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1.
Biomed Res Int ; 2020: 1807089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029490

RESUMO

Lung cancer is one of the leading triggers for cancer death worldwide. In this study, the relationship of the aberrantly methylated and differentially expressed genes in lung adenocarcinoma (LUAD) with cancer prognosis was investigated, and 5 feature genes were identified eventually. Specifically, we firstly downloaded the LUAD-related mRNA expression profile (including 57 normal tissue samples and 464 LUAD tissue samples) and Methy450 expression data (including 32 normal tissue samples and 373 LUAD tissue samples) from the TCGA database. The package "limma" was used to screen differentially expressed genes and aberrantly methylated genes, which were intersected for identifying the hypermethylated downregulated genes (DGs Hyper) and the hypomethylated upregulated genes (UGs Hypo). GO annotation and KEGG pathway enrichment analysis were further performed, and it was found that these DGs Hyper and UGs Hypo were predominantly activated in the biological processes and signaling pathways such as the regulation of vasculature development, DNA-binding transcription activator activity, and Ras signaling pathway, indicating that these genes play a vital role in the initiation and progression of LUAD. Additionally, univariate and multivariate Cox regression analyses were conducted to find the genes significantly associated with LUAD prognosis. Five genes including SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 were identified, with the former three highly expressed and the latter two poorly expressed in LUAD, indicating poor prognosis of LUAD patients as judged by survival analysis.

2.
J Hypertens ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031175

RESUMO

OBJECTIVE: Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study. METHODS: Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial-factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (>150 mmHg) were randomized to intensive (target 130-140 mmHg) or guideline-recommended (<180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (>10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2-6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0-15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09-2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43-0.92; P = 0.016). CONCLUSION: Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01422616.

3.
Arch Gynecol Obstet ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033866

RESUMO

PURPOSE: To summarize the clinical characteristics and treatments of preeclampsia complicated with hyponatremia. METHODS: We reported a new case of preeclampsia complicated with severe hyponatremia; searched for relevant articles from the PubMed, Scopus and Cochrane databases; and reviewed all reported cases. RESULTS: Twenty-one reported cases were found. Our case is 22nd, and the serum sodium level in this case was the lowest reported. After treatment comprising fluid restriction, hypertonic saline and caesarean section, a relatively good outcome was achieved. In all reported cases, SIADH, preeclampsia or the combined effect of preeclampsia and induced nephrotic syndrome were the speculated pathogeny. Termination was performed due to adverse manifestations; six cases underwent transvaginal deliveries, and sixteen cases underwent caesarean section. Fifteen patients recovered from hyponatremia within 72 h after delivery. CONCLUSION: The pathogenesis of hyponatremia occurring in patients with preeclampsia is still unclear. Termination of the pregnancy led to a stabilization of the sodium level, ICU monitoring was necessary, and fluid restriction and hypertonic saline intake were applied; however, there was no evidence of the effectiveness of the treatments.

4.
Semin Arthritis Rheum ; 50(5): 1006-1014, 2020 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-33007601

RESUMO

OBJECTIVES: To examine the effect of occupation on knee osteoarthritis (OA) and total knee replacement (TKR) in working-aged adults. METHODS: We used longitudinal data from the Chingford, Osteoarthritis Initiative (OAI) and Multicentre Osteoarthritis (MOST) studies. Participants with musculoskeletal disorders and/or a history of knee-related surgery were excluded. Participants were followed for up to 19-years (Chingford), 96-months (OAI) and 60-months (MOST) for incident outcomes including radiographic knee OA (RKOA), symptomatic RKOA and TKR. In those with baseline RKOA, progression was defined as the time from RKOA incidence to primary TKR. Occupational job categories and work-place physical activities were assigned to levels of workload. Logistic regression was used to examine the relationship between workload and incident outcomes with survival analyses used to assess progression (reference group: sedentary occupations). RESULTS: Heavy manual occupations were associated with a 2-fold increased risk (OR: 2.07, 95% CI 1.03 to 4.15) of incident RKOA in the OAI only. Men working in heavy manual occupations in MOST (2.7, 95% CI 1.17 to 6.26) and light manual occupations in OAI (2.00, 95% CI 1.09 to 3.68) had a 2-fold increased risk of incident RKOA. No association was observed among women. Increasing workload was associated with an increased risk of symptomatic RKOA in the OAI and MOST. Light work may be associated with a decreased risk of incident TKR and disease progression. CONCLUSION: Heavy manual work carries an increased risk of incident knee OA; particularly among men. Workload may influence the occurrence of TKR and disease progression.

5.
Sci China Life Sci ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33009992

RESUMO

Delayed greening of young leaves is an unusual phenomenon of plants in nature. Citrus are mostly evergreen tree species. Here, a natural mutant of "Guanxi" pummelo (Citrus maxima), which shows yellow leaves at the young stage, was characterized to identify the genes underlying the trait of delayed leaf greening in plants. A segregating population with this mutant as the seed parent and a normal genotype as the pollen parent was generated. Two DNA pools respectively from the leaves of segregating seedlings with extreme phenotypes of normal leaf greening and delayed leaf greening were collected for sequencing. Bulked segregant analysis (BSA) and InDel marker analysis demonstrated that the delayed leaf greening trait is governed by a 0.3 Mb candidate region on chromosome 6. Gene expression analysis further identified a key candidate gene (Citrus Delayed Greening gene 1, CDG1) in the 0.3 Mb region, which showed significantly differential expression between the genotypes with delayed and normal leaf greening phenotypes. There was a 67 bp InDel region difference in the CDG1 promoter and the InDel region contains a TATA-box element. Confocal laser-scanning microscopy revealed that the CDG1-GFP fusion protein signals were co-localized with the chloroplast signals in the protoplasts. Overexpression of CDG1 in tobacco and Arabidopsis led to the phenotype of delayed leaf greening. These results suggest that the CDG1 gene is involved in controlling the delayed leaf greening phenotype with important functions in chloroplast development.

7.
Sci Transl Med ; 12(563)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32998970

RESUMO

Treatment of life-threatening Epstein-Barr virus (EBV)-associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating receptor for natural killer (NK) cells (NKG2D), immunostimulatory ligands (CD80 and CD86), and antigen-presenting molecules (MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumor cells through FasL and TRAIL pathways and promoted EBV antigen-specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumors in Rag2-/-γc-/- and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, we explored the antitumor activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Here, we found that allogeneic Vδ2-T-Exos had more effective antitumor activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumor tissues and induced more robust CD4 and CD8 T cell-mediated antitumor immunity. Compared with exosomes derived from NK cells (NK-Exos) with direct cytotoxic antitumor activity or dendritic cells (DC-Exos) that induced T cell antitumor responses, Vδ2-T-Exos directly killed tumor cells and induced T cell-mediated antitumor response, thus resulting in more effective control of EBV-associated tumors. This study provided proof of concept for the strategy of using Vδ2-T-Exos, especially allogeneic Vδ2-T-Exos, to treat EBV-associated tumors.

8.
Expert Rev Vaccines ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001703

RESUMO

OBJECTIVES: More and more premature infants were born worldwide that are suffering from various complications, vaccination for whom is often delayed in China. We aim to describe current vaccination recommendations in practice, immunization status and vaccination safety for premature infants in Zhejiang. METHODS: The demographic information, medical records of treatments and adverse events following immunization (AEFI) history were collected from infants' parents by questionnaire in the Vaccination Consultation Clinic(VCC). Vaccination data were retrieved from Zhejiang Provincial Immunization Information System. The information of AEFI was collected from the Chinese National Adverse Event Following Immunization Information System. RESULTS: A total of 1515 premature infants visiting the VCC were included in the study. The majority (65.94%) of them were under 7 months. 47.59% of premature infants were advised to receive normal vaccinations, while 45.94% were advised to defer a specific vaccination and 6.47% were advised to defer all vaccinations. A total of 807 infants received 7187 vaccine doses were administered and only seven cases experienced mild and self-limiting adverse reactions (9.74/10,000). No uncommon or serious side effects were reported. CONCLUSION: Most premature infants visiting the VCC did not receive vaccines on time. The majority of them can be safely vaccinated according to the national recommended schedule.

