Hypertension and Histopathology Severity of Non-Alcoholic Fatty Liver Disease Among Adults with Obesity: A Cross-Sectional Study

Diego Chambergo-Michilot,1,* Paola K Rodrigo-Gallardo,2 Mariella R Huaman,3,* Angie Z Vasquez-Chavesta,4 Gustavo Salinas-Sedo,5 Carlos J Toro-Huamanchumo6,7,* 1Universidad Científica del Sur, Lima, Peru; 2Hospital Docente Las Mercedes, Chiclayo, Peru; 3Facultad de Medicina Humana, Universidad Nacional Mayor de San Marcos, Lima, Peru; 4Facultad de Medicina Humana, Universidad Católica Santo Toribio de Mogrovejo, Chiclayo, Peru; 5Unidad de Investigación Multidisciplinaria, Clínica Avendaño, Lima, Peru; 6Unidad de Investigación para la Generación y Síntesis de Evidencias en Salud, Universidad San Ignacio de Loyola, Lima, Peru; 7OBEMET Centro de Obesidad y Salud Metabólica, Lima, Peru*These authors contributed equally to this workCorrespondence: Carlos J Toro-Huamanchumo, Universidad San Ignacio de Loyola, Av. la Fontana 550, La Molina, Lima, 15024, Peru, Tel + 51944942888, Email [email protected]: Cardiovascular diseases are responsible for the majority of deaths resulting from non-alcoholic fatty liver disease (NAFLD). NAFLD is associated with hypertension and this is a key predictor of severe liver outcomes and an indicator of nonspecific portal fibrosis.Aim: To assess the association between hypertension and NAFLD severity.Methods: We conducted a secondary analysis of data from Peruvian adults with obesity and NAFLD who attended a Peruvian bariatric center. The severity of NAFLD was assessed using the Fatty Liver Inhibition of Progression algorithm / Steatosis, Activity and Fibrosis score. Hypertension was determined by either being recorded in the medical records or if the patient had a systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg. To evaluate the association of interest, we calculated crude and adjusted prevalence ratios (aPR) using Poisson generalized linear models with logarithmic link function and robust variances. For the multivariable models, we adjusted for age, sex, physical activity and smoking.Results: Our study included 234 participants. The prevalence of hypertension was 19.2%, while the prevalence of severe NAFLD was 46.2%. After adjusting for confounders, the prevalence of hypertension was found to be significantly higher in the severe NAFLD group compared to the non-severe group (aPR = 1.33; 95% CI: 1.03– 1.74). When stratified by the presence of metabolic syndrome (MetS), the association remained significant only in the group without MetS (aPR = 1.80; 95% CI: 1.05– 3.11).Conclusion: We found an association between hypertension and severe NAFLD in adults with obesity, particularly in those without MetS.Keywords: non-alcoholic fatty liver disease, hypertension, obesit

Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions.

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual guide RNAs in three cell lines, comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified, and these patterns replicated with combinatorial drugs at 75% precision. From these results, we anticipate that cellular context will be critical to synthetic-lethal therapies

Dynamic excitatory and inhibitory gain modulation can produce flexible, robust and optimal decision-making

<div><p>Behavioural and neurophysiological studies in primates have increasingly shown the involvement of urgency signals during the temporal integration of sensory evidence in perceptual decision-making. Neuronal correlates of such signals have been found in the parietal cortex, and in separate studies, demonstrated attention-induced gain modulation of both excitatory and inhibitory neurons. Although previous computational models of decision-making have incorporated gain modulation, their abstract forms do not permit an understanding of the contribution of inhibitory gain modulation. Thus, the effects of co-modulating both excitatory and inhibitory neuronal gains on decision-making dynamics and behavioural performance remain unclear. In this work, we incorporate time-dependent co-modulation of the gains of both excitatory and inhibitory neurons into our previous biologically based decision circuit model. We base our computational study in the context of two classic motion-discrimination tasks performed in animals. Our model shows that by simultaneously increasing the gains of both excitatory and inhibitory neurons, a variety of the observed dynamic neuronal firing activities can be replicated. In particular, the model can exhibit winner-take-all decision-making behaviour with higher firing rates and within a significantly more robust model parameter range. It also exhibits short-tailed reaction time distributions even when operating near a dynamical bifurcation point. The model further shows that neuronal gain modulation can compensate for weaker recurrent excitation in a decision neural circuit, and support decision formation and storage. Higher neuronal gain is also suggested in the more cognitively demanding reaction time than in the fixed delay version of the task. Using the exact temporal delays from the animal experiments, fast recruitment of gain co-modulation is shown to maximize reward rate, with a timescale that is surprisingly near the experimentally fitted value. Our work provides insights into the simultaneous and rapid modulation of excitatory and inhibitory neuronal gains, which enables flexible, robust, and optimal decision-making.</p></div

