Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Influence of coffee roasting degree on inflammatory and oxidative stress markers in high-fructose and saturated fat-fed rats.

The objective of this study was to evaluate the effect of roasting coffee degree on inflammatory (NF-kß F-6 and TNF-α) and stress oxidative markers (malondialdehyde (MDA), nitric oxide (NO) end product concentrations, catalase (CAT), and superoxide dismutase (SOD) in high-fructose and saturated fat (HFSFD)-fed rats. Roasting was performed using hot air circulation (200 °C) for 45 and 60 min, obtaining dark and very dark coffee, respectively. Male Wistar rats were randomly assigned to receive a) unroasted coffee, b) dark coffee, c) very dark coffee, or distilled water for the control group (n = 8). Coffee brews (7.4 mL/per day equivalent to 75 mL/day in humans) were given by gavage for sixteen weeks. All treated groups significantly decreased NF-kß F-6 (∼30 % for unroasted, ∼50 % for dark, and âˆ¼ 75 % for very dark group) and TNF-α in the liver compared with the control group. Additionally, TNF-α showed a significant reduction in all treatment groups (∼26 % for unroasted and dark groups, and âˆ¼ 39 % for very dark group) in adipose tissue (AT) compared with the negative control. Regarding oxidative stress makers, all coffee brews exerted antioxidant effects in serum, AT, liver, kidney, and heart. Our results revealed that the anti-inflammatory and antioxidant effects of coffee vary according to the roasting degree in HFSFD-fed rats.

Hypomagnesemia and 25-hydroxyvitamin D deficiency in patients with long COVID.

Clinical manifestations related to hypomagnesemia and/or deficiency of vitamin D are frequent in patients with an extended course of coronavirus disease-2019 (long COVID). To evaluate hypomagnesemia and hydroxyvitamin D deficiency in patients with long COVID. A total of 125 adults with a diagnosis of long COVID were enrolled in a cross-sectional study. Participants were allocated into a risk (hypomagnesemia and hydroxyvitamin D deficiency) or control (serum magnesium and hydroxyvitamin D within normal ranges) group. Hypomagnesemia and 25-hydroxyvitamin D deficiency were defined based on serum level ≤1.8 mg/dL and <30 ng/mL, respectively. The number of clinical manifestations of long COVID were significantly higher in the risk compared to the control group. Fatigue, memory loss, attention disorders, joint pain, anxiety, sleep disorders, myalgia, and depression, all of which are related to hypomagnesemia and/or 25-hydroxyvitamin D deficiency, were among the 10 most frequent manifestations in the risk group. The adjusted odds ratio for the association between hypomagnesemia and hydroxyvitamin D deficiency during long COVID was 3.1; 95% CI 2.3-12.4, p=0.005. Our results show that patients suffering with long COVID had a deficiency in magnesium and 25-hydroxyvitamin D which correlated with the number of associated clinical manifestations.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. AIM OF THE STUDY: Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. MATERIALS AND METHODS: Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. RESULTS: Both extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 µg/µL for O-E and 1.8 µg/µL for O-A) than the positive control (Orlistat) (0.07 µg/µL). The IC50 of α-amylase was higher (41.8 µg/µL for O-E and 25.2 µg/µL for O-A) than the Acarbose (2.5 µg/µL); while α-glucosidase results showed not statistically differences between groups (∼1.7 µg/µL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 µg/µL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 µg/µL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. CONCLUSIONS: Both extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dL in normal weight full-term healthy newborns / Polimorfismos 1304 G > A y 292 C > T del gen placentario SLC38A4 y su asociación con glucosa > 95 mg/dL en recién nacidos a término, sanos y con peso normal al nacimiento

Abstract Background: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. Methods: We conducted a case–control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. Results: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). Conclusions: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

Resumen Introducción: El gen SLC38A4 codifica la proteína SNAT4, que se ha relacionado con alteraciones en el metabolismo de la glucosa en los humanos. El objetivo de este estudio fue determinar si los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se asocian con concentraciones de glucosa > 95 mg/dL en recién nacidos a término Métodos: Se llevó a cabo un estudio de casos y controles con 50 recién nacidos a término, sanos, con peso normal al nacimiento. Los grupos se definieron de acuerdo con las concentraciones de glucosa: > 95 mg/dL (casos; n = 13) y < 95 mg/dL (controles; n = 37). Los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se genotipificaron por qPCR utilizando ADN de la placenta. La asociación entre los polimorfismos y la concentración de glucosa > 95 mg/dL se estableció mediante la estimación de la razón de momios (RM) en un análisis múltiple de regresión logística. Resultados: No se observaron diferencias estadísticamente significativas para la edad gestacional y el peso al nacer entre los grupos de estudio. El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) fue significativamente más alto en los recién nacidos del grupo de casos que en el grupo control (p < 0.0005). La RM mostró asociación significativa entre el polimorfismo de nucleótido único (SNP) 292 C > T del gen SLC38A4 y la concentración de glucosa > 95 mg/dL (RM: 7.78; p = 0.024); el SNP 1304 G > A no mostró asociación significativa (RM: 1.46; p = 0.77). Conclusiones: Los resultados de este estudio sugieren que el SNP 292 C > T del gen SLC38A4 se asocia con concentraciones de glucosa > 95 mg/dL en recién nacidos a término.

Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dl in normal weight full-term healthy newborns.

BACKGROUND: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. METHODS: We conducted a case-control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. RESULTS: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). CONCLUSIONS: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

The triglycerides and glucose index is strongly associated with hepatic steatosis in children with overweight or obesity.

Given the worldwide increase prevalence of overweight, obesity, and nonalcoholic fatty liver disease (NAFLD), the objective of this study was to evaluate whether the triglycerides and glucose (TyG) index is associated with hepatic steatosis in children with overweight or obesity. Apparently healthy children aged 5­17 years were included and allocated into the groups with and without hepatic steatosis. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Hepatic steatosis was diagnosed by ultrasonography. A total of 177 children, 66 (37.3%) girls and 111 (62.7%) boys, were included in the study. According to the hepatic ultrasonography, they were allocated into the groups with (n = 100) and without (n = 77) hepatic steatosis. The adjusted analysis by gender, body mass index, and waist circumference revealed that HDL-C (OR 0.96; 95% CI: 0.93-0.99), triglycerides (OR 1.005; 95% CI: 1.001-1.009), AST (OR 1.03; 95% CI: 1.008-1.07), ALT (OR 1.03; 95% CI: 1.01-1.05), and TyG index (OR 4.07; 95% CI: 1.26-13.15) remained associated with hepatic steatosis.Conclusion: Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight and obesity. What is known: • The triglycerides and glucose (TyG) index is effective in predicting high risk for incident nonalcoholic fatty liver disease (NAFLD) in adults. What is new: • Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight or obesity. • The triglycerides and glucose index may be a useful tool to detect children at high risk of fatty liver.

Association of the 5HTTLPR Polymorphism with Obesity in Mexican Women with High Native American Ancestry.

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).

Hypoglycemic and antioxidant effects of five commercial turmeric (Curcuma longa) supplements.

We evaluate the hypoglycemic and antioxidant effects of five commercial turmeric (Curcuma longa) supplements: (1) bulk samples, (2) turmeric root from India, (3) curcuma turmeric Pronat® , (4) turmeric & black pepper Swanson® , and (5) C3 complex® turmeric curcumin. Glucose diffusion and enzymatic starch digestion assays, using α-amylase and α-glucosidase, were performed. The antioxidant activity of turmeric supplements was measured through lipid peroxidation inhibition and the scavenging radical assay. A starch dose of 102 mg/Kg of body weight (equivalent to 1 g/day in humans) was used to perform the oral starch tolerance test (OSTT) in Wistar male rats. All turmeric supplements decreased glucose diffusion and α-glucosidase enzyme activity, and inhibited lipid peroxidation. The rats that received bulk samples and CT showed significantly lower glucose levels than rats receiving acarbose and those of negative control group. Our results show that biological activities of turmeric supplements vary according to the commercial presentation. PRACTICAL APPLICATIONS: The study results suggest that the hypoglycemic and antioxidant effects of five commercial turmeric supplements vary among them. The information provided would be useful to physicians and individuals using these supplements.

