8 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 2017/03/05

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.

The Microbiome in Allergic Disease: Current Understanding and Future Opportunities - 2017 PRACTALL Document of the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy and Clinical Immunology.

J Allergy Clin Immunol. 2017 Feb 28;:

Authors: Huang YJ, Marsland BJ, Bunyavanich S, O'Mahony L, Leung DY, Muraro A, Fleisher TA

Abstract
PRACTALL is a joint initiative of the American Academy of Allergy, Asthma and Immunology (AAAAI) with the European Academy of Allergy and Clinical Immunology (EAACI) to provide shared evidence-based recommendations on cutting-edge topics in the field of allergy and immunology PRACTALL 2017 is focused on what has been established regarding the role of the microbiome in asthma, atopic dermatitis (AD) and food allergy. This is complemented by outlining important knowledge gaps regarding its role in allergic disease and delineating strategies necessary to fill these gaps. In addition, a review of progress in approaches used to manipulate the microbiome will be addressed, identifying what has and has not worked to serve as a baseline for future directions to intervene in allergic disease development and/or progression.

PMID: 28257972 [PubMed - as supplied by publisher]

6 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 2017/03/04

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.

Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations.

PLoS One. 2017;12(3):e0173303

Authors: Matthews H, Deakin J, Rajab M, Idris-Usman M, Nirmalan NJ

Abstract
The widespread introduction of artemisinin-based combination therapy has contributed to recent reductions in malaria mortality. Combination therapies have a range of advantages, including synergism, toxicity reduction, and delaying the onset of resistance acquisition. Unfortunately, antimalarial combination therapy is limited by the depleting repertoire of effective drugs with distinct target pathways. To fast-track antimalarial drug discovery, we have previously employed drug-repositioning to identify the anti-amoebic drug, emetine dihydrochloride hydrate, as a potential candidate for repositioned use against malaria. Despite its 1000-fold increase in in vitro antimalarial potency (ED50 47 nM) compared with its anti-amoebic potency (ED50 26-32 uM), practical use of the compound has been limited by dose-dependent toxicity (emesis and cardiotoxicity). Identification of a synergistic partner drug would present an opportunity for dose-reduction, thus increasing the therapeutic window. The lack of reliable and standardised methodology to enable the in vitro definition of synergistic potential for antimalarials is a major drawback. Here we use isobologram and combination-index data generated by CalcuSyn software analyses (Biosoft v2.1) to define drug interactivity in an objective, automated manner. The method, based on the median effect principle proposed by Chou and Talalay, was initially validated for antimalarial application using the known synergistic combination (atovaquone-proguanil). The combination was used to further understand the relationship between SYBR Green viability and cytocidal versus cytostatic effects of drugs at higher levels of inhibition. We report here the use of the optimised Chou Talalay method to define synergistic antimalarial drug interactivity between emetine dihydrochloride hydrate and atovaquone. The novel findings present a potential route to harness the nanomolar antimalarial efficacy of this affordable natural product.

PMID: 28257497 [PubMed - in process]

EMA401: an old antagonist of the AT2R for a new indication in neuropathic pain.

J Pain Res. 2017;10:439-443

Authors: Keppel Hesselink JM, Schatman ME

Abstract
EMA401 is an old molecule, synthesized by Parke-Davis in the last century and characterized at that time as an AT2R antagonist. Professor Maree Smith and her group from the University of Queensland (Australia) patented the drug and many related derivatives and other compounds with high affinity for the AT2R for the indication neuropathic pain in 2004, an example of drug repositioning. After some years of university work, the Australian biotech company Spinifex Pharmaceuticals took over further research and development and characterized the S-enantiomer, code name EMA401, and related compounds in a variety of animal models for neuropathic and cancer pain. EMA401 was selected as the lead compound, based on high selectivity for the AT2R and good oral bioavailability (33%). EMA401, however, was only administered once in a chronic neuropathic pain model, and no data have been published in other pain models, or during steady state, although such data were available for the racemate EMA400 and some related compounds (EMA200, EMA400). A pilot phase IIa study demonstrated the efficacy and safety of the drug taken twice daily as two capsules of 50 mg (400 mg/day). In 2015, Novartis took over the clinical development. Two phase IIb studies designed by Spinifex Pharmaceuticals were put on hold, probably because Novartis wanted to improve the clinical design or collect additional preclinical data. Further data are eagerly awaited, especially since EMA401 is first-in-class in neuropathic pain.

