Optimization of on-site supervision strategy based on big data of quality risk in drug enterprises / 中国药房

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Preparation and quality evaluation of Eriodictyol chewable tablet / 中国药房

OBJECTIVE To prepare the Eriodictyol chewable tablet and to evaluate its quality. METHODS The chewable tablet was prepared by the wetting granulation method by using microcrystalline cellulose （MCC） and mannitol as fillers， polyvinylpyrrolidone （PVP） as adhesive， citric acid and sucralose as flavor correction agents， magnesium stearate as lubricant. The comprehensive evaluation was conducted on Eriodictyol chewable tablets with the dosage of each excipient as a factor using the appearance， taste， flavor and texture as indicators. The ratio of excipients was optimized by orthogonal test， and the quality of Eriodictyol chewable tablets prepared by optimized formulation was evaluated in terms of appearance， weight difference， hardness， fragility， eriodictyol content， dissolution and content uniformity. RESULTS The optimal formulation was as follows： 26.4% eriodictyol （50 mg each piece）， 45% mannitol， 25% MCC， 0.3% citric acid， 0.3% sucralose， 1% magnesium stearate， 2% PVP （preparing 5% solution using purified water）. The scores of 3 batches of Eriodictyol chewable tablets in the validation test were 8.76， 8.75 and 8.80 （RSD＝0.30%， n＝3）， respectively. The Eriodictyol chewable tablet had a complete appearance and a smooth surface； the average tablet weight was 192.57 mg， the average hardness was 57.36 N， the fragility was 0.09%， the average content of eriodictyol per tablet was 50.74 mg， the cumulative dissolution within 30 min was exceeding 80%， and the content uniformity was 5.51. CONCLUSIONS Eriodictyol chewable tablet prepared by optimal formulation conforms to the requirements of the 2020 edition of Chinese Pharmacopoeia.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Niveles de referencia diagnósticos en equipos de radiografía dental en Bogotá, Colombia

Introducción: Las radiografías dentales son una de las exposiciones médicas más frecuentes a la radiación ionizante. El uso de radiación ionizante está asociado a un riesgo probable de desencadenar efectos biológicos adversos y posibles daños a la salud del paciente. Para evitar que los pacientes reciban dosis innecesariamente altas durante estas exposiciones, la Comisión Internacional de Protección Radiológica recomienda la utilización de los niveles de referencia para diagnóstico, como una herramienta efectiva de ayuda a la optimización de la protección radiológica de los pacientes. Objetivo: Estimar los niveles de referencia para diagnóstico en radiografía dental intraoral y panorámica en la ciudad de Bogotá, D. C. Metodología: Se evaluaron los parámetros de exposición radiográficos de los equipos y la calidad de imagen en 68 equipos de radiografía dental periapical y 23 equipos de radiografía panorámica. Se estimaron las magnitudes dosimétricas de kerma incidente en aire (Kai) en equipos intraorales para la radiografía de un maxilar molar de un adulto y el producto kerma aire-área (PKA) en equipos de radiografía panorámica en un examen de un adulto estándar. Resultados: El tercer cuartil de la distribución de kerma incidente en aire para radiografía intraoral fue de 3,3 mGy y del producto kerma aire-área para radiografía panorámica fue de 103,9 mGycm2. En la distribución de frecuencias de kerma incidente en aire para radiografía intraoral, el porcentaje más alto de equipos estuvo en el rango de 2,0-3,0 mGy. En la distribución de frecuencias del producto kerma aire-área para los equipos de radiografía panorámica, el porcentaje más alto de equipos estuvo en el rango de 60 a 80 mGycm2. Discusión: Las instituciones consideradas para establecer los Niveles de Referencia para Diagnóstico en este estudio contaron con una adecuada calidad de la imagen evaluada con un maniquí dental, pero las variaciones en las dosis de radiación entre instituciones señalan la necesidad de implementar herramientas que contribuyan a la optimización de las prácticas. Conclusiones: Se recomienda usar los valores de los niveles de referencia para diagnóstico encontrados en esta investigación para optimizar la protección radiológica en las exposiciones radiológicas dentales, y se espera que este estudio sirva de base para nuevas investigaciones en las demás ciudades del país.

