To construct a sudden death risk score specifically for hypertension (HYSUD) patients with or without cardiovascular history.Data were collected from six randomized controlled trials of antihypertensive treatments with 8044 women and 17 604 men differing in age ranges and blood pressure eligibility criteria. In total, 345 sudden deaths (1.35%) occurred during a mean follow-up of 5.16 years. Risk factors of sudden death were examined using a multivariable Cox proportional hazards model adjusted on trials. The model was transformed to an integer system, with points added for each factor according to its association with sudden death risk.Antihypertensive treatment was not associated with a reduction of the sudden death risk and had no interaction with other factors, allowing model development on both treatment and placebo groups. A risk score of sudden death in 5 years was built with seven significant risk factors: age, sex, SBP, serum total cholesterol, cigarette smoking, diabetes, and history of myocardial infarction. In terms of discrimination performance, HYSUD model was adequate with areas under the receiver operating characteristic curve of 77.74% (confidence interval 95%, 74.13-81.35) for the derivation set, of 77.46% (74.09-80.83) for the validation set, and of 79.17% (75.94-82.40) for the whole population.Our work provides a simple risk-scoring system for sudden death prediction in hypertension, using individual data from six randomized controlled trials of antihypertensive treatments. HYSUD score could help assessing a hypertensive individual's risk of sudden death and optimizing preventive therapeutic strategies for these patients.

A plausible mechanism that may contribute to drug resistance in epilepsy is the failure of drugs to reach the brain tissue, caused by changes in the activity of ABC transporters. The main argument in favour of this hypothesis is that resistance occurs against a wide variety of antiepileptic drugs with different mechanisms of action, suggesting a non-specific underlying phenomenon that limits the effectiveness of drug treatments.A review of the literature on ABC transporters, their role in the normal physiology of the blood-brain barrier and drug resistance in epilepsy, both in human studies and in animal models, is conducted. Studies of genetic variants in the ABCB1 and ABCC2 genes, which code for these transporters, and recent genomic studies in epilepsy and related pathologies are also reviewed, followed by a discussion of their scope and limitations.To date, the association of genetic variants of ABC transporters with resistance to anticonvulsant drugs remains a matter of debate. The increasingly widespread use and accessibility of modern sequencing technologies is expected to allow the establishment of genetic markers that provide a precision medicine based approach to the treatment of epilepsy.Transportadores ABC y resistencia a fármacos en la epilepsia: plausibilidad biológica, farmacogenética y medicina de precisión.Introducción. Un mecanismo plausible que puede contribuir a la resistencia a fármacos en la epilepsia es la falta de llegada de los fármacos al tejido encefálico, causado por cambios en la actividad de los transportadores ABC. El principal argumento a favor de esta hipótesis es que la resistencia ocurre frente a una gran variedad de fármacos antiepilépticos con distintos mecanismos de acción, lo que sugiere un fenómeno subyacente no específico que limita la efectividad de los tratamientos farmacológicos. Desarrollo. Se realiza una revisión bibliográfica de los transportadores ABC, su papel en la fisiología normal de la barrera hematoencefálica y en la resistencia a fármacos en la epilepsia, tanto en estudios en humanos como en modelos animales. Se revisan además los estudios de variantes genéticas en los genes ABCB1 y ABCC2, que codifican para estos transportadores, y los recientes estudios genómicos en la epilepsia y patologías afines, discutiendo sus alcances y limitaciones. Conclusiones. Hasta ahora, la asociación de variantes genéticas de transportadores ABC con la resistencia a fármacos anticonvulsivantes sigue siendo materia de debate. Se espera que la creciente masificación y accesibilidad a tecnologías de secuenciación modernas permitan establecer marcadores genéticos que otorguen una aproximación de medicina de precisión para el tratamiento de la epilepsia.

Background Language disturbances are a core feature of schizophrenia, often studied as a formal thought disorder. The neurobiology of language in schizophrenia has been addressed within the same framework, that language and thought are equivalents considering symptoms and not signs. This review aims to systematically examine published peer-reviewed studies that employed neuroimaging techniques to investigate aberrant brain-language networks in individuals with schizophrenia in relation to linguistic signs. Methods We employed a language model for automatic data extraction. We selected our studies according to the PRISMA recommendations, and we conducted the quality assessment of the selected studies according to the STROBE guidance. Results We analyzed the findings from 37 studies, categorizing them based on patient characteristics, brain measures, and language task types. The inferior frontal gyrus (IFG) and superior temporal gyrus (STG) exhibited the most significant differences among these studies and paradigms. Conclusions We propose guidelines for future research in this field based on our analysis. It is crucial to investigate larger networks involved in language processing, and language models with brain metrics must be integrated to enhance our understanding of the relationship between language and brain abnormalities in schizophrenia

