High-Sensitivity Troponin T and Copeptin in Non-ST Acute Coronary Syndromes: Implications for Prognosis and Role of hsTnT and Copeptin in Non-STEACS

High-sensitivity TnT (hsTnT) has been proposed to improve the diagnosis and stratification in acute coronary syndromes. Copeptin has been proposed for a rapid and accurate rule out of acute myocardial infarction, but some doubts exist about its use out of the first hours from admission. Abnormalities of serum hsTnT and copeptin levels in non-STEACS and negative TnT, could have prognostic implications. Methods. We included 122 non-STEACS patients without raised TnT, 33 disease controls and 43 healthy controls. We measured hsTnT and copeptin levels. Clinical follow-up at 12 months was performed for adverse endpoints. Results. Non-STEACS patients had raised hsTnT compared with both control groups (P = 0.036 and P < 0.001). Copeptin levels were higher in non-STEACS patients than healthy controls (P = 0.021), without differences with disease controls. Raised levels of hs-TnT presented prognostic implications [HR 3.29 (95%CI: 1.33–7.49), P = 0.010]. hs-TnT could be used for invasive approach decision, as it shows prognostic relevance in conservative approach-patients whereas remains unrelevant for catheterized-patients. Copeptin levels were not associated with adverse events. Conclusion. hsTnT levels increased in non-STEACS, were predictive of adverse events and could be important for recommending an invasive management. We cannot confirm a predictive role of copeptin out of the first hours from admission

Subjective well-being, happiness, and environmental health factors related to women planning a pregnancy or pregnant, using mobile health intervention

Objectives: To compare the environmental health results in women trying to get pregnant or pregnant using a mobile health application (Green Page) through healthcare professionals or self-completed by women, and to explore the relationship between the subjective well-being of these women with their lifestyles and environmental factors. Methods: A descriptive study with mixed methods was conducted in 2018. A mobile health survey was used in two phases. Phase 1 was a cross-sectional study through professionals (n = 1100) followed by phase 2, a convenience sampling through women's self-reporting (n = 3425). A personalized report was downloadable with health recommendations for the well-being of the mother and child. Results: Of the 3205 participants (mean age = 33 years, SD = 0.2 years), 1840 were planning a pregnancy and 1365 were pregnant. One in five pregnant women had a low level of happiness. Globally, subjective well-being and happiness were found to be negatively associated with lack of contact with nature, sedentary lifestyle, excess weight, environmental exposure, and older age in pregnancy. Precisely 45%, 60%, and 14% of women were exposed to tobacco, alcohol, and illegal drugs, respectively. The women self-reported levels of risk factors higher than when the tool was used by or through professionals. Conclusions: The use of mobile health interventions focused on environmental health during planning or pregnancy periods could help improve the quality of healthcare and foster greater involvement of women in their self-care process, thus promoting empowerment, healthier environments, and lifestyles. Ensuring equity of access and data protection are global challenges to be addressed.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Foundation for Formation and Research (FFIS) from Murcia's Drug Commissioner Office (Ecosistema Saludable, Neurodesallorro Saludable), the National Plan on Drugs, Ministry of Health, Spain (ID8437); the Mount Sinai International Exchange Program for Minority Student (Grant MD001452) from the National Center on Minority Health and Health Disparities of the U.S. National Institutes of Health; and the Sociedad de Pediatría del Sureste de España and its contribution to the project “Profile of childhood and adolescence environmental health in the region of Murcia” (FFIS-DF-2022-36). EOP is supported by a postdoctoral contract from the Instituto Murciano de Investigaciones Biosanitarias Virgen de la Arrixaca (IMIB-Arrixaca, Murcia, Spain).S

Estimated Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared to Optimally Acenocoumarol Anticoagulated ‘Real-World’ in Patients With Atrial Fibrillation

