Bairdali6383
09% vs. 27.05%, OR (95% CI) = 1.731 (1.213-2.471)), and compared with the reference CC genotype, the following ORs were observed AA genotype OR = 2.404 (95% CI 1.085-5.328; P = .034) and GA genotype OR = 2.143 (95% CI 1.283-3.579; P = .005). Haplotype analyses showed that the rs2228570/rs731236/rs1544410/rs7975232 CTGA was significantly over-represented in psoriasis patients compared with controls (OR (95% CI)=1.907 (1.132-3.214); P = .020). Among the patients with PASI less then 3, the response rates to calcipotriol were significantly higher in patients with rs7975232 CC genotypes than in those with other genotypes (x2 = 9.172, P = .010). These data suggest that VDR polymorphisms are associated with psoriasis susceptibility and clinical response to calcipotriol in psoriatic patients.Coated stainless steel was used as an in-tube solid-phase microextraction for the extraction of letrozole from plasma samples. The coating process on the inner surface of the stainless steel was conducted by a simple electrodeposition process. The coated composite was prepared from 3,4-ethylenedioxythiophene and graphene oxide. In this composite, graphene oxide acts as an anion dopant and sorbent. The coated nanostructured polymer was characterized using different techniques. The operational factors affecting the extraction process, including pH, adsorption, and desorption time, the recycling flow rate of the sample solution, sample volume, desorption solvent type and its volume, and ionic strength were optimized to achieve the best extraction efficiency of the analyte. The total extraction time including adsorption and desorption steps was about 15.0 min. The developed method demonstrated a linear range of 5.0-1500.0 μg/L with a limit of detection of 1.0 μg/L. The repeatability of the developed extraction approach in terms of intraday, interday, and fiber to fiber was attained in the range of 4.9-8.3%. After finding the optimal conditions, the potential of the described approach for letrozole quantitation was investigated in plasma samples, and satisfactory results were obtained.
In this work, an integrated strategy is developed for rapid discovery, precise identification, and automated quantification for the biomarkers of food intake (BFIs) for specific food exposure using an ultra-high-pressure liquid chromatography-high-resolution mass spectrometry (MS) based targeted metabolomics approach.
Using whole grain (WG) wheat intake as an example, the combination of paired mass distance networking and parallel reaction monitoring analysis is applied to selectively extract and identify WG metabolites in human urine samples. As a result, a total of 76 wheat phytochemical-derived metabolites, including 17 alkylresorcinol metabolites, 20 benzoxazinoid derivatives, and 39 phenolic acid metabolites are identified. Subsequently, a MS spectral database consisting of the identified metabolites is created by mzVault. The characteristics of identified metabolites from the database are incorporated into the TraceFinder software to establish a quantification platform. Using a standardized urine sample, the authors are able to simultaneously quantify both free and conjugated (sulfate and glucuronide) WG wheat metabolites in real samples without further enzymatic hydrolysis, which is validated by using authentic standards to quantify these metabolites.
This novel strategy opens the window to study the biomarkers of specific food intake and make it feasible to validate the BFIs in large-scale human studies.
This novel strategy opens the window to study the biomarkers of specific food intake and make it feasible to validate the BFIs in large-scale human studies.
Elderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population.
PubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random-effects meta-analysis characterized VE of influenza vaccines among studies reporting this information.
Of 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Mfuture research.
Most bone fracture heals through enchondral bone formation that relies on the involvement of periosteal progenitor cells. However, the identity of periosteal progenitor cells and the regulatory mechanism of their proliferation and differentiation remain unclear. The aim of this study was to investigate whether Gli1-Cre
can identify a population of murine periosteal progenitor cells and the role of TGF-β signalling in periosteal progenitor cells on fracture healing.
Double heterozygous Gli1-CreER
;Rosa26-tdTomato
mice were sacrificed at different time points for tracing the fate of Gli1
cells in both intact and fracture bone. Gli1-CreER
-mediated Tgfbr2 knockout (Gli1-CreER
;Tgfbr2
) mice were subjected to fracture surgery. At 4, 7, 10, 14 and 21days post-surgery, tibia samples were harvested for tissue analyses including μCT, histology, real-time PCR and immunofluorescence staining.
Through cell lineage-tracing experiments, we have revealed that Gli1-Cre
can be used to identify a subpopulation of periosteal progenitor cells in vivo that persistently reside in periosteum and contribute to osteochondral elements during fracture repair. During the healing process, TGF-β signalling is continually activated in the reparative Gli1
periosteal cells. Conditional knockout of Tgfbr2 in these cells leads to a delayed and impaired enchondral bone formation, at least partially due to the reduced proliferation and chondrogenic and osteogenic differentiation of Gli1
periosteal cells.
