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1.
Cell Mol Neurobiol ; 43(2): 813-826, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35366170

RESUMEN

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.


Asunto(s)
Neoplasias Encefálicas , Neoplasias Cerebelosas , Meduloblastoma , Humanos , Niño , Meduloblastoma/genética , Meduloblastoma/metabolismo , Meduloblastoma/patología , Pronóstico , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/metabolismo , Neoplasias Cerebelosas/patología , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética
2.
Pediatr Blood Cancer ; 69(7): e29553, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34971073

RESUMEN

Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer. However, the role of miRNAs has been poorly explored in pediatric ACT. In this study, we performed miRNA microarray profiling on a cohort of 37 pediatric ACT and nine nonneoplastic adrenal (NNA) samples and evaluated the prognostic significance of abnormally expressed miRNAs using Kaplan-Meier plots, log-rank test, and Cox regression analysis. We identified a total of 98 abnormally expressed miRNAs; their expression profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17 presented significant associations with patients' survival. In addition, higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p, -596, -564, -1321, and -423-5p and lower expression levels of hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p, -143-3p, and 140-5p were significantly associated with poor prognosis, tumor relapse, and/or death. Importantly, the expression profile of these 17 miRNAs stratified patients into two groups of ACTs with different clinical outcomes. Although some individual miRNAs exhibit potential prognostic values in ACTs, only the 17 miRNA-based expression clustering was considered an independent prognostic factor for 5-year event-free survival (EFS) compared to other clinicopathological features. In conclusion, our study reports for the first time associations between miRNA profiles and childhood ACT prognosis, providing evidence that miRNAs could be useful biomarkers to discriminate patients with favorable and unfavorable clinical outcomes.


Asunto(s)
Perfilación de la Expresión Génica , MicroARNs , Biomarcadores , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Niño , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Pronóstico
3.
J Cell Biochem ; 122(12): 1925-1935, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34581457

RESUMEN

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 - 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune-related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Biomarcadores de Tumor/inmunología , Regulación Neoplásica de la Expresión Génica/inmunología , Proteínas de Neoplasias/inmunología , Proteínas de Unión al ARN/inmunología , Neoplasias de la Corteza Suprarrenal/inmunología , Neoplasias de la Corteza Suprarrenal/mortalidad , Carcinoma Corticosuprarrenal/inmunología , Carcinoma Corticosuprarrenal/mortalidad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esteroides/inmunología
4.
Invest New Drugs ; 35(1): 26-36, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27785591

RESUMEN

Medulloblastoma (MB) is the most common solid tumor among pediatric patients and corresponds to 20 % of all pediatric intracranial tumors in this age group. Its treatment currently involves significant side effects. Epigenetic changes such as DNA methylation may contribute to its development and progression. DNA methyltransferase (DNMT) inhibitors have shown promising anticancer effects. The agent Zebularine acts as an inhibitor of DNA methylation and shows low toxicity and high efficacy, being a promising adjuvant agent for anti-cancer chemotherapy. Several studies have reported its effects on different types of tumors; however, there are no studies reporting its effects on MB. We analyzed its potential anticancer effects in four pediatric MB cell lines. The treatment inhibited proliferation and clonogenicity, increased the apoptosis rate and the number of cells in the S phase (p < 0.05), as well as the expression of p53, p21, and Bax, and decreased cyclin A, Survivin and Bcl-2 proteins. In addition, the combination of zebularine with the chemotherapeutic agents vincristine and cisplatin resulted in synergism and antagonism, respectively. Zebularine also modulated the activation of the SHH pathway, reducing SMO and GLI1 levels and one of its targets, PTCH1, without changing SUFU levels. A microarray analysis revealed different pathways modulated by the drug, including the Toll-Like Receptor pathway and high levels of the BATF2 gene. The low expression of this gene was associated with a worse prognosis in MB. Taken together, these data suggest that Zebularine may be a potential drug for further in vivo studies of MB treatment.