Introduction: Dental X-rays are one of the most frequent medical exposures to ionizing radiation. The use of ionizing radiation is associated with a probable risk of triggering adverse biological effects and possible damage to the patient's health. To prevent patients from receiving unnecessarily high doses during these exposures, the International Commission on Radiological Protection recommends the use of diagnostic reference levels as an effective tool to help optimize radiological protection for patients. Objective: To estimate diagnostic reference levels in intraoral and panoramic dental radiography in the city of Bogotá, D.C. Methodology: In 68 periapical dental radiography equipment and 23 panoramic radiography equipment, the radiographic exposure parameters of the equipment and image quality were evaluated. The dosimetric magnitudes of incident air kerma (Ka,i) in intraoral equipment for the radiography of a maxillary molar of an adult and the air kerma-area product (PKA) in panoramic radiography equipment in a standard adult examination were estimated. Results: The third quartile of the incident air kerma distribution for intraoral radiography was 3,3 mGy and the air kerma-area product for panoramic radiography was 103,9 mGycm2. In the frequency distribution of incident air kerma for intraoral radiography, the highest percentage of equipment was in the range of 2,0-3,0 mGy, and in the frequency distribution of the air kerma-area product for equipment of panoramic radiography, the highest percentage of the equipment was in the range of 60 to 80 mGy cm2. Discussion: The institutions considered to establish the diagnostic reference levels in this study had an adequate quality of the image evaluated with a dental phantom, but the variations in radiation doses between institutions indicate the need to implement tools that contribute to the optimization of the practices. Conclusions: It is recommended to use the values of the diagnostic reference levels found in this research to optimize radiological protection in dental radiological exposures, and it is expected that this study will serve as a basis for further research in other cities of the country.

Optimization Method of Whole Wheat Flour, Soybean Flour, Oyster Meat Powder for Nutrient- Dense Composite Flour

Aim: To study the production of Nutrient – Dense Composite Flour from the blends of whole wheat flour, soybean flour (full fat) and oyster meat powder. Study Design: The study was design using the D-optimal combination design of Response Surface Methodology (RSM). Place and Duration of Study: The study was carried out at Department of Food, Nutrition and Home Science, University of Port Harcourt (Processing of raw materials) and the Department of Food Technology, Federal Institute of industrial research Oshodi, Lagos (Analysis of raw materials) between October 2021 and August 2022. Methodology: The raw materials were each processed to have wholesome flours, and then they were combined according to the matrix generated, which had ranges of 70 – 100%, 0 – 22%, and 0 – 8% for whole wheat flour (WWF), soybean flour (SBF) and oyster meat powder (OMP) respectively. Results: The design was used to assess the significance (5% probability) of the moisture, fat, and protein content, which ranged from 8.09 to 11.37%, 1.80 to 8.52% and 9.70 to 19.07% respectively; the water absorption (72.00 - 79.10BU), dough stability (9.3 - 17.5BU) and mixing tolerance index (25 - 50BU); and lightness and yellowness, which ranged from 65.48 - 83.2 and 13.77 - 23.58 respectively, of the flour blends. Protein content, water absorption dough stability, and mixing tolerance index were prioritized while moisture content, fat content, and yellowness were minimized for the numerical optimization of the responses. This study highlights the possibilities of utilizing non-conventional raw materials in the production of composite flour with balance nutritional and baking qualities. Conclusion: The best flour combination was 72.51% whole wheat flour, 19.63% soybean flour, and 7.86% oyster meat powder.

Niveles de referencia para diagnóstico según PUBMED: ¿es suficiente la información disponible? / Diagnostic reference levels according to PUBMED: is the information available sufficient?

