La evaluación de los logros del aprendizaje de la Educación Física, en época de pandemia

La Educación Física, en la actualidad, presta cada vez más atención al desarrollo de estrategias pedagógicas, con la finalidad de perfeccionar los logros del aprendizaje y que este sea sostenible y enfrenta muchos retos de cómo acceder y mantener, en cualquier edad de la vida, la participación de experiencias de aprendizaje estimulantes. El objetivo de este trabajo fue desarrollar un estudio comparativo entre dos grupos de estudiantes para evaluar la calidad del proceso de enseñanza-aprendizaje, de la Educación Física, basado en la diferencia entre la clase presencial y la clase a distancia, demostrado en los resultados académicos. La investigación fue desarrollada con enfoque cuantitativo y diseño cuasiexperimental con prestest y postest, participaron estudiantes de educación básica regular del cuarto grado, en el año 2020 y de quinto grado durante el año 2021. La prueba de hipótesis determinó que la diferencia de los promedios fue significativa, durante el año 2020 fue de 14,5 y en el año 2021, de 13,5 para 0,05. Se obtuvo el rechazo de la hipótesis nula (Sig<0,05) y se aprobó la hipótesis alterna; lo que evidenció que en el periodo de confinamiento por la pandemia del COVID-19, los promedios en el área de Educación Física disminuyeron.

A Educação Física, atualmente, dá cada vez mais atenção ao desenvolvimento de estratégias pedagógicas, com o objetivo de aperfeiçoar as conquistas da aprendizagem e torná-la sustentável e enfrenta muitos desafios de como acessar e manter, em qualquer idade da vida, o envolvimento em experiências de aprendizagem estimulantes. . O objetivo deste trabalho foi desenvolver um estudo comparativo entre dois grupos de alunos para avaliar a qualidade do processo de ensino-aprendizagem da Educação Física, a partir da diferença entre a aula presencial e a aula a distância, demonstrada no resultados acadêmicos. . A pesquisa foi desenvolvida com abordagem quantitativa e delineamento quase-experimental com pré-teste e pós-teste, participaram alunos do ensino fundamental regular da quarta série no ano de 2020 e da quinta série durante o ano de 2021. O teste de hipótese determinou que a diferença na médias foi significativa, durante o ano de 2020 foi de 14,5 e em 2021, de 13,5 para 0,05. A hipótese nula foi rejeitada (Sig<0,05) e a hipótese alternativa foi aprovada; que mostrou que no período de confinamento devido à pandemia de COVID-19, as médias na área da Educação Física diminuíram.

Physical Education, currently, pays more and more attention to the development of pedagogical strategies, with the aim of perfecting learning achievements and making it sustainable and faces many challenges of how to access and maintain, at any age of life, engaging in stimulating learning experiences. The objective of this work was to carry out a comparative study between two groups of students to evaluate the quality of the teaching-learning process of Physical Education, based on the difference between the face-to-face class and the distance class, demonstrated in the academic results. The research was developed with a quantitative approach and quasi-experimental design with pretest and posttest, regular basic education students from the fourth grade in the year 2020 and from the fifth grade during the year 2021 participated. The hypothesis test determined that the difference in the averages was significant, during the year 2020 it was 14.5 and in 2021, from 13.5 to 0.05. The null hypothesis was rejected (Sig <0.05) and the alternative hypothesis was approved; which showed that in the period of confinement due to the COVID-19 pandemic, the averages in the area of Physical Education decreased.

Role of Gut Microbiome in Atherosclerosis: Molecular and Therapeutic Aspects.

Atherosclerosis is one of the most relevant and prevalent cardiovascular diseases of our time. It is one of the pathological entities that increases the morbidity and mortality index in the adult population. Pathophysiological connections have been observed between atherosclerosis and the gut microbiome (GM), represented by a group of microorganisms that are present in the gut. These microorganisms are vital for metabolic homeostasis in humans. Recently, direct and indirect mechanisms through which GM can affect the development of atherosclerosis have been studied. This has led to research into the possible modulation of GM and metabolites as a new target in the prevention and treatment of atherosclerosis. The goal of this review is to analyze the physiopathological mechanisms linking GM and atherosclerosis that have been described so far. We also aim to summarize the recent studies that propose GM as a potential target in atherosclerosis management.

Psychosis in Parkinson's Disease: Looking Beyond Dopaminergic Treatments.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. The symptoms of PD are characterized not only by motor alterations but also by a spectrum of nonmotor symptoms. Some of these are psychiatric manifestations such as sleep disorders; depression; cognitive difficulties that can evolve into dementia; and symptoms of psychosis, which include hallucinations, illusions, and delusions. Parkinson's disease psychosis (PDP) occurs in 18-50% of patients with PD. Treating PDP is challenging because antipsychotic drugs tend to be inefficient or may even worsen the disease's motor symptoms. OBJECTIVE: This review aims to summarize the current understanding of the molecular mechanisms involved in PDP and recent innovative alternatives for its treatment. METHODS: This is a narrative review in which an extensive literature search was performed on the Scopus, EMBASE, PubMed, ISI Web of Science, and Google Scholar databases from inception to August 2021. The terms "Parkinson's disease psychosis", "Parkinson psychosis," "neurodegenerative psychosis", and "dopamine psychosis" were among the keywords used in the search. RESULTS: Recently, views on the etiology of hallucinations and illusions have evolved remarkably. PDP has been cemented as a multifactorial entity dependent on extrinsic and novel intrinsic mechanisms, including genetic factors, neurostructural alterations, functional disruptions, visual processing disturbances, and sleep disorders. Consequently, innovative pharmacological and biological treatments have been proposed. Pimavanserin, a selective 5-HT2A inverse agonist, stands out after its approval to treat PDP-associated hallucinations and illusions. CONCLUSION: Future results from upcoming clinical trials should further characterize the role of this drug in the management of PDP as well as other treatment options with novel mechanisms of action, such as saracatinib, SEP-363856, cannabidiol, electroconvulsive therapy, and transcranial magnetic stimulation.

Electroconvulsive Therapy in Psychiatric Disorders: A Narrative Review Exploring Neuroendocrine-Immune Therapeutic Mechanisms and Clinical Implications.

Electroconvulsive therapy (ECT) is based on conducting an electrical current through the brain to stimulate it and trigger generalized convulsion activity with therapeutic ends. Due to the efficient use of ECT during the last years, interest in the molecular bases involved in its mechanism of action has increased. Therefore, different hypotheses have emerged. In this context, the goal of this review is to describe the neurobiological, endocrine, and immune mechanisms involved in ECT and to detail its clinical efficacy in different psychiatric pathologies. This is a narrative review in which an extensive literature search was performed on the Scopus, Embase, PubMed, ISI Web of Science, and Google Scholar databases from inception to February 2022. The terms "electroconvulsive therapy", "neurobiological effects of electroconvulsive therapy", "molecular mechanisms in electroconvulsive therapy", and "psychiatric disorders" were among the keywords used in the search. The mechanisms of action of ECT include neurobiological function modifications and endocrine and immune changes that take place after ECT. Among these, the decrease in neural network hyperconnectivity, neuroinflammation reduction, neurogenesis promotion, modulation of different monoaminergic systems, and hypothalamus-hypophysis-adrenal and hypothalamus-hypophysis-thyroid axes normalization have been described. The majority of these elements are physiopathological components and therapeutic targets in different mental illnesses. Likewise, the use of ECT has recently expanded, with evidence of its use for other pathologies, such as Parkinson's disease psychosis, malignant neuroleptic syndrome, post-traumatic stress disorder, and obsessive-compulsive disorder. In conclusion, there is sufficient evidence to support the efficacy of ECT in the treatment of different psychiatric disorders, potentially through immune, endocrine, and neurobiological systems.

Psycho-Neuro-Endocrine-Immunological Basis of the Placebo Effect: Potential Applications beyond Pain Therapy.

The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.

[Intracardiac fungal mass in extreme premature patient]. / Masa fúngica intracardiaca en un paciente prematuro extremo.

There are few reports on intracardiac fungal masses, especially in the pediatric population. We present the case of an extremely premature patient who, after being hospitalized since birth in an intensive care unit, developed fungal masses in the right atrium, which, due to their size, location and resistance to medical treatment, required surgical excision. For this reason, at the slightest suspicion of systemic candidiasis in pediatric patients, it is mandatory to include an echocardiogram in the defocalization examinations to rule out endocarditis and thus avoid the development of intracardiac fungal masses. Therefore, early detection for timely medical management may avoid the surgical approach associated with a high risk of morbidity and mortality in extremely premature patients.

Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy?

Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.

Metabolic Syndrome: Is It Time to Add the Central Nervous System?

Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic "triumvirate" (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS.

Lipid Accumulation Product Is More Related to Insulin Resistance than the Visceral Adiposity Index in the Maracaibo City Population, Venezuela.

BACKGROUND: Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. OBJECTIVE: To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. METHODS: This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. RESULTS: 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665-0.714) and 0.645 (0.619-0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37-2.65; p < 0.01) and 3rd (OR: 5.40; 95% CI: 3.48-8.39; p < 0.01) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). CONCLUSION: Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.

Age-specific waist circumference cutoff-points for abdominal obesity diagnosis: a personalized strategy for a large Venezuelan population.

BACKGROUND: Evidence shows that the ageing process is a determining factor in fat distribution, composition, and functionality. The goal of this research was to determine cut-off points for waist circumference according to age in the adult population from Maracaibo city, Venezuela. METHODOLOGY: The Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with multi-stage randomized sampling. In this post-hoc analysis 1902 individuals ≥18 years and from both sexes were evaluated. Waist circumference ROC curves were built for each age group and sex, using metabolic phenotypes for classification. RESULTS: 52.2% (n = 992) were women, and the mean age was 38.7 ± 2. Cut-off points obtained for the <30 years age group were: 91 cm for women (Sensitivity: 96,8%, Specificity: 97,7%) and 94 cm for men (Sensitivity:100%, Specificity: 99,2%); for 30-49 years: women 94 cm (Sensitivity: 93.7%, Specificity: 97.1%) and men 95 cm (Sensitivity: 97.3%, Specificity: 100%); for ≥50 years: women 94 cm (Sensitivity: 91.8%, Specificity: 86.7%) and men 101 cm (Sensitivity: 100%, Specificity: 100%). CONCLUSION: The use of specific cut-off points according to age groups is proposed to determine abdominal obesity in Maracaibo city due to the underestimation seen in young people and the overestimation observed in older people when using a unique cut-off point.

Alzheimer's disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links.

At present, Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.

The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises.

The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.

Hallazgos de autopsias en la infección por COVID-19 / Autopsy findings in COVID-19 Infection

RESUMEN Fundamento: la neumonía por COVID-19 es una enfermedad recién conocida que se ha extendido de manera rápida por todo el mundo. Los fundamentos patogénicos y los cambios histopatológicos que provoca el COVID-19 no se comprenden en su totalidad, lo cual atenta contra la identificación clínica adecuada de los pacientes y la implementación de estrategias terapéuticos eficaces. Objetivo: describir los hallazgos histopatológicos hallados en autopsia de casos confirmados de COVID-19. Métodos: la evidencia se recopiló mediante una búsqueda en PubMed de publicaciones en idioma inglés, utilizando las palabras claves: coronavirus, COVID-19, autopsy y síndrome de dificultad respiratoria aguda en varias combinaciones en el año 2020. Solo se hallaron cinco artículos con información sobre los resultados de las autopsias de casos confirmados con COVID-19. Resultados: desde el inicio de la pandemia en diciembre de 2019 se han publicado siete informes de autopsias de casos confirmados con COVID-19, recogidos en cuatro artículos. Todas las autopsias han coincidido en el principal hallazgo: daño alveolar difuso con formación de membrana hialina, lo cual se correlaciona con las manifestaciones clínicas del síndrome de dificultad respiratoria aguda. Conclusiones: el COVID-19 produce principalmente daño alveolar, el cual consiste en edema pulmonar con formación de membrana hialina que se expresa clínicamente como un síndrome de dificultad respiratoria aguda.

ABSTRACT Background: COVID-19 pneumonia is a recently recognized disease that has spread rapidly throughout the world. The pathogenic foundations and histopathological changes caused by COVID-19 are not fully understood, which undermines the proper clinical identification of patients and the implementation of effective therapeutic strategies. Objective: to describe the histopathological findings found at autopsy of confirmed cases of COVID-19. Methods: evidence was collected by searching PubMed for English language publications, using the keywords: coronavirus, COVID-19, autopsy and acute respiratory distress syndrome in various combinations in 2020. Only five articles were found with information on the autopsy results of confirmed cases with COVID-19. Results: since the start of the pandemic in December 2019, seven autopsy reports of confirmed cases with COVID-19 have been published, collected in 4 articles. All autopsies have agreed on the main finding: diffuse alveolar damage with hyaline membrane formation, which correlates with the clinical manifestations of acute respiratory distress syndrome. Conclusions: COVID-19 mainly produces alveolar damage, which consists of pulmonary edema with hyaline membrane formation, which is clinically expressed as an acute respiratory distress syndrome.

Microbiota and Diabetes Mellitus: Role of Lipid Mediators.

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.

Exploring Phytotherapeutic Alternatives for Obesity, Insulin Resistance and Diabetes Mellitus.

At present, the pathologic spectrum of obesity-insulin resistance (IR)-diabetes mellitus (DM) represents not only a pressing matter in public health but also a paramount object of study in biomedical research, as they constitute major risk factors for cardiovascular disease (CVD), and other chronic non-communicable diseases (NCD). Phytotherapy, the use of medicinal herbs (MH) with treatment purposes, offers a wide array of opportunities for innovation in the management of these disorders; mainly as pharmacological research on small molecules accumulates. Several MH has displayed varied mechanisms of action relevant to the pathogenesis of obesity, IR and DM, including immunological and endocrine modulation, reduction of inflammation and oxidative stress (OS), regulation of appetite, thermogenesis and energy homeostasis, sensitisation to insulin function and potentiation of insulin release, among many others. However, the clinical correlates of these molecular phenomena remain relatively uncertain, with only a handful of MH boasting convincing clinical evidence in this regard. This review comprises an exploration of currently available preclinical and clinical research on the role of MH in the management of obesity, IR, and DM.

Anti-Aging Effect of Metformin: A Molecular and Therapeutical Perspective.

Aging is a time-dependent inevitable process, in which cellular homeostasis is affected, which has an impact on tissue function. This represents a risk factor for the development of numerous non-transmissible diseases. In consequence, the scientific community continues to search for therapeutic measures capable of improving quality of life and delaying cellular aging. At the center of this research is metformin, a widely used drug in Type 2 Diabetes Mellitus treatment that has a reduced adverse effects profile. Furthermore, there is evidence that this drug has beneficial health effects that go beyond its anti-hyperglycemic properties. Among these effects, its geronto-protection capability stands out. There is growing evidence that points out to an increased life expectancy as well as the quality of life in model organisms treated with metformin. Therefore, there is an abundance of research centered on elucidating the mechanism through which metformin has its anti-aging effects. Among these, the AMPK, mTORC1, SIRT1, FOXO, NF.kB, and DICER1 pathways can be mentioned. Furthermore, studies have highlighted the possibility of a role for the gut microbiome in these processes. The next step is the design of clinical essays that have as a goal evaluating the efficacy and safety of metformin as an anti-aging drug in humans to create a paradigm in the medical horizon. The question being if metformin is, in fact, the new antiaging therapy in humans?

