Sex differences in autism-like behavior and dopaminergic neurons in substantia nigra of juvenile mice prenatally exposed to valproate.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and communication and repetitive and restricted behaviors. Sex dimorphism in the brain, including midbrain dopaminergic circuits, can explain differences in social behavior impairment and stereotypic behaviors between male and female individuals with ASD. These abnormal patterns may be due to alterations in dopamine synthesis in the ventral tegmental area (VTA) and substantia nigra (SN). We used an autism-like mouse model by prenatal valproic acid (VPA) exposure. CD1 pregnant female mice were injected with 500 mg/kg VPA or 0.9% NaCl as a vehicle on gestational day 12.5. In the offspring, on postnatal day 31, we examined the social and repetitive behaviors and the number of tyrosine hydroxylase (TH)-positive cells in VTA and SN by sex. Male VPA mice showed impaired social behavior and increased repetitive behaviors when compared to male vehicles. In females, we did not find statistically significant differences in social or repetitive behaviors between the groups. Male VPA mice had fewer TH+ cells in the SN than control-vehicle mice. Interestingly, no cellular changes were observed between females. This study supports the notion that sex dimorphism of certain brain regions is involved in the etiopathogenesis and clinical presentation of ASD.

Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with increased prevalence and incidence in recent decades. Its etiology remains largely unclear, but it seems to involve a strong genetic component and environmental factors that, in turn, induce epigenetic changes during embryonic and postnatal brain development. In recent decades, clinical studies have shown that inutero exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug, is an environmental factor associated with an increased risk of ASD. Subsequently, prenatal VPA exposure in rodents has been established as a reliable translational model to study the pathophysiology of ASD, which has helped demonstrate neurobiological changes in rodents, non-human primates, and brain organoids from human pluripotent stem cells. This evidence supports the notion that prenatal VPA exposure is a valid and current model to replicate an idiopathic ASD-like disorder in experimental animals. This review summarizes and describes the current features reported with this animal model of autism and the main neurobiological findings and correlates that help elucidate the pathophysiology of ASD. Finally, we discuss the general framework of the VPA model in comparison to other environmental and genetic ASD models.

Cambios en la densidad del comercio minorista de alimentos en Hermosillo, México, en el periodo del 2010 al 2021, y su asociación con la dieta, antropometría y salud de mujeres adultas

El comercio minorista de alimentos es un componente del ambiente alimentario que influye en la selección y consumo de alimentos. En las últimas décadas, México ha experimentado cambios en el ambiente alimentario que coinciden con el incremento del sobrepeso, obesidad y las enfermedades no transmisibles (ENT) de su población. El objetivo de este estudio fue analizar los cambios en la densidad de comercios minoristas de alimentos en zonas de media y alta marginación de Hermosillo, Sonora, situado en la región Pacífico Norte de México, en el periodo del 2010 al 2021, y su asociación con la dieta, antropometría y salud de mujeres adultas. La información del comercio minorista de alimentos se obtuvo del Diccionario Estadístico Nacional de Unidades Económicas (DENUE). Se entrevistó y se tomaron medidas antropométricas a una muestra de 104 mujeres adultas. En el periodo de estudio, el comercio minorista de alimentos tuvo cambios significativos en las zonas de media y alta marginación de la localidad. El promedio de edad de las participantes fue de 47,6±15 años. La prevalencia de sobrepeso y obesidad, diabetes e hipertensión fue del 88%, 20% y 40%, respectivamente. El aumento en la densidad de tiendas de conveniencia se asoció de manera positiva con el índice de masa corporal, circunferencia de cintura y obesidad de las participantes (β: 3,22; p<0,01; β: 7,70; p<0,01; OR: 3,12; p<0,01). Los resultados muestran que el tipo de establecimiento en donde se compran los alimentos se asocia con indicadores de salud de la población.

