Imidacloprid unique and repeated treatment produces cholinergic transmission disruption and apoptotic cell death in SN56 cells.

Imidacloprid (IMI), the most widely used worldwide neonicotinoid biocide, produces cognitive disorders after repeated and single treatment. However, little was studied about the possible mechanisms that produce this effect. Cholinergic neurotransmission regulates cognitive function. Most cholinergic neuronal bodies are present in the basal forebrain (BF), regulating memory and learning process, and their dysfunction or loss produces cognition decline. BF SN56 cholinergic wild-type or acetylcholinesterase (AChE), ß-amyloid-precursor-protein (ßAPP), Tau, glycogen-synthase-kinase-3-beta (GSK3ß), beta-site-amyloid-precursor-protein-cleaving enzyme 1 (BACE1), and/or nuclear-factor-erythroid-2-related-factor-2 (NRF2) silenced cells were treated for 1 and 14 days with IMI (1 µM-800 µM) with or without recombinant heat-shock-protein-70 (rHSP70), recombinant proteasome 20S (rP20S) and with or without N-acetyl-cysteine (NAC) to determine the possible mechanisms that mediate this effect. IMI treatment for 1 and 14 days altered cholinergic transmission through AChE inhibition, and triggered cell death partially through oxidative stress generation, AChE-S overexpression, HSP70 downregulation, P20S inhibition, and Aß and Tau peptides accumulation. IMI produced oxidative stress through reactive oxygen species production and antioxidant NRF2 pathway downregulation, and induced Aß and Tau accumulation through BACE1, GSK3ß, HSP70, and P20S dysfunction. These results may assist in determining the mechanisms that produce cognitive dysfunction observed following IMI exposure and provide new therapeutic tools.

Barreras para una alimentación saludable: un análisis cualitativo de las semánticas emergentes en las comunidades escolares de Ciudad Sur

La literatura ha hecho hincapié en la centralidad que cumplen los entornos alimentarios en las elecciones alimentarias y en el estado nutricional de la población. Objetivo: identificar las percepciones de padres, madres y apoderados, profesionales de establecimientos educacionales, funcionarios municipales, y feriantes pertenecientes a la zona sur de Santiago de Chile, respecto a las barreras y limitaciones de la puesta en práctica de una alimentación saludable en el ambiente alimentario escolar. Método: se realizaron seis grupos focales agrupando a 50 actores claves vinculados a los establecimientos educacionales de Ciudad Sur utilizando una muestra no probabilística. Se aplicó un análisis de contenido mediante la técnica de codificación temática buscando relevar los universos semánticos emergentes. Resultados: se identificaron nueve barreras, o semánticas, que caracterizan limitantes a la realización de la alimentación saludable en los entornos escolares desde la perspectiva de los participantes: la familia, kioscos escolares, la salida de los establecimientos escolares, gusto, determinantes socioeconómicos, política pública, falta de conocimiento, publicidad y disponibilidad de productos sin sellos. Conclusiones: las limitaciones asociadas al ambiente alimentario doméstico tienen una representación significativamente alta (47,9%) y contienen un carácter de responsabilización individual en su enunciación. Esta cultura explicativa es opuesta a la evidencia científica y académica respecto al funcionamiento de la conducta alimentaria, y a la centralidad de los ambientes alimentarios respecto a la facilitación u obstaculización del consumo de alimentos saludables o adecuados.

Literature has emphasized on food environments centrality in food choices and nutritional status. Objective: identify social perceptions of fathers, mothers and guardians, professionals from educational establishments, municipal officials, and stallholders belonging to the southern area of Santiago de Chile, regarding limitations of healthy diet implementation on school environments. Method: six focus groups were carried out grouping 50 key actors linked to educational establishments using a non-probabilistic sample. A content analysis was applied through thematic coding technique seeking to reveal emerging semantic universes. Results: Nine barriers, or semantics, were identified characterizing limitations to healthy eating habits in school environments: family, school kiosks, leaving school establishments, taste, socioeconomic determinants, public policy, lack of knowledge, publicity, and availability of products without seals. Conclusions: limitations associated with domestic food environment have a significantly high representation (47,9%) and contain an individualized responsibility feature. This explanatory culture is opposed to scientific and academic evidence regarding the functioning of eating behavior, and the centrality of food environments facilitating or hindering healthy food consumption.

ASSOCIATION OF METFORMIN USE WITH RISK OF NEWLY ONSET NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DEVELOPMENT.

PURPOSE: To investigate if metformin use reduces the odds of developing new neovascular AMD (nAMD). METHODS: This is a case-control study of 86,930 subjects with new diagnoses of nAMD and 86,918 matched control subjects using the Merative Marketscan Research Databases. Subjects were analyzed using multivariable conditional logistic regression to identify the risks of various exposures on developing nAMD. A subgroup analysis of 22,117 diabetic cases and 21,616 diabetic control subjects was also performed. RESULTS: Metformin use was associated with reduced odds ratio of developing nAMD (odds ratio 0.95, 95% confidence interval 0.91-0.98) in full sample and diabetic cohort particularly in patients without any diabetic retinopathy-an effect that persisted after Bonferroni correction. In the diabetic cohort without diabetic retinopathy, reduced odds ratio was observed at 24-month cumulative doses of 1 to 300 g, 301 to 630 g, and 631 to 1,080 g. CONCLUSION: Metformin use was associated with reduced odds ratio of nAMD, particularly in patients without diabetic retinopathy. The protective effect was noted for 24-month cumulative doses below 1,080 g. Metformin may be a novel preventive strategy for nAMD.

Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes.

Importance: Metformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear. Objective: To assess the association between metformin use and the development of AMD in patients without diabetes. Design, Setting, and Participants: This case-control study used data from 2006 to 2017 in the Merative MarketScan Research Database, a nationwide insurance claims database that includes between 27 and 57 million patients in the US with primary or Medicare supplemental health insurance. Cases with AMD and controls without AMD aged 55 years or older were matched 1:1 by year, age, anemia, hypertension, region, and Charlson Comorbidity Index score. Then, cases and matched controls without a diagnosis of diabetes were selected. In subgroup analyses, cases with dry AMD and their matched controls were identified to explore the association between metformin use and AMD staging in patients without diabetes. Data were analyzed between March and September 2023. Exposures: Exposure to metformin in the 2 years prior to the index date (ie, date of AMD diagnosis in cases and date of a randomly selected eye examination for controls) was assessed from the claims database and categorized into quartiles based on cumulative dose (1-270, 271-600, 601-1080, and >1080 g/2 y). Exposure to other antidiabetic medications was also noted. Main Outcomes and Measures: Odds of new-onset AMD development as assessed by multivariable conditional logistic regression after adjusting for known risk factors for AMD, including female sex, hyperlipidemia, smoking, and exposures to other antidiabetic medications. Asymptotic Cochran-Armitage tests for trend were also performed. Results: We identified 231 142 patients with any AMD (mean [SD] age, 75.1 [10.4] years; 140 172 females [60.6%]) and 232 879 matched controls without AMD (mean [SD] age, 74.9 [10.5] years; 133 670 females [57.4%]), none of whom had a diagnosis of diabetes. The sample included 144 147 cases with dry AMD that were matched to 144 530 controls. In all, 2268 (1.0%) cases and 3087 controls (1.3%) were exposed to metformin in the 2 years before their index visit. After data adjustment, exposure to any metformin was associated with reduced odds of any AMD development (adjusted odds ratio [AOR], 0.83; 95% CI, 0.74-0.87), specifically in the dosing quartiles of 1 to 270, 271 to 600, and 601 to 1080 g/2 y. Any metformin use was also associated with a reduced odds of developing dry AMD (AOR, 0.85; 95% CI, 0.79-0.92), specifically in the dosing quartiles of 1 to 270 and 271 to 600 g/2 y. Adjusted odds ratios for any AMD and dry AMD development did not differ across the dosing quartiles. Asymptotic Cochran-Armitage tests for trend revealed 2-sided P = .51 and P = .66 for the any and dry AMD samples, respectively. Conclusions and Relevance: In this case-control study of a population without a diagnosis of diabetes, metformin use was associated with reduced odds of developing AMD. This association does not appear to be dose dependent. These findings provide further impetus to study metformin's usefulness in protecting against AMD in prospective clinical trials.

Associations Between Autoimmune Disease and the Development of Age-Related Macular Degeneration.

Purpose: The pathogenesis of age-related macular degeneration (AMD) likely implicates the dysregulation of immune response pathways. Several studies demonstrate that the pathogenic elements of AMD resemble those of autoimmune diseases, yet the association between AMD development and most autoimmune diseases remain unexplored. Methods: We conducted a case-control analysis of patients ages 55 and older with new-onset International Classification of Diseases (ICD) coding of dry, wet, or unspecified AMD between 2005 and 2019 in the Merative MarketScan Commercial and Medicare Databases. The diagnosis of an autoimmune disease was defined by an outpatient or inpatient claim with a relevant ICD code in the 12 months before the index visit. Conditional multivariable logistic regression, adjusted for AMD risk factors, was used to calculate odd ratios and 95% confidence intervals. Results: We identified 415,027 cases with new-onset ICD coding for AMD matched with propensity scores to 414,853 controls. In total, 16.1% of cases and 15.9% of controls were diagnosed with any autoimmune disease. The diagnosis of any autoimmune disease did not affect the odds of new-onset ICD coding for AMD in multivariable regression (OR = 1.01; 95% CI, 0.999-1.02). Discoid lupus erythematosus (OR = 1.29; 95% CI, 1.12-1.48), systemic lupus erythematosus (SLE) (OR = 1.21; 95% CI, 1.15-1.27), giant cell arteritis (OR = 1.19; 95% CI, 1.09-1.30), Sjogren's syndrome (OR = 1.17; 95% CI, 1.09-1.26), and Crohn's disease (OR = 1.13; 95% CI, 1.06-1.22) increased the odds of a new-onset ICD coding for AMD. Conclusions: Most autoimmune diseases do not affect the odds of developing AMD but several common autoimmune disorders such as SLE and Crohn's disease were associated with modestly increased odds of AMD. Further studies are needed to validate and investigate the underlying mechanisms of these associations.

Bisphenol-A Neurotoxic Effects on Basal Forebrain Cholinergic Neurons In Vitro and In Vivo.

The widely used plasticizer bisphenol-A (BPA) is well-known for producing neurodegeneration and cognitive disorders, following acute and long-term exposure. Although some of the BPA actions involved in these effects have been unraveled, they are still incompletely known. Basal forebrain cholinergic neurons (BFCN) regulate memory and learning processes and their selective loss, as observed in Alzheimer's disease and other neurodegenerative diseases, leads to cognitive decline. In order to study the BPA neurotoxic effects on BFCN and the mechanisms through which they are induced, 60-day old Wistar rats were used, and a neuroblastoma cholinergic cell line from the basal forebrain (SN56) was used as a basal forebrain cholinergic neuron model. Acute treatment of rats with BPA (40 µg/kg) induced a more pronounced basal forebrain cholinergic neuronal loss. Exposure to BPA, following 1- or 14-days, produced postsynaptic-density-protein-95 (PSD95), synaptophysin, spinophilin, and N-methyl-D-aspartate-receptor-subunit-1 (NMDAR1) synaptic proteins downregulation, an increase in glutamate content through an increase in glutaminase activity, a downregulation in the vesicular-glutamate-transporter-2 (VGLUT2) and in the WNT/ß-Catenin pathway, and cell death in SN56 cells. These toxic effects observed in SN56 cells were mediated by overexpression of histone-deacetylase-2 (HDAC2). These results may help to explain the synaptic plasticity, cognitive dysfunction, and neurodegeneration induced by the plasticizer BPA, which could contribute to their prevention.

Cadmium-promoted thyroid hormones disruption mediates ROS, inflammation, Aß and Tau proteins production, gliosis, spongiosis and neurodegeneration in rat basal forebrain.

Cadmium (Cd) produces cognition decline following single and repeated treatment, although the complete mechanisms are still unrevealed. Basal forebrain (BF) cholinergic neurons innervate the cortex and hippocampus, regulating cognition. Cd single and repeated exposure induced BF cholinergic neuronal loss, partly through thyroid hormones (THs) disruption, which may cause the cognition decline observed following Cd exposure. However, the mechanisms through which THs disruption mediate this effect remain unknown. To research the possible mechanisms through which Cd-induced THs deficiency may mediate BF neurodegeneration, Wistar male rats were treated with Cd for 1- (1 mg/kg) or 28-days (0.1 mg/kg) with or without triiodothyronine (T3, 40 µg/kg/day). Cd exposure promoted neurodegeneration, spongiosis, gliosis and several mechanisms related to these alterations (increased H202, malondialdehyde, TNF-α, IL-1ß, IL-6, BACE1, Aß and phosphorylated-Tau levels, and decreased phosphorylated-AKT and phosphorylated-GSK-3ß levels). T3 supplementation partially reversed the effects observed. Our results show that Cd induces several mechanisms that may be responsible for the neurodegeneration, spongiosis and gliosis observed in the rats' BF, which are partially mediated by a reduction in THs levels. These data may help to explain the mechanisms through which Cd induces BF neurodegeneration, possibly leading to the cognitive decline observed, providing new therapeutic tools to prevent and treat these damages.

Percepción de los pacientes hospitalizados respecto del cuidado de enfermería

Resumen: Introducción: La atención humanizada requiere la interacción entre los conocimientos científicos y los valores, generando la necesidad de particularizar los cuidados, siendo esta una actividad esencial en enfermería. Objetivo: Analizar la percepción que tienen los usuarios hospitalizados respecto del cuidado humanizado que reciben por parte de las profesionales de enfermería. Metodología: Se desarrolló una investigación de tipo cuantitativa, descriptiva, correlacional y de corte transversal, que incluyó a los usuarios hospitalizados en los Servicios Clínicos de Medicina, Cirugía, Pensionado y representantes legales de pacientes menores de 18 años en Pediatría, de un hospital público ubicado en el sur de Chile, con una muestra de 377 participantes. Posterior a aplicación de consentimiento informado, se aplicó una caracterización sociodemográfica y el instrumento Percepción de Comportamientos de Cuidado Humanizado de Enfermería - versión 3, con adaptación transcultural para la población chilena, el cual fue complementado con otros datos pertinentes a los objetivos de la investigación. Resultados: Se encontró que las personas participantes en su mayoría reconocieron al profesional de enfermería por el uniforme, y pese a existir algunas diferencias en cada servicio, refirieron satisfacción con el cuidado recibido (84,6 %). Aspectos como la edad, el tiempo de hospitalización y el reconocimiento del personal de enfermería, evidenciaron relación estadística con la satisfacción. Conclusiones: Se requiere implementar estrategias para fortalecer la percepción del cuidado humanizado de enfermería, siendo estos aspectos una contribución para la construcción de un clima y cultura organizacional que evidencien esta perspectiva de cuidado.

Resumo: Introdução: Uma atenção humanizada requer a interação entre saberes científicos e valores, gerando a necessidade de particularização ou cuidado, sendo essa uma atividade essencial na enfermagem. Objetivo: Analisar a percepção que os usuários hospitalizados têm sobre o atendimento humanizado que recebem dos profissionais de enfermagem. Método: Es uma investigação quantitativa, descritiva, correlacional e transversal, que incluiu os usuários hospitalizados nos Serviços de Medicina, Cirurgia, Pensionista e representantes legais de pacientes menores de 18 anos em Pediatria, de um hospital público localizado no sul do Chile, com uma amostra de 377 participantes, Após a aplicação do consentimento informado, foi aplicada uma caracterização sociodemográfica e foi aplicado o instrumento Percepção de Comportamentos de Assistência Humanizada de Enfermagem - versão 3, com adaptação transcultural para a população chilena, ou que foi complementado com outros dados pertinentes aos objetivos da pesquisa. Resultados: Verificou-se que os participantes, em sua maioria, reconheciam ou profissionais de enfermagem pelo uniforme e, apesar da existência de algumas diferenças em cada Serviço, relatam sentir-se satisfeitos com o atendimento recebido (84,6 %). Aspectos como a idade, tempo de internação e reconhecimento da equipe de enfermagem apresentam relação estatística com a satisfação. Conclusões: É necessário implementar estratégias que fortaleçam a percepção do cuidado humanizado de enfermagem, sendo esses aspectos uma contribuição para a construção de um clima e cultura organizacional que demonstrem essa perspectiva de cuidado.

Abstract: Introduction: Humanized care requires the interaction between scientific knowledge and values, generating the need to particularize care, which is an essential activity in nursing. Objective: To analyze the perception of hospitalized users regarding the humanized care they receive from nursing professionals. Methodology: A quantitative, descriptive, correlational, and cross-sectional research was carried out, which included hospitalized users in the Clinical Services of Medicine, Surgery, Private, and legal representatives of patients under 18 years of age in Pediatrics, of a public hospital located in the south of Chile, with a sample of 377 participants. After the application of informed consent, it was applied a sociodemographic characterization as well as the instrument Perception of Humanized Nursing Care Behaviors - Version 3, with transcultural adaptation for the Chilean population, which was complemented with other data pertinent to the objectives of the research. Results: It was found that most of the participants recognized the nursing professional by the uniform, and despite some differences in each service, they reported satisfaction with the care received (84.6%). Aspects such as age, length of hospitalization and recognition of the nursing staff showed a statistical relation with satisfaction. Conclusions: It is necessary to implement strategies to strengthen the perception of humanized nursing care, being these aspects a contribution to the construction of an organizational climate and culture that evidences this perspective of care.

Disfunción sexual en mujeres con esclerosis sistémica / Sexual dysfunction in women with systemic sclerosis

Introducción: la disfunción sexual (DS) es común entre las mujeres con enfermedades crónicas, incluyendo esclerosis sistémica (ES). Se ha asociado con características como la duración de la enfermedad, dolor, disminución de la actividad funcional, entre otras. Desde nuestro conocimiento, aún no contamos con datos locales. Objetivos: evaluar la frecuencia de DS en mujeres con ES; describir las características sociodemográficas, clínicas y psicológicas asociadas con la DS en mujeres con ES. Materiales y métodos: estudio observacional, analítico y de corte transversal. Se incluyeron mujeres de entre 20 y 59 años con diagnóstico de ES, según los criterios de clasificación del European League Against Rheumatism/American College of Rheumatology (ACR/EULAR 2013). Se excluyeron pacientes con enfermedades crónicas no controladas, otras patologías reumatológicas autoinmunes, e inactividad sexual o patología genitourinaria no relacionadas a ES en las últimas 4 semanas. La DS se evaluó con la versión en español del cuestionario índice de función sexual femenina (Female sexual function index, FSFI). Resultados: se incluyeron 56 pacientes. El 78,57% presentó DS y 19,64% era sexualmente inactiva debido a la enfermedad. Escala visual análoga (EVA) de fatiga (coeficiente ß: -0,08, IC 95%: -0,14 a -0,02; p<0,01), edad (coeficiente ß: -0,23, IC 95%: -0,40 a -0,05; p=0,01) y fibromialgia (coeficiente ß: -11,90, IC 95%: -17,98 a -5,82; p<0,01) mostraron una asociación significativa e independiente con DS en el análisis multivariado. Conclusiones: la DS es frecuente entre las mujeres con ES, y las pacientes más jóvenes, sin fibromialgia y con menor fatiga presentaron una mejor funcionalidad sexual.

Introduction: sexual impairment (SI) is common among women with chronic diseases, including systemic sclerosis (SSc). It has been associated with characteristics such as the duration of the disease, pain, decreased functional activity, among others. To the best of our knowledge, we still do not have local data. Objectives: to evaluate the frequency of SI in women with SSc. To describe the sociodemographic characteristics, disease itself and psychological items associated with SI in women with SSc. Materials and methods: observational, analytical, cross-sectional study. We included women between 20 and 59 years diagnosed with SSc according to 2013 classification criteria ACR/EULAR. We excluded patients with uncontrolled chronic diseases or other autoimmune rheumatologic diseases and patients who, in the last 4 weeks, had dyspareunia or were sexually inactive due to causes not attributable to their disease. SI was assessed using the Spanish version of female sexual function index questionnaire (FSFI). Results: 56 patients were included. 78.57% presented SI and 19.64% of them were sexually inactive patients due to the disease. Fatigue VAS (ß coefficient: -0.08, CI 95%: -0.14 to -0.02; p<0.01), age (ß coefficient: -0.23, CI 95%: -0.40 to -0.05; p=0.01) and fibromyalgia (ß coefficient: -11.90, CI 95%: -17.98 to -5.82; p<0.01) showed significant and independent association with SI in the multivariate analysis. Conclusions: SI is frequent among women with SSc, and younger patients, without fibromyalgia and with less fatigue have better sexual function.

