vgaraujov/thesis-chile huggingface dataset:
Association of IL4Rsingle-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis

Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.
Mildly elevated lactate levels are associated with microcirculatory flow abnormalities and increased mortality: a microSOAP post hoc analysis

Abstract Background Mildly elevated lactate levels (i.e., 1–2 mmol/L) are increasingly recognized as a prognostic finding in critically ill patients. One of several possible underlying mechanisms, microcirculatory dysfunction, can be assessed at the bedside using sublingual direct in vivo microscopy. We aimed to evaluate the association between relative hyperlactatemia, microcirculatory flow, and outcome. Methods This study was a predefined subanalysis of a multicenter international point prevalence study on microcirculatory flow abnormalities, the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Microcirculatory flow abnormalities were assessed with sidestream dark-field imaging. Abnormal microcirculatory flow was defined as a microvascular flow index (MFI) < 2.6. MFI is a semiquantitative score ranging from 0 (no flow) to 3 (continuous flow). Associations between microcirculatory flow abnormalities, single-spot lactate measurements, and outcome were analyzed. Results In 338 of 501 patients, lactate levels were available. For this substudy, all 257 patients with lactate levels ≤ 2 mmol/L (median [IQR] 1.04 [0.80–1.40] mmol/L) were included. Crude ICU mortality increased with each lactate quartile. In a multivariable analysis, a lactate level > 1.5 mmol/L was independently associated with a MFI < 2.6 (OR 2.5, 95% CI 1.1–5.7, P = 0.027). Conclusions In a heterogeneous ICU population, a single-spot mildly elevated lactate level (even within the reference range) was independently associated with increased mortality and microvascular flow abnormalities. In vivo microscopy of the microcirculation may be helpful in discriminating between flow- and non-flow-related causes of mildly elevated lactate levels. Trial registration ClinicalTrials.gov, NCT01179243 . Registered on August 3, 2010.
Mitochondrial permeability transition pore induces mitochondria injury in Huntington disease

Abstract Background Mitochondrial impairment has been implicated in the pathogenesis of Huntington’s disease (HD). However, how mutant huntingtin impairs mitochondrial function and thus contributes to HD has not been fully elucidated. In this study, we used striatal cells expressing wild type (STHdhQ7/Q7) or mutant (STHdhQ111/Q111) huntingtin protein, and cortical neurons expressing the exon 1 of the huntingtin protein with physiological or pathological polyglutamine domains, to examine the interrelationship among specific mitochondrial functions. Results Depolarization induced by KCl resulted in similar changes in calcium levels without compromising mitochondrial function, both in wild type and mutant cells. However, treatment of mutant cells with thapsigargin (a SERCA antagonist that raises cytosolic calcium levels), resulted in a pronounced decrease in mitochondrial calcium uptake, increased production of reactive oxygen species (ROS), mitochondrial depolarization and fragmentation, and cell viability loss. The mitochondrial dysfunction in mutant cells was also observed in cortical neurons expressing exon 1 of the huntingtin protein with 104 Gln residues (Q104-GFP) when they were exposed to calcium stress. In addition, calcium overload induced opening of the mitochondrial permeability transition pore (mPTP) in mutant striatal cells. The mitochondrial impairment observed in mutant cells and cortical neurons expressing Q104-GFP was prevented by pre-treatment with cyclosporine A (CsA) but not by FK506 (an inhibitor of calcineurin), indicating a potential role for mPTP opening in the mitochondrial dysfunction induced by calcium stress in mutant huntingtin cells. Conclusions Expression of mutant huntingtin alters mitochondrial and cell viability through mPTP opening in striatal cells and cortical neurons.
Vitamin D axis and its role in skin carcinogenesis: a comprehensive review

