RESUMEN
BACKGROUND: Health concerns about the potential impact of exposure to fluoride via drinking water (DW) on neuropsychological development include behavioral outcomes such as ADHD. OBJECTIVE: We aimed to examine the association between prenatal maternal urinary fluoride and symptoms associated with attention-deficit/hyperactivity disorder (ADHD) at the age of 8 and 11 years. METHOD: Data from 255 to 236 mother-child pairs from the "Infancia y Medio Ambiente" (INMA) birth cohort (Gipuzkoa; Spain) with maternal urinary F adjusted for creatinine (MUFcr) during pregnancy (first and third trimester) and child assessments of ADHD-like symptoms reported by Conners' Rating Scales-Revised at age of 8 and 11 years was available. Clinical approach was also used: cut off criteria (T > 66). Multiple linear regression models were fitted when outcomes were analyzed as continuous, and logistic regression models when the outcomes were analyzed with a categorical clinical approach. Covariates related to maternal characteristics, birth outcomes, childhood, quality of family context and biomarkers of neuro-toxicants were used. RESULTS: No association was found between MUFcr levels during pregnancy and cognitive problems-inattention, hyperactivity or ADHD index score of symptoms at 8 or 11 years. When results were analyzed from the perspective of a clinical approach, at the age of 11 years, there were significant inverse association between MUFcr and being categorized as a cognitive problems-inattention case. ORs were also indicative of a lower risk, although not significant, for ADHD index at age 11. Sensitivity analyses, taking into consideration quality of family context or the levels of other toxicants during pregnancy showed similar results. CONCLUSIONS: Higher levels of MUFcr in pregnant women were associated with a lower risk of cognitive problems-inattention at 11 years. These findings are inconsistent with those from previous studies and indicate the need for other population-based studies to confirm or overturn these results.
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Trastorno por Déficit de Atención con Hiperactividad , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Niño , Trastorno por Déficit de Atención con Hiperactividad/inducido químicamente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Fluoruros/toxicidad , Tercer Trimestre del Embarazo , Vitaminas , Creatinina , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
The purpose of this study was to develop a predictive model for perceived competence and to obtain an integrator evaluation of the nursing curriculum with measures of nursing self-efficacy, general self-efficacy, resilience, and stress among nursing students. A correlational study with nursing students (N = 265) from the degree in nursing was conducted. A factor analysis was used to test the construct validity of nursing self-efficacy and perceived competence. The correlational and discriminant analyses evaluated the factors in the four academic levels of the degree (2016-2017) to identify the variables involved in the classification of the students in each level. The results of exploratory and confirmatory factor analyses of nursing self-efficacy and perceived competence revealed a statistically significant good fit and consistency. Nursing self-efficacy, general self-efficacy, resilience, and year of the degree course predicted 34% of perceived competence scores. The discriminant function of nursing self-efficacy, perceived competence, and resilience classified 76% of participants in the first and last years of the degree. Nursing self-efficacy, perceived competence, and resilience increased with academic level. They help chart nursing students' progress through the curriculum.
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Competencia Clínica/normas , Resiliencia Psicológica , Autoeficacia , Autoinforme , Estudiantes de Enfermería/psicología , Adolescente , Adulto , Correlación de Datos , Bachillerato en Enfermería/métodos , Bachillerato en Enfermería/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría/instrumentación , Psicometría/métodos , España , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Several studies have related longer breastfeeding duration to better intellectual performance in children. By contrast, few studies have investigated the potential protective effects of breastfeeding against behavioral problems such as attention deficit hyperactivity disorder (ADHD) symptoms, and even fewer on autism spectrum disorders (ASD) traits. METHODS: We examined the association between breastfeeding duration and cognitive development, attention, ADHD symptoms, and autistic traits using data from the INMA Project, a Spanish multicenter birth-cohort study, and taking into account the intensity of breastfeeding. Duration of any, predominant, and exclusive breastfeeding was documented during infancy through maternal questionnaires. Children (N = 1,346; mean age = 4.9 y) were assessed using the McCarthy Scales of Children's Abilities, Conners' Kiddie Continuous Performance Test, criteria of the DSM-ADHD symptoms form list, and the Childhood Autism Spectrum Test. RESULTS: After adjustment for several confounders, longer duration of breastfeeding was independently associated with better cognitive development and with fewer autistic traits. CONCLUSION: This study provides further evidence of a positive association of breastfeeding with cognitive function apart from socio-environmental factors, and also suggests a protective role against autistic traits. Results are in agreement with recommendations for prolonged breastfeeding duration to promote child development.
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Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno del Espectro Autista/epidemiología , Lactancia Materna , Trastornos del Conocimiento/epidemiología , Factores de Tiempo , Desarrollo Infantil , Preescolar , Cognición , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Análisis de Regresión , España , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Temporomandibular disorders (TMD) refer to a group of clinical picture affecting the masticatory muscles and temporomandibular joint that are characterized by muscular or joint pain, dysfunction (limited or altered functions) and joint noises, as well as other associated symptoms, such as tension headaches, otalgia, dizziness, tinnitus, and others. Fibromyalgia (FM) is a syndrome of unknown etiology involving generalized chronic pain accompanied, in a high percentage of cases, by other symptoms such as asthenia, anxiety, depression, sleep disturbances, and other less frequent symptoms, such as temporomandibular disorders (TMD). DATA: Data were compiled by two experienced examiners following a specific form. SOURCES: An electronic search was carried out in the Cochrane Central Register of Controlled Trials (CENTRAL), PUBMED, and SCOPUS electronic databases (up to April 2016, unrestricted by date or language). STUDY SELECTION: Comparative clinical studies with patients with both clinical pictures involving the study of pathogenic processes. CONCLUSIONS: Fibromyalgia and temporomandibular disorders with muscle pain both have profiles that affect the muscular system and therefore share many epidemiological, clinical, and physiopathological symptoms. Because of this, we are led to think that there is, if not a common etiology, at least a common pathogenesis. This article revises the physiopathological processes of both clinical pictures in an attempt to determine their similarities and likenesses. This would undoubtedly help in providing a better therapeutic approach.
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Fibromialgia/fisiopatología , Dolor/fisiopatología , Trastornos de la Articulación Temporomandibular/fisiopatología , Ansiedad/fisiopatología , Depresión/fisiopatología , Femenino , Fibromialgia/etiología , Humanos , Masculino , Dolor/etiología , Síndrome , Trastornos de la Articulación Temporomandibular/etiologíaRESUMEN
INTRODUCTION: Major depressive disorder (MDD) is a very prevalent disease which pathogenic mechanism remains elusive. There are some hypotheses and pilot studies suggesting that cytokines may play an important role in MDD. In this respect, we have investigated the role of NLRP3 inflammasome complex in the maturation of caspase-1 and the processing of its substrates, IL-1ß and IL-18, in blood cells from MDD patients. METHODS: Forty MDD patients were selected for this study, twenty without treatments and twenty treated with amitriptyline, a common tricyclic antidepressant. Blood samples from twenty healthy volunteers were included in the study. The inflammasome activation was studied by Western blot and real-time PCR of NLRP3 and caspase 1 and serum levels of IL-1ß and 18. RESULTS: We observed increased gene expression of NLRP3 and caspase-1 in blood cells, and increased serum levels of IL-1ß and IL-18 in non-treated patients. IL-1ß and IL-18 correlated with Beck Depression Inventory (BDI) scores of MDD patients. Interestingly, amitriptyline treatment reduced NLRP3 and caspase-1 gene expression, and IL-1ß and IL-18 serum levels. As it is well established that oxidative stress is associated with NLRP3 inflammasome activation, we next studied mitochondrial ROS and lipid peroxidation (LPO) levels in MDD patients. Increased levels of mitochondrial ROS and LPO were observed in MDD patients, however oxidative damage was higher in MDD patients treated with amitriptyline. CONCLUSIONS: These findings provide new insight into the pathogenesis of MDD and the effects of amitriptyline treatment on NLRP3 inflammasome activation and IL-1ß and IL-18 serum levels.
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Proteínas Portadoras/metabolismo , Trastorno Depresivo Mayor/sangre , Inflamasomas/metabolismo , Interleucina-18/sangre , Interleucina-1beta/sangre , Leucocitos Mononucleares/metabolismo , Caspasa 1/metabolismo , Trastorno Depresivo Mayor/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés OxidativoRESUMEN
In order to analyze the association between body mass index (BMI), lipid profile and clinical symptoms in patients with fibromyalgia, we assessed BMI levels, lipid profile and its association with clinical symptoms in 183 patients with fibromyalgia. The patients were evaluated using tender points, FIQ and Visual Analogue Scales of pain (VAS). Serum lipid profile analysis (total cholesterol, triglyceride, HDL, LDL and VLDL), and biochemical parameters were measured in the biochemistry laboratory. The BMI distribution of the nonobese, overweight and obese patients' groups were relatively even with 37.7, 35.5 and 26.8%, respectively, with a mean BMI of 27.3 ± 4.9. The number of tender points showed significantly positive correlation with higher BMI (P < 0.05). A total of 57.9% of patients showed increased levels of total cholesterol, 63.4 % increased levels of LDL cholesterol and 19.9% high levels of triglycerides. BMI, total cholesterol and triglycerides showed high association with some clinical parameters. Overweight and lipid profile could be associated with fibromyalgia symptoms. A treatment program with weight loss strategies, and control in diet and increased physical activity is advised to patients.
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Fibromialgia/sangre , Fibromialgia/fisiopatología , Lípidos/sangre , Obesidad/sangre , Obesidad/fisiopatología , Sobrepeso/sangre , Sobrepeso/fisiopatología , Adulto , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Dieta Reductora , Ejercicio Físico , Femenino , Fibromialgia/terapia , Humanos , Masculino , Persona de Mediana Edad , Mialgia/fisiopatología , Obesidad/terapia , Sobrepeso/terapia , Dimensión del Dolor , Triglicéridos/sangreRESUMEN
Besides intervening in calcium homeostasis by means of calcitonin, C cells are also implicated in the synthesis of an increasing number of regulatory peptides that could exert a paracrine regulation on the neighbouring follicular cells. Among the latest peptides reported in C cells, there are several characteristic hypothalamic peptides, such as TRH, CART, and ghrelin, which are mainly involved in the regulation of the metabolism at hypothalamic-pituitary-thyroid axis. The main aim of the present work has been to study the synthesis of the referred hypothalamic peptides by normal and neoplastic C cells of different mammals as well as in C-cell lines of both rat (CA-77, 6-23) and human (TT) origins in order to elucidate whether this is a fact in this kind of vertebrates. With that objective, we have applied the immunoperoxidase technique to analyze the presence of TRH, CART, ghrelin, and somatostatin in thyroid tissues of different species, and immunofluorescence to study those same peptides in C-cell cultures. Furthermore, we have investigated their expression at mRNA level by RT-PCR analysis. Our results demonstrate immunocolocalization of CART, ghrelin, somatostatin and TRH with calcitonin in normal C cells of different mammals, as well as in rat and human neoplastic C cells. We also confirm the expression of those peptides in rat and human C-cell lines by RT-PCR. Consequently, we can conclude that the synthesis of those peptides by C cells is a general event characteristic of the thyroid gland in mammals.
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Glándula Tiroides/citología , Glándula Tiroides/metabolismo , Animales , Ghrelina/metabolismo , Cobayas , Humanos , Técnicas In Vitro , Proteínas del Tejido Nervioso/metabolismo , Conejos , Ratas , Somatostatina/metabolismo , Porcinos , Hormona Liberadora de Tirotropina/metabolismoRESUMEN
BACKGROUND: Patient safety is a relevant subject in the nursing curriculum. Each university programs patient safety teaching and practical training differently. However, few studies have sought to explore the relationship between patient safety as perceived by nursing students and other important psychosocial competencies in the nursing curriculum, such as self-efficacy, competence, and resilience. OBJECTIVES: To analyze differential patient safety integration into three nursing education programs, and to assess agreement levels regarding patient safety climate, students' knowledge of patient safety and correlations with specific self-efficacy, competence and resilience. METHODS: Participants were 647 undergraduate students from three universities. Patient safety climate and knowledge of patient safety (good praxis) were measured using the Hospital Survey on Patient Safety Culture for nursing students, and other psychosocial variables were also analyzed using other instruments: specific self-efficacy, perceived competence and resilience. Nursing education programs and patient safety climate were analyzed using the Rwg(j) and ICC measures of inter-rater agreement across different academic levels. RESULTS: The ICC and Rwg indexes revealed high inter-rate agreement in all three universities. Differences were observed between Univ-2 and Univ-3 in patient safety climate scores and agreement values between academic levels. Differences in good praxis were found when academic levels were compared in Univ1-and Univ-2. Patient safety climate was found to correlate significantly with the psychosocial variables studied, but only in Univ-1. CONCLUSIONS: Perceived patient safety climate differs between universities and academic levels. This competency is related to self-efficacy, competence and resilience, which endorses the assessment of patient safety integration from a broader perspective.
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Bachillerato en Enfermería , Educación en Enfermería , Estudiantes de Enfermería , Humanos , Estudiantes de Enfermería/psicología , Seguridad del Paciente , Autoeficacia , Competencia ClínicaRESUMEN
Introduction: Crohn's disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1ß pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue. Methods: Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1ß levels. Results: Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1ß levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed. Conclusion: These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).
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Antocianinas , Colitis , Enfermedad de Crohn , Animales , Ratones , Antocianinas/uso terapéutico , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Enfermedad de Crohn/inducido químicamente , Enfermedad de Crohn/tratamiento farmacológico , Inflamasomas/metabolismo , Mastocitos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptores Activados del Proliferador del PeroxisomaRESUMEN
BACKGROUND: Periodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis. METHODS: Peripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy. RESULTS: We found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy. CONCLUSION: Results from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontitis.
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Autofagia , Fibroblastos/inmunología , Encía/patología , Inflamación/patología , Leucocitos Mononucleares/inmunología , Periodontitis/patología , Porphyromonas gingivalis/patogenicidad , Adulto , Células Cultivadas , Enfermedad Crónica , Encía/inmunología , Humanos , Inflamación/inmunología , Lipopolisacáridos/inmunología , Lipopolisacáridos/toxicidad , Microscopía Electrónica , Microscopía Fluorescente , Persona de Mediana Edad , Periodontitis/inmunología , Fagosomas/metabolismo , Fagosomas/ultraestructura , Porphyromonas gingivalis/inmunologíaRESUMEN
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mtDNA. Here, we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from 2 patients with MELAS who harbored the A3243G mutation. Both mitochondrial respiratory chain enzyme activities and coenzyme Q(10) (CoQ) levels were significantly decreased in MELAS fibroblasts. A similar decrease in mitochondrial membrane potential was found in intact MELAS fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and the activation of mitochondrial permeability transition (MPT), which triggered the degradation of impaired mitochondria. Furthermore, we found defective autophagosome elimination in MELAS fibroblasts. Electron and fluorescence microscopy studies confirmed a massive degradation of mitochondria and accumulation of autophagosomes, suggesting mitophagy activation and deficient autophagic flux. Transmitochondrial cybrids harboring the A3243G mutation also showed CoQ deficiency and increased autophagy activity. All these abnormalities were partially restored by CoQ supplementation. Autophagy in MELAS fibroblasts was also abolished by treatment with antioxidants or cyclosporine, suggesting that both reactive oxygen species and MPT participate in this process. Furthermore, prevention of autophagy in MELAS fibroblasts resulted in apoptotic cell death, suggesting a protective role of autophagy in MELAS fibroblasts.
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Síndrome MELAS/metabolismo , Síndrome MELAS/patología , Mitocondrias/metabolismo , Mitocondrias/patología , Ubiquinona/análogos & derivados , Autofagia/genética , Autofagia/fisiología , Proteína 5 Relacionada con la Autofagia , Secuencia de Bases , Células Cultivadas , Cartilla de ADN/genética , ADN Mitocondrial/genética , Transporte de Electrón , Fibroblastos/metabolismo , Fibroblastos/patología , Técnicas de Silenciamiento del Gen , Humanos , Síndrome MELAS/genética , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/genética , Mitocondrias/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Poro de Transición de la Permeabilidad Mitocondrial , Mutación Puntual , ARN Interferente Pequeño/genética , ARN de Transferencia de Leucina/genética , Especies Reactivas de Oxígeno/metabolismo , Ubiquinona/deficienciaRESUMEN
INTRODUCTION: A study was conducted on histological patterns and biomolecular changes in Goitrogen-induced experimental rat thyroid tumors. The link between the histological types observed and N-ras, B-raf, and PI3KCA gene mutations widely reported in human thyroid cancers was explored. MATERIAL AND METHODS: An analysis was done on paraffin-embedded tumor tissue sections from Wistar rats receiving 1% potassium perchlorate (KClO(4)) added to the ad libitum drinking-water supply over an 18-month period. Three experimental subgroups were formed, each comprising 10 thyroids: subgroup I (control) consisted of thyroids from untreated controls; subgroups II and III (experimental) consisted of thyroids from KClO(4)-treated rats, displaying capsular, vascular, or both invasion but no metastasis (II), or distant metastasis (III). DNA was extracted from paraffin-embedded tissues. To test for the genetic mutations most widely reported in human thyroid cancers, exon 1 of the N-ras gene, exons 9 and 20 of the PI3KCA gene, and exon 15 of the B-raf gene were amplified and sequenced. RESULTS: All tumors were of the follicular type. None of the 20 experimental rat thyroids displayed the expected gene mutations reported in humans. However, 90% of them contained four new B-raf gene mutations and all were silent and did not cause an amino acid substitution in the protein chain. CONCLUSIONS: Biomolecular analysis suggested that N-ras, PI3KCA, and B-raf gene mutations may not be involved in thyroid tumor formation using the experimental procedure applied in this study. But the four mutations in B-raf, though without functional repercussions, may be a specific marker for this tumor type.
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Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/patología , Transducción de Señal/genética , Neoplasias de la Tiroides/genética , Adenocarcinoma Folicular/inducido químicamente , Animales , Secuencia de Bases , Exones , Femenino , Genes ras , Humanos , Datos de Secuencia Molecular , Mutación , Percloratos/toxicidad , Compuestos de Potasio/toxicidad , Proteínas Proto-Oncogénicas B-raf/genética , Ratas , Ratas Wistar , Análisis de Secuencia de ADN , Transducción de Señal/efectos de los fármacos , Neoplasias de la Tiroides/inducido químicamente , Neoplasias de la Tiroides/patologíaRESUMEN
The increased aging of populations and rises in immigration have prompted the design of new methodologies and instruments for fostering the invisible care of geriatric patients among health science students in accordance with the 2030 Agenda and the SDGs. A total of 656 psychology, nursing and dentistry students participated in this study, which had a pretest-posttest design and was implemented over the course of three academic years. The intervention groups received training using an active learning methodology based on a case study involving a geriatric patient; specifically, a Maghrebi woman. The control groups were not exposed to the case study. The CCI-U questionnaire was designed ad hoc to evaluate the acquisition of invisible competences for caring for geriatric patients in accordance with their age, sex, emotional situation and ethnic origin. The questionnaire had a reliability of α = 0.63 to 0.72 and its factor solution was found to have a good fit. Students in the intervention groups scored higher than those in the control groups, with the difference being statistically significant for ethnic origin in all three undergraduate courses and all three academic years. The proper application of this active learning methodology fosters the invisible care of geriatric patients among students in accordance with the 2030 Agenda.
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Diversidad Cultural , Estudiantes de Enfermería , Femenino , Humanos , Anciano , Aprendizaje Basado en Problemas , Reproducibilidad de los Resultados , Estudiantes , Pacientes , Estudiantes de Enfermería/psicologíaRESUMEN
Microtubule cytoskeleton is reformed during apoptosis, forming a cortical structure beneath plasma membrane, which plays an important role in preserving cell morphology and plasma membrane integrity. However, the maintenance of the apoptotic microtubule network (AMN) during apoptosis is not understood. In the present study, we examined apoptosis induced by camptothecin (CPT), a topoisomerase I inhibitor, in human H460 and porcine LLCPK-1α cells. We demonstrate that AMN was organized in apoptotic cells with high ATP levels and hyperpolarized mitochondria and, on the contrary, was dismantled in apoptotic cells with low ATP levels and mitochondrial depolarization. AMN disorganization after mitochondrial depolarization was associated with increased plasma membrane permeability assessed by enhancing LDH release and increased intracellular calcium levels. Living cell imaging monitoring of both, microtubule dynamics and mitochondrial membrane potential, showed that AMN persists during apoptosis coinciding with cycles of mitochondrial hyperpolarization. Eventually, AMN was disorganized when mitochondria suffered a large depolarization and cell underwent secondary necrosis. AMN stabilization by taxol prevented LDH release and calcium influx even though mitochondria were depolarized, suggesting that AMN is essential for plasma membrane integrity. Furthermore, high ATP levels and mitochondria polarization collapse after oligomycin treatment in apoptotic cells suggest that ATP synthase works in "reverse" mode during apoptosis. These data provide new explanations for the role of AMN and mitochondria during apoptosis.
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Adenosina Trifosfato/metabolismo , Apoptosis , Metabolismo Energético , Microtúbulos/metabolismo , Mitocondrias/metabolismo , Actinas/metabolismo , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Carbonil Cianuro p-Trifluorometoxifenil Hidrazona/farmacología , Línea Celular Tumoral , Colchicina/farmacología , Citocromos c/metabolismo , Metabolismo Energético/efectos de los fármacos , Glucólisis/efectos de los fármacos , Humanos , Cinética , L-Lactato Deshidrogenasa/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microtúbulos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Oligomicinas/farmacología , ATPasas de Translocación de Protón/metabolismoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the effect of the dietary supplementation of an alpha- and gamma-tocopherol mixture (1:5 ratio) in the adipose tissue expansion, hepatic steatosis, and expression of inflammatory markers induced by consumption of a high-fat diet (HFD) in mice. METHODS: Male C57BL/6 J mice were fed for 12 wk and divided into the following: 1) control diet (CD; 10% fat, 20% protein, 70% carbohydrates); 2) CD + TF (CD plus alpha-tocopherol: 0.7 mg/kg/d, gamma-tocopherol: 3.5 mg/kg/d); 3) HFD (60% fat, 20% protein, 20% carbohydrates); and 4) HFD + TF (HFD plus alpha-tocopherol: 0.7 mg/kg/d, gamma-tocopherol: 3.5 mg/kg/d). General parameters, adipocyte size, liver steatosis, adipose and hepatic tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) expression, hepatic nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor α (PPAR-α) levels were evaluated. RESULTS: Tocopherol supplementation in HFD-fed mice showed a significant decrease in the body weight (19%) and adipose tissue weight (52%), adipose tissue/body weight ratio (36%), and serum triacylglycerols (56%); a 42% decrease (P < 0.05) of adipocyte size compared to HFD; attenuation of liver steatosis by decreasing (P < 0.05) lipid vesicles presence (90%) and total lipid content (75%); and downregulation of inflammatory markers (TNF-α and IL-1ß), along with an upregulation of hepatic PPAR-α expression and its downstream-regulated genes (ACOX and CAT-1), and an inhibition of hepatic NF-κB activation. CONCLUSION: The present study suggests that alpha- and gamma-tocopherol (1:5 ratio) supplementation attenuates the adipocyte enlargement, hepatic steatosis, and metabolic inflammation induced by HFD in association with PPAR-α/NF-κB modulation.
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Dieta Alta en Grasa , Hígado Graso , Tejido Adiposo , Animales , Dieta Alta en Grasa/efectos adversos , Suplementos Dietéticos , Modelos Animales de Enfermedad , Hígado Graso/etiología , Hígado Graso/prevención & control , Hígado , Masculino , Ratones , Ratones Endogámicos C57BL , Expansión de Tejido , gamma-Tocoferol/farmacologíaRESUMEN
Quality of the family context has an important role in the physical and mental health of children; that is why it is important to have reliable and updated tools. This study aims to design and validate a new tool, the Haezi Etxadi Family Assessment Scale 7-11 (HEFAS 7-11), to assess family context quality in middle childhood. A sample of two cohorts of 772 Spanish families with children aged between 7 and 11 (M = 9.39 years; SD = 1.57; 51.2% girls), participated in the study. Results showed good psychometric properties for the instrument and the confirmatory factor analysis showed a five individual subscales structure: 1. Promotion of Cognitive and Linguistic Development (α = 0.79); 2. Promotion of Socio Emotional Development (α = 0.83); 3. Organization of Physical Environment and Social Context (α = 0.73); 4. Parental Stress & Conflict (α = 0.75); and 5. Parental Profile Fostering Child Development (α = 0.80). The association between HEFAS 7-11 and Trial Making Test was also analyzed to determine the concurrent validity of the instrument. The new scale shows its potential in the fields of research, social and educational, to know those variables that need to be promoted under the approach of positive parenting from a public health perspective.
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Responsabilidad Parental , Salud Pública , Niño , Escolaridad , Femenino , Humanos , Salud Mental , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin-Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui's anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).
RESUMEN
Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.
Asunto(s)
Amitriptilina/farmacología , Carcinoma Hepatocelular/terapia , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Oxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Neoplasias del Cuello Uterino/terapia , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Citotoxinas/farmacología , Reposicionamiento de Medicamentos , Femenino , Citometría de Flujo , Células HeLa , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/fisiología , Especificidad de Órganos , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/análisis , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and pathophysiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of FM. Furthermore, it is controversial the role of mitochondria in the oxidant imbalance documented in FM. Signs and symptoms associated with muscular alteration and mitochondrial dysfunction, including oxidative stress, have been observed in patients with FM. To this respect, Coenzyme Q10 (CoQ10) deficiency, an essential electron carrier in the mitochondrial respiratory chain and a strong antioxidant, alters mitochondria function and mitochondrial respiratory complexes organization and leading to increased ROS generation. Recently have been showed CoQ10 deficiency in blood mononuclear cells in FM patients, so if the hypothesis that mitochondrial dysfunction is the origin of oxidative stress in FM patients is demonstrated, could help to understand the complex pathophysiology of this disorder and may lead to development of new therapeutic strategies for prevention and treatment of this disease.