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Background/Aims This study aimed to compare the efficacy of a recently developed clear-cut knife with that of widely used knives for endoscopic submucosal dissection (ESD) in early gastric cancer (EGC). Materials and Methods Data were collected retrospectively from the National Health Insurance Service Ilsan Hospital between May 2017 and April 2019. The study included 105 patients (108 lesions) with EGC who underwent ESD. Fifty-six EGCs were dissected using an insulation-tipped diathermic knife in combination with a needle knife, while 52 EGCs were dissected using a clear-cut knife, a single device with an integrated needle and an insulated-tipped knife. Oncologic outcomes and technical success were compared between the two groups. Results The distribution of the tumor locations, composition of the undifferentiated types of EGCs, and the size of EGCs (14.3±8.0 vs. 16.6±7.3 mm; P=0.130) were not significantly different between the groups. The complete (98.2% vs. 94.2%; P=0.273) and curative (87.5% vs. 88.5%; P=0.878) resection rates were not statistically different. Furthermore, no significant difference between the total procedure times (39±34.1 vs. 35.7±20.1 minutes; P=0.554), areas of the dissected specimen (858.6±406.5 vs. 980.3±393.8 mm2; P=0.119) and dissected areas per minute (32.4±17.9 vs. 35.5±16.2 mm2/min; P=0.345) were noted. Regarding complications, the overall perforation rates (3.6% vs. 4.0%) and bleeding rates (3.6% vs. 8.0%) were not statistically different. Conclusions The newly developed clear-cut knife is as useful as the combination of classical knives for ESD in EGC.

Primary hepatic lymphoma is a rare disease, and primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma accounts for only 0.3% of all primary hepatic lymphomas. Herein, we report a case of primary hepatic MALT lymphoma in a male patient in his mid-40 s with chronic hepatitis B infection. The patient visited our department for further examination of a hepatic nodule initially visualized through abdominal pelvic computed tomography (CT). Based on imaging studies and elevated levels of tumor markers, the tumor was suspected to be hepatocellular carcinoma. A laparoscopic inferior sectionectomy (segment 5 and 6) was performed, and immunohistochemical staining revealed that the tumor was positive for CD20, B-cell lymphoma 2, pan-cytokeratin (CK), and CK19 markers. Pathological findings revealed it to be a primary hepatic MALT lymphoma. After surgery, bone marrow biopsies and fluorodeoxyglucose-positron emission tomography integrated with CT scanning confirmed that there was no other involvement. The patient did not receive chemotherapy, and there was no recurrence during the 24-month follow-up period. Hepatocellular carcinoma is the most common malignancy in patients with chronic hepatitis B, but rare tumors such as primary MALT lymphoma can also occur, so a careful approach is required for their differentiation.

Identification of non-alcoholic steatohepatitis (NASH) with high activity and fibrosis is a major priority in patients with non-alcoholic fatty liver disease. We validated the predictive value of the FibroScan-aspartate aminotransferase (FAST) score and other non-invasive fibrosis surrogates in predicting high-risk NASH criteria. This multicenter retrospective study recruited 251 biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients (132 [52.6%] men) between 2011 and 2014. The FAST score was calculated using transient elastography data and aspartate aminotransferase (AST) levels. The NAFLD fibrosis score (NFS), fibrosis-4 index (FIB-4), and AST to platelet ratio index (APRI) were calculated using biochemical data. The area under the receiver operating characteristic curves (AUCs) of the FAST score, liver stiffness, NFS, FIB-4, and APRI were 0.752, 0.718, 0.609, 0.650, and 0.722 for NAFLD activity score (NAS) ≥5 (n = 117, 46.6%); 0.788, 0.754, 0.649, 0.701, and 0.747 for fatty liver inhibition of progression-NASH with histologic activity ≥3 (n = 202, 80.5%); 0.807, 0.806, 0.691, 0.732, and 0.760 for severe disease with activity ≥3 and/or fibrosis ≥3 (n = 132, 52.6%); and 0.714, 0.812, 0.748, 0.738, and 0.669 for NASH with NAS ≥4 and fibrosis ≥2 (n = 70, 27.9%), respectively. The FAST score had the highest AUC for the most high-risk NASH criteria, except for in predicting NAS ≥4 and fibrosis ≥2. The liver stiffness value showed consistently acceptable performance in predicting all high-risk NASH criteria. The FAST score has acceptable performance in identifying high-risk NASH. However, liver stiffness alone was not inferior to the FAST score.

Duodenal varices are ectopic in nature and account for 40% of all ectopic bleeding cases. Ectopic variceal bleeding is rare (1%-5% of all variceal bleeding cases). The three principle approaches used to treat duodenal varices are endoscopic procedures, interventional radiological methods, and surgical interventions. A 59-year-old male with alcoholic liver cirrhosis and chronic hepatitis B infection visited our gastroenterology department with melena. Gastroduodenoscopy and computed tomography identified varices in the second part of the duodenum. We performed percutaneous transhepatic obliteration using glue and coil embolization, which obliterated the varices and resulted in immediate hemostasis. However, 3 months later, he re-visited presenting with newly developed duodenal varices and underwent endoscopic injection sclerotherapy.

Background and Aims. Endoscopic submucosal dissection (ESD) is routinely performed in treating gastric neoplasia and requires long-term higher levels of sedation. Endoscopist-directed nurse-administered sedation (EDNAS) has not been well studied in ESD. This study aimed to evaluate the safety and effectiveness of EDNAS for ESD. Methods. Patients treated with ESD for gastric tumors between 2013 and 2015 were retrospectively collected. Patients were divided into a midazolam-treated group (M group) and a midazolam plus propofol-treated group (MP group). Clinical outcome, safety, effectiveness, adverse events of ESD, and adverse events of sedation were analyzed. Results. Of 209 collected patients, 83 were in the M group and 126 were in the MP group. Of all patients, 67 patients had the circulatory adverse event during the ESD procedure. Sedation method was the only significant risk factor (M versus MP: 2.17 (1.14–4.15), p=0.019). In analysis of MP subgroups, 47 patients suffered an adverse event from sedation, and current smoking was the only significant association factor for adverse event (0.15 (0.03–0.68), p=0.014). Conclusions. In performing ESD, the effect of sedation is reduced in smoking patients. EDNAS may be acceptable for ESD under careful monitoring of vital sign and oxygen saturation.

