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Aim The role of chemokines and their receptors, which regulate trafficking and homing of leucocytes to inflamed organs in human or murine autoimmune neuritis, has not yet been elucidated in detail, Therefore, the role of the chemokine receptors CXCR4 and CXCR7 and their ligand CXCL12 was studied in autoimmune-mediated inflammation of the peripheral nervous system. Methods CXCL12/ CXCR4 and/or CXCL12/ CXCR7 interactions were specifically inhibited by the compounds AMD3100 or CCX771, respectively, in experimental autoimmune neuritis ( EAN) of C57 BL/6 J mice immunized with P0106-125 peptide. Results Disease activity was significantly suppressed by blocking CXCR7 while antagonization of CXCR4 enhanced disease activity. Enhanced disease activity was accompanied by significantly increased transcription of IFN-γ, IL-12 and TNF-α mRNA in regional lymph nodes and spleen as well as by increased serum levels of IFN-γ. Furthermore, by blocking CXCR4, expression of the cell adhesion molecules ICAM-1 and VCAM-1 was upregulated on vascular endothelial cells of the sciatic nerve, which coincided with significantly increased infiltration of the sciatic nerve by CD4+ T cells and macrophages. Remarkably, combined antagonization of both CXCR4 and CXCR7 significantly suppressed disease activity. This was accompanied by increased frequencies of activated and highly IFN-γ-expressing, P0106-125-specific T cells in regional lymph nodes and spleen; however, these cells were unable to infiltrate the sciatic nerve. Conclusion These data suggest differential and hierarchically ordered roles for CXCR4/ CXCL12- vs. CXCR7/ CXCL12-dependent effects during EAN: CXCR7/ CXCL12 interaction is a gatekeeper for pathogenic cells, regardless of their CXCR4/ CXCL12-dependent state of activation. [ABSTRACT FROM AUTHOR]

Background: A heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC)., Methods: A population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff's spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained., Results: A total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed., Conclusions: The identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer IO declared a shared affiliation with the author RE-E to the handling editor at the time of review., (Copyright © 2024 Duarte-Rodríguez, Flores-Lujano, McNally, Pérez-Saldivar, Jiménez-Hernández, Martín-Trejo, Espinoza-Hernández, Medina-Sanson, Paredes-Aguilera, Merino-Pasaye, Velázquez-Aviña, Torres-Nava, Espinosa-Elizondo, Amador-Sánchez, Dosta-Herrera, Mondragón-García, González-Ulibarri, Martínez-Silva, Espinoza-Anrubio, Paz-Bribiesca, Salcedo-Lozada, Landa-García, Ramírez-Colorado, Hernández-Mora, Santamaría-Ascencio, López-Loyola, Godoy-Esquivel, García-López, Anguiano-Ávalos, Mora-Rico, Castañeda-Echevarría, Rodríguez-Jiménez, Cibrian-Cruz, Solís-Labastida, Cárdenas-Cardos, López-Santiago, Flores-Villegas, Peñaloza-González, González-Ávila, Sánchez-Ruiz, Rivera-Luna, Rodríguez-Villalobos, Hernández-Pérez, Olvera-Durán, García-Cortés, Mata-Rocha, Sepúlveda-Robles, Bekker-Méndez, Jiménez-Morales, Meléndez-Zajgla, Rosas-Vargas, Vega, Núñez-Enríquez and Mejía-Aranguré.)

Objective: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta variant was classified as a variant of concern in May 2021 due to its increased transmissibility. It became dominant in Europe during the summer, raising concerns on the effectiveness of vaccines. We assessed the vaccine effectiveness (VE) of mRNA BNT162b2 (BioNTech-Pfizer) against SARS-CoV-2 Delta variant during an outbreak affecting long-term care facility (LTCF) residents in southern France, May 2021., Materials and Methods: We conducted a retrospective cohort study among LTCF residents. We described sex, age, dependency level, reverse transcription PCR and sequencing results, clinical evolution, vaccination status. We compared attack rates of SARS-CoV-2 infection, symptomatic coronavirus disease 2019 (COVID-19), and severe COVID-19 (respiratory support, hospitalization, and/or death) by vaccination status (two doses administered vs. none) to estimate VE (1 - Relative Risk [RR]) with 95% confidence intervals (CI). VE was adjusted by age (Poisson regression)., Results: Among 72 LTCF residents, 75.0% (n=54) were women, mean age was 88.7 (SD 8.1) years, 69% (n=49/71) were severely dependent. SARS-CoV-2 infections were identified in 39 residents (54.2%), 11 with symptomatic, and eight with severe COVID-19. All sequenced samples (n=19, 48.7%) had the same Delta variant genomic sequence. Age-adjusted BNT162b2 VE against SARS-CoV-2 Delta variant infection was 11.2% (95% CI: 0.0-61.1%), it was 88.4% (95% CI: 59.9-96.7%) against symptomatic, and 93.5% (95% CI: 67.2-98.7%) against severe COVID-19., Conclusions: We found a high BNT162b2 VE against symptomatic and severe COVID-19 caused by SARS-CoV-2 Delta variant among LTCF elderly residents, but not against Delta variant infection. This supports vaccination rollout and the implementation of control measures for close contacts among vaccinated LTCF elderly residents.

Background: The parental age at conception has been reported to be a risk factor for childhood acute leukaemia (AL); however, the relationship is controversial. The aim of the present study was to investigate the association between parental age at conception and the risk of AL in Mexican children, a population with a high incidence of the disease and a high prevalence of pregnancies in adolescents and young adults., Methods: A multicentre case-control study was conducted. Incident AL cases younger than 17 years of age diagnosed between 2010 and 2015 were included. Controls were matched with cases according to age, sex, and health institution. Using logistic regression analysis, adjusted odds ratios (aOR) and 95 % confidence intervals (95 % CI) were calculated for each maternal stratum after adjusting for paternal age at conception of index child. The maternal age between 25 and 29.99 years was selected as the reference category., Results: In most strata where maternal and paternal ages were assessed, no association was found with the risk of developing acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring. An increased risk for AML was observed when the mother was between 20 and 24.99 years of age and the father aged 25-29.99 years (aOR, 1.94; 95 % CI, 1.03-3.67). In addition, there was a positive association for ALL when the mother´s age was between 20 and 24.99 years and the father was <20 years of age, however, a very wide confidence interval was noted (aOR, 12.26; 95 % CI, 1.41-106.83)., Conclusion: In the present study, maternal and paternal ages assessed in different strata showed little association with risk of developing ALL and AML in children. Positive associations between risk of both types of childhood AL were observed with younger paternal and maternal ages., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Increasing evidence suggests a role of CD8 T cells in autoimmune demyelinating CNS disease, which, however, is still controversially discussed. Mice, which express ovalbumin (OVA) as cytosolic self-antigen in oligodendrocytes (ODC-OVA mice), respond to CNS infection induced by OVA-expressing attenuated Listeria with CD8 T cell-mediated inflammatory demyelination. This model is suitable to decipher the contribution of CD8 T cells and the pathogen in autoimmune CNS disease. Here, we show that both antigen and pathogen are required in the CNS for disease induction, though not in a physically linked fashion. Intracerebral challenge with combined toll like receptor (TLR) TLR2 and TLR9 as well as TLR7 and TLR9 agonists substituted for the bacterial stimulus, but not with individual TLR agonists (TLR2, TLR3,TLR5,TLR7, TLR9). Furthermore, MyD88 inactivation rendered ODC-OVA mice resistant to disease induction. Collectively, CD8 T cell-mediated destruction of oligodendrocytes is activated if (i) an antigen shared with an infectious agent is provided in the CNS microenvironment and (ii) innate immune signals inform the CNS microenvironment that pathogen removal warrants an immune attack by CD8 T cells, even at the expense of locally restricted demyelination., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In Mexico, due to the high rates of diabetes, overweight, and obesity, there has also been noted an increased newborn weight, which may be contributing to the elevated incidence rate of childhood acute leukemia (AL). We conducted a case-control study in public hospitals of Mexico City aimed to know whether a greater weight at birth is associated with a higher risk of developing leukemia. We included incident cases with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) diagnosed between 2010 and 2015. Controls were frequency-matched to the cases by age, sex, and health institution. Logistic regression analysis was performed adjusting risks by child's sex, overcrowding index, birth order, and mother's age at the time of pregnancy. Adjusted odds ratios (aORs) and 95% confidence intervals were calculated. A total of 1455 cases and 1455 controls were included. An evident association between ALL and child's birthweight ≥2500 g was found (aOR 2.06; 95% CI: 1.59, 2.66) and also, in those with birthweight ≥3500 g (aOR 1.19; 95% CI: 1.00, 1.41). In AML patients with birthweight ≥2500 g and ≥3500 g, an aOR of 1.77 (95% CI: 1.07, 2.94) and 1.42 (95% CI: 1.03-1.95) was observed, respectively. No association was noticed with either type of AL and a birthweight ≥4000 g. To sum up, we found a moderate association between not having a low birthweight and an increased risk of acute leukemias. Birthweight ≥3500 g was also a risk factor for both types of leukemia. This suggests that a greater birthweight may increase the risk of acute leukemias in Mexican children., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: In 2012, the Mexican National Health Survey showed a moderate prevalence rate of vitamin D deficiency, around 16%, in a national representative sample of children. A decreasing prevalence of anemia during the last 15 years has been observed in Mexico. The aim of this study was to determine the levels of vitamin D in children 3-8 years old in four different locations within the metropolitan area of Mexico City and to compare them to levels of iron and zinc as references of nutritional status., Methods: One hundred and seventeen healthy children aged 3-8 years attending four hospitals in Mexico City were invited to participate. All children received medical and nutritional evaluation, and blood samples were obtained., Results: Children were selected in the four hospitals between April and August 2008. More than half (51.3%) were boys; their average age was 5.5 ± 1.6 years. The mean height and weight of the children were 112.1 ± 11.2 cm and 20.2 ± 4.9 kg respectively, with a body mass index [BMI] of 15.8 ± 1.7 kg/m². The mean Z-score (BMI) was 0.007 ± 0.999. The prevalence of subjects with deficient levels of 25-OH-vitamin D (<50 nmol/l) was 24.77%. None of the children had haemoglobin levels below the anaemia threshold, and zinc determination revealed 8.26% of individuals with deficient levels (<65 µg/dL). These data confirm the findings reported in the latest National Nutrition Survey (ENSANUT 2012) about the sustained reduction of anaemia prevalence among preschool and schoolchildren since 1999 and the rising rates of vitamin D deficiency in the same population. Similar to other studies, we found a link between socioeconomic status and the deficiency of micronutrients, these being markers of better nutrition, and vitamin D is remarkably related to the quality of the diet. This finding has not been considered in our population before., Conclusions: There is evidence of a sustained decrease of anaemia in Mexican children due to general enrichment of foods and focus on vulnerable populations, while vitamin D deficiency seems to have increased. More studies are needed to obtain more information on vitamin D levels at different ages and definition of susceptible groups in order to investigate the possibility of general population measures such as enrichment, which have proven to be effective.

Primary lymphoma of the central nervous system (PCNSL) is defined as lymphoma of the diffuse large B-cell type confined to the CNS. To understand the effects of the CNS microenvironment on the malignant B cells and their interactions with the cells of the target organ, we analyzed a syngeneic mouse model. Transplantation of BAL17 cells into the frontal white matter of syngeneic BALB/c mice induced lymphomas with major clinical and neuropathologic features that parallel those of human PCNSL, including an angiocentric growth pattern in the brain parenchyma and tropism for the inner and outer ventricular system. Seven cycles of repeated isolation of lymphoma cells from the CNS and their intracerebral reimplantation induced genotypic and phenotypic alterations in resulting BAL17VII cells; the affected genes regulate apoptosis and are of the JAK/STAT pathway. Because lymphoma growth of BAL17VII cells was significantly accelerated, that is, shortening the time to death of the mice, these data indicate that prolonged stay of the lymphoma cells in the CNS was associated with worse outcome. These findings suggest that the CNS microenvironment fosters aggressiveness of lymphoma cells, thereby accelerating the lethal course of PCNSL.

The role of B cells in autoimmune-mediated diseases of the peripheral nervous system was studied in experimental autoimmune neuritis (EAN) in B cell deficient IgH⁰(/)⁰ C57BL/6J mice having been immunized with P0₁₀₆₋₁₂₅ peptide. Compared to coisogenic IgH(+/+) mice, onset of EAN was accelerated [100% disease incidence at day 9 post immunization (p.i.) vs. day 15 p.i.]. At day 9 p.i., numbers of P0₁₀₆₋₁₂₅-specific interferon (IFN)-γ-producing CD4(+) T cells were increased, while IL-10 mRNA and production were decreased in IgH⁰(/)⁰ mice. Beyond day 9 p.i., declining disease activity and a significant reduction of maximal disease activity were correlated with significantly reduced numbers of IFN-γ-producing CD4(+) T cells in IgH(0/0) mice as compared with IgH(+/+) mice. Correspondingly, neuropathology demonstrated only mild axonal damage, while demyelination and dying back axonopathy with spinal cord motor neuron apoptosis were absent. Thus, depending on the stage of EAN, B cells play a dual, i.e. suppressive and enhancing, role during induction and at height of EAN, respectively. The combined interaction of B cells as well as CD4(+) and CD8(+) T cells is required for the development of EAN.

Objective: To describe the content and structure of the websites of pharmaceutical companies (PC) with health information to patients., Design: Descriptive, cross-sectional., Main Measurements: health topics treated, and 9 sections: objectives and target population; editorial policy, authoring, updating of content, personal data protection, interactivity, accessibility, advertising labels., Setting: Internet., Participants: All PC websites with patient health information in Spanish., Results: We studied 60 sites found. Most common: 19.3% neurology, mental health and 12% digestive diseases. Few specify the address of the person responsible for the site (51.7%), responsible for quality (10%) or the authors of the text (15%). Nearly 2/3 show the date of publication of content (66.7%), but only 13.3% updated. Privacy and data protection are mentioned in 65%, with only 28.3% allowing control of the use of personal data. Only 10% allow expressing doubts online and 1/3 of the sites have frequently asked questions. A total of 41.7% omitted to say their information does not replace medical advice. Educational materials (for children) can be downloaded in 11.7%. Almost all (93.3%) adapted their language to the recipient, but none are accessible to disabled people. The majority (86.7%) have the company logo on all pages. Only 16.7% are fronts for advertising, and only 9 sites have a quality seal (HONcode)., Conclusions: Pages are designed to give superficial information on a disease than directly advertise a particular brand or active ingredient. However, their reliability has to be low due to the authors and sources of information being unknown. If Internet health information was truthful and backed up by authors or appropriate information sources, the Internet could well be a genuine health education tool., (Copyright 2009 Elsevier España, S.L. All rights reserved.)