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1.
Stem Cells Dev ; 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31530229

RESUMO

Stem cell-based therapies have the potential to heal burn wounds but thus far have had limited success in clinical practice. This study aimed to test and improve the therapeutic effects of adipose-derived stem cells (ASCs) on burn wound healing in a rat model. We also explored the role of ASCs in burn wound healing. We first isolated the autologous ASCs of each Sprague-Dawley rat used in this experiment and expanded them in vitro. Then, a 2 cm2 burn wound was made on the dorsal skin of each rat using a specialized heating iron. The treated rats received either one or three injections of 2×106 green fluorescent protein-labeled autologous ASCs, and the control rats received injections of the same volume of phosphate-buffered saline. A digital camera was employed to capture images of the wound area. We explored the role of ASCs in burn wound healing by cell tracing, evaluation of blood vessel number, analysis of a rat cytokine array panel and cell proliferation in vivo. Multiple injections of autologous ASCs accelerated the wound healing process more efficiently compared to that observed in the control treatment. A rat cytokine array test showed that transplanting ASCs led to significantly elevated expression of VEGF. Therefore, angiogenesis was significantly improved in ASC-treated rats, as more microvessels were observed in the wound skin of the experimental rats than in that of the control rats. Transplanted ASCs not only survived in the wound bed but also participated in the blood vessel regeneration process. ASCs also accelerated the wound healing process by increasing the rate of cell proliferation in the wound skin. Our data suggest that autologous ASCs transplantation accelerated the burn wound healing process and promoted blood vessel regeneration. ASCs could potentially be used in burn wound healing treatment.

2.
Sci Rep ; 9(1): 13253, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519966

RESUMO

Wood has been a crucial natural material for human civilization since prehistoric times. In archaeology, the examination of the wood microstructure is important for the study of architecture, musical instruments, sculptures, and so on. Scanning electron microscopy (SEM) examination is sometimes unsuitable for archaeological wood due to the limited amount of precious samples, which may be too small to be cut by microtomes and mounted on holders. Moreover, the conductive coating material cannot be uniformly deposited over uneven wood surfaces. To overcome these issues, a rapid and simple pretreatment method using room-temperature ionic liquids (RTIL) was proposed. Four common RTILs were evaluated for the pretreatment of wood chips for SEM examination. We found that water content, viscosity, density, and hydrophobicity of IL solutions were important factors affecting SEM image quality. A 7.5% solution of 1-butyl-1-methylpyrrolidium dicyanamide (BMP-DCA) in ethanol (v/v) was found to work very well. The IL pretreatment could be performed in a few minutes without special equipment. It is gentle enough to preserve delicate structures such as the torus/margo of pit membranes, even at elevated temperatures, without causing obvious damage or deformation. We successfully imaged hand-cut wood chips from 18th-century buildings, an 18th-century European violin, and a Chinese zither over 1000 years old. We therefore conclude that highly hydrophilic ionic liquids with low density and viscosity are suitable for use in SEM examinations of both modern and antique wood specimens.

3.
Clin Infect Dis ; 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31504322

RESUMO

BACKGROUND: China is thought to be a hotspot for zoonotic influenza virus emergence, yet there have been few prospective studies examining the occupational risk of such infections. METHODS: We present the first two years of data collected from a five-year, prospective cohort study of swine-exposed and unexposed participants, pigs, and six swine farms in China. We conducted serological and virological surveillance to examine evidence for swine influenza A virus infection in humans. RESULTS: Two hundred and seven (31.5%) of the 658 participants (521 swine-exposed and 137 unexposed), enrolled at any time period, seroconverted against at least one SIV subtype (swine H1N1 or H3N2). Swine-exposed participants' microneutralization titers, especially those enrolled at confined animal feeding operations (CAFOs), were higher against the swine H1N1 virus than were other participants at 12 and 24 months. Despite elevated titers, among the 187 study subjects for whom we had complete follow-up, participants working at swine CAFOs had significantly greater odds of seroconverting against both swine H1N1 (OR 19.16; 95% CI 3.55, 358.65) and swine H3N2 (OR 2.97; 95% CI 1.16, 8.01) viruses compared to unexposed and non-CAFO swine workers with less intense swine exposure. CONCLUSIONS: While some of the observed increased risk against swine viruses may have been explained by exposure to human influenza strains, study data suggest that even with elevated preexisting antibodies, swine-exposed workers are at high risk of infection with enzootic swine influenza A viruses.