Food retail is a component of the food environment that influences food selection and consumption. In recent decades, Mexico has experienced changes in the food environment that coincide with the increase in overweight, obesity, and non-communicable diseases (NCDs) among its population. The aim of this study was to analyze changes in the density of food retail from 2010 to 2021 in areas of medium and high marginalization in Hermosillo, Sonora, located in the North Pacific region of Mexico, and their association with diet, anthropometry, and adult women's health. Information on food retail was obtained from the National Statistic Directory of Economic Units (DENUE). A sample of 104 adult women was interviewed, and their anthropometric measurements were taken. The findings revealed significant changes in the density of food retail in areas of medium and high marginalization during the study period. The participant's mean age was 47,6±15 years. The prevalence of overweight and obesity, diabetes, and high blood pressure was 88%, 20%, and 40%, respectively. The increase in the density of convenience stores was positively associated with women's body mass index, waist circumference, and obesity (β: 3,22; p<0,01; β: 7,70; p<0,01; OR: 3,12; p<0,01). The results demonstrate that the type of establishment where food is purchased is associated with the population's health status.

Therapeutic Approaches for ADHD by Developmental Stage and Clinical Presentation.

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder with three presentations: inattentive, hyperactive/impulsive and combined. These may represent an independent disease entity. Therefore, the therapeutic approach must be focused on their neurobiological, psychological and social characteristics. To date, there is no comprehensive analysis of the efficacy of different treatments for each presentation of ADHD and each stage of development. This is as narrative overview of scientific papers that summarize the most recent findings and identify the most effective pharmacological and psychosocial treatments by ADHD presentation and age range. Evidence suggests that methylphenidate is the safest and most effective drug for the clinical management of children, adolescents and adults. Atomoxetine is effective in preschoolers and maintains similar efficacy to methylphenidate in adults, whereas guanfacine has proven to be an effective monotherapy for adults and is a worthy adjuvant for the management of cognitive symptoms. The psychosocial treatments with the best results in preschoolers are behavioral interventions that include training of primary caregivers. In adolescents, the combination of cognitive and cognitive-behavioral therapies has shown the best results, whereas cognitive-behavioral interventions are the most effective in adults. Pharmacological and psychosocial treatments must be adjusted to the ADHD presentation and its neurocognitive characteristics through the patient's development.

Phenytoin promotes the proliferation of oligodendrocytes and enhances the expression of myelin basic protein in the corpus callosum of mice demyelinated by cuprizone.

Oligodendrocyte loss and myelin sheet destruction are crucial characteristics of demyelinating diseases. Phenytoin promotes the proliferation of endogenous neural precursor cells in the ventricular-subventricular zone in the postnatal brain that help restore the oligodendroglial population. This study aimed to evaluate whether phenytoin promotes myelin recovery of the corpus callosum of demyelinated adult mice. CD1 male mice were exposed to a demyelinating agent (0.2% cuprizone) for 8 weeks. We assembled two groups: the phenytoin-treated group and the control-vehicle group. The treated group received oral phenytoin (10 mg/kg) for 4 weeks. We quantified the number of Olig2 + and NG2 + oligodendrocyte precursor cells (OPCs), Rip + oligodendrocytes, the expression level of myelin basic protein (MBP), and the muscle strength and motor coordination. The oligodendroglial lineage (Olig2 + cells, NG2 + cells, and RIP + cells) significantly increases by the phenytoin administration when compared to the control-vehicle group. The phenytoin-treated group also showed an increased expression of MBP in the corpus callosum and better functional scores in the horizontal bar test. These findings suggest that phenytoin stimulates the proliferation of OPCs, re-establishes the oligodendroglial population, promotes myelin recovery in the corpus callosum, and improves motor coordination and muscle strength.

Spatio-Temporal Statistical Characterization of Boundary Kinematic Phenomena of Triaxial Sand Specimens.

This paper follows up on a reference paper that inspired MDPI's Topic "Stochastic Geomechanics: From Experimentation to Forward Modeling", where global and local deformation effects on sand specimens are fully described from high resolution boundary displacement fields, and supported by its experimental database, which is open to the scientific community for further study. This paper introduces the use of spatio-temporal statistics from a subset of such an experimental database to characterize the specimens' spatio-temporal displacement fields, populated by repeating a set of triaxial compression tests on drained, dry, vacuum-consolidated sand specimens, tested under similar experimentally controlled conditions. A three-dimensional digital image correlation (3D-DIC) technique was used to measure the specimens' boundary displacement fields throughout the course of shearing under axial compression. Spatio-temporal first- and second-order statistics were computed for different data dimensionality conditions (0D, 0D-T, 1D-T, 3D-T) to identify and characterize the dominant failure mechanisms across different testing specimens. This allowed us to quantify localization phenomena's spatio-temporal uncertainty. Results show that the uncertainty captured along the deformation process across different dimensionality conditions can be directly associated with different failure mechanisms, including localization patterns, such as the onset and evolution of shear, compression, and expansion bands. These spatio-temporal observations show the dependencies between locally distinctive displacement regions over a specimen's surface, and across different times during a specimen's shearing process. Results of this work provide boundary spatio-temporal statistics of experimental evidence in sands, which sets the basis for the development of research on the numerical simulation of sand's constitutive behavior. Moreover, it allows to add a new understanding on the effect of uncertainty on the mechanistic interpretation of sands' kinematic phenomena.