Leadership has a responsibility to subordinates and organisations, and abusive leadership needs further study to determine its effects on leaders, subordinates, and organisations. Abusive leadership is associated with different terms and generated by different situations, so the aim of this study is to establish a unified framework of the antecedents of abusive leadership, including its types, factors, and effects. This study conducted protocol research as a systematic review of the literature, and its objective was developed through an analysis of articles (n= 70) organised into four clusters. The analysis identified many types of leadership, leadership styles, and management styles, which developed according to the orientation of the leader (task and/or subordinate), and according to it, inefficient leadership could lead to an abusive leadership. Also, leadership in general is a product of contextual factors, personal (leader/supervisor) behaviour, and subordinate characteristics, and abusive leadership situations have effects on the subordinate and team levels. This study has multilevel theoretical and practical implications, including personal and organisational ones, and some limits, which are why further research on this topic is recommended.

Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3–5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters, or cell signalling mechanisms. This review summarizes the evidence available on the potential involvement of the adenosine in the clinical, pathophysiology, and therapeutic features of preeclampsia.

Adenosine as well as agonists and antagonists for the four adenosine receptor subtypes (A1R, A2AR, A2BR and A3R) play a role in several key physiological and pathophysiological processes, including the regulation of vascular tone , thrombosis, immune response, inflammation, and angiogenesis . This review focuses on the adenosine-mediated regulation of lipid availability in the cell and in the systemic circulation as well in humans and animal models . Therefore, adenosine, mainly by acting on A1R, inhibits lipolysis activity , leading to reduction of the circulating fatty acid levels . This nucleoside can also participate in the early development of atherosclerosis by inhibiting the formation of foam cells via stimulation of cholesterol efflux through A2AR expressed on macrophages and reduction of the inflammatory process by activating A2AR and A2BR. Adenosine also appears to modulate intracellular cholesterol availability in Niemann-Pick type C1 disease and Alzheimer disease via A2AR and A3, respectively. Remarkably, the role of adenosine receptors in the regulation of plasma total cholesterol and triglyceride levels has been studied in animal models. Thus, an anti-atherogenic role for A2BR as well as a pro-atherogenic role of A2AR and A1 have been proposed; A3R has not been shown to participate in the control of lipid levels or the development of atherosclerosis. Surprisingly, and despite the role of A2A in the inhibition of foam cell formation among isolated cells, this receptor appears to be pro-atherogenic in mice. Remarkably, the role of adenosine receptors in human dyslipidaemia and atherosclerosis must to be elucidated. Additionally, it has been reported that increased lipid levels impair the effects of adenosine/adenosine receptors in controlling vascular tone, and we speculate on the possibility that this impairment could be due to alterations in the composition of the membrane microdomains where the adenosine receptors are located. Finally, a possible role for adenosine/adenosine receptors in the phenomena of dyslipidaemia in pregnancy has been proposed.

Introduction Ecologically valid assessments need to require tasks representative of real, everyday interactions between people in a social environment (i.e., verisimilitude) and to predict aspects of real-life performance in those same interactions (i.e., veridicality). To determine how researchers interested in social cognition among people with schizophrenia currently understand and apply ecological validity in their work, we conducted a systematic review of studies that had the ecological validity of their results as an explicit objective. Methods We performed the described systematic review following PRISMA guidelines. Results Of the 18 studies reviewed, only two defined ecological validity , 15 incorporated modifications to improve their verisimilitude, eight proposed analyses to examine their veridicality, and seven aimed to achieve both objectives. Conclusions Our systematic review suggests that very few published studies on social cognition among people with schizophrenia have explicitly defined ecological validity , and most have focused only on the verisimilitude of the tasks required while neglecting the veridicality of the results.