Background/AimsAdefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV.MethodsIn total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study.ResultsFollowing ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P

BACKGROUND/AIMS:The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). METHODS:The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. RESULTS:The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295-8.291 for LS>7.0 kPa; and P60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724-0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740-0.893). CONCLUSION:This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation.

Abstract Background Carbon nanotubes (CNTs) are engineered graphene cylinders with numerous applications in engineering, electronics and medicine. However, CNTs cause inflammation and fibrosis in the rodent lung, suggesting a potential human health risk. We hypothesized that multi-walled CNTs (MWCNTs) induce two key inflammatory enzymes in macrophages, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), through activation of extracellular signal-regulated kinases (ERK1,2). Methods RAW264.7 macrophages were exposed to MWCNTs or carbon black nanoparticles (CBNPs) over a range of doses and time course. Uptake and subcellular localization of MWCNTs was visualized by transmission electron microscopy (TEM). Protein levels of COX-2, iNOS, and ERK1,2 (total ERK and phosphorylated ERK) were measured by Western blot analysis. Prostaglandin-E2 (PGE2) and nitric oxide (NO) levels in cell supernatants were measured by ELISA and Greiss assay, respectively. Results MWCNTs, but not CBNPs, induced COX-2 and iNOS in a time- and dose-dependent manner. COX-2 and iNOS induction by MWCNTs correlated with increased PGE2 and NO production, respectively. MWCNTs caused ERK1,2 activation and inhibition of ERK1,2 (U0126) blocked MWCNT induction of COX-2 and PGE2 production, but did not reduce the induction of iNOS. Inhibition of iNOS (L-NAME) did not affect ERK1,2 activation, nor did L-NAME significantly decrease COX-2 induction by MWCNT. Nickel nanoparticles (NiNPs), which are present in MWCNTs as a residual catalyst, also induced COX-2 via ERK-1,2. However, a comparison of COX-2 induction by MWCNTs containing 4.5 and 1.8% Ni did not show a significant difference in ability to induce COX-2, indicating that characteristics of MWCNTs in addition to Ni content contribute to COX-2 induction. Conclusion This study identifies COX-2 and subsequent PGE2 production, along with iNOS induction and NO production, as inflammatory mediators involved in the macrophage response to MWCNTs. Furthermore, our work demonstrates that COX-2 induction by MWCNTs in RAW264.7 macrophages is ERK1,2-dependent, while iNOS induction by MWCNTs is ERK1,2-independent. Our data also suggest contributory physicochemical factors other than residual Ni catalyst play a role in COX-2 induction to MWCNT.

Objectives: HLA DQA1*05 has been associated with the development of anti-drug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF) and treatment failure among adults with Crohn's disease (CD). However, findings from other studies have been inconsistent with limited pediatric data., Methods: We analyzed banked serum from patients with CD < 21 years of age enrolled in COMBINE, a multi-center, prospective randomized trial of anti-TNF monotherapy vs. combination with methotrexate. The primary outcome was a composite of factors indicative of treatment failure. The secondary outcome was ADA development., Results: A trend towards increased treatment failure among HLA DQA1*05 positive participants was not significant (HR 1.58, 95% CI 0.95-2.62; p=0.08). After stratification by HLA DQA1*05 and by methotrexate vs. placebo, patients who were HLA DQA1*05 negative and assigned to methotrexate experienced less treatment failures than HLA DQA1*05 positive patients on placebo (HR 0.31, 95% CI 0.13-0.70; p=0.005).A trend toward increased ADA development among HLA DQA1*05 positive participants was not significant (odds ratio [OR] 1.96, 95% CI 0.90-4.31, p=0.09). After further stratification, HLA DQA1*05 negative participants assigned to methotrexate were less likely to develop ADA relative to HLA DQA1*05 positive patients on placebo (OR 0.12, 95% CI 0.03-0.55; p=0.008)., Conclusions: In a randomized trial of children with CD initiating anti-TNF, 40% were HLA DQ-A1*05 positive, which was associated with a trend toward increased risk of both treatment failure and ADA. These risks were mitigated, but not eliminated, by adding oral methotrexate. HLA DQ-A1*05 is an important biomarker for prognosis and risk stratification., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab)., Methods: We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization., Results: Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14)., Conclusions: LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response., Methods: We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks., Results: We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn's disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001)., Conclusions: SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Aims: COVID-19 vaccination prevents severe disease in most patients with inflammatory bowel disease (IBD), but immunosuppressive medications can blunt serologic response. We followed adults with IBD for >1 year post-COVID-19 vaccination to describe factors associated with SARS-CoV-2 infection after vaccination, evaluate for a protective SARS-CoV-2 antibody level, characterize SARS-CoV-2 antibody persistence, and identify factors associated with humoral immune response durability., Methods: Using a prospective cohort of COVID-19 immunized adults with IBD, we analyzed factors associated with SARS-CoV-2 infection after vaccination. We evaluated for an association between SARS-CoV-2 antibody level 12 weeks postvaccination and subsequent SARS-CoV-2 infection and assessed for a threshold of protection using receiver-operating characteristic curve analysis. We then conducted a separate analysis evaluating factors associated with persistence of SARS-CoV-2 antibodies 52 weeks postimmunization., Results: Almost half (43%) of 1869 participants developed COVID-19 after vaccination, but most infections were mild, and <1% required hospitalization. Older age and corticosteroid use were associated with a decreased risk of SARS-CoV-2 infection postvaccination (50-59 years of age vs 18-29 years of age: adjusted hazard ratio, 0.57; 95% confidence interval, 0.44-0.74; steroid users vs nonusers: adjusted hazard ratio, 0.58; 95% confidence interval, 0.39-0.87). Most (98%) participants had detectable antibody levels at 52 weeks postvaccination. Antibody levels at 12 weeks and number of vaccine doses were positively associated with higher antibody levels at 52 weeks, while anti-tumor necrosis factor α therapy was negatively associated., Conclusions: COVID-19 vaccination generates an effective and durable protective response for the vast majority of adults with IBD, including vulnerable populations such as corticosteroid users and older individuals. Patients with IBD benefit from COVID-19 booster vaccination., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Introduction: Parkinson's disease (PD) is a rapidly growing neurological disorder characterized by diverse movement symptoms. However, the underlying causes have not been clearly identified, and accurate diagnosis is challenging. This study aimed to identify potential biomarkers suitable for PD diagnosis and present an integrative perspective on the disease., Methods: We screened the GSE7621, GSE8397-GPL96, GSE8397-GPL97, GSE20163, and GSE20164 datasets in the NCBI GEO database to identify differentially expressed (DE) mRNAs in the substantia nigra (SN). We also screened the GSE160299 dataset from the NCBI GEO database to identify DE lncRNAs and miRNAs in plasma. We then constructed 2 lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory networks based on the ceRNA hypothesis. To understand the biological function, we performed Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology analyses for each ceRNA network. The receiver operating characteristic analyses (ROC) was used to assess ceRNA results., Results: We identified 7 upregulated and 29 downregulated mRNAs as common DE mRNAs in the 5 SN datasets. In the blood dataset, we identified 31 DE miRNAs (9 upregulated and 22 downregulated) and 332 DE lncRNAs (69 upregulated and 263 downregulated). Based on the determined interactions, 5 genes (P2RX7, HSPA1, SLCO4A1, RAD52, and SIRT4) appeared to be upregulated as a result of 10 lncRNAs sponging 4 miRNAs (miR-411, miR-1193, miR-301b, and miR-514a-2/3). Competing with 9 genes (ANK1, CBLN1, RGS4, SLC6A3, SYNGR3, VSNL1, DDC, KCNJ6, and SV2C) for miR-671, a total of 26 lncRNAs seemed to function as ceRNAs, influencing genes to be downregulated., Discussion: In this study, we successfully constructed 2 novel ceRNA regulatory networks in patients with PD, including 36 lncRNAs, 5 miRNAs, and 14 mRNAs. Our results suggest that these plasma lncRNAs are involved in the pathogenesis of PD by sponging miRNAs and regulating gene expression in the SN of the brain. We propose that the upregulated and downregulated lncRNA-mediated ceRNA networks represent mechanisms of neuroinflammation and dopamine neurotransmission, respectively. Our ceRNA network, which was associated with PD, suggests the potential use of DE miRNAs and lncRNAs as body fluid diagnostic biomarkers. These findings provide an integrated view of the mechanisms underlying gene regulation and interactions in PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chun and Kim.)

