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BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) is used in clinical practice to risk-stratify liver transplant (LT) recipients; however, there are currently little data demonstrating the relationship between VCTE and clinical outcomes. METHODS: A total of 362 adult LT recipients with successful VCTE examination between 2015 and 2022 were included. Presence of advanced fibrosis was defined as liver stiffness measurement (LSM) ≥10.5 kPa and hepatic steatosis as controlled attenuation parameter (CAP) ≥270 dB/m. The outcomes of interest included all-cause mortality, myocardial infarction (MI), and graft cirrhosis using cumulative incidence analysis that accounted for the competing risks of these outcomes. RESULTS: The LSM was elevated in 64 (18%) and CAP in 163 (45%) LT recipients. The baseline LSM values were similar in patients with elevated vs normal CAP values. After a median follow-up of 65 (interquartile range, 20-140) months from LT to baseline VCTE, 66 (18%) patients died, 12 (3%) developed graft cirrhosis, and 18 (5%) experienced an MI. Baseline high LSM was independently associated with all-cause mortality (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.11-3.50; P = .02) and new onset cirrhosis (HR, 6.74; 95% CI, 2.08-21.79; P < .01). A higher CAP value was significantly and independently associated with increased risk of experiencing a MI over study follow-up (HR, 4.14; 95% CI, 1.29-13.27; P = .017). CONCLUSIONS: The VCTE-based parameters are associated with clinical outcomes and offer the potential to be incorporated into clinical risk-stratification strategies to improve outcomes among LT recipients.
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Luminescent coupling (LC) is a key phenomenon in monolithic tandem solar cells. This study presents a nondestructive technique to quantitatively evaluate the LC effect, addressing a gap in the existing predictions made by optical modeling. The method involves measuring the ratio of photons emitted from the high bandgap top cell that escape through the rear, contributing additional current to the bottom cell, and to those escaping from the front side of top cell. The findings indicate that in the analyzed monolithic perovskite/silicon tandem solar cells, more than 85% of the emitted photons escaping from the perovskite top cell are used to generate additional current in the bottom cell. This process notably reduces the mismatch in the generated current between each subcell, particularly when the current is limited by the low bandgap subcell. The presented method is applicable to a variety of monolithic tandem structures, providing vital information for subcell characterization, providing vital information for predicting energy output and optimization for outdoor applications.
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Metabolic flexibility is the ability to match biofuel availability to utilization and is inversely associated with increased metabolic burden among liver transplant (LT) recipients. The present study evaluated the impact of metabolic flexibility on weight gain following LT. LT recipients were enrolled prospectively (n = 47) and followed for 6 months. Metabolic flexibility was measured using whole-room calorimetry and is expressed as a respiratory quotient (RQ). Peak RQ represents maximal carbohydrate metabolism and occurs in the post-prandial state, while trough RQ represents maximal fatty acid metabolism occurring in the fasted state. The clinical, metabolic, and laboratory characteristics of the study cohort of lost weight (n = 14) and gained weight (n = 33) were similar at baseline. Patients who lost weight were more likely to reach maximal RQ (maximal carbohydrate oxidation) early and rapidly transitioned to trough RQ (maximal fatty acid oxidation). In contrast, patients who gained weight had delayed time to peak RQ and trough RQ. In multivariate modeling, time to peak RQ (ß-coefficient 0.509, p = 0.01), time from peak RQ to trough RQ (ß-coefficient 0.634, p = 0.006), and interaction between time to peak RQ to trough RQ and fasting RQ (ß-coefficient 0.447, p = 0.02) directly correlated with the severity of weight gain. No statistically significant relationship between peak RQ, trough RQ, and weight change was demonstrated. Inefficient transition between biofuels (carbohydrates and fatty acids) is associated with weight gain in LT recipients that is independent of clinical metabolic risk. These data offer novel insight into the physiology of obesity after LT with the potential to develop new diagnostics and therapeutics.
