Crossover Evaluation of Compressors and Nebulizers Typically Used by Cystic Fibrosis Patients.

Respir Care. 2018 Feb 06;:

Authors: Awad SM, Berlinski A

Abstract
BACKGROUND: Compressor/nebulizer units are used to deliver inhaled medications to patients with cystic fibrosis. Practitioners and parents frequently replace either the compressor or the nebulizer with a similar component from a different brand. We hypothesized that these changes could affect the compressor/nebulizer flow-pressure and aerosol characteristics.
METHODS: The following compressors were studied: Pari Vios, Pulmo-Aide model 5650D, and Inspiration Elite model HS456. The following nebulizers were studied: Pari LC Plus, Viox, and SideStream Plus. Units that underwent intense use were tested. The recommended compressor/nebulizer combinations by the manufacturers were compared to all other combinations. In-line measurements of maximal flow and pressure were done for all combinations. A Next Generation Impactor was used to determine particle-size characteristics of albuterol (2.5 mg/3 mL). A breathing simulator programmed to deliver an adult breathing pattern was used. Albuterol concentration was measured with spectrophotometry at 276 nm. The following variables were studied: maximal flow and pressure generated by the compressor/nebulizer, mass median aerodynamic diameter, percentage of drug mass contained in particles < 5 μm, and inhaled mass in the respirable range.
RESULTS: Replacing the nebulizer resulted in changes in the flow-pressure characteristics, particle size, and inhaled mass in the respirable range of the paired compressor/nebulizers. The changes were more pronounced when the nebulizer was replaced than when the compressor was changed.
CONCLUSION: Our findings indicate that, in general, replacing the nebulizer or compressor with a different brand changes the flow-pressure and aerosol characteristics. Practitioners should be cautious when changing compressor/nebulizer pairs unless they are aware of the resulting impact on the flow-pressure and aerosol characteristics.

PMID: 29432139 [PubMed - as supplied by publisher]

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants.

CMAJ. 2018 Feb 05;190(5):E126-E136

Authors: Reuter MS, Walker S, Thiruvahindrapuram B, Whitney J, Cohn I, Sondheimer N, Yuen RKC, Trost B, Paton TA, Pereira SL, Herbrick JA, Wintle RF, Merico D, Howe J, MacDonald JR, Lu C, Nalpathamkalam T, Sung WWL, Wang Z, Patel RV, Pellecchia G, Wei J, Strug LJ, Bell S, Kellam B, Mahtani MM, Bassett AS, Bombard Y, Weksberg R, Shuman C, Cohn RD, Stavropoulos DJ, Bowdin S, Hildebrandt MR, Wei W, Romm A, Pasceri P, Ellis J, Ray P, Meyn MS, Monfared N, Hosseini SM, Joseph-George AM, Keeley FW, Cook RA, Fiume M, Lee HC, Marshall CR, Davies J, Hazell A, Buchanan JA, Szego MJ, Scherer SW

Abstract
BACKGROUND: The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing data and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers.
METHODS: Volunteers were screened for eligibility and provided informed consent for open data sharing. Using blood DNA, we performed whole genome sequencing and identified all possible classes of DNA variants. A genetic counsellor explained the implication of the results to each participant.
RESULTS: Whole genome sequencing of the first 56 participants identified 207 662 805 sequence variants and 27 494 copy number variations. We analyzed a prioritized disease-associated data set (n = 1606 variants) according to standardized guidelines, and interpreted 19 variants in 14 participants (25%) as having obvious health implications. Six of these variants (e.g., in BRCA1 or mosaic loss of an X chromosome) were pathogenic or likely pathogenic. Seven were risk factors for cancer, cardiovascular or neurobehavioural conditions. Four other variants - associated with cancer, cardiac or neurodegenerative phenotypes - remained of uncertain significance because of discrepancies among databases. We also identified a large structural chromosome aberration and a likely pathogenic mitochondrial variant. There were 172 recessive disease alleles (e.g., 5 individuals carried mutations for cystic fibrosis). Pharmacogenomics analyses revealed another 3.9 potentially relevant genotypes per individual.
INTERPRETATION: Our analyses identified a spectrum of genetic variants with potential health impact in 25% of participants. When also considering recessive alleles and variants with potential pharmacologic relevance, all 56 participants had medically relevant findings. Although access is mostly limited to research, whole genome sequencing can provide specific and novel information with the potential of major impact for health care.

PMID: 29431110 [PubMed - in process]

Management of airway mucus hypersecretion in chronic airway inflammatory disease: Chinese expert consensus (English edition).

Int J Chron Obstruct Pulmon Dis. 2018;13:399-407

Authors: Shen Y, Huang S, Kang J, Lin J, Lai K, Sun Y, Xiao W, Yang L, Yao W, Cai S, Huang K, Wen F

Abstract
Airway mucus hypersecretion is one of the most important characteristics of chronic airway inflammatory diseases. Evaluating and managing airway mucus hypersecretion is of great importance for patients with chronic airway inflammatory diseases. This consensus statement describes the pathogenesis, clinical features, and the management of airway mucus hypersecretion in patients with chronic airway inflammatory diseases in the People's Republic of China. The statement has been written particularly for respiratory researchers, pulmonary physicians, and patients.

