To have done everything

When a patient loses decisional capacity, the responsibility to make treatment decisions often falls on a family member who becomes the surrogate decision-maker. This case study provides an example of a situation where the medical team and the surrogate decision-maker initially disagreed on the best course of action for the patient. The ethicist was called in to lead a guided conversation to help the team and the surrogate decision-maker reach a consensus. This case illustrates the importance of allowing the surrogate decision-maker to ask clarifying questions and process their emotions before making a decision.

Gestación subrogada, ¿estamos preparados en Perú? Una reflexión desde la ética

El desarrollo de la tecnología médica hace posibles procedimientos increíbles que modifican las concepciones de vida y muerte. El principio de la vida biológica con la concepción y la consideración del inicio de la persona humana cuestiona los límites que se debieran establecer en consideración al respeto de la dignidad de la persona. Las técnicas de reproducción asistida han ido evolucionando, creando expectativas por los mejores resultados y abriendo posibilidades de realización de paternidad a parejas y personas solas. El reconocimiento de los derechos sexuales y reproductivos significó un hito que ha llevado a la realización de la gestación subrogada o vientre de alquiler. Sin embargo, surgen conflictos éticos y legales donde de fondo están el respeto de los derechos de las personas intervinientes y los diversos contextos culturales y económicos donde se desarrolla esta práctica médica. Las diversas legislaciones surgidas van desde aquellas laxas, permisivas y utilitaristas a las posiciones conservadoras. Entre ambas hay una serie de matices, donde la reflexión ética busca los cursos medios de acción teniendo en cuenta el principio de realidad y considerando siempre el respeto de los derechos y dignidad de las personas involucradas.

The development of medical technology makes possible incredible procedures that modify the conceptions of life and death. The beginning of biological life with conception and the consideration of the beginning of the human person question the limits that should be established in consideration of the respect for the dignity of the person. Assisted reproduction techniques have been evolving, creating expectations for the best results and opening possibilities of parenthood to couples and single persons. The recognition of sexual and reproductive rights was a milestone that led to the realization of surrogacy or surrogate motherhood. However, ethical and legal conflicts have arisen in which the basic issues are the respect for the rights of the persons involved and the different cultural and economic contexts in which this medical practice is developed. The various legislations that have arisen range from lax, permissive and utilitarian to conservative positions. Between the two, there are a series of nuances, where ethical reflection looks for the best courses of action, considering the principle of reality and always considering respect for the rights and dignity of the people involved.

La gestación solidaria, oportunidad reproductiva para las familias cubanas / The solidary gestation, reproductive opportunity for Cuban families i: en

La gestación solidaria es una técnica de reproducción humana asistida, destinada a parejas de distinto o igual sexo y a personas solas con alguna causa de infertilidad que les impide concebir el embarazo de manera natural. Al respecto, en el Código de las Familias en Cuba se esclarece que este proceder solo debe realizarse por motivos altruistas y de solidaridad humana, ajenos a cualquier tipo de honorarios. Teniendo en cuenta las consideraciones anteriores, se analizó el tema desde diferentes puntos de vista, con el objetivo de socializar esta práctica como una oportunidad de reproducción para las familias cubanas.

Solidarity gestation is an assisted human reproductive technique intended for different or same sex couples and to single people with some infertility problems which prevent them from conceiving in a natural way. In this respect, the Cuba's Family Code clarifies that this procedure should only be carried out due to altruistic reasons and human solidarity, without any fees. Taking into account the above considerations, the topic was analyzed from different points of view, aimed at socializing this practice as a reproduction opportunity for Cuban families.

El cuerpo femenino: una visión general desde la filosofía tradicional a la gestación subrogada / The female body: an overview from traditional philosophy to surrogacy / O corpo feminino: um panorama desde a filosofia tradicional até a gestação por substituição

La llamada gestación subrogada es una práctica cada vez más difundida en varios países del mundo. Tras las apariencias de una supuesta libertad de las mujeres para disponer libremente de su cuerpo, se esconde la realidad de una explotación de las mujeres pertenecientes a los grupos social y geográficamente más vulnerables, que tiene todas las características de una forma moderna de esclavitud puesta al servicio de conspicuos intereses económicos. Las raíces de este fenómeno se encuentran en una tradición secular de desvalorización de la mujer y de su corporeidad que ha impregnado las más diversas culturas y que aún hoy continúa, de forma latente, a pesar del reconocimiento oficial de su igual dignidad a nivel legal.

