Activation of neurotoxic A1-reactive astrocytes by SFTS virus infection accelerates fatal brain damage in IFNAR1-/- mice.

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.

Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation from a sibling donor for pediatric patients.

Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5 mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5 mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.

Successful Treatment of Refractory or Relapsed Hepatoblastoma With Autologous Hematopoietic Stem Cell Transplantation in Children.

BACKGROUND: The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma. METHODS: We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen. RESULTS: We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy. CONCLUSION: This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.

Elaboration of dimensional quality in 3D-printed food: Key factors in process steps.

Three-dimensional (3D) printing has been applied to produce food products with intricate and fancy shapes. Dimensional quality, such as dimensional stability, surface smoothness, shape fidelity, and resolution, are essential for the attractive appearance of 3D-printed food. Various methods have been extensively studied and proposed to control the dimensional quality of printed foods, but few papers focused on comprehensively and deeply summarizing the key factors of the dimensional quality of printed products at each stage-before, during, and after printing-of the 3D printing process. Therefore, the effects of pretreatment, printing parameters and rheological properties, and cooking and storage on the dimensional quality of the printed foods are summarized, and solutions are also provided for improving the dimensional quality of the printed products at each step. Before printing, incorporating additives or applying physical, chemical, or biological pretreatments can improve the dimensional quality of carbohydrate-based, protein-based, or lipid-based printed food. During printing, controlling the printing parameters and modifying the rheological properties of inks can affect the shape of printed products. Furthermore, post-processing is essential for some printed foods. After printing, changing formulations, incorporating additives, and selecting post-processing methods and conditions may help achieve the desired shape of 3D-printed or 4D-printed products during cooking. Additives help in the storage stability of printed food. Finally, various opportunities have been proposed to regulate the dimensional properties of 3D-printed structures. This review provides detailed guidelines for researchers and users of 3D printers to produce various printed foods with the desired shapes and appearances.

The extended fibers of the alar part of the nasalis connect to the levator labii superioris, zygomaticus minor, and skin adjacent to the nasal ala.

PURPOSE: This study aimed to elucidate the positions of the extended fibers of the alar part of the nasalis (Na), and their connections to the levator labii superioris (LLS), zygomaticus minor (Zmi), and adjacent skin near the nasal ala. METHODS: The extended fibers of the Na were investigated in 54 specimens obtained from 27 embalmed adult South Korean cadavers. RESULTS: In 51.9% of the specimens, some fibers of the Na extended over the alar facial crease, intermingling or blending with the LLS or Zmi, and attached to the skin lateral to the nasal ala. The quantity and distribution of these extended fibers varied: some fibers of the Na extended and intermingled or blended with the LLS in 25.9%, while another 25.9% exhibited the Na extending in a distinctive fan shape with longer fibers, and combining with both the LLS and Zmi. However, the Na had no extended fibers that reached the LLS, Zmi, or skin near the nasal ala in 48.1%. CONCLUSION: Contraction of the Na and its extended fibers can influence the nasal ala and also the laterally located skin and muscles, directing them inferomedially toward the incisive fossa of the maxilla, which is the origin of the nasalis. These insights offer a deeper understanding of the role and actions of facial muscles in facial expression. They will be instrumental in the comprehension and analysis of nose and mouth movements, and in conducting electromyographic analyses in this region.

Positional relationships of the origin and course of zygomaticus major with the nasal ala, tragus, philtrum, and lateral canthus for aesthetic treatments and surgeries.

PURPOSE: The aim of this study was to characterize the origin and course of the zygomaticus major muscle (Zmj) with its topographic relationships with the nasal ala, tragus, philtrum, and lateral canthus. METHODS: The Zmj was examined in 50 specimens of 25 embalmed adult Korean cadavers. Facial muscles were dissected to expose the origin and course of the Zmj in 48 specimens of 24 cadavers. The 25th cadaver was sectioned to obtain images of the Zmj. RESULTS: The positional relationships of the Zmj origin with the nasal ala and the tragus were classified into three categories. A horizontal line through the center of the Zmj origin and the nasal ala passed through the tragus in 20 of 48 specimens (41.7%), the intertragic notch in 18 specimens (37.5%), and above the tragus in 10 specimens (20.8%). In a horizontal section of the head, the Zmj origin was located near the level of the nasal ala and tragus. In a coronal section of the head, the fibers of the Zmj arising at its origin were located close to the zygomatic bone, lateral to the zygomaticus minor muscle. CONCLUSION: By combining dissection with the analysis of sectioned images and ultrasound images of the Zmj, this study has yielded positional information for easily predicting the location of the origin and the course of the Zmj and its related structures underlying the skin.

Anatomical Trajectory of the Corrugator Supercilii Muscle in Koreans: Implications for Aesthetic and Clinical Practices.

BACKGROUND: Understanding the attachment patterns of the corrugator supercilii muscle (CS) is vital for treatments designed to improve facial symmetry and functionality. OBJECTIVES: The aim of this research was to elucidate the anatomical trajectory and intricate relationships of the CS within the upper face and midface, specifically focusing on its connections with the frontalis (FT) and orbicularis oculi (OOc) muscles. METHODS: The CS was examined in 41 specimens of embalmed adult Korean cadavers using microdissection, histological analyses, and microcomputed tomography, an in-depth exploration of its anatomical positioning and intricate interactions with adjacent muscles. RESULTS: Some lower fibers of the CS extended to the upper orbital part of the OOc in 59.5% of cases, while the CS interdigitated or blended exclusively with the FT in 40.5% of cases. The fibers of the CS demonstrated diverse extensions towards the upper face and midface, exhibiting varied trajectories and lengths. Additionally, lower fibers of the CS extended to significant anatomical landmarks such as the OOc, malaris muscle, and the superficial musculoaponeurotic system (SMAS). CONCLUSIONS: This study demonstrates that precise understanding of the CS and its relationship with the FT and OOc is crucial for optimizing invasive or non-invasive treatment like botulinum toxin injection, SMAS lifting and browplasty surgery. The extension of lower fibers of the CS to significant anatomical landmarks indicates complex interactions with adjacent facial structures, highlighting the necessity of detailed anatomical knowledge for clinical applications.

A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Rapid detection of Shiga-toxin-producing Escherichia coli O157:H7 based on a colorimetric loop-mediated isothermal amplification (cLAMP) assay using a molecular beacon paired with HRPzyme.

Contamination by Escherichia coli O157:H7 is considered a threat in the livestock and food industries. Therefore, it is necessary to develop methods for the convenient and rapid detection of Shiga-toxin-producing E. coli O157:H7. This study aimed to develop a colorimetric loop-mediated isothermal amplification (cLAMP) assay using a molecular beacon to rapidly detect E. coli O157:H7. Primers and a molecular beacon were designed for targeting the Shiga-toxin-producing virulence genes (stx1 and stx2) as molecular markers. Additionally, Bst polymerase concentration and amplification conditions for bacterial detection were optimized. The sensitivity and specificity of the assay were also investigated and validated on artificially tainted (100-104 CFU/g) Korean beef samples. The cLAMP assay could detect 1 × 101 CFU/g at 65 °C for both genes, and the assay was confirmed to be specific for E. coli O157:H7. The cLAMP takes about an hour and does not require expensive devices (e.g., thermal cycler and detector). Hence, the cLAMP assay proposed herein can be used in the meat industry as a fast and simple way to detect E. coli O157:H7.

Assessment of sources variability of riverine particulate organic matter with land use and rainfall changes using a three-indicator (δ13C, δ15N, and C/N) Bayesian mixing model.

In intensive agricultural watersheds, riverine particulate organic matter (POM) may be transported from many sources such as rice paddies, crop uplands, forests, and livestock farming areas during rainy seasons. However, the impacts of land-use and rainfall changes on the POM sources are not well understood. In this study, changes in the sources of riverine POM were investigated in an agricultural area of Korea between 2014 and 2020/21. During this period, land-use and rainfall patterns changed dramatically. The δ13C, δ15N, and C/N of the POM sources as well as those of riverine POM were analyzed, and a stable isotope analysis in R (SIAR) model was utilized for source apportionment. There were differences in δ13C, δ15N, and C/N among the sources. For example, manure had higher δ13C (-22.6 ± 3.3‰) and δ15N (+10.6 ± 5.9‰) than soils (from -28.0 ± 0.8‰ to -25.1 ± 1.2‰ for δ13C and +3.6 ± 1.7‰ to +9.8 ± 1.4‰ for δ15N). For soils, the δ13C and δ15N were higher for upland soils, while C/N was greater for forest soils than for others. For riverine POM, the δ15N marginally changed; however, the δ13C and C/N increased from -26.1 ± 0.9‰ to -20.8 ± 5.3‰ and from +7.7 ± 1.7 to +18.8 ± 8.3 between 2014 and 2020/21, respectively. The SIAR model showed that the contributions of paddy (from 41.0% to 14.9%) and upland fields (from 48.1% to 23.7%) to riverine POM decreased between the periods due to decreased paddy area and the implementation of best management practice on upland fields, respectively. However, the contribution of forests (from 3.5% to 28.0%) and manure (from 7.4% to 33.5%) increased probably due to improper management of forest clear-cutting sites and livestock manure storage sites. The contributions of agricultural soils to riverine POM decreased in drier years. Our study suggests that land management rather than land-use area is critical in riverine POM management, particularly in wetter years.

Biportal endoscopic paraspinal decompressive foraminotomy for lumbar foraminal stenosis: clinical outcomes and factors influencing unsatisfactory outcomes.

BACKGROUND: Lumbar foraminal stenosis (LFS) is an important pathologic entity that causes lumbar radiculopathies. Unrecognized LFS may be associated with surgical failure, and LFS remains challenging to treat surgically. This retrospective cohort study aimed to evaluate the clinical outcomes and prognostic factors of decompressive foraminotomy performed using the biportal endoscopic paraspinal approach for LFS. METHODS: A total of 102 consecutive patients with single-level unilateral LFS who underwent biportal endoscopic paraspinal decompressive foraminotomy were included. We evaluated the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI) before and after surgery. Demographic, preoperative data, and radiologic parameters, including the coronal root angle (CRA), were investigated. The patients were divided into Group A (satisfaction group) and Group B (unsatisfaction group). Parameters were compared between these two groups to identify the factors influencing unsatisfactory outcomes. RESULTS: In Group A (78.8% of patients), VAS and ODI scores significantly improved after biportal endoscopic paraspinal decompressive foraminotomy (p < 0.001). However, Group B (21.2% of patients) showed higher incidences of stenosis at the lower lumbar level (p = 0.009), wide segmental lordosis (p = 0.021), and narrow ipsilateral CRA (p = 0.009). In the logistic regression analysis, lower lumbar level (OR = 13.82, 95% CI: 1.33-143.48, p = 0.028) and narrow ipsilateral CRA (OR = 0.92, 95% CI: 0.86-1.00, p = 0.047) were associated with unsatisfactory outcomes. CONCLUSIONS: Significant improvement in clinical outcomes was observed for a year after biportal endoscopic paraspinal decompressive foraminotomy. However, clinical outcomes were unsatisfactory in 21.2% of patients, and lower lumbar level and narrow ipsilateral CRA were independent risk factors for unsatisfactory outcomes.

Feasibility and safety of a CaO-SiO2-P2O5-B2O3 bioactive glass ceramic spacer in posterior lumbar interbody fusion compared with polyetheretherketone cage: a prospective randomized controlled trial.

PURPOSE: The CaO-SiO2-P2O5-B2O3 glass-ceramic (BGS-7) spacer is a recently developed spacer that shows chemical bonding to bone with high mechanical stability. Further, this spacer achieves similar results to those of titanium cages. However, evidence regarding the advantages of the BGS-7 spacer is weak compared to polyetheretherketone (PEEK) cage. A randomized controlled trial is therefore warranted. The purpose of this study was to compare the radiographic and clinical efficacies and safety of the BGS-7 spacer compared to those of the PEEK cage in patients who underwent posterior lumbar interbody fusion (PLIF). METHODS: The 54 participants who required one- or two-level PLIF due to lumbar degenerative disorders were randomly assigned to receive a BGS-7 spacer or PEEK cage. Visual analog scale (VAS), Oswestry Disability Index (ODI), European Quality of Life-5 Dimensions (EQ-5D), and painDETECT score were evaluated before surgery and at 3, 6, and 12 months after surgery. The fusion rate, degree of osteolysis, cage migration, and subsidence around the cage (spacer) were evaluated on computer tomography (CT) images at 12 months after surgery. RESULTS: The 12-month fusion rates were 77.8% in the BGS-7 spacer group and 81.0% in the PEEK cage group, with no significant difference (p = 0.807). The result regarding the non-inferiority of BGS-7 spacer was inconclusive. The linear mixed model showed no significant intervention effect in VAS, ODI, EQ-5D, and painDETECT score at the 3-, 6-, or 12-month follow-up. In addition, we found no significant between-group differences in the extent of osteolysis, spacer migration. However, the subsidence around the cage was significantly lower in the BGS-7 spacer group. CONCLUSIONS: This trial found similar fusion rates, and clinicoradiographic outcomes between the BGS-7 spacer and PEEK cage for PLIF. However, the non-inferiority was inconclusive. Safety concerns regarding fracture and migration of the BGS-7 spacer must be considered. Thus, the BGS-7 spacer design for PLIF surgery should be modified before further clinical use.

Biportal endoscopic extraforaminal lumbar interbody fusion using a 3D-printed porous titanium cage with large footprints: technical note and preliminary results.

PURPOSE: The aim of this study was to introduce biportal endoscopic extraforaminal lumbar interbody fusion (BE-EFLIF), which involves insertion of a cage through a more lateral side as compared to the conventional corridor of transforaminal lumbar interbody fusion. We described the advantages and surgical steps of 3D-printed porous titanium cage with large footprints insertion through multi-portal approach, and preliminary results of this technique. METHODS: This retrospective study included 12 consecutive patients who underwent BE-EFLIF for symptomatic single-level lumbar degenerative disease. Clinical outcomes, including a visual analog scale (VAS) for back and leg pain and the Oswestry disability index (ODI), were collected at preoperative months 1 and 3, and 6 months postoperatively. In addition, perioperative data and radiographic parameters were analyzed. RESULTS: The mean patient age, follow-up period, operation time, and volume of surgical drainage were 68.3 ± 8.4 years, 7.6 ± 2.8 months, 188.3 ± 42.4 min, 92.5 ± 49.6 mL, respectively. There were no transfusion cases. All patients showed significant improvement in VAS and ODI postoperatively, and these were maintained for 6 months after surgery (P < 0.001). The anterior and posterior disc heights significantly increased after surgery (P < 0.001), and the cage was ideally positioned in all patients. There were no incidences of early cage subsidence or other complications. CONCLUSIONS: BE-EFLIF using a 3D-printed porous titanium cage with large footprints is a feasible option for minimally invasive lumbar interbody fusion. This technique is expected to reduce the risk of cage subsidence and improve the fusion rate.

Biportal endoscopic discectomy versus tubular microscopic discectomy for treating single-level lumbar disc herniation in obese patients: a multicenter, retrospective analysis.

PURPOSE: In microscopic lumbar discectomy in obese patients, a correlation is found between the operation time and increase in estimated blood loss according to the increase in body mass index; however, no studies have investigated the outcomes of biportal endoscopic lumbar discectomy in obese patients. Therefore, this study aimed to compare the clinical and radiographic outcomes of microscopic and endoscopic discectomy in obese patients with lumbar herniated discs. METHODS: In this multicenter, retrospective study, clinical and radiological data were compared and analyzed in 73 obese patients with a body mass index of > 30 kg/m2 who underwent microscopic or biportal endoscopic lumbar discectomy. Clinical data on the visual analog scale (VAS), Oswestry disability index (ODI), and EuroQol-5D (EQ-5D) scores were measured, and radiological data were obtained using magnetic resonance imaging (MRI). RESULTS: This study enrolled 43 patients who underwent microscopic discectomy and 30 who underwent biportal endoscopic discectomy. The VAS, ODI, and EQ-5D scores in both groups improved after surgery compared with those before surgery, although there was no difference between the two groups. Although there was a difference in the incidence of recurrent disc herniation confirmed by MRI after surgery, no difference was found in the number of patients requiring surgery between the two groups. CONCLUSION: In obese patients with lumbar disc herniation that was not improved with conservative treatment, no significant clinical or radiological differences in outcomes were noted between microscopic and biportal endoscopic surgery methods. In contrast, minor complications were less common in the biportal group.

Nonsteroidal Anti-Inflammatory Drug Conjugated with Gadolinium (III) Complex as an Anti-Inflammatory MRI Agent.

Studies have been actively conducted to ensure that gadolinium-based contrast agents for magnetic resonance imaging (MRI) are accompanied by various biological functions. A new example is the anti-inflammatory theragnostic MRI agent to target inflammatory mediators for imaging diagnosis and to treat inflammatory diseases simultaneously. We designed, synthesized, and characterized a Gd complex of 1,4,7-tris(carboxymethylaza) cyclododecane-10-azaacetylamide (DO3A) conjugated with a nonsteroidal anti-inflammatory drug (NSAID) that exerts the innate therapeutic effect of NSAIDs and is also applicable in MRI diagnostics. Gd-DO3A-fen (0.1 mmol/kg) was intravenously injected into the turpentine oil-induced mouse model, with Gd-DO3A-BT as a control group. In the in vivo MRI experiment, the contrast-to-noise ratio (CNR) was higher and persisted longer than that with Gd-DO3A-BT; specifically, the CNR difference was almost five times at 2 h after injection. Gd-DO3A-fen had a binding affinity (Ka) of 6.68 × 106 M-1 for the COX-2 enzyme, which was 2.1-fold higher than that of fenbufen, the original NSAID. In vivo evaluation of anti-inflammatory activity was performed in two animal models. In the turpentine oil-induced model, the mRNA expression levels of inflammatory parameters such as COX-2, TNF-α, IL-1ß, and IL-6 were reduced, and in the carrageenan-induced edema model, swelling was suppressed by 72% and there was a 2.88-fold inhibition compared with the saline group. Correlation analysis between in vitro, in silico, and in vivo studies revealed that Gd-DO3A-fen acts as an anti-inflammatory theragnostic agent by directly binding to COX-2.

Digestion profile, antioxidant, and antidiabetic capacity of Morchella esculenta exopolysaccharide: in vitro, in vivo and microbiota analysis.

BACKGROUND: Novel functional polysaccharides from fungi are important nutraceuticals. An exopolysaccharide, Morchella esculenta exopolysaccharide (MEP 2), was extracted and purified from the fermentation liquor of M. esculenta. The aim of this study was to investigate its digestion profile, antioxidant capacity, and effect on the microbiota composition in diabetic mice. RESULTS: The study found that MEP 2 was stable during in vitro saliva digestion but was partially degraded during gastric digestion. The digest enzymes exerted a negligible effect on the chemical structure of MEP 2. Molecular weight and atomic force microscope (AFM) images suggest that both smaller chains and larger aggregations were produced. Scanning electron microscope (SEM) images reveal that the surface morphology was much altered after intestinal digestion. After digestion, the antioxidant ability increased as revealed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Both MEP 2 and its digested components showed strong α-amylase and moderate α-glucosidase inhibition activity, leading us to further investigate its ability to modulate the diabetic symptoms. The MEP 2 treatment ameliorated the inflammatory cell infiltration and increased the size of pancreas inlets. Serum concentration of HbA1c was significantly reduced. Blood glucose level during the oral glucose tolerance test (OGTT) was also slightly lower. The MEP 2 increased the diversity of the gut microbiota and modulated the abundance of several important bacteria including Alcaligenaceae, Caulobacteraceae, Prevotella, Brevundimonas, Demequina, and several Lachnospiraceae species. CONCLUSION: It was found that MEP 2 was partially degraded during in vitro digestion. Its potential antidiabetic bioactivity may be associated with its α-amylase inhibition and gut microbiome modulation ability. © 2023 Society of Chemical Industry.

Can 3-Dimensional Printing for Calcaneal Fracture Surgery Decrease Operation Time and Improve Quality of Fracture Reduction?

We investigated whether 3-dimensional (3D) printed models can decrease operation time and improve the quality of reduction for calcaneal fractures. The study involved 48 patients with unilateral intra-articular calcaneal fractures, who were retrospectively case-matched according to Sander's classification, age, and sex. Group A (24 patients) was operated using 3D printed models as a preoperative and intraoperative tool, and group B (24 patients) was operated using standard techniques without 3D printed model. Operation time was significantly shorter for group A, compared to group B (82.3 ± 13.2 vs 91.4 ± 16.0, p = .036). The differences between the radiological parameters of operated calcaneus, compared to the normal side was similar between the 2 groups (Böhler angle, 5.3° ± 3.9° vs 4.2° ± 4.7°, p = .45, Gissane angle, 5.9° ± 12.5° vs 8.4° ± 11.0°, p = .54). The number of screws projecting more than 5 mm from the cortex was lower in group A than in group B (7/187, 4% vs 16/208, 8%, p = .11). The number of screw holes of the plate cut intraoperatively was significantly lower for group A compared to group B (1 vs 138). Although group A started weightbearing 3 to 4 weeks earlier than group B, the radiological parameters were similar between groups that early weightbearing was possible for group A using the 3D printed models (Böhler angle, - 1.5° ± 0.8° vs - 1.8° ± 1.2°, p = .28, Gissane angle, 2.5° ± 2.6° vs 3.5° ± 4.3°, p = .39). The operation time was shorter while using the 3D printed models, compared to that of the standard technique without using the 3D printed model. The radiological parameters were not statistically different, and the quality of fracture reduction seemed similar. However, with the use of 3D printed models, early weightbearing was possible without significant subsidence of reduced fragments or failure of fracture reduction, comparable to non-weightbearing cases.

Colorimetric detection of norovirus by helicase-dependent amplification method based on specific primers integrated with HRPzyme.

Noroviruses (NoVs) are the most common causes of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and significant causes of foodborne illness. In the USA, approximately 21 million illnesses attributable to NoVs have annually occurred. Therefore, there is a great demand to develop a rapid, low-cost, and accurate detection method for NoVs. This study first reported colorimetric helicase-dependent amplification (HDA) methods based on specific primers integrated with HRPzyme for the rapid and sensitive detection of NoV GI and GII. The colorimetric HDA methods exhibited a detection limit of 10 copies mL-1 of each NoV GI and GII and were confirmed to be specific to each NoV GI and GII. The period required to complete the HDA method was 2 h, including a step of RNA extraction and cDNA synthesis without expensive instruments such as a thermal cycler and detector. The cutoff value of the method for the oyster artificially inoculated with a known amount of NoV was all 102 copies g-1 for NoV GI and GII. Therefore, the HDA method developed in this study can be useful tool for the on-site detection of NoVs in food samples.

Clinical and radiologic outcomes of biportal endoscopic lumbar discectomy in obese patients: a retrospective case-control study.

BACKGROUND: Obese patients have a higher risk of complications during spinal surgery than non-obese patients. To the best of our knowledge, no studies have examined the differences in clinical and radiological outcomes after biportal endoscopic lumbar discectomy (BELD) between obese and non-obese patients. The study evaluated the association between obesity and outcomes after BELD in patients with lumbar disc herniation. METHODS: This was a retrospective case-control study conducted from March 2017 to March 2021 at two hospitals with 360 patients who underwent BELD after showing no improvement with conservative treatment. Clinical and radiologic outcomes were retrospectively analyzed after BELD in the non-obese (body mass index [BMI] < 30 kg/m2) and obese (BMI ≥ 30 kg/m2) groups. Demographic data and surgery-related factors were compared between the two groups. Clinical outcomes were followed up for 12 months after surgery and analyzed for differences. RESULTS: A total of 211 patients were enrolled in this study, and through case-control matching, the data of 115 patients (29, obese group; 86, non-obese group) were analyzed. The two groups showed no significant differences in Oswestry Disability Index, European Quality of Life-5 Dimensions (EQ-5D), and visual analog scale scores measured immediately after BELD and 12 months after surgery. After surgery, back pain, radiating leg pain, and EQ-5D scores improved. However, there was no significant difference in improvement, residual herniated disc, hematoma, or recurrence between the groups. CONCLUSIONS: Obese patients who underwent BELD for lumbar disc herniation showed no significant difference in clinical and radiologic outcomes compared with non-obese patients.

Percutaneous transpedicular intracorporeal cage grafting for Kümmell disease.

BACKGROUND: Osteonecrosis with progressive collapse and segmental kyphosis can lead to intersegmental instability in some osteoporotic vertebral compression fractures (OVCFs). These conditions are known as Kümmell's disease and often require anterior column reconstruction in elderly patients. METHODS: We attempted anterior column reconstruction by percutaneous transpedicular intracorporeal cage grafting (PTICG) with short-segment pedicle screw fixation and described the steps, with discussions on the surgical indications and pros and cons. CONCLUSION: PTICG is expected to be an alternative to vertebral anterior column reconstruction, which can preserve the thoracolumbar posterior arch and paravertebral musculature.