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The delay in making a correct diagnosis of Candida auris causes concern in the healthcare system setting, and immunoproteomics studies are important to identify immunoreactive proteins for new diagnostic strategies. In this study, immunocompetent murine systemic infections caused by non-aggregative and aggregative phenotypes of C. auris and by Candida albicans and Candida haemulonii were carried out, and the obtained sera were used to study their immunoreactivity against C. auris proteins. The results showed higher virulence, in terms of infection signs, weight loss, and histopathological damage, of the non-aggregative isolate. Moreover, C. auris was less virulent than C. albicans but more than C. haemulonii. Regarding the immunoproteomics study, 13 spots recognized by sera from mice infected with both C. auris phenotypes and analyzed by mass spectrometry corresponded to enolase, phosphoglycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase. These four proteins were also recognized by sera obtained from human patients with disseminated C. auris infection but not by sera obtained from mice infected with C. albicans or Aspergillus fumigatus. Spot identification data are available via ProteomeXchange with the identifier PXD049077. In conclusion, this study showed that the identified proteins could be potential candidates to be studied as new diagnostic or even therapeutic targets for C. auris.
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Candida , Candidíase , Imunoglobulina G , Animais , Camundongos , Candida/imunologia , Candida/patogenicidade , Humanos , Candidíase/imunologia , Candidíase/microbiologia , Candidíase/sangue , Imunoglobulina G/sangue , Antígenos de Fungos/imunologia , Antígenos de Fungos/sangue , Proteômica/métodos , Candida albicans/imunologia , Candida albicans/patogenicidade , Proteínas Fúngicas/imunologia , Fosfoglicerato Mutase/imunologia , Fosfoglicerato Quinase/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/imunologia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Anticorpos Antifúngicos/sangue , Anticorpos Antifúngicos/imunologia , Feminino , VirulênciaRESUMO
PURPOSE: Recurrence for high-grade gliomas is inevitable despite maximal safe resection and adjuvant chemoradiation, and current imaging techniques fall short in predicting future progression. However, we introduce a novel whole-brain magnetic resonance spectroscopy (WB-MRS) protocol that delves into the intricacies of tumor microenvironments, offering a comprehensive understanding of glioma progression to inform expectant surgical and adjuvant intervention. METHODS: We investigated five locoregional tumor metabolites in a post-treatment population and applied machine learning (ML) techniques to analyze key relationships within seven regions of interest: contralateral normal-appearing white matter (NAWM), fluid-attenuated inversion recovery (FLAIR), contrast-enhancing tumor at time of WB-MRS (Tumor), areas of future recurrence (AFR), whole-brain healthy (WBH), non-progressive FLAIR (NPF), and progressive FLAIR (PF). Five supervised ML classification models and a neural network were developed, optimized, trained, tested, and validated. Lastly, a web application was developed to host our novel calculator, the Miami Glioma Prediction Map (MGPM), for open-source interaction. RESULTS: Sixteen patients with histopathological confirmation of high-grade glioma prior to WB-MRS were included in this study, totaling 118,922 whole-brain voxels. ML models successfully differentiated normal-appearing white matter from tumor and future progression. Notably, the highest performing ML model predicted glioma progression within fluid-attenuated inversion recovery (FLAIR) signal in the post-treatment setting (mean AUC = 0.86), with Cho/Cr as the most important feature. CONCLUSIONS: This study marks a significant milestone as the first of its kind to unveil radiographic occult glioma progression in post-treatment gliomas within 8 months of discovery. These findings underscore the utility of ML-based WB-MRS growth predictions, presenting a promising avenue for the guidance of early treatment decision-making. This research represents a crucial advancement in predicting the timing and location of glioblastoma recurrence, which can inform treatment decisions to improve patient outcomes.
