Ulcerative colitis (UC), a relapsing-remitting chronic inflammatory bowel disease (IBD), has a variable natural course but potentially severe disease course. Since the development of anti-tumor ...necrosis factor (TNF) agents has changed the natural disease course of moderate-to-severe UC, therapeutic options for patients who failed conventional treatments are expanding rapidly. IBD clinical trials have demonstrated the potential efficacy and safety of novel biologics such as anti-integrin α4β7 and anti-interleukin-12/23 monoclonal antibodies and small molecules such as a Janus kinase inhibitor. Anti-TNF biosimilars also have been approved and are widely used in IBD patients. Wise drug choices should be made considering evidence-based efficacy and safety. However, the best position of these drugs remains several questions, with limited data from direct comparative trials. In addition, there are still concerns to be elucidated on the effect of therapeutic drug monitoring and combination therapy with immunomodulators. The appropriate treatment regimens in acute severe UC and the risk of perioperative use of biologics are unclear. As novel biologics and small molecules have been approved in Korea, we present the Korean guidelines for medical management of adult outpatients with moderate-to-severe UC and adult hospitalized patients with acute severe UC, focusing on biologics and small molecules.
Duck hepatitis virus type 1 (DHV-1) was previously classified as an enterovirus, based primarily on observed morphology and physicochemical properties of the virion. The complete nucleotide sequences ...of two strains (DRL-62 and R85952 GenBank ) of DHV-1 have been determined. Excluding the poly(A) tail, the genomes are 7691 and 7690 nt, respectively, and contain a single, large open reading frame encoding a polyprotein of 2249 aa. The genome of DHV-1 is organized as are those of members of the family Picornaviridae: 5' untranslated region (UTR)-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' UTR. Analysis of the genomic and predicted polyprotein sequences revealed several unusual features, including the absence of a predicted maturation cleavage of VP0, the presence of two unrelated 2A protein motifs and a 3' UTR extended markedly compared with that of any other picornavirus. The 2A1 protein motif is related to the 2A protein type of the genus Aphthovirus and the adjacent 2A2 protein is related to the 2A protein type present in the genus Parechovirus. Phylogenetic analysis using the 3D protein sequence shows that the two DHV-1 strains are related more closely to members of the genus Parechovirus than to other picornaviruses. However, the two DHV-1 strains form a monophyletic group, clearly distinct from members of the genus Parechovirus.
Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study ...aims to evaluate the effect of concomitant AS on IBD outcomes.
Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients' electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised.
The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%, P= 0.036). Patients with both ulcerative colitis and AS had a significantly higher risk of biologics or small molecule therapies than patients with only ulcerative colitis (P< 0.001). For univariable logistic regression, biologics or small molecule therapies were associated with concomitant AS (odds ratio, 4.099; 95% confidence interval, 1.863-9.021; P< 0.001) and Crohn's disease (odds ratio, 3.552; 95% confidence interval, 1.590-7.934; P= 0.002).
Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their ...clinical significance in UC.
We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC.
To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval CI 2.944-11.339; area under the curve AUC 0.774, 95% CI, 0.690-0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821-7.838; AUC 0.654, 95% CI 0.556-0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 µg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio.
NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions.
The insufficient long-term durability of polymer electrolyte membrane fuel cell (PEMFC) stacks has been blocking commercialization of PEMFC technologies. An accelerated degradation test (ADT) is ...needed to facilitate the PEMFC development process by reducing the testing time. We propose an ADT procedure for a PEMFC stack with the concept of series reliability structure under startup-shutdown cycling testing conditions. The acceleration factor is estimated to fit the degradation paths of individual cells consisting of the PEMFC stack under normal use conditions via the accelerated degradation data of a single cell. We employ a nonparametric regression method to smooth the degradation curves observed from accelerated operating conditions. We illustrate the methodology for estimating the lifetime of the PEMFC stack using the theory of the smallest-order statistics. We propose a three-parameter Weibull distribution in fuel cell technology to fit the failure data of cells in a PEMFC stack.
Mesenchymal stem cells (MSCs) are multipotent and give rise to distinctly differentiated cells from all three germ layers. Neuronal differentiation of MSC has great potential for cellular therapy. We ...examined whether the cluster of mechanically made, not neurosphere, could be differentiated into neuron-like cells by growth factors, such as epidermal growth factor (EGF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF).
