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

"Cystic Fibrosis"

These pubmed results were generated on 2016/10/05

PubMed comprises more than 24 million 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 repurposing for glioblastoma based on molecular subtypes.

J Biomed Inform. 2016 Sep 30;:

Authors: Chen Y, Xu R

Abstract
A recent multi-platform analysis by The Cancer Genome Atlas identified four distinct molecular subtypes for glioblastoma (GBM) and demonstrated that the subtypes correlate with clinical phenotypes and treatment responses. In this study, we developed a computational drug repurposing approach to predict GBM drugs based on the molecular subtypes. Our approach leverages the genomic signature for each GBM subtype, and integrates the human cancer genomics with mouse phenotype data to identify the opportunity of reusing the FDA-approved agents to treat specific GBM subtypes. Specifically, we first constructed the phenotype profile for each GBM subtype using their genomic signatures. For each approved drug, we also constructed a phenotype profile using the drug target genes. Then we developed an algorithm to match and prioritize drugs based on their phenotypic similarities to the GBM subtypes. Our approach is highly generalizable for other disorders if provided with a list of disorder-specific genes. We first evaluated the approach in predicting drugs for the whole GBM. For a combined set of approved, potential and off-label GBM drugs, we achieved a median rank of 9.3%, which is significantly higher (p<e(-7)) than 45.7% for a recent approach that also uses the mouse phenotype data. Then we applied the approach on GBM subtypes. Analysis result shows the variations of enriched pathways, associated phenotypes and prioritized drugs across different subtypes. We ranked the first-line chemotherapy for GBM in different positions for each subtypes, and the rank variation was consistent with the previous finding on different drug responses among subtypes. In summary, this study makes an effort towards translating the molecular stratification into better survival for GBM.

PMID: 27697594 [PubMed - as supplied by publisher]

Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update.

J Manag Care Spec Pharm. 2016 Oct;22(10-a-s Suppl):S3-S15

Authors: Bowlus CL, Kenney JT, Rice G, Navarro R

Abstract
BACKGROUND: Chronic liver disease and cirrhosis are a leading cause of morbidity and mortality in the United States. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis and which has been designated an orphan condition, is a chronic autoimmune disease resulting in the destruction of the small bile ducts in the liver. Without effective treatment, disease progression frequently leads to liver failure and death. Until May 2016, the only FDA-approved treatment for PBC was ursodiol (UDCA), an oral hydrophilic bile acid, which can slow progression of liver damage due to PBC. However, 1 out of 3 patients taking UDCA has an inadequate biochemical response, leading to increased risk of disease progression, liver transplantation, and mortality. Given this unmet clinical need, new therapies are in development for the treatment of PBC. To provide pharmacists with an overview of the latest research on the pathophysiology of PBC and potential new treatment options and to highlight medical and specialty pharmacy approaches to managing access to drugs to treat orphan diseases such as PBC, a 2-hour satellite symposium was presented in conjunction with the 2015 Academy of Managed Care Pharmacy (AMCP) Nexus meeting. Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. The symposium was supported by an independent educational grant from Intercept Pharmaceuticals and was managed by Analysis Group. Robert Navarro, PharmD, moderated the CPE-accredited symposium titled "Medical and Specialty Pharmacy Management Update on Primary Biliary Cirrhosis." Expert panelists included Christopher L. Bowlus, MD; James T. Kenney, RPh, MBA; and Gary Rice, RPh, MS, MBA, CSP.
OBJECTIVE: To summarize the educational satellite symposium presentations and discussions.
SUMMARY: Autoimmune liver diseases, including PBC, are responsible for 15% of all liver transplants performed and an equal percentage of deaths related to liver disease. UDCA is the only FDA-approved therapy for treatment of PBC and is considered the standard of care. Nevertheless, many patients do not respond to UDCA, creating the need for new therapeutic options to improve clinical outcomes for PBC patients with inadequate response to treatment. While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results. Health plans are anticipated to assign any newly introduced therapy for the treatment of PBC to specialty pharmacy given its orphan disease status. This assignment enables the health plan to receive disease education, which is particularly important when new drugs are indicated for orphan diseases, and assistance with designing appropriate prior authorization criteria. The clinical value of any new therapeutic options that will inform formulary decisions and prior authorization criteria will be assessed based on evidence of efficacy, safety, and tolerability, among other factors, such as the potential to reduce or delay medical resource utilization (e.g., liver transplant). Key considerations for prior authorization of a new therapy will be determining which PBC patients are appropriate candidates for the new therapy and developing criteria for that determination. These are likely to include clinical diagnostic criteria and degree of response to prior treatment with UDCA. Initially, any new therapy would likely be positioned as noncovered until appropriate prior authorization criteria are established.
CONCLUSIONS: PBC is a chronic liver disease with significant morbidity and mortality, as well as a significant burden on the health care system if the disease progresses to the point at which a liver transplant is needed. Although UDCA, the current standard of care, has improved outcomes for many patients, others have an inadequate response to this treatment. This symposium discussed these issues and also addressed the overall treatment paradigm for orphan drug therapies, key implications for patient management, and the role of specialty pharmacy management and any associated needs both in general and specifically for new therapeutic options for PBC.

