Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response.

Plasma levels of endocannabinoids (eCBs) are very dynamic and variable in different circumstances and pathologies. The aim of the study was to determine the levels of the main eCBs and N-acylethanolamines (NAEs) in COVID-19 patients during the acute and post-acute phase of SARS-CoV-2 infection. Samples collected before December 31, 2020 were used for the determination of circulating eCB levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between plasma eCB measurements and biochemical and hematological parameters, as well as serum IL-6 levels, was evaluated. Samples of 64 individuals were analysed, n = 18 healthy donors, n = 30 acute, and n = 16 post-acute patients. Plasma levels of 2-arachidonoylglycerol (2-AG), were significantly elevated in COVID-19 patients when compared to healthy individuals. Plasma N-palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (AEA) levels were found to be decreased in post-acute patient samples. These results suggest that 2-AG plays an important role in the inflammatory cascade in COVID-19 disease; in addition, eCBs might be involved in the post-acute pathogenesis of COVID-19. This study provides evidence of altered levels of circulating eCBs as a consequence of SARS-CoV-2 infection.

Cannabinoid CB2 receptors in primary sensory neurons are implicated in CB2 agonist-mediated suppression of paclitaxel-induced neuropathic nociception and sexually-dimorphic sparing of morphine tolerance.

Cannabinoid CB2 agonists show therapeutic efficacy without unwanted CB1-mediated side effects. The G protein-biased CB2 receptor agonist LY2828360 attenuates the maintenance of chemotherapy-induced neuropathic nociception in male mice and blocks development of morphine tolerance in this model. However, the cell types involved in this phenomenon are unknown and whether this therapeutic profile is observed in female mice has never been investigated. We used conditional deletion of CB2 receptors to determine the cell population(s) mediating the anti-allodynic and morphine-sparing effects of CB2 agonists. Anti-allodynic effects of structurally distinct CB2 agonists (LY2828360 and AM1710) were present in paclitaxel-treated CB2f/f mice and in mice lacking CB2 receptors in CX3CR1 expressing microglia/macrophages (CX3CR1CRE/+; CB2f/f), but were absent in mice lacking CB2 receptors in peripheral sensory neurons (AdvillinCRE/+; CB2f/f). The morphine-sparing effect of LY28282360 occurred in a sexually-dimorphic manner, being present in male, but not female, mice. LY2828360 treatment (3 mg/kg per day i.p. x 12 days) blocked the development of morphine tolerance in male CB2f/f and CX3CR1CRE/+; CB2f/f mice with established paclitaxel-induced neuropathy but was absent in male (or female) AdvillinCRE/+; CB2f/f mice. Co-administration of morphine with a low dose of LY2828360 (0.1 mg/kg per day i.p. x 6 days) reversed morphine tolerance in paclitaxel-treated male CB2f/f mice, but not AdvillinCRE/+; CB2f/f mice of either sex. LY2828360 (3 mg/kg per day i.p. x 8 days) delayed, but did not prevent, the development of paclitaxel-induced mechanical or cold allodynia in either CB2f/f or CX3CR1CRE/+; CB2f/f mice of either sex. Our findings have potential clinical implications.

Type 2 cannabinoid receptor expression on microglial cells regulates neuroinflammation during graft-versus-host disease.

Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells and inflammatory cytokines play a role in this process, the precise interplay between the adaptive and innate arms of the immune system that propagates inflammation in the central nervous system remains incompletely understood. Using a murine model of GVHD, we demonstrate that type 2 cannabinoid receptor (CB2R) signaling plays a critical role in the pathophysiology of neuroinflammation. In these studies, we identify that CB2R expression on microglial cells induces an activated inflammatory phenotype that potentiates the accumulation of donor-derived proinflammatory T cells, regulates chemokine gene regulatory networks, and promotes neuronal cell death. Pharmacological targeting of this receptor with a brain penetrant CB2R inverse agonist/antagonist selectively reduces neuroinflammation without deleteriously affecting systemic GVHD severity. Thus, these findings delineate a therapeutically targetable neuroinflammatory pathway and have implications for the attenuation of neurotoxicity after GVHD and potentially other T cell-based immunotherapeutic approaches.

Diagnóstico del estado nutricional, dislipidemia y factores de riesgo asociados en escolares indígenas yaquis / Diagnosis of nutritional status, dyslipidemia and associated risk factors in indigenous Yaqui schoolchildren

Resumen Antecedentes: La malnutrición es un problema mundial que afecta a niños escolares, capaz de incrementar el riesgo de enfermedades en la edad adulta. Adultos yaquis han presentado graves problemas de salud, por lo que los escolares podrían encontrarse en una situación similar. Objetivo: Evaluar el estado nutricional, el perfil lipídico y los factores asociados en una muestra de escolares yaquis. Material y métodos: Se estudiaron 109 escolares habitantes de los pueblos originarios, en quienes se realizaron mediciones antropométricas, se extrajo una muestra de sangre venosa en condición de ayuno y se aplicaron cuestionarios. Resultados: La prevalencia de sobrepeso/obesidad fue de 38.5 %, sin que se registraran casos de desnutrición crónica; 38.6 % de los escolares presentó dislipidemia. El consumo de fibra resultó ser un factor protector contra sobrepeso/obesidad y el consumo de grasa constituyó un factor de riesgo. La puntuación de actividad física resultó ser un factor protector contra dislipidemia y los factores de riesgo fueron puntuaciones Z del índice de masa corporal/edad, circunferencia de cintura, historia familiar de dislipidemias, nivel educativo y empleo permanente. Conclusiones: Los escolares yaquis padecen por igual alta proporción de sobrepeso/obesidad y dislipidemia. Los factores asociados pueden resultar útiles para el diseño de intervenciones contextualizadas para esta población.

Abstract Background: Malnutrition is a global problem that affects schoolchildren and can increase the risk of diseases in adulthood. Adult members of the Yaqui Indigenous group have been shown to have serious health problems, and Yaqui schoolchildren could therefore find themselves in a similar situation. Objective: To evaluate the nutritional status, lipid profile and associated factors in a sample of Yaqui schoolchildren. Material and methods: A total of 109 Yaqui schoolchildren who lived in their localities of origin were recruited. Anthropometric measurements were carried out, a venous blood sample was extracted in fasting conditions, and several questionnaires were applied. Results: The prevalence of overweight/obesity was 38.5%, with no cases of chronic malnutrition being recorded; 38.6% of the children had dyslipidemia. Fiber consumption was a protective factor against overweight/obesity, while fat intake was a risk factor. The physical activity score was found to be a protective factor against dyslipidemia, and the risk factors were BMI-for-age Z-scores, waist circumference, family history of dyslipidemia, educational level, and permanent employment. Conclusions: Yaqui schoolchildren equally suffer from a high proportion of overweight/obesity and dyslipidemia. The associated factors may be useful for the design of contextualized interventions for this population.

MICROGLIAL CELL EXPRESSION OF THE TYPE 2 CANNABINOID RECEPTOR REGULATES IMMUNE-MEDIATED NEUROINFLAMMATION.

Neuroinflammation is a recognized complication of immunotherapeutic approaches such as immune checkpoint inhibitor treatment, chimeric antigen receptor therapy, and graft versus host disease (GVHD) occurring after allogeneic hematopoietic stem cell transplantation. While T cells and inflammatory cytokines play a role in this process, the precise interplay between the adaptive and innate arms of the immune system that propagates inflammation in the central nervous system remains incompletely understood. Using a murine model of GVHD, we demonstrate that type 2 cannabinoid receptor (CB2R) signaling plays a critical role in the pathophysiology of neuroinflammation. In these studies, we identify that CB2R expression on microglial cells induces an activated inflammatory phenotype which potentiates the accumulation of donor-derived proinflammatory T cells, regulates chemokine gene regulatory networks, and promotes neuronal cell death. Pharmacological targeting of this receptor with a brain penetrant CB2R inverse agonist/antagonist selectively reduces neuroinflammation without deleteriously affecting systemic GVHD severity. Thus, these findings delineate a therapeutically targetable neuroinflammatory pathway and has implications for the attenuation of neurotoxicity after GVHD and potentially other T cell-based immunotherapeutic approaches.

Associations between dietary intake and physical activity, as behavioral indicators, with body fat in adolescents from Mexico.

Introduction: Introduction: the prevention of cardiometabolic diseases is currently a priority due to its relationship with COVID-19 complications. Unhealthy lifestyles, like inadequate diet and physical inactivity, are the cornerstone for obesity and cardiometabolic risk. Objective: to examine the association between diet and physical activity with body fat in Mexican adolescents. Methods: the study was cross-sectional. Data included socio-demographic variables, health history and smoking habit obtained through questionnaires; blood pressure and anthropometry measurements; food and nutrient intake through 24-hour recalls; and physical activities through the International Physical Activity Questionnaire (IPAQ). Univariate analyses were used and multiple models were built by stepwise forward selection (p ≤ 0.05 and biological plausibility). Results: participants were n = 230 students, 18.5 ± 0.4 years and 54.8 % men. Three models associated with body fat were obtained. In the first model, saturated fatty acids (ß = 0.30, p = 0.028) were significant positive associated, while vigorous physical activity was significant negative associated as a protective factor (ß = -0.007, p = 0.023). In the second model, total fat (ß = 0.17, p = 0.005) was significant positive associated, and vigorous physical activity was significant negative associated (ß = -0.007, p = 0.023). The third model included fruits and vegetables (ß = -5.49, p = 0.092) and vigorous physical activity (ß = -0.006, p = 0.058) as protective factors. Conclusions: dietary intake of total fat and saturated fatty acids, and vigorous physical activity, were significantly associated with body fat, while fruits and vegetables trended toward significance, in Mexican adolescents. Community-based programs that promote intake of protective foods and reduction of risky foods, and encourage vigorous physical activity, are needed in adolescents.

Introducción: Introducción: la prevención de enfermedades cardiometabólicas es actualmente una prioridad por su relación con las complicaciones de la COVID-19. Los estilos de vida poco saludables son la piedra angular de la obesidad y el riesgo cardiometabólico. Objetivo: examinar la asociación entre dieta y actividad física con la grasa corporal en adolescentes mexicanos. Métodos: el estudio fue transversal. Los datos incluyeron variables sociodemográficas; mediciones de presión arterial y antropometría; ingesta de alimentos y nutrimentos con recordatorios de 24 horas; y actividades físicas con el cuestionario internacional de actividad física (IPAQ). Se utilizo análisis univariado y los modelos múltiples se construyeron mediante selección paso a paso hacia adelante (p ≤ 0.05 y plausibilidad biológica). Resultados: participaron n = 230 estudiantes, 18,5 ± 0,4 años y 54,8 % hombres. Se obtuvieron tres modelos asociados a la grasa corporal. En el primero, los ácidos grasos saturados (ß = 0,30, p = 0,028) se asociaron significativamente de forma positiva, y la actividad física vigorosa significativamente de forma negativa como factor protector (ß = -0,007, p = 0,023). En el segundo, la grasa total (ß = 0,17, p = 0,005) se asoció positivamente y la actividad física vigorosa, negativamente (ß = -0,007, p = 0,023). El tercer modelo incluyó frutas y verduras (ß = -5,49, p = 0,092) y actividad física vigorosa (ß = -0,006, p = 0,058) como factores protectores. Conclusiones: la ingesta dietética de grasas totales y saturadas y la actividad física vigorosa se asociaron significativamente con la grasa corporal, mientras que las frutas y verduras tendieron a ser significativas. Se necesitan programas comunitarios que promuevan la ingesta de alimentos protectores y la reducción de alimentos de riesgo, y fomenten la actividad física vigorosa en adolescentes.

Factors influencing adults to drop out of intensive lifestyle interventions for weight loss.

Reducing ≥5% of body weight can decrease the risk of developing chronic diseases in adults with excess weight. Although Intensive Lifestyle Interventions (ILIs) that include cognitive-behavioral techniques to improve physical activity and eating habits are the best approach for losing weight, the failure to retain participants is a barrier to their successful implementation. We aimed to investigate the factors influencing adults to drop out of ILIs for weight loss at six months. We conducted retrospective multiple logistic regression analysis of 268 participants with excess weight (body mass index ≥ 25 kg/m2) from a multicenter study (n = 237, in-person ILI in five clinics, delivered by nutrition interns), and a randomized controlled trial (n = 31, one online ILI, delivered by a master's degree student). The same research team conducted both studies in Northern Mexico, using the same intervention components, and identical instruments and techniques to collect the data. We found that older participants (≥50 years) were less likely to drop out of the ILI for weight loss compared to participants <35 years old (OR = 0.34, 95% CI = 0.16-0.70). For each unit increase in the bodily pain scale of the SF-36 (less perceived pain), the risk of dropping out decreased by 2% (OR = 0.98, 95% CI = 0.97, 0.996), while a change in the interventionist during the 6-month intervention more than doubled the risk of dropping out (OR 2.25, 95% CI = 1.23-4.14). Retention in ILIs may be improved by ensuring that the same interventionist remains during the six-month intervention. In addition, ILIs may need further tailoring for younger ages and for participants with higher perceived pain.

Weight loss is hard. The best way to do it is to enroll in an intervention that includes frequent sessions with a health coach who uses cognitive-behavioral techniques to help participants improve their eating and physical activity habits. Retaining participants in these types of intervention is a challenge for health practitioners and researchers. Our objective was to identify the factors that increase the participants' risk of dropping out of the intervention. We analyzed the data of 268 Mexican adults who participated in studies that evaluated intensive lifestyle interventions for weight loss. We found that participants who are younger, experience more pain, and whose health coaches are replaced before the intervention is completed have a higher risk of dropping out of the intervention. By accounting for these factors when designing the intervention, we could increase the chances that participants stay in the intervention until the end. This way they are more likely to be successful in losing weight.

Effectiveness of multicomponent lifestyle intervention programs on adiposity indicators in schoolchildren from vulnerable groups: a review article.

Introduction: Vulnerable groups are those who, due to their age, sex, race/ethnicity, health status, income level, etc., are at higher risk of poor health. Vulnerable school populations are distinguished by having predisposing factors to overweight and obesity, which results in a greater risk of suffering from the disease and its ravages. Additionally, the effects of the COVID-19 contingency can worsen the situation. Previous reviews of prevention, treatment and control of the disease have focused on schoolchildren from high- and middle-income countries. The objective of this review was to gather the evidence from the studies that evaluate the effectiveness of multicomponent lifestyle intervention programs (MLIP) on adiposity indicators in vulnerable populations. Five electronic databases were searched: PubMed, MEDLINE, Cochrane Library, EMBASE, and Google Scholar. The eligibility criteria were schoolchildren (5 to 12 years old), inhabitants of rural area, with low socioeconomic level and/or belonging to an indigenous community. Randomized and quasi-experimental controlled trials were included. Interventions that included two or more of the following components were considered: physical activity, nutrition, psychology, school meals and/or family/community involvement. Of the 11 interventions included 73 % had significant improvements in at least one variable related to adiposity. The most successful interventions had components of nutrition, physical activity and family/community involvement, the majority (80 %) had a duration of ≥ 6 months and were provided, in 80 % of the cases, by previously trained teachers. In conclusion, there is evidence that MLIPs are effective in improving indicators of adiposity in vulnerable schoolchildren.

