Practice and reflection on the constructional path of the Proof-of-Concept Center in clinical medicine / 中华医学科研管理杂志

Objective:To study the operation pattern and valuable experiences of the internationally renowned Proof-of-Concept Center(PoCC), and to improve the construction and management of PoCC in clinical medicine of our country.Methods:The data of basic structure, operation model, and performance in the health field of major PoCCs in the United States and Europe were compiled by literature review, policy combing, and official website search, and analyzed and summarized in combination with the basic national conditions and our practical experience.Results:The fundamental function of a PoCC consists of research and development support, science and technology evaluation, and communication services. The key points of building a PoCC include clear targets of service, widely opened resources, diversified operation patterns, and professional personnel.Conclusions:In China, PoCCs in the clinical medicine field could be built upon public hospitals with the full participation of physicians. Interdisciplinary cooperation, flexible mechanism, and versatile talents in technical management are also essential.

Practical evaluation of the R.E.N.A.L. score system in 150 laparoscopic nephron sparing surgeries

ABSTRACT Introduction: Nephrometric scores play an interesting role in nephron sparring surgery (NSS) planning. The aim of this study is to evaluate if R.E.N.A.L. score (RS) is capable to predict the occurrence of adverse events in laparoscopic NSS. Materials and Methods: We prospectively studied 150 laparoscopic NSS between 2015 and 2018 to evaluate the relationship between RS and incidence of adverse events. Clavien 3 or superior complications, warm ischemia time (WIT) over 30 minutes, tumor violation, positive surgical margins (PSM) and necessity of amplification of renal parenchyma during the resection of the masses to obtain free margins were considered as adverse events. We compared each item of the RS isolated and divided the patients between low risk and high risk. Results: Adverse results occurred in 48 cases (32%). Amplification of the margin of resection was observed in 28 cases (19%). WIT exceeded 30 minutes in 9 cases (6.1%), complications Clavien 3 or superior occurred in 13 cases (9%) and PSM were detected en 6 cases (4%). Comparing the patients with adverse outcomes and each item of the RS we did not find any statistical difference, but when divided into high risk and low risk, we found that patients in the high risk group had a higher tendency to present ad-verse results - 25.84% vs. 44.26% (p=0.03). Conclusions: RS system is a good way to predict adverse outcomes in NSS, especially in cases over 7. Further studies should focus on robotic approach and patient's characteristics other than the masses' aspects.

Perspectives for a new drug candidate for Chagas disease therapy

Chagas disease (CD), a neglected tropical illness caused by the protozoan Trypanosoma cruzi, affects more than 6 million people mostly in poor areas of Latin America. CD has two phases: an acute, short phase mainly oligosymptomatic followed to the chronic phase, a long-lasting stage that may trigger cardiac and/or digestive disorders and death. Only two old drugs are available and both present low efficacy in the chronic stage, display side effects and are inactive against parasite strains naturally resistant to these nitroderivatives. These shortcomings justify the search for novel therapeutic options considering the target product profile for CD that will be presently reviewed besides briefly revisiting the data on phosphodiesterase inhibitors upon T. cruzi.

Teoría sindémica como un enfoque para explicar la interacción entre problemas de salud pública / A teoria sindêmica como abordagem para explicar a interação entre problemas de saúde pública / Syndemics framework as an approach to explain the interaction between public health problems

La teoría sindémica proporciona un marco innovador que permite comprender ¿por qué ciertos problemas de salud pública se concentran geográfica y temporalmente?, y ¿cómo estos problemas interactúan biológica y socialmente?, generando efectos nocivos en grupos vulnerables. Sin embargo, la evidencia empírica que pone a prueba esta teoría aún es escasa y la existente tiene ciertas limitaciones en el enfoque y medición de conceptos claves. Por este motivo, este artículo tiene como propósito generar una discusión sobre algunas implicaciones conceptuales y metodológicas del uso de la teoría sindémica. El correcto abordaje de la teoría sindémica permite direccionar futuras investigaciones en este tema y promueve su importancia para el estudio de problemas de salud en el contexto de Latinoamérica.

