PIM1 is a potential therapeutic target for the leukemogenic effects mediated by JAK/STAT pathway mutations in T-ALL/LBL.

Precursor T-cell neoplasms (T-ALL/LBL) are aggressive hematological malignancies that arise from the malignant transformation of immature thymocytes. Despite the JAK/STAT pathway is recurrently altered in these neoplasms, there are not pharmacological inhibitors officially approved for the treatment of T-ALL/LBL patients that present oncogenic JAK/STAT pathway mutations. In the effort to identify potential therapeutic targets for those patients, we followed an alternative approach and focused on their transcriptional profile. We combined the analysis of molecular data from T-ALL/LBL patients with the generation of hematopoietic cellular models to reveal that JAK/STAT pathway mutations are associated with an aberrant transcriptional profile. Specifically, we demonstrate that JAK/STAT pathway mutations induce the overexpression of the PIM1 gene. Moreover, we show that the pan-PIM inhibitor, PIM447, significantly reduces the leukemogenesis, as well as the aberrant activation of c-MYC and mTOR pathways in cells expressing different JAK/STAT pathway mutations, becoming a potential therapeutic opportunity for a relevant subset of T-ALL/LBL patients.

Impact of catheterized ductal closure on renal and cerebral oximetry in premature neonates.

Percutaneous catheter-based closure is increasingly utilized in premature newborns. While near-infrared spectroscopy (NIRS) has been examined for assessment of interventional closure in surgical ligation, its application in percutaneous transcatheter closure remains unexplored. This study aims to assess cerebral and renal hemodynamic changes using NIRS during percutaneous closure compared to surgical closure in preterm infants. A prospective observational study enrolled preterm infants born at 32 weeks of gestation or less and diagnosed with hsPDA between January 2020 and December 2022. These infants received either surgical or catheter-based closure of the PDA. Cerebral and renal oxygen saturation was monitored using the INVOS 5100 device from 12 h before the intervention until 24 h after. Linear mixed-effects models were used to analyze time-dependent variables. Twenty-two patients were enrolled, with catheter-based closure performed in 16 cases and conventional surgery in 6 cases. Following ductal closure, a significant increase in renal and cerebral oximetry was observed alongside a decrease in renal and cerebral tissue oxygen extraction. These changes were particularly pronounced in the renal territory. No differences were detected between catheterization and surgical closure.   Conclusion: An improvement in cerebral and renal oximetry following hsPDA closure was observed. However, we did not identify differences in this pattern based on the type of interventional procedure for PDA, whether surgery or catheterization. What is Known: • The presence of a significant ductus is common in premature patients. Studies have shown that it affects cerebral and renal hemodynamics negatively, leading to decreased oximetry values in these areas. It has been reported that closure of the ductus, either pharmacologically or surgically, results in improved oximetry values. What is New: • This study assess the impact of percutaneous closure of ductus, revealing increased oximetry values in cerebral and renal territories without significant differences compared to surgical ligation. Notably, renal oximetry values showed a greater increase, underscoring the importance of multi-location monitoring.

Exposure to green spaces, cardiovascular risk biomarkers and incident cardiovascular disease in older adults: The Seniors-Enrica II cohort.

INTRODUCTION: The impact of residential green spaces on cardiovascular health in older adults remains uncertain. METHODS: Cohort study involving 2114 adults aged ≥ 65 years without cardiovascular disease (CVD), residing in five dense municipalities (Prince et al., 2015) of the Madrid region and with detailed characterization of their socioeconomic background, health behaviors, CVD biological risk factors, and mental, physical, and cognitive health. Greenness exposure was measured using the Normalized Difference Vegetation Index (NDVI) at varying distances from participants' homes. Traffic exposure, neighborhood environment, neighborhood walkability, and socioeconomic deprivation at the census level were also assessed. Serum N-terminal pro-B-type natriuretic peptide (NT-ProBNP), high-sensitivity troponin T (hs-TnT), interleukin 6 (IL-6), and Growth Differentiation Factor 15 (GDF-15) were measured at baseline, and incident CVD events identified through electronic medical records (International Classification of Primary Care-2 codes K74, K75, K77, K90, and K92). RESULTS: After adjusting for sex, age, educational attainment, financial hardship and socioeconomic deprivation at the census level, an interquartile range (IQR) increase in NDVI at 250, 500, 750, and 1000 m around participants' homes was associated with mean differences in ProBNP of -5.56 % (95 %CI: -9.77; -1.35), -5.05 % (-9.58; -0.53), -4.24 % (-8.19, -0.19), and -4.16 % (-7.59; -0.74), respectively; and mean differences in hs-TnT among diabetic participants of -8.03 % (95 %CI: -13.30; -2.77), -9.52 % (-16.08; -2.96), -8.05 % (-13.94, -2.16) and -5.56 % (-10.75; -0.54), respectively. Of similar magnitude, although only statistically significant at 250 and 500 m, were the observed lower IL-6 levels with increasing greenness. GDF-15 levels were independent of NDVI. In prospective analyses (median follow-up 6.29 years), an IQR increase in residential greenness at 500, 750, and 1000 m was associated with a lower risk of incident CVD. The variables that contributed most to the apparent beneficial effects of greenness on CVD were lower exposure to traffic, improved cardiovascular risk factors, and enhanced physical performance. Additionally, neighborhood walkability and increased physical activity were notable contributors among individuals with diabetes. CONCLUSION: Increased exposure to residential green space was associated with a moderate reduction in CVD risk in older adults residing in densely populated areas.

Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

Recommendations for the management of yttrium-90 radioembolization in the treatment of patients with colorectal cancer liver metastases: a multidisciplinary review.

PURPOSE: Strategies for the treatment of liver metastases from colon cancer (lmCRC) are constantly evolving. Radioembolization with yttrium 90 (Y-90 TARE) has made significant advancements in treating liver tumors and is now considered a potential option allowing for future resection. This study reviewed the scientific evidence and developed recommendations for using Y-90 TARE as a treatment strategy for patients with unresectable lmCRC. METHODS: A multidisciplinary scientific committee, consisting of experts in medical oncology, hepatobiliary surgery, radiology, and nuclear medicine, all with extensive experience in treating patients with ImCRC with Y-90 TARE, led this project. The committee established the criteria for conducting a comprehensive literature review on Y-90 TARE in the treatment of lmCRC. The data extraction process involved addressing initial preliminary inquiries, which were consolidated into a final set of questions. RESULTS: This review offers recommendations for treating patients with lmCRC using Y-90 TARE, addressing four areas covering ten common questions: 1) General issues (multidisciplinary tumor committee, indications for treatment, contraindications); 2) Previous process (predictive biomarkers for patient selection, preintervention tests, published evidence); 3) Procedure (standard procedure); and 4) Post-intervention follow-up (potential toxicity and its management, parameters for evaluation, quality of life). CONCLUSIONS: Based on the insights of the multidisciplinary committee, this document offers a comprehensive overview of the technical aspects involved in the management of Y-90 TARE. It synthesizes recommendations for applying Y-90 TARE across various phases of the treatment process.

Validación y Comparación de un Nuevo Método para Predecir el Ancho Mesiodistal de Caninos y Premolares no Erupcionados en una Población Chilena de la Región de Valparaíso, Chile

Uno de los principales problemas durante la dentición mixta es la determinación de la futura discrepancia entre tamaño dentario y el espacio disponible. Para predecir el ancho mesiodistal de los dientes permanentes no erupcionados se han introducido diferentes métodos de análisis. Objetivo: El propósito de este estudio fue comparar el método Tanaka-Johnston con una nueva ecuación de regresión para predecir el ancho mesiodistal de caninos y premolares permanentes no erupcionados en una población de la región de Valparaíso, Chile. Material y método: Este estudio fue realizado en la Facultad de Odontología de la Universidad de Valparaíso, desde octubre de 2022 a junio de 2023 (8 meses), la muestra estuvo compuesta por 202 modelos de estudio del departamento de ortodoncia (91 hombres y 111 mujeres) en el rango de edad de 11 -20 años. Resultados: Se demostró que el método elaborado por Lara-Sandoval presenta mayor fiabilidad respecto a las medidas mesiodistales reales de los pacientes (ICC 0,773 para maxilar y 0,762 para mandíbula), en comparación con el método de Tanaka-Johnston (ICC 0,665 para maxilar y 0,623 para mandíbula). No existen diferencias significativas entre los valores reales y el método de Lara-Sandoval. Conclusión: El método de Lara-Sandoval es mejor que el propuesto por Tanaka-Johnston para determinar el ancho mesiodistal de caninos y premolares para esta muestra. Es necesario validar este método en otras regiones del país para ser utilizado con mayor seguridad que el ya existente como método estándar nacional.

One of the main orthodontic problems in mixed dentition is the determination of future tooth and size arch discrepancy. In order to predict the mesiodistal widths of unerupted permanent teeth different methods of analyses have been introduced. The aim of this study is to compare the Tanaka-Johnston analysis with a new regressive equation to predict the mesiodistal width of unerupted permanent canines and premolars in a Chilean population sample, from Valparaíso region. This study was conducted at the Universidad de Valparaíso Dental Faculty, from october 2022 to june 2023 (8 months), and the sample comprised historical dental casts from 202 patients (91 boys and 111 girls) in the age range of 11-20 from the orthodontics department. All the patients are from the Valparaíso region, Chile. The results show that the predictions of the new regressive equation method are closer to the actual mesiodistal measurements of the patients (ICC 0,773 for maxilla and 0,762 for mandible), compared to the Tanaka- Johnston method (ICC 0,665 for maxilla and 0,623 for mandible). There are no significant differences between the real values and the Lara-Sandoval method. Lara-Sandoval method is better than the one proposed by Tanaka-Johnston to determine the mesiodistal width of canines and premolars in this sample population. It is necessary to validate this method in other regions of the country to be used with greater security than the ones that already exists as a national standard method.

Socio-economic inequalities in lung cancer mortality in Spain: a nation-wide study using area-based deprivation.

BACKGROUND: Lung cancer is the main cause of cancer mortality worldwide and in Spain. Several previous studies have documented socio-economic inequalities in lung cancer mortality but these have focused on specific provinces or cities. The goal of this study was to describe lung cancer mortality in Spain by sex as a function of socio-economic deprivation. METHODS: We analysed all registered deaths from lung cancer during the period 2011-2017 in Spain. Mortality data was obtained from the National Institute of Statistics, and socio-economic level was measured with the small-area deprivation index developed by the Spanish Society of Epidemiology, with the census tract of residence at the time of death as the unit of analysis. We computed crude and age-standardized rates per 100,000 inhabitants by sex, deprivation quintile, and type of municipality (rural, semi-rural, urban) considering the 2013 European standard population (ASR-E). We further calculated ASR-E ratios between the most deprived (Q5) and the least deprived (Q1) areas and mapped census tract smoothed standardized lung cancer mortality ratios by sex. RESULTS: We observed 148,425 lung cancer deaths (80.7% in men), with 73.5 deaths per 100,000 men and 17.1 deaths per 100,000 women. Deaths from lung cancer in men were five times more frequent than in women (ASR-E ratio = 5.3). Women residing in the least deprived areas had higher mortality from lung cancer (ASR-E = 22.2), compared to women residing in the most deprived areas (ASR-E = 13.2), with a clear gradient among the quintiles of deprivation. For men, this pattern was reversed, with the highest mortality occurring in areas of lower socio-economic level (ASR-E = 99.0 in Q5 vs. ASR-E = 86.6 in Q1). These socio-economic inequalities remained fairly stable over time and across urban and rural areas. CONCLUSIONS: Socio-economic status is strongly related to lung cancer mortality, showing opposite patterns in men and women, such that mortality is highest in women residing in the least deprived areas and men residing in the most deprived areas. Systematic surveillance of lung cancer mortality by socio-economic status may facilitate the assessment of public health interventions aimed at mitigating cancer inequalities in Spain.

Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.

The standard-of-care treatment of T-cell acute lymphoblastic leukaemia (T-ALL) with chemotherapy usually achieves reasonable rates of initial complete response. However, patients who relapse or do not respond to conventional therapy show dismal outcomes, with cure rates below 10% and limited therapeutic options. To ameliorate the clinical management of these patients, it is urgent to identify biomarkers able to predict their outcomes. In this work, we investigate whether NRF2 activation constitutes a biomarker with prognostic value in T-ALL. Using transcriptomic, genomic, and clinical data, we found that T-ALL patients with high NFE2L2 levels had shorter overall survival. Our results demonstrate that the PI3K-AKT-mTOR pathway is involved in the oncogenic signalling induced by NRF2 in T-ALL. Furthermore, T-ALL patients with high NFE2L2 levels displayed genetic programs of drug resistance that may be provided by NRF2-induced biosynthesis of glutathione. Altogether, our results indicate that high levels of NFE2L2 may be a predictive biomarker of poor treatment response in T-ALL patients, which would explain the poor prognosis associated with these patients. This enhanced understanding of NRF2 biology in T-ALL may allow a more refined stratification of patients and the proposal of targeted therapies, with the ultimate goal of improving the outcome of relapsed/refractory T-ALL patients.

Risk of Gastroenteritis from Swimming at a Wastewater-Impacted Tropical Beach Varies across Localized Scales.

Population growth and changing climate are expected to increase human exposure to pathogens in tropical coastal waters. We examined microbiological water quality in three rivers within 2.3 km of each other that impact a Costa Rican beach and in the ocean outside their plumes during the rainy and dry seasons. We performed quantitative microbial risk assessment (QMRA) to predict the risk of gastroenteritis associated with swimming and the amount of pathogen reduction needed to achieve safe conditions. Recreational water quality criteria based on enterococci were exceeded in >90% of river samples but in only 13% of ocean samples. Multivariate analysis grouped microbial observations by subwatershed and season in river samples but only by subwatershed in the ocean. The modeled median risk from all pathogens in river samples was between 0.345 and 0.577, 10-fold above the U.S. Environmental Protection Agency (U.S. EPA) benchmark of 0.036 (36 illnesses/1,000 swimmers). Norovirus genogroup I (NoVGI) contributed most to risk, but adenoviruses raised risk above the threshold in the two most urban subwatersheds. The risk was greater in the dry compared to the rainy season, due largely to the greater frequency of NoVGI detection (100% versus 41%). Viral log10 reduction needed to ensure safe swimming conditions varied by subwatershed and season and was greatest in the dry season (3.8 to 4.1 dry; 2.7 to 3.2 rainy). QMRA that accounts for seasonal and local variability of water quality contributes to understanding the complex influences of hydrology, land use, and environment on human health risk in tropical coastal areas and can contribute to improved beach management. IMPORTANCE This holistic investigation of sanitary water quality at a Costa Rican beach assessed microbial source tracking (MST) marker genes, pathogens, and indicators of sewage. Such studies are still rare in tropical climates. Quantitative microbial risk assessment (QMRA) found that rivers impacting the beach consistently exceeded the U.S. EPA risk threshold for gastroenteritis of 36/1,000 swimmers. The study improves upon many QMRA studies by measuring specific pathogens, rather than relying on surrogates (indicator organisms or MST markers) or estimating pathogen concentrations from the literature. By analyzing microbial levels and estimating the risk of gastrointestinal illness in each river, we were able to discern differences in pathogen levels and human health risks even though all rivers were highly polluted by wastewater and were located less than 2.5 km from one another. This variability on a localized scale has not, to our knowledge, previously been demonstrated.

SOCS3 deregulation contributes to aberrant activation of the JAK/STAT pathway in precursor T-cell neoplasms.

Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBL.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Características morfométricas de la mandíbula de rata: un estudio radiológico de un modelo experimental animal ampliamente utilizado a través de CBCT / Morphometric characteristics of rat mandibular bone: radiologic study of a widely used animal as experimental model through CBCT

La mandíbula de rata es una de las estructuras anatómicas de mayor interés en la investigación en las ciencias odontológicas, esto debido a su similitud con la mandíbula humana. El objetivo de este estudio fue caracterizar morfometricamente la mandíbula de ratas mediante CBCT. Se analizó el examen cone beam de 20 ratas hembras, adultas sanas. Mediante el software del examen, fue posible aislar la mandíbula derecha e izquierda de las otras estructuras y realizar adecuadamente las medidas morfométricas de interés. En la comparación de ambos lados, sólo dos medidas presentaron diferencias significativas. La distancia entre el punto más profundo de la escotadura sigmoidea hasta el punto más profundo de la escotadura en el margen inferior de la mandíbula, fue mayor en el lado izquierdo que en el derecho. Y la distancia entre el punto más superior del cóndilo hasta la base mandibular, en la proyección perpendicular del plano mandibular fue mayor en el lado izquierdo que en el derecho. De acuerdo a las medidas obtenidas, podemos determinar que la mandíbula de la rata es una estructura alargada, con dimensiones mayores en sentido anteroposterior en comparación con las medidas verticales. El conocimiento de la anatomía de la mandíbula de rata y sus variaciones por lado permite a los investigado- res tener referencias adecuadas para los estudios que involucren esta estructura, como por ejemplo, investigaciones que requieran la aplicación de técnicas anestésicas, estudio del dolor orofacial, estudio patofisiológico de la ATM, estudio del crecimiento óseo, testeo de biomateriales dentales o en el estudio de procesos fisiopatológicos relacionados con los tejidos dentales o periodontales. La mandíbula de la rata es un buen modelo animal debido a su reproducibilidad y bajo costo. La mandíbula derecha e izquierda son similares en sus dimensiones anteroposteriores, pero no las verticales.

SUMMARY: The rat jaw is one of the most interesting anatomical structures in dental science research, due to its similarity to the human jaw. The aim of this study was to morphometrically characterize the mandible of rats by CBCT. The cone beam examination of 20 healthy adult female rats was analyzed. Using the examination software, it was possible to isolate the right and left mandible from the other structures and adequately perform the morphometric measurements of interest. In the comparison of both sides, only two measures presented significant differences. The distance from the deepest point of the sigmoid notch to the deepest point of the notch at the lower margin of the mandible was greater on the left side than on the right. And the distance between the most superior point of the condyle to the mandibular base, in the perpendicular projection of the mandibular plane, was greater on the left side than on the right. According to the measurements obtained, we can determine that the rat jaw is an elongated structure, with larger dimensions in the anteroposterior direction compared to the vertical measurements. Knowledge of the anatomy of the rat mandible and its variations per side allows researchers to have adequate references for studies involving this structure, such as research that requires the application of anesthetic techniques, study of orofacial pain, pathophysiological study of the TMJ, study of bone growth, testing of dental biomaterials or in the study of pathophysiological processes related to den- tal or periodontal tissues. The rat mandible is a good animal model due to its reproducibility and low cost. The right and left mandible are similar in their anteroposterior dimensions, but not the vertical ones.

Rural-urban gradients and all-cause, cardiovascular and cancer mortality in Spain using individual data.

•The literature reporting on rural-urban health status disparities remains inconclusive.•We analyzed data from a longitudinal population-based study using individual observations.•Our results show that the risks of all-cause and cancer mortality are greater in large cities than in other municipalities, with no clear urban-rural gradient.•Not differences were found among territories in cardiovascular mortality.

Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Association of socioeconomic deprivation with life expectancy and all-cause mortality in Spain, 2011-2013.

Life tables summarise a population's mortality experience during a time period. Sex- and age-specific life tables are needed to compute various cancer survival measures. However, mortality rates vary according to socioeconomic status. We present sex- and age-specific life tables based on socioeconomic status at the census tract level in Spain during 2011-2013 that will allow estimating cancer relative survival estimates and life expectancy measures by socioeconomic status. Population and mortality data were obtained from the Spanish Statistical Office. Socioeconomic level was measured using the Spanish Deprivation Index by census tract. We produced sex- and age-specific life expectancies at birth by quintiles of deprivation, and life tables by census tract and province. Life expectancy at birth was higher among women than among men. Women and men in the most deprived census tracts in Spain lived 3.2 and 3.8 years less than their counterparts in the least deprived areas. A higher life expectancy in the northern regions of Spain was discovered. Life expectancy was higher in provincial capitals than in rural areas. We found a significant life expectancy gap and geographical variation by sex and socioeconomic status in Spain. The gap was more pronounced among men than among women. Understanding the association between life expectancy and socioeconomic status could help in developing appropriate public health programs. Furthermore, the life tables we produced are needed to estimate cancer specific survival measures by socioeconomic status. Therefore, they are important for cancer control in Spain.

Circulación de genes de virulencia asociados a Escherichia coli diarrogénica en aguas residuales del Gran Área Metropolitana de Costa Rica / Circulation of diarrheagenic Escherichia coli associated virulence genes in Costa Rican Great Metropolitan Area wastewaters

Resumen Introducción: la enfermedad diarreica es una de las principales causas de muerte en niños menores de cinco años. Uno de los agentes etiológicos bacterianos más reconocido es Escherichia coli, que puede causar infecciones a través de diversos mecanismos asociados a la adquisición de genes de virulencia. Metodología: se recolectaron muestras de aguas residuales en los afluentes y los efluentes de cinco plantas de tratamiento de la Gran Área Metropolitana, durante tres días consecutivos, en los meses de marzo, mayo, octubre y diciembre del año 2013, a fin de cuantificar la concentración de E. coli, mediante la técnica de fermentación en tubos múltiples, y evaluar la presencia de los genes de virulencia aatA, bfpA, eaeA, ipaH, lt, st, stx1 y stx2, vinculados con patotipos de E. coli diarrogénica, con la técnica de PCR punto final. Resultados: el estudio reveló niveles de E. coli similares a los encontrados en afluentes de otras regiones del mundo, en cambio, los efluentes presentaron concentraciones superiores a los 4 Log10 NMP/100 mL. La circulación anual de genes de virulencia fue relacionada con los patotipos enterotoxigénica, productores de toxina Shiga/enterohemorrágica, enteroagregativa y enteropatógena. No se detectaron genes referentes a la variedad enteroinvasora. Además, se determinó que no todas las plantas de tratamiento remueven significativamente la carga de E. coli. Conclusiones: el flujo de E. coli diarrogénica es común en nuestro país y su diseminación en el ambiente es posible cuando los efluentes se descargan en cuerpos de aguas superficiales

Abstract Introduction. Diarrheic disease is one of the most important diseases causes in children under five years. One of the most recognized etiological agents is Escherichia coli. This bacterium has the capacity of causing infections by multiple mechanisms associated with the acquisition of different virulence genes. Methodology: water samples were collected from the affluents and effluents of five wastewater treatment plants located in the Costa Rican Great Metropolitan Area, during three sequential days, in March, May, October, and December from 2013. The aim was to quantify E. colis concentration by multiple tubes fermentation method and to evaluate the presence of aatA, bfpA, eaeA, ipaH, lt, st, stx1, and stx2 virulence genes, related with diarrheagenic E. coli, by PCR end-point method. Results: The study revealed that the levels of E. coli into the affluents are similar to those reported in other world regions. The effluents concentration presented higher than 4 Log10 NMP/100 mL level of E. coli. A year-round circulation of virulence genes was demonstrated, and it was associated with enterotoxigenic, Shiga-toxin producers/ enterohemorrhagic, enteroaggregative, and enteropathogenic pathotypes. Genes related to enteroinvasive variety did not were detected. Not all wastewater treatment plants removed E. coli efficiently. Conclusions: Diarrheagenic E. coli circulation is common in our county with the possibility of dissemination to the environment by effluents wastewater discharge in surface water bodies.

Dimensión vertical de la cara en adultos con diferentes relaciones oclusales / Vertical dimension of face in adults with different Angle class

RESUMEN: Se ha postulado que la posición postural mandibular (PPM) no presentaría la menor actividad electromiográfica (EMG) de los músculos masetero y temporal, y que esta menor actividad se encontraría en una apertura mayor. El objetivo de este estudio fue analizar la PPM en pacientes con diferentes relaciones oclusales y según tipo de método de posicionamiento, relacionándolo con la actividad EMG de los músculos Masetero y Temporal, además del registro de la actividad EMG en diferentes aperturas orales. Se analizó una muestra de 25 adultos de 18 a 28 años. Estos fueron clasificados según su sexo y clasificación de Angle. Se realizaron simultáneamente registros de EMG de superficie -masetero y porción anterior del temporal- y de EMA -posición de la mandíbula respecto al maxilar obteniendo distancia y ángulo- en diferentes posiciones mandibulares: PPM-considerando método sin comando y de deglución- y apertura gradual hasta alcanzar la máxima apertura. Se realizó un análisis estadístico descriptivo. La menor PPM obtenida fue de 1,0 ± 0,6 mm en mujeres Clase III y utilizando la técnica sin comando; el mayor fue de 2,5 ± 0,2 mm en mujeres Clase II y utilizando la técnica de deglución. La apertura angular presentó menor variabilidad que las distancias lineales. La actividad de los músculos Maseteros derecho e izquierdo presentaron valores similares entre sí, al igual que en los rangos de apertura hasta 30 mm en hombres y mujeres y en las diferentes relaciones oclusales. La actividad de los Temporales para hombres y mujeres y en las diferentes relaciones oclusales mostraron variaciones importantes entre derecha e izquierda y en los diferentes grados de apertura. La técnica presentada permitió el estudio de la dimensión vertical y aperturas orales a través de EMA y EMG.

SUMMARY: It has been postulated that the mandibular postural position (MPP) could not present the lower electromyographic activity (EMG) of the Masseter and Temporal muscles, and that the lower activity could be found in a larger opening. The objective of this study was to analyze the PPM in patients with different occlusal relationships and according to the positioning method, relating it to the EMG activity of the Masseter and Temporal muscles, in addition to recording the EMG activity in different oral openings. A sample of 25 adults aged 18 to 28 years was analyzed. Participants were classified according to their sex and Angle classification. Simultaneous recordings of surface EMG -Masseter and anterior portion of the Temporal- and EMA -position of the Mandible with respect to the Maxilla obtaining distance and angle- were performed in different mandibular positions: PPM-considering the method "without command" and "swallowing"- and gradual opening until the maximum opening is reached. A descriptive statistical analysis was performed. The lowest PPM obtained was 1.0 ± 0.6 mm in Class III women and using the "without command" method; the largest was 2.5 ± 0.2 mm in Class II women and using the "swallowing" method. The angular opening presented less variability than the linear distances. The activity of the right and left masseter muscles presented similar values, as well as in the opening ranges up to 30 mm in men and women and in the different occlusal relationships. The activity of the Temporals for men and women and in the different occlusal relationships showed important variations between right and left and in the different degrees of opening. The presented technique allowed the study of the vertical dimension and oral openings through EMA and EMG.