Advances in immunotherapy for cervical cancer

Cervical cancer; Immunotherapy; RadiotherapyCáncer de cuello uterino; Inmunoterapia; RadioterapiaCàncer de coll uterí; Immunoteràpia; RadioteràpiaCervical cancer still represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. These figures are unacceptable since cervical cancer, an human papillomavirus-related malignancy, is a largely preventable disease by means of well-established screening and vaccination programs. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches represent a dismal prognosis population. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment landscape of this disease achieving historical overall survival improvements in both the post-platinum and frontline settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to earlier stages of the disease, as the locally advanced setting, whose standard of care has not changed in the last decades with still modest outcomes. As more innovative immunotherapy approaches are in clinical early development in advanced cervical cancer, promising efficacy data are emerging that may shape the future of this disease. This review summarizes the main treatment advances carried out in the field of immunotherapy throughout the past years

Percepción de riesgo cardiovascular y uso de tecnologías en salud en adultos con obesidad

Objective: This paper determined the relationship between the perception of risk of a cardiovascular disease with the level of use of Information and Communication Technology or ICT, as well as the explanatory effect of these ICTs and the history of cardiovascular disease in the perception of risk of cardiovascular disease in adults with obesity.Methods: This study is relevant since the relationship between the proposed variables, and the relationship of the ICTs and other variables about the risk perception of heart and brain disease is not very clear yet. An analytical-descriptive research was made on a sample of 260 obese adults. Questionnaires of risk perception of a cardiovascular disease and use of ICT in patients who receive care in a health center were used; ethical standards were observed and descriptive statistics and statistical inference were applied.Results: A relationship between risk perception of a cardiovascular disease and the use of ICTs was found (rs=0,142, p=0,022). The level of use of ICTs and personal/family history of disease for the development of a cardiovascular disease explain a 14,3% in the perception of risk of the disease.Conclusions: It was concluded that the perception of risk of cardiovascular disease was related to the level of use of Information and Communication Technologies regarding health, and it is partially explained by the level of use of the ICTs and health history.En este articulo se determinó la relación entre la Percepción del riesgo de enfermedad cardiovascular con el Nivel de uso de Tecnologías de la Información y Comunicación (TIC´s), así como el efecto explicativo del nivel de uso de las TIC´s y antecedentes para enfermedad cardiovascular en la Percepción del riesgo de enfermedad cardiovascular en adultos con obesidad. Este estudio es pertinente dado que la relación entre las variables propuestas, así como la relación de las TIC´s y otras variables sobre la percepción de riesgo de enfermedad cardiaca y cerebral aún no es del todo clara. Se realizó un estudio descriptivo-analítico realizado en una muestra de 260 adultos con obesidad. Se usaron los cuestionarios Percepción del Riesgo de enfermedad cardiovascular y Uso de TICS en pacientes atendidos en un centro de salud, se respetaron las normas éticas y se utilizó estadística descriptiva e inferencial. Se encontró relación entre la Percepción del riesgo de enfermedad cardiovascular y el uso de las TIC´s (rs =0,142, p=0,022). El Nivel de uso de TICS y antecedentes personales/familiares para el desarrollo de enfermedad cardiovascular fue un 14,3% en la percepción del riesgo de enfermedad cardiovascular. Se concluyó que la percepción del riesgo de enfermedad cardiovascular se relaciona con el Nivel de uso de Tecnologías de la información y comunicación en salud y es explicada en parte por el Nivel de uso de tecnologías de la información y comunicación y antecedentes de salud

Synthesis and characterization of extremely small gold nanoshells, and comparison of their photothermal conversion capacity with gold nanorods

The current methods for preparing gold nanoshells (AuNSs) produce shells with a diameter of approximately 40 nm or larger, with a relatively large polydispersity. However, AuNSs with smaller diameters and more monodispersity are better suited for biomedical applications. In this work, we present a modified method for the preparation of AuNSs, based on the use of sacrificial silver nanoparticles (AgNPs). We customized the Lee–Meisel method to prepare small and monodisperse AgNPs that were used as sacrificial nanoparticles to prepare extremely small monodispersed AuNSs with an average diameter from 17 to 25 ± 4 nm. We found that these AuNSs are faceted, and that the oxidized silver likely dissolves out of the nanoparticles through some of the facets on the AuNSs. This leads to a silver oxide plug on the surface of the AuNSs, which has not been reported before. The smaller AuNSs, prepared under the best conditions, absorb in the near infrared region (NIR) that is appropriate for applications, such as photothermal therapy or medical imaging. The AuNSs showed absorption peaks in the NIR similar to those of gold nanorods (AuNRs) but with better photothermal capacity. In addition, because of their negative charge, these AuNSs are more biocompatible than the positively charged AuNRs. The synthesis of small, monodisperse, stable and biocompatible nanoparticles, like the ones presented in this work, is of prime importance in biomedical applications.The current methods for preparing gold nanoshells (AuNSs) produce shells with a diameter of approximately 40 nm or larger, with a relatively large polydispersity. However, AuNSs with smaller diameters and more monodispersity are better suited for biomedical applications. In this work, we present a modified method for the preparation of AuNSs, based on the use of sacrificial silver nanoparticles (AgNPs). We customized the Lee–Meisel method to prepare small and monodisperse AgNPs that were used as sacrificial nanoparticles to prepare extremely small monodispersed AuNSs with an average diameter from 17 to 25 ± 4 nm. We found that these AuNSs are faceted, and that the oxidized silver likely dissolves out of the nanoparticles through some of the facets on the AuNSs. This leads to a silver oxide plug on the surface of the AuNSs, which has not been reported before. The smaller AuNSs, prepared under the best conditions, absorb in the near infrared region (NIR) that is appropriate for applications, such as photothermal therapy or medical imaging. The AuNSs showed absorption peaks in the NIR similar to those of gold nanorods (AuNRs) but with better photothermal capacity. In addition, because of their negative charge, these AuNSs are more biocompatible than the positively charged AuNRs. The synthesis of small, monodisperse, stable and biocompatible nanoparticles, like the ones presented in this work, is of prime importance in biomedical applications

First-trimester screening for pre-eclampsia and small for gestational age : A comparison of the gaussian and Fetal Medicine Foundation algorithms

Pre-eclampsia (PE) and small for gestational age (SGA) can be predicted from the first trimester. The most widely used algorithm worldwide is the Fetal Medicine Foundation (FMF) algorithm. The recently described Gaussian algorithm has reported excellent results although it is unlikely to be externally validated. Therefore, as an alternative approach, we compared the predictive accuracy for PE and SGA of the Gaussian and FMF algorithms. Secondary analysis of a prospective cohort study was conducted at Vall d'Hebron University Hospital (Barcelona) with 2641 singleton pregnancies. The areas under the curve for the predictive performance for early-onset and preterm PE and early-onset and preterm SGA were calculated with the Gaussian and FMF algorithms and subsequently compared. The FMF and Gaussian algorithms showed a similar predictive performance for most outcomes and marker combinations. Nevertheless, significant differences for early-onset PE prediction favored the Gaussian algorithm in the following combinations: mean arterial blood pressure (MAP) with pregnancy-associated plasma protein A, MAP with placental growth factor, and MAP alone. The first-trimester Gaussian and FMF algorithms have similar performances for PE and SGA prediction when applied with all markers within a routine care setting in a Spanish population, adding evidence to the external validity of the FMF algorithm. The first-trimester Gaussian and Fetal Medicine Foundation algorithms have similar predictive performances for pre-eclampsia and small-for-gestational-age fetuses

Describing Complexity in Palliative Home Care Through HexCom : A Cross-Sectional, Multicenter Study

Complexity has become a core issue in caring for patients with advanced disease and/or at the end-of-life. The Hexagon of Complexity (HexCom) is a complexity assessment model in the process of validation in health-care settings. Our objective is to use the instrument to describe differences in complexity across disease groups in specific home care for advanced disease and/or at the end-of-life patients, both in general and as relates to each domain and subdomain. Cross-sectional study of home care was conducted in Catalonia. The instrument includes 6 domains of needs (clinical, psychological/emotional, social/family, spiritual, ethical, and death-related), 4 domains of resources (intrapersonal, interpersonal, transpersonal, and practical), and 3 levels of complexity (High (H), Moderate (M), and Low (L)). Interdisciplinary home care teams assessed and agreed on the level of complexity for each patient. Forty-three teams participated (74.1% of those invited). A total of 832 patients were assessed, 61.4% of which were cancer patients. Moderate complexity was observed in 385 (47.0%) cases and high complexity in 347 (42.4%). The median complexity score was 51 for cancer patients and 23 for patients with dementia (p<0.001). We observed the highest level of complexity in the social/family domain. Patients/families most frequently used interpersonal resources (80.5%). This study sheds light on the high-intensity work of support teams, the importance of the social/family domain and planning the place of death, substantial differences in needs and resources across disease groups, and the importance of relationship wellbeing at the end-of-life

Carcinoma epidermoide intraoral em Palmas, Tocantins: uma análise de incidência

&nbsp; O carcinoma epidermoide oral (CE) é um neoplasma com diferenciação escamosa originado no epitélio das mucosas da cavidade bucal, além de ser a neoplasia maligna de cabeça e pescoço mais comum, excluindo-se os carcinomas de pele não-melanomas. Os Registros de Câncer de Base Populacional (RCBP) são sistemas de informações relacionados ao Instituto Nacional do Câncer (INCA), específicos para a oncologia, que coletam, classificam e analisam os casos novos de câncer diagnosticados em moradores de uma área geográfica específica, permitindo conhecer a incidência de câncer daquela área. O presente trabalho objetivou realizar uma análise do RCBP da cidade de Palmas, Tocantins, Brasil, em um período de seis anos (2008-2013), comparado com o número de casos diagnosticados em um único serviço de atendimento municipal (Centro de Especialidades Odontológicas- CEO), no mesmo intervalo de tempo (2014-2019). Em ambos os casos, houve prevalência entre homens acima de 50 anos, o que confirma os dados epidemiológicos da OMS e do INCA relacionados ao CE. Em relação à raça, no RCBP houve predomínio da raça parda, enquanto no CEO houve predomínio da raça branca, possivelmente pelo maior número de casos em CE de lábio. Em relação à localização das lesões, no RCBP houve predomínio de CE em base de língua, enquanto no CEO houve predomínio de lesões em outras localizações. Diante destes resultados, acredita-se que (1) embora o RCBP seja um meio confiável de registro de câncer, os dados referentes à incidência de CE na população de Palmas podem estar subestimados, já que, em um mesmo intervalo de tempo, um único serviço da cidade (CEO) registrou o mesmo número de casos notificados no último RCBP; ou (2) houve um aumento real incidência de CE na população de Palmas, o que poderá ser evidenciado com a próxima divulgação de dados de registro do RCBP no período correspondente aos registros do CEO (2014-2019). Desta forma, ressalta-se a importância dos exames anatomopatológicos para a confirmação diagnóstica e a necessidade da notificação da doença pelos profissionais aos setores responsáveis, o que permite uma ampla coleta de dados epidemiológicos para o desenvolvimento de ações que minimizem os riscos do CE.&nbsp;&nbsp

The dynamic assembly of distinct RNA polymerase I complexes modulates rDNA transcription

Cell growth requires synthesis of ribosomal RNA by RNA polymerase I (Pol I). Binding of initiation factor Rrn3 activates Pol I, fostering recruitment to ribosomal DNA promoters. This fundamental process must be precisely regulated to satisfy cell needs at any time. We present in vivo evidence that, when growth is arrested by nutrient deprivation, cells induce rapid clearance of Pol I-Rrn3 complexes, followed by the assembly of inactive Pol I homodimers. This dual repressive mechanism reverts upon nutrient addition, thus restoring cell growth. Moreover, Pol I dimers also form after inhibition of either ribosome biogenesis or protein synthesis. Our mutational analysis, based on the electron cryomicroscopy structures of monomeric Pol I alone and in complex with Rrn3, underscores the central role of subunits A43 and A14 in the regulation of differential Pol I complexes assembly and subsequent promoter association.The project was supported by grant BFU2013-48374-P of the Spanish MINECO and by the Ramón Areces Foundation. O.G. held a research contract under the Ramón y Cajal program of the Spanish MINECO (RYC-2011-07967). IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from the Spanish MINECO.Peer reviewe