Introduction: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD., Methods: We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization., Results: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 μg/mL (SD 67) and a median of 22 μg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant., Discussion: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination., (Copyright © 2022 by The American College of Gastroenterology.)

(1) Background: Anti-carbamylated protein (CarP) antibodies have been studied as novel markers to aid in the diagnosis and prognosis of rheumatoid arthritis. (2) Methods: A total of 265 samples were included in the evaluation, for which 98 had results for anti-cyclic citrullinated peptide (CCP), 86 for rheumatoid factor (RF), and 212 for 14-3-3 eta protein. Anti-CarP antibodies were measured using a fetal calf serum-based single-step assay (research use only, Inova Diagnostics, San Diego, CA). (3) Results: Anti-CarP antibodies were significantly higher and more frequent in anti-CCP3.1+ ( p = 0.0025), RF+ ( p = 0.0043) and 14-3-3 eta+ ( p = 0.028) samples compared to the negative counterpart group. In addition, isolated anti-CarP positivity occurred in samples negative for anti-CCP3.1, RF, or 14-3-3 eta. When anti-CarP antibodies were compared to each of the RF, anti-CCP3.1, and 14-3-3 eta by receiver operating characteristic (ROC) analyses, the area under the curve (AUC) values of 0.71 (RF), 0.68 (anti-CCP3.1), and 0.59 (14-3-3 eta), respectively, demonstrated a moderate correlation. Using an UpSet plot, we determined that 10.6% of the samples with available results for anti-CCP3.1, RF, and anti-CarP showed triple positivity. (4) Conclusions: Anti-carbamylated protein (anti-CarP) antibodies can be detected in anti-CCP, RF and 14-3-3 eta-positive and -negative patients, potentially identifying specific subsets of patients.

The human cutaneous sensory organ is a highly evolved biosensor that is efficient, sensitive, selective, and adaptable. Recently, with the development of various materials and structures inspired by sensory organs, artificial cutaneous sensors have been widely studied. In this study, the acquisition of biophysical signals is demonstrated at one point on the body using a wearable all-gel-integrated multimodal sensor composed of four element sensors, inspired by the slow/rapid adapting functions of the skin sensory receptors. The gel-type sensors ensure flexibility, compactness, portability, adherence, and integrity. The wearable all-gel multimodal sensor is easily attached to the wrist and simultaneously gathers blood pressure (BP), electrocardiogram (ECG), electromyogram (EMG), and mechanomyogram (MMG) signals related to cardiac and muscle health. Human activity causes muscle contraction, which affects blood flow; therefore, the relationship between the muscle and heart is crucial for screening and predicting heart health. Cardiac health is monitored by obtaining the two types of phase time differences (i.e., Δt be : BP and ECG, Δt em : ECG and MMG) generated during muscle movement. The suggested multimodal sensor has potential applicability in monitoring biophysical conditions and diagnosing cardiac-related health problems., (© 2022 Wiley-VCH GmbH.)

Introduction: Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD., Methods: In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level., Results: In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response., Discussion: Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD., (Copyright © 2021 by The American College of Gastroenterology.)

Recently, wearable triboelectric sensors capable of self-powering, which can be widely used in artificial skin and robotics, have received much attention. Herein, we develop a stretchable triboelectric pressure sensor with a new pattern by superimposing two patterns using both polystyrene beads and UV-ozone treatment. This patterned structure works more sensitively to pressure than a general planar and one-kind patterned structure. The sensor is constructed by sandwiching styrene butadiene rubber (SBR) and poly(dimethylsiloxane) (PDMS). It demonstrates a high sensitivity of 0.078 kPa -1 (0-20 kPa), a low detection limit (1.2 kPa), and pressure sensitivity maintained under 40% strain. The detection behavior of the strain-insensitive triboelectric sensor against pressure is very consistent with the simulation based on the theory. In applications, we successfully detect various human motions, not only small motions such as bending fingers but also large motions such as standing up and raising arms.

Mechanoreceptors in human skin are important and efficient cutaneous sensors that are highly sensitive, selective, and adaptive to the environment. Among these, Merkel disk (MD) and cilia are capable of sensing an external mechanical force through a receptor with a sharp pillar-like structure at its end. Then, the signal of the action potential is generated by pumping Na + ions through ion channels. In this study, a self-powered, stretchable, and wearable gel mechanoreceptor sensor is developed inspired by the structural features of the MD and cilia with sharp tips and the signaling characteristics of mechanoreceptor ion migration. Poly(vinylidene fluoride- co -trifluoroethylene) gel is used to implement a self-powered system, and polyvinylchloride-based elastic gel is utilized to detect sensing signals based on charge transfer and distribution. The surface of all gels is that of a conical structure to achieve high sensor sensitivity and conformal contact with a target surface. In addition, using the developed sensors, various biological signals related to pressure/strain occurring in the human body (e.g., blood pressure (BP), muscle movement, and motion) are acquired. Furthermore, the behavior of arterial BP was investigated during the contraction and relaxation of the muscles.

In the human skin, it has been well known that several mechanoreceptors uniquely sense external stimuli with specific frequencies and magnitudes. With regard to sensitivity, the output response shows nonlinearity depending on the frequency magnitude of the stimulus. We demonstrate a self-powered proton-driven solid-state somatosensor, which mimics a unique nonlinear response and intensity behavior of human mechanoreceptors. For this, a solid-state sensor is fabricated by combining a piezoelectric film and a proton generation device. The proton injection electrode and the Nafion layer conjugated with sulfonated graphene oxide are used for proton generation and transport. Two types of nonlinear signals from the sensor are similar to the Merkel/Ruffini (low deviation of threshold intensity), and in contrast, the behavior of Pacinian/Meissner (high deviation of threshold intensity) is simultaneously shown. The region of the most responsive frequency is also discriminated according to proton conduction. Moreover, it is asserted that unique signal patterns are obtained from the stimuli of various frequencies, such as respiration, radial artery pulse, and neck vibration, which naturally occur in the human body.

Background: Rapid and accurate diagnosis of acute myocardial infarction (AMI) is critical for initiating effective treatment and achieving better prognosis. We investigated the performance of copeptin for early diagnosis of AMI, in comparison with creatine kinase myocardial band (CK-MB) and troponin I (TnI)., Methods: We prospectively enrolled 271 patients presenting with chest pain (within six hours of onset), suggestive of acute coronary syndrome, at an emergency department (ED). Serum CK-MB, TnI, and copeptin levels were measured. The diagnostic performance of CK-MB, TnI, and copeptin, alone and in combination, for AMI was assessed by ROC curve analysis by comparing the area under the curve (AUC). Sensitivity, specificity, negative predictive value, and positive predictive value of each marker were obtained, and the characteristics of each marker were analyzed., Results: The patients were diagnosed as having ST elevation myocardial infarction (STEMI; N=43), non-ST elevation myocardial infarction (NSTEMI; N=25), unstable angina (N=78), or other diseases (N=125). AUC comparisons showed copeptin had significantly better diagnostic performance than TnI in patients with chest pain within two hours of onset (AMI: P =0.022, ≤1 hour; STEMI: P =0.017, ≤1 hour and P =0.010, ≤2 hours). In addition, TnI and copeptin in combination exhibited significantly better diagnostic performance than CK-MB plus TnI in AMI and STEMI patients., Conclusions: The combination of TnI and copeptin improves AMI diagnostic performance in patients with early-onset chest pain in an ED setting., Competing Interests: The authors declare that they have no conflict of interests., (© The Korean Society for Laboratory Medicine.)

In this study, we focused the mimicking of the cone photoreceptor along with ion channel system, which is similar to real optical system. By realizing the ion channel and photoreceptor based on photoresponsive material and photoelectric film, we achieved the wavelength-selective sensor with self-power ability. For the first time, we combined the photoreceptor and ion channel system without external power. For this, we used the channel membrane with pores coated with light-responsive material. We measured the sensing signals without any external power, because photoelectric film assists the sensitive operation of the ion channel system. As a result, we demonstrated a spectral ion channel sensor triggered by the photoelectric effect. Mimicking the slow and fast responses typically found in cone photoreceptor, when induced light causes photovoltaic effect from the pyrrole-coated polyvinylidene fluoride film, this helps to normally operate the ion channel system with slow and fast responses to the light wavelengths. Consequently, this research opens the new scientific fields to realize the photosensor very similar to the real vision sensory organ.

We report a novel low-noise nanopore device employing a polymer substrate. The Si substrate of a fabricated Si-substrate-based silicon nitride (Si3N4) membrane was replaced with a polymer substrate. As such, laser machining was used to make a micro-size hole through the polyimide (PI) substrate, and a thin Si3N4 membrane was then transferred onto the PI substrate. Finally, a nanopore was formed in the membrane using a transmission electron microscope for detection of biomolecules. Compared to the Si-substrate-based device, the dielectric noise was greatly reduced and the root-mean-square noise level was decreased from 146.7 to 5.4 pA. Using this device, the translocation of double-strand deoxyribonucleic acid (DNA) was detected with a high signal/noise (S/N) ratio. This type of device is anticipated to be available for future versatile sequencing technologies., Competing Interests: The authors have declared that no competing interests exist.