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Metabolismo Energético , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Aumento de Peso , Obesidade , Ácidos GraxosRESUMO
Chiral, enantiopure Yb(III) complexes exhibit circularly polarized luminescence (CPL) in the near infrared (NIR) wavelength region. This CPL is quantified by the dissymmetry factor (glum). The excited state 2F5/2 consists of six mJ' states degenerated in three Stark levels, due to the crystal-field splitting (CFS), which are populated in accordance with the Boltzmann distribution. Consequently, room temperature CPL spectra are the sum of various - either positive or negative - contributions, that are practically impossible to quantify. To address this issue, an advanced setup enabling CPL measurements over a broad temperature range (300 to 4 K) has been developed. The interrelation of CFS, glum and temperature was explored using a pair of enantiopure Yb(III) complexes, highlighting the individual contribution of each crystal-field sublevel to the overall CPL spectrum, as anticipated by simulations performed in the framework of multireference wave-functions. Hence, the CPL spectra of chiral lanthanide complexes were found to be indeed strongly temperature-dependent, as is the glum dissymmetry factor, as a consequence of the variation in thermal sublevel population.
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INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.
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Algoritmos , Técnicas de Imagem por Elasticidade , Cirrose Hepática , Transplante de Fígado , Vibração , Humanos , Técnicas de Imagem por Elasticidade/métodos , Transplante de Fígado/efeitos adversos , Pessoa de Meia-Idade , Feminino , Masculino , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Adulto , Biópsia , Idoso , Fígado/patologia , Fígado/diagnóstico por imagem , Estudos RetrospectivosRESUMO
PURPOSE: This study evaluated the ability of QuickSee to detect children at risk for significant vision conditions (significant refractive error [RE], amblyopia and strabismus). METHODS: Non-cycloplegic refraction (using QuickSee without and with +2 dioptre (D) fogging lenses) and unaided binocular near visual acuity (VA) were measured in 4- to 12-year-old children. Eye examination findings (VA, cover testing and cycloplegic retinoscopy) were used to determine the presence of vision conditions. QuickSee performance was summarised by area under the receiver operating characteristic curve (AUC), sensitivity and specificity for various levels of RE. QuickSee referral criteria for each vision condition were chosen to maximise sensitivity at a specificity of approximately 85%-90%. Sensitivity and specificity to detect vision conditions were calculated using multiple criteria. Logistic regression was used to evaluate the benefit of adding near VA (6/12 or worse) for detecting hyperopia. A paired t-test compared QuickSee without and with fogging lenses. RESULTS: The mean age was 8.2 (±2.5) years (n = 174). RE ranged up to 9.25 D myopia, 8 D hyperopia, 5.25 D astigmatism and 3.5 D anisometropia. The testability of the QuickSee was 94.3%. AUC was ≥0.92 (excellent) for each level of RE. For the detection of any RE, sensitivity and specificity were 84.2% and 87.3%, respectively, using modified Orinda criteria and 94.5% and 78.2%, respectively, using the American Academy for Pediatric Ophthalmology and Strabismus (AAPOS) guidelines. For the detection of any significant vision condition, the sensitivity and specificity of QuickSee were 81.1% and 87.9%, respectively, using modified Orinda criteria and 93% and 78.6%, respectively, using AAPOS criteria. There was no significant benefit of adding near VA to QuickSee for the detection of hyperopia ≥+2.00 (p = 0.34). There was no significant difference between QuickSee measurements of hyperopic refractive error with and without fogging lenses (difference = -0.09 D; p = 0.51). CONCLUSIONS: QuickSee had high discriminatory power for detecting children with hyperopia, myopia, astigmatism, anisometropia, any significant refractive error or any significant vision condition.
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Anisometropia , Astigmatismo , Hiperopia , Miopia , Erros de Refração , Estrabismo , Seleção Visual , Criança , Humanos , Pré-Escolar , Hiperopia/diagnóstico , Astigmatismo/diagnóstico , Erros de Refração/diagnóstico , Estrabismo/diagnósticoRESUMO
Influenza A viruses are a One Health threat because they can spill over between host populations, including among humans, swine, and birds. Surveillance of swine influenza virus in Hanoi, Vietnam, during 2013-2019 revealed gene pool enrichment from imported swine from Asia and North America and showed long-term maintenance, persistence, and reassortment of virus lineages. Genome sequencing showed continuous enrichment of H1 and H3 diversity through repeat introduction of human virus variants and swine influenza viruses endemic in other countries. In particular, the North American H1-δ1a strain, which has a triple-reassortant backbone that potentially results in increased human adaptation, emerged as a virus that could pose a zoonotic threat. Co-circulation of H1-δ1a viruses with other swine influenza virus genotypes raises concerns for both human and animal health.
