Primary intraosseous papillary intralymphatic angioendothelioma of the distal femoral epiphysis: a case report with literature review.

INTRODUCTION: Papillary intralymphatic angioendothelioma (PILA) is an exceptionally rare metastasizing soft tissue tumor. It tends to arise in the subcutaneous tissues of distal extremities in children. Only four intraosseous PILA cases have been reported until now in English language literature. CASE REPORT: We present a case of PILA arising in the distal femoral epiphysis of a 50-year-old female patient. It started as a relentless pain in her left knee. A plain radiography revealed a radiolucent area in the left internal femoral condyle. Computerized tomography revealed a 1-cm lytic lesion with a sclerotic rim. Magnetic resonance images showed a significant bone marrow edema signal focused on a 1-cm subchondral lesion suggestive of an intraarticular osteoid osteoma. Histologically, the tumor contained vascular channels covered by a single endothelial layer with intraluminal papillary endothelial structures lined with hobnail cells. Immunohistochemically, the cells were positive for ERG, CD31, and D2-40. The tumor underwent cryoablation and 6 months later, after local recurrence or tumor persistence, a wide tumor resection was referred. After 7 years of follow-up, the patient displayed neither local recurrence nor distant metastases. CONCLUSION: Primary intraosseous PILAs are exceedingly rare tumors that should be considered in the differential diagnosis of vascular bone tumors.

Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement.

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

OSNA Total Tumor Load for the Prediction of Axillary Involvement in Breast Cancer Patients: Should We use Different Thresholds According to the Intrinsic Molecular Subtype? MOTTO Study.

Aims: To assess the impact of the molecular subtype (MS) on the total number of CK19 mRNA copies in all positive SLN (TTL) threshold, to predict non-SLN affectation, and to compare 5 years progression-free survival (PFS) according to the risk of recurrence (ROR) group by PAM50. Methods: Cohort with infiltrating breast cancer with intra-operative metastatic SLN detected by one-step nucleic acid amplification (OSNA) assay who underwent subsequent ALND. Logistic regression was used to assess a possible interaction between TTL and MS(Triple Negative, Her-2-Enriched, Luminal A, or Luminal B), or hormone receptors (HR: positive or negative) by immunohistochemistry (IMH). Cox regression was used to compare PFS and OS in the 3 ROR groups (high, medium, or low). Results: TTL was predictive of non-SLN affectation in both univariate (OR [95% CI]: 1.72 [1.43, 2.05], P < .001) and multivariate (1.55 [95% CI: 1.04, 2.32], P = .030) models, but MS-IMH or HR-IMH, and their interactions with TTL were not (best multivariate model: HR + main effect OR 1.16 [95% CI: 0.18, 7.64], P = .874; interaction OR: 1.04 [0.7, 1.55], P = .835; univariate model: HR + main effect OR: 1.44 [95% CI: 0.85, 2.44], P = .180). PFS was lower in the high-risk ROR group (81.1%) than in the low-risk group (93.9%) (HR: 3.68 [95 CI: 1.70, 7.94], P < .001). Conclusions: our results do not provide evidence to support the utilization of subtype-specific thresholds for TTL values to make therapeutic decisions on the axilla. The ROR group was predictive of 5 years-PFS.

Water vapor thermal therapy: Technical variations among spanish hospitals and efficacy at 2-year follow-up.

AIM: The aim of this work is to evaluate the initial experience with water vapor thermal therapy (WVTT) for benign prostatic hyperplasia (BPH) in Spanish university hospitals, as well as to describe the differences in technique and follow-up between centers. MATERIALS AND METHODS: This retrospective observational multicenter study collected baseline characteristics, surgical, postoperative and follow-up data at 1, 3, 6, 12 and 24 months, including validated questionnaires, flowmetric variations, complications, and the need for pharmacological or surgical treatment following the procedure. Possible triggers for postoperative acute urinary retention (AUR) were also analyzed. RESULTS: A total of 105 patients were included. No differences were observed between the groups with and without AUR with respect to catheterization time (5 and 4.3 days respectively, P=.178), or prostate volume (47.9g and 41.4g respectively, P=.147). The mean improvement at 3, 6, 12 and 24 months in terms of peak flow was 5.3, 5.2, 4.2 and 3.8ml/s, respectively. As for ejaculation, an improvement was observed after 3 months of follow-up and was maintained over time. CONCLUSIONS: Minimally invasive treatment for BPH with WVTT shows good functional outcomes at 24 months follow-up, without significant impairment of sexual function and a low incidence of complications. There are minor inter-hospital variations, mainly in the immediate postoperative period.

[Translated article] Oligometastases in oncological orthopaedic surgery. Our experience.

OBJECTIVE: To analyse the incidence and survival of patients with oligometastases (solitary and normal) when they are treated in centres that are experts in multidisciplinary approach to patients with sarcoma. MATERIAL AND METHOD: Retrospective analysis of 414 patients with bone metastases secondary to carcinomas at Hospital Universitario La Paz and Hospital MD Anderson Cancer Centre (Madrid) between May 2006 and May 2019. Metastases located in the pelvis and axial skeleton were excluded, analyzing a total of 28 patients who met the criterion for solitary metastases or oligometastases with normal criteria. The study survival estimate was carried out following the Kaplan-Meier statistical method. RESULTS: The survival of the patients following the oligometastases criteria (solitary and normal) was 53%. Breast cancer was the most prevalent and had a survival rate of more than 70%. The average age of the patients was 58 years old. DISCUSSION: Systemic treatments in cancer treatment have managed to improve disease-free survival curves and lead us to redirect on the paradigm for the treatment of oligometastases, stating that treatment should be carried out in the centres that are experts in the treatment of sarcomas. CONCLUSIONS: The choice of surgical treatment for patients with oligometastases in the strict sense (solitary) and normal should be evaluated by multidisciplinary teams according to the prognoses of the patient, anatomical location and histotype of the neoplasm.

On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm.

How metastatic cells arise is unclear. Here, we search for the induction of recently characterized pro-metastatic states as a surrogate for the origin of metastasis. Since cell-death-inducing therapies can paradoxically promote metastasis, we ask if such treatments induce pro-metastatic states in human colon cancer cells. We find that post-near-death cells acquire pro-metastatic states (PAMEs) and form distant metastases in vivo. These PAME ("let's go" in Greek) cells exhibit a multifactorial cytokine storm as well as signs of enhanced endoplasmic reticulum (ER) stress and nuclear reprogramming, requiring CXCL8, INSL4, IL32, PERK-CHOP, and NANOG. PAMEs induce neighboring tumor cells to become PAME-induced migratory cells (PIMs): highly migratory cells that re-enact the storm and enhance PAME migration. Metastases are thus proposed to originate from the induction of pro-metastatic states through intrinsic and extrinsic cues in a pro-metastatic tumoral ecosystem, driven by an impending cell-death experience involving ER stress modulation, metastatic reprogramming, and paracrine recruitment via a cytokine storm.

Experimental evaluation of the injection force exerted in intraocular lens delivery with syringe-type injectors.

The process of intraocular lens (IOL) delivery within the capsular bag during cataract surgery is crucial, as the integrity of the IOL, the injector and the ocular structures should be preserved at all times. This study aims to obtain the main parameters that affect the injection force exerted in the ejection of an intraocular lens (IOL) through syringe-type injectors. For that purpose, ejection tests were carried out in vitro, measuring the resistance force throughout the entire delivery process. The effect of IOL material, haptic design, IOL thickest area and ophthalmic viscosurgical device (OVD) was studied by ejecting seven IOLs with four syringe-type injectors of different sizes, 3.0, 2.2 and 1.8 mm. In all injectors, plate hydrophilic IOLs present the lowest resistance forces; hydrated C-loop hydrophobic IOLs present higher forces and the C-loop hydrophobic IOL in dry conditions presents the highest resistance forces. All IOLs could be properly delivered with an injector size of 2.2 mm, making injector sizes of 3.0 mm outdated. The injector size of 1.8 mm damaged several IOLs. IOL material and cartridge nozzle size were the most influential parameters in IOL delivery. IOL thickest area was also relevant but in a lesser extent whereas IOL haptic design was not as relevant.

Dysplasia in oral lichen planus: relevance, controversies and challenges. A position paper.

BACKGROUND: Patients with oral lichen planus (OLP) have an increased risk of oral cancer. For this reason, OLP is classified as an oral potentially malignant disorder. However, the precise personal (or individual) risk is unknown. Recent meta-analytical studies have reported that dysplastic OLP may transform to cancer in around 6% of cases, while the rate of transformation is lower (<1.5%) in non-dysplastic cases. The presence of epithelial dysplasia has emerged as the most powerful indicator for assessing cancer risk in oral potentially malignant disorders in routine practice. However, the general acceptance of epithelial dysplasia as an accompanying histologic feature in OLP is subject to great controversy. Many pathologists consider the presence of dysplasia as a criterion to exclude OLP when routinely reporting on this disease. This practice, widespread among oral pathology professionals, has resulted in the underestimation of the potential for malignancy of OLP. MATERIAL AND METHODS: A review of the literature was carried out in order to critically analyze the relevance, controversies and challenges encountered across the diagnosis of epithelial dysplasia in OLP. RESULTS: 12 studies have been published examining dysplastic changes in OLP, reporting figures ranging from 0.54% to 25% of cases with dysplasia in the first diagnostic biopsy. The diagnosis of dysplasia in the OLP poses an additional difficulty due to the fact that the affected oral epithelium per se develops changes related to autoimmune aggression. Among the most frequent histological features of OLP that develops dysplasia are basal cell hyperplasia with basaloid appearance, loss of basal cells polarity, cellular and nuclear pleomorphism and irregular stratification. CONCLUSIONS: Epithelial dysplasia should not be considered an exclusion criterion for OLP; its evaluation requires experienced pathologists in this field.

[Results of implementation of a perioperative Patient Blood Management program in cardiovascular surgery]. / Resultados de la implementación de un programa de optimización de transfusión sanguínea en cirugía cardiovascular.

BACKGROUND AND OBJECTIVE: Cardiovascular surgery (CCV) patients have a high incidence of perioperative anemia and bleeding that determines a high rate of allogeneic blood transfusion (AST). This is associated with an increase in morbidity, mortality and prolongs length of stay in hospital. Unnecessary transfusion is one of the measures to avoid and Patient Blood Management (PBM) programs have proven their effectiveness. Our objective was to reduce the transfusion of patients in cardiac surgery, without inferior results in morbidity and mortality, length of stay in hospital and being cost-effective, through the implementation of a PBM program. MATERIAL AND METHODS: A mixed cohort study of 226 patients divided into 2 groups: retrospective pre-PBM (GP), from 2016, and intervention group (IG), prospective from 2018, with the results of the implementation of the guide. RESULTS: The clinical results obtained allowed reducing the TSA from 92.59% to 79.69% (P<.001), saving 2.59 units of CH and 2.5 of PFC per patient (P<.001). A decrease was found in patients with fever (12.35% vs 1.56% with P=.006) and the need to escalate antibiotics (64.8% vs 42.19%, P=.002). The rest of postoperative complications and mortality at 3months did not present statistically significant differences. The length of stay was reduced by an average 3.6days in the IG, (95%CI: -8.10 to 0.9, P=.18). The cost decreased by 163.29€ per patient, taking into account exclusively the saving of blood components. CONCLUSION: The PBM program is effective in reducing TSA in cardiac surgery in a tertiary hospital with high complexity patients and high transfusion rate. There are signs suggestive of a decrease in infections and a tendency to decrease the length of stay and mortality. In the economic approximation carried out, the cost of the intervention was lower than the savings implied by the decrease in transfusion.

Generation, establishment and characterization of a pluripotent stem cell line (CVTTHi001-A) from primary fibroblasts isolated from a patient with activated PI3 kinase delta syndrome (APDS2).

APDS2 is caused by mutations in PIK3R1 gene resulting in constitutive PI3Kδ activation. PI3Kδ is predominantly expressed in leukocytes and plays critical roles in regulating immune responses. Here we first derived fibroblast primary cells from a skin biopsy of a patient carrying a heterozygous single T deletion in intron 11 of the PIK3R1 gene. We next present the derivation of an induced pluripotent stem cell (iPS) line using a non-integrative reprogramming technology. Pluripotent-related hallmarks are further shown, including: iPSCs self-renewal and expression of pluripotent and differentiation markers after in vitro differentiation towards embryonic germ layers, assessed by RT-PCR and immunofluorescence.

Functional Pro-metastatic Heterogeneity Revealed by Spiked-scRNAseq Is Shaped by Cancer Cell Interactions and Restricted by VSIG1.

How cells with metastatic potential, or pro-metastatic states, arise within heterogeneous primary tumors remains unclear. Here, we have used one index primary colon cancer to develop spiked-scRNAseq to link omics-defined single-cell clusters with cell behavior. Using spiked-scRNAseq we uncover cell populations with differential metastatic potential in which pro-metastatic states are correlated with the expression of signaling and vesicle-trafficking genes. Analyzing such heterogeneity, we define an anti-metastatic, non-cell-autonomous interaction originating from non-/low-metastatic cells, and identify membrane VSIG1 as a critical mediator of this interaction. VSIG1 acts to restrict the development of pro-metastatic states autonomously and non-cell autonomously, in part by inhibiting YAP/TAZ-TEAD signaling. As VSIG1 re-expression is able to reduce metastatic behavior from multiple colon cancer cell types, the regulation of VSIG1 or its effectors opens new interventional opportunities. In general, we propose that crosstalk between cancer cells, including the action of VSIG1, dynamically defines the degree of pro-metastatic intra-tumoral heterogeneity.

Customised Selection of the Haptic Design in C-Loop Intraocular Lenses Based on Deep Learning.

In order to increase the probability of having a successful cataract post-surgery, the customisation of the haptic design of the intraocular lens (IOL) according to the characteristics of the patient is recommended. In this study, we present two prediction models based on deep neural networks (DNNs). One is capable of predicting the biomechanical stability of any C-loop IOL, whereas the other can predict the haptic design that fits a desired biomechanical response, enabling the selection of the optimal IOL as a function of the IOL diameter compression. The data used to feed the networks has been obtained from a validated finite element model in which multitude of geometries are tested according to the ISO 11979-3 compression test, a standard for the mechanical properties of the IOLs. The biomechanical response model provides a very high accurate response (Pearson's r = 0.995), whilst the IOL haptic design model shows that several IOL designs can provide the same biomechanical response (Pearson's r = 0.992). This study might help manufacturers and ophthalmologists both analyse any IOL design and select the best IOL for each patient. In order to facilitate its application, a graphical user interface (GUI) was created to show the potential of deep learning methods in cataract surgery.

Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study.

OBJECTIVES: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to pre-eclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19. DESIGN: A prospective, observational study. SETTING: Tertiary referral hospital. PARTICIPANTS: Singleton pregnancies with COVID-19 at >20+0  weeks. METHODS: Forty-two consecutive pregnancies were recruited and classified into two groups: severe and non-severe COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE. MAIN OUTCOME MEASURES: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF. RESULTS: Thirty-four cases were classified as non-severe and 8 as severe COVID-19. Five (11.9%) women presented signs and symptoms of PE, all five being among the severe COVID-19 cases (62.5%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. One case remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome. CONCLUSIONS: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Healthcare providers should be aware of its existence and monitor pregnancies with suspected pre-eclampsia with caution. TWEETABLE ABSTRACT: This study shows that a pre-eclampsia-like syndrome could be present in some pregnancies with severe COVID-19.

Use of micafungin as antifungal prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Spain (GETH-MIC).

OBJECTIVE: The fungal infections remain an important problem in the allogeneic stem cell trasnsplantation (allo-SCT) setting and thus, anti-fungal prophylaxis is commonly used. The antifungal drug should offer activity, at least against Candida and Aspergillus spp., a good safety profile and low probability interactions. Micafungin could theoretically fulfill these requisites. The aim of the study was to describe the experience with micafungin as primary prophylaxis in patients undergoing allo-SCT in a cohort of Spanish centres, and to evaluate its efficacy and tolerability in this population. METHODS: Retrospective multicentre observational study including all consecutive adult patients admitted for allo-SCT in participating centres of the Grupo Español de Trasplante Hematopoyético (GETH), from January 2010 to December 2013, who received micafungin as primary prophylaxis during the neutropenic period. RESULTS: A total of 240 patients from 13 centres were identified and 159 patients were included for the analysis. Most patients (95.6%) received 50 mg/day of micafungin. During the follow-up, 7 (4.4%) patients developed breakthrough invasive fungal disease, 1 proven and 6 probable; one patient discontinued the drug because of serious drug interactions. Prophylaxis with micafungin was considered effective in 151 (94.9%) patients. CONCLUSIONS: According to our experience, micafungin is an appropriate alternative for antifungal prophylaxis in patients undergoing an allo-HSCT, because its efficacy, its low profile of drug interactions and side-effects.

Increased survival time or better quality of life? Trade-off between benefits and adverse events in the systemic treatment of cancer.