PMID: 27700211 [PubMed - in process]

Epidemiologic Analysis of Onychomycosis in the San Diego Pediatric Population.

Pediatr Dermatol. 2016 Oct 4;:

Authors: Totri CR, Feldstein S, Admani S, Friedlander SF, Eichenfield LF

Abstract
BACKGROUND: Onychomycosis (OM) is thought to be a rare disease in children, although there are few epidemiologic studies.
METHODS: This 3-year retrospective case series of nearly 400 children seen at Rady Children's Hospital-San Diego (RCHSD) describes the characteristics of OM found in this pediatric population.
RESULTS: From 2011 to 2013, the Pediatric and Adolescent Dermatology Clinic at RCHSD saw a total of 36,634 unique patients, of whom 433 were unique patients with OM. Thirty-four patients met exclusion criteria, leaving 399 (1.1%) with a diagnosis of OM by a pediatric dermatologist. Nail cultures were obtained in 242 cases (60.7%), 116 (48.0%) of which were positive. Trichophyton rubrum was the most commonly isolated pathogen, responsible for 106 cases (91.3%) of positive cultures in the cohort.
CONCLUSIONS: Our study provides important regional information regarding epidemiologic data in pediatric onychomycosis, highlighting the diagnostic methods most commonly used and the pathogens most frequently encountered in our practice.

PMID: 27699839 [PubMed - as supplied by publisher]

Parent training education program: a pilot study, involving families of children with Prader-Willi syndrome.

Ann Ist Super Sanita. 2016 Jul-Sep;52(3):428-433

Authors: Kodra Y, Kondili LA, Ferraroni A, Serra MA, Caretto F, Ricci MA, Taruscio D

Abstract
INTRODUCTION: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by severe hypotonia during the neonatal period and the first two years of life, the onset of hyperphagia with a risk of obesity during infancy and adulthood, learning difficulties and behavioral or severe psychiatric problems. This complex disease has severe consequences and difficult management issues also for patients' families. Parents of children with PWS need appropriate psychoeducational intervention in order to better manage their children with PWS. The purpose of this study was the implementation and evaluation of a PWS psychoeducational parent training program.
METHODS: The Italian National Center for Rare Diseases implemented a pilot parent training program offered to parents of children with PWS. The intervention's effects was evaluated using questionnaires comprised of 11 items rated on a 7 point Likert scale.
RESULTS: The intervention was offered to 43 parents. The behavior problems management, dietary restrictions, autonomy and relationships were indicated by parents as the priority topics which needed to be addressed. Evaluations, immediately post-intervention and after 6 months, were reported by parents, fulfilling specific questionnaires. 90% of parents involved in the study, appreciated the methodology, 86% felt more informed about PWS, 47-62% felt more capable to better approach behaviour's problems, 20-25% felt better about the child's health situation and future expectations. Feeling more capable to help the child autonomy and relationships were reported in 62% and 63% of parents respectively, which decreased significantly (p < 0.05) according to the evaluation 6 months after the intervention. Younger age of parents (< 44 years of age) was significantly correlated with better understanding on how to help the child's autonomy (OR: 0.05; CI: 0.04-0.8) and to better collaborate with the child's teachers (OR: 0.02; CI: 0.001-0.9).
CONCLUSION: Parent training is a promising intervention for parents of children with behavior's problems. Interventions with a behaviorally oriented program, addressed to parents of PWS affected children, is a useful tool in increasing their ability to manage the problems related to the disease.

PMID: 27698302 [PubMed - in process]

A genetic variant in Rassf1a predicts outcome in mCRC patients treated with cetuximab plus chemotherapy: results from FIRE-3 and JACCRO 05 and 06 trials.

Pharmacogenomics J. 2016 Oct 04;:

Authors: Sebio A, Stintzing S, Heinemann V, Sunakawa Y, Zhang W, Ichikawa W, Tsuji A, Takahashi T, Parek A, Yang D, Cao S, Ning Y, Stremitzer S, Matsusaka S, Okazaki S, Barzi A, Berger MD, Lenz HJ

Abstract
The Hippo pathway is involved in colorectal cancer (CRC) development and progression. The Hippo regulator Rassf1a is also involved in the Ras signaling cascade. In this work, we tested single nucleotide polymorphisms within Hippo components and their association with outcome in CRC patients treated with cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab within the FIRE-3 trial and 67 Ras WT patients treated either with first-line mFOLFOX6 or SOX plus Cetuximab). In these two populations, Rassf1a rs2236947 was associated with overall survival (OS), as patients with a CC genotype had significantly longer OS compared with those with CA or AA genotypes. This association was stronger in patients with left-side CRC (hazard ratio (HR): 1.79 (1.01-3.14); P=0.044 and HR: 2.83 (1.14-7.03); P=0.025, for Fire 3 and JACCRO cohorts, respectively). Rassf1a rs2236947 is a promising biomarker for patients treated with cetuximab plus chemotherapy.The Pharmacogenomics Journal advance online publication, 4 October 2016; doi:10.1038/tpj.2016.69.

PMID: 27698403 [PubMed - as supplied by publisher]

Confirmation of an IRAK3 polymorphism as a genetic marker predicting response to anti-TNF treatment in rheumatoid arthritis.

Pharmacogenomics J. 2016 Oct 04;:

Authors: Sode J, Vogel U, Bank S, Andersen PS, Hetland ML, Locht H, Heegaard NH, Andersen V

Abstract
Several genetic variants in Toll-like receptor (TLR) and nuclear factor (NF)-κB signalling pathways have been reported associated with responsiveness to tumour necrosis factor inhibitor (anti-TNF) treatment in rheumatoid arthritis (RA). The present study was undertaken to replicate these findings. In a retrospective case-case study including 1007 Danish anti-TNF-treated RA patients, we genotyped 7 previously reported associated single-nucleotide polymorphisms (SNPs) in these pathways. Furthermore, 5 SNPs previously reported by our group were genotyped in a subcohort (N=469). Primary analyses validated the IRAK3 rs11541076 variant as associated (odds ratio (OR)=1.33, 95% confidence interval (CI): 1.00-1.77, P-value=0.047) with a positive treatment response (EULAR (European League Against Rheumatism) good/moderate vs none response at 4±2 months), and found the NLRP3 rs461266 variant associated (OR=0.75, 95% CI: 0.60-0.94, P=0.014) with a negative treatment response. Meta-analyses combining data from previous studies suggested smaller effect sizes of associations between variant alleles of CHUK rs11591741, NFKBIB rs3136645 and rs9403 and a negative treatment response. In conclusion, this study validates rs11541076 in IRAK3, a negative regulator of TLR signalling, as a predictor of anti-TNF treatment response, and suggests true positive associations of previously reported SNPs within genes encoding activators/inhibitors of NF-κB (CHUK, MYD88, NFKBIB, and NLRP3).The Pharmacogenomics Journal advance online publication, 4 October 2016; doi:10.1038/tpj.2016.66.

PMID: 27698401 [PubMed - as supplied by publisher]

Sex impact on biomarkers, pharmacokinetics and pharmacodynamic: Sex and drugs.

Curr Med Chem. 2016 Oct 03;:

Authors: Franconi F, Campesi I

Abstract
Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably, remains poor and contains many methodological issues. In this review, the current state of knowledge about sex differences in pharmacokinetics and some hints to pharmacogenomics were evaluated. Moreover, considering that many pharmacological responses are monitored through biomarkers, the influence of sex on some biomarkers has been reported. Finally, we report sex differences in pharmacodynamics, particularly analysing opioids and their use during pregnancy, labor and breastfeeding. In conclusion, a more precise sex- and gender-based approach appears necessary to achieve more evidence-based therapy in men and women.

PMID: 27697075 [PubMed - as supplied by publisher]

Dual-action Hybrid Compounds - A New Dawn in the Discovery of Multi-target Drugs: Lead Generation Approaches.

Curr Top Med Chem. 2016 Sep 27;:

Authors: Abdolmalekia A, Ghasemi JB

Abstract
Finding high quality beginning compounds is a critical job at the start of the lead generation stage for multi-target drug discovery (MTDD). Designing hybrid compounds as a selective multi-target chemical entity is a challenge, opportunity, and new idea to better act against specific multiple targets. One hybrid molecule is formed by two (or more) pharmacophore group's participation. So, these new compounds often exhibit two or more activities going about as multi-target drugs (mt-drugs) and may have superior safety or efficacy. Application of integrating a range of information and sophisticated new in silico, bioinformatics, structural biology, pharmacogenomics methods may be useful to discover/design, and synthesis of the new hybrid molecules. In this regard, many rational and screening approaches have followed by medicinal chemists for the lead generation in MTDD. Here, we review some popular lead generation approaches that have been used for designing multiple ligands (DMLs). This paper focuses on dual- acting chemical entities that incorporate a part of two drugs or bioactive compounds to compose hybrid molecules. Also, it presents some of key concepts and limitations/strengths of lead generation methods by comparing combination framework method with screening approaches. Besides, a number of examples to represent applications of hybrid molecules in the drug discovery are included.

PMID: 27697056 [PubMed - as supplied by publisher]

Time is ripe: maturation of metabolomics in chronobiology.

Curr Opin Biotechnol. 2016 Oct 1;43:70-76

Authors: Rhoades SD, Sengupta A, Weljie AM

Abstract
Sleep and circadian rhythms studies have recently benefited from metabolomics analyses, uncovering new connections between chronobiology and metabolism. From untargeted mass spectrometry to quantitative nuclear magnetic resonance spectroscopy, a diversity of analytical approaches has been applied for biomarker discovery in the field. In this review we consider advances in the application of metabolomics technologies which have uncovered significant effects of sleep and circadian cycles on several metabolites, namely phosphatidylcholine species, medium-chain carnitines, and aromatic amino acids. Study design and data processing measures essential for detecting rhythmicity in metabolomics data are also discussed. Future developments in these technologies are anticipated vis-à-vis validating early findings, given metabolomics has only recently entered the ring with other systems biology assessments in chronometabolism studies.

PMID: 27701007 [PubMed - as supplied by publisher]

Stochasticity in the miR-9/Hes1 oscillatory network can account for clonal heterogeneity in the timing of differentiation.

Elife. 2016 Oct 04;5:

Authors: Phillips NE, Manning CS, Pettini T, Biga V, Marinopoulou E, Stanley P, Boyd J, Bagnall J, Paszek P, Spiller DG, White MR, Goodfellow M, Galla T, Rattray M, Papalopulu N

Abstract
Recent studies suggest that cells make stochastic choices with respect to differentiation or division. However, the molecular mechanism underlying such stochasticity is unknown. We previously proposed that the timing of vertebrate neuronal differentiation is regulated by molecular oscillations of a transcriptional repressor, HES1, tuned by a post-transcriptional repressor, miR-9. Here, we computationally model the effects of intrinsic noise on the Hes1/miR-9 oscillator as a consequence of low molecular numbers of interacting species, determined experimentally. We report that increased stochasticity spreads the timing of differentiation in a population, such that initially equivalent cells differentiate over a period of time. Surprisingly, inherent stochasticity also increases the robustness of the progenitor state and lessens the impact of unequal, random distribution of molecules at cell division on the temporal spread of differentiation at the population level. This advantageous use of biological noise contrasts with the view that noise needs to be counteracted.

PMID: 27700985 [PubMed - in process]

Gene pathway development in human epicardial adipose tissue during early life.

JCI Insight. 2016 Aug 18;1(13):e87460

Authors: Ojha S, Fainberg HP, Wilson V, Pelella G, Castellanos M, May ST, Lotto AA, Sacks H, Symonds ME, Budge H

Abstract
Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life.

PMID: 27699231 [PubMed - in process]

Data on translatome analysis of Mycoplasma gallisepticum.

Data Brief. 2016 Dec;9:422-424

Authors: Fisunov GY, Evsyutina DV, Govorun VM

Abstract
Mycoplasma gallisepticum is a bacterium of class Mollicutes which encompasses wall-less bacteria with significantly reduced genomes. Due to their overall reduction and simplicity mycoplasmas serve as a model of minimal cell and are used for systems biology studies. Here we present raw data on translatome (ribosome-bound mRNA) analysis of Mycoplasma gallisepticum under logarithm growth and heat stress. The data supports the publication of "Ribosomal profiling of Mycoplasma gallisepticum" (G. Y. Fisunov, D. V Evsyutina, A. A. Arzamasov, I. O. Butenko, V. M. Govorun, 2015) [1].

PMID: 27699194 [PubMed - in process]

A perspective on bridging scales and design of models using low-dimensional manifolds and data-driven model inference.

