Funding Opportunity RFA-HL-19-016 from the NIH Guide for Grants and Contracts. This FOA encourages new R43 applications for design and development of technologies to monitor health or deliver care in a real-time, accessible, effective, and minimally obtrusive way for aging adults. These may be novel sensor or monitoring systems, home-use point-of-care devices, home or mobile therapy or rehabilitation tools, or information systems and should have the goal of fostering healthy and independent living. The development of such technologies should incorporate specific human factors for people with disabilities, people aging with mild impairments, as well as individuals with chronic conditions. Technology usability for these populations must be incorporated into the design early. Usability considerations include but are not limited to patient-facing displays, hearing and visual impairments considerations, tactile limitations, and literacy. These improvements in technology design could yield more accurate and earlier detection of changes that may interfere with healthy and independent living for older adults.

Notice NOT-GM-18-021 from the NIH Guide for Grants and Contracts

Notice NOT-DC-18-006 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-18-710 from the NIH Guide for Grants and Contracts. The objective of the NIH Career Transition Award (K22) is to provide support to outstanding basic or clinical investigators to develop their independent research skills through a two phase program: an initial period involving an intramural appointment at the NIH and a final period of support at an extramural institution. This NINDS K22 is specifically designed to facilitate the transition of NINDS intramural neurologist- and neurosurgeon-scientists to independent, academic faculty positions that support clinician-scientists to engage in independently funded scientific research as well as clinical activities.

Funding Opportunity PAR-18-711 from the NIH Guide for Grants and Contracts. The objective of the NIH Career Transition Award (K22) is to provide support to outstanding basic or clinical investigators to develop their independent research skills through a two phase program: an initial period involving an intramural appointment at the NIH and a final period of support at an extramural institution. This NINDS K22 is specifically designed to facilitate the transition of NINDS intramural neurologist- and neurosurgeon-scientists to independent, academic faculty positions that support clinician-scientists to engage in independently funded scientific research as well as clinical activities.

Scedosporium and Lomentospora: an updated overview of underrated opportunists.

Med Mycol. 2018 Apr 01;56(suppl_1):102-125

Authors: Ramirez-Garcia A, Pellon A, Rementeria A, Buldain I, Barreto-Bergter E, Rollin-Pinheiro R, de Meirelles JV, Xisto MIDS, Ranque S, Havlicek V, Vandeputte P, Govic YL, Bouchara JP, Giraud S, Chen S, Rainer J, Alastruey-Izquierdo A, Martin-Gomez MT, López-Soria LM, Peman J, Schwarz C, Bernhardt A, Tintelnot K, Capilla J, Martin-Vicente A, Cano-Lira J, Nagl M, Lackner M, Irinyi L, Meyer W, de Hoog S, Hernando FL

Abstract
Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

PMID: 29538735 [PubMed - in process]

Developing collaborative works for faster progress on fungal respiratory infections in cystic fibrosis.

Med Mycol. 2018 Apr 01;56(suppl_1):42-59

Authors: Schwarz C, Vandeputte P, Rougeron A, Giraud S, Dugé de Bernonville T, Duvaux L, Gastebois A, Alastruey-Izquierdo A, Martín-Gomez MT, Mazuelos EM, Sole A, Cano J, Pemán J, Quindos G, Botterel F, Bougnoux ME, Chen S, Delhaès L, Favennec L, Ranque S, Sedlacek L, Steinmann J, Vazquez J, Williams C, Meyer W, Le Gal S, Nevez G, Fleury M, Papon N, Symoens F, Bouchara JP, ECMM/ISHAM working group Fungal respiratory infections in Cystic Fibrosis (Fri-CF)

Abstract
Cystic fibrosis (CF) is the major genetic inherited disease in Caucasian populations. The respiratory tract of CF patients displays a sticky viscous mucus, which allows for the entrapment of airborne bacteria and fungal spores and provides a suitable environment for growth of microorganisms, including numerous yeast and filamentous fungal species. As a consequence, respiratory infections are the major cause of morbidity and mortality in this clinical context. Although bacteria remain the most common agents of these infections, fungal respiratory infections have emerged as an important cause of disease. Therefore, the International Society for Human and Animal Mycology (ISHAM) has launched a working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF) in October 2006, which was subsequently approved by the European Confederation of Medical Mycology (ECMM). Meetings of this working group, comprising both clinicians and mycologists involved in the follow-up of CF patients, as well as basic scientists interested in the fungal species involved, provided the opportunity to initiate collaborative works aimed to improve our knowledge on these infections to assist clinicians in patient management. The current review highlights the outcomes of some of these collaborative works in clinical surveillance, pathogenesis and treatment, giving special emphasis to standardization of culture procedures, improvement of species identification methods including the development of nonculture-based diagnostic methods, microbiome studies and identification of new biological markers, and the description of genotyping studies aiming to differentiate transient carriage and chronic colonization of the airways. The review also reports on the breakthrough in sequencing the genomes of the main Scedosporium species as basis for a better understanding of the pathogenic mechanisms of these fungi, and discusses treatment options of infections caused by multidrug resistant microorganisms, such as Scedosporium and Lomentospora species and members of the Rasamsonia argillacea species complex.

PMID: 29538733 [PubMed - in process]

Burkholderia cepacia, cystic fibrosis and outcomes following lung transplantation: experiences from a single center in Brazil.

Clinics (Sao Paulo). 2018 Mar 12;73:e166

Authors: de Souza Carraro D, Carraro RM, Campos SV, Iuamoto LR, Braga KAO, Oliveira LC, Sabino EC, Rossi F, Pêgo-Fernandes PM

Abstract
OBJECTIVES: To evaluate the impact of Burkholderia cepacia complex colonization in cystic fibrosis patients undergoing lung transplantation.
METHODS: We prospectively analyzed clinical data and respiratory tract samples (sputum and bronchoalveolar lavage) collected from suppurative lung disease patients between January 2008 and November 2013. We also subtyped different Burkholderia cepacia complex genotypes via DNA sequencing using primers against the recA gene in samples collected between January 2012 and November 2013.
RESULTS: From 2008 to 2013, 34 lung transplants were performed on cystic fibrosis patients at our center. Burkholderia cepacia complex was detected in 13 of the 34 (38.2%) patients. Seven of the 13 (53%) strains were subjected to genotype analysis, from which three strains of B. metallica and four strains of B. cenocepacia were identified. The mortality rate was 1/13 (7.6%), and this death was not related to B. cepacia infection.
CONCLUSION: The results of our study suggest that colonization by B. cepacia complex and even B. cenocepacia in patients with cystic fibrosis should not be considered an absolute contraindication to lung transplantation in Brazilian centers.

PMID: 29538493 [PubMed - in process]

Cystic fibrosis transmembrane conductance regulator modulators: precision medicine in cystic fibrosis.

Curr Opin Pediatr. 2018 Mar 13;:

Authors: Burgener EB, Moss RB

Abstract
PURPOSE OF REVIEW: The aim of this study was to describe the newest development in cystic fibrosis (CF) care, CF transmembrane conductance regulator (CFTR) modulator therapies.
RECENT FINDINGS: Phase II results showing CFTR modulator triple therapies are more effective than current CFTR modulators.
SUMMARY: CFTR modulator therapy targets the protein defective in CF and boosts its function, but the drug must match mutation pathobiology. Ivacaftor, a CFTR potentiator, was the first modulator approved in 2012, with impressive improvement in lung function and other measures of disease in patients with gating and other residual function mutations (∼10% of CF patients). In 2015, the combination of lumacaftor, a CFTR corrector, and ivacaftor was approved for patients homozygous for the F508del mutation (∼40-50% of the CF population) with positive but less impressive clinical response and 10-20% incidence of intolerance. A next-generation CFTR corrector, tezacaftor, with ivacaftor equally effective and better tolerated than lumacaftor, has also received US Food and Drug Administration approval. Novel CFTR correctors, entering Phase 3 trials in triple modulator combination with tezacaftor-ivacaftor, appear substantially more effective for patients who are homozygous for the F508del mutation and can provide benefit for patients with a single F508del mutation. This offers promise of effective CFTR modulator therapy for nearly 90% of CF patients.

