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PURPOSE: To evaluate the impact of a commercially available deep learning-based reconstruction (DLR) algorithm with varying combinations of DLR noise reduction settings and imaging parameters on quantitative and qualitative image quality, PI-RADS classification and examination time in prostate T2-weighted (T2WI) and diffusion-weighted (DWI) imaging. METHOD: Forty patients were included. Standard-of-care (SoC) prostate MRI sequences including T2WI and DWI were reconstructed without and with different DLR de-noising levels (low, medium, high). In addition, faster T2WI(Fast) and DWI(Fast) sequences, and a higher resolution T2WI(HR) sequence were evaluated. Quantitative analysis included signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and apparent diffusion coefficient (ADC) values. Two radiologists performed qualitative analysis, independently evaluating imaging datasets using 5-point scoring scales for image quality and artifacts. PI-RADS category assignment was also performed by the more experienced radiologist. RESULTS: All DLR levels resulted in significantly higher SNR and CNR compared to the DLR(off) acquisitions. DLR allowed the acquisition time to be reduced by 33% for T2WI(Fast) and 49% for DWI(Fast) compared to SoC, without affecting image quality, whilst T2WI(HR) with DLR allowed for a 73% increase in spatial resolution in the phase encode direction compared to SoC. The inter-reader agreement for image quality and artifact scores was substantial for all subjective measurements on T2WI and DWI. The T2WI(Fast) protocol with DLR(medium) and DWI(Fast) with DLR(low) received the highest qualitative quality score. CONCLUSION: DLR can reduce T2WI and DWI acquisition time and increase SNR and CNR without compromising image quality or altering PI-RADS classification.
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Aprendizado Profundo , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
AIMS: Antimicrobial resistance is one of the highest priorities in global public health with Staphylococcus aureus among the most important microorganisms due to its rapidly evolving antimicrobial resistance. Despite all the efforts of antimicrobial stewardship, research and development of new antimicrobials are still imperative. The thiazolidine ring is considered a privileged structure for the development of new antimicrobials. This study aimed to compare the antibacterial effects of two analogue series of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one against multidrug-resistant Staph. aureus clinical isolates. METHODS AND RESULTS: The derivatives 1a, 2a and 2b exhibited MIC between 1-32 µg ml-1 , with time-to-kill curves showing a bactericidal effect up to 24 h. In the antibiofilm assay, the most active derivatives were able to inhibit about 90% of biofilm formation. The 4-thioxo-thiazolidine-2-one derivatives were more active against planktonic cells, while the thiazolidine-2,4-dione derivatives were able to disrupt about 50% of the preformed biofilm. In the in vivo infection model using Caenorhabditis elegans as a host, the derivatives 1a, 2a and 2b increased nematode survival with a concentration-dependent effect. Exposure of Staph. aureus to the derivatives 2a and 2b induced surface changes and decrease cell size. None of the derivatives was cytotoxic for human peripheral blood mononuclear cells (PBMC) but showed moderate cytotoxicity for L929 fibroblasts. CONCLUSION: The 5-(3,4-dichlorobenzylidene)-4-thioxothiazolidin-2-one (2b) was the most active derivative against Staph. aureus and showed higher selective indices. SIGNIFICANCE AND IMPACT OF THE STUDY: 4-thioxo-thiazolidin-2-one is a promising scaffold for the research and development of new antimicrobial drugs against multidrug-resistant Staph. aureus.
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Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Tiazolidinas/farmacologia , Tiazolidinas/química , Testes de Sensibilidade Microbiana , Leucócitos Mononucleares , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Biofilmes , Anti-Infecciosos/farmacologiaRESUMO
Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license.
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Glioblastoma , Bicarbonatos , Glioblastoma/diagnóstico por imagem , Humanos , Lactato Desidrogenase 5 , Ácido Láctico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Pirúvico/metabolismoRESUMO
The rapid development of multidrug-resistant pathogens against conventional antibiotics is a global public health problem. The irrational use of antibiotics has promoted therapeutic limitations against different infections, making research of new molecules that can be applied to treat infections necessary. Antimicrobial peptides (AMPs) are a class of promising antibiotic molecules as they present broad action spectrum, potent activity, and do not easily induce resistance. Several AMPs from scorpion venoms have been described as a potential source for the development of new drugs; however, some limitations to their application are also observed. Here, we describe strategies used in several approaches to optimize scorpion AMPs, addressing their primary sequence, biotechnological potential, and characteristics that should be considered when developing an AMP derived from scorpion venoms. In addition, this review may contribute towards improving the understanding of rationally designing new molecules, targeting functional AMPs that may have a therapeutic application.
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Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Isótopos de Carbono/análise , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.
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Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Melanoma/diagnóstico por imagem , Melanoma/tratamento farmacológico , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Idoso , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunidade , Masculino , Pessoa de Meia-IdadeRESUMO
Chagas disease is caused by Trypanosoma cruzi and affects thousands of people. Drugs currently used in therapy are toxic and have therapeutic limitations. In addition, the genetic diversity of T. cruzi represents an important variable and challenge in treatment. Sodium diethyldithiocarbamate (DETC) is a compound with pharmacological versatility acting as metal chelators and ROS generation. Thus, the objective was to characterize the antiparasitic action of DETC against different strains and forms of T. cruzi and their mechanism. The different strains of T. cruzi were grown in LIT medium. To evaluate the antiparasitic activity of DETC, epimastigote and trypomastigote forms of T. cruzi were used by resazurin reduction methods and by counting. Different response patterns were obtained between the strains and an IC50 of DETC ranging from 9.44 ± 3,181 to 60.49 ± 7.62 µM. Cell cytotoxicity against 3T3 and RAW cell lines and evaluated by MTT, demonstrated that DETC in high concentration (2222.00 µM) presents low toxicity. Yet, DETC causes mitochondrial damage in T. cruzi, as well as disruption in parasite membrane. DETC has antiparasitic activity against different genotypes and forms of T. cruzi, therefore, representing a promising molecule as a drug for the treatment of Chagas disease.
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Doença de Chagas/parasitologia , Ditiocarb/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacosRESUMO
OBJECTIVE: To determine the accuracy of interpretation of a non-contrast MRI protocol in characterizing adnexal masses. METHODS AND MATERIALS: Two hundred ninety-one patients (350 adnexal masses) who underwent gynecological MRI at our institution between the 1st of January 2008 and the 31st of December 2018 were reviewed. A random subset (102 patients with 121 masses) was chosen to evaluate the reproducibility and repeatability of readers' assessments. Readers evaluated non-contrast MRI scans retrospectively, assigned a 5-point score for the risk of malignancy and gave a specific diagnosis. The reference standard for the diagnosis was histopathology or at least one-year imaging follow-up. Diagnostic accuracy of the non-contrast MRI score was calculated. Inter- and intra-reader agreement was analyzed with Cohen's kappa statistics. RESULTS: There were 53/350 (15.1%) malignant lesions in the whole cohort and 20/121 (16.5%) malignant lesions in the random subset. Good agreement between readers was found for the non-contrast MRI score (к = 0.73, 95% confidence interval [CI] 0.58-0.86) whilst the intra-reader agreement was excellent (к = 0.81, 95% CI 0.70-0.88). The non-contrast MRI score value of ≥ 4 was associated with malignancy with a sensitivity of 84.9%, a specificity of 95.9%, an accuracy of 94.2% and a positive likelihood ratio of 21 (area under the receiver operating curve 0.93, 95% CI 0.90-0.96). CONCLUSION: Adnexal mass characterization on MRI without the administration of contrast medium has a high accuracy and excellent inter- and intra-reader agreement. Our results suggest that non-contrast studies may offer a reasonable diagnostic alternative when the administration of intravenous contrast medium is not possible. KEY POINTS: ⢠A non-contrast pelvic MRI protocol may allow the characterization of adnexal masses with high accuracy. ⢠The non-contrast MRI score may be used in clinical practice for differentiating benign from malignant adnexal lesions when the lack of intravenous contrast medium precludes analysis with the O-RADS MRI score.
