[Spatial distribution of Echinococcus granulosus sensu lato genotypes in the american continent]. / Distribución espacial de los Genotipos de Echinococcus granulosus sensu lato por hospedero en el continente americano. Revisión sistemática.

BACKGROUND: Knowledge of the distribution cystic is required for its territorial control. AIM: To describe the spatial distribution of Echinococcus granulosus sensu lato genotypes by host in the American continent. MATERIAL AND METHODS: A systematic review of studies from the American continent, related to genotypes of the E. granulosus s.l complex were included, including any host species, without restriction of language or year of publication. Sensitive searches were performed based on sensitive searches from PubMed, EMBASE, ScienceDirect, SCOPUS and WoS; SciELO and BIREME-BVS and Trip Database. MeSH and free terms were used, including articles up to December 2020. Cartography was carried out with the Arc Map 10® program, using a world geodetic system. Result variables sought were genotype, host, geographic location, year of publication, number of samples, genes used for genotyping. RESULTS: From 1123 retrieved studies retrieved, 53 met the inclusion and exclusion criteria. The studies analyzed represent 3,397 samples from humans and animals. Thirty six percent of articles were published in the five-year period 2016-2020. Reports were mainly from Argentina (27.9%), Brazil (20.6%) and Chile (13.2%). The most reported genotypes globally were G1-G3 (47.3%), G7 (15.3%), G5 (14.6%) and G6 (13.3%). A predominance of G1-G3 and G6 genotypes was verified in South America, G8 and G10 in North America, and "epidemiological silence" in Central America and the Caribbean. CONCLUSIONS: Spatial analysis allows defining the relationship of territories and cases with their own characteristics, which can help to plan control interventions.

Echinococcus Granulosus Haplotypes in the Scientific Literature.

Echinococcus granulosus (Eg) is a parasite causing an incidental infection in humans. The disease can be observed as a hydatid cyst in the liver and lungs and is found in dogs and wolves as definitive hosts. It is considered a neglected infectious disease which has rarely been studied in Mexico1.

Andersen-Tawil Syndrome with High Risk of Sudden Cardiac Death in Four Mexican Patients. Cardiac and Extra-Cardiac Phenotypes.

BACKGROUND: Andersen-Tawil syndrome (ATS) is a cardiac channelopathy that is inherited in an autosomal dominant way, and it is characterized by a triad of periodic paralysis, ventricular arrhythmias, and includes some dysmorphic features with incom- plete penetrance and variable expression that result in a challenging diagnosis. OBJECTIVE: The objective of the study was to describe the cardiac and extra-cardiac phenotype in a cohort of patients with ATS at risk of sudden cardiac death (SCD) to improve its early clinical identification. METHODS: In an observational, transversal study, with a deviant case sampling, four female patients with ATS at high risk of SCD were included in the study. They carried the heterozygous pathogenic variants c.407C>T [p.Ser136Phe], c.652C>T [p.Arg218Trp] (n=2), and c.431G>C [p.Gly144Ala] in the KCNJ2 gene. Patients were evaluated by a cardiologist, a clinical geneticist, and a physiatrist. RESULTS: One patient had the classical facial phenotype and the other three had subtle manifestations. The group of patients presented a diverse set of clinical data such as: triangular face, broad forehead, broadening of medial eyebrows, auricular pits, low-set ears, eyelid ptosis, thin lips, mandibular hypoplasia, and diverse types of dental alterations, single transverse palmar crease, camptodactyly, and syndactyly. Long-exercise test showed a decrement in the percentage amplitude up to 44%, classifying patients in IV or V types according to Fournier's scale. CONCLUSIONS: Extra- cardiac manifestations were a common finding in this series of ATS type1 at high risk of SCD. Its recognition could help the clinician in the early identification of patients with ATS, especially for the cardiologist since they are commonly referred only for evaluation of ventricular arrhythmias.

