Literature Watch
Systems analysis of the prostate transcriptome in African-American men compared with European-American men.
Systems analysis of the prostate transcriptome in African-American men compared with European-American men.
Pharmacogenomics. 2016 Jul;17(10):1129-1143
Authors: Hardiman G, Savage SJ, Hazard ES, Wilson RC, Courtney SM, Smith MT, Hollis BW, Halbert CH, Gattoni-Celli S
Abstract
AIM: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D3 supplementation.
PATIENTS & METHODS: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery.
RESULTS: AA show higher expression of genes associated with immune response and inflammation.
CONCLUSION: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D3 supplementation.
PMID: 27359067 [PubMed - indexed for MEDLINE]
SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways.
SNPs in NRXN1 and CHRNA5 are associated to smoking and regulation of GABAergic and glutamatergic pathways.
Pharmacogenomics. 2016 Jul;17(10):1145-1158
Authors: Pérez-Rubio G, Pérez-Rodríguez ME, Fernández-López JC, Ramírez-Venegas A, García-Colunga J, Ávila-Moreno F, Camarena A, Sansores RH, Falfán-Valencia R
Abstract
AIM: To identify genetic variants associated with greater tobacco consumption in a Mexican population.
PATIENTS & METHODS: Daily smokers were classified as light smokers (LS; n = 742), heavy smokers (HS; n = 601) and nonsmokers (NS; n = 606). In the first stage, a genotyping microarray that included 347 SNPs in CHRNA2-CHRNA7/CHRNA10, CHRNB2-CHRNB4 and NRXN1 genes and 37 ancestry-informative markers was used to analyze 707 samples (187 HS, 328 LS and 192 NS). In the second stage, 14 SNPs from stage 1 were validated in the remaining samples (HS, LS and NS; n = 414 in each group) using real-time PCR. To predict the role of the associated SNPs, an in silico analysis was performed.
RESULTS: Two SNPs in NRXN1 and two in CHRNA5 were associated with cigarette consumption, while rs10865246/C (NRXN1) was associated with high nicotine addiction. The in silico analysis revealed that rs1882296/T had a high level of homology with Hsa-miR-6740-5p, which encodes a putative miRNA that targets glutamate receptor subunits (GRIA2, GRID2) and GABA receptor subunits (GABRG1, GABRA4, GABRB2), while rs1882296/C had a high level of homology with Hsa-miR-6866-5p, which encodes a different miRNA that targets GRID2 and GABRB2.
CONCLUSION: In a Mexican Mestizo population, greater consumption of cigarettes was influenced by polymorphisms in the NRXN1 and CHRNA5 genes. We proposed new hypotheses regarding the putative roles of miRNAs that influence the GABAergic and glutamatergic pathways in smoking addiction.
PMID: 27355804 [PubMed - indexed for MEDLINE]
Deep molecular response by IFN-α and dasatinib combination in a patient with T315I-mutated chronic myeloid leukemia.
Deep molecular response by IFN-α and dasatinib combination in a patient with T315I-mutated chronic myeloid leukemia.
Pharmacogenomics. 2016 Jul;17(10):1159-1163
Authors: Zhou L, Shi H, Jiang S, Ruan C, Liu H
Abstract
The T315I mutation is especially challenging as it confers resistance to all first- and second-generation tyrosine kinase inhibitors. We present here a chronic myeloid leukemia patient harboring the T315I and E255V BCR-ABL1 mutation successfully achieved deep molecular response with a combined treatment of dasatinib and IFN-α. To our knowledge, this is the second case of a T315I-bearing chronic myeloid leukemia patient displaying satisfactory response to the combination therapy of dasatinib and IFN-α.
PMID: 27347777 [PubMed - indexed for MEDLINE]
A balancing act in cardiac hypertrophy.
A balancing act in cardiac hypertrophy.
Cardiovasc Res. 2016 07 01;111(1):8-9
Authors: Matkovich SJ
PMID: 27216864 [PubMed - indexed for MEDLINE]
Survival of Patients with Cystic Fibrosis Depending on Mutation Type and Nutritional Status.
Survival of Patients with Cystic Fibrosis Depending on Mutation Type and Nutritional Status.