PMID: 29430174 [PubMed - in process]

Pediatric and Adult Recommendations Vary for Sibling Testing in Cystic Fibrosis.

J Genet Couns. 2018 Feb 10;:

Authors: Brown KL, Flume PA

Abstract
Four to 5 % of cystic fibrosis (CF) patients are diagnosed as adults and often have subtler symptoms. Their siblings are at genetic risk to also have a subtler disease state. Diagnostic testing is recommended for siblings of newly diagnosed infants, but recommendations are less clear for later diagnoses. This study explored sibling testing recommendations in pediatric and adult practice using a survey that was emailed to CF clinicians. There were 58 respondents. Results revealed that 82.5% of pediatric and 36.4% of adult care respondents reported always recommending diagnostic testing for siblings of a newly diagnosed patient. In adult care, another 33.3% reported recommending diagnostic testing if the sibling has symptoms. In pediatric care, whether the sibling had newborn screening was most influential. Most pediatric respondents prefer the sweat chloride test, while 40% in adult practice prefer familial mutation analysis. Perceived barriers included cost, insurance coverage and logistical concerns in both settings, parental emotional state in pediatrics, and concern making recommendations for someone who is not the patient in adult care. Genetic counselors may be able to meet familial needs in CF care, including sibling testing. Many newly diagnosed patients/families do not see a genetic counselor, especially in adult care. These data reveal opportunities for practice guidelines and standardization.

PMID: 29429040 [PubMed - as supplied by publisher]

Cell-Free DNA: Screening for Single-Gene Disorders and Determination of Fetal Rhesus D Genotype.

Obstet Gynecol Clin North Am. 2018 Mar;45(1):27-39

Authors: Gerson KD, O'Brien BM

Abstract
The use of cell-free DNA (cfDNA) for screening and diagnosis of single-gene disorders is an evolving technology, and its application at this time is limited. Invasive testing is currently recommended for the diagnosis of single-gene disorders. The limitations of cfDNA technology are most notable in clinical settings involving X-linked and autosomal recessive conditions, in part because maternal mutant alleles greatly outnumber those of fetal origin. Examples of single-gene disorders for which cfDNA has been used include skeletal dyplasias, cystic fibrosis, congenital adrenal hyperplasia, β-thalassemia, and muscular dystrophies.

PMID: 29428284 [PubMed - in process]

Expanded Carrier Screening.

Obstet Gynecol Clin North Am. 2018 Mar;45(1):103-112

Authors: Gregg AR

Abstract
Prenatal carrier screening has expanded to include a larger number of genes and variants offered to all couples considering or with an ongoing pregnancy. Panethnic screening for cystic fibrosis and spinal muscular atrophy and screening for a limited number of conditions based on ethnicity are recommended by the American College of Obstetricians and Gynecologists. Residual risk calculations have become an obsolete part of posttest counseling when expanded carrier screening (ECS) is selected. The Perception of Uncertainties in Genome Sequencing scale offers a useful understanding of the pretest and posttest counseling concerns that should be considered as part of ECS implementation.

PMID: 29428278 [PubMed - in process]

Related Articles

Genetic Syndromes with Pancreatic Manifestations.

Surg Pathol Clin. 2016 Dec;9(4):705-715

Authors: Pittman ME, Brosens LA, Wood LD

Abstract
Although the pancreas is affected by only a small fraction of known inherited disorders, several of these syndromes predispose patients to pancreatic adenocarcinoma, a cancer that has a consistently dismal prognosis. Still other syndromes are associated with neuroendocrine tumors, benign cysts, or recurrent pancreatitis. Because of the variability of pancreatic manifestations and outcomes, it is important for clinicians to be familiar with several well-described genetic disorders to ensure that patients are followed appropriately. The purpose of this review was to briefly describe the hereditary syndromes that are associated with pancreatic disorders and neoplasia.

PMID: 27926368 [PubMed - indexed for MEDLINE]

Related Articles

Evaluation of energy metabolism and calcium homeostasis in cells affected by Shwachman-Diamond syndrome.

Sci Rep. 2016 05 05;6:25441

Authors: Ravera S, Dufour C, Cesaro S, Bottega R, Faleschini M, Cuccarolo P, Corsolini F, Usai C, Columbaro M, Cipolli M, Savoia A, Degan P, Cappelli E

Abstract
Isomorphic mutation of the SBDS gene causes Shwachman-Diamond syndrome (SDS). SDS is a rare genetic bone marrow failure and cancer predisposition syndrome. SDS cells have ribosome biogenesis and their protein synthesis altered, which are two high-energy consuming cellular processes. The reported changes in reactive oxygen species production, endoplasmic reticulum stress response and reduced mitochondrial functionality suggest an energy production defect in SDS cells. In our work, we have demonstrated that SDS cells display a Complex IV activity impairment, which causes an oxidative phosphorylation metabolism defect, with a consequent decrease in ATP production. These data were confirmed by an increased glycolytic rate, which compensated for the energetic stress. Moreover, the signalling pathways involved in glycolysis activation also appeared more activated; i.e. we reported AMP-activated protein kinase hyper-phosphorylation. Notably, we also observed an increase in a mammalian target of rapamycin phosphorylation and high intracellular calcium concentration levels ([Ca(2+)]i), which probably represent new biochemical equilibrium modulation in SDS cells. Finally, the SDS cell response to leucine (Leu) was investigated, suggesting its possible use as a therapeutic adjuvant to be tested in clinical trials.

PMID: 27146429 [PubMed - indexed for MEDLINE]

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Funding Opportunity PA-18-658 from the NIH Guide for Grants and Contracts. The Office of Research on Women's Health (ORWH) announces the availability of administrative supplements to support research highlighting the impact of sex/gender influences in human health and illness, including basic, preclinical, clinical, translational, and behavioral studies. Of special interest are studies relevant to understanding the significance of biological sex on cells and tissue explants; comparative studies of male and female tissues, organ systems and physiological systems; sex-based comparisons of pathophysiology, biomarkers, gene expression, clinical presentation and prevention and treatment of diseases. The most robust experimental designs include consideration of both sex and gender; therefore, applications proposing to investigate the influence of both sex and gender factors are highly encouraged. The proposed research must address at least one objective from Goals 1 through 3 of the NIH Strategic Plan for Women's Health Research.

Funding Opportunity PAR-18-657 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) encourages applications for Countermeasures Against Chemical Threats (CounterACT) Research Centers of Excellence (U54s). The mission of the CounterACT program is to foster and support research and development of new and improved therapeutics for chemical threats. Chemical threats are toxic chemicals that could be used in a terrorist attack or accidentally released from industrial production, storage or shipping. They include traditional chemical warfare agents, toxic industrial chemicals, pharmaceutical-based agents, and pesticides. The scope of the research includes target and candidate identification and characterization, through candidate optimization and demonstration of in vivo efficacy consistent with the product's intended use in humans. For applicants submitting U54 renewal applications, research under this FOA should culminate in an optimized lead compound ready for advanced development. The Centers will contain at least three research projects supported by an administrative core, up to three optional scientific cores, and a research education core. Each research project must include milestones that create discrete go or no-go decision points in a progressive translational study plan.

Funding Opportunity PAR-18-656 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to solicit UG3/UH3 phased cooperative agreement research applications to plan and implement behavioral and social intervention clinical trials. Studies appropriate for this announcement include traditional clinical trials meant to develop and test behavior change interventions meant to prevent or treat dental, oral, or craniofacial conditions, as well as interventions that are used as tools to understand mechanisms of behavior change. Awards made under this FOA will initially support a milestone-driven planning phase (UG3) for up to 2 years, with possible transition to a clinical trial implementation phase of up to five years (UH3). Only UG3 projects that have met the scientific milestones and feasibility requirements may transition to the UH3 phase. The UG3/UH3 application must be submitted as a single application, following the instructions described in this FOA. The UG3 phase for behavioral and social intervention clinical trials will permit both scientific and operational planning activities. Scientific planning activities include small-scale data collection to assess the feasibility and/or acceptability of a planned behavioral or social intervention and associated study procedures (e.g., acceptability of study content or mode of delivery; feasibility of proposed data collection procedures; preliminary testing of intervention training and fidelity monitoring procedures). Operational planning activities include, at a minimum, development of: the final clinical protocol; the intervention manual or equivalent; the data management system and other tools for data and quality management, safety and operational oversight plans; recruitment and retention strategies; and other essential documents such as the Manual of Procedures for the subsequent clinical trial in the UH3 phase. The UH3 phase of the award will support the conduct of investigator-initiated intervention research at all stages, from early mech

Funding Opportunity PAR-18-655 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) encourages grant applications from investigators interested in conducting basic, mechanistic research into the biological/genetic causes of cancer health disparities. These research project grants (R01) will support innovative studies designed to investigate biological/genetic bases of cancer disparities, such as (1) mechanistic studies of biological factors associated with cancer disparities, including those related to basic research in cancer biology or cancer prevention strategies, (2) the development and testing of new methodologies and models, and (3) secondary data analyses. This FOA is also designed to aid and facilitate the growth of a nationwide cohort of scientists with a high level of basic research expertise in cancer health disparities research who can expand available resources and tools, such as biospecimens, patient derived models, and methods that are necessary to conduct basic research in cancer health disparities.

Funding Opportunity PAR-18-654 from the NIH Guide for Grants and Contracts. This Funding Opportunity Announcement (FOA) encourages grant applications from investigators interested in conducting basic, mechanistic research into the biological/genetic causes of cancer health disparities. These research project grants (R01) will support innovative studies designed to investigate biological/genetic bases of cancer disparities, such as (1) mechanistic studies of biological factors associated with cancer disparities, including those related to basic research in cancer biology or cancer prevention strategies, (2) the development and testing of new methodologies and models, and (3) secondary data analyses. This FOA is also designed to aid and facilitate the growth of a nationwide cohort of scientists with a high level of basic research expertise in cancer health disparities research who can expand available resources and tools, such as biospecimens, patient derived models, and methods that are necessary to conduct basic research in cancer health disparities.

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