Fc-independent functions of anti-CTLA-4 antibodies contribute to anti-tumor efficacy.

Ipilimumab, a monoclonal antibody that recognizes cytotoxic T-lymphocyte associated protein 4 (CTLA-4), was the first immune checkpoint inhibitor approved by the FDA to treat metastatic melanoma patients. Multiple preclinical studies have proposed that Fc effector functions of anti-CTLA-4 therapy are required for anti-tumor efficacy, in part, through the depletion of intratumoral regulatory T cells (Tregs). However, the contribution of the Fc-independent functions of anti-CTLA-4 antibodies to the observed efficacy is not fully understood. H11, a non-Fc-containing single-domain antibody (VHH) against CTLA-4, has previously been demonstrated to block CTLA-4-ligand interaction. However, in vivo studies demonstrated lack of anti-tumor efficacy with H11 treatment. Here, we show that a half-life extended H11 (H11-HLE), despite the lack of Fc effector functions, induced potent anti-tumor efficacy in mouse syngeneic tumor models. In addition, a non-Fc receptor binding version of ipilimumab (Ipi-LALAPG) also demonstrated anti-tumor activity in the absence of Treg depletion. Thus, we demonstrate that Fc-independent functions of anti-CTLA-4 antibodies contributed to anti-tumor efficacy, which may indicate that non-Treg depleting activity of anti-CTLA-4 therapy could benefit cancer patients in the clinic.

Knowledge and Patterns of Use of Emergency Oral Contraception among Portuguese Female Users of Healthcare Services.

INTRODUCTION: The lack of knowledge about the existence, effectiveness, and supply of emergency contraception as well as access to it, its effective duration and the lack of recognition of the need for its use can prevent women from using it. The aim of this study was to ascertain the attitudes, experience, level of knowledge and information sources about emergency contraception of Portuguese female users of healthcare services. MATERIAL AND METHODS: We conducted a multicentre, cross-sectional, observational study among 280 Portuguese women users of health care services through an original and anonymous questionnaire composed of 30 questions. RESULTS: The mean age of the women who replied to the questionnaire was 33.83 ± 8.76 years. Of the observed sample, 27.7% used EC, 50% of whom with no counselling. Despite 92.1% of women claiming knowledge about emergency contraception, only 31.2% of these answered 8 - 10 questions correctly (14 in total). The media were the most frequent source of information (63.4%). Most participants (67.5%) considered that emergency contraception is associated with severe adverse reactions. Furthermore, 76% did not know the time range of effectiveness after unprotected sexual intercourse. Youngest age (p = 0.038), higher education level (p < 0.001), increasing parity (p = 0.051) and previous use of emergency contraception (p = 0.011) were identified as the determinant sociodemographic factors for a higher level of knowledge about emergency contraception. DISCUSSION: The use of emergency contraception after counselling by healthcare professionals was lower than reported in the literature. CONCLUSION: This study showed that female users of healthcare services were aware of the existence of emergency contraception, but they demonstrated a low level of knowledge about it, especially regarding the correct period of use, place of acquisition and safety issues.

Introdução: A falta de conhecimento sobre a existência, eficácia e fornecimento da contraceção de emergência, bem como a sua acessibilidade, prazo efetivo e a falta de reconhecimento da possibilidade da sua utilização podem impedir as mulheres de a utilizarem. O objetivo do estudo foi conhecer a experiência, atitudes, as fontes de informação e nível de conhecimento sobre a contraceção de emergência entre mulheres portuguesas utilizadoras dos cuidados de saúde. Material e Métodos: Foi desenvolvido um estudo observacional, transversal e multicêntrico em 280 mulheres portuguesas utilizadoras dos cuidados de saúde, através da aplicação de um questionário original e anónimo constituido por 30 questões. Resultados: A idade média das mulheres que responderam ao questionário situou-se nos 33,83 ± 8,76 anos. Da amostra em estudo, 27,7% referiram utilização prévia de contraceção de emergência, das quais 50% sem aconselhamento. Apesar de 92,1% afirmar conhecer esta opção, apenas 35,9% respondeu corretamente a entre oito a 10 questões de avaliação de conhecimento (total de 14). Os media constituiram a fonte de informação mais frequente (63,4%). A maioria das participantes (67,5%) considera que a contraceção de emergência está associada a efeitos adversos graves e 76% desconhece o intervalo de tempo de eficácia da contraceção de emergência após relações sexuais desprotegidas. A idade jovem (p = 0,038), maior nível de escolaridade (p < 0,001), o aumento da paridade (p = 0,051) e a utilização prévia de contraceção de emergência (p = 0,031) foram os fatores sociodemográficos associados a maior nível de conhecimento sobre a mesma. Discussão: O uso de contraceção de emergência após aconselhamento por profissionais de saúde foi inferior ao descrito na literatura. Conclusão: O estudo demonstrou que apesar das utilizadoras dos cuidados de saúde de afirmarem ter conhecimento da existência da contraceção de emergência, revelaram baixo nível de conhecimento sobre este tipo de contraceção, particularmente em relação ao período correto de utilização, local de aquisição e questões de segurança.

