Adiponectin and resistin modulate the progression of Alzheimer´s disease in a metabolic syndrome model.

Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer's disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates Aß42 production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the Aß42/40 ratio by approximately 65%. In contrast, resistin exacerbated Aß pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology.

Inflammation context in Alzheimer's disease, a relationship intricate to define.

Alzheimer's disease (AD), the most common form of dementia, is characterized by the accumulation of amyloid ß (Aß) and hyperphosphorylated tau protein aggregates. Importantly, Aß and tau species are able to activate astrocytes and microglia, which release several proinflammatory cytokines, such as tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß), together with reactive oxygen (ROS) and nitrogen species (RNS), triggering neuroinflammation. However, this inflammatory response has a dual function: it can play a protective role by increasing Aß degradation and clearance, but it can also contribute to Aß and tau overproduction and induce neurodegeneration and synaptic loss. Due to the significant role of inflammation in the pathogenesis of AD, several inflammatory mediators have been proposed as AD markers, such as TNF-α, IL-1ß, Iba-1, GFAP, NF-κB, TLR2, and MHCII. Importantly, the use of anti-inflammatory drugs such as NSAIDs has emerged as a potential treatment against AD. Moreover, diseases related to systemic or local inflammation, including infections, cerebrovascular accidents, and obesity, have been proposed as risk factors for the development of AD. In the following review, we focus on key inflammatory processes associated with AD pathogenesis.

Acompañando la lactancia materna con eHealth: revisión integrativa

Resumen: Introducción: La Organización Mundial de la Salud recomienda la lactancia materna exclusiva durante los primeros 6 meses de vida, así como continuar complementada con alimentos apropiados hasta los 2 años y más. Es por esto, que se observa la necesidad del apoyo profesional en torno a esta, para las madres durante el embarazo y una vez iniciado el amamantamiento. La Asamblea Mundial de la Salud, reconoció el potencial de las tecnologías digitales para la mejora de la salud pública, destacando que el uso de eHealth ha transformado la salud, permitiendo la entrega de cuidados en los hogares de las personas de manera remota. Objetivo: Determinar si el apoyo profesional por medio de eHealth es una estrategia que favorece el acompañamiento a las madres que viven el proceso de amamantamiento y mejora sus resultados en la lactancia materna. Metodología: Se realizó una revisión integrativa buscando la comprensión del fenómeno o tema de interés desde diversas perspectivas. Para llevarla a cabo en junio de 2020 se consultaron las bases de datos Pubmed, Scopus, CINAHL, ProQuest, ClinicalKey y Science Direct. Resultados: Se organizaron en dos grupos: estrategias de acompañamiento profesional a través de eHealth a las madres en proceso de amamantamiento y resultados de eHealth como herramienta para el acompañamiento profesional a las madres en proceso de amamantamiento. Conclusión: La eHealth es una herramienta efectiva para brindar apoyo a mujeres embarazadas o en proceso de amamantamiento.

Resumo: Introdução: A A Organização Mundial da Saúde recomenda o aleitamento materno exclusivo durante os primeiros 6 meses de vida, e também que seja complementado com alimentos apropriados até os 2 anos ou mais. É por isso que se faz necessário o apoio profissional às mães neste processo, desde a gestação até o início da amamentação. A Assembléia Mundial da Saúde reconheceu os benefícios das tecnologias digitais para o aprimoramento da saúde pública, destacando a ferramenta eHealth, cuja utilização transformou a saúde e permitiu um atendimento especializado nos lares das pessoas, de maneira remota. Objetivo: Determinar se o apoio profissional por meio da eHealth é uma estratégia que favorece o acompanhamento às mães que estão atravessando o processo de amamentação e melhora seus resultados do aleitamento. Metodologia: Foi realizada uma revisão integrativa, procurando compreender o fenômeno ou tópico de interesse a partir de diferentes perspectivas. Para implementá-la em junho de 2020 foram consultadas as bases de dados Pubmed Scopus, CINAHL, ProQuest, ClinicalKey e Science Direct. Resultados: Eles foram organizados em dois grupos: estratégias de apoio profissional por meio da eHealth para mães em processo de amamentação e resultados da eHealth como ferramenta de apoio profissional para mães em processo de amamentação. Conclusão: A eHealth é uma ferramenta efetiva oferecem um suporte significativo às gestantes e às mães durante o aleitamento.