Philos Trans A Math Phys Eng Sci. 2016 Nov 13;374(2080):

Authors: Tegnér J, Zenil H, Kiani NA, Ball G, Gomez-Cabrero D

Abstract
Systems in nature capable of collective behaviour are nonlinear, operating across several scales. Yet our ability to account for their collective dynamics differs in physics, chemistry and biology. Here, we briefly review the similarities and differences between mathematical modelling of adaptive living systems versus physico-chemical systems. We find that physics-based chemistry modelling and computational neuroscience have a shared interest in developing techniques for model reductions aiming at the identification of a reduced subsystem or slow manifold, capturing the effective dynamics. By contrast, as relations and kinetics between biological molecules are less characterized, current quantitative analysis under the umbrella of bioinformatics focuses on signal extraction, correlation, regression and machine-learning analysis. We argue that model reduction analysis and the ensuing identification of manifolds bridges physics and biology. Furthermore, modelling living systems presents deep challenges as how to reconcile rich molecular data with inherent modelling uncertainties (formalism, variables selection and model parameters). We anticipate a new generative data-driven modelling paradigm constrained by identified governing principles extracted from low-dimensional manifold analysis. The rise of a new generation of models will ultimately connect biology to quantitative mechanistic descriptions, thereby setting the stage for investigating the character of the model language and principles driving living systems.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'.

PMID: 27698038 [PubMed - in process]

Systems biology: impressions from a newcomer graduate student in 2016.

Adv Physiol Educ. 2016 Dec;40(4):443-445

Authors: Simpson MR

Abstract
As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in 2016?" are somewhat more elusive. This seems to be due largely to the diversity of disciplines involved and the varying emphasis placed on the computational modeling and experimental aspects of systems biology. As such, the education of systems biology would benefit from multidisciplinary collaboration with both instructors and students from a range of disciplines within the same course. This essay is the personal reflection of a graduate student trying to get an introductory overview of the field of systems biology and some thoughts about effective education of systems biology.

PMID: 27697957 [PubMed - in process]

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

("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

These pubmed results were generated on 2016/10/04

PubMed comprises more than 24 million 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.

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

"Cystic Fibrosis"

These pubmed results were generated on 2016/10/04

PubMed comprises more than 24 million 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.

Design of efficient computational workflows for in silico drug repurposing.

Drug Discov Today. 2016 Sep 27;:

Authors: Vanhaelen Q, Mamoshina P, Aliper AM, Artemov A, Lezhnina K, Ozerov I, Labat I, Zhavoronkov A

Abstract
Here, we provide a comprehensive overview of the current status of in silico repurposing methods by establishing links between current technological trends, data availability, and characteristics of the algorithms used in these methods. Using the case of the computational repurposing of fasudil as an alternative autophagy enhancer, we suggest a generic modular organization of a repurposing workflow. We also review 3D structure-based, similarity-based, inference-based, and machine learning (ML)-based methods. We summarize the advantages and disadvantages of these methods to emphasize three current technical challenges. We finish by discussing current directions of research, including possibilities offered by new methods, such as deep learning.

PMID: 27693712 [PubMed - as supplied by publisher]

Drug Repurposing: New Treatments for Zika Virus Infection?

Trends Mol Med. 2016 Sep 27;:

Authors: Cheng F, Murray JL, Rubin DH

Abstract
To date, no antiviral agents have been approved for treating Zika virus (ZIKV) infection. Two recent drug-repurposing studies published in Cell Host & Microbe and Nature Medicine demonstrated that screening FDA-approved drugs for antiviral activity is a promising strategy for identifying therapeutics with novel activity against ZIKV infection.

PMID: 27692879 [PubMed - as supplied by publisher]

Pharmacogenomics of the cytochrome P450 2C family: impacts of amino acid variations on drug metabolism.

Drug Discov Today. 2016 Sep 27;:

Authors: Isvoran A, Louet M, Vladoiu DL, Craciun D, Loriot MA, Villoutreix BO, Miteva MA

Abstract
Pharmacogenomics investigates DNA and RNA variations in the human genome related to drug responses. Cytochrome P450 (CYP) is a supergene family of drug-metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical significance because it metabolizes approximately 20% of clinically administrated drugs and represents several variant alleles leading to adverse drug reactions or altering drug efficacy. Here, we review recent progress on understanding the interindividual variability of the CYP2C members and the functional and clinical impact on drug metabolism. We summarize current advances in the molecular modeling of CYP2C polymorphisms and discuss the structural bases and molecular mechanisms of amino acid variants of CYP2C members that affect drug metabolism.

PMID: 27693711 [PubMed - as supplied by publisher]