The role of donor type and pre-transplant immunosuppression on outcomes of hematopoietic stem cell transplantation in children and young adults with severe aplastic anemia.

BACKGROUND: The goal of this study was to assess the effect of donor type and pre-transplant immunotherapy (IST) on outcomes of hematopoietic stem cell transplantation (HSCT) for children and young adults with severe aplastic anemia (SAA). METHODS: This retrospective, multi-center study included 52 SAA patients, treated in 5 pediatric transplant programs in Florida, who received HSCT between 2010 and 2020 as the first- or second-line treatment. RESULTS: The median age at HSCT for all 52 patients was 15 years (range 1-25). The 3-year overall survival (OS) by donor type were as follows: 95% [95% CI 85.4-99] for matched related donors (MRD) (N = 24), 84% [95% CI 63.5-99] for haploidentical (N = 13), and 71% [95% CI 36-99] for matched unrelated donors (MUD) (N = 7). The 3-year OS was 81% [95% CI 69.7-99] for all patients, 90.5% [95% CI 79.5-99] for non-IST patients (N = 27), and 70% [95% CI 51-99] for IST patients (N = 24) (log-rank p = .04). Survival of haploidentical HSCT (haplo-HSCT) recipients with post-transplant cyclophosphamide (PTCy) (N = 13) was excellent for both groups: 100% for non-IST patients (N = 3) and 80% for IST patients (N = 10). The 3-year OS for patients with previous IST by donor type in groups where >5 patients were available was 78.8% [95% CI 52.3-99] for haplo-HSCT (N = 10) and 66.7% [95% CI 28.7-99] for MUD (N = 6). Although it appears that patients receiving HSCT ≥6 months after the start of IST had worse survival, the number of patients in each category was small and log-rank was not significant(p = .65). CONCLUSIONS: Patients receiving MUD and haplo-HSCT with PTCy had similar outcomes, suggesting that haplo-HSCT with PTCy could be included in randomized trials of upfront IST versus alternative donor HSCT.

Differential Resistance of Radish Cultivars against Bacterial Soft Rot Caused by Pectobacterium carotovorum subsp. carotovorum.

Bacterial soft rot caused by Pectobacterium carotovorum subsp. carotovorum (Pcc) is one of the most severe diseases in radish cultivation. To control this plant disease, the most effective method has been known to cultivate resistant cultivars. Previously, we developed an efficient bioassay method for investigating resistance levels with 21 resistant and moderately resistant cultivars of radish against a strain Pcc KACC 10421. In this study, our research expanded to investigate the resistance of radish cultivars against six Pcc strains, KACC 10225, KACC 10421, ATCC 12312, ATCC 15713, LY34, and ECC 301365. To this end, the virulence of the six Pcc strains was determined based on the development of bacterial soft rot in seedlings of four susceptible radish cultivars. The results showed that the Pcc strains exhibited different virulence in the susceptible cultivars. To explore the race differentiation of Pcc strains corresponding to the resistance in radish cultivars, we investigated the occurrence of bacterial soft rot caused by the six Pcc strains on the 21 resistant and moderate resistant cultivars. Our results showed that the average values of the area under the disease progress curve were positively correlated with the virulence of the strains and the number of resistant cultivars decreased as the virulence of Pcc strains increased. Taken together, our results suggest that the resistance to Pcc of the radish cultivars commercialized in Korea is more likely affected by the virulence of Pcc strains rather than by race differentiation of Pcc.

Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis.