Disfunción sexual en mujeres con esclerosis sistémica / Sexual dysfunction in women with systemic sclerosis

Introducción: la disfunción sexual (DS) es común entre las mujeres con enfermedades crónicas, incluyendo esclerosis sistémica (ES). Se ha asociado con características como la duración de la enfermedad, dolor, disminución de la actividad funcional, entre otras. Desde nuestro conocimiento, aún no contamos con datos locales. Objetivos: evaluar la frecuencia de DS en mujeres con ES; describir las características sociodemográficas, clínicas y psicológicas asociadas con la DS en mujeres con ES. Materiales y métodos: estudio observacional, analítico y de corte transversal. Se incluyeron mujeres de entre 20 y 59 años con diagnóstico de ES, según los criterios de clasificación del European League Against Rheumatism/American College of Rheumatology (ACR/EULAR 2013). Se excluyeron pacientes con enfermedades crónicas no controladas, otras patologías reumatológicas autoinmunes, e inactividad sexual o patología genitourinaria no relacionadas a ES en las últimas 4 semanas. La DS se evaluó con la versión en español del cuestionario índice de función sexual femenina (Female sexual function index, FSFI). Resultados: se incluyeron 56 pacientes. El 78,57% presentó DS y 19,64% era sexualmente inactiva debido a la enfermedad. Escala visual análoga (EVA) de fatiga (coeficiente β: -0,08, IC 95%: -0,14 a -0,02; p<0,01), edad (coeficiente β: -0,23, IC 95%: -0,40 a -0,05; p=0,01) y fibromialgia (coeficiente β: -11,90, IC 95%: -17,98 a -5,82; p<0,01) mostraron una asociación significativa e independiente con DS en el análisis multivariado. Conclusiones: la DS es frecuente entre las mujeres con ES, y las pacientes más jóvenes, sin fibromialgia y con menor fatiga presentaron una mejor funcionalidad sexual.

Introduction: sexual impairment (SI) is common among women with chronic diseases, including systemic sclerosis (SSc). It has been associated with characteristics such as the duration of the disease, pain, decreased functional activity, among others. To the best of our knowledge, we still do not have local data. Objectives: to evaluate the frequency of SI in women with SSc. To describe the sociodemographic characteristics, disease itself and psychological items associated with SI in women with SSc. Materials and methods: observational, analytical, cross-sectional study. We included women between 20 and 59 years diagnosed with SSc according to 2013 classification criteria ACR/EULAR. We excluded patients with uncontrolled chronic diseases or other autoimmune rheumatologic diseases and patients who, in the last 4 weeks, had dyspareunia or were sexually inactive due to causes not attributable to their disease. SI was assessed using the Spanish version of female sexual function index questionnaire (FSFI). Results: 56 patients were included. 78.57% presented SI and 19.64% of them were sexually inactive patients due to the disease. Fatigue VAS (β coefficient: -0.08, CI 95%: -0.14 to -0.02; p<0.01), age (β coefficient: -0.23, CI 95%: -0.40 to -0.05; p=0.01) and fibromyalgia (β coefficient: -11.90, CI 95%: -17.98 to -5.82; p<0.01) showed significant and independent association with SI in the multivariate analysis. Conclusions: SI is frequent among women with SSc, and younger patients, without fibromyalgia and with less fatigue have better sexual function.

Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption.

Cadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neurons (BFCN) regulate cognitive functions. BFCN loss or cholinergic neurotransmission dysfunction leads to cognitive disabilities. Thyroid hormones (THs) maintain BFCN viability and functions, and Cd disrupts their levels. However, Cd-induced BFCN damages and THs disruption involvement was not studied. To research this we treated male Wistar rats intraperitoneally with Cd once (1 mg/kg) or repetitively for 28 days (0.1 mg/kg) with/without triiodothyronine (T3, 40 µg/kg/day). Cd increased thyroid-stimulating-hormone (TSH) and decreased T3 and tetraiodothyronine (T4). Cd altered cholinergic transmission and induced a more pronounced neurodegeneration on BFCN, mediated partially by THs reduction. Additionally, Cd antagonized muscarinic 1 receptor (M1R), overexpressed acetylcholinesterase S variant (AChE-S), downregulated AChE-R, M2R, M3R and M4R, and reduced AChE and choline acetyltransferase activities through THs disruption. These results may assist to discover cadmium mechanisms that induce cognitive disabilities, revealing a new possible therapeutic tool.

Bisphenol A single and repeated treatment increases HDAC2, leading to cholinergic neurotransmission dysfunction and SN56 cholinergic apoptotic cell death through AChE variants overexpression and NGF/TrkA/P75NTR signaling disruption.

Bisphenol-A (BPA), a widely used plasticizer, induces cognitive dysfunctions following single and repeated exposure. Several studies, developed in hippocampus and cortex, tried to find the mechanisms that trigger and mediate these dysfunctions, but those are still not well known. Basal forebrain cholinergic neurons (BFCN) innervate hippocampus and cortex, regulating cognitive function, and their loss or the induction of cholinergic neurotransmission dysfunction leads to cognitive disabilities. However, no studies were performed in BFCN. We treated wild type or histone deacetylase (HDAC2), P75NTR or acetylcholinesterase (AChE) silenced SN56 cholinergic cells from BF with BPA (0.001 µM-100 µM) with or without recombinant nerve growth factor (NGF) and with or without acetylcholine (ACh) for one- and fourteen days in order to elucidate the mechanisms underlying these effects. BPA induced cholinergic neurotransmission disruption through reduction of ChAT activity, and produced apoptotic cell death, mediated partially through AChE-S overexpression and NGF/TrkA/P75NTR signaling dysfunction, independently of cholinergic neurotransmission disruption, following one- and fourteen days of treatment. BPA mediates these alterations, in part, through HDAC2 overexpression. These data are relevant since they may help to elucidate the neurotoxic mechanisms that trigger the cognitive disabilities induced by BPA exposure, providing a new therapeutic approach.