9.
J Cancer Res Ther ; 16(5): 1148-1150, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33004762

RESUMO

Background: Immunoglobulin G4-related disease (IgG4-RD) is an immune mediated fibro inflammatory condition characterized by abundant IgG4-positive (IgG4+) plasma cell infiltrated lesions and elevated serum IgG4 concentrations. Tubulointerstitial nephritis and glomerular lesions are the most common renal IgG4-RDs. However, solitary mass lesion is rarely observed in renal IgG4-RD. Materials and Methods: We reported a 55-year-old male patient with a space-occupying lesion in the right kidney detected during a routine ultrasound medical examination. Computed tomography indicated a 20 mm × 15 mm × 18 mm mass located at the lower pole of the right kidney. Both T1-weighted imaging and T2-weighted imaging magnetic resonance imaging scans showed a hypointense mass. Diffusion-weighted imaging (b value = 800) showed slightly hyperintensity. Results: The lesion was diagnosed as renal cell carcinoma clinically based on the laboratory and radiological findings and treated with laparoscopic resection. However, the postoperative histological examination results indicated the lesion IgG4-RD of the kidney. Conclusion: We should consider pseudotumor-like IgG4-RD as a differential diagnosis for solitary renal lesion although the incidence is low.

10.
Clin Neurol Neurosurg ; 198: 106254, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33011482

RESUMO

BACKGROUND: As hyperglycemia and leukocytosis individually predict poor outcome in acute ischemic stroke (AIS), we aimed to determine the significance of their combination on functional outcome and symptomatic intracerebral hemorrhage (sICH) among participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). METHODS: Post-hoc analyzes of the full ENCHANTED cohort, an international, multicenter, quasi-factorial, randomized, open, blinded outcome-assessed trial of low- versus standard-dose intravenous alteplase and early intensive versus standard blood pressure (BaP) lowering treatment in 4557 thrombolysis-eligible and treated AIS patients. Patients were divided into four groups according to baseline blood glucose and white blood cells (WBC) levels: A (normal glucose + WBC), B (hyperglycemia + normal WBC), C (normal glucose + high WBC), and D (hyperglycemia + high WBC). Logistic regression models were used to determine associations of each group and poor functional outcome (modified Rankin scale scores 2-6) at 90 days and sICH within 48 h, adjusted for confounders. Quality of model fit was examined with Akaike information classification (AIC), Bayesian information classification (BIC), and likelihood ratio test. RESULTS: Of 4181 AIS patients included in analyzes, and with group A as the reference, an increasing odds of poor functional outcome was evident across groups B (odds ratio [OR] 1.38, 95 % confidence interval [CI] 1.17-1.63), C (OR 1.26, 95 %CI 0.99-1.60), and D (OR 2.26, 95 %CI 1.79-2.85) (P trend <0.001). Group D patients also had a higher rate of sICH (P trend <0.05). The model fit with the combination of blood glucose and WBC was better than models of their individual components. CONCLUSIONS: Using a combination of blood glucose and WBC provides strong prognostic significance than either alone in thrombolyzed AIS patients.

11.
Theranostics ; 10(25): 11535-11548, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33052231

RESUMO

Objective: The transcription factor forkhead box protein O1 (FOXO1) is critical for regulating cytokine and chemokine secretion. However, its function in the tumor microenvironment (TME) remains largely unexplored. In this study, we characterized the prognostic value of FOXO1 and the interaction between tumor-derived FOXO1 and M2 macrophages in esophageal squamous cell carcinoma (ESCC). Methods: FOXO1 expression and macrophage infiltration in clinical samples and mouse models were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry staining. Western blotting, qRT-PCR, and enzyme-linked immunosorbent assay were used to evaluate chemokine ligand 20 (CCL20) and colony stimulating factor 1 (CSF-1) expression in FOXO1(+) and FOXO1(-) tumor cells. Macrophage phenotypes were determined using qRT-PCR, flow cytometry, and RNA sequencing. Transcriptional activity was measured using chromatin immunoprecipitation (ChIP)-qPCR. Tumor viability was investigated using XTT proliferation and foci formation assays. Results: FOXO1 upregulation in tumor tissues was found to drive the polarization of M0 macrophages and infiltration of M2 macrophages into the TME, resulting in worse prognosis in ESCC patients. CSF-1, a vital factor inducing M0-to-M2 polarization, was upregulated via a FOXO1-mediated mechanism. RNA sequencing results corroborated that the FOXO1-induced macrophages exhibited similar molecular signatures to the IL4-stimulated M2 macrophages. The transwell assays showed that FOXO1 promoted the migration of M2 macrophages via CCL20 secretion, which could be inhibited using an anti-CCL20 antibody. FOXO1(+) tumor-induced M2 macrophages promoted tumor proliferation via the FAK-PI3K-AKT pathway and the PI3K inhibitor could effectively impede the oncogenical process. Conclusions: FOXO1 facilitated M0-to-M2 polarization and the recruitment of M2 macrophages in the TME via the transcriptional modulation of CCL20 and CSF-1. Our data deciphered the FOXO1-dependent mechanism in M2 macrophage infiltration in the TME of ESCC, which has implications for the development of novel prognostic and therapeutic targets to optimize the current treatment against ESCC.

12.
J Genet Genomics ; 47(6): 289-299, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32883604

RESUMO

The intestinal epithelium is one of the most rapidly renewing tissues, which is fueled by stem cells at the base of the crypts. Strategies of genetic lineage tracing and organoids, which capture major features of original tissues, are powerful avenues for exploring the biology of intestinal stem cells in vivo and in vitro, respectively. The combination of intestinal organoid-culturing system and genetic modification approaches provides an attractive platform to uncover the mechanism of colorectal cancer and genetic disorders in the human minigut. Here, we will provide a comprehensive overview of studies on intestinal epithelium and intestinal stem cells. We will also review the applications of organoids and genetic markers in intestinal research studies. Furthermore, we will discuss the advantages and drawbacks of organoids as disease models compared with mice models and cell lines.

13.
Dev Comp Immunol ; 114: 103867, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32931839

RESUMO

14-3-3 proteins are widespread in animals, but their functions and mechanisms remain poorly defined. Here we clearly demonstrate that 14-3-3 ß/α-A is a newly identified PGN-binding protein present abundantly in the eggs/embryos of zebrafish. We also show that recombinant 14-3-3 ß/α-A acts as a pattern recognition receptor capable of identifying the bacterial signature molecule PGN, binding the bacteria, and functions as an antibacterial effector molecule directly killing the bacteria. Importantly, microinjection of r14-3-3 ß/α-A into early embryos significantly enhanced the resistance of the embryos against pathogenic A. hydrophila challenge, and this enhanced bacterial resistance was markedly reduced by co-injection of anti-14-3-3 ß/α-A antibody. Collectively, these results indicate that 14-3-3 ß/α-A is a maternal PGN-binding protein that can protect the early embryos of zebrafish against pathogenic attacks, a novel role assigned to 14-3-3 ß/α-A proteins. This work also provides new insights into 14-3-3 proteins that are widely distributed in various animals.

14.
Math Biosci Eng ; 17(4): 3637-3648, 2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32987548

RESUMO

Based on the reported data from February 16, 2020 to March 9, 2020 in South Korea including confirmed cases, death cases and recovery cases, the control reproduction number was estimated respectively at different control measure phases using Markov chain Monte Carlo method and presented using the resulting posterior mean and 95% credible interval (CrI). At the early phase from February 16 to February 24, we estimate the basic reproduction number R0 of COVID-19 to be 4.79(95% CrI 4.38 - 5.2). The estimated control reproduction number dropped rapidly to Rc ≈ 0.32(95% CrI 0.19 - 0.47) at the second phase from February 25 to March 2 because of the voluntary lockdown measures. At the third phase from March 3 to March 9, we estimate Rc to be 0.27 (95% CrI 0.14 - 0.42). We predict that the final size of the COVID-19 outbreak in South Korea is 9661 (95% CrI 8660 - 11100) and the whole epidemic will be over by late April. It is found that reducing contact rate and enhancing the testing speed will have the impact on the peak value and the peak time.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Número Básico de Reprodução/estatística & dados numéricos , Simulação por Computador , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/transmissão , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Humanos , Cadeias de Markov , Conceitos Matemáticos , Modelos Biológicos , Método de Monte Carlo , Pandemias/prevenção & controle , Pandemias/estatística & dados numéricos , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , República da Coreia/epidemiologia , Fatores de Tempo
15.
BMJ Open ; 10(9): e036563, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873668

