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1.
Ultramicroscopy ; 259: 113923, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324944

RESUMO

M-subshell X-ray production cross sections were indirectly measured for Ir and Bi targets irradiated with monoenergetic electron beams. The projectile energy range ran from 2.2 to 28 keV, impinging on Ir and Bi pure bulk targets in a scanning electron microscope. The resulting X-ray emission spectra were acquired with an energy dispersive spectrometer, and processed afterwards by means of a robust parameter optimization procedure developed previously. X-ray production cross sections were finally obtained through an approach involving an analytical prediction for the emission spectra, which relies on the ionization depth distribution function. The values obtained by this approach were compared with empirical and theoretical predictions, appealing to different relaxation data taken from the literature.

2.
Braz J Med Biol Res ; 55: e12036, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35976269

RESUMO

The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain's functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain's FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.


Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Imageamento por Ressonância Magnética/métodos , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico por imagem , Extremidade Superior
3.
ESMO Open ; 7(5): 100567, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35994791

RESUMO

BACKGROUND: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. PATIENTS AND METHODS: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. RESULTS: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). CONCLUSION: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Irinotecano/farmacologia , Irinotecano/uso terapêutico , Estudos Retrospectivos , Fluoruracila/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do Tratamento , Neoplasias do Colo/tratamento farmacológico
4.
Ultramicroscopy ; 232: 113401, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34634763

RESUMO

The cadmium L x-ray spectrum induced by electron impact was analyzed in detail. The measurements were performed on a bulk pure sample using a commercial wavelength dispersive spectrometer, and the spectrum was processed with a parameter optimization method previously developed. This procedure permitted the determination of characteristic energies, relative transition probabilities and natural linewidths for this element. The results obtained here were compared to the data found in the literature, when available. Spectral structures related to satellite and radiative Auger Effect emissions were also analyzed, assessing energy shifts and relative intensities. Some of these parameters were determined for the first time, even in overlapping peaks and weak transitions, which was possible due to the robustness of the spectral processing method used.

5.
Braz. j. med. biol. res ; 55: e12036, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1394129

RESUMO

The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain's functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain's FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.

6.
New Microbes New Infect ; 41: 100853, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33680474

RESUMO

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), resulting in acute respiratory disease, is a worldwide emergency. Because recently it has been found that SARS-CoV is dependent on host transcription factors (TF) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. By bioinformatic analysis, we investigated human TF that can bind the SARS-CoV-2 sequence and can be involved in viral transcription. In particular, we analysed the key role of TF involved in interferon (IFN) response. We found that several TF could be induced by the IFN antiviral response, specifically some induced by IFN-stimulated gene factor 3 (ISGF3) and by unphosphorylated ISGF3, which were found to promote the transcription of several viral open reading frame. Moreover, we found 22 TF binding sites present only in the sequence of virus infecting humans but not bat coronavirus RaTG13. The 22 TF are involved in IFN, retinoic acid signalling and regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle. This mechanism, by competition, may steal the human TF involved in these processes, explaining SARS-CoV-2's disruption of IFN-I signalling in host cells and the mechanism of the SARS retinoic acid depletion syndrome leading to the cytokine storm. We identified three TF binding sites present exclusively in the Brazilian SARS-CoV-2 P.1 variant that may explain the higher severity of the respiratory syndrome. These data shed light on SARS-CoV-2 dependence from the host transcription machinery associated with IFN response and strengthen our knowledge of the virus's transcription and replicative activity, thus paving the way for new targets for drug design and therapeutic approaches.

7.
Rev. esp. anestesiol. reanim ; 68(3): 149-152, Mar. 2021. ilus
Artigo em Espanhol | IBECS | ID: ibc-231009

RESUMO

La tiroidectomía endoscópica transoral por abordaje vestibular (TOETVA) constituye un procedimiento novedoso y mínimamente invasivo, libre de cicatrices visibles y que presenta resultados alentadores en cuanto a la rápida recuperación y menor dolor posoperatorio. Consiste en realizar la tiroidectomía a través de su orificio natural, empleando tres puertos en el área oral vestibular y llevando a cabo una disección cuidadosa hasta la muesca esternal y los bordes de ambos músculos esternocleidomastoideos. El objetivo es describir las diferentes implicaciones anestésicas que conlleva esta técnica quirúrgica, dado que la evidencia publicada hasta la fecha en la literatura es muy limitada. Se considera esencial la monitorización del nervio laríngeo recurrente mediante tubo endotraqueal con electromiografía para garantizar su identificación e integridad, así como la utilización de otros monitores como el TOF-watch o el índice biespectral para asegurar una adecuada profundidad anestésica y un óptimo nivel de relajación muscular.(AU)


Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a novel and minimally invasive procedure, free of visible scars and showing encouraging results in terms of rapid recovery and less postoperative pain. It consists of performing the thyroidectomy through its natural orifice, using three ports in the oral vestibular area and carrying out a careful dissection to the sternal notch and the edges of both sternocleidomastoid muscles. The objective of this article is to describe the different anesthetic implications that this surgical technique entails, given that the evidence published to date in the literature is very limited. It is considered essential to control the recurrent laryngeal nerve using an endotracheal tube with electromyography to ensure its identification and integrity, as well as the use of other monitors such as the TOF watch or the bispectral index to ensure adequate anesthetic depth and an optimal level of muscle relaxation.(AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Tireoidectomia/métodos , Anestesia , Nervo Laríngeo Recorrente/cirurgia , Intubação Intratraqueal , Eletromiografia , Traumatismos do Nervo Laríngeo Recorrente/cirurgia , Pacientes Internados , Exame Físico , Anestesiologia , Anestesia Endotraqueal
8.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(3): 149-152, 2021 Mar.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32622475

RESUMO

Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a novel and minimally invasive procedure, free of visible scars and showing encouraging results in terms of rapid recovery and less postoperative pain. It consists of performing the thyroidectomy through its natural orifice, using three ports in the oral vestibular area and carrying out a careful dissection to the sternal notch and the edges of both sternocleidomastoid muscles. The objective of this article is to describe the different anesthetic implications that this surgical technique entails, given that the evidence published to date in the literature is very limited. It is considered essential to control the recurrent laryngeal nerve using an endotracheal tube with electromyography to ensure its identification and integrity, as well as the use of other monitors such as the TOF watch or the bispectral index to ensure adequate anesthetic depth and an optimal level of muscle relaxation.


Assuntos
Anestésicos , Traumatismos do Nervo Laríngeo Recorrente , Endoscopia , Humanos , Nervo Laríngeo Recorrente , Tireoidectomia
9.
Actas dermo-sifiliogr. (Ed. impr.) ; 111(8): 671-677, oct. 2020. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-197153

RESUMO

ANTECEDENTES Y OBJETIVO: La enfermedad de Hansen o lepra es una enfermedad causada por Mycobacterium leprae y Mycobacterium lepromatosis. Estas bacterias ingresan al organismo por las vías aéreas superiores, por lo que generan manifestaciones clínicas en la mucosa nasal y en la cavidad bucal. El objetivo del estudio es caracterizar las lesiones bucales de los pacientes con una enfermedad de Hansen. MATERIALES Y MÉTODOS: Se diseñó un estudio observacional, transversal, de 100 pacientes con diagnóstico de lepra. Se examinó la cavidad bucal y se registraron los hallazgos clínicos en una ficha epidemiológica. Además, se incluyó el estudio histopatológico de las lesiones que requirieron de una biopsia. Los casos sugestivos de lepra fueron teñidos y analizados con hematoxilina y eosina, Ziehl-Neelsen y Fite-Faraco. Las variables fueron analizadas y comparadas mediante las pruebas Chi2, correlación de Spearman y U de Mann-Whitney. RESULTADOS: El grupo de estudio estuvo conformado por 67 hombres y 33 mujeres, con una media (± desviación estándar) de 48,1±16,4 años de edad. Fueron observadas lesiones bucales en 34 pacientes. Las lesiones orales relacionadas con lepra, presentes en 9 pacientes, se ubicaron en el paladar duro y el labio superior. Estas fueron significativamente más frecuentes en la lepra lepromatosa, la borderline lepromatosa (p = 0,029) y en el eritema nudoso leproso (p = 0,031). CONCLUSIONES: Las lesiones bucales asociadas a lepra ocurren con una frecuencia baja, manifestándose como lepromas y placas leprosas en el paladar duro y el labio superior