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Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Infecções por Orthomyxoviridae , Doenças dos Suínos , Suínos , Animais , Humanos , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Vietnã/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Doenças dos Suínos/epidemiologia , Vírus da Influenza A/genéticaRESUMO
While investigating the death of a hippopotamus at a zoo in Hanoi, Vietnam, we isolated SARS-CoV-2 and sequenced the RNA-dependent RNA polymerase gene from different organs. Phylogenetic analysis showed that the SARS-CoV-2 strain was closely related to 3 human SARS-CoV-2 strains in Vietnam.
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Artiodáctilos , COVID-19 , Animais , Humanos , SARS-CoV-2 , Filogenia , VietnãRESUMO
Hepatic fibrosis is a strong predictor of clinical outcomes following liver transplantation (LT).1 Despite the centrality of hepatic fibrosis in clinical outcomes, the published literature with noninvasive fibrosis assessment in LT recipients is limited and liver biopsy, despite its invasive nature, remains the reference standard. Vibration-controlled transient elastography (VCTE) and clinical prediction models (CPM) are point-of-care tests that can provide noninvasive assessment of hepatic fibrosis2-4; however, the data comparing the diagnostic performance of VCTE and CPM in LT recipients are lacking. The current study evaluated the diagnostic performance of VCTE and CPM in LT recipients using best practices in regulatory sciences for biomarker development.
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Regras de Decisão Clínica , Técnicas de Imagem por Elasticidade , Transplante de Fígado , Transplantados , Vibração , Fígado/patologia , Modelos Estatísticos , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Implementation of proton-exchange membrane water electrolyzers for large-scale sustainable hydrogen production requires the replacement of scarce noble-metal anode electrocatalysts with low-cost alternatives. However, such earth-abundant materials often exhibit inadequate stability and/or catalytic activity at low pH, especially at high rates of the anodic oxygen evolution reaction (OER). Here, the authors explore the influence of a dielectric nanoscale-thin oxide layer, namely Al2 O3 , SiO2 , TiO2 , SnO2 , and HfO2 , prepared by atomic layer deposition, on the stability and catalytic activity of low-cost and active but insufficiently stable Co3 O4 anodes. It is demonstrated that the ALD layers improve both the stability and activity of Co3 O4 following the order of HfO2 > SnO2 > TiO2 > Al2 O3 , SiO2 . An optimal HfO2 layer thickness of 12 nm enhances the Co3 O4 anode durability by more than threefold, achieving over 42 h of continuous electrolysis at 10 mA cm-2 in 1 m H2 SO4 electrolyte. Density functional theory is used to investigate the superior performance of HfO2 , revealing a major role of the HfO2 |Co3 O4 interlayer forces in the stabilization mechanism. These insights offer a potential strategy to engineer earth-abundant materials for low-pH OER catalysts with improved performance from earth-abundant materials for efficient hydrogen production.
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NAFLD is common after liver transplantation (LT) and is associated with an increased metabolic burden. Currently, there is a paucity of investigations into the treatment of post-LT NAFLD. In the present study, we evaluated the safety and efficacy of saroglitazar, a novel dual peroxisome proliferator-associated receptor α/γ agonist, on the treatment of post-LT NAFLD and metabolic burden. This is a phase 2A, single-center, open-label, single-arm study in which patients with post-LT NAFLD received saroglitazar magnesium 4 mg daily for 24 weeks. NAFLD was defined by a controlled attenuation parameter ≥264 dB/m. The primary endpoint was the reduction in liver fat as measured by MRI proton density fat fraction (MRI-PDFF). Secondary MRI-based metabolic endpoints included visceral adipose tissue, abdominal subcutaneous adipose tissue volumes, muscle fat infiltration, and fat-free muscle volume. Saroglitazar treatment led to a reduction in MRI-PDFF from 10.3±10.5% at baseline to 8.1±7.6%. A relative 30% reduction from baseline MRI-PDFF value was noted in 47% of all patients and 63% of patients with baseline MRI-PDFF >5%. Reduction in serum alkaline phosphatase was an independent predictor of MRI-PDFF response. Saroglitazar did not decrease fat-free muscle volume nor increase muscle fat infiltration, but did lead to a mild increase in visceral adipose tissue and abdominal subcutaneous adipose tissue. The study drug was well tolerated and a mild nonsignificant increase in serum creatinine was noted. Saroglitazar did not affect the weight. The study provides preliminary data demonstrating the safety and metabolic benefits of saroglitazar in LT recipients and underscores the importance of future studies to establish its efficacy after LT.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Fenilpropionatos , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Fígado/diagnóstico por imagem , Fenilpropionatos/uso terapêutico , Imageamento por Ressonância MagnéticaRESUMO
Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.