Adv Exp Med Biol. 2017 Jul 19;:
Authors: Szwed A, John A, Goździk-Spychalska J, Czaiński W, Czerniak W, Ratajczak J, Batura-Gabryel H
Abstract
The purpose of the study was to evaluate the influence of nutrition and of the severity of mutation type on survival rate in cystic fibrosis (CF) patients. Data were longitudinally collected from 60 hospitalized adult CF patients, aged 18-50. The variables consisted of body mass index (BMI) ratio, Cole's BMI cut-off points, severity of mutation type, and survival rate of CF patients. We found that the mean BMI was strongly associated with the severity of mutation type and was significantly lower in patients with severe mutations of grade I and II. The mutation type significantly affected the patients' survival rate; survival was greater in patients with mild and undefined mutation types. The BMI and Cole's cut-off points also had a significant influence on survival rate. CF patients, who suffered from malnutrition and emaciation, had a shorter survival rate than those with proper nutritional status. In conclusion, the study findings confirmed a significant effect of nutritional status and of mutation type on survival rate of CF patients.
PMID: 28721579 [PubMed - as supplied by publisher]
Reaction-diffusion theory explains hypoxia and heterogeneous growth within microbial biofilms associated with chronic infections.
Reaction-diffusion theory explains hypoxia and heterogeneous growth within microbial biofilms associated with chronic infections.
NPJ Biofilms Microbiomes. 2016;2:16012
Authors: Stewart PS, Zhang T, Xu R, Pitts B, Walters MC, Roe F, Kikhney J, Moter A
Abstract
Reaction-diffusion models were applied to gain insight into the aspects of biofilm infection and persistence by comparing mathematical simulations with the experimental data from varied bacterial biofilms. These comparisons, including three in vitro systems and two clinical investigations of specimens examined ex vivo, underscored the central importance of concentration gradients of metabolic substrates and the resulting physiological heterogeneity of the microorganisms. Relatively simple one-dimensional and two-dimensional (2D) models captured the: (1) experimentally determined distribution of specific growth rates measured in Pseudomonas aeruginosa cells within sputum from cystic fibrosis patients; (2) pattern of relative growth rate within aggregates of streptococcal biofilm harboured in an endocarditis vegetation; (3) incomplete penetration of oxygen into a Pseudomonas aeruginosa biofilm under conditions of exposure to ambient air and also pure oxygen; (4) localisation of anabolic activity around the periphery of P. aeruginosa cell clusters formed in a flow cell and attribution of this pattern to iron limitation; (5) very low specific growth rates, as small as 0.025 h(-1), in the interior of cell clusters within a Klebsiella pneumoniae biofilm in a complex 2D domain of variable cell density.
PMID: 28721248 [PubMed]
Pseudomonas aeruginosa Alters Staphylococcus aureus Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection.
Pseudomonas aeruginosa Alters Staphylococcus aureus Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection.
MBio. 2017 Jul 18;8(4):
Authors: Orazi G, O'Toole GA
Abstract
The airways of cystic fibrosis (CF) patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the susceptibility of S. aureus to frontline antibiotics used to treat CF lung infections. Using our in vitro coculture model, we observed that addition of P. aeruginosa supernatants to S. aureus biofilms grown either on epithelial cells or on plastic significantly decreased the susceptibility of S. aureus to vancomycin. Mutant analyses showed that 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), a component of the P. aeruginosa Pseudomonas quinolone signal (PQS) system, protects S. aureus from the antimicrobial activity of vancomycin. Similarly, the siderophores pyoverdine and pyochelin also contribute to the ability of P. aeruginosa to protect S. aureus from vancomycin, as did growth under anoxia. Under our experimental conditions, HQNO, P. aeruginosa supernatant, and growth under anoxia decreased S. aureus growth, likely explaining why this cell wall-targeting antibiotic is less effective. P. aeruginosa supernatant did not confer additional protection to slow-growing S. aureus small colony variants. Importantly, P. aeruginosa supernatant protects S. aureus from other inhibitors of cell wall synthesis as well as protein synthesis-targeting antibiotics in an HQNO- and siderophore-dependent manner. We propose a model whereby P. aeruginosa causes S. aureus to shift to fermentative growth when these organisms are grown in coculture, leading to reduction in S. aureus growth and decreased susceptibility to antibiotics targeting cell wall and protein synthesis.IMPORTANCE Cystic fibrosis (CF) lung infections are chronic and difficult to eradicate. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients and are associated with poor patient outcomes. Both organisms adopt a biofilm mode of growth, which contributes to high tolerance to antibiotic treatment and the recalcitrant nature of these infections. Here, we show that P. aeruginosa exoproducts decrease the sensitivity of S. aureus biofilm and planktonic populations to vancomycin, a frontline antibiotic used to treat methicillin-resistant S. aureus in CF patients. P. aeruginosa also protects S. aureus from other cell wall-active antibiotics as well as various classes of protein synthesis inhibitors. Thus, interspecies interactions can have dramatic and unexpected consequences on antibiotic sensitivity. This study underscores the potential impact of interspecies interactions on antibiotic efficacy in the context of complex, polymicrobial infections.