PMID: 29538046 [PubMed - as supplied by publisher]

Occurrence of Pseudomonas aeruginosa in waters: Implications for patients with cystic fibrosis (CF).

Lett Appl Microbiol. 2018 Mar 14;:

Authors: Caskey S, Stirling J, Moore JE, Rendall JC

Abstract
Chronic P. aeruginosa infection is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). Current understanding of risk factors for acquisition is limited and so the aim of this study was to examine a large sample of environmental waters from diverse sources. Environmental water samples [n= 7904] from jacuzzis, hydrants, swimming pools, hot tubs, plunge pools, bottled natural mineral water (NMW), taps, springs, ice machines, water coolers, bores and showers were examined for the presence of P. aeruginosa. P. aeruginosa was detected in 524/7904 (6.6%) waters examined. Hot tubs [51/243; 20.9%], tap water [3/40; 8%] and jacuzzis [432/5811; 7.4%] were the most likely environments where P. aeruginosa was isolated. P. aeruginosa was isolated from bottled water [2/67; 3%]. Our study highlights the ubiquitous nature of P. aeruginosa in the environment. Given CF patients are frequently counselled to make lifestyle changes to minimize P. aeruginosa exposure, these results have important implications. In particular, the occurrence of P. aeruginosa in tap water highlights the need to disinfect the CF patients' nebuliser after each use. This article is protected by copyright. All rights reserved.

PMID: 29537700 [PubMed - as supplied by publisher]

Response to the authors of the article "Multifocal fixed drug eruption to ceftazidime in a child with cystic fibrosis.

Pediatr Allergy Immunol. 2018 Mar 14;:

Authors: Pipet A, Rochefort-Morel C, Drouet M, Nicolie B, Bernier C, Hoarau C, Marty C, Magnan A

Abstract
We react to your very well-described and documented case of fixed-drug eruption (FDE) to ceftazidime. You assess that "this is the first case of FDE to ceftazidime in a child with cystic fibrosis". This is not completely right. This article is protected by copyright. All rights reserved.

PMID: 29537668 [PubMed - as supplied by publisher]

Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

Cochrane Database Syst Rev. 2018 Mar 14;3:CD010849

Authors: Hussein N, Weng SF, Kai J, Kleijnen J, Qureshi N

Abstract
BACKGROUND: Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review.
OBJECTIVES: To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017.
SELECTION CRITERIA: Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease when compared to usual care.
DATA COLLECTION AND ANALYSIS: We identified 25 papers, describing 16 unique trials which were potentially eligible for inclusion in the review. However, after assessment, no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were found.
MAIN RESULTS: No randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease were included. One ongoing trial has been identified which may potentially eligible for inclusion once completed.
AUTHORS' CONCLUSIONS: As no randomised controlled trials of preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis, or Tay-Sachs disease were found for inclusion in this review, the research evidence for current policy recommendations is limited to non-randomised studies.Information from well-designed, adequately powered, randomised trials is desirable in order to make more robust recommendations for practice. However, such trials must also consider the legal, ethical, and cultural barriers to implementation of preconception genetic risk assessment.

PMID: 29537064 [PubMed - as supplied by publisher]

Most bicarbonate secretion by Calu-3 cells is mediated by CFTR and independent of pendrin.

Physiol Rep. 2018 Mar;6(5):

Authors: Huang J, Kim D, Shan J, Abu-Arish A, Luo Y, Hanrahan JW

Abstract
Bicarbonate plays an important role in airway host defense, however, its transport mechanisms remain uncertain. Here we examined the relative contributions of the anion channel CFTR (cystic fibrosis transmembrane conductance regulator, ABCC7) and the anion exchanger pendrin (SLC26A4) to HCO3- secretion by the human airway cell line Calu-3. Pendrin and CFTR were both detected in parental Calu-3 cells, although mRNA and protein expression appeared higher for CFTR than for pendrin. Targeting pendrin transcripts with lentiviral shRNA reduced pendrin detection by immunofluorescence staining but did not alter the rates of HCO3- or fluid secretion, HCO3- transport under pH-stat conditions, or net HCO3- flux across basolaterally permeabilized monolayers. Intracellular pH varied with step changes in apical Cl- and HCO3- concentrations in control and pendrin knockdown Calu-3 cells, but not in CFTR deficient cells. Exposure to the proinflammatory cytokine IL-4, which strongly upregulates pendrin expression in airway surface epithelia, had little effect on Calu-3 pendrin expression and did not alter fluid or HCO3- secretion. Similar results were obtained using air-liquid interface and submerged cultures, although CFTR and pendrin mRNA expression were both lower when cells were cultured under submerged conditions. While the conclusions cannot be extrapolated to other airway epithelia, the present results demonstrate that most HCO3- secretion by Calu-3 cells is mediated by CFTR.

PMID: 29536650 [PubMed - in process]

Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

Arch Bronconeumol. 2018 Mar 10;:

Authors: Jauregui A, Deu M, Romero L, Roman A, Moreno A, Armengol M, Solé J

Abstract
INTRODUCTION: Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival.
METHODS: We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed.
RESULTS: Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO2 is an independent risk factor for the need for ECC.
CONCLUSIONS: The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO2 is a risk factor for the need for ECC during lung transplantation.

PMID: 29534846 [PubMed - as supplied by publisher]

Peptide Nucleic Acids as a Tool for Site-Specific Gene Editing.

Molecules. 2018 Mar 11;23(3):

Authors: Ricciardi AS, Quijano E, Putman R, Saltzman WM, Glazer PM

Abstract
Peptide nucleic acids (PNAs) can bind duplex DNA in a sequence-targeted manner, forming a triplex structure capable of inducing DNA repair and producing specific genome modifications. Since the first description of PNA-mediated gene editing in cell free extracts, PNAs have been used to successfully correct human disease-causing mutations in cell culture and in vivo in preclinical mouse models. Gene correction via PNAs has resulted in clinically-relevant functional protein restoration and disease improvement, with low off-target genome effects, indicating a strong therapeutic potential for PNAs in the treatment or cure of genetic disorders. This review discusses the progress that has been made in developing PNAs as an effective, targeted agent for gene editing, with an emphasis on recent in vivo, nanoparticle-based strategies.

PMID: 29534473 [PubMed - in process]

Related Articles

Health care-associated infections studies project: An American Journal of Infection Control and National Healthcare Safety Network data quality collaboration.

Am J Infect Control. 2017 Dec 01;45(12):1394-1395

Authors: Allen-Bridson K, Gross C, Anttila A, Brooks JE, Hebden JN, Leaptrot D, Ryan G, Scalise E, Smith H, Wright MO

Abstract
This case study is part of a series centered on the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) health care-associated infection (HAI) surveillance definitions. This specific case study focuses on the definitions and protocols used to make HAI infection determinations, such as the infection window period and secondary bloodstream infection attribution period. The case reflects the real-life and complex patient scenarios that infection preventionists (IPs) face when identifying and reporting HAIs to NHSN. The intent of the case study series is to foster standardized application of the NHSN HAI surveillance definitions among IPs and encourage accurate determination of HAI events. An online survey link is provided where participants may confidentially answer questions related to the case study and receive immediate feedback in the form of correct answers and explanations and rationales. Details of the case study, answers, and explanations have been reviewed and approved by NHSN staff. We hope that participants take advantage of this educational offering and thereby gain a greater understanding of NHSN HAI surveillance definitions.

PMID: 29195584 [PubMed - indexed for MEDLINE]

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Whole Exome Sequencing in a Rare Disease: A Patient with Anomalous Left Coronary Artery from the Pulmonary Artery (Bland-White-Garland Syndrome).

OMICS. 2016 05;20(5):325-7

Authors: Hekim N, Batyraliev T, Trujillano D, Wang W, Dandara C, Karben Z, Saygılı Eİ, Çetin Z, Mıhcıoğlu D, Türkmen S, İkidağ MA, Cüce MA, Rolfs A

PMID: 27195969 [PubMed - indexed for MEDLINE]

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