Introducción: Los grupos vulnerables son aquellos que, debido a sus condiciones de edad, sexo, raza/etnia, estado de salud, ingresos, etc., tienen un riesgo mayor de presentar una salud deficiente. Las poblaciones escolares vulnerables se distinguen por tener factores predisponentes de sobrepeso y obesidad, lo que redunda en mayor riesgo de padecer la enfermedad y sus complicaciones. Adicionalmente, los efectos de la contingencia por COVID-19 podrían agravar la situación. Revisiones previas sonre la prevención, tratamiento y control de la enfermedad se han enfocado en escolares de países de altos y medianos ingresos. Esta revisión tuvo como objetivo reunir la evidencia que evalúa la efectividad de los programas multicomponentes de intervención de estilo de vida (PMIEV) sobre los indicadores de adiposidad en poblaciones vulnerables. Se exploraron cinco bases de datos electrónicas: PubMed, MEDLINE, Cochrane Library, EMBASE y Google Scholar. Los criterios de elegibilidad fueron escolares (5-12 años), habitantes rurales, con bajo nivel socioeconómico y/o pertenecientes a comunidades indígenas. Se incluyeron ensayos controlados aleatorizados y cuasi-experimentales. Se consideraron intervenciones con dos o más de los siguientes componentes: actividad física, nutrición, psicología, comidas escolares y/o participación familiar/comunitaria. De las 11 intervenciones incluidas, el 73 % obtuvieron mejoras en al menos una variable relacionada con la adiposidad. Las intervenciones más exitosas incluyeron componentes de nutrición, actividad física y participación familiar/comunitaria, la mayoría (80 %) tuvo una duración ≥ 6 meses y las llevaron a cabo en un 80 % de los casos profesores entrenados. En conclusión, la evidencia indica que los PMIEV son efectivos para mejorar los indicadores de adiposidad en los escolares vulnerables.

A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse.

ABSTRACT: CB2 cannabinoid receptors (CB2) are a promising therapeutic target that lacks unwanted side effects of CB1 activation. However, the cell types expressing CB2 that mediate these effects remain poorly understood. We used transgenic mice with CB2 promoter-driven expression of enhanced green fluorescent protein (EGFP) to study cell types that express CB2 and suppress neuropathic nociception in a mouse model of chemotherapy-induced peripheral neuropathy. Structurally distinct CB2 agonists (AM1710 and LY2828360) suppressed paclitaxel-induced mechanical and cold allodynia in CB2EGFP reporter mice with established neuropathy. Antiallodynic effects of AM1710 were blocked by SR144528, a CB2 antagonist with limited CNS penetration. Intraplantar AM1710 administration suppressed paclitaxel-induced neuropathic nociception in CB2EGFP but not CB2 knockout mice, consistent with a local site of antiallodynic action. mRNA expression levels of the anti-inflammatory cytokine interleukin-10 were elevated in the lumbar spinal cord after intraplantar AM1710 injection along with the proinflammatory cytokine tumor necrosis factor alpha and chemokine monocyte chemoattractant protein-1. CB2EGFP, but not wildtype mice, exhibited anti-GFP immunoreactivity in the spleen. However, the anti-GFP signal was below the threshold for detection in the spinal cord and brain of either vehicle-treated or paclitaxel-treated CB2EGFP mice. EGFP fluorescence was coexpressed with CB2 immunolabeling in stratified patterns among epidermal keratinocytes. EGFP fluorescence was also expressed in dendritic cells in the dermis, Langerhans cells in the epidermis, and Merkel cells. Quantification of the EGFP signal revealed that Langerhans cells were dynamically increased in the epidermis after paclitaxel treatment. Our studies implicate CB2 expressed in previously unrecognized populations of skin cells as a potential target for suppressing chemotherapy-induced neuropathic nociception.

Potentiation of amyloid beta phagocytosis and amelioration of synaptic dysfunction upon FAAH deletion in a mouse model of Alzheimer's disease.

