First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance

<p>Abstract</p> <p>Background</p> <p>The prevalence of infections with <it>Mycobacterium tuberculosis </it>(MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the <it>Mycobacterium tuberculosis </it>complex strains, to determine their drug resistance profiles by colorimetric microplate Alamar Blue assay (MABA), and finally, to detect mutations present in <it>kat</it>G, <it>rpo</it>B and <it>inh</it>A genes, resulting in isoniazid (INH) and rifampin (RIF) resistance.</p> <p>Results</p> <p>Of the 67 mycobacterial strains isolated, 48 were identified as MTb, 9 as <it>M. bovis</it>, 9 as <it>M. avium </it>and 1 as <it>M. intracellulare</it>. IS<it>6110</it>-RFLP of 48 MTb strains showed 27 profiles. Spoligotyping of the 48 MTb strains yielded 21 patterns, and 9 <it>M. bovis </it>strains produced 7 patterns. Eleven new spoligotypes patterns were found. A total of 40 patterns were produced from the 48 MTb strains when MIRU-VNTR was performed. Nineteen (39.6%) MTb strains were resistant to one or more drugs. One (2.1%) multidrug-resistant (MDR) strain was identified. A novel mutation was identified in a RIF-resistant strain, GAG → TCG (Glu → Ser) at codon 469 of <it>rpo</it>B gene.</p> <p>Conclusions</p> <p>This is the first molecular analysis of mycobacteria isolated from HIV-infected patients in Mexico, which describe the prevalence of different mycobacterial species in this population. A high genetic diversity of MTb strains was identified. New spoligotypes and MIRU-VNTR patterns as well as a novel mutation associated to RIF-resistance were found. This information will facilitate the tracking of different mycobacterial species in HIV-infected individuals, and monitoring the spread of these microorganisms, leading to more appropriate measures for tuberculosis control.</p

Looking for Crumbs in the Obesity Forest: Anti-obesity Interventions and Obesity-Associated Cardiometabolic Traits in the Mexican Population. History and Systematic Review With Meta-Analyses

Mexicans and Mexican Americans share culture, genetic background, and predisposition for chronic complications associated with obesity and diabetes making imperative efficacious treatments and prevention. Obesity has been treated for centuries focused-on weight loss while other treatments on associated conditions like gout, diabetes (T2D), and hypertriglyceridemia. To date, there is no systematic review that synthesizes the origin of obesity clinics in Mexico and the efforts to investigate treatments for obesity tested by randomized clinical trials (RCT). We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve anti-obesity RCT through 2019 and without an inferior temporal limit. The systematic review included RCT of anti-obesity treatments in the Mexican adult population, covering alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions reporting metabolism-associated traits such as BMI, weight, waist circumference, triglycerides, glucose, among others. Only the studies with at least 3 months of treatment were included in the meta-analyses in order to reduce placebo effects. We found 634 entries, after removal of duplicates and screening the studies based on eligibility criteria, we analyzed 43 national, and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and the implemented strategies do not have replications in the population. The nutrition/behavioral interventions were difficult to blind, and most studies have medium-to-high risk of bias. Nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like pure water instead of sweet beverages decrease triglycerides and systolic blood pressure. Dark chocolate showed the highest effect for BMI and high blood pressure, and treatment with insulin increased weight in those with T2D. The study of obesity in Mexico has been on-going for more than four decades, the interest on RCT just increased until this millennium, but with small sample sizes and lack of replication. The interventions affect different cardiometabolic associated traits, which should be analyzed in detail in the population living near the Mexico-U.S. border; therefore, bi-national collaboration is desirable to disentangle the cultural effects on this population\u27s treatment response

Influence of adiposity and sex on SARS-CoV-2 antibody response in vaccinated university students: A cross-sectional ESFUERSO study

Prior studies have identified various determinants of differential immune responses to COVID-19. This study focused on the Ig-G anti-RBD marker, analyzing its potential correlations with sex, vaccine type, body fat percentage, metabolic risk, perceived stress, and previous COVID-19 exposure. In this study, data (available in S1 Data) were obtained from 108 participants from the ESFUERSO cohort, who completed questionnaires detailing their COVID-19 experiences and stress levels assessed through the SISCO scale. IgG anti-RBD concentrations were quantified using an ELISA assay developed by UNAM. Multiple regression analysis was employed to control for covariates, including sex, age, body fat percentage, body mass index (BMI), and perceived stress. This sample comprised young individuals (average age of 21.4 years), primarily consisting of females (70%), with a substantial proportion reporting a family history of diabetes, hypertension, or obesity. Most students had received the Moderna or Pfizer vaccines, and 91% displayed a positive anti-RBD response. A noteworthy finding was the interaction between body fat percentage and sex. In males, increased adiposity was associated with decreased Ig-G anti-RBD concentration; in females, the response increased. Importantly, this pattern remained consistent regardless of the vaccine received. No significant associations were observed for dietary habits or perceived stress variables. This research reports the impact of sex and body fat percentage on the immune response through Ig-G anti-RBD levels to COVID-19 vaccines. The implications of these findings offer a foundation for educational initiatives and the formulation of preventive policies aimed at mitigating health disparities

Project: Center for Diabetes and Metabolism [Centro de Diabetes y Metabolismo: CeDiMet], a collaborative dream comes true

Reynosa urban area has 690,000 inhabitants (384,000 adults \u3e20 years old), 35% moved from other states. The use of cell phones is in 81%, personal computer or laptop with 29%. The prevalence of overweight is 39%, obesity 36%, and T2D 13%. The expected adult population with T2D is 49,900 individuals. The are 5 clinics prepared to attend T2D, and few with specialized personnel. The CeDiMet is a collaborative clinic involving health personnel and researchers from the Universidad Mexico Americana del Norte, Universidad Autonoma de Tamaulipas, Hospital General de Mexico “Dr. Eduardo Liceaga”, University of Texas Rio Grande Valley, and the Texas Diabetes Institute in San Antonio. The funding source comes from private companies in Reynosa. The clinical structure includes physicians, nurses, nutritionists, psychologists, and a section for telemedicine for consulting specialists from USA and Mexico City. Besides clinical attendance, the CeDiMet will conduct educational activities in offices, factories, churches, and schools for prevention of obesity complications (T2D and hypertension), early detection of diabetic foot, fatty liver, and endothelial damage. “Tree of Health in the Family” is a program to encourage youth to know and understand the metabolic problems in their families to focus on prevention. Recently, we obtained a grant from COTACyT to explore the effect of COVID-19 in a cohort of 200 students and their families. The analysis of post-traumatic stress due to confinement and antibodies concentration to detect contacts and its association with metabolic problems is an example of the research we can perform

Randomized Clinical Trials of obesity treatments in Mexican population. Systematic Review and Meta-Analysis

Background: Mexicans and Mexican Americans share similar culture, genetic background, and predisposition for obesity and diabetes. Randomized clinical trials (RCT) assessing obesity treatments (ObT) are reliable to assess efficacy. To date, there is no systematic review to investigate ObT tested by RCT in Mexican adults. Methods: We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve ObT RCT from 1990 to 2019. The ObT included alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions. The analyzed RCT were at least three months of duration, and reported: BMI, weight, waist circumference, triglycerides, glucose and blood pressure. Results: We found 634 entries; after removal of duplicates and exclusions based on eligibility criteria, we analyzed 43 and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and did not have replications from other studies. The nutrition/behavioral interventions were difficult to blind, and most studies had medium to high risk of bias. Random effects meta-analysis of nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like plain water instead of sweet beverages decreased triglycerides and systolic blood pressure. Participants with obesity and hypertension had beneficial effects with antioxidants, and the treatment with insulin increased weight in those with T2D. Conclusions: The RCT’s in Mexico reported effects on metabolic components despite small sample sizes and lack of replication. In the future we should analyze ObT in population living on the U.S.-Mexico border; therefore, bi-national collaboration is desirable to disentangle cultural effects on ObT response

Neutralizing anti-RBD fraction for SARS-CoV-2 is associated with the interaction waist circumference and sex. An ESFUERSO preliminary report on university students

In a previous study we reported that 25% of college students had a family history of type 2 diabetes (T2D), and 39% of hypertension. Interestingly, between 17 to 47% reported not knowing about T2D or hypertension, neither the existing obesity-metabolic problems (ESFUERSO study). The COVID-19 pandemic forced confinement and modifications in food intake, physical activity, and psychological stress. This study aimed to analyze if the immune Ig-G anti-RBD (protective epitope in S protein) response associated with type of vaccination, metabolic risk, perceived stress, and history of COVID-19 contacts. We included 116 students at the 3th year of follow up in the ESFUERSO cohort at Reynosa. Mean age 21.4 (SD 1.04) years old, BMI 28 (6.6), females 70% (81/116). The serum concentration of Ig-G anti-RGB measured by ELISA adjusted by sex, age, body fat percentage, and BMI was analyzed. Researchers performed a multiple regression analysis with Stata V17.0. We found that 70% of the students had a family history of diabetes, hypertension, and/or obesity at baseline. Only 5 (4%) students did not have any vaccine at the time of the study, 102 (88%) were vaccinated with Moderna or Pfizer and 9 (8%) with other vaccines (Cansino, Sinovac). The prevalence of positive anti-RBD was 91%. The body fat percentage interacted with sex (p=0.034) explaining the serum concentration of anti-RBD decreased as adiposity increases in men, but increased in women. The interaction remained is spite of type of vaccination. We found no differences among metabolic risks for food consumption, distress, uncertainty, lack of sleep, sadness, and anxiety were associated with metabolic problems. Our model predicts neutralizing anti-RBD had multiplicative interaction by sex and body fat percentage (increases in females and decreases in males), with no effects on stress score or food consumption

Serum carotenoids and Pediatric Metabolic Index predict insulin sensitivity in Mexican American children

High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children

VAMOS: a Pathfinder for the HAWC Gamma-Ray Observatory

VAMOS was a prototype detector built in 2011 at an altitude of 4100m a.s.l. in the state of Puebla, Mexico. The aim of VAMOS was to finalize the design, construction techniques and data acquisition system of the HAWC observatory. HAWC is an air-shower array currently under construction at the same site of VAMOS with the purpose to study the TeV sky. The VAMOS setup included six water Cherenkov detectors and two different data acquisition systems. It was in operation between October 2011 and May 2012 with an average live time of 30%. Besides the scientific verification purposes, the eight months of data were used to obtain the results presented in this paper: the detector response to the Forbush decrease of March 2012, and the analysis of possible emission, at energies above 30 GeV, for long gamma-ray bursts GRB111016B and GRB120328B.Comment: Accepted for pubblication in Astroparticle Physics Journal (20 pages, 10 figures). Corresponding authors: A.Marinelli and D.Zaboro

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)