Literature Watch
"systems biology"; +46 new citations
46 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/03/16
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.
("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects"); +18 new citations
18 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 2017/03/16
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.
Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity.
Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity.
PLoS One. 2017;12(3):e0173783
Authors: Thamri A, Létourneau M, Djoboulian A, Chatenet D, Déziel E, Castonguay A, Perreault J
Abstract
Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics.
PMID: 28296935 [PubMed - in process]
Sequential Burkholderia cenocepacia Isolates from Siblings with Cystic Fibrosis Show Increased Lung Cell Attachment.
Sequential Burkholderia cenocepacia Isolates from Siblings with Cystic Fibrosis Show Increased Lung Cell Attachment.
Am J Respir Crit Care Med. 2017 Mar 15;195(6):832-835
Authors: Cullen L, O'Connor A, Drevinek P, Schaffer K, McClean S
PMID: 28294652 [PubMed - in process]
Evaluation of Functional Characteristics of 4 Oscillatory Positive Pressure Devices in a Simulated Cystic Fibrosis Model.
Evaluation of Functional Characteristics of 4 Oscillatory Positive Pressure Devices in a Simulated Cystic Fibrosis Model.
Respir Care. 2017 Mar 14;:
Authors: Van Fleet H, Dunn DK, McNinch NL, Volsko TA
Abstract
BACKGROUND: Oscillatory positive expiratory pressure (OPEP) is an airway clearance therapy that delivers positive pressure and air-flow oscillations during exhalation. This study described functional characteristic differences of 4 OPEP devices during an active exhalation in a simulated model. We hypothesized peak pressure (Ppeak), positive expiratory pressure (PEP), oscillatory frequency (f), and pressure amplitude will differ, depending upon the device used, device resistance setting, and time (repeated consecutive active exhalations through the device).
METHODS: The ASL 5000 was scripted to simulate pulmonary mechanics of a pediatric cystic fibrosis patient with moderate to severe lung disease. Airway resistance was standardized at 17.1 cm H2O/L/s, pulmonary compliance at 42.1 mL/cm H2O, active exhalation at 22 breaths/min, and tidal volume at 409 mL. Resistance settings for the Acapella, RC-Cornet, Flutter, and Aerobika were adjusted to low, medium, and high. Values for f, Ppeak, PEP, and pressure amplitude were recorded for 1 min and graphically displayed.
RESULTS: Significant effects for time, device, and resistance (P < .01) were noted for Ppeak, PEP, and pressure amplitude at each resistance level, demonstrating that the devices functioned differently as more than one repetition of a series of consecutive active exhalations are performed. Significant interaction effects for device, resistance level, and time indicate inconsistent output for Ppeak (P < .01), PEP (P < .01), and pressure amplitude (P < .01). Oscillatory f values fell within the respective manufacturers' operational parameters. The Aerobika provided the most consistent pressure amplitude across resistance settings and produced the highest mean pressure amplitude at medium and high resistance settings.
CONCLUSION: Statistically significant and clinically relevant variations in Ppeak, PEP, and pressure amplitude occurred between devices and within a device, as the resistance setting changed. The combination of device, time, and resistance settings affects OPEP device output for pressure, amplitude, and oscillatory frequency. Functional variations may impact therapeutic effectiveness, warranting additional study to determine clinical impact.
PMID: 28292973 [PubMed - as supplied by publisher]
Lung organoids: current uses and future promise.
Lung organoids: current uses and future promise.
Development. 2017 Mar 15;144(6):986-997
Authors: Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL
Abstract
Lungs are composed of a system of highly branched tubes that bring air into the alveoli, where gas exchange takes place. The proximal and distal regions of the lung contain epithelial cells specialized for different functions: basal, secretory and ciliated cells in the conducting airways and type II and type I cells lining the alveoli. Basal, secretory and type II cells can be grown in three-dimensional culture, with or without supporting stromal cells, and under these conditions they give rise to self-organizing structures known as organoids. This Review summarizes the different methods for generating organoids from cells isolated from human and mouse lungs, and compares their final structure and cellular composition with that of the airways or alveoli of the adult lung. We also discuss the potential and limitations of organoids for addressing outstanding questions in lung biology and for developing new drugs for disorders such as cystic fibrosis and asthma.
PMID: 28292845 [PubMed - in process]
Adherence and Recursive Perception Among Young Adults with Cystic Fibrosis.
Adherence and Recursive Perception Among Young Adults with Cystic Fibrosis.
Anthropol Med. 2017 Apr;24(1):65-80
Authors: Oddleifson DA, Sawicki GS
Abstract
Adherence to prescribed treatment is a pressing issue for adolescents and young adults with cystic fibrosis (CF). This paper presents two narratives from the thematic analysis of unstructured interviews with 14 adolescents, young adults, and older adults living with CF. Through a new identity-based framework termed recursive perception that draws focus on how an individual perceives how others view them, it explores the social context of adherence and self-care among young adults with CF. It demonstrates that an individual's understanding of self and desire to maintain a certain image for peers can be deeply embedded in adherence and self-care patterns, leading individuals to feel they need to choose between tending to their health needs and living their lives. This suggests that current biomedical innovation in CF care must be complemented with renewed efforts to find effective means to empower young adults with CF to successfully navigate the social challenges of their illness and avoid the pitfalls of nonadherence that can lead to a permanent worsening of their health condition.
PMID: 28292207 [PubMed - in process]
Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa.
Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa.
J Microbiol Immunol Infect. 2017 Feb 20;:
Authors: Hassan R, El-Naggar W, Abd El-Aziz AM, Shaaban M, Kenawy HI, Ali YM
Abstract
BACKGROUND: Pseudomonas aeruginosa is a Gram-negative opportunistic bacterium, which considered as a common cause of nosocomial infection and life-threatening complications in immunocompromized and cystic fibrosis patients. Here, we evaluate the protective effect of recombinant vaccines composed of outer membrane proteins OprF and OprI alone or in combination with flagellin B against mucoid and nonmucoid pseudomonas infection.
METHODS: BALB/C mice were immunized subcutaneous using OprF and OprI with or without flagellin B and antibody titers were determined. Serum bactericidal and opsonophagocytosis activities of immunized and control sera were estimated against mucoid and nonmucoid pseudomonas strains. Lung tissue sections from immunized and nonimmunized mice were analyzed and the levels of peripheral neutrophils infiltration into the lung and tissue inflammation were scored.
RESULTS: Subcutaneous immunization using OprF and OprI with or without flagellin B elicited higher antibody titers against OprF, OprI, and flagellin B. The produced antibodies successfully opsonized both mucoid and nonmucoid strains with subsequent activation of the terminal pathway of complement that enhances killing of nonmucoid strains via complement-mediated lysis. Furthermore, opsonized mucoid and nonmucoid strains showed enhanced opsonophagocytosis via human peripheral neutrophils, a mechanism that kills P. aeruginosa when complement mediated lysis is not effective especially with mucoid strains. Immunized mice also showed a significant prolonged survival time, lower bacteremia, and reduced lung damage when compared with control nonimmunized mice.
CONCLUSION: Our data showed that mice immunized with OprF/OprI or OprF/OprI and flagellin B are significantly protected from infection caused by mucoid and nonmucoid strains of P. aeruginosa.
PMID: 28291719 [PubMed - as supplied by publisher]
Outcomes Following Bronchial Artery Embolisation for Haemoptysis in Cystic Fibrosis.
Outcomes Following Bronchial Artery Embolisation for Haemoptysis in Cystic Fibrosis.
Cardiovasc Intervent Radiol. 2017 Mar 13;:
Authors: Flight WG, Barry PJ, Bright-Thomas RJ, Butterfield S, Ashleigh R, Jones AM
Abstract
BACKGROUND: Bronchial artery embolisation (BAE) is recommended for the treatment of massive haemoptysis in cystic fibrosis (CF), but there are no randomised controlled trials of this therapy and its role in sub-massive haemoptysis is unclear. This study aimed to determine the outcomes and safety of BAE in adults with CF.
