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1.
J Pharm Biomed Anal ; 177: 112888, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31563758

RESUMO

Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography-mass spectrometry (LC-MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.

2.
Ecotoxicol Environ Saf ; 188: 109842, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31707322

RESUMO

Twelve commercial pesticide formulations containing sixteen active ingredients were applied on greenhouse strawberries at recommended and double doses. The dynamics and dietary risk analysis were investigated. A modified QuEChERS method based on the use of multi-walled carbon nanotubes (MWCNTs) as adsorbent followed by LC-MS/MS and GC-MS/MS detection was utilized for sample analysis. The half-lives of studied pesticides were 4.6-12.6 days and 3.8-15.8 days from two application doses. Dietary levels from the residue concentrations of the individual pesticides at harvest was contrasted with the acceptable daily intake (ADI) and acute reference dose (ARfD). The dietary risk assessment adopt the risk quotient (RQ) for chronic risk and risk probability (RP) for long-term dietary intake risk, respectively. The dietary risk induced by the studied pesticide residues in strawberry was acceptable for consumers except the pesticide fumigants. The pesticide residues at different pre-harvest intervals (PHIs) under greenhouse conditions were compared with the established maximum residue limits (MRLs). To reduce the residue levels and potential safety risk, a longer PHI or reduced application rates should be conducted.

3.
J Immunother ; 43(1): 32-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31219975

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy demonstrates impressive efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T therapy-related severe cytokine release syndrome and neurological toxicity limit its clinical application in R/R DLBCL patients with high tumor burden. Here, we conducted a phase II clinical trial testing the efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin lymphoma patients (NCT03196830). Among the enrolled patients, 10 R/R DLBCL patients with high tumor burden were analyzed. Before CAR-T therapy, 4 were treated with intensive combined chemotherapy (C-CAR-cohort), and 6 were exposed to radiotherapy (R-CAR-cohort). Patients in the R-CAR-T-cohort showed a higher overall response rate (100% vs. 25%, P=0.033) and less severe cytokine release syndrome (0% vs. 100%, P=0.0048) and neurotoxicity (0% vs. 75%, P=0.033) incidences than patients in the C-CAR-T-cohort. Furthermore, one case who responded to CAR-T therapy initially and who suffered a relapse shortly was exposed to radiation and achieved complete remission, with an increase in the number of CAR-T copies detected. This study demonstrates that radiotherapy is an optimal debulking regimen to managing R/R DLBCL patients before CAR-T therapy and a promising alternative salvage therapy for patients who suffer a relapse after CAR-T therapy by fuelling CAR-T copies.

4.
Sci Total Environ ; 701: 134881, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31710900

RESUMO

During unplanned indirect potable reuse, treated wastewater that contains effluent organic matter (EOM) enters the drinking water source, resulting in different toxicity from natural organic matter (NOM) in surface water during chlorination. This study found that, during chlorination, EOM formed more total organic halogen (TOX) and highly toxic nitrogenous disinfection byproducts (DBPs) like dichloroacetonitrile and trichloronitromethane than NOM did. Oxidative stress including both reactive oxygen species (ROS) and reactive nitrogen species (RNS) in Chinese hamster ovary (CHO) cells substantially increased when exposed to chlorinated EOM and chlorinated NOM. The excessive ROS damaged biological macromolecules including DNA, RNA to form 8-hydroxy-(deoxy)guanosine and proteins to form protein carbonyls. Impaired macromolecule further triggered cell cycle arrest at the S and G2 phases, led to cell apoptosis and eventual necrosis. Cytotoxicity and genotoxicity of chlorinated EOM were both higher than those of chlorinated NOM. Adding the blocker L-buthionine-sulfoximine of intracellular antioxidant glutathione demonstrating that oxidative stress might be responsible for toxicity. ROS was further identified to be the main cause of toxicity induction. These findings highlight the risk from chlorinated EOM in the case of unplanned indirect potable reuse, because it showed higher level of cytotoxicity and genotoxicity than chlorinated NOM via inducing more ROS in mammalian cells.

5.
Food Chem ; 308: 125674, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669944

RESUMO

Cadmium-contaminated rice has been a serious food safety issue in China. In this research, carboxymethyl rice starch (CMS) from cadmium-contaminated rice and native rice was prepared to remove the cadmium in rice. The preparation of native rice starch (NRS) and starch from cadmium-contaminated rice (Cd-CRS) was similar, and carboxymethyl starch was prepared following the same steps. A single factor experiment was performed to obtain the carboxymethyl starch prepared under the optimal conditions. Cadmium content was reduced from 0.38 mg/kg to 0.04 mg/kg after alkalization. The physical properties, including particle size, degree of crystallinity, water absorption and freeze-thaw stability, of NRS and Cd-CRS and their carboxymethyl starches were studied. The results showed that the cadmium was significantly removed after extracting starch from cadmium-contaminated rice by alkalization and carboxymethylation. Then, starch samples and carboxymethyl starch samples were characterized. All results showed no obvious difference between Cd-CMS and NCMS, indicating that carboxymethyl starch from cadmium-contaminated rice could be widely used in both food and nonfood industries.

6.
Blood Cells Mol Dis ; 80: 102369, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31677454

RESUMO

People with sickle cell disease often report severe bone pain with repeated bouts of vaso-occlusive crises, but the extent of skeletal injury incurred during these painful episodes remain unclear. We sought to quantify bone degradation by comparing urinary concentrations of carboxyterminal cross-linked telopeptide of type I collagen (CTX-1), a well-described marker of bone resorption, in a prospective cohort of 52 adults with sickle cell disease enrolled in the Sickle Cell Pain Markers Study. We also questioned if changes in urinary CTX-1 concentrations correlated with changes in hemolysis and inflammatory markers measured both during and after resolution of a painful vaso-occlusive episode. Thirty-one of the 52 adults enrolled in the study had paired urine samples for CTX-1 analysis. Urinary CTX-1, corrected for urine creatinine, significantly decreased from a mean of 3.45 µg/mmol during vaso-occlusive crises to 2.62 µg/mmol at recovery (p = 0.01). Thus, increased bone loss appears to correlate with acute vaso-occlusive crises in sickle cell disease. Our finding that urinary CTX-1 can be used to probe bone degradation in sickle cell disease provides an important new tool for diagnosing and monitoring response to therapy for people with sickle cell-related bone loss.

7.
J Nanosci Nanotechnol ; 20(4): 2095-2103, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492217

RESUMO

To select the optimal graphene oxide (GO) for anticaries dental applications, aqueous dispersions containing GO nanosheets with various oxygen-containing functional groups were prepared and characterized using atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The antibacterial effect towards Streptococcus mutans (S. mutans) in both planktonic and biofilm forms was studied by colony forming units (CFU) counting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay, live/dead fluorescent staining, and confocal laser scanning microscopy (CLSM) observation. The oxidation capacity of different GO nanosheets was examined by 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay and in vitro glutathione (GSH) oxidation assay. The results indicated that GO exerted strong antibacterial activities in a concentration-dependent manner towards S. mutans in both planktonic and biofilm forms. The minimum bactericidal concentration (MBC) was 40 µg/mL for planktonic S. mutans. When the concentration was higher than 80 µg/mL, 80% of the bacteria in the biofilms were devitalized. GO nanosheets with more oxygen-containing functional groups exerted higher toxicity at low concentrations. The functional groups of GO played a crucial role in its antibacterial outcome.

