Laparoscopic versus open total gastrectomy for T4a gastric cancer: a propensity score-matched analysis of long-term outcomes.

Evidence of implementation of laparoscopic total gastrectomy (LTG) for surgical T4a stage (sT4a) gastric cancer (GC) remains inadequate. This study aimed to compare short- and long-term outcomes of LTG versus open total gastrectomy (OTG) for sT4a GC. This retrospective cohort study was conducted using data from patients with sT4a GC underwent total gastrectomy from 2014 to 2020. Short-term outcomes included operative characteristics and postoperative complications. Long-term oncological outcomes focused on 3-, and 5-year overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) was applied to reduce potential biases in baseline characteristics between groups. There was a total of 161 patients, in which 96 underwent LTG and 65 underwent OTG. After PSM, both groups consisted of 51 patients each, with balanced baseline characteristics. There were no significant differences between the two groups regarding blood loss, length of proximal resected margin, postoperative hospital stays, and overall and major postoperative complications. Most of the complications were classified as minor according to the Clavien-Dindo classification. Operating time was significantly longer in the LTG group (mean: 257 min vs. 231 min, p = 0.006). LTG was superior to OTG groups in time to flatus (mean: 3.0 days vs 3.9 days, p < 0.001). Five-year OS and DFS rates were similar between the two groups (44% and 33% vs. 43% and 28% in the LTG and OTG groups, respectively). Our findings indicate that LTG is a feasible and safe technique, exhibiting comparable long-term oncological outcomes to OTG for sT4a GC. LTG may be an acceptable alternative to OTG for the treatment of sT4a GC.

Role of indocyanine green fluorescence imaging for evaluating blood supply in the gastric conduit via the substernal route after McKeown minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a determining factor of morbidity and mortality after esophagectomy. Adequate perfusion of the gastric conduit is crucial for AL prevention. This study aimed to determine whether intraoperative angiography using indocyanine green (ICG) fluorescence improves the incidence of AL after McKeown minimally invasive esophagectomy (MIE) with gastric conduit via the substernal route (SR). METHODS: This retrospective cohort study included 120 patients who underwent MIE with gastric conduit via SR for esophageal cancer between February 2019 and April 2023. Of 120 patients, 88 experienced intraoperative angiography using ICG (ICG group), and 32 patients experienced intraoperative angiography without ICG (no-ICG group). Baseline characteristics and operative outcomes, including AL as the main concern, were compared between the 2 groups. In addition, the outcomes among patients in the ICG group with different levels of fluorescence intensity were compared. RESULTS: The ICG and no-ICG groups were comparable in baseline characteristics and operative outcomes. There was no significant difference between the 2 groups regarding the rate of AL (31.0% vs 37.5%; P = .505), median dates of AL (9 vs 9 days; P = .810), and severity of AL (88.9%, 11.11%, and 0.0% vs 66.7%, 16.7%, and 16.7% for grades I, II, and III, respectively; P = .074). Patients in the ICG group with lower intensity of ICG had higher rates of leakage (24.6%, 39.3%, and 100% in levels I, II, and III of ICG intensity, respectively; P = .04). CONCLUSION: The use of ICG did not seem to reduce the rate of AL. However, abnormal intensity of ICG fluorescence was associated with a higher rate of AL, which implies a predictive potential.

Billroth-II modified with hinged anti-peristaltic afferent loop versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: A propensity-score match analysis.