Abstract Vitamin D (VD) is a secosteroid hormone that is mainly synthesized in the skin upon exposure to UVB radiation. VD is widely known for its role in calcium metabolism; however, multiple endocrine, paracrine and autocrine functions of VD have been described, including a prominent role on carcinogenesis. In recent years, multiple associations between VD deficiency and different types of cancer have been described, supported by evidence of anti-proliferative, anti-angiogenic, pro-apoptotic, cell-differentiating and anti-invasive effects of this hormone. An immunomodulatory role of VD associated to cancer microenvironment has also been suggested. Regarding skin cancer, it has been shown that VD inhibits tumor development in basal cell carcinoma, squamous cell carcinoma, and melanoma in vitro. Some studies have suggested that lower VD levels may be a risk factor for skin cancer, while others have shown the opposite; there is also preliminary evidence on the role of VD supplementation for the prevention of melanoma in vivo. In this review, we explore the mechanisms of VD effects on carcinogenesis and the available scientific evidence of the interplay between VD and the genesis of both non-melanoma and melanoma skin cancer.
Molecular phylogenetic analyses reveal the importance of taxon sampling in cryptic diversity: Liolaemus nigroviridis and L. monticola (Liolaeminae) as focal species

Abstract Background Mitochondrial markers are widely used as a first approach in determining evolutionary relationships among vertebrate taxa at different hierarchical scales. Cytochrome b and cytochrome oxidase I are among the most common markers; they are particularly useful in phylogeography and species delineation studies. Simulation and empirical studies show that increasing the taxon sampling has a clear and strong effect on the accuracy of the inferred trees and therefore on hypothesized phylogenetic relationships (and eventually in new taxonomic rearrangements); this should be considered in the design of studies. The lizard genus Liolaemus is widely distributed in southern South America and includes more than 250 described species. The number of taxa and the distribution of Liolaemus species/populations makes them a good model for testing different hypotheses in systematics. Methods We studied two Liolaemus species, Liolaemus nigroviridis and L. monticola as focal species to evaluate their monophyly and the influence of adding new samples from related taxa in the resulting phylogenies. We performed phylogenetic analyses (maximum likelihood and Bayesian inference) using 141 sequences of the mitochondrial DNA Cytochrome b (cyt-b) of 11 Liolaemus species. Results Our study show that using intensive taxon sampling for phylogenetic reconstructions, two species (L. uniformis and L. nitidus) are placed within the clades of the two focal species (L. nigroviridis and L. monticola, respectively). Conclusions Our study confirms the importance of taxon sampling to infer more accurate phylogenetic relationships, particularly to reveal hidden polyphyly or paraphyly, which may have a strong impact on taxonomic proposals and/or inferring cryptic diversity.
Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

Abstract Background and aims Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Methods and results: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. Conclusions Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
Morphometric and phytochemical characterization of chaura fruits (Gaultheria pumila): a native chilean berry with commercial potential

Abstract Background For the first time, a morphometric characterization of chaura (Gaultheria pumila) fruits has been conducted between natural populations growing in the Villarrica National Park, Araucania Region, Chile. Chaura is a native Ericaceae from Chile that produces aromatic and tasty fruits which could be of agricultural interest. Results To influence the decision for a further domestication of G. pumila, both the fruit sizes (indicator of productivity) and the nutritional properties of the fruits have been determined from different subpopulations. Samples were a total of 74 plants and 15 fruits per plant which were randomly harvested following its natural distribution around the Villarrica volcano. Altogether, fresh weight, shape, color, diameter in the pole and the equatorial dimensions were determined as phenotypic traits of the G. pumila fruits. Meanwhile the total soluble solids, anthocyanin and pectin contents were calculated as nutritional traits of the Chaura fruits. Results showed a high phenotypic diversity between the sampled population with three main fruit shapes and three predominant colors. The round shapes were the most abundant, whereas a significant correlation was found among fruit size with weight and color. The highest fresh weight (597.3 mg), pole diameter (7.1 mm) and equatorial diameter (6.5 mm) were estimated in the pink color fruits. Conclusions The total amount of anthocyanin was higher in red fruits, while the maximum pectin content was obtained in the round white fruits. Overall results must pave the way for a further domestication and introduction of the Chaura species in the agro-productive system in Chile.
Expanding a dynamic flux balance model of yeast fermentation to genome-scale

