Association of Polymorphisms of the IL-17A and IL-17F Genes with Increased Risk of Hypertension and Obesity in Mexican Patients with COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2). COVID-19 can cause a cytokine release syndrome in which cytokines, including interleukin 17 (IL-17), are massively secreted in response to a specific stimulus. This can contribute to mortality and severe forms of COVID-19. The study aimed to determine the association of SARS-CoV2 infection with the IL-17A rs2275913 and IL-17F rs763780 variants, as well as with the associated comorbidities in COVID-19-positive Mexican patients. The study included 178 patients positive to COVID-19 and 177 COVID-19 negative subjects. For genotyping, the samples were amplified with a TaqMan® probe. There was no association between the AA genotype and A allele of IL-17A variant or the IL-17F C allele with the presence of COVID-19. In regard to comorbidities, a statistically significant association was found between IL-17A rs2275913 AA genotype and hypertension, as well as with the presence of obesity (P = 0.003, OR 23, 95% CI: 2.97-178.092 and P = 0.025, OR 28, 95% CI: 1.52-178.029, respectively) in patients with COVID-19. In conclusion, rs2275913 IL-17A polymorphism in COVID-19 patients seems to confer a higher susceptibility to the presence of hypertension and obesity, increasing the risk of premature cardiovascular disease in this population. However, more studies should be conducted for a better understanding of their relation.

Role of ß-Klotho and Malondialdehyde in Metabolic Disorders, HIV Infection, and Antiretroviral Therapy.

Metabolic alterations, resulting from factors such as obesity or infections (HIV), generate inflammation in the body, affecting the immune system and causing oxidative stress. Prolonged exposure to antiretroviral therapy (ART) conditions the appearance of alterations considered risk factors for metabolic syndrome (MetS), affecting the quality of life in people living with HIV/AIDS (PLWHA). ß-klotho is a protein that can counteract levels of oxidative stress. The aim was to determine the relation of ß-klotho and oxidative stress with metabolic alterations in PLWHA. We hypothesized that levels of ß-klotho and malondialdehyde (MDA) are related in PLWHA on ART with overweight/obesity. As a result of comparing cases versus controls, significant differences were obtained in levels of ß-klotho (p = 0.011), MDA (p < 0.0001), body mass index (p = 0.001), and weight (p < 0.0001). The presence of MetS in PLWHA was 21.2% and 10.6% according to the World Health Organization and ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria, respectively. The founded correlations were of ß-klotho (r = 0.019) and MDA (r = 0.0001), both with CD4+ cells in PLWHA. In controls, ß-klotho was correlated with very low-density lipoprotein (r = 0.035) and atherogenic index (AI; r = 0.037), MDA with AI (r = 0.039), cholesterol, and low-density lipoprotein (r = 0.002). The increase of inflammation in the organism, owing to HIV infection and/or the presence of obesity, conditions metabolic disruption or depletion of elements needed for homeostasis in the human body.

FGF21 serum levels are related to insulin resistance, metabolic changes and obesity in Mexican people living with HIV (PLWH).

BACKGROUND: Antiretroviral therapy has significantly improved prognosis in treatment against HIV infection, however, prolonged exposure is associated to cardiovascular diseases, lipodystrophy, type 2 diabetes, insulin resistance, metabolic alteration, as obesity which includes the accumulation of oxidative stress in adipose tissue. FGF21 is a peptide hormone that is known to regulate glucose and lipid metabolism. FGF21 is expressed and secreted primarily in the liver and adipose tissue, promoting oxidation of glucose/fatty acids and insulin sensitivity. Alterations in FGF21 may be associated with the development of insulin resistance, metabolic syndrome and cardiovascular disease. We hypothesized that FGF21 protein levels are associated with metabolic abnormalities, placing special attention to the alterations in relation to the concurrence of overweight/obesity in people living with HIV (PLWH). DESIGN: Serum FGF21 was analyzed in 241 subjects, 160 PLWH and 81 unrelated HIV-uninfected subjects as a control group. Clinical records were consulted to obtain CD4+ cell counting and number of viral RNA copies. Serum FGF21 levels were tested for correlation with anthropometric and metabolic parameters; glucose, cholesterol, HDL, LDL, VLDL, triglycerides, insulin and indexes of atherogenesis and insulin resistance (HOMA). RESULTS: The participants were classified into four groups: (i) PLWH with normal weight, (ii) PLWH with overweight/obesity, (iii) HIV-uninfected with normal weight, and (iv) HIV-uninfected with overweight/obesity. Insulin levels were higher in normal-weight PLWH than in the HIV-uninfected group but not statistically significant, however, for the overweight/obesity PLWH group, insulin levels were significantly higher in comparison with the other three groups (p<0.0001). For FGF21, serum levels were slightly higher in the overweight/obesity groups in both patients and controls. In HIV-infected subjects, FGF21 levels showed a strong positive correlation with triglycerides, insulin levels and insulin resistance with a p-value <0.0001. In the seronegative group, FGF21 was only correlated with weight and waist circumference, showing an important association of FGF21 levels with the degree of obesity of the individuals. CONCLUSION: Insulin resistance and FGF21 elevations were observed in overweight-obese PLWH. FGF21 elevation could be viewed as a compensation mechanism as, in the control group, FGF21 correlations appeared to be confined to weight and waist circumference. This can be explained based on the action of FGF21 promoting the uptake of glucose in adipose tissue. In PLWH, FGF21 was low, possibly as a result of a change in adiposity leading to a metabolic disruption.

