Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

AIM: To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). MATERIALS AND METHODS: This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. RESULTS: Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). CONCLUSIONS: This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

Corrigendum: Intra-accumbens raclopride administration prevents behavioral changes induced by intermittent access to sucrose solution.

[This corrects the article DOI: 10.3389/fnins.2018.00074.].

The central blockade of the dopamine DR4 receptor decreases sucrose consumption by modifying the microstructure of drinking behavior in male rats.

Sugar solutions promote hedonic feeding and increase the risk of obesity and binge-type behavior. In rodents, ingestion of sugar solutions enhances dopamine release to mesolimbic regions, suggesting changes in hedonic intake and brain reward processes. Moreover, dopaminergic D2R/D3R receptors contribute to the hedonic intake of palatable solutions. Although the experimental evidence indicate that the dopaminergic D4 receptor (D4R) modulates feeding at homeostatic levels, it is currently unknown whether D4R also regulate the hedonic intake of sugar solutions. In this study, we evaluated the effect of the central blockade of D4R on the consumption of a 20% sucrose solution, the drinking microstructure parameters, and levels of locomotor activity in sated rats. In the first experiment, male Wistar rats were daily exposed to a 20% sugar solution in the first hour of the light phase of the light:dark cycle. On day 10, rats received i.c.v injections of the D4R antagonist, L-745870 (0, 1 or 2 µg/5 µl) and sucrose consumption and drinking microstructure parameters (latency to start drinking, bouts, drinking duration, bout size, inter-bout interval, time in activity and time in resting) were evaluated. In the second experiment, rats were trained to receive the 20% sucrose solution as described in experiment 1. On day 10, after the 1 h of sucrose access, the rats were placed in the open field for 5-min (habituation phase). Then, rats received i.c.v injections of L-745870 (0, 1 or 2 µg/ 5 µl), and were placed again in the open-field test for 10-min (pharmacological phase). The number or crosses trough squares and number of rears were scored for both the habituation and pharmacological phase. Here we found that administration of L-745870 decreased the consumption of sucrose in a dose-depended manner. Moreover, L-745870-treated rats displayed microstructural changes, including greater number of bouts and reduced drinking duration, bout size and inter-bout intervals. Furthermore, the number of crosses and number of rears in the open field test remained unchanged for habituation and pharmacological phase. Finally, present findings suggest that D4R modulates the consumption of sugar solutions by alteration of hedonic responses, but the contribution of homeostatic systems is discussed. These results open perspectives for the potential use of the D4R antagonists for treating obesity or binge-eating behavior.

Food-grade titanium dioxide (E171) differentially affects satiation in mice fed a regular or a high fat diet.

Food-grade titanium dioxide (E171) is a widely used food additive and the toxicity after oral consumption is still under research, although it has been already banned in some countries. The consumption of this additive occurs mainly through ultra-processed food products which also contain high amounts of fat. High fat diets (HFD) impair the physiological system controlling satiation and satiety, which are responsible for control of food intake and energy status. The impact of E171 on animal behavior has been poorly explored and here we hypothesize that E171 could worsen the effects on feeding behavior induced by HFD. Therefore, we aimed to evaluate the effects of E171 on the feeding pattern and the behavioral satiety sequence (BSS) of mice fed with a regular diet (RD) or a HFD after 1 and 16 weeks of exposure. The results showed that RD + E171 increased food intake and feeding time, but the prototypical structure of the BSS pattern (feeding→ grooming-activity → resting), was preserved. Conversely, food consumption was not altered in HFD + E171, but the BSS pattern was disrupted as the animals prolonged resting time and spent less time being active. Our findings suggest that E171 delayed the onset of satiation in mice fed with RD but induced the opposite effect in mice fed with HFD.

The relationship between attribution of blame and the perception of resistance in relation to victims of sexual violence.

Several studies have examined victim blaming in rape scenarios. However, there is limited research on the analysis of the perception of blame when two or more perpetrators are involved. The present article explores the perception of blame in cases involving rape based on the level of resistance shown by the victim and the presence of one or more perpetrators. A study was carried out involving 351 university students who responded to a survey after reading a hypothetical assault scenario. Six situations were established where the victim showed either low or high resistance, depending on whether the resistance was verbal or physical and verbal, and in the presence of one or two male perpetrators. It is expected that perpetrators are more culpable when acting in groups and that less resistance from the victim leads to greater attribution of blame. The results confirm that more blame is attributed to the perpetrators when they act in groups than when they act alone. Likewise, women consider the victim generally exerts greater resistance and this variable influences the attribution of greater blame.

Bioassays in workers exposed to long time random intakes.

Workers who are occupationally exposed to radioactive aerosols are usually subjected to periodic controls of internal contamination by performing bioassays (whole body or partial body monitoring and measurement of excreta samples). The intakes are also estimated by using Static Air Samples (SAS). These measurements are used to estimate the radioactive intakes of the workers. A typical assumption is the workers are chronically (constant) exposed for long periods of time. However, the intakes are random and there are also periods without any exposure (weekends, holidays, etc.). The method presented here considers both facts. Simulations help to choose the most appropriate method of evaluation to minimize the statistical uncertainties in the intake. It has been applied to evaluate workers exposed to UO2 aerosols for a long time (30 years or more for most of them) in the same working area (sintering). Results of measurements of uranium in urine and daily intakes (from SAS) of these workers have been used. For this evaluation, the new Occupational Intakes of Radionuclides (OIR) biokinetic models of the International Commission on Radiological Protection (ICRP) for uranium have been solved. For some workers the evaluation gives a significative deviation between the intake estimated from urine samples and the intake estimated using the SAS values, supporting the idea that the physiological standard parameters of the reference worker are not always applicable. The computations have been implemented in the BIOKMOD code.

Política mundial de yodación de sal: desafíos / Global policy of salt iodization: challenges

RESUMEN Objetivo Identificar los desafíos que conlleva la implementación de la política mundial de yodación de sal para el consumo humano. Métodos Se realizó una revisión de la literatura publicada entre el año 2000 y 2021 en PubMed, con los términos MeSH yodo, política pública, cloruro de sodio y los términos complementarios yodo/deficiencia, exceso. Se obtuvieron 141 artículos y se revisaron 50 aplicando como criterio de inclusión el abordaje de la implementación de la política de yodación. Resultados Se identificaron siete desafíos: sostenibilidad de la política, eliminar la brecha entre la explotación y la comercialización de la sal, prevenir la fortificación indiscriminada de los alimentos, promover la educación sobre la ingesta de sal yodada, controlar la ingesta excesiva de yodo, equilibrar la ingesta óptima de yodo con la reducción del consumo de cloruro de sodio y producir suficiente información oficial sobre la política. Conclusión La yodación universal de la sal es una política que requiere mayor sensibilidad a las situaciones locales de cada país para mitigar efectivamente el problema de salud pública de los desórdenes por deficiencia y exceso en la ingesta de yodo alrededor del mundo.

ABSTRACT Objective To identify the challenges involved in the implementation of the global policy on salt iodization for human consumption. Methods A review of the literature published between 2000 and 2021 in PubMed was carried out with the MeSH terms iodine, public policy, sodium chloride and supplementary terms iodine/deficiency, excess. 141 articles were obtained and 50 were reviewed, applying the iodization policy implementation approach as an inclusion criterion. Results Seven challenges were identified: sustainability of the policy, closing the gap between exploitation and commercialization of salt, preventing indiscriminate fortification of food, promoting education on iodized salt intake, controlling excessive iodine intake, balance optimal iodine intake with reduced sodium chloride intake and produce sufficient official policy information. Conclusion The universal iodization of salt is a policy that requires greater sensitivity to the local situations of each country to effectively mitigate the public health problem of disorders due to deficiency and excess intake of iodine around the world.

Food-grade titanium dioxide (E171) induces anxiety, adenomas in colon and goblet cells hyperplasia in a regular diet model and microvesicular steatosis in a high fat diet model.

Food-grade titanium dioxide (E171) is a white additive widely used in solid and liquid food products. There is still debate about E171 toxic effects after oral consumption since this additive is deposited in colon, liver, spleen, testis and brain. The consumption of E171 commonly occurs with Western diets that are characterized by a high fat content. Thus, E171 could worsen adverse effects associated with a high fat diet (HFD) such as anxiety, colon diseases and testicular damage. We aimed to evaluate the effects of E171 on anxiety-like behavior, colon, liver and testis and to analyze if the administration of a HFD could exacerbate adverse effects. E171 was administered at ~5 mg/kgbw by drinking water for 16 weeks and mice were fed with a Regular Diet or a HFD. E171 promoted anxiety, induced adenomas in colon, goblet cells hypertrophy and hyperplasia and mucins overexpression, but had no toxic effects on testicular tissue or spermatozoa in regular diet fed-mice. Additionally, E171 promoted microvesicular steatosis in liver in HFD fed-mice and the only HFD administration decreased the spermatozoa concentration and motility. In conclusion, E171 administration increases the number of adenomas in colon, induces hypertrophy and hyperplasia in goblet cells and microvesicular steatosis.

