Miocardiopatía Hipertrófica en ausencia de criterios de hipertrofia. Serie de casos / Hypertrophic cardiomyopathy in the absence of hypertrophy criteria. Case series

La miocardiopatía hipertrófica (MCH) es la miocardiopatía hereditaria más frecuente, su principal expresión fenotípica consiste en hipertrofia ventricular izquierda (HVI) en ausencia de condiciones de carga que la justifiquen. Cuando existe una variante genética patogénica se denomina MCH sarcomérica. Los criterios diagnósticos más aceptados son HVI ≥ 15 mm en cualquier segmento o ≥ 13 en ciertas condiciones, criterios que tienen tres inconvenientes: 1) La HCM es una patología donde la HVI es evolutiva, existiendo otros elementos más precoces, pero menos precisos, como criptas, bandas musculares y alteraciones de la válvula mitral y músculos papilares; 2) Pacientes de baja estatura pueden no alcanzar estos umbrales; 3) La MCH apical no queda siempre bien representada usando estos grosores, requiriendo indexar por tamaño del paciente y/o considerar la HVI relativa (relación grosor apical / basal que no debe superar 1). Presentamos una serie de casos con genotipo confirmado para MCH que no cumplen los criterios de HVI aceptados para MCH y donde se debe individualizar el diagnóstico considerando los tres elementos señalados.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac condition; its phenotypic expression consists of ventricular hypertrophy (LVH) unrelated to loading conditions. In patients with a genetic pathogenic variant, the condition is termed sarcomeric HCM. Current diagnostic criteria are based on absolute left ventricular thickness, requiring ≥15 mm in any segment or ≥13 mm in particular conditions. These criteria have three pitfalls: 1) HCM is an evolving disease where LVH occurs gradually, with other early -but less precisephenotypic expressions such as myocardial crypts, muscular bands, or mitral and papillary muscle alterations; 2) Patients with short stature tend to have less LVH and do not reach the proposed thickness threshold. 3) Apical HCM is not correctly addressed in this cut-off as the heart tapers from base to apex, warranting indexing wall thickness to body size and using relative LVH in the apex (ratio from apex/base, abnormal,>1). This small case series includes three patients with a pathogenic genetic variant for HCM that doesn't satisfy the current criteria of LVH. For its precise assessment, the aforementioned points must be considered.

Cultura de seguridad del paciente en el personal sanitario del Centro de Salud de Canoa

Fundamento: la calidad y seguridad en la atención de los pacientes es obligación técnica y ética de los prestadores de los servicios a través de la transparencia de los procesos y resultados de las acciones realizadas por los referidos sistemas de salud. Objetivo: determinar la cultura de la seguridad del paciente en el personal sanitario del Centro de Salud Canoa. Métodos: s e realizó un estudio mixto de corte trasversal, descriptivo; la población estuvo compuesta por 19 profesionales de la salud y 379 usuarios que han asistido desde el mes de agosto del 2021 hasta julio del 2022 a la unidad operativa. La técnica utilizada fue una encuesta de nueve preguntas cerradas y la observación con una guía de observación. Resultados: se evidenció que la mayoría de los profesionales de salud cumplen con los protocolos de preparación y administración de medicamentos. Todos los participantes preparan y administran los medicamentos por sí mismos, y el 94,7 % administra el medicamento correcto con la dosis adecuada, verificando la fecha de caducidad y brindando educación al paciente y su familia. Sin embargo, el 42,1 % de los profesionales evaluados no verifica los antecedentes alérgicos antes de administrar un medicamento. Conclusiones: el estudio permitió identificar muchas debilidades en cultura de seguridad del paciente en el personal sanitario del centro de salud de Canoa. Por ello, establecer estrategias de mejora en calidad de atención, en la comunicación, les permitirá reducir los riesgos de eventos adversos y fomentar una cultura de seguridad en el personal sanitario.

Foundation: the quality and safety in patient care is the service providers' technical and ethical obligation through the processes and results transparency of the actions carried out by the aforementioned health systems. Objective: to determine the patient safety's culture in the health staff of the Canoa Health Center Methods: a mixed cross-sectional, descriptive study was carried out, the population was made up of 19 health professionals and 379 users who have attended the operating unit from August 2021 to July 2022. The technique used was a nine closed questions survey and observation with an observation guide. Results: it was evidenced that the health professionals vast majority fulfill with the protocols for the medications preparation and administration. All participants prepare and administer the medications themselves, and 94.7% administer the correct medication with the proper dosage, checking the expiration date and providing education to the patient and the family. However, 42.1% of the evaluated professionals do not verify the allergic history before administering a medication. Conclusions: the study made it possible to identify many weaknesses in the health staff's culture of patient safety of the Canoa health center. Therefore, establishing strategies to improve the quality of care, in communication, will allow them to reduce the risks of adverse events and promote a culture of safety in health staff.