BACKGROUND: This study aimed to evaluate the effectiveness of modified Billroth-II with a hinged anti-peristaltic afferent loop by comparing it with the Roux-en-Y method. METHODS: We retrospectively analyzed 344 patients with gastric cancer who underwent distal gastrectomy between 2016 and 2021. Propensity score matching was conducted to balance baseline characteristics. RESULTS: After propensity score matching, there were 117 patients in each group. The Billroth-II group was significantly better regarding operating time (184.7 vs 225.3 minutes), postoperative hospital stays (7.9 vs 9.2 days), and time to semi-solid diet tolerance (2.8 vs 3.8 days). The Billroth-II group demonstrated comparable results with the Roux-en-Y group in weight loss, hemoglobin changes, reflux esophagitis, food residue, and gastritis severity. Presentation of bile in gastric remnant was significantly higher in the Billroth-II group (42.9% vs 10.3%). CONCLUSION: There were no significant differences in functional outcomes between Billroth-II and Roux-en-Y reconstructions. The Billroth-II was superior to Roux-en-Y in operating time, hospital stays, and time to semi-solid diet tolerance. The Billroth-II could be considered an acceptable alternative reconstruction after distal gastrectomy.

Poly-ϵ-caprolactone scaffold as staple-line reinforcement of rectal anastomosis: an experimental piglet study.

PURPOSE: Rectal anastomoses have a persisting high incidence of anastomotic leakage. This study aimed to assess whether the use of a poly-ϵ-caprolactone (PCL) scaffold as reinforcement of a circular stapled rectal anastomosis could increase tensile strength and improve healing compared to a control in a piglet model. METHOD: Twenty weaned female piglets received a stapled rectal anastomosis and were randomised to either reinforcement with PCL scaffold (intervention) or no reinforcement (control). On postoperative day five the anastomosis was subjected to a tensile strength test followed by a histological examination to evaluate the wound healing according to the Verhofstad scoring. RESULTS: The tensile strength test showed no significant difference between the two groups, but histological evaluation revealed significant impaired wound healing in the intervention group. CONCLUSION: The incorporation of a PCL scaffold into a circular stapled rectal anastomosis did not increase anastomotic tensile strength in piglets and indicated an impaired histologically assessed wound healing.

Extracting lignin from sugarcane bagasse for methylene blue and hexavalent chromium adsorption in textile wastewater: a facile, green, and sustainable approach.

This study presents the process of extracting lignin from sugarcane bagasse collected in the Mekong Delta, Vietnam by the alkali method. NaOH has been used as an effective, environmentally friendly chemical to enhance the extraction process. The obtained lignin was applied for methylene blue (MB) and hexavalent chromium (Cr(vi)) removal. Factors influencing lignin extraction and adsorption processes of MB and Cr(vi) were investigated, showcasing the sustainable reusability of lignin extracted from sugarcane bagasse. Lignin characterization was also carried out by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA) techniques. The results showed that the extracted lignin content reached 38.61% under optimal conditions (NaOH concentration of 10%, reaction temperature of 90 °C and reaction time of 90 min). The adsorption efficiency and capacity of lignin reached 90.90% and 9.09 mg g-1 for MB and 80.10% and 28.04 mg g-1 for Cr(vi), respectively, under optimum adsorption conditions (pH, adsorption time, initial methylene blue concentration, and used lignin content). The adsorption process obeyed Langmuir adsorption and was principally physical adsorption. These findings prove sugarcane bagasse based lignin as a cheap and efficient adsorbent for MB and Cr(vi) removal, which contributes to the utilization of the abundant agricultural by-product for wastewater treatment.

Comparison of substernal and posterior mediastinal route of reconstruction after minimally invasive esophagectomy for esophageal cancer.

