Mycobacterium tuberculosis Complex Genotype Diversity and Drug Resistance Profiles in a Pediatric Population in Mexico

The aim of this study was to determine the frequency of drug resistance and the clonality of genotype patterns in M. tuberculosis clinical isolates from pediatric patients in Mexico (n = 90 patients from 19 states; time period—January 2002 to December 2003). Pulmonary disease was the most frequent clinical manifestation (71%). Children with systemic tuberculosis (TB) were significantly younger compared to patients with localized TB infections (mean 7.7 ± 6.2 years versus 15 ± 3.4 years P = 0.001). Resistance to any anti-TB drug was detected in 24/90 (26.7%) of the isolates; 21/90 (23.3%) and 10/90 (11.1%) were resistant to Isoniazid and Rifampicin, respectively, and 10/90 (11.1%) strains were multidrug-resistant (MDR). Spoligotyping produced a total of 55 different patterns; 12/55 corresponded to clustered isolates (n = 47, clustering rate of 52.2%), and 43/55 to unclustered isolates (19 patterns were designated as orphan by the SITVIT2 database). Database comparison led to designation of 36 shared types (SITs); 32 SITs (n = 65 isolates) matched a preexisting shared type in SITVIT2, whereas 4 SITs (n = 6 isolates) were newly created. Lineage classification based on principal genetic groups (PGG) revealed that 10% of the strains belonged to PGG1 (Bovis and Manu lineages). Among PGG2/3 group, the most predominant clade was the Latin-American and Mediterranean (LAM) in 27.8% of isolates, followed by Haarlem and T lineages. The number of single drug-resistant (DR) and multidrug-resistant (MDR-TB) isolates in this study was similar to previously reported in studies from adult population with risk factors. No association between the spoligotype, age, region, or resistance pattern was observed. However, contrary to a study on M. tuberculosis spoligotyping in Acapulco city that characterized a single cluster of SIT19 corresponding to the EAI2-Manila lineage in 70 (26%) of patients, not a single SIT19 isolate was found in our pediatric patient population. Neither did we find any shared type belonging to the EAI family which represents ancestral PGG1 strains within the M. tuberculosis complex. We conclude that the population structure of pediatric TB in our setting is different from the one prevailing in adult TB patient population of Guerrero

The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors

Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular “chat” is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells

Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme’s structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman’s method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis

Naturally occurring deamidated triosephosphate isomerase is a promising target for cell-selective therapy in cancer

Human triosephosphate isomerase (HsTIM) is a central glycolytic enzyme and is overexpressed in cancer cells with accelerated glycolysis. Triple-negative breast cancer is highly dependent on glycolysis and is typically treated with a combination of surgery, radiation therapy, and chemotherapy. Deamidated HsTIM was recently proposed as a druggable target. Although thiol-reactive drugs affect cell growth in deamidated HsTIM-complemented cells, the role of this protein as a selective target has not been demonstrated. To delve into the usefulness of deamidated HsTIM as a selective target, we assessed its natural accumulation in breast cancer cells. We found that deamidated HsTIM accumulates in breast cancer cells but not in noncancerous cells. The cancer cells are selectively programmed to undergo cell death with thiol-reactive drugs that induced the production of methylglyoxal (MGO) and advanced glycation-end products (AGEs). In vivo, a thiol-reactive drug effectively inhibits the growth of xenograft tumors with an underlying mechanism involving deamidated HsTIM. Our findings demonstrate the usefulness of deamidated HsTIM as target to develop new therapeutic strategies for the treatment of cancers and other pathologies in which this post translationally modified protein accumulates

Asociación de vitíligo y tiroiditis crónica autoinmune en adolescente masculino con obesidad

Vitiligo is the most common acquired depigmentation disorder with a worldwide preva-lence from 0.5 to 2%. It is highest incidence occurs between the ages of 10 to 30 years old. Frequently, it is associated with autoimmune thyroid disorders and related to the presence of anti-thyroid peroxidase antibodies in 20% of the times. We present the case of 15 years old male, diagnosed with vitiligo at 10 years old with currently dermatology followup under treatment. The patient is in medical monitoring due to obesity. It has been described an association between Vitiligo and Thyroiditis, doubling the risk of presence in five years from the concomitant diagnose to a previous autoimmune pathology. Considering that vitiligo usually precedes the onset of thyroid dysfunction, periodic monitoring in patients with this disorder it is of great importance.El vitíligo es el trastorno despigmentante adquirido más frecuente, con una prevalencia mundial del 0.5-2%. Su mayor incidencia se produce entre los 10 y 30 años. Se asocia a trastornos tiroideos autoinmunes con presencia de anticuerpos antitiroperoxidasa hasta en un 20%. Se presenta el caso de masculino de 15 años de edad, diagnosticado con vitíligo a los 10 años de edad con seguimiento por dermatología, actualmente en tratamiento. El paciente se encuentra en seguimiento médico por obesidad. Se ha descrito asociación positiva entre vitiligo y tiroiditis autoinmune, duplicando el ries-go a los cinco años de diagnóstico concomitante a patología autoinmune previa. Teniendo en cuenta que el vitiligo precede generalmente al inicio de la disfunción tiroidea, el seguimiento periódico de pacientes con vitiligo es de gran importancia

Morbilidad y mortalidad por sepsis neonatal en un hospital de tercer nivel de atención

OBJETIVO: Comparar el comportamiento de un grupo de recién nacidos sépticos que fallecieron contra un grupo de recién nacidos sépticos vivos. MATERIAL Y MÉTODOS: Revisión retrospectiva de expedientes de un grupo de recién nacidos con sepsis neonatal, atendidos en el Instituto Nacional de Pediatría, de la Secretaría de Salud de México, en la Ciudad de México, D.F., entre 1992 y 2000, los cuales se dividieron en recién nacidos sépticos vivos y fallecidos a los 90 días de seguimiento máximo. Se compararon las variables entre los grupos a través de U de Mann Whitney en el caso de variables numéricas, y ji cuadrada o prueba exacta de Fisher en el caso de variables categóricas. Las variables significativas en el análisis bivariado se incluyeron en uno de riesgos proporcionales de Cox. En todos los análisis se consideró como significativo un valor de p< 0.05. RESULTADOS: Se incluyeron 116 casos (65 vivos, 51 fallecidos). El antecedente de sufrimiento fetal, la presencia de dificultad respiratoria, el llenado capilar prolongado, la presencia de plaquetopenia y el hemocultivo positivo a Klebsiella pneumoniae estuvieron significativamente asociados con mayor riesgo de muerte en el modelo multivariado. CONCLUSIONES: Existen antecedentes epidemiológicos, clínicos, de laboratorio y microbiológicos capaces de predecir significativamente el riesgo de muerte a lo largo de la hospitalización de un recién nacido séptico

Acumulación de masa ósea medida por DEXA periférica en niños mexicanos sanos de entre 6 a 12 años de edad Bone mass accretion in healthy Mexican 6 to 12 year-olds measured by DEXA

OBJETIVO:Conocer la densidad mineral ósea (DMO), evaluada a través de DEXA periférica, ajustada por sexo, en una muestra de escolares mexicanos sanos de entre 6 a 12 años de edad. MATERIAL Y MÉTODOS: Estudio transversal efectuado en 1 965 escolares (982 masculinos), seleccionados de forma aleatoria en la Ciudad de México en 2006 y 2007. Se aplicó estadística descriptiva para variables nominales o categóricas y numéricas. RESULTADOS:La curva de cambio de la DMO en niñas muestra dos etapas: un crecimiento lineal (entre los 6 a 9 años de edad) y uno exponencial (a partir de los 10 años), mientras que en los niños las tasas de crecimiento son menos pronunciadas. CONCLUSIONES:Las intervenciones para mejorar la DMO y el pico máximo de masa ósea deben realizarse entre los 6 a los 12 años de edad.OBJECTIVE:To describe bone mass density in a group of healthy 6 to 12 year-old Mexican children by a peripheral DEXA, adjusted for gender. MATERIAL AND METHODS: A cross-sectional study between 2006 and 2007 conducted in 1 965 children (982 male), without any medical condition, randomized from elementary schools in Mexico City. RESULTS:Changes in bone mineral density in girls show two phases: a lineal accretion (6-9 years) and an exponential curve (10 years and older); in boys these growth rates are less pronounced. CONCLUSIONS:It is considered that optimal interventions to improve bone mass density and peak bone mass should be performed between 6 to 12 years of age

Morbilidad y mortalidad por sepsis neonatal en un hospital de tercer nivel de atención