Diabetes Detection Models in Mexican Patients by Combining Machine Learning Algorithms and Feature Selection Techniques for Clinical and Paraclinical Attributes: A Comparative Evaluation.

The development of medical diagnostic models to support healthcare professionals has witnessed remarkable growth in recent years. Among the prevalent health conditions affecting the global population, diabetes stands out as a significant concern. In the domain of diabetes diagnosis, machine learning algorithms have been widely explored for generating disease detection models, leveraging diverse datasets primarily derived from clinical studies. The performance of these models heavily relies on the selection of the classifier algorithm and the quality of the dataset. Therefore, optimizing the input data by selecting relevant features becomes essential for accurate classification. This research presents a comprehensive investigation into diabetes detection models by integrating two feature selection techniques: the Akaike information criterion and genetic algorithms. These techniques are combined with six prominent classifier algorithms, including support vector machine, random forest, k-nearest neighbor, gradient boosting, extra trees, and naive Bayes. By leveraging clinical and paraclinical features, the generated models are evaluated and compared to existing approaches. The results demonstrate superior performance, surpassing accuracies of 94%. Furthermore, the use of feature selection techniques allows for working with a reduced dataset. The significance of feature selection is underscored in this study, showcasing its pivotal role in enhancing the performance of diabetes detection models. By judiciously selecting relevant features, this approach contributes to the advancement of medical diagnostic capabilities and empowers healthcare professionals in making informed decisions regarding diabetes diagnosis and treatment.

Recidiva de hernias inguinales. Estudio de 52 casos / Recurrence of Inguinal Hernias. Study of 52 cases

Las hernias inguinales son una patología para tratamiento quirúrgico frecuente, afecta entre un 3 a 5 % de toda la población en general, su reparación resulta difícil y peligrosa en caso de recurrencia; un paciente sometido a cirugía tiene entre19 ­ 39 % de probabilidades de recidiva, y esto aumenta con cada nuevo procedimiento. Objetivo: caracterizar la prevalencia de recidivas de hernias inguinales en pacientes intervenidos quirúrgicamente en el Servicio de Cirugía General del Hospital Universitario de Caracas entre los años 2015-2020. Métodos: estudio retrospectivo, descriptivo y analítico. Resultados: se estudiaron 52 casos de recidivas de hernias inguinales, 43 % de un total de 120 pacientes sometidos a hernioplastia inguinal, las técnicas quirúrgicas con mayor número de recidivas fueron: la de Bassini con 14 %, la de Rutkow-Robbins con 10 % y la de Linchtenstein con 9 % de los casos; con un tiempo de recidiva posterior a la primera intervención el cual fue mayor al año de la primera intervención. Conclusiones: la recidiva resultó un poco mayor al promedio, el tiempo en el cual ocurrió es mayor al año de la intervención y las técnicas más involucradas fueron, enorden decreciente: Bassini, Rutkow-Robbins, y Linchtenstein(AU)

Inguinal hernias are a pathology for frequent surgical treatment, affecting between 3 to 5 % of the entire population in general, their repair is difficult and dangerousin case of recurrence; a patient undergoing surgery has a19-39 % chance of recurrence, and this increases with eachnew procedure. Objective: to characterize the prevalence of recurrences of inguinal hernias in patients undergoing surgery at the General Surgery Service of the Hospital Universitario de Caracas between the years 2015-2020. Methods: retrospective, descriptive and analytical study. Results: 52 cases of inguinalhernia recurrences were studied, 43 % of a total of 120 patients undergoing inguinal hernioplasty, the surgical techniques with the highest number of recurrences were: Bassini with 14 %,that of Rutkow-Robbins with 10 % and that of Linchtensteinwith 9 % of the cases; with a recurrence time after the first intervention which was greater than a year after the first intervention. Conclusions: the recurrence was a little high erthan the average, the time in which it occurred is greater than a year othehe intervention and the techniques most involved were,in decreasing order: Bassini, Rutkow-Robbins, and Lichtenstei(AU)

Effect of the combination of bumetanide plus chlorthalidone on hypertension and volume overload in patients with chronic kidney disease stage 4-5 KDIGO without renal replacement therapy: a double-blind randomized HEBE-CKD trial.