Klotho-HIV and Oxidative Stress: The Role of Klotho in Cardiovascular Disease Under HIV Infection-A Review.

Combined antiretroviral therapy has improved quality and life expectancy of people living with human immunodeficiency virus (HIV). However, this therapy increases oxidative stress (OS), which in turn causes alterations in lipid and carbon metabolism, kidney disease, liver cirrhosis, and increased risk of cardiovascular disease. The Klotho gene has been implicated in cardiovascular risk increase. Klotho protein expression at X level decreases the risk of heart disease. HIV-positive people usually present low plasma levels of Klotho; thus, contributing to some extent to an increase in cardiovascular risk for these types of patients, mostly by favoring atherosclerosis. Therefore, our aim is to provide an overview of the effect of OS on Klotho protein and its consequent cardiometabolic alterations in HIV-positive patients on antiretroviral therapy.

Clinical Profile of Autism Spectrum Disorder in a Pediatric Population from Northern Mexico.

Autism spectrum disorder (ASD) is a neurodevelopmental condition classified based on needs of support, in order to address impairments in the areas of social communication and restricted and repetitive behavior. The aim of this work is to describe the main clinical features of the ASD severity levels in a group of Mexican pediatric patients. The results show firstly that this condition was more frequent in males than females. Secondly, an inverse relationship was found between the intellectual coefficient and the level of severity of the disorder. Thirdly, deficits in social reciprocity and communication were more evident in Level 3, than in Levels 1 and 2, while the difference was less evident in restricted and repetitive patterns of behavior.

[¿Azitromicina como tratamiento contra Chlamydia trachomatis?]

Azithromycin and doxycycline effectiveness has been demonstrated in the treatment of urogenital chlamydiasis, which has remained unchanged for a long time. Autoinoculation has been proposed as a method of reinfection and persistence of the disease in women and probably also owing to azithromycin pharmacokinetics in this tissue. With the new diagnostic methods and tests of cure, a difference has been demonstrated in favor of doxycycline in the treatment of rectal chlamydiasis Antimicrobial resistance has not played a relevant role since no treatment-resistant strains have been found in vivo. Nevertheless, azithromycin remains a first-choice drug, since it can be administered as a single dose, which favors therapeutic adherence.

Se ha demostrado la efectividad de la azitromicina y la doxiciclina en el tratamiento de la clamidiasis urogenital, lo que se ha mantenido sin cambios por mucho tiempo. Se ha propuesto la autoinoculación como método de reinfección y persistencia de la enfermedad en las mujeres y también debido a la farmacocinética de la azitromicina en este tejido. Con los nuevos métodos diagnósticos y las pruebas de curación se ha comprobado una diferencia a favor de la doxiciclina en el tratamiento de la clamidiasis rectal. La resistencia antimicrobiana no ha desempeñado un papel relevante porque no se han encontrado cepas resistentes in vivo al tratamiento. A pesar de ello, la azitromicina sigue siendo un fármaco de primera elección ya que puede administrarse como una dosis única, lo que favorece el apego terapéutico.

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer.

OBJECTIVE: To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8-T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. MATERIALS AND METHODS: Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ(2) and Hardy-Weinberg test. RESULTS: Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. CONCLUSION: The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican's.

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer / Polimorfismos IVS24-9delT, IVS38-8T>C y 5557G>A en el gen ATM en mujeres mexicanas con cáncer de mama familiar o de inicio temprano

Objective. To assess whether in Mexican population the frequencies of ATM polymorphisms IVS24-9delT, IVS38-8-T>C, and 5557G>A in breast cancer (BC) cases and healthy controls were different from those found in other countries. Materials and methods. Frequencies of polymorphisms conferring BC risk IVS24-9delT, IVS38-8T>C, and 5557G>A were analyzed by PCR-RFLP in 94 patients with familial and/or early onset BC, and 97 healthy controls randomly selected. Allele frequencies analysis was done using χ² and Hardy-Weinberg test. Results. Frequencies of heterozygous were: for 5557G>A, 13% cases, 0%controls (p=0.0009); for IVS24-9delT, 21% cases, 8% controls (p=0.0122); for IVS38-8T>C, only one case. 5557G>A and IVS24-9delT were more frequent in cases than in controls. The allelic frequencies found in 5557G>A are similar to those described by González-Hormazábal in Chile. Conclusion. The similarity of results in this polymorphism between Chilean and Mexican populations may be due to both being crossbred with an Amerindian-Spanish component, while differences may be due to fact that Chilean population has a greater European component than Mexican's.

