Senescence induction; a possible cancer therapy

Cellular immortalization is a crucial step during the development of human cancer. Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli: they have altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. During immortalization, cells acquire genetic alterations that override senescence. Tumor suppressor genes and oncogenes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screening to search for genes involved in senescence, several candidate oncogenes and putative tumor suppressor genes have been recently isolated, including subtypes of micro-RNAs. These findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy

Traumatic rupture of the tricuspid valve

Traumatic rupture of the tricuspid valve is a rare and difficult entity to diagnose as it usually courses asymptomatic; therefore, clinical suspicion is key to identify it. We report the case of a 48-year-old male patient who was admitted due to closed thoracic trauma after falling from 4 meters high. The echocardioscopy performed in the Emergency Room was normal. The patient was transferred to the Intensive Care Unit due to pulmonary contusion and multiple rib fractures. Lab tests revealed elevation of myocardial necrosis markers, and ECG showed RBBB. A new echocardiography, performed 48 hours later to rule out complications secondary to myocardial contusion, targeted the tricuspid valve with papillary muscle rupture and eversion of the anterior leaflet causing massive tricuspid regurgitation (TR) (opacifying the right atrium; Doppler triangular flow did not allow pulmonary pressure measurement; there was systolic inversion in suprahepatic vein flow, paradoxical septal motion associated with volume overload), slightly enlarged right chambers with preserved right ventricular systolic function, and mild pericardial effusion. ... La rotura traumática de la válvula tricúspide es una entidad infrecuente y difícil de diagnosticar, ya que habitualmente cursa de forma asintomática, lo que hace fundamental la sospecha clínica para poder identificarla. Presentamos el caso de un varón de 48 años que ingresa por traumatismo torácico cerrado tras precipitarse desde 4 metros de altura. Se realizó ecocardioscopia en urgencias que fue normal. El paciente ingresó en la unidad de cuidados intensivos por contusión pulmonar y múltiples fracturas costales. En la analítica presentó elevación de marcadores de necrosis miocárdica y en ECG BRDHH, por lo que a las 48 h se realizó un nuevo ecocardiograma para descartar complicaciones secundarias a la contusión miocárdica; en este se observó la válvula tricúspide con rotura del músculo papilar y eversión del velo anterior, lo que produce insuficiencia tricuspídea (IT) masiva (opacifica toda la aurícula derecha; el flujo Doppler triangular no permite estimar la presión pulmonar; inversión sistólica del flujo en las venas suprahepáticas, movimiento paradójico del septo en relación con sobrecarga de volumen), cavidades derechas ligeramente dilatadas con función sistólica VD conservada y derrame pericárdico ligero. El paciente presentó una evolución tórpida con volet costal complicado con fracaso multiorgánico, por lo que, dada la ausencia de signos de insuficiencia cardíaca derecha, se decidió demorar la cirugía cardíaca. A los 6 meses, se realizó la reparación de la válvula tricúspide mediante anuloplastia, neocuerda a velo anterior y plicatura al nivel de la comisura entre el velo septal y el anterior. Posteriormente, el paciente presentó buena evolución clínica y ecocardiográfica con IT grado II/IV y normalización de la dilatación de cavidades derechas

Utility of international normative 20 m shuttle run values for identifying youth at increased cardiometabolic risk

The purpose of this study was to examine the ability of international normative centiles for the 20 m shuttle run test (20mSRT) to identify youth at increased cardiometabolic risk. This was a cross-sectional study involving 961 children aged 10–17 years (53% girls) from the United Kingdom. Receiver operating characteristic (ROC) curves determined the discriminatory ability of cardiorespiratory fitness percentiles for predicting increased cardiometabolic risk. ROC analysis demonstrated a significant but poor discriminatory accuracy of cardiorespiratory fitness in identifying low/high cardiometabolic risk in girls (AUC = 0.58, 95% CI: 0.54–0.63; p = 0.04), and in boys (AUC = 0.59, 95% CI: 0.54–0.63; p = 0.03). The cardiorespiratory fitness cut-off associated with high cardiometabolic risk was the 55th percentile (sensitivity = 33.3%; specificity = 84.5%) in girls and the 60th percentile (sensitivity = 42.9%; specificity = 73.6%) in boys. These 20mSRT percentile thresholds can be used to identify children and adolescents who may benefit from lifestyle intervention. Nonetheless, further work involving different populations and cardiometabolic risk scores comprising of different variables are needed to confirm our initial findings

miR-125b Acts as a Tumor Suppressor in Breast Tumorigenesis via Its Novel Direct Targets ENPEP, CK2-α, CCNJ, and MEGF9

