Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene

BACKGROUND: Little information is available on phenotype-genotype correlations in familial hypertrophic cardiomyopathy that are related to the cardiac myosin binding protein C (MYBPC3) gene. The aim of this study was to perform this type of analysis. METHODS AND RESULTS: We studied 76 genetically affected subjects from nine families with seven recently identified mutations (SASint20, SDSint7, SDSint23, branch point int23, Glu542Gln, a deletion in exon 25, and a duplication/deletion in exon 33) in the MYBPC3 gene. Detailed clinical, ECG, and echocardiographic parameters were analyzed. An intergene analysis was performed by comparing the MYBPC3 group to seven mutations in the beta-myosin heavy-chain gene (beta-MHC) group (n=52). There was no significant phenotypic difference among the different mutations in the MYBPC3 gene. However, in the MYBPC3 group compared with the beta-MHC group, (1) prognosis was significantly better (P<0.0001), and no deaths occurred before the age of 40 years; (2) the age at onset of symptoms was delayed (41+/-19 versus 35+/-17 years, P<0.002); and (3) before 30 years of age, the phenotype was particularly mild because penetrance was low (41% versus 62%), maximal wall thicknesses lower (12+/-4 versus 16+/-7 mm, P<0.03), and abnormal T waves less frequent (9% versus 45%, P<0.02). CONCLUSIONS: These results are consistent with specific clinical features related to the MYBPC3 gene: onset of the disease appears delayed and the prognosis is better than that associated with the beta-MHC gene. These findings could be particularly important for the purpose of clinical management and genetic counseling in familial hypertrophic cardiomyopathy.     

The Photosensitising Clinical Agent Verteporfin Is an Inhibitor of SPAK and OSR1 Kinases

STE20/SPS1‐related proline/alanine‐rich kinase (SPAK) and oxidative‐stress‐responsive kinase 1 (OSR1) are two serine/threonine protein kinases that play key roles in regulating ion homeostasis. Various SPAK and OSR1 mouse models exhibited reduced blood pressure. Herein, the discovery of verteporfin, a photosensitising agent used in photodynamic therapy, as a potent inhibitor of SPAK and OSR1 kinases is reported. It is shown that verteporfin binds the kinase domains of SPAK and OSR1 and inhibits their catalytic activity in an adenosine triphosphate (ATP)‐independent manner. In cells, verteporfin was able to suppress the phosphorylation of the ion co‐transporter NKCC1; a downstream physiological substrate of SPAK and OSR1 kinases. Kinase panel screening indicated that verteporfin inhibited a further eight protein kinases more potently than that of SPAK and OSR1. Although verteporfin has largely been studied as a modifier of the Hippo signalling pathway, this work indicates that the WNK‐SPAK/OSR1 signalling cascade is also a target of this clinical agent. This finding could explain the fluctuation in blood pressure noted in patients and animals treated with this drug.     

Bicarbonate Effect in the Ozone-UV Process in the Presence of Nitrate

Ozonation and advanced oxidation processes (AOP) are very efficient methods for the destruction of refractory organic matters. These virtues have always been related to the production of hydroxyl radicals HO^?, which are extremely powerful and non-selective oxidants. In this study, the O₃-UV process is used as an AOP, where hydroxyl radicals are generated from the photodecomposition of ozone by short wavelength ultraviolet radiation. The obtained results indicated a weak scavenging effect of tert-butanol proving that hydroxyl radicals and ozone are not the only oxidants existing in the medium. Moreover, bicarbonate, known for a long time as effective HO^? radical scavengers, does not slow down the oxidation of benzoic acid, but surprisingly increases it. Chlorides significantly decrease the degradation of organic compounds through their reaction with HO^? radicals to produce chlorine. Carbonate radicals, nitrate and nitrogenated species as peroxynitrite/?peroxynitrous acid are involved in the oxidative mechanisms.     

Formation of silicon nanocrystals by thermal annealing of low-pressure chemical-vapor deposited amorphous SiNx (x=0.16) thin films

Silicon nanocrystals have been produced by thermal annealing of SiN_x thin film obtained by low pressure chemical vapor deposition using a mixture between disilane and ammonia. Morphological, structural, and photoluminescence properties of the thin film were investigated using X-ray diffraction, scanning electron microscopy, Raman spectroscopy and photoluminescence spectroscopy. The results revealed a high crystallinity of film with a crystalline volume fraction exceeded 70%, and a dominance of silicon nanocrystallites having the sizes within the range 2.5–5 nm and density ~1.98.10¹²/cm². The PL peaks consist of nanocrystalline silicon and amorphous silicon. The luminescence from the silicon nanocrystals was dominant.     

A review of induction motors signature analysis as a medium forfaults detection

This paper is intended as a tutorial overview of induction motors signature analysis as a medium for fault detection. The purpose is to introduce in a concise manner the fundamental theory, main results, and practical applications of motor signature analysis for the detection and the localization of abnormal electrical and mechanical conditions that indicate, or may lead to, a failure of induction motors. The paper is focused on the so-called motor current signature analysis which utilizes the results of spectral analysis of the stator current. The paper is purposefully written without “state-of-the-art” terminology for the benefit of practising engineers in facilities today who may not be familiar with signal processing     

Embedded System Prototype to Fight Covid-19 Pandemic Contamination with Less Cost

Wireless Personal Communications - In the shadow of the coronavirus (Covid-19) pandemic, the sterilization has become a major necessity for humans to avoid exponential Infection. In order to avoid...     

Towards the Development of Small‐Molecule MO25 Binders as Potential Indirect SPAK/OSR1 Kinase Inhibitors

The binding of the scaffolding protein MO25 to SPAK and OSR1 protein kinases, which regulate ion homeostasis, causes increases of up to 100‐fold in their catalytic activity. Various animal models have shown that the inhibition of SPAK and OSR1 lowers blood pressure, and so here we present a new indirect approach to inhibiting SPAK and OSR1 kinases by targeting their protein partner MO25. To explore this approach, we developed a fluorescent polarisation assay and used it in screening of a small in‐house library of ≈4000 compounds. This led to the identification of one compound—HK01—as the first small‐molecule inhibitor of the MO25‐dependent activation of SPAK and OSR1 in vitro. Our data confirm the feasibility of targeting this protein–protein interaction by small‐molecule compounds and highlights their potential to modulate ion co‐transporters and thus cellular electrolyte balance.     

A study of the braided corrugated hoses: Behavior and life estimation

This work presents the virtual simulation of the hoses hydroforming; the main objective is to predict when and where cracks can appear during a cyclic loading.     

Influence of calcined kaolin on mortar properties

The use of calcined clay, in the form of metakaolin (MK), as a pozzolanic material for mortar and concrete has received considerable attention in recent years. The present paper describes the results of a research project initiated to study the calcination of local kaolin at various temperatures (650–950 °C) and durations (2, 3 and 4 h) to produce MK with a high pozzolanic activity. The pozzolanic activity was assessed by 28-days compressive strength and hydration heat methods. The maximum identified activity was obtained at 850 °C for 3 h duration. An increase of both hydration heat and compressive strength was obtained when ordinary Portland cement was replaced by 10% MK. The use of ternary blended cement improves the early age and the long-term compressive strength. The durability was also enhanced as better acidic resistance was observed.