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1.
Talanta ; 207: 120293, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594564

RESUMO

Droplet digital PCR (ddPCR) has attracted much attention in the detection of genetic signatures of cancer present at low levels in circulating tumor DNA (ctDNA) in blood. A growing number of laboratory-developed liquid biopsy tests based on such technology have become commercially available for clinical settings. To obtain consistent and comparable results, an international standard is necessary for validation of the analytical performance. In this study, a novel and SI-traceable "ctDNA" reference material (RM) carrying BRAF V600E was prepared by gravimetrically mixing a 152 bp PCR amplicon and sonicated wild-type genomic DNA. The ddPCR performance was evaluated by analyzing serial "ctDNA" dilutions using a competitive MGB assay. The mutant frequency concordance (k) between ddPCR and the gravimetrical value was 1.03 in the range from 53.9% to 0.1%. The limit of blank (LoB), detection (LoD) and quantification (LoQ) of ddPCR assay were determined to be 0.01%, 0.02% and 0.1%, respectively. Results from the interlaboratory study, using challenging low levels of BRAF V600E ctDNA RMs, demonstrated that the participating laboratories had the appropriate technical competency to perform accurate ddPCR-based low level of ratio measurements. However, a systematic error caused by uncorrected droplet volume in Naica Crystal ddPCR platform was found by using the ctDNA RM. Between-laboratory consistency in copy number measurement was greatly improved when a correct droplet volume was applied for the ddPCR measurement by using the ctDNA RM. This confirms that the "ctDNA" RM is fit for the validation of ddPCR systems for ctDNA quantification. This would also support translation of tests for circulating tumor DNA by ddPCR into routine use.

2.
J Hazard Mater ; 382: 121041, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31470295

RESUMO

The high concentration of chloride (Cl-) ions in leachate often has negative effects in their harmless treatments, and the common treatments containing the ion exchange method consume excessive antichlors due to their large particle sizes and unfavorable morphologies. Herein, the antichlors of the Bi(III) containing oxides with quantum dots (QDs) or two-dimensional (2D) structures are first explored for the removal and recovery of Cl- ions in concentrated leachate. By using the QDs/2D flakes constructed antichlors of Bi2O3 and the magnetite Bi-Ti composite, the maximum Cl- removal rates of 61.8% and 66.1% are respectively achieved under the optimum conditions. The higher removal efficiency of the magnetite Bi-Ti composite is contributed by its less stable crystal phases of Bi25FeO40/Bi12TiO20, which can proceed more deeply in the removal of Cl- ions compared with that of Bi2O3. The recovered terminal magnetite Bi-Ti precipitate with Bi2O3/BiOCl heterostructure exhibits excellent photocatalytic activity in the degradation of the dechlorinated leachate, where a total organic carbon removal rate of 87.2% is achieved under UV-vis-near-infrared irradiation. Therefore, the selection of Bi(III) containing oxides opens a promising and high-value method for the removal and recovery of Cl- ions in leachate and other waste waters.

3.
Sensors (Basel) ; 19(21)2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31684132

RESUMO

Bioradar-based noncontact breathing detection technology has been widely studied due to its superior detection performance. In this paper, a breath detection mechanism based on the change in radar cross section (RCS) is proposed by using a forward scatter radar and the deduction of the mathematical model of the received signal. Furthermore, we completed human breathing detection experiments in an anechoic chamber and in an ordinary chamber; we obtained the breathing rate through envelope detection in cases where the human orientation angle was 0, 30, 60, and 90°. The analysis of the measured data shows that the theoretical model fits well with the measured results. Compared with the existing single-base radar detection schemes, the proposed scheme can detect human respiratory rates in different orientations.

4.
Pharmacol Res ; : 104501, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689520

RESUMO

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has lagged behind seriously. However, natural products have always inspired the development of drugs. Meanwhile, there is evidence that some natural products can also play a certain role in the treatment of ALD. Thus, we reviewed the natural products, extracts and formulations with potential anti-ALD activities by consulting the relevant data in the databases of PubMed, Web of Science and CNKI databases, in order to elucidate the regulated mechanism of these natural products. Sum up, the insights provided in present review will be needed for further exploration of botanical drugs in the development of ALD therapy.