BACKGROUND: The co-administration of loop diuretics with thiazide diuretics is a therapeutic strategy in patients with hypertension and volume overload. The aim of this study was to assess the efficacy and safety of treatment with bumetanide plus chlorthalidone in patients with chronic kidney disease (CKD) stage 4-5 KDIGO. METHODS: A double-blind randomized study was conducted. Patients were randomized into two groups: bumetanide plus chlorthalidone group (intervention) and the bumetanide plus placebo group (control) to evaluate differences in TBW, ECW and ECW/TBW between baseline and 30 Days of follow-up. Volume overload was defined as 'bioelectrical impedance analysis as fluid volume above the 90th percentile of a presumed healthy reference population. The study's registration number was NCT03923933. RESULTS: Thirty-two patients with a mean age of 57.2 ± 9.34 years and a median estimated glomerular filtration rate (eGFR) of 16.7 ml/min/1.73 m2 (2.2-29) were included. There was decreased volume overload in the liters of total body water (TBW) on Day 7 (intervention: -2.5 vs. control: -0.59, p = 0.003) and Day 30 (intervention: -5.3 vs. control: -0.07, p = 0.016); and in liters of extracellular water (ECW) on Day 7 (intervention: -1.58 vs. control: -0.43, p < 0.001) and Day 30 (intervention: -3.05 vs. control: -0.15, p < 0.000). There was also a decrease in systolic blood pressure on Day 7 (intervention: -18 vs. control: -7.5, p = 0.073) and Day 30 (intervention: -26.1 vs. control: -10, p = 0.028) and in diastolic blood pressure on Day 7 (intervention: -8.5 vs. control: -2.25, p = 0.059) and Day 30 (intervention: -13.5 vs. control: -3.4, p = 0.018). CONCLUSION: In CKD stage 4-5 KDIGO without renal replacement therapy, bumetanide in combination with chlorthalidone is more effective in treating volume overload and hypertension than bumetanide with placebo.

Powdery Mildew Resistance Genes in Vines: An Opportunity to Achieve a More Sustainable Viticulture.

Grapevine (Vitis vinifera) is one of the main fruit crops worldwide. In 2020, the total surface area planted with vines was estimated at 7.3 million hectares. Diverse pathogens affect grapevine yield, fruit, and wine quality of which powdery mildew is the most important disease prior to harvest. Its causal agent is the biotrophic fungus Erysiphe necator, which generates a decrease in cluster weight, delays fruit ripening, and reduces photosynthetic and transpiration rates. In addition, powdery mildew induces metabolic reprogramming in its host, affecting primary metabolism. Most commercial grapevine cultivars are highly susceptible to powdery mildew; consequently, large quantities of fungicide are applied during the productive season. However, pesticides are associated with health problems, negative environmental impacts, and high costs for farmers. In paralleled, consumers are demanding more sustainable practices during food production. Therefore, new grapevine cultivars with genetic resistance to powdery mildew are needed for sustainable viticulture, while maintaining yield, fruit, and wine quality. Two main gene families confer resistance to powdery mildew in the Vitaceae, Run (Resistance to Uncinula necator) and Ren (Resistance to Erysiphe necator). This article reviews the powdery mildew resistance genes and loci and their use in grapevine breeding programs.

Isolation and molecular characterization of MYB60 in Solanum lycopersicum.

Stomatal closure is a common adaptation response of plants to the onset of drought condition and its regulation is controlled by transcription factors. MYB60, a transcription factor involved in the regulation of light-induced stomatal opening, has been characterized in arabidopsis and grapevine. In this work, we studied the role of MYB60 homolog SIMYB60 in tomato plants. We identified, isolated, and sequenced the SIMYB60 coding sequence, and found domains and motifs characteristic of other MYB60 proteins. We determined that SlMYB60 is mainly expressed in leaves, and its expression is repressed by abscisic acid. Next, we isolated a putative promoter region containing regulatory elements responsible for guard cell expression and other putative regulatory elements related to ABA repression and vascular tissue expression. Protein localization assays demonstrated that SlMYB60 localizes to the nucleus. Finally, SlMYB60 is able to complement the mutant phenotype of atmyb60-1 in Arabidopsis. Together, these results indicate that SlMYB60 is the homologous gene in tomato and potentially offer a molecular target to improve crops.

Association of AMY1A/AMY2A copy numbers and AMY1/AMY2 serum enzymatic activity with obesity in Mexican children.

