Association Between Changes in Sleep, Nap Duration and Bone Mineral Density in Mexican Adults.

Studies have found associations between sleep, nap duration, and bone mineral density (BMD). However, the longitudinal relationship between sleep, nap duration, and BMD has not been explored. We evaluated the association between the change in sleep and nap duration and BMD in Mexican adults. Data come from 1,337 adult participants of the Health Workers Cohort Study (341 were men and 996 were women, including 450 women < 45 years old and 546 ≥ 45 years old), with two study waves. At each wave, sleep and nap duration was assessed using self-administered questionnaires and BMD in g/cm2 was determined by dual X-ray absorptiometry. We used fixed-effect regression models stratified by sex and adjusted for BMI, diet, physical activity, vitamin supplements, and hormone replacement therapy. Women who changed from < 7 to ≥ 7 h/day of sleep from baseline to follow-up were associated with increases in the total hip (ß = 0.012 g/cm2; 95% CI: 0.002, 0.022) and lumbar spine BMD (ß = 0.024 g/cm2; 95% CI: 0.009, 0.039). Furthermore, most of these associations were observed in women ≥ 45 years. For women, a changing from 0 to > 60 min/day of napping was associated with a significant increase in total hip BMD of 0.012 g/cm2 (95% CI: 0.004, 0.024) and lumbar spine BMD of 0.027 g/cm2 (95% CI: 0.009, 0.045). No significant associations were observed for men. Our results suggest that increased sleep and nap duration are associated with gains in BMD in Mexican women, emphasizing sleep's role in promoting bone health and supporting established recommendations.

Healthy lifestyle interventions within the curriculum in school-age children: systematic review and meta-analysis.

Childhood obesity is a major public health challenge. Previous research has identified the impact of school-based interventions for preventing and treating obesity; we hypothesized that when curricular changes are integrated, results could be exponentiated. This study aimed to systematically review and conduct a meta-analysis of the published literature analyzing information about school-based interventions inserted in the curriculum. The Cochrane Handbook methodology was followed. An electronic search was conducted in five databases, with a specific design strategy per database. Randomized controlled trials or quasi-experimental studies of children with nutrition and physical activity (PA) interventions inserted into the school curricula were included. The risk of bias was assessed with the Risk of Bias tool. The mean differences were pooled using a fixed-effects model for the meta-analysis. The certainty of the evidence was evaluated according to the guidelines of the Grading of the Recommendations, Assessment, Development, and Evaluations working group (Protocol ID: CRD42021270557). After the screening and selection process, 12 studies were included. The interventions identified, based on the school curricula, include classroom activities and homework, among others. A meta-analysis with five intervention groups presented an overall mean difference of -0.14 body mass index (BMI) Z-score (95% CI: -0.25, -0.03) after this intervention with high certainty of the evidence. This systematic review and meta-analysis suggest that nutrition and PA lessons inserted into the curricula and supported with additional activities (i.e. homework, workshops, etc.) could increase nutrition knowledge and improve attitudes toward fruit, vegetables, and water consumption, and BMI Z-score reduction.

The mitochondrial genome of the mountain wooly tapir, Tapirus pinchaque and a formal test of the effect of altitude on the adaptive evolution of mitochondrial protein coding genes in odd-toed ungulates.

BACKGROUND: The harsh conditions of high-altitude environments are known to drive the evolution of physiological and morphological traits in endothermic animals. These conditions are expected to result in the adaptive evolution of protein coding genes encoded in mitochondrial genomes that are vital for the oxidative phosphorylation pathway. In this study, we formally tested for signatures of adaptive evolution on mitochondrial protein coding genes in Tapirus pinchaque and other odd-toed ungulates inhabiting high-elevation environments. RESULTS: The AT-rich mitochondrial genome of T. pinchaque is 16,750 bp long. A phylomitogenomic analysis supports the monophyly of the genus Tapirus and families in the Perissodactyla. The ratio of non-synonymous to synonymous substitutions demonstrated that all mitochondrial genes undergo purifying selection in T. pinchaque and other odd ungulates living at high elevations. Over this negative background selection, Branch Models suggested that cox3 and nad6 might be undergoing stronger purifying selection than other mitochondrial protein coding genes. Furthermore, Site Models suggested that one and four sites in nad2 and nad5, respectively, could be experiencing positive selection. However, these results were supported by Likelihood Ratio Tests but not Bayesian Empirical Bayes posterior probabilities. Additional analyses (in DataMonkey) indicated a relaxation of selection strength in nad6, evidence of episodic diversifying selection in cob, and revealed episodic positive/diversifying selection signatures for two sites in nad1, and one site each in nad2 and nad4. CONCLUSION: The mitochondrial genome of T. pinchaque is an important genomic resource for conservation of this species and this study contributes to the understanding of adaptive evolution of mitochondrial protein coding genes in odd-toed ungulates inhabiting high-altitude environments.

