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BACKGROUND: Focal cortical dysplasia (FCD) is a malformation of cortical development that causes medical refractory seizures, and one of the main treatments may be surgical resection of the affected area of the brain. People affected by FCD may present with seizures of variable severity since childhood. Despite many medical treatments available, only surgery can offer cure. The pathophysiology of the disease is not yet understood; however, it is known that several gene alterations may play a role. The WNT/ß-catenin pathway is closely related to the control and balance of cell proliferation and differentiation in the central nervous system. The aim of this study was to explore genes related to the WNT/ß-catenin pathway in lesional and perilesional brain tissue in patients with FCD type II. METHODS: Dysplastic and perilesional tissue from the primary dysplastic lesion of patients with FCD type IIa were obtained from two patients who underwent surgical treatment. The analysis of the relative expression of genes was performed by a qRT-PCR array (super array) containing 84 genes related to the WNT pathway. RESULTS: Our results suggest the existence of molecular alteration in some genes of the WNT pathway in tissue with dysplastic lesions and of perilesional tissue. We call this tissue of normal-appearing adjacent cortex (NAAC). Of all genes analyzed, a large number of genes show similar behavior between injured, perilesional and control tissues. However, some genes have similar characteristics between the perilesional and lesional tissue and are different from the control brain tissue, presenting the perilesional tissue as a molecularly altered material. CONCLUSION: Our results suggest that the perilesional area after surgical resection of tissue with cortical dysplasia presents molecular changes that may play a role in the recurrence of seizures in these patients. The perilesional tissue should receive expanded attention beyond the somatic mutations described and associated with FCD, such as mTOR, for example, to new signaling pathways that may play a crucial role in seizure recurrence.
Asunto(s)
Epilepsia Refractaria , Displasia Cortical Focal , Humanos , Niño , Epilepsia Refractaria/genética , Epilepsia Refractaria/cirugía , Vía de Señalización Wnt/genética , beta Catenina , ConvulsionesRESUMEN
BACKGROUND: Patients who present to an emergency department (ED) with respiratory symptoms are often conservatively triaged in favour of hospitalisation. We sought to determine if an inflammatory biomarker panel that identifies the host response better predicts hospitalisation in order to improve the precision of clinical decision making in the ED. METHODS: From April 2020 to March 2021, plasma samples of 641 patients with symptoms of respiratory illness were collected from EDs in an international multicentre study: Canada (n=310), Italy (n=131) and Brazil (n=200). Patients were followed prospectively for 28â days. Subgroup analysis was conducted on confirmed coronavirus disease 2019 (COVID-19) patients (n=245). An inflammatory profile was determined using a rapid, 50-min, biomarker panel (RALI-Dx (Rapid Acute Lung Injury Diagnostic)), which measures interleukin (IL)-6, IL-8, IL-10, soluble tumour necrosis factor receptor 1 (sTNFR1) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1). RESULTS: RALI-Dx biomarkers were significantly elevated in patients who required hospitalisation across all three sites. A machine learning algorithm that was applied to predict hospitalisation using RALI-Dx biomarkers had a mean±sd area under the receiver operating characteristic curve of 76±6% (Canada), 84±4% (Italy) and 86±3% (Brazil). Model performance was 82±3% for COVID-19 patients and 87±7% for patients with a confirmed pneumonia diagnosis. CONCLUSIONS: The rapid diagnostic biomarker panel accurately identified the need for inpatient care in patients presenting with respiratory symptoms, including COVID-19. The RALI-Dx test is broadly and easily applicable across many jurisdictions, and represents an important diagnostic adjunct to advance ED decision-making protocols.
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COVID-19 , Infecciones del Sistema Respiratorio , Humanos , COVID-19/diagnóstico , Curva ROC , Biomarcadores , Servicio de Urgencia en Hospital , Interleucina-6RESUMEN
The effects of short-chain fatty acids (SCFAs) have been explored against cancer due to the crosstalk between gut microbiota alterations and the immune system as a crucial role in cancer development. We evaluated the SCFAs effects in both in vitro and in vivo breast cancer models. In vitro, the SCFAs displayed contrasting effects on viability index, according to the evaluation of breast cancer cells with different phenotypes, human MCF-7, SK-BR-3, MDA-MD-231, or the mouse 4T1 lineage. Acetate displayed minimal effects at concentrations up to 100 mM. Alternatively, propionate increases or reduces cell viability depending on the concentration. Butyrate and valerate showed consistent time- and concentration-dependent effects on the viability of human or mouse breast cancer cells. The selective FFA2 4-CMTB or FFA3 AR420626 receptor agonists failed to overtake the SCFA actions, except by modest inhibitory effects on MDA-MB-231 and 4T1 cell viability. The FFA2 CATPB or FFA3 and ß-hydroxybutyrate receptor antagonists lacked significant activity on human cell lines, although CATPB reduced 4T1 cell viability. Butyrate significantly affected cell morphology, clonogenicity, and migration, according to the evaluation of MDA-MB-231 and 4T1 cells. A preliminary examination of in vivo oral effects of butyrate, propionate, or valerate, dosed in prophylactic or therapeutic regimens, on several parameters evaluated in an orthotopic breast cancer model showed a reduction of lung metastasis in post-tumor induction butyrate-treated mice. Overall, the present results indicate that in vitro effects of SCFAs did not rely on FFA2 or FFA3 receptor activation, and they were not mirrored in vivo, at least at the tested conditions. Overall, the present results indicate potential in vitro inhibitory effects of SCFAs in breast cancer, independent of FFA2 or FFA3 receptor activation, and, in the metastatic breast cancer model, the butyrate-dosed therapeutic regimen reduced the number of lung metastases.
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Multifunctional surfaces may display the potential to accelerate and promote the healing process around dental implants. However, the initial cellular biocompatibility, molecular activity, and the release of functionalized molecules from these novel surfaces require extensive investigation for clinical use. Aiming to develop and compare innovative surfaces for application in dental implants, the present study utilized titanium disks, which were treated and divided into four groups: machined (Macro); acid-etched (Micro); anodized-hydrophilic surface (TNTs); and anodized surface coated with a rifampicin-loaded polymeric layer (poly(lactide-co-glycolide), PLGA) (TNTsRIMP). The samples were characterized regarding their physicochemical properties and the cumulative release of rifampicin (RIMP), investigated at different pH values. Additionally, differentiated osteoblasts from mesenchymal cells were used for cell viability and qRT-PCR analysis. Antibacterial properties of each surface treatment were investigated against Staphylococcus epidermidis. TNTsRIMP demonstrated controlled drug release for up to 7 days in neutral pH environments. Osteogenic cell cultures indicated that all the evaluated surfaces showed biocompatibility. The TNTs group revealed up-regulated values for bone-related gene quantification in 7 days, followed by the TNTsRIMP group. Furthermore, the antibiotic-functionalized surface revealed effectiveness to inhibit S. epidermidis and stimulate promising conditions for osteogenic cell behavior. Characteristics such as nanomorphology and hydrophilicity were determinants for the up-regulated quantification of osteogenic biomarkers related to early bone maturation, encouraging application in intra-osseous implant surfaces; in addition, antibiotic-functionalized surfaces demonstrated significant higher antibacterial properties compared to the other groups. Our findings suggest that polymeric-antibiotic-loaded coating might be applied for the prevention of early infections, favoring its application in multifunctional surfaces for intra- and/or trans-mucosal components of dental implants, while, hydrophilic nanotextured surfaces promoted optimistic properties to stimulate early bone-related cell responses, favoring its application in bone-anchored surfaces.