BASIC AND CLINICAL INSIGHTS IN CATECHOLAMINERGIC (FAMILIAL) POLYMORPHIC VENTRICULAR TACHYCARDIA.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

POLYMORPHISMS IN ß-ADRENERGIC RECEPTORS ARE ASSOCIATED WITH INCREASED RISK TO HAVE A POSITIVE HEAD-UP TILT TABLE TEST IN PATIENTS WITH VASOVAGAL SYNCOPE.

BACKGROUND: Vasovagal syncope (VVS) is a frequent clinical condition in which a genetic background seems to be implicated. Considering that the adrenergic receptors (ARs) may play a role in VVS, the present study has as principal aim to determine if the α- and ß-AR (ADRA and ADRB) gene polymorphisms are associated with an increased risk to have a positive head-up tilt table (HUTT) test in patients with VVS. Methods: Nine polymorphisms in the ADRA1A (rs1048101, rs1383914, rs574584, and rs573542), ADRB1 (rs1801252 and rs1801253), ADRB2 (rs1042713 and rs1042714), and ADRB3 (rs4994) genes were analyzed using the 5' exonuclease TaqMan genotyping assay in a group of 134 patients with VVS. RESULTS: Under different models, the rs1801252 (OR = 8.63, 95% CI: 0.95-78.72, Precessive = 0.02), rs1042713 (OR = 1.94, 95% CI: 1.02-3.66, Padditive = 0.04), and rs4994 (OR = 2.46, 95% CI: 1.01-6.01, Pdominant = 0.042 and OR = 2.62, 95% CI: 1.04-6.63, Pover-dominant = 0.03) polymorphisms were associated with increased risk for a positive HUTT. All models were adjusted for statistically significant covariates. CONCLUSION: These results suggest that some polymorphisms of the ß-AR genes could contribute to a positive tilt test in patients with VVS.

Optogenetic modulation of cardiac autonomic nervous system.

The following is a narrative review of the fundamentals of optogenetics. It focuses on the advantages and constraints of manipulating the autonomic nervous system by modifying the pathophysiological characteristics that arise in different diseases. Although the use of this technique is currently experimental, we will discuss improvements that have been implemented and identify the necessary measures for potential preclinical translation in the control of the cardiac autonomic nervous system.

Variants in the Control Region of Mitochondrial Genome Associated with type 2 Diabetes in a Cohort of Mexican Mestizos.

BACKGROUND: According to the International Diabetes Federation, Mexico is seventh place in the prevalence of type 2 diabetes (T2D) worldwide. Mitochondrial DNA variant association studies in multifactorial diseases like T2D are scarce in Mexican populations. AIM OF THE STUDY: The objective of this study was to analyze the association between 18 variants in the mtDNA control region and T2D and related metabolic traits in a Mexican mestizo population from Mexico City. METHODS: This study included 1001 participants divided into 477 cases with T2D and 524 healthy controls aged between 42 and 62 years and 18 mtDNA variants with frequencies >15%. RESULTS: Association analyses matched by age and sex showed differences in the distribution between cases and controls for variants m.315_316insC (p = 1.18 × 10-6), m.489T>C (p = 0.009), m.16362T>C (p = 0.001), and m.16519T>C (p = 0.004). The associations between T2D and variants m.315_316ins (OR = 6.13, CI = 3.42-10.97, p = 1.97 × 10-6), m.489T>C (OR = 1.45, CI = 1.00-2.11, p = 0.006), m.16362T>C (OR = 2.17, CI = 1.57-3.00, p = 0.001), and m.16519T>C (OR = 1.69, CI = 1.23-2.33, p = 0.006) were significant after performing logistic regression models adjusted for age, sex, and diastolic blood pressure. Metabolic traits in the control group through linear regressions, adjusted for age, sex and BMI, and corrected for multiple comparisons showed nominal association between glucose and variants m.263A>G (p <0.050), m.16183A>C (p <0.010), m.16189T>C (p <0.020), and m.16223C>T (p <0.024); triglycerides, and cholesterol and variant m.309_310insC (p <0.010 and p <0.050 respectively); urea, and creatinine, and variant m.315_316insC (p <0.007, and p <0.004 respectively); diastolic blood pressure and variants m.235A>G (p <0.016), m.263A>G (p <0.013), m.315_316insC (p <0.043), and m.16111C>T (p <0.022). CONCLUSION: These results demonstrate a strong association between variant m.315_316insC and T2D and a nominal association with T2D traits.

PROTEOMIC PROFILE OF ECHINOCOCCUS GRANULOSUS: A SYSTEMATIC REVIEW.

Cystic echinococcosis is a zoonotic disease caused by the larval stage of Echinococcus granulosus. This affliction is an endemic worldwide condition that represents a neglected parasitic disease with important socioeconomic repercussions. Proteomic characterization of larval and adult stages of E. granulosus, as well as the association between expression profiles and host interactions, is relevant for a better understanding of parasite biology, and eventually for drug design and vaccine development. This study aimed to develop a synthesis of the evidence available related to proteomics of E. granulosus. A systematic review was carried out to collect data concerning the proteomics of E. granulosus, without language or host restriction, published between 1980 and 2019. A systematic search was carried out in the Trip Database, BIREME-BVS, SciELO, Web of Science, PubMed, EMBASE, SCOPUS, EBSCO host, and LILACS, using MeSH terms, free words, and Boolean connectors, and adapting strategies to each source of information. Additionally, a manual cross-reference search was performed. Variables studied were the year of publication, geographic origin of the study, number of samples, hosts, parasitic organs, proteomic techniques, and parasite proteins verified. Nine-hundred and thirty-six related articles were identified: 17 fulfilled selection criteria, including slightly more than 188 samples. Most articles were published between 2014 and 2019 (64.7%) and were from Brazil and China (35.3% each). In reference to confirmed hosts in the primary articles, cattle (41.2%) and humans (23.5%) were the most frequently reported. Concerning proteomic techniques applied in the primary articles, LC-MS/MS was the most used (41.1%), and 890 proteins were reported by the primary articles. As the results of our search suggest, the information related to E. granulosus proteomics is scarce, heterogeneous, and scattered throughout several articles that include a diversity of tissues, samples, intermediate hosts, and proteomic techniques. Consequently, the level of evidence generated by our search is type 4.

Echinococcus granulosus sensu lato Genotypes in Different Hosts Worldwide: A Systematic Review.

INTRODUCTION: The aim of this study was to develop a synthesis of the evidence available regarding verified E. granulosus sensu lato (s.l.) genotypes in different species worldwide. MATERIAL AND METHODS: A systematic review was performed including studies concerning genotypes of E. granulosus s.l. without language or genotyped method restriction, published between 1990 and 2020. A systematic search was carried out in Trip Database, BIREME, SciELO, LILACS, IBECS, PAHO-WHO, EMBASE, PubMed, Scopus, and WoS. Variables of interest were year of publication, country, number of samples, and hosts; genotypes, molecular marker, haplotypes and molecular biology techniques used. Descriptive statistics were applied. RESULTS: 2411 articles were analyzed, however 135 met the selection criteria, representing 8643 liver and lung samples. Of the samples selected 24% were human, the remaining samples pertained to non-human animal hosts; cattle and sheep prevailed with 28.6% and 26.6% of the studied samples, respectively. The reported evidence is mainly from Iran, Turkey, Argentina, China and Chile; with 50, 11, 6, 6 and 5 studies, respectively, published between 1992 and 2020 [most frequently during 2015-2020 (76/135 studies; 56.3%)]. The mitochondrial gene cox1 was generally sequenced and informative (91.8%). Genotypes most frequently identified were E. granulosus sensu stricto (s.s.) (83.2%). CONCLUSIONS: Based on this overall evidence, it can be concluded that publications related to genotypes of E. granulosus s.l. are heterogeneous. E. granulosus ss accounts for the vast majority of the global burden of E. granulosus s.l. worldwide. Further studies including larger number of cases and adequate internal validity are required to specify the distribution of genotypes in various host species. TRIAL REGISTRATION: PROSPERO CRD42018099827.

The hemodynamic effects of diazepam versus dexmedetomidine in the treatment of alcohol withdrawal syndrome: A randomized clinical trial.