Nonvitamin K antagonist oral anticoagulants (NOACs) have been proposed as an alternative to vitamin K antagonists in atrial fibrillation (AF) patients but the comparative benefits between NOACs and optimally anticoagulated patients is unknown. We estimated the absolute benefit in clinical outcomes rates of real-world effect of NOACs in optimally anticoagulated AF patients with acenocoumarol. We included 1,361 patients stable on acenocoumarol with time in therapeutic range of 100% and 6.5 years of follow-up. Estimation of clinical events avoided was calculated applying hazard ratio, absolute and relative risk reduction from the real-world meta-analysis. Compared with an optimally anticoagulated population, dabigatran 110 mg had the highest estimated stroke reduction (0.97%/year vs 1.47%/year; p = 0.002), and the benefit was higher than in RE-LY trial. For major bleeding, apixaban showed the highest estimated reduction (1.81%/year vs 2.83%/year; p &lt;0.001). For mortality, the largest estimated reduction was with apixaban (2.68%/year). For gastrointestinal bleeding, only apixaban had a significant reduction compared with acenocoumarol (0.69%/year vs 1.10%/year; p = 0.004), and the reduction was significantly higher than in ARISTOTLE trial. All NOACs showed significantly lower rates for intracranial hemorrhage and had a positive Net Clinical Benefit compared with acenocoumarol. Apixaban showed the highest extended estimated Net Clinical Benefit 2.64 (95%CI 2.34 to 2.96). In conclusion, in optimally acenocoumarol anticoagulated AF patients, estimated reductions in all clinical outcomes with various NOACs are evident, with the best effectiveness and safety profile with apixaban. Indeed, the estimated effect with “real world” NOACs would probably be higher than that seen in phase-III clinical trials

Purificación y clonación de sistemas enzimáticos para la bioconversión de monofenoles en difenoles : polifenol oxidasa, tirosinasa y fenol hidroxilasa.

Los difenoles son compuestos con alto valor comercial por su capacidad antioxidante que se obtienen a partir de la hidroxilación de monofenoles. Dos enzimas se encargan de esta bioconversión, tirosinasa, también llamada polifenol oxidasa en plantas, y fenol hidroxilasa. Hasta el momento, no se han descrito procesos biocatalíticos eficientes para la obtención de difenoles. Por tanto, el objetivo de este proyecto de tesis es la obtención, mediante purificación y clonación, de polifenol oxidasa/tirosinasa y fenol hidroxilasa de tres fuentes separadas en la escala filogenética y el estudio de la capacidad de biosíntesis de estas enzimas ya sea mediante inmovilización enzimática en diferentes soportes o mediante un sistema de bioconversión de células transformadas completas. Los substratos utilizados, fenol y tirosol, tienen gran importancia comercial. El primero es un compuesto altamente contaminante en refinerías petrolíferas y plantas petroquímicas, y el segundo, da lugar tras su hidroxilación al hidroxitirosol, un nutracéutico de alto valor añadido con gran capacidad antioxidante y que estabiliza al aceite de oliva. El sistema de células transformadas completas permitió bioconversiones de los monofenoles en sus correspondientes difenoles del 100% por vez primera en la bibliografía

Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Our body is constantly exposed to pathogens or external threats, but with the immune response that our body can develop, we can fight off and defeat possible attacks or infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as the existence of a tumour also cause our immune system (IS) to be put on alert. Indeed, the link between immunology and cancer is evident these days, with IS being used as one of the important targets for treating cancer. Our IS is able to eliminate those abnormal or damaged cells found in our body, preventing the uncontrolled proliferation of tumour cells that can lead to cancer. However, in several cases, tumour cells can escape from the IS. It has been observed that immune cells, the extracellular matrix, blood vessels, fat cells and various molecules could support tumour growth and development. Thus, the developing tumour receives structural support, irrigation and energy, among other resources, making its survival and progression possible. All these components that accompany and help the tumour to survive and to grow are called the tumour microenvironment (TME). Given the importance of its presence in the tumour development process, this review will focus on one of the components of the TME: immune cells. Immune cells can support anti-tumour immune response protecting us against tumour cells; nevertheless, they can also behave as pro-tumoural cells, thus promoting tumour progression and survival. In this review, the anti-tumour and pro-tumour immunity of several immune cells will be discussed. In addition, the TME influence on this dual effect will be also analysed

Gut microbiota and diet effect on neurological diseases

Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa

Proteomics and metabolomics in thyroid cancer

Thyroid cancer (TC) is the most common endocrine malignancy and its incidence has been increasing sharply since the mid-1990s, being the fastest-increasing cancers in both men and women. Increased medical surveillance, the effect of environmental factors and more sensitive diagnostic tests, such as ultrasound and confirmation via fine-needle aspiration biopsy, are thought to account for this increased incidence. There are several histological types of thyroid cancer, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma, and anaplastic thyroid carcinoma. Determining the type of thyroid cancer is crucial for the assessment of prognosis and treatment selection. Unfortunately, approximately 20–30% of patients undergoing fine-needle aspiration biopsy have inconclusive or indeterminate results, leading to unnecessary surgical intervention in 80% of patients with benign nodules. To resolve this diagnosis dilemma, new biomarkers of thyroid cancer are needed. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome in a certain physiological time. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, and RNA levels are not informative of protein degradation. Clinically, there is increasing evidence for the role of proteomic and metabolomic technologies in biomarker discovery, providing novel information on the molecular events associated with TC, and potentially lead to the identification of novel drug targets. In this review, we will thoroughly describe the importance of novel proteomic and metabolomic approaches to identify new biomarkers associated with TC

Evidence for a lack of inotropic and chronotropic effects of glucagon and glucagon receptors in the human heart

Abstract Background Glucagon is thought to increase heart rate and contractility by stimulating glucagon receptors and increasing 3′,5′-cyclic adenosine monophosphate (cAMP) production in the myocardium. This has been confirmed in animal studies but not in the human heart. The cardiostimulatory effects of glucagon have been correlated with the degree of cardiac dysfunction, as well as with the enzymatic activity of phosphodiesterase (PDE), which hydrolyses cAMP. In this study, the presence of glucagon receptors in the human heart and the inotropic and chronotropic effects of glucagon in samples of failing and nonfailing (NF) human hearts were investigated. Methods Concentration‒response curves for glucagon in the absence and presence of the PDE inhibitor IBMX were performed on samples obtained from the right (RA) and left atria (LA), the right (RV) and left ventricles (LV), and the sinoatrial nodes (SNs) of failing and NF human hearts. The expression of glucagon receptors was also investigated. Furthermore, the inotropic and chronotropic effects of glucagon were examined in rat hearts. Results In tissues obtained from failing and NF human hearts, glucagon did not exert inotropic or chronotropic effects in the absence or presence of IBMX. IBMX (30 µM) induced a marked increase in contractility in NF hearts (RA: 83 ± 28% (n = 5), LA: 80 ± 20% (n = 5), RV: 75 ± 12% (n = 5), and LV: 40 ± 8% (n = 5), weaker inotropic responses in the ventricular myocardium of failing hearts (RV: 25 ± 10% (n = 5) and LV: 10 ± 5% (n = 5) and no inotropic responses in the atrial myocardium of failing hearts. IBMX (30 µM) increased the SN rate in failing and NF human hearts (27.4 ± 3.0 beats min −1 , n = 10). In rat hearts, glucagon induced contractile and chronotropic responses, but only contractility was enhanced by 30 µM IBMX (maximal inotropic effect of glucagon 40 ± 8% vs. 75 ± 10%, in the absence or presence of IBMX, n = 5, P  0.05). Glucagon receptors were not detected in the human heart samples. Conclusions Our results conflict with the view that glucagon induces inotropic and chronotropic effects and that glucagon receptors are expressed in the human heart