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The selection of a "perfect tool" for the theoretical determination of acid-base dissociation constants (Ka) is still puzzling. Recently, we developed a user-friendly model exploiting CAM-B3LYP for determining pKa with impressive reliability. Herein, a new challenge is faced, examining a panel of functionals belonging to different rungs of the "Jacob's ladder" organization, which classifies functionals according to their level of theory. Specifically, meta-generalized gradient approximations (GGAs), hybrid-GGAs, and the more complex range-separated hybrid (RSH)-GGAs were investigated in predicting the pKa of differently substituted carboxylic acids. Therefore, CAM-B3LYP, WB97XD, B3PW91, PBE1PBE, PBEPBE and TPSSTPSS were used, with 6-311G+(d,p) as the basis set and the solvation model based on density (SMD). CAM-B3LYP showed the lowest mean absolute error value (MAE = 0.23) with relatively high processing time. PBE1PBE and B3PW91 provided satisfactory predictions (MAE = 0.34 and 0.38, respectively) with moderate computational time cost, while PBEPBE, TPSSTPSS and WB97XD led to unreliable results (MAE > 1). These findings validate the reliability of our model in predicting carboxylic acids pKa, with MAE well below 0.5 units, using a simplistic theoretical level and a low-cost computational approach.
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PURPOSE: To assess and compare the diagnostic accuracy of whole-body (WB) DW-MRI with 2-[18F]FDG PET for staging and treatment monitoring of children with Langerhans cell histiocytosis (LCH). METHODS: Twenty-three children with LCH underwent 2-[18F]FDG PET and WB DW-MRI at baseline. Two nuclear medicine physicians and two radiologists independently assessed presence/absence of tumors in 8 anatomical areas. Sixteen children also performed 2-[18F]FDG PET and WB DW-MRI at follow-up. One radiologist and one nuclear medicine physician revised follow-up scans and collected changes in tumor apparent diffusion (ADC) and standardized uptake values (SUV) before and after therapy in all detectable lesions. 2-[18F]FDG PET results were considered the standard of reference for tumor detection and evaluation of treatment response according to Lugano criteria. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of WB DW-MRI at baseline were calculated, and the 95% confidence intervals were estimated by using the Clopper-Pearson (exact) method; changes in tumor SUVs and ADC were compared using a Mann-Whitney U test. Agreement between reviewers was assessed with a Cohen's weighted kappa coefficient. Analyses were conducted using SAS software version 9.4. RESULTS: Agreement between reviewers was perfect (kappa coefficient = 1) for all analyzed regions but spine and neck (kappa coefficient = 0.89 and 0.83, respectively) for 2-[18F]FDG PET images, and abdomen and pelvis (kappa coefficient = 0.65 and 0.88, respectively) for WB DW-MRI. Sensitivity and specificity were 95.5% and 100% for WB DW-MRI compared to 2-[18F]FDG PET. Pre to post-treatment changes in SUVratio and ADCmean were inversely correlated for all lesions (r: -0.27, p = 0·06) and significantly different between responders and non-responders to chemotherapy (p = 0.0006 and p = 0·003 for SUVratio and ADCmean, respectively). CONCLUSION: Our study showed that WB DW-MRI has similar accuracy to 2-[18F]FDG PET for staging and treatment monitoring of LCH in children. While 2-[18F]FDG PET remains an approved radiological examination for assessing metabolically active disease, WB DW-MRI could be considered as an alternative approach without radiation exposure. The combination of both modalities might have advantages over either approach alone.