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Antibacterianos , Implantes Dentales , Antibacterianos/farmacología , Rifampin/farmacología , Propiedades de Superficie , Diferenciación Celular , Titanio/farmacología , Titanio/química , OseointegraciónRESUMEN
Environmental pollution by pesticide residues is a major environmental concern due to the extensive use of these substances in agriculture. The insecticide beta-cyfluthrin is a synthetic pyrethroid widely used in agricultural and other domestic activities. The aim of the present study was to assess the genotoxic effects of a sublethal exposure of the fish Bryconamericus iheringii (Characidae) to a commercial formulation of beta-cyfluthrin using the comet assay. Fish were exposed to sublethal concentrations (4.2 and 5.6 microg/L) of beta-cyfluthrin under static conditions during 24- and 48-h exposure periods. Fish in tap water were used as negative controls. Results obtained by the comet assay revealed genotoxic effects of the pyrethroid in the higher concentration and at the longer exposure period. The mean DNA damage index of fish exposed to 5.6 microg/L beta-cyfluthrin for 48 h was significantly higher (145.9 +/- 51.8) than in the control group (69.3 +/- 39.5). These findings indicate that native fish species might be at risk for genotoxic damage in waters contaminated with beta-cyfluthrin.
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Characidae/genética , Insecticidas/toxicidad , Mutágenos/toxicidad , Nitrilos/toxicidad , Piretrinas/toxicidad , Animales , Ensayo CometaRESUMEN
The aim of this study was to evaluate the degree of conversion, cytotoxicity, solubility and pH of photopolymerizable calciumbased cements submitted to preheating. The degree of conversion was analyzed by Fourier transform infrared, cytotoxicity by the MTT test and solubility through loss of mass. The data were subjected to statistical tests (ANOVA / Tukey's, p<0.05). The photopolymerizable materials showed a low degree of conversion, regardless of preheating. All materials caused a reduction in cell viability at 24 hours and 7 days, with the Dycal (control) being more cytotoxic. Heat had a positive effect on Biocal at 7 days. Dycal is the most soluble material. Heat had no effect on the solubility or pH of the polymerizable materials. It is concluded that photopolymerizable calcium-based cements have a low degree of conversion and are soluble, which results in mild to moderate cytotoxicity.
O objetivo do presente estudo foi avaliar o grau de conversão, citotoxicidade, solubilidade e pH de cimentos à base de cálcio fotopolimerizáveis submetidos a pré-aquecimento. O grau de conversão foi analisado por espectroscopia no infravermelho com transformada de Fourier, a citotoxicidade pelo teste de MTT e a solubilidade através da perda de massa. Os dados foram submetidos a testes estatísticos (ANOVA/Tukey, p<0,05). Os materiais fotopolimerizáveis apresentaram baixo grau de conversão, independente do pré-aquecimento. Todos os materiais causaram redução da viabilidade celular nas análises de 24 horas e 7 dias, sendo que o Dycal (controle) apresentouse mais citotóxico e o calor apresentou efeito positivo sobre o Biocal na análise de 7 dias. O Dycal é o material mais solúvel e o calor não causou efeito na solubilidade e pH dos materiais polimerizáveis. Assim, conclui-se que os cimentos à base de cálcio fotopolimerizáveis apresentam baixo grau de conversão e são solúveis, que resulta em citotoxicidade suave e moderada.