Expanding Clinical Indications of Mechanically Isolated Stromal Vascular Fraction: A Systematic Review.

BACKGROUND: Mechanically isolated stromal vascular fraction (tSVF, tissue SVF) is a potent regenerative solution, increasingly used as a therapeutic modality for a variety of pathologies. With recent evidence conclusively favoring mechanical isolation over enzymatic alternatives, the therapeutic share and indications of tSVF are expected to grow even further. OBJECTIVES: The aim of this study was to provide a systematic review of all studies reporting on the use of tSVF. METHODS: A systematic search was undertaken of the Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials databases. Outcome measures included clinical indications, such as recipient area, adverse events, clinical results recipient area, method of application, follow-up duration and evaluation methods. RESULTS: Of the total of 4505 articles identified, 186 full-texts were screened. Thirty-four studies, reporting on 1443 patients were included. tSVF-based therapy was observed for 10 different pathologies, including aged skin (8 studies), scars (5), wounds (6), osteoarthritis (6), tendinopathy (2), temporomandibular joint disorders (1), androgenic alopecia (1), perianal fistula (3), migraine (1), and vocal fold scarring (1). Across all studies, tSVF-based therapy resulted in favorable clinical results. Overall, 50 (3.43%) minor and one (0.07%) major adverse events were observed, mainly related to the liposuction procedure. CONCLUSIONS: tSVF offers a safe, easy and legal treatment modality for a range of indications. Future research is indicated to identify the optimal isolation protocol, dose and timing. In addition, basic research remains crucial to identify the mechanism of action of SVF within different pathologies.

Impact of acute-on-chronic liver failure on post-transplant survival and on kidney outcomes.

OBJECTIVES: We aimed to evaluate the effect of acute-on-chronic liver failure (ACLF) on patients' 1-year post-liver transplant (LT) survival. In addition, we evaluated the effect of ACLF on the development of post-LT chronic kidney disease (CKD) and early allograft dysfunction (EAD). PATIENTS AND METHODS: A retrospective cohort of patients who underwent transplantation from 2010 to 2016 was studied. EASL-CLIF's definition of ACLF was used. The risk of post-LT death, CKD, and EAD was estimated with regression models weighted by inverse probability weighting considering the recipients' characteristics. Donor's BMI and donor risk index were included in the models as well. RESULTS: A total of 185 patients were included: 125 (67.6%) without ACLF and 60 (32.4%) with ACLF. The 1-year post-LT survival rate was 91.2% [95% confidence interval (CI): 84.6-95.1%] in patients without ACLF versus 84.9% (95% CI: 73.1-91.9%) in patients with ACLF. Post-LT CKD occurred in 43 (38.7%) patients without ACLF versus 26 (52.0%) patients with ACLF. EAD occurred in 40 (32.3%) patients without ACLF versus 15 (28.8%) patients with ACLF. No effect of ACLF was found on survival (hazard ratio 1.75; 95% CI: 0.64-4.75, P = 0.272), CKD (odds ratio: 1.31; 95% CI: 0.60-2.86; P = 0.491), or EAD (odds ratio: 0.74; 95% CI: 0.38-1.66, P = 0.473). CONCLUSION: In this study, which included mainly patients with grade 1 ACLF at the time of LT, its presence had no impact on post-LT survival or on the occurrence of CKD or EAD.

Spontaneous bacterial peritonitis recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin.

OBJECTIVE: Few studies carried out more than 20 years ago have evaluated spontaneous bacterial peritonitis (SBP) recurrence in patients receiving secondary antibiotic prophylaxis. These studies reported a 1-year recurrence rate of 20-26%. Changes in the bacteriology of SBP over the last few years might have negative effects on secondary prophylaxis. Our primary aim was to estimate the incidence of SBP recurrence in patients with cirrhosis receiving secondary prophylaxis with norfloxacin and to explore the factors associated with SBP recurrence. PATIENTS AND METHODS: This was a retrospective cohort study of patients receiving norfloxacin for the secondary prophylaxis of SBP from 1 March 2003 to 31 March 2016. Follow-up was performed for 365 days after secondary prophylaxis was started. A competing risk analysis approach was used. RESULTS: A total of 115 patients were included. The prevalence of quinolone-resistant and multiresistant bacteria in the first episode of SBP among patients with culture-positive SBP was 70.96% [95% confidence interval (CI): 51.96-85.77%] and 12.90% (95% CI: 3.63-29.83%), respectively. The cumulative incidence of SBP recurrence was 28.53% (95% CI: 20.15-37.45%) after 365 days. Male patients showed an estimated subhazard ratio of SBP recurrence of 2.52 (95% CI: 1.07-5.91, P=0.034). No other risk factors for SBP recurrence were identified. The overall cumulative incidence of death after 365 days was 21.57% (95% CI: 14.14-30.04%), without significant differences among patients with or without SBP recurrence. CONCLUSION: Even though changes in the bacteriology of SBP occurred over time, its recurrence rate in patients receiving norfloxacin remains similar to what was reported in the initial studies.

Intra-accumbens Raclopride Administration Prevents Behavioral Changes Induced by Intermittent Access to Sucrose Solution.

Overeating is one of the most relevant clinical features in Binge Eating Disorder and in some obesity patients. According to several studies, alterations in the mesolimbic dopaminergic transmission produced by non-homeostatic feeding behavior may be associated with changes in the reward system similar to those produced by drugs of abuse. Although it is known that binge-eating is related with changes in dopaminergic transmission mediated by D2 receptors in the nucleus accumbens shell (NAcS), it has not been determined whether these receptors may be a potential target for the treatment of eating pathology with binge-eating. Accordingly, the aim of the present study was to evaluate whether sugar binging induced by intermittent access to a sucrose solution produced changes in the structure of feeding behavior and whether blocking D2 receptors prevented these changes. We used the intermittent access model to a 10% sucrose solution (2 h/day for 4 weeks) to induce sugar binging in Sprague Dawley female rats. Experimental subjects consumed in a 2-h period more than 50% of the caloric intake consumed by the subjects with ad-lib access to the sweetened solution without any increase in body weight or fat accumulation. Furthermore, we evaluated whether sugar binging was associated to the estrous cycle and we did not find differences in caloric intake (estrous vs. diestrus). Subsequently, we characterized the structure of feeding behavior (microstructural analysis) and the motivation for palatable food (breakpoints) of the subjects with sugar binging and found that feeding episodes had short latencies, high frequencies, as well as short durations and inter-episode intervals. The intermittent access model did not increase breakpoints, as occurred in subjects with ad-lib access to the sucrose. Finally, we evaluated the effects of D2 receptor blockade in the NAcS, and found that raclopride (18 nM) prevented the observed changes in the frequency and duration of episodes induced by intermittent access to the sucrose solution. Our results suggest that alterations in behavioral patterns associated with binge-eating behavior depend in part on the dopaminergic transmission in the NAcS and that the antagonism of D2 receptors may be a therapeutic tool for feeding pathology with binge-eating.

Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity.

The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions.

NFATc3 and VIP in Idiopathic Pulmonary Fibrosis and Chronic Obstructive Pulmonary Disease.

Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are both debilitating lung diseases which can lead to hypoxemia and pulmonary hypertension (PH). Nuclear Factor of Activated T-cells (NFAT) is a transcription factor implicated in the etiology of vascular remodeling in hypoxic PH. We have previously shown that mice lacking the ability to generate Vasoactive Intestinal Peptide (VIP) develop spontaneous PH, pulmonary arterial remodeling and lung inflammation. Inhibition of NFAT attenuated PH in these mice suggesting a connection between NFAT and VIP. To test the hypotheses that: 1) VIP inhibits NFAT isoform c3 (NFATc3) activity in pulmonary vascular smooth muscle cells; 2) lung NFATc3 activation is associated with disease severity in IPF and COPD patients, and 3) VIP and NFATc3 expression correlate in lung tissue from IPF and COPD patients. NFAT activity was determined in isolated pulmonary arteries from NFAT-luciferase reporter mice. The % of nuclei with NFAT nuclear accumulation was determined in primary human pulmonary artery smooth muscle cell (PASMC) cultures; in lung airway epithelia and smooth muscle and pulmonary endothelia and smooth muscle from IPF and COPD patients; and in PASMC from mouse lung sections by fluorescence microscopy. Both NFAT and VIP mRNA levels were measured in lungs from IPF and COPD patients. Empirical strategies applied to test hypotheses regarding VIP, NFATc3 expression and activity, and disease type and severity. This study shows a significant negative correlation between NFAT isoform c3 protein expression levels in PASMC, activity of NFATc3 in pulmonary endothelial cells, expression and activity of NFATc3 in bronchial epithelial cells and lung function in IPF patients, supporting the concept that NFATc3 is activated in the early stages of IPF. We further show that there is a significant positive correlation between NFATc3 mRNA expression and VIP RNA expression only in lungs from IPF patients. In addition, we found that VIP inhibits NFAT nuclear translocation in primary human pulmonary artery smooth muscle cells (PASMC). Early activation of NFATc3 in IPF patients may contribute to disease progression and the increase in VIP expression could be a protective compensatory mechanism.

Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males.

Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases.

Impact of vigorous exercise on serum levels of L-Carnitine in prisoners in Colombia / Impacto del ejercicio vigoroso sobre los niveles séricos de L-Carnitina en prisioneros de Colombia

Objective To assess the effect of a program of vigorous physical exercises on the serum concentration of free and total L-carnitine, in male inmates at a prison in Boyacá, Colombia. Methods Pre-post intervention population-based study. 44 male prisoners with overweight and/or obesity, from a jail in Boyacá, Colombia were randomly assigned into two groups: an intervention group and a control group. The intervention consisted in participating in a vigorous exercise program over twelve weeks. Anthropometric measures and levels of free and total L-carnitine were every four weeks. Results There were significant increases in serum levels of free and total L-carnitine in the intervention group compared to the control group. Concurrently, in this group there was a reduction in body mass index (BMI), while in the control group there were no changes. Conclusion In overweight and/or obese patients, the routine practice of vigorous exercise plus caloric restriction offers significant benefits in reducing body fat volumes through the mechanisms of energetic consumption of long chain fatty acids.(AU)

Objetivo Evaluar el efecto de un programa de ejercicio físico intenso sobre las concentraciones séricas de L-Carnitina libre y total, en varones recluidos en una prisión de Boyacá, Colombia. Métodos Estudio de intervención antes - después, de base poblacional. 44 internos con sobrepeso y/o obesidad, de una prisión en Boyacá, Colombia, fueron aleatoriamente asignados a dos grupos: Uno de intervención y uno de control. La intervención consistió en un programa de práctica sistemática de ejercicio intenso, durante doce semanas continuas. Cada cuatro semanas se realizaron mediciones antropométricas y se determinaron los niveles séricos de L-Carnitina libre y total. Resultados Hubo un incremento significativo en los niveles séricos de L-Carnitina libre y Total en el grupo de intervención, comparado con lo registrado en el grupo control; simultáneamente, en el grupo de intervención se registró disminución en el índice de masa corporal (IMC), mientras que en el grupo control no se registraron cambios. Conclusión En presencia de sobrepeso y/o obesidad, la práctica rutinaria de ejercicios físicos intensos además de la restricción calórica, ofrece significativos beneficios en la reducción del volumen de grasa corporal por el mecanismo de consumo energético de los ácidos grasos de cadena larga.(AU)

Impact of vigorous exercise on serum levels of L-carnitine in prisoners in Colombia.

Objective To assess the effect of a program of vigorous physical exercises on the serum concentration of free and total L-carnitine, in male inmates at a prison in Boyacá, Colombia. Methods Pre-post intervention population-based study. 44 male prisoners with overweight and/or obesity, from a jail in Boyacá, Colombia were randomly assigned into two groups: an intervention group and a control group. The intervention consisted in participating in a vigorous exercise program over twelve weeks. Anthropometric measures and levels of free and total L-carnitine were every four weeks. Results There were significant increases in serum levels of free and total L-carnitine in the intervention group compared to the control group. Concurrently, in this group there was a reduction in body mass index (BMI), while in the control group there were no changes. Conclusion In overweight and/or obese patients, the routine practice of vigorous exercise plus caloric restriction offers significant benefits in reducing body fat volumes through the mechanisms of energetic consumption of long chain fatty acids.

Curso virtual sobre Metodología de la Investigación y Bioestadística para profesionales de Estomatología / Virtual course on research Methodology and Biostatistics for Odontology professionals

Fundamento: las Tecnologías de la Información y la Comunicación han facilitado el uso de plataformas y el desarrollo del e-learning en la enseñanza universitaria. Objetivo: confeccionar un curso de posgrado virtual sobre Metodología de la Investigación y Bioestadística para profesionales de la Estomatología.Métodos: se realizó una investigación descriptiva en la Universidad de Ciencias Médicas de Villa Clara, curso 2012-2013. Se utilizaron métodos teóricos: análisis-síntesis e inductivo-deductivo, para los referentes teóricos del tema y revisión de la bibliografía más actualizada, y la modelación para conformar el curso; empíricos: revisión de investigaciones o artículos científicos para conocer las deficiencias de aplicación de la Metodología de la Investigación Científica y la Bioestadística, y la encuesta: para diagnosticar necesidades de aprendizaje de los profesionales en su función investigativa. Resultados: se diagnosticaron dificultades en la redacción de resúmenes, situación problémica, objetivos y problema científico, formulación de la hipótesis, clasificación de la investigación, elaboración del marco teórico, determinación de la población y tipo de muestreo, operacionalización de las variables, definición de métodos y tratamiento de la información, calidad del procesamiento estadístico y uso de sus técnicas, por lo que se diseñó un curso de posgrado mediante la modalidad virtual. Conclusiones: el producto fue valorado por especialistas los cuales lo consideraron satisfactorio en cuanto a: secuencia lógica de los contenidos, calidad de la redacción, el vocabulario utilizado, novedad científica, necesidad del curso, pertinencia, y la preparación que permite en la labor investigativa(AU)

Pulsioximetría en la prueba marcha de seis minutos como predictor de alteración funcional respiratoria en trabajadores de minería artesanal del carbón / Pulse oximetry in six minutes walking test as a predictor of functional respiratory alteration in workers at artisanal coal mining

Objetivo: Evaluar prospectivamente y mediante comparación, durante la prueba de marcha de 6 minutos, el comportamiento de la saturación arterial de oxígeno (SPO2) y otras variables vitales, en dos grupos, uno de mineros del carbón (expuestos) y otro de trabajadores universitarios (controles). Materiales y métodos:Estudio prospectivo de cohortes. Se realizó la prueba (PM6M) en 72 trabajadores mineros y 46 trabajadores universitarios. Se midió minuto a minuto SPO2, frecuencia cardiaca y distancia recorrida. Resultados: Se encontró una significativa desaturación de oxígeno, ante un ejercicio moderado, en los trabajadores mineros, equivalente a una manifestación precoz de alteración funcional del intercambio alveolo-capilar. Conclusiones: La exposición respiratoria sostenida a polvo de carbón y sílice podría ocasionar alteración funcional del intercambio gaseoso alveolo capilar. La pulsioximetría en la prueba de marcha de 6 minutos se perfila como una herramienta útil y costo-efectiva en salud ocupacional para el seguimiento y control de la salud de los mineros del carbón.

Objective: To evaluate prospectively and through comparison the behavior of the arterial oxygen saturation (SPO2) and other vital variables in two groups, one of coal miners (exposed) and another formed by university workers (controls) during the test run of 6 minutes. Materials and methods: Prospective cohort study. The test (6MWT) was performed in 72 miners and 46 university workers. SpO2, heart rate and walked distance were estimated every minute. Results: A significant oxygen desaturation was found in the mineworkers when practicing a moderate exercise, which is equivalent to an early manifestation of functional impairment of the alveolar-capillary exchange. Conclusions: The sustained respiratory exposure to coal dust and silica may cause functional impairment of alveolar capillary gas exchange. The pulse oximetry in the 6 minutes walking test is emerging as a useful and cost-effective occupational health tool to monitor and health surveillance of coal miners.

Design optimality for models defined by a system of ordinary differential equations.

Many scientific processes, specially in pharmacokinetics (PK) and pharmacodynamics (PD) studies, are defined by a system of ordinary differential equations (ODE). If there are unknown parameters that need to be estimated, the optimal experimental design approach offers quality estimators for the different objectives of the practitioners. When computing optimal designs the standard procedure uses the linearization of the analytical expression of the ODE solution, which is not feasible when this analytical form does not exist. In this work some methods to solve this problem are described and discussed. Optimal designs for two well-known example models, Iodine and Michaelis-Menten, have been computed using the proposed methods. A thorough study has been done for a specific two-parameter PK model, the biokinetic model of ciprofloxacin and ofloxacin, computing the best designs for different optimality criteria and numbers of points. The designs have been compared according to their efficiency, and the goodness of the designs for the estimation of each parameter has been checked. Although the objectives of the paper are focused on the optimal design field, the methodology can be used as well for a sensitivity analysis of ordinary differential equation systems.