4.
Nat Med ; 25(9): 1377-1384, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31501601

RESUMO

People living with HIV (PLWH) have expressed concern about the life-long burden and stigma associated with taking pills daily and can experience medication fatigue that might lead to suboptimal treatment adherence and the emergence of drug-resistant viral variants, thereby limiting future treatment options1-3. As such, there is strong interest in long-acting antiretroviral (ARV) agents that can be administered less frequently4. Herein, we report GS-CA1, a new archetypal small-molecule HIV capsid inhibitor with exceptional potency against HIV-2 and all major HIV-1 types, including viral variants resistant to the ARVs currently in clinical use. Mechanism-of-action studies indicate that GS-CA1 binds directly to the HIV-1 capsid and interferes with capsid-mediated nuclear import of viral DNA, HIV particle production and ordered capsid assembly. GS-CA1 selects in vitro for unfit GS-CA1-resistant capsid variants that remain fully susceptible to other classes of ARVs. Its high metabolic stability and low solubility enabled sustained drug release in mice following a single subcutaneous dosing. GS-CA1 showed high antiviral efficacy as a long-acting injectable monotherapy in a humanized mouse model of HIV-1 infection, outperforming long-acting rilpivirine. Collectively, these results demonstrate the potential of ultrapotent capsid inhibitors as new long-acting agents for the treatment of HIV-1 infection.

5.
J Invest Dermatol ; 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31421124

RESUMO

Both Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) are autoimmune diseases sharing similar genetic backgrounds. Genome-wide association studies (GWASs) have constantly disclosed numerous genetic variants conferring to both disease risks at 7q32.1, but the functional mechanisms underlying them are still largely unknown. Through a series of bioinformatics and functional analyses, we prioritized a potential independent functional SNP (rs13239597) within TNPO3 promoter region, residing in a putative enhancer element and validated that IRF5 is the distal target gene (∼118kb) of rs13239597, which is a key regulator involved in pathogenic autoantibody dysregulation increasing risk of both SLE and SSc. We experimentally validated the long-range chromatin interactions between rs13239597 and IRF5 using chromosome conformation capture (3C) assay. We further demonstrated that rs13239597-A acted as an allele-specific enhancer regulating IRF5 expression, independently of TNPO3 by using dual-luciferase reporter assays and CRISPR-Cas9. Particularly, the transcription factor EVI1 could preferentially bind to rs13239597-A allele and increase the enhancer activity to regulate IRF5 expression. Taken together, our results uncovered a mechanistic insight of a noncoding functional variant acting as an allele-specific distal enhancer to directly modulate IRF5 expression, which might obligate in understanding of complex genetic architectures of SLE and SSc pathogenesis.

6.
ACS Appl Mater Interfaces ; 11(36): 33006-33011, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31414589

RESUMO

A new fused-chrysene electron-donating core is synthesized, where chrysene is condensed with two thiophenes via two dihydrobenzene rings. Based on this building block coupled with two electron-accepting end groups of 1,1-dicyanomethylene-3-indanone, a new Z-shaped fused-ring electron acceptor, FCIC, is designed and synthesized. FCIC shows intense absorption in the 500-850 nm region, with a maximum molar absorptivity of 1.5 × 105 M-1 cm-1, a bandgap of 1.50 eV, and a charge mobility of 2.5 × 10-4 cm2 V-1 s-1. The ternary organic photovoltaic cells based on PTB7-Th/F8IC/FCIC yield an efficiency of 12.6%, higher than that of the binary cells of PTB7-Th/F8IC (10.7%) and PTB7-Th/FCIC (7.21%). Relative to the PTB7-Th/F8IC binary blend, the addition of FCIC leads to improvement in the open-circuit voltage, short-circuit current, and fill factor.

7.
J Food Sci ; 84(8): 2234-2241, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313313

RESUMO

In order to rapidly and nondestructively identify tea grades, fluorescence hyperspectral imaging (FHSI) technology was proposed in this paper. A total of 309 Tieguanyin tea samples with three different grades were collected and the fluorescence hyperspectral data was acquired by hyperspectrometer (400 to 1000 nm). The characteristic wavelengths were respectively selected by Bootstrapping Soft Shrinkage (BOSS), Variable Iterative Space Shrinkage Approach (VISSA) and Model Adaptive Space Shrinkage (MASS) algorithms. Then, Support Vector Machine (SVM) was applied to establishing the relationship between the characteristic peaks, the full spectra, three characteristic spectra and the labels of tea grades. The results showed that VISSA-SVM model had the best classification performance, but the model precision can still be improved. Thus, Artificial Bee Colony (ABC) algorithm was introduced to optimize the parameters of SVM model. The accuracy and Kappa coefficient of test set of VISSA-ABC-SVM model were improved to 97.436% and 0.962, respectively. Therefore, the combination of fluorescence hyperspectra with VISSA-ABC-SVM model can accurately identify the grade of Tieguanyin tea. PRACTICAL APPLICATION: The rapid and accurate nondestructive tea grade identification method contributes to the construction of the tea online grade detection system. FHSI technology can solve the shortcomings of the reported methods and improved the identification accuracy of tea grades. It can be applied to the rapid detection of tea quality by tea companies, tea market, tea farmers and other demanders.

8.
J Orthop Res ; 37(11): 2420-2428, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31297900

RESUMO

We assessed whether adding magnetic resonance (MR)-based features to a base model of clinically accessible participant characteristics (i.e., serological, radiographic, demographic, symptoms, and physical function) improved classification of adults who developed accelerated radiographic knee osteoarthritis (AKOA) or not over the subsequent 4 years. We conducted a case-control study using radiographs from baseline and the first four annual visits of the osteoarthritis initiative to define groups. Eligible individuals had no radiographic KOA in either knee at baseline (Kellgren-Lawrence [KL] grade <2). We classified two groups matched on sex (i) AKOA: at least one knee developed advanced-stage KOA (KL = 3 or 4) within 48 months and (ii) did not develop AKOA within 48 months. The MR-based features were assessments of bone, effusion/synovitis, tendons, ligaments, cartilage, and menisci. All characteristics and MR-based features were from the baseline visit. Classification and regression tree analyses were performed to determine classification rules and identify statistically important variables. The CART models with and without MR features each explained approximately 40% of the variability. Adding MR-based features to the model yielded modest improvements in specificity (0.90 vs. 0.82) but lower sensitivity (0.62 vs. 0.70) than the base model. There was consistent evidence that serum glucose, effusion-synovitis volume, and cruciate ligament degeneration are statistically important variables in classifying individuals who will develop AKOA. We found common MR-based measures failed to dramatically improve classification. These findings also show a complex interplay among participant characteristics and a need to identify novel characteristics to improve classification. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2420-2428, 2019.

9.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2806-2812, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359694

RESUMO

A total of twelve compounds were isolated from the ethyl acetate of the water extract of honey-fried Eriobotrya japonica through column chromatography over silica gel,Sephadex LH-20,RP-18,and preparative HPLC. Their structures were established by MS,1 D NMR and 2 D NMR data as japonicanoside A( 1),nerolidol-3-O-α-L-rhamnopyranosyl-( 1→2)-ß-D-glucopyranoside( 2),nerolidol-3-O-α-L-rhamnopyranosyl-( l→4)-α-L-rhamnopyranosyl-( 1 → 2)-[α-L-( 4-trans-feruloyl)-rhamnopyranosyl-( 1 → 6) ]-ß-D-glucopyranoside( 3),( +)-catechin( 4),(-)-epicatechin( 5),kaempferol 3-O-α-L-rhamnopyranoside( 6),quercitrin( 7),quercetin-3-O-ß-D-galactopyranoside( 8),quercetin-3-O-ß-glucopyranoside( 9),vanillin( 10),protocatechuic aldehyde( 11),and maltol( 12). Among them,1 is a new phenolic glycoside.


Assuntos
Eriobotrya/química , Glicosídeos/isolamento & purificação , Mel , Cromatografia Líquida de Alta Pressão , Glicosídeos/química , Espectroscopia de Ressonância Magnética , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
10.
BMC Musculoskelet Disord ; 20(1): 308, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31253142

RESUMO

BACKGROUND: To determine if adults with incident accelerated knee osteoarthritis (KOA) are more likely to have degenerative knee ligaments or tendons compared to individuals with typical or no KOA. METHODS: We identified 3 sex-matched groups among Osteoarthritis Initiative participants who had a knee without radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2): 1) accelerated KOA: at least 1 knee had KL grade ≥ 3 in ≤48 months, 2) typical KOA: at least 1 knee increased in radiographic scoring within 48 months, 3) no KOA: both knees had the same KL grade at baseline and 48 months. We evaluated knee magnetic resonance images up to 2 years before and after a visit when the accelerated or typical KOA criteria were met (index visit). Radiologists reported degenerative signal changes for cruciate and collateral ligaments, and extensor mechanism and proximal gastrocnemius tendons. We used generalized linear mixed models with 2 independent variables: group and time. RESULTS: Starting at least 2 years before onset, adults with accelerated KOA were twice as likely to have degenerative cruciate ligaments than no KOA (odds ratio = 2.10, 95% CI = 1.18, 3.74). A weaker association (not statistically significant) was detected for adults with accelerated versus typical KOA (OR = 1.72, 95%CI = 0.99, 3.02). Regardless of time, adults with accelerated (odds ratio = 2.13) or typical KOA (odds ratio = 2.16) were twice as likely to have a degenerative extensor mechanism than no KOA. No other structural features were statistically significant. CONCLUSIONS: Degenerative cruciate ligaments or extensor mechanism antedate radiographic onset of accelerated KOA. Hence, knee instability may precede accelerated KOA, which might help identify patients at high-risk for accelerated KOA and novel prevention strategies.

11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(6): 671-675, 2019 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-31197991

RESUMO

Objective: To explore the impact of preoperative traction on the osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures. Methods: Between February 2013 and May 2016, 120 patients with femoral neck fractures, who were treated with screw fixation, were collected. Sixty patients with fractures of Garden type Ⅰ and Ⅱ were non-displaced fracture group; 60 cases with fractures of Garden type Ⅲ and Ⅳ were displaced fracture group. The patients in 2 groups were randomly divided into traction and non-traction subgroups ( n=30). There was no significant difference in gender, age, injury mechanism, damage side, the time from injury to operation, and fracture classification between 2 subgroups ( P>0.05). Intracapsular pressure was recorded before operation. The quality of fracture reduction and the satisfaction ratio of screw implant were evaluated during operation. Visual analogue scale (VAS), Harris score, joint mobility, and the incidence of ONFH would be evaluated at 6 months, 1 year, and 2 years after operation. Results: All incisions of 2 groups healed by first intention after operation. There was no infection or deep vein thrombosis of lower extremity. All patients were followed up 2 years. In displaced and non-displaced fracture groups, the intracapsular pressure of traction subgroups were higher than that of non-traction group ( P<0.05); the differences of the quality of fracture reduction and the satisfaction ratio of screw implant were not significant ( P>0.05) between 2 subgroups. At 6 months, 1 year, and 2 years after operation, VAS scores were higher in traction subgroup than in non-traction subgroup ( P<0.05); and the joint mobility and Harris scores were lower in traction subgroup than in non-traction subgroup ( P<0.05). X-ray films showed all fractures healed. Except for the non-displaced group at 6 months, the incidences of ONFH were higher in traction subgroup than in non-traction subgroup at other time points ( P< 0.05). Conclusion: Preoperative traction may increase the risk of ONFH, which can increase the intracapsular pressure and affect the blood supply of femoral head.


