Bacterial community assessment of drinking water and downstream distribution systems in highland localities of Ecuador.

Bacterial communities in drinking water provide a gauge to measure quality and confer insights into public health. In contrast to urban systems, water treatment in rural areas is not adequately monitored and could become a health risk. We performed 16S rRNA amplicon sequencing to analyze the microbiome present in the water treatment plants at two rural communities, one city, and the downstream water for human consumption in schools and reservoirs in the Andean highlands of Ecuador. We tested the effect of water treatment on the diversity and composition of bacterial communities. A set of physicochemical variables in the sampled water was evaluated and correlated with the structure of the observed bacterial communities. Predominant bacteria in the analyzed communities belonged to Proteobacteria and Actinobacteria. The Sphingobium genus, a chlorine resistance group, was particularly abundant. Of health concern in drinking water reservoirs were Fusobacteriaceae, Lachnospiraceae, and Ruminococcaceae; these families are associated with human and poultry fecal contamination. We propose the latter families as relevant biomarkers for establishing local standards for the monitoring of potable water systems in highlands of Ecuador. Our assessment of bacterial community composition in water systems in the Ecuadorian highlands provides a technical background to inform management decisions.

Receiver operating characteristic (ROC) to determine cut-off points of clinical and biomolecular markers to discriminate mortality in severe COVID-19 living at high altitude.

BACKGROUND: In 2020, Ecuador had one of the highest death rates because of COVID-19. The role of clinical and biomolecular markers in COVID disease prognosis, is still not well supported by available data. In order for these markers to have practical application in clinical decision-making regarding patient treatment and prognosis, it is necessary to know an optimal cut-off point, taking into consideration ethnic differences and geographic conditions. AIM: To determine the value of clinical and biomolecular markers, to predict mortality of patients with severe COVID-19 living at high altitude. METHODS: In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of ROC, sensitivity, specificity and likelihood ratios were calculated to determine levels of clinical and biomolecular markers that best differentiate survivors versus non-survivors in severe COVID subjects that live at a high altitude setting. RESULTS: Selected cut-off values for ferritin (≥ 1225 ng/dl, p = 0.026), IL-6 (≥ 11 pg/ml, p = 0.005) and NLR (≥ 22, p = 0.008) at 24 h, as well as PaFiO2 (≤ 164 mmHg, p = 0.015), NLR (≥ 16, p = p = 0.013) and SOFA (≥ 6, p = 0.031) at 72 h, appear to have good discriminating power to differentiate survivors versus non-survivors. Additionally, odds ratios for ferritin (OR = 3.38); IL-6 (OR = 17.07); PaFiO2 (OR = 4.61); NLR 24 h (OR = 4.95); NLR 72 h (OR = 4.46), and SOFA (OR = 3.77) indicate increased risk of mortality when cut-off points were taken into consideration. CONCLUSIONS: We proposed a straightforward and understandable method to identify dichotomized levels of clinical and biomolecular markers that can discriminate between survivors and non-survivors patients with severe COVID-19 living at high altitudes.

Prevalence of Helicobacter pylori genotypes: cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, oipA and their association with gastrointestinal diseases. A cross-sectional study in Quito-Ecuador.

BACKGROUND: The most prevalent stomach infection in the world is caused by Helicobacter pylori (H. pylori). Several pathogenicity genes, including cagA, vacA, babA2, dupA, iceA, and oipA, are associated with an increased risk of gastrointestinal disease such as peptic ulcer and stomach cancer. This research aims to determine the prevalence of different H. pylori genotypes and correlate their risk in the development of gastrointestinal diseases in the Ecuadorian population. METHODS: A cross-sectional research of 225 patients at the Calderón Hospital in Quito, Ecuador, was conducted. End point PCRs were run to determine the presence of 16S rRNA, cagA, vacA (m1), vacA (s1), babA2, dupA, iceA1, and oipA virulence genes. Chi-square test, odds ratios (OR) and 95% confidence intervals (CI) were utilized for the statistical analysis. RESULTS: H. pylori infection was present in 62.7% of people. Peptic ulcers were seen in 22.2% and malignant lesions in 3.6% of patients. Genes oipA (93.6%), vacA (s1) (70.9%), and babA2 (70.2%) were the most prevalent. cagA/vacA (s1m1) and cagA/oipA (s1m1) combinations were found in 31.2% and 22.7% of the cases, respectively. Acute inflammation has a significant correlation with the genes cagA (OR = 4.96 95% CI: 1.1-22.41), babA2 (OR = 2.78 95% CI: 1.06-7.3), and the cagA/oipA combination (OR = 4.78, 95% CI: 1.06-21.62). Follicular hyperplasia was associated with iceA1 (OR = 3.13; 95% CI: 1.2-8.16), babA2 (OR = 2.56; 95% CI: 1.14-5.77), cagA (OR = 2.19; 95% CI: 1.06-4.52), and the cagA/oipA combination (OR = 2.32, 95% CI: 1.12-4.84). The vacA (m1) and vacA (s1m1) genes were associated with gastric intestinal metaplasia (OR = 2.71 95% CI: 1.17-6.29) (OR = 2.33 95% CI: 1.03-5.24). Finally, we showed that cagA/vacA (s1m1) gene combination increased the risk of duodenal ulcer development (OR = 2.89, 95% CI 1.10-7.58). CONCLUSION: This study makes a significant contribution by offering genotypic information regarding H. pylori infection. The presence of several H. pylori genes was associated with the onset of gastrointestinal illness in the Ecuadorian population.

