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IntroductionAlthough the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown.ObjectivesThis study aimed to assess in vivo the physiological role of sEH-P.MethodsCRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity.ResultsThe sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia-reperfusion injury.ConclusionOur study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.

Background: Recent data from European studies (EUROASPIRE V, DA VINCI, SANTORINI) indicate that achieving the LDL cholesterol (LDL-C) target in patients at very high cardiovascular risk is uncommon. Additionally, using a combination therapy involving statins and ezetimibe remains infrequent. Methods: A single-center assessment of a pre-defined lipid lowering treatment algorithm's effectiveness at achieving the LDL-C target in patients at very high cardiovascular risk one month and one year after hospitalization. Results: 81 patients were included, all in secondary prevention. The average age of the patient was 66.9 years, and the main cardiovascular risk factors included hypertension, diabetes mellitus, and smoking history. Following the predefined lipid-lowering algorithm specific to our study, which involves initiating high-intensity statin therapy or a combination of statin and ezetimibe depending on initial LDL-C levels and patient history; 30 (37%) patients initiated high-intensity statin therapy (Atorvastatin (40 mg, 80 mg) or Rosuvastatin (20 mg, 40 mg)), while 51 (63%) started combination therapy with high-intensity statin and ezetimibe 10 mg. After one year, 57 (70.4%) remained adherent to their initial treatment, achieving a mean LDL-C of 49.5 ± 16.9 mg/dL, with 36 (63.2%) of them reaching the LDL-C target of <55 mg/dL. A total of 13 patients discontinued treatment, and 9 were lost to follow-up, withdrew from the study, or died. Conclusion: Initiating dual statin and ezetimibe therapy or high-intensity statin therapy early, based on the expected treatment efficacy, holds the potential to more rapidly and effectively achieve LDL-C targets in a larger proportion of very high-risk cardiovascular patients. [ABSTRACT FROM AUTHOR]

Lung transplantation (LT) constitutes the last therapeutic option for selected patients with end-stage respiratory disease. Primary graft dysfunction (PGD) is a form of severe lung injury, occurring in the first 72 h following LT and constitutes the most common cause of early death after LT. The presence of pulmonary hypertension (PH) has been reported to favor PGD development, with a negative impact on patients' outcomes while complicating medical management. Although several studies have suggested a potential association between pre-LT left ventricular diastolic dysfunction (LVDD) and PGD occurrence, the underlying mechanisms of such an association remain elusive. Importantly, the heterogeneity of the study protocols and the various inclusion criteria used to define the diastolic dysfunction in those patients prevents solid conclusions from being drawn. In this review, we aim at summarizing PGD mechanisms, risk factors, and diagnostic criteria, with a further focus on the interplay between LVDD and PGD development. Finally, we explore the predictive value of several diastolic dysfunction diagnostic parameters to predict PGD occurrence and severity. [ABSTRACT FROM AUTHOR]

This comprehensive review explores the intricate aspects of left ventricular thrombus (LVT), a potential complication in both ischemic and non-ischemic cardiomyopathies. It provides a thorough understanding of left ventricular thrombus, revealing its uncommon incidence in the general population (7 cases per 10,000 patients), predominantly linked to ischemic heart diseases (ICMs) at an 80% prevalence rate. Diagnostic tools, notably transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (CMR), demonstrate varying sensitivity but remain indispensable in specific clinical contexts related to LVT as non-invasive diagnostic modalities. A detailed comparison between ICM patients and those with non-ischemic cardiomyopathy (NICM) who have left ventricular thrombus reveals subtle distinctions with significant clinical implications. This analysis underscores the importance of these imaging techniques in distinguishing between the two conditions. Additionally, we explored the occurrence of LVT in specific non-ischemic cardiomyopathies, including Takotsubo syndrome, hypertrophic cardiomyopathy, eosinophilic myocarditis, Chagas disease, cardiac amyloidosis, and several other conditions. The article further delves into anticoagulation strategies, thoroughly examining their impact on LVT regression and patient outcomes. Pharmacological interventions, with a focus on direct oral anticoagulants, emerge as promising alternatives; however, there is insufficient information on their efficiency and safety, especially in NICM population. In conclusion, this review highlights the complex nature of LVT, incorporating a range of etiopathogenic factors, diagnostic complexities, and evolving therapeutic approaches. It emphasizes the pressing need for ongoing research in this field. [ABSTRACT FROM AUTHOR]

La investigación realizada busca proponer un nuevo material que reemplace los materiales tradicionales empleados en las construcciones civiles, debido al fuerte impacto ambiental que estos generan en el medio donde se desarrollan, así como en los seres vivos, por un material ecológico y amigable con el planeta, que cumpla con un buen comportamiento físico- mecánico, así como características que evidencien una mejora en el tiempo de ejecución, costo, trabajabilidad, confort, etc. Es así que se propone el uso del bambú, considerado como una bendición de la naturaleza. Se tuvo como objetivo destacar los beneficios que se logran con el empleo del bambú como material de construcción. La investigación fue de tipo descriptivo con un diseño no experimental, donde se usó una ficha de observación para evaluar las actividades de una obra en ejecución y así determinar en campo las bondades de este material, además se hizo uso del material informativo, para que de esta manera sea reforzada la investigación llevada a cabo. Los resultados en tablas y figuras de elaboración propia, los que serán puestos en discusión y comparación con las investigaciones tomadas como referencia. Por último, se llegó a la conclusión de que el bambú es un material adecuado, viable, alternativo, sostenible y ecológico que puede usarse en construcción.

This article concerns the improvement of digital image quality using mathematical tools such as nonlinear partial differential operators. In this paper, to perform smoothing on digital images, we propose to use the p(x)-Laplacian operator. Its smoothing power plays a main role in the restoration process. This enables us to dynamically process certain areas of an image. We used a mathematical model of image regularisation that is described by a nonlinear diffusion Equation (this diffusion is modelled by the p(x)-Laplacian operator). We implemented the continuous model in order to observe the steps of the regularisation process to understand the effects of the different parameters of the model on an image. This will enable parameters to be used and adapted in order to provide a proposed solution. [ABSTRACT FROM AUTHOR]