MATERIALS AND METHODS: All patients with CF undergoing BAE at our centre between March 2011 and January 2015 were identified at the time of the procedure. Patient records were reviewed at hospital discharge, death or one month post-procedure (whichever was soonest). Follow-up continued to January 2016. Severity of haemoptysis was classified as: massive (>240 ml/24 h or >100 ml/day for ≥2 days), moderate-severe (>20 ml/24 h) or mild (<20 ml/24 h).
RESULTS: Twenty-seven patients underwent 51 BAE procedures over a median follow-up period of 26 months (range 1-54). Ten patients (37%) required more than one BAE during the study. BAE was performed for massive haemoptysis in 18 cases (35%). Haemoptysis recurred after 31 (61%) of BAE procedures with no difference in recurrence rates between massive and sub-massive haemoptysis. Side effects were reported after 61% of procedures with chest pain the most common adverse event . Mortality after first BAE in the study was 3.9% at 30 days and 14.8% at 12 months. No significant predictors of mortality were identified.
CONCLUSIONS: BAE is often effective in controlling haemoptysis but is associated with considerable morbidity and high recurrence rates.
PMID: 28289842 [PubMed - as supplied by publisher]
The Cystic Fibrosis Survival Gap: Why Do Canadians Fare Better Than Americans?
The Cystic Fibrosis Survival Gap: Why Do Canadians Fare Better Than Americans?
Ann Intern Med. 2017 Mar 14;:
Authors: Flume PA, VanDevanter DR
PMID: 28289748 [PubMed - as supplied by publisher]
Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography.
Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography.
JCI Insight. 2017 Mar 09;2(5):e91702
Authors: Solomon GM, Francis R, Chu KK, Birket SE, Gabriel G, Trombley JE, Lemke KL, Klena N, Turner B, Tearney GJ, Lo CW, Rowe SM
Abstract
Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). Ccdc39(-/-) mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, Dnah5(-/-) mice, with a missense mutation of the outer dynein arms, had reduced ciliary beat frequency (CBF) but preserved motile area and ciliary stroke, maintaining some MCT. Wdr69(-/-) PCD mice exhibited normal motile area and CBF and partially delayed MCT due to abnormalities of ciliary ARC. Visualization of ciliary motion using μOCT provides quantitative assessment of ciliary motion and MCT. Comprehensive ciliary motion investigation in situ classifies ciliary motion defects and quantifies their contribution to delayed mucociliary clearance.
PMID: 28289722 [PubMed - in process]
DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis.
DNA methylation at modifier genes of lung disease severity is altered in cystic fibrosis.
Clin Epigenetics. 2017;9:19
Authors: Magalhães M, Rivals I, Claustres M, Varilh J, Thomasset M, Bergougnoux A, Mely L, Leroy S, Corvol H, Guillot L, Murris M, Beyne E, Caimmi D, Vachier I, Chiron R, De Sario A
Abstract
BACKGROUND: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients.
RESULTS: We profiled DNA methylation at CFTR, the disease-causing gene, and at 13 lung modifier genes in nasal epithelial cells and whole blood samples from 48 CF patients and 24 healthy controls. CF patients homozygous for the p.Phe508del mutation and ≥18-year-old were stratified according to the lung disease severity. DNA methylation was measured by bisulfite and next-generation sequencing. The DNA methylation profile allowed us to correctly classify 75% of the subjects, thus providing a CF-specific molecular signature. Moreover, in CF patients, DNA methylation at specific genes was highly correlated in the same tissue sample. We suggest that gene methylation in CF cells may be co-regulated by disease-specific trans-factors. Three genes were differentially methylated in CF patients compared with controls and/or in groups of pulmonary severity: HMOX1 and GSTM3 in nasal epithelial samples; HMOX1 and EDNRA in blood samples. The association between pulmonary severity and DNA methylation at EDNRA was confirmed in blood samples from an independent set of CF patients. Also, lower DNA methylation levels at GSTM3 were associated with the GSTM3*B allele, a polymorphic 3-bp deletion that has a protective effect in cystic fibrosis.
CONCLUSIONS: DNA methylation levels are altered in nasal epithelial and blood cell samples from CF patients. Analysis of CFTR and 13 lung disease modifier genes shows DNA methylation changes of small magnitude: some of them are a consequence of the disease; other changes may result in small expression variations that collectively modulate the lung disease severity.
