14 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

(exome OR "exome sequencing") AND disease

These pubmed results were generated on 2018/05/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

55 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2018/05/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

13 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2018/05/01

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Repurposing HAMI3379 to Block GPR17 and Promote Rodent and Human Oligodendrocyte Differentiation.

Cell Chem Biol. 2018 Apr 18;:

Authors: Merten N, Fischer J, Simon K, Zhang L, Schröder R, Peters L, Letombe AG, Hennen S, Schrage R, Bödefeld T, Vermeiren C, Gillard M, Mohr K, Lu QR, Brüstle O, Gomeza J, Kostenis E

Abstract
Identification of additional uses for existing drugs is a hot topic in drug discovery and a viable alternative to de novo drug development. HAMI3379 is known as an antagonist of the cysteinyl-leukotriene CysLT2 receptor, and was initially developed to treat cardiovascular and inflammatory disorders. In our study we identified HAMI3379 as an antagonist of the orphan G protein-coupled receptor GPR17. HAMI3379 inhibits signaling of recombinant human, rat, and mouse GPR17 across various cellular backgrounds, and of endogenous GPR17 in primary rodent oligodendrocytes. GPR17 blockade by HAMI3379 enhanced maturation of primary rat and mouse oligodendrocytes, but was without effect in oligodendrocytes from GPR17 knockout mice. In human oligodendrocytes prepared from inducible pluripotent stem cells, GPR17 is expressed and its activation impaired oligodendrocyte differentiation. HAMI3379, conversely, efficiently favored human oligodendrocyte differentiation. We propose that HAMI3379 holds promise for pharmacological exploitation of orphan GPR17 to enhance regenerative strategies for the promotion of remyelination in patients.

PMID: 29706593 [PubMed - as supplied by publisher]

Coping with stress by mothers of children and adolescents with cystic fibrosis.

Adv Respir Med. 2018;86(2):86-91

Authors: Zubrzycka R

Abstract
INTRODUCTION: Studies of coping with stress of parents of children with cystic fibrosis (CF) are relatively rare and their results are inconsistent. The aim of the work was to determine the strategies of coping with stress of Polish mothers of children and adolescents with CF.
MATERIAL AND METHODS: The research was conducted in the group of 89 Polish mothers of children with CF (0-18) and used the Brief COPE by Carver in the Polish adaptation by Juczyński and Ogińska-Bulik (2009). The data were compared with the normative results obtained from Polish adults.
RESULTS: The strategies of coping most often used by mothers of children with CF are as follows: active coping, planning and acceptance. A comparison of mean results obtained in the research group and mean results of adults in Polish population revealed that mothers of ill children significantly more often use: active coping, planning, positive reframing, acceptance, religion, seeking of instrumental support and venting. They less often use sense of humour and take psychoactive substance. Use of problem- -oriented strategies dominated over use of coping strategies focusing on emotions.
CONCLUSION: Social support provided to mothers of children with CF should be oriented on strengthening cognitive strategies of coping with stress.

PMID: 29709048 [PubMed - in process]

Prevalence and predictors of readmissions among adults with cystic fibrosis in the United States.

Adv Respir Med. 2018;86(2):75-77

Authors: Chatterjee K, Goyal A, Reddy D, Koppurapu V, Innabi A, Alzghoul B, Jagana R

Abstract
INTRODUCTION: Patients with Cystic Fibrosis (CF) have increasing rates of hospitalization. We analyzed the burden and predictors of thirty-day readmission among patients with CF in the U.S.
MATERIAL AND METHODS: Nationwide Readmission Database (NRD) 2013 was used to identify adults with CF who were hospitalized. These individuals were followed to determine the prevalence of readmission within thirty days of index discharge. Cox proportional hazard regression was used to identify independent predictors of readmission.
RESULTS: There were 14,616 index admissions of adults with CF in 2013. Of these, 2,606 (17.8%) patients were readmitted within 30 days of discharge. Female sex and chronic anemia were independent predictors of readmission. The most common causes of readmission were pulmonary exacerbation (31%), lung transplant complications (5.2%), and septicemia (3.4%).
CONCLUSION: Readmissions are frequent among adults with CF and contribute to significant healthcare burden and cost among this population.

PMID: 29709046 [PubMed - in process]

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study.

J Vis Exp. 2018 Apr 11;(134):

Authors: Brewington JJ, Filbrandt ET, LaRosa FJ, Moncivaiz JD, Ostmann AJ, Strecker LM, Clancy JP

Abstract
While the introduction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drugs has revolutionized care in Cystic Fibrosis (CF), the genotype-directed therapy model currently in use has several limitations. First, rare or understudied mutation groups are excluded from definitive clinical trials. Moreover, as additional modulator drugs enter the market, it will become difficult to optimize the modulator choices for an individual subject. Both of these issues are addressed with the use of patient-derived, individualized preclinical model systems of CFTR function and modulation. Human nasal epithelial cells (HNEs) are an easily accessible source of respiratory tissue for such a model. Herein, we describe the generation of a three-dimensional spheroid model of CFTR function and modulation using primary HNEs. HNEs are isolated from subjects in a minimally invasive fashion, expanded in conditional reprogramming conditions, and seeded into the spheroid culture. Within 2 weeks of seeding, spheroid cultures generate HNE spheroids that can be stimulated with 3',5'-cyclic adenosine monophosphate (cAMP)-generating agonists to activate CFTR function. Spheroid swelling is then quantified as a proxy of CFTR activity. HNE spheroids capitalize on the minimally invasive, yet respiratory origin of nasal cells to generate an accessible, personalized model relevant to an epithelium reflecting disease morbidity and mortality. Compared to the air-liquid interface HNE cultures, spheroids are relatively quick to mature, which reduces the overall contamination rate. In its current form, the model is limited by low throughput, though this is offset by the relative ease of tissue acquisition. HNE spheroids can be used to reliably quantify and characterize CFTR activity at the individual level. An ongoing study to tie this quantification to in vivo drug response will determine if HNE spheroids are a true preclinical predictor of patient response to CFTR modulation.

PMID: 29708545 [PubMed - in process]

The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials.

ERJ Open Res. 2018 Jan;4(1):

Authors: Foong RE, Harper AJ, Skoric B, King L, Turkovic L, Davis M, Clem CC, Rosenow T, Davis SD, Ranganathan S, Hall GL, Ramsey KA

Abstract
The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3-6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible.

PMID: 29707562 [PubMed]

Aberrant epithelial remodeling with impairment of cilia architecture in non-cystic fibrosis bronchiectasis.

J Thorac Dis. 2018 Mar;10(3):1753-1764

Authors: Chen ZG, Li YY, Wang ZN, Li M, Lim HF, Zhou YQ, Cai LM, Li YT, Yang LF, Zhang TT, Wang DY

Abstract
Background: Aberrant epithelial remodeling and/or abnormalities in mucociliary apparatus in airway epithelium contribute to infection and inflammation. It is uncertain if these changes occur in both large and small airways in non-cystic fibrosis bronchiectasis (non-CF bronchiectasis). In this study, we aim to investigate the histopathology and inflammatory profile in the epithelium of bronchi and bronchioles in bronchiectasis.
Methods: Excised lung tissue sections from 52 patients with non-CF bronchiectasis were stained with specific cellular markers and analyzed by immunohistochemistry and immunofluorescence to assess the epithelial structures, including ciliated cells and goblet cells morphology. Inflammatory cell counts and ciliary proteins expression levels of centrosomal protein 110 (CP110) and dynein heavy chain 5, axonemal (DNAH5) were assessed.
Results: Epithelial hyperplasia is found in both bronchi and bronchioles in all specimens, including hyperplasia and/or hypertrophy of goblet cells. The median cilia length is longer in hyperplastic epithelium [bronchi: 8.16 (7.03-9.14) µm, P<0.0001; bronchioles: 7.46 (6.41-8.48) µm, P<0.0001] as compared to non-hyperplastic epithelium (bronchi: 5.60 µm; bronchioles: 4.89 µm). Hyperplastic epithelium is associated with overexpression of CP110 and decreased intensity of DNAH5 expression in both bronchial and bronchiolar epithelium. Though infiltration of neutrophils is predominant (63.0% in bronchi and 76.7% in bronchioles), eosinophilic infiltration is also present in the mucosa of bronchi (30.8%) and bronchioles (54.8%).
Conclusions: Aberrant epithelial remodeling with impaired mucociliary architecture is present in both large and small airways in patients with refractory non-CF bronchiectasis. Future studies should evaluate the interplay between these individual components in driving chronic inflammation and lung damage in patients.

PMID: 29707330 [PubMed]

Cystic fibrosis: a gastrointestinal cancer syndrome.

Lancet Oncol. 2018 Apr 26;:

Authors: Slae M, Wilschanski M

PMID: 29706381 [PubMed - as supplied by publisher]

Risk of gastrointestinal cancers in patients with cystic fibrosis: a systematic review and meta-analysis.