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Histiocitose de Células de Langerhans , Neoplasias , Humanos , Criança , Fluordesoxiglucose F18 , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Compostos Radiofarmacêuticos , Imagem Corporal Total/métodos , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/terapia , Tomografia por Emissão de Pósitrons/métodos , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: Radiographic skeletal survey (R-SS) is the standard imaging technique for the initial staging of Langerhans cell histiocytosis (LCH). Whole-body magnetic resonance imaging (WB-MRI) has been proposed as an effective, radiation-free alternative. METHODS: We prospectively assessed patients with LCH followed at three tertiary centers in Italy and Austria. Two national study protocols were independently designed, and data were then pooled to increase the power of their findings. R-SS and WB-MRI were performed at diagnosis and repeated at the follow-up to confirm the nature of the identified lesions and to study their evolution. RESULTS: Data from 67 patients were analyzed (52 from Italy and 15 from Austria). Compared to R-SS, WB-MRI identified 29 additional skeletal lesions in 14 patients (including two false-positive lesions). Two skeletal lesions were detected at R-SS and missed at WB-MRI (false negative). Per-lesion sensitivity rates were 78.6% (95% CI: 71.0-85.9) for R-SS and 98.4% (95% CI: 94.4-99.8) for WB-MRI, respectively. Based on WB-MRI findings, six patients would have been upstaged to a higher risk class than staging with R-SS. CONCLUSIONS: WB-MRI had a significantly higher detection rate for skeletal lesions compared to R-SS. Clinical and radiology expertise is required to avoid upstaging and overtreatment.
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Doenças Ósseas , Histiocitose de Células de Langerhans , Humanos , Criança , Adulto Jovem , Imageamento por Ressonância Magnética/métodos , Imagem Corporal Total/métodos , Radiografia , Histiocitose de Células de Langerhans/diagnóstico por imagem , Estadiamento de Neoplasias , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Whole body magnetic resonance imaging (WB-MRI) is a promising emerging imaging technology for detecting bone and soft tissue pathology, especially in the onco-hematological field. This study aims to evaluate cancer patients' experience of WB-MRI performed on a 3T scanner compared to other diagnostic total body examinations. MATERIAL AND METHOD: In this prospective committee-approved study, patients completed a questionnaire in person (n = 134) after undergoing a WB-MRI scan to collect data on their physical and psychological reactions during the scan, the global satisfaction level, and preference for other types of MRI or computed tomography (CT), or positron emission tomography (PET/CT). Of all patients who had performed a CT or PET/CT the previous year, 61.9% had already undergone an MRI. The most common symptoms reported were: 38.1% perceived a localized increase in temperature and 34.4% numbness and tingling of the limbs. The scan time averaged 45 min and was well tolerated by most patients (112, 85.5%). Overall, WB-MRI was appreciated by the majority (121/134-90.3%) of patients who said they would probably undergo the procedure again. Patients preferred the WB-MRI in 68.7% of cases (92/134), followed by CT in 15.7% of cases (21/134) and by PET/CT in 7.4% (10/134), with 8.4% (11/134) of patients without any preference. The preference for imaging modalities was age-dependent (p = 0.011), while (p > 0.05) was independent of sex and a primary cancer site. CONCLUSION: These results demonstrate a high degree of WB-MRI acceptance from a patient's point of view.
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Neoplasias , Radiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Imagem Corporal Total/métodos , Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Assistência Centrada no Paciente , Fluordesoxiglucose F18 , Estadiamento de NeoplasiasRESUMO
Whole-body magnetic resonance imaging (WB-MRI) is an all-in-one non-invasive technique that can be used also in early cancer diagnosis in asymptomatic individuals. The aim of this work was to identify the personal characteristics predicting the satisfaction for the WB-MRI in a sample of healthy subjects. Before undergoing a WB-MRI examination, 154 participants completed a questionnaire covering sociodemographics (age, gender, education), personality traits (agreeableness, conscientiousness, emotional stability, extroversion, openness), and expectations about the procedure (expected usefulness, risks, noise, lack of air, duration). After the examination, participants reported their satisfaction with the WB-MRI. Results showed that agreeableness had a significant and positive effect on satisfaction. Expectations about its utility and the possible noise had a positive effect on satisfaction. Expectations of lack of air showed a negative significant effect on satisfaction. Sociodemographics showed no significant effects. Our study confirmed the important impact of individuals' personality and expectations on satisfaction with the procedure. Moreover, it provides useful insights for developing consultations aimed at increasing the acceptability of the procedure.
