Single nucleotide polymorphisms associated with susceptibility for development of colorectal cancer: Case-control study in a Basque population

Given the significant population diversity in genetic variation, we aimed to investigate whether single nucleotide polymorphisms (SNPs) previously identified in studies of colorectal cancer (CRC) susceptibility were also relevant to the population of the Basque Country (North of Spain). We genotyped 230 CRC cases and 230 healthy controls for 48 previously reported CRC-susceptibility SNPs. Only the rs6687758 in DUPS10 exhibited a statistically significant association with CRC risk based on the crude analysis. The rs6687758 AG genotype conferred about 2.13-fold increased risk for CRC compared to the AA genotype. Moreover, we found significant associations in cases between smoking status, physical activity, and the rs6687758 SNP. The results of a Genetic Risk Score (GRS) showed that the risk alleles were more frequent in cases than controls and the score was associated with CRC in crude analysis. In conclusion, we have confirmed a CRC susceptibility locus and the existence of associations between modifiable factors and the rs6687758 SNP; moreover, the GRS was associated with CRC. However, further experimental validations are needed to establish the role of this SNP, the function of the gene identified, as well as the contribution of the interaction between environmental factors and this locusto the risk of CRC.This work was supported by two projects (from the Department of Health and Consumer Affairs, Basque Government 2011111153; and Saiotek, Basque Government S-PE12UN058), by a pre-doctoral grant from the Basque Government (PRE_2016_2_0046), by the CIBERehd and by the U.S. Department of Agriculture-Agricultural Research Service (ARS), under agreement. 581950-4-003. Neither Basque Government nor U.S. Department of Agriculture-Agricultural Research Service (ARS) had a role in the design, analysis or writing of this article. CIBERehd is funded by the Instituto de Salud Carlos III

Food groups, diet quality and colorectal cancer risk in the Basque Country

BACKGROUND The results obtained to date concerning food groups, diet quality and colorectal cancer (CRC) risk vary according to criteria used and the study populations. AIM To study the relationships between food groups, diet quality and CRC risk, in an adult population of the Basque Country (North of Spain). METHODS This observational study included 308 patients diagnosed with CRC and 308 ageand sex-matched subjects as controls. During recruitment, dietary, anthropometric, lifestyle, socioeconomic, demographic and health status information was collected. Adherence to the dietary recommendations was evaluated utilizing the Healthy Eating Index for the Spanish Diet and the MedDietScore. Conditional logistic regressions were used to evaluate the associations of food group intakes, diet quality scores, categorized in tertiles, with CRC risk. RESULTS The adjusted models for potential confounding factors showed a direct association between milk and dairy products consumption, in particular high-fat cheeses [odds ratio (OR) third tertile vs first tertile = 1.87, 95% confidence intervals (CI): 1.11-3.16], and CRC risk. While the consumption of fiber-containing foods, especially whole grains (OR third tertile vs first tertile = 0.62, 95%CI: 0.39-0.98), and fatty fish (OR third tertile vs first tertile = 0.53, 95%CI: 0.27-0.99) was associated with a lower risk for CRC. Moreover, higher MD adherence was associated with a reduced CRC risk in adjusted models (OR third tertile vs first tertile = 0.40, 95%CI: 0.20-0.80). CONCLUSION Direct associations were found for high-fat cheese, whereas an inverse relation was reported for fiber-containing foods and fatty fish, as well as adherence to a Mediterranean dietary pattern.Supported by the Department of Health and Consumer Affairs, Basque Government, No. 2011111153; Saiotek, Basque Government, No. S-PE12UN058; Pre-doctoral grant from the Basque Government, No. PRE_2015_2_0084; and United States Department of Agriculture—Agricultural Research Service, No. 58-1950-4-003

Gene–Diet Interactions in Colorectal Cancer: Survey Design, Instruments, Participants and Descriptive Data of a Case–Control Study in the Basque Country

