Kazrin promotes dynein/dynactin-dependent traffic from early to recycling endosomes.

Kazrin is a protein widely expressed in vertebrates whose depletion causes a myriad of developmental defects, in part derived from altered cell adhesion and migration, as well as failure to undergo epidermal to mesenchymal transition. However, the primary molecular role of kazrin, which might contribute to all these functions, has not been elucidated yet. We previously identified one of its isoforms, kazrin C, as a protein that potently inhibits clathrin-mediated endocytosis when overexpressed. We now generated kazrin knock-out mouse embryonic fibroblasts to investigate its endocytic function. We found that kazrin depletion delays juxtanuclear enrichment of internalized material, indicating a role in endocytic traffic from early to recycling endosomes. Consistently, we found that the C-terminal domain of kazrin C, predicted to be an intrinsically disordered region, directly interacts with several early endosome (EE) components, and that kazrin depletion impairs retrograde motility of these organelles. Further, we noticed that the N-terminus of kazrin C shares homology with dynein/dynactin adaptors and that it directly interacts with the dynactin complex and the dynein light intermediate chain 1. Altogether, the data indicate that one of the primary kazrin functions is to facilitate endocytic recycling by promoting dynein/dynactin-dependent transport of EEs or EE-derived transport intermediates to the recycling endosomes.

CoQ10 reduces glioblastoma growth and infiltration through proteome remodeling and inhibition of angiogenesis and inflammation.

PURPOSE: Most monotherapies available against glioblastoma multiforme (GBM) target individual hallmarks of this aggressive brain tumor with minimal success. In this article, we propose a therapeutic strategy using coenzyme Q10 (CoQ10) as a pleiotropic factor that crosses the blood-brain barrier and accumulates in cell membranes acting as an antioxidant, and in mitochondrial membranes as a regulator of cell bioenergetics and gene expression. METHODS: Xenografts of U251 cells in nu/nu mice were used to assay tumor growth, hypoxia, angiogenesis, and inflammation. An orthotopic model was used to explore microglial infiltration, tumor growth, and invasion into the brain parenchyma. Cell proliferation, migration, invasion, proteome remodeling, and secretome were assayed in vitro. Conditioned media were used to assay angiogenesis, monocyte chemoattraction, and differentiation into macrophages in vitro. RESULTS: CoQ10 treatment decreased tumor volume in xenografts and orthotopic models, although its effect on tumor cell proliferation was not direct. Tumors from mice treated with CoQ10 were less hypoxic and vascularized, having less infiltration from inflammatory cells. Treatment-induced downregulation of HIF-1α and NF-kB led to a complete remodeling of the tumor cells proteome and secretome, impacting angiogenesis, monocyte infiltration, and their differentiation into macrophages. Besides, tumor cell migration and invasion were drastically restricted by mechanisms involving modulation of the actin cytoskeleton and downregulation of matrix metalloproteases (MMPs). CONCLUSIONS: CoQ10 has a pleiotropic effect on GBM growth, targeting several hallmarks simultaneously. Thus, its integration into current treatments of this fatal disease should be considered.

Antifibrotics and lung transplantation: A Spanish multicentre case-controlled study.

BACKGROUND AND OBJECTIVE: Antifibrotic drugs are the standard treatments for patients with idiopathic pulmonary fibrosis (IPF). This study aims to assess the safety of antifibrotic treatment in IPF patients undergoing lung transplantation. METHODS: Patients with a diagnosis of IPF who received a lung transplant between January 2015 and June 2019 at four Spanish hospitals specialized in lung transplantation were retrospectively recruited. Cases were defined as patients receiving antifibrotic treatments at time of transplant. Each case was matched with a control who did not receive antifibrotic treatment. RESULTS: A total of 164 patients were included in the study cohort (103 cases and 61 controls). There were no statistically significant differences between the cases and controls in any of the items studied related to transplantation except the time until the appearance of chest wall dehiscence: although there were no differences in the incidence of wall dehiscence in either group (12.3% vs. 13.7%; p = 0.318), the patients on antifibrotic drugs experienced it earlier (21 days [IQR = 12.5-41.5] vs. 63 days [IQR = 46.75-152.25]; p = 0.012). There were no differences in overall post-transplant survival between the two groups (p = 0.698) or in conditional survival at 30 days, 90 days, 3 years or 5 years. However, 1 year survival was significantly greater among controls (80.6% vs. 93.3%; p = 0.028). CONCLUSION: There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

Subchronic Graphene Exposure Reshapes Skin Cell Metabolism.

In recent years, the toxicity of graphene-related materials (GRMs) has been evaluated in diverse models to guarantee their safety. In most applications, sublethal doses of GRMs contact human barriers such as skin in a subchronic way. Herein, the subchronic effect (30 day exposure) of three GRMs (GO 1, GO 2, and FLG) with different oxidation degrees and sizes was studied. The effects of these materials on human skin cells, HaCaTs, were assayed through high-throughput metabolic-based readout and other cell-based assays. A differential effect was found between the different GRMs. GO 2 induced a metabolic remodeling in epithelial cells, increasing the level of tricarboxylic acid components, mirrored by increased cell proliferation and changes in cell phenotype. The oxidation degree, size, and method of manufacture of GRMs dictated harmful effects on cell metabolism and behavior generated by nontoxic exposures. Therefore, a "safe by design" procedure is necessary when working with these nanomaterials.

Rapid and efficient testing of the toxicity of graphene-related materials in primary human lung cells.

Graphene and its derivative materials are manufactured by numerous companies and research laboratories, during which processes they can come into contact with their handlers' physiological barriers-for instance, their respiratory system. Despite their potential toxicity, these materials have even been used in face masks to prevent COVID-19 transmission. The increasingly widespread use of these materials requires the design and implementation of appropriate, versatile, and accurate toxicological screening methods to guarantee their safety. Murine models are adequate, though limited when exploring different doses and lengths of exposure-as this increases the number of animals required, contrary to the Three R's principle in animal experimentation. This article proposes an in vitro model using primary, non-transformed normal human bronchial epithelial (NHBE) cells as an alternative to the most widely used model to date, the human lung tumor cell line A549. The model has been tested with three graphene derivatives-graphene oxide (GO), few-layer graphene (FLG), and small FLG (sFLG). We observed a cytotoxic effect (necrosis and apoptosis) at early (6- and 24-h) exposures, which intensified after seven days of contact between cells and the graphene-related materials (GRMs)-with cell death reaching 90% after a 5 µg/mL dose. A549 cells are more resistant to necrosis and apoptosis, yielding values less than half of NHBE cells at low concentrations of GRMs (between 0.05 and 5 µg/mL). Indeed, GRM-induced cell death in NHBE cells is comparable to that induced by toxic compounds such as diesel exhaust particles on the same cell line. We propose NHBE as a suitable model to test GRM-induced toxicity, allowing refinement of the dose concentrations and exposure timings for better-designed in vivo mouse assays.

Evaluation of a Clinic Dedicated to People Aging with HIV at Chelsea and Westminster Hospital: Results of a 10-Year Experience.

Successful management of HIV infection as a chronic condition has resulted in a demographic shift where the proportion of people living with HIV (PLWH) older than 50 years is steadily increasing. A dedicated clinic to PLWH older than 50 years was established at Chelsea and Westminster Hospital in January 2009 and then extended to HIV services across the directorate. We report the results of a service evaluation reviewing 10 years of activities of this clinic between January 2009 and 2019. We aimed to estimate the prevalence of major noninfectious comorbidities, polypharmacy (≥5 medications), and multimorbidity (≥2 non-HIV-related comorbidities) and describe algorithms devised for use in HIV outpatient clinics across the directorate. A cohort of 744 PLWH older than 50 years attending this service were analyzed (93% male; mean age of 56 ± 5.5 years; 84% white ethnicity); 97.7% were on antiretroviral treatment and 95.9% had undetectable HIV-RNA at the time of evaluation. The most common comorbidities diagnosed were dyslipidemia (50.1%), hypertension (21.5%), mental health disorders (depression and/or anxiety disorders, 15.7%), osteoporosis (12.2%), obesity (11.9%), chronic kidney disease (7.5%), and diabetes (5.8%). Low vitamin D levels were found in 62% of patients [43% with vitamin D deficiency (<40 mmol/liter) and 57% with vitamin D insufficiency (40-70 mmol/liter)]. The overall prevalence of polypharmacy and multimorbidity was 46.6% and 69.3%, respectively. This study showed significant rates of non-HIV-related comorbidities and polypharmacy in PLWH older than 50 years, leading on to the implementation of clinical care pathways and new joint HIV/specialty clinics (cardiology, nephrology, neurology, metabolic, menopause, and geriatric) to improve prevention, diagnosis, and management of major comorbidities in people aging with HIV.

Deprescribing of non-antiretroviral therapy in HIV-infected patients.

PURPOSE: In recent decades, the life expectancy of HIV-infected patients has increased considerably, to the extent that the disease can now be considered chronic. In this context of progressive aging, HIV-infected persons have a greater prevalence of comorbid conditions. Consequently, they usually take more non-antiretroviral drugs, and their drug therapy are more complex. This supposes a greater risk of drug interactions, of hospitalization, falls, and death. In the last years, deprescribing has gained attention as a means to rationalize medication use. METHODS: Review of the different therapeutic approach that includes optimization of polypharmacy and control and reduction of potentially inappropriate prescription. RESULTS: There are several protocols for systematizing the deprescribing process. The most widely used tool is the Medication Regimen Complexity Index, an index validated in HIV-infected persons. Anticholinergic medications are the agents that have been most associated with major adverse effects so, various scales have been employed to measure it. Other tools should be employed to detect and prevent the use of potentially inappropriate drugs. Prioritization of candidates should be based, among others, on drugs that should always be avoided and drugs with no justified indication. CONCLUSIONS: The deprescribing process shared by professionals and patients definitively would improve management of treatment in this population. Because polypharmacy in HIV-infected patients show that a considerable percentage of patients could be candidates for deprescribing, we must understand the importance of deprescribing and that HIV-infected persons should be a priority group. This process would be highly feasible and effective in HIV-infected persons.

Are there differences between the loading of an anaerobic capacity test and an agility test in basketball players? / Há diferenças entre a carga de um teste de capacidade anaeróbica e um teste de agilidade em jogadores de basquete?

Abstract The objective of this article was to know players' needs in the selected tests, to search for differences between categories and to know if there is any relationship between different tests. The sample consists of 2 teams (u-14, u-16, n=24), which were equipped with a WimuR inertial device. The selected tests were 2 agility tests and a lactic anaerobic capacity test. Neuromuscular and kinematic variables were selected. Descriptive analysis, inferential analysis and analysis of correlation among variables were carried out. Once players' needs are described, there are no significant differences among kinematic variables depending on the sample category. Nonetheless, there is relationship between kinematic and neuromuscular variables of the different tests. It is frequently claimed that capacity tests are those that cause more fatigue in athletes. For this reason, an analysis was carried out comparing a lactic anaerobic capacity test with an agility test in its two versions. The obtained results can facilitate the work and the evaluation time of a physical condition test since results of athletes in a capacity test could be known by performing tests of lesser requirement. In addition, this would avoid players from experiencing a situation of maximum effort and possible injury, also saving training time.

Resumo O objetivo desse trabalho foi conhecer as demandas dos jogadores nos testes selecionados, buscar diferenças entre categorias e buscar conhecer se havia alguma diferença entre distintas provas. A amostra foi formada por duas equipes (sub-14, sub-16; n = 24) que foram monitorados com dispositivo de inércia WimuR. Selecionaram-se dois testes de agilidade e um teste de capacidade anaeróbica lática, e testes para variáveis neuromusculares e cinemáticas. Empregou-se a análise descritiva e inferencial. Não houve diferenças significativas entre as variáveis cinemáticas, dependendo da categoria da amostra, porém houve relação entre as variáveis cinemáticas e neuromusculares. Afirma-se frequentemente queos testes de capacidade são os que causam maior fadiga no atleta. Por esse motivo, foi realizada uma análise na qual um teste de capacidade anaeróbica lática foi comparado com um teste de agilidade em suas duas versões. Os resultados obtidos podem facilitar o trabalho e o tempo de avaliação do teste de aptidão física, pois, ao realizar testes de menor exigência, os resultados do atleta podem ser conhecidos em um teste de capacidade, evitando que ele enfrente uma situação de esforço máximo, uma possível lesão e economia tempo de treinamento .

Differences in the physical demands between handball and beach handball players / Diferenças nas exigências físicas entre jogadores de handebol e handebol de praia

Abstract Handball is one of the most practiced team sports worldwide that consists of different modalities, with the aim of reaching as many users as possible. One of the modalities with increasing interest in the last years is Beach Handball, as it takes the advantage of the absence of competitive calendar in the standardized modality so that users continue practicing. A comparative analysis was performed between standard handball (indoor) and beach handball athletes in order to determine the demands of both modalities and determine if they are similar. The competition was evaluated by analyzing external load variables: number of steps, jumps, impacts and Player load. The selected sample was composed of U-16 players from both modalities. Each player was equipped with WIMUTM inertial device. The results showed that the standard modality requires greater physical demands than the beach modality. For this reason, the physical demands of the different modalities require different training processes to obtain the best possible results in the competition.

Resumo O handebol é um dos esportes coletivos mais praticados em todo o mundo, que consiste em diferentes modalidades, com o objetivo de atingir o maior número possível de usuários. Uma das modalidades em expansão nos últimos anos é o Handebol de Praia, pois aproveita a ausência de calendário competitivo na modalidade padronizada para que os usuários continuem praticando. Uma análise comparativa foi realizada entre atletas de handebol padronizado (na pista) e handebol de praia, a fim de determinar as demandas de ambas as modalidades e determinar se essas demandas são semelhantes. A competição foi avaliada através da análise das variáveis externas de carga: número de etapas, saltos, impactos e Player Load. A mostra selecionada foram jogadores de ambas as disciplinas na categoria cadete. Cada jogador foi equipado com um dispositivo inercial WIMUTM. Os resultados mostraram que a modalidade padronizada exige dos atletas maior demanda física que a modalidade de praia. Por esse motivo, os requisitos físicos de ambas as modalidades exigem diferentes processos de treinamento para obter os melhores resultados possíveis na competição.

Traducción y adaptación cultural del cuestionario exercise fear avoidance scale para su uso en adultos mayores chilenos / Translation and cultural adaptation of the Exercise Fear Avoidance Scale for Chilean older adults / Tradução e adaptação cultural do questionário de escala do exercício para evitar o uso em idosos chilenos

RESUMEN Objetivo Traducir y adaptar culturalmente el cuestionario Exercise Fear Avoidance Scale (EFAS) al español para su uso en adultos mayores chilenos. Materiales y Métodos Doble traducción directa con armonización de versiones, retro-traducción y análisis de la comprensibilidad mediante entrevistas cognitivas. En el proceso de entrevistas cognitivas participaron 20 adultos mayores con edades comprendidas entre 63 y 83 años. Resultados Todos los ítems fueron evaluados como claros y comprensibles. Mediante la técnica de parafraseo e indagación 3 ítems (de un total de 16) se tuvieron que adaptar para lograr una mejor comprensión. Dos de estas adaptaciones consistieron en reemplazar un concepto por uno más utilizado en el contexto chileno y otra modificación fue en relación con la redacción, puesto que su lectura resultaba compleja para esta población. Conclusiones Se obtuvo una versión en español del cuestionario EFAS, la cual demostró ser comprensible y adaptada para su uso en adultos mayores chilenos.(AU)

ABSTRACT Objective To translate and culturally adapt the Exercise Fear Avoidance Scale (EFAS) Into Spanish for Chilean older adults. Materials and Methods Double direct translation with harmonization, back translation and analysis of text comprehensibility through cognitive interviews. A sample of 20 older adults between the ages of 63 and 83 participated in the cognitive interview process. Results All items were assessed as clear and understandable. Using the paraphrasing and inquiry techniques, 3 items (out of 16) were adapted to achieve better understanding. Two of these adaptations consisted in replacing one concept with another, as the latter was more used in the Chilean context, and making a non-literal translation, since the literal one was too complex for the elderly to understand. Conclusions A Spanish version of the EFAS was obtained, which proved to be understandable and adapted for its use with Chilean older adults.(AU)

OBJETIVO Traduza e adapte culturalmente o questionário da Escala de Evitação do Medo do Exercício (EFAS) ao espanhol para uso em idosos chilenos. MATERIAIS E MÉTODOS Tradução direta dupla com harmonização de versões, retrotradução e análise de compreensibilidade por meio de entrevistas cognitivas. Vinte idosos entre 63 e 83 anos participaram do processo de entrevista cognitiva. RESULTADOS Todos os itens foram avaliados como claros e compreensíveis. Usando a paráfrase e a técnica de investigação, três itens (de um total de 16) tiveram que ser adaptados para alcançar uma melhor compreensão. Duas dessas adaptações consistiram em substituir um conceito por outro mais utilizado no contexto chileno e outra modificação em relação à redação, uma vez que sua leitura era complexa para essa população. CONCLUSÕES Foi obtida uma versão em espanhol do questionário EFAS, que se mostrou compreensível e adaptado para uso em idosos chilenos.(AU)

Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.

OBJECTIVES: To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. MATERIAL AND METHODS: Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O2-) and H2O2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time. Hif-1α, SOD1, SOD2 and NQO1 were determined by immunolabeling. Catalase activity was measured by classic enzymatic assay. Glutathione levels and total antioxidant capacity were quantified using commercial kits. RESULTS: CoQ did not affect oxygen consumption but reduced the level of O2- and H2O2 while shifted to a pro-oxidant cell status mainly due to a decrease in catalase activity and SOD2 level. Hif-1α was dampened, echoed by a decrease lactate and several key metabolites involved in glutathione synthesis. CoQ-treated cells were twofold more sensitive than control to radiation-induced DNA damage and apoptosis in short and long-term clonogenic assays, potentiating TMZ-induced cytotoxicity, without affecting non-transformed astrocytes. CONCLUSIONS: CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology.

How to reduce the superior mesenteric vein bleeding risk during laparoscopic right hemicolectomy.

PURPOSE: The superior right colic vein (SRCV) has been proposed as the main cause of superior mesenteric vein bleeding by avulsion during laparoscopic right hemicolectomy. Our objective is to identify the main vessel causing transverse mesocolic tension during the extraction of the surgical specimen or extracorporeal anastomosis and to perform an anatomical description of the SRCV. METHODS: In this cadaveric study, we performed a simulation of right hemicolectomy and anatomical description of the surgical area of the gastrocolic trunk of Henle (SAGCTH), the gastrocolic trunk of Henle (GCTH), and SRCV. The length of the exteriorization of the anastomotic transverse colon (ATC) was measured before and after sectioning the vascular vessel causing the exteriorization tension. RESULTS: Five fresh cadavers and 12 formalin were dissected. In 100% of the specimens, the SRCV was present and drained in 95% into the GCTH and in 5% directly into the superior mesenteric vein (SMV). In 100% of the specimens, the SRCV caused the tension when extracting the ATC. The mean length of exteriorization of the ATC before and after SRCV section was 7.2 and 10.4 cm in formalin cadavers, meaning a 44% of increment in the length of exteriorization. In fresh cadavers, the mean length of exteriorization increased to 2.7 cm, meaning a 28% of the initial length of exteriorization. CONCLUSIONS: The SRCV is the main cause of tension in the extraction of the surgical specimen after right hemicolectomy. Its high tie increases the length of the ATC exteriorization, in about 3 cm, and could reduce the risk of SMV bleeding during laparoscopic right hemicolectomy and facilitate an extracorporeal anastomosis free of tension.

[ASSOCIATION BETWEEN HEALTH RELATED QUALITY OF LIFE, BODYWEIGHT STATUS (BMI) AND PHYSICAL ACTIVITY AND FITNESS LEVELS IN CHILEAN ADOLESCENTS]. / ASOCIACIÓN ENTRE LA CALIDAD DE VIDA RELACIONADA CON LA SALUD, EL ESTADO NUTRICIONAL (IMC) Y LOS NIVELES DE ACTIVIDAD FÍSICA Y CONDICIÓN FÍSICA EN ADOLESCENTES CHILENOS.

AIM: the objective of this study was to analyze the potential relationships between Health Related Quality of Life (HRQoL) with weight status, physical activity (PA) and fitness in Chilean adolescents in both, independent and combined analysis. METHOD: a sample of 767 participants (47.5% females) and aged between 12 and 18 (mean age 15.5) was employed. All measurements were carried out using selfreported instruments and Kidscreen-10, iPAQ and IFIS were used to assess HRQoL, PA and Fitness respectively. One factor ANOVA and linear regression models were applied to analyze associations between HRQoL, weight status, PA and fitness using age and sex as confounders. RESULTS: body mass index, level of PA and fitness were independently associated with HRQoL in Chilean adolescents. However, the combined and adjusted by sex and age analysis of these associations showed that only the fitness was significantly related with HRQoL. CONCLUSION: general fitness is associated with HRQoL independently of sex, age, bodyweight status and level of PA. The relationship between nutritional status and weekly PA with HRQoL are mediated by sex, age and general fitness.

Objetivos: el objetivo del presente estudio fue analizar las posibles relaciones entre la Calidad de Vida Relacionada con la Salud (CVRS) con el estado nutricional y los niveles de Actividad Física (AF) y Condición Física (CF) en adolescentes chilenos, de manera independiente e interactiva. Método: se utilizó una muestra de 767 participantes (47,5% chicas) con edades comprendidas entre los 12 y los 18 años de edad (edad media 15,5 años). Todas las medidas utilizadas se obtuvieron mediante instrumentos auto- administrados. Se utilizó el Kidscreen-10, iPAQ e IFIS para evaluar la CVRS, la AF y la CF, respectivamente. Se realizaron análisis de ANOVA de un factor y modelos de regresión lineal para analizar las asociaciones entre la CVRS, el estado nutricional, la AF y la CF utilizando la edad y el sexo como variables confusoras. Resultados: se ha encontrado una asociación independiente del Índice de Masa Corporal, el nivel de AF y de CF con el nivel de CVRS de adolescentes chilenos. Sin embargo, al analizar esta asociación de forma combinada y ajustada por sexo y edad tan solo el nivel de CF general se asocia de forma significativa con la CVRS. Conclusión: el nivel de CF general se asocia con la CVRS en adolescentes chilenos independientemente del sexo, la edad, el estado nutricional y el nivel de AF. La relación entre el estado nutricional y el nivel de AF semanal con la CVRS están mediadas por el sexo, la edad y el nivel de CF general.

Traducción y adaptación cultural del cuestionario de independencia física Composite Physical Function para su uso en Chile / Translation and cultural adaptation of the Composite Physical Function for its use in Chile

Aging is directly related with loss of physical independency. Composite Physical Function questionnaire (CPF) assess, throw 12 items, a range of daily life activities in order to determine dependency levels in elderly. However, there is not a Spanish version of this instrument. Aim: To translate and culturally adapt the CPF to Spanish for its use in Chilean elderly. Method: Standardized international methodology was used in this study, which consisted in double direct translation to Spanish, harmonization of versions and back-translation to English. Acceptability and familiarity of the obtained version was analyzed using probing and paraphrasing methods using a sample of 20 older adults aged from 65 to 80 years old. Results: All items were clear and understandable, although minor adaptations needed to be done in order to improve the understandability of two items. These adaptations consisted in adding information in brackets at the end of the sentence. Conclusion: Spanish version of the CPF questionnaire was obtained to its use in Chile. This questionnaire has been proved to be understandable and adapted to its use in Chilean older adults. Its ease of use makes this questionnaire potentially useful in future researches and surveys.

