Opportunities and challenges of incretin-based hypoglycemic agents treating type 2 diabetes mellitus from the perspective of physiological disposition

The treatment of patients with diabetes mellitus, which is characterized by defective insulin secretion and/or the inability of tissues to respond to insulin, has been studied for decades. Many studies have focused on the use of incretin-based hypoglycemic agents in treating type 2 diabetes mellitus (T2DM). These drugs are classified as GLP-1 receptor agonists, which mimic the function of GLP-1, and DPP-4 inhibitors, which avoid GLP-1 degradation. Many incretin-based hypoglycemic agents have been approved and are widely used, and their physiological disposition and structural characteristics are crucial in the discovery of more effective drugs and provide guidance for clinical treatment of T2DM. Here, we summarize the functional mechanisms and other information of the drugs that are currently approved or under research for T2DM treatment. In addition, their physiological disposition, including metabolism, excretion, and potential drug-drug interactions, is thoroughly reviewed. We also discuss similarities and differences in metabolism and excretion between GLP-1 receptor agonists and DPP-4 inhibitors. This review may facilitate clinical decision making based on patients' physical conditions and the avoidance of drug-drug interactions. Moreover, the identification and development of novel drugs with appropriate physiological dispositions might be inspired.

Physiological pharmacokinetic model of children and its application of modeling software / 药学学报

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

Cumplimiento de objetivos en pacientes adultos con diabetes mellitus tipo 1: tasa estimada de disposición de glucosa como marcador clínico / Achievement of objectives in adult patients with type 1 diabetes mellitus: estimated glucose disposition rate as a clinical marker

Resumen Introducción: las guías de práctica clínica en diabetes mellitus (DM) establecen objetivos clínicos precisos sobre el buen manejo de la enfermedad, pero poco se sabe sobre el adecuado cumplimiento en nuestro medio. El sobrepeso y el sedentarismo han generado estigmas de síndrome metabólico en la población con DM1. Objetivos: evaluar el cumplimiento en cinco de dichos criterios: HbA1c <7%, c-LDL ≤100 mg/dl, actividad física ≥3 veces/ semana, tensión arterial sistólica (TAS) <140 mm Hg y no tabaquismo, y su asociación con insulinorresistencia determinada por la tasa estimada de disposición de glucosa (TeDG). Materiales y métodos: en 415 DM1 ≥18 años, 52% mujer y una edad de 34,8±13,9 años, se evaluó HbA1c, c-LDL, frecuencia semanal de actividad física (AF) estructurada, TAS y tabaquismo actual. Se determinó el grado de asociación a género, edad, antigüedad de la DM, nivel de educación, cobertura médica, índice de masa corporal (IMC) y sensibilidad a la insulina medida a través de la TeDG. Las variables cualitativas se analizaron por test de chi. y las cuantitativas por test de ANOVA I con post hoc por test de Tukey. Un valor de p<0,05 se consideró estadísticamente significativo. En todos los casos se utilizó un intervalo de confianza del 95%. Resultados: el 94,8% presentó TAS <140 mm Hg, el 82,2% no tabaquismo actual, el 56,5% c-LDL ≤100 mg/dL, el 39% AF ≥3 veces/semana y el 20,3% HbA1c <7%. Solo 26 pacientes (6,2%) alcanzaron en forma combinada los cinco objetivos analizados. El cumplimiento de dichos objetivos se asoció a nivel de educación secundaria o mayor (p=0,002) y cobertura de salud con obra social o prepaga (p=0,002). Hubo asociación significativa entre la TeDG en quienes cumplieron los cinco objetivos (p=0,02) y en forma individual en cuatro de ellos (TAS, c-LDL, HbA1c y AF). Conclusiones: de los 415 pacientes evaluados, el 6,2% cumplió los cinco objetivos. Solo el control de la TAS, no fumar y un c-LDL <100 mg/dL lo cumplió la mayoría de los pacientes. Una HbA1c <7% fue el objetivo individual que presentó menor grado de cumplimiento.

Abstract Introduction: the clinical practice guidelines in diabetes mellitus (DM) establish precise clinical objectives for the good management of the disease, but little is known about adequate compliance in our environment. Being overweight and sedentary have generated stigmas of metabolic syndrome in the population with DM1. Objectives: to evaluate the compliance with 5 of these criteria: HbA1c <7%, c-LDL ≤100 mg/dL, physical activity (PA) ≥3 times/week, systolic blood preasure (SBP) <140 mm Hg, and no smoking and its association with insulin resistance determined by the estimated glucose disposition rate (eGDR). Materials and methods: in 415 DM1 ≥18 years, 52% women, age 34.8±13.9 years, HbA1c, c-LDL, weekly frequency of structured PA, SBP, and current smoking were evaluated. The degree of association with gender, age, age of DM, level of education, medical coverage, BMI, and insulin sensitivity measured through eGDR was determined. Qualitative variables were analyzed by chi-square test and quantitative variables by ANOVA I test and analysis post hoc by Tukey's test for multiple comparisons. A value of p<0.05 was considered statistically significant. A 95% confidence interval was used in all cases. Results: systolic BP <140 mm Hg presented 94.8%, current non-smoking 82.2%, c-LDL ≤ 100 mg/dL 56.5%, physical activity (PA) ≥3 times a week 39% and HbA1c <7% 20.3%. Only 26 patients (6.2%) achieved the 5 objectives analyzed in combination. The fulfillment of the 5 objectives was associated at the level of ≥ secondary education (p=0.002) and health coverage with social welfare or prepaid (p=0.002). There was a significant association between TeDG in those who fulfilled the 5 objectives (p=0.02) and individually in 4 of them (SPB, c-LDL, HbA1c, and PA). Conclusions: of the 415 patients evaluated in our study, only 6.2% met the 5 criteria under consideration. Only control of SBP, non-smoking and c-LDL <100 were complied with by the majority of the patients. HbA1c <7% was the individual objective with the lowest degree of compliance.

