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

pharmacogenomics

These pubmed results were generated on 2017/07/19

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.

12 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 2017/07/19

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.

39 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 2017/07/19

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.

Related Articles

Identification of driver copy number alterations in diverse cancer types and application in drug repositioning.

Mol Oncol. 2017 Jul 18;:

Authors: Zhou W, Zhao Z, Wang R, Han Y, Wang C, Yang F, Han Y, Liang H, Qi L, Wang C, Guo Z, Gu Y

Abstract
Results from numerous studies suggest an important role for somatic copy number alterations (SCNAs) in cancer progression. Our work aimed to identify the drivers (oncogenes or tumor suppressor genes) that reside in recurrently aberrant genomic regions, including a large number of genes or non-coding genes, which remain a challenge for decoding the SCNAs involved in carcinogenesis. Here, we propose a new approach to comprehensively identify drivers, using 8740 cancer samples involving 18 cancer types from The Cancer Genome Atlas (TCGA). On average, 84 drivers were revealed for each cancer type, including protein-coding genes, long non-coding RNAs (lncRNA) and microRNAs (miRNAs). We demonstrated that the drivers showed significant attributes of cancer genes, and significantly overlapped with known cancer genes, including MYC, CCND1, and ERBB2 in breast cancer, and the lncRNA PVT1 in multiple cancer types. Pan-cancer analyses of drivers revealed specificity and commonality across cancer types, and the non-coding drivers showed a higher cancer-type specificity than that of coding drivers. Some cancer types from different tissue origins were found to converge to high similarity because of the significant overlap of drivers, such as head and neck squamous cell carcinoma (HNSC) and lung squamous cell carcinoma (LUSC). The lncRNA SOX2-OT, a common driver of HNSC and LUSC, showed significant expression correlation with the oncogene SOX2. In addition, because some drivers are common in multiple cancer types and have been targeted by known drugs, we revealed that some drugs could be successfully repositioned which was validated by the datasets of drug response assays in cell lines. Our work reported a new method to comprehensively identify drivers in SCNAs across diverse cancer types, providing a feasible strategy for cancer drug repositioning as well as novel findings regarding cancer-associated non-coding RNA discovery. This article is protected by copyright. All rights reserved.

PMID: 28719033 [PubMed - as supplied by publisher]

Related Articles

Drugs currently under investigation for the treatment of invasive candidiasis.

Expert Opin Investig Drugs. 2017 Jul;26(7):825-831

Authors: McCarthy MW, Walsh TJ

Abstract
INTRODUCTION: The widespread implementation of immunosuppressants, immunomodulators, hematopoietic stem cell transplantation and solid organ transplantation in clinical practice has led to an expanding population of patients who are at risk for invasive candidiasis, which is the most common form of fungal disease among hospitalized patients in the developed world. The emergence of drug-resistant Candida spp. has added to the morbidity associated with invasive candidiasis and novel therapeutic strategies are urgently needed. Areas covered: In this paper, we explore investigational agents for the treatment of invasive candidiasis, with particular attention paid to compounds that have recently entered phase I or phase II clinical trials. Expert opinion: The antifungal drug development pipeline has been severely limited due to regulatory hurdles and a systemic lack of investment in novel compounds. However, several promising drug development strategies have recently emerged, including chemical screens involving Pathogen Box compounds, combination antifungal therapy, and repurposing of existing agents that were initially developed to treat other conditions, all of which have the potential to redefine the treatment of invasive candidiasis.

PMID: 28617137 [PubMed - indexed for MEDLINE]

Related Articles

Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease.

Gut. 2017 Jan;66(1):180-190

Authors: Rotman Y, Sanyal AJ

Abstract
Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease.

PMID: 27646933 [PubMed - indexed for MEDLINE]

Related Articles

Global Carrier Rates of Rare Inherited Disorders Using Population Exome Sequences.

PLoS One. 2016;11(5):e0155552

Authors: Fujikura K

Abstract
Exome sequencing has revealed the causative mutations behind numerous rare, inherited disorders, but it is challenging to find reliable epidemiological values for rare disorders. Here, I provide a genetic epidemiology method to identify the causative mutations behind rare, inherited disorders using two population exome sequences (1000 Genomes and NHLBI). I created global maps of carrier rate distribution for 18 recessive disorders in 16 diverse ethnic populations. Out of a total of 161 mutations associated with 18 recessive disorders, I detected 24 mutations in either or both exome studies. The genetic mapping revealed strong international spatial heterogeneities in the carrier patterns of the inherited disorders. I next validated this methodology by statistically evaluating the carrier rate of one well-understood disorder, sickle cell anemia (SCA). The population exome-based epidemiology of SCA [African (allele frequency (AF) = 0.0454, N = 2447), Asian (AF = 0, N = 286), European (AF = 0.000214, N = 4677), and Hispanic (AF = 0.0111, N = 362)] was not significantly different from that obtained from a clinical prevalence survey. A pair-wise proportion test revealed no significant differences between the two exome projects in terms of AF (46/48 cases; P > 0.05). I conclude that population exome-based carrier rates can form the foundation for a prospectively maintained database of use to clinical geneticists. Similar modeling methods can be applied to many inherited disorders.

PMID: 27219052 [PubMed - indexed for MEDLINE]

Related Articles

Variants in the IL-8 gene and the response to inhaled bronchodilators in cystic fibrosis.

J Pediatr (Rio J). 2017 Jul 15;:

Authors: Furlan LL, Ribeiro JD, Bertuzzo CS, Salomão Junior JB, Souza DRS, Marson FAL

Abstract
OBJECTIVE: IL-8 (interleukin 8) protein promotes inflammatory responses, even in airways. The presence of IL-8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators (BD). Thus, this study analyzed the IL-8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to BD in cystic fibrosis (CF) patients.
METHODS: Analysis of IL-8 gene variants was performed by RFLP-PCR. The association between spirometry markers and the response to BD was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all CF patients, and subsequently patients with two mutations in the CFTR gene belonging to classes I to III.
RESULTS: This study included 186 CF patients. There was no association of the rs2227307 variant with the response to BD. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the CFTR gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%) dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC).
CONCLUSIONS: This study highlighted the importance of the rs4073 variant of the IL-8 gene, regarding response to BD, and of the assessment of mutations in the CFTR gene.

PMID: 28719800 [PubMed - as supplied by publisher]

Related Articles

A systematic review of the prevalence and impact of urinary incontinence in cystic fibrosis.

Respirology. 2017 Jul 18;:

Authors: Frayman KB, Kazmerski TM, Sawyer SM

Abstract
This systematic review synthesizes published articles investigating the prevalence, severity and impact of urinary incontinence (UI), a condition associated with cystic fibrosis (CF). References were identified through searching Medline, Embase and PubMed using the medical subject headings 'cystic fibrosis' AND 'urinary incontinence'. Articles were included if UI prevalence was investigated as an outcome. Twelve studies met selection criteria. The prevalence of UI ranged from 5% to 76%. Age and gender contributed to this variability. When assessed, UI commonly limited airway clearance, exercise and/or spirometry, and had a variable impact on patients' lives. Worry and embarrassment were features for many; others were less affected. In CF, UI is common and can interfere with respiratory care and social well-being. The prevalence, characteristics and impact are poorly understood, which is made worse by inconsistent definitions across studies. Future research is needed to improve approaches to prevention, identification, management and education.

PMID: 28718995 [PubMed - as supplied by publisher]

Related Articles

Evolution of the Pseudomonas aeruginosa mutational resistome in an international Cystic Fibrosis clone.

Sci Rep. 2017 Jul 17;7(1):5555

Authors: López-Causapé C, Sommer LM, Cabot G, Rubio R, Ocampo-Sosa AA, Johansen HK, Figuerola J, Cantón R, Kidd TJ, Molin S, Oliver A

Abstract
Emergence of epidemic clones and antibiotic resistance development compromises the management of Pseudomonas aeruginosa cystic fibrosis (CF) chronic respiratory infections. Whole genome sequencing (WGS) was used to decipher the phylogeny, interpatient dissemination, WGS mutator genotypes (mutome) and resistome of a widespread clone (CC274), in isolates from two highly-distant countries, Australia and Spain, covering an 18-year period. The coexistence of two divergent CC274 clonal lineages was revealed, but without evident geographical barrier; phylogenetic reconstructions and mutational resistome demonstrated the interpatient transmission of mutators. The extraordinary capacity of P. aeruginosa to develop resistance was evidenced by the emergence of mutations in >100 genes related to antibiotic resistance during the evolution of CC274, catalyzed by mutator phenotypes. While the presence of classical mutational resistance mechanisms was confirmed and correlated with resistance phenotypes, results also showed a major role of unexpected mutations. Among them, PBP3 mutations, shaping up β-lactam resistance, were noteworthy. A high selective pressure for mexZ mutations was evidenced, but we showed for the first time that high-level aminoglycoside resistance in CF is likely driven by mutations in fusA1/fusA2, coding for elongation factor G. Altogether, our results provide valuable information for understanding the evolution of the mutational resistome of CF P. aeruginosa.

PMID: 28717172 [PubMed - in process]

Related Articles

Lower exhaled nitric oxide in infants with Cystic Fibrosis compared to healthy controls.

J Cyst Fibros. 2017 Jul 14;:

Authors: Korten I, Liechti M, Singer F, Hafen G, Rochat I, Anagnostopoulou P, Müller-Suter D, Usemann J, Moeller A, Frey U, Latzin P, Casaulta C, SCILD and BILD study group

Abstract
Exhaled nitric oxide (FENO) is a well-known, non-invasive airway biomarker. In patients with Cystic Fibrosis (CF) FENO is decreased. To understand if reduced FENO is primary related to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) dysfunction or an epiphenomenon of chronic inflammation, we measured FENO in 34 infants with CF prior to clinical symptoms and in 68 healthy controls. FENO was lower in CF compared to controls (p=0.0006) and the effect was more pronounced in CF infants without residual CFTR function (p<0.0001). This suggests that FENO is reduced in CF early in life, possibly associated with underlying CFTR dysfunction.

PMID: 28716479 [PubMed - as supplied by publisher]

Related Articles

Multidrug-resistant Pseudomonas aeruginosa lower respiratory tract infections in the intensive care unit: Prevalence and risk factors.

Diagn Microbiol Infect Dis. 2017 Jun 19;:

Authors: Trinh TD, Zasowski EJ, Claeys KC, Lagnf AM, Kidambi S, Davis SL, Rybak MJ

Abstract
Intensive care unit (ICU) admission is a risk for multidrug-resistant (MDR) Pseudomonas aeruginosa, but factors specific to critically ill pneumonia patients are not fully characterized. Objective was to determine risk factors associated with MDR P. aeruginosa pneumonia among ICU patients. This was a retrospective case-control study of P. aeruginosa pneumonia in the ICU; cystic fibrosis and colonizers were excluded. Risk factors included comorbid conditions and prior healthcare exposure (anti-pseudomonal antibiotics, hospitalizations, nursing home, P. aeruginosa colonization/infection, mechanical ventilation). Of 200 patients, 47 (23.5%) had MDR P. aeruginosa pneumonia. Independent predictors for MDR were ≥24h antibiotics in the preceding 90days (carbapenems, fluoroquinolones, and piperacillin-tazobactam) (odds ratio, 3.6 [95% CI, 1.6-8.1]) and nursing home residence (2.3 [1.1-4.9]). MDR P. aeruginosa remains prevalent among ICU patients with pneumonia. Given poor outcomes with delayed therapy, patients should be thoroughly assessed for prior anti-pseudomonal antibiotic exposure and nursing home residency.

PMID: 28716451 [PubMed - as supplied by publisher]

Related Articles

Diffuse edema suggestive of cytokine release syndrome in a metastatic lung carcinoma patient treated with pembrolizumab.

Immunotherapy. 2017 Mar;9(4):309-311

Authors: Rassy EE, Assi T, Rizkallah J, Kattan J

Abstract
Immune checkpoint inhibitors (ICIs) are actually being indicated more commonly in the management of chemoresistant cancer patients in view of their favorable toxicity profile in comparison to cytotoxic chemotherapy. In this paper, we report, to our knowledge, the first case suggestive of cytokine release syndrome secondary to pembrolizumab in a patient with metastatic lung squamous cell carcinoma. In view of the quick approvals of ICI and the absence of sufficient knowledge of the corresponding toxicity profile, the occurrence of any clinical or biological sign or symptom in patients receiving ICI requires further investigation.

PMID: 28303768 [PubMed - indexed for MEDLINE]

Related Articles

Case report of nivolumab-related pneumonitis.

Immunotherapy. 2017 Mar;9(4):313-318

Authors: Tada K, Kurihara Y, Myojo T, Kojima F, Ishikawa Y, Yoshiyasu N, Morimoto M, Ito R, Koyamada R, Yamashita T, Bando T, Mori S, Heike Y

Abstract
We report a case with suggestive antiprogrammed death-1 inhibitor-related pneumonitis in an endometrial cancer patient. This case presented with fever and cough after three dosages of nivolumab. Computed tomography initially showed centrilobular nodularities in a unilateral lung, which was compatible with aspiration pneumonia. However, diffuse ground-glass opacities (GGO) rapidly developed in the unilateral lung over 4 days despite the use of broad-spectrum antibiotics. Development of GGO was considered to be related to a nivolumab-mediated immune reaction. Corticosteroid was administered and the GGO subsequently disappeared. The present report focuses on the computed tomography diagnostic features of nivolumab-related pneumonitis. The accumulation of knowledge regarding various types of antiprogrammed death-1-related pneumonitis will lead to appropriate treatment for this newly emerging adverse event.

PMID: 28303763 [PubMed - indexed for MEDLINE]

Related Articles

Show drugs work before selling them.

Nature. 2017 03 08;543(7644):174-175

Authors: Sipp D, McCabe C, Rasko JE

PMID: 28277530 [PubMed - indexed for MEDLINE]

Related Articles

Nurses' Perceived Skills and Attitudes About Updated Safety Concepts: Impact on Medication Administration Errors and Practices.

J Nurs Care Qual. 2017 Jul/Sep;32(3):226-233

Authors: Armstrong GE, Dietrich M, Norman L, Barnsteiner J, Mion L

Abstract
Approximately a quarter of medication errors in the hospital occur at the administration phase, which is solely under the purview of the bedside nurse. The purpose of this study was to assess bedside nurses' perceived skills and attitudes about updated safety concepts and examine their impact on medication administration errors and adherence to safe medication administration practices. Findings support the premise that medication administration errors result from an interplay among system-, unit-, and nurse-level factors.

PMID: 27607849 [PubMed - indexed for MEDLINE]

Related Articles

Anticholinergic properties of medications.

Geriatr Nurs. 2016 Jul-Aug;37(4):302-3

Authors: Simonson W

PMID: 27393158 [PubMed - indexed for MEDLINE]

Funding Opportunity PA-17-328 from the NIH Guide for Grants and Contracts. The purpose of the NIMH Administrative Supplement Program to Enable Continuity of Research Experiences of MD/PhDs during Clinical Training is to support advanced research opportunities for exceptional individuals holding the MD/PhD degree who are early in their research careers and thereby help these individuals transition efficiently and effectively from the period of clinical training to the next stage of their research careers. This administrative supplement program will provide focused, protected research time for eligible individuals during residency and/or clinical fellowship. The proposed research experience must have the potential to contribute significantly to the candidates research career. Administrative supplements must support work within the scope of the original project. All applicants are encouraged to discuss potential requests with the NIMH prior to submission (see Section VII. Agency Contacts).

Funding Opportunity PA-17-326 from the NIH Guide for Grants and Contracts. The National Institutes of Health (NIH) announces the continuation of the U.S. entity of the U.S.-Japan Brain Research Cooperative Program (BRCP). This administrative supplement program will provide funds to research projects that are currently supported by the participating NIH Institutes and Centers.

Funding Opportunity PAR-17-327 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage cooperative agreement applications to support early stage clinical trials of novel mechanism of action, investigational drugs or drug candidates for the treatment of psychiatric disorders in areas of unmet medical need. The FOA will support milestone-driven early stage trials in pediatric and adult populations. First in human (FIH) and Phase Ib studies of novel Agents must assess target engagement (brain exposure), pharmacological effects, safety, and tolerability to assess feasibility for Phase II/proof of concept (PoC) studies in psychiatric disorders. PoC studies must evaluate the drugs impact on clinically relevant physiological systems (functional measures) and clinical indicators of effect. The FOA also supports FIH and early feasibility studies (EFS) of novel devices to evaluate target engagement, safety, tolerability, and efficacy. The overall objective is to facilitate rapid collection of data to "de-risk" novel mechanism of action investigational drugs, novel drugs for use in pediatric populations with psychiatric disorders, and devices or combination treatments in order to attract private funding for further clinical development as FDA-approved treatments. A key aspect of this FOA is the formation of collaborative partnerships between the biomedical researchers and biotechnology or industry researchers to facilitate psychiatric drug or device development.