1,721,020 research outputs found
New genetic loci link adipose and insulin biology to body fat distribution
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
DEspR T/CATAAAA-box promoter variant decreases DEspR transcription and is associated with increased BP in Sardinian males.
DEspR T/CATAAAA-box promoter variant decreases DEspR transcription and is associated with increased BP in Sardinian males.
Glorioso N, Herrera VL, Didishvili T, Argiolas G, Troffa C, Bulla P, Bulla E, Ruiz-Opazo N.
Source
Hypertension and Related Diseases Center, Azienda Ospedaliero Universitaria-Università di Sassari, Sassari, Sardinia, Italy.
Abstract
Essential hypertension is highly prevalent in the elderly population, exceeding 70% in people older than 60 yr of age, and remains a leading risk factor for heart disease, stroke, and chronic renal disease. Elucidation of genetic determinants is critical but remains a challenge due to its complex, multifactorial pathogenesis. We investigated the role DEspR promoter variants, previously associated with male essential hypertension susceptibility, in blood pressure (BP) regulation. We detected a single nucleotide polymorphism within the DEspR 5'-regulatory region associated with increased BP in a male Sardinian cohort accounting for 11.0 mmHg of systolic BP (P<10(-15)) and 9.3 mmHg of diastolic BP (P<10(-15)). Sequence analysis of three normotensive subjects homozygous for the rs6535847 "normotension-associated T-allele" identified a canonical TATAAAA-box in contrast to a CATAAAA-motif in three hypertensive subjects homozygous for the rs6535847 "hypertension-associated C-allele." In vitro analysis detected decreased transcription activity with the CATAAAA-motif promoter-construct compared with the canonical TATAAAA-box promoter-construct. Although BP did not differ between DEspR+/- knockout male mice and wild-type littermates at 6 mo of age, radiotelemetric BP measurements in 18 mo old inbred DEspR+/- knockout male mice known to have decreased DEspR RNA and protein detected higher systolic, mean, and diastolic BPs in DEspR+/- mice compared with littermate wild-type controls (P<0.05). Our results demonstrate that promoter variants in DEspR associated with hypertension susceptibility and increased BP in Sardinian males affect transcription levels, which then affect BP in an age-dependent and male-specific manner. This finding is concordant with the late-onset and sex-specific characteristics of essential hypertension, thus reiterating the mandate for sex-specific analyses and treatment approaches for essential hypertension
Antihypertensive efficacy and tolerability of aliskiren/amlodipine single- pill combinations in patients with an inadequate response to aliskiren monotherapy.
Abstract
Many patients with hypertension will require multiple antihypertensive drugs to achieve blood pressure (BP) control. This double-blind study evaluated the efficacy and safety of aliskiren/amlodipine single-pill combinations (SPCs) in patients with mild-to-moderate hypertension who were non-responsive to aliskiren monotherapy. After a 4-week run-in with aliskiren 300 mg, patients with mean sitting diastolic BP (msDBP) ≥ 90 and < 110 mmHg were randomized to oncedaily aliskiren/ amlodipine 300/10 mg or 300/5 mg, or aliskiren 300 mg for 8 weeks. Aliskiren/amlodipine SPCs provided significantly greater mean reductions in mean sitting systolic BP/msDBP (300/10 mg, 18.0/13.1 mmHg; 300/5 mg, 14.4/10.5 mmHg) than aliskiren 300 mg (6.4/5.8 mmHg) at week 8 endpoint. This represents additional mean reductions of 11.6/7.2 mmHg (300/10 mg) and 8.0/4.7 mmHg (300/5 mg) over aliskiren alone (both p < 0.0001). Significantly more patients achieved BP control ( < 140/90 mmHg) with aliskiren/amlodipine 300/10 mg (65.5%) and 300/5 mg (56.6%) than with aliskiren (31.5% both p < 0.0001). Aliskiren, alone and in combination with amlodipine, was well tolerated, with a slightly higher incidence of adverse events with SPCs (29.0-30.1%) than with monotherapy (22.7%). In conclusion, aliskiren/amlodipine SPCs offer an effective next step for patients who have an inadequate BP response to aliskiren alone
Effect of the HMG-CoA reductase inhibitors on blood pressure in patients with essential hypertension and primary hypercholesterolemia
11beta-hydroxysteroid dehydrogenase type 2 activity is associated with left ventricular mass in essential hypertension
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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