BACKGROUND: Dexmedetomidine (DEX) is an alpha-2 adrenergic drug used for short sedation and as an alternative to diazepam (DZP) in the treatment of alcohol withdrawal syndrome (AWS). PURPOSE: This study aims to compare the hemodynamic effect of DZP versus DEX on heart rate (HR) and blood pressure in patients with AWS. METHODS: Prospective randomized clinical trial that includes 40 patients with AWS from Mérida, Yucatán, México. RESULTS: Forty patients were randomly divided into two groups: one group DZP (n=20) patients received diazepam (doses 5-20mg IV) and the other group (n=20) received DEX (dexmedetomidine infusion .2-.7mcg/kg/min). We obtained statistical significance in sedation with the DEX group in the degree of traumatic brain injury I/II (p=.003). The DEX group remained haemodynamically stable in the first 24h, the mean HR (73.85±8.39) was significant comparing both groups (p=.002). In the comparison of the figures for the DEX group with the DZP (143.85±2.30-137.95±5.62) the SBP was significant with a (p=.0001). Furthermore, DEX treatment was shorter. CONCLUSION: Although DEX is not indicated for the routine treatment of AWS, this study proposes a positive effect on HR, SBP and fewer days of treatment compared to the standard DZP treatment for AWS. Clinical Trials.gov ID: NCT03877120-https://clinicaltrials.gov/ct2/show/NCT03877120.

[Echinococcus granulosus genotypes verified in human hydatid disease around the world. Systematic review]. / Genotipos de Echinococcus granulosus en hidatidosis humana alrededor del mundo. Revisión sistemática.

BACKGROUND: The evidence regarding genotypic characteristics of Echinococcus granulosus infection in humans worldwide is scarce. AIM: To develop a synthesis of the available evidence regarding genotypes of E. granulosus verified in humans worldwide. METHODS: Systematic review. Articles related with genotypes of E. granulosus, in humans, without language neither genotyped method restriction, published between 1990-2019 were included. A systematic in WoS, EMBASE, MEDLINE, SCOPUS, Trip Database, BIREME, SciELO, LILACS, IBECS, and PAHO-WHO was carried out. In study variables were year of publication, country, number of samples, host and parasite organs, genotype identified, molecular marker and genes. Descriptive statistics were applied. RESULTS: 701 related articles were identified; 62 fulfilled selection criteria, representing 1,511 samples. The existing evidence was published between 1994 and 2019; and mainly comes from Iran (45.2%). The most commonly used sequencing method was PCR amplification and Sanger type sequencing with partial or total genotyping of the cox1 gene. Genotyped method most frequently used was cox1 (79,0%). Genotypes most frequently identified were G1 and G1/G3 complex (49.1% and 32.2%). CONCLUSIONS: Publications related to genotypes of Eg in humans are scarce, heterogeneous, and presenting differing results. Eg G1/G3 accounts for most of the global burden worldwide.

Genes frequently associated with sudden death in primary hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy is characterized by left ventricular hypertrophy without apparent cardiac justification. Sudden cardiac death may be the first manifestation of the disease. It occurs mainly in adulthood and can be seen in childhood and adolescence where genetic origin predominates. Primary HCM ("familial") is inherited in an autosomal dominant pattern in the 25 subtypes informed in Online Mendelian Inheritance in Man. The proteins encoded by the mutated genes are part of the sarcomere in the cardiac cells, being the thick filament the most frequently affected, with the worst prognosis. In the present article, we describe the Mendelian inheritance of the disease and the two most associated genes with sudden death: MYBPC3 and MYH7.

La miocardiopatía hipertrófica (MCH) es el aumento de grosor de la pared ventricular izquierda no relacionada con otras alteraciones cardíacas. Es una enfermedad que puede presentar como primera manifestación clínica la muerte súbita y de ahí su relevancia clínica. Aunque se presenta sobre todo en la edad adulta, puede aparecer durante la infancia y adolescencia, en las que predominan los casos de origen hereditario. La MCH primaria, de causa genética, muestra en particular un patrón de herencia autosómico dominante en los 25 subtipos reconocidos en OMIM (Online Mendelian Inheritance in Man). Las proteínas codificadas por los genes mutantes forman parte del sarcómero en células musculares cardíacas, y las variantes patogénicas de filamentos gruesos son las de mayor frecuencia y peor pronóstico. En este artículo se describen la herencia mendeliana de la enfermedad y la relación con muerte súbita de los genes más frecuentemente encontrados en ella: MYBPC3 y MYH7.

