Funding Opportunity RFA-OD-17-008 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to invite R03 applications to support biomedical and behavioral research that will provide scientific data to inform regulation of tobacco products to protect public health. Research Projects must address the research priorities related to the regulatory authority of the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). The awards under this FOA will be administered by NIH using funds that have been made available through FDA CTP and the Family Smoking Prevention and Tobacco Control Act (P.L. 111-31). Research results from this FOA are expected to generate findings and data that are directly relevant in informing the FDA's regulation of the manufacture, distribution, and marketing of tobacco products to protect public health.

Funding Opportunity RFA-OD-17-007 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to invite R01 applications to support biomedical and behavioral research that will provide scientific data to inform regulation of tobacco products to protect public health. Research Projects must address the research priorities related to the regulatory authority of the Food and Drug Administration (FDA) Center for Tobacco Products (CTP). The awards under this FOA will be administered by NIH using funds that have been made available through FDA CTP and the Family Smoking Prevention and Tobacco Control Act (P.L. 111-31). Research results from this FOA are expected to generate findings and data that are directly relevant in informing the FDA's regulation of the manufacture, distribution, and marketing of tobacco products to protect public health.

Notice NOT-CA-17-062 from the NIH Guide for Grants and Contracts

Notice NOT-HS-17-016 from the NIH Guide for Grants and Contracts

Notice NOT-EY-17-006 from the NIH Guide for Grants and Contracts

Notice NOT-HL-17-512 from the NIH Guide for Grants and Contracts

Notice NOT-DA-17-035 from the NIH Guide for Grants and Contracts

Notice NOT-DA-17-034 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-17-273 from the NIH Guide for Grants and Contracts. To facilitate genomic research and the dissemination of its products, NHGRI supports genomic resources that are crucial for basic research, disease studies, model organism studies, and other biomedical research. Awards under this FOA will support the development and distribution of genomic resources that will be valuable for the broad research community, using cost-effective approaches. Such resources include (but are not limited to) databases and informatics resources (such as human and model organism databases, ontologies, and analysis toolsets), comprehensive identification and collections of genomic features (such as functional genomic elements), and standard data types produced using central sets of samples (such as structural variants in 1000 Genomes or GTEx samples). NCI is interested in any of the above types of resources that focus on cancer.

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HAART in HIV/AIDS Treatments, Future Trends.

Infect Disord Drug Targets. 2017 May 05;:

Authors: Lu DY, Yarla NS, Xu B, Ding J, Lu TR, Wu HY

Abstract
AIDS (acquired immune deficient syndrome) is a deadly human viral infectious disease caused by HIV (human immune-deficient virus) infection. Almost every AIDS patient losses his/her life before mid 1990s. AIDS was once the 1st disease killer in US (1993). After one decade hard work, antiviral drug cocktails-high active anti-retroviral therapy (HAART) have been invented for almost all HIV infection treatments. Due to the invention of HAART, 80-90% HIV/AIDS patients still effectively response to HAART for deadly AIDS episode controls and life saving. Yet, this type of HIV therapeutics is incurable. HIV/AIDS patients need to take HAART medications regularly and even life-long. To counteract this therapeutic drawback, more revolutionary efforts (different angles of therapeutic modes/attempts) are urgently needed. In this article, the major progresses and drawbacks of HIV/AIDS chemotherapy (HAART) to HIV/AIDS patients have been discussed. Future trends (updating pathogenesis study, next generations of drug developments, new drug target discovery, different scientific disciplinary and so on) are highlighted.

PMID: 28474549 [PubMed - as supplied by publisher]

Related Articles

[Genetics of bipolar disorder].

Nervenarzt. 2017 May 04;:

Authors: Budde M, Forstner AJ, Adorjan K, Schaupp SK, Nöthen MM, Schulze TG

Abstract
Bipolar disorder (BD) has a multifactorial etiology. Its development is influenced by genetic as well as environmental factors. Large genome-wide association studies (GWAS), in which genetic risk allelic variants for the disorder could be replicated for the first time, marked the breakthrough in the identification of the responsible risk genes. In addition to these common genetic variants with moderate effects identified by GWAS, rare variants with a higher penetrance are expected to play a role in disease development. The results of recent studies suggest that copy number variants might contribute to BD development, although to a lesser extent than in other psychiatric disorders, such as schizophrenia or autism. Results from the initial next generation sequencing studies indicate an enrichment of rare variants in pathways and genes that were previously found to be associated with BD. In the field of pharmacogenetics, a risk gene that influences the individual variance in the response to lithium treatment was identified for the first time in a recent large international GWAS. Currently the reported risk alleles do not sufficiently explain the phenotypic variance to be used for individual prediction of disease risk, disease course or response to medication. Future genetic research will provide important insights into the biological basis of BD by the identification of additional genes associated with BD. This knowledge of genetics will help identify potential etiological subgroups as well as cross-diagnostic disease mechanisms.

PMID: 28474173 [PubMed - as supplied by publisher]

Related Articles

Involvement of P2 receptors in regulation of glomerular permeability to albumin by extracellular nucleotides of intra-/extra-glomerular origins.

J Physiol Pharmacol. 2016 Apr;67(2):177-83

Authors: Kasztan M, Jankowski M

Abstract
Plasma filtration through glomerular filtration barrier (GFB) is a key process to maintain fluid and electrolyte homeostasis. GFB consisting of endothelial cells, podocytes and basement membrane restricts passage of albumin but is permeable for smaller plasma molecules. Various biological agents, such as extracellular nucleotides influence activity of cells, which in turn affects permeability of GFB. Nucleotides are released from cells outside and within the glomeruli that activate the purinoceptors - P2Rs classified into ATP-gated non-selective ion channels, P2X receptors (P2XRs), and G-protein-coupled metabotropic P2Y receptors (P2YRs). P2Rs are expressed on cellular components of GFB. P2Rs activation triggers intracellular calcium concentration and calcium-dependent metabolism with subsequent affect on glomerular permeability to albumin. Purinergic-dependent glomerular cell activation also affects the biophysical properties of acelluar glomerular basement membrane (GMB). Finally, P2Rs stimulation may lead to increased proteins excretion in urine. The involvement of P2Rs in increased GFB permeability to albumin may be expected under pathophysiological conditions characterized by increased albumin excretion in urine.

PMID: 27226177 [PubMed - indexed for MEDLINE]

Related Articles

House dust mite-specific immunotherapy with two licensed vaccines: Outcome under clinical routine conditions.

Immun Inflamm Dis. 2017 Jun;5(2):132-140

Authors: Mahler V, Klein C, Sager A, Zimmermann J

Abstract
INTRODUCTION: House dust mite (HDM) allergens are major causes for the development of allergic diseases. A disease modifying effect and clinical benefit of allergen immunotherapy (AIT) has been demonstrated in a number of clinical trials. Clinical trials, however, are carried out in selected populations under specific conditions based on inclusion and exclusion criteria and may not represent the entire patient population from medical practice. Objective of this study conducted in patients with HDM allergy was to systematically collect information about the benefit of AIT under clinical routine conditions.
METHODS: In this prospective, multi-center non-interventional study, 220 patients (117 adults, 103 children) with HDM allergy receiving subcutaneous AIT with Depigoid(®) were monitored for 2 years. Organ-specific key symptoms, health-related quality of life (QoL), and the use of concomitant anti-allergic medication were assessed at baseline and after 12 and 24 months. Effectiveness and tolerability of the AIT was assessed by physicians and patients. Occurrence of adverse events (AEs) was continuously monitored.
RESULTS: Two hundred and nineteen patients (116 adults, 103 children) were evaluated. A major improvement of the total symptom-score was observed after 24 (12) months in 76% (72%) and 80% (79%) of adults and children, respectively, accompanied by a reduction in concomitant anti-allergic medication and a pronounced improvement in QoL. The effectiveness and tolerability of the AIT was estimated as very good/good by 80-90% of physicians and patients. AEs were observed in 4/117 adults (3.4%) and in 7/103 children (6.8%). Serious AEs were reported in three adults and one child: A grade-II anaphylactic reaction (one adult) controlled by oral antihistamines (no hospitalization) classified as "definitely," three others as not (2) or possibly (1) drug-related.
CONCLUSIONS: The data collected from 220 patients confirm the efficacy, tolerability/safety, and acceptance of AIT with Depigoid(®) in adults and children with HDM allergy under routine clinical conditions.

PMID: 28474505 [PubMed - in process]

Related Articles

Clinical Outcomes Associated with Medication Regimen Complexity in Older People: A Systematic Review.