Global and Local Deformation Effects of Dry Vacuum-Consolidated Triaxial Compression Tests on Sand Specimens: Making a Database Available for the Calibration and Development of Forward Models.

A comprehensive experimental database containing results of a series of dry vacuum-consolidated triaxial compression tests was populated. The tests were performed on sand specimens and conducted under similar experimental conditions, in which specimens' boundary deformation was captured using a three-dimensional digital image correlation analysis (3D-DIC). The use of a standard triaxial device along with the 3D-DIC technology allowed the specimens' global and local boundary displacement fields to be computed from start to end of the compression phase. By repeating each test under the same experimental conditions and building the specimens using the same type of sand, the boundary deformation patterns could be identified, and the statistics associated with both global and local displacement fields could be assessed. Making this experimental database available to others should serve to calibrate as well as develop new forward models to account for effects associated with the specimens' local displacements and material heterogeneity and include statistics to represent a specimen's random response. Moreover, this work will serve as a basis for the statistical characterization of spatio-temporal boundary localization effects used to develop stochastic models and machine-learning models, and simulate virtual triaxial tests.

Biopsychological correlates of repetitive and restricted behaviors in autism spectrum disorders.

BACKGROUND: Autism Spectrum Disorder (ASD) is considered a neurodevelopmental condition that is characterized by alterations in social interaction and communication, as well as patterns of restrictive and repetitive behaviors (RRBs). RRBs are defined as broad behaviors that comprise stereotypies, insistence on sameness, and attachment to objects or routines. RRBs can be divided into lower-level behaviors (motor, sensory, and object-manipulation behaviors) and higher-level behaviors (restrictive interests, insistence on sameness, and repetitive language). According to the DSM-5, the grade of severity in ASD partially depends on the frequency of RRBs and their consequences for disrupting the life of patients, affecting their adaptive skills, and increasing the need for parental support. METHODS: We conducted a systematic review to examine the biopsychological correlates of the symptomatic domains of RRBs according to the type of RRBs (lower- or higher-level). We searched for articles from the National Library of Medicine (PubMed) using the terms: autism spectrum disorders, ASD, and autism-related to executive functions, inhibitory control, inflexibility, cognitive flexibility, hyper or hypo connectivity, and behavioral approaches. For describing the pathophysiological mechanism of ASD, we also included animal models and followed PRISMA guidelines. RESULTS: One hundred and thirty-one articles were analyzed to explain the etiology, continuance, and clinical evolution of these behaviors observed in ASD patients throughout life. CONCLUSIONS: Biopsychological correlates involved in the origin of RRBs include alterations in a) neurotransmission system, b) brain volume, c) inadequate levels of growth factors, d) hypo- or hyper-neural connectivity, e) impairments in behavioral inhibition, cognitive flexibility, and monitoring and f) non-stimulating environments. Understanding these lower- and higher-level of RRBs can help professionals to improve or design novel therapeutic strategies.

Role of Oligodendrocytes and Myelin in the Pathophysiology of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is an early neurodevelopmental disorder that involves deficits in interpersonal communication, social interaction, and repetitive behaviors. Although ASD pathophysiology is still uncertain, alterations in the abnormal development of the frontal lobe, limbic areas, and putamen generate an imbalance between inhibition and excitation of neuronal activity. Interestingly, recent findings suggest that a disruption in neuronal connectivity is associated with neural alterations in white matter production and myelination in diverse brain regions of patients with ASD. This review is aimed to summarize the most recent evidence that supports the notion that abnormalities in the oligodendrocyte generation and axonal myelination in specific brain regions are involved in the pathophysiology of ASD. Fundamental molecular mediators of these pathological processes are also examined. Determining the role of alterations in oligodendrogenesis and myelination is a fundamental step to understand the pathophysiology of ASD and identify possible therapeutic targets.

