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Introduction: Kidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors. Methods: This is a retrospective, observational cohort study. Patients with IBD in whom a native kidney biopsy was performed at Mayo Clinic (Rochester, MN) between 1994 and 2022, were included. Demographic, clinical, and histologic characteristics of prognostic interest were collected. The main outcomes were kidney failure, disease remission, kidney function changes at last follow-up, and death. Results: From a total cohort of 318 patients, we selected a study group of 111 patients followed-up with at our institution (45 ulcerative colitis [UC] and 66 Crohn's disease [CD]), with a mean age of 48 ± 17 years (40% females). IgA nephropathy (IgAN), chronic interstitial nephritis (CIN), and acute interstitial nephritis (AIN) were the most common diagnoses (22%, 19%, 13%, respectively). Median estimated glomerular filtration rate (eGFR) at presentation was 30 ml/min per 1.73 m2 (interquartile range [IQR]: 17-54) and urinary protein-to-creatinine ratio [UPCR] 0.8 g/g (0.3-3.4), without differences between IBD types. During a median follow-up of 59 months (12-109), 29 patients (26%) reached kidney failure. By multivariable analysis, the main predictors of kidney failure were age (hazard ratio [HR]: 1.04; P = 0.002), baseline eGFR (HR: 0.94; P = 0.003) and histologic chronicity score (HR: 4.01; P < 0.001). Therapeutic management varied according to underlying etiology. Global survival (kidney failure + death) was significantly better in patients who achieved complete or partial remission, or stabilization or improvement of kidney function. Conclusion: One-fourth of patients with IBD with kidney disease may reach kidney failure, and the main determinants of this outcome is age, baseline eGFR, and degree of chronicity in kidney biopsy.
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Eco-friendly chemical methods using FDA-approved Pluronic F127 (PLU) block copolymer have garnered much attention for simultaneously forming and stabilizing Au nanoparticles (AuNPs). Given the remarkable properties of AuNPs for usage in various fields, especially in biomedicine, we performed a systematic study to synthesize AuNP-PLU nanocomposites under optimized conditions using UV irradiation for accelerating the reaction. The use of UV irradiation at 254 nm resulted in several advantages over the control method conducted under ambient light (control). The AuNP-PLU-UV nanocomposite was produced six times faster, lasting 10 min, and exhibited lower size dispersion than the control. A set of experimental techniques was applied to determine the structure and morphology of the produced nanocomposites as affected by the UV irradiation. The MTT assay was conducted to estimate IC50 values of AuNP-PLU-UV in NIH 3T3 mouse embryonic fibroblasts, and the results suggest that the sample is more compatible with cells than control samples. Afterward, in vivo maternal and fetal toxicity assays were performed in rats to evaluate the effect of AuNP-PLU-UV formulation during pregnancy. Under the tested conditions, the treatment was found to be safe for the mother and fetus. As a proof of concept or application, the synthesized Au:PLU were tested as contrast agents with an X-ray computed tomography scan (X-ray CT).
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Tirzepatide is a twincretin recently approved to improve glycemic control in type 2 diabetes mellitus (T2DM). More specifically, tirzepatide is an agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP1) receptors. In recent clinical trials in persons with obesity or overweight with associated conditions, tirzepatide decreased body weight and other cardiorenal risk factors (blood pressure, low-density lipoprotein cholesterol, glycated hemoglobin and albuminuria). Moreover, in a post hoc analysis of the SURPASS-4 randomized clinical trial, tirzepatide decreased albuminuria and total estimated glomerular filtration rate (eGFR) slopes and nearly halved the risk of a pre-specified composite kidney endpoint (eGFR decline ≥40%, renal death, kidney failure or new-onset macroalbuminuria) in participants with T2DM and high cardiovascular risk when compared with insulin glargine. Similar to other kidney-protective drugs, tirzepatide, alone or combined with sodium-glucose co-transporter 2 inhibitors, caused an early dip in eGFR. Moreover, tirzepatide also decreased eGFR slopes in participants with eGFR >60 mL/min/1.73 m2 or with normoalbuminuria. We now review the potential kidney health implications of tirzepatide, addressing its structure and function, relationship to current GLP1 receptor agonists, impact of recent results for the treatment and prevention of kidney disease, and expectations for the future.
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Given the ability of dendritic cells (DCs) to modulate other immune players, their manipulation holds great potential for inducing efficient antitumor immunity. However, DC vaccine manufacturing deserve optimization since tumor cell cargo and DC functional state induced by maturation signals influence their in vivo immunogenic potential. We reported that triiodothyronine (T3) stimulates mice DCs' maturation and their ability to promote pro-inflammatory and cytotoxic T-cell responses. This study aimed to evaluate the efficacy of T3-conditioned DC vaccination in a murine model of colon carcinoma, deciphering the molecular players involved; and to examine the effects of T3 on the maturation and activation of human DCs (huDCs). Bone marrow-derived DCs were exposed to T3 and MC38 cancer cells that underwent cell death (MC38-Apo/Nec) by UVB irradiation. Our results showed that MC38-Apo/Nec cells are efficiently uptaken by DCs and that T3 upregulates CD86 expression with increased production of the pro-inflammatory cytokines IL-12, IL-6 and TGF-ß. In a colon cancer model, vaccination with T3-stimulated and tumor antigen-loaded DCs inhibited tumor growth in wild type mice, an effect that was eliminated in IL-17-deficient animals. Notably, secretion of high levels of IFN-γ and IL-17, induction of Th1, Th17 and tumor-specific cytotoxic T lymphocytes characterized the antitumor response upon vaccination. Moreover, our initial findings demonstrated a significant increase in CD86 expression and IL-12 production by huDCs induced by T3. Overall, these results reinforce the adjuvant properties of T3-conditioned DCs to potentiate T-cell-mediated antitumor immunity and support promising advances in the translation process to human oncotherapy.
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Vacinas Anticâncer , Neoplasias do Colo , Animais , Vacinas Anticâncer/uso terapêutico , Células Dendríticas , Humanos , Interleucina-12/metabolismo , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Tri-Iodotironina/metabolismo , Tri-Iodotironina/farmacologia , VacinaçãoRESUMO
Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.
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Vesículas Extracelulares , Neoplasias da Glândula Tireoide , Matriz Extracelular , Vesículas Extracelulares/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Proteômica/métodos , Neoplasias da Glândula Tireoide/metabolismo , Microambiente TumoralRESUMO
Medical and scientific advances have made it possible to carry out more and more early procedures involving human life within the mother's womb. Based on the above, the dilemma surrounding the perception or experience of fetal pain has emerged and its implications in various fields such as: prenatal diagnosis, fetal surgery and especially around abortion. This document seeks to carry out an approach to the embryological development of pain pathways and their components, to assess the relevance of the current definition of pain in this context, and the bioethical implications of the different interventions carried out on the fetus. We consider that despite the need for scientific evidence in this field, the available knowledge indicates that it is possible to experience pain in the mother's womb especially since the 20th week of gestation, so it is important to reflect on fetal pain and the need to become aware of this, before performing any intervention involving the fetus as a patient.
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Aborto Induzido , Feto , Feminino , Humanos , Dor/etiologia , Gravidez , Diagnóstico Pré-NatalRESUMO
INTRODUCTION AND OBJECTIVES: Liver cirrhosis is a major public health issue associated with high morbidity and mortality. The ANSWER trial showed that long-term human albumin (LTA) infusions led to significant reduction of complications and mortality in patients with uncomplicated ascites. The present study aimed to assess the incremental cost of cirrhosis patients treated with LTA plus standard medical treatment (SMT) versus those treated with SMT from the perspective of the Mexican Social Security Institute (IMSS). MATERIAL AND METHODS: Cost of illness for patients with cirrhosis and grade 2-3 ascites treated with SMT or with SMT and LTA (following the treatment regimen from ANSWER) over a one-year period was estimated according to the IMSS perspective. Rates of treatments, complications and hospitalizations were based on results from the ANSWER trial. Unit costs from IMSS were gathered from public sources and transformed to 2020 Mexican $ (Mex$). RESULTS: The use of LTA is estimated to require additional annual expenditure derived from the pharmacological cost of human albumin and by the follow up visits required for LTA administration (Mex$28,128). However, this cost may potentially be counterbalanced by the reduction in paracentesis, cirrhosis-related complications and hospitalizations which would lead to cost savings of Mex$33,417 per patient/year. CONCLUSIONS: Based on the ANSWER trial results, our study suggests that LTA may result in improved clinical outcomes and reduced costs for the IMSS when administered to cirrhosis patients with uncomplicated ascites.