Effect of the US-Mexico border region in cardiovascular mortality: ecological time trend analysis of Mexican border and non-border municipalities from 1998 to 2012

Abstract Background An array of risk factors has been associated with cardiovascular diseases, and developing nations are becoming disproportionately affected by such diseases. Cardiovascular diseases have been reported to be highly prevalent in the Mexican population, but local mortality data is poor. The Mexican side of the US-Mexico border has a culture that is closely related to a developed nation and therefore may share the same risk factors of cardiovascular diseases. We wanted to explore if there was higher cardiovascular mortality in the border region of Mexico compared to the rest of the nation. Methods We conducted a population based cross-sectional time series analysis to estimate the effects of education, insurance and municipal size in Mexican border (n = 38) and non-border municipalities (n = 2360) and its association with cardiovascular age-adjusted mortality rates between the years 1998–2012. We used a mixed effect linear model with random effect estimation and repeated measurements to compare the main outcome variable (mortality rate), the covariates (education, insurance and population size) and the geographic delimiter (border/non-border). Results Mortality due to cardiovascular disease was consistently higher in the municipalities along the US-Mexico border, showing a difference of 78 · 5 (95% CI 58 · 7-98 · 3, p < 0 · 001) more cardiovascular deaths after adjusting for covariates. Larger municipal size and higher education levels showed a reduction in cardiovascular mortality of 12 · 6 (95% CI 11 · 4-13 · 8, p < 0 · 001) deaths and 8 · 6 (95% CI 5 · 5-11 · 8, p < 0 · 001) deaths respectively. Insurance coverage showed an increase in cardiovascular mortality of 3 · 6 (95% CI 3 · 1-4 · 0, p < 0 · 001) deaths per decile point increase. There was an increase in cardiovascular mortality of 0 · 3 (95% CI −0 · 001-0 · 6, p = 0 · 050) deaths per year increase in the non-border but a yearly reduction of 2 · 9 (95% CI 0 · 75-5.0, p = 0 · 008) deaths in the border over the time period of 1998–2012. Conclusion We observed that the Mexican side of the US-Mexico border region is disproportionately affected by cardiovascular disease mortality as compared to the non-border region of Mexico. This was not explained by education, population density, or insurance coverage. Proximity to the US culture and related diet and habits can be explanations of the increasing mortality trend

A Gap Analysis Methodology for Collecting Crop Genepools: A Case Study with Phaseolus Beans

Background The wild relatives of crops represent a major source of valuable traits for crop improvement. These resources are threatened by habitat destruction, land use changes, and other factors, requiring their urgent collection and long-term availability for research and breeding from ex situ collections. We propose a method to identify gaps in ex situ collections (i.e. gap analysis) of crop wild relatives as a means to guide efficient and effective collecting activities. Methodology/Principal Findings The methodology prioritizes among taxa based on a combination of sampling, geographic, and environmental gaps. We apply the gap analysis methodology to wild taxa of the Phaseolus genepool. Of 85 taxa, 48 (56.5%) are assigned high priority for collecting due to lack of, or under-representation, in genebanks, 17 taxa are given medium priority for collecting, 15 low priority, and 5 species are assessed as adequately represented in ex situ collections. Gap “hotspots”, representing priority target areas for collecting, are concentrated in central Mexico, although the narrow endemic nature of a suite of priority species adds a number of specific additional regions to spatial collecting priorities. Conclusions/Significance Results of the gap analysis method mostly align very well with expert opinion of gaps in ex situ collections, with only a few exceptions. A more detailed prioritization of taxa and geographic areas for collection can be achieved by including in the analysis predictive threat factors, such as climate change or habitat destruction, or by adding additional prioritization filters, such as the degree of relatedness to cultivated species (i.e. ease of use in crop breeding). Furthermore, results for multiple crop genepools may be overlaid, which would allow a global analysis of gaps in ex situ collections of the world's plant genetic resource

Adaptation and conservation insights from the koala genome

The koala, the only extant species of the marsupial family Phascolarctidae, is classified as ‘vulnerable’ due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala’s ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala’s survival in the wild