Avocado consumption is associated with a reduction in hypertension incidence in Mexican women.

Avocado is a fruit rich in dietary fibre, potassium, Mg, mono and PUFA and bioactive phytochemicals, which are nutritional components that have been associated with cardiovascular health. Yet, despite the boom in avocado consumption, we lack evidence on its association with CVD risk in the general population. To estimate the prospective association between avocado consumption and incident hypertension in Mexican women, we estimated the association in participants from the Mexican Teachers' Cohort who were ≥ 25 years, free of hypertension, CVD and cancer at baseline (n 67 383). We assessed baseline avocado consumption with a semi-quantitative FFQ (never to six or more times per week). Incident hypertension cases were identified if participants self-reported a diagnosis and receiving treatment. To assess the relation between categories of avocado consumption (lowest as reference) and incident hypertension, we estimated incidence rate ratios (IRR) and 95 % CI using Poisson regression models and adjusting for confounding. We identified 4002 incident cases of hypertension during a total of 158 706 person-years for a median follow-up of 2·2 years. The incidence rate of hypertension was 25·1 cases per 1000 person-years. Median avocado consumption was 1·0 (interquartile range: 0·23, 1·0) serving per week (half an avocado). After adjustment for confounding, consuming 5 + servings per week of avocado was associated with a 17 % decrease in the rate of hypertension, compared with non- or low consumers (IRR = 0·83; 95 % CI: 0·70, 0·99; Ptrend = 0·01). Frequent consumption of avocado was associated with a lower incidence of hypertension.

Diagnostic accuracy of blood biomarkers and non-invasive scores for the diagnosis of NAFLD and NASH: Systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Fatty liver disease is an important public health problem. Early diagnosis is critical to lower its rate of progression to irreversible/terminal stages. This study aimed to evaluate the accuracy of non-invasive prediction scores for fatty liver disease (NAFLD and NASH) diagnosis in adults. MATERIALS AND METHODS: A search was conducted in 10 databases, a qualitative synthesis of 45 studies, and quantitative analysis of the six most common scores. There were 23 risk scores found for NAFLD diagnosis and 32 for NASH diagnosis. The most used were Fatty Liver Index (FLI), aspartate aminotransferase (AST) to Platelet Ratio Index, Fibrosis-4 Index (FIB-4), AST/alanine aminotransferase (ALT) ratio, BARD score, and NAFLD fibrosis score (NFS). RESULTS: The results from the meta-analysis for FLI: Area under the curve (AUC) of 0.76 (95% Confidence Interval [CI] 0.73, 0.80), sensitivity 0.67 (CI 95% 0.62, 0.72) and specificity 0.78 (CI 95% 0.74, 0.83). The AST to Platelet Ratio Index: AUC 0.83 (CI 95% 0.80, 0.86), sensitivity 0.45 (95% CI 0.29, 0.62), and specificity of 0.89 (95% CI 0.83, 0.92). The NFS: AUC of 0.82 (CI 95% 0.78, 0.85), sensitivity 0.30 (CI 95% 0.27, 0.33) and specificity 0.96 (CI 95% 0.95,0.96). CONCLUSIONS: The FLI for NAFLD and AST to Platelet Ratio Index for NASH were the risk scores with the highest prognostic value in the included studies. Further research is needed for the application of new diagnostic risk scores for NAFLD and NASH.

Modelling the impact of sodium intake on cardiovascular disease mortality in Mexico.