So-called surrogacy is a widespread practice in several countries around the world. Behind the appearance of a supposed freedom to dispose of their bodies, lies the exploitation of women belonging to the most socially and geographically vulnerable groups, which has all the characteristics of a modern form of slavery in the service of economic interests. The roots of this phenomenon lie in a secular tradition of devaluation of women and their corporeality that has permeated the most diverse cultures and which, despite the official recognition of their equal dignity at the national legal level, continues latently to this day.

A chamada gravidez por substituição é uma prática cada vez mais difundida em vários países do mundo. Por trás das aparências de uma suposta liberdade das mulheres de disporem de seus corpos, esconde-se a realidade de exploração das mulheres pertencentes aos grupos sociais e geográficos mais vulneráveis, que tem todas as características de uma forma moderna de escravidão a serviço de interesses econômicos conspícuos. As raízes desse fenômeno estão em uma tradição secular de desvalorização da mulher e de sua corporeidade, que permeou as mais diversas culturas e que continua até hoje, de forma latente, apesar do reconhecimento oficial de sua igual dignidade no plano jurídico.

Factors Associated with Difficulties Faced by Ward Nurses When Providing Support to Families of Patients with Advanced Cancer in Surrogate Decision-making

This study aimed to describe the types of support that ward nurses provide to families of patients with advanced cancer in surrogate decision-making and the factors associated with the difficulties these nurses experienced . An anonymous self-administered questionnaire survey was conducted among 285 nurses practicing in the cancer wards of four facilities. In total, 230 (80.7%) nurses provided support in surrogate decision-making, such as attending discussions. Additionally, 41 (17.8%) of the respondents often experienced difficulties performing this task. Results of a binary logistic regression analysis showed that the factors associated with the nurses’ recognition of difficulties were frequency of surrogate decision-making support requirements (OR=2.41, P=0.009) and incomprehension of the relationships between patients and their families (OR=2.41, P=0.009). To promote nurses’ support in surrogate decision-making, we suggest routinely collecting information on the relationships between patients and their families.

Assessing reservoir host status in leishmaniasis with special reference to the infectiousness of Leishmania (Viannia) braziliensis infections in wild rodents

ABSTRACT Molecular methods have been responsible for a notable increase in the detection of Leishmaniinae infections in wild animals. Determining their infectiousness is of paramount importance in evaluating their epidemiological significance. One of the most efficient ways of determining infectiousness for vector borne diseases is xenodiagnosis with the appropriate vector. However, this is logistically very difficult to accomplish in the field, and an ideal solution is to find a molecular surrogate for xenodiagnosis. In this review we discuss different approaches to the problem by focusing on the infectiousness of Leishmania (Viannia) braziliensis in rodents under laboratory and field conditions. Comparisons with similar studies for other Leishmania species emphasizes that there are pivotal differences in the infectiousness and the importance of asymptomatic infections in different hosts. Potentially the most promising surrogate is the real time quantitative PCR (qPCR). However, its success depends on choosing a tissue that relates to the vector's feeding location and the parasite's tissue tropism. This requires detailed knowledge of the infection of each species in its wild hosts. We conclude that for L. (V.) braziliensis infections in wild rodents the tissue of choice for a molecular xenodiagnostic test, based on the qPCR is blood, providing that a significant number of samples must be examined.