BACKGROUND: The complex pathophysiology of Alzheimer's disease (AD) hampers the development of effective treatments. Attempts to prevent neurodegeneration in AD have failed so far, highlighting the need for further clarification of the underlying cellular and molecular mechanisms. Neuroinflammation seems to play a crucial role in disease progression, although its specific contribution to AD pathogenesis remains elusive. We have previously shown that the modulation of the endocannabinoid system (ECS) renders beneficial effects in a context of amyloidosis, which triggers neuroinflammation. In the 5xFAD model, the genetic inactivation of the enzyme that degrades anandamide (AEA), the fatty acid amide hydrolase (FAAH), was associated with a significant amelioration of the memory deficit. METHODS: In this work, we use electrophysiology, flow cytometry and molecular analysis to evaluate the cellular and molecular mechanisms underlying the improvement associated to the increased endocannabinoid tone in the 5xFAD mouse- model. RESULTS: We demonstrate that the chronic enhancement of the endocannabinoid tone rescues hippocampal synaptic plasticity in the 5xFAD mouse model. At the CA3-CA1 synapse, both basal synaptic transmission and long-term potentiation (LTP) of synaptic transmission are normalized upon FAAH genetic inactivation, in a CB1 receptor (CB1R)- and TRPV1 receptor-independent manner. Dendritic spine density in CA1 pyramidal neurons, which is notably decreased in 6-month-old 5xFAD animals, is also restored. Importantly, we reveal that the expression of microglial factors linked to phagocytic activity, such as TREM2 and CTSD, and other factors related to amyloid beta clearance and involved in neuron-glia crosstalk, such as complement component C3 and complement receptor C3AR, are specifically upregulated in 5xFAD/FAAH-/- animals. CONCLUSION: In summary, our findings support the therapeutic potential of modulating, rather than suppressing, neuroinflammation in Alzheimer's disease. In our model, the long-term enhancement of the endocannabinoid tone triggered augmented microglial activation and amyloid beta phagocytosis, and a consequent reversal in the neuronal phenotype associated to the disease.

Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells.

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this receptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism of CB2R signaling, especially in cell-type and tissue-dependent contexts. Herein, we report for the first time a versatile ligand platform for the modular design of a collection of highly specific CB2R fluorescent probes, used successfully across applications, species, and cell types. These include flow cytometry of endogenously expressing cells, real-time confocal microscopy of mouse splenocytes and human macrophages, as well as FRET-based kinetic and equilibrium binding assays. High CB2R specificity was demonstrated by competition experiments in living cells expressing CB2R at native levels. The probes were effectively applied to FACS analysis of microglial cells derived from a mouse model relevant to Alzheimer's disease.

Cannabinoid CB2R receptors are upregulated with corneal injury and regulate the course of corneal wound healing.

CB2R receptors have demonstrated beneficial effects in wound healing in several models. We therefore investigated a potential role of CB2R receptors in corneal wound healing. We examined the functional contribution of CB2R receptors to the course of wound closure in an in vivo murine model. We additionally examined corneal expression of CB2R receptors in mouse and the consequences of their activation on cellular signaling, migration and proliferation in cultured bovine corneal epithelial cells (CECs). Using a novel mouse model, we provide evidence that corneal injury increases CB2R receptor expression in cornea. The CB2R agonist JWH133 induces chemorepulsion in cultured bovine CECs but does not alter CEC proliferation. The signaling profile of CB2R activation is activating MAPK and increasing cAMP accumulation, the latter perhaps due to Gs-coupling. Lipidomic analysis in bovine cornea shows a rise in acylethanolamines including the endocannabinoid anandamide 1 h after injury. In vivo, CB2R deletion and pharmacological block result in a delayed course of wound closure. In summary, we find evidence that CB2R receptor promoter activity is increased by corneal injury and that these receptors are required for the normal course of wound closure, possibly via chemorepulsion.

The fat mass index, not the fat-free mass index, is associated with impaired physical performance in older adult subjects: Evidence from a cross-sectional study.

BACKGROUND: Impaired physical performance (IPP) and physical disability (PD) are two serious public health problems in older adult populations worldwide. While studies show that changes in body composition are important risk factors for developing these conditions, there is little evidence that the fat-free mass (FFM) and fat mass (FM) indices (FFMI and FMI, respectively) are associated with IPP in older men and women. This study assessed the association among FFMI, FMI, and IPP using Short Physical Performance Battery (SPPB) in Mexican men and women aged over 60 years. METHODS: This cross-sectional study included 217 older people (men 34.6%, women 65.4%; 60-92 years). FFM and FM were assessed by dual X-ray absorptiometry, assuming a two-compartment model. FFM and FM were adjusted by height squared and the indices were obtained. After assessment of physical performance by SPPB, subjects with scores ≤6 were classified as having IPP. Associations were tested by multiple logistic regression analysis in separated models. RESULTS: IPP prevalence was 14.3%. Women were affected more than men. Regression analysis showed no significant association between FFMI and IPP, but FMI was strongly-associated, as for each unit increase in FMI, the risk of IPP rose significantly (OR: 1.14), and this result remained significant after adjusting for age, comorbidity, polypharmacy, and the appendicular skeletal muscle mass index (OR: 1.23; p ≤ 0.001). These results emphasize the importance of preventing increases in FM and avoiding overweight and obesity in older men and women.

Prevalence of previous diagnosis of hypertension and associated factors in the Yaqui indigenous of Sonora / Prevalencia de diagnóstico previo de hipertensión arterial y factores asociados en indígenas Yaquis de Sonora

Abstract: Introduction: The hypertension (HT) is a public health problem worldwide. This disease is a risk factor for heart diseases and, cerebrovascular and renal failure, which are considered the main causes of mortality. Objective: This study aimed to describe factors associated with a previous diagnosis of HT in a group of Yaqui adults from Sonora, Mexico. Material and methods: We conducted a cross-sectional epidemiological study in which 108 individuals ≥ 18 years of age were included. HT was considered as prior diagnosis. In addition, anthropometric assessment, medical history and sociodemographic questionnaires were also applied. The sex- and age adjusted prevalence was estimated using the direct method of standardization using the studied sample as the standard population. The factors associated with previous diagnosis of HT were determined using multiple logistic regression analysis. Results: The sex- and age-adjusted prevalence of a previous diagnosis of HT was 12.0% (95% CI: 6.3-17.6) in the overall population. The age-adjusted prevalence in men was 7.1%, and it was 14.0% in women with no significant difference between genders. The independent factors associated with HT were increased waist circumference (cm) (OR: 1.07, 95% CI: 1.01-1.14) and a previous diagnosis of diabetes (OR: 4.14, 95% CI: 1.03-16.61). Conclusions: The prevalence of a previous diagnosis of HT was high, and it could be higher after confirmation of new diagnosis cases in the population. The identification of factors associated with HT may be useful for creating programs to prevent chronic diseases in this ethnic group.(AU)

Resumen: Introducción: La hipertensión arterial (HTA) es un problema de salud pública a nivel mundial. Esta enfermedad es un factor de riesgo para enfermedades del corazón, cerebrovasculares y falla renal, las cuales son consideradas entre las principales causas de mortalidad. Objetivo: Describir factores asociados con el diagnóstico previo de HTA en un grupo de adultos Yaquis de Sonora, México. Material y métodos: Llevamos a cabo un estudio epidemiológico con diseño transversal donde fueron estudiados 108 individuos ≥ 18 años de edad. La HTA fue considerada como diagnóstico previo, se hizo una evaluación antropométrica y se aplicaron cuestionarios de historial clínico y sociodemográficos. La prevalencia de HTA ajustada por edad y sexo se estimó por el método directo de estandarización utilizando la población estudiada como población estándar. Los factores asociados con el diagnóstico previo de HTA fueron obtenidos mediante análisis de regresión logística múltiple. Resultados: La prevalencia de diagnóstico previo de HTA fue 12.0% (IC 95%, 6.3-17.6) en la población total. La prevalencia ajustada por edad en hombres fue 7.1 y 14.0% en mujeres; sin diferencias significativas entre sexo. Los factores asociados de manera independiente con HTA fueron una mayor circunferencia de cintura (cm) (RM: 1.07; IC 95%, 1.01-1.14) y el diagnóstico previo de diabetes (RM: 4.14; IC 95%, 1.03-16.61). Conclusiones: La prevalencia de diagnóstico previo de HTA fue alta y podría incrementar con la confirmación de diagnóstico de casos nuevos en la población. La identificación de factores asociados con HTA puede servir para crear programas de prevención de enfermedades crónicas en este grupo étnico.(AU)

Phytoestrogen Concentrations in Human Urine as Biomarkers for Dietary Phytoestrogen Intake in Mexican Women.

There has been substantial interest in phytoestrogens, because of their potential effect in reducing cancer and heart disease risk. Measuring concentrations of phytoestrogens in urine is an alternative method for conducting epidemiological studies. Our objective was to evaluate the urinary excretion of phytoestrogens as biomarkers for dietary phytoestrogen intake in Mexican women. Participants were 100 healthy women from 25 to 80 years of age. A food frequency questionnaire (FFQ) and a 24 h recall were used to estimate habitual and recent intakes of isoflavones, lignans, flavonols, coumestrol, resveratrol, naringenin, and luteolin. Urinary concentrations were measured by liquid chromatography (HPLC) coupled to mass spectrometry (MS) using the electrospray ionization interface (ESI) and diode array detector (DAD) (HPLC-DAD-ESI-MS). Spearman correlation coefficients were used to evaluate associations between dietary intake and urine concentrations. The habitual consumption (FFQ) of total phytoestrogens was 37.56 mg/day. In urine, the higher compounds were naringenin (60.1 µg/L) and enterolactone (41.7 µg/L). Recent intakes (24 h recall) of isoflavones (r = 0.460, p < 0.001), lignans (r = 0.550, p < 0.0001), flavonoids (r = 0.240, p < 0.05), and total phytoestrogens (r = 0.410, p < 0.001) were correlated to their urinary levels. Total phytoestrogen intakes estimated by the FFQ showed higher correlations to urinary levels (r = 0.730, p < 0.0001). Urinary phytoestrogens may be useful as biomarkers of phytoestrogen intake, and as a tool for evaluating the relationship of intake and disease risk in Mexican women.

Antineoplastic treatment effect on bone mineral density in Mexican breast cancer patients.

BACKGROUND: Breast cancer is the most deadly malignancy in Mexican women. Although treatment has improved, it may significantly affect bone mineral status in those who receive it. The aim of this study was to assess the impact of cancer treatment on bone mineral density (BMD) and bone mineral content (BMC), in patients with breast cancer and explore the interaction of menopausal status and clinical stage with cancer treatment on such changes. METHODS: A quasi-experimental design was applied with measurements before and after a chemotherapy treatment in 40 patients with primary diagnosis of invasive breast cancer. BMD and body composition measurements were taken by dual X-ray absorptiometry (DXA) and changes in these variables due to therapy were analyzed using mixed regression for repeated measurements. RESULTS: Significant loss was found in femoral neck and L2-L4 BMD (p < 0.001). Patients diagnosed with osteopenia or osteoporosis received calcium + vitamin D supplementation (600 mg/200 IU day). It showed a protective effect in the decrease of femoral neck BMD and total BMC. BMD loss in both femoral neck and L2-L4 BMD was higher in premenopausal women: 0.023 g/cm2 in femoral neck and 0.063 g/cm2 in L2-L4 (p < 0.001), while in postmenopausal women BMD loss was 0.015 g/cm2 in femoral neck and 0.035 g/cm2 in L2-L4 (p = 0.021 and p = 0.001 respectively). Change in lumbar spine BMD was prominent in premenopausal women with advanced clinical stage (IIB, IIIA, IIIB): 0.066 g/cm2 (p = 0.003). CONCLUSION: The antineoplastic breast cancer treatment with chemotherapy had a negative impact on BMD, in premenopausal women overall, although a differential effect was found according to clinical stage and calcium supplementation status.

Endocannabinoids regulate the activity of astrocytic hemichannels and the microglial response against an injury: In vivo studies.

Anandamide (AEA) is an endocannabinoid (EC) that modulates multiple functions in the CNS and that is released in areas of injury, exerting putative neuroprotective actions. In the present study, we have used intravital microscopy to analyze the role of the EC system in the glial response against an acute insult. Our data show that AEA modulates astroglial function in vivo by increasing connexin-43 hemichannel (HC) activity. Furthermore, the genetic inactivation of the AEA-degrading enzyme, fatty acid amide hydrolase (FAAH), also increased HC activity and enhanced the microglial response against an acute injury to the brain parenchyma, effects that were mediated by cannabinoid CB1 receptors. The contribution of ATP released through an astrocytic HC was critical for the microglial response, as this was prevented by the use of the HC blocker flufenamic acid and by apyrase. As could be expected, brain concentrations of AEA, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were elevated in FAAH-null mice, while 2-arachidonoylglycerol (2-AG) concentrations remained unaltered. In summary, these findings demonstrate that AEA modifies glial functions by promoting an enhanced pro-inflammatory glial response in the brain.

[Antineoplastic treatment impact on nutritional status in patients with breast cancer]. / Impacto del tratamiento antineoplásico en el estado nutricional en pacientes con cáncer de mama.

BACKGROUND: Breast cancer is the most commonly diagnosed malignancy in women in Mexico and also has the highest mortality. Although treatment has improved significantly, it can affect the nutritional status of the recipients. OBJECTIVE: The aim of this study was to assess the impact of the initial phase of antineoplastic therapy on the nutritional status in patients with breast cancer. METHODS: Forty subjects with primary diagnosed of invasive breast cancer were studied in a before and after intervention (six month apart) using a quasi-experimental design. Basal and six month after intervention measurements included were anthropometry, body composition by dual X-ray absorptiometry (DEXA), diet by 24-hour recall and food frequency questionnaire, as well as serum -carotene and retinol. The therapy effect was analyzed using repeated measurements mixed linear regression. RESULTS: Lean tissue decreased after the studied period (p=0.032). Addicionally, there was an interaction between weight, BMI and body fat parameters with menopausal status, increasing in these variables due to therapy only premenopausal patients (p=0.005, 0.006 and 0.001, respectively). Decreased serum retinol (p=0.049) despite the improvement in -carotene status (p=0.03). In general there was an increase the consumption of vegetables food products whilst a decrease in animal foods. CONCLUSION: The breast cancer antineoplastic treatment had a negative effect on weight and body fat, especially in young women. Although there were some positive dietary changes, vegetables consumption remained insufficient, which was also reflected in serum biomarkers.