Aryl Hydrocarbon Receptor Activation Produces Heat Shock Protein 90 and 70 Overexpression, Prostaglandin E2/Wnt/ß-Catenin Signaling Disruption, and Cell Proliferation in MCF-7 and MDA-MB-231 Cells after 24 h and 14 Days of Chlorpyrifos Treatment.

The biocide chlorpyrifos (CPF) was described to increase breast cancer risk in humans, to produce breast cancer in animals, and to induce cell proliferation in MCF-7 and MDA-MB-231 cells after 1 and 14 days of treatment. The entire mechanisms related to these CPF actions remain unknown. CPF induced cell proliferation in MCF-7 and MDA-MB-231 cells after 1 and 14 days of treatment by AhR activation through the PGE2/Wnt/ß-catenin pathway and HSP90 and HSP70 overexpression. Our results reveal new information on CPF toxic mechanisms induced in human breast cancer cell lines, which could assist in elucidating its involvement in breast cancer.

Chlorpyrifos induces cell proliferation in MCF-7 and MDA-MB-231 cells, through cholinergic and Wnt/ß-catenin signaling disruption, AChE-R upregulation and oxidative stress generation after single and repeated treatment.

Chlorpyrifos (CPF) biocide, is associated with breast cancer. The processes underlying this association have not been elucidated to date. CPF increases MCF-7 and MDA-MB-231 cell proliferation after acute and long-term treatment, partially through KIAA1363 overexpression and aryl-hydrocarbon receptor activation but also through estrogen receptor-alpha activation after 24 h exposure in MCF-7 cells, suggesting other mechanisms may be involved. CPF induces reactive oxygen species (ROS) generation, acetylcholine accumulation, and overexpression of acetylcholinesterase-R/S (AChE-R/S) variants, while it also alters the Wnt/ß-catenin pathway, both in vitro and in vivo, in processes different from cancer. These latter mechanisms are also linked to cell proliferation and could mediate this effect induced by CPF. Our results show that CPF (0.01-100 µM), following one-day and fourteen-days treatment, respectively, induced ROS generation and lipid peroxidation, and acetylcholine accumulation due to AChE inhibition, Wnt/ß-catenin up- or downregulation depending on the CPF treatment concentration, and AChE-R and AChE-S overexpression, with the latter being mediated through GSK-3ß activity alteration. Finally, CPF promoted cell division through ACh and ROS accumulation, AChE-R overexpression, and Wnt/ß-catenin signaling disruption. Our results provide novel information on the effect of CPF on human breast cancer cell lines that may help to explain its involvement in breast cancer.

Cambios en la ergonomía en tiempos de COVID-19 en estudiantes de una universidad Peruana / Changes in ergonomics in times of COVID-19 in students of a Peruvian university

La enfermedad por COVID-19 ha traído consigo cambios que forman parte de la nueva normalidad. Muchos de estos cambios podrían repercutir de mala manera en la población y traer enfermedades o riesgo de comorbilidades como diabetes, estrés, obesidad o problemas ergonómicos. El presente estudio tuvo como objetivo evaluar los factores asociados a la ergonomía en estudiantes universitarios durante el contexto de clases virtuales en Lima, Perú debido a la COVID-19. Se realizó una encuesta virtual mediante la plataforma de Google Forms, a 121 estudiantes del primer ciclo en una universidad limeña. La encuesta contenía preguntas sobre los cambios ergonómicos percibidos durante las clases virtuales debido a la COVID-19. Respecto al peso, 43.85 % presentó variación, mientras que el 44,6% reportó que no. Sobre las molestias corporales y visuales el 83.5 % presentaron dolores musculares, mientras que el 16.5 % no tenían estas molestias. Entre estos prevalecían el dolor de espalda, cuello, cintura, hombros y piernas. Por otro lado, el 78.5 % presentaban incomodidad visual, mientras que el otro 21.5 % no lo presentó. Entre las molestias visuales más frecuentes estaban ardor, picazón, sensación de ojo seco, cansancio de la vista y lagrimeo durante las clases. El dispositivo más usado por los estudiantes para las clases virtuales fue la laptop (81 %). Respecto a los ejercicios físicos, el 46,3 % sí lo realizaban terminada las clases, y los estiramientos un 62.8 %. Igualmente, se evaluó la ingesta de líquidos, frutas y comida chatarra. De los encuestados, un 52.9 % no varió su ingesta de líquidos, el 60.3 % no varió el de frutas, y el 48.8 % disminuyó la ingesta de comida chatarra. Los problemas ergonómicos que se evaluaron, podrían estar relacionados con los altos periodos de tiempo que los estudiantes se exponen al uso de los equipos electrónicos debido a las clases virtuales y también al no tener un lugar fijo de estudio, por lo que se debería realizar otras actividades adicionales como hacer ejercicio y/o estiramientos después de clase, además de ingerir más frutas, líquidos y mantener un estilo de vida saludable.

The increasing attention that is given to the protection of health professionals and patients has stimulated researchers and organizations to create alternatives to improve safety practices in health services, including in the Magnetic Resonance Imaging (MRI) environment. However, this theme still needs to be further explored in the MRI field. This paper aims to review the current literature, explore the approach to the MRI Safety Supervisor, to describe the role of the MRI Safety Supervisor and how it could serve as an agent to enhance the safety of health professionals and patients in the MRI environment. To achieve this, a narrative literature review was carried out in the electronic databases: ScienceDirect, PubMed, Scielo and Google Scholar, using as inclusion criteria, articles published in Portuguese and English between the years 2008 to 2019. The articles were filtered according to relevant aspects, such as authorship, title, year of publication, objectives, methodology and main results. Lastly, it considered aspects related to adverse events, international and national regulations on security and safety management in the MRI sector. Nevertheless, in the search for actions that effectively mitigate risks on this modality, it was observed that studies on the MRI Safety Supervisor are scarce, which reinforce the need for further studies on this matter.

Mesenchymal Cells Support the Oncogenicity and Therapeutic Response of the Hedgehog Pathway in Triple-Negative Breast Cancer.

The paracrine interaction between tumor cells and adjacent stroma has been associated with the oncogenic activity of the Hedgehog (Hh) pathway in triple-negative breast tumors. The present study developed a model of paracrine Hh signaling and examined the impact of mesenchymal cell sources and culture modalities in the oncogenicity of the Hh pathway in breast tumor cells. Studies consisted of tumor cell monocultures and co-cultures with cancer-associated and normal fibroblasts, tumor cells that undergo epithelial-mesenchymal transition (EMT), or adipose-derived mesenchymal stem cells (ADMSCs). Hh ligand and pathway inhibitors, GANT61 and NVP-LDE225 (NVP), were evaluated in both cell cultures and a mouse xenograft model. Results in monocultures show that tumor cell viability and Hh transcriptional activity were not affected by Hh inhibitors. In co-cultures, down-regulation of GLI1, SMO, and PTCH1 in the stroma correlated with reduced tumor growth rates in xenografted tumors and cell cultures, confirming a paracrine interaction. Fibroblasts and EMT cells supported Hh transcriptional activity and enhanced tumor cell growth. Mixed and adjacent culture modalities indicate that tumor growth is supported via fibroblast-secreted soluble factors, whereas enriched tumor stemness requires close proximity between tumor and fibroblasts. Overall this study provides a tumor-mesenchymal model of Hh signaling and highlights the therapeutic value of mesenchymal cells in the oncogenic activity of the Hh pathway.

PlayStation PortableTM como tratamiento de la ambliopía en los niños / PlayStation PortableTM as treatment for children with amblyopia

Objetivo: Determinar la efectividad de la terapia visual con el uso del PlayStation PortableTM en la ambliopía. Método: Se incluyeron 40 pacientes de 5-10 años de edad con ambliopía estrábica, anisometrópica o ambas, aleatorizados en 4 grupos según el tipo de terapia a utilizar (10 pacientes por grupo): grupo 1, PlayStation PortableTM y lentes rojo-verde; grupo 2, PlayStation PortableTM y lentes con vidrio esmerilado en el ojo fijador (no ambliope); grupo 3, PlayStation PortableTM y parche oclusivo en el ojo fijador; grupo 4, parche oclusivo en el ojo fijador sin el PlayStation PortableTM. Todos los pacientes utilizaron su refracción. Las actividades de los grupos 1 al 3 incluyeron jugar videojuegos y ver películas 1-2 horas al día; el grupo 4 podía realizar cualquier actividad. Se valoró la agudeza visual mejor corregida semanalmente, hasta completar 3 meses de tratamiento. En el postratamiento se valoró la agudeza visual mejor corregida mensualmente durante 3 meses. Resultados: En total se estudiaron 40 pacientes, de los cuales el 60 por ciento fueron del sexo femenino, con un promedio de edad de 8,2 años, rango de 5-10 años. El tipo más frecuente de ambliopía fue la estrábica (55 por ciento), seguido de la anisometrópica (37,5 por ciento) y ambas (7,5 por ciento). En cuanto al ojo afectado, en el 62,5 por ciento fue el ojo izquierdo y en el 37,5 por ciento el ojo derecho. Conclusiones: En este estudio el grupo con mejores resultados fue el de filtro rojo-verde. Al suspender la terapia se observó un deterioro visual en los cuatro grupos, sin regresar a la basal. Se demuestra que el PlayStation PortableTM funciona como terapia en la ambliopía con una mejoría en la agudeza visual mejor corregida(AU)

Objective: Determine the effectiveness of visual therapy with PlayStation PortableTM for amblyopia. Methods: The study sample was composed of 40 patients aged 5-10 years with strabismic amblyopia, anisometropic amblyopia or both, randomized to 4 groups according to the therapy to be used (10 patients per group): Group 1: PlayStation PortableTM and red-green lenses; Group 2: PlayStation PortableTM and frosted glass lenses on the fixating (non-amblyopic) eye; Group 3: PlayStation PortableTM and occlusive patch on the fixating eye; Group 4: occlusive patch on the fixating eye without PlayStation PortableTM. All the patients used their refraction. The activities performed by Groups 1-3 included playing video games and watching movies 1-2 hours per day; Group 4 could perform any activity. Best corrected visual acuity was measured weekly until completing 3 months of treatment. In the post-treatment period best corrected visual acuity was measured monthly for 3 months. Results: A total 40 patients were studied, of whom 60 percent were female, with a mean age of 8.2 years, range of 5-10 years. Strabismic amblyopia was the most common type (55 percent), followed by anisometropic amblyopia (37,5 percent) and both (7.5 percent). The affected eye was the left eye in 62.5 percent and the right eye in 37.5 percent. Conclusions: It was found that PlayStation PortableTM is effective as therapy for amblyopia, improving best corrected visual acuity. The group with the best results was the red-green filter group. Upon suspension of the therapy, visual deterioration was observed in the 4 groups, without returning to baseline values(AU)

Trafficking of the transcription factor Nrf2 to promyelocytic leukemia-nuclear bodies: implications for degradation of NRF2 in the nucleus.

Ubiquitylation of Nrf2 by the Keap1-Cullin3/RING box1 (Cul3-Rbx1) E3 ubiquitin ligase complex targets Nrf2 for proteasomal degradation in the cytoplasm and is an extensively studied mechanism for regulating the cellular level of Nrf2. Although mechanistic details are lacking, reports abound that Nrf2 can also be degraded in the nucleus. Here, we demonstrate that Nrf2 is a target for sumoylation by both SUMO-1 and SUMO-2. HepG2 cells treated with As2O3, which enhances attachment of SUMO-2/3 to target proteins, increased SUMO-2/3-modification (polysumoylation) of Nrf2. We show that Nrf2 traffics, in part, to promyelocytic leukemia-nuclear bodies (PML-NBs). Cell fractions harboring key components of PML-NBs did not contain biologically active Keap1 but contained modified Nrf2 as well as RING finger protein 4 (RNF4), a poly-SUMO-specific E3 ubiquitin ligase. Overexpression of wild-type RNF4, but not the catalytically inactive mutant, decreased the steady-state levels of Nrf2, measured in the PML-NB-enriched cell fraction. The proteasome inhibitor MG-132 interfered with this decrease, resulting in elevated levels of polysumoylated Nrf2 that was also ubiquitylated. Wild-type RNF4 accelerated the half-life (t½) of Nrf2, measured in PML-NB-enriched cell fractions. These results suggest that RNF4 mediates polyubiquitylation of polysumoylated Nrf2, leading to its subsequent degradation in PML-NBs. Overall, this work identifies Nrf2 as a target for sumoylation and provides a novel mechanism for its degradation in the nucleus, independent of Keap1.

O valor terapêutico da ação humana e suas concepções em Terapia Ocupacional / The therapeutic value of human action and its concepts in Occupational Therapy

Diante de uma inquietação compartilhada pelos proponentes da pesquisa a respeito de quando o fazer humano se torna terapêutico no processo da Terapia Ocupacional, propôs-se discutir o valor terapêutico da ação humana em Terapia Ocupacional, de acordo com as diferentes concepções desenvolvidas sobre o assunto. Para tanto, realizou-se um estudo exploratório com pesquisa bibliográfica, dentro da estratégia do Laboratório de Estudos em Terapia Ocupacional (LETO) adotada no quinto ano do curso de Terapia Ocupacional da Universidade do Estado do Pará. Após compreender diferentes ideias de atividade e ocupação desenvolvidas por autores da Terapia Ocupacional, analisar o processo terapêutico e o significado da ação humana dentro desse processo, pôde-se verificar que as diferentes concepções para o valor terapêutico da intervenção estão relacionadas a momentos históricos, áreas de atuação e formação profissional. Para os pesquisadores, o valor terapêutico relaciona-se a mudanças construtivas, para o sujeito, relaciona-se a um processo de transformação de si e de sua realidade por meio do fazer.

In view of the unrest shared by the proponents of this research regarding the human ?doing? as therapeutic action in the process of Occupational Therapy, we proposed to discuss the therapeutic value of this action according to the different concepts developed on the subject. To this end, we carried out an exploratory literature survey, within the study strategy of the Laboratory for Research on Occupational Therapy (LETO), which was adopted in the fifth year of the Occupational Therapy course of the University of the State of Pará. After learning different ideas of activity and occupation developed by authors of Occupational Therapy, analyzing the therapeutic process and the meaning of human action within this process, we verified that the different conceptions of the therapeutic value of intervention are related to historical moments, areas of expertise, and professional training. In the researchers? opinion, the therapeutic value relates to constructive changes to the subject, a process of transformation of the self and its reality, through ?doing?.

Aracnoiditis secundaria a bloqueo epidural lumbar con lidocaína simple al 2 por ciento para operación cesárea: reporte de Caso / Adhesive arachnoiditis after epidural block for cesarean section

Contaminantes inespecíficos, detergentes, o bien toxicidad directa de soluciones de anestésicos locales o de sus aditivos como el bisulfito, pueden producir reacción proliferativa progresiva de las meninges con desarrollo de aracnoiditis adhesiva cuando se aplican en el espacio epidural o subaracnoideo. Esta es probablemente, la complicación más severa de la anestesia espinal y puede ser mortal. Aquí se informa de un caso de una paciente de 15 años de edad manejada con anestesia epidural continua con lidocaína simple al 2 por ciento para operación cesárea, que cursó con paraplejia bilateral en el postoperatorio inmediato y a quien se le diagnosticó posterior a la realización de tomografía axial computarizada y resonancia magnética de columna toraco-lumbar un proceso inflamatorio aracnoideo de T12 a L3 secundario a evento anestésico