Continue with ICU care – she is a spiritual being

This case study discusses a dispute between the healthcare team and the patient’s surrogate decision maker at a cancer centre. While the healthcare team deemed further care to be futile, the patient’s husband argued that they should continue to try to reverse his wife’s acute decline. This case study illustrates the inertia and moral distress that can result when there are differences between patients/surrogates and the healthcare team in their goals for intensive care. The issues of moral distress and an inability to make decisions were addressed by involving an ethics consultant, and by creating institutional mechanisms to address end-of-life issues at an earlier stage

A técnica da maternidade substitutiva: uma revisão bibliográfica / The technique of substitutive maternity: a bibliographic review / La técnica de la maternidad sustitutiva: una revisión bibliográfica

Objetivo: contribuir com reflexões acerca da maternidade substitutiva. Metodologia: realizou-se uma revisão bibliográfica sistemática, de artigos em português, em bases de dados eletrônicas (PubMed, Scielo, BVS e Periódicos CAPES), de 2015 a 2020, resultando em quatro artigos que compõem a revisão. Resultados: os quatro estudos apontam para a inexistência de legislação específica no Brasil sobre as técnicas de reprodução assistida e a maternidade substitutiva e suas consequências. Um artigo destaca a importância do envolvimento de um(a) profissional psicólogo(a) na maternidade substitutiva. Conclusão: atualmente, devido à inexistência de legislação brasileira específica, são seguidas as resoluções do Conselho Federal de Medicina sobre as técnicas de reprodução assistida e maternidade substitutiva. O(a) profissional psicólogo(a) pode contribuir no processo da maternidade substitutiva. Ressaltamos a importância de discussões e disseminação do tema.

Objective: to contribute with reflections on surrogate motherhood. Methods: a systematic bibliographic review of articles in Portuguese was conducted in electronic databases (PubMed, Scielo, BVS, and Capes Periodicals) in the last five years, with four articles comprising the review. Results: the studies showed the lack of specific legislation in Brazil on assisted reproduction techniques and surrogate motherhood and its consequences. One study pointed out the importance of the involvement of a professional psychologist in surrogate motherhood. Conclusion: due to the lack of Brazilian legislation, the citizens follow the Federal Council of Medicine's regulations on assisted reproduction techniques and surrogate motherhood. A professional psychologist can contribute to the process of substitutive motherhood. We emphasize the importance of discussions and dissemination of the theme.

Objetivo: contribuir con reflexiones sobre la maternidad subrogada. Metodología: se realizó una revisión bibliográfica sistemática de artículos en portugués en bases de datos electrónicas (PubMed, Scielo, BVS y Capes Periodicals) en los últimos cinco años, con cuatro artículos que componen la revisión. Resultados: los estudios apuntan a la falta de legislación específica en Brasil sobre técnicas de reproducción asistida y maternidad subrogada y sus consecuencias. Un artículo destaca la importancia de la participación de un psicólogo profesional en la maternidad subrogada. Conclusíon: actualmente, debido a la falta de legislación brasileña específica, se siguen las resoluciones del Consejo Federal de Medicina sobre técnicas de reproducción asistida y maternidad subrogada. El psicólogo profesional puede contribuir al proceso de la maternidad subrogada. Destacamos la importancia de la discusión y difusión del tema.

Significance of emerging clinical oncology endpoints in support of overall survival

Despite a better understanding of the pathophysiology and development of newer therapeutic options, cancer remains an area with several unmet needs. Although overall survival (OS) remains a gold standard endpoint for all cancer therapies, it poses challenges such as the requirement of a long?term follow?up, a higher number of patients, and a higher financial burden. Therefore, surrogate endpoints such as progression?free survival, time to progression, duration of response, and objective response rate are being investigated and used in oncology studies. Patient?related outcomes that measure the patient抯 overall health, quality of life, and satisfaction in the long term are crucial surrogate endpoints considered for drug approval. Surrogate endpoints shorten oncology clinical studies and accelerate the evaluation and implementation of newer therapies. Emerging surrogate endpoints such as biomarkers, immune?related response criteria, minimal residual disease, and pathological complete response are increasingly being considered in oncology trials. Validation of surrogate endpoints enables their substitution for OS and gain market approval. The selection of surrogate endpoints for an oncology trial depends on cancer type and stage, the purpose of treatment, and expected duration of survival for the relevant disease. With the advent of individualized approach and complex study designs, the field of oncology is currently undergoing a paradigm shift. The use of newer surrogate endpoints will aid in accelerating the drug development process, making patient care for oncology more accessible

Indução da lactação em mulheres nuligestas: relato de experiência / Inducción de la lactancia en mujeres nuligestas: informe de experiencia / Lactation induction in women who never got pregnant: experience report

Resumo Objetivo relatar a experiência de indução da lactação em nuligestas realizada por enfermeira consultora em aleitamento. Método relato de experiência. O processo de indução láctea foi realizado com três mulheres por motivo de gestação em útero de substituição e relacionamento homoafetivo. Resultados todas perceberam o aumento de tamanho e a sensibilidade nas mamas, bem como apresentaram secreção láctea. No entanto, a continuidade da amamentação foi diferenciada entre elas. A primeira não recebeu apoio de profissionais de saúde no contexto de pós-parto hospitalar, nem em casa, e não deu continuidade à amamentação. A segunda recebeu apoio da equipe do hospital e da parceira, amamentando por três meses. A terceira, com o apoio da parceira, amamentou por dois meses, mas interrompeu por sentir-se inibida por familiares. Conclusão e implicações para a prática a técnica de indução é capaz de desencadear a produção láctea. Já o processo de amamentação só se estabeleceu mediante a associação com a rede de apoio, o acolhimento, o incentivo da equipe de saúde e o olhar integral à mulher e sua família. Dessa forma, o cuidado de Enfermagem na indução láctea não deve focar apenas no manejo da indução, mas transcender o aspecto técnico, o que se mostra como fundamental para a proteção, o estabelecimento e a continuidade da amamentação.

Resumen Objetivo reportar la experiencia de inducir la lactancia en nuligestas realizada por una consultora de enfermería en lactancia materna. Método relato de experiencia. El proceso de inducción de la leche se realizó con tres mujeres por embarazo en útero de reemplazo y relación homoafectiva. Resultados todas notaron el aumento de tamaño y la sensibilidad en las mamas, además de presentar secreción de leche. Sin embargo, la continuidad de la lactancia materna se diferencia entre ellos. La primera no recibió apoyo de los profesionales de la salud en el contexto posparto hospitalario, ni en el domicilio, y no continuó con la lactancia. La segunda recibió apoyo del personal del hospital y su pareja, amamantando durante tres meses. La tercera, con el apoyo de su pareja, amamantó durante dos meses, pero la interrumpió porque se sentía inhibida por familiares. Conclusión e implicaciones para la práctica la técnica de inducción es capaz de desencadenar la producción de leche. El proceso de lactancia materna, en cambio, solo se estableció a través de la asociación con la red de apoyo, la acogida, el estímulo del equipo de salud y la mirada integral a la mujer y su familia. Así, el cuidado de Enfermería en la inducción de la leche no debe enfocarse solo en el manejo de la inducción, sino trascender el aspecto técnico, que se muestra fundamental para la protección, el establecimiento y la continuidad de la lactancia materna.

Abstract Objective to report the experience of lactation induction in women who never got pregnant by a lactation consultant nurse. Method experience report. The process of lactation induction was performed with three women due to surrogate pregnancy and homosexual relationships. Results all noticed an increase in the size and sensitivity of the breasts, as well as milk secretion. However, the continuity of breastfeeding was different between them. The first did not receive support from health professionals in the postpartum hospital setting, nor at home, and did not continue breastfeeding. The second received support from the hospital staff and her partner, breastfeeding for three months. The third, with the support of her partner, breastfed for two months, but stopped because she felt inhibited by family members. Conclusion and implications for practice the induction technique is capable of triggering milk production. However, the breastfeeding process was only established through the association with the support network, the reception, the encouragement of the health team, and the comprehensive view of the woman and her family. Thus, nursing care in lactation induction should not focus only on the management of induction, but transcend the technical aspect, which is essential for the protection, establishment, and continuity of breastfeeding.

