Efficacy and safety of MC-003 solution for endoscopic mucosal or submucosal resection: a prospective, multicenter, randomized, triple-blinded, parallel-group, phase III study.

BACKGROUND AND AIMS: The safety and efficacy of solutions for submucosal injection are critical for endoscopic resection of gastric adenomas or early gastric cancers. Although several injectable solutions have been introduced for endoscopic resection, they have some limitations. We aimed to compare the efficacy of the new sodium alginate-based solution MC-003 with that of normal saline (NS; 0.9% sodium chloride). METHODS: In this randomized, triple-blind study, 70 patients were initially enrolled for EMR or endoscopic submucosal dissection (ESD). The main outcomes included the need for additional injections, completion of en bloc resection, and occurrence of adverse events. RESULTS: Each group ultimately included 34 patients. Complete en bloc resections were achieved in all patients (P = 1.000). The MC-003 group had more peri-neoplasm tissue fibrosis (P = .056) and needed fewer additional injections for lesions >15 mm (P = .037), located in the distal portion of the stomach (P = .007), and during ESD procedures (P = .001). The adverse event rate was comparable in both groups. CONCLUSIONS: MC-003 outperformed NS in reducing the need for additional injections during en bloc resection, particularly in larger lesions located in the distal portion of the stomach (where most lesions were found) during ESD procedures, without increasing the incidence of serious adverse events. MC-003 is a promising submucosal injectable solution in real-world clinical settings.

Metal-Organic Frameworks Marry Sponge: New Opportunities for Advanced Water Treatment.

Metal-organic frameworks (MOFs) have garnered attention across various fields due to their noteworthy features like high specific surface area, substantial porosity, and adjustable performance. In the realm of water treatment, MOFs exhibit great potential for eliminating pollutants such as organics, heavy metals, and oils. Nonetheless, the inherent powder characteristics of MOFs pose challenges in terms of recycling, pipeline blockage, and even secondary pollution in practical applications. Addressing these issues, the incorporation of MOFs into sponges proves to be an effective solution. Strategies like one-pot synthesis, in situ growth, and impregnation are commonly employed for loading MOFs onto sponges. This review comprehensively explores the synthesis strategies of MOFs and sponges, along with their applications in water treatment, aiming to contribute to the ongoing advancement of MOF materials.

Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules.

This corrects the article DOI: 10.1038/nature23874.

Comparative evaluation of endoscopic anti-reflux mucosectomy and stretta radiofrequency ablation in the management of gastroesophageal reflux disease: insights from a retrospective multicenter cohort study.

BACKGROUND: Treatment options for gastroesophageal reflux disease (GERD) that is unresponsive to proton pump inhibitors (PPIs) remain limited. Therefore, we compared the therapeutic effects of anti-reflux mucosectomy (ARMS) and Stretta radiofrequency (SRF) for intractable GERD in over 400 individuals who underwent either procedure. METHODS: We conducted a retrospective study between 2016 and 2023 to evaluate the effectiveness of SRF and ARMS treatments for refractory GERD. The primary measure of success was the change in the GERD questionnaire (GERDQ) score. The secondary outcomes were various GERD-related indicators, including endoscopic Los Angeles (LA) classification, Hill's type-based flap valve grade (FVG), EndoFLIP™ distensibility index (DI), rate of PPI discontinuation, resolution rate of Barrett's esophagus, and incidence of adverse events. RESULTS: The ARMS group included patients with high GERDQ scores, FVG, LA grade, and Barrett's esophagus. Both groups had similar rates of improvements in GERDQ score (P = 0.884) and PPI withdrawal (P = 0.866); however, the ARMS group had significantly more side effects and improvements in the median change in GERDQ score (P = 0.011), FVG (P < 0.001), LA grade (P < 0.001), EndoFLIP™ DI (P < 0.001), and resolution of Barrett's esophagus (P < 0.001). CONCLUSIONS: The ARMS group had a greater GERDQ score improvement than the SRF group but had symptom relief and PPI discontinuation rates similar to those of the SRF group. However, objective measures, including EndoFLIP™ DI and endoscopic evaluations, were better in the ARMS group than in the SRF group.