PMID: 28720732 [PubMed - in process]
The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways.
The potential of phage therapy in cystic fibrosis: Essential human-bacterial-phage interactions and delivery considerations for use in Pseudomonas aeruginosa-infected airways.
J Cyst Fibros. 2017 Jul 15;:
Authors: Trend S, Fonceca AM, Ditcham WG, Kicic A, Cf A
Abstract
As antimicrobial-resistant microbes become increasingly common and a significant global issue, novel approaches to treating these infections particularly in those at high risk are required. This is evident in people with cystic fibrosis (CF), who suffer from chronic airway infection caused by antibiotic resistant bacteria, typically Pseudomonas aeruginosa. One option is bacteriophage (phage) therapy, which utilises the natural predation of phage viruses upon their host bacteria. This review summarises the essential and unique aspects of the phage-microbe-human lung interactions in CF that must be addressed to successfully develop and deliver phage to CF airways. The current evidence regarding phage biology, phage-bacterial interactions, potential airway immune responses to phages, previous use of phages in humans and method of phage delivery to the lung are also summarised.
PMID: 28720345 [PubMed - as supplied by publisher]
Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.
Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.
Cell Stem Cell. 2016 Aug 04;19(2):217-31
Authors: Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu YC, Rajagopal J
Abstract
Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We find that TGFβ/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stem cells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia.
PMID: 27320041 [PubMed - indexed for MEDLINE]
Retinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye.
Retinal Pigment Epithelial Cells are a Potential Reservoir for Ebola Virus in the Human Eye.
Transl Vis Sci Technol. 2017 Jul;6(4):12
Authors: Smith JR, Todd S, Ashander LM, Charitou T, Ma Y, Yeh S, Crozier I, Michael MZ, Appukuttan B, Williams KA, Lynn DJ, Marsh GA
Abstract
PURPOSE: Success of Ebola virus (EBOV) as a human pathogen relates at the molecular level primarily to blockade the host cell type I interferon (IFN) antiviral response. Most individuals who survive Ebola virus disease (EVD) develop a chronic disease syndrome: approximately one-quarter of survivors suffer from uveitis, which has been associated with presence of EBOV within the eye. Clinical observations of post-Ebola uveitis indicate involvement of retinal pigment epithelial cells.
METHODS: We inoculated ARPE-19 human retinal pigment epithelial cells with EBOV, and followed course of infection by immunocytochemistry and measurement of titer in culture supernatant. To interrogate transcriptional responses of infected cells, we combined RNA sequencing with in silico pathway, gene ontology, transcription factor binding site, and network analyses. We measured infection-induced changes of selected transcripts by reverse transcription-quantitative polymerase chain reaction.
RESULTS: Human retinal pigment epithelial cells were permissive to infection with EBOV, and supported viral replication and release of virus in high titer. Unexpectedly, 28% of 560 upregulated transcripts in EBOV-infected cells were type I IFN responsive, indicating a robust type I IFN response. Following EBOV infection, cells continued to express multiple immunomodulatory molecules linked to ocular immune privilege.
CONCLUSIONS: Human retinal pigment epithelial cells may serve as an intraocular reservoir for EBOV, and the molecular response of infected cells may contribute to the persistence of live EBOV within the human eye.
TRANSLATIONAL RELEVANCE: This bedside-to-bench research links ophthalmic findings in survivors of EVD who suffer from uveitis with interactions between retinal pigment epithelial cells and EBOV.
PMID: 28721309 [PubMed]
Microbial metal resistance and metabolism across dynamic landscapes: high-throughput environmental microbiology.
Microbial metal resistance and metabolism across dynamic landscapes: high-throughput environmental microbiology.