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Ascite , Cirrose Hepática , Albuminas/uso terapêutico , Ascite/etiologia , Ascite/terapia , Análise Custo-Benefício , Atenção à Saúde , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/terapia , Albumina Sérica Humana/uso terapêuticoRESUMO
Resumo Objetivo Projetar e validar uma escala para medir a carga de trabalho de enfermagem em Unidades de Internação de Adultos com base na Classificação de Intervenções de Enfermagem (NIC). Métodos Estudo analítico, descritivo, observacional, prospectivo, utilizando principalmente metodologia de pesquisa qualitativa, por meio de grupos focais, comitê de especialistas e entrevistas individuais, para validar uma Escala de Medição da Carga de Trabalho em Unidades de Internação de Adultos, a partir das intervenções selecionadas (NIC), com base nas características inerentes a tais unidades. Foi utilizada seleção aleatória para determinar os participantes (enfermeiros e especialistas) e é representativa das unidades de hospitalização em estudo. O estudo foi realizado de outubro de 2018 a abril de 2019. Resultados Não apenas os grupos focais, mas também as entrevistas individuais e o comitê de especialistas demonstraram concordância sobre a importância de se obter um instrumento para medir a carga de trabalho validado pelos próprios profissionais e representativo de seu trabalho, com linguagem padronizada e adaptada à saúde real. A análise quantitativa conduzida pelo comitê de especialistas mostra uma maior relevância (91,67%) nos itens: "Prevenção" e "Educação para a saúde", bem como a consistência com a construto e a redação apropriada em 99% dos itens selecionados. Os avaliadores mantiveram a ação em todos os itens com uma taxa de aceitação de 75% a 100%. Conclusão O estudo qualitativo realizado fornece os dados necessários para a concepção e validação de uma escala para medir as cargas de trabalho de enfermagem, identificadas a partir das intervenções de enfermagem (NIC), como indicadores da gestão de recursos humanos.
Resumen Objetivo Proyectar y validar una escala para medir la carga de trabajo de enfermería en unidades de internación de adultos con base en la Clasificación de Intervenciones de Enfermería (NIC). Métodos Estudio analítico, descriptivo, observacional, prospectivo, que utilizó principalmente metodología de investigación cualitativa, por medio de grupos focales, comité de especialistas y entrevistas individuales, para validar una Escala de Medición de Carga de Trabajo en Unidades de Internación de Adultos, a partir de las intervenciones seleccionadas (NIC), con base en las características inherentes a tales unidades. Se utilizó selección aleatoria para definir los participantes (enfermeros y especialistas), que es representativa de las unidades de hospitalización en estudio. El estudio fue realizado de octubre de 2018 a abril de 2019. Resultados No solo los grupos focales, como también las entrevistas individuales y el comité de especialistas demostraron concordancia sobre la importancia de obtener un instrumento para medir la carga de trabajo, validado por los propios profesionales y representativo de su trabajo, con un lenguaje estandarizado y adaptado a la salud real. El análisis cuantitativo conducido por el comité de especialistas muestra una mayor relevancia (91,67 %) en los ítems: "Prevención" y "Educación para la salud", así como una consistencia respecto a la elaboración y redacción apropiada en el 99 % de los ítems seleccionados. Los evaluadores mantuvieron la acción en todos los ítems con un índice de aceptación de 75 % a 100 %. Conclusión El estudio cualitativo realizado proporciona los datos necesarios para la elaboración y validación de una escala para medir la carga de trabajo en enfermería, identificada a partir de las intervenciones de enfermería (NIC), como indicadores de la gestión de recursos humanos.
Abstract Objective To design and validate a scale to measure nursing workloads in Adult Hospitalization Units based on Nursing Interventions (NIC). Methods Analytical, descriptive, observational, prospective study, using mainly qualitative research methodology, by means of focus groups, committee of experts and individual interviews, to validate a Workload Measurement Scale in Adult Hospitalization Units, from the selected interventions (NIC) on a basis of the inherent characteristics of such units. A random selection was used to determine the participants (nurses and experts) and it is representative of the hospitalization units under study. It was carried out from October 2018 to April 2019. Results Not only the focus groups but also the individual interviews and the committee of experts conducted agree on the importance of obtaining an instrument to measure workloads validated by the professionals themselves and representative of their work, with standardized language and adapted to actual healthcare. The quantitative analysis conducted by the committee of experts shows a highest relevance (91,67%) in the items: "Prevention" and "Health education", as well as consistency with the construct and appropriate wording in 99% of the items selected. Evaluators maintained the action on all items with a 75% to 100% acceptance rate. Conclusion The qualitative study carried out provides the necessary data for the design and validation of a scale to measure nursing workloads, identified from the nursing interventions (NIC), as indicators of human resources management.
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Humanos , Carga de Trabalho , Unidades de Internação , Terminologia Padronizada em Enfermagem , Hospitalização , Serviço Hospitalar de Enfermagem , Gestão de Recursos Humanos , Métodos de Análise Laboratorial e de Campo , Epidemiologia Descritiva , Estudos de Avaliação como Assunto , Estudo Observacional , Recursos Humanos de Enfermagem HospitalarRESUMO
ABSTRACT Objetive To determine the validity and reliability of the CUCACE (Quality of Nursing Care Questionnaire) in Colombia. Every day there is a growing interest in measuring the quality of care received from nursing personnel as a tangible element of care; however, not having reliable and valid instruments is an obstacle, especially in Colombia. Method A psychometric and evaluative instrumental study was conducted. Data of interest from CUCACE filled out in Spanish were extracted together with demographic information of the participants. Results Confirmed the validity of the content and construct validity of the scales of care, attention to nursing care and the perception of care in a Colombian hospital. Cronbach's alpha was higher than 0.7, and its reliability is accepted in the context. Conclusion The CUCACE is adequate to measure the satisfaction and experience of patients with nursing care in the Colombian context. The questionnaire with its two scales is useful, clear, precise, valid and reliable to evaluate the quality of nursing care.
ABSTRACT Objetivo Determinar la validez y confiabilidad del CUCACE (Cuestionario de Calidad de la Atención de Enfermería) en Colombia. Cada día hay un interés creciente en medir la calidad de la atención recibida por parte del personal de enfermería como elemento tangible de la atención; sin embargo, un obstáculo para medir la satisfacción del paciente es la no tenencia de instrumentos confiables y válidos, especialmente en Colombia. Método Se realizó un estudio instrumental psicométrico y evaluativo. Se extrajeron datos de interés del CUCACE cumplimentados en español, junto con la información demográfica de los participantes. Resultados Se confirmó la validez del contenido y construcción de las escalas de atención, atención al cuidado de enfermería y percepción del cuidado en un hospital colombiano. El alfa de Cronbach fue superior a 0,7; por lo tanto su fiabilidad se acepta en el contexto. Conclusión El CUCACE es adecuado para medir la satisfacción y experiencia de los pacientes con los cuidados de enfermería en el contexto colombiano. El cuestionario con sus dos escalas es útil, claro, preciso, válido y confiable para evaluar la calidad de la atención de enfermería.
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Cutaneous leishmaniasis (CL) is one of the illnesses caused by Leishmania parasite infection, which can be asymptomatic or severe according to the infecting Leishmania strain. CL is commonly diagnosed by directly detecting the parasites or their DNA in tissue samples. New diagnostic methodologies target specific proteins (biomarkers) secreted by the parasite during the infection process. However, specific bioreceptors for the in vivo or in vitro detection of these novel biomarkers are rather limited in terms of sensitivity and specificity. For this reason, we here introduce three novel peptides as bioreceptors for the highly sensitive and selective identification of acid phosphatase (sAP) and proteophosphoglycan (PPG), which have a crucial role in leishmaniasis infection. These high-affinity peptides have been designed from the conservative domains of the lectin family, holding the ability to interact with the biological target and produce the same effect than the original protein. The synthetic peptides have been characterized and the affinity and kinetic constants for their interaction with the targets (sAP and PPG) have been determined by a surface plasmon resonance biosensor. Values obtained for KD are in the nanomolar range, which is comparable to high-affinity antibodies, with the additional advantage of a high biochemical stability and simpler production. Pep2854 exhibited a high affinity for sAP (KD = 1.48 nM) while Pep2856 had a good affinity for PPG (KD 1.76 nM). This study evidences that these peptidomimetics represent a novel alternative tool to the use of high molecular weight proteins for biorecognition in the diagnostic test and biosensor devices for CL.
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Fosfatase Ácida/análise , Leishmania/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Proteínas de Membrana/análise , Peptídeos/química , Proteoglicanas/análise , Proteínas de Protozoários/análise , Ressonância de Plasmônio de Superfície/métodos , Sítios de Ligação , Humanos , Leishmania/enzimologia , Leishmaniose Cutânea/diagnóstico , Modelos Moleculares , Peptídeos/síntese química , Peptidomiméticos/síntese química , Peptidomiméticos/químicaRESUMO
The communication of Corporate Social Responsibility (CSR) of a sample of eight restaurant and fast food companies is analyzed. An exploratory and descriptive method, based on the content analysis technique, is used to analyze the formal and informal CSR communication channels used to promote healthy eating on their respective websites and Twitter profiles. This study is complemented by a survey (n = 383) applied to a sample of young Spaniards to investigate their interest in healthy eating information, their assessment of CSR actions carried out in this area as well as the communication channels used for this purpose. The results confirm that the CSR policies of the companies include actions aimed at guaranteeing and promoting healthy eating. It is concluded about the convenience of using their own social networks and influencers to encourage healthy eating habits more effectively in their publics. (AU)
É analisada a comunicação de Responsabilidade Social Corporativa (RSC) de uma amostra de oito empresas de restaurantes e fast food. Um método exploratório e descritivo, baseado na técnica de análise de conteúdo é usado para analisar os canais de comunicação formais e informais de RSC usados para promover uma alimentação saudável nos seus respectivos sites e perfis no Twitter. Este estudo é complementado por uma pesquisa para descobrir o interesse na alimentação dos jovens espanhóis (n = 383), sua avaliação da RSC nessa área e os canais de informação usados para esse fim. Os resultados verificam a integração em suas políticas de RSE de ações relacionadas à promoção de hábitos alimentares saudáveis. Conclui-se sobre a conveniência de utilizar redes sociais próprias e influenciadores para estimular esse tipo de hábitos, dentro de suas políticas de RSE de maneira mais eficaz. (AU)
Se analiza la comunicación de la Responsabilidad Social Corporativa (RSC) de una muestra de ocho empresas de restauración y fast food. Se sigue una metodología exploratoria y descriptiva para analizar mediante un análisis de contenido la comunicación formal e informal de RSC respecto de la promoción de una alimentación saludable en sus respectivas webs y perfiles en Twitter. Este estudio se complementa con una encuesta (n = 383) sobre el interés por la alimentación de los jóvenes españoles, su valoración de la RSC en este ámbito y los canales de información utilizados al respecto. Los resultados verifican la integración en sus políticas de RSC de acciones relativas a la promoción de hábitos alimenticios saludables. Se concluye acerca de la conveniencia de uso de sus propias redes sociales y de influencers, para incentivar este tipo de hábitos, dentro de sus políticas de RSC. (AU)
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Humanos , Masculino , Feminino , Adolescente , Adulto , Responsabilidade Social , Indústria Alimentícia , Comunicação , Mídias Sociais , Restaurantes , Espanha , Comportamento Alimentar , Fast FoodsRESUMO
Resumen El desarrollo científico y médico, sumado a la realidad que vivimos en Colombia, demanda la formación de profesionales coherentes con los principios éticos y con conceptos teóricos claros sobre la normativa actual para trabajar por el respeto de la vida humana. La actualidad constitucional del país evidencia un reto para todo tipo de profesionales, no solo en el campo jurídico o de la salud, ya que se han puesto en pugna derechos fundamentales como la vida y la libertad de conciencia. Este artículo muestra la necesidad y la importancia de fomentar y acceder a la práctica de la objeción de conciencia como respuesta al panorama jurídico al que se enfrenta la protección de la vida en Colombia y que puede ser ejemplo para otros países en Latinoamérica.
Abstract Scientific and medical developments, added to our reality in Colombia, demand the training of professionals consistent with ethical principles and clear theoretical concepts on current regulations that are aimed at respect for human life. The country's current constitutional situation poses a challenge to any professional, beyond the legal or health fields, since fundamental rights such as life and freedom of conscience are being questioned. This paper demonstrates the need and importance of promoting and accessing conscientious objection as a response to the legal landscape of the protection of life in Colombia, which may be an example for other countries in Latin America.
Resumo O desenvolvimento científico e médico, somado à realidade que vivemos na Colômbia, exige a formação de profissionais coerentes com os princípios éticos e com conceitos teóricos claros sobre a legislação atual para trabalhar em prol do respeito pela vida humana. A atualidade constitucional do país evidencia um desafio para todo tipo de profissionais, tanto no campo jurídico quanto no da saúde, já que direitos fundamentais como a vida e a liberdade de consciência têm sido colocados em conflito. Este artigo mostra a necessidade e a importância de fomentar e acessar a prática da objeção de consciência como resposta ao panorama jurídico no qual a proteção da vida na Colômbia se encontra e que pode ser exemplo para outros países na América Latina.
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Bioética , Saúde , Consciência , Vida , Fertilização , Liberdade , Direitos HumanosRESUMO
In the present study, iron oxide nanoparticles, in the form of maghemite core coated with lauric acid (ION), were synthesized and loaded with finasteride (FIN) or dutasteride (DUT) as a novel drug delivery system for the topical treatment of alopecia. Additionally, developed formulations (FIN-ION and DUT-ION) were completely elaborated with components involved in the follicle metabolism, i.e., lauric acid, which acts as a 5α-reductase inhibitor, and iron which deficiency has been related to hair loss aggravation. Stability assessment conducted over the course of 90 days showed they are highly stable, with pH 7.4, constant EE% (>99%), and practically unchanged particle size and zeta potential. Besides drug distribution, the actual number of iron oxide nanoparticles, through a newly developed method using ferromagnetic resonance, was determined in each skin layer following permeation experiments. Despite the same donor concentration of colloids, nanoparticle distribution in the skin varied according to the loaded molecule. While DUT did not interfere with the nanoparticle natural tendency to accumulate within the hair follicle shafts, FIN presence hampered nanosystem interaction with the skin. Still, both formulations provided a higher skin drug penetration, compared to each respective control solution. Additionally, iron nanocarriers present a desirable visual characteristic, as the dark color aspect might instantly help disguise scarce hair follicle areas. These findings suggest the nanoformulations are highly promising for alopecia therapies.
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Alopecia , Finasterida , Inibidores de 5-alfa Redutase , Alopecia/tratamento farmacológico , Dutasterida , Compostos Férricos , HumanosRESUMO
The therapeutic administration of cytokines has been introduced aiming to modulate the immune response system, seeking for different approaches to face pathologies such as cancer, auto immune and infectious diseases. The objective of this study was to investigate the effects of a stable oil-in-water (O/W) nanoemulsion system carrying the cytokine Interferon gamma (IFN-γ) on the activity of phagocytes and MCF-7 human breast cancer cells. Nanoemulsions were prepared through ultra-homogenization, and they consisted of distilled water, triglycerides of capric acid/caprylic, sorbitan-oleate, polysorbate 80, and 1-butanol. IFN-γ (100 ng ml-1 ) was incorporated into two O/W nanoemulsion formulations, and these formulations were characterized in terms of their preliminary and accelerated physicochemical stability, rheological properties, droplet size, polydispersity and surface charge. We identified the most optimal IFN-γ nanoemulsion (IFN-γNE2), which remained stable under extreme temperature variations for 90 days, contained an average dose of 97 ng ml-1 of IFN-γ and exhibited a biocompatible pH and a relative stable rheological profile. Cell viability and intracellular Ca2+ release assays conducted showed that IFN-γNE2 reduced the cell viability of MCF-7 cells without affecting the cell viability of phagocytes. Furthermore, IFN-γNE2 was able to induce cellular activity of phagocytes as evidenced by increased intracellular Ca2+ release in these cells. Our findings on this IFN-γ nanoemulsion suggest that it can be a promising therapeutic agent for immunostimulation and cancer treatment.
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Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Emulsões/química , Fatores Imunológicos/administração & dosagem , Interferon gama/administração & dosagem , Adulto , Antineoplásicos/farmacologia , Células Cultivadas , Feminino , Humanos , Fatores Imunológicos/farmacologia , Interferon gama/farmacologia , Células MCF-7 , Masculino , Neoplasias/tratamento farmacológico , Adulto JovemRESUMO
La investigación realizada sobre Burnout ha mostrado de manera reiterada que es un síndrome presente en el contexto laboral con graves consecuencias para la salud del trabajador. De manera reciente, se ha propuesto la teoría de la conservación de Recursos de Hobfoll como un marco teórico válido para explicar la relación del Burnout con otras variables. Sin embargo, los estudios que proponen medidas eficaces para reducir los niveles de exposición al Burnout son escasos. El capital psicológico ha sido propuesto como una variable que podría ayudar a prevenir o disminuir los efectos de estresores de diversa índole sobre la salud de los trabajadores. Investigaciones previas han relacionado al capital psicológico de manera negativa y significativa con el Burnout. El objetivo de este trabajo es analizar el papel mediador del capital psicológico en la relación entre las tres dimensiones del Burnout y la salud autopercibida de los trabajadores. La muestra está compuesta por 195 trabajadores españoles de distintos sectores de actividad. Los resultados muestran, por un lado, una asociación negativa y significativa de las tres dimensiones del Burnout con la salud autopercibida, y, por otro lado, una relación mediadora del capital psicológico entre las tres dimensiones del Burnout y la salud autopercibida de los trabajadores. Para finalizar, se pone de manifiesto la importancia de los recursos psicológicos personales para reducir las consecuencias negativas del Burnout en el bienestar de los empleados.
Previous Burnout research has repeatedly shown it as a workplace syndrome with serious consequences for employees' health and wellbeing. Recently Hobfoll's Conservation or Resources Theory has been proposed as a valid theoretical framework to explain the relationship of Burnout with other variables. However, the presence of effective measures to reduce Burnout exposure levels is scarce. Psychological capital has been proposed as a variable that could help prevent or reduce the effects of various kind of stressors on workers' health. Previous empirical evidence has argued that psychological capital is related in a negative and significant way to Burnout. The objective of this work is to analyze the mediating role of psychological capital in the relationship between the three Burnout dimensions (emotional exhaustion, cynicism, and lack of self-efficacy) and employees' self-perceived health. For that purpose, the sample is composed of 195 Spanish workers from different economic sectors. The results show, on the one hand, a negative and significant association of the three dimensions of Burnout with self-perceived health, and, on the other hand, a mediating relationship of psychological capital between the three dimensions of Burnout and employees' self-perceived health. Finally, the importance of personal psychological resources to reduce Burnout negative consequences on employees' well-being is highlighted
Assuntos
Humanos , Síndrome , Local de Trabalho , Pesquisa , Trabalho , Saúde Ocupacional , Impactos da Poluição na Saúde , Esgotamento PsicológicoRESUMO
BACKGROUND/AIMS: Although a cross-talk between immune and endocrine systems has been well established, the precise pathways by which these signals co-regulate pro- and antiinflammatory responses on antigen-presenting cells remain poorly understood. In this work we investigated the mechanisms by which triiodothyronine (T3) controls T cell activity via dendritic cell (DC) modulation. METHODS: DCs from wild-type (WT) and IL-6-deficient mice were pulsed with T3. Cytokine production and programmed death protein ligands (PD-L) 1 and 2 expression were assayed by flow cytometry and ELISA. Interferon-regulatory factor-4 (IRF4) expression was evaluated by RT-qPCR and flow cytometry. The ability of DCs to stimulate allogenic splenocytes was assessed in a mixed lymphocyte reaction and the different profile markers were analyzed by flow cytometry and ELISA. For in vivo experiments, DCs treated with ovalbumin and T3 were injected into OTII mice. Proliferation, cytokine production, frequency of FoxP3+ regulatory T (Treg) cells and PD-1+ cells were determined by MTT assay, ELISA and flow cytometry, respectively. RESULTS: T3 endows DCs with pro-inflammatory potential capable of generating IL-17-dominant responses and down-modulating expression of PD-L1 and 2. T3-stimulated WT-DCs increased the proportion of IL-17-producing splenocytes, an effect which was eliminated when splenocytes were incubated with T3-treated DCs derived from IL-6-deficient mice. Enhanced IL-17 expression was recorded in both, CD4- and CD4+ populations and involved the IRF-4 pathway. Particularly, γδ-T cells but not natural killer (NK), NKT, B lymphocytes nor CD8+ T cells were the major source of IL-17-production from CD4- cells. Moreover, T3-conditioned DCs promoted a decrease of the FoxP3+ Treg population. Furthermore, T3 down-modulated PD-1 expression on CD4- cells thereby limiting inhibitory signals driven by this co-inhibitory pathway. Thus, T3 acts at the DC level to drive proinflammatory responses in vitro. Accordingly, we found that T3 induces IL-17 and IFNγ-dominant antigen-specific responses in vivo. CONCLUSION: These results emphasize the relevance of T3 as an additional immune-endocrine checkpoint and a novel therapeutic target to modulate IL-17-mediated pro-inflammatory responses.
Assuntos
Células Dendríticas/imunologia , Interleucina-17/imunologia , Transdução de Sinais/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Animais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Dendríticas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Fatores Reguladores de Interferon/genética , Fatores Reguladores de Interferon/imunologia , Interleucina-17/genética , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Camundongos , Camundongos Knockout , Proteína 2 Ligante de Morte Celular Programada 1/genética , Proteína 2 Ligante de Morte Celular Programada 1/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Transdução de Sinais/imunologiaRESUMO
OBJECTIVES: to evaluate the effectiveness of an educational intervention on the knowledge, skills and attitudes of evidence-based practice among second-year nursing students. METHOD: a quasi-experimental before-and-after study. The study population consisted of 120 students enrolled in the Nursing Care in Healthcare Processes course. The educational intervention was based on theoretical and practical classes about the evidence-based practice process and the use of the critical incident technique during the clinical clerkship. Effectiveness was measured with the Evidence-Based Practice Competence Questionnaire in three paired measures using repeated-measures analysis of variance. RESULTS: the mean scores of the Evidence-Based Practice Competence Questionnaire were 79.83 (CI 95% 78.63-81.03) for the basal measurement, 84.53 (CI 95% 83.23-85.83) for the intermediate measurement, and 84.91 (CI 95% 83.26-86.55) for the final measurement, with a statistically significant difference among the three paired measurements (p<0.001). There were statistically significant differences in Attitudes (p = 0.034) and Knowledge (p <0.001) but not in Skills (p = 0.137). CONCLUSION: this educational intervention based on theoretical and practical classes about the evidence-based practice process and the use of the critical incident technique during the clinical clerkship enhances evidence-based practice competence among second-year nursing degree students.