Contribuiçoes do programa de televisão "Saúde em Foco" para acadêmicos integrantes do Pet-Saúde / Contributions of television "Health Focus" program for academic members of Pet-Health / Contribuciones del programa de television "Salud en Foco" a estudiantes integrantes del Pet-Salud

Objetivo: conhecer as contribuições do programa de Televisão "Saúde em Foco" para acadêmicos integrantes do projeto PET-SAÚDE. Método: Trata-se de um estudo exploratório-descritivo, de caráter qualitativo, realizado entre agosto e dezembro de 2013, com nove acadêmicos integrantes dos projetos PET-SAÚDE, de diferentes cursos. Os dados foram coletados mediante a técnica de entrevista e interpretados pela análise de conteúdo temática, preconizada por Bardin. Resultados: Programa "Saúde em foco": estratégia instigadora do novo; Programa "Saúde em foco": ferramenta para a superação de limitações pessoais; Programa "Saúde em foco": oportunidade para a consolidação de vínculos profissionais. Concluiu-se que o programa é capaz de instigar os acadêmicos participantes desta atividade a construírem novos saberes e práticas interdisciplinares, além de desenvolver habilidades interativas e de socialização das vivências acadêmicas (AU).

Objective: to know the contributions of the television program "Health Focus" by academic members of PET-HEALTH project. Method: a qualitative, descriptive-exploratory study, carried out from August to December 2013, with nine academic members of PET-HEALTH project, in different courses. Data were collected using interview technique and interpreted by thematic content analysis by Bardin. Results: the study resulted in three categories: program "health in focus" as the instigator of the new strategy; "Health in focus" program as a tool for overcoming personal limitations; "Health in focus" program as an opportunity to build interprofessional links. Conclusion: this study concludes that the program is able to instigate the academic participating in this activity to build new knowledge and interdisciplinary practices, and develop interactive skills and socialization of academic experiences (AU).

Objetivo: saber qué aportes realiza el programa de televisión "Salud en Foco" a los estudiantes integrantes del proyecto PET-SALUD. Método: estudio exploratorio descriptivo, cualitativo, realizado entre agosto y diciembre de 2013, con nueve estudiantes que integran los proyectos PET-SALUD de diferentes carreras. Los datos fueron recolectados mediante la técnica de entrevista e interpretados por el análisis de contenido temático propuesto por Baldin. Resultados: Del estudio surgieron tres categorías: Programa "Salud en Foco": estrategia que fomenta lo nuevo; "Salud en Foco": herramienta para superar de las limitaciones personales; "Salud en Foco": oportunidad para consolidar vínculos profesionales. Conclusión: el programa es capaz de incentivar a los estudiantes que han participado de esta actividad a construir nuevos saberes y prácticas interdisciplinarias, además de desarrollar habilidades interactivas y de socialización de las experiencias académicas (AU).

Validating a Nursing Assessment instrument in a Pediatric Intensive Care Unit.

OBJECTIVE: To develop and validate a Nursing History instrument for a Pediatric Intensive Care Unit, based on the Theory of Basic Human Needs. METHODS: Methodological study, developed between October 2018 and April 2019, based on the establishment of a theoretical-conceptual structure; construction of items and of the response scale; selection and organization of items; structuring the instrument; expert opinion; and content and appearance validation. RESULTS: The instrument was organized in three sequential and complementary stages. The first stage considered data collection; the second, the collection of additional information, like Psychobiological, Psychosocial and Psychospiritual Needs; and the third collected data related to a physical examination. The instrument had good internal consistency (0,75) and an agreement percentage equal to or greater than 0,83. CONCLUSION: The Nursing History instrument developed and validated here can be considered relevant and pertinent in terms of content, clarity, scope, and appearance.

Anti-sortilin1 Antibody Up-Regulates Progranulin via Sortilin1 Down-Regulation.

Progranulin (PGRN) haploinsufficiency associated with loss-of-function mutations in the granulin gene causes frontotemporal dementia (FTD). This suggests that increasing PGRN levels could have promising therapeutic implications for patients carrying GRN mutations. In this study, we explored the therapeutic potential of sortilin1 (SORT1), a clearance receptor of PGRN, by generating and characterizing monoclonal antibodies against SORT1. Anti-SORT1 monoclonal antibodies were generated by immunizing Sort1 knockout mice with SORT1 protein. The antibodies were classified into 7 epitope bins based on their competitive binding to the SORT1 protein and further defined by epitope bin-dependent characteristics, including SORT1-PGRN blocking, SORT1 down-regulation, and binding to human and mouse SORT1. We identified a positive correlation between PGRN up-regulation and SORT1 down-regulation. Furthermore, we also characterized K1-67 antibody via SORT1 down-regulation and binding to mouse SORT1 in vivo and confirmed that K1-67 significantly up-regulated PGRN levels in plasma and brain interstitial fluid of mice. These data indicate that SORT1 down-regulation is a key mechanism in increasing PGRN levels via anti-SORT1 antibodies and suggest that SORT1 is a potential target to correct PGRN reduction, such as that in patients with FTD caused by GRN mutation.