Insulin resistance is characteristic of pregnancies where the mother shows metabolic alterations, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), or abnormal maternal conditions such as pregestational maternal obesity (PGMO). Insulin signalling includes activation of insulin receptor substrates 1 and 2 (IRS1/2) as well as Src homology 2 domain-containing transforming protein 1, leading to activation of 44 and 42 kDa mitogen-activated protein kinases and protein kinase B/Akt (Akt) signalling cascades in the human foetoplacental vasculature. PE, GDM, and PGMO are abnormal conditions coursing with reduced insulin signalling, but the possibility of the involvement of similar cell signalling mechanisms is not addressed. This review aimed to determine whether reduced insulin signalling in PE, GDM, and PGMO shares a common mechanism in the human foetoplacental vasculature. Insulin resistance in these pathological conditions results from reduced Akt activation mainly due to inhibition of IRS1/2, likely due to the increased activity of the mammalian target of rapamycin (mTOR) resulting from lower activity of adenosine monophosphate kinase. Thus, a defective signalling via Akt/mTOR in response to insulin is a central and common mechanism of insulin resistance in these diseases of pregnancy. In this review, we summarise the cell signalling mechanisms behind the insulin resistance state in PE, GDM, and PGMO focused in the Akt/mTOR signalling pathway in the human foetoplacental endothelium.

Obesity and type 2 diabetes mellitus (T2DM) are diseases associated with hypertension and metabolic alterations. A significant group of patients present both obesity and T2DM, a condition defined as diabesity. One of the metabolic features in these conditions is the clinical presentation of insulin resistance. Several tissues, including the liver, skeletal muscle, and vasculature, and patients with T2DM, gestational diabetes, and obesity show insulin resistance. The vascular effect of insulin, including vasodilation, is mainly mediated by the generation of nitric oxide. Several mechanisms are proposed to elucidate the origin of insulin resistance; nevertheless, a common finding is the endothelial dysfunction in these diseases. Endothelial cells from subjects with obesity show reduced nitric oxide synthesis, an effect that is unaltered by insulin. Individuals with T2DM show a misbalance between the synthesis, release, and biological actions of vasodilators and vasoconstrictors such as nitric oxide and endothelin-1. However, whether these mechanisms are involved in the vascular alterations seen in patients with diabesity is unclear. In this review, we discussed the modifications on insulin signalling, insulin resistance in obesity and T2DM, and the reported changes in signalling pathways in diabesity.

Background The common femoral artery and radial artery constitute the most common access sites in contemporaneous endovascular neurosurgery. Oftentimes, it may be impossible to reach the vascular target safely due to different circumstances, necessitating alternative approaches. We aim to review these “last resource” access sites described in the literature, focusing on the technical aspects as a convenient reference. Methods We performed a comprehensive literature search of PubMed capturing articles from 1958 to 2022. Results We identified nine alternative approaches for endovascular access, after excluding direct carotid stick: superficial temporal artery access in 60 patients, calvarial foramina access in five patients, occipital artery access in seven patients, middle meningeal artery access in six patients, vertebral artery access in 23 patients and external carotid artery, internal maxillary artery, facial artery or lingual artery in 40 patients. Indications for the use of alternative access points included tortuous or occluded vessels, small vessel calibers, or anatomic variation. Pathologies treated included dural arteriovenous fistulas, arteriovenous malformations, intracranial aneurysms, acute stroke, and intracranial stenosis. Diagnostic brain angiograms were also performed. Conclusions Alternative vascular access routes expand the proceduralists' toolkit, enhancing the capability to manage complex cerebrovascular interventions. This review advocates for a broader understanding and consideration of these techniques, given their potential to significantly increase treatment options in neuroendovascular surgery.

Introduction: Despite being commonly recommended, the impact of anticancer drugs (ACDs) on patient-important outcomes beyond survival for advanced hepatobiliary cancers (HBCs) may not have been sufficiently assessed. We aim to identify and map the evidence regarding ACDs versus best supportive care (BSC) for advanced HBCs, considering patient-centered outcomes. Methods: In this mapping review, we included systematic reviews, randomized controlled trials, quasi-experimental, and observational studies comparing ACDs (chemotherapy, immunotherapy, biological/targeted therapy) versus BSC for advanced HBCs. We searched MEDLINE (PubMed), EMBASE (Ovid), Cochrane Library, Epistemonikos, PROSPERO and clinicaltrials.gov for eligible studies. Two reviewers performed the screening and data extraction processes. We developed evidence maps for each type of cancer. Results: We included 87 studies (60 for advanced liver cancer and 27 for gallbladder or bile duct cancers). Most of the evidence favored ACDs for survival outcomes, and BSC for toxicity. We identified several evidence gaps for non-survival outcomes, including quality of life or quality of end-of-life care. Discussion: Patient-important outcomes beyond survival in advanced HBCs are insufficiently assessed by the available evidence. Future studies need to address these gaps to better inform decision-making processes. Keywords: liver neoplasms, gallbladder neoplasms, bile duct neoplasms, antineoplastic agents, immunotherapy, biological therapy, palliative care