RESUMO

INTRODUCTION: The Systemic Lupus Erythematosus (SLE) Prospective Observational Cohort Study (SPOCS) aims to describe the disease course of SLE and its association with type I interferon gene signature (IFNGS) status. METHODS AND ANALYSIS: SPOCS is an international, multicentre, prospective, observational cohort study designed to follow patients through biannual study visits during a 3-year observation period. Patients ≥18 years old with a physician diagnosis that meets the American College of Rheumatology or Systemic Lupus International Collaborating Clinics SLE classification criteria will be included. SPOCS will comprehensively analyse clinical features, disease progression and treatment, SLE outcomes, health status assessments and quality of life, and healthcare resource utilisation of patients with moderate to severe SLE. A four-gene test will be used to measure IFNGS status; scores will be compared with a pre-established cut-off. Patients will be stratified by low or high IFNGS expression levels. Enrolment began in June 2017, and study completion is expected in 2022. The total number of anticipated patients was initially planned for 1500 patients and was amended to 900 patients owing to slow accrual of eligible patients. ETHICS AND DISSEMINATION: The ethics committee/institutional review board/independent ethics committee at each study site approved the SPOCS protocol prior to study initiation (protocol number: D3461R00001, version 3.0, 26 June 2019). Study findings will be disseminated through peer-reviewed publications and presentations at scientific meetings. TRIAL REGISTRATION NUMBER: NCT03189875.

16.
Stroke Vasc Neurol ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989012

RESUMO

BACKGROUND: The COVID-19 pandemic and physical distancing guidelines have compelled stroke practices worldwide to reshape their delivery of care significantly. We aimed to illustrate how the stroke services were interrupted during the pandemic in China. METHODS: A 61-item questionnaire designed on Wenjuanxing Form was completed by doctors or nurses who were involved in treating patients with stroke from 1 February to 31 March 2020. RESULTS: A total of 415 respondents completed the online survey after informed consent was obtained. Of the respondents, 37.8%, 35.2% and 27.0% were from mild, moderate and severe epidemic areas, respectively. Overall, the proportion of severe impact (reduction >50%) on the admission of transient ischaemic stroke, acute ischaemic stroke (AIS) and intracerebral haemorrhage (ICH) was 45.0%, 32.0% and 27.5%, respectively. Those numbers were 36.9%, 27.9% and 22.3%; 36.5%, 22.1% and 22.6%; and 66.4%, 47.5% and 41.1% in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For AIS, thrombolysis was moderate (20%-50% reduction) or severely impacted (>50%), as reported by 54.4% of the respondents, while thrombectomy was 39.3%. These were 44.4%, 26.3%; 44.2%, 39.4%; and 78.2%, 56.5%, in mild, moderate and severe epidemic areas, respectively (all p<0.0001). For patients with acute ICH, 39.8% reported the impact was severe or moderate for those eligible for surgery who had surgery. Those numbers were 27.4%, 39.0% and 58.1% in mild, moderate and severe epidemic areas, respectively. For staff resources, about 20% (overall) to 55% (severe epidemic) of the respondents reported moderate or severe impact on the on-duty doctors and nurses. CONCLUSION: We found a significant reduction of admission for all types of patients with stroke during the pandemic. Patients were less likely to receive appropriate care, for example, thrombolysis/thrombectomy, after being admitted to the hospital. Stroke service in severe COVID-19 epidemic areas, for example, Wuhan, was much more severely impacted compared with other regions in China.