Validating a Nursing Assessment instrument in a Pediatric Intensive Care Unit / Validación de instrumento de histórico de enfermería para Unidad De Terapia Intensiva Pediátrica / Validação de instrumento de Histórico de Enfermagem para Unidade de Terapia Intensiva Pediátrica

ABSTRACT Objective: To develop and validate a Nursing History instrument for a Pediatric Intensive Care Unit, based on the Theory of Basic Human Needs. Methods: Methodological study, developed between October 2018 and April 2019, based on the establishment of a theoretical-conceptual structure; construction of items and of the response scale; selection and organization of items; structuring the instrument; expert opinion; and content and appearance validation. Results: The instrument was organized in three sequential and complementary stages. The first stage considered data collection; the second, the collection of additional information, like Psychobiological, Psychosocial and Psychospiritual Needs; and the third collected data related to a physical examination. The instrument had good internal consistency (0,75) and an agreement percentage equal to or greater than 0,83. Conclusion: The Nursing History instrument developed and validated here can be considered relevant and pertinent in terms of content, clarity, scope, and appearance.

RESUMEN Objetivo: Elaborar y validar instrumento de Histórico de Enfermería para Unidad de Terapia Intensiva Pediátrica, basada en la Teoría de las Necesidades Humanas Básicas. Métodos: Estudio metodológico, desarrollado entre octubre/2018 y abril/2019, basado en el establecimiento de la estructura teórico-conceptual; construcción de los ítems y escala de respuesta; selección y organización de los ítems; estructuración del instrumento; opinión de especialistas; y validación de contenido y apariencia. Resultados: El instrumento ha sido organizado en tres etapas secuenciales y complementarias. La primera consideró la recogida de datos; la segunda, la recogida de informaciones adicionales, referente a las Necesidades Psicobiológicas, Psicosociales y Psicoespirituales; y la tercera, datos relativos al examen físico. El instrumento presentó consistencia interna (0,75) y porcentual de concordancia igual o superior a 0,83. Conclusión: El instrumento de Histórico de Enfermería desarrollado y validado puede ser considerado relevante y pertinente cuanto al contenido, clareza, abarcamiento y apariencia.

RESUMO Objetivo: Elaborar e validar instrumento de Histórico de Enfermagem para Unidade de Terapia Intensiva Pediátrica, com base na Teoria das Necessidades Humanas Básicas. Métodos: Estudo metodológico, desenvolvido entre outubro/2018 e abril/2019, com base no estabelecimento da estrutura teórico-conceitual; construção dos itens e escala de resposta; seleção e organização dos itens; estruturação do instrumento; opinião de especialistas; e validação de conteúdo e aparência. Resultados: O instrumento foi organizado em três etapas sequenciais e complementares. A primeira considerou a coleta de dados; a segunda, a coleta de informações adicionais, referente às Necessidades Psicobiológicas, Psicossociais e Psicoespirituais; e a terceira, dados relativos ao exame físico. O instrumento apresentou consistência interna (0,75) e percentual de concordância igual ou superior a 0,83. Conclusão: O instrumento de Histórico de Enfermagem desenvolvido e validado pode ser considerado relevante e pertinente quanto ao conteúdo, clareza, abrangência e aparência.

Validating a Nursing Assessment instrument in a Pediatric Intensive Care Unit / Validación de instrumento de histórico de enfermería para Unidad De Terapia Intensiva Pediátrica / Validação de instrumento de Histórico de Enfermagem para Unidade de Terapia Intensiva Pediátrica

ABSTRACT Objective: To develop and validate a Nursing History instrument for a Pediatric Intensive Care Unit, based on the Theory of Basic Human Needs. Methods: Methodological study, developed between October 2018 and April 2019, based on the establishment of a theoretical-conceptual structure; construction of items and of the response scale; selection and organization of items; structuring the instrument; expert opinion; and content and appearance validation. Results: The instrument was organized in three sequential and complementary stages. The first stage considered data collection; the second, the collection of additional information, like Psychobiological, Psychosocial and Psychospiritual Needs; and the third collected data related to a physical examination. The instrument had good internal consistency (0,75) and an agreement percentage equal to or greater than 0,83. Conclusion: The Nursing History instrument developed and validated here can be considered relevant and pertinent in terms of content, clarity, scope, and appearance.

RESUMEN Objetivo: Elaborar y validar instrumento de Histórico de Enfermería para Unidad de Terapia Intensiva Pediátrica, basada en la Teoría de las Necesidades Humanas Básicas. Métodos: Estudio metodológico, desarrollado entre octubre/2018 y abril/2019, basado en el establecimiento de la estructura teórico-conceptual; construcción de los ítems y escala de respuesta; selección y organización de los ítems; estructuración del instrumento; opinión de especialistas; y validación de contenido y apariencia. Resultados: El instrumento ha sido organizado en tres etapas secuenciales y complementarias. La primera consideró la recogida de datos; la segunda, la recogida de informaciones adicionales, referente a las Necesidades Psicobiológicas, Psicosociales y Psicoespirituales; y la tercera, datos relativos al examen físico. El instrumento presentó consistencia interna (0,75) y porcentual de concordancia igual o superior a 0,83. Conclusión: El instrumento de Histórico de Enfermería desarrollado y validado puede ser considerado relevante y pertinente cuanto al contenido, clareza, abarcamiento y apariencia.

RESUMO Objetivo: Elaborar e validar instrumento de Histórico de Enfermagem para Unidade de Terapia Intensiva Pediátrica, com base na Teoria das Necessidades Humanas Básicas. Métodos: Estudo metodológico, desenvolvido entre outubro/2018 e abril/2019, com base no estabelecimento da estrutura teórico-conceitual; construção dos itens e escala de resposta; seleção e organização dos itens; estruturação do instrumento; opinião de especialistas; e validação de conteúdo e aparência. Resultados: O instrumento foi organizado em três etapas sequenciais e complementares. A primeira considerou a coleta de dados; a segunda, a coleta de informações adicionais, referente às Necessidades Psicobiológicas, Psicossociais e Psicoespirituais; e a terceira, dados relativos ao exame físico. O instrumento apresentou consistência interna (0,75) e percentual de concordância igual ou superior a 0,83. Conclusão: O instrumento de Histórico de Enfermagem desenvolvido e validado pode ser considerado relevante e pertinente quanto ao conteúdo, clareza, abrangência e aparência.

Construção e validação de um histórico de Enfermagem para consulta pré-natal / Construction and validation of a Nursing history for prenatal consultation

Objetivo: construir e validar um modelo de Histórico de Enfermagem para consulta pré-natal. Metodologia: Trata-se de uma pesquisa metodológica, realizada entre maio de 2018 e fevereiro de 2019. A análise e validação de conteúdo ocorreram por meio da Técnica de Delphi, utilizando uma escala Likert. Os itens do instrumento apresentaram índice de validade do conteúdo maior ou igual a 0,80. Participaram da validação, no primeiro Ciclo de Delphi, doze juízes com conhecimento nas áreas materno-infantil, obstétrica e saúde da mulher, e dez no segundo Ciclo. Resultados: o instrumento final conta com 57 itens validados que contemplam as necessidades humanas básicas das gestantes e local para registro do exame físico. Conclusão: o instrumento construído e validado qualifica, orienta e traz cientificidade ao registro do Histórico de Enfermagem. Ao ser utilizado poderá sustentar o registro das demais etapas do Processo de Enfermagem. (AU)

Objective: Develop and validate a model of nursing history to prenatal consultation. Methodology: It is a methodological research, held between May 2018 and February 2019. The analysis and content validation occurred using the Delphi technique, using a Likert scale. For validation the items of the instrument showed Content validity Index greater than or equal to 0.80. In the first Cycle of Delphi, twelve judges with knowledge in the maternal-child, obstetric and women's health areas participated in the validation, and ten in the second Cycle. Results: The final instrument has 57 items validated, which contemplate the basic human needs of pregnant women, and a place to record the physical examination. Final considerations: The instrument constructed and validated qualifies, guides and brings scientific to the Nursing History record. When used it can sustain the registration of the other stages of the Nursing Process. (AU)

Objetivo: Construir y validar un modelo de histórico de enfermería para la consulta prenatal. Metodología: Se trata de una investigación metodológica, realizada entre mayo de 2018 y febrero de 2019. El análisis y validación de contenido ocurrió por medio de la Técnica de Delphi, utilizando una escala Likert. Para validación los ítems del instrumento presentaron índice de validez del contenido mayor o igual a 0,80. En el primer Ciclo de Delphi, doce jueces con conocimiento en las áreas materno-infantil, obstétrica y salud de la mujer participaron en la validación, y diez en el segundo Ciclo. Resultados: El instrumento final cuenta con 57 ítems validados, los cuales contemplan las necesidades humanas básicas de las mujeres embarazadas, y local para registro del examen físico. Consideraciones finales: El instrumento construido y validado califica, orienta y trae cientificidad al registro del histórico de enfermería. Al ser utilizado podrá sostener el registro de las demás etapas del Proceso de Enfermería. (AU)

A Case Study Comparing Heterogeneous Lysine- and Site-Specific Cysteine-Conjugated Maytansinoid Antibody-Drug Conjugates (ADCs) Illustrates the Benefits of Lysine Conjugation.