Assuntos
Fraturas do Colo Femoral , Fixação Interna de Fraturas , Fraturas do Colo Femoral/terapia , Consolidação da Fratura , Humanos , Tração , Resultado do Tratamento
13.
BMC Musculoskelet Disord ; 20(1): 241, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31113401

RESUMO

BACKGROUND: Accelerated knee osteoarthritis (AKOA) is characterized by more pain, impaired physical function, and greater likelihood to receive a joint replacement compared to individuals who develop the typical gradual onset of disease. Prognostic tools are needed to determine which structural pathologies precede the development of AKOA compared to individuals without AKOA. Therefore, the purpose of this manuscript was to determine which pre-radiographic structural features precede the development of AKOA. METHODS: The sample comprised participants in the Osteoarthritis Initiative (OAI) who had at least one radiographically normal knee at baseline (Kellgren-Lawrence [KL] grade < 1). Participants were classified into 2 groups based on radiographic progression from baseline to 48 months: AKOA (KL grade change from < 1 to > 3) and No AKOA. The index visit was the study visit when participants met criteria for AKOA or a matched timepoint for those who did not develop AKOA. Magnetic resonance (MR) images were assessed for 12 structural features at the OAI baseline, and 1 and 2 years prior to the index visit. Separate logistic regression models (i.e. OAI baseline, 1 and 2 years prior) were used to determine which pre-radiographic structural features were more likely to antedate the development of AKOA compared to individuals not developing AKOA. RESULTS: At the OAI baseline visit, degenerative cruciate ligaments (Odds Ratio [OR] = 2.2, 95% Confidence Interval [CI] = 1.3,3.5), infrapatellar fat pad signal intensity alteration (OR = 2.0, 95%CI = 1.2,3.2), medial/lateral meniscal pathology (OR = 2.1/2.4, 95%CI = 1.3,3.4/1.5,3.8), and greater quantitative knee effusion-synovitis (OR = 2.2, 95%CI = 1.4,3.4) were more likely to antedate the development of AKOA when compared to those that did not develop AKOA. These results were similar at one and two years prior to disease onset. Additionally, medial meniscus extrusion at one year prior to disease onset (OR = 3.5, 95%CI = 2.1,6.0) increased the likelihood of developing AKOA. CONCLUSIONS: Early ligamentous degeneration, effusion/synovitis, and meniscal pathology precede the onset of AKOA and may be prognostic biomarkers.

14.
Emerg Infect Dis ; 25(6): 1192-1195, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31107220

RESUMO

Human infections with vaccinia virus (VACV), mostly from laboratory accidents or contact with infected animals, have occurred since smallpox was eradicated in 1980. No recent cases have been reported in China. We report on an outbreak of VACV from occupational exposure to rabbit skins inoculated with VACV.