A low-powered and highly selective photomechanical sensor system mimicking stomata in the epidermis of leaves harvested from nature is demonstrated. This device uses a light-responsive composite consisting of 4-amino-1,1'-azobenzene-3,4'-disulfonic acid monosodium salt (AZO) and poly(diallyldimethylammonium chloride) (PDDA) coated on a membrane with tens of nanometer-size pores. The ionic current change through the pore channels as a function of pore size variation is then measured. The tran-cis isomerism of AZO-PDDA during light irradiation and the operation mechanism of photomechanical ion channel sensor are discussed and analyzed using UV-vis spectroscopy and atomic force microscopy analysis. It presents the discriminative current levels to the different light wavelengths. The response time of the photoreceptor is about 0.2 s and it consumes very low operating power (≈15 nW) at 0.1 V bias. In addition, it is found that the change of the pore diameter during the light irradiation is due to the photomechanical effect, which is capable of distinguishing light intensity and wavelength., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Highly efficient human skin systems transmit fast adaptive (FA) and slow adaptive (SA) pulses selectively or consolidatively to the brain for a variety of external stimuli. The integrated analysis of these signals determines how humans perceive external physical stimuli. Here, a self-powered mechanoreceptor sensor based on an artificial ion-channel system combined with a piezoelectric film is presented, which can simultaneously implement FA and SA pulses like human skin. This device detects stimuli with high sensitivity and broad frequency band without external power. For the feasibility study, various stimuli are measured or detected. Vital signs such as the heart rate and ballistocardiogram can be measured simultaneously in real time. Also, a variety of stimuli such as the mechanical stress, surface roughness, and contact by a moving object can be distinguished and detected. This opens new scientific fields to realize the somatic cutaneous sensor of the real skin. Moreover, this new sensing scheme inspired by natural sensing structures is able to mimic the five senses of living creatures., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With advances in implant technology, total ankle arthroplasty (TAA) has become an increasingly popular alternative to arthrodesis for the management of end-stage ankle arthritis. However, reports in the literature do not focus on the imaging features of TAA. Through a literature review, we demonstrate basic design features of the current ankle arthroplasty system, and the normal and abnormal postoperative imaging features associated with such devices. Pre- and postoperative evaluations of ankle arthroplasty mainly include radiography; in addition, computed tomography and magnetic resonance imaging provide further characterization of imaging abnormalities. Familiarization with multimodal imaging features of frequent procedural complications at various postoperative intervals is important in radiological practice.

Biological ion channels have led to much inspiration because of their unique and exquisite operational functions in living cells. Specifically, their extreme and dynamic sensing abilities can be realized by the combination of receptors and nanopores coupled together to construct an ion channel system. In the current study, we demonstrated that artificial ion channel pressure sensors inspired by nature for detecting pressure are highly sensitive and patchable. Our ion channel pressure sensors basically consisted of receptors and nanopore membranes, enabling dynamic current responses to external forces for multiple applications. The ion channel pressure sensors had a sensitivity of ∼5.6 kPa(-1) and a response time of ∼12 ms at a frequency of 1 Hz. The power consumption was recorded as less than a few μW. Moreover, a reliability test showed stability over 10 000 loading-unloading cycles. Additionally, linear regression was performed in terms of temperature, which showed no significant variations, and there were no significant current variations with humidity. The patchable ion channel pressure sensors were then used to detect blood pressure/pulse in humans, and different signals were clearly observed for each person. Additionally, modified ion channel pressure sensors detected complex motions including pressing and folding in a high-pressure range (10-20 kPa).

Objective: To evaluate the prevalence of deltoid ligament and distal tibiofibular syndesmosis injury on 3T magnetic resonance imaging (MRI) in patients with chronic lateral ankle instability (CLAI)., Materials and Methods: Fifty patients (mean age, 35 years) who had undergone preoperative 3T MRI and surgical treatment for CLAI were enrolled. The prevalence of deltoid ligament and syndesmosis injury were assessed. The complexity of lateral collateral ligament complex (LCLC) injury was correlated with prevalence of deltoid or syndesmosis injuries. The diagnostic accuracy of ankle ligament imaging at 3T MRI was analyzed using arthroscopy as a reference standard., Results: On MRI, deltoid ligament injury was identified in 18 (36%) patients as follows: superficial ligament alone, 9 (50%); deep ligament alone 2 (11%); and both ligaments 7 (39%). Syndesmosis abnormality was found in 21 (42%) patients as follows: anterior inferior tibiofibular ligament (AITFL) alone, 19 (90%); and AITFL and interosseous ligament, 2 (10%). There was no correlation between LCLC injury complexity and the prevalence of an accompanying deltoid or syndesmosis injury on both MRI and arthroscopic findings. MRI sensitivity and specificity for detection of deltoid ligament injury were 84% and 93.5%, and those for detection of syndesmosis injury were 91% and 100%, respectively., Conclusion: Deltoid ligament or syndesmosis injuries were common in patients undergoing surgery for CLAI, regardless of the LCLC injury complexity. 3T MRI is helpful for the detection of all types of ankle ligament injury. Therefore, careful interpretation of pre-operative MRI is essential.

Heat-driven ionic gate nanochannels have been recently demonstrated, which exploit temperature-responsive polymer brushes based on wettability. These heat-sensing artificial nanochannels operate in a broad temperature-response boundary and fixed liquid cell environment, thereby experiencing limited system operation in the flat and solid state. Here we have developed a patchable and flexible heat-sensing artificial ionic gate nanochannel, which can operate in the range of the human body temperature. A wax-elastic copolymer, coated onto a commercial nanopore membrane by a controlled-vacuum filtration method, was used for the construction of temperature-responsive nanopores. The robust and flexible nanochannel heat sensor, which is combined with an agarose gel electrolyte, can sustain reversible thermo-responsive ionic gating based on the volumetric work of the wax-composite layers in a selective temperature range. The ionic current is also effectively distinguished in the patchable bandage-type nanochannel for human heat-sensing.

