NiMoO4@Co3O4 Core–Shell Nanorods: In Situ Catalyst Reconstruction toward High Efficiency Oxygen Evolution Reaction

The sluggish kinetics of the oxygen evolution reaction (OER) is the bottleneck for the practical exploitation of water splitting. Here, the potential of a core–shell structure of hydrous NiMoO4 microrods conformally covered by Co3O4 nanoparticles via atomic layer depositions is demonstrated. In situ Raman and synchrotron-based photoemission spectroscopy analysis confirms the leaching out of Mo facilitates the catalyst reconstruction, and it is one of the centers of active sites responsible for higher catalytic activity. Post OER characterization indicates that the leaching of Mo from the crystal structure, induces the surface of the catalyst to become porous and rougher, hence facilitating the penetration of the electrolyte. The presence of Co3O4 improves the onset potential of the hydrated catalyst due to its higher conductivity, confirmed by the shift in the Fermi level of the heterostructure. In particular NiMoO4@Co3O4 shows a record low overpotential of 120 mV at a current density of 10 mA cm−2, sustaining a remarkable performance operating at a constant current density of 10, 50, and 100 mA cm−2 with negligible decay. Presented outcomes can significantly contribute to the practical use of the water-splitting process, by offering a clear and in-depth understanding of the preparation of a robust and efficient catalyst for water-splitting

Beyond gene-disease validity: capturing structured data on inheritance, allelic-requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions

Background: As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. Results: For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing

What factors affect patients' recall of general practitioners' advice?

<p>Abstract</p> <p>Background</p> <p>In order for patients to adhere to advice, provided by family doctors, they must be able to recall it afterwards. However, several studies have shown that most patients do not fully understand or memorize it. The aim of this study was to determine the influence of demographic characteristics, education, amount of given advice and the time between consultations on recalled advice.</p> <p>Methods</p> <p>A prospective survey, lasting 30 months, was conducted in an urban family practice in Slovenia. Logistic regression analysis was used to identify the risk factors for poorer recall.</p> <p>Results</p> <p>250 patients (87.7% response rate) received at least one and up to four pieces of advice (2.4 ± 0.8). A follow-up consultation took place at 47.4 ± 35.2 days. The determinants of better recall were high school (OR 0.4, 95% CI 0.15-0.99, p = 0.049) and college education (OR 0.3, 95% CI 0.10-1.00, p = 0.050), while worse recall was determined by number of given instructions three or four (OR 26.1, 95% CI 3.15-215.24, p = 0.002; OR 56.8, 95% CI 5.91-546.12, p < 0.001, respectively) and re-test interval: 15-30 days (OR 3.3, 95% CI 1.06-10.13, p = 0.040), 31-60 days (OR 3.2, 95% CI 1.28-8.07, p = 0.013) and more than 60 days (OR 2.5, 95% CI 1.05-6.02, p = 0.038).</p> <p>Conclusions</p> <p>Education was an important determinant factor and warrants further study. Patients should be given no more than one or two instructions in a consultation. When more is needed, the follow-up should be within the next 14 days, and would be of a greater benefit to higher educated patients.</p

Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions

Background: As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings. // Methods: We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering. // Results: For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches. // Conclusions: Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing

TRAF6 Promotes Myogenic Differentiation via the TAK1/p38 Mitogen-Activated Protein Kinase and Akt Pathways

p38 mitogen-activated protein kinase (MAPK) is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways

An International Multi-Center Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multi-center collaboration. Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (JLNS2, N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc > 460ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. Results: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 JLNS2 patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9 ± 38.6ms) compared to genotype positive family members (441.8 ± 30.9ms, p<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR]: 11.6, 95% confidence interval [CI]: 2.6-52.2; p=0.001). Event incidence did not differ significantly for JLNS2 patients relative to the overall heterozygous cohort (10.5% [2/19]; HR: 1.7, 95% CI: 0.3-10.8, p=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database (gnomAD), which is a human database of exome and genome sequencing data from now over 140,000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs. 0.001%). Conclusions: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT-prolongation, however the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for JLNS2 patients

Soy isoflavones and their relationship with microflora: beneficial effects on human health in equol producers

The bioavailability of soy isoflavones depends on the composition of the microflora for each subject. Bacteria act on different isoflavones with increased or reduced absorption and cause biotransformation of these compounds into metabolites with higher biological activity. S-equol is the most important metabolite and only 25–65 % of the population have the microflora that produces this compound. The presence of equol-producing bacteria in soy product consumers means that the consumption of such products for prolonged periods leads to lower cardiovascular risk, reduced incidence of prostate and breast cancer, and greater relief from symptoms related to the menopause such as hot flushes and osteoporosis

Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?

Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart