Novel mutations and deletions in cystic fibrosis in a tertiary cystic fibrosis center in Istanbul.

Pediatr Pulmonol. 2019 Apr 02;:

Authors: Atag E, Bas Ikizoglu N, Ergenekon AP, Gokdemir Y, Eralp EE, Ata P, Ersu R, Karakoc F, Karadag B

Abstract
BACKGROUND: Cystic fibrosis (CF) genotyping has garnered increased attention since the discovery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 1989 led to the identification of over 1700 mutations on chromosome 7. Yet, little is known about the genetic profile of CF patients in Turkey. This study sought to determine the mutation distribution among CF patients seeking care at Marmara University.
METHODS: Two hundred fifty previously diagnosed CF patients were included in the study. CFTR gene exons 1 to 27 were amplified by a polymerase chain reaction and whole DNA sequencing was performed. Duplications and deletions were investigated by the multiplex ligation-dependent probe amplification (MLPA) technique in patients with one or two unidentified mutations in sequence analysis.
RESULTS: CFTR mutation analysis revealed 80 mutations and five large deletions were present in our study population. The five most common mutations were (delta) F508 (c.1521-1523delCTT) (28.4%), 1677delTA (c.1545-1546delTA) (6.4%), 2789 + 5G- > A (c.2657 + 5G > A) (5.8%), N1303K (c.3909C > G) (2.4%), and c.2183AA- > G (c.2051-2052delAAinsG) (4.0%). Large deletions were found in 16 patients. Four novel mutations and two novel deletions were detected in this study.
CONCLUSIONS: We have identified four novel mutations and two novel deletions using next-generation DNA sequencing and the MLPA technique and obtained an overall mutation detection rate of 91.4%. Detection of novel variants in CF patients will assist in genetic counseling and in determining appropriate patients for new therapies.

PMID: 30938940 [PubMed - as supplied by publisher]

Nonsystemic allergic bronchopulmonary aspergillosis in cystic fibrosis: A suggested paradigm for the evolution from topical to systemic disease.

Pediatr Pulmonol. 2019 Apr 01;:

Authors: Miranda C, Cardenas M, Bedoya M, Retsch-Bogart G, Colin AA

PMID: 30938080 [PubMed - as supplied by publisher]

Identification of a lytic Pseudomonas aeruginosa phage depolymerase and its anti-biofilm effect and bactericidal contribution to serum.

Virus Genes. 2019 Apr 01;:

Authors: Mi L, Liu Y, Wang C, He T, Gao S, Xing S, Huang Y, Fan H, Zhang X, Yu W, Mi Z, Tong Y, Bai C, Han F

Abstract
Pseudomonas aeruginosa (P. aeruginosa) infection has imposed a great threat to patients with cystic fibrosis. With the emergence of multidrug-resistant P. aeruginosa, developing an alternative anti-microbial strategy is indispensable and more urgent than ever. In this study, a lytic P. aeruginosa phage was isolated from the sewage of a hospital, and one protein was predicted as the depolymerase-like protein by genomic sequence analysis, it includes two catalytic regions, the Pectate lyase_3 super family and Glycosyl hydrolase_28 super family. Further analysis demonstrated that recombinant depolymerase-like protein degraded P. aeruginosa exopolysaccharide and enhanced bactericidal activity mediated by serum in vitro. Additionally, this protein disrupted host bacterial biofilms. All of these results showed that the phage-derived depolymerase-like protein has the potential to be developed into an anti-microbial agent that targets P. aeruginosa.

PMID: 30937696 [PubMed - as supplied by publisher]

Shadow cost of oral corticosteroids-related adverse events: A pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry.

World Allergy Organ J. 2019;12(1):100007

Authors: Canonica GW, Colombo GL, Bruno GM, Di Matteo S, Martinotti C, Blasi F, Bucca C, Crimi N, Paggiaro P, Pelaia G, Passalaqua G, Senna G, Heffler E, SANI Network

Abstract
Background: Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry.
Methods: The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication.
Results: Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%.Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown.
Conclusions: Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs.

PMID: 30937132 [PubMed]

Resistance to leukocytes ties benefits of quorum sensing dysfunctionality to biofilm infection.

Nat Microbiol. 2019 Apr 01;:

Authors: He L, Le KY, Khan BA, Nguyen TH, Hunt RL, Bae JS, Kabat J, Zheng Y, Cheung GYC, Li M, Otto M

Abstract
Social interactions play an increasingly recognized key role in bacterial physiology1. One of the best studied is quorum sensing (QS), a mechanism by which bacteria sense and respond to the status of cell density2. While QS is generally deemed crucial for bacterial survival, QS-dysfunctional mutants frequently arise in in vitro culture. This has been explained by the fitness cost an individual mutant, a 'quorum cheater', saves at the expense of the community3. QS mutants are also often isolated from biofilm-associated infections, including cystic fibrosis lung infection4, as well as medical device infection and associated bacteraemia5-7. However, despite the frequently proposed use of QS blockers to control virulence8, the mechanisms underlying QS dysfunctionality during infection have remained poorly understood. Here, we show that in the major human pathogen Staphylococcus aureus, quorum cheaters arise exclusively in biofilm infection, while in non-biofilm-associated infection there is a high selective pressure to maintain QS control. We demonstrate that this infection-type dependence is due to QS-dysfunctional bacteria having a significant survival advantage in biofilm infection because they form dense and enlarged biofilms that provide resistance to phagocyte attacks. Our results link the benefit of QS-dysfunctional mutants in vivo to biofilm-mediated immune evasion, thus to mechanisms that are specific to the in vivo setting. Our findings explain why QS mutants are frequently isolated from biofilm-associated infections and provide guidance for the therapeutic application of QS blockers.

PMID: 30936487 [PubMed - as supplied by publisher]

Nanometric ion pair complexes of tobramycin forming microparticles for the treatment of Pseudomonas aeruginosa infections in cystic fibrosis.

Int J Pharm. 2019 Mar 29;:

Authors: Sardo C, Di Domenico EG, Porsio B, De Rocco D, Santucci R, Ascenzioni F, Giammona G, Cavallaro G

Abstract
Sustained pulmonary delivery of tobramycin from microparticles composed of drug/ polymer nanocomplexes offers several advantages against traditional delivery methods. Namely, in patients with cystic fibrosis, microparticle delivery can protect the tobramycin being delivered from strong mucoadhesive interactions, thus avoiding effects on its diffusion toward the infection site. Polymeric ion-pair complexes were obtained starting from two synthetic polyanions, through impregnation of their solid dissociated forms with tobramycin in aqueous solution. The structure of these polymeric systems was characterized, and their activities were examined against various biofilm-forming Pseudomonas aeruginosa. Once dried, the nanocomplexes can change their aggregation state, to form microparticle-based aggregates with a spherical shape and a micrometer size. In aqueous dispersions, the ion-pair complexes produced had nanometric size, negative ζ potential, and high biocompatibility toward human bronchial epithelium cells. The antibiofilm activity of these formulations was more efficient than for free tobramycin, with the antibiofilm activity against P. aeruginosa mucoid and nonmucoid end-stage strains isolated from cystic fibrosis lungs being of particular relevance.

PMID: 30935918 [PubMed - as supplied by publisher]

Mycobacterium bolletii lung disease in cystic fibrosis.

Chest. 2019 Mar 29;:

Authors: Rollet-Cohen V, Roux AL, Le Bourgeois M, Sapriel G, El Bahri M, Jais JP, Heym B, Mougari F, Raskine L, Véziris N, Gaillard JL, Sermet-Gaudelus I

Abstract
BACKGROUND: The cystic fibrosis (CF) pathogen, Mycobacterium abscessus complex, covers three "subspecies": "M. abscessus", "M. massiliense", and "M. bolletii". There are no clinical outcome data concerning M. bolletii. Our aim was to characterize M. bolletii lung infections in CF patients.
METHODS: We included cases of M. bolletii lung infection recorded between 1994 and 2012 in France. Data were collected from the CF registry, medical records, and questionnaires submitted to the CF primary physician. Strains were typed by Multilocus Sequence Typing (MLST) analysis.
RESULTS: Fifteen cases were identified in nine CF centers. Nine patients (60%) presented with nontuberculous mycobacteria pulmonary disease (NTM-PD). Follow up of 13 patients showed a trend to a more rapid decline in FEV1 the first year of colonization (-9.4% (19.3)) in comparison to non-infected controls (-2.3% (12.1); p=0.16). Twelve patients were treated, and 11 received oral macrolides. Treatment-induced eradication occured in 5 patients (41.7%). Four patients died (26.7%), including 1 case of fatal NTM-PD. Inducible macrolide resistance was demonstrated in all strains. Patients always harbored unique strains..
CONCLUSION: Our study reports the largest study cohort of CF patients infected with M. bolletii. M bolletii infection affects both children and young adults, is most often symptomatic and may be fatal. Macrolide-based therapies have poor effectiveness. There is no evidence of patient-to-patient transmission.

PMID: 30935892 [PubMed - as supplied by publisher]

The impact of cystic fibrosis-related diabetes on health-related quality of life.

J Cyst Fibros. 2019 Mar 29;:

Authors: Kwong E, Desai S, Chong L, Lee K, Zheng J, Wilcox PG, Quon BS

Abstract
Cystic fibrosis-related diabetes (CFRD) is a well-known comorbidity among the CF population. To investigate whether CFRD impacts health-related quality of life (HRQoL), domain scores from the Cystic Fibrosis Questionnaire-Revised for adolescents and adults over 14 years old (CFQ-R 14+) were compared between CF individuals with CFRD on insulin, CFRD not on insulin, impaired glucose tolerance, and normal blood glucose tolerance. The median score for the Treatment Burden domain was significantly worse for individuals with CFRD on insulin (p < 0.001) compared to the other diagnostic groups, and this association remained significant following adjustment for confounding variables. In conclusion, the additional requirement for insulin significantly contributes to treatment burden in adults with CFRD and therefore novel strategies to reduce treatment burden for this group are urgently needed.

PMID: 30935840 [PubMed - as supplied by publisher]

Meconium Ileus in Two Irish Newborns: The Presenting Feature of Cystic Fibrosis

Ir Med J. 2019 Mar 14;112(3):901

Authors: Smith A, Ryan E, O’Keeffe D, O’Donovan D

Abstract
Introduction Meconium Ileus (MI) is the presenting feature of CF in approximately 10-15% of cases. This report outlines the clinical presentation, imaging and management of two neonates with MI and subsequent diagnosis of Cystic Fibrosis (CF). Methods A retrospective chart review was performed to evaluate the clinical course of two neonates with MI. Results Case 1 and 2 presented clinically with signs of abdominal obstruction. Subsequent laparotomies confirmed MI. MI is strongly associated with CF and CF is the most common genetically inherited disease in Ireland. Genetic testing was positive for a homozygous ∆ F508 mutation in both case 1 and 2, securing a diagnosis of MI secondary to CF. Conclusion Our cases highlight that all infants born in Ireland with MI should be considered as CF positive until proven otherwise.

PMID: 30932447 [PubMed - as supplied by publisher]

Pressure gradients, laboratory changes, and outcomes with transjugular intrahepatic portosystemic shunts in pediatric portal hypertension.

Pediatr Transplant. 2019 Apr 01;:e13387

Authors: Slowik V, Monroe EJ, Friedman SD, Hsu EK, Horslen S

Abstract
INTRODUCTION: Indications for TIPS are well described in adults and involve complications of PHTN. Complications from PHTN are associated with PSG of > 12 mm Hg in adults. It is unclear if these parameters apply to children with PHTN.
OBJECTIVE: To assess whether adult criteria for TIPS placement can be utilized in children, describe laboratory changes over time, and report outcomes.
METHODS: We performed a retrospective review of 34 pediatric patients who underwent TIPS, examining indications, radiology, PSG reductions, laboratory changes, and outcomes.
RESULTS: Most patients had PHTN due to parenchymal liver disease including congenital hepatic fibrosis (n = 5), biliary atresia (n = 5), cystic fibrosis-related liver disease (n = 3) and cavernous transformation of the portal vein (n = 6). Indications for TIPS included variceal bleeding, recurrent ascites, and maintenance of portal vein flow following thrombolysis. Variceal bleeding was observed in six children with PSG < 12 mm Hg. Minor complications occurred in eight subjects. Continued bleeding occurred in one patient. Six patients were successfully bridged to transplantation, and three patients died secondary to end-stage disease. Standard laboratory tests stabilized after TIPS placement and hematocrit increased.
CONCLUSION: TIPS placement in pediatric patients was performed for complications of PHTN. Unlike adult series, a substantial proportion of our cases treated extrahepatic PHTN from cavernous transformation of the portal vein. Children presented with sequelae of PHTN with PSG below 12 mm Hg, below the adult standard. We found TIPS in pediatrics to be safe and effective with laboratory stabilization and improvement in hematocrit.