Asunto(s)
Antineoplásicos/farmacología , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Neoplasias Cerebelosas/tratamiento farmacológico , Citidina/análogos & derivados , Metilasas de Modificación del ADN/antagonistas & inhibidores , Meduloblastoma/tratamiento farmacológico , Proteínas Supresoras de Tumor/genética , Adolescente , Adulto , Apoptosis/efectos de los fármacos , Biomarcadores , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Neoplasias Cerebelosas/genética , Neoplasias Cerebelosas/metabolismo , Niño , Preescolar , Cisplatino/farmacología , Citidina/farmacología , Metilasas de Modificación del ADN/metabolismo , Interacciones Farmacológicas , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Lactante , Recién Nacido , Masculino , Meduloblastoma/genética , Meduloblastoma/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Vincristina/farmacología , Adulto Joven
5.
Reprod Fertil Dev ; 29(3): 458-467, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28442058

RESUMEN

Abnormal placental development is frequent in nuclear transfer (NT) pregnancies and is likely to be associated with altered epigenetic reprogramming. In the present study, fetal and placental measurements were taken on Day 60 of gestation in cows with pregnancies produced by AI, IVF and NT. Placentas were collected and subjected to histological evaluation, the expression of genes important in trophoblast differentiation and expression of the placental imprinted gene pleckstrin homology-like domain, family A, member 2 (PHLDA2), as well as chromatin immunoprecipitation (ChIP) for histone marks within the promoter of PHLDA2. Fewer binucleated cells were observed in NT cotyledons, followed by IVF and AI cotyledons (P<0.05). Expression of heart and neural crest derivatives expressed 1 (HAND1), placental lactogen (PL), pregnancy-associated glycoprotein 9 (PAG-9) and PHLDA2 was elevated in NT cotyledons compared with AI cotyledons. Expression of PHLDA2 was higher in IVF than AI samples (P<0.05). ChIP revealed an increase in the permissive mark dimethylation of lysine 4 on histone H3 (H3K4me2), surprisingly associated with the silent allele of PHLDA2, and a decrease in the inhibitory mark H3K9me2 in NT samples. Thus, genes critical for placental development were altered in NT placentas, including an imprinted gene. Allele-specific changes in the permissive histone mark in the PHLDA2 promoter indicate misregulation of imprinting in clones. Abnormal trophoblast differentiation could have resulted in lower numbers of binucleated cells following NT. These results suggest that the altered expression of imprinted genes associated with NT are also caused by changes in histone modifications.


Asunto(s)
Expresión Génica , Código de Histonas , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Técnicas de Transferencia Nuclear/veterinaria , Placenta/metabolismo , Alelos , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Bovinos , Femenino , Histonas/genética , Proteínas Nucleares/genética , Lactógeno Placentario/genética , Lactógeno Placentario/metabolismo , Placentación/fisiología , Embarazo , Proteínas Gestacionales/genética , Proteínas Gestacionales/metabolismo , Trofoblastos/metabolismo
6.
Mycoses ; 60(9): 616-622, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28657120

RESUMEN

Fusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 µg/mL), followed by voriconazole (34.2%, MIC ≤4 µg/mL). In general, Fusarium species presented MIC values >64 µg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis.


Asunto(s)
Antifúngicos/farmacología , Fusarium/efectos de los fármacos , Fusarium/genética , Variación Genética , Onicomicosis/microbiología , Anfotericina B/farmacología , Femenino , Fluconazol/farmacología , Fusariosis/microbiología , Fusarium/aislamiento & purificación , Fusarium/patogenicidad , Humanos , Itraconazol/farmacología , Pruebas de Sensibilidad Microbiana , Uñas/microbiología , Naftalenos/farmacología , Terbinafina , Voriconazol/farmacología
7.
Mol Cell Biochem ; 401(1-2): 147-53, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25524601