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Hidróxido de Calcio/toxicidad , Supervivencia Celular/efectos de los fármacos , Cementos Dentales/química , Materiales de Recubrimiento Pulpar y Pulpectomía/toxicidad , Calcio , Hidróxido de Calcio/química , Cementos Dentales/toxicidad , Recubrimiento de la Pulpa Dental , Humanos , Concentración de Iones de Hidrógeno , Curación por Luz de Adhesivos Dentales , Procesos Fotoquímicos , Polimerizacion , Materiales de Recubrimiento Pulpar y Pulpectomía/químicaRESUMEN
Temporal lobe epilepsy (TLE) is a highly prevalent syndrome among people with epilepsy, and is usually refractory to drug treatment. Structural and physiological changes, such as hippocampal sclerosis, are often present in TLE patients. The objective of this study is to evaluate the feasibility and safety of intra-arterial infusion of autologous bone marrow mononuclear cells (BMMC) in adults with medically refractory mesial TLE (MTLE) and unilateral hippocampal sclerosis (HS). We enrolled 20 patients who had been diagnosed with MTLE-HS and were refractory to medical treatment. All patients underwent a neurological evaluation, magnetic resonance imaging with hippocampal volumetry, video-electroencephalography (EEG) with ictal recording, and a neuropsychological test battery focusing on verbal and nonverbal memory domains. After bone marrow aspiration and subsequent cell preparation, the BMMC were infused by selective posterior cerebral artery catheterization. Patients were followed for 6 months. Safety of the procedure, seizure frequency, neuropsychological evaluation, EEG variables, routine brain magnetic resonance imaging and hippocampal volumetry were considered measurements of outcome. Any serious intercurrent clinical event or adverse effects related to the procedure were reported. No additional lesions and no significant hippocampal volumetric changes were observed. EEG recordings showed a decrease in theta activity and spike density. At 6 months, eight patients (40%) were seizure free. A significant increase in the memory scores over time was observed. The BMMC autologous transplant for the treatment of temporal lobe epilepsy is feasible and safe. The seizure control achieved in this novel study supports the therapeutic potential of stem cell transplants in MTLE-HS patients. Copyright © 2016 John Wiley & Sons, Ltd.
Asunto(s)
Células de la Médula Ósea/citología , Trasplante de Médula Ósea/efectos adversos , Epilepsia del Lóbulo Temporal/terapia , Leucocitos Mononucleares/trasplante , Convulsiones/terapia , Adulto , Electroencefalografía , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Inyecciones Intraarteriales , Masculino , Memoria , Persona de Mediana Edad , Convulsiones/patología , Convulsiones/fisiopatología , Trasplante Autólogo , Grabación en Video , Adulto JovenRESUMEN
ABSTRACT The aim of this study was to evaluate the degree of conversion, cytotoxicity, solubility and pH of photopolymerizable calciumbased cements submitted to preheating. The degree of conversion was analyzed by Fourier transform infrared, cytotoxicity by the MTT test and solubility through loss of mass. The data were subjected to statistical tests (ANOVA / Tukey's, p<0.05). The photopolymerizable materials showed a low degree of conversion, regardless of preheating. All materials caused a reduction in cell viability at 24 hours and 7 days, with the Dycal (control) being more cytotoxic. Heat had a positive effect on Biocal at 7 days. Dycal is the most soluble material. Heat had no effect on the solubility or pH of the polymerizable materials. It is concluded that photopolymerizable calcium-based cements have a low degree of conversion and are soluble, which results in mild to moderate cytotoxicity.
RESUMO O objetivo do presente estudo foi avaliar o grau de conversão, citotoxicidade, solubilidade e pH de cimentos à base de cálcio fotopolimerizáveis submetidos a pré-aquecimento. O grau de conversão foi analisado por espectroscopia no infravermelho com transformada de Fourier, a citotoxicidade pelo teste de MTT e a solubilidade através da perda de massa. Os dados foram submetidos a testes estatísticos (ANOVA/Tukey, p<0,05). Os materiais fotopolimerizáveis apresentaram baixo grau de conversão, independente do pré-aquecimento. Todos os materiais causaram redução da viabilidade celular nas análises de 24 horas e 7 dias, sendo que o Dycal (controle) apresentouse mais citotóxico e o calor apresentou efeito positivo sobre o Biocal na análise de 7 dias. O Dycal é o material mais solúvel e o calor não causou efeito na solubilidade e pH dos materiais polimerizáveis. Assim, conclui-se que os cimentos à base de cálcio fotopolimerizáveis apresentam baixo grau de conversão e são solúveis, que resulta em citotoxicidade suave e moderada.