BACKGROUND AND OBJECTIVE: Hansen disease, or leprosy, is caused by Mycobacterium leprae or Mycobacterium lepromatosis. Because these bacteria enter the body via the upper airways, they generate clinical manifestations in the nasal mucous membranes and the mouth. We aimed to describe the characteristics of oral lesions in patients with Hansen disease. MATERIAL AND METHODS: Cross-sectional observational study of 100 patients diagnosed with Hansen disease. We examined the oral cavity and recorded clinical findings on a disease reporting form for each patient. We also included the histopathologic findings for lesions that required a biopsy. Samples suggestive of Hansen disease were processed with hematoxylin-eosin, Ziehl-Neelsen, and Fite-Faraco staining. Variables were analyzed, as appropriate, with the χ2 test, the Mann-Whitney U test, or the Spearman correlation coefficient. RESULTS: Sixty-seven men and 33 women were included. The mean (SD) age was 48.1±16.4 years. Thirty-four patients had oral lesions. Lesions related to Hansen disease were found in 9 patients. The locations were the hard palate and upper lip. Oral lesions were significantly more frequent in patients with lepromatous leprosy, borderline lepromatous leprosy (P = .029), and erythema nodosum leprosum (P = .031). CONCLUSIONS: The frequency of oral lesions is low in Hansen disease. Such lesions present as lepromas and leprous plaques on the hard palate and upper lip


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Hanseníase/patologia , Mucosa Bucal/patologia , Doenças da Boca/patologia , Estudos Transversais , Hanseníase/epidemiologia , Biópsia , Estatísticas não Paramétricas , Doenças da Boca/epidemiologia , Distribuição por Sexo , Venezuela/epidemiologia
10.
Actas Dermosifiliogr (Engl Ed) ; 111(8): 671-677, 2020 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32574720

RESUMO

BACKGROUND AND OBJECTIVE: Hansen disease, or leprosy, is caused by Mycobacterium leprae or Mycobacterium lepromatosis. Because these bacteria enter the body via the upper airways, they generate clinical manifestations in the nasal mucous membranes and the mouth. We aimed to describe the characteristics of oral lesions in patients with Hansen disease. MATERIAL AND METHODS: Cross-sectional observational study of 100 patients diagnosed with Hansen disease. We examined the oral cavity and recorded clinical findings on a disease reporting form for each patient. We also included the histopathologic findings for lesions that required a biopsy. Samples suggestive of Hansen disease were processed with hematoxylin-eosin, Ziehl-Neelsen, and Fite-Faraco staining. Variables were analyzed, as appropriate, with the χ2 test, the Mann-Whitney U test, or the Spearman correlation coefficient. RESULTS: Sixty-seven men and 33 women were included. The mean (SD) age was 48.1±16.4 years. Thirty-four patients had oral lesions. Lesions related to Hansen disease were found in 9 patients. The locations were the hard palate and upper lip. Oral lesions were significantly more frequent in patients with lepromatous leprosy, borderline lepromatous leprosy (P = .029), and erythema nodosum leprosum (P = .031). CONCLUSIONS: The frequency of oral lesions is low in Hansen disease. Such lesions present as lepromas and leprous plaques on the hard palate and upper lip.


Assuntos
Hanseníase Virchowiana , Hanseníase , Mycobacterium , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Climacteric ; 23(4): 360-368, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32396739

RESUMO

With the increase in life expectancy, women now live up to one-third of their life in menopause. Postmenopausal bleeding (PMB) is a common gynecologic complaint encountered by the clinician. Endometrial cancer is present in about 10% of patients with PMB. Nevertheless, many other conditions such as endometrial or cervical polyps, genital atrophy, or non-gynecologic conditions may also be present. Hysteroscopy has replaced blind diagnostic procedures and is now considered the gold-standard technique for the diagnosis and management of intrauterine pathology. Gynecologists in clinical practice should be familiar with the use of hysteroscopy in the diagnosis and treatment of the menopausal patient presenting with gynecologic complaints. The aim of this article is to report the current evidence on the role of hysteroscopy in the evaluation and management of the postmenopausal patient with intrauterine pathology.