RESUMEN

Chronic renal failure (CRF) is a complex clinical condition associated with accelerated atherosclerosis and thrombosis leading to cardiovascular events. The aim of this study was to investigate in detail the NO pathway in neutrophils obtained from hemodialysis patients and its association with platelet function and oxidative status. Fifteen CRF patients on hemodialysis and fifteen controls were included in this study. Laboratory and experimental evaluations were performed after hemodialysis in CRF patients. We evaluated L-[³H] arginine transport, NO synthase (NOS) activity, amino acid concentration in neutrophils, and expressions of NOS isoforms and p47(phox) by western blotting. Platelet aggregation was analyzed in the presence or absence of neutrophils. Oxidative status was measured through glutathione peroxidase, catalase activities, protein oxidation, lipid peroxidation, and DNA/RNA oxidation in serum. Basal NOS activity (pmol/106 cells/min) was impaired in CRF patients on hemodialysis (0.33 ± 0.17) compared to controls (0.65 ± 0.12), whereas the expression of NOS isoforms remained unaltered. L-Arginine transport into neutrophils was similar in CRF patients on hemodialysis and controls. In addition, intracellular concentration of L-arginine was increased fourfold in the patient group. Systemic oxidative stress markers were not affected by CRF. On the other hand, NADPH oxidase subunit p47(phox) in neutrophils was overexpressed in CRF. In the presence of neutrophils, there was a reduction time-dependent in platelet aggregation in both groups with no difference between them. This data suggest that reduced basal generation of NO by neutrophils in CRF patients on hemodialysis occurs independently of L-arginine bioavailability and is able to suppress platelet activation.


Asunto(s)
Fallo Renal Crónico/sangre , Neutrófilos/metabolismo , Óxido Nítrico/sangre , Activación Plaquetaria , Adulto , Arginina/sangre , Femenino , Regulación de la Expresión Génica , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa/metabolismo , Agregación Plaquetaria , Diálisis Renal
8.
Cancers (Basel) ; 16(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38539429

RESUMEN

Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. The PRKAB2 gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs. We have evaluated how PRKAB2 is associated with clinical and biological characteristics in 63 pediatric patients with ACTs and conducted in vitro studies on the human NCI-H295R ACC cell line. An analysis of our cohort and the public ACC pediatric dataset GSE76019 showed that lower PRKAB2 expression was associated with relapse, death, metastasis, and lower event-free and overall survival rates. Multivariate analysis showed that PRKAB2 expression was an independent prognostic factor when associated with age, tumor weight and volume, and metastasis. In vitro tests on NCI-H295R cells demonstrated that Rottlerin, a drug that can activate AMPK, modulated several pathways in NCI-H295R cells, including AMPK/mTOR, Wnt/ß-catenin, SKP2, HH, MAPK, NFKB, and TNF. Treatment with Rottlerin decreased cell proliferation and migration, clonogenic capacity, and steroid production. Together, these results suggest that PRKAB2 is a potential prognostic marker in pediatric ACTs, and that Rottlerin is promising for investigating drugs that can act against ACTs.

9.
Hum Cell ; 36(6): 2129-2139, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37460706

RESUMEN

Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.

12.
Clin Cosmet Investig Dermatol ; 15: 483-488, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35330623

RESUMEN

Facial seborrheic dermatitis is common in HIV-positive patients, and the presence of facial lesions can affect quality of life. The management and control of lesions can be frustrating for both physicians and patients. In this pilot clinical study, we clinically evaluated the effectiveness of a topical non-steroidal cream in treating mild to moderate facial seborrheic dermatitis in 20 HIV-positive patients. The patients applied a twice-a-day topical cream containing zinc PCA, piroctone olamine, hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2, and stearyl glycyrrhetinate for 12 weeks with no topical or oral antifungal or corticosteroid treatment. Signs and symptoms and tolerance were assessed before, during, and at the end of treatment. All of the patients showed clinical improvement after 4 and 12 weeks of treatment. None of the patients had no response to treatment, and no adverse effects were reported. No rescue therapy with corticosteroids was needed. The patients reported a very noticeable improvement in their skin which contributed to high compliance with the protocol requirement.