RESUMEN Los Niveles de Referencia para Diagnóstico (NRD) son una herramienta dinámica que gana cada vez una mayor importancia para la optimización de las exposiciones médicas. La disponibilidad de información científica es esencial en este proceso de optimización para Medicina Nuclear (MN) y Radiología Diagnóstica (RD). Este trabajo presenta un estudio de la disponibilidad de información sobre los NRD para MN y RD en la base PubMed, en los últimos 20 años, empleando diferentes palabras clave. Se analizó de forma crítica la información disponible, buscando los cambios principales que se han producido como tendencia en diferentes aspectos del establecimiento de los NRD. Se verificó un desbalance significativo en la disponibilidad de literatura científica en estas dos áreas, aunque se ha incrementado la información para equipos híbridos y de forma general para todas las tecnologías. Este desbalance se hace mayor para estudios de medicina nuclear en pediatría. Se observaron avances en la forma de recolectar datos, la manera de organizar la información y analizarla, en especial con la disponibilidad de sistemas de monitoreo de dosis. Se encontró que, en los estudios TC e intervencionismo, las agrupaciones por localización anatómica están siendo acotadas o restringidas, por indicaciones clínicas que tienen similitudes en los requisitos de calidad de imagen para el diagnóstico adecuado. Similarmente en MN se vislumbra la incorporación de la actividad por peso como NRD en las tecnologías híbridas y estudios pediátricos. Este estudio demuestra que, en general, la literatura científica disponible sobre los NRD es mucho más amplia para pacientes adultos. Se requiere más estudios pediátricos, especialmente en el área de MN

ABSTRACT Diagnostic Reference Levels (DRLs) are a dynamic tool that is gaining more and more importance for the optimization of medical exposures. The availability of scientific information is essential in this optimization process for Nuclear Medicine (NM) and Diagnostic Radiology (DR). This work presents a revision of the information's availability about DRL in the PubMed database, in the last 20 years, using different search combinations. The available information was critically analyzed, looking for the main changes that have occurred as a trend in different aspects of the establishment of the NRD. A significant disparity in the amount of information between the two areas on the subject was verified, although there has been an increase of available scientific papers for hybrid equipment, and in general for all technologies. The disparity becomes greater for NM studies in pediatrics population. The way to collect data, the mode to organize the information and analyze it, has also undergone changes, mainly with radiation dose management systems. In CT and interventional studies, the grouping by anatomical locations is being constrained or modulated by clinical indications with analogous image quality requirements for proper diagnosis. Something similar happens in MN, where the incorporation of activity/patient's weight is envisioned as NRD for hybrid technologies and pediatric studies. In general, the study showed that, the scientific paper's availability about DRL for adult population are much wider. More pediatric studies on these subjects are needed, especially in NM

On the use of radiobiological-based optimization functions in radiotherapy treatment planning for prostate and head and neck cases on Monaco and Eclipse TPS / Sobre el uso de funciones de costo basadas en radiobiología en la planeación de tratamientos de radioterapia para casos de próstata y cabeza y cuello en los TPS Monaco y Eclipse

INTRODUCTION Radiobiological-based optimization functions for radiotherapy treatment planning involve dose-volume effects that could allow greater versatility when shaping dose distributions and DVHs than traditional dose volume (DV) criteria. Two of the most commercially available TPS (Monaco and Eclipse) already offer biological-based optimization functions, but they are not routinely used by most planners in clinical practice. Insight into the benefits of using EUD, TCP/NTCP-based cost functions in Monaco and Eclipse TPS was gained by comparing biological-based optimizations and physical-based optimizations for prostate and head and neck cases. METHODS Three prostate and three H&N cases were retrospectively optimized in Monaco and Eclipse TPS, using radiobiological-based cost functions vs DV-based cost functions. Plan comparison involved ICRU Report 83 parameters D95%, D50%, D2% and TCP for the PTV, and NTCP and RTOG tolerance doses for OARs. RESULTS Although there were differences between Monaco and Eclipse plans due to their dissimilar optimization and dose calculation algorithms as well as optimization functions, both TPS showed that radiobiological-based criteria allow versatile tailoring of the DVH with variation of only one parameter and at most two cost functions, in contrast to the use of three to four DV-based criteria to reach a similar result. CONCLUSION Despite the use of a small sample, optimization of three prostate and three head and neck cases allowed the exploration of optimization possibilities offered by two of the most commercially available TPS on two anatomically dissimilar regions. Radiobiological-based optimization efficiently drives dose distributions and DVH shaping for OARs without sacrifice of PTV coverage. Use of EUD-based cost functions should be encouraged in addition to DV cost functions to obtain the best possible plan in daily clinical practice