Antibody-drug conjugates are an emerging class of cancer therapeutics constructed from monoclonal antibodies conjugated with small molecule effectors. First-generation molecules of this class often employed heterogeneous conjugation chemistry, but many site-specifically conjugated ADCs have been described recently. Here, we undertake a systematic comparison of ADCs made with the same antibody and the same macrocyclic maytansinoid effector but conjugated either heterogeneously at lysine residues or site-specifically at cysteine residues. Characterization of these ADCs in vitro reveals generally similar properties, including a similar catabolite profile, a key element in making a meaningful comparison of conjugation chemistries. In a mouse model of cervical cancer, the lysine-conjugated ADC affords greater efficacy on a molar payload basis. Rather than making general conclusions about ADCs conjugated by a particular chemistry, we interpret these results as highlighting the complexity of ADCs and the interplay between payload class, linker chemistry, target antigen, and other variables that determine efficacy in a given setting.

O consumo de bebida alcoólica e o binge drink entre os graduandos de Medicina de uma Universidade de Minas Gerais / The consumption of alcoholic beverages and the binge drink among Medicine graduating in a Minas Gerais University

RESUMO Objetivos O estudo objetivou verificar o padrão de consumo de bebidas alcoólicas e a presença do beber pesado episódico (BPE) entre os estudantes de Medicina de uma universidade do centro-oeste de Minas Gerais. Métodos Trata-se de um estudo transversal, exploratório e descritivo, realizado com 202 graduandos do curso de Medicina de uma universidade do centro-oeste de Minas Gerais. A coleta de dados foi realizada no primeiro semestre de 2015, com a utilização de um questionário sociodemográfico e do questionário Audit. O tratamento estatístico dos dados foi realizado com a utilização da análise bivariada, por meio do teste qui-quadrado ou do teste de Fisher e de modelos multivariados de regressão logística. Resultados Observou-se que o álcool é utilizado por 76,6% dos estudantes pesquisados, e 53,7% praticavam o BPE. O consumo de bebidas alcoólicas teve associação significativa com a idade e o fato de não morar com a família e estar acima do terceiro ano de graduação. O BPE, por sua vez, esteve associado com o sexo masculino e com o fato de não morar com a família. Conclusões Este trabalho mostrou que o consumo de álcool entre os estudantes de Medicina é maior do que o da população geral e que a prática do BPE possui alta prevalência nesse grupo. Idade, não morar com a família e período mais avançado do curso foram associados a maior consumo de álcool. Ser do sexo masculino e não morar com a família se associaram a maior risco de BPE.

ABSTRACT Objectives The study had as its goal to verify the pattern of the alcoholic beverages consumption and the presence of drinking heavily snatchy (BPE) among the Medicine students of a Minas Gerais Midwest university. Methods It is about a transversal, exploratory and descriptive study, performed on 202 graduating students of the Medicine course of a Minas Gerais Midwest university. The data collet was performed on the first term of 2015, a sociodemographic questionnaire and the Audit questionnaire were used. The statistical treatment of the data was performed with the use of the bivariate analysis, through the chi-square test or by the Fisher test, and multivariate logistic regression models. Results It was noticed that the alcohol is used by 76,6% of the students surveyed, being that 53,7% practiced the drinking heavily episodic. The alcoholic beverages consumption had meaningful association with the age, not living with family and being above the 3rd year of graduation. Drinking heavily episodic had meaningful association with the males and not living with family. Conclusions This paperwork has shown that the alcohol consumption among Medicine students is bigger than among the general population and the binge drink practice has high prevalence on that group. Age, not living with the family and more advanced period of the course were associated with higher alcohol consumption. Being male and not living with the family were associated with a higher risk of BPE.

Clinical and radiological analysis of a series of periapical cysts and periapical granulomas diagnosed in a Brazilian population.

BACKGROUND: Periapical cysts (PC) and periapical granulomas (PG) are the two most common chronic inflammatory periapical diseases, but their clinicoradiological characteristics can vary depending on the methods employed in each study. The aim of the present work was to analyze the clinical and radiological profile of a series of PC and PG diagnosed in a Brazilian population. MATERIAL AND METHODS: The files of two Oral Pathology laboratories were reviewed and all cases diagnosed as PG and PC were selected for the study. Clinical and radiological information were retrieved and data were tabulated and descriptively and comparatively analyzed. RESULTS: Final sample was composed by 647 inflammatory periapical lesions, including 244 PG (38%) and 403 PC (62%). The number of women affected by PG was significantly higher than the number of women affected by PC (p=0.037). Anterior region of the maxilla was the most common affected area for both entities (39% of the cases), but the most common anatomical location of PG (anterior maxilla and posterior maxilla) was different from PC (anterior maxilla and posterior mandible) (p<0.0001). Upper lateral incisor was the most affected tooth. The mean radiological size of the PC was larger than the mean radiological size of the PG (p<0.0001) and PC showed well-defined radiological images more frequently than PG (p<0.0001). CONCLUSIONS: PC were more common than PG, both showed predilection for adult females, most lesions affected predominantly the anterior maxilla and PC presented larger mean radiological diameter and well-defined images when compared with PG. Key words:Periapical granuloma, periapical cyst, radicular cyst, diagnosis, Oral Pathology.

Transport of chaotic trajectories from regions distant from or near to structures of regular motion of the Fermi-Ulam model.

The chaotic portion of phase space of the simplified Fermi-Ulam model is studied under the context of transport of trajectories in two scenarios: (i) the trajectories are originated from a region distant from the islands of regular motion and are transported to a region located at a high portion of phase space and (ii) the trajectories are originated from chaotic regions around the islands of regular motion and are transported to other regions around islands of regular motion. The transport is investigated in terms of the observables histogram of transport and survival probability. We show that the histogram curves are scaling invariant and we organize the survival probability curves in four kinds of behavior, namely (a) transition from exponential decay to power law decay, (b) transition from exponential decay to stretched exponential decay, (c) transition from an initial fast exponential decay to a slower exponential decay, and (d) a single exponential decay. We show that, depending on choice of the regions of origin and destination, the transport process is weakly affected by the stickiness of trajectories around islands of regular motion.

Enmascaramiento de sabores en formas farmacéuticas sólidas orales / Taste masking in oral solid dosage forms

Aunque tradicionalmente ligado a formas farmacéuticas líquidas orales, el enmascaramiento del sabor como parámetro crítico en la formulación de medicamentos ha cobrado recientemente un nuevo auge en respuesta al desarrollo de formas farmacéuticas sólidas orales que persiguen una disgregación, bien ex vivo, bien en la cavidad bucal. El enmascaramiento no sólo comprende la neutralización del potencial sabor desagradable inherente al principio activo, sino también la obtención de un sabor agradable en la formulación final, con repercusión tanto a nivel sanitario, puesto que cuanto mayor sea la aceptación por parte del paciente, mayor será su adherencia al tratamiento; como a nivel económico, ya que el sabor del producto puede marcar la diferencia entre el éxito y el fracaso comercial. Mediante esta revisión se ponen de relieve las estrategias aplicables en el enmascaramiento de sabores de formas farmacéuticas sólidas orales, se clasifican y describen los principales excipientes correctores del sabor, así como se efectúa una compilación exhaustiva de las técnicas de evaluación de la eficacia de los distintos recursos empleados en el enmascaramiento del sabor desagradable. De esta forma, se amplía el ámbito de aplicación del concepto enmascaramiento del sabor, demostrándose que es un área del cual aún hay mucho por decir

Despite being traditionally associated with oral liquid dosage forms, taste masking as critical attribute in the formulation of drug products has recently experienced a renaissance, mostly due to the development of oral solid dosage forms aimed at achieving disintegration either under ex vivo conditions or even more relevantly into the oral cavity. Not only does taste masking involve the neutralization of the potential unpleasant flavour inherent to the drug substance, but also seeks to achieve tasty flavour in the final drug product, since it has influence both to a sanitary extent (the higher the patient acceptance, the better the patient compliance) and to an economical extent (since the flavour of a marketed product can make the difference between commercial success or commercial failure). The purpose of this review is to outline the strategies likely to be applied in taste masking of oral solid dosage forms, to sort out and describe the major flavour-modifying agents in the pharmaceutical field, as well as to compile comprehensively testing techniques of the efficacy of the various taste masking strategies. Consequently, this review adds to the scope of taste masking a further dimension, serving thus as a proof-of-concept that much remains still to be said in this area

IMGN853, a Folate Receptor-α (FRα)-Targeting Antibody-Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors.