Food Security and Obesity among Mexican Agricultural Migrant Workers.

Mexican migrant farm workers are one of the poorest and most marginalized social groups within the country. They face the double burden of malnutrition, food insecurity, as well as harsh living and labor conditions. Objective: To examine the relationship between household food insecurity (HFI) and obesity in a population of migrant farm workers in highly modernized agribusiness areas of Northwest Mexico. Methods: This was a cross-sectional study with a concentric (site) (n = 146 households) and systematic selection of participants (adult men and women). Methods included questionnaires regarding socio-demographic characteristics, food security, diet (two non-consecutive 24-h recalls), and physical activity (PA). Anthropometric data included height, weight, and waist circumference. Data analysis covered descriptive statistics, multivariate linear and logistic regression. Results: Sample showed 75% prevalence of overweight and obesity, while 87% of households reported some level of HFI. Mild HFI resulted in five times more probability of farm workers' obesity (OR = 5.18, 95% CI: 1.37-19.58). However, there was a protective effect of HFI for obesity among men (OR 0.089, 95% CI: 0.01-0.58) in a context of intense labor-related PA. Conclusion: There is a difference by gender in the relationship of HFI with obesity prevalence related perhaps to the energy expenditure of male agricultural migrant workers.

El papel de la paradoja de la obesidad y el conteo linfocitario en sepsis / The role of the obesity paradox and lymphocytic count on sepsis / O papel do paradoxo da obesidade e contagem de linfócitos na sepse

Resumen: Introducción: La obesidad es un factor protector para mortalidad en la sepsis, a este fenómeno se le conoce como «paradoja de la obesidad¼. La obesidad es un estado inflamatorio crónico, que incluye mediadores de la inmunidad innata y adaptativa. Un marcador de inmunidad adaptativa es la linfopenia, ésta es relacionada con peor evolución y mayor mortalidad. Objetivo: Determinar la relación del índice de masa corporal (IMC) con conteo linfocitario y su relación con supervivencia en pacientes sépticos. Material y métodos: Estudio de cohortes, retrospectivo, en pacientes con sepsis y/o choque séptico mayores de 18 años, sin enfermedades autoinmunes, ni tratamiento inmunosupresor, determinando IMC y linfopenia. Resultados: Se incluyeron 206 pacientes, 8.7% con peso bajo, 46.6% peso normal, 24.8% con sobrepeso, 19.9% con obesidad. El grupo de mayor mortalidad con linfopenia tuvo los menores valores de IMC 21.37 kg/m2. El análisis de supervivencia reveló que un IMC < 22.5 kg/m2 y linfopenia son factores de riesgo independientes para mortalidad. Conclusiones: La obesidad se relaciona con mayor conteo linfocitario y mayor supervivencia en sepsis y choque séptico, por lo que el IMC y el conteo linfocitario son factores independientes para mortalidad estadísticamente significativos, proponemos la escala APACHE II ajustada con estas variables.

Abstract: Introduction: Obesity is a mortality protector factor in sepsis; this phenomenon is known as «obesity paradox¼. Furthermore, obesity is a chronic inflammatory state in which adaptive and innate immunity mediators play key roles. Lymphopenia is an adaptive immunity marker and it has been related to poor outcomes and greater mortality. Objective: To determine the relationship between body mass index and lymphocyte count and its association with the survival of septic patients. Methods and materials: A cohort retrospective study of patients older than 18 years old with sepsis, septic shock and no history of autoimmune diseases nor immunosuppressor treatments. Outcomes included determining BMI and lymphopenia. Results: 206 patients were included, 8.7% with low weight, 46.6% with normal weight, 24.8% with normal weight, 19.9% with obesity. The group with the lowest BMI (median of 21.37) and lymphopenia was associated with the greatest mortality. The survival analysis revealed that a BMI lower than 22.5 and lymphopenia are independent risk factors for mortality. Conclusions: Obesity is associated to a higher lymphocyte count and a greater survival in sepsis and septic shock. Since BMI and lymphocyte count are statistically significant independent risk factors for mortality, we propose an APACHE II score adjusted to these variables.