INTRODUCCION Las funciones de optimización basadas en radiobiología para la planificación del tratamiento de radioterapia implican efectos dosis volumen que podrían permitir una mayor versatilidad a la hora de dar forma a las distribuciones de dosis y DVH que los tradicionales criterios dosis-volumen (DV). Dos de los TPS más disponibles comercialmente (Mónaco y Eclipse) ya ofrecen productos de funciones de optimización de base biológica, pero la mayoría de los planificadores no las utilizan de forma rutinaria en la práctica clínica. El conocimiento de los beneficios del uso de las funciones de costos basadas en EUD, TCP/NTCP en Mónaco y Eclipse TPS se obtuvo comparando optimizaciones de base biológica y optimizaciones físicas para casos de próstata y cabeza y cuello. MÉTODOS Tres próstatas y tres casos de H&N en Mónaco y Eclipse TPS fueron optimizadas retrospectivamente usando funciones de costos basadas en radiobiología vs funciones de costos basadas en DV. La comparación de planes involucró los parámetros del Informe ICRU 83 D95%, D50%, D2% y TCP para el PTV, y dosis de tolerancia NTCP y RTOG para OAR. Resultados. Aunque hubo diferencias entre los planes Mónaco y Eclipse, debido a sus diferentes algoritmos de optimización y cálculo de dosis, así como funciones de optimización, ambos TPS demostraron que el criterio basado en radiobiología permiten una adaptación versátil del DVH con variación de un solo parámetro y como máximo dos funciones de costos, en contraste con el uso de tres o cuatro criterios basados en DV para alcanzar un resultado similar. CONCLUSIÓN A pesar del uso de una muestra pequeña, la optimización de tres casos de próstata y tres de cabeza y cuello permitió la exploración de las posibilidades de optimización que ofrecen dos de los TPS más disponibles comercialmente en dos regiones anatómicamente diferentes. La optimización basada en radiobiología impulsa de manera eficiente las distribuciones de dosis y la configuración de DVH para OAR sin sacrificar Cobertura de PTV. Se debe fomentar el uso de funciones de costos basadas en EUD además de las funciones de costos DV para obtener el mejor posible plan en la práctica clínica diaria

Mejoramiento de un método no comercial para la extracción de ADN de moscas de interés médico-legal

La obtención de ADN de moscas de interés médico-legal es de relevancia para una variedad de aplicaciones. Aunque existen métodos de extracción comerciales de ADN, su uso rutinario es limitado, en algunos escenarios. En este contexto, el uso de métodos no comerciales constituye una alternativa; sin embargo, su optimización es clave para mejorar el flujo de trabajo y los resultados. Este trabajo evaluó el impacto de variaciones a un método de precipitación salina sobre la concentración y la pureza del ADN recuperado. No se encontraron diferencias significativas en la concentración de ADN extraído entre los diferentes tiempos de incubación, probados durante la fase de extracción, mientras que el incremento en el volumen de etanol absoluto, en la fase de precipitación de ADN, mejoró significativamente la concentración de ADN obtenido. Las modificaciones propuestas reducen el tiempo de ejecución y la concentración de ADN obtenido comparado con el protocolo original.

Obtaining DNA from flies of medico-legal interest is relevant for a variety of applications. Although commercial extraction methods offer optimal DNA, their routine use is limited in some settings. In this context, the use of non-commercial methods constitutes an alternative in laboratories with limited resources however, its optimization is key to improving the workflow and the results. This work evaluated the impact of variations to a saline precipitation method on the concentration and purity of the recovered DNA. No significant differences were found in the concentration of extracted DNA between the different incubation times tested during the extraction phase. In contrast, the increased volume of absolute ethanol in the DNA precipitation phase significantly improved the concentration of DNA obtained. The proposed modifications reduce the runtime and DNA concentration obtained compared with the original protocol.

Cirugía en horario extendido: una visión de los actores involucrados / Extended hours surgery: a vision of the actors involved