BACKGROUND: Cardiovascular diseases (CVD) represent the main cause of death in Mexico, while high blood pressure is suffered by about half of the adult population. Sodium intake is one of the main risk factors for these diseases. The Mexican adult population consumes about 3.1 g/day, an amount that exceeds what is recommended by the World Health Organization (WHO) < 2 g sodium/day. The objective of this study was to estimate the impact of reducing sodium intake on CVD mortality in Mexico using a scenario simulation model. METHODS: The Integrated Model of Preventable Risk (PRIME) was used to estimate the number of deaths prevented or postponed (DPP) due to CVD in the Mexican adult population following the following sodium intake reduction scenarios: (a) according to the WHO recommendations; (b) an "optimistic" reduction of 30%; and (c) an "intermediate" reduction of 10%. RESULTS: The results show that a total of 27,700 CVD deaths could be prevented or postponed for scenario A, 13,900 deaths for scenario B, and 5,800 for scenario C. For all scenarios, the highest percentages of DPP by type of CVD are related to ischemic heart disease, hypertensive disease, and stroke. CONCLUSIONS: The results show that if Mexico considers implementing policies with greater impact to reduce sodium/salt consumption, a significant number of deaths from CVD could be prevented or postponed.

Risk Prediction Score for Chronic Kidney Disease in Healthy Adults and Adults With Type 2 Diabetes: Systematic Review.

INTRODUCTION: Chronic kidney disease (CKD) is an important public health problem. In 2017, the global prevalence was estimated at 9.1%. Appropriate tools to predict the risk of developing CKD are necessary to prevent its progression. Type 2 diabetes is a leading cause of CKD; screening the population living with the disease is a cost-effective solution to prevent CKD. The aim of our study was to identify the existing prediction scores and their diagnostic accuracy for detecting CKD in apparently healthy populations and populations with type 2 diabetes. METHODS: We conducted an electronic search in databases, including Medline/PubMed, Embase, Health Evidence, and others. For the inclusion criteria we considered studies with a risk predictive score in healthy populations and populations with type 2 diabetes. We extracted information about the models, variables, and diagnostic accuracy, such as area under the receiver operating characteristic curve (AUC), C statistic, or sensitivity and specificity. RESULTS: We screened 2,359 records and included 13 studies for healthy population, 7 studies for patients with type 2 diabetes, and 1 for both populations. We identified 12 models for patients with type 2 diabetes; the range of C statistic was from 0.56 to 0.81, and the range of AUC was from 0.71 to 0.83. For healthy populations, we identified 36 models with the range of C statistics from 0.65 to 0.91, and the range of AUC from 0.63 to 0.91. CONCLUSION: This review identified models with good discriminatory performance and methodologic quality, but they need more validation in populations other than those studied. This review did not identify risk models with variables comparable between them to enable conducting a meta-analysis.

Espacios cardioprotegidos en México: acciones para prevenir la muerte súbita cardiaca. Una postura de profesionales de la salud.

La muerte súbita cardiaca es un problema de salud pública a nivel mundial. Aunque su incidencia no es conocida, se estima que causa hasta 50% de la mortalidad de origen cardíaco y hasta 20% de la mortalidad total en los adultos. En México, estimaciones previas sugieren que causa en promedio 33 000 muertes al año; sin embargo, los datos no son precisos. La  mitad de los eventos por muerte súbita cardiaca se deben a un paro cardiaco súbito extrahospitalario que, de no ser atendido oportunamente, deriva en una muerte súbita cardiaca. Por tanto, la capacidad de responder pronta y adecuadamente a estos eventos con las maniobras y equipos necesarios mejora la sobrevida de las víctimas. Para atender este problema, en algunos estados del país se han creado espacios cardioprotegidos que permiten realizar maniobras de reanimación cardiopulmonar y desfibrilación cardiaca de acceso público oportunamente. Como objetivo, los profesionales de la salud establecen la importancia de implementar espacios cardioprotegidos y crear políticas públicas al respecto en todo el país.

Recognition of a novel variant of phosphoglycerate kinase 1 deficiency PGK1 Galveston (c.472G > C) in a child with hemolytic anemia, neurologic dysfunction and myopathy.

The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of PGK1 present clinically with varying manifestations including hemolytic anemia, central nervous system (CNS) dysfunction and myopathy. Various PGK1 mutations have been described in the literature at the clinical and molecular level. Herein, we describe a novel case PGK1 mutation (PGK1 Galveston) in a 4-year-old boy who presented with all three manifestations. We discuss the characteristic hematopathology findings from this patient as well as provide a comparison with previously described neuroimaging findings. The variable clinical presentation of this condition along with its inherent uniqueness provide a diagnostic challenge for physicians. This presentation will add to the current body of knowledge for this condition and help guide future investigation and management.

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.

Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer's disease (AD). Although neurologic symptoms triggered by mild traumatic brain injuries (mTBI), the most common form of TBI, typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid ß peptide (Aß), a cleaved fragment of amyloid precursor protein (APP), is a key pathologic outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport. However, relationships among mTBI, amyloidogenesis, and axonal transport remain unclear, in part because of the dearth of human models to study the neuronal response following mTBI. Here, we implemented a custom-microfabricated device to deform neurons derived from human-induced pluripotent stem cells, derived from a cognitively unimpaired male individual, to mimic the mild stretch experienced by neurons during mTBI. Although no cell lethality or cytoskeletal disruptions were observed, mild stretch was sufficient to stimulate rapid amyloidogenic processing of APP. This processing led to abrupt cessation of APP axonal transport and progressive formation of aberrant axonal accumulations that contained APP, its processing machinery, and amyloidogenic fragments. Consistent with this sequence of events, stretch-induced defects were abrogated by reducing amyloidogenesis either pharmacologically or genetically. In sum, we have uncovered a novel and manipulable stretch-induced amyloidogenic pathway directly responsible for APP axonal transport dysregulation. Our findings may help to understand and ultimately mitigate the risk of developing AD following mTBI.SIGNIFICANCE STATEMENT Mild traumatic brain injury is a risk factor for sporadic Alzheimer's disease (AD). Increased amyloid ß peptide generation after injury may drive this risk. Here, by using a custom-built device to impose mild stretch to human neurons, we found that stretch triggers amyloid precursor protein (APP) cleavage, and thus amyloid ß peptide generation, consequently disrupting APP axonal transport. Compellingly, protecting APP from cleavage was sufficient to spare axonal transport dysregulation and the consequent aberrant axonal accumulation of APP. Supporting such protective mechanism, the expression of the AD-protective APPA673T genetic variant conferred protection against stretch-induced APP axonal transport phenotypes. Our data reveal potential subcellular pathways contributing to the development of AD-associated phenotypes following mild traumatic brain injury, and putative strategies for intervening in these pathways.

Dietary inflammatory index and bone mineral density in Mexican population.

Dietary inflammatory index has been associated with bone loss. In this longitudinal study, we reported that changes in dietary inflammatory index were associated with a reduction in bone mineral density of the total hip and femoral neck in males and females ≥ 45 years, but not in individuals < 45 years. PURPOSE: Previous studies have suggested that an inflammatory environment can affect bone mineral density (BMD). However, most of the studies have been done in postmenopausal women. Thus, longitudinal studies in different age groups and sex are necessary to evaluate the longitudinal association between dietary inflammatory index (DII) and BMD in Mexican adults. METHODS: A total of 1,486 participants of the Health Workers Cohort Study were included in this study. The DII was estimated with data retrieved through a semi-quantitative food frequency questionnaire. Total hip, femoral neck, and lumbar spine BMD were measured by dual-energy X-ray absorptiometry. Linear regression models for cross-sectional associations and fixed effects linear regression models for longitudinal association were estimated, and both models were stratified by sex and age groups (< 45 and ≥ 45 years). RESULTS: We did not observe cross-sectional associations between DII and the different BMD sites at baseline. In contrast, women and men ≥ 45 years in the 25th quartile of changes in DII were associated with a gain of 0.067 g/cm2 and 0.062 g/cm2 of total hip BMD, while those in the 75th quartile of DII was associated with a reduction of - 0.108 g/cm2 and - 0.100 g/cm2, respectively. These results were similar for femoral neck BMD in women. In contrast, we did not observe association with femoral neck BMD in men. We did not observe statistically significant changes for lumbar spine BMD. CONCLUSION: Our data suggest that changes in the DII score are associated with changes in total hip and femoral neck BMD among Mexican population.

Muscle Strength Reference Values and Correlation with Appendicular Muscle Mass in Mexican Children and Adolescents.

Strength and muscle mass are important determinants of health status, and reference values for pediatric populations from every country or geographic region are needed. The aim of this study was to develop age- and sex-specific reference values of muscle strength and evaluate the correlation between muscle strength and appendicular lean mass in Mexican children and adolescents. A cross-sectional study was conducted in 1111 healthy subjects ages 5 to 19 years of age participating in the "Body Composition Reference Values in Mexican Children and Adolescents" study. Smoothed reference values for the 1, 3, 5, 15, 25, 50, 75, 85, 95, 97, and 99 percentiles of muscle strength for upper and lower limbs were developed based on age and sex using Jamar® and Microfet2® dynamometers. Mean values were derived using the Generalized Additive Models for Location, Scale and Shape (GAMLSS), and lean mass was determined using dual-energy X-ray absorptiometry. Highly positive correlations of muscle strength with lean mass in upper limbs were found r-values 0.87-0.92 for boys and r = 0.80-0.86 for girls. High and moderate positive correlations for lower limbs were also noted for upper limbs: r = 0.74-0.86 for boys and r = 0.67-0.82 for girls. The reference values for appendicular muscle strength established in this study demonstrated a high and positive correlation between appendicular mass and muscle strength. These data will be useful when evaluating conditions and diseases affecting muscle or sports.

Association between physical activity and physical and functional performance in non-institutionalized Mexican older adults: a cohort study.

BACKGROUND: Aging is an independent risk factor for deterioration in functional capacity. Some studies have reported that physical activity (PA) improves functional capacity and physical performance among older adults (OA). Thus the objective of the present study was to assess the longitudinal association between PA and functional and physical performance in non-institutionalized OA. METHODS: A longitudinal analysis using data from the Frailty, Dynapenia and Sarcopenia in Mexican adults (FRADYSMEX, by its Spanish acronym) cohort study was conducted. PA was assessed through the Community Healthy Activities Model Program for Seniors (CHAMPS) instrument. Functionality was measured with the Barthel index and the Lawton and Brody scale, while physical performance was measured with the Short Physical Performance Battery (SPPB). To evaluate the association between the level of PA and physical and functional performance as a continuous variable, a linear regression of mixed effects was performed. To assess PA and dependence in basic activities of the daily life (BADL), instrumental activities of the daily life (IADL), and low physical performance (PP), generalized estimation equation models [to compute odds ratios (OR) and 95% confidence intervals (95%CI)] were computed. RESULTS: Older people who performed moderate to vigorous-intensity PA had a lower risk of dependence in IADL (OR = 0.17; 95%CI: 0.10, 0.80) and lower risk of low PP (OR = 0.18; 95%CI: 0.11, 0.58) compared to those in lower categories of PA. CONCLUSIONS: Older adults living in the community who perform PA of moderate to vigorous intensity have a lower risk of dependence in BADL and IADL and have a lower risk of low PP.

Validity and reliability of the International Physical Activity Questionnaire (IPAQ) long-form in a subsample of female Mexican teachers.

OBJECTIVE: To evaluate the test-retest reliability and validity of the long-form International Physical Activity Questionnaire (IPAQ-long form). MATERIALS AND METHODS: A subsample of 86 teachers underwent telephone interviews and clinic visits in Mexico City. Through 22 months, physical activity (PA) levels were obtained from accelerometers (months 6 and 22) and IPAQ long-form (months 1, 3, 6, 9 and 12). Minutes per week of moderate (MPA), walking (WPA), vigorous (VPA) and moderate-to-vigorous physical activity (MVPA) were calculated for each intensity and domain. Variables were loga-rithmically transformed. Intra-class and Pearson correlations were used to determine the relationship between instru-ments. RESULTS: Test-retest reliability of the average IPAQs long-form varied across intensities and domains (ranged from r= 0.24 to r= 0.65). Minutes per week of VPA and MVPA ac-celerometer 1 (AC1) were fairly associated to International Physical Activity Questionnaire-long form 3 (IPAQ3) (r= 0.60 and r= 0.31, respectively) one week apart. CONCLUSIONS: IPAQ long-form is fairly reliable for MVPA and valid for as-sessing MVPA and VPA in a subsample of Mexican teachers.

The Mexican Consortium of Epidemiological Studies for the Prevention, Diagnosis, and Treatment of Chronic Kidney Disease: a review of collaborating studies.

OBJECTIVE: To harmonize participants' information from five epidemiological studies. MATERIALS AND METHODS: The Mexican Consortium of Epidemiological Studies for the Prevention, Diagnosis, and Treatment of Chronic Kidney Disease (RenMex, by its Spanish acronym) was established in 2018. RenMex is a consortium of five studies: The Mexican Teachers Cohort Study; the Mexico City Diabetes Study; the Health Workers Cohort Study; the Comitán Study; and the Salt Consumption in Mexico Study, which assessed baseline serum creatinine, albumin, and C-reactive protein, all performed with standardized techniques. RESULTS: RenMex includes 3 133 participants, with a mean age of 44.8 years, 68.8% women, 10.8% with a previous medical diagnosis of type 2 diabetes, and 24.1% living with obesity. CONCLUSIONS: In the future, RenMex will work on more detailed analyses with each cohort allowed to opt in or out for each topic according to their individual data.

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud.

La creciente epidemia de obesidad ha sido uno de los retos más importantes de salud pública en México durante los últimos años. Con apoyo de la Federación Mundial de Obesidad, en 2021 formamos un grupo de profesionales para identificar y resumir las acciones prioritarias en las que puede enfocarse nuestro país para hacer frente a esta epidemia. Al proceso de desarrollo y discusión de este grupo se sumaron más de 1 000 profesionales de la salud para retomar recomendaciones de documentos y guías de alto nivel previamente publicados. En conmemoración del Día Mundial de la Obesidad, en este 2022 se presenta esta postura como insumo para el desarrollo de acciones en el ámbito profesional y de los diferentes sectores, en la que se incluyen 10 recomendaciones de acción, desde la perspectiva poblacional hasta la atención individualizada, y se enfatiza en la importancia de la participación social, de las intervenciones integrales con visión centrada en la persona y de la sostenibilidad planetaria, además de mejorar la educación y las campañas de difusión, propiciar un ambiente promotor de entornos activos y blindar de conflictos de interés los esfuerzos de prevención y control. La postura hace un llamado para abordar la obesidad de manera seria, con base en la evidencia científica, oportuna e integral, con enfoque de curso de vida, de forma ética y sensible, y sin perpetuar las barreras del estigma de peso en la sociedad.

Elastic wrinkling of keratocyte lamellipodia driven by myosin-induced contractile stress.

During actin-based cell migration, the actin cytoskeleton in the lamellipodium both generates and responds to force, which has functional consequences for the ability of the cell to extend protrusions. However, the material properties of the lamellipodial actin network and its response to stress on the timescale of motility are incompletely understood. Here, we describe a dynamic wrinkling phenotype in the lamellipodium of fish keratocytes, in which the actin sheet buckles upward away from the ventral membrane of the cell, forming a periodic pattern of wrinkles perpendicular to the cell's leading edge. Cells maintain an approximately constant wrinkle wavelength over time despite new wrinkle formation and the lateral movement of wrinkles in the cell frame of reference, suggesting that cells have a preferred or characteristic wrinkle wavelength. Generation of wrinkles is dependent upon myosin contractility, and their wavelength scales directly with the density of the actin network and inversely with cell adhesion. These results are consistent with a simple physical model for wrinkling in an elastic sheet under compression and suggest that the lamellipodial cytoskeleton behaves as an elastic material on the timescale of cell migration despite rapid actin turnover.

Tau/MAPT disease-associated variant A152T alters tau function and toxicity via impaired retrograde axonal transport.

Mutations in the microtubule-associated protein tau (MAPT) underlie multiple neurodegenerative disorders, yet the pathophysiological mechanisms are unclear. A novel variant in MAPT resulting in an alanine to threonine substitution at position 152 (A152T tau) has recently been described as a significant risk factor for both frontotemporal lobar degeneration and Alzheimer's disease. Here we use complementary computational, biochemical, molecular, genetic and imaging approaches in Caenorhabditis elegans and mouse models to interrogate the effects of the A152T variant on tau function. In silico analysis suggests that a threonine at position 152 of tau confers a new phosphorylation site. This finding is borne out by mass spectrometric survey of A152T tau phosphorylation in C. elegans and mouse. Optical pulse-chase experiments of Dendra2-tau demonstrate that A152T tau and phosphomimetic A152E tau exhibit increased diffusion kinetics and the ability to traverse across the axon initial segment more efficiently than wild-type (WT) tau. A C. elegans model of tauopathy reveals that A152T and A152E tau confer patterns of developmental toxicity distinct from WT tau, likely due to differential effects on retrograde axonal transport. These data support a role for phosphorylation of the variant threonine in A152T tau toxicity and suggest a mechanism involving impaired retrograde axonal transport contributing to human neurodegenerative disease.

Diet Modulates the Effects of Genetic Variants on the Vitamin D Metabolic Pathway and Bone Mineral Density in Mexican Postmenopausal Women.

BACKGROUND: Macro- and micronutrients, such as proteins, vitamin D, and calcium (Ca), are important dietary factors that can modify bone mineral density (BMD). Genetic factors can interact with diet, affecting an individual's predisposition to osteoporosis. OBJECTIVES: This study aimed to evaluate the associations between macro- and micronutrient intakes and BMD in Mexican postmenopausal women, and their interactions with genetic polymorphisms involved in the vitamin D metabolic pathway. METHODS: We analyzed data from 317 postmenopausal women from the Health Workers Cohort Study, a longitudinal cohort studied in Cuernavaca, Mexico. Postmenopausal women participated in 2 data collection waves (2004-2006 and 2010-2011), with a mean time of 6.4 years. Dietary intake was assessed with a semi-quantitative FFQ. BMD (femoral neck, hip, and lumbar spine) was measured by DXA. Hybrid mixed-effects regression models were used to assess the associations of dietary macro- and micronutrients on BMD, after adjusting for confounding factors and for diet and single nucleotide polymorphism interactions. RESULTS: At baseline, the median age was 57 years (IQR, 50-64). Mean femoral neck, hip, and lumbar spine BMDs decreased over time. We observed statistically significant longitudinal associations for diet (Ca, vitamin D, magnesium, phosphorus, and protein intake) and BMD. Increases of vitamin D, Ca, and protein intakes by 1 SD were associated with mean increases in the femoral neck BMD (0.083 SD, 0.064 SD, and 0.130 SD, respectively). Multiple significant interactions were identified between several loci (CYP2R1, CYP24A1, CYP27B1, VDR, and DHCR7/NADSYN1) and diet for BMDs (femoral neck, hip, and lumbar spine), mainly for protein intake. CONCLUSIONS: Our data support associations of vitamin D, Ca, protein, phosphorous, and magnesium consumption with BMD in Mexican postmenopausal women and suggest possible gene-diet interactions. These results could facilitate future personalized nutrition recommendations to help prevent low BMD.

Dietary Patterns and Breast Cancer Risk in Women from Northern Mexico.

We evaluated the association between dietary patterns and breast cancer (BC) subtypes among women from Northern Mexico. From a study of incident cases and population controls that was carried out from 2007 to 2011, a subsample of 509 cases matched 1:1 by age with 509 controls was selected. Information about expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) was available from medical records to classify BC on luminal (ER + and/or PR+/HER2-), HER2+ (ER+/- and/or PR+/-/HER2+), or triple negative (ER- and PR-/HER2-). Dietary information was gathered using a semiquantitative food frequency questionnaire and a factor analysis was used to obtain dietary patterns. The association between each dietary pattern and BC molecular subtypes was assessed through conditional logistic regression models. Two dietary patterns were identified. The first (mainly characterized by meat, high fat, and sugary cereals) was positively associated with BC (odds ratio, OR = 12.62; 95% CI: 7.42, 21.45); the second (consisting of corn, legumes, and other vegetables) was inversely associated with BC (OR = 0.50; 95% CI: 0.40, 0.62). Both associations remained significant by BC molecular subtypes. These findings could contribute to the development of public health strategies for BC prevention.