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Cystic fibrosis [keywords]
- Development of a multiple-locus variable-number tandem repeat (VNTR) typing scheme for genetic fingerprinting of Burkholderia cenocepacia and application to nation-wide epidemiological analysis. [JOURNAL ARTICLE]
- J Clin Microbiol 2014 Nov 19.
Burkholderia cepacia complex organisms are especially important pathogens in cystic fibrosis (CF), with a propensity for patient-to-patient spread and long-term respiratory colonization. B. cenocepacia and B. multivorans account for the majority of infections in CF, and major epidemic clones have been recognized throughout the world. The aim of the present study was to develop and evaluate a multilocus variable number of tandem repeat (VNTR) analysis (MLVA) scheme for B. cenocepacia. Potential VNTR loci were identified upon analysis of the annotated genome sequences of strain AU1054, J2315 and MCO-3, and 10 of them were selected on the basis of polymorphism and size. A collection of 100 B. cenocepacia strains, including epidemiologically related and unrelated strains, as well as representatives of the major epidemic lineages, was used to evaluate typeability, epidemiological concordance and discriminatory power of MLVA, compared with pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Longitudinal stability was assessed by testing 39 successive isolates from 14 patients. Typeability ranged from 0.91 to 1, except for one marker, which was not amplified in 53% of B. cenocepacia IIIA strains. MLVA types were shown to be stable in chronically colonized patients, and within outbreak-related strains, with an excellent epidemiological concordance. Epidemic and/or globally distributed lineages (ET-12, ST-32, ST-122, ST-234, ST-241) were successfully identified. Conversely, the discriminatory power of MLVA was lower than that of PFGE or MLST, though PFGE variations within epidemic lineages sometimes masked genetic relatedness. In conclusion, MLVA represents a promising cost-effective first-line tool in B. cenocepacia surveillance.
- Effects of Pilates mat exercises on muscle strength and on pulmonary function in patients with cystic fibrosis. [JOURNAL ARTICLE]
- J Bras Pneumol 2014 Oct; 40(5):521-527.
To analyze the effects of Pilates mat exercises in patients with cystic fibrosis (CF).This was a clinical trial involving 19 CF patients recruited from either the CF Outpatient Clinic of the State University at Campinas Hospital de Clínicas or the Children's Institute of the University of São Paulo School of Medicine Hospital das Clínicas. All of the patients performed Pilates mat exercises for four months (one 60-min session per week). The variables studied (before and after the intervention) were respiratory muscle strength, MIP, MEP, FVC, and FEV1.After the intervention, MIP was significantly higher in the male patients (p = 0.017), as were MIP and MEP in the female patients (p = 0.005 and p = 0.007, respectively). There were no significant differences between the pre- and post-intervention values of FVC or FEV1, neither in the sample as a whole nor among the patients of either gender.Our results show that Pilates mat exercises have beneficial effects on respiratory muscle strength in CF patients.
- Impact of glycerol-3-phosphate dehydrogenase on virulence factor production by Pseudomonas aeruginosa. [JOURNAL ARTICLE]
- Can J Microbiol 2014 Oct 7.:1-7.
Pseudomonas aeruginosa establishes life-long chronic infections in the cystic fibrosis (CF) lung by utilizing various adaptation strategies. Some of these strategies include altering metabolic pathways to utilize readily available nutrients present in the host environment. The airway sputum contains various host-derived nutrients that can be utilized by P. aeruginosa, including phosphatidylcholine, a major component of lung surfactant. Pseudomonas aeruginosa can degrade phosphatidylcholine to glycerol and fatty acids to increase the availability of usable carbon sources in the CF lung. In this study, we show that some CF-adapted P. aeruginosa isolates utilize glycerol more efficiently as a carbon source than nonadapted isolates. Furthermore, a mutation in a gene required for glycerol utilization impacts the production of several virulence factors in both acute and chronic isolates of P. aeruginosa. Taken together, the results suggest that interference with this metabolic pathway may have potential therapeutic benefits.
- Characterization and quantification of the fungal microbiome in serial samples from individuals with cystic fibrosis. [JOURNAL ARTICLE]
- Microbiome 2014.:40.