[Association between dietary habits and the presence of overweight/obesity in a sample of 21,385 chilean adolescents]. / ASOCIACIÓN ENTRE LOS HÁBITOS DIETÉTICOS Y LA PRESENCIA DE SOBREPESO/OBESIDAD EN UNA MUESTRA DE 21.385 ADOLESCENTES CHILENOS.

AIM: The main aim of the present study was to explore the potential associations between dietary habits and the presence of overweight and obesity in Chilean adolescents. METHODS: For the present study dietary habits of 21,385 Chilean students were analyzed and weight and height assessed, in order to determine potential associations between eating patterns and body mass index (BMI) values. RESULTS: The majority of participants have lunch and a snack in the afternoon every day a week (81% and 71.2%, respectively), although only a 59.5% have breakfast every day and a 22% have dinner every night. To have breakfast is common for thin and normal weight subjects, but only a half of overweight and obese individuals usually have it. The obese is the group having less dairy products. A 50.2% of all subjects have legumes once or never in a week. Around a 15% have sweets all days and nearly a 50% of all the participants consume fizzy drinks every day of the week. Interestingly, having breakfast was found to be associated with less truancy. CONCLUSIONS: Nutritional education strategies should be carried out within students in Chile, since inadequate dietary habits are related to the higher values of BMI.

Objetivos: El principal objetivo del presente trabajo fue evaluar las posibles asociaciones entre los hábitos dietéticos y la presencia de sobrepeso y obesidad en adolescentes Chilenos. Método: Para este trabajo se analizaron los hábitos dietéticos de 21.385 estudiantes Chilenos y se determinaron el peso y la talla, con el fin de explorar posibles asociaciones entre los patrones de alimentación y los valores de índice de masa corporal (IMC). Resultados: La mayoría de los participantes realiza la toma del almuerzo (81%) y de la merienda (71,2%) todos los días de la semana. Sólo el 59,5% de los encuestados toma desayuno cada día y un 22% cena todas las noches. Desayunar es común entre los sujetos delgados y con peso normal, pero únicamente la mitad de los individuos con sobrepeso u obesidad desayuna habitualmente. Los obesos son el grupo que consume menos productos lácteos. Un 50,2% de todos los participantes nunca toma legumbres o lo hace una vez por semana. En torno a un 15% toma dulces todos los días y casi la mitad de los encuestados ingiere bebidas carbonatadas cada día de la semana. Además, tomar desayuno de forma habitual se asoció inversamente con el absentismo escolar. Conclusión: Se necesitan llevar a cabo estrategias de educación nutricional entre los estudiantes chilenos, ya que los hábitos dietéticos inadecuados se encuentran asociados con valores más elevados de IMC.

Enfermedad de Paget extramamaria: reporte de caso / Extramammary Paget's disease: case report

Se presenta el caso de una mujer de 67 años de edad, sin antecedentes de importancia, con un tiempo de enfermedad de un año. La paciente refiere una lesión tipo placa amarronada con áreas eritematosas y de bordes definidos, localizada en la región púbica izquierda, con extensión a la región inguinal, asociada a intenso prurito. Se le diagnosticó eccema y recibió tratamiento con corticoides tópicos, sin mostrar mejoría. Al momento de la evaluación, el examen físico no reveló adenopatías y los exámenes de laboratorio resultaron normales. El diagnóstico fue inmunohistopatológico, mediante el hallazgo de células de Paget y la tinción positiva para CK-7 y panqueratina, compatible con una enfermedad de Paget extramamaria, debida a diseminación intraepidérmica de un tumor primario de glándulas sudoríparas tipo adenocarcinoma in situ. La paciente fue sometida a una evaluación general para descartar una diseminación a distancia, pero no se encontró evidencia alguna. Se la trató exitosamente con cirugía escisional estándar con bordes libres y cursó favorablemente sin recurrencias cinco meses después.

A 67-year-old woman presented with a history of one year of pruriginous well defined brownish-reddish patch lesion on pubic area, which extended to inguinal area. An external diagnosis of eccema was made and the patient initiated treatment with topical corticosteroids for several months, without results. At present time, physical examination and laboratory evaluation did not reveal major alteration. A biopsy was taken and immunohistochemistry analysis was made, which revealed the presence of Paget's cells positive to CK-7 and pan Keratin. The results were compatible with extramammary Paget's disease secondary to intraepidermal dissemination of primary apocrine sweat glands adenocarcinoma. The patient underwent further evaluation to rule out distant metastases and was treated successfully with surgical excision alone with free margins. At follow-up five months later was still free of recurrences.

HLA-G(∗)01:05N null allele in Mayans (Guatemala) and Uros (Titikaka Lake, Peru): evolution and population genetics.

HLA-G molecules seem to have a protective effect for the semi-allogeneic fetus by mother immunosuppression. Also, pregnancy pathologies have been associated to HLA-G(∗)01:05N "null allele". In addition, other general regulatory immune functions have been associated to HLA-G in infections, tumors and autoimmunity. Thus, it is striking that HLA(∗)01:05N allele is maintained in a substantial frequency in certain human populations. In the present work, we have analysed HLA-G allele frequencies in Amerindian Mayans from Guatemala and in Uros from Titikaka Lake "totora" (reed) floating islands (Peru). No HLA-G(∗)01:05N has been found in both of these Amerindian populations. Further studies in Worldwide populations show that the highest HLA-G(∗)01:05 allele frequencies are found in Middle East; these findings have a bearing in future clinical/epidemiological studies in Amerindians. This would suggest that either this area was close to the "null" allele origin (as predicted by us) and/or some evolutive pressures are maintaining these high frequencies in Middle East. However, the fact that Cercopithecinae primate family (primates postulated as distant human ancestors) has also a MHC-G "null" allele in all individuals suggests that this allele may confer some advantage either at maternal/fetal interface or at other immune HLA-G function level (tumors, infections, autoimmunity). Human HLA-G(∗)01:05N may produce HLA-G isoforms, like Cercopithecinae monkeys may, which may suffice for function.

Coexistent intraurothelial carcinoma and muscle-invasive urothelial carcinoma of the bladder: clonality and somatic down-regulation of DNA mismatch repair.

Muscle-invasive urothelial carcinomas are heterogeneous neoplasms for which the clonal relationship with low-grade urothelial dysplasia and carcinomas in situ remains unknown, and both monoclonal and field change models have been proposed. Low-grade dysplasia (18) and carcinoma in situ (12) associated with muscle-invasive urothelial carcinoma were microdissected and topographically analyzed (intraepithelial and invasive superficial and deep to muscularis mucosa) for methylation pattern of androgen receptor alleles, TP53, RB1, WT1, and NF1 microsatellite analysis to assess clonal identity; MLH1 and MSH2 sequencing/immunostaining. Appropriate controls were run. Carcinoma in situ (100%) and invasive urothelial carcinoma (100%) revealed monoclonal patterns, whereas low-grade dysplasia was preferentially polyclonal (80%). Carcinoma in situ showed aneuploid DNA content and more abnormal microsatellites than the corresponding invasive compartments, opposite to low-grade dysplasia. Absent MLH1 protein expression with no gene mutations were identified in carcinoma in situ and nodular-trabecular urothelial carcinoma with high microsatellite abnormalities. Somatic mismatch repair protein down-regulation and the accumulation of tumor suppressor gene microsatellite abnormalities contribute to a molecular evolution for monoclonal carcinoma in situ divergent from coexistent muscle-invasive urothelial carcinoma. Low-grade dysplasia is however unlikely connected with this molecular progression.