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Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of β-cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (Avy) mice that overexpress hIAPP in β cells (Avy hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when Avy hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese Avy hIAPP mice in fasting and fed conditions throughout the study. This effect was paralleled by a decrease in hyperinsulinemia. Importantly, PBA treatment reduced the prevalence and the severity of islet amyloid deposition in Avy hIAPP mice. Collectively, these results show that PBA treatment elicits a marked reduction of hyperglycemia and reduces amyloid deposits in obese and diabetic mice, highlighting the potential of chaperones for T2D treatment.

Corticobasal degeneration (CBD) is a pathology of low incidence and prevalence worldwide; it is accompanied by symptoms such as dystonia, rigid akinetic syndrome (bradykinesia), gait disturbances, neurological deterioration associated with severe cortical subcortical atrophy, and progressive to moderate to severe neurocognitive deficits, especially in immediate verbal memory and dorsolateral or dysexecutive syndrome. We identified neurocognitive impairment and neuropsychiatric symptoms in a patient diagnosed with CBD. Participant was a 70-year-old female patient, single; she presented progressive memory loss of an immediate verbal nature. Initially, she was diagnosed with Alzheimer’s disease and Lewy body dementia, finding that she had no characteristic signs and symptoms of these pathologies. The patient presented conciliation insomnia, gait disturbances, and severe neurocognitive deficit, especially in executive functions, immediate verbal memory, and visuospatial functioning. It was found that the patient presented neurocognitive alterations of the executive type (frontal lobe) such as decision making, planning, inhibition and operative memory, correlated with a severe alteration in her basic, instrumental and advanced activities of daily life, with a high risk factor for developing dementia. It is necessary to diagnose in an assertive and timely manner in order to generate functional neurorehabilitation plans in people diagnosed with CBD, with the main objective of positively impacting quality of life, at the individual, family, and social level.

Resumen: Introducción: El cáncer de mama es el tipo de cáncer que se diagnostica con mayor frecuencia en mujeres y la segunda causa más común de muerte por cáncer en este género. Dentro de las indicaciones de tratamiento, se encuentran: cirugía, radioterapia, quimioterapia y terapia endocrina. Esta última se basa en el uso de tamoxifeno, cuyo uso de forma prolongada puede producir efectos secundarios como sequedad vaginal, ardor, irritación, picazón, disuria, incontinencia urinaria, entre otros. Objetivo: Caracterizar la incontinencia urinaria en mujeres premenopáusicas con cáncer de mama en tratamiento con tamoxifeno por 5 años en el Instituto Nacional del Cáncer. Material y método: Estudio descriptivo de corte transversal. Se incluyeron mujeres diagnosticadas con cáncer de mama inscritas y tratadas en el Instituto Nacional del Cáncer. Se aplicó cuestionario ICIQ –SF a la población de estudio con el fin de caracterizar la presencia de incontinencia urinaria. Además, se calculó la proporción entre mujeres con incontinencia urinaria y nuliparidad/mujeres con incontinencia urinaria y paridad. Resultados: Se evaluaron 15 pacientes. 93,33% presentaron incontinencia urinaria. El promedio de edad de mujeres con incontinencia urinaria fue de 51,21 (± 4,74) años. La razón de mujeres con nuliparidad/con paridad fue de 4:15. Conclusión: 99,33% de las pacientes presentaron incontinencia urinaria. Los resultados entregados en este estudio deben ser considerados como un elemento que contribuya a detectar la magnitud del problema en la población inscrita y tratada en el Instituto Nacional del Cáncer. Summary: Background: Breast cancer is the type of cancer diagnosed most frequently in women, and the second most common cause of death from cancer in this gender. Within the indications of treatment, they are: surgery, radiotherapy, chemotherapy and endocrine therapy. The last is based on the use of tamoxifen, whose prolonged use can produce side effects such as vaginal dryness, burning, irritation, itching, dysuria, urinary incontinence, among others. Objective: To characterize urinary incontinence in pre-menopausal women with breast cancer treated with tamoxifen for 5 years at the Instituto Nacional del Cáncer. Material and method: Descriptive cross-sectional study. We included women diagnosed with breast cancer enrolled and treated at the Instituto Nacional del Cáncer. The ICIQ -SF questionnaire was applied to the study population to characterize the presence of urinary incontinence. In addition, the proportion between women with urinary incontinence and nulliparity / women with urinary incontinence and parity was calculated. Results: 93,33% presented urinary incontinence. The average age of women with urinary incontinence was 51,21 (± 4,74) years. The ratio of women with nulliparity / with parity was 4:15. Conclusion: 99,33% of the patients presented urinary incontinence. The results delivered in this study should be considered as one element that helps to detect the magnitude of this problem in the population registered and treated in the Instituto Nacional del Cáncer.

Resumen Objetivo: Determinar el efecto del programa «Cuidando a los cuidadores® » sobre la habilidad de cuidado de los cuidadores familiares de personas con artritis reumatoide en una institución prestadora de servicios de salud de la ciudad de Barranquilla. Metodología: Estudio cuantitativo pre-experimental, con diseño pretest-postest con un grupo. La muestra se constituyó con 40 cuidadores familiares. Se usó una ficha de caracterización de la diada cuidador-persona con enfermedad crónica para la caracterización sociodemográfica del cuidador y el Inventario de habilidad de cuidado (Care Skill Inventory [CAI]) antes de iniciar el programa y luego de finalizar. Se realizó un análisis a partir de estadística descriptiva y medidas de tendencia central, con el fin de conocer el perfil de los cuidadores, en las dimensiones: conocimiento, valor y paciencia, y en la habilidad de cuidado. Se usaron pruebas inferenciales. Resultados: Los cuidadores familiares de personas con artritis reumatoide en su mayoría son mujeres, casadas o en unión libre, ocupación hogar, de estratos socioeconómicos bajos. La realización del programa «Cuidando a los cuidadores®» tuvo un efecto sobre la habilidad de cuidado de los cuidadores familiares, como se ha reportado en diferentes estudios. Se identificó que el conocimiento y el valor aumentaron de manera significativa, mientras que el componente paciencia presentó un ligero cambio. Conclusiones: El programa «Cuidando a los cuidadores®» tuvo un efecto sobre la habilidad de cuidado; se debe considerar la intervención como una iniciativa en el desarrollo de la habilidad de cuidado en cuidadores de personas con artritis reumatoide. Abstract Objective: To determine the effect of the "Caring for caregivers®" program on the care ability of family caregivers of people with rheumatoid arthritis in a health service provider institution in the city of Barranquilla. Methodology: Pre-experimental quantitative study, with pre-test-post-test design with a group. The sample consisted of 40 family caregivers. A characterisation card of the pair caregiver-person with chronic illness was used for the sociodemographic profile of the caregiver, as well as the Care Skill Inventory (CAI) before starting the program and after finishing. An analysis was made from descriptive statistics and measures of central tendency, in order to determine the profile of the caregivers in the dimensions: knowledge, value, and patience, and in the care ability. Inferential tests were used. Results: The family caregivers of people with rheumatoid arthritis are mostly women, married or in free union, home occupation, and of low socioeconomic strata. The implementation of the "Caring for caregivers" program had an effect on the care ability of family caregivers, as reported in different studies. It was identified that knowledge and value increased significantly, while the patience component showed a slight change. Conclusions: The "Caring for caregivers" program had an effect on the ability to care. Intervention should be considered as an initiative in the development of care ability in caregivers of people with rheumatoid arthritis.