5.
J Cell Biochem ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696964

RESUMO

The proliferation of hepatic progenitor cells (HPCs) is observed in reactive conditions of the liver and primary liver cancers. Ring1 as a member of polycomb-group proteins which play vital roles in carcinogenesis and stem cell self-renewal was increased in HCC patients and promoted proliferation and survival of cancer cell by degrading p53. However, the mechanisms of Ring1 driving the progression of hepatocarcinogenesis have not been elucidated. In this study, forced expression Ring1 and Ring1 siRNA lentiviral vectors were utilized to stably overexpression and silence Ring1 in HPC cell line (WB-F344), respectively. Our finding indicated that overexpression of Ring1 in HPCs promoted colony formation, cell multiplication, and invasion in vitro, conversely depletion of Ring1 repressed the biological functions of HPCs relative to controls. The expression of ß-catenin was upregulated in the HPCs with overexpression of Ring1, and the correlation analysis also showed that ß-catenin and Ring1 had a significant correlation in the liver cancer tissues and adjacent tissues. The activation of the Wnt/ß-catenin signaling pathway significantly increased the expression of liver cancer stem cells related (LCSCs)-related molecular markers CD90 and EpCAM, which led to the transformation of HPCs into LCSCs. Most importantly, the injection of HPCs with overexpressed Ring1 into the subcutaneous of nude mice leads to the formation of poorly differentiated HCC neoplasm. Our findings elucidate that overexpression of Ring1 the activated Wnt/ß-catenin signaling pathway and drove the transformation of HPCs into cancer stem cell-like cells, suggesting Ring1 has extraordinary potential in early diagnosis of HCC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31697226

RESUMO

A novel Vogesella strain, YM-1T, was recovered from human urine in PR China in 2017. Cells of strain YM-1T were Gram-stain-negative, rod-shaped, aerobic, motile, non-spore-forming and poly-ß-hydroxybutyrate-accumulating. The strain contained C16:1ω6c/C 16:1ω7c, C16:0 and C18:0ω7c as major fatty acids; phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid as major polar lipids; and ubiquinone-8 as the predominant respiratory quinone. Comparison of 16S rRNA gene sequences indicated that this strain had highest similarities to Vogesella perlucida DS-28T (98.8 %) and Vogesella mureinivorans 389T (98.1 %). The results of phylogenetic analysis based on the 16S rRNA gene sequences revealed that the novel strain was clustered and well separated with V. perlucida DS-28T and V. mureinivorans 389T within the genus Vogesella. The average nucleotide identity (ANI) and amino acid identity (AAI) analyses showed that this strain was not identified as V. perlucida DS-28T or V. mureinivorans 389T, with values well below the threshold limit for species demarcation (ANI <88.1 %, AAI <88.6 %). Based on the above results, strain YM-1T is proposed to be a novel species of the genus Vogesella with the name Vogesella urethralis sp. nov. (YM-1T=NBRC 113779=CGMCC 1.17135).

7.
Artigo em Inglês | MEDLINE | ID: mdl-31705568

RESUMO

RATIONALE: In chemical isotope labeling (CIL) LC/MS metabolome analysis, the peak pairs of the same metabolite detected from different samples are aligned according to their mass and retention time (RT). Any RT shift of a peak pair in one of the sample files that falls outside the tolerance window will result in misalignment of the pair as a different metabolite. Thus, determination and correction of any significant RT shift are important to ensure the generation of high-quality metabolome results. METHODS: In CIL LC/MS, the heavy-isotope-labeled pooled sample is spiked into all light-isotope-labeled individual samples. As a result, in the analysis of labeled samples of the same type, many common metabolites are detectable with high intensity in all LC/MS runs. We have developed a method to select a few of these metabolites as internal RT reference markers to check the occurrence of any RT shift in a LC/MS run. If significant shift is found, an expanded list of these markers with their RT values covering the entire LC retention time window is selected to serve as internal RT calibrants to re-calibrate the chromatogram to correct any RT shift. RESULTS: We wrote a software program in R to perform RT check (RTC) and re-calibration (RT-calib). This program can quickly determine the occurrence of any RT shift falling outside a user-defined threshold in a LC/MS run, thereby triggering a timely intervention to correct the problem (e.g., fixing a small leak or changing a column). In the analysis of 278 dansylation LC/MS runs of human urine samples, we show that the RT values can be corrected to be within a 30-s window. CONCLUSIONS: A RT-check method and program tailored to CIL LC/MS metabolome analysis have been developed for quick detection and correction of RT shifts during the course of running many metabolome samples.

8.
Hepatology ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31675427

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver condition. Predicting its progression could help clinicians manage and potentially prevent complications. We evaluated the independent and joint effects of metabolic traits on the risk of cirrhosis and hepatocellular carcinoma (HCC) among patients with NAFLD. We assembled a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration between 1/1/2004 and 12/31/2008 with follow-up through 12/31/2015. We performed competing risk, adjusted cause-specific Cox models to evaluate the effects of metabolic traits (diabetes, hypertension, dyslipidemia, obesity) as additive or combined indicators on time to develop cirrhosis or HCC or a composite endpoint of both. Of the 271,906 patients, 22,794 developed cirrhosis, and 253 developed HCC during a mean of 9 years follow up. At baseline, the mean BMI was 31.6 (SD, 5.6), 28.7% had diabetes, 70.3% hypertension, and 62.3% had dyslipidemia with substantial overlap among the these traits. The risk of progression was the lowest in patients with only one or no metabolic trait. There was a stepwise increase in risk with each additional metabolic trait. Compared to patients with no metabolic trait, patients with both hypertension and dyslipidemia had 1.8-fold higher risk of progression to cirrhosis/HCC (hazard ratio (HR) =1.8, 95% CI=1.59-2.06); the risk was 2.6-fold higher in patients with diabetes, obesity, dyslipidemia and hypertension (HR=2.6, 95% CI=2.3,2.9). These associations were stronger for HCC. Diabetes had the strongest association with HCC in this cohort. CONCLUSIONS: Each additional metabolic trait increased the risk of cirrhosis and HCC in patients with NAFLD. Diabetes conferred the highest risk of progression to HCC. Diabetic patients with co-existing hypertension and obesity may be important targets for secondary prevention.

9.
Front Immunol ; 10: 2394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681286

RESUMO

Type III interferon-lambda (IFN-λ) plays a critical role against infection, particularly in mucosal infection in the respiratory and gastrointestinal tract. Our study and other previous studies have shown that porcine IFN-λ more efficiently curtails the infection of porcine epidemic diarrhea virus (PEDV) in the intestine epithelia than type I IFN, whereas IFN-λ3 exerts a more potent effect than IFN-λ1. However, the underlying mechanism remains elusive, and in particular, the transcriptional profile induced by IFN-λ3 has not been reported. Here, to resolve the mechanism responsible for the disparity between IFN-λ3 and type I IFN in anti-mucosal virus infection, we compared the transcription profiles induced by the two IFNs in porcine intestinal epithelial (IPEC-J2) cells by RNA-Seq. Our results showed that the pretreatment of IPEC-J2 cells with IFN-λ3 resulted in the differential expression of 983 genes. In contrast, IFN-α only modified the expression of 134 genes, and 110 of these genes were also observed in the response to IFN-λ3. A transcriptional enrichment analysis indicated that IFN-λ3 or IFN-α regulates multiple cellular processes and that IFN-λ3 activates more robust signaling pathways, particularly the antiviral Jak-STAT signaling pathway, than IFN-α. Furthermore, we verified the RNA-Seq results through an RT-qPCR analysis of IPEC-J2 cells and porcine enteroids. Moreover, transient expression of the porcine rsad2 and mx2 genes among the top 10 genes induced by IFN-λ3 significantly inhibited PEDV infection. Collectively, the data showed that IFN-λ3 induces a unique transcriptional profile that does not completely overlap with that induced by IFN-α and strongly elicits a set of genes responsible for the antiviral activity of IFN-λ3. These findings provide important knowledge regarding the elicited ISGs of type I and III IFNs in restricting porcine intestinal viral infection.

10.
Math Biosci Eng ; 16(6): 7659-7670, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31698632

RESUMO

Objectives: The purpose of this meta-analysis was to evaluate the efficacy and toxicity profile of apatinib for the treatment of advanced non-small cell lung cancer (NSCLC). Methods: We systematically searched databases for randomized clinical trials published as of November 25, 2017, in which apatinib treatment was compared to placebo or chemotherapy in patients with advanced NSCLC. Two investigators independently assessed the articles and extracted their data. The hazard ratios (HRs) for progression-free survival (PFS), relative risks (RRs) for overall response rates (ORRs), disease control rates (DCRs), and odds ratios (ORs) for main toxicity were analyzed using the RevMan 5.3 software (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Results: Our analysis included 413 patients from 5 clinical studies. The pooled HR for PFS was 0.32 (95% confidence interval (CI) 0.21-0.48; P < 0.00001). The pooled RRs for ORR and DCR were 2.03 (95% CI 1.36-3.01; P = 0.0005) and 1.66 (95% CI 1.07-2.57; P = 0.02), respectively. The pooled OR for main toxicity was 1.34 (95% CI, 0.57-3.17; P = 0.5). Conclusions: Apatinib was a viable treatment alternative for advanced NSCLC, as it offered a clinically meaningful and statistically significant improvement in PFS, ORR, and DCR. Moreover, therapy with apatinib did not significantly increase toxicity.

11.
Hum Cell ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586299

RESUMO

Long noncoding RNAs (lncRNAs) have been found to be abnormally expressed in cancer, and lncRNA small nucleolar RNA host genes (SNHGs) play critical roles in tumour progression. SNHG3 has been identified as an oncogene in multiple tumour types. However, the role of SNHG3 in breast cancer has not been reported. In this study, we found that SNHG3 was upregulated and associated with tumour malignancy in patients with breast cancer. SNHG3 knockdown inhibited the growth and metastatic capabilities of breast cancer cells in vitro and vivo. We used bioinformatics prediction and functional assay validation to determine that SNHG3 upregulation inhibited miR-384 activity and led to hepatoma-derived growth factor (HDGF) overexpression in breast cancer cells. The findings of this study show that SNHG3 functions as an oncogene in breast cancer and promotes breast cancer cell proliferation and invasion by regulating the miR-384/HDGF axis. The present study might provide a new target for the treatment of breast cancer.

12.
Elife ; 82019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570119

RESUMO

Quantitative behavioral measurements are important for answering questions across scientific disciplines-from neuroscience to ecology. State-of-the-art deep-learning methods offer major advances in data quality and detail by allowing researchers to automatically estimate locations of an animal's body parts directly from images or videos. However, currently-available animal pose estimation methods have limitations in speed and robustness. Here we introduce a new easy-to-use software toolkit, DeepPoseKit, that addresses these problems using an efficient multi-scale deep-learning model, called Stacked DenseNet, and a fast GPU-based peak-detection algorithm for estimating keypoint locations with subpixel precision. These advances improve processing speed >2× with no loss in accuracy compared to currently-available methods. We demonstrate the versatility of our methods with multiple challenging animal pose estimation tasks in laboratory and field settings-including groups of interacting individuals. Our work reduces barriers to using advanced tools for measuring behavior and has broad applicability across the behavioral sciences.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31574238

RESUMO

RATIONALE: When stereotactic ablative radiotherapy (SABR) is an option for non-small cell lung cancer (NSCLC) patients, distinguishing between N0, N1 and N2 or N3 (N2|3) disease is important. OBJECTIVES: To develop a prediction model for estimating the probability of N0, N1, and N2|3 disease. METHODS: Consecutive patients with clinical-radiographic stage T1-3/N0-3/M0 NSCLC that underwent endobronchial ultrasound-guided staging from a single center were included. Multivariate ordinal logistic regression analysis was used to predict the presence of N0, N1 or N2|3 disease. Temporal validation used consecutive patients from three years later at the same center. External validation used three other hospitals. RESULTS: In the model development cohort (n=633), younger age, central location, adenocarcinoma and higher PET-CT nodal stage were associated with a higher probability of having advanced nodal disease. Area under the receiver operating characteristic curves (AUC) were 0.84 and 0.86 for predicting N1 or higher (vs. N0) disease and N2|3 (vs. N0|1) disease respectively. Model fit was acceptable (Hosmer-Lemeshow p=0.960; Brier score 0.36). In the temporal validation cohort (n=473) AUCs were 0.86 and 0.88. Model fit was acceptable (Hosmer-Lemeshow p=0.172; Brier score 0.30). In the external validation cohort (n=722), AUCs were 0.86 and 0.88, but required calibration (Hosmer-Lemeshow p<0.001; Brier score 0.38). Calibration using the general calibration method resulted in acceptable model fit (Hosmer-Lemeshow p=0.094; Brier score, 0.34). CONCLUSIONS: This prediction model can estimate the probability of N0, N1 and N2|3 disease in NSCLC patients. The model has the potential to facilitate decision-making in NSCLC patients when SABR is an option.