Affordability and quality of cross-border reproductive care from the perspective of surrogacy mediating agencies in Spain / Asequibilidad y calidad de la atención reproductiva transfronteriza desde la perspectiva de las agencias mediadoras de gestación por sustitución en españa

RESUMEN La gestación por sustitución contribuye a la transformación de las concepciones sociales de la filiación y los cambios en las estrategias reproductivas de las familias. En la presente contribución se relaciona la teoría de la atención reproductiva transfronteriza con las teorías posmodernas de la vida familiar, con el propósito de explorar qué temáticas, elementos y contenidos utilizan las agencias intermediarias de gestación por sustitución que tienen por destinatarios a las madres y padres de intención españoles. Se utiliza la metodología cualitativa y la técnica de análisis de contenido temático tras el registro de la información online recogida de las agencias. Los resultados evidencian el papel de estas agencias mediadoras en los procesos de gestación por sustitución en España, además de generar conocimiento en el área de las nuevas formas familiares constituidas mediante técnicas de reproducción asistida.

ABSTRACT Substitution pregnancy contributes to the transformation of social conceptions of filiation and changes in the reproductive strategies of families. This contribution relates the theory of cross-border reproductive care with post-modern theories of family life in order to explore which themes, elements and contents are used by intermediary surrogate pregnancy agencies which target Spanish mothers and fathers. The qualitative methodology and the technique of thematic content analysis after registration of the online information collected from the agencies is used. The results show the role of these intermediary agencies in the process of gestation by substitution in Spain, as well as generating knowledge in the area of new family forms constituted by assisted reproduction techniques.

Peptidomimetic-based antibody surrogate for HER2

Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers. Although monoclonal antibodies are currently used as marketed drugs, their large molecular weight, high cost of production and susceptibility to proteolysis could be a hurdle for long-term application. In this study, we reported a strategy for the development of artificial antibody based on

Serum antithyroglobulin antibody levels are not a good predictive factor on detection of disease activity in patients with papillary thyroid carcinoma

Objective: Thyroglobulin antibodies (TgAb) are detected in thyroid cancer patients up to 25%. We investigated the prognostic value of TgAb positivity in patients with papillary thyroid carcinoma (PTC) after initial therapy. Patients and Methods: A database of 109 consecutive patients who underwent total thyroidectomy and therapeutic lateral neck dissection followed by remnant ablation for PTC between January 1989 and December 2014 was reviewed We recorded the patients' all serum Tg and TgAb levels over time to establish changing trends. Patients were classified as either positive or negative according to serum TgAb levels. The recurrence or persistence rates in both groups were compared. Results: Of the 109 patients enrolled 14 patients had TgAb positivity. Thirty-two (29.3%) showed disease recurrence or persistent disease during 101 months of follow-up. Twenty-seven of 95 patients (28.4%) with negative TgAb had persistent or recurrent disease, whereas 5 of 14 patients (35.7%) with positive TgAb had persistence or recurrence (P = 0.57). No significant difference in disease-free survival (115.3 ± 10.8 vs. 224.1 ± 16.6 months, P = 0.78) and overall survival (P = 0.59) was observed between TgAb positive and TgAb negative patients. Conclusions: TgAb status is not useful as a prognostic and predictive factor for clinical outcomes in patients with PTC in our experience

In vivo phagocytosis and hematology in Astyanax altiparanae, a potential model for surrogate technology / Fagocitose in vivo e hematologia em Astyanax altiparanae, um potencial modelo para tecnologia de propagação mediada

Abstract Although the potential of surrogate propagation technology for aquaculture and conservation of Neotropical fish, the poor understanding of the host immune system may results in rejection and destruction of the donor material. Thus, it is necessary to study and to develop methods to evaluate the effects of immunosuppressive drugs employment and to evaluate the immunocompatibility between donor and receptor. Thus, the present study aimed to optimize a methodology to assess in vivo phagocytosis in Astyanax altiparanae using Saccharomyces cerevisiae and to evaluate their hematological response resultant from the inflammatory induction. To this, S. cerevisiae were labeled with Congo red and injected in the coelomic cavity of A. altiparanae at the concentration of 2.5 x 106 cells mL-1. A PBS solution and a non-injected group were kept as control. Fish blood was sampled and the phagocytic capacity and index were determined at 1, 2, 3 and 6 h post-injection (hpi). The yeast injection successfully stimulated phagocytosis, with the best result for phagocytosis assessment after 2 hpi. Moreover, it was achieved a high traceability of phagocytized and non-phagocytized yeast under optic microscopy analysis due to the Congo red labeling. The hematological profile was similar to usually observed in early infections, indicating lymphocyte migration to inflammatory site and increase in number of circulating phagocytes due to natural response to inflammatory stimulus. In conclusion, our method was efficient to assess in vivo phagocytosis in A. altiparanae and will be an important tool to evaluate the efficacy of immunosuppressive drugs in this species. Additionally, these results may serve as support for further studies in fish immunocompetence, both in laboratory and in field conditions.