Health-related reasons patients transfer from a clinic or health post to the Emergency Department in a District Hospital in Botswana

Introduction: Rural health clinics in low-resource settings worldwide are usually staffed with health care workers with limited knowledge and skills in managing acute emergencies. The Emergency Centre (EC) at the district hospital or primary hospital serves as an entry point for patients with diverse medical needs from health posts and community clinics. The study described the socio-demographic characteristics, primary diagnosis, and disposition of patients transferred from the clinics and health posts to the district hospital in the Kweneng district. Method: This study is a chart audit of the triage sheets and admitting medical records (Botswana Integrated Patient Management System, IPMS) conducted for the period June through to December 2020. Descriptive statistics were used to analyze the quantitative data. Frequencies, percentages, and measures of central tendency were calculated using the software, SPSS version 27. Results: A total of 1565 charts were reviewed; 56% (n = 877) were females and 43.5% (n = 681) were males. Half of the patients presenting to the EC ranged from ages 21 to 50, with a mean age of 36.49. The most frequently reported reason for referral was "trauma," (23.5%, n = 368) whereas the second common reason for referral was abortion-related complications (14.2%, n = 222). The highest admissions were from abortion-related complications (20.2%, n = 169). Most patients' transfers were from clinics and health posts outside Molepolole (59.4%, n = 930). More than half of the patients (64.2%, n = 537) transferred from outside Molepolole were admitted than discharged from the EC. Discussion: Our study has shown significant transfers to a higher facility for emergency care. The higher number of transfers are trauma-related cases, whereas most patients were admitted for abortion-related complications indicating the need for skill-building in trauma care and management of abortions.

Correlates between sexual desire and disposition to sexual fantasies with inhibitory control and cognitive planning in young Colombians / Correlación del deseo sexual y disposición a fantasías sexuales con control inhibitorio y planificación cognitiva en jóvenes colombianos

Abstract Objective: the research was oriented to investigate the correlation between some executive functions (inhibitory control, risk-benefit calculation, cognitive flexibility, the planning ability, and decision making) and the general, dyadic and solitary sexual desire, sexual desire inhibition and disposition to sexual fantasies in a 17-to-30-year-old people sample. Method: An observational cross-sectional study in a purposive sample of 64 young college students, aged between17 and -30, who were in a couple relationship at the time of the study and gave their consent for their participation in the research. The participants completed the Neuropsychological Battery of Executive Functions and Frontal Lobes tasks (BANFE for its abbreviation in Spanish): Stroop, card games, card classification and Hanoi Tower, and it was administered the Inhibited Sexual Desire Test, the Sexual Desire Inventory (SDI-2) and the Scale of Attitude Towards Sexual Fantasies. Results: The results indicate a correlation between the executive functions and sexual desire; it was found a correlation between total and dyadic sexual desire and disposition towards sexual fantasies with inhibitory control; and the inhibited sexual desire was correlated to planning ability and inhibitory control. Discussion: Although the study presents some methodological limitations (size of the sample and need of a more rigorous validation of instruments in the Colombian population), the results confirm previous research findings, allowing to formulate new hypotheses in the field of sexuality and neurosciences. The study findings draw attention to the educational implications aimed to develop the executive functions in adolescents and young people to prevent risky sexual behavior.

Resumen Objetivo: El estudio se orientó a indagar la relación entre algunas funciones ejecutivas (FE) (control inhibitorio, cálculo de riesgo-beneficio, flexibilidad cognitiva, habilidad de planeación y toma de decisiones) con el deseo sexual general, diádico y solitario, inhibición del deseo sexual y disposición hacia las fantasías sexuales en una muestra de jóvenes entre 17 y 30 años. Método: Estudio de enfoque cuantitativo de corte transversal. Mediante un muestreo intencional por conveniencia se seleccionaron 64 jóvenes entre 17 y 30 años, estudiantes universitarios que se encontraban en una relación de pareja. Para evaluar las variables de las FE se utilizaron tareas de la Batería Neuropsicológica de Funciones Ejecutivas y Lóbulos Frontales (BANFE): Stroop, juego de cartas, clasificación de cartas y Torre de Hanoi, y las variables relacionadas con el deseo sexual fueron valoradas mediante el Test del Deseo Sexual Inhibido, el Inventario del Deseo Sexual (SDI-2, sigla de Sexual Desire Inventory) y la Escala de la Actitud hacia las Fantasías Sexuales. Resultados: Se encontraron correlaciones entre las variables del deseo sexual, disposición hacia las fantasías sexuales y el deseo sexual inhibido; deseo sexual total y diádico y disposición hacia las fantasías sexuales correlacionó con el control inhibitorio; y el deseo sexual inhibido correlacionó con la planificación y el control de impulsos. Discusión: Los hallazgos del estudio llaman la atención sobre las implicaciones educativas encaminadas a desarrollar las funciones ejecutivas en adolescentes y jóvenes con el fin prevenir conductas sexuales de riesgo.

Perspectivas filosóficas a partir del problema del suicidio / Philosophical perspectives from the problem of suicide / Perspectivas filosóficas a partir do problema do suicídio

Resumen Varias de las actuales discusiones bioéticas parten del supuesto de que tenemos absoluto dominio/disposición sobre nuestro cuerpo. Bajo la tesis de la autonomía, del dominio de la vida propia y de la libertad para hacer cualquier cosa, al menos con nuestro cuerpo, se suele justificar la bondad o legitimidad de actos como el suicidio y la eutanasia. Supuesto lo anterior, el trabajo aborda la cuestión de la naturaleza de la disposición -principal atributo del dominio o propiedad- sobre el cuerpo. Se argumentará sobre la base de la teoría de Tomás de Aquino y de la exposición de Immanuel Kant, muchas veces consideradas, erróneamente a mi juicio, como doctrinas rivales. El escrito estará orientado a revisar las relaciones del moderno principio de autonomía con la problemática de la moralidad del suicidio.

Abstract Many of the actual bioethical discussions start from the assumption that we have absolute dominance/disposition over our body. Based on the thesis of autonomy, control over one's own life and the freedom to do anything, at least with one's body, the goodness or legitimacy of acts such as suicide and euthanasia are often justified. Considering the last statements, this paper seeks to approach the question of the nature of the disposition -main attribute of dominion or property- over the body. It will be argued on the basis of Thomas Aquinas' theory and Immanuel Kant's exposition, often wrongly considered, in my opinion, as rival doctrines. The whole writing will be oriented to review the relations of the modern principle of autonomy with the problem of the morality of suicide.

Resumo Várias das atuais discussões bioéticas partem do pressuposto de que temos absoluto domínio/disposição sobre nosso corpo. Sob a tese da autonomia, do domínio da vida própria e da liberdade para fazer qualquer coisa, ao menos com nosso corpo, costuma-se justificar a bondade ou legitimidade de atos como o suicídio e a eutanásia. Levando em consideração o anterior, este trabalho pretende abordar a questão da natureza da disposição -principal atributo do domínio ou da propriedade- sobre o corpo. Argumenta-se com base na teoria de Tomás de Aquino e na exposição de Immanuel Kant, muitas vezes conceituadas, erroneamente, em minha opinião, como doutrinas rivais. Este texto estará orientado a revisar as relações do moderno princípio de autonomia com a problemática da moralidade do suicídio.

La relación entre la edad, el engagement y la disposición al cambio organizacional / The relationship between age, engagement and disposition to organizational change

Resumen La gestión de recursos humanos como función estratégica en las organizaciones de trabajo constituye en la actualidad una actividad de alta complejidad que implica importantes retos para los líderes de gestión humana a nivel global, debido a los procesos de cambio constante que viven las organizaciones de todo tipo. Estos procesos están dados tanto por exigencias provenientes de las transformaciones del entorno como por los requerimientos internos de ajuste en las organizaciones para mantener su productividad y competitividad en la dinámica de los mercados actuales, condiciones que imprimen serias implicaciones en la gestión del cambio y su relación con el comportamiento, desempeño y compromiso de los trabajadores. El objetivo de esta investigación fue identificar la posible relación entre la edad, el engagement, y la disposición al cambio organizacional, ya que estas variables resultan tener un papel clave en la gestión de recursos humanos en el contexto actual del mundo del trabajo, según se concluye de estudios previos que muestran relaciones entre diferentes tipos de compromiso y procesos de cambio organizacional. La presente investigación se enmarca en la perspectiva de la psicología positiva, un enfoque reciente que busca alejarse del énfasis en lo patológico del comportamiento para centrarse en los aspectos positivos y el potencial del ser humano. Esta perspectiva de la psicología en el campo del estudio del comportamiento organizacional se ha denominado "psicología organizacional positiva". Para lograr los objetivos de identificar la relación entre las variables, se realizó un estudio predictivo, que se orienta fundamentalmente a indagar la relación funcional entre dos o más variables, con un diseño correlacional simple en el que no se utilizan formas de control de variables extrañas que puedan tener influencia en la relación funcional investigada. La muestra estuvo compuesta por 808 personas divididas en dos submuestras (35.5 % colombianos y 65.5 % ecuatorianos), seleccionadas de manera no probabilística accidental. Para la evaluación de las variables se utilizó el autorreporte en la edad, el cuestionario Utrecht Work Engagement Scale (UWES) y el instrumento Disposición al Cambio Organizacional. Los resultados mostraron relaciones significativas entre las variables disposición al cambio organizacional y engagement, tanto a nivel general como en las submuestras. Sin embargo, al indagar sobre el posible papel moderador de la edad entre las otras dos variables, no se encontraron evidencias al respecto. Otros análisis sugieren la posibilidad de un efecto mediado por aspectos culturales que puede incidir en la disposición al cambio. El presente estudio constituye un importante aporte en la comprensión del comportamiento humano en el trabajo en relación con procesos de cambio organizacional, específicamente la asociación de este con variables como el engagement y la edad. Sin embargo, sucesos recientes como la situación mundial derivada de la pandemia por el virus SARSCOV2 y su impacto en las dinámicas de trabajo sugieren la necesidad de avanzar en estudios complementarios al realizado por los autores y que se presenta en este artículo, puesto que las actividades laborales han migrado para muchas personas del contexto de la empresa al contexto del hogar, lo que pone en escena otras variables que podrían incidir en la relación aquí indagada.