La fisiopatología del tinnitus crónico no pulsátil es poco clara, pero se reconoce un componente psicológico relevante, por tanto, existen distintas aproximaciones psicoterapéuticas que han sido estudiadas. La terapia cognitivo conductual es la que cuenta con mayor evidencia. Ella contempla la reestructuración de las cogniciones disfuncionales que favorecen la presencia del tinnitus. Se ha verificado su eficacia en los niveles de distrés, calidad de vida, severidad, sintomatología depresiva e insomnio asociados. La desensibilización y reprocesamiento por movimientos oculares recoge algunos presupuestos de la terapia cognitivo conductual, pero considera técnicas como la estimulación bilateral. Sus resultados en patologías crónicas somáticas han sugerido la aplicación en tinnitus, corroborando su eficacia en calidad de vida, distrés y sintomatología depresiva. Dos psicoterapias basadas en mindfulness aplicadas en tinnitus son la reducción del estrés basado en el mindfulness y la terapia cognitiva basada en mindfulness. La primera ha demostrado eficacia en la calidad de vida y en la disminución y el refuerzo de cogniciones negativas y positivas, respectivamente. La segunda, es eficaz en la severidad, intensidad, distrés, ansiedad, depresión y discapacidad asociadas a tinnitus. Finalmente, la terapia de aceptación y compromiso promueve la aceptación como componente central del tratamiento de condiciones crónicas, considerando el control que ejerce el contexto sobre la vivencia de estas condiciones y el compromiso terapéutico. Esta terapia es eficaz en calidad de vida. Se promueve la investigación en aproximaciones psicoterapéuticas para el tinnitus, lo que posibilitará la aplicación de terapias más específicas y la clarificación de su fisiopatología.

Metacognitive training (MCT) for psychosis is a group intervention that combines cognitive-behavioural therapy and psychoeducation. It has proven efficacy in reducing psychotic symptoms and correcting cognitive biases implicated in the development and maintenance of psychotic symptoms. However, other outcomes, such as patient satisfaction with the intervention, have not been well studied despite their importance for adherence and overall success. A systematic review of randomized clinical trials was conducted to assess satisfaction with MCT among adults with psychotic spectrum disorders.

Introduction: Diabetes mellitus (DM) is a prevalent chronic metabolic disorder worldwide, with Type II DM (T2DM) emerging as the most widespread variant. In Chile, approximately 11% of adults aged 20 to 79 suffer from this condition. Given its high prevalence, dental surgeons should be trained to evaluate risk factors, particularly the potential complications linked to tooth extraction in individuals with T2DM. Objetive: To describe the available scientific evidence on post-exodontia complications associated with hyperglycemia in patients with Type II diabetes mellitus. Materials and Methods: An exploratory systematic review was conducted following the PRISMA-ScR extension protocols using the databases PubMed, EBSCO, Scopus and the Cochrane Library. The search employed the following algorithms: ((“Diabetic patient complications” AND “Dental extractions”)), ((“Diabetes” AND “tooth extraction”)), ((“Glycemia” AND “Tooth extraction complications”), ((“Blood glucose” AND “Tooth extractions”), ((“Dental extraction sockets” AND “Diabetics”). Results: Out of a total of 973 articles, 25 were included for this review. Six relevance criteria were considered, revealing safety parameters for conducting extractions in patients with T2DM, with capillary blood glucose levels not exceeding 200 mg/dL for elective extractions and 240 mg/dL for emergency extractions. Conclusions: There is limited evidence correlating threshold values of hyperglycemia with post-extraction complications in patients with T2DM. Most authors agree that the primary concern is not T2DM itself, but hyperglycemia. Furthermore, there is minimal consistency in the recommended care protocols for these patients.

Gestational Diabetes Mellitus (GDM) and preeclampsia (PE) affects 6–25% of pregnancies and are characterized by an imbalance in natural prooxidant/antioxidant mechanisms. Due to their antioxidant and anti-inflammatory properties, polyphenols consumption during the pregnancy might exert positive effects by preventing GDM and PE development. However, this association remains inconclusive. This systematic review and metanalysis is aimed to analyze the association between polyphenol-rich food consumption during pregnancy and the risk of GDM and PE. A systematic search in MEDLINE, EMBASE, and Web of Science (Clarivate Analytics, London, United Kingdom) for articles dated between 1 January 1980 and July 2022 was undertaken to identify randomized controlled trials and observational studies evaluating polyphenol-rich food consumption and the risk of GDM and PE. The Newcastle-Ottawa Scale was used to evaluate the quality of these included studies. Twelve studies were included, of which eight articles evaluated GDM and four studied PE. A total of 3785 women presented with GDM (2.33%). No association between polyphenol consumption and GDM was found (ES = 0.85, 95% CI 0.71–1.01). When total polyphenol intake was considered, a lower likelihood to develop GDM was noted (ES = 0.78, 95% CI 0.69–0.89). Furthermore, polyphenol consumption was not associated with PE development (ES = 0.90, 95% CI 0.57–1.41). In conclusion, for both outcomes, pooled analyses showed no association with polyphenol-rich food consumption during pregnancy. Therefore, association of polyphenol intake with a decreased risk of GDM and PE remains inconclusive.