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Detecção Precoce de Câncer , Neoplasias , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/psicologia , Imagem Corporal Total/métodos , Imagem Corporal Total/psicologia , Satisfação PessoalRESUMO
Boron presents an important role in chemistry, biology, and materials science. Diatomic transition-metal borides (MBs) are the building blocks of many complexes and materials, and they present unique electronic structures with interesting and peculiar properties and a variety of bonding schemes which are analyzed here. In the first part of this paper, we present a review on the available experimental and theoretical studies on the first-row-transition-metal borides, i.e., ScB, TiB, VB, CrB, MnB, FeB, CoB, NiB, CuB, and ZnB; the second-row-transition-metal borides, i.e., YB, ZrB, NbB, MoB, TcB, RuB, RhB, PdB, AgB, and CdB; and the third-row-transition-metal borides, i.e., LaB, HfB, TaB, WB, ReB, OsB, IrB, PtB, AuB, and HgB. Consequently, in the second part, the second- and third-row MBs are studied via DFT calculations using the B3LYP, TPSSh, and MN15 functionals and, in some cases, via multi-reference methods, MRCISD+Q, in conjunction with the aug-cc-pVQZ-PPM/aug-cc-pVQZB basis sets. Specifically, bond distances, dissociation energies, frequencies, dipole moments, and natural NPA charges are reported. Comparisons between MB molecules along the three rows are presented, and their differences and similarities are analyzed. The bonding of the diatomic borides is also described; it is found that, apart from RhB(X1Σ+), which was just recently found to form quadruple bonds, RuB(X2Δ) and TcB(X3Σ-) also form quadruple σ2σ2π2π2 bonds in their X states. Moreover, to fill the gap existing in the current literature, here, we calculate the TcB molecule.
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BACKGROUND: Restraint and seclusion continue to be used with patients demonstrating aggressive and violent behaviors while in the emergency department and as inpatients in behavioral health (BH) units. The use of sensory interventions such as the weighted blanket (WB) is garnering interest as alternatives to aid in managing anxiety, anger, and aggressive behaviors. Reports of the effectiveness of the WB have primarily been anecdotal, and results of research with children have been mixed. Only one study has been conducted with the WB with adults on an inpatient psychiatric unit. AIMS: The aim of this pilot study was to assess the effectiveness of the WB by determining whether it decreases anxiety and/or anger in adult emergency department patients with preexisting psychiatric diagnoses. METHODS: The study used a quasi-experimental, nonequivalent control group design with pre- and posttests for anxiety and anger. The intervention was a 15-pound WB. Participants (N = 15) were in one of three groups, which included no weighted blanket (NWB), WB for 15 minutes, or WB for 30 minutes. RESULTS: All three groups showed a decrease in anxiety and anger scores. However, participants in the WB groups had a greater decrease in anxiety and anger posttest scores. CONCLUSIONS: The small sample size in this study did not allow for the determination of any differences between groups on anxiety or anger scores that could be viewed as a significant finding.
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Agressão , Pacientes Internados , Adulto , Criança , Humanos , Projetos Piloto , Ansiedade , Serviço Hospitalar de EmergênciaRESUMO
The combination of strength training with complementary whole-body electromyostimulation (WB-EMS) and plyometric exercises has been shown to increase strength and jumping performance in athletes. In elite sport, however, the mesocycles of training are often organized according to block periodization. Furthermore, WB-EMS is often applied onto static strength exercises, which may hamper the transfer into more sport-specific tasks. Thus, this study aimed at investigating whether four weeks of strength training with complementary dynamic vs. static WB-EMS followed by a four-week block of plyometric training increases maximal strength and jumping performance. A total of n = 26 (13 female/13 male) trained adults (20.8 ± 2.2 years, 69.5 ± 9.5kg, 9.7 ± 6.1h of training/w) were randomly assigned to a static (STA) or volume-, load- and work-to-rest-ratio-matched dynamic training group (DYN). Before (PRE), after four weeks (three times weekly) of WB-EMS training (MID) and a subsequent four-week block (twice weekly) of plyometric training (POST), maximal voluntary contraction (MVC) at leg extension (LE), leg curl (LC) and leg press machines (LP) and jumping performance (SJ, Squat Jump; CMJ, counter-movement-jump; DJ, drop-jump) were assessed. Furthermore, perceived effort (RPE) was rated for each set and subsequently averaged for each session. MVC at LP notably increased between PRE and POST in both STA (2335 ± 539 vs. 2653 ± 659N, standardized mean difference [SMD] = 0.528) and DYN (2483 ± 714N vs. 2885 ± 843N, SMD = 0.515). Reactive strength index of DJ showed significant differences between STA and DYN at MID (162.2 ± 26.4 vs. 123.1 ± 26.5 cm·s-1, p = 0.002, SMD = 1.478) and POST (166.1 ± 28.0 vs. 136.2 ± 31.7 cm·s-1, p = 0.02, SMD = 0.997). Furthermore, there was a significant effect for RPE, with STA rating perceived effort higher than DYN (6.76 ± 0.32 vs. 6.33 ± 0.47 a.u., p = 0.013, SMD = 1.058). When employing a training block of high-density WB-EMS both static and dynamic exercises lead to similar adaptations.