15.
BMC Ophthalmol ; 19(1): 94, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31014258

RESUMO

BACKGROUND: The exact pathogenesis of idiopathic choroidal neovascularization (ICNV) remains unclear. Cytokine-mediated inflammation has been thought to be involved in the pathophysiology of ICNV. The purpose of this study was to investigate serum cytokine profiles in patients with ICNV and to explore the relationship between serum cytokine levels and ICNV severity. METHODS: This case-control study was conducted in 32 ICNV patients and 30 healthy volunteers. Clinical and demographic information was obtained from the medical data platform and the serum was analysed with a multiplex assay to determine the levels of seven cytokines: interleukin (IL)-2, IL-10, IL-15, IL-17, basic fibroblast growth factor (basic FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF). RESULTS: Serum levels of IL-2, IL-10, IL-17, basic FGF, and VEGF were elevated in ICNV patients compared to controls. Serum GM-CSF levels were positively related to central retinal thickness, and serum IL-17 levels were positively related to CNV lesion area. CONCLUSION: Serum inflammatory cytokines were significantly elevated in ICNV patients compared to controls. This suggests that systemic inflammation may play a critical role in the physiopathology of ICNV.


Assuntos
Neovascularização de Coroide/sangue , Citocinas/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Neovascularização de Coroide/fisiopatologia , Feminino , Humanos , Inflamação/fisiopatologia , Masculino , Pessoa de Meia-Idade , Retina/patologia , Acuidade Visual/fisiologia
16.
Genome Biol ; 20(1): 79, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30999938

RESUMO

BACKGROUND: Pistachio (Pistacia vera), one of the most important commercial nut crops worldwide, is highly adaptable to abiotic stresses and is tolerant to drought and salt stresses. RESULTS: Here, we provide a draft de novo genome of pistachio as well as large-scale genome resequencing. Comparative genomic analyses reveal stress adaptation of pistachio is likely attributable to the expanded cytochrome P450 and chitinase gene families. Particularly, a comparative transcriptomic analysis shows that the jasmonic acid (JA) biosynthetic pathway plays an important role in salt tolerance in pistachio. Moreover, we resequence 93 cultivars and 14 wild P. vera genomes and 35 closely related wild Pistacia genomes, to provide insights into population structure, genetic diversity, and domestication. We find that frequent genetic admixture occurred among the different wild Pistacia species. Comparative population genomic analyses reveal that pistachio was domesticated about 8000 years ago and suggest that key genes for domestication related to tree and seed size experienced artificial selection. CONCLUSIONS: Our study provides insight into genetic underpinning of local adaptation and domestication of pistachio. The Pistacia genome sequences should facilitate future studies to understand the genetic basis of agronomically and environmentally related traits of desert crops.


Assuntos
Adaptação Biológica , Domesticação , Evolução Molecular , Genoma de Planta , Pistacia/genética , Família Multigênica , Tolerância ao Sal/genética , Transcriptoma
17.
Arthritis Rheumatol ; 71(9): 1472-1482, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30951251

RESUMO

OBJECTIVE: To evaluate rheumatoid arthritis (RA) disease activity and risk of RA-associated interstitial lung disease (RA-ILD). METHODS: We investigated disease activity and risk of RA-ILD using the Brigham RA Sequential Study (BRASS, 2003-2016). All patients were diagnosed as having RA according to accepted criteria. Disease Activity Scores in 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. Diagnosis of RA-ILD was determined by review of images from clinically indicated chest computed tomography scans. We analyzed patients without RA-ILD at baseline. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD, using annually updated DAS28 data, with adjustment for known RA-ILD risk factors (age, sex, smoking status, RA duration, and serologic status). We performed alternative analyses that did not censor at the time of missing DAS28 data and included adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, and presence of rheumatoid nodules. RESULTS: Among 1,419 participants, the mean ± SD age was 55.8 ± 14.2 years, and 68.6% were seropositive for either cyclic citrullinated peptide or rheumatoid factor. We identified 85 incident cases of RA-ILD during a mean ± SD follow-up duration of 8.9 ± 4.2 years per patient. The moderate/high disease activity group had a multivariable HR of 2.22 (95% CI 1.28-3.82) for RA-ILD compared to the remission/low disease activity group. Risk of RA-ILD increased across disease activity categories: multivariable HR 1.00 (reference) for remission, 1.41 (95% CI 0.61-3.28) for low disease activity, 2.08 (95% CI 1.06-4.05) for moderate disease activity, and 3.48 (95% CI 1.64-7.38) for high disease activity (P for trend = 0.001). For each unit increase in the DAS28, the risk of RA-ILD increased by 35% (95% CI 14-60%). Results were similar in analyses that included follow-up for missing DAS28 data and with adjustment for use of methotrexate, use of glucocorticoids, presence of bone erosions, or presence of rheumatoid nodules. CONCLUSION: Active articular RA was associated with an increased risk of developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.

