Abstract Due to the aging population and the increasing need for total joint replacements, osseointegration is of a great interest for various clinical disciplines. Our objective was to investigate ...the molecular and cellular foundation that underlies this process. Here, we used an in vivo mouse model to study the cellular and molecular response in three distinct areas of unloaded implants: the periosteum, the gap between implant and cortical bone, and the marrow space. Our analyses began with the early phases of healing, and continued until the implants were completely osseointegrated. We investigated aspects of osseointegration ranging from vascularization, cell proliferation, differentiation, and bone remodeling. In doing so, we gained an understanding of the healing mechanisms of different skeletal tissues during unloaded implant osseointegration. To continue our analysis, we used a micromotion device to apply a defined physical stimulus to the implants, and in doing so, we dramatically enhanced bone formation in the peri-implant tissue. By comparing strain measurements with cellular and molecular analyses, we developed an understanding of the correlation between strain magnitudes and fate decisions of cells shaping the skeletal regenerate.
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•Synthesis of a novel thermally-induced clear coat containing DA cycloadduct crosslinks.•Comprehensive analysis of reversible crosslinking/de-crosslinking.•Dynamic nature confirmed by ...combined rheological and thermal analysis.•Excellent mechanical and scratch-resistant properties.•Better scratch-healable performance over commercial clear coats.
This study investigated the application of a thermally reversible polymer network fabricated using Diels-Alder (DA)/retro-DA (rDA) reactions for use as a scratch-healing automotive clear coat. For this purpose, a new scratch-healing poly(urethane acrylate) network containing a DA adduct unit (DA-CL) was prepared, and its material properties and scratch-healing performance were compared to the properties of a commercial clear coat system (C-CL). The thermally reversible crosslinking and de-crosslinking reactions among the DA-CL, via DA and rDA reactions, were systematically evaluated using in-situ oscillatory rheology coupled with FT-IR spectroscopy. The material properties of the DA-CL and C-CL materials, including the thermal stability, thermal transitions, hardness, and scratch resistance, were measured using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), nanoindentation, and nanoscratch test methods. The scratch-healing performance of the DA-CL was quantitatively characterized and compared to the performance of the C-CL using a nanoscratch tester equipped with an optical microscope (OM) and an atomic force microscope (AFM). The DA-CL polymer network exhibited superior scratch healing and scratch resistance compared to the C-CL polymer network. These data indicated that the DA self-healing polymer network is potentially useful as a scratch-healing clear coat for the automotive industry.
A microsatellite instability (MSI) test is crucial for screening for HNPCC (Hereditary nonpolyposis colorectal cancer; Lynch syndrome) and optimization of colorectal cancer (CRC) treatment. Mismatch ...repair (MMR) deficiency is a predictor for good response of immune checkpoint inhibitors in various malignancies. In this study, we evaluated the results of a newly developed plasma-based real-time PCR kit for the detection of MSI in CRC patients. We assessed a peptide nucleotide acid (PNA) probe-mediated real-time PCR test (U-TOP MSI Detection Kit Plus) that determines MSI status by using amplicon melting analysis of five markers (NR21, NR24, NR27, BAT25, and BAT26) from plasma. Eighty-four CRC patients (46 dMMR and 38 pMMR) with colorectal cancer were analyzed. The concordance rate of MSI status assessment between the plasma kit and IHC was 63.0% in dMMR patients (29/46), but in the pMMR evaluation, a 100% (38/38) concordance rate was observed. In the evaluation of the performance of a custom tissue U-TOP MSI Detection Kit and plasma kit in 28 patients, sensitivity, specificity, PPV (positive predictive value) and NPV (negative predictive value) of plasma kit were 68.4, 100, 100, and 44.4%, respectively, with the tissue U-TOP MSI Detection Kit. Our results demonstrate the feasibility of a non-invasive and rapid plasma-based real-time PCR kit (U-TOP MSI Detection Kit Plus) for the detection of MSI in colorectal cancer.
