Childhood acute lymphoblastic leukemia survival and spatial analysis of socio-environmental risks in Mexico.

Background: Acute lymphoblastic leukemia (ALL) etiology remains largely unknown; incidence patterns by age, sex, and geographical distribution suggest a potential environmental role. Aim: To identify ALL clusters from four contrasting urban areas of Mexico and to characterize the sources of environmental carcinogens. Methods: Hospital-based ALL cases (n = 443) diagnosed in children <19 years old from the Metropolitan Zones of Merida and San Luis Potosi, the State of Mexico, and Tijuana were analyzed (2015-2020). ALL cases were coded according to the International Classification of Diseases for Oncology. ALL clusters were identified by Kernel Density, and excess risk was estimated. Data of particulate matter ≤2.5 µm (PM2.5) concentrations measured by community-monitoring stations were analyzed. Geocoded datasets of benzene, polycyclic aromatic hydrocarbons, and PM2.5 sources were analyzed to characterize patterns of exposure in ALL clusters. Results: The survival rate for ALL ranged from 61.5% to 78.6%. Seven ALL clusters with excess risk (RR 1.4-2.3, p < 0.05) were identified. The carcinogen sources included artisanal brick kilns, gas stations, cement works, carpentry, paint, and chemical manufacturing establishments. PM2.5 levels ranged from 15 µg/m3 to 37 µg/m3 among study areas. Conclusion: ALL clusters were identified at the community level; the excess risk could be explained by small-scale carcinogen sources. The levels of PM2.5 in outdoor air ranged from 3 to 6 times above the World Health Organization (WHO) air quality guidelines. Healthcare providers must raise awareness of the increased risk of ALL in children living near sources of environmental carcinogens; cancer control and prevention strategies must be steered from a multi-sectoral and multi-action perspective to protect children's health.

Cancer Incidence in Merida, Mexico 2015-2018: First Report from the Population-based Cancer Registry.

BACKGROUND: Cancer registries are essential for monitoring cancer burden and patterns, and document changes in time for cancer control. Hereby, we present the first results of four years of the Merida population-based cancer registry in Mexico. METHODS: The registry collects data on all new cancers diagnosed since 2015 using both active and passive methods including a total of 104 information sources. Definitions and coding follow international standards. Using CanReg5 software, age-standardized incidence rates (ASR/100,000 person years) were computed by direct method using the world standard population. RESULTS: A total of 5684 new cancer cases were registered during 2015-2018, 2321 in males and 3363 in females corresponding to age-adjusted incidence rates (ASR per 100,000) of 128.5, and 153.1, respectively. Most frequent cancers among males were prostate cancer (ASR 29.8), lymphomas (ASR 10.9) and colorectal cancer (ASR 9.7) while among females it was breast cancer (ASR 49.3), cervical cancer (ASR 17.5) and corpus uteri (ASR 11.5). Childhood cancers (0-14 year) represented 2.9% of all cancers, with leukemias accounting for 52% of the new cases. Overall, 87.6% of new cases were microscopically verified. CONCLUSIONS: The data reported provide information on the cancer profile in Merida. Prostate and breast cancer are the main incident cancers. Cervical cancers present high rates among women, while lymphomas and liver cancer data merit further exploration. Efforts to support the Merida cancer registry as well as other registries in Mexico need to be pursued in order to have locally recorded data to support cancer control measures.

Circulating Levels of Sex Steroid Hormones and Gastric Cancer.

BACKGROUND AND AIMS: Men develop gastric cancer more frequently than women, yet little is known about the mechanisms underlying this sex difference. Sex steroid hormones may influence gastric cancer risk. We therefore assessed whether major circulating adrenal precursors, androgens and estrogens were associated with gastric cancer in a high-risk Mexican population. METHODS: Blood samples were collected at time of diagnosis from 50 noncardia gastric cancer patients and 50 histologically confirmed non-atrophic gastritis controls. Serum levels of estradiol, testosterone and dehydroepiandrosterone (DHEA) measured with a validated mass spectrometry method were categorized in tertiles as low (T1), middle (T2), and high (T3). Unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and education. RESULTS: Levels of DHEA were inversely associated with gastric cancer (p-trend per tertile increase: <0.0001), with adjusted ORs (95% CI) of T2 and T3 (vs. T1) of 0.25 (0.09-0.70) and 0.10 (0.03-0.34), respectively. Levels of estradiol and testosterone were not significantly associated with gastric cancer. CONCLUSIONS: Our study provides evidence that higher concentration of circulating DHEA may be associated with lower risk of noncardia gastric cancer. Longitudinal studies are needed to evaluate the temporality of this association and investigate mechanisms of disease pathogenesis.