BACKGROUND: Mexican children are characterized by a high-starch intake diet and high prevalence of obesity. OBJECTIVES: To investigate the association of AMY1A/AMY2A copy numbers (CNs) and AMY1/AMY2 serum enzymatic activity with childhood obesity in up to 427 and 337 Mexican cases and controls. METHODS: Anthropometric and dietary starch intake data were collected. CN of AMY1A/AMY2A and AMY1/AMY2 serum enzymatic activity were determined using droplet digital PCR (ddPCR) and enzymatic colorimetry, respectively. An individual participant level data meta-analysis of association between AMY1A CNVs and obesity was also performed. RESULTS: A positive association between AMY1A/AMY2A CNs and their corresponding AMY1/AMY2 serum enzyme activity was observed in children with normal weight and obesity. The serum enzyme activity of AMY1 and AMY2 was negatively associated with childhood obesity risk, and the association was restricted to kids eating medium/high amount of starch (Pinteraction = .004). While no association between AMY1A and AMY2A CNs and childhood obesity was observed in our sample, we confirmed a significant association between AMY1A CN and obesity in a meta-analysis of 3100 Mexican children. CONCLUSIONS: Our data suggest that genetically determined salivary and pancreatic amylase activity can increase/decrease the risk of obesity in Mexican children, this effect being blunted by a low-starch diet.

The Melanocortin 4 Receptor p.Ile269Asn Mutation Is Associated with Childhood and Adult Obesity in Mexicans.

CONTEXT: Rare partial/complete loss-of-function mutations in the melanocortin-4 receptor (MC4R) gene are the most common cause of Mendelian obesity in European populations, but their contribution to obesity in the Mexican population is unclear. OBJECTIVE AND DESIGN: We investigated whether deleterious mutations in MC4R contribute to obesity in Mexican children and adults. RESULTS: We provide evidence that the MC4R p.Ile269Asn (rs79783591) mutation may have arisen in modern human populations from a founder event in native Mexicans. The MC4R Isoleucine 269 is perfectly conserved across 184 species, which suggests a critical role for the amino acid in MC4R activity. Four in silico tools (SIFT, PolyPhen-2, CADD, MutPred2) predicted a deleterious impact of the p.Ile269Asn substitution on MC4R function. The MC4R p.Ile269Asn mutation was associated with childhood (Ncontrols = 952, Ncases = 661, odds ratio (OR) = 3.06, 95% confidence interval (95%CI) [1.94-4.85]) and adult obesity (Ncontrols = 1445, Ncases = 2,487, OR = 2.58, 95%CI [1.52-4.39]). The frequency of the MC4R p.Ile269Asn mutation ranged from 0.52 to 0.59% and 1.53 to 1.59% in children and adults with normal weight and obesity, respectively. The MC4R p.Ile269Asn mutation co-segregated perfectly with obesity in 5 multigenerational Mexican pedigrees. While adults with obesity carrying the p.Ile269Asn mutation had higher BMI values than noncarriers, this trend was not observed in children. The MC4R p.Ile269Asn mutation accounted for a population attributable risk of 1.28% and 0.68% for childhood and adult obesity, respectively, in the Mexican population. CONCLUSION: The MC4R p.Ile269Asn mutation may have emerged as a founder mutation in native Mexicans and is associated with childhood and adult obesity in the modern Mexican population.

Adiponectin is associated with cardio-metabolic traits in Mexican children.

The adipocyte-derived adiponectin hormone bridges obesity and its cardio-metabolic complications. Genetic variants at the ADIPOQ locus, in ADIPOR1, and ADIPOR2 have been associated with adiponectin concentrations and cardio-metabolic complications in diverse ethnicities. However, no studies have examined these associations in Mexican children. We recruited 1 457 Mexican children from Mexico City. Six genetic variants in or near ADIPOQ (rs182052, rs2241766, rs266729, rs822393), ADIPOR1 (rs10920533), and ADIPOR2 (rs11061971) were genotyped. Associations between serum adiponectin, genetic variants, and cardio-metabolic traits were assessed using linear and logistic regressions adjusted for age, sex, and recruitment center. Serum adiponectin concentration was negatively associated with body mass index, waist to hip ratio, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, dyslipidemia and overweight/obesity status (7.76 × 10-40 ≤ p ≤ 3.00 × 10-3). No significant associations between genetic variants in ADIPOQ, ADIPOR1, and ADIPOR2 and serum adiponectin concentration were identified (all p ≥ 0.30). No significant associations between the six genetic variants and cardio-metabolic traits were observed after Bonferroni correction (all p < 6.9 × 10-4). Our study suggests strong associations between circulating adiponectin concentration and cardio-metabolic traits in Mexican children.