PMID: 28255254 [PubMed - in process]

From ancient herb to versatile, modern drug: Artemisia annua and artemisinin for cancer therapy.

Semin Cancer Biol. 2017 Feb 27;:

Authors: Efferth T

Abstract
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.

PMID: 28254675 [PubMed - as supplied by publisher]

Text mining for improved exposure assessment.

PLoS One. 2017;12(3):e0173132

Authors: Larsson K, Baker S, Silins I, Guo Y, Stenius U, Korhonen A, Berglund M

Abstract
Chemical exposure assessments are based on information collected via different methods, such as biomonitoring, personal monitoring, environmental monitoring and questionnaires. The vast amount of chemical-specific exposure information available from web-based databases, such as PubMed, is undoubtedly a great asset to the scientific community. However, manual retrieval of relevant published information is an extremely time consuming task and overviewing the data is nearly impossible. Here, we present the development of an automatic classifier for chemical exposure information. First, nearly 3700 abstracts were manually annotated by an expert in exposure sciences according to a taxonomy exclusively created for exposure information. Natural Language Processing (NLP) techniques were used to extract semantic and syntactic features relevant to chemical exposure text. Using these features, we trained a supervised machine learning algorithm to automatically classify PubMed abstracts according to the exposure taxonomy. The resulting classifier demonstrates good performance in the intrinsic evaluation. We also show that the classifier improves information retrieval of chemical exposure data compared to keyword-based PubMed searches. Case studies demonstrate that the classifier can be used to assist researchers by facilitating information retrieval and classification, enabling data gap recognition and overviewing available scientific literature using chemical-specific publication profiles. Finally, we identify challenges to be addressed in future development of the system.

PMID: 28257498 [PubMed - in process]

Pharmacogenomics and tailored polypharmacy: an 80-year-old lady with rosuvastatin-associated rhabdomyolysis and maprotiline-related Ogilvie's syndrome
.

Int J Clin Pharmacol Ther. 2017 Mar 03;:

Authors: Sreter KB, Barisic B, Popovic-Grle S

Abstract
What is known and objectives: Multiple adverse drug reactions (ADRs) are expected, and thus should be prevented in the elderly comorbid patient on polypharmacy. Rosuvastatin is commonly prescribed for the treatment and prevention of atherosclerotic diseases, and in rare cases, is associated with rhabdomyolysis. Maprotiline is a tetracyclic antidepressant, infrequently used in the United States, but seemingly more broadly in European countries. Acute colonic pseudo-obstruction (Ogilvie's syndrome) caused by maprotiline has thus far, to our knowledge, not yet been described in the literature.
CASE SUMMARY: We present a unique case of synchronous rhabdomyolysis and Ogilvie's syndrome in an 80-year-old lung cancer survivor following a recent ischemic stroke for which she was prescribed clopidogrel and rosuvastatin for secondary prevention, and maprotiline for post-stroke, new-onset insomnia and anxiety. The ADRs resolved on removal of the offending agents and initiation of conservative treatment. Retrospective pharmacogenetic testing of the patient's drug-metabolizing enzymes and transporters was performed to guide further management and prevent future potential drug interactions and ADRs. What is novel and conclusions: This is an interesting, albeit unfortunate, complex case that depicts the risk of rare adverse effects to medications and their potential relationship to pharmacogenetics. The impact of anticholinergic side effects of antidepressants on gastrointestinal motility, risk of myopathies with statins, increased susceptibility to ADRs caused by drug-drug interactions, and the utility of pharmacogenomic testing are discussed. The question whether commercially available pharmacogenomic tools are relevant for everyday use to direct patient care and reduce harmful drug-drug interactions is addressed and warrants further research.
.

PMID: 28257284 [PubMed - as supplied by publisher]

Small airway dysfunction in well-treated never-smoking HIV-infected individuals.

Eur Respir J. 2017 Mar;49(3):

Authors: Ronit A, Mathiesen IH, Gelpi M, Benfield T, Gerstoft J, Pressler T, Christiansen A, Lundgren J, Vestbo J, Dam Nielsen S

PMID: 28254767 [PubMed - in process]

Impaired rib bone mass and quality in end-stage cystic fibrosis patients.