Abstract: Introduction: The World Health Organization recommends exclusive breastfeeding during the first 6 months of life, as well as continuing it supplemented with appropriate foods up, to 2 years and more. Therefore, the need of professional support around it is observed for mothers during pregnancy and once breastfeeding has begun. The World Health Assembly recognized the potential of digital technologies to improve public health, highlighting that the use of eHealth has transformed health, allowing the delivery of care in people's homes remotely. Objective: To determine if professional support through eHealth is a strategy that favors the support to mothers who are going through the breastfeeding process and improves their breastfeeding results. Methodology: A integrative review was carried out seeking to understand the phenomenon or topic of interest from different perspectives. To carry it out in June 2020, the databases Pubmed, Scopus, CINAHL, ProQuest, ClinicalKey and Science Direct were consulted. Results: They were organized into two groups: professional support strategies through eHealth to mothers in breastfeeding process and results of eHealth as a tool for professional support to mothers in breastfeeding process. Conclusion: eHealth is an effective tool to provide meaningful support to pregnant or breastfeeding women.

Disruption of Glucose Metabolism in Aged Octodon degus: A Sporadic Model of Alzheimer's Disease.

Alzheimer's disease is a progressive neurodegenerative disorder and the most common cause of dementia. Although transgenic Alzheimer's disease (AD) animal models have greatly contributed to our understanding of the disease, therapies tested in these animals have resulted in a high rate of failure in preclinical trials for AD. A promising model is Octodon degus (degu), a Chilean rodent that spontaneously develops AD-like neuropathology. Previous studies have reported that, during aging, degus exhibit a progressive decline in cognitive function, reduced neuroinflammation, and concomitant increases in the number and size of amyloid ß (Aß) plaques in several brain regions. Importantly, in humans and several AD models, a correlation has been shown between brain dysfunction and neuronal glucose utilization impairment, a critical aspect considering the high-energy demand of the brain. However, whether degus develop alterations in glucose metabolism remains unknown. In the present work, we measured several markers of glucose metabolism, namely, glucose uptake, ATP production, and glycolysis and pentose phosphate pathway (PPP) flux, in hippocampal slices from degus of different ages. We found a significant decrease in hippocampal glucose metabolism in aged degus, caused mainly by a drop in glucose uptake, which in turn, reduced ATP synthesis. Moreover, we observed a negative correlation between age and PPP flux. Together, our data further support the use of degus as a model for studying the neuropathology involved in sporadic AD-like pathology and as a potentially valuable tool in the search for effective treatments against the disease.

Neurodevelopmental impact of the offspring by thyroid hormone system-disrupting environmental chemicals during pregnancy.

Everyday use chemicals have been demonstrated to be endocrine disruptors. Since normal thyroid function during pregnancy is transcendental for the neurodevelopment of the offspring, knowledge of endocrine disrupting chemicals (EDC) is of main importance. The aim of our study is to recognize and describe EDC actions in pregnant women and focus on neurodevelopmental processes that can lead to neurotransmitter imbalance and cognitive impairment, and the possible clinical outcomes in the newborn and child. We searched PubMed databases for animal studies and clinical trials evaluating chemicals recognized as thyroid disruptors -perchlorate, phthalates, bisphenol A-, as well as chemicals with potential thyroid disruption activity -parabens, pesticides and persistent organic pollutants, on thyroid hormones (THs) levels and their bioavailability during pregnancy, and the outcome in newborns, infants and children. We also exhibit evidence from worldwide cohort studies to this regard. The publications reviewed show: 1) known endocrine disruptors have an association with hormonal thyroid levels, where an effect of increase or decrease in TH concentrations has been reported depending on the chemical exposed 2) associations between TH, EDCs and neurocognitive disorders have been addressed, such as ADHD, though no conclusive impact on potential related disorders as autism has been established, 3) perchlorate has demonstrated effects on thyroid levels on iodine uptake. In conclusion, detrimental risks and long-term consequences after in-utero exposure to EDCs are being reported in several cohort studies and further research must be conducted to establish a well-known cause-effect association.

Significado de la experiencia materna en torno al apoyo durante su proceso de amamantamiento

Introducción: Se ha descrito la existencia de experiencias de la vida de las personas que tienen la capacidad de modular el sistema nervioso, lo que influye directamente en el desarrollo humano. Intervenir oportunamente en la primera infancia tiene el potencial de impactar positivamente en su desarrollo. En esta lógica, la lactancia materna cobra especial protagonismo, ya que aumenta la probabilidad de sobrevivir, brinda una nutrición y estimulación adecuada, favorece un entorno seguro, además de ser un inmenso aporte en el fortalecimiento de los lazos sociales, entre otros beneficios. El apoyo que reciba la madre durante el proceso es fundamental para lograr un amamantamiento exitoso. Objetivo: Develar el significado de la experiencia materna en torno al apoyo en el proceso de amamantamiento. Metodología: Estudio de diseño fenomenológico en el cual se realizó un análisis con datos secundarios, según la perspectiva de Edmund Husserl. Para asegurar el rigor metodológico de esta investigación se aplicaron los criterios de Guba y Lincoln. Los aspectos éticos de la investigación fueron abordados desde los siete requisitos éticos de Ezekiel Emanuel. Resultados: El significado de la experiencia materna en torno al apoyo en el proceso de amamantamiento se develó en cuatro categorías comprensivas: la experiencia materna de amamantamiento, experiencia de apoyo de los profesionales de la salud, experiencia de apoyo de la pareja y experiencia de apoyo de otros familiares. Conclusiones: Las tres fuentes de apoyo identificadas nutren y modulan la experiencia de amamantamiento de manera complementaria, por lo que la indivisibilidad de las influencias ejercidas por ellas es una característica constitutiva para que el apoyo sea percibido por las madres como comprensivo y contenedor.

Introdução: Descreveu-se a existência de experiências de vida de pessoas que têm a capacidade de moldar o sistema nervoso, o que influencia diretamente no desenvolvimento humano. Intervir oportunamente na primeira infância tem o potencial de impactar positivamente no seu desenvolvimento. Seguindo esta lógica, o aleitamento materno ganha um protagonismo especial, já que aumenta a probabilidade de sobrevivência, oferece nutrição e estimulacão adequadas, favorece um ambiente seguro, além de ser uma imensa contribuição no fortalecimento de laços sociais, entre outros benefícios. O apoio que a mãe recebe durante o processo é fundamental para conseguir uma amamentação de sucesso. Objetivo: Revelar o significado da experiência materna ao redor do apoio no processo do aleitamento materno. Metodologia: Estudo do desenho fenomenológico, para o qual se realizou a análise com dados secundários, conforme a perspectiva de Edmund Husserl. Para garantir o rigor metodológico desta investigação foram aplicados os critérios de Guba e Lincoln. Os aspectos éticos da investigação foram abordados desde os sete requisitos éticos de Ezekiel Emanuel. Resultados: O significado da experiência materna ao redor do apoio no processo da amamentação foi dividido em quatro categorias compreensivas: a experiência materna do aleitamento, a experiência do apoio dos profissionais da saúde, a experiência do apoio do parceiro e a experiência do apoio de outros familiares. Conclusões: As três fontes de apoio identificadas nutrem e moldam a experiência do aleitamento de forma complementária. Por tanto, a indivisibilidade das influências que cada um destes atores exercem é uma característica constitutiva para que o apoio seja percebido pelas mães como compreensivo e acolhedor.

Introduction: It has been described that there are experiences in people's lives that have the capacity to modulate the nervous system, which directly influences human development. Timely intervention in early childhood has the potential to have a positive impact on their development. In this logic, breastfeeding takes on special importance, since it increases the probability of survival, provides adequate nutrition and stimulation, favors a safe environment, and is an immense contribution to the strengthening of social ties, among other benefits. The support the mother receives during the process is fundamental for successful breastfeeding. Objective: To unveil the meaning of the maternal experience on support during the breastfeeding process. Methodology: A phenomenological design study in which an analysis was carried out with secondary data, according to Edmund Husserl's perspective. To ensure the methodological rigor of this research, the criteria of Guba and Lincoln were applied. The ethical aspects of the research were approached from Ezekiel Emanuel's seven ethical requirements. Results: The meaning of the maternal experience of support during the breastfeeding process was unveiled in four comprehensive categories: maternal experience of breastfeeding, experience of support from health professionals, experience of support from partners, and experience of support from other family members. Conclusions: The three sources of support identified nurture and modulate the breastfeeding experience in a complementary manner, so that the indivisibility of the influences exerted by them is a constitutive characteristic for the support to be perceived by the mothers as comprehensive and supportive.

Statements, recommendations, proposals, guidelines, checklists and scales available for reporting results in biomedical research and quality of conduct: a systematic review / Declaraciones, recomendaciones, propuestas, directrices, listas de verificación y escalas disponibles para informar resultados y calidad metodológica en investigación biomédica: revisión sistemática

SUMMARY: Research reporting statements, recommendations, proposals, guidelines, checklists and scales can improve quality of reporting results in biomedical research. The aim of this study was to describe statements, recommendations, proposals, guidelines, checklists and scales available for reporting results and quality of conduct in biomedical research. Systematic review. All types statements, recommendations, proposals, guidelines, checklists and scales generated to improve the quality of the biomedical research results report were included. Data sources: EMBASE, HINARI, MEDLINE and Redalyc; in the libraries BIREME-BVS, SciELO and The Cochrane Library; in the meta-searchers Clinical Evidence and TRIP Database; and on the Websites of EQUATOR Network, BMC Medical Education and EUROPE PMC were used. The recovered documents were grouped as study design related to systematic reviews (SR) meta-analysis and meta-reviews, CT and RCTs and quasi-experimental studies, observational studies, diagnostic accuracy studies, clinical practice guidelines; biological material, animal and preclinical studies; qualitative studies; economic evaluation and decision analysis studies; and methodological quality (MQ) scales). The 93 documents were obtained. 19 for SR (QUOROM, MOOSE, AMSTAR, AMSTAR 2, PRISMA, PRISMA-Equity, PRISMA-C, PRISMA-IPD, PRISMA-NMA, PRISMA-RR, PRESS, PRISMA-Search, PRISMA-TCM, PRISMA-ScR, PRISMA-DTA, PRISMA-P, MARQ, GRAPH, ROBIS), 32 for CT and RCTs (CONSORT and it update, STRICTA, RedHot, NPT, CONSORT-PRO, CONSORT-SPI, IMPRINT, TIDieR, CT in orthodontics, "n-de-1", PAFS, KCONSORT, STORK, Protocol health data, SW-CRT, ADs, MAPGRT, PRT, TREND, GNOSIS, ISPOR RCT Report, Newcastle-Ottawa, REFLECT, Ottawa, SPIRIT, SPIRIT-C, SPAC, StaRI, TRIALS, ROBINS-I, ROB 2), 11 for observational studies (STROBE, STREGA, STROBE-nut, INSPIRE, STROME-ID, STROBE-Vet, RECORD, ORION, STNS, MInCir-ODS, GATHER), 10 for diagnostic accuracy studies (STARD and it update, ARDENT, QUADAS, QUADAS-2, QAREL and it update, GRRAS, TRIPOD, APOSTEL), 3 for clinical practice guidelines (AGREE, AGREE II, RIGHT), 10 for biological material, animal and preclinical studies (MIAME, REMARK, SQUIRE, SQUIRE 2.0, REHBaR, ARRIVE, GRIPS, CARE, AQUA, PREPARE), 5 for qualitative studies (COREQ, ENTREQ, GREET and it update, SRQR), and 3 for economic evaluations (NHS-HTA, NICE-STA, CHEERS). There are a great variety of statements, recommendations, proposals, guidelines, checklists with its extensions and scales available. These can be used to improve the quality of the report and the quality of conduct of scientific articles, by authors, reviewers and editors.

RESUMEN: El uso de recomendaciones, propuestas, listas de verificación y escalas pueden mejorar la calidad del informe de resultados en investigación biomédica. El objetivo de este estudio fue describir las declaraciones, recomendaciones, propuestas, directrices, listas de verificación y escalas disponibles para informar resultados y calidad metodológica en investigación biomédica. Revisión sistemática. Se incluyeron todas las tipos de declaraciones, recomendaciones, propuestas, pautas, listas de verificación y escalas disponibles para informar resultados y calidad metodológica en investigación biomédica. Fuentes de datos: EMBASE, HINARI, MEDLINE y Redalyc; bibliotecas BIREME-BVS, SciELO y The Cochrane Library; metabuscadores Clinical Evidence y TRIP Database; sitios Web EQUATOR Network, BMC Medical Education y EUROPE PMC. Los documentos recuperados se agruparon por tipo de diseño de estudio: revisiones sistemáticas (RS), ensayos clínicos (EC), estudios cuasi experimentales, observacionales, de precisión diagnóstica, guías de práctica clínica (GPC); de material biológico, estudios animales y preclínicos; estudios cualitativos; estudios de evaluación económica y estudios de análisis de decisiones; y escalas de calidad metodológica (CM). se obtuvieron 93 documentos. 19 para RS (QUOROM, MOOSE, AMSTAR, AMSTAR 2, PRISMA, PRISMA-Equity, PRISMA-C, PRISMA-IPD, PRISMA-NMA, PRISMA-RR, PRESS, PRISMA-Search, PRISMA-TCM, PRISMAScR, PRISMA-DTA, PRISMA-P, MARQ, GRAPH, ROBIS), 32 para EC (CONSORT y su actualización, STRICTA, RedHot, NPT, CONSORT-PRO, CONSORT-SPI, IMPRINT, TIDieR, CT en ortodoncia, "n-de-1 ", PAFS, KCONSORT, STORK, datos de salud del protocolo, SW-CRT, ADs, MAPGRT, PRT, TREND, GNOSIS, ISPOR RCT Report, Newcastle-Ottawa, REFLECT, Ottawa, SPIRIT, SPIRIT-C, SPAC, StaRI , PRUEBAS, ROBINS-I, ROB 2), 11 para estudios observacionales (STROBE, STREGA, STROBE-nut, INSPIRE, STROME-ID, STROBE-Vet, RECORD, ORION, STNS, MInCir-ODS, GATHER), 10 para estudios de precisión diagnóstica (STARD y su update, ARDENT, QUADAS, QUADAS-2, QAREL y su update, GRRAS, TRIPOD, APOSTEL), 3 para GPC (AGREE, AGREE II, RIGHT), 10 para material biológico, animal y estudios preclínicos (MIAME, REMARK, SQUIRE, SQUIRE 2.0, REHBaR, ARRIVE, GRIPS, CARE, AQUA, PREPARE), 5 para estudios cualitativos (COREQ, ENTREQ, GREET y su update, SRQR), y 3 para evaluaciones económicas (NHS-HTA, NICE-STA, CHEERS). Existe una gran variedad de instrumentos disponibles. Estos pueden ser utilizados por autores, revisores y editores; para mejorar la calidad del informe y de la CM de artículos científicos.

Hypothyroidism and Cognitive Disorders during Development and Adulthood: Implications in the Central Nervous System.

Thyroid hormones (THs) play a critical function in fundamental signaling of the body regulating process such as metabolism of glucose and lipids, cell maturation and proliferation, and neurogenesis, to name just a few. THs trigger biological effects both by directly affecting gene expression through the interaction with nuclear receptors (genomic effects) and by activating protein kinases and/or ion channels (short-term effects). For years, a close relationship between the THs hormones and the central nervous system (CNS) has been described, not only for neuronal cells but also for glial development and differentiation. A deficit in thyroid hormones triiodothyronine (T3) and thyroxine (T4) is observed in the hypothyroid condition, generated by a iodine deficiency or an autoimmune response of the body. In the hypothyroid condition, several cellular deregulation and alterations have been described in dendrite spine morphology, cell migration and proliferation, and impaired synaptic transmission in the hippocampus, among others. The aim of this review is to describe the role of the thyroid hormones with focus in brain function and neurodegenerative disorders.

[Reliability, precision or reproducibility of the measurements. Methods of assessment, utility and applications in clinical practice]. / Confiabilidad, precisión o reproducibilidad de las mediciones. Métodos de valoración, utilidad y aplicaciones en la práctica clínica.

Reliability (accuracy, consistency and reproducibility) is a psychometric property, which is related to the absence of measurement error, or, to the degree of consistency and stability of the scores obtained through successive measurement processes with the same instrument. Thus a greater variability of results will lower the accuracy or reliability of instrument used, fact that is transverse from the laboratory to the clinical practice. It is determined by applying the reliability coefficient, which is the correlation between the scores obtained by the subjects in two parallel forms of a test. Assuming that the two forms of the test are parallel (measure the same), the scores of the subjects under study should be the same in both applications. In this way, when the correlation is 1, the reliability or precision is maximum. On the other hand, reliability could be influenced by the observer (the one that measures), the measuring instrument (by that with which it is measured), and by the observed (by what is measured). Therefore, the variability of each of these components must be taken into account when planning the measurement of the variable under study, in such a way to reduce measurement biases as much as possible. The most common ways to determine reliability are the models of parallel forms, test-retest and two halves. This manuscript focuses on the concepts of measurement and the various statistical techniques used for this, as a step prior to application in the clinic. Therefore, the aim of this manuscript is to generate a consultation document related to the reliability or reproducibility of the measurement process.

Confiabilidad, precisión o reproducibilidad de las mediciones. Métodos de valoración, utilidad y aplicaciones en la práctica clínica / Reliability, precision or reproducibility of the measurements. Methods of assessment, utility and applications in clinical practice

Resumen En investigación, la confiabilidad (precisión, consistencia y reproducibilidad), corresponde a una propiedad psicométrica que dice relación con la ausencia de error de la medición; o del grado de consistencia y estabilidad de las puntuaciones obtenidas a lo largo de sucesivos procesos de medición con un mismo instrumento. Por ello, es esperable que, a mayor variabilidad de resultados, menor sea la precisión del instrumento de medición utilizado, concepto que aplica desde el laboratorio a la práctica clínica. La reproducibilidad se determina aplicando el coeficiente de confiabilidad, que es la correlación entre las puntuaciones obtenidas por los sujetos, en dos formas paralelas de una prueba (porque se supone que miden lo mismo). Por ello, asumiendo que midan lo mismo, las puntuaciones de los sujetos en estudio deberían ser iguales en ambas aplicaciones. De este modo, cuando la correlación es 1, la confiabilidad, precisión o reproducibilidad es máxima; y mientras más cercana a 0 es peor. La precisión en las mediciones está influenciada por el que mide (observador), por aquello con lo que se mide (instrumento de medición), y por lo que es medido (lo observado). Por ende, se ha de tomar en cuenta la variabilidad de cada uno de estos componentes al momento de planificar la medición de la variable en estudio; de tal modo de reducir al máximo los sesgos de medición. Así, las formas más comunes de determinar confiabilidad son: modelos de formas paralelas, test-retest y de dos mitades. Este manuscrito se centra en los conceptos de medición y las diversas técnicas estadísticas utilizadas para ello, como paso previo a la aplicación en la clínica. Por ello, el objetivo de este manuscrito es generar un documento de estudio y consulta relacionado con la confiabilidad, reproducibilidad o precisión del proceso de medición.

Reliability (accuracy, consistency and reproducibility) is a psychometric property, which is related to the absence of measurement error, or, to the degree of consistency and stability of the scores obtained through successive measurement processes with the same instrument. Thus a greater variability of results will lower the accuracy or reliability of instrument used, fact that is transverse from the laboratory to the clinical practice. It is determined by applying the reliability coefficient, which is the correlation between the scores obtained by the subjects in two parallel forms of a test. Assuming that the two forms of the test are parallel (measure the same), the scores of the subjects under study should be the same in both applications. In this way, when the correlation is 1, the reliability or precision is maximum. On the other hand, reliability could be influenced by the observer (the one that measures), the measuring instrument (by that with which it is measured), and by the observed (by what is measured). Therefore, the variability of each of these components must be taken into account when planning the measurement of the variable under study, in such a way to reduce measurement biases as much as possible. The most common ways to determine reliability are the models of parallel forms, test-retest and two halves. This manuscript focuses on the concepts of measurement and the various statistical techniques used for this, as a step prior to application in the clinic. Therefore, the aim of this manuscript is to generate a consultation document related to the reliability or reproducibility of the measurement process.

Induction of hypothyroidism during early postnatal stages triggers a decrease in cognitive performance by decreasing hippocampal synaptic plasticity.

Thyroid hormones are vital in the control of multiple body functions, including the correct performance of the brain. Multiple diseases are associated with thyroid gland functioning, including hypothyroidism. To date, little is known regarding the effects of the establishment of this condition at a young age on brain function. Here, we evaluated the effect of hypothyroidism in an early postnatal stage in cognitive abilities with focus on the hippocampus. In our model, hypothyroidism was induced in young rats at 21days of age using 0.05% 6-propyl-2-thiouracil (PTU) for 4weeks reaching significantly lower levels of fT4 (control: 1.337ng/dL±0.115, PTU: 0.050ng/dL±0.001). Following the induction of hypothyroidism, several cognitive tasks were assessed to investigate the effects of hypothyroidism on cognition performance. We determined that hypothyroidism triggers a significant dysfunction in learning and memory processes observed in the Morris Water Maze were the latency times were higher in PTU rats (controls: 37s; PTU: 57s). The cognitive impairment was correlated with a reduction in hippocampal plasticity with respect to both long-term potentiation (LTP) (control: 1.45, PTU: 1.00) and depression (LTD) (control: 0.71, PTU: 1.01). Furthermore, a decrease in the rate of glucose utilization (control: 223nmol∗mg of protein, PTU:148nmol∗mg of protein) was observed, along with an increase in oxidative stress and a decrease in MAP2 marker in the hippocampus. Our findings suggest that the induction of hypothyroidism in a young rat model alters numerous functions at the level of the hippocampus.

