Caracterização físico-química de complexos de insulina: dimetil-beta-ciclodextrina e insulina: hidroxipropil-beta-ciclodextrina e avaliação da influência do tipo de complexo na produção de microesferas biodegradáveis

The main stage in the linking and activation of the specific receptors by the insulin is the dissociation of this peptide hexamers, normally present in pharmaceutical formulations, in the monomeric active form. Because of this, the use of different cyclodextrins as adjuvants in the formulations containing insulin has been explored and the realized studies have demonstrated that the cyclodextrins can increase the absorption of the insulin mainly by reducing the ability of insulin oligomerization in aqueous media. In this work, complexes of INS:HP-beta-CD and INS:DM-beta-CD have been characterized by the use of isothermal calorimetry titration (ICT) and dynamic scattering of light. By means of ICT, the thermodynamic parameters of interaction between insulin and the cyclodextrins have been determined, and it was observed that the complexation occurs with an increase of entropy for both systems. The experiments of dynamic scattering of light have not showed reduction in the size of insulin particles, which could indicate the dissociation of insulin hexamers after the complexation with cyclodextrins. Then, the INS: HP-beta-CD and INS:DM-beta-CD complexes were encapsulated in PLGA microspheres. These systems were characterized and it was not observed any significant difference in the microspheres diameter, but a considerable increase in the hormone loading after the complexation with HP-beta-CD and DM-beta-CD was shown.A etapa principal na ativação e ligação da insulina ao seu receptor é a dissociação dos hexâmeros do hormônio, normalmente presente nas preparações farmacêuticas, para a forma monomérica bioativa. A utilização de diferentes ciclodextrinas (CDs) como adjuvantes em formulações contendo insulina vem sendo explorada e os estudos realizados demonstram que estas substâncias podem aumentar a absorção da insulina principalmente por diminuírem sua capacidade de formar dímeros e hexâmeros em meio aquoso. No presente trabalho, complexos de insulina:hidroxipropil-beta-ciclodextrina (INS:HP-beta-CD) e insulina:dimetil-beta-ciclodextrina (INS:DM-beta-CD) foram caracterizados utilizando técnicas de titulação calorimétrica isotérmica e espalhamento dinâmico de luz. Por meio da titulação calorimétrica foram determinados os parâmetros termodinâmicos de interação entre a insulina e as CDs utilizadas, sugerindo que o mecanismo de complexação ocorre com aumento de entropia para ambos os sistemas. Os experimentos de espalhamento dinâmico de luz não indicaram diminuição do diâmetro hidrodinâmico das espécies moleculares de insulina após a complexação com as CDs. Os complexos INS:HP-beta-CD e INS:DM-beta-CD foram encapsulados em microesferas (MEs) de PLGA 50:50. A caracterização das MEs obtidas revelou aumento considerável na taxa de encapsulamento de insulina quando complexada com as CDs sem que ocorresse diferença significativa no diâmetro das partículas em função da complexação

El modelo 1 a 1 en las Escuelas Secundarias. Un estudio a partir de la experiencia de las provincias de Entre Ríos, Formosa y Misiones. 16H362

En el Marco del Convenio de Cooperación, N° 375/12, suscripto entre la Universidad Nacional de Misiones, el Ministerio de Educación de la Nación y la Organización de Estados Iberoamericanos (OEI), el presente proyecto pretende conocer y analizar los cambios y/o continuidades que se estarían produciendo en las aulas, instituciones, sujetos y comunidades de las provincias de Entre Ríos, Formosa y Misiones, a partir de la implementación del Programa Conectar Igualdad. Programa que resulta ser uno de los principales pilares y referentes significativos de un nuevo perfil de política educativa, por parte de un estado nacional que asume su centralidad y responsabilidad como garante del derecho a la educación y la inclusión social, educativa y digital. Cuyo fin, en última instancia, es la revalorización de la escuela pública, a partir de la promoción de la inclusión digital y el mejoramiento de la calidad de la educación, garantizando el acceso y uso de las TIC’s en los procesos de enseñanza-aprendizaje

The impact of the COVID-19 pandemic on the mental health of healthcare workers:study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study

BACKGROUND: Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia. METHODS: Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country’s income level. RESULTS: As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly. CONCLUSIONS: This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00127-021-02211-9

Aplicaciones electroquímicas al tratamiento de aguas residuales

El presente libro tiene como finalidad compilar numerosas investigaciones en el campo de la tecnología electroquímica y sus aplicaciones ambientales, contando con la colaboración de un gran número de investigadores tanto nacionales como extranjeros, proponiendo con ello una visión amplia dentro de la aplicación de la electroquímica. Los temas que integran esta obra se escogieron cuidadosamente considerando desde los principios básicos de la electroquímica aplicada al tratamiento de aguas residuales hasta los parámetros a considerar durante el diseño, operación y evaluación de dichos sistemas, sin dejar de lado las aplicaciones utilizadas en la actualidad en la industria, la docencia y la investigación. Este libro reúne diversas temáticas por lo que puede considerarse como un compendio de aquellos elementos que el lector requiere para poder tener una visión amplia de las aplicaciones de la electroquímica en el campo del tratamiento de agua residual.En el Capítulo 1 se presenta una primera impresión de los Fundamentes de la Electroquímica Ambiental, en donde los autores explican cómo esta disciplina es una nueva área de la ciencia en donde se emplean conocimientos de Electroquímica, Ingeniería Química y Ciencia de Materiales, así como las aplicaciones específicas para la remediación ambiental. En el Capítulo 2 los autores ofrecen una descripción de los principales parámetros fisicoquímicos y biológicos que se emplean para definir a la calidad del agua. Este capítulo describe en función de qué características físicas, químicas y biológicas se puede evaluar a un agua residual así como también la aplicación de estas características como variables de control de un proceso de tratamiento y también como el empleo de ellas para limitar las concentraciones máximas permisibles de descarga de aguas residuales. El Capítulo 3 se refiere a uno de los procesos más empleados en el tratamiento de agua: la coagulación-floculación. Se aborda desde una óptica teórica hasta la descripción de un ejemplo de aplicación en la industria. Resulta importante incluir este capítulo ya que uno de los métodos más prometedores en la electroquímica ambiental es la electrocoagulación, la cual se narra en el Capítulo 6. Las bases de las celdas de laboratorio y reactores industriales electroquímicos se relatan en el Capítulo 4. En particular, se refieren las implicaciones que tienen las principales características físicas y de diseño de celdas de laboratorio y reactores electroquímicos industriales que permiten obtener transformaciones eficientes gracias a un correcto control del potencial de electrodo en estos sistemas. La implementación de procesos electroquímicos para su aplicación a nivel industrial, requiere del diseño eficiente del dispositivo central: el reactor electroquímico. Por lo que, en el Capítulo 5 se presentan los elementos de análisis de reactores electroquímicos para su diseño y caracterización. El Capítulo 7 describe bajo qué circunstancias se puede llevar a cabo el proceso de electroflotación. Los autores muestran cómo este proceso está influenciado por el pH de la solución acuosa, la densidad de corriente y el tipo de electrodos que se emplean. El lector encontrará en el Capítulo 8 las bases teóricas de uno de los procesos que involucra la química de la reacción de Fenton, así como las aplicaciones ambientales para el tratamiento de soluciones sintéticas y reales con diferentes contaminantes refractarios, tales como plaguicidas, colorantes, productos de cuidado personal, fármacos y residuos químicos industriales. En el Capítulo 9 se presentan algunos conceptos fundamentales sobre la Electrooxidación, también conocida como oxidación electroquímica, la cual está enfocada a realizar la oxidación de contaminantes presentes en aguas residuales sobre la superficie de electrodos. La tecnología para la electrogeneración de peróxido de hidrógeno y su empleo en el tratamiento de agua residual se describe en el Capítulo 10. Uno de los metales pesados que tienen un alto grado de toxicidad en el ambiente es el Cr(VI), el cual no puede ser removido por métodos convencionales por lo que una tecnología que puede emplearse en este tratamiento se relata en el Capítulo 11. En el Capítulo 12 se presentan los avances más recientes cuando se emplean los métodos electroquímicos con algún otro tipo de tratamiento, lo que ha resultado en la obtención de sinergias en los procesos, lo que implica una reducción en los costos de operación. Finalmente, en el Capítulo 13, se presenta el tema de usos y aplicaciones de sensores químicos y electroquímicos para la detección de contaminantes en agua y agua residual

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation