TOX3 rs3803662 Polymorphism Is Associated With Breast Cancer Protection In Northeastern Mexican Woman

Introduction: Low penetrance genes are involved in breast cancer (BC) and confer risk for the development of this neoplasia. Different single nucleotide polymorphisms (SNPs) associated with BC have been identified, such as rs3803662 (TOX3), which is related to estrogen receptors in European and African-American women. The contribution of this variant in the Mexican population is unknown. The objective of this study was to evaluate, through a case-control design, the association of the SNP rs3803662 (TOX3), with the risk of BC in women from northeastern Mexico. Methods: We included 434 cases and 228 controls. Genotyping was carried out using RFLPs. The SPSS 7.0 statistical program was used to determine the gene frequencies, the estimation of the relative risk (Odds ratio [OR]), and the Hardy-Weinberg equilibrium (EHW). Results: The homocygote (T/T) genotype of the SNP TOX3 rs3803662 was identified as a protective allele for BC (OR: 0.47, 95% CI: 0.29 - 0.78). Conclusions; The T allele of the SNP rs3803662 can be considered as a protective factor for BC from northeastern Mexico women

Una especie nueva de rana del género Chiasmocleis (Microhylidae: Gastrophryninae) de la Cordillera del Cóndor, Ecuador

We describe a new species of frog of the genus Chiasmocleis from the montane forests of southeastern Ecuador, at the western slopes of Cordillera del Cóndor, between 1,224‑1,630 m of elevation. Based on new sequences of mitochondrial and nuclear DNA we present phylogenetic relationships of the new species and its congeners. The phylogeny shows a close relationship to C. antenori, C. carvalhoi, C. magnova and C. tridactyla. The new species is part of a clade of species that were previously assigned to the genus Syncope. This clade has a sister relationship to a clade that contains all remaining species of Chiasmocleis. The new species differs from its congeners by its reddish-brown to dark-brown (sepia) dorsum with minute yellowish-white spots. Chiasmocleis parkeri sp. nov. is similar to Chiasmocleis antenori in lacking digit I of both hands and feet but Chiasmocleis parkeri differs in coloration, arrangement and size of pale spots, and the absence of a pale line in the canthal region. We describe the calls, which are characterized by having non-pulsed notes, and we provide ecological data from the type locality and adjacent areas

Risk factors for thrombotic microangiopathy in allogeneic hematopoietic stem cell recipients receiving GVHD prophylaxis with tacrolimus plus MTX or sirolimus

Post-transplant complications.-- et al.Transplantation-associated thrombotic microangiopathy (TA-TMA) is a feared complication of allogeneic hematopoietic SCT (HSCT) owing to its high mortality rate. The use of calcineurin inhibitors or sirolimus (SIR) for GVHD prophylaxis has been suggested as a potential risk factor. However, the impact of tacrolimus (TAC) and SIR combinations on the increased risk of TA-TMA is currently not well defined. We retrospectively analyzed the incidence of TA-TMA in 102 allogeneic HSCT recipients who consecutively received TAC plus SIR (TAC/SIR) (n=68) or plus MTX (TAC/MTX)±ATG (n=34) for GVHD prophylaxis. No significant differences were observed in the incidence of TA-TMA between patients receiving TAC/SIR vs TAC/MTX±ATG (7.4% vs 8.8%, P=0.8). Only grade III-IV acute GVHD, previous HSCT and serum levels of TAC >25 ng/mL were associated with a greater risk of TA-TMA. Patients developing TA-TMA have significantly poorer survival (P<0.001); however, TA-TMA ceased to be an independent prognostic factor when it was included in a multivariate model. In conclusion, the combination of TAC/SIR does not appear to pose a higher risk of TA-TMA. By contrast, we identified three different risk groups for developing TA-TMA.Peer Reviewe

Risk Association of TOX3 and MMP7 Gene Polymorphisms with Sporadic Breast Cancer in Mexican Women

Breast cancer (BC) has one of the highest incidences and mortality worldwide. Single nucleotide polymorphisms (SNPs) in TOX3 rs3803662 and MMP7 rs1943779 have been associated with susceptibility to BC. In this case-control study, we evaluated the association of rs3803662 (TOX3)/rs1943779 (MMP7) SNPs with clinical features, immunohistochemical reactivity, and risk association with BC in women from northeastern Mexico. We compared 212 BC cases and 212 controls. DNA was isolated from peripheral blood to perform the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We calculated genotype frequencies, odds ratios, and 95% confidence intervals. We found that CT (Cytocine-Thymine) and TT (Thymine -Thymine) genotypes, and T alleles of TOX3 rs3803662, were associated with BC risk (p = 0.034, p = 0.011, respectively). SNP TOX3 rs3803662 was associated with positive progesterone receptors (PR) and triple-negative BC (TNBC) but not with estrogen receptor (ER) or HER2 reactivity. CT and TT genotypes (p = 0.006) and T alleles (p = 0.002) of SNP MMP7 rs1943779 were associated with risk of BC. We found that T alleles of TOX3 rs3803662 and MMP7 rs1943779 SNPs are associated with BC risk. These findings contribute to personalized medicine in Mexican women

Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients

This is an open-access paper.-- et al.Allogeneic hematopoietic stem cell transplantation recipients have an increasing risk of both hemorrhagic and thrombotic complications. However, the competing risks of two of these life-threatening complications in these complex patients have still not been well defined. We retrospectively analyzed data from 431 allogeneic transplantation recipients to identify the incidence, risk factors and mortality due to thrombosis and bleeding. Significant clinical bleeding was more frequent than symptomatic thrombosis. The cumulative incidence of a bleeding episode was 30.2% at 14 years. The cumulative incidence of a venous or arterial thrombosis at 14 years was 11.8% and 4.1%, respectively. The analysis of competing factors for venous thrombosis revealed extensive chronic graft-versus-host disease to be the only independent prognostic risk factor. By contrast, six factors were associated with an increased risk of bleeding; advanced disease, ablative conditioning regimen, umbilical cord blood transplantation, anticoagulation, acute III-IV graft-versus-host disease, and transplant-associated microangiopathy. The development of thrombosis did not significantly affect overall survival (P=0.856). However, significant clinical bleeding was associated with inferior survival (P<0.001). In allogeneic hematopoietic stem cell transplantation, significant clinical bleeding is more common than thrombotic complications and affects survival.Peer Reviewe

In silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19

Background: There is pressing urgency to identify therapeutic targets and drugs that allow treating COVID-19 patients effectively.Methods: We performed in silico analyses of immune system protein interactome network, single-cell RNA sequencing of human tissues, and artificial neural networks to reveal potential therapeutic targets for drug repurposing against COVID-19.Results: We screened 1,584 high-confidence immune system proteins in ACE2 and TMPRSS2 co-expressing cells, finding 25 potential therapeutic targets significantly overexpressed in nasal goblet secretory cells, lung type II pneumocytes, and ileal absorptive enterocytes of patients with several immunopathologies. Then, we performed fully connected deep neural networks to find the best multitask classification model to predict the activity of 10,672 drugs, obtaining several approved drugs, compounds under investigation, and experimental compounds with the highest area under the receiver operating characteristics.Conclusion: After being effectively analyzed in clinical trials, these drugs can be considered for treatment of severe COVID-19 patients. Scripts can be downloaded at

Addressing the disparities in dementia risk, early detection and care in Latino populations: Highlights from the Second Latinos and Alzheimer's Symposium

The Alzheimer's Association hosted the second Latinos & Alzheimer's Symposium in May 2021. Due to the COVID-19 pandemic, the meeting was held online over 2 days, with virtual presentations, discussions, mentoring sessions, and posters. The Latino population in the United States is projected to have the steepest increase in Alzheimer's disease (AD) in the next 40 years, compared to other ethnic groups. Latinos have increased risk for AD and other dementias, limited access to quality care, and are severely underrepresented in AD and dementia research and clinical trials. The symposium highlighted developments in AD research with Latino populations, including advances in AD biomarkers, and novel cognitive assessments for Spanish-speaking populations, as well as the need to effectively recruit and retain Latinos in clinical research, and how best to deliver health-care services and to aid caregivers of Latinos living with AD

Human Milk Secretory Antibodies against Attaching and Effacing Escherichia coli Antigens

Secretory immunoglobulin A (sIgA) is a primary factor responsible for preventing attachment of enteropathogens to gut epithelium in breastfeeding infants. We compared the frequency of sIgA to major surface antigens of enterohemorrhagic Escherichia coli (EHEC) in milk of 123 women from the United States and Mexico to determine whether regional differences existed in the frequency of antibodies to these surface antigens. In both groups of women, milk commonly has sIgA against various EHEC lipopolysaccharides, EspA, EspB, intimin, and less frequently against Shiga toxin. The study suggests that persons living in the U.S. are exposed to attaching/effacing enteropathogens more frequently than is generally assumed. The low frequency of antibodies to Stx1 (in 12% of Mexican and in 22% of U.S. samples) suggests that the rare appearance of hemolytic uremic syndrome in adults is not due to neutralization of toxin at the gut level. Only anti-EspA is found in most milk samples from both populations of women. EspA may represent a useful target for an immunization strategy to prevent EHEC disease in humans

Phase III Trial of Adjuvant Capecitabine After Standard Neo-/Adjuvant Chemotherapy in Patients With Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01)

Altres ajuts: Agustí Barnadas: Honoraria: Pfizer. Consulting or Advisory Role: Pfizer, Novartis, Eli Lilly. Speakers'Bureau: Roche, Pfizer, Novartis, Genomic Health International. Travel, Accommodations, Expenses: Roche, Pfizer; Miguel A. Seguí: Consulting or Advisory Role: Roche, Pfizer, Novartis, Amgen, Eisai, Eli Lilly. Speakers' Bureau: Roche, Pfizer, Amgen. Research Funding: Roche (Inst), Novartis (Inst). Travel, Accommodations, Expenses: Roche, Pfizer, Novartis, Amgen.Operable triple-negative breast cancers (TNBCs) have a higher risk of relapse than non-TNBCs with standard therapy. The GEICAM/2003-11_CIBOMA/2004-01 trial explored extended adjuvant capecitabine after completion of standard chemotherapy in patients with early TNBC. Eligible patients were those with operable, node-positive-or node negative with tumor 1 cm or greater-TNBC, with prior anthracycline- and/or taxane-containing chemotherapy. After central confirmation of TNBC status by immunohistochemistry, patients were randomly assigned to either capecitabine or observation. Stratification factors included institution, prior taxane-based therapy, involved axillary lymph nodes, and centrally determined phenotype (basal v nonbasal, according to cytokeratins 5/6 and/or epidermal growth factor receptor positivity by immunohistochemistry). The primary objective was to compare disease-free survival (DFS) between both arms. Eight hundred seventy-six patients were randomly assigned to capecitabine (n = 448) or observation (n = 428). Median age was 49 years, 55.9% were lymph node negative, 73.9% had a basal phenotype, and 67.5% received previous anthracyclines plus taxanes. Median length of follow-up was 7.3 years. DFS was not significantly prolonged with capecitabine versus observation [hazard ratio (HR), 0.82; 95% CI, 0.63 to 1.06; P =.136]. In a preplanned subgroup analysis, nonbasal patients seemed to derive benefit from the addition of capecitabine with a DFS HR of 0.53 versus 0.94 in those with basal phenotype (interaction test P =.0694) and an HR for overall survival of 0.42 versus 1.23 in basal phenotype (interaction test P =.0052). Tolerance of capecitabine was as expected, with 75.2% of patients completing the planned 8 cycles. This study failed to show a statistically significant increase in DFS by adding extended capecitabine to standard chemotherapy in patients with early TNBC. In a preplanned subset analysis, patients with nonbasal phenotype seemed to obtain benefit with capecitabine, although this will require additional validation

Informe del GTM sobre COVID persistente

El Grupo de Trabajo Multidisciplinar (GTM) asesora y apoya al Ministerio de Ciencia e Innovación en materias científicas relacionadas con el COVID-19 y sus consecuencias futuras. El GTM está compuesto por: José M. Ordovás (presidente), Mariano Esteban, Rocío García-Retamero, Beatriz González López- Valcárcel, Alfonso Gordaliza, Marco Inzitari, Pedro Jordano, Itziar de Lecuona, Laura M. Lechuga, Ramón López de Mántaras, José Molero, Agustín Portela, Diego Puga, José Javier Ramasco, Francisco Sánchez- Madrid y Alfonso Valencia. Enric Banda actúa como observador, y Maria Sol Serrano Alonso como secretaria. Todos los componentes del GTM colaboran de forma desinteresada con el Ministerio de Ciencia e Innovación. Este informe ha sido elaborado por Jose María Ordovás y Francisco Sánchez-Madrid en colaboración con Julio Ancochea, Silvia Guerrero, Lourdes Mateu, Roger Paredes, Pilar Rodríguez Ledo y Joan B. Soriano.La enfermedad por coronavirus 2019 (COVID-19) y su pandemia continúa afectando la sociedad.1 A finales de la primavera de 2020, cuando se estaba empezando a controlar la primera ola de casos en España y en otros países, se observó algo inusual: algunos pacientes de COVID-19 todavía tenían síntomas semanas después de superar la infección inicial. Se manifestaban problemas como fatiga, disnea, dolor torácico, palpitaciones, síntomas gastrointestinales, confusión mental, ansiedad y depresión, entre más de 50 síntomas posibles asociados.2 Estas personas sufren una variedad de síntomas, a menudo debilitantes, después de la infección aguda por SARS-CoV-2, y muchos han estado sufriéndolos durante semanas o meses.3 Pero más allá del nombre, lo que se necesita es una definición universal y consensuada de este cuadro de síntomas con sociedades, organismos y pacientesPeer reviewe