Influence of obesity, parental history of diabetes, and genes in type 2 diabetes: A case-control study.

Obesity, parental history (PH) of type 2 diabetes (T2D), and genes play an important role in T2D development. However, the influence of each factor on T2D variability is unclear. This study aimed to investigate the influence of obesity (body mass index [BMI], waist/hip ratio), PH, and 16 single-nucleotide polymorphisms (SNPs) associated with T2D on T2D variability in Mexico, comparing 1234 non-diabetic controls and 1219 diabetic patients. To replicate the data, a case-control (n = 2904) and a cross-sectional (n = 1901) study were also included. In a multivariate logistic regression model, all factors accounted for only 27.3% of T2D variability: SNPs (8.4%); PH (11.8%) and obesity (7.1%). These factors contributed more in men (33.2%) than in women (25%), specifically when the disease was diagnosed before the age of 46 (46.7% vs. 30%). Genes played a substantially more important role in men than in women (14.9% vs. 5.5%), while obesity and PH played a similar role in both genders. Genes and PH appeared to play a greater role than obesity in T2D. However, obesity contribution was calculated at the time of recruitment and may be underestimated in patients because the BMI decreased linearly with the number of years with the disease. The data suggest that sexual hormones may play important roles in genes that are associated with T2D.

Fine-mapping of 98 obesity loci in Mexican children.

BACKGROUND/OBJECTIVES: Mexico has one of the highest prevalence of childhood obesity in the world. Genome-wide association studies (GWAS) for obesity have identified multiple single-nucleotide polymorphisms (SNPs) in populations of European, East Asian, and African descent. The contribution of these loci to obesity in Mexican children is unclear. We assessed the transferability of 98 obesity loci in Mexican children and fine-mapped the association signals. SUBJECTS/METHODS: The study included 405 and 390 Mexican children with normal weight and obesity. Participants were genotyped with a genome-wide dense SNP array designed for Latino populations, allowing for the analysis of GWAS index SNPs as well as fine-mapping SNPs, totaling 750 SNPs covering 98 loci. Two genetic risk scores (GRS) were constructed: a "discovery GRS" and a "best-associated GRS", representing the number of effect alleles at the GWAS index SNPs and at the best-associated SNPs after fine-mapping for each subject. RESULTS: Seventeen obesity loci were significantly associated with obesity, and five had fine-mapping SNPs significantly better associated with obesity than their corresponding GWAS index SNPs in Mexican children. Six obesity-associated SNPs significantly departed from additive to dominant (N = 5) or recessive (N = 1) models, and a significant interaction was found between rs274609 (TNNI3K) and rs1010553 (ITIH4) on childhood obesity risk. The best-associated GRS was significantly more associated with childhood obesity (OR = 1.21 per additional risk allele [95%CI:1.17-1.25], P = 4.8 × 10-25) than the discovery GRS (OR = 1.05 per additional risk allele [95%CI:1.02-1.08], P = 8.0 × 10-4), and was also associated with waist-to-hip ratio, fasting glucose, fasting insulin and triglyceride levels, the association being mediated by obesity. An overall depletion of obesity risk alleles was observed in Mexican children with normal weight when compared to GWAS discovery populations. CONCLUSIONS: Our study indicates a partial transferability of GWAS obesity loci in Mexican children, and supports the pertinence of post-GWAS fine-mapping experiments in the admixed Mexican population.

Genetic contribution to waist-to-hip ratio in Mexican children and adolescents based on 12 loci validated in European adults.