Human-associated microbial communities include fungi, but we understand little about which fungal species are present, their relative and absolute abundances, and how antimicrobial therapy impacts fungal communities. The disease cystic fibrosis (CF) often involves chronic airway colonization by bacteria and fungi, and these infections cause irreversible lung damage. Fungi are detected more frequently in CF sputum samples upon initiation of antimicrobial therapy, and several studies have implicated the detection of fungi in sputum with worse outcomes. Thus, a more complete understanding of fungi in CF is required.We characterized the fungi and bacteria in expectorated sputa from six CF subjects. Samples were collected upon admission for systemic antibacterial therapy and upon the completion of treatment and analyzed using a pyrosequencing-based analysis of fungal internal transcribed spacer 1 (ITS1) and bacterial 16S rDNA sequences. A mixture of Candida species and Malassezia dominated the mycobiome in all samples (74%-99% of fungal reads). There was not a striking trend correlating fungal and bacterial richness, and richness showed a decline after antibiotic therapy particularly for the bacteria. The fungal communities within a sputum sample resembled other samples from that subject despite the aggressive antibacterial therapy. Quantitative PCR analysis of fungal 18S rDNA sequences to assess fungal burden showed variation in fungal density in sputum before and after antibacterial therapy but no consistent directional trend. Analysis of Candida ITS1 sequences amplified from sputum or pure culture-derived genomic DNA from individual Candida species found little (<0.5%) or no variation in ITS1 sequences within or between strains, thereby validating this locus for the purpose of Candida species identification. We also report the enhancement of the publically available Visualization and Analysis of Microbial Population Structures (VAMPS) tool for the analysis of fungal communities in clinical samples.Fungi are present in CF respiratory sputum. In CF, the use of intravenous antibiotic therapy often does not profoundly impact bacterial community structure, and we observed a similar stability in fungal species composition. Further studies are required to predict the effects of antibacterials on fungal burden in CF and fungal community stability in non-CF populations.
- The findings of a clinical surveillance bronchoalveolar lavage programme in pre-school patients with cystic fibrosis. [JOURNAL ARTICLE]
- Pediatr Pulmonol 2014 Nov 18.
Evidence suggests infection is present in the lower airways of young children with cystic fibrosis (CF), even when clinically stable. Oropharyngeal samples (OPS) are typically used for airway surveillance in these children but have been shown to have low positive predictive values and low sensitivity in detecting lower airway infection when compared with the reference standard, bronchoalveolar lavage (BAL).The aim of this study was to determine the prevalence of pathogens in lower airway samples detected as part of a pilot clinical BAL surveillance programme, in young children aged from one to six years old, and to ascertain if their detection resulted in a change in treatment.During the study 78 bronchoscopies were performed on 38 patients. The average age at the time of bronchoscopy was 2.7 years (range 0.3-7.0 year). A significant organism was detected in 58 (74.5%) BALs. Haemophilus influenzae was detected in 27 (34.6%) samples, 16 (20.5%) samples had Staphylococcus aureus, and nine (11.5%) had Pseudomonas aeruginosa. Change in treatment occurred after 46 (58.9%) BALs.This study suggests that, in young non-expectorating children with CF, routine surveillance bronchoscopy allows the detection of significant lower airway pathogens and provides the opportunity for targeted treatment of sub-clinical infection. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.
- Erythema nodosum of non-lower extremity sites - a histopathologic reappraisal. [JOURNAL ARTICLE]
- G Ital Dermatol Venereol 2014 Nov 19.
We recently saw a 51 year--old female with a tender, erythematous nodule on the left elbow and histopathology consistent with Erythema nodosum (EN). A subsequent literature review of EN in non--lower extremity (LE) sites identified only three reports, with minimal histopathology, prompting the current study. We identified nine EN cases on non--LE sites over a 14--year period. Histopathology typical of EN observed included septal panniculitis, fibrosis and edema, a mixed septal inflammatory infiltrate with and spillover into adjacent lobules and Miescher's radial granulomas. Atypical features observed included a mixed (septal and lobular) panniculitis, leukocytoclastic vasculitis, changes in septal small vessels (lymphocytic cuffing of septal venules, endothelial swelling), lipomembranous cystic change and asteroid bodies. To the best of our knowledge, this is the first study to detail the histopathologic findings of EN on non--LE sites. Similar to that noted in classical EN in the LE, findings from the current study indicate that EN in non--LE sites display typical as well as atypical features. Limitations include retrospective design and the unspecified duration of biopsied lesions relative to clinical presentation.
- An easy test but a hard decision: ethical issues concerning non-invasive prenatal testing for autosomal recessive disorders. [JOURNAL ARTICLE]
- Eur J Hum Genet 2014 Nov 5.