Implementation of the population-based cancer registry in the city of Mérida, Mexico: process and early results / Implementación del registro de cáncer de base poblacional de la ciudad de Mérida en México: procesos y resultados preliminares

Abstract: Objective: To briefly describe the process of establishment and preliminary results of the Mérida Population-based Cancer Registry (Mérida-PBCR) Materials and methods: Mérida-PBCR started in 2016 as a research project in the IMSS, with a gradual increase in its information sources. It covers a population of 908 536 inhabitants. Data collection is active and passive, international standards are used; CanReg5 software enables data entry, storage and analysis. Results: Current data include 71.5% of sources. For the period 2015-2016, a total of 2 623 new cancer cases were registered, the majority of these (60.1%) among females. 81.5% of the cases had morphological verification. Prostate (17.4%), colorectal (8.5%) and stomach (8.1%) cancers were the most common among males, and breast (31.6%), cervix (12%) and corpus uteri (7.6%) cancers, the most common among females. Age-adjusted cancer incidence rates (per 100 000) for all sites combined were 114.9 among males and 145.1 among females. Conclusion: The implementation of the Mérida-PBCR has followed particular parameters, with important efforts to include new information sources. Although the data are still preliminary and must be interpreted with great caution, the main cancers follow a similar pattern to that of the national and regional estimates.

Resumen: Objetivo: Describir brevemente el proceso de implementación y resultados preliminares del Registro de Cáncer de Base Poblacional (RCBP) de Mérida. Material y métodos: RCBP-Mérida inició en 2016 como un proyecto de investigación del IMSS, con cobertura poblacional de 908 536 habitantes. El número de fuentes de información ha incrementado gradualmente. Se realizó colección de datos de forma pasiva y activa en software CanReg5 utilizando estándares internacionales. Resultados: Se han incluido al RCBP-Mérida 71.5% de las fuentes de información. Durante 2015-2016 se registraron 2 623 casos nuevos, la mayoría (60.1%) mujeres. El 81.5% de los casos tuvo verificación morfológica. En hombres, el cáncer de próstata (17.4%), colorrectal (8.5%) y estómago (8.1%) son los más comunes; en mujeres, mama (31.6%), cérvix (12.0%) y cuerpo-uterino (7.6%). Las tasas de incidencia ajustadas por edad (100 000 habitantes) para todos los sitios combinados son 114.9 hombres y 145.1 mujeres. Conclusión: La implementación del RCBP-Mérida ha seguido parámetros particulares, con importante esfuerzo para incluir fuentes de información. Aunque los datos son preliminares y se deben interpretar con precaución; los principales tipos de cáncer siguen un patrón similar a las estimaciones nacionales y regionales

Implementation of the population-based cancer registry in the city of Mérida, Mexico: process and early results.

OBJECTIVE: To briefly describe the process of establishment and preliminary results of the Mérida Population-based Cancer Registry (Mérida-PBCR). MATERIALS AND METHODS: Mérida-PBCR started in 2016 as a research project in the IMSS, with a gradual increase in its information sources. It covers a population of 908 536 inhabitants. Data collection is active and passive, international standards are used; CanReg5 software enables data entry, storage and analysis. RESULTS: Current data include 71.5% of sources. For the period 2015- 2016, a total of 2 623 new cancer cases were registered, the majority of these (60.1%) among females. 81.5% of the cases had morphological verification. Prostate (17.4%), colorectal (8.5%) and stomach (8.1%) cancers were the most common among males, and breast (31.6%), cervix (12%) and corpus uteri (7.6%) cancers, the most common among females. Ageadjusted cancer incidence rates (per 100 000) for all sites combined were 114.9 among males and 145.1 among females. CONCLUSIONS: The implementation of the Mérida-PBCR has followed particular parameters, with important efforts to include new information sources. Although the data are still preliminary and must be interpreted with great caution, the main cancers follow a similar pattern to that of the national and regional estimates.

OBJETIVO: Describir brevemente el proceso de implementación y resultados preliminares del Registro de Cáncer de Base Poblacional (RCBP) de Mérida. MATERIAL Y MÉTODOS: RCBP-Mérida inició en 2016 como un proyecto de investigación del IMSS, con cobertura poblacional de 908 536 habitantes. El número de fuentes de información ha incrementado gradualmente. Se realizó colección de datos de forma pasiva y activa en software CanReg5 utilizando estándares internacionales. RESULTADOS: Se han incluido al RCBP-Mérida 71.5% de las fuentes de información. Durante 2015-2016 se registraron 2 623 casos nuevos, la mayoría (60.1%) mujeres. El 81.5% de los casos tuvo verificación morfológica. En hombres, el cáncer de próstata (17.4%), colorrectal (8.5%) y estómago (8.1%) son los más comunes; en mujeres, mama (31.6%), cérvix (12.0%) y cuerpo-uterino (7.6%). Las tasas de incidencia ajustadas por edad (100 000 habitantes) para todos los sitios combinados son 114.9 hombres y 145.1 mujeres. CONCLUSIONES: La implementación del RCBP-Mérida ha seguido parámetros particulares, con importante esfuerzo para incluir fuentes de información. Aunque los datos son preliminares y se deben interpretar con precaución; los principales tipos de cáncer siguen un patrón similar a las estimaciones nacionales y regionales.

Cytokine profile as diagnostic and prognostic factor in neonatal sepsis.

Antecedents: The serum levels of some cytokines can be useful in the diagnosis of neonatal sepsis; the prognostic value of a cytokine profile has not, to our knowledge, been explored in this disease. Objective: The objective of this study is to evaluate the diagnostic value of the serum levels of cytokines IL-1, -2, -4, -5, -6, -7, -8, -10, -12, -13, and -17, TNF, IFNγ, G-CSF, GM-CSF, MCP1, and MIP1ß in neonates with high risk of developing sepsis. Methods: Sepsis was evaluated in 96 high-risk neonates. We assessed cytokine levels on hospital admission and during or not during sepsis. Results: Fifty (52%) presented sepsis (26 early and 24 late). Sepsis was associated with high levels of IL-6, IL-10, G-CSF, and MCP1 and low levels of IFNγ, early sepsis with high levels of IL-6 and G-CSF, severe sepsis with high levels of IL-6 and IL-10, while deaths or sequelae was associated with low levels of IL-4, IL-12, IFNγ, and high levels of GM-CSF. IL-6 values of ≥40.1 pg/mL were associated with the development of any type of sepsis (relative risk [RR]: 1.70; 95% confidence interval [95% CI]: 1.18-2.24; p = .01), while IL-6 values of ≥44.9 pg/mL were associated with early sepsis (RR: 1.29; 95% CI: 1.29-4.56; p = .01). Conclusion: In neonates with high risk for the development of sepsis, there is an association between levels of IL-6, IL-10, and G-SCF and the disease development/outcome.

Increased expression of deleted in malignant brain tumors (DMBT1) gene in precancerous gastric lesions: Findings from human and animal studies.