13.
Hum Cell ; 35(6): 1952-1960, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36053456

RESUMEN

Pediatric adrenocortical tumor (ACT) is a rare and aggressive neoplasm, with incidence in southern and southeastern Brazil 10-15 times higher than worldwide. Although microRNAs (miRNAs) have been reported to act as tumor suppressors or oncogenes in several cancers, the role of miR-149-3p in ACT remains unknown. In this study, we evaluated the expression of miR-149-3p in 67 pediatric ACT samples and 19 non-neoplastic adrenal tissues. The overexpression of miR-149-3p was induced in H295A cell line, and cell viability, proliferation, colony formation, and cell cycle were assessed by in miR-149-3p mimic or mimic control. In silico analysis were used to predict miR-149-3p putative target genes. CDKN1A expression at the mRNA and protein levels was evaluated by qRT-PCR and western blot, respectively. Higher miR-149-3p expression was associated with unfavorable ACT outcomes. Compared to the mimic control, miR-149-3p overexpression increased cell viability and colony formation, and affected cell cycle progression. Also, we identified CDKN1A as a potential miR-149-3p target gene, with decreased expression at both the gene and protein levels in miR-149-3p mimic cells. Collectively, these findings suggest that miR-149-3p promotes H295A cell viability by downregulating CDKN1A and provide evidence that miR-149-3p may be useful as a novel therapeutic target for pediatric ACT.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , MicroARNs , Neoplasias de la Corteza Suprarrenal/genética , Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Niño , Regulación Neoplásica de la Expresión Génica/genética , Humanos , MicroARNs/genética , ARN Mensajero
14.
J Mol Neurosci ; 72(3): 633-641, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34822110

RESUMEN

The Group 3 Medulloblastoma (Grp3-MB) is an aggressive molecular subtype with a high incidence of metastasis and deaths. In this study, were used an RNA sequencing data (RNA-Seq) from a Brazilian cohort of MBs to identify hub genes associated with the metastatic risk. Data validation were performed by using multiple large datasets from MBs (GSE85217, GSE37418, and EGAS00001001953). DESeq2 package in R software was used to identify the differentially expressed genes (DEGs) in our RNA-Seq data. The DEGs data were accessed to construct the modules/graphs of co-expression and to identify hub genes through Cytoscape platform. The coregulated genes were enriched by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) network was visualized by Cytoscape. The Kaplan-Meier plotter and ROC curves were used to validate the diagnostic and prognostic values of specific biomarkers identified through this model. We identified that inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as a downregulated hub gene, with a high diagnostic accuracy to Grp3-MBs and associated with tumor metastasis. In addition, we identified genes significantly correlated with ITPR1 that were associated with metastasis in Grp3-MB (ATP1A2, MTTL7A, and RGL1) and worst overall survival in MBs (ANTXR1 and RGL1). Our findings suggest that the ITPR1 hub gene is potentially involved in the metastatic process for Grp3-MB. Our data also provide evidence of targets that may serve as prognostic predictors and/or regulators for the metastatic process that maybe explored for further research of individualized therapy to Grp3-MBs.


Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Cerebelosas/genética , Biología Computacional , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Inositol , Receptores de Inositol 1,4,5-Trifosfato/genética , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Meduloblastoma/genética , Proteínas de Microfilamentos/metabolismo , Pronóstico , Receptores de Superficie Celular/genética
15.
JAMA Dermatol ; 158(5): 561-572, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35353175

RESUMEN

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.


Asunto(s)
Metotrexato , Psoriasis , Adulto , Niño , Consenso , Ácido Fólico , Humanos , Psoriasis/terapia , Encuestas y Cuestionarios
16.
Clinics (Sao Paulo) ; 75: e1973, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33146358

RESUMEN

OBJECTIVES: This study aimed to analyze the incidence and epidemiological, angiographic, and surgical aspects associated with incomplete clipping of brain aneurysms in a cohort of patients undergoing microsurgical treatment. METHODS: The medical record data of patients who underwent microsurgery for cerebral aneurysm treatment and postoperative digital subtraction angiography, treated at the same teaching hospital between 2014 and 2019, were retrospectively analyzed. The studied variables involved epidemiological and clinical data, as well as neurological status and findings on neuroimaging. The time elapsed between hemorrhage and microsurgical treatment, data on the neurosurgical procedure employed for aneurysm occlusion, and factors associated with the treated aneurysm, specifically location and size, were also evaluated. RESULTS: One hundred and seventeen patients were submitted to 139 neurosurgical procedures, in which 167 aneurysms were clipped. The overall rate of residual injury was 23%. Smoking (odds ratio [OR]: 3.38, 95% confidence interval [CI95%]: 1.372-8.300, p=0.008), lesion size >10 mm (OR: 5.136, CI95%: 2.240-11.779, p<0.001) and surgery duration >6 h (OR: 8.667, CI95%: 2.713-27.681, p<0.001) were found to significantly impact incomplete aneurysm occlusion in the univariate analyses. CONCLUSION: Incomplete microsurgical aneurysm occlusion is associated with aneurysm size, complexity, and current smoking status. Currently, there is no consensus on postoperative assessment of clipped aneurysms, hindering the correct assessment of treatment outcomes.