Epidemiologic studies have revealed inconsistent evidence of gene-diet interaction in relation to colorectal cancer (CRC). The aim of this study was to analyze them in a sample of cases and controls from the population-based bowel cancer screening program of the Osakidetza/Basque Health Service. This study analyzed dietetic, genetic, demographic, socioeconomic factors and lifestyles. In the present manuscript, the survey design, sampling, instruments, measurements and related quality management were presented. Moreover, we analyze di erences between cases and controls in some data, especially those related to diet. The participants were 308 cases and 308 age- and sex-matched subjects as controls. Cases were more likely than controls to have overweight/obesity (67.5% vs. 58.1%, p < 0.05), a lower intake of vitamin B2 (0.86 0.23 vs. 0.92 0.23 mg/1000 kcal, p < 0.01) and calcium:phosphorus ratio (0.62 0.12 vs. 0.65 0.13, p < 0.01). A higher proportion of cases than controls did not meet the Nutritional Objectives for saturated fatty acids (85.7% vs. 67.5%, p < 0.001) or cholesterol (35.4% vs. 25.0%, p < 0.01). In conclusion, the present study provides valuable data for analyzing the complexity of gene-diet interaction in relation to CRC. The results presented here suggest that overweight/obesity and a high intake of certain dietary components, especially saturated fatty acids and cholesterol, are more frequent in cases than in controls.This research was supported by the Department of Health and Consumer A airs of the Basque Government (2011111153) and Saiotek program of the Basque Government (S-PE12UN058). I.A.-L. was founded by a pre-doctoral grant from the Basque Government (PRE_2014_1_161, PRE_2015_2_0084, EP_2016_1_0098, EP_2016_1_0098 and PRE_2017_2_0006). The U.S. Department of Agriculture—Agricultural Research Service (ARS), under Agreement No. 58-1950-4-003. CIBERehd is funded by the Instituto de Salud Carlos III

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

Background: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. Methods: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27–36 weeks’ gestation with crossover 72-hourpostpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/ neonate-related AEs of interest were recorded. Results: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5–19.2) for anti-filamentous hemagglutinin, 20.7 (15.9–26.9) for anti-pertactin and 8.5 (7.0–10.2) for anti-pertussis toxoid. Rates of pregnancy-/ neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. Conclusions: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease.post-print502 K

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Caerulines A and B, Flavonol Diacylglycosides from Persea caerulea

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.Two undescribed 4′-O-methylkaempferol-[3″,4″-di-p-coumaroyl]-α-l-rhamnopyranosides, caerulines A and B (1-2), along with three known 4′-O-methylkaempferol diacylrhamnosides isomers (3-5) were isolated from an ethanol extract of the leaves of Persea caerulea, a native plant growing on the Colombian Caribbean coast. The chemical structures of 1 and 2 were elucidated by spectroscopic methods. The effect of compounds 1-5 against four pathogenic microorganisms [i.e., methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumannii, Candida albicans, and Aspergillus fumigatus] was tested in vitro. The compounds exhibited no activity against these pathogens except MRSA (MIC 12-48 μg/mL). Caeruline B (2) was found to be the most active compound with a modest anti-MRSA activity (MIC = 12 μg/mL).Fundación MEDINAUniversidad Nacional de ColombiaUniversidad del Magdalena proyecto VIN2016225UMNG proyecto IMP-CIAS-292

Reducing Inert Materials for Optimal Cell–Cell and Cell–Matrix Interactions within Microphysiological Systems