J Am Geriatr Soc. 2017 Apr;65(4):747-753

Authors: Wimmer BC, Cross AJ, Jokanovic N, Wiese MD, George J, Johnell K, Diug B, Bell JS

Abstract
OBJECTIVES: To systematically review clinical outcomes associated with medication regimen complexity in older people.
DESIGN: Systematic review of EMBASE, MEDLINE, International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane library.
SETTING: Hospitals, home, and long-term care.
PARTICIPANTS: English-language peer-reviewed original research published before June 2016 was eligible if regimen complexity was quantified using a metric that considered number of medications and at least one other parameter, regimen complexity was calculated for participants' overall regimen, at least 80% of participants were aged 60 and older, and the study investigated a clinical outcome associated with regimen complexity.
MEASUREMENTS: Quality assessment was conducted using an adapted version of the Joanna Briggs Institute critical appraisal tool.
RESULTS: Sixteen observational studies met the inclusion criteria. Regimen complexity was associated with medication nonadherence (2/6 studies) and higher rates of hospitalization (2/4 studies). One study found that participants with less-complex medication administration were more likely to stop medications when feeling worse. One study each identified an association between regimen complexity and higher ability to administer medications as directed, medication self-administration errors, caregiver medication administration hassles, hospital discharge to non-home settings, postdischarge potential adverse drug events, all-cause mortality, and lower patient knowledge of their medication. Regimen complexity had no association with postdischarge medication modification, change in medication- and health-related problems, emergency department visits, or quality of life as rated by nursing staff.
CONCLUSION: Research into whether medication regimen complexity is associated with nonadherence and hospitalization has produced inconsistent results. Moderate-quality evidence from four studies (two each for nonadherence and hospitalization) suggests that medication regimen complexity is associated with nonadherence and higher rates of hospitalization.

PMID: 27991653 [PubMed - indexed for MEDLINE]

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Team-based Medical Care for Cardiac Failure-The Pharmacist's Expected Role.

Yakugaku Zasshi. 2016;136(8):1137-9

Authors: Takahashi M

Abstract
The pharmacist's role in home care is increasingly important. We are required to collaborate with multiple other professions. As home care pharmaceutical managers, pharmacists verify the timeline of side effects and the onset of expected effects. It is also important to verify all prescriptions from the pharmaceutical viewpoint, and to point out potential negative interactions or consequences of each prescribed medication, suggesting changes or dosage reduction in drugs as appropriate. Additionally, we verify the cause of unused drugs (i.e. patient non-compliance) and take action. As an effort to provide quality home care, pharmacists share information with other professions for collaborative management of a patient's needs. We act as a bridge between related government, agencies and citizens, assisting in creating a healthy lifestyle for the residents of our community. The days when pharmacists just sit in their pharmacies and dispense drugs are gone. Therefore, we need to collaborate more with medical, nursing care, and governmental professionals in our communities.

PMID: 27477732 [PubMed - indexed for MEDLINE]

Related Articles

Current status and future prospects for biologic treatments of psoriasis.

Expert Rev Clin Immunol. 2016 Dec;12(12):1273-1287

Authors: Cline A, Hill D, Lewallen R, Feldman SR

Abstract
INTRODUCTION: Biological agents have transformed psoriasis treatment by selectively targeting immune signaling molecules involved in psoriasis pathogenesis. While biologics offer the most effective treatment of moderate to severe psoriasis, they are not without complications. Some patients treated with biologics have poor clinical responses, form anti-drug antibodies, or develop adverse events. Additionally, there is growing need for head-to-head studies comparing biologic treatment regimens, efficacy, and safety. Areas covered: Here we review the literature surrounding biologics already in clinical use and those undergoing development and clinical trials. We also investigate the development and approval of small molecules inhibitors and biosimilars used to treat psoriasis. Expert commentary: As the psoriasis treatment armamentarium continues to expand, it is important to follow the safety profile of these drugs both in clinical trials and in post-marketing registries to ensure their long-term safety. Physicians must be aware of the limitations of existing safety data of a drug and the potential risk for rare adverse events when selecting appropriate treatments and monitoring patient outcomes.

PMID: 27327580 [PubMed - indexed for MEDLINE]

Related Articles

Use of nonsteroidal anti-inflammatory drugs and renal failure in nursing home residents-results of the study "Inappropriate Medication in Patients with Renal Insufficiency in Nursing Homes".

Wien Klin Wochenschr. 2016 Apr;128(7-8):287-90

Authors: Dörks M, Herget-Rosenthal S, Schmiemann G, Hoffmann F

Abstract
BACKGROUND: Use of potentially inappropriate medications may result in increased morbidity, mortality and resource utilisation. Due to polypharmacy and age-related decline in renal function the elderly population is at particular risk. Therefore, the Beers Criteria include use of nonsteroidal anti-inflammatory drugs in chronic renal failure stage 4 and 5 as these drugs may worsen renal function. According to the summary of product characteristics, the nonsteroidal anti-inflammatory drugs ibuprofen and diclofenac are contraindicated in these patients. Objective was to assess the extent of nonsteroidal anti-inflammatory drug use in nursing homes with a focus on residents with severe renal failure.
METHODS: Multi-centre cross-sectional study in 21 German nursing homes. The study population comprised residents for whom at least one serum creatinine value and information about sex were available, so that creatinine clearance rate could be estimated.
RESULTS: In all, 685 of 852 residents were included as they fulfilled the abovementioned criteria. Renal failure was severe (estimated creatinine clearance rate < 30 ml/min) in 106 residents (15.5 %). Approximately one-fifth was treated with at least one nonsteroidal anti-inflammatory drug in both the total study population (20.3 %) and that with severe renal failure (20.8 %). With one exception, all residents prescribed nonsteroidal anti-inflammatory drugs with severe renal failure were treated with at least one nonsteroidal anti-inflammatory drug that was contraindicated due to the underlying renal function.
CONCLUSIONS: Notwithstanding their classification as potentially inappropriate medications and underlying contraindications, use of nonsteroidal anti-inflammatory drugs is common among nursing home residents with severe renal failure.

PMID: 26759317 [PubMed - indexed for MEDLINE]

Related Articles

Cinnarizine and dimenhydrinate in the treatment of vertigo in medical practice.

Wien Klin Wochenschr. 2016 May;128(9-10):341-7

Authors: Scholtz AW, Ilgner J, Loader B, Pritschow BW, Weisshaar G

Abstract
The efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in the treatment of vertigo of various origins have been investigated in a prospective, noninterventional study involving private practices throughout Germany. A total of 1275 patients with an average age of 61.2 years participated in the study. The vertigo symptoms, measured by a validated mean vertigo score (primary efficacy endpoint) improved by 61 % in the course of the observational period (median: 6 weeks). Concomitant symptoms frequently associated with vertigo such as nausea, vomiting and tinnitus were also markedly reduced by 84, 85 and 51 %, respectively. Overall efficacy has been rated by the physicians as 'very much improved' or 'much improved' in 95 % of the patients. A total of 47 patients (3.7 %) reported 51 adverse drug reactions (all nonserious). The results indicate a good tolerability and efficacy of the fixed combination of cinnarizine and dimenhydrinate in the treatment of vertigo in daily medical practice, which is in line with previous findings of numerous interventional, randomised, double-blind, controlled clinical trials.

PMID: 26659910 [PubMed - indexed for MEDLINE]

Related Articles

Filling the gap in CNS drug development: evaluation of the role of drug repurposing.

J Mark Access Health Policy. 2017;5(1):1299833

Authors: Caban A, Pisarczyk K, Kopacz K, Kapuśniak A, Toumi M, Rémuzat C, Kornfeld A

Abstract
Background and objective: Background and objective: Drug repurposing has been considered a cost-effective and reduced-risk strategy for developing new drugs. Little is known and documented regarding the efficiency of repurposing strategies in drug development. The objective of this article is to assess the extent and meaning of this process in the CNS area. Methods: In order to identify repurposed drugs that target the CNS, an extensive search was performed. For each identified case, its initial and target indication, development status and the type of repurposing strategy (repositioning, reformulation or both) was recorded. Results: One hundred and eighteen source products were identified. They were repurposed (mainly repositioned) 203 times with 81 products repurposed once and 38 products repurposed twice or more. The highest number of source drugs originated from the CNS area. Alzheimer's disease was targeted most often. Half of the new indications were approved. Regarding repurposing within the CNS area, epilepsy, schizophrenia and depression were the richest sources of repurposed drugs. Conclusions: Repurposing drugs into CNS is an efficient and very active drug development method, exemplified by the considerable number of new indications that have been found via this strategy, with approximately half of the target indications currently under development.

PMID: 28473889 [PubMed - in process]