Phytochemical profile of petals from black Dahlia pinnata by flow injection analysis-electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry.

INTRODUCTION: Dahlia pinnata Cav. is a flower native to Mexico that has many applications; in particular, its petals have been used for ornamental, food, and medicinal purposes, for example to treat skin rashes and skin cracks. It has been reported that the medicinal properties of plants are generally related to the phytochemical constituents they possess. However, there are few studies on black D. pinnata. OBJECTIVES: The present study was aimed at qualitatively and quantitatively determining the phytochemical profile of petals from black D. pinnata. METHODOLOGY: Phytochemicals from Dahlia petals were extracted by consecutive maceration (hexane, dichloromethane, and methanol); then, the extracts were analyzed through colorimetric assays and UV-Vis spectroscopy for qualitative identification and quantification of phytochemical compounds, respectively. The methanolic extract was analyzed by flow injection analysis-electrospray ionization-Fourier transform ion cyclotron resonance mass spectrometry (FIA-ESI-FTICR-MS) in negative and positive mode. RESULTS: Quantitative phytochemical profiling of the methanolic extract by UV-Vis spectroscopy indicated high contents of phenolic compounds (34.35 ± 3.59 mg EQ/g plant) and sugars (23.91 ± 1.99 mg EQ/g plant), while the qualitative profiling by FIA-ESI-FTICR-MS allowed the tentative identification of several flavonoids and phenolic acids. Kaempferol-3-rutinoside, pelargonidin-3-(6″-malonylglucoside)-5-glucoside, rutin, kaempferol-3-(2″,3″-diacetyl-4″-p-coumaroylrhamnoside), and myricetin-3-(2‴-galloylrhamnoside) were the main compounds detected. CONCLUSION: The results expand our knowledge of the phytochemical constituents of petals from black D. pinnata.

Cannabis Extraction Technologies: Impact of Research and Value Addition in Latin America.

The Cannabis genus of plants has been widely used in different cultures for various purposes. It is separated into three main species: sativa, indica, and ruderalis. In ancient practices, the plant was used as a multipurpose crop and valued for its fiber, food, and medicinal uses. Since methodologies for the extraction, processing, and identification of components have become available, medical, and food applications have been increasing, allowing potential development in the pharmaceutical and healthy functional food industries. Although the growing legalization and adoption of cannabis for the treatment of diseases are key factors pushing the growth of its market, the biggest challenge is to obtain higher-quality products in a time- and cost-effective fashion, making the process of extraction and separation an essential step. Latin American countries exhibit great knowledge of extraction technologies; nevertheless, it is still necessary to verify whether production costs are economically profitable. In addition, there has been an increase in commercial cannabis products that may or may not be allowed, with or without quality fact sheets, which can pose health risks. Hence, legalization is mandatory and urgent for the rest of Latin American countries. In this article, the phytochemical compounds (cannabinoids, terpenes, and phenolic compounds), the current status of legalization, extraction techniques, and research advances in cannabis in Latin America are reviewed.

Two-methods approach to follow up biomass by impedance spectroscopy: Bacillus thuringiensis fermentations as a study model.

Impedance spectroscopy is used for the characterization of electrochemical systems as well as for the monitoring of bioprocesses. However, the data obtained using this technique allow multiple interpretations, depending on the methodology implemented. Hence, it is necessary to establish a robust methodology to reliably follow-up biomass in fermentations. In the present work, two methodological approaches, mainly used for the characterization of electrochemical systems, were employed to characterize and determine a frequency that allows the monitoring of biomass in Bacillus thuringiensis fermentations by impedance spectroscopy. The first approach, based on a conventional analysis, revealed a single distribution with a characteristic frequency of around 2 kHz. In contrast, the second approach, based on the distribution of relaxation times, gave three distributions (A, B, and C). The C distribution, found near 9 kHz, was more related to the microbial biomass than the distribution at 2 kHz using the equivalent circuits. The time course of the B. thuringiensis fermentation was followed; bacilli, spores, glucose, and acid and base consumption for pH were determined out of line; and capacitance at 9 kHz was monitored. The correlation between the time course data and the capacitance profile indicated that the monitoring of B. thuringiensis at 9 kHz mainly corresponds to extracellular activity and, in a second instance, to the cellular concentration. These results show that it is necessary to establish a robust and reliable methodology to monitor fermentation processes by impedance spectroscopy, and the distribution of relaxation times was more appropriate. KEY POINTS: • Application of impedance spectroscopy for bioprocess monitoring • Low-frequency monitoring of biomass in fermentations • Analysis of impedance data by two methodological approaches.

Engineering of global transcription factors in Bacillus, a genetic tool for increasing product yields: a bioprocess overview.

Transcriptional factors are well studied in bacteria for their global interactions and the effects they produce at the phenotypic level. Particularly, Bacillus subtilis has been widely employed as a model Gram-positive microorganism used to characterize these network interactions. Bacillus species are currently used as efficient commercial microbial platforms to produce diverse metabolites such as extracellular enzymes, antibiotics, surfactants, industrial chemicals, heterologous proteins, among others. However, the pleiotropic effects caused by the genetic modification of specific genes that codify for global regulators (transcription factors) have not been implicated commonly from a bioprocess point of view. Recently, these strategies have attracted the attention in Bacillus species because they can have an application to increase production efficiency of certain commercial interest metabolites. In this review, we update the recent advances that involve this trend in the use of genetic engineering (mutations, deletion, or overexpression) performed to global regulators such as Spo0A, CcpA, CodY and AbrB, which can provide an advantage for the development or improvement of bioprocesses that involve Bacillus species as production platforms. Genetic networks, regulation pathways and their relationship to the development of growth stages are also discussed to correlate the interactions that occur between these regulators, which are important to consider for application in the improvement of commercial-interest metabolites. Reported yields from these products currently produced mostly under laboratory conditions and, in a lesser extent at bioreactor level, are also discussed to give valuable perspectives about their potential use and developmental level directed to process optimization at large-scale.

Use of equivalent circuit analysis and Cole-Cole model in evaluation of bioreactor operating conditions for biomass monitoring by impedance spectroscopy.

The most important parameter in bioprocesses is biomass, where not only the quantity produced in a culture but also the behavior that is presented are important concerns. It is clear that conditions of operation in a bioreactor affect biomass production, but how operation conditions affect the measurement of biomass on-line is of special interest. We studied the effect of bioreactor operating condition variations on model parameters using impedance spectroscopy for biomass monitoring. The model parameters analyzed were capacitance, resistance, alpha (α), conductivity delta (∆σ) and critical frequency (fc). These model parameters were obtained by fitting data from impedance measurements to an equivalent circuit model and Cole-Cole conductivity model. The effect of operating conditions on the medium with no cells was estimated by the percentage of change in each model parameter. The operating conditions with the most significant percentage of change were determined, by comparing to the percentage of change of the same model parameters obtained, during a fermentation of Bacillus thuringiensis as a cellular model. Equivalent circuit parameters were mainly affected by variation in pH, temperature and aeration, whereas Cole-Cole parameters were affected by variation in agitation, aeration, temperature and pH. Therefore, any variation in these operating conditions (within the test interval) during a fermentation may generate changes in monitoring parameters, which will not be a direct consequence of any change in the properties of the biomass.

[Implementation of telemedicine in the Americas: Barriers and facilitatorsBarreiras e facilitadores para a implementação da telemedicina nas Américas]. / Barreras y facilitadores a la implementación de la telemedicina en las Américas.

With millions of people in the world in situations of physical distancing because of COVID-19, information and communication technology (ICT) has become as one of the principal means of interaction and collaboration. The following advantages of ICT have been cited since the start of the new millennium: increased access to information and service delivery, educational strengthening, quality control of screening programs, and reduction of health care costs. In the case of telemedicine, however, a number of barriers-especially technological, human and social, psychosocial, anthropological, economic, and governance-related-have stood in the way of its adoption. The past 20 years have seen an increase in the availability of resources and technical capacity, improvements in digital education, empowerment of patients regarding their treatment, and increased public interest in this area. Successes have included the use of interdisciplinary teams, academic and professional networking, and virtual medical consultations. After reviewing the state of telemedicine in the Region of the Americas, the authors recommend the urgent adoption of measures aimed at implementing national telemedicine policies and programs, including a regulatory framework and adequate funding. Implementation of the measures should be integrated and interoperable and include the support of academic networks and the collaboration of specialized institutions. The policies should generate an enabling context that ensures sustainability of the progress achieved, bearing in mind the possible barriers mentioned.