A chitosan/polypyrrole composited fiber as bio-compatible materials for artificial muscles is investigated. The chitosan/polypyrrole fiber (CPF) is fabricated by in-situ chemical polymerization of pyrrole monomer solution using FeCl3 as an oxidant. The electrical resistivity of the fiber is changed according to the strain variation applied to the both ends of the specimen. The sensor built by using the CPF has a higher gauge factor (4) compared to conventional metal strain gauges (~2) indicating a suitable material for delicate force control in sensing work.

Torsional behaviors of polymer-infiltrated carbon nanotube (CNT) yarn muscles have been investigated in relation to molecular architecture by using atomic force microscopy (AFM). Two polymers with different stiffnesses, polystyrene (PS) and poly(styrene-b-isoprene-b-styrene) (SIS), were uniformly infiltrated into CNT yarns for electrothermal torsional actuation. The torsional behaviors of hybrid yarn muscles are completely explained by the volume change of each polymer, based on the height and full width at half maximum profiles from the AFM morphological images. The volume expansion of the PS yarn muscle (1.7 nm of vertical change and 22 nm of horizontal change) is much larger than that of the SIS yarn muscle (0.3 nm and 11 nm change in vertical and horizontal directions) at 80 °C, normalized by their values at 25 °C. We demonstrate that their maximum rotations are consequently 29.7 deg mm(-1) for the PS-infiltrated CNT yarn muscle (relatively larger rotation) and 14.4 deg mm(-1) for the SIS-infiltrated CNT yarn muscle (smaller rotation) at 0.75 V m(-1). These hybrid yarn muscles could be applied in resonant controllers or damping magnetoelectric sensors.

Torsional artificial muscles generating fast, large-angle rotation have been recently demonstrated, which exploit the helical configuration of twist-spun carbon nanotube yarns. These wax-infiltrated, electrothermally powered artificial muscles are torsionally underdamped, thereby experiencing dynamic oscillations that complicate positional control. Here, using the strategy spiders deploy to eliminate uncontrolled spinning at the end of dragline silk, we have developed ultrafast hybrid carbon nanotube yarn muscles that generated a 9,800 r.p.m. rotation without noticeable oscillation. A high-loss viscoelastic material, comprising paraffin wax and polystyrene-poly(ethylene-butylene)-polystyrene copolymer, was used as yarn guest to give an overdamped dynamic response. Using more than 10-fold decrease in mechanical stabilization time, compared with previous nanotube yarn torsional muscles, dynamic mirror positioning that is both fast and accurate is demonstrated. Scalability to provide constant volumetric torsional work capacity is demonstrated over a 10-fold change in yarn cross-sectional area, which is important for upscaled applications.

Multi-walled carbon nanotubes (MWNTs) have been amine-functionalized by eco-friendly supercritical water oxidation. The facilely functionalized MWNTs have high solubility (~84 mg L(-1)) in water and 78% transmittance at 30-fold dilution. The Tyndall effect is also shown for several liquids.

The prospect of electronic circuits that are stretchable and bendable promises tantalizing applications such as skin-like electronics, roll-up displays, conformable sensors and actuators, and lightweight solar cells. The preparation of highly conductive and highly extensible materials remains a challenge for mass production applications, such as free-standing films or printable composite inks. Here we present a nanocomposite material consisting of carbon nanotubes, ionic liquid, silver nanoparticles, and polystyrene-polyisoprene-polystyrene having a high electrical conductivity of 3700 S cm(-1) that can be stretched to 288% without permanent damage. The material is prepared as a concentrated dispersion suitable for simple processing into free-standing films. For the unstrained state, the measured thermal conductivity for the electronically conducting elastomeric nanoparticle film is relatively high and shows a non-metallic temperature dependence consistent with phonon transport, while the temperature dependence of electrical resistivity is metallic. We connect an electric fan to a DC power supply using the films to demonstrate their utility as an elastomeric electronic interconnect. The huge strain sensitivity and the very low temperature coefficient of resistivity suggest their applicability as strain sensors, including those that operate directly to control motors and other devices.

Pure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational choriocarcinoma of the ovary is extremely rare, and its diagnosis is very difficult during the reproductive years. We present a case of a 33-year-old woman diagnosed with pure nongestational ovarian choriocarcinoma. Following surgery, multiple courses of a chemotherapy regimen of etoposide, methotrexate, and actinomycin-D (EMA) were effective.

We demonstrated that the structural formation of vertically aligned carbon nanotube (CNT) forests is primarily affected by the geometry-related gas flow, leading to the change of growth directions during the chemical vapor deposition (CVD) process. By varying the growing time, flow rate, and direction of the carrier gas, the structures and the formation mechanisms of the vertically aligned CNT forests were carefully investigated. The growth directions of CNTs are found to be highly dependent on the nonlinear local gas flows induced by microchannels. The angle of growth significantly changes with increasing gas flows perpendicular to the microchannel, while the parallel gas flow shows almost no effect. A computational fluid dynamics (CFD) model was employed to explain the flow-dependent growth of CNT forests, revealing that the variation of the local pressure induced by microchannels is an important parameter determining the directionality of the CNT growth. We expect that the present method and analyses would provide useful information to control the micro- and macrostructures of vertically aligned CNTs for various structural/electrical applications.