Depression as an Immunometabolic Disorder: Exploring Shared Pharmacotherapeutics with Cardiovascular Disease.

Modern times have seen depression and cardiovascular disease (CVD) become notorious public health concerns, corresponding to alarming proportions of morbidity, mortality, decreased quality of life, and economic costs. Expanding comprehension of the pathogenesis of depression as an immunometabolic disorder has identified numerous pathophysiologic phenomena in common with CVD, including chronic inflammation, insulin resistance, and oxidative stress. These shared components could be exploited to offer improved alternatives in the joint management of these conditions. Abundant preclinical and clinical data on the impact of established treatments for CVD in the management of depression have allowed for potential candidates to be proposed for the joint management of depression and CVD as immunometabolic disorders. However, a large proportion of the clinical investigation currently available exhibits marked methodological flaws which preclude the formulation of concrete recommendations in many cases. This situation may be a reflection of pervasive problems present in clinical research in psychiatry, especially pertaining to study homogeneity. Therefore, further high-quality research is essential in the future in this regard.

Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Depression as a Neuroendocrine Disorder: Emerging Neuropsychopharmacological Approaches beyond Monoamines.

Depression is currently recognized as a crucial problem in everyday clinical practice, in light of ever-increasing rates of prevalence, as well as disability, morbidity, and mortality related to this disorder. Currently available antidepressant drugs are notoriously problematic, with suboptimal remission rates and troubling side-effect profiles. Their mechanisms of action focus on the monoamine hypothesis for depression, which centers on the disruption of serotonergic, noradrenergic, and dopaminergic neurotransmission in the brain. Nevertheless, views on the pathophysiology of depression have evolved notably, and the comprehension of depression as a complex neuroendocrine disorder with important systemic implications has sparked interest in a myriad of novel neuropsychopharmacological approaches. Innovative pharmacological targets beyond monoamines include glutamatergic and GABAergic neurotransmission, brain-derived neurotrophic factor, various endocrine axes, as well as several neurosteroids, neuropeptides, opioids, endocannabinoids and endovanilloids. This review summarizes current knowledge on these pharmacological targets and their potential utility in the clinical management of depression.

Metabolic Syndrome and Subclinical Hypothyroidism: A Type 2 Diabetes-Dependent Association.

INTRODUCTION: Subclinical hypothyroidism (ScH) is an endocrine alteration that is related to cardiovascular risk factors, including those categorized as components of the Metabolic Syndrome (MS). However, findings in prior reports regarding an association between these alterations are inconsistent. The purpose of this study was to determine the relationship between both entities in adult subjects from Maracaibo City, Venezuela. MATERIALS AND METHODS: The Maracaibo City Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with random and multistage sampling. In this substudy, 391 individuals of both genders were selected and TSH, free T3, and free T4 tests were performed as well as a complete lipid profile, fasting glycaemia, and insulin blood values. ScH was defined according to the National Health and Nutrition Examination Survey (NHANES) criteria: high TSH (≥4.12mUI/L) and normal free T4 (0.9-1,9 ng/dL) in subjects without personal history of thyroid disease. MS components were defined according to IDF/AHA/NHLBI/WHF/IAS/IASO-2009 criteria. A multiple logistic regression analysis was used to assess the relationship between MS components and ScH diagnosis. RESULTS: Of the evaluated population, 10.5% (n=41) was diagnosed with ScH, with a higher prevalence in women (female: 13.6% versus male: 7.7%; χ2=3.56, p=0.05). Likewise, 56.1% (n=23) of the subjects with ScH were diagnosed with MS (χ2=4.85; p=0.03), being hyperglycemia the main associated criterion (χ2=11.7; p=0.001). In multivariable analysis, it was observed that the relationship was exclusive with the presence of type 2 diabetes mellitus (T2DM) OR: 3.22 (1.14-9.14); p=0.03. CONCLUSION: The relationship between ScH and MS in our population is dependent on the presence of hyperglycemia, specifically T2DM diagnosis, findings that vary from those previously reported in Latin American subjects.