Introducción. Las listas de espera para cirugía de alta prevalencia son producto de una limitada oferta ante una elevada demanda de jornadas quirúrgicas. Tienen un impacto sobre las condiciones médicas de los pacientes y la consulta por urgencias. Como respuesta, se han incorporado los espacios quirúrgicos adicionales en horarios no convencionales. Su creciente implementación, aunque controversial, se reconoce cada vez más como una nueva normalidad en cirugía. Hay una limitada documentación de la efectividad de la medida, debido a la complejidad e intereses de los participantes. Métodos. Se analizó desde una posición crítica y reflexiva la perspectiva de los actores involucrados en un programa de cirugía en horario extendido, estableciendo las posibles barreras y los elementos facilitadores de una política enfocada a procedimientos en horario no convencional. Asimismo, se describen posibles oportunidades de investigación en el tema. Discusión. Los programas quirúrgicos en horarios no convencionales implican un análisis de los determinantes de su factibilidad y éxito para establecer la pertinencia de su implementación. La disponibilidad de las salas de cirugía, una estandarización de los procedimientos y una cultura de seguridad institucional implementada por la normativa vigente, favorecen estas acciones operacionales. Los aspectos económicos del prestador y del asegurador inciden en la planeación y ejecución de esta modalidad de trabajo. Conclusión. La realización segura y el éxito de un programa de cirugía en horario no convencional dependen de la posibilidad de alinear los intereses de los actores participantes en el proceso

Introduction. Waiting lists for high-prevalence surgeries are the product of limited supply due to a high demand for surgical days. They have an impact on patients' medical conditions and emergency consultation. In response, additional surgical spaces have been incorporated at unconventional times. Its growing implementation, although controversial, is increasingly recognized as a new normal in surgery. There is limited documentation of the effectiveness of the measure due to the complexity and interests of the participants. Methods. The perspective of the actors involved in an extended hours surgery program was analyzed from a critical and reflective position, establishing the possible barriers, and facilitating elements of a policy focused on procedures during unconventional hours. Possible research opportunities on the topic are also described. Discussion. Surgical programs at unconventional times involve an analysis of the determinants of their feasibility and success to establish the relevance of implementation. The availability of operating rooms, a standardization of procedures and a culture of institutional security implemented by current regulations, favor these operational actions. The economic aspects of the provider and the insurer affect the planning and execution of this type of work. Conclusion. The safe realization and success of a surgical program in unconventional hours depend on the possibility of aligning the interests of the actors involved in the process

Optimization of Growth Parameters for Enhancing the Production of Biosurfactants from Pediococcus pentosaceus S-2

Numerous Lactic acid bacteria (LAB) have been found to be capable of synthesizing surface-active compounds i.e biosurfactants. These are amphiphilic compounds produced by microorganisms on their cell surface or secreted extracellularly that have a tendency to reduce surface and interfacial tension. In the present study, different process parameters including nitrogen and carbon source, pH, temperature, aeration and agitation were optimized to maximize the production of biosurfactants from Pediococcus pentosaceus S-2. Xylose (1.5%) and yeast extract (1.5%) act as better carbon and nitrogen sources respectively for the production of biosurfactants. Maximum biosurfactant yield was observed at pH 6, a temperature of 35o C, an agitation rate of 200 rpm and with inoculum size of 3%. The high yield of biosurfactants produced from Pediococcus pentosaceus S-2 by utilizing media supplemented with whey under optimized conditions.

Prueba de microneutralización para la detección de anticuerpos contra el virus dengue serotipo 2

Objetivo: Optimizar la prueba de microneutralización (MNT) para detección de anticuerpos neutralizantes contra el virus dengue serotipo 2 (DENV-2) en la línea celular Vero-76. Materiales y métodos: Se evaluaron diferentes concentraciones celulares (0.6 x105 cel/mL, 0.9 x105 cel/mL, 1.2 x105 cel/mL), porcentajes de 2 %, 3 % y 4 % de suero bovino fetal (SBF), número de pasajes del stock de virus y los días de incubación. La semilla viral se confirmó por RT-qPCR. El DENV-2 se propagó realizando 5 pasajes en células Vero-76, seguidamente se tituló el virus en placas de 96 pozos y se evaluaron 2 métodos de infección celular: monocapa y células en suspensión, además se determinó el día óptimo de coloración de las células. Obtenidos los resultados, se procesaron mediante MNT para DENV-2 las siguientes muestras: 5 sueros negativos a DENV-2 y YFV (Virus de la Fiebre Amarilla), 5 sueros negativos de anticuerpos a DENV-2 y positivos de anticuerpos a YFV y 5 sueros positivos de anticuerpos a DENV-2 seleccionados mediante la prueba de neutralización por reducción de placas (PRNT). Resultados: El método óptimo para MNT utilizó células en suspensión (0.9 x 105 cel/mL), 2 % de SBF y semilla viral pasaje 5. La mínima dilución capaz de diferenciar una muestra positiva a DENV-2 fue 1:40 y el tiempo de incubación para la MNT para DENV-2 fue de 10 días. Conclusión: La MNT con el método de células en suspensión y medio de cultivo con 2 % de SBF permite detectar anticuerpos neutralizantes IgG contra DENV-2 con resultados confiables, pudiendo analizar un mayor número de muestras con ahorro de materiales.