BMSCs grown confluent were mechanically separated with cell scrapers and masses of separated cells were cultured to form cluster BMSCs. As described here cluster of BMSCs were differentiated into neuron-like cells by EGF, HGF, and VEGF. Differentiated cells were analyzed by means of phase-contrast inverted microscopy, reverse transcriptase-polymerase chain reaction (RT-PCR), immunofluorescence, and immunocytochemistry to identify the expression of neural specific markers.
For the group with growth factors, the shapes of neuron-like cells was observable a week later, and two weeks later, most cells were similar in shape to neuron-like cells. Particularly, in the group with chemical addition, various shapes of filament structures were seen among the cells. These culture conditions induced MSCs to exhibit a neural cell phenotype, expressing several neuro-glial specific markers.
bone marrow-derived mesenchymal stem cells (BMSCs) could be easily induced to form clusters using mechanical scraping, not neurospheres, which in turn could differentiate further into neuron-like cells and might open an attractive possibility for clinical cell therapy for neurodegenerative diseases. In the future, we consider that neuron-like cells differentiated from clusters of BMSCs are needed to be compared and analyzed on a physiological and molecular biological level with preexisting neuronal cells, and studies on the possibility of their transplantation and differentiation capability in animal models are further required.
This study investigated distinct neuroimaging features measured by cortical thickness and subcortical structural shape abnormality in early-onset (EO, onset age <65 years) and late-onset (LO, onset ...age ≥65 years) nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) patients. Cortical thickness and subcortical structural shape analyses were performed using a surface-based method from 38 patients with nfvPPA and 76 cognitively normal individuals. To minimize the effects of physiological aging, we used W-scores in comparisons between the groups. The EO-nfvPPA group exhibited more extensive cortical thickness reductions predominantly in the left perisylvian, lateral and medial prefrontal, temporal, posterior cingulate, and precuneus regions than the LO-nfvPPA group. The EO-nfvPPA group also exhibited significantly greater subcortical structural shape abnormality than the LO-nfvPPA group, mainly in the left striatum, hippocampus, and amygdala. Our findings suggested that there were differences in neuroimaging features between these groups by the age of symptom onset, which might be explained by underlying heterogeneous neuropathological differences or the age-related brain reserve hypothesis.
•Nonfluent/agrammatic variant primary progressive aphasia by the age of onset.•Differences in neuroimaging features of the early- and late-onset groups.•Innovative imaging method; the early-onset group shows severe neurodegeneration.
An analytical method to detect phorate and its metabolites, including phorate sulfone, phorate sulfoxide, phoratoxon, phoratoxon sulfone, and phoratoxon sulfoxide, in porcine and chicken muscles and ...table eggs was developed and validated. Extraction was performed using a quick, easy, cheap, effective, rugged, and safe method and analysis was conducted using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Matrix‐matched calibrations were linear over the tested concentrations, with determination coefficient ≥ 0.995 for all tested analytes in the different matrices. The limits of detection and quantification were 0.001 and 0.004 mg/kg, respectively. The calculated recovery rates at three fortification levels were satisfactory, with values between 74.22 and 119.89% and relative standard deviations < 10%. The method was applied successfully to commercial samples collected from locations throughout the Korean Peninsula, and none of them showed any traces of the tested analytes. Overall, the developed method is simple and versatile, and can be used for monitoring phorate and its metabolites in animal products rich in protein and fat.
Many studies and meta-analyses have investigated the associations among proton pump inhibitors (PPIs), spontaneous bacterial peritonitis (SBP), portosystemic encephalopathy (PSE), and other ...infections. However, these studies had limitations, including the omission of several relevant studies and drawing conclusions, based on the abstracts without consulting the full-text of the articles. To evaluate the association between PPIs and complications arising from cirrhosis and risks of PPI use in patients with cirrhosis.
Data were extracted from the EMBASE, PubMed, Cochrane, and Google Scholar databases. The Newcastle-Ottawa scale was used to assess the quality of the selected studies.
A total of 29 studies (13 case-control and 16 cohort studies) involving 20,484 patients were included in the meta-analysis. The total relative risk (RR) for the 23 studies which investigated SBP was 1.31, and the 95% CI was 1.10-1.55 (I2 = 73.0%). The total RR for the 7 studies which examined PSE was 1.25 (95% CI 0.85-1.84, I2 = 96.1%). For the 7 studies which analyzed overall infection, the total RR was 1.37 (95% CI 1.07-1.76, I2 = 79.3%). The RR for the 2 cohort studies that assessed mortality was 1.39 (95% CI 0.85-2.27, I2 = 0.0%).
PPI use in cirrhosis patients increased the SBP and overall infection risk. PPIs should be considered with appropriate indications when the benefits exceed the risks in cirrhosis patients with ascites.
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