PMID: 28289476 [PubMed - in process]
Staphylococcus aureus survives in cystic fibrosis macrophages forming a reservoir for chronic pneumonia.
Staphylococcus aureus survives in cystic fibrosis macrophages forming a reservoir for chronic pneumonia.
Infect Immun. 2017 Mar 13;:
Authors: Li C, Wu Y, Riehle A, Ma J, Kamler M, Gulbins E, Grassmé H
Abstract
Staphylococcus aureus (S. aureus) plays an important role in sepsis, pneumonia, wound infections and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator (Cftr). Pulmonary S. aureus infections in CF often occur very early and prior to colonization with other pathogens, in particular Pseudomonas aeruginosa Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with S. aureus and fail to clear the pathogen during infection. S. aureus is internalized by Cftr-deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria. This failure might be caused by a defect in fusion of phagosomes with lysosomes, while this process rapidly occurs in wild-type macrophages and serves to kill intracellular pathogens. Transplantation of infected Cftr-deficient alveolar macrophages into the lung of non-infected CF mice is sufficient to induce pneumonia. This suggests that intracellular survival of S. aureus in macrophages may serve the pathogen to chronically infect CF lungs.
PMID: 28289144 [PubMed - as supplied by publisher]
Research Supplements to Promote Sharing Data in Cancer Epidemiology Studies (Admin Supp)
Supplement Opportunity to Support Population-Based Research Studies of Rare Cancers (Admin Supp)
Enhancing Science, Technology, EnginEering, and Math Educational Diversity (ESTEEMED) Research Education Experiences (R25)
"drug repositioning" OR "drug repurposing"; +7 new citations
7 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"drug repositioning" OR "drug repurposing"
These pubmed results were generated on 2017/03/14
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.
"systems biology"; +33 new citations
33 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/03/14
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.
A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop.
A Novel Missense Variant in the AGRN Gene; Congenital Myasthenic Syndrome Presenting With Head Drop.
J Clin Neuromuscul Dis. 2017 Mar;18(3):147-151
Authors: Karakaya M, Ceyhan-Birsoy O, Beggs AH, Topaloglu H
Abstract
Congenital myasthenic syndromes (CMS) are a heterogeneous group of diseases of the neuromuscular junction caused by compromised synaptic transmission. Clinical features include early-onset weakness of limbs and oculobulbar muscles resulting in hypotonia, bulbar paresis, ptosis, and hypoventilation. The first dropped head syndrome in children were detected in 2 patients with LMNA and SEPN1 mutations. We report a 17-month-old boy with dropped head and limb-girdle weakness, who had no ptosis or ophthalmoplegia at presentation. We performed whole exome sequencing, which revealed a homozygous missense variant in the AGRN gene c.5023G>A, p.Gly1675Ser in the LG2 domain, which is predicted to be likely disease causing by in silico tools. Agrin is known to play a critical role in the development and maintenance of the neuromuscular junction. Agrin-related CMS is one of the rarest subtypes. Of note, our patient is the first described patient with agrin-related CMS with dropped head phenotype.
PMID: 28221305 [PubMed - indexed for MEDLINE]
Giant Interfrontal Encephalocele in an Infant: A Rare Entity.
Giant Interfrontal Encephalocele in an Infant: A Rare Entity.
Pediatr Neurosurg. 2016;51(6):309-312
Authors: Faheem M, Singh SK, Ojha BK, Chandra A, Srivastava C, Jaiswal M, Zeeshan Q
Abstract
Interfrontal encephalocele is one of the rare varieties of anterior encephalocele, and a giant interfrontal encephalocele is extremely rare. The authors could find only one case report of giant interfrontal encephalocele in the literature. Anterior encephaloceles are more prevalent in South-East Asia and some northern parts of India. Giant encephalocele poses a great challenge to neurosurgeons and neuroanesthetists during surgery, as these infants usually have a low birth weight and a large sac, thus making the infant prone to hypothermia and blood loss among other risks. We encountered a patient with a giant interfrontal encephalocele aged 1 month. The rarity of this case prompted us to this report.
PMID: 27513987 [PubMed - indexed for MEDLINE]
Pages