Biomarkers as predictors of mortality in critically ill obese patients with COVID-19 at high altitude.

BACKGROUND: Obesity is a common chronic comorbidity of patients with COVID-19, that has been associated with disease severity and mortality. COVID-19 at high altitude seems to be associated with increased rate of ICU discharge and hospital survival than at sea-level, despite higher immune levels and inflammation. The primary aim of this study was to investigate the survival rate of critically ill obese patients with COVID-19 at altitude in comparison with overweight and normal patients. Secondary aims were to assess the predictive factors for mortality, characteristics of mechanical ventilation setting, extubation rates, and analytical parameters. METHODS: This is a retrospective cohort study in critically ill patients with COVID-19 admitted to a hospital in Quito-Ecuador (2,850 m) from Apr 1, 2020, to Nov 1, 2021. Patients were cathegorized as normal weight, overweight, and obese, according to body mass index [BMI]). RESULTS: In the final analysis 340 patients were included, of whom 154 (45%) were obese, of these 35 (22.7%) were hypertensive and 25 (16.2%) were diabetic. Mortality in obese patients (31%) was lower than in the normal weight (48%) and overweight (40%) groups, but not statistically significant (p = 0.076). At multivariable analysis, in the overall population, older age (> 50 years) was independent risk factor for mortality (B = 0.93, Wald = 14.94, OR = 2.54 95%CI = 1.58-4.07, p < 0.001). Ferritin and the neutrophil/lymphocyte ratio were independent predictors of mortality in obese patients. Overweight and obese patients required more positive and-expiratory pressure compared to normal-weight patients. In obese patients, plateau pressure and mechanical power were significantly higher, whereas extubation failure was lower as compared to overweight and normal weight. CONCLUSIONS: This preliminary study suggests that BMI was not associated with mortality in critically ill patients at high altitude. Age was associated with an increase in mortality independent of the BMI. Biomarkers such as ferritin and neutrophils/lymphocytes ratio were independent predictors of mortality in obese patients with COVID-19 at high altitude.

Cardiovascular risk among 6-8-year-old children living in urban and rural communities in Ecuador: A cross-sectional analysis.

Cardiovascular diseases have their origins in childhood. At least 20% of children and adolescents in Latin America are overweight or obese. However, little is known regarding the cardiovascular risk of young children living in the region. This paper aims to identify associations between socio-demographics, adiposity, and dietary intake with cardiometabolic risk among children between 6- and 8-years old living in urban and rural Andean regions of Ecuador. A cross-sectional study was conducted among 267 children attending elementary schools between February and August 2018. Sociodemographic data were collected using a structured interview. Bodyweight, height, and waist circumference were measured in duplicate; blood samples were taken after overnight fasting to determine blood lipids, hepatic enzymes, and adipokines; food intake data was assessed by two 24-h recalls administered to the guardians. Associations between cardiometabolic risk (i.e., blood lipids, hepatic enzymes, and adipokines) with sociodemographic characteristics, dietary intake, and waist circumference were tested using multiple hierarchical regression models. Twenty-nine percent of the children were overweight or obese, 12% had low HDL levels, and over 18% had high levels of LDL and triglycerides. Children living in the urban region had lower levels of HDL (ß-4.07 mg/dL; 95% CI: -7.00; -1.15; P = 0.007) but higher levels of LDL cholesterol (ß 8.52 mg/dL; 95% CI: 1.38; 15.66; P = 0.019). Hepatic enzymes were also higher among urban children (SGOT: ß% 22.13; 95% CI: 17.33; 26.93; P < 0.001; SGPT: ß 0.84 U/L; 95% CI: 0.09; 1.59; P = 0.028). Leptin blood levels were higher (ß% 29.27; 95% CI: 3.57; 54.97; P = 0.026), meanwhile adiponectin plasma concentrations were lower among urban children (ß%-103.24; 95% CI: -58.9; -147.58; P = < 0.001). Fiber intake was inversely associated with total cholesterol (ß-9.27 mg/dL; 95% CI -18.09; -0.45; P = 0.040) and LDL cholesterol blood levels (ß-9.99 mg/dL; 95% CI: -18.22; -1.75; P = 0.018). Our findings demonstrate that young children are at high cardiovascular risk; if no actions are taken, the burden of non-communicable diseases will be substantial. The differences in risk between rural and urban areas are evident; urbanization might predispose children to a different reality and, in most cases, result in poor habits.