BACKGROUND: Substernal (ST) and posterior mediastinal (PM) routes are the two most common for reconstruction after esophagectomy with cervical anastomosis. Recent evidence showed similar outcomes between the routes; thus, the superior choice remained controversial. This study aimed to compare the short-term outcomes of the ST to the PM route for reconstruction after esophagectomy for esophageal cancer (EC). METHOD: This retrospective cohort study included 132 patients who underwent McKeown minimally invasive esophagectomy (MIE) with gastric conduit for EC between March 2015 and December 2022. Among these, 89 and 43 patients received the ST route and PM route for reconstruction, respectively. Short-term outcomes including operative characteristics, postoperative morbidity, and mortality were evaluated. RESULT: There was no conversion from ST to PM route. The ST group had longer operating time (375 min vs. 341 min). Oral feeding initiation, postoperative hospital stays, and overall complication rates were comparable in the two groups. The rate and severity of anastomotic leakage were similar between the groups. The ST group had a significantly lower incidence of postoperative ICU admission and pneumonia compared to the PM group (5.6% vs. 16.3% and 19.1% vs. 37.2%, respectively). Azygos vein bleeding, obstruction at feeding jejunostomy site, and conduit-trachea fistula were severe complications that only occurred in PM route. CONCLUSION: ST route was superior to PM route in term of postoperative ICU admission and pneumonia. This route may prevent severe complications that only occur in PM route. ST route can be favorable option for reconstruction after McKeown MIE for EC.

Rational design of novel diaryl ether-linked benzimidazole derivatives as potent and selective BACE1 inhibitors.

Due to the large size and high flexibility of the catalytic active site of BACE1 enzyme, the development of nonpeptide inhibitors with optimal pharmacological properties is still highly demanding. In this work, we have discovered 2-aminobenzimidazole-containg ether scaffolds having potent and selective inhibitory potentials against BACE1 enzyme. We have synthesized novel 29 compounds and optimization of aryl linker region resulted in highly potent BACE1 inhibitory activities with EC50 values of 0.05-2.71 µM. The aryloxy-phenyl analogs 20j showed the EC50 value as low as 0.07 µM in the enzyme assay, whereas, the benzyloxyphenyl dervative 24b was comparatively less effective in the enzyme assay. But interestingly the latter was more effective in the cell assay (EC50 value 1.2 µM). While comparing synthesized derivatives in the cell assay using PC12-APPSW cell, compound 27f appeared as the most potent BACE1 inhibitor having EC50 value 0.7 µM. This scaffold also showed high selectivity over BACE2 enzyme and cathepsin D. Furthermore, the research findings were bolstered through the incorporation of molecular docking, molecular dynamics, and DFT studies. We firmly believe that these discoveries will pave the way for the development of a novel class of small-molecule selective BACE1 inhibitors.

Stomach-partitioning versus conventional gastrojejunostomy for unresectable gastric cancer with gastric outlet obstruction: A propensity score matched cohort study.

BACKGROUND: Stomach partitioning gastrojejunostomy (SPGJ) was introduced to deal with delayed gastric emptying (DGE). This study aimed to compare the short- and long-term outcomes of SPGJ versus conventional gastrojejunostomy (CGJ). METHOD: This cohort study analyzed 108 patients who underwent gastrojejunostomy for unresectable gastric cancer: 70 patients underwent SPGJ, and 38 patients underwent CGJ between 2018 and 2022. Propensity score-matched (PSM) analysis was used to balance the baseline characteristics. RESULTS: After PSM, there were 26 patients in each group. SPGJ group had significantly lower incidence of DGE (3.8% vs. 34.6%), vomiting (3.8% vs. 42.3%), and prokinetics requirement (11.5% vs. 46.2%). SPGJ group had significantly shorter time to solid diet tolerance (4.1 days vs. 5.7 days) and postoperative hospital stay (7.7 days vs. 9.3 days). There was no significant difference in relapse reinterventions, gastric outlet obstruction (GOO) recurrence, conversion surgery, and survival outcomes. CONCLUSIONS: SGPJ was associated with lower rate of DGE, prokinetics requirement, and shorter time of solid diet tolerance compared to CGJ in the treatment of unresectable gastric cancer patients with GOO.

Multimodal analysis of methylomics and fragmentomics in plasma cell-free DNA for multi-cancer early detection and localization.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening.

Health of migrants and other vulnerable populations across Asian countries: Build Forward Better beyond the COVID-19 pandemic.