Objetivo. Evaluar si en la población mexicana las frecuencias de los polimorfismos IVS-9delT, IVS38-8T>C y 5557G>A en casos de cáncer de mama y en controles sanos son diferentes de las encontradas en otros países. Material y métodos. Los polimorfismos IVS24-9delT, IVS38-8T>C y 5557G>A fueron analizados mediante PCR-RFLPs en 94 pacientes con CM de tipo familiar o de inicio temprano y 97 testigos seleccionadas de forma aleatoria. El análisis de la frecuencia alélica se hizo mediante χ² y equilibrio de Hardy-Weinberg. Resultados. Las frecuencias de heterocigotos fueron 5557G>A, 13% de casos, 0% de testigos (p=0.0009); IVS24-9delT, 21% de casos, 8% de testigos (p=0.0l22); IVS38-8T>C, sólo un caso. 5557G>A y IVS24-9delT fueron más frecuentes en casos que en testigos. Las frecuencias alélicas encontradas en 5557G>A son similares a las descritas por González-Hormazábal en Chile. Conclusión. La similitud de resultados en este polimorfismo entre la población chilena y mexicana puede ser debida a que ambas son mestizas con un componente amerindio-español. Las diferencias encontradas podrían explicarse porque la población chilena tiene mayor componente europeo que la mexicana.

YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

BACKGROUND AND AIMS: Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. METHODS: There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). RESULTS: There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). CONCLUSIONS: YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC.

Serum levels of polychlorinated biphenyls in Mexican women and breast cancer risk.

The most prevalent female cancer across the world is breast cancer. Current established breast cancer risk factors explain only a fraction of the breast cancer cases diagnosed, and for this reason, other environmental factors have been studied. Exposure to organochlorine compounds has been linked to an increased incidence of breast cancer, although not all data have been consistent. This study was designed to evaluate the relation between polychlorinated biphenyls (PCB) exposure and breast cancer risk in Mexican women. We recruited 140 women from the General Hospital. The cases were 70 newly diagnosed women. We collected environmental and reproductive information by questionnaire. Blood samples were taken for measurement of serum levels of 20 PCB congeners. Risk of breast cancer was found to be positively associated with heavy congeners, age, postmenopausal status, family history of breast cancer and living close to an industrial facility. When PCB were grouped by structure-activity relationships, the risk of breast cancer was positively associated with groups 2b (odds ratio, OR = 1.90, 95% confidence interval, CI, 1.25-2.88), 3 (OR = 1.81, 95% CI 1.08-3.04) and group 4 (OR = 1.57, 95% CI 1.20-2.07). Among postmenopausal women, PCB levels from groups 1a, 2b, and 4 and total PCB were higher in cases, and an association between risk of breast cancer with groups 1a (OR = 7.59, 95% CI 1.1-51.4), 2b (OR = 3.7, 95% CI 1.2-11.2) and 4 (OR = 1.8, 95% CI 1.1-3.1) was found in this group of women. This study showed an association between heavy and potentially estrogenic PCB congeners and breast cancer risk.

Molecular epidemiology of HIV type 1 in Mexico: emergence of BG and BF intersubtype recombinants.

The molecular epidemiology of subtypes and intersubtype recombinants (IRs) of human immunodeficiency virus type 1 (HIV-1) in Mexico has not been characterized fully. Understanding its regional distribution, prevalence, adaptability, viral fitness, pathogenicity, and immunogenicity is decisive for any design of an effective HIV vaccine. The aim of this study was to describe the presence of IRs types BG and BF in a Mexican population. Protease and reverse transcriptase regions of the pol gene were sequenced using an automated sequencing system. A phylogenic tree was constructed and genetic distances were calculated using MEGA 3.1. Recombination analysis was done by bootscan using SimPlot software. Two hundred and twenty-three HIV-1-positive individuals were enrolled in the study. At baseline, the mean plasma viral load was 285,500 HIV-1 RNA copies/ml and the mean CD4 cell count was 213 cells/ml. Subtype B was found in 220 (98.6%) samples, whereas IRs were found in three patients (1.4%): two (0.9%) with BG and one (0.45%) with BF. IRs were observed in 2/124 (1.6%) samples from treated patients and in 1/99 (1.0%) from naive patients. The presence of these HIV forms at low frequency points to the need for research on the diversity, geographic distribution, and evolution of other subtypes including circulating recombinant forms and IRs to understand the molecular epidemiology and tendencies of the HIV infection in Mexico.