A majority of ovarian and non-small cell lung adenocarcinoma cancers overexpress folate receptor α (FRα). Here, we report the development of an anti-FRα antibody-drug conjugate (ADC), consisting of a FRα-binding antibody attached to a highly potent maytansinoid that induces cell-cycle arrest and cell death by targeting microtubules. From screening a large panel of anti-FRα monoclonal antibodies, we selected the humanized antibody M9346A as the best antibody for targeted delivery of a maytansinoid payload into FRα-positive cells. We compared M9346A conjugates with various linker/maytansinoid combinations, and found that a conjugate, now denoted as IMGN853, with the N-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB) linker and N(2')-deacetyl-N(2')-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4) exhibited the most potent antitumor activity in several FRα-expressing xenograft tumor models. The level of expression of FRα on the surface of cells was a major determinant in the sensitivity of tumor cells to the cytotoxic effect of the conjugate. Efficacy studies of IMGN853 in xenografts of ovarian cancer and non-small cell lung cancer cell lines and of a patient tumor-derived xenograft model demonstrated that the ADC was highly active against tumors that expressed FRα at levels similar to those found on a large fraction of ovarian and non-small cell lung cancer patient tumors, as assessed by immunohistochemistry. IMGN853 displayed cytotoxic activity against FRα-negative cells situated near FRα-positive cells (bystander cytotoxic activity), indicating its ability to eradicate tumors with heterogeneous expression of FRα. Together, these findings support the clinical development of IMGN853 as a novel targeted therapy for patients with FRα-expressing tumors.

Validation of the Brazilian version of the Spinal Cord Independence Measure III.

INTRODUCTION: The Spinal Cord Independence Measure (SCIM III) specifically assesses individuals with spinal cord injuries. OBJECTIVE: To translate and validate the Brazilian version of SCIM III. METHOD: SCIM III was translated, back-translated and adapted to the Portuguese language. Two interviewers assessed 83 subjects with spinal cord injuries in each one of seven collaborating rehabilitation centers. Functional Independence Measure (FIM™) and ASIA motor and sensory indices were also used. After six months, subjects were re-evaluated with the same instruments. RESULTS: Examiners clearly understood the Brazilian version of SCIM III. Inter-rater intraclass correlation coefficient (ICC) was 0.918, and test-retest ICC was 0.991. After six months, the variation of gains in the FIM™ positively correlated with gains in SCIM III. CONCLUSION: The Brazilian version of the SCIM III is easy to understand, has good psychometric properties, and is valid.

Validation of the Brazilian version of the Spinal Cord Independence Measure III / Validação da versão brasileira da Medida de Independência da Medula Espinhal III

Introduction : The Spinal Cord Independence Measure (SCIM III) specifically assesses individuals with spinal cord injuries. Objective : To translate and validate the Brazilian version of SCIM III. Method : SCIM III was translated, back-translated and adapted to the Portuguese language. Two interviewers assessed 83 subjects with spinal cord injuries in each one of seven collaborating rehabilitation centers. Functional Independence Measure (FIM™) and ASIA motor and sensory indices were also used. After six months, subjects were re-evaluated with the same instruments. Results : Examiners clearly understood the Brazilian version of SCIM III. Inter-rater intraclass correlation coefficient (ICC) was 0.918, and test-retest ICC was 0.991. After six months, the variation of gains in the FIM™ positively correlated with gains in SCIM III. Conclusion : The Brazilian version of the SCIM III is easy to understand, has good psychometric properties, and is valid. .

Introdução : A Medida de Independência da Medula Espinhal III (SCIM III) avalia especificamente a funcionalidade de indivíduos com lesões da medula espinhal. Objetivo : Traduzir e validar a versão brasileira da SCIM III. Método : A SCIM III foi traduzida, contra-traduzida e adaptada para o idioma português brasileiro. Dois entrevistadores avaliaram 83 indivíduos com lesões da medular espinhal em sete centros de reabilitação colaboradores. A Medida de Independência Funcional (FIM™) e índices motor e sensitivo da ASIA também foram usados. Após seis meses, os sujeitos foram reavaliados com os mesmo instrumentos. Resultados : Os avaliadores entenderam claramente a versão brasileira da SCIM III. O coeficiente de correlação intraclasse (ICC) inter-examinadores foi 0,918, e de teste-reteste foi 0,991. Após seis meses, a variação de ganhos na FIM™ correlacionou-se positivamente com os ganhos da SCIM III. Conclusão : A versão brasileira da SCIM III é de fácil entendimento, apresenta boas propriedades psicométricas e é válida. .

Ultrastructural alterations in adult Schistosoma mansoni, harbored in non-antihelminthic treated and low-inflammatory mice by transmission electron microscopy (TEM).

This original study suggests that alterations observed on tegumental structure and egg quality of adult Schistosoma mansoni harvested from TS mice are due to their high immune tolerogenic and low-inflammatory capacity. The tegument of worms harvested from genetically selected mice for extreme phenotypes of immune oral tolerance, resistance (TR) and susceptibility (TS) were analyzed by transmission electron microscopy (TEM). Parasites recovered from TR mice showed no tegumental morphological changes. However, specimens collected from TS mice exhibited tubercle swelling with blunted and shortened spines in lower density. These tegumental alterations were similar to those described with artemether or praziquantel treatment, but without to affecting the worm surveillance, supporting observations that the host immune system influences the development and function of the tegument of worms harbored in non-antihelminthic treated TS mice. TS mice showed a higher percentage of dead eggs and a lower percentage of immature eggs than TR mice, but had similar quantities of collected eggs. This suggests that in TS mice the alterations in adult worm tegument prevented egg development, but not egg production or worm survival. These results corroborate our previous scanning electron microscopy (SEM) study indicating the influence of the host immune regulatory profile on the development and function of the worm's reproductive system and tegument.

Educação continuada/permanente como estratégia no gerenciamento de enfermagem no Sistema Único de Saúde: uma revisão integrativa / La educación continua / permanente como una estrategia para la gestión de enfermería en el sistema único de salud: una revisión integradora / Continuing/permanent education as a strategy for managing of nursing in the unique health system: an integrative review

RESUMOObjetivo: analisar as publicações que enfocam o processo de Educação continuada no âmbito da enfermagem, no período de 2008 a 2011. Método: revisão integrativa realizada nas Bases de Dados da Biblioteca Virtual da Saúde (Lilacs e Scielo), com os seguintes critérios de inclusão: possuir relação ao objetivo proposto; ano de publicação de 2008 a 2011; abordar a temática de educação continuada no âmbito da Enfermagem; possuir o texto na íntegra disponível on line; idioma em português, inglês ou espanhol. Resultados: Após a busca, foram analisados e categorizados nove artigos. Conclusão: percebeu-se que os desafios e ações por parte da equipe multiprofissional na atualidade estão relacionados à carência de incentivo às ações de Educação continuada. No âmbito da Enfermagem são ainda mais imprescindíveis essas ações, pois observa-se no cotidiano, problemas decorrentes de falta de atualização e treinamento, implicando diretamente em uma diminuição no rendimento da qualidade da assistência em saúde

Objective: To analyze the publications that focus on the process of continuing education in nursing in the period from 2008 to 2011. Method: integrative review conducted in Databases Virtual Health Library (Lilacs and SciELO), with the following inclusion criteria: having regard to its purpose; publication year from 2008 to 2011, addressing the issue of continuing education within the nursing; having the text available on line; language in English, Portuguese or Spanish. Results: After the search, were analyzed and categorized nine articles. Conclusion: it was realized that the challenges and actions by the multidisciplinary team at present are related to the lack of incentive shares of Continuing Education. Within the Nursing areeven more essential these actions, as observed in everyday life, problems arising from lack of updating and training, directly implying a decrease in the yield of the quality of health care

Objetivo: Analizar las publicaciones que se centran en el proceso de educación continua en enfermería en el período de 2008 a 2011. Método: revisión integradora a cabo en la Biblioteca de Bases de Datos Virtual en Salud (LILACS y SciELO), con los siguientes criterios de inclusión: tener en cuenta su finalidad, año publicación a partir de 2008 a 2011, abordando la cuestión de la formación continua dentro de la Enfermería, tener el texto disponible en línea, en idioma Inglés, portugués o español. Resultados: Después de la búsqueda, fueron analizados y categorizados nueve artículos. Conclusión: se dio cuenta de que los desafíos y las acciones realizadas por el equipo multidisciplinario en la actualidad están relacionados con la falta de acciones de incentivo de Educación Continua. Dentro de la Enfermería son aún más importantes estas acciones, como se observa en la vida cotidiana, los problemas derivados de la falta de actualización y capacitación, lo que implica directamente una disminución en el rendimiento de la calidad de la atención de salud

IBC's 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences and the 2012 Annual Meeting of The Antibody Society: December 3-6, 2012, San Diego, CA.

The 23rd Annual Antibody Engineering, 10th Annual Antibody Therapeutics international conferences, and the 2012 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 3-6, 2012 in San Diego, CA. The meeting drew over 800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a prelude to the main events, a pre-conference workshop held on December 2, 2012 focused on intellectual property issues that impact antibody engineering. The Antibody Engineering Conference was composed of six sessions held December 3-5, 2012: (1) From Receptor Biology to Therapy; (2) Antibodies in a Complex Environment; (3) Antibody Targeted CNS Therapy: Beyond the Blood Brain Barrier; (4) Deep Sequencing in B Cell Biology and Antibody Libraries; (5) Systems Medicine in the Development of Antibody Therapies/Systematic Validation of Novel Antibody Targets; and (6) Antibody Activity and Animal Models. The Antibody Therapeutics conference comprised four sessions held December 4-5, 2012: (1) Clinical and Preclinical Updates of Antibody-Drug Conjugates; (2) Multifunctional Antibodies and Antibody Combinations: Clinical Focus; (3) Development Status of Immunomodulatory Therapeutic Antibodies; and (4) Modulating the Half-Life of Antibody Therapeutics. The Antibody Society's special session on applications for recording and sharing data based on GIATE was held on December 5, 2012, and the conferences concluded with two combined sessions on December 5-6, 2012: (1) Development Status of Early Stage Therapeutic Antibodies; and (2) Immunomodulatory Antibodies for Cancer Therapy.