Global migration has been increasing since before the COVID-19 pandemic. The pandemic has clearly shown a lack of preparedness for the next public health emergency when it comes to vulnerable populations including migrants. To include the issues of migration and health in the current global health agenda, it is important to establish/strengthen a network for collaboration among various stakeholders from both the migrant-sending and host countries of migrants especially in the Asian-Pacific region. As the initial step for networking in Asia, in March 2023, a hybrid style international symposium was held in Japan and agreed on a goal and five pillars: surveillance and monitoring, risk communications, community engagement, access to health and social protection services, and supportive environments. Considering the transition of context from the COVID-19 crisis to 'Build Forward Better', through the Asian network, we will envisage the better world, where vulnerable populations including migrants will not be left behind from health security.

Enhanced Degradability, Mechanical Properties, and Flame Retardation of Poly(Lactic Acid) Composite with New Zealand Jade (Pounamu) Particles.

Plastic pollution has become a global concern, demanding urgent attention and concerted efforts to mitigate its environmental impacts. Biodegradable plastics have emerged as a potential solution, offering the prospect of reduced harm through degradation over time. However, the lower mechanical strength and slower degradation process of biodegradable plastics have hindered their widespread adoption. In this study, we investigate the incorporation of New Zealand (NZ) jade (pounamu) particles into poly(lactic acid) (PLA) to enhance the performance of the resulting composite. We aim to improve mechanical strength, flame retardation, and degradability. The material properties and compatibility with 3D printing technology were examined through a series of characterization techniques, including X-ray diffraction, dispersive X-ray fluorescence spectrometry, scanning electron microscopy, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, 3D printing, compression molding, pycnometry, rheometry, tensile tests, three-point bending, and flammability testing. Our findings demonstrate that the addition of NZ jade particles significantly affects the density, thermal stability, and mechanical properties of the composites. Compounding NZ jade shows two different changes in thermal stability. It reduces flammability suggesting potential flame-retardant properties, and it accelerates the thermal degradation process as observed from the thermogravimetric analysis and the inferred decrease in molecular weight through rheometry. Thus, the presence of jade particles can also have the potential to enhance biodegradation, although further research is needed to assess its impact. The mechanical properties differ between compression-molded and 3D-printed samples, with compression-molded composites exhibiting higher strength and stiffness. Increasing jade content in composites further enhances their mechanical performance. Th results of this study contribute to the development of sustainable solutions for plastic pollution, paving the way for innovative applications and a cleaner environment.

Regional Lymph Node Metastasis Distribution in Resectable Middle-Third Gastric Cancer: A Cross-Sectional Study.

Introduction Lymph node (LN) metastasis happens even in early gastric cancer (GC) even in LN stations that are not adjacent to the primary tumor. Total or subtotal gastrectomy (TG or sTG) can be performed in the middle third of the GC if the negative proximal margin is maintained. These procedures differed in the extent of LN dissection; therefore, oncology considerations must be taken into consideration when selecting the appropriate procedure. Methods This was a cross-sectional study involving 98 patients suffering from middle-third GC. The metastatic lymph nodes (mLN) ratio was calculated in each case by the ratio between the number of mLN and the number of total LNs retrieved. We compare the difference in the total LN retrieved, number of mLN, and rate of positive LN (N+) between the two groups TG and sTG. Results The majority of patients had advanced GC (82.7% pT2-4). About 65.3% of patients had metastasis LN. The events of LN metastasis and skipped LN metastasis happened even in tumors contained in the submucosal layer. The metastasis rates in each LN station were also increasing in correlation with the depth of tumor invasion. For LN station No. 2, 4sa, 10, 11d (which are not mandatory) in sTG, the rate of mLN was 0% for the pT1-3 tumor, regardless of tumor longitudinal location. The rate of mLN for each station was higher in adjacent stations of the tumor (No. 1-3-5-7 in lesser curvature, No. 4sb-4d-6 in greater curvature, No.1-3-4sb in the anterior wall, No. 3-7-12a in the posterior wall). The total LN retrieved, number of mLN, and rate of positive LN were statistically higher in the TG group compared to the sTG group. However, the mean mLN ratios between the two groups were comparable (p = 0.116). Conclusion In accordance with the macroscopic and microscopic characteristics, we observed a stratified distribution of mLN in the middle third of the GC. With these early results, sTG combined with standard lymphadenectomy was an acceptable treatment for T1-T3 middle-third GC in terms of mLN distribution. Total No. 4sb LN dissection might also be reserved in gastrectomy for T1-T3 GC.

Stable biogenic silver nanoparticles from Syzygium nervosum bud extract for enhanced catalytic, antibacterial and antifungal properties.

In the present study, the biosynthesis of stable silver nanoparticles (BioAgNPs) was accomplished successfully for the first time by using an aqueous extract derived from the buds of Syzygium nervosum (SN) as both a reducing and a stabilizing agent. Transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM) investigations revealed that the biosynthesized BioAgNPs were predominantly spherical with an average size of 10-30 nm. It was found that the outstanding stability of the BioAgNPs colloidal solution was assigned to the additive effect of the surrounding protective organic layer and the highly negatively charged surface of the nanoparticles. Consequently, good antibacterial activity was demonstrated by the colloidal BioAgNPs solution against four distinct bacterial strains, including Gram-positive S. aureus and B. subtilis as well as Gram-negative E. coli and S. typhi. Interestingly, the biosynthesized BioAgNPs displayed greater antibacterial activity even when tested at low doses against Gram-negative S. typhi. In addition, the biogenic AgNPs demonstrated a significant level of catalytic activity in the process of converting 2-NP, 3-NP, and 4-NP into aminophenols within 15 min, with reaction rate constants of 9.0 × 10-4, 10 × 10-4, and 9.0 × 10-4 s-1, respectively. BioAgNPs formulations were assessed against anthracnose disease in tea plants and were found to be as effective as the positive control at a dose of 20-fold dilution, but less effective at a dose of 30-fold dilution. Both doses of BioAgNPs formulations significantly suppressed Colletotrichum camelliae (anthracnose disease) without affecting the growth of the tea plants.

Desmodinosides A-E: New Flavonoid C-glycosides from Desmodium heterocarpon var. stigosum with hepatoprotective and antifungal activity.

Five new flavonoid C-glycosides named desmodinosides A-E (1-5) and one known compound, apigenin 6-C-ß-d-xylopyranosyl-2''-O-ß-D-glucopyranoside (6) have been isolated from the methanol extract of the aerial parts of Desmodium heterocarpon var. stigosum. These compounds were determined by 1D and 2D-NMR and HR-MS spectroscopies. The methanol extract of this plant, in particular, demonstrated hepatoprotection and antifungal inhibition. This extract has a remarkable hepatoprotection and activity-dose response with an EC50 of 43.07 µg/mL. The hepatoprotective effect on human liver hepatoma cells (HepG2) of the isolated flavonoid C-glycosides 1-6 was observed. Desmodinosides A-C (1-3) were found to exhibit moderate hepatoprotective activity on HepG2 cells. Of these, compound 2 showed the best hepatoprotective activity with an EC50 value of 74.12 µg/mL. While compounds 1 and 3 displayed EC50 values of 271.21 and 211.99 µg/mL, respectively. Quercetin, a positive control, also caused an EC50 value of 36.42 µg/mL. In addition to having hepatoprotective effect, the methanol extract had an inhibitory effect on the growth of oomycete; it inhibited Phytophthora infestans with IC50 of 13.3 µg/mL and IC90 of 78.7 µg/mL. The oomycete inhibition was directly attributed to compounds 5 and 6, which significantly inhibited P. infestans with IC50 values of 27.4 and 24.7 µg/mL, respectively. Both 5 and 6 and methanol extract were active against P. infestanse in a dose-dependent manner. Our study demonstrated for the first time the new flavonoid C-glycosides from D. heterocarpon var. stigosum and their novel pharmacological properties. The study findings also suggest the plant extract and its metabolites could be used as a new botanical source of bioactive compounds.

Purpurascenines A-C, Azepino-Indole Alkaloids from Cortinarius purpurascens: Isolation, Biosynthesis, and Activity Studies on the 5-HT2A Receptor.

Three previously undescribed azepino-indole alkaloids, named purpurascenines A-C (1-3), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 1-3 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet-Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A-C (1-3). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor's active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.

On-Site Detection of Neonicotinoid Pesticides Using Functionalized Gold Nanoparticles and Halogen Bonding.

Neonicotinoid (NN) pesticides have emerged globally as one of the most widely used agricultural tools for protecting crops from pest damage and boosting food production. Unfortunately, some NN compounds, such as extensively employed imidacloprid-based pesticides, have also been identified as likely endangering critical pollinating insects like honey bees. To this end, NN pesticides pose a potential threat to world food supplies. As more countries restrict or prohibit the use of NN pesticides, tools are needed to effectively and quickly identify the presence of NN compounds like imidacloprid on site (e.g., in storage areas on farms or pesticide distribution warehouses). This study represents a proof-of-concept where the colloidal properties of specifically modified gold nanoparticles (Au-NPs) able to engage in the rare intermolecular interaction of halogen bonding (XB) can result in the detection of certain NN compounds. Density functional theory and diffusion-ordered NMR spectroscopy (DOSY NMR) are used to explore the fundamental XB interactions between strong XB-donor structures and NN compounds, with the latter found to possess multiple XB-acceptor binding sites. A fundamental understanding of these XB interactions allows for the functionalization of alkanethiolate-stabilized Au-NPs, known as monolayer-protected gold clusters (MPCs), with XB-donor capability (f-MPCs). In the presence of certain NN compounds such as imidacloprid, the f-MPCs subsequently exhibit visual XB-induced aggregation that is also measured with absorption (UV-vis) spectroscopy and verified with transmission electron microscopy (TEM) imaging. The demonstrated f-MPC-aggregation detection scheme has a number of favorable attributes, including quickly reporting the presence of the NN target, requiring only micrograms of suspect material, and being highly selective for imidacloprid, the most prevalent and most important NN insecticide compound. Requiring no instrumentation, the presented methodology can be envisioned as a simple screening test in which dipping a cotton swab of an unknown powder from a surface in a f-MPC solution causes f-MPCs to aggregate and yield a preliminary indication of imidacloprid presence.

Nanomaterial-Doped Xerogels for Biosensing Measurements of Xanthine in Clinical and Industrial Applications.

First-generation amperometric xanthine (XAN) biosensors, assembled via layer-by-layer methodology and featuring xerogels doped with gold nanoparticles (Au-NPs), were the focus of this study and involved both fundamental exploration of the materials as well as demonstrated usage of the biosensor in both clinical (disease diagnosis) and industrial (meat freshness) applications. Voltammetry and amperometry were used to characterize and optimize the functional layers of the biosensor design including a xerogel with and without embedded xanthine oxidase enzyme (XOx) and an outer, semi-permeable blended polyurethane (PU) layer. Specifically, the porosity/hydrophobicity of xerogels formed from silane precursors and different compositions of PU were examined for their impact on the XAN biosensing mechanism. Doping the xerogel layer with different alkanethiol protected Au-NPs was demonstrated as an effective means for enhancing biosensor performance including improved sensitivity, linear range, and response time, as well as stabilizing XAN sensitivity and discrimination against common interferent species (selectivity) over time-all attributes matching or exceeding most other reported XAN sensors. Part of the study focuses on deconvoluting the amperometric signal generated by the biosensor and determining the contribution from all of the possible electroactive species involved in natural purine metabolism (e.g., uric acid, hypoxanthine) as an important part of designing XAN sensors (schemes amenable to miniaturization, portability, or low production cost). Effective XAN sensors remain relevant as potential tools for both early diagnosis of diseases as well as for industrial food monitoring.

Rheumatic Immune-Related Adverse Events due to Immune Checkpoint Inhibitors-A 2023 Update.

With the aging of the population, malignancies are becoming common complications in patients with rheumatoid arthritis (RA), particularly in elderly patients. Such malignancies often interfere with RA treatment. Among several therapeutic agents, immune checkpoint inhibitors (ICIs) which antagonize immunological brakes on T lymphocytes have emerged as a promising treatment option for a variety of malignancies. In parallel, evidence has accumulated that ICIs are associated with numerous immune-related adverse events (irAEs), such as hypophysitis, myocarditis, pneumonitis, and colitis. Moreover, ICIs not only exacerbate pre-existing autoimmune diseases, but also cause de novo rheumatic disease-like symptoms, such as arthritis, myositis, and vasculitis, which are currently termed rheumatic irAEs. Rheumatic irAEs differ from classical rheumatic diseases in multiple aspects, and treatment should be individualized based on the severity. Close collaboration with oncologists is critical for preventing irreversible organ damage. This review summarizes the current evidence regarding the mechanisms and management of rheumatic irAEs with focus on arthritis, myositis, and vasculitis. Based on these findings, potential therapeutic strategies against rheumatic irAEs are discussed.

Surgical outcomes and quality of life assessment of esophagectomy for cancer with colon conduit via retrosternal route.

PURPOSE: Colon conduit is an alternative to a gastric conduit for esophagectomy in patients that stomach is not available. Surgical technique is complex and has a high risk of morbidities and mortality. Outcomes of patients are still lacking in the literature, thus aims of this study are to evaluate the safety, feasibility and long-term functional outcomes of patients who underwent esophagectomy for cancer with colon conduit via retrosternal route. METHODS: Twenty-six patients underwent operation between August 2016 and June 2021 for malignancies. Minimally invasive esophagectomy and laparotomy were performed in accordance with the 2017 Japan Esophageal Society's guidelines. Colonic interposition was used for esophageal replacement. Outcomes were technical success, complications assessed using Clavien-Dindo classification, and patient's quality of life (QOL) based on EORTC-QOL-OES18 questionnaire. RESULTS: Mean age was 56.0 ± 9.9 years and 21 patients (80.8%) were men. Mean operating time was 432 ± 66 min. Technical success was 100%. The average number of resected lymph nodes was 26 ± 14. Twelve patients (46.2%) experienced postoperative complications: 7/12 were classified as grade I-II, 3/12 as grade III, 1/12 as grade IV, and 1/12 as grade V (death). Patient's QOL improved during the follow-up period with median (25-75th percentiles) global EORTC-QOL-OES18 score was 29 (17-34); 13 (9-21), and 9 (6-16) at 3, 6, and 12 months, respectively. During the follow-up period, there were 4 late complications, 3 lymphatic recurrences, 5 distant metastases, and 6 deaths. CONCLUSIONS: Colon conduit via retrosternal route after esophagectomy is feasible, safe, and could provide acceptable long-term functional outcomes.

Characterization of thymol derivatives from Eupatorium fortunei Turcz. aerial parts.

From the aerial parts of Eupatorium fortunei, four thymol derivatives (1-4) were isolated and structurally elucidated by NMR and mass spectroscopic methods. Of which, a new dimeric thymol derivative (1) was characterized and its absolute configuration was established by electronic circular dichroism quantum method. In addition, the 1D and 2D NMR as well as HR-ESI mass spectral data of 2 were provided for the first time. Compounds 2-4 were evaluated for their inhibitory activity against α-glucosidase and acetylcholinesterase enzymes. All tested compounds showed weak inhibition at the concentration range of 1-256 µg/mL in both enzymatic assays.