Genotyping, sequencing and analysis of 140,000 adults from Mexico City.

The Mexico City Prospective Study is a prospective cohort of more than 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City1. Here we generated genotype and exome-sequencing data for all individuals and whole-genome sequencing data for 9,950 selected individuals. We describe high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Indigenous American, European and African ancestry, with extensive admixture from Indigenous populations in central, southern and southeastern Mexico. Indigenous Mexican segments of the genome had lower levels of coding variation but an excess of homozygous loss-of-function variants compared with segments of African and European origin. We estimated ancestry-specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Indigenous Mexican ancestry at exome variants, all available through a public browser. Using whole-genome sequencing, we developed an imputation reference panel that outperforms existing panels at common variants in individuals with high proportions of central, southern and southeastern Indigenous Mexican ancestry. Our work illustrates the value of genetic studies in diverse populations and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States, where the Hispanic/Latino population is predominantly of Mexican descent.

Modeling environmentally mediated rotavirus transmission: The role of temperature and hydrologic factors.

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a meta-analysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P [Formula: see text] 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates.

Dióxido de Carbono - una substancia que debe manipularse con cuidado / Carbon Dioxide - a Substance to be Manipulated with Care

La hiperventilación ha sido parte del manejo del paciente neuroquirúrgico desde hace más de medio siglo. Ya desde 1936 se había observado una relación entre el dióxido de carbono arterial y el flujo sanguíneo cerebral (FSC)1; sin embargo, no fue sino hasta 20 años más tarde que esta relación vino a formar parte de la práctica clínica en forma más regular. Lundberg, Lassen y, posteriormente, Gordon utilizaron y recomendaron su uso en pacientes con presión intracraneal elevada después de trauma cefálico y Furness describió su uso en craneotomía electiva2-5. En estudios de aquella época, incluyendo el reporte por Furness, no queda claro si los pacientes tenían un nivel reducido de dióxido de carbono y en hasta qué punto no se medían siempre los gases arteriales. Por lo tanto, los beneficios podrían haberse debido a un mejor manejo de la vía aérea y a la oxigenación por intubación y ventilación, en comparación con ventilación espontánea. También es evidente a partir de la literatura que los efectos de la hiperventilación no eran consistentes en todos los pacientes; es decir, algunos pacientes respondían y otros no6-7. A pesar de ello, la hiperventilación se convirtió en el manejo estándar de los pacientes con presión intracraneal elevada sometidos a cirugía electiva o en la unidad de cuidados intensivos.