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Doenças dos Anexos , Neoplasias Ovarianas , Doenças dos Anexos/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Ovarianas/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
Commiphora leptophloeos (Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of C. leptophloeos against Candida spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of C. leptophloeos stem bark. The extract and the n-butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by 1H NMR and MS analyses. Candida spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the n-butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 µg/mL and were found to significantly reduce the biofilm formed in all the Candida strains investigated. BDP showed a fungicidal potential against strains of Candida spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 µg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant Candida spp. (FICI = 0.31-1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that C. leptophloeos has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in C. leptophloeos, was found to exhibit antifungal effect against Candida spp. either when applied alone or in combination with fluconazole.
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Facilitating clinical translation of quantitative imaging techniques has been suggested as means of improving interobserver agreement and diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) of the prostate. One such technique, magnetic resonance fingerprinting (MRF), has significant competitive advantages over conventional mapping techniques in terms of its multi-site reproducibility, short scanning time and inherent robustness to motion. It has also been shown to improve the detection of clinically significant prostate cancer when added to standard mpMRI sequences, however, the existing studies have all been conducted on 3.0 T MRI systems, limiting the technique's use on 1.5 T MRI scanners that are still more widely used for prostate imaging across the globe. The aim of this proof-of-concept study was, therefore, to evaluate the cross-system reproducibility of prostate MRF T1 in healthy volunteers (HVs) using 1.5 and 3.0 T MRI systems. The initial validation of MRF T1 against gold standard inversion recovery fast spin echo (IR-FSE) T1 in the ISMRM/NIST MRI system revealed a strong linear correlation between phantom-derived MRF and IR-FSE T1 values was observed at both field strengths (R2 = 0.998 at 1.5T and R2 = 0.993 at 3T; p = < 0.0001 for both). In young HVs, inter-scanner CVs demonstrated marginal differences across all tissues with the highest difference of 3% observed in fat (2% at 1.5T vs 5% at 3T). At both field strengths, MRF T1 could confidently differentiate prostate peripheral zone from transition zone, which highlights the high quantitative potential of the technique given the known difficulty of tissue differentiation in this age group. The high cross-system reproducibility of MRF T1 relaxometry of the healthy prostate observed in this preliminary study, therefore, supports the technique's prospective clinical validation as part of larger trials employing 1.5 T MRI systems, which are still widely used clinically for routine mpMRI of the prostate.
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Imageamento por Ressonância Magnética/métodos , Próstata/diagnóstico por imagem , Adulto , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Adulto JovemRESUMO
This study investigates the relationship between collective motion and propulsion of bacterial consortia and their biopolymer production efficiency. Rheological tests were conducted for suspensions of two different methanotrophic bacterial consortia obtained after enrichment of sediment samples from mangrove sites in Brazil. We considered the linear viscoelasticity region and analyzed the values of storage and loss moduli as functions of days of cultivation, for different values of the volume fraction. The suspensions' rheological behaviors reflected the bacterial growth stage. We found that the formation of structures over time in some types of consortia can hinder the movement of bacteria in the search for nutrients. The change in complex viscosity of the two consortia followed a different and rich behavior that appears to be closely related to their capacity to capture methane. Our analysis showed a possible correlation between collective motion, viscosity reduction, and biopolymer production. The pieces of evidence from this study suggest that the efficiency of bacterial motion is directly related to biopolymer production, and this could facilitate the process of identifying the best consortium of biopolymer producing bacteria.