Conductive films that are both stretchable and flexible could have applications in electronic devices, sensors, actuators and speakers. A substantial amount of research has been carried out on conductive polymer composites, metal electrode-integrated rubber substrates and materials based on carbon nanotubes and graphene. Here we present highly conductive, printable and stretchable hybrid composites composed of micrometre-sized silver flakes and multiwalled carbon nanotubes decorated with self-assembled silver nanoparticles. The nanotubes were used as one-dimensional, flexible and conductive scaffolds to construct effective electrical networks among the silver flakes. The nanocomposites, which included polyvinylidenefluoride copolymer, were created with a hot-rolling technique, and the maximum conductivities of the hybrid silver-nanotube composites were 5,710 S cm⁻¹ at 0% strain and 20 S cm⁻¹ at 140% strain, at which point the film ruptured. Three-dimensional percolation theory reveals that Poisson's ratio for the composite is a key parameter in determining how the conductivity changes upon stretching.

We investigated the effects of catalyst (Fe)/buffer layer (Al2O3) on the vertical growth multiwalled carbon nanotubes (CNTs) synthesized by thermal chemical vapor deposition. The Fe was deposited onto Al2O3/SiO2/Si wafer by using e-beam evaporator. Ethylene was used as a feeding gas while argon was used as a carrier gas. Hydrogen was also introduced. The catalyst layers were optimized to control the length, diameter, purity, and alignment of CNTs. For the optimized conditions we produced vertically aligned CNTs of about 1 cm in length during 10 h. The effects of catalysts on nanotube characteristics were systematically analyzed using SEM, TEM, and Raman measurement.

Thin multi-walled carbon nanotubes (MWCNTs) were successfully synthesized by a rapid thermal chemical vapor deposition (RTCVD) method using a liquid catalyst. The growth of the thin MWCNTs was achieved by decomposition of C2H2 over Fe-Mo/MgO/citric acid directly at 700 degrees C for 30 min. Most thin MWCNTs, which had about 6 approximately 8 graphene layers, showed high purity (approximately 90%) and good crystallinity. Moreover, they showed homogenous morphology and uniform diameters. The average outer diameter of the thin MWCNTs was about 8 nm. The uniform diameter and good homogeneity of thin MWCNTs were mainly attributed to prevention of catalyst agglomeration at high temperature due to a short reaction time, and the high purity of thin MWCNTs was caused by suppression of the residual CNT growth after finishing a reaction in RTCVD process. Field emission properties of the thin MWCNTs were measured in a vacuum chamber at a pressure of less than 2 x 10(-7) Torr. The turn-on field was about 3.35 V/microm at the emission current density of 0.1 microA/cm2, and the emission current density was 2.5 mA/cm2 at an applied field of 6.7 V/microm. Particularly, the thin MWCNTs showed strong emission stability at emission current density of 0.8 mA/cm2 for 20 h.

Background: The recent interest of clinical laboratories in developing serum testosterone assays based on isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) stems from the lack of accuracy of direct immunoassays. In this study, we assessed the accuracy and state of standardization (traceability) of 4 published ID-LC-MS/MS procedures in a method comparison with an ID-gas chromatography (GC)-MS reference measurement procedure listed in the database of the Joint Committee for Traceability in Laboratory Medicine., Methods: The study used 58 specimens from different patient categories. Each specimen was measured in triplicate (ID-LC-MS/MS) and quadruplicate (ID-GC-MS) in independent runs., Results: The testosterone concentrations by ID-GC-MS were 0.2-4.4 nmol/L (women), 0.2-2.0 nmol/L (hypogonadal man), and 10.1-31.3 nmol/L (normogonadal men). For ID-GC-MS, the CV was nearly constant, with a median of 1.0%; for ID-LC-MS/MS, it was concentration-dependent, with a median of up to 8%. Weighted Deming regression gave mean slopes, intercepts, and correlation coefficients of 0.90-1.11, -0.055-0.013 nmol/L, and 0.993-0.997, respectively. The % difference plot showed between 7% and 26% of the results outside a total error limit of 14%, with median deviations from ID-GC-MS between -9.6 and 0.4%., Conclusions: This study demonstrated fairly good accuracy and standardization of the tested ID-LC-MS/MS procedures. Performance differences between procedures were evident in some instances, due to improper calibration and between-run calibration control. This emphasizes the need for thorough validation, including traceability, of new ID-LC-MS/MS procedures.

Opsoclonus-myoclonus syndrome is one of a few corticotropin (ACTH)-responsive central nervous system disorders of childhood. We measured cerebrospinal fluid ACTH and cortisol in 69 children with opsoclonus-myoclonus and 25 age- and sex-matched control subjects to determine endogenous levels and look for hypothesized differential hormonal effects of ACTH and corticosteroid treatment. Cerebrospinal fluid cortisol was 10-fold higher with ACTH treatment (n = 26), but was unchanged with oral steroid treatment (n = 18) or no treatment (n = 25). It was significantly higher in children receiving daily high-dose ACTH than alternate day ACTH. In ACTH-treated children, cerebrospinal fluid and serum cortisol were highly correlated (r = 0.96, P = 0.0001), with a mean ratio of cerebrospinal fluid to serum cortisol of approximately 1:10. Cerebrospinal fluid ACTH concentration did not differ significantly between untreated opsoclonus-myoclonus and control subjects but was lower with ACTH (-29%) or steroid treatment (-36%), suggesting feedback inhibition of ACTH release. These data delineate differences in the central effects of ACTH and corticosteroid therapy, as well as between high and low ACTH doses, and support the integrity of the brain-adrenal axis in pediatric opsoclonus-myoclonus.

Participants in marathon races may require medical attention and the performance of laboratory assays. We report the changes in basic biochemical parameters, cardiac markers, CBC counts, and WBC differentials observed in participants in a marathon before, within 4 hours, and 24 hours after a race. The concentrations of glucose, total protein, albumin, uric acid, calcium, phosphorus, serum urea nitrogen, creatinine, bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, total creatine kinase, creatine kinase-MB, myoglobin, and the anion gap were increased after the race, consistent with the effects of exertional rhabdomyolysis and hemolysis. The increase in WBC counts was due mainly to neutrophilia and monocytosis, with a relative decrease in circulating lymphocytes, consistent with an inflammatory reaction to tissue injury. A significant percentage of laboratory results were outside the standard reference ranges, indicating that modified reference ranges derivedfrom marathon runners might be more appropriatefor this population. We provide a table of modified reference ranges (or expected ranges) for basic biochemical, cardiac, and hematologic laboratory parameters for marathon runners.