Seladelpar, a selective peroxisome proliferator-activated receptor δ (PPARδ) agonist, improves markers of hepatic injury in human liver diseases, but histological improvement of nonalcoholic steatohepatitis (NASH) and liver fibrosis has been challenging with any single agent. To discover how complementary agents could work with seladelpar to achieve optimal outcomes, this study evaluated a variety of therapeutics (alone and in combination) in a mouse model of NASH. Mice on a high-fat amylin liver NASH (AMLN) diet were treated for 12 wk with seladelpar, GLP-1-R (glucagon-like peptide-1 receptor) agonist liraglutide, apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib, farnesoid X receptor (FXR) agonist obeticholic acid, and with seladelpar in combination with liraglutide or selonsertib. Seladelpar treatment markedly improved plasma markers of liver function. Seladelpar alone or in combination resulted in stark reductions in liver fibrosis (hydroxyproline, new collagen synthesis rate, mRNA indices of fibrosis, and fibrosis staining) compared with vehicle and the other single agents. Robust reductions in liver steatosis were also observed. Seladelpar produced a reorganization of metabolic gene expression, particularly for those genes promoting peroxisomal and mitochondrial lipid oxidation. In summary, substantial improvements in NASH and NASH-induced fibrosis were observed with seladelpar alone and in combination with liraglutide in this model. Broad gene expression analysis suggests seladelpar should be effective in concert with diverse mechanisms of action.NEW & NOTEWORTHY NASH is a chronic, progressive, and increasingly problematic liver disease that has been resistant to treatment with individual therapeutics. In this study using a diet-induced mouse model of NASH, we found that the PPARδ agonist seladelpar reduced fibrosis and NASH pathology alone and in combinations with a GLP-1-R agonist (liraglutide) or an ASK1 inhibitor (selonsertib). Liver transcriptome analysis comparing each agent and coadministration suggests seladelpar should be effective in combination with a variety of therapeutics.

A Case of Linear Hypertrophic Lichen Planus in a Pediatric Patient.

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucosa. Of the various types, the hypertrophic type is characterized by thickened, purplish hyperkeratotic plaques and nodules. The course of hypertrophic LP tends to be more chronic than those of other types. A 12-year-old girl presented with a 2-year history of warty papules and plaques in a zosteriform configuration along one flank. Histopathology revealed hyperkeratosis and papillomatosis with wedge-shaped hypergranulosis. A lichenoid lymphocytic infiltrate with vacuolar change in the basal layer was evident. She was prescribed oral doxycycline, a topical corticosteroid, and tacrolimus. After 7 weeks, the skin lesions became significantly flattened and faded. LP is less common but more severe in children than in adults. The unilateral, linear hypertrophic type of LP is uncommon. Herein, we report a rare case of linear hypertrophic LP in a child.

Current Status of Q Fever and the Challenge of Outbreak Preparedness in Korea: One Health Approach to Zoonoses.

Human Q fever, a zoonosis caused by Coxiella burnetii, presents with diverse clinical manifestations ranging from mild self-limited febrile illnesses to life-threatening complications such as endocarditis or vascular infection. Although acute Q fever is a benign illness with a low mortality rate, a large-scale outbreak of Q fever in the Netherlands led to concerns about the possibility of blood transfusion-related transmission or obstetric complications in pregnant women. Furthermore, a small minority (< 5%) of patients with asymptomatic or symptomatic infection progress to chronic Q fever. Chronic Q fever is fatal in 5-50% of patients if left untreated. In South Korea, Q fever in humans was designated as a notifiable infectious disease in 2006, and the number of Q fever cases has increased sharply since 2015. Nonetheless, it is still considered a neglected and under-recognized infectious disease. In this review, recent trends of human and animal Q fever in South Korea, and public health concerns regarding Q fever outbreaks are reviewed, and we consider how a One Health approach could be applied as a preventive measure to prepare for zoonotic Q fever outbreaks.

Quantitative analysis of tendon histopathology using digital pathology in rat models with Achilles tendon injury.

Although digital image analysis methods that quantify histopathologic features have emerged, no validated quantitative methods are available to evaluate tendon injury. This study aimed to propose and validate a quantitative analysis method to identify the histopathologic features of tendon injuries. The histopathologic features of two Achilles tendon injury models (a partial full-thickness defect model and a collagenase injection model) using Sprague-Dawley rats were evaluated by semiquantitative grading and a quantitative analysis method using a digital pathology software at weeks 1 and 4 after tendon injury (six tendons per group at each time point). The outcome variables between tendon injury models and between time points were compared, and the correlation between semiquantitative scores and the results of the quantitative analysis was investigated. The proposed analysis method quantified the severity of the histopathological features after tendon injury. Quantitative analysis differentiated the cell morphology between tendon injury models and time points better than semiquantitative scoring. The results from quantitative measurements correlated significantly with the semiquantitative scores. The proposed quantitative method can be effective in evaluating the histopathology of tendon injuries.

Clinical evaluation of the fit of lithium disilicate crowns fabricated with three different CAD-CAM systems.

STATEMENT OF PROBLEM: The fit and performance of prostheses fabricated using various computer-aided design and computer-aided manufacturing (CAD-CAM) systems have been evaluated. However, most studies were conducted in vitro, and relatively few have addressed gingival parameters and prosthesis fit under clinical conditions. PURPOSE: This clinical study aimed to compare the fit of lithium disilicate crowns produced using 3 CAD-CAM systems and evaluate clinical results up to 6 months after delivery. MATERIAL AND METHODS: Forty participants requiring a single crown were recruited. Three monolithic lithium disilicate crowns were fabricated per participant by using 3 different CAD-CAM systems (intraoral scanners, CAD software, and milling machines): CEREC group (CEREC Bluecam, CEREC AC, CEREC MC); EZIS group (EZIS PO, EZIS VR, EZIS HM); and TRIOS group (TRIOS 3, EXO-CAD, ARUM-4X). The fit of the prostheses was assessed via a silicone replica technique, and the most acceptable crown was delivered; 12 were selected from the CEREC group, 16 from the EZIS group, and 12 from the TRIOS group. Follow-up clinical examinations were performed at 1, 3, and 6 months after delivery. The Kruskal-Wallis test with the post hoc Mann-Whitney U test was conducted to analyze significant differences in crown fit and periodontal conditions among the groups (α=.05). RESULTS: The marginal gap of the CEREC group was significantly higher than that of the EZIS group, and the occlusal gap of the EZIS group was significantly lower than those of the CEREC and TRIOS groups (P<.05). Probing depth, bleeding index, and plaque index showed no intergroup differences at 6 months (P>.05). CONCLUSIONS: The lithium disilicate crowns of all groups showed clinically acceptable fit. No significant differences were found among the groups in terms of periodontal conditions after 6 months.

Comparison of Quality Characteristics of Commercial Kimchi Manufactured in Korea, China, and the United States.

Recently, kimchi has been recognized as a healthy food worldwide, prompting increased interest in its health benefits and quality characteristics. Although commercial kimchi is manufactured in various countries, little is known about quality differences between the kimchi from different countries. To clarify differences in quality characteristics, minerals, free sugars, organic acids, free amino acids, and volatile compounds, commercial kimchi manufactured in Korea, China, and the United States were investigated. The composition of the microbial community and antioxidant activity were compared. Mineral and free sugar contents were high in Korean commercial kimchi, while the organic acid content was relatively low. The free amino acid content was markedly higher in Korean kimchi than that in kimchi manufactured in China and the United States. In addition, the volatile compound content differed between the kimchi produced in different countries. Considering the microbial communities, Leuconostoc and Weissella were more abundant in commercial kimchi from Korea than that from China or the United States. Commercial kimchi in Korea showed the highest antioxidant activity. These results support the high quality and antioxidant activity of commercial kimchi manufactured in Korea, emphasizing its importance in the global kimchi industry.

Protection of palmitic acid treatment in RAW264.7 cells and BALB/c mice during Brucella abortus 544 infection.

BACKGROUND: We previously elucidated the protective mechanism of Korean red ginseng oil (RGO) against Brucella abortus infection, and our phytochemical analysis revealed that palmitic acid (PA) was an abundant component of RGO. Consequently, we investigated the contribution of PA against B. abortus. OBJECTIVES: We aimed to investigate the efficacy of PA against B. abortus infection using a murine cell line and a murine model. METHODS: Cell viability, bactericidal, internalization, and intracellular replication, western blot, nitric oxide (NO), and superoxide (O2⁻) analyses and flow cytometry were performed to determine the effects of PA on the progression of B. abortus infection in macrophages. Flow cytometry for cytokine analysis of serum samples and bacterial counts from the spleens were performed to determine the effect of PA in a mouse model. RESULTS: PA did not affect the growth of B. abortus. PA treatment in macrophages did not change B. abortus uptake but it did attenuate the intracellular survivability of B. abortus. Incubation of cells with PA resulted in a modest increase in sirtuin 1 (SIRT1) expression. Compared to control cells, reduced nitrite accumulation, augmented O2⁻, and enhanced pro-inflammatory cytokine production were observed in PA-treated B. abortus-infected cells. Mice orally treated with PA displayed a decreased serum interleukin-10 level and enhanced bacterial resistance. CONCLUSIONS: Our results suggest that PA participates in the control of B. abortus within murine macrophages, and the in vivo study results confirm its efficacy against the infection. However, further investigations are encouraged to completely characterize the mechanisms involved in the inhibition of B. abortus infection by fatty acids.

Discovery and Biochemical Characterization of a Methanol Dehydrogenase From Lysinibacillus xylanilyticus.

Bioconversion of C1 chemicals such as methane and methanol into higher carbon-chain chemicals has been widely studied. Methanol oxidation catalyzed by methanol dehydrogenase (Mdh) is one of the key steps in methanol utilization in bacterial methylotrophy. In bacteria, few NAD+-dependent Mdhs have been reported that convert methanol to formaldehyde. In this study, an uncharacterized Mdh gene from Lysinibacillus xylanilyticus (Lxmdh) was cloned and expressed in Escherichia coli. The maximum alcohol oxidation activity of the recombinant enzyme was observed at pH 9.5 and 55°C in the presence of 10 mM Mg2+. To improve oxidation activity, rational approach-based, site-directed mutagenesis of 16 residues in the putative active site and NAD+-binding region was performed. The mutations S101V, T141S, and A164F improved the enzyme's specific activity toward methanol compared to that of the wild-type enzyme. These mutants show a slightly higher turnover rate than that of wild-type, although their K M values were increased compared to that of wild-type. Consequently, according the kinetic results, S101, T141, and A164 positions may related to the catalytic activity in the active site for methanol dehydrogenation. It should be further studied other mutant variants with high activity for methanol. In conclusion, we characterized a new Lxmdh and its variants that may be potentially useful for the development of synthetic methylotrophy in the future.

Automated Cardiovascular Pathology Assessment Using Semantic Segmentation and Ensemble Learning.

Cardiac magnetic resonance imaging provides high spatial resolution, enabling improved extraction of important functional and morphological features for cardiovascular disease staging. Segmentation of ventricular cavities and myocardium in cardiac cine sequencing provides a basis to quantify cardiac measures such as ejection fraction. A method is presented that curtails the expense and observer bias of manual cardiac evaluation by combining semantic segmentation and disease classification into a fully automatic processing pipeline. The initial processing element consists of a robust dilated convolutional neural network architecture for voxel-wise segmentation of the myocardium and ventricular cavities. The resulting comprehensive volumetric feature matrix captures diagnostic clinical procedure data and is utilized by the final processing element to model a cardiac pathology classifier. Our approach evaluated anonymized cardiac images from a training data set of 100 patients (4 pathology groups, 1 healthy group, 20 patients per group) examined at the University Hospital of Dijon. The top average Dice index scores achieved were 0.940, 0.886, and 0.849 for structure segmentation of the left ventricle (LV), myocardium, and right ventricle (RV), respectively. A 5-ary pathology classification accuracy of 90% was recorded on an independent test set using the trained model. Performance results demonstrate the potential for advanced machine learning methods to deliver accurate, efficient, and reproducible cardiac pathological assessment.

Implant-supported fixed dental prosthesis with a microlocking implant prosthetic system: A clinical report.

A microlocking implant prosthetic system has recently been developed to address the limitations of conventional screw- and cement-retained implant-supported fixed dental prostheses. This prosthesis system consists of a precision-machined abutment and an attachment that includes zirconia balls and a nickel-titanium spring, thus providing retrievability and constant retention of the prosthesis. In addition, screw-related complications are avoided because there is no retention screw. The occlusal access hole is of a smaller diameter than that of conventional screw-retained prostheses, which is beneficial for esthetics and occlusion. It also prevents common complications of cement-retained prostheses because residual cement around the prosthesis can be removed extraorally. This article presents a clinical treatment with this new prosthetic system.

Comparison of the Trueness of Lithium Disilicate Crowns Fabricated From All-in-One and Combination CAD/CAM Systems.

PURPOSE: To examine and compare the trueness between a computer-aided design (CAD) file and the final milled prosthesis. MATERIALS AND METHODS: For each included patient (n = 30), two lithium disilicate crowns were produced (n = 60) using two different CAD/computer-assisted manufacture (CAD/CAM) systems (all-in-one type and combination type). To compare the trueness, the scanned internal surfaces of the fabricated prostheses were compared to the design files in CAD using 3D analysis software (Geomagic Control X, 3D Systems). RESULTS: The mean ± standard deviation root mean square value for posterior teeth was 32.2 ± 9.4 in the combination type group and 43.8 ± 11.7 in the all-in-one type group, indicating higher trueness for the combination type (P < .05). CONCLUSION: This study has shown that the final milled prosthesis in combination type CAD/CAM systems had better trueness than the all-in-one system.

Wear Characteristics of Dental Ceramic CAD/CAM Materials Opposing Various Dental Composite Resins.

The aim of this study was to evaluate the wear properties of opposed dental ceramic restorative CAD/CAM materials and several posterior direct restorative composite resins. Three kinds of dental ceramics CAD/CAM materials (monolithic zirconia, lithium disilicate, leucite) and four dental composite resins-that is, MI Gracefil, Gradia Direct P, Estelite Σ Quick, and Filtek Supreme Ultra-were used in this study. For each of the 12 groups (three ceramics × four composite resins), five each of a canine-shaped ceramic specimen and a cuboidal shape opposing composite resin were prepared. All of the specimens were tested in a thermomechanical loading machine (50 N, 100,000 cycles, 5/55 °C). Wear losses of ceramic specimens and composite resin specimens were evaluated using a three-dimensional profiling system and an electronic scale, respectively. Statistical analyses were performed using the Kruskal-Wallis test and Mann-Whitney U test with Bonferroni's correction. Zirconia showed significantly less volumetric loss than lithium disilicate or leucite regardless of composite resin type (p > 0.05/3 = 0.017), and that Estelite Σ Quick showed significantly more weight loss than Filtek Supreme Ultra, MI Gracefil, or Gradia Direct P regardless of ceramic type (p > 0.05/6 = 0.083). Zirconia showed less volumetric loss than lithium disilicate or leucite. Some composite resins opposing ceramics showed considerable weight loss.

Effect of Titanium Implants Coated with Radiation-Crosslinked Collagen on Stability and Osseointegration in Rat Tibia.

This study aimed to evaluate the titanium (Ti) implants coated with collagen type Ⅰ crosslinked using gamma-irrigation or glutaraldehyde (GA). The in vitro surface observations, quantification assay, and cell studies using human mesenchymal stem cells (hMSCs) were conducted. For in vivo experiments, the implants were divided into three groups and inserted into the rat tibias: control group (non-treated Ti implant), GA group (Ti implants coated with GA-crosslinked collagen) and 25 kGy group (Ti implants coated with gamma-radiation-crosslinked collagen at dose of 25 kGy). The animals were sacrificed at 4 weeks after implantation and the tissue sections were obtained. New bone volume (mm³) and bone-to-implant contact (BIC, %) within the region of interest (ROI) was measured. The in vitro results showed the highest osteogenic differentiation and levels of osteogenesis-related gene expressions in the 25 kGy group without cytotoxicity. The new bone volume of GA group was significantly higher than the control (p < 0.05). In the result of the BIC, the 25 kGy group was significantly higher than the control (p < 0.05). However, there was no significant difference between the experimental groups. Within the limitations of this study, Ti implant coated with gamma-radiation-crosslinked collagen has potential utility without side effects from chemical agents.

Successfully removed uterine angioleiomyoma by robot-assisted laparoscopic myomectomy.

Angioleiomyoma is a rare type of leiomyoma variant and there are a few cases reported to date. Herein, we present a case of angioleiomyoma in a 36-year-old woman with lower abdominal pain, initially diagnosed by degenerated uterine leiomyoma. The transvaginal ultrasonogram showed an ovoid-shaped heterogeneously hyperechoic lesion in left cornual site of uterus and pelvic magnetic resonance image showed an about 5.1 cm sized heterogenous T2 intermediate high mass with poor enhancement. The patient underwent a robot-assisted laparoscopic myomectomy, and final histopathologic diagnosis revealed uterine angioleiomyoma. This case is the first case of angioleiomyoma resected by robotic surgery. The patient is on follow up for over 1 year and shows no evidence of recurrence until now.

