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  • 1
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    Will Exercise Advice Be Sufficient for Treatment of Young Adults With Prehypertension and Hypertension? A Systematic Review and Meta-Analysis [Epidemiology/Population] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-06-09
    Description: Previous studies report benefits of exercise for blood pressure control in middle age and older adults, but longer-term effectiveness in younger adults is not well established. We performed a systematic review and meta-analysis of published randomized control trials with meta-regression of potential effect modifiers. An information specialist completed a comprehensive search of available data sources, including studies published up to June 2015. Authors applied strict inclusion and exclusion criteria to screen 9524 titles. Eligible studies recruited younger adults with a cardiovascular risk factor (with at least 25% of cohort aged 18–40 years); the intervention had a defined physical activity strategy and reported blood pressure as primary or secondary outcome. Meta-analysis included 14 studies randomizing 3614 participants, mean age 42.2±6.3 (SD) years. At 3 to 6 months, exercise was associated with a reduction in systolic blood pressure of –4.40 mm Hg (95% confidence interval, –5.78 to –3.01) and in diastolic blood pressure of –4.17 mm Hg (95% confidence interval, –5.42 to –2.93). Intervention effect was not significantly influenced by baseline blood pressure, body weight, or subsequent weight loss. Observed intervention effect was lost after 12 months of follow-up with no reported benefit over control, mean difference in systolic blood pressure –1.02 mm Hg (95% confidence interval, –2.34 to 0.29), and in diastolic blood pressure –0.91 mm Hg (95% confidence interval, –1.85 to 0.02). Current exercise guidance provided to reduce blood pressure in younger adults is unlikely to benefit long-term cardiovascular risk. There is need for continued research to improve age-specific strategies and recommendations for hypertension prevention and management in young adults.
    Keywords: Exercise, Lifestyle, High Blood Pressure, Hypertension, Meta Analysis
    Print ISSN: 0194-911X
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 2
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    Predictors of the Home-Clinic Blood Pressure Difference: A Systematic Review and Meta-Analysis (2016)
    Oxford University Press
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    Publication Date: 2016-04-13
    Description: BACKGROUND Patients may have lower (white coat hypertension) or higher (masked hypertension) blood pressure (BP) at home compared to the clinic, resulting in misdiagnosis and suboptimal management of hypertension. This study aimed to systematically review the literature and establish the most important predictors of the home-clinic BP difference. METHODS A systematic review was conducted using a MEDLINE search strategy, adapted for use in 6 literature databases. Studies examining factors that predict the home-clinic BP difference were included in the review. Odds ratios (ORs) describing the association between patient characteristics and white coat or masked hypertension were extracted and entered into a random-effects meta-analysis. RESULTS The search strategy identified 3,743 articles of which 70 were eligible for this review. Studies examined a total of 86,167 patients (47% female) and reported a total of 60 significant predictors of the home-clinic BP difference. Masked hypertension was associated with male sex (OR 1.47, 95% confidence interval (CI) 1.18–1.75), body mass index (BMI, per kg/m 2 increase, OR 1.07, 95% CI 1.01–1.14), current smoking status (OR 1.32, 95% CI 1.13–1.50), and systolic clinic BP (per mm Hg increase, OR 1.10, 95% CI 1.01–1.19). Female sex was the only significant predictor of white coat hypertension (OR 3.38, 95% CI 1.64–6.96). CONCLUSIONS There are a number of common patient characteristics that predict the home-clinic BP difference, in particular for people with masked hypertension. There is scope to incorporate such predictors into a clinical prediction tool which could be used to identify those patients displaying a significant masked or white coat effect in routine clinical practice.