Objetivo. Comparar el comportamiento de un grupo recién nacidos sépticos que fallecieron contra un grupo de recién nacidos sépticos vivos. Material y métodos. Revisión retrospectiva de expedientes de un grupo de recién nacidos con sepsis neonatal, atendidos en el Instituto Nacional de Pediatría, de la Secretaría de Salud de México, la Ciudad de México, D.F., entre 1992 y 2000, los cuales dividieron en recién nacidos sépticos vivos y fallecidos a 90 días de seguimiento máximo. Se compararon las variables entre los grupos a través de U de Mann Whitney en caso de variables numéricas, y ji cuadrada o prueba exacta de Fisher en el caso de variables categóricas. Las variables significativas en el análisis bivariado se incluyeron en uno riesgos proporcionales de Cox. En todos los análisis se consideró como significativo un valor de p< 0.05. Resultados. Se incluyeron 116 casos (65 vivos, 51 fallecidos). El antecedente de sufrimiento fetal, la presencia de dificultad respiratoria, el llenado capilar prolongado, la presencia plaquetopenia y el hemocultivo positivo a Klebsiella pneumoniae estuvieron significativamente asociados con mayor riesgo de muerte en el modelo multivariado. Conclusiones. Existen antecedentes epidemiológicos, clínicos, laboratorio y microbiológicos capaces de predecir significativamente el riesgo de muerte a lo largo de la hospitalización de un recién nacido séptico. El texto completo inglés de este artículo está disponible en: http://www.insp.mx/ salud/index.htm

Morbilidad y mortalidad por sepsis neonatal en un hospital de tercer nivel de atención Morbidity and mortality due to neonatal sepsis in a tertiary care hospital

OBJETIVO: Comparar el comportamiento de un grupo de recién nacidos sépticos que fallecieron contra un grupo de recién nacidos sépticos vivos. MATERIAL Y MÉTODOS: Revisión retrospectiva de expedientes de un grupo de recién nacidos con sepsis neonatal, atendidos en el Instituto Nacional de Pediatría, de la Secretaría de Salud de México, en la Ciudad de México, D.F., entre 1992 y 2000, los cuales se dividieron en recién nacidos sépticos vivos y fallecidos a los 90 días de seguimiento máximo. Se compararon las variables entre los grupos a través de U de Mann Whitney en el caso de variables numéricas, y ji cuadrada o prueba exacta de Fisher en el caso de variables categóricas. Las variables significativas en el análisis bivariado se incluyeron en uno de riesgos proporcionales de Cox. En todos los análisis se consideró como significativo un valor de p< 0.05. RESULTADOS: Se incluyeron 116 casos (65 vivos, 51 fallecidos). El antecedente de sufrimiento fetal, la presencia de dificultad respiratoria, el llenado capilar prolongado, la presencia de plaquetopenia y el hemocultivo positivo a Klebsiella pneumoniae estuvieron significativamente asociados con mayor riesgo de muerte en el modelo multivariado. CONCLUSIONES: Existen antecedentes epidemiológicos, clínicos, de laboratorio y microbiológicos capaces de predecir significativamente el riesgo de muerte a lo largo de la hospitalización de un recién nacido séptico.<br>OBJECTIVE: To compare the epidemiological, clinical and microbiological profiles between patients with neonatal sepsis who lived or died. MATERIAL AND METHODS: The medical records of patients with neonatal sepsis were retrospectively reviewed at Instituto Nacional de Pediatría (National Pediatric Institute) of Secretaría de Salud (Ministry of Health) in Mexico City, between 1992 and 2000. Neonatal sepsis cases were classified as surviving or not after 90 days of postnatal follow-up. The survivor and deceased groups were compared using Mann-Whitney's U test for continuous variables, and the chi-squared test or the Fisher's exact test for categorical variables. Significantly associated variables were included in a Cox proportional hazards model. A p-value <0.05 was considered statistically significant for all analyses. RESULTS: A total of 116 patients with neonatal sepsis were included (65 live and 51 dead). Multivariate analysis showed that fetal distress, respiratory distress, a delayed capillary fill up, a low platelet count, and a positive hemoculture for Klebsiella pneumoniae were significant risk factors for death. CONCLUSIONS: Epidemiological, clinical, laboratory, and microbiological variables are significant predictors of death in newborns with neonatal sepsis