A continuous flow bioreactor system for high-throughput hyperpolarized metabolic flux analysis.

Hyperpolarized carbon-13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell metabolism in real-time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo. We demonstrate here a proof-of-concept bioreactor and microcoil receive array setup that allows for ex vivo preservation and metabolic NMR spectroscopy on up to three biopsy samples simultaneously, creating an easy-to-use and robust way to simultaneously run multisample carbon-13 hyperpolarization experiments. Experiments using hyperpolarized [1-13C]pyruvate on ML-1 leukemic cells in the bioreactor setup were performed and the kinetic pyruvate-to-lactate rate constants ( k PL ) extracted. The coefficient of variation of the experimentally found k PL s for five repeated experiments was C V = 35 % . With this statistical power, treatment effects of 30%-40% change in lactate production could be easily differentiable with only a few hyperpolarization dissolutions on this setup. Furthermore, longitudinal experiments showed preservation of ML-1 cells in the bioreactor setup for at least 6 h. Rat brain tissue slices were also seen to be preserved within the bioreactor for at least 1 h. This validation serves as the basis for further optimization and upscaling of the setup, which undoubtedly has huge potential in high-throughput studies with various biomarkers and tissue types.

Advances in the discovery of heterocyclic-based drugs against Alzheimer's disease.

INTRODUCTION: Alzheimer's disease is a multifactorial neurodegenerative disorder characterized by beta-amyloid accumulation and tau protein hyperphosphorylation. The disease involves interconnected mechanisms, which can be clustered into two target-packs based on the affected proteins. Pack-1 focuses on beta-amyloid accumulation, oxidative stress, and metal homeostasis dysfunction, and Pack-2 involves tau protein, calcium homeostasis, and neuroinflammation. Against this background heterocyclic system, there is a powerful source of pharmacophores to develop effective small drugs to treat multifactorial diseases like Alzheimer's. AREAS COVERED: This review highlights the most promising heterocyclic systems as potential hit candidates with multi-target capacity for the development of new drugs targeting Alzheimer's disease. The selection of these heterocyclic systems was based on two crucial factors: their synthetic versatility and their well-documented biological properties of therapeutic potential in neurodegenerative diseases. EXPERT OPINION: The synthesis of small drugs against Alzheimer's disease requires a multifactorial approach that targets the key pathological proteins. In this context, the utilization of heterocyclic systems, with well-established synthetic processes and facile functionalization, becomes a crucial element in the design phases. Furthermore, the selection of hit heterocyclic should be guided by a full understanding of their biological activities. Thus, the identification of promising heterocyclic scaffolds with known biological effects increases the potential to develop effective molecules against Alzheimer's disease.

Physical activity in a rural community in Colombia / Actividad física en una comunidad rural de Colombia

ABSTRACT Objective To characterize physical activity profiles in a rural community in the southwest of Colombia and to identify knowledge gaps on this issue in the country. Methods Cross-sectional study conducted in a rural area in Puerto Caldas, Pereira, Risaralda. The population of the study was obtained by convenience sampling from people participating in the activities of the Second Multidisciplinary Camp for Research and Services (CUMIS, for its acronym in Spanish), which was organized by the Colombian Association of Medical Students' Scientific Societies (ASCEMCOL, for its acronym in Spanish). The International Physical Activity Questionnaire (IPAQ) was used in order to measure and classify the physical activity behaviors of this population. Results Data from 100 subjects with a mean age of 43±18 years were collected. 6 % of the population did not perform any kind of physical activity, while 61 % performed vigorous physical activity. Men spent more time in doing vigorous and moderate physical activity than women did (p<0.05). The World Health Organization (WHO) recommendations on physical activity were followed by 72.29 % (n=60) and 82.35 % (n=14) of the people with an age of 18 to64 and ≥65 years, respectively. Conclusion It is necessary to build up evidence regarding physical activity in rural areas in order to implement public policies that promote its practice in communities where socioeconomic and health inequities exist. Part of the population living in the community where the study was carried out does not follow the WHO recommendations on physical activity; therefore, the lack of public health interventions is highlighted. A better coherence between international resolutions, national public policies and their implementation could lead to an increase in practice levels of physical activity.(AU)

RESUMEN Objetivo Caracterizar la actividad física en una comunidad rural del suroeste de Colombia e identificar los vacíos de conocimiento alrededor del tema en el país. Métodos Estudio de corte transversal en una zona rural de Puerto Caldas, Pereira, Risaralda. La población fue seleccionada, mediante muestreo por conveniencia, entre las personas que participaron en las actividades del II Campamento Multidisciplinar de Investigación y Servicios (CUMIS), dirigido por la Asociación Colombiana de Sociedades Científicas de Estudiantes de Medicina (ASCEMCOL). Se utilizó el International Physical Activity Questionnaire (IPAQ) para medir y clasificar los comportamientos de esta población en términos de actividad física. Resultados Se recogieron datos de 100 sujetos con edad promedio de 43±18 años. El 6 % de la población no realizó ningún tipo de actividad física, mientras que el 61 % realizó actividad física vigorosa. Los hombres dedicaron más tiempo a la práctica de actividad física vigorosa y moderada que las mujeres (p<0,05). Las recomendaciones sobre actividad física de la Organización Mundial de la Salud (OMS) fueron seguidas por el 72,3 % (n=60) y el 82,4 % (n=14) de las personas en los grupos de edad de 18 a 64 y ≥65 años, respectivamente Conclusión Es necesario construir evidencia en torno a la actividad física en el área rural, a fin de implementar políticas públicas que promuevan su práctica en comunidades que presenten desigualdades socioeconómicas y en salud. Parte de la población de la comunidad donde se llevó a cabo el estudio no sigue las recomendaciones de la OMS para actividad física, en consecuencia, la falta de intervenciones en salud pública se pone en evidencia. Una mayor coherencia entre las resoluciones internacionales, las políticas públicas nacionales y su aplicación podría conducir a un aumento en los niveles de actividad física.(AU)

Physical activity in a rural community in Colombia.

OBJECTIVE: To characterize physical activity profiles in a rural community in the southwest of Colombia and to identify knowledge gaps on this issue in the country. METHODS: Cross-sectional study conducted in a rural area in Puerto Caldas, Pereira, Risaralda. The population of the study was obtained by convenience sampling from people participating in the activities of the Second Multidisciplinary Camp for Research and Services (CUMIS, for its acronym in Spanish), which was organized by the Colombian Association of Medical Students' Scientific Societies (ASCEMCOL, for its acronym in Spanish). The International Physical Activity Questionnaire (IPAQ) was used in order to measure and classify the physical activity behaviors of this population. RESULTS: Data from 100 subjects with a mean age of 43±18 years were collected. 6 % of the population did not perform any kind of physical activity, while 61 % performed vigorous physical activity. Men spent more time in doing vigorous and moderate physical activity than women did (p<0.05). The World Health Organization (WHO) recommendations on physical activity were followed by 72.29 % (n=60) and 82.35 % (n=14) of the people with an age of 18 to64 and ≥65 years, respectively. CONCLUSION: It is necessary to build up evidence regarding physical activity in rural areas in order to implement public policies that promote its practice in communities where socioeconomic and health inequities exist. Part of the population living in the community where the study was carried out does not follow the WHO recommendations on physical activity; therefore, the lack of public health interventions is highlighted. A better coherence between international resolutions, national public policies and their implementation could lead to an increase in practice levels of physical activity.

Assessment of English language development: a validity study of a district initiative.

The San Francisco Unified School District (SFUSD) uses the Language and Literacy Assessment Rubric (LALAR) as the secondary measurement required by the No Child Left Behind (NCLB) Act to measure English proficiency of English language learners (ELLs). In this analysis, the Rasch model is used to identify whether the LALAR is a valid measurement instrument and scale to measure the "English proficiency" of ELLs. This analysis investigates the relationship between student ability () and the probability that the student will respond correctly to an item on the LALAR. Controlling for this relationship, the item characteristics of each item, ability of each student, and measurement error associated with each score were mathematically derived. This will allow for validity and reliability tests to be conducted, which will help determine if the LALAR is a useful accountability measure for ELLs.

Correlación de diez rasgos morfológicos dentales coronales entre molares deciduos y permanentes en tres grupos étnicos colombianos / Correlation of ten non-metric dental traits between deciduous and permanent molars of three ethnic colombian groups

Objetivos: Determinar la correlación de diez Rasgos Morfológicos Dentales Coronales RMDC (Carabelli, hipocono, puente de esmalte, metacónulo, protostílido, pliegue acodado, patrón cuspídeo, numero de cúspides y cúspide 6 y 7) entre los segundos molares deciduos superiores (um2) e inferiores (lm2), los primeros molares permanentes superiores (UM1) e inferiores (LM1) y los segundos molares permanentes superiores (UM2) e inferiores (LM2). Materiales y métodos: Este es un estudio descriptivo transversal para determinar la correlación de diez RMDC mediante su frecuencia y variabilidad, observados en 201 modelos de yeso de mestizos caucasoides de Cali, 84 modelos de yeso de afrocolombianos de Puerto Tejada y 60 modelos de yeso de indígenas del Amazonas. Resultados: Los indígenas del Amazonas entre um2/UM1 presentan correlación alta en Carabelli y número de cúspides; y muy alta en metacónulo y patrón cuspídeo. Los mestizos caucasoides entre um2/UM1 moderada en Carabelli, pliegue acodado y patrón cuspídeo; y alta en cúspide 6; y entre UM1/UM2/LM1/LM2 moderada en pliegue acodado, y alta en protostílido, patrón cuspídeo y cúspide 6. Los afrocolombianos entre UM1/UM2/LM1/LM2 moderada en pliegue acodado; y alta en protostílido, patrón cuspídeo y cúspide 6. Conclusiones: Los hallazgos soportan lo propuesto por la teoría de los campos morfogenéticos, la cual manifiesta que el diente gradiente de los molares deciduos y permanentes es um2/lm2, dado que retiene la configuración básica del patrón de contacto y el número de cúspides, Por tanto UM1/UM2/LM1/LM2 variarán de acuerdo al origen étnico y a la influencia ambiental de cada una de los tres grupos estudiados.

Aim: To determine correlations of ten non-metric dental crown traits NMDCT (Carabelli, hipocon2, enamel bridge, metaconule, protostylid, deflecting wrinkle, pattern cusp, cusp number and 6 and 7 cusp) between deciduous second upper (um2) and low (lm2) molars, permanent first upper (UM1) and lower (LM1) molars and permanent second upper (UM2) and lower (LM2) molars were studied. Materials y methods: This descriptive study determines the correlation of ten NMDCT through of the frequency and variability, observed on 201 dental casts of Cali racially mixed population, 84 dental casts of Puerto Tejada African-Colombian population and 60 dental casts of Colombian Amazons natives. Results: The Colombian Amazon natives showed high correlation in Carabelli and cusp number between um2/UM1; and very high in metaconule and pattern cusp. Cali racially mixed population showed moderated correlation in Carabelli, deflecting wrinkle and pattern cusp between um2/UM1; and high in 6 cusp. And between UM1/UM2/LM1/LM2 moderate in deflecting wrinkle; and high in protostylid, pattern cusp and 6 cusp. Puerto Tejada African-Colombian population showed moderated correlation between UM1/UM2/LM1/LM2 in deflecting wrinkle; and high in protostylid, pattern cusp and 6 cusp. Conclusions: Findings support the proposal of morphogenetic field theory, which exposes that the key tooth in deciduous and permanent molars is um2/lm2 because it retains the basic configuration of contact and number of cusps pattern, so UM1/UM2/LM1/LM2 will vary according to ethnic origin and to the environmental influence of each of three studied ethnic groups.