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Terapia por Estimulação Elétrica , Treinamento Resistido , Adulto , Humanos , Masculino , Feminino , Exercício Físico/fisiologia , Terapia por Exercício , Levantamento de PesoRESUMO
Wheat bran (WB), a low-cost industrial by-product, is a vital source of high-quality proteins, minerals, vitamins, and several bioactive compounds. The present study encompasses the identification of appropriate bran streams of a commercial roller flour mill (CRFM) essentially based on hector liter weight, (HLW), optimization of WB protein isolation process, amino acid characterization, rendering more emphasis on simple water-soluble albumins, having higher commercial viability, and its application in food formulation. Total WB protein was 16.18% protein, the sum of the extracted proteins viz. albumin (2.43%), a prolamin (2.47%), glutelin (5.25%), globulin (1.92%), and insoluble proteins (4.09%) was 12.08%. Following albumin extraction, residual WB was subjected to ultra-sonication which further increased albumin protein yield from 2.43 to 3.07%. The extracted WB albumin isolate (WBAI) was utilized to develop high protein bread having significantly high volume and protein content, compared to control bread. The structural and sensorial attributes of the developed bread were superior compared to control bread. Thus, WBAI has a tremendous scope as a natural, affordable potential inexpensive food improver/fortificant to address protein-energy malnutrition (PEM). The process has the great advantage of being eco-friendly, besides, residual bran can still be used as cattle feed, enhancing profitability and viability.
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BACKGROUND: There is increasing interest in leukoreduced whole blood (WB) as a transfusion product for trauma patients. In some jurisdictions, few leukoreduced filters are approved or appropriate for WB leukoreduction and quality information is therefore limited. This study assessed the impact of filtration timing of WB collected in CPDA-1 versus CPD on in vitro quality. STUDY DESIGN AND METHODS: WB was collected in CPDA-1 or CPD and leukoreduction filtered either after 3-8 h (early) or 18-24 h (late) from stop bleed time. In vitro quality was assessed after filtration and throughout 5 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation. RESULTS: Although there were some data points which showed statistically significant differences associated with anticoagulant choices or the filtration timing, no general trend in inferiority/performance could be discerned. After 35 days' storage, only clotting time, alpha angle and factor II in the early filtration arm comparing anticoagulants and prothrombin time and factor II in the CPDA-1 study arm comparing filtration timing showed a significant difference. CONCLUSION: In vitro WB quality seems to be independent on the choice of anticoagulant and filtration timing supporting WB hold-times to up to 24 h, increasing operational flexibility for transfusion services.