14.
Elife ; 82019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31635693

RESUMO

The subjective inner experience of mental imagery is among the most ubiquitous human experiences in daily life. Elucidating the neural implementation underpinning the dynamic construction of mental imagery is critical to understanding high-order cognitive function in the human brain. Here, we applied a frequency-tagging method to isolate the top-down process of speech mental imagery from bottom-up sensory-driven activities and concurrently tracked the neural processing time scales corresponding to the two processes in human subjects. Notably, by estimating the source of the magnetoencephalography (MEG) signals, we identified isolated brain networks activated at the imagery-rate frequency. In contrast, more extensive brain regions in the auditory temporal cortex were activated at the stimulus-rate frequency. Furthermore, intracranial stereotactic electroencephalogram (sEEG) evidence confirmed the participation of the inferior frontal gyrus in generating speech mental imagery. Our results indicate that a disassociated neural network underlies the dynamic construction of speech mental imagery independent of auditory perception.

15.
Biomed Res Int ; 2019: 4834202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637257

RESUMO

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS.

16.
J Glaucoma ; 28(11): 974-978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31567910

RESUMO

PRECIS: Chinese Glaucoma Study Consortium (CGSC) as the first nationwide glaucoma registry in China, we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics. AIM: As a leading cause of blindness in China, glaucoma affects 2% to 4% of adults over the age of 40 and will become increasingly prevalent as the population ages. At the national level, there are few reports on the current medical practice for glaucoma patients. CGSC will be considered as the first nationwide glaucoma registry in China. Here we describe its design, rationale, the geographic distribution of the hospitals, and baseline patient characteristics. METHODS: From December 21, 2015 to September 9, 2018, CGSC recruited patients with the diagnoses of primary angle-closure suspect, primary angle-closure, primary angle-closure glaucoma, acute primary angle closure, primary open-angle glaucoma (POAG), pigmentary glaucoma (PG), and pseudoexfoliative glaucoma (PXG) from 111 hospitals covering 67 cities from 22 provinces, 4 municipalities, and 5 autonomous regions in mainland China. Clinical data were collected using an Electronic Data Capture System designed by Tongren hospital and Gauss informed Ltd. Blood samples were collected from every patient for further genetic analysis. RESULTS: Medical records of 10,892 patients were collected, of which 5762 patients have complete information. The average age of those with complete information (n=5762) was 62.05±11.26 years old, and 35.25% were males. Primary angle-closure disease, including primary angle-closure suspect/primary angle-closure/primary angle-closure glaucoma/acute primary angle closure, was predominant (4588, 79.63%), and the distribution for others is as follows: POAG (1116, 19.37%), PXG (41, 0.71%) and PG (17, 0.30%). A total of 16,684 blood samples were collected, of which 9917 (82.68%) were primary angle-closure disease, 1987 (16.57%) were POAG, 69 (0.58%) were PXG, 22 (0.18%) were PG, and 4689 were normal controls. CONCLUSIONS: The CGSC is the first national-level glaucoma registry study in China. Clinical data and blood samples will provide the opportunity to study the epidemiology of glaucoma in Chinese hospitals, to evaluate the level of medical diagnosis and treatment of glaucoma in China, and to identify the susceptibility loci for glaucoma.

17.
Aging (Albany NY) ; 11(19): 8701-8709, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613794

RESUMO

After spine surgery, venous thromboembolism (VTE) is not uncommon in aged patients. This study investigates time-to-event risk factors of postoperative VTE based on medical records of aged patients (age≥60 yr) between January 2013 and December 2018. All participants had undergone lower extremity ultrasonography pre- and postoperatively at the first, second, fourth, eighth, and twelfth weeks. Mann-Whitney U tests and chi-square tests were used for univariate analyses, and Cox regression was utilized for multivariate analyses. A total of 1620 cases were recruited, VTE group (N=382, 23.6%) and non-VTE group (N=1238, 76.4%), aged 67 (IQR 11) years and 65 (IQR 6) years, respectively. The univariate analyses indicated significant differences between the VTE and non-VTE groups regarding advanced age, VTE history, hypertension, fusion, hospital stay, FIB, HDL, D-dimer, and TC (all P<0.05). The Cox regression showed that advanced age (OR=1.108; 95% CI, 1.091-1.126), VTE history (OR=4.962; 95% CI, 3.849-6.397), and hypertension (OR=1.344; 95% CI, 1.084-1.667) were the risk factors for postoperative VTE (P<0.05). The time-to-event analyses indicated that the hazard of VTE formation was highest in the first postoperative week. In conclusion, advanced age, VTE history, and hypertension are main risks for VTE formation, particularly in the first postoperative week.

18.
J Autoimmun ; 104: 102333, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31564474

RESUMO

During host immune response, an initial and sufficient activation is required to avoid infection and cancer, yet an excessive activation bears the risk of autoimmune reactivity and disease development. This fastidious balance of the immune system is regulated by co-stimulatory and co-inhibitory molecules, also known as immune checkpoints. Both excessive co-stimulation and insufficient co-inhibition can induce the activation and proliferation of autoreactive cells that may lead to the development of autoimmune diseases. During the last decade, a growing number of new immune checkpoint receptors and ligands have been discovered, providing an attractive approach to investigate their implication in the pathogenesis of autoimmune diseases and their potential role as targets for effective therapeutic interventions. In this review, we focus on the roles and underlying mechanisms of co-stimulatory and co-inhibitory receptors and other molecules that function as immune checkpoints in autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, Sjögren's syndrome, type I diabetes and inflammatory bowel disease. We also summarize previous and current clinical trials targeting these checkpoint pathways in autoimmune diseases and discuss further therapeutic implications and possible risks and challenges.

19.
Ann Behav Med ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31612218

RESUMO

BACKGROUND: Low socioeconomic status (SES) is linked to failure to quit smoking. Health inequity models suggest that low SES smokers experience barriers to quitting in part due to greater exposure to pro-smoking social contexts. PURPOSE: The current study examined longitudinal associations among socioeconomic status, pro-smoking social context factors (i.e., exposure to other smokers, places where smoking was allowed), cigarette availability, and smoking lapse during a quit attempt. METHODS: Ecological momentary assessments (EMA) were gathered from a multiethnic sample of 365 smokers engaged in a quit attempt. A multilevel structural equation model estimated a latent variable for SES indicated by income, education, health insurance, and employment, associations among EMAs for pro-smoking social contexts and cigarette availability, and indirect effects of SES through, pro-smoking social contexts and cigarette availability to subsequent smoking lapse. RESULTS: Lower SES scores were associated with a higher likelihood of smoking lapse. Decomposition of the path from SES to smoking lapse into indirect effects showed significant paths through exposure to places where smoking is allowed and cigarette availability. Additionally, significant serial indirect paths from SES through both exposure to other smokers and places where smoking was allowed, in turn, through cigarette availability, and, ultimately, to smoking lapse were noted. CONCLUSIONS: Consistent with models positing that SES influences health behaviors via contextual factors, the current study demonstrated that low SES smokers attempting to quit experienced greater pro-smoking social contexts that affected subsequent risk for lapse.

20.
Magn Reson Med ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31631404

RESUMO

PURPOSE: To investigate direct imaging of trabecular bone using a 3D adiabatic inversion recovery prepared ultrashort TE cones (3D IR-UTE-Cones) sequence. METHODS: The proposed 3D IR-UTE-Cones sequence used a broadband adiabatic inversion pulse together with a short TR/TI combination to suppress signals from long T2 tissues such as muscle and marrow fat, followed by multispoke UTE acquisition to detect signal from short T2 water components in trabecular bone. The feasibility of this technique for robust suppression of long T2 tissues was first demonstrated through numerical simulations. The proposed IR-UTE-Cones sequence was applied to a hip agarose bone phantom and to 6 healthy volunteers for morphologic and quantitative T 2 ∗ and proton density mapping of trabecular bone. RESULTS: Numeric simulation suggests that the IR technique with a short TR/TI combination provides sufficient suppression of long T2 tissues with a wide range of T1 s. High contrast imaging of trabecular bone can be achieved ex vivo and in vivo, with fitted T 2 ∗ values of 0.3-0.45 ms and proton densities of 5-9 mol/L. CONCLUSION: The 3D IR-UTE-Cones sequence with a short TR/TI combination provides robust suppression of long T2 tissues and allows both selective imaging and quantitative ( T 2 ∗ and proton density) assessment of short T2 water components in trabecular bone in vivo.

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