Com milhões de pessoas no mundo em situação de distanciamento físico devido à COVID-19, as tecnologias da informação e comunicação (TICs) se enquadraram como um dos meios principais de interação e colaboração. Já no início deste milênio, começaram a ser mencionadas as seguintes vantagens: maior acesso à informação e à prestação de serviços; fortalecimento da educação; controle de qualidade dos programas de detecção e redução dos custos na atenção à saúde. No entanto, entre as principais barreiras de adoção da telemedicina se encontram as de caráter: tecnológico; humano e social; psicossocial e antropológico; de governança e econômico. Nestes 20 anos, houve um aumento nos recursos e na capacidade técnica, uma melhora na educação digital, um empoderamento do paciente em seu tratamento e um maior interesse público nessa área. Em especial, são consideradas bem-sucedidas a constituição de equipes interdisciplinares e as redes acadêmicas e profissionais, e as consultas médicas virtuais. Após revisar o estado da telemedicina na Região das Américas, os autores recomendam a adoção de medidas urgentes para implementar políticas e programas nacionais de telemedicina, incluindo o marco normativo e o orçamento necessário. Essa implementação deve ser realizada de maneira integral e interoperável e sustentada por redes acadêmicas, de parceria e instituições especializadas. Tais políticas devem gerar um contexto favorável, dando sustentabilidade ao avanço obtido e considerando os aspectos mencionados nas possíveis barreiras.

Positive Tests for Lyme Disease and Emergency Department Visits for Bell's Palsy Patients.

BACKGROUND: Etiologies for Bell's palsy include herpes viruses and Lyme disease, with highest incidence in the colder and warmer months, respectively. In New Jersey, a Lyme-endemic area, the months with the most Lyme disease (80% of cases) are May through October ("Lyme months"). OBJECTIVE: Our aim was to determine whether positive tests for Lyme disease and visits are greater in the Lyme months than the rest of the year for patients with Bell's palsy in New Jersey emergency departments (EDs). METHODS: We conducted a retrospective chart review from two New Jersey suburban EDs with consecutive patients from February 1, 2013 to January 31, 2018.We identified patients having Bell's palsy using the emergency physician diagnosis. We tabulated positive Lyme tests and visits for Bell's palsy by month of year. We calculated the ratio of positive tests and visits between the Lyme months and the rest of the year along with 95% confidence intervals (CIs). RESULTS: There were 442 visits for Bell's palsy, 359 (81%) of these patients were tested for Lyme disease and 57 (16%) of the tests were positive. The Lyme months had 7.1 (95% CI 3.5-14.4) times more positive tests and 1.3 (95% CI 1.1-1.4) times more Bell's palsy visits than the rest of the year. Both measures peaked in July. CONCLUSIONS: In a Lyme-endemic area, positive Lyme tests and ED visits for Bell's palsy are greatest in the Lyme months, peaking in July. This finding can help guide testing and treatment for patients in the ED with Bell's palsy during various months of the year.

[Evaluation of the teleconsultation process from the perspective of the provider (Oaxaca Telehealth Program, Mexico)]. / Evaluación del proceso de teleconsulta desde la perspectiva del proveedor, Programa de Telesalud de Oaxaca, México.

OBJECTIVE: Identify barriers to implementation of the teleconsultation process in order to develop strategies to improve the program's operation. METHODS: A process evaluation strategy was used to study the implementation of the teleconsultation service. The program's operating manuals were compared with the qualitative and quantitative information compiled on the practical implementation of the teleconsultation process. RESULTS: The factors reported as obstacles to the teleconsultation process were: slow Internet connection, the hours available to the public, the specialized services offered, and insufficient clinical history included in teleconsultation requests. It was determined that 60% of internal medicine patients received two or more teleconsultations in the study period, as did 44% of patients of the gynecology service. Four consulting medical units accounted for 75% of the teleconsultations and the rest were distributed among 12 medical units. CONCLUSIONS: The barriers identified in the teleconsultation process mainly affect consulting physicians; even so, productivity is on an upward trend. Despite the existing barriers, it was determined that some patients receive follow-up through the program, which favors access to care. It is necessary to standardize implementation and to conduct subsequent research on patients' health condition.

Bioprocess of Gibberellic Acid by Fusarium fujikuroi: The Challenge of Regulation, Raw Materials, and Product Yields.

Gibberellic acid (GA3) is a tetracyclic diterpenoid carboxylic acid synthesized by the secondary metabolism of Fusarium fujikuroi. This phytohormone is widely studied due to the advantages it offers as a plant growth regulator, such as growth stimulation, senescence delay, flowering induction, increased fruit size, and defense against abiotic or biotic stress, which improve the quality and yield of crops. Therefore, GA3 has been considered as an innovative strategy to improve agricultural production. However, the yields obtained at large scale are insufficient for the current market demand. This low productivity is attributed to the lack of adequate parameters to optimize the fermentation process, as well as the complexity of its regulation. Therefore, this article describes the latest advances for potentializing the GA3 production process, including an analysis of its origins from crops, the benefits of its application, the related biosynthetic metabolism, the maximum yields achieved from production processes, and their association with genetic engineering techniques for GA3 producers. This work provides a new perspective on the critical points of the production process, in order to overcome the limits surrounding this modern line of bioengineering.

On-line monitoring of industrial interest Bacillus fermentations, using impedance spectroscopy.

Impedance spectroscopy is a technique used to characterize electrochemical systems, increasing its applicability as well to monitor cell cultures. During their growth, Bacillus species have different phases which involve the production and consumption of different metabolites, culminating in the cell differentiation process that allows the generation of bacterial spores. In order to use impedance spectroscopy as a tool to monitor industrial interest Bacillus cultures, we conducted batch fermentations of Bacillus species such as B. subtilis, B. amyloliquefaciens, and B. licheniformis coupled with this technique. Each fermentation was characterized by the scanning of 50 frequencies between 0.5 and 5 MHz every 30 min. Pearson's correlation between impedance and phase angle profiles (obtained from each frequency scanned) with the kinetic profiles of each strain allowed the selection of fixed frequencies of 0.5, 1.143, and 1.878 MHz to follow-up of the fermentations of B. subtilis, B. amyloliquefaciens and B. licheniformis, respectively. Dielectric profiles of impedance, phase angle, reactance, and resistance obtained at the fixed frequency showed consistent changes with exponential, transition, and spore release phases.

Barreras y facilitadores a la implementación de la telemedicina en las Américas

[RESUMEN]. Con millones de personas en el mundo en situación de distanciamiento físico por el COVID-19, las tecnologías de la información y comunicaciones (TICs) se han posicionado como uno de los medios principales de interacción y colaboración. Ya al inicio de este milenio se empezaban a mencionar las siguientes ventajas: mayor acceso a la información y a la prestación de servicios; fortalecimiento educativo; control de calidad de los programas de detección y reducción de los costos de la atención de en salud. Sin embargo, entre las principales barreras de adopción de la telemedicina se encuentran las de índole: tecnológicas; humanas y sociales; psicosociales y antropológicas; de Gobernanza y económicas. En estos 20 años se logró un aumento en los recursos y capacidad técnica, una mejora en la educación digital, un empoderamiento del paciente en su tratamiento y un mayor interés público en esta área. En especial se considera exitosa la conformación de equipos interdisciplinarios, las redes académicas y profesionales y las consultas médicas virtuales. Después de revisar el estado de la telemedicina en la Región de las Américas, los autores recomiendan adoptar medidas urgentes para poner en práctica políticas y programas nacionales de telemedicina, incluyendo el marco normativo y presupuesto necesario, cuya implementación se realice de manera integral e interoperable y que se sustente de redes académicas, de colaboración e instituciones especializadas. Dichas políticas deben generar un contexto habilitante que den sostenibilidad al avance logrado, considerando los aspectos mencionados en las posibles barreras.

[ABSTRACT]. With millions of people in the world in situations of physical distancing because of COVID-19, information and communication technology (ICT) has become as one of the principal means of interaction and collaboration. The following advantages of ICT have been cited since the start of the new millennium: increased access to information and service delivery, educational strengthening, quality control of screening programs, and reduction of health care costs. In the case of telemedicine, however, a number of barriers—especially technological, human and social, psychosocial, anthropological, economic, and governance-related—have stood in the way of its adoption. The past 20 years have seen an increase in the availability of resources and technical capacity, improvements in digital education, empowerment of patients regarding their treatment, and increased public interest in this area. Successes have included the use of interdisciplinary teams, academic and professional networking, and virtual medical consultations. After reviewing the state of telemedicine in the Region of the Americas, the authors recommend the urgent adoption of measures aimed at implementing national telemedicine policies and programs, including a regulatory framework and adequate funding. Implementation of the measures should be integrated and interoperable and include the support of academic networks and the collaboration of specialized institutions. The policies should generate an enabling context that ensures sustainability of the progress achieved, bearing in mind the possible barriers mentioned.