Helicobacter pylori infection triggers a cascade of inflammatory stages that may lead to the appearance of non-atrophic gastritis, multifocal atrophic, intestinal metaplasia, dysplasia, and cancer. Deleted in malignant brain tumors 1 (DMBT1) belongs to the group of secreted scavenger receptor cysteine-rich proteins and is considered to be involved in host defense by binding to pathogens. Initial studies showed its deletion and loss of expression in a variety of tumors but the role of this gene in tumor development is not completely understood. Here, we examined the role of DMBT1 in gastric precancerous lesions in Caucasian, African American and Hispanic individuals as well as in the development of gastric pathology in a mouse model of H. pylori infection. We found that in 3 different populations, mucosal DMBT1 expression was significantly increased (2.5 fold) in individuals with dysplasia compared to multifocal atrophic gastritis without intestinal metaplasia; the increase was also observed in individuals with advanced gastritis and positive H. pylori infection. In our animal model, H. pylori infection of Dmbt1-/- mice resulted in significantly higher levels of gastritis, more extensive mucous metaplasia and reduced Il33 expression levels in the gastric mucosa compared to H. pylori-infected wild type mice. Our data in the animal model suggest that in response to H. pylori infection DMBT1 may mediate mucosal protection reducing the risk of developing gastric precancerous lesions. However, the increased expression in human gastric precancerous lesions points to a more complex role of DMBT1 in gastric carcinogenesis.

The importance of registries in cancer control.

Cancer is one of the major causes of morbidity and mortality in the world, with 14.1 million new cases and 8.2 million deaths annually. A marked disparity exists between developed countries and developing countries, with 57% of new cases and 65% of deaths in 2012 occurring in developing countries. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow cancer estimations for different geographic areas. Our objective is to perform a review of different types of registries and their role in the control of cancer. These types of registries are lacking in developing countries. In Central and South America, only 6% of the population is included in cancer registries versus 83% in North America. It is necessary to increase the coverage of cancer registries to obtain more reliable data that will more appropriately guide control programs.

The importance of registries in cancer control / Importancia de los registros para el control del cáncer

Abstract Cancer is one of the major causes of morbidity and mortality in the world, with 14.1 million new cases and 8.2 million deaths annually. A marked disparity exists between developed countries and developing countries, with 57% of new cases and 65% of deaths in 2012 occurring in developing countries. This global picture can only be obtained because of data obtained from population-based cancer registries, which allow cancer estimations for different geographic areas. Our objective is to perform a review of different types of registries and their role in the control of cancer. These types of registries are lacking in developing countries. In Central and South America, only 6% of the population is included in cancer registries versus 83% in North America. It is necessary to increase the coverage of cancer registries to obtain more reliable data that will more appropriately guide control programs.

Resumen El cáncer es una de las principales causas de morbi-mortalidad en el mundo con 14.1 millones de casos nuevos y 8.2 millones de muertes. Existe marcada disparidad entre países desarrollados y en vías de desarrollo: 57% de los casos nuevos y 65% de las muertes registradas en 2012 ocurrieron en países en vías de desarrollo. Sólo es posible describir este panorama mundial a partir de los datos obtenidos de los registros poblacionales de cáncer, que permiten realizar estas estimaciones en las diferentes áreas geográficas. El objetivo de este trabajo es realizar una revisión sobre los diferentes tipos de registros y su papel en el control del cáncer. En los países en vías de desarrollo existe una notable carencia de este tipo de registros. En Centro y Sur América sólo 6% de la población cuenta con registros de cáncer frente a 83% en América del Norte. Es necesario ampliar la cobertura de los registros de cáncer para la obtención de datos más confiables que guíen más oportunamente los programas de control.

Analysis of Thiopurine S-Methyltransferase Deficient Alleles in Acute Lymphoblastic Leukemia Patients in Mexican Patients.

BACKGROUND AND AIMS: It has been demonstrated that heterozygote and homozygote thiopurine S-methyltransferase (TPMT) mutant allele carriers are at high risk to develop severe and potentially fatal hematopoietic toxicity after treatment with standard doses of 6-mercaptopurine (6-MP) and methotrexate (MX). Those drugs are the backbone of acute lymphoblastic leukemia (ALL) and several autoimmune disease treatments. We undertook this study to determine the frequency of the TPMT deficient alleles in children with ALL and non-ALL subjects from Mexico City and Yucatan, Mexico. METHODS: We included 849 unrelated subjects, of which 368 ALL children and 342 non-ALL subjects were from Mexico City, and 60 ALL cases and 79 non-ALL individuals were from Yucatan. Genotyping of the rs1800462, rs1800460 and rs1142345 SNPs was performed by 5'exonuclease technique using TaqMan probes (Life Technologies Foster City, CA). RESULTS: The mutant TPMT alleles were present in 4.8% (81/1698 chromosomes) and only 0.2% were homozygote TPMT*3A/TPMT*3A. We did not find statistically significant differences in the distribution of the mutant alleles between patients from Mexico City and Yucatan in either ALL cases or non-ALL. Nonetheless, the TPMT*3C frequency in ALL patients was higher than non-ALL subjects (p = 0.03). To note, the null homozygous TPMT*3A/TPMT*3A genotype was found in 2.5% of the non-ALL subjects. CONCLUSIONS: TPMT mutant alleles did not exhibit differential distribution between both evaluated populations; however, TPMT*3C is overrepresented in ALL cases in comparison with non-ALL group. Assessing the TPMT mutant alleles could benefit the ALL children and those undergoing 6-MP and MX treatment.

ARID5B, CEBPE and PIP4K2A Germline Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia in Mexican Patients: A MIGICCL Study.

BACKGROUND AND AIMS: Childhood acute lymphoblastic leukemia (ALL) is the leading cause of childhood cancer-related deaths worldwide. Multiples studies have shown that ALL seems to be originated by an interaction between environmental and genetic susceptibility factors. The ARID5B polymorphisms are among the most reproducible ALL associated-risk alleles in different populations. The aim of the present study was to examine the contribution of ARID5B, CEBPE, and PIP4K2 risk alleles for the development of ALL in children from Mexico City and Yucatan, Mexico. METHODS: A study was conducted with a total of 761 unrelated subjects. Two hundred eighty five ALL cases (111 from Yucatan and 174 from Mexico City) and 476 healthy subjects. Genotyping included the rs7088318 (PIP4K2A), rs10821936 (ARID5B), rs7089424 (ARID5B) and rs2239633 (CEBPE) polymorphisms. RESULTS: Associations between ALL and rs10821936 and rs7089424 ARID5B SNPs were found (OR = 1.9, 95% CI (1.5-2.4) and OR = 2.0, 95% CI (1.6-2.5), respectively). Moreover, a higher risk was observed in the homozygous risk genotypes of carriers from Mexico City (OR = 3.1, 95% CI (2.0-4.9) and OR 3.1, CI 95% (2.0-4.8), respectively). Otherwise, the rs7088318 (PIP4K2A) and rs2239633 (CEBPE) polymorphisms were not associated with ALL risk. CONCLUSIONS: Our analysis suggests that ARID5B confers risk for childhood ALL in a Mexican population.

Evidence of Epstein-Barr virus association with gastric cancer and non-atrophic gastritis.

Different lines of evidence support an association between Epstein-Barr virus (EBV) and gastric cancer (GC). The main understood risk factor to develop GC is infection by Helicobacter pylori (H. pylori), which triggers a local inflammatory response critical for progression from gastritis to GC. The role of EBV in early inflammatory gastric lesions has been poorly studied. A recent study proposed a cutoff value of 2000 EBV particles to identify patients with increased chances of infection of the gastric epithelium, which may favor the inflammatory process. To better understand the role of EBV in cancer progression, we analyzed 75 samples of GC, 147 control samples of non-tumor gastric tissue derived from GC patients and 75 biopsies from patients with non-atrophic gastritis (NAG). A first-round PCR was used for EBV detection in tumor and non-tumor controls and a more sensitive nested PCR for gastritis samples; both PCRs had lower detection limits above the proposed cutoff value. With this strategy 10.67% of GC, 1.3% of non-tumor controls and 8% of gastritis samples were found positive. An EBER1 in situ hybridization showed EBV infection of epithelial cells in GC and in a third of NAG samples, while in the other NAGs infection was restricted to the mononuclear cell infiltrate. EBV-positive GCs were enriched in lace and cribriform patterns, while these rare patterns were not observed in EBV negative samples. Our results support a role for EBV in GC and early precursor lesions, either as directly oncogenic infecting epithelial cells or indirectly as an inflammatory trigger.

No association between Epstein-Barr Virus and Mouse Mammary Tumor Virus with breast cancer in Mexican women.

Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.

An amebic anti-inflammatory peptide down-regulates ex vivo IL-1Beta expression in patients with rheumatoid arthritis

El factor inhibidor de la locomoción de monocitos (FILM) es un pentapéptido termoestable producido por Entamoeba histolytica en cultivo. Este factor presenta diversas propiedades antiinflamatorias, a saber: inhibición de la locomoción y estallido respiratorio en monocitos, abatimiento de la hipersensibilidad por contacto al dinitroclorobenceno y retraso de la quimitoaxis de células mononucleares, disminución en la expresión de moléculas de adhesión y quimiocinas entre otros genes. En ratones el FILM reduce la inflamación inducida por carragenina y retrasa el proceso inflamatorio de la artritis inducida por colágena. Objetivo: Evaluar in vitro el efecto del FILM sobre la expresión de IL-1Beta en la línea celular promonocítica humana (U-937) y en células mononucleares de sangre periférica provenientes de donadores sanos y de pacientes con artritis reumatoide. Material y Métodos: Se realizaron cultivos celulares en presencia de FILM, lipopolisacárido o ambos. Después del cultivo se determinó expresión relativa e inmunoreactividad de IL-1Beta en los botones celulares y sobrenadantes respectivamente. Resultados: El péptido amibiano pudo reducir la expresión de IL-1Beta inducida por LPS en células U937, sin mostrar un efecto detectable sobre la biodisponibilidad de la citocina. En condiciones de cultivo similares, el FILM fue capaz de disminuir la expresión de IL-1Beta, basal e inducida por LPS, sólo en células mononucleares provenientes de pacientes con artritis. Su efecto sobre la inmunoreactividad de la citocina no fue significativo estadísticamente. Conclusiones: El FILM ejerce en las células activadas propiedades antiinflamatorias exquisitas que merecen ser exploradas mecanísticamente (AU)

The monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide produced by Entamoeba histolytica in culture. This factor displays several anti-inflammatory properties (i.e., inhibition of locomotion and respiratory burst in monocytes, reduction of skin hypersensitivity and delay of mononuclear cells in human Rebuck skin windows) with inhibition of adhesion molecules, chemokines, and other genes including interleukin-1Beta (IL-1Beta). In animal models, it reduces carragenin-induced inflammation and delays the inflammatory process in murine collagen-induced arthritis (CIA). Objectives: To test, in vitro, the anti-inflammatory capacity of MLIF on a promonocytic human cell line (U-937) cells and peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients with rheumatoid arthritis (RA). Material and methods: IL-1Beta gene expression was evaluated in cell cultures either in the presence of MLIF, lipopolysaccharide (LPS), or both. Relative gene expression and immunoreactivity of IL-1Beta were assayed in cells and supernatants, respectively. Results: Amebic peptide was able to down-regulate LPS-induced expression of IL-1Beta, in U-937 cells without a detectable effect upon the bioavailability of the cytokine. In similar culture conditions, MLIF was capable to down-regulate baseline and LPS-induced expression of IL-Beta only in PBMC from patients with RA. Peptide effect on immunoreactivity of IL-1Beta was not statistically significant. Conclusions: MLIF exerts, in primed cells, exquisite anti-inflammatory properties that deserve to be explored mechanistically (AU)

An amebic anti-inflammatory peptide down-regulates ex vivo IL-1ß expression in patients with rheumatoid arthritis.

UNLABELLED: The monocyte locomotion inhibitory factor (MLIF) is a heat-stable pentapeptide produced by Entamoeba histolytica in culture. This factor displays several anti-inflammatory properties (i.e., inhibition of locomotion and respiratory burst in monocytes, reduction of skin hypersensitivity and delay of mononuclear cells in human Rebuck skin windows) with inhibition of adhesion molecules, chemokines, and other genes including interleukin-1ß (IL-1ß). In animal models, it reduces carragenin-induced inflammation and delays the inflammatory process in murine collagen-induced arthritis (CIA). OBJECTIVES: To test, in vitro, the anti-inflammatory capacity of MLIF on a promonocytic human cell line (U-937) cells and peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: IL-1ß gene expression was evaluated in cell cultures either in the presence of MLIF, lipopolysaccharide (LPS), or both. Relative gene expression and immunoreactivity of IL-1ß were assayed in cells and supernatants, respectively. RESULTS: Amebic peptide was able to down-regulate LPS-induced expression of IL-1ß, in U-937 cells without a detectable effect upon the bioavailability of the cytokine. In similar culture conditions, MLIF was capable to down-regulate baseline and LPS-induced expression of IL-ß only in PBMC from patients with RA. Peptide effect on immunoreactivity of IL-1ß was not statistically significant. CONCLUSIONS: MLIF exerts, in primed cells, exquisite anti-inflammatory properties that deserve to be explored mechanistically.

