at regions of non-homology between reference and sample caused by structural rearrangements. As gains and losses of prophage or genomic islands are frequent causes of chromosomal rearrangements within microbial populations, this filter has broad appeal for mitigating false-positive variant calls. Both algorithms are available in a Python package.

PMID: 28348847 [PubMed - in process]

Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of Cystic Fibrosis.

Chem Sci. 2017 Jan 01;8(1):550-558

Authors: Kim JP, Xie Z, Creer M, Liu Z, Yang J

Abstract
Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.

PMID: 28348728 [PubMed - in process]

Potential effect of centre size on continuity of care and healthcare performance.

BMJ. 2017 Mar 27;356:j1514

Authors: Hoo ZH, Curley RE, Wildman MJ

PMID: 28348139 [PubMed - in process]

HOST IMMUNE RECOGNITION OF THE EPIDEMIC CYSTIC FIBROSIS PATHOGEN BURKHOLDERIA DOLOSA.

Infect Immun. 2017 Mar 27;:

Authors: Roux D, Weatherholt M, Clark B, Gadjeva M, Renaud D, Scott D, Skurnik D, Priebe GP, Pier G, Gerard C, Yoder-Himes DR

Abstract
Burkholderia dolosa caused an outbreak in the cystic fibrosis (CF) clinic at Boston Children's Hospital from 1998 to 2005 and led to the infection of over 40 patients, many of whom died due to complications from infection by this organism. To assess whether B. dolosa significantly contributes to disease or is recognized by the host immune response, mice were infected with a sequenced outbreak B. dolosa strain, AU0158, and responses compared to the well-studied CF pathogen, Pseudomonas aeruginosa In parallel, mice were also infected with a polar flagellin mutant of B. dolosa to examine the role of flagella in B. dolosa lung colonization. The results showed a higher persistence in the host by B. dolosa strains and yet neutrophil recruitment and cytokine production were lower compared to P. aeruginosa The ability of host immune cells to recognize B. dolosa was then assessed and B. dolosa induced a robust cytokine response in cultured cells and this effect was dependent on the flagella only when bacteria were dead. Together, these results suggest that B. dolosa can be recognized by host cells in vitro but may avoid or suppress the host immune response in vivo through unknown mechanisms. B. dolosa was then compared to other Burkholderia species and found to induce similar levels of cytokine production despite being internalized by macrophages more than B. cenocepacia strains. These data suggest that B. dolosa AU0158 may act differently with host cells and is it recognized differently by immune systems compared other Burkholderia strains or species.

PMID: 28348057 [PubMed - as supplied by publisher]