Objective: To optimize the microneutralization test (MNT) for the detection of neutralizing antibodies against serotype 2 of dengue fever virus (DENV-2) in a Vero-76 cell line. Materials and methods: Different cell concentrations were assessed (0.6 X 105 cells/mL, 0.9 X 105 cells/mL, and 1.2 x 105 cells/mL) with 2%, 3%, and 4% fetal bovine serum, virus stock passage number, and incubation days. Viral particles were confirmed using RT-qPCR. DENV-2 disseminated with 5 passages in Vero-76 cells, then, the virus was titrated in 96-well plaques, and two methods for cell infection were evaluated: single layer, and suspended cells. Also, the optimum day for cell staining was determined. Once results were obtained, the following samples were processed using MNT for DENV-2: five sera negative for DENV-2 and yellow fever virus (YFV), five sera negative for antibodies against DENV-2 and positive for antibodies against YFV, and five sera positive for antibodies against DENV-2 that were selected using the plate reduction neutralization test. Results: The optimum method for MNT used suspended cells (0.9 X 105 cells/mL), 2% fetal bovine serum, and viral particles at the 5th passage. The minimal dilution able to differentiate a positive sample for DENV2 was 1:40, and the MNT incubation time for DENV-2 was ten days. Conclusion: MNT with the cell suspension method and a culture medium with 2% fetal bovine serum allows the detection of IgG neutralizing antibodies against DENV-2 with reliable results, so that larger sample sizes may be assessed, saving materials to be used.

Simultaneous detection of thirteen exons of dystrophin gene by optimized multiplex PCR assay to screen Duchenne/Becker muscular dystrophy

Advancements in Polymerase Chain Reaction (PCR) technology and other techniques like Deoxyribonucleic acid (DNA)signal and target amplification have become key procedures in molecular diagnostics. PCR enables the synthesis of nucleic acids in vitro through which a DNA segment can be specifically replicated in a semiconservative way that sets forth deletion and mutation analysis. Multiplex PCR (M-PCR) is beneficial over standard and long PCR as this can amplify more than one locus using the respective primer sets. In harmony with this, the present study aimed to optimize M-PCR followed by its chemistry and condition to screen Duchenne Muscular Dystrophy (DMD) [OMIM #310200] and Becker Muscular Dystrophy (BMD) [OMIM #300376]. Muscular Dystrophies (MDs) are a broad group of hereditary, progressive, and degenerative disorders of muscles. X-linked recessive D/BMD are caused by mutation/s in the dystrophin gene [OMIM #300377] that encodes for dystrophin protein [UniProt#P11532]. As dystrophin is the human metagene with 79 exons, mutational analysis is very challenging. Chamberlain set (10 plex), Beggs set (9 Plex), and Kunkel set (7 Plex) is used for many years to diagnose this condition. However, in this study, Beggs set is customized with 13 exons to screen DMD gene mutation in a single reaction. Optimization of M-PCR was designed with many physicochemical parameters. According to the literature and after many appraisals the present study demonstrated the most sufficient concentration of various chemical components and optimal cycling conditions to optimize the modified Beggs set (13 Plex). 50 µL PCR reaction includes primer(s) (0.3–0.5 µM each), dNTP mixture (160 µM each), Dream Taq buffer (1X), Taq DNA polymerase (6U/50 µL), DNA template (250 ng/50 µL), BSA (0.4 µg/µL), and MgCl2 (1.4 mM). To get the most effective results cyclic conditions obtained were 10 min initial denaturation at 94°C, 62°C annealing temperature, and 35 PCR cycles at 72°C extending temperature. Consequently, the study successfully formulated a less expensive and simple approach for >3000 bp that was used to screen D/BMD. Finally, a developed M-PCR mix with a unique combination of specificity and sensitivity coupled with great flexibility has led to a true revolution in molecular diagnostics.

