Acute-to-chronic glycemic ratio as an outcome predictor in ischemic stroke in patients with and without diabetes mellitus.

OBJECTIVE: Elevated plasma glucose levels are common in patients suffering acute ischemic stroke (AIS), and acute hyperglycemia has been defined as an independent determinant of adverse outcomes. The impact of acute-to-chronic glycemic ratio (ACR) has been analyzed in other diseases, but its impact on AIS prognosis remains unclear. The main aim of this study was to assess whether the ACR was associated with a 3-month poor prognosis in patients with AIS. RESEARCH, DESIGN AND METHODS: Retrospective analysis of patients admitted for AIS in Hospital del Mar, Barcelona. To estimate the chronic glucose levels (CGL) we used the formula eCGL= [28.7xHbA1c (%)]-46.7. The ACR (glycemic at admission / eCGL) was calculated for all subjects. Tertile 1 was defined as: 0.28-0.92, tertile 2: 0.92-1.13 and tertile 3: > 1.13. Poor prognosis at 3 months after stroke was defined as mRS score 3-6. RESULTS: 2.774 subjects with AIS diagnosis were included. Age, presence of diabetes, previous disability (mRS), initial severity (NIHSS) and revascularization therapy were associated with poor prognosis (p values < 0.05). For each 0.1 increase in ACR, there was a 7% increase in the risk of presenting a poor outcome. The 3rd ACR tertile was independently associated with a poor prognosis and mortality. In the ROC curves, adding the ACR variable to the classical clinical model did not increase the prediction of AIS prognosis (0.786 vs. 0.781). CONCLUSIONS: ACR was positively associated with a poor prognosis and mortality at 3-months follow-up after AIS. Subjects included in the 3rd ACR tertile presented a higher risk of poor prognosis and mortality. Baseline glucose or ACR did not add predictive value in comparison to only using classical clinical variables.

Rapid Reduction of HbA1c and Early Worsening of Diabetic Retinopathy: A Real-world Population-Based Study in Subjects With Type 2 Diabetes.

OBJECTIVE: Early worsening of diabetic retinopathy (EWDR) due to the rapid decrease of blood glucose levels is a concern in diabetes treatment. The aim of the current study is to evaluate whether this is an important issue in subjects with type 2 diabetes with mild or moderate nonproliferative DR (NPDR), who represent the vast majority of subjects with DR attended in primary care. RESEARCH DESIGN AND METHODS: This is a retrospective nested case-control study of subjects with type 2 diabetes and previous mild or moderate NPDR. Using the SIDIAP ("Sistema d'informació pel Desenvolupament de la Recerca a Atenció Primària") database, we selected 1,150 individuals with EWDR and 1,150 matched control subjects (DR without EWDR). The main variable analyzed was the magnitude of the reduction of HbA1c in the previous 12 months. The reduction of HbA1c was categorized as rapid (>1.5% reduction in <12 months) or very rapid (>2% in <6 months). RESULTS: We did not find any significant difference in HbA1c reduction between case and control subjects (0.13 ± 1.21 vs. 0.21 ± 1.18; P = 0.12). HbA1c reduction did not show significant association with worsening of DR, neither in the unadjusted analyses nor in adjusted statistical models that included the main confounding variables: duration of diabetes, baseline HbA1c, presence of hypertension, and antidiabetic drugs. In addition, when stratification by baseline HbA1c was performed, we did not find that those patients with higher levels of HbA1c presented a higher risk to EWDR. CONCLUSIONS: Our results suggest that the rapid reduction of HbA1c is not associated with progression of mild or moderate NPDR.

Telehealth model versus in-person standard care for persons with type 1 diabetes treated with multiple daily injections: an open-label randomized controlled trial.

Objective: Increasing evidence indicates that the telehealth (TH) model is noninferior to the in-person approach regarding metabolic control in type 1 diabetes (T1D) and offers advantages such as a decrease in travel time and increased accessibility for shorter/frequent visits. The primary aim of this study was to compare the change in glycated hemoglobin (HbA1c) at 6 months in T1D care in a rural area between TH and in-person visits. Research design and methods: Randomized controlled, open-label, parallel-arm study among adults with T1D. Participants were submitted to in-person visits at baseline and at months 3 and 6 (conventional group) or teleconsultation in months 1 to 4 plus 2 in-person visits (baseline and 6 months) (TH group). Mixed effects models estimated differences in HbA1c changes. Results: Fifty-five participants were included (29 conventional/26 TH). No significant differences in HbA1c between groups were found. Significant improvement in time in range (5.40, 95% confidence interval (CI): 0.43-10.38; p < 0.05) and in time above range (-6.34, 95% CI: -12.13- -0.55;p < 0.05) in the TH group and an improvement in the Diabetes Quality of Life questionnaire (EsDQoL) score (-7.65, 95% CI: -14.67 - -0.63; p < 0.05) were observed. In TH, the costs for the participants were lower. Conclusions: The TH model is comparable to in-person visits regarding HbA1c levels at the 6-month follow-up, with significant improvement in some glucose metrics and health-related quality of life. Further studies are necessary to evaluate a more efficient timing of the TH visits.

Transmisión vertical de Toxoplasma gondii asociado a la edad gestacional / Vertical transmission of Toxoplasma gondii associated with gestational age

Una de las principales consecuencias de la infección por Toxoplasma gondii en mujeres embarazadas es la transmisión vertical al feto. Aunque es poco frecuente, la toxoplasmosis congénita puede causar enfermedades neurológicas u oculares graves. La infección primaria por T. gondii durante el embarazo puede tener consecuencias peligrosas, como retinocoroiditis, hidrocefalia, calcificaciones cerebrales, encefalitis, esplenomegalia, pérdida de audición, ceguera y muerte. La atención prenatal debe incluir educación sobre la prevención de la toxoplasmosis. Se trata de un estudio observacional, analítico y transversal. Se evaluaron 209 mujeres gestantes e igual número de recién nacidos; 136 de las mujeres embarazadas resultaron con infección aguda positiva a IgM. De estas 51,20% y 64,71% resultaron primoinfectadas según la determinación de IgA e IgG avidez, respectivamente. 20 de los 35 neonatos provenientes de madres primoinfectadas, adquirieron la infección congénita en el tercer trimestre de la gestación. La conciencia sobre la prevención y el control de la toxoplasmosis es baja entre las poblaciones de alto riesgo. Es necesario fortalecer la educación en salud relacionada con la prevención y el control de la toxoplasmosis en las mujeres en edad reproductiva para prevenir la transmisión vertical a sus productos de gestación y evitar los efectos negativos y hasta mortales de la inefcción por el parásito(AU)

One of the main consequences of Toxoplasma gondii infection in pregnant women is vertical transmission to the fetus. Although rare, congenital toxoplasmosis can cause serious neurological or ocular disease. Primary T. gondii infection during pregnancy can have dangerous consequences, including retinochoroiditis, hydrocephalus, cerebral calcifications, encephalitis, splenomegaly, hearing loss, blindness, and death. Prenatal care should include education on the prevention of toxoplasmosis. This is an observational, analytical and cross-sectional study. 209 pregnant women and the same number of newborns were evaluated; 136 of the pregnant women were acutely infected with IgM. Of these, 51.20% and 64.71% were primary infected according to the determination of IgA and IgG avidity, respectively. 20 of the 35 neonates from mothers with primary infection acquired the congenital infection in the third trimester of pregnancy. Awareness of toxoplasmosis prevention and control is low among high-risk populations. It is necessary to strengthen health education related to the prevention and control of toxoplasmosis in women of reproductive age to prevent vertical transmission to their gestational products and avoid the negative and even fatal effects of infection by the parasite(AU)

Consequences of telomere dysfunction in fibroblasts, club and basal cells for lung fibrosis development.

TRF1 is an essential component of the telomeric protective complex or shelterin. We previously showed that dysfunctional telomeres in alveolar type II (ATII) cells lead to interstitial lung fibrosis. Here, we study the lung pathologies upon telomere dysfunction in fibroblasts, club and basal cells. TRF1 deficiency in lung fibroblasts, club and basal cells induced telomeric damage, proliferative defects, cell cycle arrest and apoptosis. While Trf1 deletion in fibroblasts does not spontaneously lead to lung pathologies, upon bleomycin challenge exacerbates lung fibrosis. Unlike in females, Trf1 deletion in club and basal cells from male mice resulted in lung inflammation and airway remodeling. Here, we show that depletion of TRF1 in fibroblasts, Club and basal cells does not lead to interstitial lung fibrosis, underscoring ATII cells as the relevant cell type for the origin of interstitial fibrosis. Our findings contribute to a better understanding of proper telomere protection in lung tissue homeostasis.