Selon une méthodologie qualitative de type biographique, l’article analyse sur le mode du cas unique le récit de vie d’une femme de 73 ans qui fut prisonnière politique et torturée lors de la dictature civile et militaire chilienne. On cherche à cerner le sens que prend l’autre comme altérité dans son expérience subjective. En premier lieu, c’est la figure de l’autre qui apparait dans le récit de prison, de torture et de violence politique. Dans ce cas, l’altérité se vit dans le passage entre des lieux de confort et d’appui, comme dans la camaraderie politique, et d’autres caractérisés par la violence et la crudité incarnés dans le rôle du tortionnaire et des forces armées. Une situation particulière se produit lorsque l’agresseur est paradoxalement perçu comme un être bon. En deuxième lieu, l’altérité se présente a posteriori, en aval de la situation de violence politique, dans la transmission de cette expérience. Elle prend forme dans le rôle du témoin, comme une expérience réparatrice associée à la reconnaissance qu’elle implique mais à la fois redoutée en raison du risque de « faire mal » au récepteur du récit. En troisième lieu, le cadre de la recherche se présente comme une instance particulière qui fait apparaître la rencontre entre le participant et un autre, chercheur, qui, à l’image de ce qui se produit dans le cas précédent, outre son rôle de chercheur, fait office de témoin.

Methylphenidate-induced psychosis has been scarcely studied due to bioethical and neurobiological issues regarding its research. Although some authors have hypothesized that there might be a vulnerability for the development of a major psychiatric disorder in the long term, there is no agreement about the predictive value of this type of psychosis in children and adolescents, and its origin is also uncertain. It has been suggested that higher dopamine levels in some cerebral regions and a family history of mental disorders might increase the risk of psychosis secondary to psychostimulants. We present the case of a nine-year-old child diagnosed with attention deficit disorder and oppositional defiant disorder, who exhibited visual and auditory hallucinations and delirious ideas about harm during methylphenidate treatment. The patient s symptoms regressed after drug removal. We discuss the key issues related to the origin, causality, management, and prognosis of psychostimulant-induced psychosis.La psicosis inducida por metilfenidato ha sido escasamente estudiada debido a los problemas bioéticos y neurobiológicos relacionados con su investigación. Si bien evidenciaría una vulnerabilidad a largo plazo para el desarrollo de un trastorno psiquiátrico mayor, no hay consenso sobre su valor predictivo en la población infanto-juvenil, mientras que su origen es incierto. Se ha sugerido que los mayores niveles de dopamina en ciertas zonas cerebrales y el antecedente familiar de algunos trastornos mentales, aumentaría el riesgo de presentar psicosis secundaria a psicoestimulantes. Presentamos el caso de un niño de nueve años de edad, con diagnóstico de trastorno por déficit de atención comórbido a una oposición desafiante, que durante el tratamiento con metilfenidato presentó alucinaciones visuales y auditivas e ideas deliriosas de daño que cedieron con la suspensión del fármaco. Se discuten los principales aspectos relacionados con el origen, la causalidad, el manejo y el pronóstico de la psicosis inducida por psicoestimulantes.

Brassinosteroids are plant hormones whose main function is to stimulate plant growth. However, they have been studied for their biological applications in humans. Brassinosteroid compounds have displayed an important role in the study of cancer pathology and show potential for developing novel anticancer drugs. In this review we describe the relationship of brassinosteroids with cancer with focus on the last decade, the mechanisms of cytotoxic activity described to date, and a structure–activity relationship based on the available information.

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of cannabis‐based medicines, compared to placebo or an alternative treatment strategy, for preventing nausea and vomiting during the postoperative period among adults undergoing elective surgery.

Objective: to understand the perception by Nursing professionals of the “Care Management” construct, and its relationship with quality of care.