Resumo: Introdução: Na sepse, a obesidade é um fator de proteção para mortalidade, denominando esse fenômeno de «paradoxo da obesidade¼. A obesidade é um estado inflamatório crônico, incluindo mediadores da imunidade inata e adaptativa. Um marcador de imunidade adaptativa é a linfopenia, que está relacionada a uma evolução desfavorável e maior mortalidade. Objetivo: Determinar a relação do índice de massa corporal (IMC) com a contagem de linfócitos e sua relação com a sobrevida em pacientes sépticos. Material e métodos: Estudo de coorte, retrospectivo em pacientes com sepse e / ou choque séptico com mais de 18 anos, sem doenças autoimunes ou tratamento imunossupressor, determinando o IMC e a linfopenia. Resultados: Foram incluídos 206 pacientes, sendo 8.7% com baixo peso, 46.6% com peso normal, 24.8% com sobrepeso, 19.9% com obesidade. O grupo com maior mortalidade com linfopenia apresentou os menores valores de IMC de 21.37 kg/m2. A análise de sobrevivência revelou que um IMC < 22.5 kg/m2 e a linfopenia são fatores de risco independentes para a mortalidade. Conclusão: A obesidade está relacionada à maior contagem de linfócitos e maior sobrevida em sepse e choque séptico. Como o IMC e a contagem de linfócitos são fatores independentes para mortalidade estatisticamente significante, propomos a escala APACHE II ajustada com essas variáveis.

Variables hemodinámicas y desenlace de la función renal en pacientes de terapia intensiva / Haemodynamic variables and outcomes of renal function on intensive care patients / Variáveis hemodinâmicas e resultados da função renal em pacientes de terapia intensiva

Resumen: Introducción: Las variables hemodinámicas nos informan sobre la progresión de lesión renal aguda (AKI por sus siglas en inglés). Material y métodos: Estudio prospectivo, observacional, longitudinal, de pacientes ingresados a la Unidad de Terapia Intensiva del 2017 al 2018. Se incluyeron mayores de 18 años, con lesión renal aguda (AKI 1 o 2), monitoreo hemodinámico de tensión arterial media (TAM), tensión arterial diastólica (PAD), frecuencia cardiaca (FC) y de presión venosa central (PVC). Determinados desde las 24 horas del diagnóstico hasta el egreso. Resultados: Fueron 164 pacientes, 105 (64%) presentaron progresión de AKI cuando TAM < 75.98 mmHg. PAD < 61, PVC >8 cm H2O, FC > 90 x', TAM-PVC < 67.64 mmHg, PAD-PVC < 53.28 mmHg. Conclusiones: La TAM, PAD y la PVC tienen el mayor impacto en el riesgo de progresión de AKI cuando se calcula la presión de perfusión media con estas variables.

Abstract: Introduction: Haemodynamic variables inform us about the progression of acute kidney injury (AKI). Material and methods: Prospective, observational and longitudinal study of patients admitted to Intensive Care (ICU) from 2017-2018. patients over 18 years were included, with acute kidney injury (AKI 1, 2), and hemodynamic monitoring of mean arterial blood pressure (MAP), diastolic blood pressure (DBP), heart rate (HR) and central venous pressure (CVP). Determined from 24 hours after diagnosis and its evolution was recorded until discharge. Results: A total of 164 patients were included, progression of AKI presented when MAP < 75.98 mmHg, DBP < 61 mmHg, CVP < 8 cmH2O, FC 90 x', MAP-CVP 67.64 mmHg, DBP-CVP 53.28 mmHg, HR > 90 beats/minute. Conclusions: MAP, DBP and CVP have the greatest impact on the risk of AKI progression, especially when the mean perfusion pressure (PPM) is calculated with these two variables.

Resumo: Introdução: As variáveis hemodinâmicas informam sobre a progressão da lesão renal aguda (LRA). Materiais e métodos: Estudo prospectivo, observacional, longitudinal de pacientes admitidos em terapia intensiva (UTI) de 2017-2018. Foram incluídos pacientes maiores de 18 anos, com lesão renal aguda (LRA 1 ou 2), monitorização hemodinâmica da pressão arterial média (TAM), pressão arterial diastólica (PAD), freqüência cardíaca (FC) e pressão venosa central (PVC). Determinada a partir de 24 horas de diagnóstico até a alta. Resultados: 164 pacientes (p), 105 p (64%) apresentaram progressão da LRA quando TAM < 75.98 mmHg, PAD < 61 mmHg, PVC > 8 cmH2O, FC > 90 x´, TAM-PVC < 67.64 mmHg, PAD- PVC < 53.28 mmHg. Conclusões: TAM, PAD e PVC têm o maior impacto no risco de progressão da LRA quando a pressão média de perfusão (PMP) é calculada com essas variáveis.

Melatonin modifies SOX2+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation.

Melatonin is a pleiotropic molecule that, after a short-term sleep deprivation, promotes the proliferation of neural stem cells in the adult hippocampus. However, this effect has not been observed in long-term sleep deprivation. The precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated, but evidence indicates that epigenetic regulators may be involved in this process. In this study, we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword clusterization. Our results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate gyrus. We observed that let-7b, mir-132, and mir-124 were highly expressed in the dentate gyrus after melatonin administration, but they were not modified by sleep deprivation. In addition, we found more Sox2+/5-bromo-2'-deoxyuridine (BrdU)+ cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated group. These findings may support the notion that melatonin modifies the expression of epigenetic mediators that, in turn, regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived conditions. All procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara, Mexico (approval No. CI-16610) on January 2, 2016.

Puntaje LVIS como predictor de mortalidad en choque séptico / LVIS as mortality predictor in septic shock / Pontuação LVIS como preditor de mortalidade em choque séptico

Resumen: Introducción: El uso de vasopresores en choque séptico es parte fundamental del tratamiento. El uso de un puntaje que integre los múltiples vasopresores e inotrópicos como LVIS (levosimendan vasopressor inotropic score), puede ser de utilidad para el seguimiento y pronóstico de estos pacientes. Se ha estudiado en población pediátrica y no ha sido validada en población adulta. Material y métodos: Estudio retrospectivo, longitudinal, retrolectivo en pacientes adultos admitidos a UCI con diagnóstico de choque séptico con el fin de investigar si el puntaje LVIS es capaz de predecir mortalidad y lesión renal aguda. Seguimiento a 30 días. Resultados: Incluimos 77 pacientes, 24 (21.2%) pacientes murieron y 41 (53.23%) presentaron lesión renal aguda. Se observó un AUC (área bajo la curva) para LVIS 0.89 con un punto de corte de 21.3 (sensibilidad 50% y especificidad de 82%). El puntaje LVIS > 21.3 con RR 2.09 (IC95% 1.15-3.7, p = 0.003) y un HR de 3.8 (IC95% 1.5-9.3, p = 0.003), LR+ 2.81 y LR- 0.61 para mortalidad. LVIS no fue significativo para predecir LRA (lesión renal aguda). Conclusiones: LVIS es útil para predecir mortalidad en choque séptico, con un punto de corte 21.3. Es necesario continuar estudios para validarlo en población adulta con otras formas de choque.

Abstract: Introduction: Vasopressors have a fundamental roll in the treatment of septic shock. LVIS (levosimendan vasopressor inotropic score) as a score that integrates the main vasopressors and inotropic drugs may be useful for monitoring and prognosis. It's been studied in pediatric population, but not validated in adult patients so far. Material and methods: Retrospective, longitudinal, retrolective study in adults admitted in ICU with septic shock. We looked to investigate if LVIS score is useful to predict mortality and acute kidney injury in ICU, with a follow-up of 30 days. Results: We included 77 patients, 24 (21.2%) patients died and 41 (53.23%) developed acute kidney injury. LVIS had an AUC of 0.89 with a cut-off of 21.3 (50% sensitivity and 82% of specificity). LVIS score above the cut-off 21.3, had RR 2.09 (CI95% 1.15-3.7, p = 0.003), HR de 3.8 (CI 1.5-9.3, p = 0.003), LR+ 2.81 and LR- 0.61 for mortality. LVIS could not predict AKI (acute kidney). Conclusions: LVIS score is useful to predict mortality in patients with septic shock, with a cut-off of 21.3. More research is left to be done to validate this score in other forms of shock in adult population.