F1000Res. 2017;6:1026
Authors: Carlson H, Deutschbauer A, Coates J
Abstract
Multidimensional gradients of inorganic compounds influence microbial activity in diverse pristine and anthropogenically perturbed environments. Here, we suggest that high-throughput cultivation and genetics can be systematically applied to generate quantitative models linking gene function, microbial community activity, and geochemical parameters. Metal resistance determinants represent a uniquely universal set of parameters around which to study and evaluate microbial fitness because they represent a record of the environment in which all microbial life evolved. By cultivating microbial isolates and enrichments in laboratory gradients of inorganic ions, we can generate quantitative predictions of limits on microbial range in the environment, obtain more accurate gene annotations, and identify useful strategies for predicting and engineering the trajectory of natural ecosystems.
PMID: 28721211 [PubMed]
[Decision aids in complex polypharmacy : Medication data bases and counselling by clinical pharmacists].
[Decision aids in complex polypharmacy : Medication data bases and counselling by clinical pharmacists].
Z Gerontol Geriatr. 2017 Jul 18;:
Authors: Weinrebe W, Preda R, Bischoff S, Nussbickel D, Humm M, Jeckelmann K, Goetz S
Abstract
The number of older people with polypharmacy (more than six drugs taken simultaneously) is increasing. The greatest proportion consists of guideline drugs, analgesics and psychopharmaceuticals because in many cases of geriatric multimorbidity several underlying main diseases are present which must be treated according to the guidelines. Polypharmacy is a complex and difficult situation for all treating physicians because substantial side effects and intoxication can be induced but it can also be very difficult to recognize which drug was at fault and how a reduction can be safely made. This article describes the exemplary case of a 77-year-old patient with drug-induced delirium and demonstrates the procedure followed. The question of rapid assistance by the utilization of medication data bases is described and the importance of clinical pharmacists is demonstrated. In the future working with medication data bases will possibly become increasingly more important for physicians and hopefully simpler. The case presented here also shows that the effective and justified reduction of drugs can show a very good effect and is possible.
PMID: 28721543 [PubMed - as supplied by publisher]
The efficacy and safety of sugammadex for reversing postoperative residual neuromuscular blockade in pediatric patients: A systematic review.
The efficacy and safety of sugammadex for reversing postoperative residual neuromuscular blockade in pediatric patients: A systematic review.
Sci Rep. 2017 Jul 18;7(1):5724
Authors: Liu G, Wang R, Yan Y, Fan L, Xue J, Wang T
Abstract
The aim of this study is to evaluate the efficacy and safety of sugammadex for reversing neuromuscular blockade in pediatric patients. MEDLINE and other three Databases were searched. Randomized clinical trials were included if they compared sugammadex with neostigmine or placebo in pediatric patients undergoing surgery involving the use of rocuronium or vecuronium. The primary outcome was the time interval from administration of reversal agents to train-of-four ratio (TOFr, T4/T1) > 0.9. Incidences of any drug-related adverse events were secondary outcomes. Trial inclusion, data extraction, and risk of bias assessment were performed independently. Mean difference and relative risk were used as summary statistics with random effects models. Statistical heterogeneity was assessed by the I(2) statistic. Funnel plot was used to detect publication bias. Ten studies with 580 participants were included. Although considerable heterogeneity (I(2) = 98.5%) was detected in primary outcome, the results suggested that, compared with placebo or neostigmine, sugammadex can reverse rocuronium-induced neuromuscular blockade more rapidly with lower incidence of bradycardia. No significant differences were found in the incidences of other adverse events. Compared with neostigmine or placebo, sugammadex may reverse rocuronium-induced neuromuscular blockade in pediatric patients rapidly and safely.
PMID: 28720838 [PubMed - in process]
Using constrained information entropy to detect rare adverse drug reactions from medical forums.
Using constrained information entropy to detect rare adverse drug reactions from medical forums.
Conf Proc IEEE Eng Med Biol Soc. 2016 Aug;2016:2460-2463
Authors: Yi Zheng, Chaowang Lan, Hui Peng, Jinyan Li
Abstract
Adverse drug reactions (ADRs) detection is critical to avoid malpractices yet challenging due to its uncertainty in pre-marketing review and the underreporting in post-marketing surveillance. To conquer this predicament, social media based ADRs detection methods have been proposed recently. However, existing researches are mostly co-occurrence based methods and face several issues, in particularly, leaving out the rare ADRs and unable to distinguish irrelevant ADRs. In this work, we introduce a constrained information entropy (CIE) method to solve these problems. CIE first recognizes the drug-related adverse reactions using a predefined keyword dictionary and then captures high- and low-frequency (rare) ADRs by information entropy. Extensive experiments on medical forums dataset demonstrate that CIE outperforms the state-of-the-art co-occurrence based methods, especially in rare ADRs detection.