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Técnicas de Imagem por Elasticidade , Transplante de Fígado , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/cirurgia , Fibrose , Curva ROC , Técnicas de Imagem por Elasticidade/métodos , BiópsiaRESUMO
Immune cell therapy has been incorporated into cancer therapy over the past few years. Chimeric antigen receptor T cells (Car-T cells) transplantation is a novel and promising therapy for cancer treatment and introduces a new age of immune cell therapy. However, the expensive nature of genetic modification procedures limits the accessibility of Car-T cells for cancer treatment. Cytokine-induced killer cells (CIKs) can kill the target cells in an MHC-non-restricted manner; these cells can be developed to "off-the-shelf" immune cell products for cancer treatment. However, the anti-tumor potency of freshly thawed CIKs is not well documented. This study aimed to fill this gap, evaluating the anti-tumor potency of freshly thawed CIKs compared to that of freshly cultured CIKs. CIKs were produced from the human umbilical cord blood in accordance with published protocols. CIKs were cryopreserved in xeno-free cryomedium that contains 5% DMSO, 10% human serum in phosphate buffer saline at - 86 °C. These cells were thawed and immediately utilized in assays (called freshly thawed CIKs) with freshly cultured cells are control. The expression of the surface markers of CIKs, cytokine production, and in vitro anti-tumor cytotoxic cells of freshly thawed CIKs were evaluated and compared to freshly cultured CIKs. Additionally, the freshly thawed CIKs were injected into the breast of tumor-bearing mice to assess the anti-tumor potency in vivo. The results obtained in freshly thawed CIKs and freshly cultured CIKs demonstrated that the expression of CD3, and CD56 were comparable in both cases. The production of TNF-α, IFN-γ, and IL-10 was slightly reduced in freshly thawed cells compared to the freshly cultured cells. The in vitro lysis toward MCF-7 cancer cells was similar between freshly thawed and freshly cultured CIKs. Moreover, the freshly thawed CIKs displayed anti-breast tumor activity in the breast tumor-bearing mice. The volume of tumors significantly reduced in the mice grafted with freshly thawed CIKs while, conversely, the tumor volume in mice of the placebo group gradually increased. This study substantiated that freshly thawed CIKs preserved their anti-tumor potency in both in vitro and in vivo conditions. The results initially revealed the great potential of UCB-CIKs for "off-the-shelf" CIK product manufacturing. However, further studies on the effects of cryomedia, freezing rate, and thawing procedure should be undertaken before freshly thawed off-the-shelf UCB-CIKs are utilized in clinical trials.
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Células Matadoras Induzidas por Citocinas , Neoplasias , Animais , Humanos , Camundongos , Proliferação de Células , Células Cultivadas , Sangue Fetal , Neoplasias/patologiaRESUMO
Apoptosis plays an essential role in maintaining cellular homeostasis and preventing cancer progression. Bcl-xL, an anti-apoptotic protein, is an important modulator of the mitochondrial apoptosis pathway and is a promising target for anticancer therapy. In this study, we identified octenidine as a novel Bcl-xL inhibitor through structural feature-based deep learning and molecular docking from a library of approved drugs. The NMR experiments demonstrated that octenidine binds to the Bcl-2 homology 3 (BH3) domain-binding hydrophobic region that consists of the BH1, BH2, and BH3 domains in Bcl-xL. A structural model of the Bcl-xL/octenidine complex revealed that octenidine binds to Bcl-xL in a similar manner to that of the well-known Bcl-2 family protein antagonist ABT-737. Using the NanoBiT protein-protein interaction system, we confirmed that the interaction between Bcl-xL and Bak-BH3 domains within cells was inhibited by octenidine. Furthermore, octenidine inhibited the proliferation of MCF-7 breast and H1299 lung cancer cells by promoting apoptosis. Taken together, our results shed light on a novel mechanism in which octenidine directly targets anti-apoptotic Bcl-xL to trigger mitochondrial apoptosis in cancer cells.