Resumo: Introdução: O uso de vasopressores no choque séptico é uma parte fundamental do tratamento. O uso de um escore que integra múltiplos vasopressores e drogas inotrópicas como o LVIS (Levosimendan Vasopressor Inotropic Score), pode ser útil para o acompanhamento e prognóstico desses pacientes. Foi estudado na população pediátrica e não foi validado na população adulta. Material e métodos: Estudo retrospectivo, longitudinal, retrolectivo em pacientes adultos admitidos na UTI com o diagnóstico de choque séptico para investigar se o escore LVIS é capaz de predizer a mortalidade e a lesão renal aguda em um acompanhamento de 30 dias. Resultados: Foram incluídos 77 pacientes, 24 (21.2%) pacientes morreram e 41 (53.23%) apresentaram lesão renal aguda. Uma AUC (área sob a curva) foi observada para LVIS 0.89 com um ponto de corte de 21.3 (sensibilidade 50% e especificidade 82%). O escore LVIS > 21.3 com RR 2.09 (IC95% 1.15-3.7, p = 0.003) e uma HR de 3.8 (IC95% 1.5-9.3, p = 0.003), LR + 2.81 e LR -0.61 para mortalidade. O LVIS não foi significativa na predição da LRA (lesão renal aguda). Conclusões: O LVIS é útil para prever a mortalidade no choque séptico, com um ponto de corte de 21.3. É necessário continuar os estudos para validá-lo na população adulta com outras formas de choque.

Prevalencia de los factores asociados a la no coincidencia del método de planificación familiar electo en la atención prenatal y el aplicado post-evento obstétrico / Prevalence of the factors associated with the non-coincidence of the method of elected family planning in prenatal care and applied post-event obstetric

RESUMEN Marco teórico: La atención prenatal tiene varios objetivos y entre ellos está el fomentar y sentar bases para una decisión adecuada sobre planificación familiar con base en las condiciones clínicas de la mujer. Es frecuente encontrar en la atención de puerperio que la paciente no haya recibido un método de planificación familiar por distintos factores. Objetivo: Identificar la prevalencia de los factores asociados a la no coincidencia del método de planificación familiar electo en la atención prenatal y el aplicado post-evento obstétrico. Metodología: Diseño transversal descriptivo en pacientes en puerperio inmediato cuyo método de planificación familiar solicitado en consentimiento informado firmado en la atención prenatal no coincidió con el aplicado post-evento obstétrico. Se midieron factores intrínsecos y extrínsecos Resultados: El factor intrínseco más importante fue el cambio de decisión personal 59.0% (IC 95%; 53.10-64.90) y el factor extrínseco la falta de insumos en el 31.20% (IC 95%; 25.60-36.80). Cuando se realizó la evaluación conjunta la prevalencia del cambio de decisión personal se modificó a 35.20% (IC 95%; 29.4-41.0) y la falta de insumos a 12.6% (IC95%; 8.6-16.6) Conclusión: Los factores intrínsecos y extrínsecos asociados a la no coincidencia del método de planificación familiar con mayor prevalencia son el cambio de decisión por la paciente y la falta de insumos respectivamente.

ABSTRACT Background: Prenatal care has several objectives and among them is to promote and lay the groundwork for an adequate decision on family planning based on the clinical conditions of women. It is common to find in puerperium care that the patient has not received a family planning method due to different factors. Objective: To identify the prevalence of the factors associated with the non-coincidence of the method of family planning elected in prenatal care and the post-obstetric event applied. Methods: Descriptive cross-sectional design in patients in the immediate puerperium whose family planning method requested in signed informed consent in prenatal care did not coincide with the applied post-obstetric event. Intrinsic and extrinsic factors were measured Results: The most important intrinsic factor was the change of personal decision 59.0% (95% CI, 53.10-64.90) and the extrinsic factor the lack of inputs in 31.20% (95% CI, 25.60-36.80). When the joint evaluation was carried out, the prevalence of the personal decision change was modified to 35.20% (95% CI, 29.4-41.0) and the lack of inputs to 12.6% (95% CI, 8.6-16.6). Conclusion: The intrinsic and extrinsic factors associated with the non-coincidence of the family planning method with the highest prevalence are the change of decision by the patient and the lack of inputs, respectively.

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder.

Growth factors (GFs) are cytokines that regulate the neural development. Recent evidence indicates that alterations in the expression level of GFs during embryogenesis are linked to the pathophysiology and clinical manifestations of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). In this concise review, we summarize the current evidence that supports the role of brain-derived neurotrophic factor, insulin-like growth factor 2, hepatocyte growth factor (HGF), glial-derived neurotrophic factor, nerve growth factor, neurotrophins 3 and 4, and epidermal growth factor in the pathogenesis of ADHD and ASD. We also highlight the potential use of these GFs as clinical markers for diagnosis and prognosis of these neurodevelopmental disorders.