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Bactérias/crescimento & desenvolvimento , Hidroxibutiratos/metabolismo , Metano/metabolismo , Consórcios Microbianos , Poliésteres/metabolismo , ReologiaRESUMO
Magnetic resonance imaging of the pancreas is increasingly used as an important diagnostic modality for characterisation of pancreatic lesions. Pancreatic MRI protocols are mostly qualitative due to time constraints and motion sensitivity. MR Fingerprinting is an innovative acquisition technique that provides qualitative data and quantitative parameter maps from a single free-breathing acquisition with the potential to reduce exam times. This work investigates the feasibility of MRF parameter mapping for pancreatic imaging in the presence of free-breathing exam. Sixteen healthy participants were prospectively imaged using MRF framework. Regions-of-interest were drawn in multiple solid organs including the pancreas and T1 and T2 values determined. MRF T1 and T2 mapping was performed successfully in all participants (acquisition time:2.4-3.6 min). Mean pancreatic T1 values were 37-43% lower than those of the muscle, spleen, and kidney at both 1.5 and 3.0 T. For these organs, the mean pancreatic T2 values were nearly 40% at 1.5 T and < 12% at 3.0 T. The feasibility of MRF at 1.5 T and 3 T was demonstrated in the pancreas. By enabling fast and free-breathing quantitation, MRF has the potential to add value during the clinical characterisation and grading of pathological conditions, such as pancreatitis or cancer.
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Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Pâncreas/diagnóstico por imagem , Respiração , Adulto , Algoritmos , Feminino , Humanos , Masculino , Movimento (Física) , Reconhecimento Automatizado de Padrão , Imagens de Fantasmas , Estudos ProspectivosRESUMO
OBJECTIVE: To introduce capped biparametric (bp) MRI slots for follow-up imaging of prostate cancer patients enrolled in active surveillance (AS) and evaluate the effect on weekly variation in the number of AS cases and total MRI workload. METHODS: Three 20 min bpMRI AS slots on two separate days were introduced at Addenbrooke's Hospital, Cambridge. The weekly numbers of total prostate MRIs and AS cases recorded 15 months before and after the change (Groups 1 and 2, respectively). An intergroup variation in the weekly scan numbers was assessed using the coefficient of variance (CV) and mean absolute deviation; the Mann-Whitney U test was used for an intergroup comparison of the latter. RESULTS: In AS patients, a shift from considerable to moderate variation in weekly scan numbers was observed between the two groups (CV, 51.7 and 26.8%, respectively); mean absolute deviation of AS scans also demonstrated a significant decrease in Group 2 (1.28 vs 2.58 in Group 1; p < 0.001). No significant changes in the variation in total prostate MRIs were observed, despite a 10% increased workload in Group 2. CONCLUSION: A significant reduction in weekly variation of AS cases was demonstrated following the introduction of capped bpMRI slots, which can be used for more accurate long-term planning of MRI workload. ADVANCES IN KNOWLEDGE: The paper illustrates the potential of introducing capped AS MRI slots using a bp protocol to reduce weekly variation in demand and allow for optimising workflow, which will be increasingly important as the demands on radiology departments increase worldwide.
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Imageamento por Ressonância Magnética/estatística & dados numéricos , Vigilância da População , Neoplasias da Próstata/diagnóstico por imagem , Carga de Trabalho/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fatores de TempoRESUMO
Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.