Assuntos
Ginecologia/tendências , Histeroscopia/tendências , Pós-Menopausa , Doenças Uterinas/cirurgia , Feminino , Humanos , Histeroscopia/métodos , Pessoa de Meia-Idade , Doenças Uterinas/diagnóstico , Doenças Uterinas/patologia
12.
Biomed Phys Eng Express ; 6(3): 035030, 2020 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33438675

RESUMO

Motor imagery (MI) constitutes a recurrent strategy for signals generation in brain-computer interfaces (BCIs) - systems that aim to control external devices by directly associating brain responses to distinct commands. Although great improvement has been achieved in MI-BCIs performance over recent years, they still suffer from inter- and intra-subject variability issues. As an attempt to cope with this, some studies have suggested that MI training should aid users to appropriately modulate their response for BCI usage: generally, this training is performed based on the sensorimotor rhythms' modulation over the primary sensorimotor cortex (PMC), with the signal being feedbacked to the user. Nonetheless, recent studies have revisited the actual involvement of the PMC into MI, and little to no attention has been devoted to understanding the participation of other cortical areas into training protocols. Therefore, in this work, our aim was to analyze the response induced by hands MI of 10 healthy subjects in the form of event-related desynchronizations (ERDs) and to assess whether features from beyond the PMC might be useful for hands MI classification. We investigated how this response occurs for distinct frequency intervals between 7-30 Hz, and ex0plored changes in their evocation pattern across 12 MI training sessions without feedback. Overall, we found that ERD patterns occur differently for the frequencies encompassed by the µ and ß bands, with its evocation being favored for the first band. Over time, the no-feedback approach was inefficient to aid in enhancing ERD evocation (EO). Moreover, to some extent, EO tends to decrease over blocks within a given run, and runs within an MI session, but remains stable within an MI block. We also found that the C3/C4 pair is not necessarily optimal for data classification, and both spectral and spatial subjects' specificities should be considered when designing training protocols.


Assuntos
Retroalimentação , Imaginação , Córtex Sensório-Motor/fisiologia , Adulto , Algoritmos , Interfaces Cérebro-Computador , Eletrodos , Eletroencefalografia , Desenho de Equipamento , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Modelos Estatísticos , Destreza Motora , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Adulto Jovem
13.
J Microsc ; 270(2): 136-141, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29178425

RESUMO

In electron probe microanalysis, secondary fluorescence can occur leading to an increase of the volume analysed, degrading the lateral resolution of this technique. An adequate knowledge of the interaction volumes from where the different signals of interest are detected is determinant to estimate the minimum size of the zone that can be characterized. In this work, the size of the signal source volume is surveyed for a wide set of samples at different beam energies. To this aim, the PENELOPE software package was chosen to run Monte Carlo simulations for several experimental situations in order to produce the various lateral radiation distributions of interest. A comparison between the interaction volumes of the different signals was performed by taking into account the different fluorescence enhancement possibilities. An unexpected behaviour was found in the particular cases of aluminium and alumina, where the secondary photons signal exhibits a decreasing trend up to certain beam energy (∼17 keV); this implies that lower beam energies may degrade the lateral resolution of the technique in these materials.

14.
Allergy ; 73(1): 77-92, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28600902

RESUMO

The overarching goals of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) are to enable European citizens to lead healthy, active and independent lives whilst ageing. The EIP on AHA includes 74 Reference Sites. The aim of this study was to transfer innovation from an app developed by the MACVIA-France EIP on AHA reference site (Allergy Diary) to other reference sites. The phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly will be compared using validated information and communication technology (ICT) tools (i.e. the Allergy Diary and CARAT: Control of Allergic Rhinitis and Asthma Test) in 22 Reference Sites or regions across Europe. This will improve the understanding, assessment of burden, diagnosis and management of rhinitis in the elderly by comparison with an adult population. Specific objectives will be: (i) to assess the percentage of adults and elderly who are able to use the Allergy Diary, (ii) to study the phenotypic characteristics and treatment over a 1-year period of rhinitis and asthma multimorbidity at baseline (cross-sectional study) and (iii) to follow-up using visual analogue scale (VAS). This part of the study may provide some insight into the differences between the elderly and adults in terms of response to treatment and practice. Finally (iv) work productivity will be examined in adults.


Assuntos
Asma/epidemiologia , Rinite Alérgica/epidemiologia , Fatores Etários , Idoso , Tomada de Decisão Clínica , Comorbidade , Avaliação Geriátrica , Humanos , Avaliação de Resultados em Cuidados de Saúde , Vigilância da População
15.
Leukemia ; 32(3): 675-684, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28804123

RESUMO

Genome studies of diffuse large B-cell lymphoma (DLBCL) have revealed a large number of somatic mutations and structural alterations. However, the clinical significance of these alterations is still not well defined. In this study, we have integrated the analysis of targeted next-generation sequencing of 106 genes and genomic copy number alterations (CNA) in 150 DLBCL. The clinically significant findings were validated in an independent cohort of 111 patients. Germinal center B-cell and activated B-cell DLBCL had a differential profile of mutations, altered pathogenic pathways and CNA. Mutations in genes of the NOTCH pathway and tumor suppressor genes (TP53/CDKN2A), but not individual genes, conferred an unfavorable prognosis, confirmed in the independent validation cohort. A gene expression profiling analysis showed that tumors with NOTCH pathway mutations had a significant modulation of downstream target genes, emphasizing the relevance of this pathway in DLBCL. An in silico drug discovery analysis recognized 69 (46%) cases carrying at least one genomic alteration considered a potential target of drug response according to early clinical trials or preclinical assays in DLBCL or other lymphomas. In conclusion, this study identifies relevant pathways and mutated genes in DLBCL and recognizes potential targets for new intervention strategies.


Assuntos
Variação Genética , Genômica , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/metabolismo , Transdução de Sinais , Adulto , Idoso , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Variações do Número de Cópias de DNA , Feminino , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Janus Quinases/metabolismo , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Receptores Notch/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
J Viral Hepat ; 24(6): 464-471, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27976490

RESUMO

Limited data are available on direct-acting antivirals for treating hepatitis C virus (HCV) infection in patients with severe renal impairment. The aim of this study was to evaluate the effectiveness and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) ± ribavirin (RBV) in patients with stage 4 or 5 chronic kidney disease (CKD) and HCV genotype 1 or 4 infection in real clinical practice, and to investigate pharmacological interactions. This retrospective study included patients treated with OBV/PTV/r+DSV±RBV or OBV/PTV/r+RBV with CKD stage 4 (eGFR: 15-29 mL/min/1.73m2 ) or 5 (eGFR<15 mL/min/1.73m2 or requiring dialysis) and HCV infection by genotypes 1 and 4 between April 2015 and October 2015 in nine Spanish centres. Sustained virological response at 12 weeks (SVR12) was assessed, and clinical and laboratory data, fibrosis stage, adverse events and pharmacological interactions were reported. Forty-six patients were included: 10 (21.7%) had CKD stage 4 and 36 (78.2%) CKD stage 5. Seventeen (36.9%) had cirrhosis. SVR12 rate in the intention-to-treat population was 95.7%. Twenty-one (45.6%) received RBV, which was discontinued in two (9.5%) patients. Anaemia (haemoglobin <10 g/dl) occurred in 12 patients (57.1%) with RBV vs 10 (40.0%) without RBV (P=.246). Renal function remained stable during antiviral therapy. Nine patients (19.5%) experienced serious adverse events unrelated to antiviral therapy. Concomitant medication was discontinued or modified in 41.3% of patients. In conclusion, the effectiveness of OBV/PTV/r±DSV±RBV in patients with CKD 4-5 was similar to that observed in those with normal renal function and was not associated with severe adverse events.


Assuntos
Antivirais/uso terapêutico , Quimioterapia Combinada/métodos , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Insuficiência Renal/complicações , Insuficiência Renal/terapia , Adulto , Idoso , Antivirais/efeitos adversos , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha , Resposta Viral Sustentada , Resultado do Tratamento
17.
Kasmera ; 44(2): 111-120, dic. 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-954879

RESUMO

Staphylococcus aureus se presenta como un patógeno cada vez más importante, debido al arsenal de factores de virulencia que presenta, sumado a su elevada capacidad de generar resistencia a los antimicrobianos Los objetivos de esta investigación fueron: confirmar la resistencia a meticilina mediante la amplificación del gen mecA y detectar la presencia de los genes que codifican el factor de virulencia leucocidina de Panton Valentine (PVL). Se investigaron estos genes empleando la reacción en cadena de polimerasa (PCR). Todos los aislamientos presentaron el gen mecA, el 50% de estas cepas resultó portador del gen para PVL. El 54,17% de las muestras de pacientes pediátricos, dio positivo para esta leucocidina. El mayor porcentaje de aislamiento se encontró en muestras de piel y tejidos blandos (85,7%).