Lancet Oncol. 2018 Apr 26;:

Authors: Yamada A, Komaki Y, Komaki F, Micic D, Zullow S, Sakuraba A

Abstract
BACKGROUND: The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis.
METHODS: In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396.
FINDINGS: Our search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; p<0·0001; log SIR 2·10, 95% CI 1·87-2·32; p<0·0001, I2=93·93%). Subgroup analyses showed that the risk of gastrointestinal cancer among patients with cystic fibrosis who had a lung transplant was increased compared with that of patients who did not receive a transplant (pooled SIR 21·13, 95% CI 14·82-30·14; p<0·0001; log SIR 3·05, 95% CI 2·70-3·41; p<0·0001, I2=28·52% vs pooled SIR 4·18, 3·10-5·62; p<0·0001; log SIR 1·43, 1·13-1·73; p<0·0001, I2=22·66%). The risk for the following site-specific cancers was also significantly increased in patients with cystic fibrosis compared with the general population: small bowel cancer (pooled SIR 18·94, 95% CI 9·37-38·27; p<0·0001; log SIR 2·94, 95% CI 2·24-3·64; p<0·0001, I2=38·61%), colon cancer (10·91, 8·42-14·11; p<0·0001; log SIR 2·39, 2·13-2·65; p<0·0001, I2=88·09%), biliary tract cancer (17·87, 8·55-37·36; p<0·0001; log SIR 2·88, 2·15-3·62; p<0·0001, I2=10·16%), and pancreatic cancer (6·18, 1·31-29·27; p=0·022; log SIR 1·82, 0·27-3·38; p<0·0001, I2=62·57%).
INTERPRETATION: Our study suggests that patients with cystic fibrosis had a significantly increased risk of gastrointestinal cancer compared with the general population, including small bowel, colon, biliary tract, and pancreatic cancers. These findings highlight the need to develop individualised screening strategies for site-specific gastrointestinal cancers in patients with cystic fibrosis.
FUNDING: None.

PMID: 29706374 [PubMed - as supplied by publisher]

Clinical epidemiology of carbapenem-resistant gram-negative sepsis among hospitalized patients: Shifting burden of disease?

Am J Infect Control. 2018 Apr 26;:

Authors: Britt NS, Ritchie DJ, Kollef MH, Burnham CD, Durkin MJ, Hampton NB, Micek ST

Abstract
BACKGROUND: Infections caused by carbapenem-resistant gram-negative bacilli are an emerging public health threat. However, there is a paucity of data examining comparative incidence rates, risk factors, and outcomes in this population.
METHODS: This single-center retrospective cohort study was conducted at an urban tertiary-care academic medical center. We included patients admitted from 2012 to 2015 who met the following criteria: i) age ≥ 18 years; and ii) culture positive for carbapenem-resistant Enterobacteriaceae (CRE) or carbapenem-resistant non-Enterobacteriaceae (CRNE) from any site. Exclusion criteria were: i) < 2 systemic inflammatory response criteria; ii) cystic fibrosis; and iii) no targeted treatment. We evaluated hospital survival by Cox regression and year-by-year differences in the distribution of cases by the Cochran-Armitage test.
RESULTS: 448 patients were analyzed (CRE, n = 111 [24.8%]; CRNE, n = 337 [75.2%]). CRE sepsis cases increased significantly over the study period (P <.001), driven primarily by increasing incidence of Enterobacter spp. infection (P = .004). No difference was observed in hospital survival between patients with CRE versus CRNE sepsis (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.83-2.02; P = .285), even after adjusting for confounding factors (adjusted HR, 1.08; 95% CI, 0.62-1.87; P = .799).
CONCLUSIONS: Clinical outcomes did not differ between patients with CRE versus CRNE sepsis. Dramatic increases in CRE, particularly Enterobacter spp., appear to be causing a shift in the burden of clinically significant carbapenem-resistant gram-negative infection.

PMID: 29706365 [PubMed - as supplied by publisher]

3He diffusion MRI in human lungs.

J Magn Reson. 2018 Apr 25;:

Authors: Woods JC, Conradi MS

Abstract
Hyperpolarized 3He gas allows the air spaces of the lungs to be imaged via MRI. Imaging of restricted diffusion is addressed here, which allows the microstructure of the lung to be characterized through the physical restrictions to gas diffusion presented by airway and alveolar walls in the lung. Measurements of the apparent diffusion coefficient (ADC) of 3He at time scales of milliseconds and seconds are compared; measurement of acinar airway sizes by determination of the microscopic anisotropy of diffusion is discussed. This is where Dr. JJH Ackerman's influence was greatest in aiding the formation of the Washington University 3He group, involving early a combination of physicists, radiologists, and surgeons, as the first applications of 3He ADC were to COPD and its destruction/modification of lung microstructure via emphysema. The sensitivity of the method to early COPD is demonstrated, as is its validation by direct comparison to histology. More recently the method has been used broadly in adult and pediatric obstructive lung diseases, from severe asthma to cystic fibrosis to bronchopulmonary dysplasia, a result of premature birth. These applications of the technique are discussed briefly.

PMID: 29705031 [PubMed - as supplied by publisher]

Voriconazole-Induced Periostitis Deformans: A Mimicker of Hypertrophic Pulmonary Osteoarthropathy.

Clin Med Res. 2017 Jun;15(1-2):19-20

Authors: Ladak K, Rubin L

PMID: 28487449 [PubMed - indexed for MEDLINE]