Abstract Human resource management as a strategic function in work organizations is currently a highly complex activity that implies significant challenges for human management leaders at a global level, due to the processes of constant change that all kind of organizations must experience, due to demands arising from the transformations of the environment and the internal requirements of adjustment in organizations to maintain their productivity and competitiveness in the dynamics of current markets, conditions that have serious implications in the management of change and its relationship with behavior , performance and commitment of the workers.. In this context, the human resources area has the important task of contributing to the management of human talent to achieve high levels of commitment from people in organizations and facilitate change processes, if organizational leaders want to achieve strategic objectives in a much more effective way. To achieve this, it is necessary to identify key variables that affect human behavior in work contexts and understand the possible relationships between these variables. The main objective of this research was to identify the relationship between age, engagement, and disposition to organizational change since these variables turn out to have a key role in human resource management in the current context of the world of work. The present investigation is framed in the perspective of positive psychology, a recent approach that seeks to move away from the emphasis on the pathological behavior to focus on the positive aspects and potential of the human being. This is the perspective of psychology in the field of the study of organizational behavior has been called positive organizational psychology. To achieve the objectives of identifying the relationship between the variables, a predictive study with a simple correlational design was performed. This kind of study is mainly oriented to investigate the functional relationship between two or more variables in which no forms of control of strange variables are used. The sample was made up of 808 people divided into two sub-samples (35.5 % Colombian and 65.5 % Ecuadorian), selected in an accidental non-probabilistic way; The self-report on age, the Utrecht Work Engagement Scale (UWES) questionnaire and the instrument Disposition to organizational change were used to evaluate the variables. The results showed significant relationships between the variables disposition to organizational change and engagement, both in general and in the subsamples; however, when investigating the possible role of age in moderating the other two variables, no evidence was found in this regard. Other analyzes suggest the possibility of an effect mediated by cultural aspects that may affect the readiness to change. However, recent events such as the world situation derived from the SARSCOV2 virus pandemic and its impact on work dynamics, suggest the need to advance in complementary studies to the one carried out by the authors and presented in this article, since the Work activities have migrated for many people from the context of the company to the context of the home, which highlights other variables that could affect the relationship investigated here.

Relationships between general self-efficacy and mobile game addiction among middle school students： mediating effect of time management disposition / 四川精神卫生

ObjectiveTo discuss the relationship between general self-efficacy and mobile game addiction among middle school students， and to analyse the mediating role of time management disposition. MethodsFrom November 2020 to February 2021， a sample of 667 students were recruited from three middle schools in Jiangxi and Sichuan provinces using cluster sampling method. All selected students were assessed using General Self-Efficacy Scale （GSES）， Mobile Game Addiction Scale and Adolescence Time Management Disposition Inventory （ATMD）. Further， Bootstrap method was used to test the mediating effect. Results①The total score of Mobile Game Addiction Scale was negatively correlated with the total scores of GSES and ATMD （r=-0.122， -0.333， P<0.01）. The total score of ATMD was positively correlated with the total score of GSES （r=0.536， P<0.01）. ②General self-efficacy and time management disposition could predict the mobile game addiction negatively （β=-0.333， -0.122， P<0.01）， and general self-efficacy could predict the time management disposition positively （β=0.536， P<0.01）. ③Time management disposition played a full mediating role between general self-efficacy and mobile game addiction， with a mediating effect size of -0.159 （95% CI： -0.213~-0.112， P<0.01）， accounting for 70.38% of the total effect. ConclusionGeneral self-efficacy indirectly affects mobile game addiction via time management disposition.