17.
Aust J Gen Pract ; 49(9): 582-584, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32864676

RESUMO

BACKGROUND: Osteoarthritis (OA) is one of the most common chronic joint diseases and a leading cause of pain and disability in Australia. A National Osteoarthritis Strategy (the Strategy) was developed to outline a national plan to achieve optimal health outcomes for people at risk of, or with, OA. OBJECTIVE: This article focuses on the theme of advanced care of patients with OA within the Strategy. DISCUSSION: The Strategy was developed in consultation with a leadership group, thematic working groups, an implementation advisory committee, multisectoral stakeholders and the public. This Strategy identified three priorities in advanced care for osteoarthritis. In brief, these include surgical decision making, referral for evidence-informed non-surgical alternatives and surgical services. A set of goals within these priority areas and strategies was also proposed by the working group in consultation with stakeholders nationwide. Peak arthritis bodies and major healthcare professional associations currently endorse the Strategy.

18.
J Recept Signal Transduct Res ; : 1-15, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900249

RESUMO

BACKGROUND: Endothelial dysfunction is a driving force during the development and progression of cardiovascular complications in diabetes. Targeting endothelial injury may be an attractive avenue for the management of diabetic vascular disorders. Chicoric acid is reported to confer antioxidant and anti-inflammatory properties in various diseases including diabetes. However, the role and mechanism of chicoric acid in hyperglycemia-induced endothelial damage are not well understood. METHODS: In the present study, human umbilical vein endothelial cells (HUVECs) were incubated with high glucose/high fat (HG + HF) to induce endothelial cell injury. RESULTS: We found that exposure of HUVECs to HG + HF medium promoted the release of cytochrome c (cytc) from mitochondrion into the cytoplasm, stimulated the cleavage of caspase-3 and poly ADP-ribose-polymerase (PARP), then inducing cell apoptosis, the effects that were prevented by administration of chicoric acid. Besides, we found that chicoric acid diminished HG + HF-induced phosphorylation and degradation of IκBα, and subsequent p65 NFκB nuclear translocation, thereby contributing to its anti-inflammatory effects in HUVECs. We also confirmed that chicoric acid mitigated oxidative/nitrative stresses under HG + HF conditions. Studies aimed at exploring the underlying mechanisms found that chicoric acid activated the AMP-activated protein kinase (AMPK) signaling pathway to attenuate HG + HF-triggered injury in HUVECs as AMPK inhibitor Compound C or silencing of AMPKα1 abolished the beneficial effects of chicoric acid in HUVECs. CONCLUSION: Collectively, chicoric acid is likely protected against diabetes-induced endothelial dysfunction by activation of the AMPK signaling pathway. Chicoric acid could be a novel candidate for the treatment of the diabetes-associated vascular endothelial injury.

19.
Anal Methods ; 12(19): 2434-2442, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32930232

RESUMO

Covalent organic frameworks with tunable porous crystallinity and outstanding stability have recently exhibited fascinating pretreatment performance as solid-phase microextraction coatings. In this report, a ß-ketoenamine-linked covalent organic framework (TpPa-1) was successfully constructed through a Schiff-base-type reaction between 1,3,5-triformylphloroglucinol (Tp) and para-phenylenediamine (Pa-1). A TpPa-1 coating was then fabricated on a stainless-steel fiber for capturing trace synthetic musks. This TpPa-1 coating exhibited strong interaction with synthetic musks because of its hydrophobicity and π-π affinity. This TpPa-1-based solid-phase microextraction methodology, coupled with gas chromatography-tandem mass spectrometry, provided high enrichment factors (1214-12 487), wide linearity (0.5-1000 ng L-1), low limits of detection (0.04-0.31 ng L-1), and acceptable reproducibility (relative standard deviation, <10%) for nine synthetic musks. Recoveries at three spiked levels in three types of water samples were between 76.2% and 118.7%. These results indicated the promising applicability of the TpPa-1 as a solid-phase microextraction fiber coating for reliably detecting trace concentrations of synthetic musks in the environment.

20.
J Hypertens ; 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32897905

RESUMO

OBJECTIVE: As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke. METHODS: Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015-2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3-6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120-139 and 70-89 mmHg, respectively). RESULTS: Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear 'J-shaped' relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02-1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke. CONCLUSION: The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.

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