Abstract Background Yeast is considered to be a workhorse of the biotechnology industry for the production of many value-added chemicals, alcoholic beverages and biofuels. Optimization of the fermentation is a challenging task that greatly benefits from dynamic models able to accurately describe and predict the fermentation profile and resulting products under different genetic and environmental conditions. In this article, we developed and validated a genome-scale dynamic flux balance model, using experimentally determined kinetic constraints. Results Appropriate equations for maintenance, biomass composition, anaerobic metabolism and nutrient uptake are key to improve model performance, especially for predicting glycerol and ethanol synthesis. Prediction profiles of synthesis and consumption of the main metabolites involved in alcoholic fermentation closely agreed with experimental data obtained from numerous lab and industrial fermentations under different environmental conditions. Finally, fermentation simulations of genetically engineered yeasts closely reproduced previously reported experimental results regarding final concentrations of the main fermentation products such as ethanol and glycerol. Conclusion A useful tool to describe, understand and predict metabolite production in batch yeast cultures was developed. The resulting model, if used wisely, could help to search for new metabolic engineering strategies to manage ethanol content in batch fermentations.
Narrative review: clinical assessment of peripheral tissue perfusion in septic shock

Abstract Sepsis is one of the main reasons for intensive care unit admission and is responsible for high morbidity and mortality. The usual hemodynamic targets for resuscitation of patients with septic shock use macro-hemodynamic parameters (hearth rate, mean arterial pressure, central venous pressure). However, persistent alterations of microcirculatory blood flow despite restoration of macro-hemodynamic parameters can lead to organ failure. This dissociation between macro- and microcirculatory compartments brings a need to assess end organs tissue perfusion in patients with septic shock. Traditional markers of tissue perfusion may not be readily available (lactate) or may take time to assess (urine output). The skin, an easily accessible organ, allows clinicians to quickly evaluate the peripheral tissue perfusion with noninvasive bedside parameters such as the skin temperatures gradient, the capillary refill time, the extent of mottling and the peripheral perfusion index.
Factors affecting the implementation of childhood vaccination communication strategies in Nigeria: a qualitative study

Abstract Background The role of health communication in vaccination programmes cannot be overemphasized: it has contributed significantly to creating and sustaining demand for vaccination services and improving vaccination coverage. In Nigeria, numerous communication approaches have been deployed but these interventions are not without challenges. We therefore aimed to explore factors affecting the delivery of vaccination communication in Nigeria. Methods We used a qualitative approach and conducted the study in two states: Bauchi and Cross River States in northern and southern Nigeria respectively. We identified factors affecting the implementation of communication interventions through interviews with relevant stakeholders involved in vaccination communication in the health services. We also reviewed relevant documents. Data generated were transcribed verbatim and analysed using thematic analysis. Results We used the SURE framework to organise the identified factors (barriers and facilitators) affecting vaccination communication delivery. We then grouped these into health systems and community level factors. Some of the commonly reported health system barriers amongst stakeholders interviewed included: funding constraints, human resource factors (health worker shortages, training deficiencies, poor attitude of health workers and vaccination teams), inadequate infrastructure and equipment and weak political will. Community level factors included the attitudes of community stakeholders and of parents and caregivers. We also identified factors that appeared to facilitate communication activities. These included political support, engagement of traditional and religious institutions and the use of organised communication committees. Conclusions Communication activities are a crucial element of immunization programmes. It is therefore important for policy makers and programme managers to understand the barriers and facilitators affecting the delivery of vaccination communication so as to be able to implement communication interventions more effectively.
Fecal bile acid excretion and messenger RNA expression levels of ileal transporters in high risk gallstone patients

Abstract Background Cholesterol gallstone disease (GS) is highly prevalent among Hispanics and American Indians. In GS, the pool of bile acids (BA) is decreased, suggesting that BA absorption is impaired. In Caucasian GS patients, mRNA levels for ileal BA transporters are decreased. We aimed to determine fecal BA excretion rates, mRNA levels for ileal BA transporter genes and of regulatory genes of BA synthesis in Hispanic GS patients. Results Excretion of fecal BA was measured in seven GS females and in ten GS-free individuals, all with a body mass index < 29. Participants ingested the stool marker Cr2O3 (300 mg/day) for 10 days, and fecal specimens were collected on the last 3 days. Chromium was measured by a colorimetric method, and BA was quantitated by gas chromatography/mass spectroscopy. Intake of calories, nutrients, fiber and cholesterol were similar in the GS and GS-free subjects. Mean BA excretion levels were 520 ± 80 mg/day for the GS-free group, and 461 ± 105 mg/day for the GS group. Messenger RNA expression levels were determined by RT-PCR on biopsy samples obtained from ileum during diagnostic colonoscopy (14 GS-free controls and 16 GS patients) and from liver during surgery performed at 8 and 10 AM (12 GS and 10 GS-free patients operated on for gastrointestinal malignancies), all with a body mass index < 29. Messenger RNA level of the BA transporter genes for ileal lipid binding protein, multidrug resistance-associated protein 3, organic solute transporter alpha, and organic solute transporter beta were similar in GS and GS-free subjects. Messenger RNA level of Cyp27A1, encoding the enzyme 27α-hydroxylase, the short heterodimer partner and farnesoid X receptor remained unchanged, whereas the mRNA level of Cyp7A1, the rate limiting step of BA synthesis, was increased more than 400% (p < 0.01) in the liver of GS compared to GS-free subjects. Conclusion Hispanics with GS have fecal BA excretion rates and mRNA levels of genes for ileal BA transporters that are similar to GS-free subjects. However, mRNA expression levels of Cyp7A1 are increased in GS, indicating that regulation of BA synthesis is abnormal in Hispanics with GS.
First meeting “Cystic echinococcosis in Chile, update in alternatives for control anddiagnostics in animals and humans”

