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PURPOSE: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. METHODS: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. RESULTS: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048). CONCLUSION: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis.
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Proteína BRCA2 , Recombinação Homóloga , Neoplasias da Próstata , Humanos , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/mortalidade , Idoso , Proteína BRCA2/genética , Mutação , Prognóstico , DNA Tumoral Circulante/genética , DNA Tumoral Circulante/sangue , Idoso de 80 Anos ou mais , Mutação em Linhagem Germinativa , Proteína BRCA1/genética , AdultoRESUMO
PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.
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Carboplatina , Dislipidemias , Hipertensão , Hipogonadismo , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Estudos Retrospectivos , Hipogonadismo/epidemiologia , Hipogonadismo/complicações , Dislipidemias/epidemiologia , Dislipidemias/complicações , Hipertensão/epidemiologia , Hipertensão/complicações , Adulto , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/patologia , Seminoma/complicações , Seminoma/epidemiologia , Seminoma/patologia , Pessoa de Meia-Idade , Incidência , Espanha/epidemiologia , Carboplatina/administração & dosagem , Adulto Jovem , Estadiamento de Neoplasias , Fatores de Risco , IdosoRESUMO
Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.
Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.
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Aim: This work aimed to synthesize magnesium-doped zinc oxide, silver and gold nanoparticles (Nps) and to evaluate their potential to prevent and eradicate Escherichia coli, Proteus mirabilis, Staphylococcus aureus, Acinetobacter baumannii and Pseudomonas aeruginosa biofilms. Materials & methods: The Nps were synthesized by precipitation and metallic reduction techniques. Physicochemical and biological characterization of Nps was performed. Results: All the Nps tested were able to inhibit the formation of E. coli, P. mirabilis, S. aureus and A. baumannii biofilms. The effects on the eradication of preformed biofilms were variable, although all the Nps tested were able to eradicate A. baumannii biofilms. Conclusion: The observed effects make the Nps suitable for coating surfaces and/or antibiotic carriers with medical interest.
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Nanopartículas Metálicas , Óxido de Zinco , Ouro/farmacologia , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Magnésio/farmacologia , Prata/farmacologia , Prata/química , Zinco/farmacologia , Nanopartículas Metálicas/química , Staphylococcus aureus , Óxido de Magnésio/farmacologia , Escherichia coli , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/químicaRESUMO
INTRODUCTION: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma (GB) regions. OBJECTIVE: To compare the efficacy of GB biomarkers using "zombie plots". METHODS: Retrospective cohort of 29 subjects with GB who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. RESULTS: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. CONCLUSIONS: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.
INTRODUCCIÓN: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. OBJETIVO: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. MÉTODOS: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. RESULTADOS: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. CONCLUSIONES: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.
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Neoplasias Encefálicas , Glioblastoma , Anisotropia , Teorema de Bayes , Biomarcadores , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Análise de Dados , Testes Diagnósticos de Rotina , Imagem de Tensor de Difusão/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Humanos , Necrose , Estudos RetrospectivosRESUMO
The objective of this study was to develop clarithromycin-loaded lipid nanocarriers and incorporate them into microcapsules for pH-specific localized release of clarithromycin in the Helicobacter pylori microenvironment in order to obtain a gastro-retentive and pH-sensitive formulation. A Plackett-Burman design was applied to identify the effect of 5 factors on 3 responses. Then, a central composite design was applied to estimate the most important factors leading to the best compromise between lower particle size, polydispersity index and particle size changes. The optimized clarithromycin-loaded nanocapsules were employed to generate microcapsules by different methodologies. Nanocarriers and microcapsules were characterized in vitro. Experimental design and conditions were optimized to obtain nanocapsules of around 100 nm by a modified phase inversion-based process. High particle size homogeneity and high stability were achieved. At 4 °C both optimized lipid nanocapsules were stable during at least 365 days, confirming stability under those conditions. Clarithromycin incorporation in the nanocarrier was effective. Both types of microcoating were evaluated regarding their pH sensitivity. Spray drying microcapsules exhibited similar and uncontrolled release profiles at pH 2 and 7.4. Alternatively, when microcoatings were generated using an Encapsulator, release was insignificant at pH 2, while at pH 7.4 release was triggered, and appeared more appropriate to formulate microcapsules that release nanocarriers under pH neutral Helicobacter pylori microenvironment conditions, thereby permitting effective drug delivery in infected locations. The release of clarithromycin from lipid nanocarrier loaded microcapsules was pH-sensitive suggesting that this could be an effective strategy for clarithromycin delivery to the Helicobacter pylori microenvironment. Clarithromycin nanocapsules with and without microcoating showed a high anti-Helicobacter pylori activity in vitro.
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Infecções por Helicobacter , Helicobacter pylori , Nanocápsulas , Antibacterianos/química , Cápsulas , Claritromicina/química , Claritromicina/farmacologia , Sistemas de Liberação de Medicamentos , Infecções por Helicobacter/tratamento farmacológico , Humanos , Lipídeos/farmacologia , Projetos de PesquisaRESUMO
Resumen Introducción: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. Objetivo: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. Métodos: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. Resultados: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. Conclusiones: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.
Abstract Introduction: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma regions. Objective: To compare the efficacy of glioblastoma biomarkers using "zombie plots". Methods: Retrospective cohort of 29 subjects with glioblastoma who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. Results: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. Conclusions: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.
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Magnetic resonance images from 197 patients with calcified neurocysticercosis (NCC), 38 with viable NCC and 197 NCC-free healthy rural villagers were evaluated to compare the frequency of hippocampal atrophy/sclerosis (HAS) across these populations. Scheltens' medial temporal atrophy scale was used for hippocampal rating. The median age of the 432 study participants was 46 years (interquartile range, 29-62 years), and 58% were women. Hippocampal atrophy/sclerosis was disclosed in 26.9% patients with calcified NCC, compared with 7.9% in patients with viable NCC and 8.1% in healthy rural villagers. After adjusting for age, gender, and history of epilepsy, hippocampal atrophy/sclerosis was more frequent in patients with calcified NCC than in those with viable cysts (RR, 3.60; 95% CI, 1.18- 0.99; P = 0.025) and healthy rural villagers (RR, 3.43; 95% CI, 1.94-6.06; P < 0.001), suggesting that hippocampal damage develops late in the course of this parasitic disease.
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Calcinose/complicações , Hipocampo/patologia , Neurocisticercose/complicações , Adulto , Atrofia , Calcinose/diagnóstico por imagem , Calcinose/patologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/parasitologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Doenças Negligenciadas/complicações , Doenças Negligenciadas/diagnóstico por imagem , Doenças Negligenciadas/patologia , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/patologia , EscleroseRESUMO
Urinary tract infection (UTI) is one of the most common reasons for antibiotic treatment. Nevertheless, uropathogens are steadily becoming resistant to currently available therapies. In this context, nanotechnology emerges as an innovative and promising approach among diverse strategies currently under development. In this review we deeply discuss different nanoparticles (NPs) used in UTI treatment, including organic NPs, nanodiamonds, chemical and green synthesized inorganic NPs, and NPs made of composite materials. In addition, we compare the effects of different NPs against uropathogens in vivo and in vitro and discuss their potential impact the in the near future.