Individuals With Higher CD4/CD8 Ratio Exhibit Increased Risk of Acute Respiratory Distress Syndrome and In-Hospital Mortality During Acute SARS-CoV-2 Infection.

Background: CD4/CD8 ratio has been used as a quantitative prognostic risk factor in patients with viral infections. This study aims to assess the association between in-hospital mortality and at admission CD4/CD8 ratio among individuals with acute SARS-CoV-2 infection. Methods: This is a longitudinal cohort study with data of all consecutive patients admitted to the COVID-19 unit at Hospital del Mar, Barcelona, Spain for ≥48 h between March to May 2020. The CD4+ CD8+ T-cell subset differentiation was assessed by flow cytometry at admission as well as a complete blood test. Patients were classified according to CD4/CD8 ratio tertiles. The primary outcome was in-hospital mortality and the secondary outcome was acute respiratory distress (ARDS). Results: A total of 338 patients were included in the cohort. A high CD4/CD8 ratio (third tertile) was associated with a higher in-hospital mortality [adjusted Cox model hazard ratio (HR) 4.68 (95%CI 1.56-14.04, p = 0.006), reference: second tertile HR 1]. Similarly, a high CD4/CD8 ratio (third tertile) was associated with a higher incidence of ARDS [adjusted logistic regression model OR 1.97 (95%CI 1.11-3.55, p = 0.022) reference: second tertile HR 1]. There was a trend of higher in-hospital mortality and incidence of ARDS in patients within the first tertile of CD4/CD8 ratio compared with the second one, but the difference was not significant. No associations were found with total lymphocyte count or inflammatory parameters, including D-dimer. Conclusion: CD4/CD8 ratio is a prognostic factor for the severity of COVID-19, reflecting the negative impact on prognosis of those individuals whose immune response has abnormal CD8+ T-cell expansion during the early response to the infection.

A mouse model for Li-Fraumeni-Like Syndrome with cardiac angiosarcomas associated to POT1 mutations.

The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Longer telomeres in Pot1a+/ki MEFs are dependent on telomerase activity as they are not found in double mutant Pot1a+/ki Tert-/- telomerase-deficient MEFs. By using complementation assays we further show that POT1a pR117C exerts dominant-negative effects at telomeres. As in human Li-Fraumeni patients, heterozygous Pot1a+/ki mice spontaneously develop a high incidence of angiosarcomas, including cardiac angiosarcomas, and this is associated to the presence of abnormally long telomeres in endothelial cells as well as in the tumors. The Pot1a+/R117C mouse model constitutes a useful tool to understand human cancers initiated by POT1 mutations.

Stromal oncostatin M cytokine promotes breast cancer progression by reprogramming the tumor microenvironment.

The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

Genomic and Functional Regulation of TRIB1 Contributes to Prostate Cancer Pathogenesis.

Prostate cancer is the most frequent malignancy in European men and the second worldwide. One of the major oncogenic events in this disease includes amplification of the transcription factor cMYC. Amplification of this oncogene in chromosome 8q24 occurs concomitantly with the copy number increase in a subset of neighboring genes and regulatory elements, but their contribution to disease pathogenesis is poorly understood. Here we show that TRIB1 is among the most robustly upregulated coding genes within the 8q24 amplicon in prostate cancer. Moreover, we demonstrate that TRIB1 amplification and overexpression are frequent in this tumor type. Importantly, we find that, parallel to its amplification, TRIB1 transcription is controlled by cMYC. Mouse modeling and functional analysis revealed that aberrant TRIB1 expression is causal to prostate cancer pathogenesis. In sum, we provide unprecedented evidence for the regulation and function of TRIB1 in prostate cancer.

Study of the bioremediatory capacity of wild yeasts.

Microbial detoxification has been proposed as a new alternative for removing toxins and pollutants. In this study, the biodetoxification activities of yeasts against aflatoxin B1 and zinc were evaluated by HPLC and voltammetric techniques. The strains with the best activity were also subjected to complementary assays, namely biocontrol capability and heavy-metal resistance. The results indicate that the detoxification capability is toxin- and strain-dependent and is not directly related to cell growth. Therefore, we can assume that there are some other mechanisms involved in the process, which must be studied in the future. Only 33 of the 213 strains studied were capable of removing over 50% of aflatoxin B1, Rhodotrorula mucilaginosa being the best-performing species detected. As for zinc, there were 39 strains that eliminated over 50% of the heavy metal, with Diutina rugosa showing the best results. Complementary experiments were carried out on the strains with the best detoxification activity. Biocontrol tests against mycotoxigenic moulds showed that almost 50% of strains had an inhibitory effect on growth. Additionally, 53% of the strains grew in the presence of 100 mg/L of zinc. It has been proven that yeasts can be useful tools for biodetoxification, although further experiments must be carried out in order to ascertain the mechanisms involved.

Obesidad mórbida y dislipemia: impacto de la cirugía bariátrica / Morbid obesity and dyslipidaemia: The impact of bariatric surgery

La prevalencia de la obesidad ha aumentado de manera exponencial en las últimas décadas, convirtiéndose en un problema de salud pública de primer orden. La dislipemia de la obesidad, caracterizada por niveles bajos de colesterol de las lipoproteínas de alta densidad (HDL), hipertrigliceridemia y partículas pequeñas y densas de lipoproteínas de baja densidad (LDL), es responsable en parte del elevado riesgo cardiovascular residual de esta situación clínica. Por otro lado, la cirugía bariátrica (CB) es el tratamiento más eficaz para la obesidad; con ella se obtiene una mayor pérdida ponderal que con el tratamiento médico convencional y favorece la mejoría o remisión de las comorbilidades asociadas. Las técnicas de CB más utilizadas en la actualidad son el bypass gástrico laparoscópico en Y de Roux (BGYRL) y la gastrectomía tubular laparoscópica (GTL). Estas han obtenido resultados similares tanto en cuanto a la pérdida de peso como a la remisión de ciertas comorbilidades como la diabetes mellitus tipo 2 o la hipertensión arterial. Un rasgo diferencial entre ambas técnicas podría ser el diferente impacto sobre el perfil lipoproteico. Así, estudios previos con seguimiento a corto y a medio plazo han objetivado una superioridad del BGYRL frente a la GTL en la reducción del colesterol total y del colesterol LDL. Existen resultados discordantes en cuanto a la evolución del colesterol HDL y los triglicéridos. Por todo ello, hemos considerado de interés revisar los efectos de la CB a corto y a medio plazo en el perfil lipoproteico, así como las tasas de remisión de las diferentes alteraciones lipídicas y los posibles factores relacionados

Obesity prevalence has presented an exponential increase in the last decades, becoming a first order public health issue. Dyslipidemia of obesity, characterized by low levels of high density lipoprotein (HDL) cholesterol, hypertriglyceridemia and small and dense low-density lipoprotein (LDL) particles, is partly responsible for the high residual cardiovascular risk of this clinical situation. On the other hand, bariatric surgery (BS) is the most effective treatment for obesity, obtaining a greater weight loss than achieved with conventional medical therapy and favoring the improvement or remission of associated comorbidities. The most commonly used BS techniques nowadays are laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). Both of these procedures have obtained similar results in terms of weight loss and comorbidity remission such as type 2 diabetes mellitus or hypertension. A differential feature between both techniques could be the different impact on the lipoprotein profile. In this respect, previous studies with short and mid-term follow-up have proved LRYGB to be superior to LSG in total and LDL cholesterol reduction. Results regarding triglycerides and HDL cholesterol are contradictory. Therefore, we consider of interest to review the effects of BS at short and mid-term follow-up on lipoprotein profile, as well as the remission rates of the different lipid abnormalities and the possible related factors

The mTOR pathway is necessary for survival of mice with short telomeres.

Telomerase deficiency leads to age-related diseases and shorter lifespans. Inhibition of the mechanistic target of rapamycin (mTOR) delays aging and age-related pathologies. Here, we show that telomerase deficient mice with short telomeres (G2-Terc-/-) have an hyper-activated mTOR pathway with increased levels of phosphorylated ribosomal S6 protein in liver, skeletal muscle and heart, a target of mTORC1. Transcriptional profiling confirms mTOR activation in G2-Terc-/- livers. Treatment of G2-Terc-/- mice with rapamycin, an inhibitor of mTORC1, decreases survival, in contrast to lifespan extension in wild-type controls. Deletion of mTORC1 downstream S6 kinase 1 in G3-Terc-/- mice also decreases longevity, in contrast to lifespan extension in single S6K1-/- female mice. These findings demonstrate that mTOR is important for survival in the context of short telomeres, and that its inhibition is deleterious in this setting. These results are of clinical interest in the case of human syndromes characterized by critically short telomeres.

Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer.

Gene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.

Morbid obesity and dyslipidaemia: The impact of bariatric surgery. / Obesidad mórbida y dislipemia: impacto de la cirugía bariátrica.

Obesity prevalence has presented an exponential increase in the last decades, becoming a first order public health issue. Dyslipidemia of obesity, characterized by low levels of high density lipoprotein (HDL) cholesterol, hypertriglyceridemia and small and dense low-density lipoprotein (LDL) particles, is partly responsible for the high residual cardiovascular risk of this clinical situation. On the other hand, bariatric surgery (BS) is the most effective treatment for obesity, obtaining a greater weight loss than achieved with conventional medical therapy and favoring the improvement or remission of associated comorbidities. The most commonly used BS techniques nowadays are laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). Both of these procedures have obtained similar results in terms of weight loss and comorbidity remission such as type2 diabetes mellitus or hypertension. A differential feature between both techniques could be the different impact on the lipoprotein profile. In this respect, previous studies with short and mid-term follow-up have proved LRYGB to be superior to LSG in total and LDL cholesterol reduction. Results regarding triglycerides and HDL cholesterol are contradictory. Therefore, we consider of interest to review the effects of BS at short and mid-term follow-up on lipoprotein profile, as well as the remission rates of the different lipid abnormalities and the possible related factors.

SOX9 promotes tumor progression through the axis BMI1-p21CIP.

The developmental regulator SOX9 is linked to cancer progression mainly as a result of its role in the regulation of cancer stem cells (CSCs). However, its activity in the differentiated cells that constitute the heterogeneous tumor bulk has not been extensively studied. In this work, we addressed this aspect in gastric cancer, glioblastoma and pancreatic adenocarcinoma. SOX9 silencing studies revealed that SOX9 is required for cancer cell survival, proliferation and evasion of senescence in vitro and tumor growth in vivo. Gain of-SOX9 function showed that high levels of SOX9 promote tumor cell proliferation in vitro and in vivo. Mechanistically, the modulation of SOX9 changed the expression of the transcriptional repressor BMI1 in the same direction in the three types of cancer, and the expression of the tumor suppressor p21CIP in the opposite direction. In agreement with this, SOX9 expression positively correlated with BMI1 levels and inversely with p21CIP in clinical samples of the different cancers. Moreover, BMI1 re-establishment in SOX9-silenced tumor cells restored cell viability and proliferation as well as decreased p21CIP in vitro and tumor growth in vivo. These results indicate that BMI1 is a critical effector of the pro-tumoral activity of SOX9 in tumor bulk cells through the repression of p21CIP. Our results highlight the relevance of the SOX9-BMI1-p21CIP axis in tumor progression, shedding novel opportunities for therapeutic development.

The mitochondrial negative regulator MCJ modulates the interplay between microbiota and the host during ulcerative colitis.

Recent evidences indicate that mitochondrial genes and function are decreased in active ulcerative colitis (UC) patients, in particular, the activity of Complex I of the electron transport chain is heavily compromised. MCJ is a mitochondrial inner membrane protein identified as a natural inhibitor of respiratory chain Complex I. The induction of experimental colitis in MCJ-deficient mice leads to the upregulation of Timp3 expression resulting in the inhibition of TACE activity that likely inhibits Tnf and Tnfr1 shedding from the cell membrane in the colon. MCJ-deficient mice also show higher expression of Myd88 and Tlr9, proinflammatory genes and disease severity. Interestingly, the absence of MCJ resulted in distinct microbiota metabolism and composition, including a member of the gut community in UC patients, Ruminococcus gnavus. These changes provoked an effect on IgA levels. Gene expression analyses in UC patients showed decreased levels of MCJ and higher expression of TIMP3, suggesting a relevant role of mitochondrial genes and function among active UC. The MCJ deficiency disturbs the regulatory relationship between the host mitochondria and microbiota affecting disease severity. Our results indicate that mitochondria function may be an important factor in the pathogenesis. All together support the importance of MCJ regulation during UC.