Prevalence of overweight and obesity in school-age children.

INTRODUCTION: Childhood obesity is a public health challenge. Between 1999 and 2012, the prevalence in Mexico of overweight and obesity in schoolchildren went from 25.5 to 32 %. OBJECTIVE: To report current prevalence of overweight and obesity in schoolchildren from the municipality of Durango, Mexico. METHOD: Cross-sectional survey conducted between January 2017 and December 2018. A total of 24,600 children aged between six and 11 years from 138 schools of the municipality of Durango were included. The body mass index reference values established by the World Health Organization were used to determine the presence of overweight and obesity. RESULTS: The prevalence of overweight was 19.7 %, of obesity, 16 %, and of overweight and obesity combined, 35.7 %. In the six-year-old group, a prevalence of overweight-obesity of 25.4 % was found, and in the 11-year-old group, 41.1 %. CONCLUSIONS: The prevalence of overweight-obesity in children aged from 6 to 11 years in the municipality of Durango is higher than those reported in the national survey by states in 2012 and in the 2016 national survey; a trend towards an increase with age was observed.

INTRODUCCIÓN: La obesidad infantil es un reto de salud pública. Entre 1999 y 2012, en México la prevalencia de sobrepeso y obesidad (SO) en niños escolares pasó de 25.5 a 32 %. OBJETIVO: Reportar la prevalencia actual de SO en niños escolares del municipio de Durango, México. MÉTODO: Encuesta transversal realizada entre enero de 2017 y diciembre de 2018. Se incluyeron 24 600 niños de seis a 11 años, de 138 escuelas del municipio de Durango. Se utilizaron los valores de referencia del índice de masa corporal establecidos por la Organización Mundial de la Salud para determinar la presencia de SO. RESULTADOS: La prevalencia de sobrepeso fue de 19.7 %, la de obesidad de 16 % y la de SO de 35.7 %. En el grupo de seis años se encontró una prevalencia de SO de 25.4 % y en el de 11 años, de 41.1 %. CONCLUSIONES: La prevalencia de SO en niños de seis a 11 años del municipio de Durango es más elevada que la reportada en la encuesta nacional por entidad federativa en 2012 y la nacional en 2016; se observó tendencia al incremento en la prevalencia conforme aumenta la edad.

Prevalencia de sobrepeso y obesidad en niños escolares / Prevalence of overweight and obesity in school-age children

Resumen Introducción: La obesidad infantil es un reto de salud pública. Entre 1999 y 2012, en México la prevalencia de sobrepeso y obesidad (SO) en niños escolares pasó de 25.5 a 32 %. Objetivo: Reportar la prevalencia actual de SO en niños escolares del municipio de Durango, México. Método: Encuesta transversal realizada entre enero de 2017 y diciembre de 2018. Se incluyeron 24 600 niños de seis a 11 años, de 138 escuelas del municipio de Durango. Se utilizaron los valores de referencia del índice de masa corporal establecidos por la Organización Mundial de la Salud para determinar la presencia de SO. Resultados: La prevalencia de sobrepeso fue de 19.7 %, la de obesidad de 16 % y la de SO de 35.7 %. En el grupo de seis años se encontró una prevalencia de SO de 25.4 % y en el de 11 años, de 41.1 %. Conclusiones: La prevalencia de SO en niños de seis a 11 años del municipio de Durango es más elevada que la reportada en la encuesta nacional por entidad federativa en 2012 y la nacional en 2016; se observó tendencia al incremento conforme aumenta la edad.

Abstract Introduction: Childhood obesity is a public health challenge. Between 1999 and 2012, the prevalence in Mexico of overweight and obesity in schoolchildren went from 25.5 to 32 %. Objective: To report current prevalence of overweight and obesity in schoolchildren from the municipality of Durango, Mexico. Method: Cross-sectional survey conducted between January 2017 and December 2018. A total of 24,600 children aged between six and 11 years from 138 schools of the municipality of Durango were included. The body mass index reference values established by the World Health Organization were used to determine the presence of overweight and obesity. Results: The prevalence of overweight was 19.7 %, of obesity, 16 %, and of overweight and obesity combined, 35.7 %. In the six-year-old group, a prevalence of overweight-obesity of 25.4 % was found, and in the 11-year-old group, 41.1 %. Conclusions: The prevalence of overweight-obesity in children aged from 6 to 11 years in the municipality of Durango is higher than those reported in the national survey by states in 2012 and in the 2016 national survey; prevalence showed a tendency to increase with age.

The role of xenobiotic-metabolizing enzymes in the placenta: a growing research field.

Introduction: The placenta is a temporary and unique organ that allows for the physical connection between a mother and fetus; this organ regulates the transport of gases and nutrients mediating the elimination of waste products contained in the fetal circulation. The placenta performs metabolic and excretion functions, on the basis of multiple enzymatic systems responsible for the oxidation, reduction, hydrolysis, and conjugation of xenobiotics. These mechanisms give the placenta a protective role that limits the fetal exposure to harmful compounds. During pregnancy, some diseases require uninterrupted treatment even if it is detrimental to the fetus. Drugs and other xenobiotics alter gene expression in the placenta with repercussions for the fetus and mother's well-being.Areas covered: This review provides a brief description of the human placental structure and function, the main drug and xenobiotic transporters and metabolizing enzymes, placenta-metabolized substrates, and alterations in gene expression that the exposure to xenobiotics may cause.Expert opinion: Research should be focused on the identification and validation of biological markers for the assessment of the harmful effects of some drugs in pregnancy, including the evaluation of polymorphisms and methylation patterns in chorionic villous samples and/or amniotic fluid.

Respiratory viruses detected in Mexican children younger than 5 years old with community-acquired pneumonia: a national multicenter study.

BACKGROUND: Acute respiratory infections are the leading cause of mortality in children worldwide, especially in developing countries. Pneumonia accounts for 16% of all deaths of children under 5 years of age and was the cause of death of 935000 children in 2015. Despite its frequency and severity, information regarding its etiology is limited. The aim of this study was to identify respiratory viruses associated with community-acquired pneumonia (CAP) in children younger than 5 years old. METHODS: One thousand four hundred and four children younger than 5 years of age with a clinical and/or radiological diagnosis of CAP in 11 hospitals in Mexico were included. Nasal washes were collected, placed in viral medium, and frozen at -70°C until processing. The first 832 samples were processed using the multiplex Bio-Plex/Luminex system and the remaining 572 samples using the Anyplex multiplex RT-PCR. Clinical data regarding diagnosis, clinical signs and symptoms, radiographic pattern, and risk factors were obtained and recorded. RESULTS: Of the samples tested, 81.6% were positive for viruses. Respiratory syncytial virus (types A and B) was found in 23.7%, human enterovirus/rhinovirus in 16.6%, metapneumovirus in 5.7%, parainfluenza virus (types 1-4) in 5.5%, influenza virus (types A and B) in 3.6%, adenovirus in 2.2%, coronavirus (NL63, OC43, 229E, and HKU1) in 2.2%, and bocavirus in 0.4%. Co-infection with two or more viruses was present in 22.1%; 18.4% of the samples were negative. Using biomass for cooking, daycare attendance, absence of breastfeeding, and co-infections were found to be statistically significant risk factors for the presence of severe pneumonia. CONCLUSIONS: Respiratory syncytial virus (types A and B), human enterovirus/rhinovirus, and metapneumovirus were the respiratory viruses identified most frequently in children younger than 5 years old with CAP. Co-infection was present in an important proportion of the children.

The D543N polymorphism of the SLC11A1/NRAMP1 gene is associated with treatment failure in male patients with pulmonary tuberculosis.

BACKGROUND: Polymorphisms in SLC11A1/NRAMP1 have shown an important association with susceptibility to tuberculosis and progression to active disease. However, whether there is an association of these polymorphisms with treatment failure is unknown. The aim of this study was to determine the association of SLC11A1 polymorphisms with treatment failure in Mexican subjects with pulmonary tuberculosis. METHODS: Thirty-three subjects with treatment failure were paired by age and body mass index with 33 patients who successfully completed treatment and were considered cured. We assessed the polymorphisms of SLC11A1 in the regions of D543N and INT4 via polymerase chain reaction real-time TaqMan® single nucleotide polymorphism (SNP) genotyping. RESULTS: We found that D543N (G/A genotype) was associated with treatment failure in patients with pulmonary tuberculosis [odds ratio (OR) 11.61, 95% confidence interval (CI) 3.66-36.78]. When adjusted by gender, this association remained significant in males (OR 11.09, 95% CI 3.46-35.51). CONCLUSIONS: In our male population, the presence of the D543N polymorphism of SLC11A1 is a risk factor for treatment failure. This finding should be confirmed in other populations.

Rhinovirus is an important pathogen in upper and lower respiratory tract infections in Mexican children.

BACKGROUND: Most of the studies characterizing the incidence of rhinovirus (RV) have been carried out in hospitalized children and in developed countries. In those studies, RV-C has been associated with more severe respiratory tract infections than RV species A and B. In this study we determined the frequency and diversity of RV strains associated with upper and lower respiratory tract infections (URTI, LRTI) in Mexico, and describe the clinical characteristics of the illness associated with different RV species. METHODS: A prospective surveillance of 526 and 250 children with URTI and LRTI was carried out. Respiratory samples were analyzed by RT-PCR for viruses. The 5' untranslated region of the RV genome was amplified and sequenced. RESULTS: In the case of URTI, 17.5% were positive for RV, while this virus was found in 24.8% of LRTI. The RV species was determined in 73 children with URTI: 61.6% were RV-A, 37% RV-C and, 1.4% RV-B; and in 43 children with LRTI: 51.2% were RV-A, 41.8% RV-C, and 7% RV-B. No significant differences in clinical characteristics were found in patients with RV-A or RV-C infections. A high genetic diversity of RV strains was found in both URTI and LRTI. CONCLUSIONS: Both RV-A and RV-C species were frequently found in hospitalized as well as in outpatient children. This study underlines the high prevalence and genetic diversity of RV strains in Mexico and the potential severity of disease associated with RV-A and RV-C infections.

Associated Risk Factors for Latent Tuberculosis Infection in Subjects with Diabetes.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (DM2) confers a higher risk for active tuberculosis (TB). However, information on associated risk factors for latent tuberculosis infection (LTBI) inpatients with DM2 is limited. We conducted a cross-sectional study to elucidate the prevalence of LTBI and its associated factors on Mexican adults with DM2 receiving medical care at the Mexican Social Security Institute (IMSS). METHODS: Six hundred patients with DM2 without a prior history of TB from outpatient diabetes clinics were enrolled in the study. The tuberculin-skin-test (TST) was performed. The presence of LTBI was defined by a TST value of ≥ 5 mm. A standardized interview and physical examination were conducted to obtain clinical, demographic, and LTBI risk factor information; all subjects were laboratory tested to determine the presence of exclusion criteria. Microscopic examination of sputum samples and chest x-rays was performed to identify potential active TB. Subjects with any finding suggesting active TB or malignancy were excluded. A logistic regression model was used to identify variables associated with LTBI. RESULTS: LTBI prevalence among patients with DM2 was 51.3%. Risk factors for LTBI were living with a relative with TB, having been in prison, having hemoglobin values >14 g/dL, and glycosylated hemoglobin (HbA1c) values of > 7%. Blood pressure, economic income, or anthropometric measurements were not associated risk factors. CONCLUSIONS: Over one half of patients with DM harbor LTBI. Exposure to certain environmental conditions and poorly controlled DM2 (HbA1c > 7.0%) were risk factors for having LTBI in persons with DM2.