Growth factors as clinical biomarkers of prognosis and diagnosis in psychiatric disorders.

The psychiatric disorders are one of the most disabling illnesses in the world and represent a major problem for public health. These disorders are characterized by neuroanatomical or biochemical changes and it has been suggested that such changes may be due to inadequate neurodevelopment. Diverse alterations in the gene expression and/or serum level of specific growth factors have been implicated in the etiology, symptoms and progression of some psychiatric disorders. Herein, we summarize the latest information regarding the role of brain-derived neurotrophic factor (BDNF), epidermal growth factor (EGF), fibroblast growth factor (FGF), Insulin-like growth factor (IGF-1), neuroregulin-1 (NGR-1), erythropoietin (EPO), vascular growth factor (VEGF), transforming growth factor beta (TGF-ß), nerve growth factor (NGF) and others cytokines in the pathogenesis of schizophrenia, depression, bipolar and anxiety disorders. Focusing on the role of these growth factors and their relationship with the main impairments (cognitive, emotional and social) of these pathologies. Some of these signaling molecules may be suitable biological markers for diagnosis and prognosis in cognitive, mood and social disabilities across different mental disorders.

Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation.

Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal.

Sex-related effects of sleep deprivation on depressive- and anxiety-like behaviors in mice.

Anxiety and depressive symptoms are generated after paradoxical sleep deprivation (PSD). However, it is not clear whether PSD produces differential effects between females and males. The aim of this study was to assess the effect of PSD on anxiety- and depressive-like behaviors between sexes. Male and female BALB/c mice were divided in three groups: the control group, the 48-h PSD group and the 96-h PSD group. Immediately after PSD protocols, the forced swimming and open field test were applied. Sucrose consumption test was used to evaluate the middle-term effect of PSD. We found that corticosterone serum levels showed significant differences in the 96-h PSD females as compared to 96-h PSD males. In the open-field test, the 48-h and 96-h PSD females spent more time at the periphery of the field, and showed high locomotion as compared to males. In the elevated plus maze, the 48-h PSD females spent more time in closed arms than males, which is compatible with anxiety-like behavior. The forced swim test indicated that the 96-h PSD males spent more time swimming as compared to the 96-h PSD females. Remarkably, the 96-h PSD males had lower sucrose intake than the 96-h PSD females, which suggest that male mice have proclivity to develop a persistent depressive-like behavior late after PSD. In conclusion, male mice showed a significant trend to depressive-like behaviors late after sleep deprivation. Conversely, female have a strong tendency to display anxiety- and depressive-like behaviors immediately after sleep deprivation.

Cyclohexane produces behavioral deficits associated with astrogliosis and microglial reactivity in the adult hippocampus mouse brain.

Cyclohexane is a volatile substance that has been utilized as a safe substitute of several organic solvents in diverse industrial processes, such as adhesives, paints, paint thinners, fingernail polish, lacquers, and rubber industry. A number of these commercial products are ordinarily used as inhaled drugs. However, it is not well known whether cyclohexane has noxious effects in the central nervous system. The aim of this study was to analyze the effects of cyclohexane inhalation on motor behavior, spatial memory, and reactive gliosis in the hippocampus of adult mice. We used a model that mimics recreational drug use in male Balb/C mice (P60), divided into two groups: controls and the cyclohexane group (exposed to 9,000 ppm of cyclohexane for 30 days). Both groups were then evaluated with a functional observational battery (FOB) and the Morris water maze (MWM). Furthermore, the relative expression of AP endonuclease 1 (APE1), and the number of astrocytes (GFAP+ cells) and microglia (Iba1+ cells) were quantified in the hippocampal CA1 and CA3 areas. Our findings indicated that cyclohexane produced severe functional deficits during a recreational exposure as assessed by the FOB. The MWM did not show statistically significant changes in the acquisition and retention of spatial memory. Remarkably, a significant increase in the number of astrocytes and microglia cells, as well as in the cytoplasmic processes of these cells were observed in the hippocampal CA1 and CA3 areas of cyclohexane-exposed mice. This cellular response was associated with an increase in the expression of APE1 in the same brain regions. In summary, cyclohexane exposure produces functional deficits that are associated with an important increase in the APE1 expression as well as the number of astrocytes and microglia cells and their cytoplasmic complexity in the CA1 and CA3 regions of the adult hippocampus.