Background/AimsEndoscopic submucosal dissection (ESD) of gastric neoplasm involving the pyloric channel (GNPC) is technically challenging due to difficulty in precise assessment of resection margin ...and inadequate visualization. The aim of this study was to evaluate the effectiveness and long-term outcome of ESD for GNPC and introduce a noble technique for resection of GNPC. MethodsA total of 97 patients with GNPC underwent ESD from January 2007 to October 2017. We divided them into a conventional anterograde resection group and a retrograde resection group according to the method of procedure. We compared their clinical outcomes and investigated risk factors for postprocedural complications. ResultsThe en bloc resection rate was 87.6%, and complete resection rate was 83.5%. Postprocedure stenosis occurred in 16 cases (16.5%). GNPCs of the retrograde resection group were more frequently located from antrum to bulb, were significantly larger, were related to ≥75% resection of the circumference, and involved significantly longer procedure times than those in the anterograde resection group. Multivariate analysis showed that resection ≥75% of the circumference was the only significant risk factor for postprocedure stenosis. ConclusionsESD by retrograde resection method is a novel technique to make the procedure easier, depending on the size, location, and circumference of resection.
Background/Aims: Endoscopic submucosal dissection (ESD) of gastric neoplasm involving the pyloric channel (GNPC) is technically challenging due to difficulty in precise assessment of resection margin ...and inadequate visualization. The aim of this study was to evaluate the effectiveness and long-term outcome of ESD for GNPC and introduce a noble technique for resection of GNPC.
Methods: A total of 97 patients with GNPC underwent ESD from January 2007 to October 2017. We divided them into a conventional anterograde resection group and a retrograde resection group according to the method of procedure. We compared their clinical outcomes and investigated risk factors for postprocedural complications.
Results: The en bloc resection rate was 87.6%, and complete resection rate was 83.5%. Postprocedure stenosis occurred in 16 cases (16.5%). GNPCs of the retrograde resection group were more frequently located from antrum to bulb, were significantly larger, were related to ≥75% resection of the circumference, and involved significantly longer procedure times than those in the anterograde resection group. Multivariate analysis showed that resection ≥75% of the circumference was the only significant risk factor for postprocedure stenosis.
Conclusions: ESD by retrograde resection method is a novel technique to make the procedure easier, depending on the size, location, and circumference of resection. (Gut Liver 2022;16:892-898)
Background/Aims: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the stomach. We evaluated the clinical outcomes of endoscopic treatment for gastric GISTs.
Methods: ...This is a single center, retrospective study that enrolled 135 cases of gastric subepithelial tumors (SETs) resected by endoscopic procedures and confirmed as GISTs by histopathology from March 2005 to July 2019. The immediate and long-term clinical outcomes were analyzed retrospectively.
Results: The mean patient age was 57.9 years, and the mean tumor size was 2.1 cm. Of the tumors, 43.0% were located in the body, followed by the fundus (26.7%) and cardia (17.0%). Most tumors (85.2%) were resected by endoscopic submucosal dissection, followed by endoscopic mucosal resection (6.7%), submucosal tunneling endoscopic resection (5.9%), and endoscopic full-thickness resection (2.2%). Macroperforation occurred in 4.4% and microperforation in 6.7% of the cases. The R0 resection rate was 15.6%. However, the rate of complete resection by the endoscopic view was 90.4%, of which 54.8% of cases were in the very-low-risk group, followed by the low-risk group (28.1%), intermediate-risk group (11.9%), and high-risk group (5.2%). During 36.5 months of follow-up, recurrence was found in four (3.4%) of the 118 patients who were monitored for more than 6 months (low-risk group, 1/37 2.7%; intermediate-risk group, 2/11 18.2%; high-risk group, 1/6 16.7%).
Conclusions: Endoscopic treatment of a GIST appears to be a feasible procedure in selected cases. However, additional surgery should be considered if the pathologic results correspond to intermediate- or high-risk groups. (Gut Liver 2023;17:217-225)
Small bowel malignancies often present a diagnostic challenge due to their relative rarity and nonspecific clinical symptoms. However, technical developments in endoscopic instruments, including ...video capsule endoscopy (VCE) and enteroscopy, have allowed for the visualization of the entire small bowel. This study aimed to investigate the clinicopathological features of small bowel malignant tumors diagnosed by VCE and double-balloon enteroscopy (DBE) in a single tertiary center.
We retrospectively analyzed VCE and DBE findings from Korea University Guro Hospital from January 2010 through September 2018.
A total of 510 VCE and 126 DBE examinations were performed in 438 patients. Small bowel malignancies were diagnosed in 28 patients (15 males; mean age, 61.0 years; range, 42 to 81 years). Among them, 8 had lymphoma, 8 had primary adenocarcinoma, 7 had gastrointestinal stromal tumor (GIST) and 5 had metastatic cancer. Abdominal pain and obstructive symptoms were the most common findings in metastatic cancers (4/5, 80%). On the other hand, obscure gastrointestinal bleeding was the most common symptom of GIST (6/7, 85.7%) and adenocarcinoma (3/8, 37.5%).
