The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

BACKGROUND: Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). METHODS: Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. RESULTS: No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. CONCLUSIONS: The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease

High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children

Objective. To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. Materials and methods. Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative RealTime PCR assays. Results. Anthropometric and biochemical parameters were statistically higher in overweigth/ obese children (OW/O) than in lean (NW), Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. Conclusions. Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children

Lethality risk markers by sex and age-group for COVID-19 in Mexico: a cross-sectional study based on machine learning approach

Abstract Background Mexico ranks fifth worldwide in the number of deaths due to COVID-19. Identifying risk markers through easily accessible clinical data could help in the initial triage of COVID-19 patients and anticipate a fatal outcome, especially in the most socioeconomically disadvantaged regions. This study aims to identify markers that increase lethality risk in patients diagnosed with COVID-19, based on machine learning (ML) methods. Markers were differentiated by sex and age-group. Methods A total of 11,564 cases of COVID-19 in Mexico were extracted from the Epidemiological Surveillance System for Viral Respiratory Disease. Four ML classification methods were trained to predict lethality, and an interpretability approach was used to identify those markers. Results Models based on Extreme Gradient Boosting (XGBoost) yielded the best performance in a test set. This model achieved a sensitivity of 0.91, a specificity of 0.69, a positive predictive value of 0.344, and a negative predictive value of 0.965. For female patients, the leading markers are diabetes and arthralgia. For males, the main markers are chronic kidney disease (CKD) and chest pain. Dyspnea, hypertension, and polypnea increased the risk of death in both sexes. Conclusions ML-based models using an interpretability approach successfully identified risk markers for lethality by sex and age. Our results indicate that age is the strongest demographic factor for a fatal outcome, while all other markers were consistent with previous clinical trials conducted in a Mexican population. The markers identified here could be used as an initial triage, especially in geographic areas with limited resources

Prevalence and Risk Factors for High-Risk Human Papillomavirus Infection and Cervical Disorders: Baseline Findings From an Human Papillomavirus Cohort Study

Background A persistent infection by high-risk human papillomavirus (HR-HPV) is a prerequisite for the development of cervical neoplasms; however, most studies have focused on risk factors associated with HPV-16 and HPV-18 only. Objectives We assessed the association of risk factors with the prevalence of HPV-16, HPV-18, and non-16/18 HR-HPV infection and with the occurrence of cervical lesions in the baseline of a cohort study of HPV persistence in a Mexican population. Methods Cross-sectional study within the baseline of a 5-year dynamic cohort study of HR-HPV persistence in women with an abnormal cytology study result from 2015 to 2021. HPV DNA was detected using the Anyplex II HPV 28 kit. Data on lifestyle, sociodemographic, and reproductive factors were assessed using bivariate and multivariate analyses to determine the association of risk factors with HR-HPV infection status and histopathologic diagnosis. Results A total of 373 women were included in the study. The overall prevalence of HR-HPV infection was 69.97%. The most prevalent HR-HPV genotypes, including single and multiple infections, were HPV-53 (13.4%), HPV-16 (11.8%), HPV-58 (10.9%), HPV-31 (10.9%), and HPV-66 (10.7%). We found 90 multiple HR-HPV infection patterns, all of them with α-6 and -9 species. Significant associations of multiple HPV-16 and non-16/18 HR-HPV infections were found with marital status, number of lifetime sexual partners, and smoking history. The most prevalent genotype in CIN1 and CIN2 patients was HPV-16. No association was found between biological plausibility risk factors and cervical lesions. Conclusions The risk factors for non-16/18 HR-HPV multiple infections are no different than those linked to HPV-16 multiple infections

Cervical Cancer Genetic Susceptibility: A Systematic Review and Meta-Analyses of Recent Evidence.

Cervical cancer (CC) has one of the highest mortality rates among women worldwide. Several efforts have been made to identify the genetic susceptibility factors underlying CC development. However, only a few polymorphisms have shown consistency among studies.We conducted a systematic review of all recent case-control studies focused on the evaluation of single nucleotide polymorphisms (SNPs) and CC risk, stringently following the "PRISMA" statement recommendations. The MEDLINE data base was used for the search. A total of 100 case-control studies were included in the meta-analysis. Polymorphisms that had more than two reports were meta-analyzed by fixed or random models according to the heterogeneity presented among studies.We found significant negative association between the dominant inheritance model of p21 rs1801270 polymorphism (C/A+A/A) and CC (pooled OR = 0.76; 95%CI: 0.63-0.91; p<0.01). We also found a negative association with the rs2048718 BRIP1 polymorphism dominant inheritance model (T/C+C/C) and CC (pooled OR = 0.83; 95%CI: 0.70-0.98; p = 0.03), as well as with the rs11079454 BRIP1 polymorphism recessive inheritance model and CC (pooled OR = 0.79; 95%CI: 0.63-0.99; p = 0.04). Interestingly, we observed a strong tendency of the meta-analyzed studies to be of Asiatic origin (67%). We also found a significant low representation of African populations (4%).Our results provide evidence of the negative association of p21 rs1801270 polymorphism, as well as BRIP1 rs2048718 and rs11079454 polymorphisms, with CC risk. This study suggests the urgent need for more replication studies focused on GWAS identified CC susceptibility variants, in order to reveal the most informative genetic susceptibility markers for CC across different populations

Na política centrada no programa de vacinação contra o HPV no México: Suas dilema ético

This article raises an ethical analysis of issues related to the introduction of new vaccines against Human Papillomavirus in Mexico, whose distribution policy attend to equity more than equality, and has as fundamental axes to cover the most vulnerable people and the lowest cost possible, i.e. serving the principles of distributive justice. The initial scheme of vaccination against this virus in Mexico has been focused on the most marginalized female population, which focuses on indigenous women. Distribution strategies for new vaccines must take into account the specific characteristics that develop these groups and analyze the ethical implications that such measures will involve; without this public health policy could increase health inequalities.Se plantea un análisis ético de aspectos relacionados con la introducción de nuevas vacunas contra el Virus del Papiloma Humano en México, cuya política de distribución atiende a la equidad más que a la igualdad y tiene como ejes fundamentales abarcar a las personas más vulnerables y al costo más bajo posible, es decir, atiende a los principios de justicia distributiva. El esquema inicial de vacunación contra este virus en México se ha focalizado a la población femenina más marginada, la cual se concentra en las mujeres indígenas. Las estrategias de distribución de nuevas vacunas deberán tomar en consideración las características específicas en que se desenvuelven estos grupos y analizar las implicaciones éticas que tales medidas conllevan. Sin ello, una política de salud pública podría aumentar las desigualdades en materia de salud.O propósito foi fazer uma análise ética das questões relacionadas com a introdução de novas vacinas contra o Papilomavírus Humano, no México, cuja política de distribuição serve apenas para a equidade mais do que para a igualdade e tem como eixos fundamentais abrangir os mais vulneráveis e os menores custos possíveis, isto é, servindo aos princípios de justiça distributiva. O regime inicial da vacinação contra esse vírus no México tem sido focado na população feminina mais marginalizada, que incide sobre as mulheres indígenas. As estratégias de distribuição de novas vacinas devem tomar em consideração as características específicas que desses grupos e analisar as implicações éticas que tais medidas implicam, sem isso a política de saúde pública poderia aumentar as desigualdades na saúde