PMID: 30932316 [PubMed - as supplied by publisher]

Quality of Life and Impact of Endoscopic Sinus Surgery in Adult Patients With Cystic Fibrosis.

Am J Rhinol Allergy. 2019 Apr 01;:1945892419839260

Authors: Lazio MS, Luparello P, Mannelli G, Santoro GP, Bresci S, Braggion C, Gallo O, Maggiore G

Abstract
BACKGROUND: Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasian population. Due to its pathological mechanism, chronic rhino sinusitis (CRS) associated or not with nasal polyposis usually occurs in adults and affects close to one-half of all CF patients. The goal of our work was to evaluate the impact of endoscopic sinus surgery (ESS) in the quality of life (QoL) of the CF patients and demonstrate an improvement of the functional outcomes in the patients undergoing the surgical procedure rather than in the not treated ones. Methodology: We studied 54 adult patients affected by CF. Lund-Kennedy, Lund-Mackay scores, and Sino-Nasal Outcome Test-22 (SNOT-22) were analyzed.
RESULTS: Twenty-two (40.7%) of the 54 CF patients underwent ESS. This group presented more likely complaints consistent with CRS. Lund-Kennedy and Lund-Mackay scores appeared higher in the ESS group: 10 (range of 6-12) and 16 (range of 12-20), respectively. SNOT-22 showed median values for non-ESS and ESS group of 17.5 (range of 3-68) and 44 (range of 10-73), respectively.
CONCLUSIONS: ESS represents the best option to improve clinical QoL of CF patients who do not response to conventional medical therapy.

PMID: 30931587 [PubMed - as supplied by publisher]

The moral status of cerebral organoids.

Regen Ther. 2019 Jun;10:118-122

Authors: Hostiuc S, Rusu MC, Negoi I, Perlea P, Dorobanţu B, Drima E

Abstract
Organoids are 3D biological structures constructed from stem cells in vitro. They partially mimic the function of real organs. Although the number of articles detailing this technology has increased in recent years, papers debating their ethical issues are few. In addition, many of such articles outline a mere summary of potential ethical concerns associated with organoids, although some have focused on consciousness assessment or organoid use in cystic fibrosis treatment. This article seeks to evaluate the moral status of cerebral organoids and to determine under which conditions their use should be allowed from a bioethical standpoint. We will present an overview of recent steps in developing highly advanced cerebral organoids, followed by an analysis of their ethics based on three factors: human origin, a specific biological threshold (which, once crossed, grants an entity moral status), and the potential to generate human beings. We will also make practical recommendations for researchers working in this biological field.

PMID: 30931367 [PubMed]

Response to the Letter to the Editor From Dr. Boudreau et al, "Validation of a Stepwise Approach Using Glycated Hemoglobin Levels to Reduce the Number of Required Oral Glucose Tolerance Tests to Screen for Cystic Fibrosis-Related Diabetes in Adults".

Can J Diabetes. 2019 Apr;43(3):163

Authors: Gilmour JA

PMID: 30929664 [PubMed - in process]

Safety and efficacy of treatment with lumacaftor in combination with ivacaftor in younger patients with cystic fibrosis.

Expert Rev Respir Med. 2019 Mar 30;:

Authors: Cheng PC, Alexiou S, Rubenstein RC

Abstract
INTRODUCTION: Cystic fibrosis (CF) is the most common autosomal recessive disorder affecting approximately 70,000 people worldwide. The lack of functional cystic fibrosis transmembrane conductance regulator (CFTR) causes dysregulation of epithelial fluid transport in the lungs, gastrointestinal tract, and sweat glands. Areas covered: The most common disease-causing CFTR mutation, F508del, is present in nearly 75% of those affected and results in a defective protein. Therapies to improve the function of this mutant protein have the promise to reduce morbidity and mortality in the majority of patients with CF. The combination of lumacaftor, which corrects the aberrant intracellular trafficking of F508del, and ivacaftor, which potentiates CFTR function, is known as OrkambiTM, and is the first drug approved for the treatment of cystic fibrosis (CF) in patients who are homozygous for F508del. OrkambiTM is currently approved for use in children aged 2 and older based on recent data from open-label Phase 3 clinical safety studies. In older patients, treatment with lumacaftor/ivacaftor is associated with a modest, statistically significant improvement in lung function and reduced pulmonary exacerbations in placebo-controlled trials; these findings are also observed in Phase IV observational studies. While severe side effects are rare, chest tightness, elevation of transaminases, and cataracts have been reported and recommendations for monitoring have been established. Expert opinion: OrkambiTM somewhat improves clinical outcomes for people with CF who are homozygous for the F508del mutation, and does so with a reasonable safety profile. This therapy represents a major advance in the therapy for CF, but further advances are needed, perhaps with addition of a third agent to this combination small molecule therapy, in order to expand both the targeted population and beneficial effects.

PMID: 30929526 [PubMed - as supplied by publisher]

Another step in the journey: From CFTR mutation to sweat chloride concentration to survival.

J Cyst Fibros. 2018 01;17(1):3-4

Authors: VanDevanter DR, Mayer-Hamblett N

PMID: 29198838 [PubMed - indexed for MEDLINE]

Exercise and its varied impact on airway dynamics.

J Cyst Fibros. 2018 01;17(1):e5

Authors: Stevens D

PMID: 28784288 [PubMed - indexed for MEDLINE]

Markers of bone turnover are reduced in patients with CF related diabetes; the role of glucose.

J Cyst Fibros. 2019 Mar 27;:

Authors: Mathiesen IH, Hitz MF, Katzenstein TL, Oturai P, Skov M, Jørgensen NR, Jensen PO, Mikkelsen CR, Krogh-Madsen R, Pressler T, Faurholt-Jepsen D

Abstract
BACKGROUND: Cystic fibrosis(CF) related diabetes(CFRD) and osteoporosis are prevalent in adult patients with CF. We aimed to evaluate if CFRD and markers of glucose metabolism and inflammation are associated with bone turnover in CF.
METHODS: Cross sectional study at the adult section at the Copenhagen CF Center from January-October 2017. Fasting blood samples, including bone turnover markers(BTMs) and cytokines, Dual-x-ray absorptiometry scan and oral glucose tolerance test were performed. Lung-transplanted participants and patients in antiosteoporotic treatment were excluded from analyses.
RESULTS: 102 patients were included of whom 19 had a prior CFRD diagnosis. CFRD patients had lower procollagen type 1 N-terminal propeptide(P1NP) and C-Terminal cross-linked Telopeptide(CTX) levels compared to CF patients without diabetes (median[IQR]) 49.5 μg/l [29.6,57.1] vs 56.9 μg/l [38.2,74.3], p = .03 and 0.2 μg/l [0.1,0.3] vs 0.4 μg/l [0.3,0.6], p < .01, respectively. Fasting plasma glucose(FPG) was negatively associated with the bone formation markers P1NP and osteocalcin and bone resorption marker CTX. In multivariate linear regression FPG remained a significant predictor of P1NP -1.07 [-1.09;-0.01] and CTX -1.13 [-1.21;-1.06]. Bone mineral density Z-score was not different between patients with and without CFRD but FPG was negatively associated with hip and femoral neck Z-score. There was no consistent association between inflammatory cytokines and BTMs.
CONCLUSIONS: Bone turnover markers are reduced in CF patients with CFRD and negatively associated with glucose levels. Extra attention towards frequent hyperglycemia in CF patients should be taken when evaluating decreased BMD. Glycemia may be a future target for improving outcome in CFBD.

PMID: 30928333 [PubMed - as supplied by publisher]

Childbearing concerns, information needs and preferences of women with cystic fibrosis: An online discussion group.