TGF-β signalling plays an essential role on fracture repair via regulating enchondral bone formation process of Gli1
periosteal cells.
TGF-β signalling plays an essential role on fracture repair via regulating enchondral bone formation process of Gli1+ periosteal cells.
To assess class I-histone deacetylase (HDAC) inhibition on formation of lipid-accumulating, disease-promoting phagocytes upon myelin load in vitro, relevant for neuroinflammatory disorders like multiple sclerosis (MS) and cerebral X-linked adrenoleukodystrophy (X-ALD).
Immunohistochemistry on postmortem brain tissue of acute MS (n=6) and cerebral ALD (n=4) cases to analyze activation and foam cell state of phagocytes. RNA-Seq of in vitro differentiated healthy macrophages (n=8) after sustained myelin-loading to assess the metabolic shift associated with foam cell formation. RNA-Seq analysis of genes linked to lipid degradation and export in MS-275-treated human HAP1 cells and RT-qPCR analysis of HAP1 cells knocked out for individual members of class I HDACs or the corresponding enzymatically inactive knock-in mutants. Methylnitronitrosoguanidine Investigation of intracellular lipid/myelin content after MS-275 treatment of myelin-laden human foam cells. Analysis of disease characteristic very long-chain fatty acid (VLCFA) metabolism and inflammatory state in MS-275-treated X-ALD macrophages.
Enlarged foam cells coincided with a pro-inflammatory, lesion-promoting phenotype in postmortem tissue of MS and cerebral ALD patients. Healthy in vitro myelin laden foam cells upregulated genes linked to LXRα/PPARγ pathways and mimicked a program associated with tissue repair. Treating these cells with MS-275, amplified this gene transcription program and significantly reduced lipid and cholesterol accumulation and, thus, foam cell formation. In macrophages derived from X-ALD patients, MS-275 improved the disease-associated alterations of VLCFA metabolism and reduced the pro-inflammatory status of these cells.
These findings identify class I-HDAC inhibition as a potential novel strategy to prevent disease promoting foam cell formation in CNS inflammation.
These findings identify class I-HDAC inhibition as a potential novel strategy to prevent disease promoting foam cell formation in CNS inflammation.
The Getting It Right First Time programme aims to reduce variation in clinical practice that unduly impacts on outcomes for patients in the National Health Service (NHS) in England; often termed "unwarranted variation." However, there is no "gold standard" method for detecting unwarranted variation. The aim of this study was to describe a method to allow such variation in recorded practice or patient outcomes between NHS trusts to be detected using data over multiple time periods. By looking at variation over time, it was hoped that patterns that could be missed by looking at data at a single time point, or averaged over a longer time period, could be identified.
This was a retrospective time-series analysis of observational administrative data. Data were extracted from the Hospital Episodes Statistics database for two exemplar aspects of clinical practice within the field of urology (a) use of ureteric stents on first emergency admission to treat urinary tract stones and (b) waiting times for definitive surgery for urinary retention. Data were categorized into 3-month time periods and three rules were used to detect unwarranted variation in the outcome metric relative to the national average (a) two of any three consecutive values greater than two standard deviations above the mean, (b) four of any five consecutive values greater than one standard deviation above the mean, and (c) eight consecutive values above the mean.
For the urinary tract stones dataset, 24 trusts were identified as having unwarranted variation in the outcomes using funnel plots and 23 trusts using the time-series method. For the urinary retention data, 18 trusted were identified as having unwarranted variation in the outcomes using funnel plots and 22 trusts using the time-series method.
The time-series method may complement other methods to help identify unwarranted variation.
The time-series method may complement other methods to help identify unwarranted variation.
The recent development of ultra-thin delivery systems, which enable simultaneous insertion of two metal stents, has encouraged wider adoption of side-by-side (SBS) stent placement for malignant hilar biliary obstruction (MHBO). However, the management of stent occlusion after SBS placement has not been well-characterized. This study aimed to examine the outcomes of endoscopic reintervention (E-RI) after SBS placement in patients with MHBO.
Sixty-seven patients who underwent E-RI for stent occlusion after SBS placement between 2013 and 2020 at three tertiary-care referral centers were investigated. We evaluated the technical success, clinical success, recurrent biliary obstruction (RBO), and adverse events other than RBO rates associated with E-RI. Furthermore, the factors associated with successful E-RI were also evaluated.
The technical success and clinical success rates were 79.1% (53/67) and 76.1% (51/67), respectively. Early adverse events other than RBO occurred in 4.5% (3/67) and late events in 3.