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Neoplasias da Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Isótopos de Carbono/química , Isótopos de Carbono/metabolismo , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Imageamento por Ressonância Magnética/instrumentação , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Ácido Pirúvico/química , Ácido Pirúvico/metabolismo , Simportadores/genética , Simportadores/metabolismoRESUMO
INTRODUCTION: The emergence of minimally invasive techniques has expanded the use of plates and improved their safety for the repair of humeral diaphyseal fractures with proximal extension. In this study, we aimed to determine the best contouring method for long locking plates in the repair of humeral fractures using this approach. PATIENTS AND METHODS: Comparative observations were performed between helical and spiral modelling in plastic models to identify which shape best fits the contours of the humerus. To determine the best shape, we attempted to assess the torsion required for the plate to settle laterally in the greater tuberosity and anteriorly in the diaphyseal region of the humerus. After establishing the best approach, we transferred the method to two anatomical specimens and confirmed the viability of the method and pathways. Additionally, to confirm the clinical applicability of the method, we applied the method in ten patients. RESULTS: After placing the plates in the bone models, it was found that the helical plate was more distant from the bone. On the other hand, the spiral plate achieved better accommodation along the contours of the humerus. The amount of twist was tested at 50°, 70° and 90°. When the plate was twisted at 70°, it maintained contact with the greater tuberosity proximally and the anterior cortical diaphyseal region. Eight patients completed the follow-up. Radiographic consolidation and good functional outcomes were achieved in all patients. CONCLUSIONS: Spiral modelling at 70° allows anatomical accommodation at the greater tuberosity proximally and in the diaphyseal region.
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Placas Ósseas , Fixação Interna de Fraturas , Fraturas do Úmero/cirurgia , Ajuste de Prótese/métodos , Amplitude de Movimento Articular , Articulação do Ombro , Diáfises/lesões , Diáfises/cirurgia , Desenho de Equipamento , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Humanos , Modelos Anatômicos , Avaliação de Resultados em Cuidados de Saúde , Radiografia/métodos , Recuperação de Função Fisiológica , Lesões do Ombro , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologiaRESUMO
Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variation-results similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.
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Substituição de Aminoácidos , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Venenos de Escorpião/genética , Trypanosoma cruzi/efeitos dos fármacos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Dicroísmo Circular , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Modelos Moleculares , Simulação de Dinâmica Molecular , Estabilidade Proteica , Estrutura Secundária de Proteína , Venenos de Escorpião/química , Tripanossomicidas/química , Tripanossomicidas/farmacologiaRESUMO
Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variationresults similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.
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Scorpion venom constitutes a rich source of biologically active compounds with high potential for therapeutic and biotechnological applications that can be used as prototypes for the design of new drugs. The aim of this study was to characterize the structural conformation, evaluate the antimicrobial activity, and gain insight into the possible action mechanism underlying it, for two new analog peptides of the scorpion peptide Stigmurin, named StigA25 and StigA31. The amino acid substitutions in the native sequence for lysine residues resulted in peptides with higher positive net charge and hydrophobicity, with an increase in the theoretical helical content. StigA25 and StigA31 showed the capacity to modify their structural conformation according to the environment, and were stable to pH and temperature variationresults similar to the native peptide. Both analog peptides demonstrated broad-spectrum antimicrobial activity in vitro, showing an effect superior to that of the native peptide, being non-hemolytic at the biologically active concentrations. Therefore, this study demonstrates the therapeutic potential of the analog peptides from Stigmurin and the promising approach of rational drug design based on scorpion venom peptide to obtain new anti-infective agents.
RESUMO
Motor coordination and physical fitness are multidimensional concepts which cannot be reduced to a single variable. This study evaluated multivariate relationships among morphology, physical fitness and motor coordination in 74 pre-pubertal girls 8.0-8.9 years of age. Data included body dimensions, eight fitness items and four motor coordination tasks (KTK battery). Maturity status was estimated as percentage of predicted mature stature attained at the time of observation. Canonical correlation analysis was used to examine the relationships between multivariate domains. Significant pairs of linear functions between indicators of morphology and fitness (rc = 0.778, Wilks' Lambda = 0.175), and between fitness and motor coordination (rc = 0.765, Wilks' Lambda = 0.289) were identified. Girls who were lighter and had a lower waist-to-stature ratio and % fat mass attained better scores in the endurance run, sit-ups and standing long jump tests, but poorer performances in hand grip strength and 2-kg ball throw. Better fitness test scores were also associated with better motor coordination scores. Relationships between body size and estimated fatness with motor fitness suggested an inverse relationship that was particularly evident in performance items that required the displacement of the body through space, while motor coordination was more closely related with fitness than with somatic variables.