A teoria sindêmica fornece um modelo inovador que nos permite entender por que determinados problemas de saúde pública estão geograficamente e temporalmente concentrados e como esses problemas interagem biológica e socialmente, gerando efeitos nocivos sobre grupos vulneráveis. No entanto, as evidências empíricas que testam essa teoria ainda são escassas e a existente apresenta certas limitações na abordagem e mensuração de conceitos-chave. Por esse motivo, este artigo tem como objetivo gerar uma discussão sobre algumas implicações conceituais e metodológicas do uso da teoria sindêmica. A correta abordagem da teoria sindêmica permite direcionar pesquisas futuras sobre o tema e promove sua importância para o estudo dos problemas de saúde no contexto da América Latina.

The syndemics theory provides an innovative framework that allows to understand why some public health problems are geographically and temporarily concentrated?, and how these problems interact biologically and socially?, generating harmful effects on vulnerable groups. However, the empirical evidence that supports this theory is still scarce and the existing has certain limitations in the approach and measurement of key concepts. For this reason, this article aims to generate a discussion about some conceptual and methodological implications of the use of syndemics theory. The correct approach to syndemics theory allows directing future research on this topic and promotes its importance for the study of health problems in the Latin American context.

Recommendations for improving photo quality in close range photogrammetry, exemplified in hand bones of chimpanzees and gorillas / Recomendaciones para mejorar la calidad de las fotos en fotogrametría de corto alcance, ejemplificado en huesos de las manos de chimpancés y gorillas

SUMMARY: Photogrammetry is becoming increasingly popular in morphological research and teaching due to its portability, ability to reliably render 3D models, and quality-to-price relationship relative to some popular surface scanners. Compared to surface scanners, however, the learning process in photogrammetry can be very time consuming. Here we describe common mistakes of photo capture in close-range photogrammetry that greatly affect 3D output and tips to improve them. Problems were identified after the 3D model construction of 780 hand bones of chimpanzees and gorillas from museum collections. Their hands are composed of 27 bones which vary in length and complexity. We show how lighting, object position and orientation, camera angle, and background affect the 3D output. By taking these factors into account, time and error rates for beginners can be greatly reduced and 3D model quality can be considerably improved.

RESUMEN: La fotogrametría está siendo cada vez más popular en la investigación y enseñanza morfológica. Esto debido a su portabilidad, confiabilidad de los modelos 3D y buena relación calidadprecio. Comparada con los escáneres de superficie, sin embargo, el proceso de aprendizaje de la fotogrametría puede llevar mucho tiempo. Aquí se describen errores comunes en la toma de fotos para fotogrametería que afectan de manera importante la creación de los modelos 3D, así como consejos para superarlos. Los problemas descritos fueron identificados luego de la construcción de 780 modelos 3D de huesos de la mano de chimpancés y gorillas depositados en distintas colecciones de museos. Las manos de estas especies están compuestas por 27 huesos que varían en tamaño y complejidad. En este artículo mostramos como la luz, la posición y orientación del objeto, el ángulo de la cámara y el fondo de la imagen afectan el resultado en 3D. Considerando estos factores, personas que están aprendiendo esta técnica pueden reducir de manera importante el tiempo y la probabilidad de error, y mejorar considerablemente la calidad de los modelos 3D.

Um diálogo teórico-metodológico sobre a técnica no pensamento de Vitor Marinho / A theoretical-methodological dialogue about the technique in Vitor Marinho's thought / Un diálogo teórico-metodológico sobre la técnica en el pensamiento de Vitor Marinho

Os anos de 1980 foram marcantes para a Educação Física, pois disseminou-se o pensamento renovador e surgiu a perspectiva sociocultural. Nesse período, houve críticas à luz das Ciências Humanas e Sociais aos paradigmas positivistas (como o tecnicismo) nas produções da época. Dessa forma, o presente estudo teve por objetivo identificar a concepção da técnica na perspectiva sociocultural por meio da análise da obra de Vitor Marinho, um dos intelectuais responsáveis pela difusão do movimento renovador. Para tal, foram analisados três textos publicados pelo autor na década de 80, evidenciando os elementos explícitos e implícitos sobre a técnica e suas questões. Os dados foram tratados qualitativamente, embasados pelo referencial teórico de Álvaro Vieira Pinto. Os resultados apontaram que a mudança de referencial teórico-epistemológico que ocorreu com o pensamento renovador promoveu contribuições para pensar a técnica em uma perspectiva crítica e humanista, embora de forma imperfeita relativamente ao referencial teórico escolhido.

The years of 1980 were important for Physical Education, because the renewing thought was disseminated and the sociocultural perspective emerged. In this period, there were criticisms in the light of the Human and Social Sciences to the positivist paradigms (like technicalism) in the productions of the time. Thus, the present study aimed to identify the conception of the technique in the sociocultural perspective through the analysis of the work of Vitor Marinho, one of the intellectuals responsible for the diffusion of the renovating movement. For that, three texts published by the author in the 80s were analyzed, evidencing the explicit and implicit elements about the technique and its questions. The data were treated qualitatively, based on the theoretical reference of Álvaro Vieira Pinto. The results pointed out that the change of theoretical-epistemological referential that occurred with the renewing thought promoted contributions to think the technique in a critical and humanistic perspective, albeit imperfectly in relation to the here chosen theoretical framework.

Los años de 1980 fueron importantes para la Educación Física, pues se diseminó el pensamiento renovador y surgió la perspectiva sociocultural. En ese período, hubo críticas a la luz de las Ciencias Humanas y Sociales a los paradigmas positivistas (como el tecnicismo) en las producciones de la época. De esta forma, el presente estudio tuvo por objetivo identificar la concepción de la técnica en la perspectiva sociocultural por medio del análisis de la obra de Vitor Marinho, uno de los intelectuales responsables de la difusión del movimiento renovador. Para ello, fueron analizados tres textos publicados por el autor en la década de 80, evidenciando los elementos explícitos e implícitos sobre la técnica y sus cuestiones. Los datos fueron tratados cualitativamente, basados en el referencial teórico de Álvaro Vieira Pinto. Los resultados apuntaron que el cambio de referencial teórico-epistemológico que ocurrió con el pensamiento renovador promovió contribuciones para pensar la técnica desde una perspectiva crítica y humanista, aunque de forma imperfecta respecto al referencial teórico escogido

Falácia dilemática nas discussões da bioética / False dilemma in bioethics discussions / Falacia dilemática en las discusiones de bioética

Resumo O artigo objetiva explicitar o sentido e a presença da falácia dilemática na discussão bioética, quando a argumentação se reduz a duas posições antagônicas, não permitindo o debate ao eliminar soluções intermediárias. A falácia acontece na deliberação dos comitês de ética clínica ou investigativa quando os membros confundem a argumentação retórica com a demonstração lógica, desconsiderando que a solução é sempre contingente. Ela também está presente nos debates públicos da sociedade sobre desafios éticos quando os participantes não assumem perspectiva pragmática, mas defendem posição ideológica que dificulta o diálogo e a discussão de soluções consensuais, sempre passíveis de revisão. A falta de certeza e a possibilidade de rever as propostas, que dependem da referência ética necessária aos contextos, são condições hermenêuticas da racionalidade prática, retórica e pragmática, bases para uma bioética crítica.

Abstract The article aims to explain the meaning and the presence of the false dilemma in the bioethics discussion, when the argumentation is reduced to two antagonistic positions, not allowing the debate because it eliminates intermediary solutions. The fallacy occurs in the deliberation of clinical or investigative ethics committees when members confuse rhetorical argumentation with logical demonstration, not taking into account that the solution is always contingent. It is also present in society's public debates on current ethical challenges, when participants do not take a pragmatic perspective, but advocate an ideological position that hinders dialogue and discussion of consensual solutions, which can always be reviewed. The lack of absolute certainty to the contexts, with is the hermeneutical condition required by practical, rhetorical and pragmatic rationality and the basis for a critical bioethics.

Resumen El artículo tiene el objetivo de explicitar el sentido y la presencia de la falacia dilemática en la discusión bioética, cuando la argumentación se reduce a dos posiciones antagónicas, no permitiendo el debate, ya que elimina las soluciones intermedias. La falacia tiene lugar en la deliberación de los comités de ética clínica o investigativa, cuando los miembros confunden la argumentación retórica con la demostración lógica, sin tomar en consideración que la solución es siempre contingente. Ésta también está presente en los debates públicos de la sociedad sobre los desafíos éticos actuales, cuando los participantes no asumen una perspectiva pragmática, sino que defienden una posición ideológica que dificulta el diálogo y la discusión de soluciones consensuales, siempre pasibles de revisión. La falta de certeza absoluta y la posibilidad de revisión de las propuestas, que dependen de la necesaria referencia ética a los contextos, condición hermenéutica exigida por la racionalidad práctica, retórica y pragmática, bases para una bioética crítica.

In Vitro Evaluation of Fusiform-Shaped Stents for Wide-Neck Intracranial Aneurysm Treatment / 신경중재치료의학

PURPOSE: Wide-neck aneurysms (WNAs) associated with a dilated parent artery (PA) are not uncommon morphological abnormalities and usually cause inappropriate wall apposition and incomplete neck coverage of a tubular stent in stent-assisted coiling of aneurysms. We aimed to introduce a fusiform-shaped stent (FSS) and test its effectiveness in treating intracranial WNAs associated with a dilated PA using a three-dimensional (3D) model. MATERIALS AND METHODS: Two FSS types were designed with the middle one-third segment dilated by 10% (FSS10) and 20% (FSS20) and were compared with the tubular-shaped stent (TSS). A patient-specific 3D WNA model was prototyped and produced, and in vitro stent placement was performed. Angiographic images of the three stent types were analyzed and compared using predetermined parameters. RESULTS: The stent lumens were significantly larger in FSS10 and FSS20 than in TSS in the middle segments (P=0.046), particularly FSS20 (P=0.018). The non-covered area at the ostium tended to be smaller in FSS10 and FSS20 than in TSS, but the difference was not significant (P>0.05). The stent length was significantly longer in FSS10 and FSS20 than in TSS. The stent cell size was significantly larger in FSS than in TSS. CONCLUSION: Better vessel wall apposition and aneurysmal neck coverage was observed for FSS than for TSS. No significant difference was observed between FSS10 and FSS20.

On the molecular drug design from viewpoint of precision medicine / 药学学报

Precision medicine (PM) involves the application of "omics" analysis and system biology to analyze the cause of disease at the molecular level for targeted treatments of individual patient. Based on the targeted treatment PM is closely related to pharmaceuticals, which, as a therapeutic means and supply front, mainly embody the two aspects:drug discovery/development, and clinical administration. Innovation of new molecular entities with safety and specific efficacy is the prerequisite and guarantee for the PM practice; on the other hand, the outcome and clues in clinical PM feedback to new drug research. PM and drug research/application are interdependent and promote each other. Aimed at precision medicine, drug discovery and development involve well-known contents:the discovery and validation of targets, the association between target functions and indications (proof of concept), lead discovery and optimization, the association between preclinical investigations and clinical trials, the lean of industrialization and pharmacoeconomics. At the molecular level the therapeutic efficacy originates from the interactive binding between specific atoms or groups of the drug molecule and the complementary atoms or groups of the macromolecular target in three-dimensional space. The strict arrangement of such critical atoms, groups, or fragments reflect specific features for a precise binding to the corresponding target. An alteration of amino acid residues in mutational targets leads to the change in conformation of the target protein, and an accurate structure of drug is necessary for binding to the mutant species and avoiding off-targeting effect. For the tailoring of clinical treatment to the individual patient design and development of various new molecular entities are critical for treatment choice according to the molecular features of biological markers of patients. This article provides some examples and methods of drug design and development in the new period.

Challenges and opportunities of drug research and development in rare diseases / 国际药学研究杂志

Rare diseases, although individually rare, affect approximately 6%-8% of the total population with more than 6000 diseases identified. The significance of and unmet need in rare diseases for both patients and society are high. Development of new treatments for rare diseases is associated with significant challenges such as low market potential for innovative pharmaceutical companies, often unclear regulatory path, lack of validated clinical endpoints and patient reported outcomes and insufficient data regarding the disease. Special incentivizing strategies such as market exclusivity, waiver or reduction of regulatory submission fees and assistance in clinical trial protocol development and tax incentives have been implemented to enhance drug development in rare and neglected diseases. The ultimate goal of these strategies is to help patients receive adequate treatments irrespective of the epidemiology of their disease. Furthermore, rare diseases, often with a well-defined pathogenesis, represent a unique opportunity for drug discovery in a given homogeneous disease with subsequent indication expansions. Although the number of rare disease treatments that became available for patients has increased, the unmet medical need is still high in this special population.