Publisher Correction: SERPINB1-mediated checkpoint of inflammatory caspase activation.

In the version of this article initially published, the label (CASP4-C285A-HA) above the second and fifth lanes in the right blot in Fig. 1e is incorrect; the correct label is CASP4-C258A-HA. Also, the two labels at right above the plot in Fig. 6c were switched; the far right label should be 'Co-housed Serpinb1a-/-' (in red font) and the label just to its left (above the fourth column) should be 'Co-housed WT' (in black font). Finally, the bottom two symbols in the key to Fig. 7d were switched; the red circle should identify 1CARD-SUMO (TEV) and the blue triangle should identify 1CARD-SUMO + SERPINB1 (TEV). The errors have been corrected in the HTML and PDF versions of the article.

SERPINB1-mediated checkpoint of inflammatory caspase activation.

Inflammatory caspases (caspase-1, caspase-4, caspase-5 and caspase-11 (caspase-1/-4/-5/-11)) mediate host defense against microbial infections, processing pro-inflammatory cytokines and triggering pyroptosis. However, precise checkpoints are required to prevent their unsolicited activation. Here we report that serpin family B member 1 (SERPINB1) limited the activity of those caspases by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation. While the reactive center loop of SERPINB1 inhibits neutrophil serine proteases, its carboxy-terminal CARD-binding motif restrained the activation of pro-caspase-1/-4/-5/-11. Consequently, knockdown or deletion of SERPINB1 prompted spontaneous activation of caspase-1/-4/-5/-11, release of the cytokine IL-1ß and pyroptosis, inducing elevated inflammation after non-hygienic co-housing with pet-store mice and enhanced sensitivity to lipopolysaccharide- or Acinetobacter baumannii-induced endotoxemia. Our results reveal that SERPINB1 acts as a vital gatekeeper of inflammation by restraining neutrophil serine proteases and inflammatory caspases in a genetically and functionally separable manner.

Autophagic UVRAG Promotes UV-Induced Photolesion Repair by Activation of the CRL4(DDB2) E3 Ligase.

UV-induced DNA damage, a major risk factor for skin cancers, is primarily repaired by nucleotide excision repair (NER). UV radiation resistance-associated gene (UVRAG) is a tumor suppressor involved in autophagy. It was initially isolated as a cDNA partially complementing UV sensitivity in xeroderma pigmentosum (XP), but this was not explored further. Here we show that UVRAG plays an integral role in UV-induced DNA damage repair. It localizes to photolesions and associates with DDB1 to promote the assembly and activity of the DDB2-DDB1-Cul4A-Roc1 (CRL4(DDB2)) ubiquitin ligase complex, leading to efficient XPC recruitment and global genomic NER. UVRAG depletion decreased substrate handover to XPC and conferred UV-damage hypersensitivity. We confirmed the importance of UVRAG for UV-damage tolerance using a Drosophila model. Furthermore, increased UV-signature mutations in melanoma correlate with reduced expression of UVRAG. Our results identify UVRAG as a regulator of CRL4(DDB2)-mediated NER and suggest that its expression levels may influence melanoma predisposition.

Preoperative increased pronation angle of the first metatarsus associated with correction loss after hallux valgus surgery: A semi-weight-bearing computed tomography study.

BACKGROUND: The effect of preoperative first metatarsal pronation on postoperative prognosis of hallux valgus (HV) surgery is under investigation. Utilizing semi-weight-bearing computed tomography, the preoperative pronation angle was assessed to quantify its impact on postoperative prognosis. METHODS: In a retrospective analysis of 31 feet, those with re-increased hallux valgus angle postoperatively were classified as the non-maintained group, and the remainder as the maintained group. Preoperative pronation angles were compared to establish a threshold. Subsequently, feet were re-classified into high or low-pronation categories. The relative risk of non-maintenance in high-pronation category was calculated. RESULTS: The non-maintained group exhibited a significantly higher preoperative pronation angle (p = 0.021), with a 28.4º threshold. The high-pronation category had a relative risk of 2.34 for non-maintenance. CONCLUSIONS: Increased preoperative first metatarsal pronation angle is associated with correction loss after HV surgery. Utilizing sWBCT to measure the pronation angle provides valuable insights into postoperative prognosis. LEVEL OF EVIDENCE: III.