Assuntos
Força da Mão , Destreza Motora , Aptidão Física , Índice de Massa Corporal , Criança , Feminino , Humanos , Resistência Física , Razão Cintura-EstaturaRESUMO
Fogo é necessário para a humanidade, entretanto, muitas vezes, fica fora de controle e passa a ser um agente causador de incêndios, destruição do meio ambiente e mortes, seja na área urbana ou na área rural. Os extintores de incêndio são aparelhos destinados a combater o princípio de incêndio. O objetivo deste estudo foi verificar, nos estabelecimentos comerciais de Vitória da Conquista, Bahia, Brasil, se os extintores portáteis de combate a incêndio estão instalados de acordo com as normas vigentes de proteção, enfatizando a instalação, a visibilidade e se estão desobstruídos. Trata-se de um estudo exploratório descritivo, com abordagem qualitativa, executado mediante a técnica de observação, que envolveu 30 estabelecimentos comerciais. Utilizou-se a técnica de observação descritiva, por ser uma importante fonte de coleta de informações sobre o objeto de análise proposto os extintores portáteis de incêndio. Os resultados mostraram que todos os estabelecimentos comerciais observados tinham extintores. Todos eles (100%) estavam obstruídos e 80% sem sinalização. Concluiu-se que os extintores de incêndio dos 30 estabelecimentos comerciais de Vitória da Conquista encontravam-se em desacordo com as normas vigentes, no tocante à instalação, localização, sinalização, visibilidade e desobstrução.
Fire is a necessity to mankind. However, fire is also a threat because when out of control it causes deaths, destructions and damages to rural and urban environments. Fire extinguishers are equipment used to fight the beginning of fire. The objective of this study was to verify whether the portabel fire extinguishers installed in the commercial buildings of Vitória da Conquista, Bahia, Brasil are in compliance to regulatory norms with emphasis on installation, visibility and unblock aspects. It´s a descriptive exploratory study with a qualitative approach, executed through the technique of observation, comprising 30 commercial buildings. It was used the technique of descriptive observation because this is an important source of information collection about the subject under analysis - portable fire extinguishers. The results shows that all observed commercial buildings have extinguishers installed. All of them (100%) were obstructed and 80% have no indication of safety sign. It was possible to conclude that the fire extinguishers of the 30 commercial establishments of Vitória da Conquista were not compliance to regulatory norms regarding installation, localization, signalization, visibility and unblock.
Fuego es necesario para la humanidad, todavía, cuando fuera de control, provoca incendios, destrucción del medio ambiente y muertes tanto en áreas urbanas como rurales. Los extintores son aparatos que se destinan al combate del principio de incendio. El objetivo de este trabajo fue averiguar en los establecimientos comerciales de Vitória da Conquista, Bahia, Brasil, si los extintores portátiles de combate a incendio están instalados en consonancia con las normas reglamentares, con énfasis en aspectos relacionados con la instalación, con la visibilidad y con la desobstrucción. Tratase de un estudio exploratorio descriptivo, con abordaje cualitativo, ejecutado mediante la técnica de observación, que envolvió 30 estabelecimientos comerciales. Fue utilizada la técnica de observación descriptiva por ser una importante fuente de recopilación de informaciones sobre el objeto de análisis propuesto los extintores portátiles de incendio. Los resultados muestran que todos los estabelecimientos comerciales observados tenían extintores. Pero, el 100% de estos estaban obstruidos y el 80% no estaban señalizados. Concluyóse que la los extintores de incendio de los 30 establecimientos comerciales de Vitória da Conquista estaban en desacuerdo con las normas reglamentares en lo que se refiere a la instalación, localización, señalización, visibilidad y desobstrucción.