BACKGROUND/OBJECTIVES: The prevalence of abdominal obesity in Mexican children has risen dramatically in the past decade. Genome-wide association studies (GWAS) for waist-to-hip ratio (WHR) performed predominantly in European descent adult  populations have identified multiple single-nucleotide polymorphisms (SNPs) with larger effects in women. The contribution of these SNPs to WHR in non-European children is unknown. SUBJECTS/METHODS: Mexican children and adolescents (N = 1421, 5-17 years) were recruited in Mexico City. Twelve GWAS SNPs were genotyped using TaqMan Open Array and analyzed individually and as a gene score (GS). RESULTS: Mexican boys and girls displayed 2.81 ± 0.29 and 3.10 ± 0.31 WHR standard deviations higher than children and adolescents from the United States. WHR was positively associated with TG (ß = 0.733 ± 0.190, P = 1.1 × 10-4) and LDL-C (ß = 0.491 ± 0.203, P = 1.6 × 10-2), and negatively associated with HDL-C (ß = -0.652 ± 0.195, P = 8.0 × 10-4), independently of body mass index. The effect allele frequency (EAF) of 8 of 12 (67%) SNPs differed significantly (P < 4.17 × 10-3) in Mexican children and European adults, with no evidence of effect allele enrichment in both populations (4 depleted and 4 enriched; binomial test, P = 1). Ten out of 12 SNPs (83.3%) had effects that were directionally consistent with those reported in GWAS (P = 0.04). HOXC13 rs1443512 displayed the best fit when modeled recessively, and was significantly associated with WHR under a recessive mode of inheritance (ß = 0.140 ± 0.06, P = 2.3 × 10-2). Significant interactions with sex were also observed for HOXC13 rs1443512 and the GS on WHR (P = 2.2 × 10-2 and 1.2 × 10-2, respectively). HOXC13 rs1443512 (ß = 0.022 ± 0.012, P = 4.7 × 10-2) and the GS (ß = 0.007 ± 0.003, P = 7.0 × 10-3) were significantly associated with WHR in girls only. CONCLUSIONS: This study demonstrates that Mexican children are at high risk for abdominal obesity and detrimental lipid profiles. Our data support a partial transferability of sex-specific European GWAS WHR association signals in children and adolescents from the admixed Mexican population.

Biocontrol of Sirex noctilio by the parasitic nematode Deladenus siricidicola: A five season field study in southern Chile.

In 2001, the woodwasp Sirex noctilio was detected in Pinus radiata plantations in the Biobio region of southern Chile. Subsequently, an intense biological control program using the female sterilizing nematode Deladenus siricidicola was implemented in 2010. During five seasons between 2012 and 2017, we studied the parasitism of D. siricidicola nematode and its effect on woodwasp populations and infestation of P. radiata in different locations within the Biobio region. Parasitism was assessed by dissecting adult females of S. noctilio obtained from infested P. radiata logs. The total population of S. noctilio was determined by the emergence of individuals from the same logs. The level of damage caused by the S. noctilio pest was determined by establishing plots in stands of P. radiata at an intensity of 1 plot every 5 ha-1. During the study period, parasitism of S. noctilio by the nematode D. siricidicola increased from 29.6% in 2012 to 93.1% in 2016, while pest population decreased 3.4% in the same time period. Infestation increased from 0.3 to 11,6% of trees between 2012 and 2015, but subsequently decreased to 5.9% by 2017. We confirmed establishment of the nematode in the region under study and its natural dispersion to non-inoculated areas. Finally, we determined that the effect of inoculation age (antiquity) on parasitism levels reached 90% after three years of inoculation.

Optimization of antimalarial, and anticancer activities of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate.

Chemically modified versions of bioactive substances, are particularly useful in overcoming barriers associated with drug formulation, drug delivery and poor pharmacokinetic properties. In this study, a series of fourteen (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (2-15) were prepared by using a one step synthesis from 1 previously described by us as potential antimalarial and antitumor agent. Molecules were evaluated as inhibitors of ß-hematin formation, where most of them showed a significant inhibition value (% > 70). The best inhibitors were tested in vivo as potential antimalarials in mice infected with P. berghei ANKA, chloroquine susceptible strain. Three of them (5, 6, and 15) displayed antimalarial activity comparable to that of chloroquine. Also, molecules were evaluated for their cytotoxic activity against two human cancer cell lines (Jurkat E6.1 and HL60) and primary culture of human lymphocytes. Most of the synthesized compounds, except for analogs 2-6, 8, and 10-12, displayed cytotoxicity against cancer cell lines without affecting normal cells. The potency of the compounds was 15 ≫ 1, and 14 > 7, 9, and 13. Flow cytometry analysis demonstrated an increase in apoptotic cell death after 24 h. The compounds may affect tumor cell autophagy and consequently increase cell apoptosis.