Abstract This report summarizes the outcomes of a meeting on cystic echinococcosis (CE) in animals and humans in Chile held in Santiago, Chile, between the 21st and 22nd of January 2016. The meeting participants included representatives of the Departamento de Zoonosis, Ministerio de Salud (Zoonotic Diseases Department, Ministry of Health), representatives of the Secretarias Regionales del Ministerio de Salud (Regional Department of Health, Ministry of Health), Instituto Nacional de Desarrollo Agropecuario (National Institute for the Development of Agriculture and Livestock, INDAP), Instituto de Salud Pública (National Institute for Public Health, ISP) and the Servicio Agrícola y Ganadero (Animal Health Department, SAG), academics from various universities, veterinarians and physicians. Current and future CE control activities were discussed. It was noted that the EG95 vaccine was being implemented for the first time in pilot control programmes, with the vaccine scheduled during 2016 in two different regions in the South of Chile. In relation to use of the vaccine, the need was highlighted for acquiring good quality data, based on CE findings at slaughterhouse, previous to initiation of vaccination so as to enable correct assessment of the efficacy of the vaccine in the following years. The current world’s-best-practice concerning the use of ultrasound as a diagnostic tool for the screening population in highly endemic remote and poor areas was also discussed.
Functional and transcriptomic characterization of carboplatin-resistant A2780 ovarian cancer cell line

Abstract Background Ovarian cancer is a significant cancer-related cause of death in women worldwide. The most used chemotherapeutic regimen is based on carboplatin (CBDCA). However, CBDCA resistance is the main obstacle to a better prognosis. An in vitro drug-resistant cell model would help in the understanding of molecular mechanisms underlying this drug-resistance phenomenon. The aim of this study was to characterize cellular and molecular changes of induced CBDCA-resistant ovarian cancer cell line A2780. Methods The cell selection strategy used in this study was a dose-per-pulse method using a concentration of 100 μM for 2 h. Once 20 cycles of exposure to the drug were completed, the cell cultures showed a resistant phenotype. Then, the ovarian cancer cell line A2780 was grown with 100 μM of CBDCA (CBDCA-resistant cells) or without CBDCA (parental cells). After, a drug sensitivity assay, morphological analyses, cell death assays and a RNA-seq analysis were performed in CBDCA-resistant A2780 cells. Results Microscopy on both parental and CBDCA-resistant A2780 cells showed similar characteristics in morphology and F-actin distribution within cells. In cell-death assays, parental A2780 cells showed a significant increase in phosphatidylserine translocation and caspase-3/7 cleavage compared to CBDCA-resistant A2780 cells (P < 0.05 and P < 0.005, respectively). Cell viability in parental A2780 cells was significantly decreased compared to CBDCA-resistant A2780 cells (P < 0.0005). The RNA-seq analysis showed 156 differentially expressed genes (DEGs) associated mainly to molecular functions. Conclusion CBDCA-resistant A2780 ovarian cancer cells is a reliable model of CBDCA resistance that shows several DEGs involved in molecular functions such as transmembrane activity, protein binding to cell surface receptor and catalytic activity. Also, we found that the Wnt/β-catenin and integrin signaling pathway are the main metabolic pathway dysregulated in CBDCA-resistant A2780 cells.