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Preservação de Sangue , Procedimentos de Redução de Leucócitos , Anticoagulantes/metabolismo , Anticoagulantes/farmacologia , Plaquetas/metabolismo , Humanos , ProtrombinaRESUMO
The starch in waste bread (WB) from industrial sandwich production was directly converted to ethanol by an amylolytic, ethanologenic thermophile (Parageobacillus thermoglucosidasius strain TM333) under 5 different simultaneous saccharification and fermentation (SSF) regimes. Crude α-amylase from TM333 was used alone or in the presence of amyloglucosidase (AMG), a starch monomerizing enzyme used in industry, with/without prior gelatinisation/liquefaction treatments and P. thermoglucosidasius TM333 fermentation compared with Saccharomyces cerevisiae as a control. Results suggest that TM333 can ferment WB using SSF with yields of 94-100% of theoretical (based on all sugars in WB) in 48 h without the need for AMG addition or any form of heat pre-treatment. This indicates that TM333 can transport and ferment all of the malto-oligosaccharides generated by its α-amylase. In the yeast control experiments, addition of AMG together with the crude α-amylase was necessary for full fermentation over the same time period. This suggests that industrial fermentation of WB starch to bio-ethanol or other products using an enhanced amylolytic P. thermoglucosidasius strain could offer significant cost savings compared to alternatives requiring enzyme supplementation.
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Pão , Glucana 1,4-alfa-Glucosidase , Fermentação , Amilases , alfa-Amilases , Amido , Etanol , Saccharomyces cerevisiaeRESUMO
The majority of leptospirosis is subclinical or mild self-limiting systemic illness. A rapid and accurate diagnostic test for the detection of leptospirosis is essential to prevent disease progression from acute non-severe illness to potentially fatal infection. Rapid diagnostic tests (RDTs) recognized as point-of-care (PoC) tests may support clinical decision-making in resource-poor settings. We aimed to assess the accuracy of PoC (Leptocheck-WB) for the detection of acute leptospirosis by meta-analysis of data from eligible studies. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guideline. The pooling of data was done only when there were two or more studies that used a particular type of reference test. A total of ten studies (n = 5369) were identified. The majority (70%) were from the Asian region. Using microscopic agglutination test (MAT) as reference test, the pooled sensitivity (0.75, 95% CI: 0.64 to 0.84, 10 studies, I2: 85.9%) and specificity (0.87, 95% CI: 0.77 to 0.94, 10 studies, I2: 97.37%) of Leptocheck-WB in the detection of leptospirosis were moderate. With the use of enzyme-linked immunosorbent assay (ELISA) reference test, the pooled sensitivity 0.85 (95% CI: 0.79 to 0.9, 4 studies, I2: 27.49%) and specificity 0.79 (95% CI: 0.71 to 0.85, 4 studies, I2: 58.9%) of Leptocheck-WB were also moderate. Diagnostic odds ratio of Leptocheck-WB with MAT (21, 95% CI: 10-44) or with ELISA as reference test (21, 95% CI: 9-46) showed an acceptable level of accuracy. Meta-regression analysis showed methodological quality of studies (p: 0.06) and study design (p: 0.09) were potential factors that affected the accuracy of Leptocheck-WB test. Findings suggest that Leptocheck-WB has a moderate level of acceptance for detection of acute leptospirosis. Further confirmation with large-sampled, prospectively designed studies using the same samples for evaluating test accuracy is recommended.
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Testes Diagnósticos de Rotina , Leptospirose , Anticorpos Antibacterianos , Ensaio de Imunoadsorção Enzimática , Humanos , Leptospirose/diagnóstico , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This study aims to investigate the effect of Bacillus subtilis WB800N on diabetic wounds. METHODS: Haematoxylin & eosin (H&E) staining was used to observe the healing of skin wounds. Collagen deposition was assessed by Masson staining. Western blotting and qRT-PCR were used to detect vascular endothelial-related factors (VWF), CD31, TLR2, NLRP3, ASC and Caspase-1 expression. 16S rDNA sequencing detected microbiota distribution. The concentrations of IL-1ß and IL-37 were measured by ELISA. Apoptosis was measured by the TUNEL assay. RESULTS: Compared with the control group, wound healing was delayed in diabetic mice. The wound area in the Bacillus subtilis group decreased more significantly than the diabetic wound group. H&E staining showed that Bacillus subtilis WB800N promoted wound healing and increased re-epithelialization. Masson staining showed that Bacillus subtilis WB800N increased collagen deposition in mice with diabetic wounds. Bacillus subtilis WB800N upregulated VWF and CD31 protein expression in diabetic wounds mice. The 16S rDNA results showed that Bacillus subtilis WB800N reduced the diversity of the gut microbiota of diabetic wounds mice and regulated the microbial composition. At the genus level, Bacillus subtilis WB800N reduced the relative abundance of Muribaculaceae and CG - 005 in diabetic wounds mice, whilst increasing the relative abundance of Lactobacillus. Bacillus subtilis WB800N increased the expression of TLR2, NLRP3, ASC and Caspase-1. Bacillus subtilis WB800N increased the concentrations of IL-1ß and IL-37 in serum. Bacillus subtilis WB800N upregulated cell apoptosis. The TLR2 antagonist Sparstolonin B (SsnB) reduced the expression of TLR2, NLRP3, ASC, Caspase-1, IL-1ß and IL-37 and the apoptosis in diabetic wounds mice, whilst the combined intervention of Bacillus subtilis and SsnB reversed the effect of SsnB treatment alone. CONCLUSION: Bacillus subtilis WB800N alleviated diabetic wound healing by regulating gut microbiota homeostasis and TLR2. SIGNIFICANCE AND IMPACT OF RESEARCH: Our findings might provide potential therapeutic targets for diabetic wounds.
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Diabetes Mellitus Experimental , Microbioma Gastrointestinal , Receptor 2 Toll-Like , Animais , Bacillus subtilis/genética , Caspases , DNA Ribossômico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/terapia , Homeostase , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Receptor 2 Toll-Like/genética , Fator de von WillebrandRESUMO
This study aimed to investigate the effects of different exercise training programs on fasting plasma levels of oxylipins, endocannabinoids (eCBs), and eCBs-like molecules in middle-aged sedentary adults. A 12-week randomized controlled trial was conducted using a parallel group design. Sixty-five middle-aged adults (40-65 years old) were randomly assigned to: (a) no exercise (control group), (b) concurrent training based on international physical activity recommendations (PAR group), (c) high-intensity interval training (HIIT group), and (d) HIIT together with whole-body electromyostimulation (HIIT + EMS group). Plasma levels of oxylipins, eCBs, and eCBs-like molecules were determined in plasma samples before and after the intervention using targeted lipidomics. Body composition was assessed through dual-energy X-ray absorptiometry, and dietary intake through a food frequency questionnaire and three nonconsecutive 24-hr recalls. The physical activity recommendations, HIIT, and HIIT-EMS groups showed decreased plasma levels of omega-6 and omega-3-derived oxylipins, and eCBs and eCBs-like molecules after 12 weeks (all Δ ≤ -0.12; all p < .05). Importantly, after Bonferroni post hoc corrections, the differences in plasma levels of omega-6 and omega-3 oxylipins were not statistically significant compared with the control group (all p > .05). However, after post hoc corrections, plasma levels of anandamide and oleoylethanolamide were increased in the physical activity recommendations group compared with the control group (anandamide: Δ = 0.05 vs. -0.09; oleoylethanolamide: Δ = -0.12 vs. 0.013, all p ≤ .049). In conclusion, this study reports that a 12-week exercise training intervention, independent of the modality applied, does not modify fasting plasma levels of omega-6 and omega-3 oxylipins, eCBs, and eCBs-like molecules in middle-aged sedentary adults.
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Treinamento Intervalado de Alta Intensidade , Oxilipinas , Adulto , Idoso , Endocanabinoides , Exercício Físico/fisiologia , Jejum , Humanos , Pessoa de Meia-IdadeRESUMO
This article reviews Bretton Woods Institutions' approach to public services, including during the recent COVID-19 crisis. Drawing on the specific case of IMF and World Bank's response to the multiple crisis triggered by the pandemic, it shows that there is a discourse-practice disjuncture in the institutions approach to public services as they continue to favour austerity and market-oriented solutions for the delivery of public services. The article therefore seeks to demystify the Bretton Woods institutions rhetoric and demand the adoption of a different way of understanding public services, and social policy more broadly.
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BACKGROUND: Leukoreduced whole blood (LR-WB) has received renewed attention as alternative to component-based transfusion in trauma. According to the manufacturer's instructions, leukoreduction should be carried out within 8 h after collection. This study assessed impact of (1) WB collection bag, (2) LR filtration, and (3) timing of filtration on in vitro quality. STUDY DESIGN AND METHODS: WB collected into different vendor bags was held at room temperature for <8 h or >16 h but <24 h prior to LR. In vitro quality was assessed before and after filtration, and throughout 3 weeks of storage at 4°C. Cell count and hemoglobin levels were determined by hematology analyzer, platelet activation, and responsiveness to ADP by surface expression of P-selectin by flow cytometry, hemolysis by HemoCue, and metabolic parameters by blood gas analyzer. Hemostatic properties were assessed by rotational thromboelastometry. Plasma protein activities and clotting times were determined by automated coagulation analyzer or quantitative immunoblotting. RESULTS: Bag type had no impact on WB in vitro quality. LR by filtration had some impact, but is aligned with data in the literature. The time between donation and filtration resulted in some statistically significant differences in metabolic activity, platelet yield, platelet activation, and factor protein activity initially; however, these differences in in vitro quality attributes decreased throughout 21-day cold storage. CONCLUSION: WB hold time showed only a minor impact on WB in vitro quality, so it may be possible for blood processing facilities to explore extended hold times prior to filtration in order to provide greater operational flexibility.
Assuntos
Preservação de Sangue/métodos , Contagem de Células Sanguíneas , Temperatura Baixa , Hemólise , Hemostasia , Humanos , Procedimentos de Redução de Leucócitos/métodos , Ativação Plaquetária , TromboelastografiaRESUMO
BACKGROUND: The use of whole blood (WB) to treat trauma patients is becoming more common. Similar to the treatment of individual components, pathogen inactivation (PI) technologies are available to treat WB. The impact of PI on WB function is not well understood. This study investigated the impact of PI of WB with riboflavin/ultraviolet (UV) light on its hemostatic function by modeling transfusion scenarios for trauma patients and assessing transfusion efficacy by rotational thromboelastometry (ROTEM). As fibrinogen is affected by PI of WB, the effect of fibrinogen supplementation commonly used in trauma patients was also analyzed in this model. STUDY DESIGN AND METHODS: Trauma transfusion scenarios were simulated by mixing untreated WB or WB treated with the Mirasol PI technology (riboflavin/UV) in different ratios with hemodiluted blood, and the thromboelasticity was monitored by ROTEM. The impact of supplementation with the fibrinogen concentrate RiaSTAP was investigated in this model. RESULTS: Pathogen-inactivated WB (PI-WB) showed decreased activity in the hemostatic profile compared to the untreated control. Hemodiluted blood at a hematocrit (hct) of 20%, which was reconstituted with PI-WB or untreated WB, exhibited increased alpha values, maximum clot firmness, and clot formation time. Simulating transfusion scenarios by blood replacement with PI-WB resulted in a significant difference in ROTEM parameters between reconstituted PI-treated and -untreated WB (p ≥ .05). The effect of PI treatment waned when PI-WB was enriched with fibrinogen. CONCLUSION: ROTEM investigations suggest that PI treatment has a negative impact on WB clot formation unless fibrinogen supplementation is used.
Assuntos
Coagulação Sanguínea , Segurança do Sangue/métodos , Transfusão de Sangue , Fibrinogênio/uso terapêutico , Ferimentos e Lesões/terapia , Transfusão de Sangue/métodos , Fibrinogênio/análise , Hemostasia , Humanos , Esterilização/métodos , Tromboelastografia , Ferimentos e Lesões/sangueRESUMO
BACKGROUND: Accurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer. METHODS: This retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard. RESULTS: For overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%. CONCLUSIONS: WB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.