Unacylated ghrelin modulates circulating angiogenic cell number in insulin-resistant states.

BACKGROUND: Type 2 diabetes (T2D) is associated with reduced numbers and impaired function of circulating angiogenic cells (CAC) which contributes to the progression of atherosclerosis and microvascular disease. Previous studies suggest that short-term infusion of unacylated ghrelin (UAG) normalizes CAC number in patients with T2D. To determine dose-dependent effects of short-term infusion of UAG in T2D patients using a cross-over model, and of long-term infusion of UAG in obese mice, on differentiation of monocyte progenitors into CAC. METHODS: Eight overweight T2D patients were infused overnight with 3 and 10 µg/kg/h of UAG in a double-blind, placebo-controlled cross-over study. To assess the effects of long-term UAG treatment, obese mice were infused with UAG for 4 weeks. Monocyte progenitors were assessed for their ability to differentiate into CAC in vitro. RESULTS: In T2D patients, UAG treatment caused a reduction in differentiation of CAC, dependent on UAG dose and differentiation method. However, mice treated with UAG showed a significant increase in differentiation of bone marrow progenitors into CAC. CONCLUSION: UAG causes a minor suppressive effect on CAC development after short-term treatment in humans, but experiments in mice suggest that long-term treatment has beneficial effects on CAC formation. The Netherlands Trial Register: TC=2487.

Study on inflammation-related genes and microRNAs, with special emphasis on the vascular repair factor HGF and miR-574-3p, in monocytes and serum of patients with T2D.

BACKGROUND: Recently, we reported signs of inflammation (raised IL-8, reduced miR-146a) and signs of vascular repair (raised HGF) in the serum of Ecuadorian patients with type 2 diabetes (T2D). In contrast, we found that the circulating monocytes lacked up-regulation of classical inflammatory genes (IL-1B, IL-6, and TNF) and there was even significant down-regulation of PTGS2. Notably, genes and a microRNA involved in adhesion, cell differentiation and morphology (CD9, DHRS3, PTPN7 and miR-34c-5p) were up-regulated in the T2D monocytes, suggesting a role of the anti-inflammatory cells in adhesion, vascular repair and invasion. AIM: To determine the gene expression of the vascular repair factor HGF in the circulating monocytes of patients with T2D and to investigate the relationship between HGF and the expression of the other previously tested monocyte genes and the contribution to the raised serum level of HGF. In addition, we tested the level of 6 microRNAs, which were previously found abnormal in the circulating monocytes, in the serum of the patients. METHODS: A gene and microRNA expression study in monocytes and serum of 64 Ecuadorian patients with T2D (37-85 years) and 44 non-diabetic controls (32-87 years). RESULTS: The gene expression of HGF was significantly raised in the monocytes of the patients with T2D and associated with the expression of genes involved in adhesion, cell differentiation and morphology. HGF gene expression did not correlate with the serum level of HGF. The monocyte expression of pro-inflammatory cytokine genes was also not associated with the serum levels of these cytokines. The level of miR-574-3p was significantly decreased in the serum of the patients with T2D, and correlated in expression with the decreased well-established inflammation-regulating miR-146a. The level of the microRNAs in serum did not correlate with their expression level in monocytes. CONCLUSION: In circulating monocytes of Ecuadorian T2D patients, the microRNA and gene expression of important inflammatory/chemotactic/motility/vascular repair factors differs from the expression in serum. While monocytes show a gene expression profile compatible with an anti-inflammatory state, serum shows a molecular profile compatible with an inflammatory state. Both compartments show molecular signs of vascular repair support, i.e. up-regulated HGF levels.

Des-acyl ghrelin analogs prevent high-fat-diet-induced dysregulation of glucose homeostasis.

There is clinical evidence that des-acyl ghrelin (DAG) favorably modulates glucose and lipid metabolism, although its mode of action is unknown. A murine model of prediabetes was used to assess possible mechanisms of action for DAG and a newly developed bioactive analog, AZP531. C57BL/6J mice were infused with saline, DAG, or AZP531 continuously for 4 wk, and fed either normal diet (ND) or normal diet for 2 wk followed by a high-fat diet (HFD) for 2 wk. Compared with mice in the ND group, HFD increased body and fat mass, caused glucose intolerance and insulin resistance, had proinflammatory effects in white adipose tissue, and caused lipid accumulation in brown adipose tissue. DAG and AZP531 treatment prevented HFD-induced proinflammatory effects, stimulated expression of mitochondrial function markers in brown adipose tissue, and prevented development of a prediabetic metabolic state. AZP531 also prevented a HFD-induced increase in acyl ghrelin levels. Our data indicate DAG analogs as potential treatment for the prevention of metabolic syndrome.