PATRONES DE LA MACROFAUNA EDAFICA EN UN CULTIVO DE ZEA MAIZ DURANTE LA FASE POSTCOSECHA EN LA MANCHA, VERACRUZ, MEXICO

The soil macrofauna of a cornfield was studied during the fallow period in El Centro de Investigaciones Costeras "La Mancha", Veracruz. Patterns of soil macrofauna density, spatial distribution and diversity were described and their relationships with soil temperature, moisture, organic matter and pH were explored. Four strategies were combined to undertake this aim: a) sampling of soil macrofauna was carried out in seven ten cm soil layers from 0 to 70 cm depth; b) soil macrofauna was identified to morphospecies level; c) the size of morphospecies aggregations was determined following a the two-term local quadrat variance method (TTLQV); d) analysis of canonical correspondence was used to arrange morphospecies distribution in an spatial and environmental framework of reference. Density of soil macrofauna in the studied site seems to be the lowest value ever recorded in similar studies (246 individuals m-2). Forty-six morphospecies were collected that are mainly distributed in the top 20 cm soil layer and present an aggregated horizontal pattern of distribution. The diameter of aggregations of Oligochaeta juveniles, larvae of Tenebrionidae and Diplopoda juveniles was >1.5m, 0.9 m and 1.2 m respectively. It was possible to arrange different groups of soil Macrofauna according with their ranges of tolerance to environmental variables. Therefore, it is suggested that these patterns do reflect preferences of soil biota to microenvironments and do respond to soil degradation.Estudiamos la macrofauna del suelo de un cultivo de Zea maiz durante la fase postcosecha en el Centro de Investigaciones Costeras La Mancha, Veracruz. Describimos patrones de densidad, distribución espacial y diversidad en relación con la temperatura, humedad y pH del suelo. Para esto conjuntamos cuatro estrategias: a) muestreamos la macrofauna en estratos de 10 cm hasta los 70 cm de profundidad; b) separamos la fauna a nivel de morfoespecie; c) estimamos el tamaño de las agregaciones de las morfoespecies mediante una técnica de cuadrante-varianza; y d) ordenamos, mediante un análisis de correspondencia canónica, morfoespecies y estratos en un marco de referencia ambiental. La densidad de la macrofauna del suelo estudiado es la más baja reportada hasta la fecha para agroecosistemas en el mundo (246 individuos/m2). Colectamos 46 morfoespecies, que se distribuyeron generalmente en el primer o segundo estrato del suelo y presentaron una distribución agregada. El diametro de las agregaciones de los Oligochaeta juveniles fue superior a 1.5 m y para las larvas de Tenebrionidae y los Diplopoda juveniles fue de 0.9 y 1.2 m, respectivamente. Debido a que es posible separar distintos grupos de acuerdo con sus rangos de tolerancia a la temperatura, pH, humedad y materia orgánica en el suelo, es factible que los patrones de distribución registrados sean un reflejo de las preferencias de la biota a diferentes microambientes y al estado de degradación del suelo

Prognostic value of cardiac troponin T elevation is independent of renal function and clinical findings in heart failure patients

Background: The aim of this study is to determine the prevalence and prognostic value of elevated cardiac troponin (cTnT) and its association with clinical characteristics according to renal function status in patients with stable heart failure. Methods: In a prospective observational study, 152 consecutive patients from the Heart Failure Clinic of the INCMNSZ were followed for a period of 42 months. All underwent clinical evaluation, echocardiography, and determination of body composition by electric bioimpedance to identify hypervolemia. Concentrations of cTnT were quantified by immunoassay with electrochemoluminescence and &#8805; 0.02 ng/mL levels were considered elevated. Also glomerular filtration rate (eGFR) was estimated using the Cockcroft-Gault equation. Results: Elevated cTnT was significantly associated with increased all-cause mortality in the observational period even after adjusting for eGFR < 60 mL/min/1.73 m2 and clinical findings such as hypertension, functional class, loop diuretics, angiotensin converting enzyme inhibitors, pulmonary pressure and hypervolemia in Cox regression analysis with a hazard ratio of 4.58 (95% confidence interval: 1.84&#8211;11.45). Conclusions: Heart failure patients with elevated cardiac-specific troponin T are at increased risk of death independently of the presence of chronic kidney disease. (Cardiol J 2010; 17, 1: 42-48

Association between the plasma/whole blood lead ratio and history of spontaneous abortion: a nested cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Blood lead has been associated with an elevated risk of miscarriage. The plasmatic fraction of lead represents the toxicologically active fraction of lead. Women with a tendency to have a higher plasma/whole blood Pb ratio could tend towards an elevated risk of miscarriage due to a higher plasma Pb for a given whole blood Pb and would consequently have a history of spontaneous abortion.</p> <p>Methods</p> <p>We studied 207 pregnant Mexico City residents during the 1^sttrimester of pregnancy, originally recruited for two cohorts between 1997 and 2004. Criteria for inclusion in this study were having had at least one previous pregnancy, and having valid plasma and blood Pb measurements. Pb was measured in whole blood and plasma by inductively coupled plasma mass spectrometry using ultra-clean techniques. History of miscarriage in previous pregnancies was obtained by interview. The incidence rate of spontaneous abortion was defined as the proportion of previous pregnancies that resulted in miscarriage. Data were analyzed by means of Poisson regression models featuring the incidence rate of spontaneous abortion as the outcome and continuous or categorized plasma/blood Pb ratios as predictor variables. All models were adjusted for age and schooling. Additionally, logistic regression models featuring inclusion in the study sample as the outcome were fitted to assess potential selection bias.</p> <p>Results</p> <p>The mean number of miscarriages was 0.42 (range 0 to 4); mean Pb concentrations were 62.4 and 0.14 μg/L in whole blood and plasma respectively. Mean plasma/blood Pb ratio was 0.22%. We estimated that a 0.1% increment in the plasma/blood Pb ratio lead was associated to a 12% greater incidence of spontaneous abortion (p = 0.02). Women in the upper tertile of the plasma/blood Pb ratio had twice the incidence rate of those in the lower tertile (p = 0.02). Conditional on recruitment cohort, inclusion in the study sample was unrelated to observable characteristics such as number of abortions, number of pregnancies, blood Pb levels, age schooling, weight and height.</p> <p>Conclusion</p> <p>Women with a large plasma/whole blood Pb ratio may be at higher risk of miscarriage, which could be due to a greater availability of placental barrier-crossing Pb.</p

Sexual Relationships in Hispanic Countries: a Literature Review

This is a pre-print of an article published in Current Sexual Health Reports. The final authenticated version is available online at: https://doi.org/10.1007/s11930-020-00272-6Purpose of Review: Sexuality is a complex dimension for which culture seems to play an important role, particularly in countries that are more traditional. This review summarizes the knowledge about sexual relationships in Hispanic countries, considering sexual debut, attitudes, behaviors, and satisfaction. Recent Findings: In line with the literature reviewed, the sexual double standard seems to be continuing to influence sexual relationships. Some countries show more open expressions of sexuality based on the level of gender inequality or sexualized context, and within countries, variables such as religious commitment, family characteristics, and access to resources may play important roles in sexuality. Summary: Future research, policies, and interventions should consider these specific characteristics, including these forms of expression of sexuality, in the adjustment of cross-cultural and cross-national strategies

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.We thank all members of the Brain Metastasis Group and A. Chalmers, E. Wagner, O. Fernández-Capetillo, R. Ciérvide and A. Hidalgo for critical discussion of the manuscript; the CNIO Core Facilities for their excellent assistance; and Fox Chase Cancer Center Transgenic Facility for generation of S100A9 mice. We thank EuCOMM repository for providing S100A9 targeted embryonic stem cells. We also thank J. Massagué (MSKCC) for some of the BrM cell lines and M. Bosenberg (Yale) for the YUMM1.1 cell line. Samples from patients included in this study that provided by the Girona Biomedical Research Institute (IDIBGI) (Biobanc IDIBGI, B.0000872) are integrated into the Spanish National Biobanks Network and in the Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by the Pla Director d’Oncologia de Catalunya. All patients consented to the storage of these samples in the biobank and for their use in research projects. This study was funded by MINECO (SAF2017-89643-R) (M.V.), Fundació La Marató de TV3 (201906-30-31-32) (J.B.-B., M.V. and A.C.), Fundación Ramón Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V. and E.C.-J.M.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Portuguese Foundation for Science and Technology (SFRH/bd/100089/2014) (C.M.), Boehringer-Ingelheim Fonds MD Fellowship (L.M.), La Caixa International PhD Program Fellowship-Marie Skłodowska-Curie (LCF/BQ/DI17/11620028) (P.G.-G.), La Caixa INPhINIT Fellowship (LCF/BQ/DI19/11730044) (A.P.-A.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A.-E.) and an AECC postdoctoral fellowship (POSTD19016PRIE) (N.P.). M.V. is an EMBO YIP member (4053). Additional support was provided by Gertrud and Erich Roggenbuck Stiftung (M.M.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award with the generous support of Walk the Walk (2019AugSF1310) (D.V.), Science Foundation Ireland (20/FFP-P/8597) (D.V.), Paradifference Foundation (C.F.-T.), “la Caixa” Foundation (ID 100010434) (A.I.), European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 847648 (CF/BQ/PI20/11760029) (A.I.), Champalimaud Centre for the Unknown (N.S.), Lisboa Regional Operational Programme (Lisboa 2020) (LISBOA01-0145-FEDER-022170) (N.S.), NCI (R01 CA227629; R01 CA218133) (S.I.G.), Fundació Roses Contra el Càncer (J.B.-B.), Ministerio de Universidades FPU Fellowship (FPU 18/00069) (P.T.), MICIN-Agencia Estatal de Investigación Fellowships (PRE2020-093032 and BES-2017-080415) (P.M. and E. Cintado, respectively), Ministerio de Ciencia, Innovación y Universidades-E050251 (PID2019-110292RB-I00) (J.L.T.), FCT (PTDC/MED-ONC/32222/2017) (C.C.F.), Fundação Millennium bcp (C.C.F.), private donations (C.C.F.) and the Foundation for Applied Cancer Research in Zurich (E.L.R. and M.W.)

DNA Methylation-Independent Reversion of Gemcitabine Resistance by Hydralazine in Cervical Cancer Cells

BACKGROUND: Down regulation of genes coding for nucleoside transporters and drug metabolism responsible for uptake and metabolic activation of the nucleoside gemcitabine is related with acquired tumor resistance against this agent. Hydralazine has been shown to reverse doxorubicin resistance in a model of breast cancer. Here we wanted to investigate whether epigenetic mechanisms are responsible for acquiring resistance to gemcitabine and if hydralazine could restore gemcitabine sensitivity in cervical cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The cervical cancer cell line CaLo cell line was cultured in the presence of increasing concentrations of gemcitabine. Down-regulation of hENT1 & dCK genes was observed in the resistant cells (CaLoGR) which was not associated with promoter methylation. Treatment with hydralazine reversed gemcitabine resistance and led to hENT1 and dCK gene reactivation in a DNA promoter methylation-independent manner. No changes in HDAC total activity nor in H3 and H4 acetylation at these promoters were observed. ChIP analysis showed H3K9m2 at hENT1 and dCK gene promoters which correlated with hyper-expression of G9A histone methyltransferase at RNA and protein level in the resistant cells. Hydralazine inhibited G9A methyltransferase activity in vitro and depletion of the G9A gene by iRNA restored gemcitabine sensitivity. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that acquired gemcitabine resistance is associated with DNA promoter methylation-independent hENT1 and dCK gene down-regulation and hyper-expression of G9A methyltransferase. Hydralazine reverts gemcitabine resistance in cervical cancer cells via inhibition of G9A histone methyltransferase

A Proof-Of-Principle Study of Epigenetic Therapy Added to Neoadjuvant Doxorubicin Cyclophosphamide for Locally Advanced Breast Cancer

BACKGROUND: Aberrant DNA methylation and histone deacetylation participate in cancer development and progression; hence, their reversal by inhibitors of DNA methylation and histone deacetylases (HDACs) is at present undergoing clinical testing in cancer therapy. As epigenetic alterations are common to breast cancer, in this proof-of-concept study demethylating hydralazine, plus the HDAC inhibitor magnesium valproate, were added to neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess their safety and biological efficacy. METHODOLOGY: This was a single-arm interventional trial on breast cancer patients (ClinicalTrials.gov Identifier: NCT00395655). After signing informed consent, patients were typed for acetylator phenotype and then treated with hydralazine at 182 mg for rapid-, or 83 mg for slow-acetylators, and magnesium valproate at 30 mg/kg, starting from day –7 until chemotherapy ended, the latter consisting of four cycles of doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 21 days. Core-needle biopsies were taken from primary breast tumors at diagnosis and at day 8 of treatment with hydralazine and valproate. MAIN FINDINGS: 16 patients were included and received treatment as planned. All were evaluated for clinical response and toxicity and 15 for pathological response. Treatment was well-tolerated. The most common toxicity was drowsiness grades 1–2. Five (31%) patients had clinical CR and eight (50%) PR for an ORR of 81%. No patient progressed. One of 15 operated patients (6.6%) had pathological CR and 70% had residual disease <3 cm. There was a statistically significant decrease in global 5(m)C content and HDAC activity. Hydralazine and magnesium valproate up- and down-regulated at least 3-fold, 1,091 and 89 genes, respectively. CONCLUSIONS: Hydralazine and magnesium valproate produce DNA demethylation, HDAC inhibition, and gene reactivation in primary tumors. Doxorubicin and cyclophosphamide treatment is safe, well-tolerated, and appears to increase the efficacy of chemotherapy. A randomized phase III study is ongoing to support the efficacy of so-called epigenetic or transcriptional cancer therapy

Evidence for associated production of a Higgs boson with a top quark pair in final states with electrons, muons, and hadronically decaying τ leptons at s=13 \sqrt{s}=13 TeV

Results of a search for the standard model Higgs boson produced in association with a top quark pair (tt¯H) in final states with electrons, muons, and hadronically decaying τ leptons are presented. The analyzed data set corresponds to an integrated luminosity of 35.9 fb−1 recorded in proton-proton collisions at s√=13 TeV by the CMS experiment in 2016. The sensitivity of the search is improved by using matrix element and machine learning methods to separate the signal from backgrounds. The measured signal rate amounts to 1.23 − 0.43 + 0.45 times the production rate expected in the standard model, with an observed (expected) significance of 3.2σ (2.8σ), which represents evidence for tt¯H production in those final states. An upper limit on the signal rate of 2.1 times the standard model production rate is set at 95% confidence level