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells.

Wnt5a Increases the Glycolytic Rate and the Activity of the Pentose Phosphate Pathway in Cortical Neurons.

In the last few years, several reports have proposed that Wnt signaling is a general metabolic regulator, suggesting a role for this pathway in the control of metabolic flux. Wnt signaling is critical for several neuronal functions, but little is known about the correlation between this pathway and energy metabolism. The brain has a high demand for glucose, which is mainly used for energy production. Neurons use energy for highly specific processes that require a high energy level, such as maintaining the electrical potential and synthesizing neurotransmitters. Moreover, an important metabolic impairment has been described in all neurodegenerative disorders. Despite the key role of glucose metabolism in the brain, little is known about the cellular pathways involved in regulating this process. We report here that Wnt5a induces an increase in glucose uptake and glycolytic rate and an increase in the activity of the pentose phosphate pathway; the effects of Wnt5a require the intracellular generation of nitric oxide. Our data suggest that Wnt signaling stimulates neuronal glucose metabolism, an effect that could be important for the reported neuroprotective role of Wnt signaling in neurodegenerative disorders.

The increased potassium intake improves cognitive performance and attenuates histopathological markers in a model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by hallmarks that include an accumulation of amyloid-ß peptide (Aß), inflammation, oxidative stress and synaptic dysfunction, which lead to a decrease in cognitive function. To date, the onset and progression of AD have been associated with pathologies such as hypertension and diabetes. Hypertension, a disease with a high incidence worldwide, is characterized by a chronic increase in blood pressure. Interestingly, this disease has a close relationship to the eating behavior of patients because high Na(+) intake is a significant risk factor for hypertension. In fact, a decrease in Na(+) consumption, along with an increase in K(+) intake, is a primary non-pharmacological approach to preventing hypertension. In the present work, we examined whether an increase in K(+) intake affects the expression of certain neuropathological markers or the cognitive performance of a murine model of AD. We observed that an increase in K(+) intake leads to a change in the aggregation pattern of the Aß peptide, a partial decrease in some epitopes of tau phosphorylation and improvement in the cognitive performance. The recovery in cognitive performance was correlated with a significant improvement in the generation of long-term potentiation. We also observed a decrease in markers related to inflammation and oxidative stress such as glial fibrillary acidic protein (GFAP), interleukin 6 (IL-6) and 4-hydroxynonenal (4-HNE). Together, our data support the idea that changes in diet, such as an increase in K(+) intake, may be important in the prevention of AD onset as a non-pharmacological therapy.

Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance.

Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of metabolic disorders comprising diabetes and obesity. The impact of MetS on the brain is becoming to be a concern, however, the poor understanding of mechanisms involved has limited the development of therapeutic strategies. We induced a MetS-like condition by exposing mice to fructose feeding for 7weeks. There was a dramatic deterioration in the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD). Mice exposed to fructose showed a reduction in the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation likely associated with a deficiency in plasma membrane excitability. Consistent with an overall hippocampal dysfunction, there was a subsequent decrease in hippocampal dependent learning and memory performance, i.e., spatial learning and episodic memory. Most of the pathological sequel of MetS in the brain was reversed three month after discontinue fructose feeding. These results are novel to show that MetS triggers a cascade of molecular events, which disrupt hippocampal functional plasticity, and specific aspects of learning and memory function. The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders.

A novel functional low-density lipoprotein receptor-related protein 6 gene alternative splice variant is associated with Alzheimer's disease.

We previously found that single nucleotide polymorphisms in the low-density lipoprotein receptor-related protein 6 (LRP6) gene are associated with Alzheimer's disease (AD). Here, we studied the posttranscriptional metabolism of the LRP6 message scanning sequentially the 23 LRP6 exons in human tissues and found a novel LRP6 isoform that completely skips exon 3 (LRP6Δ3) in all tissues examined and was also conserved in mice. Expression levels of the LRP6 isoforms were determined in 47 cortical brain messenger (m)RNA samples including 22 AD cases, 11 control subjects, and 14 individuals with other neurological disorders. LRP6Δ3 mRNA levels were significantly augmented in AD brains compared with controls (1.6-fold; p = 0.037) or other pathological samples (2-fold; p = 0.007). Functional analysis in Wnt/ß-catenin signaling assays revealed that skipping of exon 3 reduced significantly the signaling activity of the LRP6 coreceptor. We conclude that the LRP6Δ3 isoform is a novel splice variant, which shows diminished Wnt/ß-catenin signaling activity and might have a functional role in individuals with AD.

Síndrome de lisis tumoral / Tumor lysis syndrome

El Síndrome de Lisis Tumoral se define como una triada metabólica compuesta por hiperuricemia, hiperkalemia, hiperfosfatemia e hipocalcemia que puede estar asociada a fallo renal, todo esto, secundario a una destrucción masiva de células neoplásicas de proliferación rápida, con una alta sensibilidad a la quimioterapia. La terapia está dirigida a aumentar la excreción de sustancias liberadas del contenido intracelular y minimizar la producción de ácido úrico a través de hiperhidratación, diuresis altas y control de la hiperuricemia con alopurinol como profiláctico y rasburicace para el tratamiento.

Diabetes mellitus in a subgroup of older Mexicans: prevalence, association with cardiovascular risk factors, functional and cognitive impairment, and mortality.

OBJECTIVES: To examine the prevalence and effects of diabetes mellitus in a subgroup of older Mexicans to allow comparisons to older persons of Mexican origin living in the United States. DESIGN: Longitudinal study. SETTING: High-rise retirement housing in Mexico City. PARTICIPANTS: Seven hundred eighty-five public servants and their family members aged 65 and older. MEASUREMENTS: Geriatric survey of function; mental status and depression; a physical examination; and blood samples for glucose and cholesterol. RESULTS: The prevalence of diabetes mellitus in this population was 15.1%, substantially lower than the prevalence reported in people of Mexican origin living in the United States. Nondiabetics were more obese than diabetics. Diabetes mellitus was more common in men than women. The mortality rate was greater in diabetics than nondiabetics (relative risk=1.73, P <.05). Diabetics had more coronary artery disease and were more likely to die from myocardial infarction and neoplasms than nondiabetics. Diabetics were more likely to be functionally impaired (P <.0001) but no more likely to fall or to have fractures. Diabetics did not differ from nondiabetics in cognitive impairment or level of dysphoria. CONCLUSION: These studies highlight some important similarities and differences in comparing a middle class subgroup of older diabetics in Mexico City with diabetics of Mexican origin living in the United States.

Histología testicular humana comparada, adulto joven y senil / Human testicular histology in young and senile men

La fisiología del envejecimiento implica cambios morfológicos que interfieren con la función testicular normal. El hombre senil mantiene la potencia fecundante, aunque su eficacia disminuye. Posiblemente, asociada a una presentación histopatológica testicular. Se utilizaron muestras de tejidos testicular de 3 individuos seniles (69 años), sometidos a orquiectomía terapéutica y de un joven adulto (25 años). Fallecido por causa desconocida. Las gónadas fueron procesadas por técnicas histológicas para Hematoxina-P.A.S. Al microscopio se evaluaron la morfometría, celularidad e histopatología del epitelio seminífero. En los resultados se obtuvo una reducción del diámetro tubular y altura del epitelio seminífero en los individuos seniles, al ser comparados con el individuo joven. Paralelamente, en los testículos de individuos seniles se describio una drástica disminución en el número de células de De Sertoli, y un poco menor para espermatogonias tipo A oscuras, A claras y B; con una relación gonia/Sertori alterada. Asociado a lo anterior, se encontró un porcentaje reducido de espermátidas redondas y alargadas y de espermatozoides, en lumen por túbulo. La evaluación histopatológica en los individuos seniles reveló un epitelio seminífero severamente dañado, con presencia de vacuolización, discontinuidad del epitelio y detención de la espermatogénesis. Por lo tanto, se concluye la existencia de un notorio efecto adverso del progreso de la edad hacia senil, en la estructura histológica testicular, involucrando las diferentes poblaciones celulares y la relación entre ellas, como también la integridad del epitelio seminífero