Resumo Apesar do potencial apresentado pela tecnologia de propagação mediada para a aquicultura e conservação de peixes Neotropicais, o pobre entendimento do sistema imune do hospedeiro pode resultar na rejeição e destruição do material do doador. Com isso, se fazem necessários o estudo e o desenvolvimento de métodos para análise tanto dos efeitos de drogas imunossupressoras quanto para a avaliação da imunocompatibilidade entre doadores e receptores. Logo, o presente estudo teve como objetivo aperfeiçoar um método para analisar a fagocitose in vivo em Astyanax altiparanae usando Saccharomyces cerevisiae marcado e avaliar seu perfil hematológico resultante da indução inflamatória. Para isso, S. cerevisiae foram marcados com vermelho Congo e injetados na cavidade celomática dos A. altiparanae na concentração de 2,5 x 106 células.mL-1. Peixes injetados com PBS e peixes não injetados foram mantidos como controle. Sangue foi colhido e a capacidade fagocítica e o índice fagocítico foram determinados após 1, 2, 3 e 6 horas após à injeção (hpi). A injeção de levedura estimulou a fagocitose com sucesso, com o melhor resultado atingido após 2 hpi. Ainda, foi observada uma alta rastreabilidade das leveduras fagocitadas e não fagocitadas sob microscopia óptica devido à marcação com vermelho Congo. O perfil hematológico foi similar ao observado usualmente em infecções recém-induzidas, indicando migração de linfócitos ao sítio inflamatório e aumento no número de fagócitos circulantes devido à resposta natural ao estímulo inflamatório. Como conclusão, nosso método foi eficiente para analisar a fagocitose in vivo em A. altiparanae e será uma ferramenta importante para a avaliação de eficácia de drogas imunossopressoras para esta espécie. Em adição, estes resultados podem contribuir para futuros estudos em imunocompetência em peixes, tanto em âmbito laboratorial quanto a campo.

Time to untreatable progression is an appropriate surrogate endpoint for overall survival in patients with hepatocellular carcinoma after transarterial chemoembolization

Aims: The aim of the study was to determine whether the time to progression (TTP) or time to untreatable progression (TTUP) is an appropriate surrogate endpoint for overall survival (OS) in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Materials and Methods: Eighty-four patients with Barcelona clinic liver cancer (BCLC) stage B or C HCC underwent TACE. The correlations of TTP and TTUP with OS were evaluated after a log transformation of the indicated values. After identifying independent prognostic factors of TTP, TTUP, and OS, the partial correlations of TTP and TTUP with OS were analyzed in all patients and subgroups. Subsequently, the prognostic value of TTP and TTUP was compared by the multivariate survival analysis of OS. Results: Both the BCLC stage and tumor number were correlated with TTP and TTUP. In addition, the BCLC stage, initial treatment failure, and sorafenib administration were associated with OS. In all patients, the correlation coefficients of TTP and TTUP with OS were 0.559 and 0.789, respectively. Adjustment for independent prognostic factors yielded partial correlation coefficients which were 0.433 and 0.697, respectively. Furthermore, OS was found to be associated with TTUP (P = 0.003; hazard ratio: 0.253; 95% confidence interval: 0.10–0.63) but not with TTP. Conclusion: Untreatable progression is more representative of clinical progression in patients with HCC who underwent TACE. In the current study, TTUP is a more appropriate surrogate endpoint for OS than TTP. Future studies should explore whether untreatable progression is a valuable endpoint event in clinical trials or an indicator of the need for second-line therapy

Preventive Effects of Enicostemma littorale Blume Extract against Dexamethasone Induced Insulin Resistance in Wistar Rats.

Background: Insulin resistance is a pathological condition in which physiological levels of insulin produce only subnormal biological responses. In such instances, β cells of the pancreas produce more insulin but the cells in other body tissues are resistant to insulin leading to hyperinsulinemia, and subsequent hyperglycemia further results in metabolic syndrome. Aim and Objectives: This study was aimed to evaluate the hydro-alcoholic extract of Enicostemma littorale (ELE) in preventing dexamethasone 8mg/kg induced insulin resistance. Materials and Methods: Thirty-six male Wistar rats were categorized into Group I plain control that received distilled water, Group II dexa control that received dexamethasone 8mg/kg. Group III and Group IV received dexamethasone 8 mg/kg along with Metformin 500 mg/kg and 1g/kg respectively. Group V and VI received dexamethasone along with ELE 2.5 g/kg and 3.5 g/kg respectively. At the end, the fasting and repeated blood samples were collected at 30, 60 and 120 min for the esti tion of post Intraperitoneal Glucose Tolerance Test (IPGTT), serum glucose and insulin. Data were utilized for the assessment of the homeostasis model of assessment for insulin resistance and sensitivity, Gutt, Matsuda, fasting glucose to insulin ratio and disposition indices. Results: All insulin sensitivity indices were worsened in dexa control group as compared to plain control (P<0.05). ELE 3.5 g/kg significantly lowered fasting glucose and insulin compared to metformin 1 g/kg (P<0.05), and significantly prevented the fall of insulin sensitivity indices compared to dexa control group (P<0.05). Glycosuria and ketonuria were also absent in ELE 3.5 g/kg group. Conclusion: ELE 3.5 g/kg showed efficacy in preventing insulin resistance evidenced by improved insulin sensitivity indices comparable with that of metformin 1 mg/kg.

Research progress of the surrogate of protection of pneumococcal conjugate vaccine / 中华预防医学杂志

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 μg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.

Substitution gestation: the family in the discussions of the brazilian written media / Gestación por sustitución: la familia en los discursos de los medios de comunicación escritos brasileños / Gestação de substituição: a família nos discursos da mídia escrita brasileira

ABSTRACT Objective: to understand the different positions of the subject attributed to the family in the substitution gestation process. Method: documentary-type qualitative research, based on Cultural Studies, in the post-structuralism field, based on Michel Foucault's discourse and statement tools. For such, there were analyzed discourses published in the Brazilian written media, between September and December in the year 2016, on subjects who experienced the substitution gestation. Results: The speeches point out that the biological parents should monitor and control gestation. They emphasize that the cares with the baby, especially maternal breastfeeding, must be accompanied by the father and realized by the biological mother. Another point is that such technology makes it possible to experience the position of culturally constituted father and mother for the subjects who wish to have children. The discourses reinforce distinct roles for biological father and mother and surrogate mothers, presented as happy with this family formation. The statements divide, distribute and order the roles of motherhood between the two mothers in order in order to naturalize the substitution gestation. To this end, they reinforce the discourses on maternal breastfeeding and emphasize the medicalization of the female body in the substitution gestation. Conclusion: the substitution gestation was recognized as a distinct conception form, but reinforce that it does not entail another maternity form. The media are concerned with demonstrating the rituals that assist in the constitution of maternal and paternal subjects, in order to teach ways of living this gestation. Therefore, experiencing the substitution gestation is one of the possibilities for constituting a family.

RESUMEN Objetivo: comprender las diferentes posiciones de sujetos atribuidas a la familia en el proceso de gestación por sustitución. Método: estudio cualitativo, tipo documental, con base en los Estudios Culturales, en la vertiente posestructuralista, fundamentada en las herramientas de discurso y anunciado por Michel Foucault. Para ello, se analizaron discursos publicados en los medios de comunicación escritos de Brasil, entre septiembre y diciembre de 2016, respecto a sujetos que vivenciaron la gestación por sustitución. Resultados: los discursos señalan que los padres biológicos deben acompañar y controlar la gestación. Además, se resalta que los cuidados con el bebé, en especial la lactancia materna, deben ser asistidos por el padre y realizados por la madre biológica. Otra cuestión es que tal tecnología permite vivenciar la posición del padre y de la madre, constituidos culturalmente a los sujetos que desean tener hijos. Los discursos refuerzan diferentes roles para el padre y la madre biológicos y las madres por sustitución, presentados como felices con esta formación familiar. Los enunciados dividen, distribuyen y orden los roles de la maternidad entre ambas madres, con el objetivo de naturalizar la gestación por sustitución. Por lo tanto, se refuerzan los discursos sobre la lactancia materna y se enfatiza la medicalización del cuerpo femenino en la gestación por sustitución. Conclusión: la gestación por sustitución fue reconocida como una forma distinta de concebir, pero hacen hincapié en que no conduce a otra forma distinta de la maternidad. Los medios de comunicación se ocupan en demonstrar los rituales que auxilian en la constitución de sujetos maternos y paternos, para enseñar los modos de vivir de esta gestación. Por ende, vivenciar la gestación por sustitución es una de las posibilidades de constituirse una familia.

RESUMO Objetivo: compreender as diferentes posições de sujeito atribuídas à família no processo de gestação de substituição. Método: pesquisa qualitativa, do tipo estudo documental com base nos Estudos Culturais, na vertente pós-estruturalista, fundamentada nas ferramentas de discurso e enunciado de Michel Foucault. Para tanto, foram analisados discursos publicados na mídia escrita brasileira, entre setembro e dezembro no ano de 2016, sobre sujeitos que vivenciaram a gestação de substituição. Resultados: os discursos apontam que os pais biológicos devem acompanhar e controlar a gestação. Destacam que os cuidados com o bebê, especialmente o aleitamento materno, devem ser acompanhados pelo pai e realizados pela mãe biológica. Outro apontamento, é que tal tecnologia possibilita vivenciar a posição de pai e mãe constituídos culturalmente aos sujeitos que desejam ter filhos. Os discursos reforçam papéis distintos para pai e mãe biológicos e mães substitutas, apresentados como felizes com essa formação familiar. Os enunciados dividem, distribuem e ordenam os papéis da maternidade entre as duas mães visando naturalizar a gestação de substituição. Para tanto, reforçam os discursos sobre aleitamento materno e enfatizam a medicalização do corpo feminino na gestação de substituição. Conclusão: os discursos reconhecem a gestação de substituição foi reconhecida como forma distinta de concepção, mas reforçam que não acarreta em outra forma distinta de maternidade. As mídias se ocupam em demonstrar os rituais que auxiliam na constituição de sujeitos maternos e paternos, para ensinar modos de viver essa gestação. Portanto, vivenciar a gestação de substituição é uma das possibilidades de constituir família.

In vitro-engineered non-antibody protein therapeutics

Antibodies have proved to be a valuable mode of therapy for numerous diseases, mainly owing to their high target binding affinity and specificity. Unfortunately, antibodies are also limited in several respects, chief amongst those being the extremely high cost of manufacture. Therefore, non-antibody binding proteins have long been sought after as alternative therapies. New binding protein scaffolds are constantly being designed or discovered with some already approved for human use by the FDA. This review focuses on protein scaffolds that are either already being used in humans or are currently being evaluated in clinical trials. Although not all are expected to be approved, the significant benefits ensure that these molecules will continue to be investigated and developed as therapeutic alternatives to antibodies. Based on the location of the amino acids that mediate ligand binding, we place all the protein scaffolds under clinical development into two general categories: scaffolds with ligand-binding residues located in exposed flexible loops, and those with the binding residues located in protein secondary structures, such as α-helices. Scaffolds that fall under the first category include adnectins, anticalins, avimers, Fynomers, Kunitz domains, and knottins, while those belonging to the second category include affibodies, β-hairpin mimetics, and designed ankyrin repeat proteins (DARPins). Most of these scaffolds are thermostable and can be easily produced in microorganisms or completely synthesized chemically. In addition, many of these scaffolds derive from human proteins and thus possess very low immunogenic potential. Additional advantages and limitations of these protein scaffolds as therapeutics compared to antibodies will be discussed.