Bone. 2017 Feb 22;98:9-17

Authors: Mailhot G, Dion N, Farlay D, Rizzo S, Bureau NJ, Jomphe V, Sankhe S, Boivin G, Lands LC, Ferraro P, Ste-Marie LG

Abstract
BACKGROUND: Advancements in research and clinical care have considerably extended the life expectancy of cystic fibrosis (CF) patients. However, with this extended survival come comorbidities. One of the leading co-morbidities is CF-related bone disease (CFBD), which progresses with disease severity and places patients at high risk for fractures, particularly of the ribs and vertebrae. Evidence that CF patients with vertebral fractures had higher bone mineral density (BMD) than the nonfracture group led us to postulate that bone quality is impaired in these patients. We therefore examined rib specimens resected at the time of lung transplant in CF patients to measure parameters of bone quantity and quality.
METHODS: In this exploratory study, we analysed 19 end-stage CF and 13 control rib specimens resected from otherwise healthy lung donors. BMD, bone microarchitecture, static parameters of bone formation and resorption and microcrack density of rib specimens were quantified by imaging, histomorphometric and histological methods. Variables reflecting the mineralization of ribs were assessed by digitized microradiography. The degree of bone mineralization (g/cm(3)) and the heterogeneity index of the mineralization (g/cm(3)) were calculated for trabecular and cortical bone.
RESULTS: Compared to controls, CF ribs exhibited lower areal and trabecular volumetric BMD, decreased trabecular thickness and osteoid parameters, and increased microcrack density, that was particularly pronounced in specimens from patients with CF-related diabetes. Static parameters of bone resorption were similar in both groups. Degree of mineralization of total bone, but not heterogeneity index, was increased in CF specimens.
CONCLUSION: The combination of reduced bone mass, altered microarchitecture, imbalanced bone remodeling (maintained bone resorption but decreased formation), increased microdamage and a small increase of the degree of mineralization, may lead to decreased bone strength, which, when coupled with chronic coughing and chest physical therapy, may provide an explanation for the increased incidence of rib fractures previously reported in this population.

PMID: 28254466 [PubMed - as supplied by publisher]

The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

J Cyst Fibros. 2017 Jan;16(1):13-23

Authors: Bos AC, Passé KM, Mouton JW, Janssens HM, Tiddens HA

Abstract
BACKGROUND: Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree.
OBJECTIVES: To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF.
METHODS: Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included.
RESULTS: 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics.
CONCLUSIONS: After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa.

PMID: 28254026 [PubMed - in process]

Anesthesia for Patients with Concomitant Hepatic and Pulmonary Dysfunction.

Anesthesiol Clin. 2016 Dec;34(4):797-808

Authors: Diaz GC, O'Connor MF, Renz JF

Abstract
Hepatic function and pulmonary function are interrelated with failure of one organ system affecting the other. With improved therapies, patients with concomitant hepatic and pulmonary failure increasingly enjoy a good quality of life and life expectancy. Therefore, the prevalence of such patients is increasing with more presenting for both emergent and elective surgical procedures. Hypoxemia requires a thorough evaluation in patients with end-stage liver disease. The most common etiologies respond to appropriate therapy. Portopulmonary hypertension and hepatopulmonary syndrome are associated with increased perioperative morbidity and mortality. It is incumbent on the anesthesiologist to understand the physiology of liver failure and its early effect on pulmonary function to ensure a successful outcome.

PMID: 27816135 [PubMed - indexed for MEDLINE]

Integrated systems biology analysis of KSHV latent infection reveals viral induction and reliance on peroxisome mediated lipid metabolism.