Maya gene variants related to the risk of type 2 diabetes in a family-based association study.

Mexican Maya populations have a notably high prevalence of type 2 diabetes (T2D) as a consequence of the interaction between environmental factors and a genetic component. To assess the impact of 24 single nucleotide variants (SNVs) located in 18 T2D risk genes, we conducted a family-based association evaluation in samples from Maya communities with a high incidence of the disease. A total of four hundred individuals were recruited from three Maya communities with a high T2D incidence. Family pedigrees (100) and 49 nuclear families were included. Genotyping was performed by allelic discrimination with TaqMan probes. This study also included the family-based association test (FBAT) statistic U to assess the genetic associations with T2D, and the multivariate statistical and haplotype analyses. A positive association with TD2 risk was found for WFS1 rs6446482 (p = 0.046, Z = 1.994) under an additive model, and SIRT1 rs7896005 (p = 0.038, Z = 2.073) under the dominant model. Multivariate model analysis, including T2D status, age, and body mass index (BMI), displayed significant covariance in PPARGC-1α rs8192678; SIRT1 rs7896005; TCF7L2 rs7903146 and rs122243326; UCP3 rs3781907; and HHEX rs1111875 with a P < 0.05. This study revealed an association of SIRT1 and WFS1 with T2D risk.

Data on a genome-wide association study of type 2 diabetes in a Maya population.

Maya communities have been shown to exhibit type 2 diabetes (T2D) with high prevalence compared with Mexican mestizo populations. Furthermore, some variants associated with the risk for T2D have been described. In this study, we describe the results of a pilot genome wide association study (GWAS) using 817,823 single nucleotide polymorphisms (SNPs) to identify candidate variants for replication in future studies. Herein, we present the GWAS study data, which were divided into three parts: first, 1289 ancestry informative markers (AIMs) were selected for Latino populations containing European, African, and Native American SNPs obtained from the literature; second, a GWAS hypothesis free to select candidate genes associated with T2D was performed, which identified 24 candidate genes; and third, 39 SNPs previously associated with T2D or related traits were replicated. This article is associated with the original article published in "Gene" under the title "Pilot genome-wide association study identifying novel risk loci for type 2 diabetes in a Maya population".

Single Nucleotide Variants in the Angiotensin II Receptor Type 2 and its Association With Arterial Hypertension: A Systematic Review

Abstract Background: Arterial hypertension (AH) is a chronic disease distributed worldwide, and the Angiotensin II receptor type 2 (AGTR2) gene variants are potential DNA markers to study in association with this disease. Objective: This systematic review (SR) aimed to identify single nucleotide variants in the AGTR2 gene as genetic markers associated with AH. Methods: The electronic databases MEDLINE, Web of Science, SCOPUS, Cochrane Central Register, EMBASE, SciELO, and TripDatabase were searched for research up to September 2023. Case-control studies with DNA variants in the AGTR2 gene associated with AH as the outcome were included in the review. Boolean connectors and keywords were used according to each database. Results: After diverse rounds of scrutiny, a final number of eight articles were included for 8911 participants, comprising 5451 cases and 3460 controls. A significant proportion of the selected studies were performed in Asian populations and were heterogeneous. Although 238 variants were shown in the gnomAD v2.1.1 database for September 2023, only six variants were identified in all the analyzed studies. Conclusions: The results obtained were not conclusive that a specific variant located in the AGTR2 gene has a strong association with AH. The study of this gene re-emerged last year as an essential target to investigate due to its participation in the development of agonist therapy to treat mild COVID-19 cases. Future studies with better statistical power are desirable to replicate the primary findings.