Potential health benefits of resveratrol: a pharmacokinetics-caused conundrum / 中国临床药理学与治疗学

Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) was first identified from white hellebore (Veratrum grandiflorum) root and began to attract interest when its presence in red wine and cardiovascular activities were reported, leading to speculation of its contribution to the 'French paradox'. Besides the cardiovascular protection, potential health benefits of resveratrol include calorie restriction-like effects, cancer prevention and adjunctive therapy, and neuroprotection. In order to achieve translational applications of these potential benefits, pharmacokinetic research was performed for plasma pharmacokinetics and related disposition of orally dosed resveratrol. This paper summarizes the known human pharmacokinetic characteristics of resveratrol after oral administration and various attempts to improve its systemic exposure level from the perspectives of systemic exposure and in vivo process. However, available pharmacokinetic data of resveratrol has raised conundrums that limit translating potential benefits to clinics: (1) differences between the unchanged resveratrol used in bioactivity studies and its major circulating forms (i.e., metabolites) after dosing; (2) resveratrol's test concentrations used to exert in vitro bioactivities related to the benefits significantly higher than the compound's clinically achievable concentrations; (3) resveratrol's concentrations achievable (estimated from the pharmacokinetics) from doses used to produce in vivo efficacy significantly lower than the effective concentrations found in studies of related action mechanism (suggesting unreliability of test mechanism). In the last part of this review, we provide recommendations for future pharmacokinetic investigations of resveratrol, including a more systematic investigation of systemic exposure to resveratrol metabolites, their access to in vivo loci responsible for the benefits, and their disposition in target cells; an investigation of colon-luminal exposure to resveratrol and its metabolites for accessing colonic microbiota; and a multi-compound pharmacokinetic investigation of red wine.

Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Aspectos de la cultura organizacional y su relación con la disposición al cambio organizacional / Aspects of organizational culture and its relation to the organizational change disposition

Resumen El objetivo de esta investigación fue determinar la relación entre la cultura organizacional y la disposición al cambio organizacional. Se trata de una investigación empírica que, de acuerdo con el objetivo de investigación, responde a una estrategia asociativa, en un estudio predictivo desarrollado bajo un diseño correlacional simple. La muestra estuvo compuesta por 558 participantes de cuatro entidades de educación superior. Para la evaluación de las variables se emplearon la adaptación para Colombia del OCAI (Organizational Culture Assessment Instrument) y la prueba Disposición al Cambio Organizacional. Los resultados mostraron relaciones significativas entre los factores y los tipos de cultura organizacional con las macro y microdimensiones de la disposición al cambio organizacional. También se encontraron diferencias significativas entre las instituciones en las dimensiones grupal y organizacional de la disposición al cambio, en el factor organizacional y en el tipo de cultura jerárquica. Se evidencia cómo la cultura organizacional se relaciona particularmente con aspectos organizacionales y la comunicación empresarial.

Abstract The objective of this research was to determine the relationship between aspects of organizational culture and the disposition to organizational change. A quantitative, nonexperimental study was carried out under a comparative design; with a sample of 558 participants from four higher education institutions. The instruments used allowed the evaluation of the organizational culture -OCAI- and the willingness to change. The results showed significant relationships between the factors and the types of organizational culture with the macro and micro dimensions of the disposition to organizational change. Significant differences were also found between the institutions in the group and organizational dimensions of the disposition to change; in the organizational factor and the type of hierarchical culture. It is evident how the organizational culture is particularly related to organizational aspects and business communication.

Attitudinal Disposition and Management Perception among Diabetes Mellitus Patients in Selected Hospitals in Ibadan, Oyo State, Nigeria

Background:Diabetes mellitus is an emerging metabolic disorder of the 21stcentury and has continued to attract the attention of health practitioners, as it continues to decrease the efficiency of its victims without any promise of change in the near or far future if more is not done to avert the progressing chronic condition. Aim:To determine the attitudinal disposition and management perception among diabetics Mellitus patients in selected hospitals in Ibadan, Nigeria.Study Design:The study was a cross sectional survey design guided by a behavioral theory.Place and Duration of Study:using purposive sampling, the study was carried out among diabetic patient attending University College Hospital, Ring-Road State Hospital and Oluyoro Catholic Hospital, Ibadan, Oyo State Materials and Methodology:A systematic random sampling was used to select 600 out of 2,115 diabetes patients receiving treatment at University College Hospital, Ring-Road State Hospital and Oluyoro Catholic Hospital. A semi-structured questionnaire was used for data collection on respondents’ socio-demographic characteristics, attitudinal disposition and management perception. Descriptive statistics was used for data analysis.Results:Mean age of the respondents was 63.9 ± 8.6 years, 75.3% were married and 62.7% were females. Majority (94.0%) of the respondents had a positive attitude towards compliance with management of DM. Majority (91.5%) were of the attitude that it is not necessary for people living with DM to do regular exercise as exercise will not make them to breakdown and 97.0% were of the attitude that diabetic patients cannot take any amount of alcohol beverages he/she wants. Respondents’ mean perception score was 21.8 ± 4.8 and 69.2% had a positive perception to management of DM. most (69.2%) of the respondents were of the perception that DM is a lifelong disease and can only be controlled but cannot be cured. Conclusion:Many of the respondents had appropriate perceptions needed to cope with the disease. However, the positive attitude sustenance demonstrated by the respondent should be promoted if compliance with the management of DM must be ensured.

Los actos de libre disposición del cuerpo humano / Atos de livre disposição do corpo humano / The acts of free disposal of the human body

Resumen: El cuerpo es la estructura biológica del ser humano. Determina al hombre en su existencia físico material. Los sujetos de derechos individuales tienen un cuerpo sobre el cual pueden decidir qué hacer, de forma directa o consentida, incluso cabe la posibilidad de actos de injerencia corporal indirectos o impuestos. La persona puede aspirar a un cuerpo mejor o utilizarlo en beneficio de los demás. El cuerpo humano, como base fisiológica de la personalidad, está protegido en el marco del núcleo duro de dignidad que le es atribuida per se. El derecho a los actos de libre disposición del cuerpo humano es la facultad de hacer con nuestro cuerpo lo que mejor creamos conveniente, siempre que no vaya contra las normas de orden público, las buenas costumbres o implique una disminución de la integridad y salud.

Resumo: O corpo é a estrutura biológica do ser humano e determina o homem em sua existência física material. Os sujeitos de direitos individuais têm um corpo sobre o qual podem decidir o que fazer, de forma direta ou consentida, incluso cabe a possibilidade de atos de ingerência corporal indireta ou imposta. A pessoa pode aspirar a um corpo melhor, ou usá-lo em benefício de demais. O corpo humano, como base fisiológica da personalidade, está protegido no marco do núcleo rígido da dignidade que a ele é atribuído per se. O direito aos atos de livre disposição do corpo humano é a faculdade de fazer com nossos corpos o que melhor entendemos que seja conveniente, sempre que isso não seja contra as normas de ordem pública, os bons costumes ou implique uma diminuição na integridade e saúde.

Abstract: The body is the biological structure of the human being. It determines man in his natural physical existence. Individual law subjects have a body over which they can decide what to do, directly or consensually, including the possibility of acts of indirect or imposed corporal interference. The person can aspire to a better body or use it for the benefit of others. The human body, as the physiological basis of personality, is protected within the framework of the hard core of dignity attributed to it per se. The right to acts of free disposal of the human body is the ability to do with our bodies what we believe best, provided that it does not go against the rules of public order, good manners or implies a decrease in integrity and health.

Diagnóstico de áreas contaminadas pela disposição final de resíduos sólidos no município de Paço do Lumiar (MA) / Diagnosis of contaminated areas by final disposal of solid waste in the municipality of Paço do Lumiar (MA), Brazil

RESUMO A disposição final de resíduos sólidos é considerada uma fonte potencial de contaminação e tem merecido destaque em função dos problemas ambientais e socioeconômicos que pode gerar. O município de Paço do Lumiar, no Maranhão, utiliza um lixão como forma de disposição de resíduos sólidos urbanos mesmo após ter cessado o prazo para o fim dos lixões no Brasil conforme a Política Nacional de Resíduos Sólidos, Lei Federal nº 12.305, de 2 de agosto de 2010. Em virtude disso, este estudo teve como objetivo detectar áreas contaminadas pela disposição de resíduos sólidos em Paço do Lumiar com base na metodologia do Manual de Gerenciamento de Áreas Contaminadas do projeto CETESB/GTZ (1999), utilizando os compartimentos ambientais solo e água superficial como objetos de análise. Assim, verificou-se que o lixão tem contribuído para a contaminação do solo com metais pesados no local de disposição e a 200 m a sua jusante, o que pode significar contaminação potencial da água subterrânea em virtude de a geologia local e o solo arenoso serem facilitadores no processo de transporte de contaminantes. Já a análise da água superficial revelou que a disposição de resíduos sólidos pode estar contribuindo menos que outras fontes de contaminação, destacando-se, nesse contexto, os efluentes gerados pelas comunidades que ocupam a bacia. Portanto, como a contaminação verificada compromete alguns usos da terra (residencial e agrícola), estudos posteriores poderão contemplar o processo de remediação de áreas contaminadas conforme material da CETESB/GTZ (1999) para que medidas corretivas minimizem os impactos ambientais na região.

ABSTRACT The final disposal of solid waste is considered a potential source of contamination and has been highlighted due to the environmental problems and socioeconomic factors that it can generate. The municipality of Paço do Lumiar, Maranhão, uses a garbage dump as a way of disposing urban solid waste, even after the deadline for the end of dumps in Brazil, as established by the National Solid Waste Policy, Federal Law No. 12,305, dated August 2, 2010. As a result, the objective of this study was to detect areas contaminated by disposal of solid waste in Paço do Lumiar, based on the Workshop Management of Contaminated Areas' methodology, a part of the project CETESB/GTZ (1999), using the environmental compartments soil and surface water as objects of analysis. Thus, it was found that the garbage dump has contributed to the contamination of soil with heavy metals in the place of provision and 200m to its downstream, which can mean potential contamination of ground water due to the local geology and the fact that sandy soil facilitates the process of transporting contaminants. The analysis of the surface water revealed that the disposal of solid waste can contribute less than other sources of contamination, highlighting in this context those generated by the communities that occupy the basin. Therefore, as the verified contamination compromises some land uses (residential and agricultural), further studies may contemplate the remediation process of these contaminated areas according to the CTESB/GTZ (1999) material for stablishing measures to minimize this region's environmental impacts.

Relación entre apoyo social percibido y disposición resiliente en adolescentes paraguayos / Relation between perceived social support and resilient disposition in paraguayan adolescents

Resumen El estudio de la adolescencia ha destacado la vulnerabilidad del proceso asociado con variables como la disposición resiliente, presente en aquellos recursos que pueden hacer la diferencia para el sustento del bienestar o su ausencia. De estos recursos se destaca el apoyo social que el adolescente percibe de su entorno. El objetivo de la investigación se centró en establecer la relación entre el apoyo social percibido y la disposición resiliente, y compararlas conforme el sexo y la edad de una muestra de adolescentes paraguayos escolarizados. Se llevó a cabo un diseño comparativo y correlacional, con 1334 adolescentes escolarizados de 12 a 18 años (ME= 14.99; DE= 1.66), 725 mujeres y 609 varones. Se empleó la Escala de Apreciación de Apoyo Social -EAAS y el Inventario de Resiliencia IRES. Los datos evidenciaron que no existe correlación entre apoyo social y disposición resiliente en esta muestra específica de adolescentes paraguayos, por factores que habrá que seguir investigando. Se observan diferencias en el apoyo social de amigos y de otros, mayormente en los varones. En las mujeres, se observan diferencias significativas en las escalas de resiliencia, en el sentido del humor, autoeficiencia y empatía. En cuanto a edad, los adolescentes de 16 a 18 años puntúan más en religiosidad y en el apoyo social, familiar, de amigos y de otros. Se sugiere estudiar otras variables relacionadas con el apoyo social y la disposición resiliente, en tanto muchas de las políticas públicas preventivas de atención a la salud positiva refuerzan su importancia en la adolescencia.

Abstract The study of adolescence has highlighted the vulnerability of the process associated with variables such as the resilient disposition, present in those resources that can make a difference for the sustenance of well-being or its absence. Of these resources, the social support that adolescents perceive of their environment stands out. The objective of the research is to establish the relationship between perceived social support and resilient disposition, and compare them according to the sex and age of a sample of Paraguayan adolescents attending school. A comparative and correlational design is carried out, with 1334 school-age adolescents aged 12 to 18 (ME = 14.99, SD = 1.66), 725 women and 609 men. The instruments used were the Sociodemographic Certificate for Adolescents and their Families, the Scale of Appreciation of Social Support -EAAS de Martínez (2004) and the Inventory of Resilience IRES (Gaxiola Romero, Frias Armenta, Hurtado Abril, Salcido Noriega, Figueroa Franco, 2011). The results indicate that there is no correlation between social support and resilience, probably due to individual characteristics that generate resilient dispositions in adolescents. Regarding the scales of social support, there are differences in the social support of friends and others, mainly in males. In women, significant differences are observed in the scales of resilience, in the sense of humor, self-efficacy and empathy. Differences were found in the ages of the adolescents, the age group of 16 to 18 years obtained a higher score in religiosity and in social, family, friends and other support. It is suggested to study simultaneously more variables related to social support and the resilient disposition, since many of the preventive public policies of attention to positive health reinforces its importance in adolescence.

Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins

There are many factors that can influence the pharmacokinetics (PK) of a mAb or Fc-fusion molecule with the primary determinant being FcRn-mediated recycling. Through Fab or Fc engineering, IgG-FcRn interaction can be used to generate a variety of therapeutic antibodies with significantly enhanced half-life or ability to remove unwanted antigen from circulation. Glycosylation of a mAb or Fc-fusion protein can have a significant impact on the PK of these molecules. mAb charge can be important and variants with pI values of 1-2 unit difference are likely to impact PK with lower pI values being favorable for a longer half-life. Most mAbs display target mediated drug disposition (TMDD), which can have significant consequences on the study designs of preclinical and clinical studies. The PK of mAb can also be influenced by anti-drug antibody (ADA) response and off-target binding, which require careful consideration during the discovery stage. mAbs are primarily absorbed through the lymphatics via convection and can be conveniently administered by the subcutaneous (sc) route in large doses/volumes with co-formulation of hyaluronidase. The human PK of a mAb can be reasonably estimated using cynomolgus monkey data and allometric scaling methods.

Comparison of Two Biopharmaceutics Classification Systems and Discussion of Their Applications / 中国药学杂志

OBJECTIVE: To compare the difference between two kinds of biopharmaceutics classification systems and their applications. METHODS: Literatures and guidelines on biopharmaceutics classification system(BCS) and biopharmaceutics drug disposition classification system(BDDCS) were collected, the differences in conception, classification criteria, and application were compared, and problems which should be paid attention to in application were summarized. RESULTS:A lot of issues such as solubility, permeability, extent of metabolism and so on are involved in the application of BCS and BDDCS. Different classification criteria may have different results. The recognition for the two kinds of pharmaceutics classification systems by different administration organizations is not yet completely consistent. CONCLUSION:BCS and BDDCS play important roles in understanding the properties of drugs, especially in drug development and evaluation of generic drug conformance, however, the source of data should be identified when quoting the data. Possible risks should be considered for rational use of the data.

Characteristic analysis of insulin secretion and sensitivity in pre-diabetes populations under new diagnostic criteria / 上海交通大学学报（医学版）

Objective: To investigate the characteristics of insulin secretion function and sensitivity and blood glucose disposition capacity in the prediabetes populations. Methods: A total of 1 317 subjects were enrolled in this study, including 382 with normal glucose tolerance (NGT) and 935 with pre-diabetes. All pre-diabetes populations were divided into seven subgroups according to the cut-off points of 2010 American Diabetes Association standards. Homeostasis model assessment (HOMA) was used to access baseline insulin secretion (HOMA-β) and insulin sensitivity (HOMA-IR). Insulin secretion and sensitivity after glucose load were evaluated by area under curve (AUC) for insulin/AUC for glucose (AUCINS120/AUCGLU120) and insulin sensitivity index (ISI) calculated from Cederholm formula, respectively. Disposition index (DI) was used to reflect blood glucose disposition capacity. Results: The most common type of pre-diabetes was impaired fasting glucose (IFG) combined with impaired glucose tolerance (IGT) and glycated hemoglobin A1c (HbA1c ) 5.7%-6.4%, followed by isolated IGT, while the proportion of isolated IFG was the lowest. The insulin sensitivity of isolated HbA1c 5.7%-6.4% group was better than that of isolated IFG group, isolated IGT group, and IFG combined with IGT group (P<0.05). And its β-cell function was similar with the other subgroups. The DI value of isolated HbA1c 5.7%-6.4% group was about 1.5 times of that of isolated IGT group and IFG combined with IGT group (P=0.000), which was similar with isolated IFG group. The function of β cell or insulin sensitivity in the pre-diabetes subjects with HbA1c 5.7%-6.4% was further damaged compared with the pre-diabetes people whose HbA1c were lower than 5.7%. Conclusion: Different types of pre-diabetes are significantly heterogeneous under new diagnostic criteria, and further prospective studies with a larger sample size are needed to clarify whether HbA1c 5.7%-6.4% is suitable as a diagnostic criteria for pre-diabetes in Chinese population.

Correlation between FOXO3 gene polymorphisms and susceptibility to occupational noise-induced deafness / 中华劳动卫生职业病杂志

Objective@#To investigate the association between the single nucleotide polymorphisms of rs12212067 in FOXO3 gene and the susceptibility to occupational noise-induced deafness in a Chinese Han population.@*Methods@#A total of 1 066 cases of noise exposure workers from a large chemical fiber factory in Jiangsu Province were selected as the study subjects. All subjects’ basic data and field exposure data were collected through questionnaires and occupational health surveys. The subjects were divided into case group (531 persons, double ear high frequency average hearing threshold>25 dB) and control group (535 persons, double ear high frequency average hearing threshold≤25 dB) according to their results of pure tone hearing test .2ml fasting venous blood was collected for DNA extraction and genotyping was performed by TaqMan-PCR technique.@*Results@#Genotyping results suggested that the GT+GG genotype is a risk factor for occupational noise-induced deafness, with an adjusted OR 95% confidence interval of 2.044 (1.51-2.78) . After the noise exposure intensity was stratified, the adjusted OR values and the 95% confidence intervals of noise intensity ≤85, 85-92 and>92 dB respectively 2.43 (1.52-3.90) , 2.17 (1.03-4.59) and 1.74 (1.07-2.83) .@*Conclusion@#GT-GG genotype in rs12212067 of FOXO3 gene may be a risk factor for occupational noise-induced deafness.

Relationship between emergency department disposition, level of emergency base on Korean Triage and Acuity Scale, visit mode

OBJECTIVE: The policy to judge the level of emergency (emergent vs non-emergent) based on Korean Triage and Acuity Scale (KTAS) has been introduced by government to control the flow of emergency patients. The purpose of this study is to identify the variables expected to affect the disposition and to compare the relative importance of the variables. And we also evaluate the validity of the policy to judge the level of emergency based on KTAS. METHODS: We enrolled a total of 29,865 patients who visited a Wide Regional Emergency Center in Busan from Jan 2016 to Dec 2016. Data of those patients were extracted from National Emergency Department Information System (NEDIS) and analysed retrospectively. We determined disposition as the outcome variable. We evaluated the relationship between disposition and visit time, visit mode (firehouse ambulance, inter-facility transfer and self-transport), level of emergency based on KTAS, cause of morbidity. And we also evaluated general and conditional dominances of those variables to compare their relative importance each other. RESULTS: The disposition of the patients was discharge to home (53.5%), general ward admission (30.3%), intensive care unit admission (11.6%), and inter-facility transfer (4.8%). In the univariate analysis, age, gender, visit time, visit mode, cause of morbidity, KTAS level had a significant effect on the disposition. All variables that had a significant effect on univariate analysis also had a significant effect on disposition in multivariate analysis. As a result of dominance analysis, visit mode was the most important variable in both general dominance and conditional dominance. However, if KTAS was devided into 5 levels, it was the most important variable. CONCLUSION: Level of emergency based on KTAS was significantly effective on patient disposition, however it was relatively less important compared to the visit mode. If the visit mode is reflected in the triage system, triage accuracy is expected to be improved. And it also can be a good option to construct triage system based on 5 level KTAS.