© 2021 The Author(s)., [Objective]: Pancreatic β-cell dysfunction is a central feature in the pathogenesis of type 2 diabetes (T2D). Accumulating evidence indicates that β-site APP-cleaving enzyme 2 (BACE2) inhibition exerts a beneficial effect on β-cells in different models of T2D. Thus, targeting BACE2 may represent a potential therapeutic strategy for the treatment of this disease. Here, we aimed to investigate the effects of BACE2 suppression on glucose homeostasis in a model of diet-induced obesity., [Methods]: BACE2 knock-out (BKO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 2 or 16 weeks. Body weight, food intake, respiratory exchange ratio, locomotor activity, and energy expenditure were determined. Glucose homeostasis was evaluated by glucose and insulin tolerance tests. β-cell proliferation was assessed by Ki67-positive nuclei, and β-cell function was determined by measuring glucose-stimulated insulin secretion. Leptin sensitivity was evaluated by quantifying food intake and body weight after an intraperitoneal leptin injection. Neuropeptide gene expression and insulin signaling in the mediobasal hypothalamus were determined by qPCR and Akt phosphorylation, respectively., [Results]: After 16 weeks of HFD feeding, BKO mice exhibited an exacerbated body weight gain and hyperphagia, in comparison to WT littermates. Glucose tolerance was similar in both groups, whereas HFD-induced hyperinsulinemia, insulin resistance, and β-cell expansion were more pronounced in BKO mice. In turn, leptin-induced food intake inhibition and hypothalamic insulin signaling were impaired in BKO mice, regardless of the diet, in accordance with deregulation of the expression of hypothalamic neuropeptide genes. Importantly, BKO mice already showed increased β-cell proliferation and glucose-stimulated insulin secretion with respect to WT littermates after two weeks of HFD feeding, before the onset of obesity., [Conclusions]: Collectively, these results reveal that BACE2 suppression in an obesogenic setting leads to exacerbated body weight gain, hyperinsulinemia, and insulin resistance. Thus, we conclude that inhibition of BACE2 may aggravate the adverse metabolic effects associated with obesity., This work was supported by projects from the Instituto de Salud Carlos III (PI17/00879 to AN and JMS) and by the Spanish Ministry of Economy and Competitiveness (BFU2017-89336-R to MV), co-funded by the Fondo Europeo de Desarrollo Regional (FEDER; A way to build Europe), and by the CERCA Programme and Generalitat de Catalunya (grant 2014_SGR_520). DDC was supported by Conicyt’s fellowship from the Government of Chile (72170321-6357/2016). SR is a recipient of a Juan de la Cierva Incorporación (IJC2018-037341-I) program from the Spanish Ministry of Science and Innovation. This work was developed at the Center Esther Koplowitz (Barcelona). CIBERDEM (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas) is an initiative of the Instituto de Salud Carlos III.

Objective Pancreatic β-cell failure is central to the development and progression of type 2 diabetes (T2D). The aggregation of human islet amyloid polypeptide (hIAPP) has been associated with pancreatic islet inflammation and dysfunction in T2D. Alpha1-antitrypsin (AAT) is a circulating protease inhibitor with anti-inflammatory properties. Here, we sought to investigate the potential therapeutic effect of AAT treatment in a mouse model characterized by hIAPP overexpression in pancreatic β-cells. Methods Mice overexpressing hIAPP (hIAPP-Tg) in pancreatic β-cells were used as a model of amyloid-induced β-cell dysfunction. Glucose homeostasis was evaluated by glucose tolerance tests and insulin secretion assays. Apoptosis and amyloid formation was assessed in hIAPP-Tg mouse islets cultured at high glucose levels. Dissociated islet cells were cocultured with macrophages obtained from the peritoneal cavity. Results Nontreated hIAPP-Tg mice were glucose intolerant and exhibited impaired insulin secretion. Interestingly, AAT treatment improved glucose tolerance and restored the insulin secretory response to glucose in hIAPP-Tg mice. Moreover, AAT administration normalized the expression of the essential β-cell genes MafA and Pdx1, which were downregulated in pancreatic islets from hIAPP-Tg mice. AAT prevented the formation of amyloid deposits and apoptosis in hIAPP-Tg islets cultured at high glucose concentrations. Since islet macrophages mediate hIAPP-induced β-cell dysfunction, we investigated the effect of AAT in cocultures of macrophages and islet cells. AAT prevented hIAPP-induced β-cell apoptosis in these cocultures without reducing the hIAPP-induced secretion of IL-1β by macrophages. Remarkably, AAT protected β-cells against the cytotoxic effects of conditioned medium from hIAPP-treated macrophages. Similarly, AAT also abrogated the cytotoxic effects of exogenous proinflammatory cytokines on pancreatic β-cells. Conclusions These results demonstrate that treatment with AAT improves glucose homeostasis in mice overexpressing hIAPP and protects pancreatic β-cells from the cytotoxic actions of hIAPP mediated by macrophages. These results support the use of AAT-based therapies to recover pancreatic β-cell function for the treatment of T2D., Graphical abstract Image 1, Highlights • Alpha1-antitrypsin (AAT) ameliorates glucose intolerance in hIAPP transgenic mice. • AAT improves insulin secretion in hIAPP transgenic mice. • AAT prevents apoptosis and amyloid deposition in cultured hIAPP transgenic islets. • AAT protects β-cells from hIAPP-induced cytotoxicity mediated by macrophages. • AAT abrogates the cytotoxic effects of proinflammatory cytokines on β-cells.