Asunto(s)
Aneurisma Roto , Aneurisma Intracraneal , Aneurisma Roto/cirugía , Angiografía de Substracción Digital , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/cirugía , Microcirugia , Procedimientos Neuroquirúrgicos , Estudios Retrospectivos , Resultado del Tratamiento
17.
Int J Radiat Biol ; 96(7): 910-918, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32159405

RESUMEN

Purpose: The main goal of this study was to evaluate the impact of different ionizing radiation doses on the mineral (carbonate/phosphate ratio, crystallinity index [CI]) and organic (amide III/phosphate, amide I sub-band ratios) structures, as well as the microhardness, of enamel and dentin, along with their influence on the bonding strength stability of the etch-and-rinse (ER) and self-etch (SE) dental adhesive strategies.Materials and methods: Enamel and dentin human tissue specimens were irradiated (with 0, 20, 40, and 70 Gy radiation doses, respectively) and sectioned to perform an attenuated total reflection-Fourier transform IR spectroscopy assay (ATR-FTIR) and the Vickers microhardness (VHN) test to conduct a biochemical and biomechanical evaluation of the tissues. Regarding the adhesive properties, restored enamel and dentin specimens exposed to the same radiation doses were submitted to microshear bond strength (µSBS) tests for enamel in immediate time (IM) and to microtensile bond strength (µTBS) tests after for IM and 12-month (12 M) period of time, Mann-Whitney U tests were implemented, using the ATR-FTIR data for significant differences (α < 0.05), and three- and two-way analyses of variance, along with post-testing, were performed on the µTBS and µSBS data (MPa), respectively (Tukey post hoc test at α = 0.05).Results: The ATR-FTIR results showed a significant decrease (p < .05) in the amide III/phosphate ratio after 20 Gy for the enamel and after 40 Gy for the dentin. The CI was significantly reduced for both tissues after a dose of 70 Gy (p < .05). All radiation doses significantly decreased microhardness values, relative to the respective enamel and dentin controls (p < .05). In both tissues and adhesive strategies, the decrease in bond strength was influenced by ionizing radiation starting from 40 Gy. The ER strategy showed high percentages of enamel cohesive failure. In general, ER in both tissues showed greater and more stable bond strength than SE against increased radiation doses and long term.Conclusions: It is possible to conclude that structural alterations of enamel and dentin are generated by all radiation doses, decreasing the microhardness of dental hard tissues and influencing bond strength over time, starting at 40 Gy radiation dose. The etch-and-rinse strategy demonstrates better adhesive performance but generates cohesive fractures in the enamel.


Asunto(s)
Restauración Dental Permanente , Diente Molar/efectos de la radiación , Radioterapia/efectos adversos , Diente/efectos de la radiación , Esmalte Dental/citología , Esmalte Dental/efectos de la radiación , Dentina/citología , Dentina/efectos de la radiación , Dureza/efectos de la radiación , Humanos , Diente Molar/citología
18.
Arq Bras Oftalmol ; 83(3): 250-261, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32490972

RESUMEN

To identify and classify available information regarding COVID-19 and eye care according to the level of evidence, within four main topics of interest: evidence of the virus in tears and the ocular surface, infection via the conjunctival route, ocular manifestations, and best practice recommendations. A structured review was conducted in PubMed, ScienceDirect, LILACS, SciELO, the Cochrane Library and Google Scholar on COVID-19 and ophthalmology. The Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence worksheet was used for quality assessments. 1018 items were identified in the search; 26 records were included in the qualitative synthesis, which encompassed 6 literature reviews, 10 case series or cross-sectional studies, 4 case reports, and 6 intervention descriptions. Seventeen out of 26 records (65%) were categorized as level 5 within the Oxford CBME methodology grading system, the rest were level 4. The evidence generated on COVID-19 and ophthalmology to date is limited, although this is understandable given the circumstances. Both the possible presence of viral particles in tears and conjunctiva, and the potential for conjunctival transmission remain controversial. Ocular manifestations are not frequent and could resemble viral infection of the ocular surface. Most recommendations are based on the strategies implemented by Asian countries during previous coronavirus outbreaks. There is a need for substantive studies evaluating these strategies in the setting of SARS-CoV-2. In the meantime, plans for applying these measures must be implemented with caution, taking into account the context of each individual country, and undergo regular evaluation.