[RESUMO]. Com milhões de pessoas no mundo em situação de distanciamento físico devido à COVID-19, as tecnologias da informação e comunicação (TICs) se enquadraram como um dos meios principais de interação e colaboração. Já no início deste milênio, começaram a ser mencionadas as seguintes vantagens: maior acesso à informação e à prestação de serviços; fortalecimento da educação; controle de qualidade dos programas de detecção e redução dos custos na atenção à saúde. No entanto, entre as principais barreiras de adoção da telemedicina se encontram as de caráter: tecnológico; humano e social; psicossocial e antropológico; de governança e econômico. Nestes 20 anos, houve um aumento nos recursos e na capacidade técnica, uma melhora na educação digital, um empoderamento do paciente em seu tratamento e um maior interesse público nessa área. Em especial, são consideradas bem-sucedidas a constituição de equipes interdisciplinares e as redes acadêmicas e profissionais, e as consultas médicas virtuais. Após revisar o estado da telemedicina na Região das Américas, os autores recomendam a adoção de medidas urgentes para implementar políticas e programas nacionais de telemedicina, incluindo o marco normativo e o orçamento necessário. Essa implementação deve ser realizada de maneira integral e interoperável e sustentada por redes acadêmicas, de parceria e instituições especializadas. Tais políticas devem gerar um contexto favorável, dando sustentabilidade ao avanço obtido e considerando os aspectos mencionados nas possíveis barreiras.

Barreras y facilitadores a la implementación de la telemedicina en las Américas / Barriers and facilitators to the implementation of the telemedicine in the Americas

Con millones de personas en el mundo en situación de distanciamiento físico por el COVID-19, las tecnologías de la información y comunicaciones (TICs) se han posicionado como uno de los medios principales de interacción y colaboración. Ya al inicio de este milenio se empezaban a mencionar las siguientes ventajas: mayor acceso a la información y a la prestación de servicios; fortalecimiento educativo; control de calidad de los programas de detección y reducción de los costos de la atención de en salud. Sin embargo, entre las principales barreras de adopción de la telemedicina se encuentran las de índole: tecnológicas; humanas y sociales; psico-sociales y antropológicas; de Gobernanza y económicas. En estos 20 años se logró un aumento en los recursos y capacidad técnica, una mejora en la educación digital, un empoderamiento del paciente en su tratamiento y un mayor interés público en esta área. En especial se considera exitosa la conformación de equipos interdisciplinarios, las redes académicas y profesionales y las consultas médicas virtuales. Después de revisar el estado de la telemedicina en la Región de las Américas, los autores recomiendan adoptar medidas urgentes para poner en práctica políticas y programas nacionales de telemedicina, incluyendo el marco normativo y presupuesto necesario, cuya implementación se realice de manera integral e interoperable y que se sustente de redes académicas, de colaboración e instituciones especializadas. Dichas políticas deben generar un contexto habilitante que den sostenibilidad al avance logrado, considerando los aspectos mencionados en las posibles barreras

Evaluación del proceso de teleconsulta desde la perspectiva del proveedor, Programa de Telesalud de Oaxaca, México / Evaluation of the teleconsultation process from the perspective of the provider (Oaxaca Telehealth Program, Mexico)

RESUMEN Objetivo Identificar las barreras en la implementación relacionadas con el proceso de teleconsulta para desarrollar estrategias que mejoren la operación del programa. Métodos Se estudió la implementación del servicio de teleconsulta mediante una estrategia de evaluación de procesos. Los referentes fueron los manuales operativos del programa, los cuales fueron comparados con información qualitativa y cuantitativa de la práctica del proceso de teleconsulta. Resultados Los factores reportados como obstáculos en el proceso de teleconsultas fueron la lentitud de la conexión a internet, el horario de atención, la oferta de especialidades y la insuficiencia de antecedentes clínicos en la solicitud de teleconsulta. Se identificó que 60% de los pacientes del servicio de medicina interna recibieron dos o más teleconsultas en el período de estudio, así como 44% de las pacientes del servicio de ginecología. Cuatro unidades médicas consultantes concentraron 75% de las teleconsultas, el resto se distribuyó en 12 unidades médicas. Conclusiones Las barreras identificadas en el proceso de teleconsulta afectan principalmente al médico consultante; aun así, la productividad se halla en aumento. Pese a las barreras existentes, se identificó que hay pacientes que reciben seguimiento por parte del programa, lo que favorece el acceso a la atención. Se requiere fortalecer la implementación y realizar investigaciones posteriores sobre las condiciones de salud de los pacientes.

ABSTRACT Objective Identify barriers to implementation of the teleconsultation process in order to develop strategies to improve the program’s operation. Methods A process evaluation strategy was used to study the implementation of the teleconsultation service. The program’s operating manuals were compared with the qualitative and quantitative information compiled on the practical implementation of the teleconsultation process. Results The factors reported as obstacles to the teleconsultation process were: slow Internet connection, the hours available to the public, the specialized services offered, and insufficient clinical history included in teleconsultation requests. It was determined that 60% of internal medicine patients received two or more teleconsultations in the study period, as did 44% of patients of the gynecology service. Four consulting medical units accounted for 75% of the teleconsultations and the rest were distributed among 12 medical units. Conclusions The barriers identified in the teleconsultation process mainly affect consulting physicians; even so, productivity is on an upward trend. Despite the existing barriers, it was determined that some patients receive follow-up through the program, which favors access to care. It is necessary to standardize implementation and to conduct subsequent research on patients’ health condition.

Evaluación del proceso de teleconsulta desde la perspectiva del proveedor, Programa de Telesalud de Oaxaca, México / Evaluation of the teleconsultation process from the perspective of the provider (Oaxaca Telehealth Program, Mexico)

Objetivo. Identificar las barreras en la implementación relacionadas con el proceso de teleconsulta para desarrollar estrategias que mejoren la operación del programa. Métodos. Se estudió la implementación del servicio de teleconsulta mediante una estrategia de evaluación de procesos. Los referentes fueron los manuales operativos del programa, los cuales fueron comparados con información qualitativa y cuantitativa de la práctica del proceso de teleconsulta. Resultados. Los factores reportados como obstáculos en el proceso de teleconsultas fueron la lentitud de la conexión a internet, el horario de atención, la oferta de especialidades y la insuficiencia de antecedentes clínicos en la solicitud de teleconsulta. Se identificó que 60% de los pacientes del servicio de medicina interna recibieron dos o más teleconsultas en el período de estudio, así como 44% de las pacientes del servicio de ginecología. Cuatro unidades médicas consultantes concentraron 75% de las teleconsultas, el resto se distribuyó en 12 unidades médicas. Conclusiones. Las barreras identificadas en el proceso de teleconsulta afectan principalmente al médico consultante; aun así, la productividad se halla en aumento. Pese a las barreras existentes, se identificó que hay pacientes que reciben seguimiento por parte del programa, lo que favorece el acceso a la atención. Se requiere fortalecer la implementación y realizar investigaciones posteriores sobre las condiciones de salud de los pacientes.

Objective. Identify barriers to implementation of the teleconsultation process in order to develop strategies to improve the program’s operation. Methods. A process evaluation strategy was used to study the implementation of the teleconsultation service. The program’s operating manuals were compared with the qualitative and quantitative information compiled on the practical implementation of the teleconsultation process. Results. The factors reported as obstacles to the teleconsultation process were: slow Internet connection, the hours available to the public, the specialized services offered, and insufficient clinical history included in teleconsultation requests. It was determined that 60% of internal medicine patients received two or more teleconsultations in the study period, as did 44% of patients of the gynecology service. Four consulting medical units accounted for 75% of the teleconsultations and the rest were distributed among 12 medical units. Conclusions. The barriers identified in the teleconsultation process mainly affect consulting physicians; even so, productivity is on an upward trend. Despite the existing barriers, it was determined that some patients receive follow-up through the program, which favors access to care. It is necessary to standardize implementation and to conduct subsequent research on patients’ health condition.