Efficacy of rhBMP-2 Loaded PCL/ß-TCP/bdECM Scaffold Fabricated by 3D Printing Technology on Bone Regeneration.

This study was undertaken to evaluate the effect of 3D printed polycaprolactone (PCL)/ß-tricalcium phosphate (ß-TCP) scaffold containing bone demineralized and decellularized extracellular matrix (bdECM) and human recombinant bone morphogenetic protein-2 (rhBMP-2) on bone regeneration. Scaffolds were divided into PCL/ß-TCP, PCL/ß-TCP/bdECM, and PCL/ß-TCP/bdECM/BMP groups. In vitro release kinetics of rhBMP-2 were determined with respect to cell proliferation and osteogenic differentiation. These three reconstructive materials were implanted into 8 mm diameter calvarial bone defect in male Sprague-Dawley rats. Animals were sacrificed four weeks after implantation for micro-CT, histologic, and histomorphometric analyses. The findings obtained were used to calculate new bone volumes (mm3) and new bone areas (%). Excellent cell bioactivity was observed in the PCL/ß-TCP/bdECM and PCL/ß-TCP/bdECM/BMP groups, and new bone volume and area were significantly higher in the PCL/ß-TCP/bdECM/BMP group than in the other groups (p < .05). Within the limitations of this study, bdECM printed PCL/ß-TCP scaffolds can reproduce microenvironment for cells and promote adhering and proliferating the cells onto scaffolds. Furthermore, in the rat calvarial defect model, the scaffold which printed rhBMP-2 loaded bdECM stably carries rhBMP-2 and enhances bone regeneration confirming the possibility of bdECM as rhBMP-2 carrier.

Load-Bearing Capacity and Retention of Newly Developed Micro-Locking Implant Prosthetic System: An In Vitro Pilot Study.

The aim of this study was to introduce the newly developed micro-locking implant prosthetic system and to evaluate the resulting its characteristics. To evaluate load-bearing capacity, 25 implants were divided into five groups: external-hexagon connection (EH), internal-octagon connection (IO), internal-hexagon connection (IH), one-body implant (OB), micro-locking implant system (ML). The maximum compressive load was measured using a universal testing machine (UTM) according to the ISO 14801. Retention was evaluated in two experiments: (1) a tensile test of the structure modifications of the components (attachment and implant) and (2) a tensile test after cyclic loading (total 5,000,000 cycles, 100 N, 2 Hz). The load-bearing capacity of the ML group was not significantly different from the other groups (p > 0.05). The number of balls in the attachment and the presence of a hexagonal receptacle did not show a significant correlation with retention (p > 0.05), but the shape of the retentive groove in the implant post had a statistically significant effect on retention (p < 0.05). On the other hand, the retention loss was observed during the initial 1,000,000 cycles, but an overall constant retention was maintained afterward. Various preclinical studies on this novel micro-locking implant prosthetic system should continue so that it can be applied in clinical practice.

Development and Assessment of a 3D-Printed Scaffold with rhBMP-2 for an Implant Surgical Guide Stent and Bone Graft Material: A Pilot Animal Study.

In this study, a new concept of a 3D-printed scaffold was introduced for the accurate placement of an implant and the application of a recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded bone graft. This preliminary study was conducted using two adult beagles to evaluate the 3D-printed polycaprolactone (PCL)/ß-tricalcium phosphate (ß-TCP)/bone decellularized extracellular matrix (bdECM) scaffold conjugated with rhBMP-2 for the simultaneous use as an implant surgical guide stent and bone graft material that promotes new bone growth. Teeth were extracted from the mandible of the beagle model and scanned by computed tomography (CT) to fabricate a customized scaffold that would fit the bone defect. After positioning the implant guide scaffold, the implant was placed and rhBMP-2 was injected into the scaffold of the experimental group. The two beagles were sacrificed after three months. The specimen block was obtained and scanned by micro-CT. Histological analysis showed that the control and experimental groups had similar new bone volume (NBV, %) but the experimental group with BMP exhibited a significantly higher bone-to-implant contact ratio (BIC, %). Within the limitations of this preliminary study, a 3D-printed scaffold conjugated with rhBMP-2 can be used simultaneously as an implant surgical guide and a bone graft in a large bone defect site. Further large-scale studies will be needed to confirm these results.