We discussed the design and fabrication consideration for an Intraocular Pressure (IOP) systems according to surgical and biocompatibility implant limitations. A new less invasive IOP system is implanted successfully in the eye of a rabbit by a minimum invasive surgical procedure. The MEMS array is over a flexible, biocompatible polyimide substrate in a maximum 8×8mm area. The substrate flexibility allows it to fit a small surface of the eye. The implanted coil is under the conjunctiva, out of the interior chamber. However, the pressure sensor is deposed inside the interior chamber through a minimum invasive procedure. The capacitive sensor is fabricated considering a maximum area of 0.5×0.5mm2. Increasing sensor capacitance is achieved by a set of windows cavities getting a sensible reduction of the separation of its capacitor plates at the base of the windows anchored. The coil and pressure sensor consist of alternating layers of polyimide-metal-polyimide, patterned using reactive ion etching over a thin silicon wafer that is used only as a sacrificial layer. We pointed out the way micron-scale metal layers can be incorporated in a thin flexible plastic substrate to integrate into the same process both: the coil and the intraocular pressure sensor. The whole structure encapsulated in a biocompatible polymer fits into the shape of the ocular globe. Display Omitted A new less invasive IOP system is implanted successfully in the eye of a rabbit by a minimum invasive surgical procedure.The MEMS array is fabricated on a flexible, biocompatible polyimide substrate in a maximum of 8×8mm area.The capacitive sensor is microfabricated considering a maximum area of 0.5×0.5mm2The artefact has capabilities to measure IOP as frequently as interrogated

The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children.To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia.A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability.Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22,Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.La aparición de reacciones adversas a medicamentos es un tópico importante debido a la escasa información sobre seguridad de medicamentos en niños.Describir las reacciones adversas a medicamentos en niños menores de 6 años de edad hospitalizados en dos servicios de pediatría general en Barranquilla, Colombia.Estudio prospectivo de una cohorte de pacientes basado en farmacovigilancia intensiva, realizado durante seis meses para monitorizar la aparición de reacciones adversas a medicamentos en niños menores de 6 años de edad hospitalizados y con indicación de al menos un medicamento. El estudio fue conducido en dos servicios de pediatría general de dos hospitales en Barranquilla, Colombia. El algoritmo de Naranjo fue usado para evaluar imputabilidad, la escala modificada de Hartwig y Siegel para establecer severidad y los criterios de Schumock y Thornton para determinar evitabilidad.En total se monitorizaron 772 pacientes. Se detectaron 156 reacciones adversas a medicamentos en 147 niños. La incidencia acumulada de las reacciones adversas a medicamentos fue 19.0% (147/772); la densidad de incidencia fue de 37.6 reacciones adversas a medicamentos por 1,000 pacientes-día (147/3,913). La frecuencia de reacciones adversas fue mayor en niños2 años de edad (12.7%). La ocurrencia de reacciones adversas a medicamentos fue mayor en pacientes masculinos (RR= 1.66; IC 95% =1.22-2.22,Las reacciones adversas a medicamentos son comunes en niños hospitalizados y representan una morbilidad adicional y mayor riesgo, particularmente en aquellos que usaron varios medicamentos, incluyendo antibióticos.

Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is. Using myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) as a MS model, we previously showed that daily administration of sildenafil starting at peak disease rapidly ameliorates clinical symptoms while administration at symptoms onset prevents disease progression. These beneficial effects of the drug involved down-regulation of adaptive and innate immune responses, protection of axons and oligodendrocytes (OLs) and promotion of remyelination. In this work we have investigated mechanisms involved in the remyelinating effect of sildenafil. Using demyelinated organotypic cerebellar slice cultures we demonstrate that sildenafil stimulates remyelination by direct effects on CNS cells in a nitric oxide (NO)-cGMP-protein kinase G (PKG)-dependent manner. We also show that sildenafil treatment enhances OL maturation and induces expression of the promyelinating factor ciliary neurotrophic factor (CNTF) in spinal cord of EAE mice and in cerebellar slice cultures. Furthermore, we demonstrate that sildenafil promotes a M2 phenotype in bone marrow derived macrophages (BMDM) and increases myelin phagocytosis in these cells and in M2 microglia/macrophages in the spinal cord of EAE mice. Taken together these data indicate that promotion of OL maturation directly or through induction of growth factor expression, regulation of microglia/macrophage inflammatory phenotype and clearance of myelin debris may be relevant mechanisms involved in sildenafil enhancement of remyelination in demyelinated tissue and further support the contention that this well tolerated drug could be useful for ameliorating MS pathology.

Introducción: los programas enfocados en el envejecimiento activo no siempre cuentan con acciones que orienten a los adultos mayores en torno a la alimentación saludable. Esta situación hace poco conocida la concordancia entre los hábitos de alimentación con las características morfológicas de este grupo de la población. Objetivo: relacionar los índices antropométricos de salud con la frecuencia en el consumo de alimentos en adultos mayores físicamente activos (AMFA). Métodos: la muestra incluyó 307 adultos mayores chilenos físicamente activos de ambos sexos (8,4% varones), con una edad media de 70,1 años. Las variables estudiadas correspondieron al estado nutricional, adiposidad abdominal, riesgo cardiovascular y frecuencia en el consumo de alimentos. Se aplicó un modelo de regresión logística, considerando un α < 0,05. Resultados: la ingesta de frutas (OR = 0,12; IC 95%, 0,02-0,92) y el consumo de agua (OR = 0,20; IC 95%, 0,04-0,90) se exhiben como factores protectores frente a la obesidad. En cambio, el consumo de alcohol (OR = 4,19; IC 95%, 1,03-17,02) y snacks dulces (OR = 10,68; IC 95%, 1,85-61,74) se presentan como factores de riesgo para la obesidad. Además, la ingesta de verduras (OR = 0,32; IC 95%, 0,11-0,92) se asoció como un factor protector frente a la adiposidad abdominal, y el consumo de snacks dulces (OR = 6,45; IC 95%, 1,08-38,43), como un factor para presentar riesgo cardiovascular. Conclusión: los AMFA que presentan mayor frecuencia en el consumo de alimentos saludables manifiestan también mejor estado nutricional, adiposidad abdominal y menor riesgo cardiovascular respecto a los adultos mayores chilenos activos que exhiben conductas de alimentación menos saludables.

Introducción. La aparición de reacciones adversas a medicamentos es un tema relevante debido a la escasez de datos de seguridad de medicamentos en la población neonatal.Objetivo. Identificar el comportamiento de las reacciones adversas a medicamentos en neonatos hospitalizados en dos servicios de neonatología de Barranquilla, Colombia.Materiales y métodos. Estudio descriptivo prospectivo de corte transversal de período en farmacovigilancia intensiva centrada en el paciente. El seguimiento y monitorización de aparición de las reacciones adversas (RAMs) en neonatos, se realizó durante 6 meses. Se utilizaron el algoritmo de Naranjo para evaluar la causalidad, la escala modificada de Hartwig y Siegel para establecer severidad y los criterios de Schumock y Thornton para determinar la evitabilidad.Resultados. De 284 pacientes monitorizados, se detectaron 123 RAMs en 78 neonatos. La incidencia de RAMs fue de 27,4% (78/284); la densidad de incidencia fue de 30,60 RAMs por 1000 pacientes –día (78/2549). El sistema orgánico más afectado fue el digestivo (33,6%); los anti-infecciosos sistémicos fueron el grupo terapéutico más implicado en las RAMs. La mayoría de las RAMs fueron leves (58,5%), el 83% se clasificaron como probables, el 16,2% posibles y el 0,8% definitivas.Conclusiones. La incidencia de RAMs en neonatos es alta, y se incrementa en pacientes prematuros (

This paper reports the novel design of a touch mode capacitive pressure sensor (TMCPS) system with a wireless approach for a full-range continuous monitoring of ventricular pressure. The system consists of two modules: an implantable set and an external reading device. The implantable set, restricted to a 2 &times, 2 cm2 area, consists of a TMCPS array connected with a dual-layer coil, for making a reliable resonant circuit for communication with the external device. The capacitive array is modelled considering the small deflection regime for achieving a dynamic and full 5&ndash, 300 mmHg pressure range. In this design, the two inductive-coupled modules are calculated considering proper electromagnetic alignment, based on two planar coils and considering the following: 13.56 MHz frequency to avoid tissue damage and three types of biological tissue as core (skin, fat and muscle). The system was validated with the Comsol Multiphysics and CoventorWare softwares, showing a 90% power transmission efficiency at a 3.5 cm distance between coils. The implantable module includes aluminum- and polyimide-based devices, which allows ergonomic, robust, reproducible, and technologically feasible integrated sensors. In addition, the module shows a simplified and low cost design approach based on PolyMEMS INAOE&reg, technology, featured by low-temperature processing.