Optimización del control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2

Objetivo: Optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, utilizando los valores Cq de controles negativos y positivos. Material y método: Estudio prospectivo-longitudinal. La muestra estuvo constituida por 143 valores Cq para los controles negativos de alicuotado y extracción, así como para el control positivo. Se analizó la distribución normal de los valores Cq mediante la prueba de Anderson-Darling (AD) y se aplicaron pruebas de aleatoriedad. Se calculó límites de control a partir de 51 valores Cq, para luego, mediante gráficas de control, monitorizar 92 valores Cq obtenidos desde noviembre del 2020 hasta marzo del 2021. Se evaluó aceptación de lote e índices Cpk como indicadores de optimización. Los cálculos se hicieron con el programa Minitab. Resultados: Se aceptaron los lotes de valores Cq y se obtuvieron índices Cpk superiores a 1.33 para los tres tipos de control. Discusión: No existen estudios publicados que apliquen control estadístico de calidad a la detección cualitativa de SARS-CoV-2. Conclusiones: Es posible utilizar los valores Cq de los controles para optimizar el control interno de calidad de RT-PCR en tiempo real para detección cualitativa de SARS-CoV-2, como si se tratara de una técnica de tipo cuantitativo.

Objective: To optimize the internal quality control of real-time RT-PCR for the qualitative detection of SARS-CoV-2, using the Cq values ​​of negative and positive controls. Material and method : Prospective-longitudinal study. The sample consisted of 143 Cq values for the negative aliquot and extraction controls, as well as for the positive control. The normal distribution of Cq values ​​was analyzed using the Anderson-Darling (AD) test and randomness tests were applied. Control limits were calculated from 51 Cq values, and then, using control charts, to monitor 92 Cq values ​​obtained from November 2020 to March 2021. Lot acceptance and Cpk indices were evaluated as optimization indicators. The calculations were made with the Minitab program. Results: The batches of Cq values ​​were accepted and Cpk indices higher than 1.33 were obtained for the three types of control. Discussion : There are no published studies that apply statistical quality control to the qualitative detection of SARS-CoV-2. Conclusions : It is possible to use the Cq values ​​of the controls to optimize the internal quality control of real-time RT-PCR for qualitative detection of SARS-CoV-2, as if it were a quantitative technique.

Optimization of the ellagic acid synthesis process at the bioreactor level using non-conventional yeasts

Abstract Ellagic acid (EA) is a phenolic biomolecule. For its biosynthesis, a source of ellagitannins is required, such as strawberries and yeasts, as precursors of the tannase and ß-glucosidase enzymes responsible for hydrolysis of ellagitannins. Two experimental mixture designs were applied., varying the yeast concentration and the number of ellagitannins in the culture medium, evaluating the enzymatic activity and ellagic acid biosynthesis. Aiming to find the optimal compositions of the non-conventional yeasts assessed in the research to biosynthesize ellagic acid feasibly and efficiently using a response surface performing the statistical analysis in the StatGraphics® program for obtaining a higher yield and optimizing the ellagic acid synthesis process, the results indicate that the strains Candida parapsilosis ITM LB33 and Debaryomyces hansenii ISA 1510 have a positive effect on the synthesis of ellagic acid, since as its concentration increases in the mixture the concentration of ellagic acid in the medium also increases; on the other hand, the addition of Candida utilis ITM LB02 causes a negative effect, resulting in the compositions of 0.516876, 0.483124 and 2.58687E-9 respectively, for a treatment under the same conditions, an optimal value of ellagic acid production would be obtained. With an approximate value of 7.33036 mg/mL

Spatial variability of soil fertility under agroforestry system and native forest in eastern Amazonia, Brazil

The usage of spatial tools might be helpful in the optimization of decision-making regarding soil management, with technologies that assist in the interpretation of information related to soil fertility. Therefore, the present study evaluated the spatial variability of chemical attributes of the soil under an agroforestry system compared to a native forest in the municipality of Tomé-açu, Eastern Amazon, Brazil. Soil samples were performed at 36 points arranged in a 55 x 55 m grid. The soils were prepared and submitted to analysis in order to determine pH in H2O, exchangeable calcium, magnesium, potassium and aluminium, available phosphorus, potential acidity, organic matter, bases saturation and aluminium saturation. For each soil attribute, the spherical, gaussian and exponential models were adjusted. After the semivariograms fitting, data interpolation for assessment of spatial variability of the variables was performed through ordinary kriging. The spherical and gaussian models were the most efficient models in estimation of soil attributes spatial variability, in most cases. Most of variables presented a regular spatial variability in their respective kriging maps, with some exceptions. In general, the kriging maps can be used, and we can take them as logistical maps for management and intervention practices in order to improve the soil fertility in the study areas. The results principal components indicate the need for integrated management of soil chemical attributes, with localized application of acidity correctors, fertilizers and other types of incomes, using the spatial variability of these fertility variables.

Difficulties and Countermeasures for Ortho Process Optimization in DR System / 中国医疗器械杂志

Making an Ortho image is an important method to diagnose spinal and leg lesions in clinic. As the whole process requires multiple exposures in different positions, and it is very complicated and time consuming, it leads to low efficiency and it's hard to obtain ideal stitching result from image quality. The optimization of the workflow can not only reduce the workload of the operator, improve the work efficiency, but also improve the comfort of the patient in the process, finally to ensure the quality of the stitching image. This paper firstly introduces the background and workflow of making an Ortho image. Then, each optimization solutions are elaborated, including the encountered difficulties and the countermeasures. It provides a detailed reference about how to realize the Ortho function in DR system.

Research on mild cognitive impairment diagnosis based on Bayesian optimized long-short-term neural network model / 生物医学工程学杂志

The recurrent neural network architecture improves the processing ability of time-series data. However, issues such as exploding gradients and poor feature extraction limit its application in the automatic diagnosis of mild cognitive impairment (MCI). This paper proposed a research approach for building an MCI diagnostic model using a Bayesian-optimized bidirectional long short-term memory network (BO-BiLSTM) to address this problem. The diagnostic model was based on a Bayesian algorithm and combined prior distribution and posterior probability results to optimize the BO-BiLSTM network hyperparameters. It also used multiple feature quantities that fully reflected the cognitive state of the MCI brain, such as power spectral density, fuzzy entropy, and multifractal spectrum, as the input of the diagnostic model to achieve automatic MCI diagnosis. The results showed that the feature-fused Bayesian-optimized BiLSTM network model achieved an MCI diagnostic accuracy of 98.64% and effectively completed the diagnostic assessment of MCI. In conclusion, based on this optimization, the long short-term neural network model has achieved automatic diagnostic assessment of MCI, providing a new diagnostic model for intelligent diagnosis of MCI.

Research on eye movement data classification using support vector machine with improved whale optimization algorithm / 生物医学工程学杂志

When performing eye movement pattern classification for different tasks, support vector machines are greatly affected by parameters. To address this problem, we propose an algorithm based on the improved whale algorithm to optimize support vector machines to enhance the performance of eye movement data classification. According to the characteristics of eye movement data, this study first extracts 57 features related to fixation and saccade, then uses the ReliefF algorithm for feature selection. To address the problems of low convergence accuracy and easy falling into local minima of the whale algorithm, we introduce inertia weights to balance local search and global search to accelerate the convergence speed of the algorithm and also use the differential variation strategy to increase individual diversity to jump out of local optimum. In this paper, experiments are conducted on eight test functions, and the results show that the improved whale algorithm has the best convergence accuracy and convergence speed. Finally, this paper applies the optimized support vector machine model of the improved whale algorithm to the task of classifying eye movement data in autism, and the experimental results on the public dataset show that the accuracy of the eye movement data classification of this paper is greatly improved compared with that of the traditional support vector machine method. Compared with the standard whale algorithm and other optimization algorithms, the optimized model proposed in this paper has higher recognition accuracy and provides a new idea and method for eye movement pattern recognition. In the future, eye movement data can be obtained by combining it with eye trackers to assist in medical diagnosis.

Effect of dwell time deviation constraint on the three-dimensional brachytherapy plans for cervical cancer / 中华放射肿瘤学杂志

Objective:To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer.Methods:A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test.Results:As the smooth value was increased, the modulation factor was gradually decreased and the D 2 cm3 of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant ( P=0.004, 0.002, 0.002, 0.002). The bladder D 2 cm3 of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D 2 cm3 of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences ( P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D 90% was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D 2 cm3 of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions:The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.