PLoS Pathog. 2017 Mar 03;13(3):e1006256

Authors: Sychev ZE, Hu A, DiMaio TA, Gitter A, Camp ND, Noble WS, Wolf-Yadlin A, Lagunoff M

Abstract
Kaposi's Sarcoma associated Herpesvirus (KSHV), an oncogenic, human gamma-herpesvirus, is the etiological agent of Kaposi's Sarcoma the most common tumor of AIDS patients world-wide. KSHV is predominantly latent in the main KS tumor cell, the spindle cell, a cell of endothelial origin. KSHV modulates numerous host cell-signaling pathways to activate endothelial cells including major metabolic pathways involved in lipid metabolism. To identify the underlying cellular mechanisms of KSHV alteration of host signaling and endothelial cell activation, we identified changes in the host proteome, phosphoproteome and transcriptome landscape following KSHV infection of endothelial cells. A Steiner forest algorithm was used to integrate the global data sets and, together with transcriptome based predicted transcription factor activity, cellular networks altered by latent KSHV were predicted. Several interesting pathways were identified, including peroxisome biogenesis. To validate the predictions, we showed that KSHV latent infection increases the number of peroxisomes per cell. Additionally, proteins involved in peroxisomal lipid metabolism of very long chain fatty acids, including ABCD3 and ACOX1, are required for the survival of latently infected cells. In summary, novel cellular pathways altered during herpesvirus latency that could not be predicted by a single systems biology platform, were identified by integrated proteomics and transcriptomics data analysis and when correlated with our metabolomics data revealed that peroxisome lipid metabolism is essential for KSHV latent infection of endothelial cells.

PMID: 28257516 [PubMed - as supplied by publisher]

A Systems Biology Approach to Understanding the Mechanisms of Action of an Alternative Anticancer Compound in Comparison to Cisplatin.

Proteomes. 2014 Nov 10;2(4):501-526

Authors: Wright EP, Padula MP, Higgins VJ, Aldrich-Wright JR, Coorssen JR

Abstract
Many clinically available anticancer compounds are designed to target DNA. This commonality of action often yields overlapping cellular response mechanisms and can thus detract from drug efficacy. New compounds are required to overcome resistance mechanisms that effectively neutralise compounds like cisplatin and those with similar chemical structures. Studies have shown that 56MESS is a novel compound which, unlike cisplatin, does not covalently bind to DNA, but is more toxic to many cell lines and active against cisplatin-resistant cells. Furthermore, a transcriptional study of 56MESS in yeast has implicated iron and copper metabolism as well as the general yeast stress response following challenge with 56MESS. Beyond this, the cytotoxicity of 56MESS remains largely uncharacterised. Here, yeast was used as a model system to facilitate a systems-level comparison between 56MESS and cisplatin. Preliminary experiments indicated that higher concentrations than seen in similar studies be used. Although a DNA interaction with 56MESS had been theorized, this work indicated that an effect on protein synthesis/ degradation was also implicated in the mechanism(s) of action of this novel anticancer compound. In contrast to cisplatin, the different mechanisms of action that are indicated for 56MESS suggest that this compound could overcome cisplatin resistance either as a stand-alone treatment or a synergistic component of therapeutics.

PMID: 28250393 [PubMed]

Text mining for improved exposure assessment.

PLoS One. 2017;12(3):e0173132

Authors: Larsson K, Baker S, Silins I, Guo Y, Stenius U, Korhonen A, Berglund M

Abstract
Chemical exposure assessments are based on information collected via different methods, such as biomonitoring, personal monitoring, environmental monitoring and questionnaires. The vast amount of chemical-specific exposure information available from web-based databases, such as PubMed, is undoubtedly a great asset to the scientific community. However, manual retrieval of relevant published information is an extremely time consuming task and overviewing the data is nearly impossible. Here, we present the development of an automatic classifier for chemical exposure information. First, nearly 3700 abstracts were manually annotated by an expert in exposure sciences according to a taxonomy exclusively created for exposure information. Natural Language Processing (NLP) techniques were used to extract semantic and syntactic features relevant to chemical exposure text. Using these features, we trained a supervised machine learning algorithm to automatically classify PubMed abstracts according to the exposure taxonomy. The resulting classifier demonstrates good performance in the intrinsic evaluation. We also show that the classifier improves information retrieval of chemical exposure data compared to keyword-based PubMed searches. Case studies demonstrate that the classifier can be used to assist researchers by facilitating information retrieval and classification, enabling data gap recognition and overviewing available scientific literature using chemical-specific publication profiles. Finally, we identify challenges to be addressed in future development of the system.

PMID: 28257498 [PubMed - in process]

Prediction of advertisement preference by fusing EEG response and sentiment analysis.

Neural Netw. 2017 Feb 16;:

Authors: Gauba H, Kumar P, Roy PP, Singh P, Dogra DP, Raman B

Abstract
This paper presents a novel approach to predict rating of video-advertisements based on a multimodal framework combining physiological analysis of the user and global sentiment-rating available on the internet. We have fused Electroencephalogram (EEG) waves of user and corresponding global textual comments of the video to understand the user's preference more precisely. In our framework, the users were asked to watch the video-advertisement and simultaneously EEG signals were recorded. Valence scores were obtained using self-report for each video. A higher valence corresponds to intrinsic attractiveness of the user. Furthermore, the multimedia data that comprised of the comments posted by global viewers, were retrieved and processed using Natural Language Processing (NLP) technique for sentiment analysis. Textual contents from review comments were analyzed to obtain a score to understand sentiment nature of the video. A regression technique based on Random forest was used to predict the rating of an advertisement using EEG data. Finally, EEG based rating is combined with NLP-based sentiment score to improve the overall prediction. The study was carried out using 15 video clips of advertisements available online. Twenty five participants were involved in our study to analyze our proposed system. The results are encouraging and these suggest that the proposed multimodal approach can achieve lower RMSE in rating prediction as compared to the prediction using only EEG data.

PMID: 28254237 [PubMed - as supplied by publisher]

Natural Language Processing in Oncology: A Review.

JAMA Oncol. 2016 Jun 01;2(6):797-804

Authors: Yim WW, Yetisgen M, Harris WP, Kwan SW

Abstract
IMPORTANCE: Natural language processing (NLP) has the potential to accelerate translation of cancer treatments from the laboratory to the clinic and will be a powerful tool in the era of personalized medicine. This technology can harvest important clinical variables trapped in the free-text narratives within electronic medical records.
OBSERVATIONS: Natural language processing can be used as a tool for oncological evidence-based research and quality improvement. Oncologists interested in applying NLP for clinical research can play pivotal roles in building NLP systems and, in doing so, contribute to both oncological and clinical NLP research. Herein, we provide an introduction to NLP and its potential applications in oncology, a description of specific tools available, and a review on the state of the current technology with respect to cancer case identification, staging, and outcomes quantification.
CONCLUSIONS AND RELEVANCE: More automated means of leveraging unstructured data from daily clinical practice is crucial as therapeutic options and access to individual-level health information increase. Research-minded oncologists may push the avenues of evidence-based research by taking advantage of the new technologies available with clinical NLP. As continued progress is made with applying NLP toward oncological research, incremental gains will lead to large impacts, building a cost-effective infrastructure for advancing cancer care.

PMID: 27124593 [PubMed - indexed for MEDLINE]

Biallelic mutations in human DCC cause developmental split-brain syndrome.

Nat Genet. 2017 Feb 27;:

Authors: Jamuar SS, Schmitz-Abe K, D'Gama AM, Drottar M, Chan WM, Peeva M, Servattalab S, Lam AN, Delgado MR, Clegg NJ, Zayed ZA, Dogar MA, Alorainy IA, Jamea AA, Abu-Amero K, Griebel M, Ward W, Lein ES, Markianos K, Barkovich AJ, Robson CD, Grant PE, Bosley TM, Engle EC, Walsh CA, Yu TW

Abstract
Motor, sensory, and integrative activities of the brain are coordinated by a series of midline-bridging neuronal commissures whose development is tightly regulated. Here we report a new human syndrome in which these commissures are widely disrupted, thus causing clinical manifestations of horizontal gaze palsy, scoliosis, and intellectual disability. Affected individuals were found to possess biallelic loss-of-function mutations in the gene encoding the axon-guidance receptor 'deleted in colorectal carcinoma' (DCC), which has been implicated in congenital mirror movements when it is mutated in the heterozygous state but whose biallelic loss-of-function human phenotype has not been reported. Structural MRI and diffusion tractography demonstrated broad disorganization of white-matter tracts throughout the human central nervous system (CNS), including loss of all commissural tracts at multiple levels of the neuraxis. Combined with data from animal models, these findings show that DCC is a master regulator of midline crossing and development of white-matter projections throughout the human CNS.

PMID: 28250456 [PubMed - as supplied by publisher]

Should clinical trials be approached differently for rare cancers?

Future Oncol. 2016 May;12(10):1207-9

Authors: Olver I

PMID: 26939845 [PubMed - indexed for MEDLINE]