Background: The performance of point-of-care testing under controlled laboratory conditions may vary from results obtained in actual patient care settings. User errors are a major cause of this discrepancy., Methods: We studied the clinical performance of the Cardiac STATus (Spectral USA, Frederick, MD), a qualitative triple cardiac marker point-of-care test, under controlled laboratory conditions and in actual practice in an emergency department (ED) satellite laboratory. First-draw samples obtained from patients presenting to the hospital emergency department with chest pain were used for the study. Tests were performed in the chemistry research laboratory by a company product specialist or in an emergency department satellite laboratory by hospital staff. Test results were analyzed by correlation to the clinical discharge diagnosis., Results: In the emergency department, for the test system as a whole (any one or more marker(s) positive versus all three markers negative), sensitivity was 63%, specificity was 81%, positive predictive value was 26%, and negative predictive value was 95%. A manufacturer-supplied product specialist in a laboratory setting achieved very similar sensitivity, specificity, and positive and negative predictive values., Conclusions: The performance of this system under controlled laboratory conditions can be applied to estimate its performance at the point of care., (Copyright 2002 Elsevier Science B.V.)

Inactivation of HMG-CoA synthase by a carboxyl-directed reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), in a concentration-dependent and substrate-protectable manner suggested that the active site contains reactive acidic amino acids. This observation prompted functional evaluation of 11 invariant acidic amino acids by site-directed mutagenesis. Characterization of the isolated synthase variants' ability to catalyze overall and partial reactions identified three mutant synthases (D99A, D159A, and D203A) that exhibit significant diminution of k(cat) for the overall reaction (10(2)-, 10(3)-, and 10(4)-fold decreases, respectively). D99A, D159A, and D203A form the acetyl-S-enzyme intermediate very slowly (0.0025, 0.0026, 0.0015 U/mg, respectively, measured at pH 7. 0 and 22 degrees C) as compared to the wild-type synthase (1.59 U/mg), where intermediate formation approaches rate-limiting status. Differences in substrate saturation do not account for impaired activities or rates of intermediate formation. The structural integrity of the purified mutants' active sites is demonstrated by their abilities to bind a spin-labeled acyl-CoA analogue (R.CoA) with affinities and stoichiometries comparable to values measured for wild-type synthase. The impact of three distinct amino acids on reaction intermediate formation supports a mechanism of acetyl-S-enzyme formation that probably requires formation and directed collapse of a tetrahedral adduct. (18)O-induced shift of the (13)C NMR signal of (13)C acetyl-S-enzyme demonstrates that an analogous tetrahedral species is produced upon solvent exchange with the acetyl-S-enzyme. Partial discrimination between the functions of D99, D159, and D203 becomes possible based on the observation that D159A and D203A synthases exhibit retarded kinetics of solvent (18)O exchange while D99A fails to support (18)O exchange.

Replacement of 3-hydroxy-3-methylglutaryl-CoA synthase's glutamate 95 with alanine diminishes catalytic activity by over 5 orders of magnitude. The structural integrity of E95A enzyme is suggested by the observation that this protein contains a full complement of acyl-CoA binding sites, as indicated by binding studies using a spin-labeled acyl-CoA. Active site integrity is also demonstrated by (13)C NMR studies, which indicate that E95A forms an acetyl-S-enzyme reaction intermediate with the same distinctive spectroscopic characteristics measured using wild type enzyme. The initial reaction steps are not disrupted in E95A, which exhibits normal levels of Michaelis complex and acetyl-S-enzyme intermediate. Likewise, E95A is not impaired in catalysis of the terminal reaction step, as indicated by efficient catalysis of a hydrolysis partial reaction. Single turnover experiments indicate defective C-C bond formation. The mechanism-based inhibitor, 3-chloropropionyl-CoA, efficiently alkylates E95A. This is compatible with the presence of a functional general base, raising the possibility that Glu(95) functions as a general acid. Demonstration of a significant upfield shift for the methyl protons of HMG-CoA synthase's acetyl-S-enzyme reaction intermediate suggests a hydrophobic active site environment that could elevate the pK(a) of Glu(95) as required to support its function as a general acid.

The effect of nonhydrolyzable guanine nucleotides on mammalian acetyl CoA carboxylase (ACC) activity was examined. Using porous rat adipocytes and crude fat cell homogenates to study metabolic pathway flux, GMPPNP and/or GTP gamma S inhibited [14C]fatty acid formation by up to 95% when either [6-14C]glucose-6-phosphate or [1-14C]acetyl CoA was used as substrate. If [2-14C]malonyl CoA initiated flux, however, no inhibition was apparent. These pathway flux studies suggested that ACC was the locus of inhibition, and that the mechanism might involve a disruption of guanine nucleotide hydrolysis by the nonhydrolyzable analogues. Using partially and avidin-sepharose-purified ACC preparations from rat fat, liver and mammary tissue, citrate-stimulated ACC activity was inhibited by 25-75% with 50 microM GTP gamma S. Related compounds and nucleotides had absent-to-minimal effects on ACC. ATP gamma S was inhibitory (10-30% at 5-15 microM), but always to a lesser degree than equimolar GTP gamma S. Filter binding assays with [alpha-32P]GTP or [35S]GTP gamma S were negative, but low-level GTPase activity was detected. Using photoaffinity labelling techniques, [alpha-32P]GTP was found to bind ACC and not pyruvate carboxylase. The hypothesis that citrate-responsive ACC activity may be modulated by an intrinsic or associated GTP binding site is explored. Since ACC forms polymers, as does the cytoskeletal protein beta-tubulin, amino acid sequence comparisons between ACC and atypical GTP binding domain of beta tubulin are presented.