Risk factors and prognosis for neonatal sepsis in southeastern Mexico: analysis of a four-year historic cohort follow-up.

BACKGROUND: Neonatal sepsis is a worldwide public health issue in which, depending on the studied population, marked variations concerning its risk and prognostic factors have been reported. The aim of this study was to assess risk and prognostic factors for neonatal sepsis prevailing at a medical unit in southeastern Mexico. Thus, we used a historic cohort design to assess the association between a series of neonates and their mothers, in addition to hospital evolution features and the risk and prognosis of neonatal sepsis (defined by Pediatric Sepsis Consensus [PSC] criteria) in 11,790 newborns consecutively admitted to a Neonatology Service in Mérida, Mexico, between 2004 and 2007. RESULTS: Sepsis was found in 514 of 11,790 (4.3 %) newborns; 387 of these cases were categorized as early-onset (<72 h) (75.3 %) and 127, as late-onset (>72 h) (24.7 %). After logistic regression, risk factors for sepsis included the following: low birth weight; prematurity; abnormal amniotic fluid; premature membrane rupture (PMR) at >24 h; respiratory complications, and the requirement of assisted ventilation, O(2) Inspiration fraction (IF) >60 %, or a surgical procedure. Some of these factors were differentially associated with early- or late-onset neonatal sepsis. The overall mortality rate of sepsis was 9.5 %. A marked difference in the mortality rate was found between early- and late-onset sepsis (p >0.0001). After Cox analysis, factors associated with mortality in newborns with sepsis comprised the following: prematurity; low birth weight; low Apgar score; perinatal asphyxia, and the requirement of any invasive medical or surgical procedure. CONCLUSIONS: The incidence of neonatal sepsis in southeastern Mexico was 4.3 %. A different risk and prognostic profile between early- and late-onset neonatal sepsis was found.

13C-urea breath test for the diagnosis of Helicobacter pylori infection in children: a systematic review and meta-analysis.

BACKGROUND: The (13) C-urea breath test ((13) C-UBT) is a safe, noninvasive and reliable method for diagnosing H. pylori infection in adults. However, the test has shown variable accuracy in the pediatric population, especially in young children. We aimed to carry out a systematic review and meta-analysis to evaluate the performance of the (13) C-UBT diagnostic test for H. pylori infection in children. METHODS: We conducted a systematic review of the PubMed, Embase and Liliacs databases including studies from January 1998 to May 2009. Selection criteria included studies with at least 30 children and reporting the comparison of (13) C-UBT against a gold standard for H. pylori diagnosis. Thirty-one articles and 135 studies were included for analysis. Children were stratified in subgroups of <6 and ≥6 years of age, and we considered variables such as type of meal, cutoff value, tracer dose, and delta time for the analysis. DISCUSSION: The (13) C-UBT performance meta-analyses showed 1, good accuracy in all ages combined (sensitivity 95.9%, specificity 95.7%, LR+ 17.4, LR- 0.06, diagnostic odds ratio (DOR) 424.9), 2, high accuracy in children >6 years (sensitivity 96.6%, specificity 97.7%, LR+ 42.6, LR- 0.04, DOR 1042.7), 3, greater variability in accuracy estimates and on average a few percentage points lower, particularly specificity, in children ≤6 years (sensitivity 95%, specificity 93.5%, LR+ 11.7, LR- 0.12, DOR 224.8). Therefore, the meta-analysis shows that the (13) C-UBT test is less accurate for the diagnosis of H. pylori infection in young children, but adjusting cutoff value, pretest meal, and urea dose, this accuracy can be improved.