Association of common polymorphisms in the VEGFA and SIRT1 genes with type 2 diabetes-related traits in Mexicans.

INTRODUCTION: Genetic variants have been replicated for association with type 2 diabetes mellitus (T2D) and many of them with diabetes-related traits. Because T2D is highly prevalent in Mexico, this study aimed to test the association of CDKN2A/B, PPARGC1A, VEGFA, SIRT1 and UCP2 gene polymorphisms (rs10811661, rs8192678, rs2010963, rs7896005 and rs659366 respectively) with metabolic traits in 415 unrelated Mexican mestizos with T2D under three models of inheritance. MATERIAL AND METHODS: A total of 415 unrelated Mexican mestizos were genotyped by TaqMan assays. Triglycerides, cholesterol, glucose, high-density lipoprotein cholesterol (HDL-C), insulin and anthropometric measurements were determined and the HOMA-IR was calculated. Association studies were tested by the Kruskal-Wallis test, linear regression, statistical power analysis, Bonferroni correction, paired SNP analysis, and physical interaction by GeneMANIA. RESULTS: All polymorphisms were in Hardy-Weinberg equilibrium, and the association by genotype with T2D-related traits displayed nominal significance for rs8192678 with glucose (p = 0.023) and triglycerides (p = 0.013); rs2010963 with diastolic blood pressure (DBP) (p = 0.012) and cholesterol (p = 0.013); rs7896005 with DBP (p = 0.012) and insulin (p = 0.011); and rs659366 with cholesterol (p = 0.034), glucose (p = 0.031) and triglycerides (p = 0.028); and the association of rs2010963 with HDL-C (p = 0.0007) was significant. Linear regression performed with three models of inheritance, adjusted by age + sex + BMI and corrected with Bonferroni, showed a significant association of rs2010963 with HDL-C in an additive model (p = 0.007); and rs7896005 was significantly associated with DBP in the recessive model (p = 0.006). CONCLUSIONS: Rigorous analysis evidenced the association of VEGFA rs2010963 and SIRT1 rs7896005 with HDL-C and DBP respectively; these traits are known predictors of cardiovascular complications, which increase the risk of cardiovascular diseases in this population.

The ADRA2A rs553668 variant is associated with type 2 diabetes and five variants were associated at nominal significance levels in a population-based case-control study from Mexico City.

Type 2 diabetes (T2D) is a disease with a prevalence of 9.4% in Mexicans. Its etiology is complex involving environmental and genetic factors. The aim of this study was to analyse the association between PPARG rs1801282, PPARGC1A rs8192678, VEGFA rs2010963, ADRA2A rs553668, KCNQ1 rs2237892, SIRT1 rs7896005, IGF2BP2 rs4402960, and UCP3 rs3781907 single nucleotide variants (SNVs) with T2D and metabolic traits in a case-control study of a population from Mexico City. A total of 831 blood samples of non-diabetic, with healthy control participants (416) and individuals with T2D (415) were collected over a five-year period. After DNA extraction, genotyping was performed with TaqMan probes using real-time PCR. The genotypes were analysed for association with T2D in linear and logistic regressions adjusting for age, sex, and body mass index using the dominant, recessive, and additive models with a Bonferroni correction for multiple comparisons p < 0.001 and for association with related T2D traits fixed with a p < 2.3 × 10-4. The univariate analysis gives a significant (p < 1 × 10-4) for sex, triglycerides, and HOMA-IR. Significant association with T2D was found for ADRA2A rs553668 under the recessive model (OR = 3.640 and 95% CI of 2.330-5.690 (p < 1 × 10-4); statistical power 0.999) and under the additive model (OR = 1.640 and 95% CI of 1.340-2.000 (p < 1 × 10-4); statistical power 0.997). Variants PPARG rs1801282, PPARGC1A rs8192678, SIRT1 rs7896005, IGF2BP2 rs4402960 and UCP3 rs3781907 were nominally associated (p > 0.001 and <0.050). Results describe association of ADRA2A rs553668 with T2D in a Mexican population. Variants with nominal association with T2D require to be replicated in additional Mexican populations.