INTRODUCTION: Primary objective of the study was to assess the relative weighting between benefit in survival time (SV), benefit in quality of life (QoL) and willingness to experience adverse events (AEs), in patient preferences for chemotherapy treatment. MATERIALS AND METHODS: We included cancer patients with current or past systemic treatment of cancer (STC) as well as physicians placed as hypothetical patients. Participants filled a choice-based conjoint analysis questionnaire with 19 choices among three STC scenarios with variable amounts of benefit in SV or QoL and different types AEs. RESULTS: One hundred patients (50 on curative and 50 on palliative intention treatment) and 114 physicians (61 oncologists and 53 non-oncologists) were included and asked about their preferred chemotherapy treatment. The relative weighting (sum 100%) of SV-QoL-AEs for making the choice in the 100 patients was SV35%-CV33%-AEs31% what was not significantly different from a random distribution (Goodness of fit Chi square P = 0.91) just as it was not for both subgroups, palliative (SV37%-QoL29%-AEs34%; GoF Chi square P = 0.55) and curative (SV34%-QoL36%-AEs30%; GoF Chi square P = 0.73) treatment. The observed distribution in the group of 114 physicians (SV46%-QoL31%-AEs23%) was significantly different from a random distribution (GoF Chi square P = 0.018) just as it was for both subgroups, medical oncologists (SV48%-QoL29%-AEs23%; GoF Chi square P = 0.006) and non-medical oncologists (SV44%-QoL33%-AEs23%; GoF Chi square P = 0.04). CONCLUSIONS: The three attributes (SV, QoL, and AEs) are considered in the same way by cancer patients to make choices on their STC. On the contrary, when placed as hypothetical patients, physicians prefer for themselves those treatments that provide more SV.

Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells.

Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CAR T cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.

Valor nutricional de los alimentos ofrecidos en las máquinas de vending de la universidad complutense de madrid, españa. Habitos de consumo de los estudiantes universitarios

RESUMEN Introducción: El NutriScore es una herramienta diseñada con el objetivo de simplificar la información que aporta el etiquetado nutricional de los alimentos. Clasifica los alimentos en cinco colores que van desde el verde (más saludable) hasta el rojo (menos saludable). Estos colores están asociados a cinco letras (A/B/C/D/E). Los estudiantes universitarios pasan muchas horas en las facultades y tienen un consumo elevado de snacks y refrescos Objetivos: Calcular el NutriScore de los alimentos y bebidas disponibles en las máquinas expendedoras de las facultades de la Universidad Complutense de Madrid y obtener datos de los hábitos de consumo de los estudiantes de dicha universidad. Material y Métodos: El estudio ha sido realizado en 16 facultades y la biblioteca universitaria analizando los alimentos y bebidas de las máquinas expendedoras de dichas facultades en marzo de 2019. Se calculó la puntuación de cada uno y según la puntuación obtenida se clasificaron en una de las cinco categorías. 146 estudiante rellenaron una encuesta sobre la frecuencia de consumo y tipo de productos preferidos de las máquinas expendedoras. Resultados: Se clasificaron 143 alimentos y 53 bebidas que estaban disponibles en máquinas expendedoras. Los alimentos se distribuyeron: A 4,2%, B 4,2%, C 21,6%, D 53% y E 47% y las bebidas: A 1,9%, B 9,4%, C 13,2%, D 35,9% y E 39,6%. Los estudiantes consumen algún producto de las maquinas expendedoras fundamentalmente cuando tienen hambre, en momentos entre horas y eligiendo agua como primera opción seguido de refrescos azucarados como bebidas y bollería industrial seguido de patatas fritas como snacks más consumidos Conclusión: Aunque la universidad debería desarrollar una función en la promoción de un estado de vida saludable, las máquinas expendedoras de las facultades ofrecen un número muy elevado de productos con baja calidad nutricional.

ABSTRACT Introduction: NutriScore is a tool designed with the aim of simplify the information of the nutritional composition obtained from the labelling. It classify foods in five colors ranging from green (healthier) to red (less healthy). These colors are associated with five letters (A/B/C/D/E). University students spend many hours in faculties and have a high consumption of snacks and beverages. Objective: We aimed to examine the nutritional value of foods sold in vending machines of the Complutense University of Madrid, by calculating the nutriscore and to obtain data of the snacking habits of the students of this university. Methods: The study was conducted in sixteen universities and in the university library of the Complutense University of Madrid. One hundred and forty six undergraduate university students volunteered to complete a questionnaire to assess frequency of consumption and snack choices of vending machines. Results: We analized 143 snacks and 53 beverages. Snacks were: A 4,2%, B 4,2%, C 21,6%, D 53% y E 47% and beverages A 1,9%, B 9,4%, C 13,2%, D 35,9% y E 39,6%. The students use them when they are hungry and between meals. Water was the first option followed by sugary soft drinks as beverages and processed baked goods followed by chips as more consumed snacks. Conclusión: Although the university should play a role in promoting a healthy lifestyle, the vending machines of the faculties offer a very high number of products with low nutritional quality. group, we can conclude that DTC in acromegaly does not have a worse evolution.

The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.

How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of canonical WNT signaling upon knockdown (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFα as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the biogenesis, and thus function, of TGFα. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFα exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior, and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFα ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFα, and GLI1 that enhances metastases. We propose that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities.