Abstract
Background
The dietary approaches to stop hypertension (DASH) diet is recognized as an effective dietary intervention to reduce blood pressure (BP). However, among randomized controlled ...trials (RCTs) investigating the DASH diet mediated BP reduction,there are significant methodological and clinical differences.
Purpose
The purpose of this study was to comprehensively assess the effect of the DASH diet on BP levels in adults with and without hypertension, accounting for underlying methodological and clinical confounders.
Methods
We systematically searched Medline and the Cochrane Collaboration Library databases and identified 30 RCTs (n=5,545 participants) that investigated the BP effects of the DASH diet compared to a control diet in hypertensive and non-hypertensive adults. Both random-effects and fixed-effect models were used to calculate the mean attained systolic BP (SBP) and diastolic BP (DBP) differences during follow-up. Subgroup and meta-regression analyses were also conducted.
Results
The DASH diet reduced SBP and DBP significantly more compared to the control diet (difference in means: −3.2 mm Hg; 95% CI: −4.2, −2.3; P<0.001, and −2.5 mm Hg; 95% CI: −3.5, −1.5; P<0.001, respectively). Hypertension status did not modify the effect on BP reduction. The DASH diet compared to the control diet reduced SBP levels to a higher extent in trials with sodium intake >2,400 mg/day compared to trials with sodium intake ≤2,400 mg/day, while both SBP and DBP were reducedmore in trials with mean age <50 years compared to trials of older participants. The quality of evidence was rated as moderate forboth outcomes according to the Grading of Recommendations, Assessment, Development and Evaluation approach.
Conclusion
The adoption of the DASH diet was accompanied by significant BP reduction in adults with and without hypertension, while higher daily sodium intake and younger age enhanced the BP-lowering effect of the intervention. This meta-analysis was registered in the International Prospective Register of Systematic Reviews as CRD42019128120.
Funding Acknowledgement
Type of funding source: None
Abstract
Background/Introduction
Exaggerated blood pressure response (EBPR) during the exercise treadmill test (ETT) is often observed in individuals without known cardiovascular disease. Although it ...is generally considered as an abnormal response and a risk factor for hypertension development, its clinical significance remains controversial. On the other hand, regression of left ventricular hypertrophy (LVH) is independently associated with improved cardiovascular outcome.
Purpose
In this study we aimed to investigate the role of EBPR during exercise in LVH regression in hypertensive subjects over time.
Methods
1413 hypertensive subjects, (mean age 57±11 years), 51% males, with baseline office blood pressure (BP) 144/89mmHg were followed for a mean period of 6.4±3.0 years. At baseline and last follow-up visit all patients underwent office BP, laboratory tests and echocardiographical determination of left ventricular mass index (LVMI). At baseline, all subjects underwent treadmill exercise testing (Bruce protocol) in order to identify the presence of EBPR based on the systolic BP elevation at peak exercise (> or =210 mmHg for men and > or =190 mmHg for women). Main outcome variable was LVH Regression/prevention (LVH Regr/prev), defined as: LVH at baseline visit with normal LVMI values at last visit or absence of LVH at baseline and last visit. BP control was considered optimal when the mean of office BP measurements during follow-up was <140/90mmHg.
Results
46% of study population presented LVH Regr/prev during follow-up period. Cox-regression analysis, after adjustment for clinical and biochemical variables, revealed that low levels of baseline LVMI (HR=0.98, 95% CI 0.97–0.99, p<0.0001), absence of EBPR (HR=0.81, 95% CI 0.67–0.98, p=0.02) and optimal BP control during follow-up (HR=1.19, 95% CI 1.01–1.56, p=0.03) were independent predictors of LVH Regr/prev during follow-up.
Conclusions
Beyond optimal BP control, EBPR is a significant predictor of left ventricular mass changes overtime. Hence, ETT can provide clinical relevant information, including EBPR, which may help in the improvement of risk stratification of hypertensive subjects.
Funding Acknowledgement
Type of funding source: None
Spinal muscular atrophy (SMA), a recessive neuromuscular disorder, is caused by diminished function of the Survival Motor Neuron (SMN) protein. To define the cellular processes pertinent to SMA, ...parallel genetic screens were undertaken in Drosophila and Caenorhabditis elegans SMA models to identify modifiers of the SMN loss of function phenotypes. One class of such genetic modifiers was the small conductance, Ca(2+)-activated K(+) (SK) channels. SK channels allow efflux of potassium ions when intracellular calcium increases and can be activated by the neuroprotective drug riluzole. The latter is the only drug with proven, albeit modest, efficacy in the treatment of amyotrophic lateral sclerosis. It is unclear if riluzole can extend life span or ameliorate symptoms in SMA patients as previous studies were limited and of insufficient power to draw any conclusions. The critical biochemical target of riluzole in motor neuron disease is not known, but the pharmacological targets of riluzole include SK channels. We examine here the impact of riluzole in two different SMA models. In vertebrate neurons, riluzole treatment restored axon outgrowth caused by diminished SMN. Additionally, riluzole ameliorated the neuromuscular defects in a C. elegans SMA model and SK channel function was required for this beneficial effect. We propose that riluzole improves motor neuron function by acting on SK channels and suggest that SK channels may be important therapeutic targets for SMA patients.
Spinal muscular atrophy is an inherited motor neuron disease that results from a deficiency of the survival of motor neuron (SMN) protein. SMN is ubiquitinated and degraded through the ubiquitin ...proteasome system (UPS). We have previously shown that proteasome inhibition increases SMN protein levels, improves motor function, and reduces spinal cord, muscle, and neuromuscular junction pathology of spinal muscular atrophy (SMA) mice. Specific targets in the UPS may be more efficacious and less toxic. In this study, we show that the E3 ubiquitin ligase, mind bomb 1 (Mib1), interacts with and ubiquitinates SMN and facilitates its degradation. Knocking down Mib1 levels increases SMN protein levels in cultured cells. Also, knocking down the Mib1 orthologue improves neuromuscular function in Caenorhabditis elegans deficient in SMN. These findings demonstrate that Mib1 ubiquitinates and catalyzes the degradation of SMN, and thus represents a novel therapeutic target for SMA.
Higgs boson production via gluon-gluon fusion and vector-boson fusion in proton-proton collisions is measured in the H → WW *→ eνμν decay channel. The Large Hadron Collider delivered proton-proton ...collisions at a center-of-mass energy of 13 TeV between 2015 and 2018, which were recorded by the ATLAS detector, corresponding to an integrated luminosity of 139 fb −1 . The total cross sections for Higgs boson production by gluon-gluon fusion and vector-boson fusion times the H → WW* branching ratio are measured to be 12.0±1.4 and <img src="http://www.diva-portal.org/cgi-bin/mimetex.cgi?0.75_%7B-0.16%7D%5E%7B+0.19%7D" data-classname="equation" /> pb, respectively, in agreement with the Standard Model predictions of 10.4±0.6 and 0.81±0.02 pb. Higgs boson production is further characterized through measurements of Simplified Template Cross Sections in a total of 11 kinematic fiducial regions.
Spinal muscular atrophy (SMA), a recessive neuromuscular disorder, is caused by diminished function of the Survival Motor Neuron (SMN) protein. To define the cellular processes pertinent to SMA, ...parallel genetic screens were undertaken in
Drosophila
and
Caenorhabditis elegans
SMA models to identify modifiers of the SMN loss of function phenotypes. One class of such genetic modifiers was the small conductance, Ca
2+
-activated K
+
(SK) channels. SK channels allow efflux of potassium ions when intracellular calcium increases and can be activated by the neuroprotective drug riluzole. The latter is the only drug with proven, albeit modest, efficacy in the treatment of amyotrophic lateral sclerosis. It is unclear if riluzole can extend life span or ameliorate symptoms in SMA patients as previous studies were limited and of insufficient power to draw any conclusions. The critical biochemical target of riluzole in motor neuron disease is not known, but the pharmacological targets of riluzole include SK channels. We examine here the impact of riluzole in two different SMA models. In vertebrate neurons, riluzole treatment restored axon outgrowth caused by diminished SMN. Additionally, riluzole ameliorated the neuromuscular defects in a
C. elegans
SMA model and SK channel function was required for this beneficial effect. We propose that riluzole improves motor neuron function by acting on SK channels and suggest that SK channels may be important therapeutic targets for SMA patients.
Paternal mitochondrial DNA is normally eliminated from mammalian embryos. We have shown the presence of paternal mtDNA at the blastocyst stage in some abnormal human embryos.
Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used ...genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species.
PDF