Sex Reprod Healthc. 2019 Mar;19:31-35

Authors: Holton S, Fisher J, Button B, Williams E, Wilson J

Abstract
OBJECTIVE: The life expectancy of women with cystic fibrosis (CF) has increased, enabling many to reach reproductive age. However, little is known about the childbearing concerns and information needs of women with CF or their preferences for information about the effect of their condition and its treatment on childbearing. The aim of this study was to identify the childbearing concerns and related information needs and preferences of women with CF.
METHODS: To ensure access to a diverse group of women with CF throughout Australia and to minimise the risk of cross infection, an online group was advertised and convened on Facebook from October through December 2017. In a closed-group moderated discussion, participants responded to questions about childbearing concerns and the related information needs and preferences of women with CF. Non-identifiable demographic information was sought via an online anonymous survey. The discussion transcript was analysed thematically.
RESULTS: Participants (n = 11) identified a number of concerns about childbearing including uncertainty about whether to have children; achieving or maintaining a pregnancy and giving birth; treatment and treatment adherence during pregnancy, breastfeeding and motherhood; and the impact of pregnancy and childbirth on future health. Women wanted information about childbearing as it related to their CF but reported difficulties accessing up-to-date accurate relevant information.
CONCLUSIONS: Women with CF want to be better informed about childbearing, and identified a need for personalised information as well as regular reviews with their CF treating team so that they can make informed decisions about having children.

PMID: 30928132 [PubMed - in process]

Alginate Lyase Immobilized Chitosan Nanoparticles of Ciprofloxacin for the improved antimicrobial activity against the Biofilm associated mucoid P. aeruginosa infection in Cystic Fibrosis.

Int J Pharm. 2019 Mar 26;:

Authors: Patel KK, Tripathi M, Pandey N, Agrawal AK, Gade S, Anjum M, Tilak R, Singh S

Abstract
Dense colonization of mucoid Pseudomonas aeruginosa within the self-secreted extracellular matrix (mainly alginate), called biofilm, is a principal reason for the failure of antimicrobial therapy in cystic fibrotic patients. Alginate is a key component in the biofilm of mucoid P. aeruginosa and responsible for surface adhesion and stabilization of biofilm. To overcome this problem, alginate lyase functionalized chitosan nanoparticles of ciprofloxacin were developed for the effective treatment of P. aeruginosa infection in cystic fibrosis patients. The developed nanoparticles were found to have desired quality attributes and demonstrated sustained release following the Higuchi release kinetics. Drug compatibility with the chitosan was confirmed by FTIR while powder X-ray diffraction analysis confirmed the entrapment of drug within the nanoparticle matrix. Lactose adsorbed NPs showed promising aerodynamic property. Nanoparticles showed prolonged MIC and significant reduction in biofilm aggregation and formation in planktonic bacterial suspension. Nanoparticles exhibited significantly higher inhibitory effect against biofilm of P. aeruginosa and reduced the biomass, thickness and density confirmed by confocal microscopy. Furthermore, developed nanoparticles were haemocompatible and did not exhibit any toxicity in vitro MTT assay and in vivo on lungs male Wistar rats. The data in hand collectively suggest the proposed strategy a better alternative for the effective treatment of cystic fibrosis infections.

PMID: 30926526 [PubMed - as supplied by publisher]

Aligning patients' needs and research priorities towards a comprehensive CF research program.

J Cyst Fibros. 2019 Mar 26;:

Authors: Noordhoek JJ, Gulmans VAM, Heijerman HGM, van der Ent CK

Abstract
The Dutch CF Foundation started to focus on scientific research thirteen years ago. The patient organization defined the patients perspective and unmet needs bottom-up, and through a structured process. The patients research priorities were matched with the research priorities of Dutch basic scientists and clinicians. The Dutch patient organization facilitated the process, in which mutual dependency between patients, scientists and clinicians is the keyword. The, at that time initiated dialogue, maintained. Subsequently a research program called "HIT CF" was composed and executed over five years. HIT CF was financially supported mainly by the patient community and some other stakeholders.

PMID: 30926323 [PubMed - as supplied by publisher]