Impacto de la aplicación de una guía clínica basada en la evidencia en el tratamiento del reflujo vesicoureteral primario en el niño / Impact of using an evidence-based clinical guideline for the management of primary vesicoureteral reflux in children

Objetivo: Analizar en qué manera se ha modificado la actitud terapéutica en un hospital de tercer nivel tras la implementación de la guía clínica para el tratamiento del reflujo vesicoureteral (RVU) primario en niños. Población y métodos: Estudio retrospectivo sobre una cohorte de pacientes con RVU primario (1989-2015), de entre 0 y 15 años, en un hospital terciario. Se comparó la conducta terapéutica antes y después de la aparición de la guía clínica (2008). Resultados: Se incluyeron 297 pacientes (49, 8% de niños, 50, 2% de niñas), edad media al momento del diagnóstico de 21, 71 meses. El grado de RVU fue: RVU I-III 45, 1%, RVU IV-V 54, 9%; 124 fueron tratados tras la implementación de la guía clínica (grupo 1), 173, con anterioridad (grupo 2). El período medio de seguimiento fue de 124, 32 meses. El tratamiento conservador fue la terapia de inicio en el 70, 3% de los pacientes del grupo 1 y en el 67, 9% del grupo 2. El número de cirugías se mantuvo constante (31, 45% vs. 31, 79%), con un incremento en el número de procedimientos endoscópicos (p < 0, 005). El perfil de paciente se ha modificado a raíz de la aplicación del algoritmo propuesto por dicha guía. Hubo menos intervenciones en pacientes con RVU IV-V (82, 32% vs. 59, 9%, p= 0, 000) y daño renal al momento del diagnóstico (49, 4% vs. 9, 8%, p= 0, 000). Conclusiones: La aplicación de la guía clínica ha favorecido una conducta conservadora inicial en pacientes con RVU de alto grado y nefropatía, en los que, tradicionalmente, se indicaba la cirugía desde el inicio. La utilización de las guías clínicas favorece una conducta unánime basada en la evidencia, que disminuye los procedimientos invasivos innecesarios.

Objective: To analyze changes in the therapeutic approach at a tertiary care hospital following the implementation of a clinical guideline for the treatment of primary vesicoureteral reflux (VUR) in children. Population and methods: Retrospective study conducted in a cohort of patients with primary VUR (1989-2015) aged 0-15 years at a tertiary care hospital. The therapeutic approach before and after the development of the clinical guideline (2008) was compared. Results: A total of297 patients (49.8% boys, 50.2% girls) were included; their mean age at the time of diagnosis was 21.71 months. VUR grading was: VUR I-III 45.1%, VUR IV-V 54, 9%; 124 were treated after the implementation of the clinical guideline (group 1), and 173, before (group 2). The mean follow-up period was 124.32months. A conservative approach was the initial treatment in 70.3% of group 1 patients and 67.9% of group 2 patients. The number of surgeries remains constant (31.45% versus 31.79%), with an increase in the number of endoscopic surgeries (p < 0.005). The profile of patients has changed based on the application of the algorithm proposed by the guideline. Fewer surgeries were done in patients with VUR IV-V (82.32% versus 59.9%, p= 0.000) and there were fewer cases of kidney damage at diagnosis (49.4% versus 9.8%, p= 0.000). Conclusions: The implementation of the clinical guideline has favored an initially conservative approach in patients with severe grade VUR and nephropathy, for whom surgery was traditionally indicated initially. Using clinical guidelines favors a unanimous, evidence-based approach that reduces the performance of unnecessary invasive procedures.

Impact of using an evidence-based clinical guideline for the management of primary vesicoureteral reflux in children. / Impacto de la apación de una guía clínica basada en la evidencia en el tratamiento del reflujo vesicoureteral primario en el niño.

OBJETIVE: To analyze changes in the therapeutic approach at a tertiary care hospital following the implementation of a clinical guideline for the treatment of primary vesicoureteral reflux (VUR) in children. POPULATION AND METHODS: Retrospective study conducted in a cohort of patients with primary VUR (1989-2015) aged 0-15 years at a tertiary care hospital. The therapeutic approach before and after the development of the clinical guideline (2008) was compared. RESULTS: A total of 297 patients (49.8% boys, 50.2% girls) were included; their mean age at the time of diagnosis was 21.71 months. VUR grading was: VUR I-III 45.1%, VUR IV-V 54,9%; 124 were treated after the implementation of the clinical guideline (group 1), and 173, before (group 2). The mean follow-up period was 124.32 months. A conservative approach was the initial treatment in 70.3% of group 1 patients and 67.9% of group 2 patients. The number of surgeries remains constant (31.45% versus 31.79%), with an increase in the number of endoscopic surgeries (p < 0.005). The profile of patients has changed based on the application of the algorithm proposed by the guideline. Fewer surgeries were done in patients with VUR IV-V (82.32% versus 59.9%, p= 0.000) and there were fewer cases of kidney damage at diagnosis (49.4% versus 9.8%, p= 0.000). CONCLUSIONS: The implementation of the clinical guideline has favored an initially conservative approach in patients with severe grade VUR and nephropathy, for whom surgery was traditionally indicated initially. Using clinical guidelines favors a unanimous, evidencebased approach that reduces the performance of unnecessary invasive procedures.

OBJETIVO: Analizar en qué manera se ha modificado la actitud terapéutica en un hospital de tercer nivel tras la implementación de la guía clínica para el tratamiento del reflujo vesicoureteral (RVU) primario en niños. POBLACIÓN Y MÉTODOS: Estudio retrospectivo sobre una cohorte de pacientes con RVU primario (1989-2015), de entre 0 y 15 años, en un hospital terciario. Se comparó la conducta terapéutica antes y después de la aparición de la guía clínica (2008). RESULTADOS: Se incluyeron 297 pacientes (49,8% de niños, 50,2% de niñas), edad media al momento del diagnóstico de 21,71 meses. El grado de RVU fue: RVU I-III 45,1%, RVU IV-V 54,9%; 124 fueron tratados tras la implementación de la guía clínica (grupo 1), 173, con anterioridad (grupo 2). El período medio de seguimiento fue de 124,32 meses. El tratamiento conservador fue la terapia de inicio en el 70,3% de los pacientes del grupo 1 y en el 67,9% del grupo 2. El número de cirugías se mantuvo constante (31,45% vs. 31,79%), con un incremento en el número de procedimientos endoscópicos (p < 0,005). El perfil de paciente se ha modificado a raíz de la aplicación del algoritmo propuesto por dicha guía. Hubo menos intervenciones en pacientes con RVU IV-V (82,32% vs. 59,9%, p= 0,000) y daño renal al momento del diagnóstico (49,4% vs. 9,8%, p= 0,000). CONCLUSIONES: La aplicación de la guía clínica ha favorecido una conducta conservadora inicial en pacientes con RVU de alto grado y nefropatía, en los que, tradicionalmente, se indicaba la cirugía desde el inicio. La utilización de las guías clínicas favorece una conducta unánime basada en la evidencia, que disminuye los procedimientos invasivos innecesarios.

Copy Number Variations in Candidate Genes and Intergenic Regions Affect Body Mass Index and Abdominal Obesity in Mexican Children.

Introduction. Increase in body weight is a gradual process that usually begins in childhood and in adolescence as a result of multiple interactions among environmental and genetic factors. This study aimed to analyze the relationship between copy number variants (CNVs) in five genes and four intergenic regions with obesity in Mexican children. Methods. We studied 1423 children aged 6-12 years. Anthropometric measurements and blood levels of biochemical parameters were obtained. Identification of CNVs was performed by real-time PCR. The effect of CNVs on obesity or body composition was assessed using regression models adjusted for age, gender, and family history of obesity. Results. Gains in copy numbers of LEPR and NEGR1 were associated with decreased body mass index (BMI), waist circumference (WC), and risk of abdominal obesity, whereas gain in ARHGEF4 and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d and losses in INS were associated with increased BMI and WC. Conclusion. Our results indicate a possible contribution of CNVs in LEPR, NEGR1, ARHGEF4, and CPXCR1 and the intergenic regions 12q15c, 15q21.1a, and 22q11.21d to the development of obesity, particularly abdominal obesity in Mexican children.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs.

BACKGROUND: Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. METHODS: Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. RESULTS: The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. CONCLUSION: Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

Evaluating the transferability of 15 European-derived fasting plasma glucose SNPs in Mexican children and adolescents.

Genome wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with fasting plasma glucose (FPG) in adult European populations. The contribution of these SNPs to FPG in non-Europeans and children is unclear. We studied the association of 15 GWAS SNPs and a genotype score (GS) with FPG and 7 metabolic traits in 1,421 Mexican children and adolescents from Mexico City. Genotyping of the 15 SNPs was performed using TaqMan Open Array. We used multivariate linear regression models adjusted for age, sex, body mass index standard deviation score, and recruitment center. We identified significant associations between 3 SNPs (G6PC2 (rs560887), GCKR (rs1260326), MTNR1B (rs10830963)), the GS and FPG level. The FPG risk alleles of 11 out of the 15 SNPs (73.3%) displayed significant or non-significant beta values for FPG directionally consistent with those reported in adult European GWAS. The risk allele frequencies for 11 of 15 (73.3%) SNPs differed significantly in Mexican children and adolescents compared to European adults from the 1000G Project, but no significant enrichment in FPG risk alleles was observed in the Mexican population. Our data support a partial transferability of European GWAS FPG association signals in children and adolescents from the admixed Mexican population.