Prenatal testing based on cell-free fetal DNA in maternal serum is now possible for specific monogenic conditions, and studies have shown that the use of non-invasive testing is supported by prospective parents and health professionals. However, some ethical issues have been raised concerning informed consent and paternal rights. The objective of this study was to explore ethical aspects of the use of non-invasive prenatal diagnostic testing for autosomal recessive disorders. We used a qualitative cross-sectional design, based on Thematic Analysis, and recruited 27 individuals of reproductive age who were carriers of one of four conditions: thalassaemia, sickle cell disease, cystic fibrosis or spinal muscular atrophy. Data were collected via focus groups or interviews. Participants were aware of the potential for such tests to be viewed as routine and suggested that obtaining written consent and allowing time for consideration is needed to facilitate autonomous choice and informed consent. All participants felt that mothers should be able to request such tests, but fathers who declined carrier testing should be made aware that fetal test results may reveal their status. We suggest that a written record of consent for non-invasive prenatal diagnosis should be used as a standard to help reinforce the serious nature of the test results. Where the father's carrier status could be revealed through fetal testing, he should be made aware of this before the results are available. Health professionals should discuss with the pregnant woman the best way to manage unsought information about the father's carrier status to minimise family disruption.European Journal of Human Genetics advance online publication, 5 November 2014; doi:10.1038/ejhg.2014.238.
- Modulation of the Maladaptive Stress Response to Manage Diseases of Protein Folding. [JOURNAL ARTICLE]
- PLoS Biol 2014 Nov; 12(11):e1001998.
Diseases of protein folding arise because of the inability of an altered peptide sequence to properly engage protein homeostasis components that direct protein folding and function. To identify global principles of misfolding disease pathology we examined the impact of the local folding environment in alpha-1-antitrypsin deficiency (AATD), Niemann-Pick type C1 disease (NPC1), Alzheimer's disease (AD), and cystic fibrosis (CF). Using distinct models, including patient-derived cell lines and primary epithelium, mouse brain tissue, and Caenorhabditis elegans, we found that chronic expression of misfolded proteins not only triggers the sustained activation of the heat shock response (HSR) pathway, but that this sustained activation is maladaptive. In diseased cells, maladaptation alters protein structure-function relationships, impacts protein folding in the cytosol, and further exacerbates the disease state. We show that down-regulation of this maladaptive stress response (MSR), through silencing of HSF1, the master regulator of the HSR, restores cellular protein folding and improves the disease phenotype. We propose that restoration of a more physiological proteostatic environment will strongly impact the management and progression of loss-of-function and gain-of-toxic-function phenotypes common in human disease.
- Diagnosis of allergic bronchopulmonary aspergillosis: a case-based approach. [JOURNAL ARTICLE]
- Future Microbiol 2014 Oct.:1195-1208.
ABSTRACT Allergic bronchopulmonary aspergillosis is a pulmonary disease occurring in patients with asthma or cystic fibrosis, consequent to a dysregulated immune response to inhaled Aspergillus conidia. The usual presentation is with poorly controlled asthma. Patients may also present with expectoration of mucus plugs, hemoptysis, constitutional symptoms and radiological opacities. Patients may experience smoldering lung destruction despite well-controlled asthma. With emerging data, the diagnostic criteria transcribed by an International Expert Committee in 2013 are the latest evidence-based guidelines. Herein, we utilize a case-based approach to elaborate on the diagnosis of this disease. The review intends to provide a lucid understanding of the diagnostic process for the expert as well as the primary physician, involved in management of this enigmatic disorder.
- Development of a community residency program with a focus on specialty pharmacy. [Journal Article]
- Am J Health Syst Pharm 2014 Dec 1; 71(23):2067-72.
An innovative community residency program that provides training in the clinical and administrative aspects of specialty pharmacy practice is described.An ongoing rapid rise in U.S. approvals of specialty therapies for chronic diseases and conditions (e.g., Crohn's disease, cystic fibrosis, infertility, hepatitis C infection, multiple sclerosis) is fueling demand for pharmacists trained to meet the complex needs of patients receiving those therapies, which are typically subject to risk evaluation and mitigation strategy (REMS) requirements and limited distribution arrangements. In 2011, Duquesne University Mylan School of Pharmacy partnered with Walgreens Specialty Pharmacy to launch a one-year community residency program designed to (1) provide enhanced education on diseases and conditions targeted by specialty therapies, (2) develop well-rounded clinicians who are fully knowledgeable of the medications used to treat those disorders, and (3) prepare trainees for the operational and business-related challenges of specialty pharmacy practice. The first half of the residency year emphasizes direct patient care experiences, with team-based rotations focusing on specific disease states and health conditions; the second half of the residency program emphasizes operational-administrative training in areas such as clinical program development, resource utilization review, REMS compliance, contracting, and navigating manufacturer-sponsored patient assistance programs. Other program components include a one-month external rotation at a managed care organization, research projects, and teaching experiences.A unique community residency program jointly developed by Duquesne University and Walgreens Specialty Pharmacy prepares trainees for careers in diverse clinical, managed care, community-based, and academic practice settings.