Endoscopic resection and laparoscopic lymph node dissection for early gastric cancer beyond conventional endoscopic treatment indications: a 10-year outcome study.

BACKGROUND: Endoscopic full-thickness gastric resection (EFTGR) with laparoscopic regional lymph node dissection (LLND) and endoscopic submucosal dissection (ESD) with LLND have been investigated as treatment options for early gastric cancer beyond the absolute indications for ESD. However, comparative studies on the long-term outcomes of these procedures are lacking. This study aimed to analyze and compare the 10-year outcomes of both procedures in a real clinical setting. METHODS: Between January 2009 and December 2013, 28 and 37 patients diagnosed with EGC beyond the absolute indications for ESD were treated with EFTGR with LLND and ESD with LLND, respectively. In both procedures, the dye was injected into the tumor. However, after injection and LLND, EFTGR was performed immediately in the EFTGR with LLND group, whereas LLND was followed by ESD in the ESD with LLND group. The primary endpoint was the 10-year survival rate. RESULTS: The EFTGR with LLND group had one case of local recurrence (3.6%) and mortality (3.6%) each, while the ESD with LLND group had none (0.0% for both); however, the differences were not statistically significant (P = 0.247 for each). Furthermore, there was no significant difference in complications such as ischemia and anastomosis leakage between the groups (P = 0.247). CONCLUSIONS: When the procedures were properly applied, EFTGR with LLND and ESD with LLND did not increase the 10-year mortality in patients with EGC beyond the absolute ESD indications compared with conventional radical gastrectomy.

Da Vinci robot-assisted endoscopic full-thickness gastric resection with regional lymph node dissection using a 3D near-infrared video system: a single-center 5-year clinical outcome.

BACKGROUND: Endoscopic full-thickness gastric resection (EFTGR) with regional lymph node dissection (LND) has been used for early gastric cancer (EGC) exceeding the indications for endoscopic submucosal dissection (ESD). The extent of the dissected lymph nodes is crucial. A 3D near-infrared (NIR) video robot system significantly enhances visualization of the lymphatic system. However, this system has not been used in EFTGR with LND. Thus, this study assessed the benefits of the 3D NIR video robot system in a clinical setting. METHODS: Between February 2015 and September 2018, 24 patients with EGC exceeding the indications for ESD were treated with EFTGR and LND using a 3D NIR video system with the da Vinci surgical robot. Indocyanine green (ICG) was injected endoscopically around the tumor, and basin node (BN) dissection around the nodes was examined using the 3D NIR video system of the da Vinci Si surgical robot. Subsequently, robot-assisted EFTGR was performed. The primary outcome was the 5-year survival rate. RESULT: During a 5-year follow-up of all 24 patients, an 80-year-old patient with an ulcer and T2 invasion was lost to follow-up. Among the remaining 23 patients, no mortality or recurrence was observed. CONCLUSION: No metastasis or mortality occurred using the da Vinci robot-assisted EFTGR with LLND and a 3D NIR video system for patients who required radical gastrectomy for EGC in over 5 years. Hence, this may be a safe and effective method for radical gastrectomy; further studies are required confirming its effectiveness.

Transumbilical Silicone Breast Augmentation: A 13-Year Experience and 5-Year Analysis.