8.
BMC Ophthalmol ; 19(1): 244, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796021

RESUMO

BACKGROUND: To investigate the therapeutic effectiveness and safety of endoscopic dacryocystorhinostomy (EN-DCR) to treat congenital nasolacrimal canal dysplasia (CNCD). METHODS: Forty children (50 eyes) with congenital nasolacrimal duct obstruction (CNLDO) and lacrimal bony dysplasia, including 8 children with bony atresia (10 eyes) and 32 with bony stenosis (40 eyes), were recruited in this retrospective study. Standardized EN-DCR was performed in all cases. The postoperative observations included relief of symptoms, fluorescein dye disappearance test (FDDT), syringing of lacrimal passages and anastomotic patency under nasal endoscopy. Patients were followed up for 8-18 months. RESULTS: Standardized EN-DCR surgery had a success (cure and improvement) rate of 100%, including a cure rate of 82% and an improvement rate of 18%. The cure rate among 40 cases of bony nasolacrimal duct stenosis was 82.5%, while that of 10 cases of bony nasolacrimal duct atresia was 80%. Statistical analysis showed that nether the receipt of other treatments before surgery nor the type of bony nasolacrimal duct dysplasia affected the cure rate. No significant complications were observed during postoperative follow-up except for four cases (4 eyes) that suffered middle turbinate and nasal mucosal adhesion and two cases with sinusitis. CONCLUSIONS: CNCD is a type of CNLDO that does not respond to conservative and conventional treatment. EN-DCR represents a safe and effective treatment for children with CNCD. In addition, the combination of EN-DCR with lacrimal CT scanning provides advantages over traditional lacrimal surgery in that it has a high success rate with a low incidence of complications.

9.
Clin Cancer Res ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31796519

RESUMO

BACKGROUND: This clinical trial combined pembrolizumab and vorinostat in recurrent/metastatic squamous cell carcinomas of the head and neck(HN), and salivary gland cancer(SGC). METHODS: Patients with progressing incurable HN and SGC ECOG ≤1, no prior immunotherapy, RECIST1.1 measurable disease, normal organ function were eligible. Pembrolizumab 200mg was given IV q21 days, and vorinostat 400 mg given orally 5 days on and 2 days off at the start of each 21 day cycle. Primary endpoints were safety and objective response rates. RESULTS: From 11/2015 to 8/2017, 25 HN and 25 SGC pts were enrolled. Median age was 61(range 33-86) yrs, 39(78%) were male, 21(62%) were never smokers, 27(54%) had ECOG 0. In HN, 13(52%) were p16+ oropharynx. Most common SGC histologies were adenoid cystic(ACC) 12(48%), acinic cell(AciC) 3(12%), mucoepidermoid 3(12%). Adverse events (AEs) in all pts were: 27(54%) Grade≥1, 18(36%) Grade≥3. The most common AEs in all pts were renal insufficiency 7(14%), fatigue 6(12%) and nausea 3(6%). There were 3(12%) deaths on study. Responses in HN were: complete response(CR) 0, partial response(PR) 8 (32%), stable disease(SD) 5(20%). Efficacy in SGC:CR 0, PR 4(16%) in 1 lymphoepithelioma-like carcinoma (LEL-C)C, 2 AciC and 1 ACC, SD 14(56%). In the HN group, median follow up(mFUP) was 12.6 months, median overall survival(mOS) was 12.6 months, and median progression free survival (mPFS) was 4.5 months. In SGC, mFUP was 13.1 months, mOS was 14.0 months, and mPFS was 6.9 months. CONCLUSION: This combination demonstrated activity in HN, with fewer responses in SGC. Toxicities were higher than reported with pembrolizumab alone.

10.
Brain Behav Immun ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785398

RESUMO

Obesity is often accompanied by lower working memory (e.g., a lower ability to keep goal-relevant information in mind) relative to healthy weight individuals. Understanding this relative working memory impairment has important clinical implications, as working memory is thought to facilitate adherence to weight management programs. Theoretical models of obesity, self-regulation, and inflammation suggest that inflammation plays a role in obesity-related working memory impairments, but to date no study has tested this prediction. Therefore, the current study examined whether inflammation statistically mediated the relationship between obesity and working memory in a nationally representative dataset of U.S. adults from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N=11,546, age range 25-34). Inflammation was quantified via C-reactive protein (CRP) level, and working memory was assessed using a modified digit span backward task. As expected, cross-sectional analyses showed that a body mass index (BMI) indicative of obesity-as well as greater BMI when BMI was analyzed continuously-and greater CRP were each related to lower working memory. Critically, we found that CRP levels statistically mediated the relationships between obesity/greater BMI and working memory, with CRP accounting for 44.1% of the variance explained in working memory by BMI. Moreover, these findings held both with and without controlling for relevant covariates, including demographic characteristics (e.g., age), socioeconomic status, and behavioral factors (e.g., smoking). Our results therefore point to inflammation as playing an important role in the relationship between obesity and working memory, and suggest that interventions aimed at reducing inflammation may help lessen the cognitive burden of obesity.

11.
Medicine (Baltimore) ; 98(49): e18140, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804325

RESUMO

RATIONALE: Acute fibrinous and organizing pneumonia (AFOP) is a newly evolving rare non-infectious lung pathology, characterized by intra-alveolar fibrin balls on histology. It is usually difficult to be diagnosed and mistaken for other lung diseases. PATIENT CONCERNS: In this article, an interesting case about a male patient with a 15-day history of high-grade fever, chills, and no productive cough was presented. He was misdiagnosed as the lung infection early, but exhibited no response to the antibiotic therapy. DIAGNOSIS: The diagnosis of AFOP was determined by the lung biopsy and pathology. INTERVENTIONS: With the diagnosis of AFOP, all antibiotics were discontinued, and 40 mg methylprednisolone daily was given intravenously. OUTCOMES: The patient responded well to the treatment with steroids. LESSONS: AFOP is a rare lung disease characterized by bilateral basilar infiltrates and histological findings of organizing pneumonia and intra-alveolar fibrin in the form of "fibrin balls". Lung biopsy and histopathology were the most important diagnostic methods for the AFOP. Glucocorticoid was an effective drug for the treatment. Subacute patients of AFOP have excellent prognosis with corticosteroids.

12.
Eat Behav ; 35: 101338, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707244

RESUMO

A growing body of research has linked obesity to lower working memory performance. However, sex differences are often found in associations between obesity and cognition, and little work has examined potential sex differences in the association between obesity and working memory. To address this issue, the present research uses data from Wave IV of The National Longitudinal Study of Adolescent to Adult Health (N = 4,769, mean age = 29) to examine whether sex moderated the association between excess weight and working memory. As expected, we found that obesity was associated with poorer working memory, but-importantly-this association was exclusively seen in women, not men. These results held when treating BMI as a continuous or categorical variable (e.g., normal weight, obese), as well as with and without controlling for covariates. The present results therefore indicate that the association between obesity and poorer working memory performance may be sex-dependent. These results suggest that interventions targeted at reducing obesity should be tailored to an individual's sex, as adherence to these interventions often requires working memory.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31714245

RESUMO

Transcranial infrared laser stimulation (TILS) is a promising noninvasive intervention for neurological diseases. Though some experimental work has been done to understand the mechanism of TILS, the reported statistical analysis of data is quite simple and could not provide a comprehensive picture on the effect of TILS. This study learns the effect of TILS on hemodynamics of the human brain from experimental data using longitudinal data analysis methods. Specifically, the repeated measures analysis of variance (ANOVA) is first applied to confirm the significance of the TILS effect and its characteristics. Based on that, two parametric mixed-effect models and non-parametric functional mixed-effect model are proposed to model the population-level performance and individual variation of this effect. Interpretation on the fitted models are provided, and comparison of the three proposed models in terms of their fitting and prediction performance is made to select the best model. According to the selected model, TILS increases the concentration of oxygenated hemoglobin in the brain and this effect sustains even after the treatment stops. Also, there is considerable variation among individual responses to TILS.

14.
Vaccine ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31740094

RESUMO

Mycoplasma bovis is an important pathogenic bacterium affecting cows and cattle. Clinically, an inactivated vaccine of M. bovis is mainly used to prevent infection by this bacterium. The changes that occur in the antigen when M. bovis is continuously passaged in vitro remain unknown. Therefore, we performed an in vitro serial passage of the M. bovis NM-28 strain, which was isolated and identified in our laboratory. An isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics method was used to analyse the differences between generations 3 and 60. Many major membrane proteins or protective antigens reported in the literature did not exhibit changes between these generations. We found an imbalance between growth rate and nutrition in the 60th generation. The proteomics results were verified by western blotting and real-time PCR. Growth curves were also prepared based on colony-forming units (CFUs) between the 3rd and 60th generations. The number of colonies in the 60th generation in the stationary phase was 5 × 109 CFU mL-1, which was 10-fold higher than that in the 3rd generation. The 60th generation of the NM-28 strain can be used as an inactivated vaccine strain of M. bovis to lower production costs compared to use of the 3rd generation.

15.
J Clin Lab Anal ; : e23076, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692082

RESUMO

BACKGROUND: Tuberculosis remains a global public health problem. Genetic polymorphisms may affect the susceptibility, clinical characteristics, and adverse drug reactions of patients with TB. The present study aimed to examine the association of single nucleotide polymorphisms of lncRNA-HNF1B-3:1 with the clinical manifestation of TB in a Western Chinese population. METHOD: A total of 526 tuberculosis patients and 561 healthy subjects were recruited in Western China. The correlation between lnc-HNF1B-3:1 polymorphism and tuberculosis susceptibility was investigated. Moreover, the influence on adverse drug reactions following treatment was explored. A total of 7 SNPs within the lnc-HNF1B-3:1 locus was genotyped by the improved multiplex ligation detection reaction method. RESULTS: No significant associations were noted between TB susceptibility and the presence of all 7 SNPs of the lnc-HNF1B-3:1 as determined by single-locus analysis (All P > .05). The AA genotype of rs12939622 (in the dominant model) and the AA genotype of rs4262994 (in the recessive model) caused increased susceptibility of the subjects to fever (P < .001 and P = .008, respectively). The Rs2542670 G allele was associated with increased risk of thrombocytopenia, leukopenia, and chronic kidney damage following drug administration (P = .007, .029, .003, respectively). CONCLUSION: The present study reported for the first time that the rs12939622, rs4262994 and rs2542670 genotypes in lnc-HNF1B-3:1 locus may influence the clinical manifestations of tuberculosis.

16.
Blood ; 134(Supplement_1): 40, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31724020

RESUMO

DISCLOSURES: Schmidt: Kypha Inc: Employment, Equity Ownership. Lee:Incyte: Research Funding; Syndax: Research Funding; Amgen: Research Funding; Novartis: Research Funding; Takeda: Research Funding; Kadmon: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; AstraZeneca: Research Funding.

17.
Physiol Genomics ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682178

RESUMO

Long non-coding RNAs have been implicated in the development and progression of atherosclerosis. However, the expression and mechanism of action of lncRNAs in atherosclerosis are still unclear. We implemented microarray analysis in human advanced atherosclerotic plaques and normal arterial intimae to detect the lncRNA and mRNA expression profile. Gene Ontology functional enrichment and pathway analyses were applied to explore the potential functions and pathways involved in the pathogenesis of atherosclerosis. A total of 236 lncRNAs and 488 mRNAs were selected for further Ingenuity Pathway Analysis. Moreover, qRT-PCR tests of most selected lncRNAs and mRNAs with high fold changes were consistent with the microarray data. We also performed ELISA to investigate the corresponding proteins levels of selected genes and showed that serum levels of SPP1, CD36, ATP6V0D2, CHI3L1, MYH11 and BDNF were differentially expressed in patients with coronary heart disease compared with healthy subjects.These proteins correlated with some biochemical parameters used in the diagnosis of cardiovascular diseases. Furthermore, receiver operating characteristic analysis showed a favorable diagnostic performance.The microarray profiling analysis and validation of differentially-expressed lncRNAs and mRNAs in atherosclerosis not only provide new insights into the pathogenesis of this disease, but may also reveal new biomarkers for its diagnosis and treatment.

18.
BMC Infect Dis ; 19(1): 993, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752713

RESUMO

BACKGROUND: The goal of this study was to further investigate the clinical effectiveness of the T-SPOT.TB test in diagnosing tuberculosis (TB), including the effects of T-SPOT.TB test on evaluating diverse TB types and locations. METHODS: We collected 20,332 specimens from patients suspected to have TB. Afterwards, we performed an integrative analysis of T-SPOT.TB results and clinical diagnoses, and evaluated the composition ratio and positive detection rate of the T-SPOT.TB test in various age groups, sample types, and hospital departments. In addition, we compared the spot number and composition rate between latent TB infection (LTBI), active TB infection, and old TB infection groups. The active TB group was then further divided into pulmonary TB (PTB), pulmonary and extrapulmonary TB (PETB), and extrapulmonary TB (EPTB) subgroups, and we evaluated whether there were statistical differences in spot number and composition rate between subgroups. RESULTS: Positive results from the T-SPOT.TB test were found across different age groups, specimen types, and hospital departments. Elderly patient groups, pleural effusion samples, and thoracic surgery departments showed the highest rates of positivity. There were no statistically significant differences in spot number of CFP-10 and ESAT-6 wells between disease groups or active TB subgroups. The composition rate, however, was significantly different when ESAT-6 and CFP-10 wells were double-positive. The spot number and composition rate were statistically different between the three disease groups, but showed no significant differences between the three subgroups of active TB. CONCLUSIONS: The results of T-SPOT. TB test showed differences in LTBI, active TB and old TB. Additionally, a higher spot number level was observed in the active TB group.

19.
Ann Hematol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773215

RESUMO

It is uncertain if different immunomodulatory drugs (IMID) pose distinct thrombotic risk in patients with newly diagnosed multiple myeloma (MM). Among 2397 MM patients from the SEER-Medicare database from 2007 to 2013, 78% received lenalidomide, and 22% received thalidomide. After inverse probability weighting to balance confounders, the 12-month incidences of venous thromboembolism (VTE 10%) and arterial thromboembolism (ATE 5%) were similarly high in both groups. Lenalidomide versus thalidomide had a subdistribution hazard ratio of 1.11 (0.59-2.02) for VTE and a subdistribution hazard ratio of 0.96 (0.45-1.98) for ATE. Overall survival was not significantly different with a hazard ratio of 0.88 (0.60-1.18) for lenalidomide versus thalidomide. Concurrent anticoagulant prophylaxis was infrequently prescribed in < 20% of both groups. Our study demonstrates that despite improvement in myeloma-directed therapy and supportive care, thrombosis remains an important consideration for all IMID-treated MM patients. Appropriate risk stratification and vigilant thromboprophylaxis remain essential to prevent this complication.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31729216

RESUMO

Two-dimensional hydrogen evolution reaction (HER) electrocatalysts are outstanding alternatives to high-cost Pt due to their good material properties. However, the few existing two-dimensional HER electrocatalysts have shortcomings that restrict their performance. Here, we report a first-principles study of single-layer A2BS4 (A = Ag, Cu; B= Mo, W) as HER electrocatalysts and identify single-layer Cu2WS4 as a promising candidate. Single-layer A2BS4 is found to be chemically, dynamically, and thermally stable. They require only a small energetic cost to be created from their layered bulks, suggesting the possibility of their exfoliation in experiments. Most importantly, without significant density of vacancies and in the absence of large applied strain, the basal plane of single-layer Cu2WS4 shows excellent electrocatalytic activity toward HER. Such an activity is attributed to the introduced in-gap states and d band center shifting upon adsorbing hydrogen. These characteristics suggest that single-layer Cu2WS4 is an extraordinary two-dimensional HER electrocatalyst.

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