Staphylococcus aureus is an increasingly important pathogen, due to the arsenal of virulence factors which presents, in addition to its high capacity to generate antimicrobial resistance. The objectives of this research were: confirm methicillin resistance by amplification the mecA gene and the presence of genes that encode Panton Valentine leucocidin (PVL) virulence factor. These genes have been investigated using polymerase chain reaction (PCR). All isolates showed the mecA gene, 50% of these strains were carrying the gene for PVL. 54,17% of the samples from pediatric patients, yield positive for this leukocidin. The highest percentage of isolation was found in samples of skin and soft tissues (85.7%).

18.
Kasmera ; 44(2): 121-133, dic. 2016. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-954880

RESUMO

Algunas especies de Aeromonas han emergido como patógenos importantes, asociadas al desarrollo de infecciones gastrointestinales y extraintestinales. El objetivo de este estudio fue evaluar el potencial de virulencia de cepas de Aeromonas procedentes de vegetales. Se analizó los factores de virulencia: DNAsa, lecitinasa, caseinasa, gelatinasa, β-hemolisinas y hemaglutininas, en 59 cepas de A. hydrophila y 61 de A. caviae, aisladas de cilantro, perejil y lechuga, comercializados en Maracaibo. Los resultados fueron analizados mediante el estadístico χ². Los factores de virulencia estudiados fueron expresados por más del 80% de las cepas. Cuatro de los 6 factores fueron expresados en mayor proporción por las cepas de A. hydrophila, aunque la diferencia entre las especies sólo resultó significativa para la expresión de caseinasa (94,9% vs 72,1% p 0,05). Se evidenció una diferencia significativa en el número de factores de virulencia expresado por las dos especies, siendo mayor para A. hydrophila (p < 0,05). La expresión de un número elevado de factores de virulencia por las cepas de Aeromonas analizadas, permite atribuirles un potencial de patogenicidad similar al descrito en las cepas procedentes de infecciones humanas.


Some species of Aeromonas have emerged as important pathogens associated with the development of gastrointestinal and extra-intestinal infections. The objective of this study was to evaluate the potential virulence of Aeromonas strains from vegetables. Virulence factors were analyzed: DNase, lecitinasa, caseinase, gelatinase, hemolysines and hemaglutinies, in 59 strains of A. hydrophila and 61 of A. caviae, isolated from coriander, parsley and lettuce obtained in establishments in Maracaibo city. The results were analyzed through statistics χ2. The virulence factors studied were expressed for more of the 80% of the strains. Four of the 6 factors were expressed in greater proportion in Aeromonas hydrophila strains, although the difference between the species only significant in for caseinase expression (94.9% vs 72.1%, p 0.05). A significant difference was evident in the number of virulence factors expressed by the two species, being higher for A. hydrophila (p <0.05). The expression of a large number of virulence factors the analyzed Aeromonas strains, allow to attribute a potential of pathogenicity to the strain of human infections.

19.
Ultramicroscopy ; 171: 177-185, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27690348

RESUMO

The spatial resolution of the electron backscatter diffraction signal is explored by Monte Carlo simulation for the sigma phase in steel at a typical instrumental set-up. In order to estimate the active volume corresponding to the diffracted electrons, the fraction of the backscattered electrons contributing to the diffraction signal was inferred by extrapolating the Kikuchi pattern contrast measured by other authors, as a function of the diffracted electron energy. In the resulting estimation, the contribution of the intrinsic incident beam size and the software capability to deconvolve patterns were included. A strong influence of the beam size on the lateral resolution was observed, resulting in 20nm for the aperture considered. For longitudinal and depth directions the resolutions obtained were 75nm and 16nm, respectively. The reliability of this last result is discussed in terms of the survey of the last large-angle deflection undergone by the backscattered electrons involved in the diffraction process. Bearing in mind the mean transversal resolution found, it was possible to detect small area grains of sigma phase by EBSD measurements, for a stabilized austenitic AISI 347 stainless steel under heat treatments, simulating post welding (40h at 600°C) and aging (284h at 484°C) effects-as usually occurring in nuclear reactor pressure vessels.

20.
Neurotox Res ; 30(3): 521-9, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27270586

RESUMO

We hypothesized that the IL-1ß-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1ß-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1ß-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1ß-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits.


Assuntos
Antineoplásicos/efeitos adversos , Predisposição Genética para Doença , Homozigoto , Interleucina-1beta/genética , Síndromes Neurotóxicas/genética , Polimorfismo de Nucleotídeo Único , Antineoplásicos/uso terapêutico , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Testes Neuropsicológicos
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