BACKGROUND: Transumbilical breast augmentation (TUBA) with saline implants has been considered a safe and efficient technique for decades. However, because silicone implants are more popular than saline ones, TUBA with saline implants is not widely performed. In 2014, we published a report on transumbilical breast augmentation using silicone cohesive gel implants. As we have performed transumbilical silicone breast augmentation (TUSBA) for 13 years with slight modifications, this study aimed to describe this novel technique and present accompanying patient outcomes over 5 years. METHODS: We enrolled patients desiring breast augmentation at a single center. The preoperative design was initially determined with the patients in standing positions before they underwent surgery under general anesthesia in a supine position. RESULTS: Between January 2018 and December 2022, 69 women and one man underwent TUSBA at a single center. All patients underwent cohesive gel silicone implantation in the subpectoral pocket. The implant size varied from 225 to 300 mL (average 272 mL) because two patients underwent surgery with implants of different sizes due to breast asymmetry. All patients were satisfied with the surgery outcome except one who was dissatisfied because of abdominal bulging. CONCLUSIONS: TUSBA offers advantages such as minimal scarring and unrestricted arm movement; thus, it can be an alternative option for patients seeking breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

Comparative Analysis of Temperature-Responsive Hydrogel (PF 72) for Postoperative Pain After Bimaxillary Surgery: A Retro-spective Study.

Bimaxillary surgery is a painful invasive procedure in plastic surgery. Pain control is typically achieved using intravenous analgesics. We aimed to investigate the efficacy of a novel temperature-responsive hydrogel, PF72, mixed with ropivacaine, as a local pain management solution when applied directly to the surgical site following orthognathic surgery. The study was conducted from October 2022 to July 2023 and included a cohort of 40 candidates for orthognathic surgery, encompassing LeFort I maxillary ostectomy and sagittal split ramus osteotomy. The participants were divided into an Injection group (n = 20), where PF72 was administered at the surgical site before the orthognathic surgery, and a Control group (n = 20), which relied solely on intravenous analgesics. Pain was evaluated at 3, 6, 24, 48, and 72 h after surgery using a numerical rating scale (NRS). The mean NRS scores at 24 h were 6.35 and 4 for the Control and Injection groups, respectively. The mean NRS scores at 72 h were 3.4 and 2.55 for the Control and Injection groups, respectively. Patients who received PF72 experienced less pain than those who received intravenous analgesics. These findings underscore the potential of PF72 as an effective alternative for enhancing pain management in patients undergoing orthognathic surgery.Level of Evidence III Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Light-Scattering Analysis of Drying Behavior in Suspension Droplets with Silica and Polystyrene Particles and a Hydrosoluble Polymer.

The coffee-ring structure, which is the final drying pattern of a sessile suspension droplet, is a key factor in controlling the uniformity of the particulate deposits in various coatings. Two light-scattering methods, diffusing wave spectroscopy (DWS) and multispeckle DWS (MSDWS), were used to quantitatively distinguish temporal changes in particle mobility in evaporating suspension droplets containing micrometer-sized silica and polystyrene (PS) particles. The characteristic particle mobility was measured in terms of the mean square displacement in the early stage of drying, and the local particle dynamics around the edge and center regimes of the droplets during drying were analyzed using MSDWS. Hydroxyethyl cellulose (HEC), a hydrosoluble polymer, was added to the silica and PS suspensions to further investigate its role in suppressing or enhancing coffee-ring patterns based on particle-polymer interactions. Consequently, dried microstructures can be directly correlated with real-time drying dynamics, as well as the interactions between solutes by comprehensive light-scattering methods.

Commensal bacteria make GPCR ligands that mimic human signalling molecules.

Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands, although future studies are needed to define their potential physiological role in humans. Our results suggest that chemical mimicry of eukaryotic signalling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a possible small-molecule therapeutic modality (microbiome-biosynthetic gene therapy).

Comparison of cardiovascular mortality between MAFLD and NAFLD: A cohort study.

BACKGROUND AND AIMS: A new diagnostic criterion of metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed. However, only few studies have shown that MAFLD predicts cardiovascular disease (CVD) mortality better than non-alcoholic fatty liver disease (NAFLD). Therefore, a cohort study was conducted to assess this relationship. METHODS AND RESULTS: Health examination data from health care centers in South Korea were assessed after excluding participants with missing covariates and cancer history (n = 701,664). Liver ultrasonography reports, laboratory and anthropometric data were extracted. Diagnoses of NAFLD and MAFLD were performed according to standard definitions. Participants were categorized based on the presence of NAFLD and MAFLD. In addition, participants were classified into five categories: no fatty liver disease (no FLD), NAFLD-only, MAFLD-only, both FLDs, and alcoholic FLD (AFLD) and non-MAFLD. Multivariable regression modeling was performed. The median follow-up duration was 8.77 years, and 52.56% of participants were men. After stratifying the cohort into no-MAFLD and MAFLD groups, MAFLD was associated with increased CVD mortality (adjusted HR 1.14, 95% CI 1.02-1.28). When participants were divided into no-NAFLD and NAFLD groups, there was a non-significant trend towards an increase in CVD mortality in NAFLD group (adjusted HR 1.07, 95% CI 0.95-1.21). When participants were divided into five categories, MAFLD-only group showed increased CVD mortality (adjusted HR 1.35, 95% CI 1.07-1.70) while NAFLD-only group showed no significant association with CVD mortality (adjusted HR 0.67, 95% CI 0.38-1.19). CONCLUSIONS: In conclusion, MAFLD is associated with increased CVD mortality in a relatively young Korean population.

Combined Lateral Extra-Articular Tenodesis or Combined Anterolateral Ligament Reconstruction and Anterior Cruciate Ligament Reconstruction Improves Outcomes Compared to Isolated Reconstruction for Anterior Cruciate Ligament Tear: A Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: To conduct a network meta-analysis (NMA) comparing the results of randomized controlled trials (RCTs) among patients who underwent either isolated anterior cruciate ligament (ACL) reconstruction or combined lateral extra-articular tenodesis (LET) or anterolateral ligament reconstruction (ALLR). METHODS: RCTs that compared isolated ACL reconstruction and combined LET or ALLR were included with minimum 12 months follow-up. Studies that used the double-bundle technique were excluded. Outcome assessment included the number of positive pivot shifts, amount of anterior tibial translation, and International Knee Documentation Committee (IKDC) subjective, Tegner, and Lysholm scores. Bayesian NMA and the surface under the cumulative ranking area (SUCRA) were evaluated. RESULTS: A total of 1,077 patients from 11 RCTs were enrolled in this study. In NMA, the odds ratios (ORs) of positive pivot shift were significantly lower in ACL + ALLR (OR: 0.17; 95% CI: 0.027-0.67) than isolated ACL reconstruction, but no difference between ACL + ALLR and ACL + LET. There were no significant differences in anterior tibial translation among the techniques, but the IKDC subjective and Lysholm scores of ACL + ALLR and ACL + LET were significantly higher than isolated ACL reconstruction. ACL + ALLR were the most preferred in terms of residual pivot shift, anterior tibial translation, and IKDC subjective scores (SUCRA = 88.2%, 86.4%, and 93.1%, respectively). Additional lateral procedures resulted in significantly lower risk of graft failure (OR: 0.27; 95% CI: 0.1-0.71) than isolated ACL reconstruction. CONCLUSIONS: ACL + ALLR were found to have significantly better outcomes in terms of knee rotational stability and graft failure rate than isolated ACL reconstructions, but the clinical outcomes were uncertain after a minimum 12 months follow-up. Considering the greatest probability of obtaining better knee rotational stability in this NMA, ACL + ALLR was found to be the most preferred technique for patients with ACL injury. LEVEL OF EVIDENCE: Level II, network meta-analysis and systematic review of Level I and II studies.

Incidence and type of meniscal tears in multilligament injured knees.

PURPOSE: Meniscal injuries occurring during multi-ligament knee injuries (MLKI) are underreported. The purpose of this study was to compare the incidence and type of meniscal tears seen at the time of multi-ligament reconstruction surgery compared to those occurring during isolated anterior cruciate ligament (ACL) surgery. METHODS: Patients undergoing surgical treatment for MLKI and ACL-only injuries between 2010 and 2020 were reviewed. Two-hundred and thirty-five patients were included in the MLKI group. There were 131 chronic injuries and 104 acute injuries. Two-hundred and twenty-two ACL-only chronic injuries were used as a control group for comparison with the chronic MLKI group. Demographic data, type of meniscal tears, ligament injury patterns (Schenck classification) and time from injury to surgery were recorded. A delayed procedure was defined by a 4-week interval after the knee injury. RESULTS: A meniscus was torn in 69 knees (29.4%): 36 knees (15.3%) with an isolated medial meniscus tear, 33 knees (17.9%) with an isolated lateral meniscus tear,.Nine knees (3.8%) had both menisci torn. MLKI with medial or lateral-sided bicruciate ligament injuries (KDIIIM-KDIIIL) were significantly associated with a lower rate of meniscal tears than knee injuries involving the ACL-only and medial/lateral-sided ligament injuries (KDI) (medial-sided injuries p = 0.025; lateral-sided injuries p = 0.049). Lateral-sided injuries had significantly less meniscal damage than medial-sided injuries: 22/124 (17.7%) vs. 41/100 (41%); (p < 0.001). No significant differences were found for frequency, type and distribution of meniscal tears between acute and chronic MLKI surgery. ACL-only chronic injuries were associated with a higher rate of meniscal tears: 123/222 knees (55.4%) vs. 35/131 (26.9%) chronic MLKI; (p < 0.001), mainly involving the medial meniscus: 102/222 (46%) vs. 18/131 (13.7%); (p < 0.001). CONCLUSIONS: Meniscal tears were less common in the MLKI group than in the isolated ACL injury group. The degree of ligament injury patterns and the side of the injured collateral ligament influenced the type and incidence of meniscal damage. Contrary to isolated ACL injuries, a delayed procedure was not associated with a higher rate of meniscal lesions but did influence the type of treatment. Understanding of meniscal tears patterns in MLKI helps to improve the treatment management of these complex injuries.

Endoscopically Assisted Correction of Malpositioned Breast Implants Using Absorbable Barbed Sutures.

INTRODUCTION: Breast implant malpositioning is the second most common reason for revisional breast surgery. Multiple correction methods are suggested, depending on the malposition, but most of the methods, such as the inframammary fold incision, result in additional scars. We performed transaxillary endoscopic breast implant bottoming out corrections and used V-Loc thread for capsulorrhaphy. METHODS: Fourteen patients who underwent correction for breast implant bottoming out after transaxillary breast augmentation were included in this study. Transaxillary endoscopic correction was performed using a V-Loc thread. RESULTS: All the 14 patients were satisfied with the result immediately after surgery. One case of overcorrection and one with implant bottoming out occurred, but did not require additional surgery. CONCLUSIONS: Transaxillary endoscopic bottoming out correction is a useful technique for those individuals who underwent primary transaxillary incisional breast augmentation. V-Loc thread is useful for endoscopic capsulorrhaphy. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Assessing the Practical Application of Rheological Properties of Hyaluronic Acid Fillers: A 1-Year Follow-Up Photographic Analysis.

BACKGROUND: A hyaluronic acid filler is a viscoelastic substance that can be evaluated by rheology. Rheological properties are important for the longevity of the filler, which can be deformed due to the various forces that exist on the face. This study aimed to evaluate the maintenance of the lifting capacity of hyaluronic acid filler injection. METHODS: Rheological evaluation of five different products was performed on nine patients who had undergone hyaluronic acid filler injection from Jan 18, 2021 to Jan 27, 2022. Photographs from different time points up to 1 year after filler injection were used to determine the maintenance of the lifting effect of the filler injection. RESULTS: After 1 year of follow-up, the filler on the forehead, temple area, nose, chin, nasojugal fold, and mid-cheek groove areas showed good maintenance, while the nasolabial fold slightly improved. CONCLUSIONS: Appropriate rheological parameters of hyaluronic acid fillers should be considered before injection into different facial areas. A good choice of filler can result in a good aesthetic effect 1 year after injection. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Radiologic findings associated with mucoid degeneration of the anterior cruciate ligament.

INTRODUCTION: Mucoid degeneration (MD) of the anterior cruciate ligament (ACL) is a well-recognized pathology characterized by the degradation of collagen fibers and infiltration of a mucoid-like substance. This study is to determine the anatomical associated factors for MD-ACL using radiographic and magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a retrospective study on patients who had undergone knee arthroscopy between 2011 and 2020. The patients with MD-ACL were defined and enrolled by the MRI and arthroscopy. Eventually, 52 patients in the MD-ACL group (group 1) and 52 patients in the control group (group 2) were enrolled, following sex and age matching. Radiologic evaluation included the assessment of Kellgren-Lawrence (K-L) grade, mechanical hip-knee-ankle (HKA) angle, posterior tibial slope (PTS) angle, and Insall-Salvati ratio. The notch width index and transverse notch angle were measured on MRI, and the grade of trochlear dysplasia was defined. Logistic regression analysis, receiver operating characteristic (ROC) curves, and area under curve (AUC) were performed. RESULTS: The ROM was significantly decreased in group 1, whereas the PTS angle was significantly larger in group 1. Combined ganglion cysts of ACL were found in 42/52 patients (80.7%) in group 1. The risk of MD-ACL was associated with a steeper PTS angle, increased Insall-Salvati ratio, male sex, higher K-L grade, and decreased transverse notch angle and notch width index. The cutoff values in ROC analysis were found to be ≤ 28.27% for the notch width index (AUC, 0.849; p < 0.001), > 12.2° for the PTS angle (AUC, 0.765; p < 0.001), and ≤ 47.4° for the transverse notch angle (AUC, 0.711; p < 0.001), but not significant for Insall-salvati ratio. CONCLUSION: A steeper PTS angle, decreased notch width index, and transverse notch angle are significantly associated with the presence of MD-ACL. These factors should be considered during diagnosis or when determining the treatment strategy for symptomatic MD-ACL patients. LEVEL OF EVIDENCE: Level IIIb.

Analysis and management of pathogens isolated from patients with complicated facial lacerations and abrasions.

Plastic surgeons commonly encounter patients with facial lacerations and/or abrasions in the emergency room. If they are properly treated, facial wounds generally heal well without complications. However, infection can sometimes cause delayed wound healing. We performed wound culture for the early detection of infection and to promote the healing of infected facial wounds. We included 5033 patients with facial wounds who visited the emergency room of Kangnam Sacred Heart Hospital between January 2018 and February 2021. Among them, 104 patients underwent wound culture. We analysed the pathogens isolated and the patients' age, sex, wound site, mechanism of injury, wound healing time, time from injury to culture, time to culture results, and dressing methods used. Pathogens were isolated in slightly less than half of the patients (38.46%); among them, Staphylococcus epidermidis was the most common (47.5%). Methicillin-resistant coagulase-negative staphylococci were isolated in six (15%) patients. Patients with complicated wounds had a longer mean wound healing time (10.83 ± 5.91 days) than those with non-complicated wounds (6.06 ± 1.68 days). Wound culture of complicated facial wounds resulted in the isolation of various types of pathogens, including antibiotic-resistant bacteria and fungi. We recommend the use of wound culture for early detection of infection to prevent delayed wound healing.

Anti-neuroinflammatory Effects and Brain Pharmacokinetic Properties of Selonsertib, an Apoptosis signal-regulating Kinase 1 Inhibitor, in mice.

Selonsertib is a first-in-class apoptosis signal-regulating kinase 1 (ASK1) inhibitor in clinical trials for treating NASH and diabetic kidney disease due to its anti-inflammatory and anti-fibrotic activities. In the present study, we investigated the anti-neuroinflammatory effects and brain pharmacokinetic properties of selonsertib. It inhibited inflammatory cytokines and NO production by suppressing phosphorylated ASK1 in the LPS-stimulated microglial cell line, BV2 cells. Consistent with the in vitro results, selonsertib attenuated plasma and brain TNF-α levels in the LPS-induced murine neuroinflammation model. In vitro and in vivo pharmacokinetic studies of selonsertib were conducted in support of central nervous system (CNS) drug discovery. In both Caco-2 and MDR-MDCK cells, selonsertib exhibited a high efflux ratio, showing that it is a P-gp substrate. Selonsertib was rapidly and effectively absorbed into the systemic circulation after oral treatment, with a Tmax of 0.5 h and oral bioavailability of 74%. In comparison with high systemic exposure with Cmax of 16.2 µg/ml and AUC of 64 µg·h/mL following oral dosing of 10 mg/kg, the brain disposition of selonsertib was limited, with Cmax of 0.08 µg/g and Kp value of 0.004. This study demonstrates that selonsertib can be a therapeutic agent for neuroinflammatory diseases.

Discovery and Photoisomerization of New Pyrrolosesquiterpenoids Glaciapyrroles D and E, from Deep-Sea Sediment Streptomyces sp.

Two new pyrrolosesquiterpenes, glaciapyrroles D (1) and E (2) were discovered along with the previously reported glaciapyrrole A (3) from Streptomyces sp. GGS53 strain isolated from deep-sea sediment. This study elucidated the planar structures of 1 and 2 using nuclear magnetic resonance (NMR), mass spectrometry (MS), ultraviolet (UV), and infrared (IR) spectroscopic data. The absolute configurations of the glaciapyrroles were determined by Mosher's method, circular dichroism spectroscopy, and X-ray crystallography. Under 366 nm UV irradiation, the glaciapyrroles were systematically converted to the corresponding photoglaciapyrroles (4-6) via photoisomerization, resulting in the diversification of the glaciapyrrole family compounds. The transformation of the glaciapyrrole Z to E isomers occurred in a 1:1 ratio, based on virtual validation of the photoisomerization of these olefinic compounds by 1H-NMR spectroscopy and liquid chromatography/mass spectrometry (LC/MS) analysis. Finally, when encapsulated in poly(lactic-co-glycolic acid) nanoparticles, glaciapyrrole E and photoglaciapyrrole E displayed significant inhibitory activity against influenza A virus. This is the first report of antiviral effects from glaciapyrrole family compounds, whose biological functions have only been subjected to limited studies so far.

No Differences In Clinical Outcomes Between Rectangular and Round Tunnel Techniques For Anterior Crucial Ligament Reconstruction.

PURPOSE: To compare the clinical outcomes between conventional round tunnel and rectangular tunnel in anatomic anterior cruciate ligament (ACL) reconstruction. METHODS: This was a retrospective comparative cohort study between March 2015 and September 2018. The primary ACL reconstructions using anteromedial portal technique with minimum of 2 years follow-up were enrolled for this study. The exclusion criteria were patients with revision ACL reconstruction, high tibial osteotomy, multiligament injuries, and associated fractures around the knee. Outcome measures included the subjective International Knee Documentation Committee score, Tegner activity score, knee laxity testing, and measurement of the centers of the femoral and tibial tunnels on postoperative computed tomography (CT) images. RESULTS: Forty-seven patients with ACL reconstruction with rectangular tunnel (group 1) and 108 patients with ACL reconstructions with conventional rounded tunnel (group 2) were included consecutively. There were no significant differences between groups in terms of clinical scores or knee laxity, as well as femoral and tibial tunnel positions on CT. One patient in group 2 had ACL failure because of trauma and was treated with revision surgery. Two patients had incomplete tibial fracture, but they healed spontaneously and showed no residual laxity at final follow-up. The intraobserver and interobserver reliability for the radiological measurements ranged from 0.78 to 0.86. CONCLUSIONS: There were no differences in radiological and clinical results between rectangular tunnel group and conventional round tunnel group for arthroscopic ACL reconstruction. ACL reconstruction with a rectangular tunnel could be considered as a reliable technique, but care should be taken during tunnel establishment because of risk of fractures and malposition of rectangular tunnel.