Approximately 6% of the patients who underwent either VCE or DBE were diagnosed with small bowel malignancy. These findings demonstrated the different clinical characteristics among small bowel malignancies and merit further study.
A healthy skeleton relies on bone's ability to respond to external mechanical forces. The molecular mechanisms by which bone cells sense and convert mechanical stimuli into biochemical signals, a ...process known as mechanotransduction, are unclear. Focal adhesions play a critical role in cell survival, migration and sensing physical force. Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that controls focal adhesion dynamics and can mediate reparative bone formation in vivo and osteoblast mechanotransduction in vitro. Based on these data, we hypothesized that FAK plays a role in load-induced bone formation. To test this hypothesis, we performed in vitro fluid flow experiments and in vivo bone loading studies in FAK-/- clonal lines and conditional FAK knockout mice, respectively. FAK-/- osteoblasts showed an ablated prostaglandin E(2) (PGE(2)) response to fluid flow shear. This effect was reversed with the re-expression of wild-type FAK. Re-expression of FAK containing site-specific mutations at Tyr-397 and Tyr-925 phosphorylation sites did not rescue the phenotype, suggesting that these sites are important in osteoblast mechanotransduction. Interestingly, mice in which FAK was conditionally deleted in osteoblasts and osteocytes did not exhibit altered load-induced periosteal bone formation. Together these data suggest that although FAK is important in mechanically-induced signaling in osteoblasts in vitro, it is not required for an adaptive response in vivo, possibly due to a compensatory mechanism that does not exist in the cell culture system.
To evaluate the efficacy of cola treatment for gastric phytobezoars, including diospyrobezoars.
A total of 17 patients (range: 48 to 78 years) with symptomatic gastric phytobezoars treated with cola ...and adjuvant endoscopic therapy were reviewed. Three liters of cola lavage (10 cases) or drink (7 cases) were initially used, and then endoscopic fragmentation was done for the remnant bezoars by using a lithotripsy basket or a polypectomy snare. The overall success of dissolving a gastric phytobezoars with using three liters of cola and the clinical and endoscopic findings were compared retrospectively between four cases of complete dissolution by using only cola and 13 cases of partial dissolution with cola.
After 3 L of cola lavage or drinking, a complete dissolution of bezoars was achieved in four patients (23.5%), while 13 cases (76.5%) were only partially dissolved. Phytobezoars (4 of 6 cases) were observed more frequently than diospyrobezoars (0 of 11) in the group that underwent complete dissolution (P = 0.006). Gender, symptom duration, size of bezoar and method of cola administration were not significantly different between the two groups. Twelve of 13 patients with residual bezoars were completely treated with a combination of cola and endoscopic fragmentation.
The rate of complete dissolution with three liters of cola was 23.5%, but no case of diospyrobezoar was completely dissolved using this method. However, pretreatment with cola may be helpful and facilitate endoscopic fragmentation of gastric phytobezoars.
Abstract Objectives The purpose of this study was to investigate the association between organochlorine (OC) pesticides and the prevalence of peripheral arterial disease (PAD). Methods and results ...This study included 2032 participants from the National Health and Nutrition Examination Survey (1999–2004), in which the ankle brachial index (ABI) and serum levels of OC pesticides ( p , p ′-DDE, trans-nonachlor, oxychlordane, dieldrin, and β-HCH) were measured simultaneously. A diagnosis of PAD was determined on the basis of an ABI < 0.9. The obesity status was categorized as obese group (BMI ≥ 25 kg/m2 ) or non-obese group (BMI < 25 kg/m2 ). Compared with subjects without PAD, those with PAD had significantly higher lipid-standardized and wet-weight concentrations of OC pesticides. Obese subjects with PAD had significantly increased mean lipid-standardization value of p , p ′-DDE (OR = 1.47; 95% CI, 1.08–1.99), trans-nonachlor (OR = 1.68; 95% CI, 1.10–2.56), oxychlordane (OR = 1.82; 95% CI, 1.09–3.03), dieldrin (OR = 2.36; 95% CI, 1.69–3.31), and sums of all five pesticides (OR = 1.19; 95% CI, 1.07–1.33). For non-obese group, increases in the levels of OC pesticides and their sums did not account for increased risk ratio of PAD. Conclusion OC pesticides are a potent risk factor for PAD. Additionally, obesity may modulate the association between OC pesticides and the development of PAD.
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