PMID: 28268822 [PubMed - indexed for MEDLINE]
Henoch-Schönlein purpura and drug and vaccine use in childhood: a case-control study.
Henoch-Schönlein purpura and drug and vaccine use in childhood: a case-control study.
Ital J Pediatr. 2016 Jun 18;42(1):60
Authors: Da Dalt L, Zerbinati C, Strafella MS, Renna S, Riceputi L, Di Pietro P, Barabino P, Scanferla S, Raucci U, Mores N, Compagnone A, Da Cas R, Menniti-Ippolito F, Italian Multicenter Study Group for Drug and Vaccine Safety in Children
Abstract
BACKGROUND: Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood; nevertheless, its etiology and pathogenesis remain unknown despite the fact that a variety of factors, mainly infectious agents, drugs and vaccines have been suggested as triggers for the disease. The aim of this study was to estimate the association of HSP with drug and vaccine administration in a pediatric population.
METHODS: An active surveillance on drug and vaccine safety in children is ongoing in 11 clinical centers in Italy. All children hospitalized through the local Paediatric Emergency Department for selected acute clinical conditions of interest were enrolled in the study. Data on drug and vaccine use in children before the onset of symptoms leading to hospitalization were collected by parents interview. A case-control design was applied for risk estimates: exposure in children with HSP, included as cases, was compared with similar exposure in children with gastroduodenal lesions, enrolled as controls. HSP cases were validated according to EULAR/PRINTO/PRES criteria. Validation was conducted retrieving data from individual patient clinical record.
RESULTS: During the study period (November 1999-April 2013), 288 cases and 617 controls were included. No increased risk of HSP was estimated for any drug. Among vaccines, measles-mumps-rubella (MMR) vaccine showed an increased risk of HSP (OR 3.4; 95 % CI 1.2-10.0).
CONCLUSIONS: This study provides further evidence on the possible role of MMR vaccine in HSP occurrence.
PMID: 27316345 [PubMed - indexed for MEDLINE]
Initial development of the Systems Approach to Home Medication Management (SAHMM) model.
Initial development of the Systems Approach to Home Medication Management (SAHMM) model.
Res Social Adm Pharm. 2017 Jan - Feb;13(1):39-47
Authors: Doucette WR, Vinel S, Pennathur P
Abstract
BACKGROUND: Adverse drug events and medication nonadherence are two problems associated with prescription medication use for chronic conditions. These issues often develop because patients have difficulty managing their medications at home. To guide patients and providers for achieving safe and effective medication use at home, the Systems Approach to Home Medication Management (SAHMM) model was derived from a systems engineering model for health care workplace safety.
OBJECTIVE: To explore how well concepts from the SAHMM model can represent home medication management by using patient descriptions of how they take prescription medications at home.
METHODS: Twelve patients were interviewed about home medication management using an interview guide based on the factors of the SAHMM model. Each interview was audio-taped and then transcribed verbatim. Interviews were coded to identify themes for home medication management using MAXQDA for Windows.
RESULTS: SAHMM concepts extracted from the coded interview transcripts included work system components of person, tasks, tools & technology, internal environment, external environment, and household. Concepts also addressed work processes and work outcomes for home medication management.
CONCLUSIONS: Using the SAHMM model for studying patients' home medication management is a promising approach to improving our understanding of the factors that influence patient adherence to medication and the development of adverse drug events.
PMID: 26853834 [PubMed - indexed for MEDLINE]
"Rare Diseases"[Mesh] OR "orphan disease"; +15 new citations
15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
"Rare Diseases"[Mesh] OR "orphan disease"
These pubmed results were generated on 2017/07/20
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(exome OR "exome sequencing") AND disease; +13 new citations
13 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 2017/07/20
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.
Discovery of Small Molecule Immunomodulators for Cancer Therapy (R01)
Using Small Molecules and Molecular Genetics to Identify Novel Targets and Mechanisms Contributing to Tumor Immune Evasion (R01)
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