Is there still room for novel viral pathogens in pediatric respiratory tract infections?

Viruses are the most frequent cause of respiratory disease in children. However, despite the advanced diagnostic methods currently in use, in 20 to 50% of respiratory samples a specific pathogen cannot be detected. In this work, we used a metagenomic approach and deep sequencing to examine respiratory samples from children with lower and upper respiratory tract infections that had been previously found negative for 6 bacteria and 15 respiratory viruses by PCR. Nasal washings from 25 children (out of 250) hospitalized with a diagnosis of pneumonia and nasopharyngeal swabs from 46 outpatient children (out of 526) were studied. DNA reads for at least one virus commonly associated to respiratory infections was found in 20 of 25 hospitalized patients, while reads for pathogenic respiratory bacteria were detected in the remaining 5 children. For outpatients, all the samples were pooled into 25 DNA libraries for sequencing. In this case, in 22 of the 25 sequenced libraries at least one respiratory virus was identified, while in all other, but one, pathogenic bacteria were detected. In both patient groups reads for respiratory syncytial virus, coronavirus-OC43, and rhinovirus were identified. In addition, viruses less frequently associated to respiratory infections were also found. Saffold virus was detected in outpatient but not in hospitalized children. Anellovirus, rotavirus, and astrovirus, as well as several animal and plant viruses were detected in both groups. No novel viruses were identified. Adding up the deep sequencing results to the PCR data, 79.2% of 250 hospitalized and 76.6% of 526 ambulatory patients were positive for viruses, and all other children, but one, had pathogenic respiratory bacteria identified. These results suggest that at least in the type of populations studied and with the sampling methods used the odds of finding novel, clinically relevant viruses, in pediatric respiratory infections are low.

Methamidophos alters sperm function and DNA at different stages of spermatogenesis in mice.

Methamidophos (MET) is a highly toxic organophosphate (OP) pesticide that is widely used in developing countries. MET has male reproductive effects, including decreased fertility. We evaluated MET effects on sperm quality, fertilization and DNA integrity, exploring the sensitivity of different stages of spermatogenesis. Adult male mice received MET (3.75 or 5mg/kg-bw/ip/day/4 days) and were euthanized 1, 28 or 45 days post-treatment (dpt) to evaluate MET's effects on epididymal maturation, meiosis or mitosis, respectively. Spermatozoa were obtained from the cauda epididymis-vas deferens and were evaluated for sperm quality, acrosome reaction (AR; Coomassie staining), mitochondrial membrane potential (by JC-1), DNA damage (comet assay), oxidative damage (malondialdehyde (MDA) production), in vitro fertilization and protein phosphorylation (immunodetection), and erythrocyte acetylcholinesterase (AChE) activity. At 1-dpt, MET inhibited AChE (43-57%) and increased abnormal cells (6%). While at 28- and 45-dpt, sperm motility and viability were significantly reduced with an increasing MET dose, and abnormal morphology increased at 5mg/kg/day/4 days. MDA and mitochondrial activity were not affected at any dose or time. DNA damage (OTM and %DNA) was observed at 5mg/kg/day/4 days in a time-dependent manner, whereas both parameters were altered in cells from mice exposed to 3.75 mg/kg/day/4 days only at 28-dpt. Depending on the time of collection, initial-, spontaneous- and induced-AR were altered at 5mg/kg/day/4 days, and the fertilization capacity also decreased. Sperm phosphorylation (at serine and tyrosine residues) was observed at all time points. Data suggest that meiosis and mitosis are the more sensitive stages of spermatogenesis for MET reproductive toxicity compared to epididymal maturation.