Utility of stool sample-based tests for the diagnosis of Helicobacter pylori infection in children.

OBJECTIVE: Helicobacter pylori antigen or DNA in stool are meant to detect the bacteria; however, in children the colonization of the gastric mucosa by H pylori is usually weak and fecal excretion of antigen or DNA varies considerably, challenging the utility of these tests in this age group. The aim of the present study was to carry out a systematic review and meta-analysis to evaluate the performance of stool H pylori DNA and antigen tests for the diagnosis of infection in children. METHODS: We conducted a systematic review and meta-analysis to assess the accuracy of stool tests for diagnosis of H pylori infection in children. We searched PubMed, EMBASE, and LILACS databases. Selection criteria included participation of at least 30 children and the use of a criterion standard for H pylori diagnosis. In a comprehensive search, we identified 48 studies. RESULTS: Regarding antigen-detection tests, enzyme-linked immunosorbent assay (ELISA) monoclonal antibodies showed the best performance, with sensitivity and specificity of 97%, positive likelihood ratio (LR+) of 29.9, and negative likelihood ratio (LR-) of 0.03. ELISA polyclonal antibodies had sensitivity of 92%, specificity of 93%, LR+ of 16.2, LR- of 0.09, and high heterogeneity (P < 0.0001). One-step monoclonal antibody tests demonstrated sensitivity of 88%, specificity of 93%, LR+ of 10.6, and LR- of 0.11. For DNA detection, polymerase chain reaction-based test showed sensitivity of 80.8%, specificity of 98%, LR+ of 17.1, and LR- of 0.18. CONCLUSIONS: Detection of H pylori antigen in stools with ELISA monoclonal antibodies is a noninvasive efficient test for diagnosis of infection in children. One-step tests showed low accuracy and more studies are needed to obtain a useful office-based screening test. The available molecular tests are still unreliable.

Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes.

OBJECTIVE AND DESIGN: Monocyte locomotion inhibitory factor (MLIF), an amebic peptide with antiinflammatory properties, was evaluated in collagen-induced arthritis (CIA) to test its effects on the onset and acute inflammatory response of arthritis. MATERIAL: DBA1/J mice at 8-10 weeks of age were divided into four groups (eight mice per group). TREATMENT: The adjuvant group received Freund adjuvant, the CIA group was immunized with collagen II, the MLIF/CIA group received collagen II and MLIF, and the MLIF group received MLIF and Freund adjuvant. METHODS: All groups were evaluated clinically. Seven weeks after the collagen injection, at the peak of the clinical arthritis score, limb specimens were collected and histological studies and gene expression analysis using microarrays were performed. RESULTS: MLIF administered weekly as a preventive scheme delayed and reduced the severity of acute arthritis. MLIF induced gene changes in functional categories including adhesion molecules, matrix metalloproteinases, and inflammatory cytokines. CONCLUSIONS: MLIF could be an interesting new molecule to investigate in the field of rheumatoid arthritis pathogenesis research for its potential to prevent inflammation.

Seroepidemiology of giardiasis in Mexico.

Prevalence of antibodies against Giardia duodenalis was determined by enzyme-linked immunosorbent assay in serum samples from a national serologic survey of Mexico that included all geographic areas and socioeconomic and demographic data for each person sampled. The country was divided into four regions on the basis of development (high, medium high, medium low, and low). Of 3,461 serum samples tested, 1,914 (55.3%) were positive for IgG antibodies against Giardia duodenalis. Seropositivity was age-specific; the probability of seropositivity increased 4.9-fold (95% confidence interval [CI] = 3.16-7.64) in adolescents 10-19 years of age, 8.0-fold (95% CI = 5.19-12.53) in young adults 20-39 years of age, and 12.6-fold (95% CI = 7.93-20.28) in adults more than 40 years of age. Giardia duodenalis seropositivity was associated with male sex (odds ratio = 1.40, 95% CI = 1.22-1.61). No association was found between seropositivity and socioeconomic variables or regional development status.