Asunto(s)
Infecciones por Coronavirus/complicaciones , Oftalmopatías/complicaciones , Neumonía Viral/complicaciones , COVID-19 , Conjuntiva/virología , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Medicina Basada en la Evidencia , Humanos , Oftalmología , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Literatura de Revisión como Asunto , Lágrimas/virología
19.
Cad Saude Publica ; 35(4): e00088618, 2019 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-31066774

RESUMEN

The objective of this study is to describe the experience of displaced women in Medellín, Colombia, and how this circumstance has an impact on the roles and perceptions of health/illness. This was a qualitative study using symbolic interactionism. Instruments from the Grounded Theory methodology were used. The study population was composed of adult women who have been displaced for at least 1 year and who live in 3 settlements in the city of Medellín. The instruments for data collection were 15 semi-structured interviews, 6 focus groups, and 6 in-depth interviews. Coding, categorization and interpretation, and, lastly, theorizing were used for analysis. What women go through displacement affects the roles they play both in relation to their family - one of the most significant components of their lives -, and in the social/community and health/illness processes, turning them into people with high degrees of vulnerability and social marginalization. Women who have been displaced face multiple obstacles, losses, and transformations, leading to a decline in their physical and mental health.


Asunto(s)
Migración Humana , Salud de la Mujer , Adolescente , Adulto , Anciano , Colombia , Femenino , Grupos Focales , Equidad en Salud , Humanos , Persona de Mediana Edad , Investigación Cualitativa , Factores Socioeconómicos , Poblaciones Vulnerables , Adulto Joven
20.
Rev. Soc. Colomb. Oftalmol ; 56(2): 54-62, 2023. tab
Artículo en Español | LILACS, COLNAL - Colombia-Nacional | ID: biblio-1525442

RESUMEN

Antecedentes: La pérdida de visión tiene consecuencias tanto en la salud como en la estabilidad económica, ya que promueve retrasos en el desarrollo emocional, social, además de reducciones en la productividad laboral. Objetivo: Estimar la carga económica de la degeneración macular asociada a la edad neovascular (DMAEn) y el edema macular diabético (EMD) en Colombia para el año 2022. Método: Para una perspectiva social se incluyeron costos directos utilizando la aproximación de Bottom-up y costos indirectos relacionados con la pérdida de productividad. Resultados: El costo directo de un paciente con DMAEn fue 5.974 USD$ desde una base teórica. A nivel nacional, la DMAEn costaría 179,9 millones USD$. Los costos indirectos de DMAEn se estimaron en 13,9 millones USD$. Los costos directos teóricos en EMD fueron 741,6 millones USD$. El costo nacional sería de 132,04 millones USD$. Para los costos indirectos de EMD, se estimó un costo de 93,3 millones USD$. Conclusiones: La DMAEn y el EMD tienen un alto impacto para el sistema de salud y la sociedad.


Background: The vision loss has consequences for both health and economic stability, since it promotes delays in emotional and social development, as well as reductions in labor productivity. Objective: To estimate the economic burden of age-related macular degeneration (AMD) and diabetic macular edema (DME) in Colombia for 2022. Method: For a social perspective, direct costs were included using the bottom-up approach, and indirect costs related to lost productivity. Results: The direct costs of treating a patient with AMD were USD $5,974 from a theoretical background. At national level, the AMD would cost USD $179.9 million. The AMD indirect cost in Colombia was estimated in USD $13.9 million. Patients theoretical direct cost of DME was USD $741.6 million. The cost at national level is USD $132.04 million. Regarding the indirect costs result for DME, a cost of USD $93.31 million was estimated. Conclusions: The AMD and the DME have a considerable impact on the health system and society.


Asunto(s)
Humanos , Colombia , Diabetes Mellitus
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