In the pursuit of achieving a more realistic in vitro simulation of human biological tissues, microfluidics has emerged as a promising technology. Organ-on-a-chip (OoC) devices, a product of this technology, contain miniature tissues within microfluidic chips, aiming to closely mimic the in vivo environment. However, a notable drawback is the presence of inert material between compartments, hindering complete contact between biological tissues. Current membranes, often made of PDMS or plastic materials, prevent full interaction between cell types and nutrients. Furthermore, their non-physiological mechanical properties and composition may induce unexpected cell responses. Therefore, it is essential to minimize the contact area between cells and the inert materials while simultaneously maximizing the direct contact between cells and matrices in different compartments. The main objective of this work is to minimize inert materials within the microfluidic chip while preserving proper cellular distribution. Two microfluidic devices were designed, each with a specific focus on maximizing direct cell–matrix or cell–cell interactions. The first chip, designed to increase direct cell–cell interactions, incorporates a nylon mesh with regular pores of 150 microns. The second chip minimizes interference from inert materials, thereby aiming to increase direct cell–matrix contact. It features an inert membrane with optimized macropores of 1 mm of diameter for collagen hydrogel deposition. Biological validation of both devices has been conducted through the implementation of cell migration and cell-to-cell interaction assays, as well as the development of epithelia, from isolated cells or spheroids. This endeavor contributes to the advancement of microfluidic technology, aimed at enhancing the precision and biological relevance of in vitro simulations in pursuit of more biomimetic models

Simultaneous assessment of nitrogen and water status in winter wheat using hyperspectral and thermal sensors

Remote sensing is a valuable tool for reducing the environmental impact of agricultural practices by detecting crop nitrogen (N) and water status for site-specific N fertilization and irrigation. The interaction between N and water status may produce confounding effects in the acquired spectral reflectance, making it difficult to separate crop deficiencies. The objective of this study was to evaluate the potential of visible and infrared hyperspectral and thermal imaging sensors for N and water status assessment with reduced confounding effects. A winter wheat (Triticum aestivum L.) field experiment combining four N and two irrigation levels was conducted in Central Spain over 2 years. The Nitrogen Nutrition Index (NNI) was monitored (mid stem elongation, final stem elongation, flowering stage) and the crop water status was measured with a leaf porometer at flowering. Two hyperspectral sensors covering the visible and near infrared regions (400–850 nm) and part of the short-wave infrared (950–1750 nm) together with a thermal camera were installed on-board an aircraft to acquire images 300 m above the experiment. In addition, canopy reflectance (400−1000 nm) was measured with a handheld spectroradiometer at ground level. The relationship between the ground-based determination of N and water status with indicators based on remote sensors was analyzed. The planar domain Canopy Chlorophyll Content Index (CCCI) reduced soil background noise and correlated with the NNI in all cases (R2 > 0.44; P <  0.001). Reliable assessment of water status was achieved by using the Water Deficit Index (WDI), which is calculated using the Vegetation Index-Temperature trapezoid. The CCCI distinguished between N levels reducing the confounding effect of the water status, in contrast to the WDI which was mostly affected by the water status. Combining the CCCI and WDI to assess the crop NNI reduced the root mean square error to 0.109, suggesting that the combination of spectral and thermal information could improve the adjustment of N fertilization and irrigation to crop requirements. However, the approach must be validated in other cultivars and environments before making N fertilization and irrigation recommendations.This work was funded by the Ministerio de Economía y Competitividad (Spain; AGL2017-83283-C2-1-R; PRE2018-084215) and Ministerio de Educación (Spain; FPU17/01251). Comunidad de Madrid, Spain (AGRISOST-CM S2018/BAA-4330 project) and Structural Funds 2014-2020 (ERDF and ESF)

Prolonged on-tree maturation vs. cold storage of Hass avocado fruit: Changes in metabolites of bioactive interest at edible ripeness

When the recipient of the product is relatively distant from the production area, it is necessary to use cold storage and controlled humidity to transport the avocado fruits. One of the main advantages of local avocado consumption lies on the possibility of prolonging on-tree maturation; this could foreseeably modify the metabolic profile of the fruit which arrives to the consumer. In this work, the effect of prolonged on tree maturation (during different time intervals) on the final composition of avocado fruit (at edible ripeness) was evaluated and compared with the impact of the same periods after prolonged cold storage. The quantitative evolution of nine bioactive metabolites (7 phenolic compounds, pantothenic and abscisic acids) over 40 days (10-days intervals) was studied by using a solid-liquid extraction protocol and a LC-MS methodology. The results were discussed both considering the quantitative evolution of each individual compound and the sum of all of them.Universidad de Granada/CBU