Safety of Whole-Body Abrogation of the TRF1 Shelterin Protein in Wild-Type and Cancer-Prone Mouse Models.

Telomeres are considered potential anti-cancer targets. Most studies have focused on telomerase inhibition, but this strategy has largely failed in clinical trials. Direct disruption of the shelterin complex through TRF1 inhibition can block tumorigenesis in cancer mouse models by a mechanism that involves DNA damage induction and reduction of proliferation and stemness. Any anti-cancer target, however, must fulfill the requisite of not showing deleterious effects in healthy tissues. Here, we show that Trf1 genetic deletion in wild-type and cancer-prone p53- and Ink4Arf-deficient mice does not affect organismal viability and only induces mild phenotypes like decreased body weight and hair graying or hair loss, the skin being the most affected tissue. Importantly, we found that Trf1 is essential for tumorigenesis in p53- and Ink4Arf-deficient mice, as we did not find a single tumor originating from Trf1-deleted cells. These findings indicate a therapeutic window for targeting Trf1 in cancer treatment.

Characterization of the pattern of food consumption in severely obese patients prior to bariatric surgery / Caracterización del patrón de consumo de alimentos en pacientes con obesidad severa antes de la cirugía bariátrica

Introduction: severe obesity is increasing rapidly in several countries, as well as the number of bariatric surgeries performed. However, the pattern of food consumption of the population is not well defined. Objectives: the aim of the present study was to describe the food consumption pattern (comparing men and women) of severely obese patient candidates to bariatric surgery and to determine the promoting and protecting factors. Methods: food consumption and nutrient intake were measured by a validated food frequency questionnaire (FFQ), including food and beverages. Multivariate principal component analysis (PCA) was done to analyze the component that best relates to the food pattern consumption dividing the different food groups in promotors and protectors. Results: significant differences in the food consumption pattern of men and women with severe obesity addressed for bariatric surgery were found. A positive correlation was found between the food groups that are protective factors for obesity such as the fiber (r = 0.84), vegetables (r = 0.767) and fruits (r = 0.83), whereas a negative correlation was found with those factors that are promotors of obesity such as fats (r = -0.341), saturated fats (r = -0.411), soft drinks (r = -0.386), and fast food (r = -0.17).Multivariate analysis of principal components revealed that calorie consumption is the component that correlates better with the pattern. Conclusions: there are significant differences in the food consumption pattern of men and women with severe obesity addressed for bariatric surgery and these differences should be taken into account when planning nutritional intervention. Therefore, a healthy lifestyle behaviour should be highly encouraged among the severe obese population

Introducción: la obesidad mórbida así como el número de cirugías bariátricas que se practican van en aumento en varios países. Sin embargo, el patrón de consumo alimentario de estos pacientes no está bien definido. Objetivos: describir el patrón de consumo de alimentos (comparando hombres y mujeres) de pacientes con obesidad severa candidatos a cirugía bariátrica y determinar los factores promotores y protectores de la obesidad. Métodos: el consumo de alimentos y la ingesta de nutrientes se midieron mediante un cuestionario de frecuencia de consumo de alimentos validado que incluye alimentos y bebidas. Se realizó un análisis multivariado de componentes principales para determinar qué componente se relaciona mejor con el consumo de patrones alimentarios promotores y protectores de obesidad. Resultados: el estudio mostró diferencias significativas en el patrón de consumo de alimentos entre hombres y mujeres. Se encontró una correlación positiva entre los grupos de alimentos considerados factores de protección para la obesidad, como la fibra (r = 0,84), las verduras (r = 0,767) y las frutas (r = 0,83), mientras que la correlación fue negativa con los factores promotores de la obesidad como las grasas (r = -0,341), las grasas saturadas (r = -0,411), los refrescos (r = -0,386) y la comida rápida (r = -0,17). El análisis multivariado de los componentes principales reveló que el consumo de calorías es el componente que se correlaciona mejor con el patrón. Conclusiones: existen diferencias significativas en el patrón de consumo de alimentos entre hombres y mujeres con obesidad severa y estas deben tenerse en cuenta al planificar la intervención nutricional. Asimismo, un consumo alimentario saludable debe promocionarse en la población obesa