Presentación: El cáncer de mama es el tipo de tumor más frecuentemente diagnosticado entre las mujeres de México y también el de más alta mortalidad. Aunque el tratamiento ha mejorado significativamente, puede afectar al estado nutricional del paciente. Objetivo: El objetivo de este estudio era evaluar el impacto de la fase inicial de la terapia antineoplásica sobre el estado nutricional en pacientes con cáncer de mama. Métodos: Cuarenta sujetos con diagnóstico primario de cáncer de mama invasivo fueron estudiados antes y después de la intervención (con seis meses de desfase) usando un diseño quasi-experimental. Las mediciones al inicio y seis meses después de la intervención incluyeron antropometría, composición corporal mediante absorciometría dual de rayos X (DEXA), cuestionario de recopilación de dieta en 24 horas y frecuencia de comidas, y suero beta-caroteno y retinol. El efecto de la terapia fue analizado empleando mediciones repetidas y regresión lineal mixta. Resultados: El tejido magro disminuyó tras el periodo de estudio (p=0.032). Además, se dio una interacción entre los parámetros de peso, IMC y grasa corporal con el estado de menopausia, aumentando en estas variables debido a la terapia solo en pacientes premenopáusicas (p=0.005, 0.006 y 0.001, respectivamente). Descenso de retinol sérico (p=0.049) a pesar de la mejoría en el estado de beta-caroteno (p=0.03). En general hubo un aumento en el consumo de verdura y un descenso de productos animales. Conclusión: El tratamiento antineoplásico del cáncer de mama tuvo un efecto negativo sobre el peso y la grasa corporal, especialmente en mujeres jóvenes. Aunque se observaron algunos cambios positivos en la dieta, el consumo de verdura siguió siendo insuficiente, lo que también se reflejó en los biomarcadores séricos.

[Educational program had a positive effect on the intake of fat, fruits and vegetables and physical activity in students attending public elementary schools of Mexico]. / Programa educativo afecta positivamente el consumo de grasa, frutas, verduras y actividad física en escolares Mexicanos.

INTRODUCTION: Poor diet and lack of physical activity are the most important risk factors of mortality and burden of disease in Mexico and many other countries around the world. OBJECTIVE: The purpose of this research was to analyze the effect of an educational intervention on The consumption of fruits, vegetables, fat, physical activity and inactivity in students attending public primary school of Sonora Mexico. METHODS: The intervention consisted of educational workshops on nutrition and physical activity aimed to the students and educational talks on nutrition and physical activity aimed to parents. Anthropometric, 24 hours recall, nutrition-knowledge, and physical-activity questionnaires pre- and post-intervention were applied in order to evaluate changes in both groups. RESULTS: 126 of the initial 129 students (97.7%) were evaluated at the end of the intervention. the consumption of fruits and vegetables was significantly higher after the intervention (p=0.0032) and the consumption of total fat decreased (p=0.02) in the intervention schools. Moreover, intervention increased physical activity (p=0.04) and decreased sedentary activities (p=0.006). Intervention students obtained higher knowledge in nutrition (p=0.05) at the end of intervention. CONCLUSION: The intervention had a positive effect on improve fruits, vegetables and fat consumption, physical activity and nutrition knowledge.

Introducción: Una dieta inadecuada y la falta de actividad física, son de los factores de riesgo más importantes de mortalidad y carga de enfermedad en México y muchos otros países alrededor del mundo. Objetivo: El propósito de esta investigación fue analizar el efecto de una intervención educativa sobre el consumo de frutas, verduras, grasa y actividad física en escolares de Sonora México. Métodos: Se contó con dos grupos homogéneos de escuelas; 3 con programa de intervención y 3 sin programa de intervención. La intervención consistió de un taller educativo en nutrición y otro en actividad física para escolares y pláticas educativas en nutrición y actividad física para padres de familia. Se aplicaron pre y post-intervención recordatorio de 24-h, cuestionario de actividad física, conocimientos en nutrición y mediciones antropométricas. Resultados: Ciento veintiséis de los 129 escolares que iniciaron la intervención fueron medidos al final de la intervención (97.7%). Después del programa de intervención el consumo de frutas y verduras de los escolares intervenidos fue significativamente mayor (p=0.032) y el consumo de grasa total disminuyó (p=0.02). Los escolares intervenidos aumentaron el número de horas de actividad física y disminuyeron las actividades sedentarias (p=0.04 y p=0.006 respectivamente). Además, mostraron mayor conocimiento en nutrición que los no intervenidos (p=0.05). Conclusión: El programa fue efectivo en mejorar el consumo de frutas, verduras y grasas en la dieta de los escolares, además mostró efecto positivo en la actividad física y los conocimientos en nutrición.

Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study.

BACKGROUND: The phytocannabinoid cannabidiol (CBD) exhibits antioxidant and antiinflammatory properties. The present study was designed to explore its effects in a mouse model of sepsis-related encephalitis by intravenous administration of lipopolysaccharide (LPS). METHODS: Vascular responses of pial vessels were analyzed by intravital microscopy and inflammatory parameters measured by qRT-PCR. RESULTS: CBD prevented LPS-induced arteriolar and venular vasodilation as well as leukocyte margination. In addition, CBD abolished LPS-induced increases in tumor necrosis factor-alpha and cyclooxygenase-2 expression as measured by quantitative real time PCR. The expression of the inducible-nitric oxide synthase was also reduced by CBD. Finally, preservation of Blood Brain Barrier integrity was also associated to the treatment with CBD. CONCLUSIONS: These data highlight the antiinflammatory and vascular-stabilizing effects of CBD in endotoxic shock and suggest a possible beneficial effect of this natural cannabinoid.