19.
Arthritis Rheumatol ; 71(9): 1460-1471, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30920773

RESUMO

OBJECTIVE: To evaluate the effects of long-term physical activity on subsequent risk of rheumatoid arthritis (RA) in a prospective cohort study. METHODS: This study investigated physical activity and RA risk among women from the Nurses' Health Study II (1989-2015). Physical activity exposures and covariates were prospectively obtained using biennial questionnaires. Two rheumatologists independently reviewed the medical records of women who self-reported a new diagnosis of RA on biennial questionnaires and who screened positive for RA based on a supplemental survey. All incident RA cases met the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA. The primary analysis investigated the long-term cumulative average number of hours spent in recreational physical activity 2-8 years prior to the RA diagnosis, a time span chosen to reduce the potential for reverse causation bias, since early RA affects physical activity prior to diagnosis. Estimated Cox regression hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the risk of RA serologic phenotypes (all, seropositive, or seronegative) in relation to physical activity categories. The analyses were adjusted for body mass index (BMI) at age 18 years and time-varying potential confounders, and the mediating effect of updated BMI on the interaction between physical activity and RA risk was quantified. RESULTS: Among the 113,366 women analyzed, 506 incident RA cases (67.0% with seropositive RA) were identified during 2,428,573 person-years of follow-up. After adjustment for confounders, including smoking, dietary quality, and BMI at age 18 years, increasing cumulative average total hours of recreational physical activity was associated with a reduced risk of RA, as follows: HR 1.00 for <1 hour/week (reference), HR 1.00 (95% CI 0.78-1.29) for 1 to <2 hours/week, HR 0.92 (95% CI 0.72-1.17) for 2 to <4 hours/week, HR 0.84 (95% CI 0.63-1.12) for 4 to <7 hours/week, and HR 0.67 (95% CI 0.47-0.98) for ≥7 hours/week (P for trend = 0.02). The proportion of the effect between physical activity and RA mediated by updated BMI was 14.0% (P = 0.002) for all RA and 20.0% (P = 0.001) for seropositive RA. CONCLUSION: Higher levels of physical activity were associated with reduced RA risk. These results add to the literature implicating metabolic factors in the pathogenesis of RA.

20.
Bioanalysis ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30767560

RESUMO

AIM: MK-8591 (EFdA), a novel anti-HIV nucleoside analog, is converted to mono-, di- and tri-phosphates (MK-8591-MP, MK-8591-DP and MK-8591-TP) intracellularly, among which MK-8591-TP is the active pharmacological form. An ultrasensitive LC-MS/MS assay was required to measure MK-8591-DP and MK-8591-TP levels in human peripheral blood mononuclear cells (PBMCs). Sensitivity and reproducibility were major bottlenecks in these analyses. MATERIALS AND METHODS: Human PBMCs were isolated from blood and lysed with 70/30 methanol/RPMI-1640. An LC-MS/MS method was developed to simultaneously quantify MK-8591-DP and MK-8581-TP in PBMC lysates. Results: Low flow LC and dimethyl sulfoxide mediated signal enhancement enabled an extreme sensitivity with limit of quantitation at 0.1 ng/ml. Assay accuracy was 92.5-106% and precision was 0.7-12.1% for a linear curve range of 0.1-40 ng/ml. Matrix variability and interference liability were comprehensively evaluated. CONCLUSION: Our study findings and steps taken in addressing clinical sample issues help understand and overcome the challenges facing intracellular nucleotide analog analysis.

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