MicroRNAs (miRNAs) play important roles in diverse biological processes and are emerging as key regulators of tumorigenesis and tumor progression. To explore the dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of 939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were aberrantly expressed between breast cancer tissue and adjacent normal breast tissue and several novel miRNAs were identified as potential oncogenes or tumor suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest decrease in expression. Enforced miR-125b expression in mammary cells decreased cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage-independent cell growth of cells of mammary origin. miR-125b was found to perform its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP, CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the biological effects of miR-125b overexpression, confirming that they are modulated by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%, and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was inversely correlated with miR-125b expression in breast tumors, indicating the relevance of these potential oncogenic proteins in breast cancer patients. Our results support a prognostic role for CK2-alpha, whose expression may help clinicians predict breast tumor aggressiveness. In particular, our results show that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ, or MEGF9 may provide novel approaches for the treatment of breast cancer

Validity and reliability of the international fItness scale (IFIS) in preschool children

Objectives Examine the validity and reliability of parent-reported International FItness Scale (IFIS) in preschoolers. Method A cross-sectional study of 3051 Spanish preschoolers (3-5 years). Fitness was measured by PREFIT battery and reported by parents using an adapted version of the IFIS. Waist circumference was evaluated, and the waist-to-height ratio (WHtR) was calculated. Seventy-six parents of randomly selected schoolchildren completed the IFIS twice for a reliability assessment. Results ANCOVA, adjusted for sex, age and WHtR, showed that preschoolers who were scored by their parents as having average-to-very good fitness had better levels of measured physical fitness than those preschoolers who were classified as having very poor/poor fitness levels (18.1laps to 22.1laps vs 15.6laps for cardiorespiratory fitness; 6.6 kg to 7.5 kg vs 5.3 kg for muscular fitness-handgrip-; 71.7 cm to 76.4 cm vs 62.0 cm for muscular fitness-standing long jump-; 17.2s to 16.2s vs 18.2s for speed/agility; and 11.2s to 15.6s vs 8.7s for balance; p < 0.001). The weighted kappa for concordance between parent-reported fitness levels and objective assessment was poor (kappa <= 0.18 for all fitness measures). Overall, the mean values of the abdominal adiposity indicators were significantly lower in high-level fitness categories reported by parents than in low-level fitness categories (p < 0.05). The test-retest reliability ranged from 0.46 to 0.62. Conclusions The reliability of the parent-reported IFIS are acceptable, but the concordance between parents reported and objectively measures fitness levels is poor, suggesting that parents' responses may not be able to correctly classify preschoolers according to their fitness level.The PREFIT project takes place thanks to the funding linked to the Ramon y Cajal grant held by Ortega FB (RYC-2011-09011)

Atopic dermatitis incidence and risk factors in young adults in Castellon (Spain): A prospective cohort study

Introduction: There are few atopic dermatitis (AD) incidence cohort studies in young adults, the etiology of this disease remains obscure, and AD risk factors in adults are not well understood. The objective of this study was to estimate AD ten-year incidence and prevalence in a cohort of adolescent aged 14–16 at inception in Castellon province in Valencia Region, Spain and describe related risk factors. Material and methods: From 2002 to 2012, a population-based prospective cohort study was carried out. Questionnaires from the International Study of Asthma and Allergies in Childhood (ISAAC) were used with an additional questionnaire for related factors completed by participants and their parents, respectively, in 2002. In 2012 the same questionnaires were completed by the participants’ through a telephone interview, and incidence and prevalence of AD were estimated. Directed acyclic graphs, Poisson regression and inverse probability weighted regression adjustment were used. Results: The participation rate was 79.5% (1435/1805) with AD lifetime prevalence of 34.9% and AD incidence of 13.5 per 1000 person years. Females presented higher prevalence and incidence than males. After adjustment significant risk factors were being female, history of asthma or allergic rhinitis, family history of AD, history of respiratory infections, history of bronchitis, history of pneumonia, history of sinusitis, and birthplace outside Castellon province. The highest AD population attributable risks were female, 30.3%, and history of respiratory infections 15.3%. Differences with AD childhood risk factors were found. Conclusions: AD incidence in our cohort was high and several risks factors were related to AD