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Inteligência Artificial , Iminas/farmacologia , Piridinas/farmacologia , Proteína bcl-X/antagonistas & inibidores , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Humanos , Iminas/química , Simulação de Acoplamento Molecular , Neoplasias/patologia , Ligação Proteica/efeitos dos fármacos , Piridinas/química , Proteína Killer-Antagonista Homóloga a bcl-2/química , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína bcl-X/químicaRESUMO
ABSTRACT: Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration-controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM-based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM-based fibrosis models (FibroScan-AST [FAST], AGILE-3+, and AGILE-4) were included ( n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0-2 vs. 3-4) were determined by optimal cut-off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89-0.99), FAST was 0.65 (95% CI, 0.50-0.79), AGILE-3+ was 0.90 (95% CI, 0.83-0.97), and AGILE-4 was 0.90 (95% CI, 0.83-0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM-based scores. The false-positive rates for AGILE-3+ and AGILE-4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false-positive rates in LSM-based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM-based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM-based scores that are specific to LT patients.
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Cardiovascular disease (CVD) is an important cause of mortality among liver transplantation (LT) recipients; however, the data on CVD risk stratification following LT are limited. Thus, the primary aim of this study was to evaluate the association between decline in renal function early after LT and atherosclerotic events. This retrospective study included all patients receiving LT between 2007 and 2019. Early renal function was quantified as estimated glomerular filtration rate (GFR) 6 months after LT. The primary endpoint for the study was a composite atherosclerotic cardiovascular event of three-point major adverse cardiovascular events (MACEs), which includes nonfatal myocardial infarction (MI), nonfatal stroke, or death from CVD. A total of 553 LT recipients met entry criteria. After a median follow-up of 74 months (interquartile range 46-111), 94 (17%) LT recipients died and CVD-associated death occurred in 20 patients. MACE-3 occurred in 66 (12%) patients, with nonfatal MI being the most common event (n = 30). A strong inverse relationship between early GFR and MACE-3 was noted in unadjusted analysis with hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.95-0.98; p = 0.0001) and remained significant even after accounting for age, sex, coronary artery disease, diabetes mellitus, hypertension, calcineurin inhibitor use, and Framingham Risk Score (FRS; HR 0.96, 95% CI 0.95-0.97; p = 0.0001 per unit increase in GFR). Furthermore, an independent interaction between GFR, FRS, and likelihood of developing an MACE-3 was noted. GFR 6 months following LT is a strong predictor of developing atherosclerotic events. This relationship is independent of traditional CVD risk stratification models (e.g. FRS) and thus has the potential to be incorporated into CVD risk assessment after LT but requires further validation.
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Doenças Cardiovasculares , Transplante de Fígado , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Taxa de Filtração Glomerular , Humanos , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
1,1,4,4-Tetracyanobutadienes (TCBDs) bearing a large diversity of fluorophores were prepared following a multi-step synthesis. In a crucial last step, all compounds were obtained from the corresponding ynamides, which were particularly suitable for the formation of the TCBDs in the presence of tetracyanoethylene via a [2+2] cycloaddition/retroelectrocyclization step (CA-RE). Several fluorenyl derivatives in addition to phenanthrenyl and terphenyl ones provided ynamide-based TCBDs affording remarkable emission properties covering a large range of wavelengths. Those compounds emit both in solid state and in solution from the visible region to the NIR range, depending on the molecular structures. Quantum yields in cyclohexane reached unforeseen values for such derivatives, up to 7.8 %. A huge sensitivity to the environment of the TCBDs has also been unraveled for most of the compounds since we observed a dramatic fall of the quantum yields when changing the solvent from cyclohexane to toluene, while they are almost non-emissive in dichloromethane.
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Corantes Fluorescentes , Reação de Cicloadição , Corantes Fluorescentes/química , Ionóforos , Estrutura MolecularRESUMO
Glaucoma is a heterogeneous group of progressive optic neurodegenerative. Although most patients with primary open angle glaucoma (POAG) are stable for many years, certain subgroups of POAG patients could progress over time even with treatment. This study is to identify aqueous humor (AH) biomarkers that may be associated with disease progression in POAG patients. Gene differential expression study of prospectively collected AH from patients with stable or progressive POAG. Metagenomic deep sequencing (MDS) was performed on the aqueous fluid of 20 patients with stable POAG and 20 patients with progressive POAG. Differential gene expression analysis was performed to identify host transcriptome signatures. A total of 21 transcripts were differentially expressed between groups. Differential transcripts identified by MDS. Twenty transcripts were up-regulated and 1 transcript was down-regulated in progressive POAG patients compared to stable patients. Of those, 11 transcripts were eye-related, and 5 transcripts were related to glaucomatous phenotypes (Fibronectin type III domain containing 3B (FNDC3B), Clusterin (CLU), Proprotein convertase subtilisin/kexin type 6 (PCSK6), Cadherin EGF LAG seven-pass G-type receptor 1 (Celsr1), and Rho guanine nucleotide exchange factor 4 (ARHGEF4)). Biomarkers associated with POAG progression can be identified from aqueous fluid. Identification of the biomarkers may improve glaucoma surveillance for progressive POAG.
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Glaucoma de Ângulo Aberto , Glaucoma , Humor Aquoso/metabolismo , Biomarcadores/metabolismo , Olho/metabolismo , Glaucoma/metabolismo , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Fatores de Troca de Nucleotídeo Guanina Rho/metabolismoRESUMO
Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT). METHODS: Patients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation). RESULTS: The two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p < .001), indicative of impaired FA utilization. In subgroup analysis of the NASH cohort, body mass index but not liver fat content (MRI-PDFF) was an independent predictor of fasting RQ. In NASH, fasting RQ inversely correlated with fat-free muscle volume and directly with visceral adipose tissue. CONCLUSION: Reduced metabolic flexibility in patients transplanted for NASH cirrhosis may precede the development of non-alcoholic fatty liver disease after LT.
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Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica , Carboidratos , Humanos , Cirrose Hepática/complicações , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicaçõesRESUMO
BACKGROUND: Vietnam has encountered difficulties in ensuring an adequate and equitable distribution of health workforce. The traditional staffing norms stated in the Circular 08/TT-BYT issued in 2007 based solely on population or institutional size and do not adequately take into consideration the variations of need such as population density, mortality and morbidity patterns. To address this problem, more rigorous approaches are needed to determine the number of personnel in health facilities. One such approach is Workload Indicators of Staffing Need (WISN) developed by the World Health Organization (WHO), a facility-based workforce planning method that assists managers in defining the responsibilities of different workforce categories and improving the appropriateness and efficiency of a staff mix. METHODS: This study applied the WISN approach and was employed in 22 clinical departments at four hospitals in Vietnam between 2015 and 2018. 22 targeted group discussions involving nurses were conducted. Hospital personnel records have been retrieved. The data were analyzed according to WISN instructions. RESULTS: Of the 22 departments, there was a shortage of 1 to 2 nurses in 10 departments, with WISN ratios ranging between 0.88 and 0.95. Only 01 clinical colleges at Can Tho Hospital lacked 05 nurses, facing a high workload with a WISN ratio of 0.78. Administrative time represented 20-40% of the total work time of a nurse. In comparison, nurses at Can Tho Hospital spent time on administration from 24 onwards. 5-41.7% of their working time while nurses at Thanh Hoa Hospital spent 21-33%. CONCLUSIONS: The application of the WISN enabled health managers to analyze the workload of nurses, calculate staffing needs, and thus effectively contribute to the workforce planning process. It is expected that the results of this research will encourage the use of the WISN tool in other hospitals and health facilities across the health system. At provincial and national levels, this study provides important evidence to help policy makers develop guidelines for personnel norms for health facilities in the context of limited resources, while the existing regulation is no longer appropriate.