    Print ISSN: 0895-7061
    Electronic ISSN: 1879-1905
    Topics: Medicine
    Published by Oxford University Press
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  • 3
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    Protein Ontology: a controlled structured network of protein entities (2013)
    Oxford University Press
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    Publication Date: 2013-12-29
    Description: The Protein Ontology (PRO; http://proconsortium.org ) formally defines protein entities and explicitly represents their major forms and interrelations. Protein entities represented in PRO corresponding to single amino acid chains are categorized by level of specificity into family, gene, sequence and modification metaclasses, and there is a separate metaclass for protein complexes. All metaclasses also have organism-specific derivatives. PRO complements established sequence databases such as UniProtKB, and interoperates with other biomedical and biological ontologies such as the Gene Ontology (GO). PRO relates to UniProtKB in that PRO’s organism-specific classes of proteins encoded by a specific gene correspond to entities documented in UniProtKB entries. PRO relates to the GO in that PRO’s representations of organism-specific protein complexes are subclasses of the organism-agnostic protein complex terms in the GO Cellular Component Ontology. The past few years have seen growth and changes to the PRO, as well as new points of access to the data and new applications of PRO in immunology and proteomics. Here we describe some of these developments.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    A comparative analysis of algorithms for somatic SNV detection in cancer (2013)
    Oxford University Press
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    Publication Date: 2013-08-28
    Description: Motivation: With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer–normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer–normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm. Results: Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates. Availability: Data accession number SRA081939, code at http://code.google.com/p/snv-caller-review/ Contact: david.adelson@adelaide.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
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    Heparanase 2, mutated in urofacial syndrome, mediates peripheral neural development in Xenopus (2014)
    Oxford University Press
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    Publication Date: 2014-07-19
    Description: Urofacial syndrome (UFS; previously Ochoa syndrome) is an autosomal recessive disease characterized by incomplete bladder emptying during micturition. This is associated with a dyssynergia in which the urethral walls contract at the same time as the detrusor smooth muscle in the body of the bladder. UFS is also characterized by an abnormal facial expression upon smiling, and bilateral weakness in the distribution of the facial nerve has been reported. Biallelic mutations in HPSE2 occur in UFS. This gene encodes heparanase 2, a protein which inhibits the activity of heparanase. Here, we demonstrate, for the first time, an in vivo developmental role for heparanase 2. We identified the Xenopus orthologue of heparanase 2 and showed that the protein is localized to the embryonic ventrolateral neural tube where motor neurons arise. Morpholino-induced loss of heparanase 2 caused embryonic skeletal muscle paralysis, and morphant motor neurons had aberrant morphology including less linear paths and less compactly-bundled axons than normal. Biochemical analyses demonstrated that loss of heparanase 2 led to upregulation of fibroblast growth factor 2/phosphorylated extracellular signal-related kinase signalling and to alterations in levels of transcripts encoding neural- and muscle-associated molecules. Thus, a key role of heparanase 2 is to buffer growth factor signalling in motor neuron development. These results shed light on the pathogenic mechanisms underpinning the clinical features of UFS and support the contention that congenital peripheral neuropathy is a key feature of this disorder.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement [Cardiomyopathies] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-08-18
    Description: Background— Calcific aortic stenosis (cAS) affects 3% of individuals aged 〉75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance. Methods and Results— A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and 99m TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and 〉65 years (prevalence 5.6% in cAS 〉65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69–85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age 〉65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5–35.8]; P =0.001). Conclusions— Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged 〉65 years undergoing surgical aortic valve replacement and was associated with a poor outcome.
    Keywords: Computerized Tomography (CT), Magnetic Resonance Imaging (MRI)
    Print ISSN: 1941-9651
    Electronic ISSN: 1942-0080
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 7
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    Quantifying the Association Between Physical Activity and Cardiovascular Disease and Diabetes: A Systematic Review and Meta-Analysis [Epidemiology] (2016)
    American Heart Association (AHA)
    Details
    Publication Date: 2016-10-08
    Description: Background The relationships between physical activity (PA) and both cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) have predominantly been estimated using categorical measures of PA, masking the shape of the dose-response relationship. In this systematic review and meta-analysis, for the very first time we are able to derive a single continuous PA metric to compare the association between PA and CVD/T2DM, both before and after adjustment for a measure of body weight. Methods and Results The search was applied to MEDLINE and EMBASE electronic databases for all studies published from January 1981 to March 2014. A total of 36 studies (3 439 874 participants and 179 393 events, during an average follow-up period of 12.3 years) were included in the analysis (33 pertaining to CVD and 3 to T2DM). An increase from being inactive to achieving recommended PA levels (150 minutes of moderate-intensity aerobic activity per week) was associated with lower risk of CVD mortality by 23%, CVD incidence by 17%, and T2DM incidence by 26% (relative risk [RR], 0.77 [0.71–0.84]), (RR, 0.83 [0.77–0.89]), and (RR, 0.74 [0.72–0.77]), respectively, after adjustment for body weight. Conclusions By using a single continuous metric for PA levels, we were able to make a comparison of the effect of PA on CVD incidence and mortality including myocardial infarct (MI), stroke, and heart failure, as well as T2DM. Effect sizes were generally similar for CVD and T2DM, and suggested that the greatest gain in health is associated with moving from inactivity to small amounts of PA.
    Keywords: Epidemiology, Exercise, Primary Prevention, Health Services, Meta Analysis
    Electronic ISSN: 2047-9980
    Topics: Medicine
    Published by American Heart Association (AHA)
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  • 8
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    Human Alveolar Macrophages May Not Be Susceptible to Direct Infection by a Human Influenza Virus (2016)
    Oxford University Press
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    Publication Date: 2016-11-15
    Description: The current studies were undertaken to determine the susceptibility of human alveolar macrophages (AMs) to influenza A virus (IAV) infection in comparison with autologous peripheral blood–derived monocytes-macrophages (PBMs). AMs and PBMs were exposed to IAV in vitro and examined for their ability to bind and internalize IAV, and synthesize viral proteins and RNA. PBMs but not AMs demonstrated binding and internalization of the virus, synthesizing viral proteins and RNA. Exposure of AMs in the presence of a sialidase inhibitor or anti-IAV antibody resulted in viral protein synthesis by the cells. Exposure of AMs to fluorescein isothiocyanate–labeled IAV in the presence of anti–fluorescein isothiocyanate antibody also resulted in viral protein synthesis. Thus, human AMs are apparently not susceptible to direct infection by a human IAV but are likely to be infected indirectly in the setting of exposure in the presence of antibody that binds the challenging strain of IAV.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
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