SFTSV Gn-Head mRNA vaccine confers efficient protection against lethal viral challenge.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne virus, causing thrombocytopenia and hemorrhagic fever, with a fatality rate ranging from 12% to 30%. SFTSV possesses Gn and Gc glycoproteins, which are responsible for host cell receptor attachment and membrane fusion, respectively, to infect host cells. We have previously reported a protein subunit vaccine candidate (sGn-H-FT) of the SFTSV soluble Gn head region (sGn-H) fused with self-assembling ferritin (FT) nanoparticles, displaying strong protective immunogenicity. In this study, we present messenger RNA (mRNA) vaccine candidates encoding sGn-H or sGn-H-FT, both of which exhibit potent in vivo immunogenicity and protection capacity. Mice immunized with either sGn-H or sGn-H-FT mRNA lipid nanoparticle (LNP) vaccine produced strong total antibodies and neutralizing antibodies (NAbs) against sGn-H. Importantly, NAb titers remained high for an extended period. Finally, mice immunized with sGn-H or sGn-H-FT mRNA LNP vaccine were fully protected from a lethal dose of SFTSV challenge, showing no fatality. These findings underscore the promise of sGn-H and sGn-H-FT as vaccine antigen candidates capable of providing protective immunity against SFTSV infection.

Monocular Depth Estimation Using a Laplacian Image Pyramid with Local Planar Guidance Layers.

It is important to estimate the exact depth from 2D images, and many studies have been conducted for a long period of time to solve depth estimation problems. Recently, as research on estimating depth from monocular camera images based on deep learning is progressing, research for estimating accurate depths using various techniques is being conducted. However, depth estimation from 2D images has been a problem in predicting the boundary between objects. In this paper, we aim to predict sophisticated depths by emphasizing the precise boundaries between objects. We propose a depth estimation network with encoder-decoder structures using the Laplacian pyramid and local planar guidance method. In the process of upsampling the learned features using the encoder, the purpose of this step is to obtain a clearer depth map by guiding a more sophisticated boundary of an object using the Laplacian pyramid and local planar guidance techniques. We train and test our models with KITTI and NYU Depth V2 datasets. The proposed network constructs a DNN using only convolution and uses the ConvNext networks as a backbone. A trained model shows the performance of the absolute relative error (Abs_rel) 0.054 and root mean square error (RMSE) 2.252 based on the KITTI dataset and absolute relative error (Abs_rel) 0.102 and root mean square error 0.355 based on the NYU Depth V2 dataset. On the state-of-the-art monocular depth estimation, our network performance shows the fifth-best performance based on the KITTI Eigen split and the eighth-best performance based on the NYU Depth V2.

Apoptosis Occurs in the Anterior Talofibular Ligament of Patients With Chronic Lateral Ankle Instability: An In Vitro Study.

BACKGROUND: Chronic lateral ankle instability is treated operatively, whereas most acute ankle sprains associated with acute anterior talofibular ligament injury are usually treated nonoperatively. This treatment strategy is widely accepted and has been validated using a variety of clinical or radiological methods. We suspected that there may be biological differences between chronic and acutely injured ligaments, particularly with respect to apoptosis. Apoptosis is known to cause ligament degeneration. If it could be demonstrated that apoptosis occurs more in the anterior talofibular ligament tissues of patients with chronic lateral ankle instability compared with patients with acute anterior talofibular ligament injury, biological evidence could be supported. QUESTIONS/PURPOSES: We sought to (1) elucidate the difference in the extent of apoptosis between patients with chronic lateral ankle instability and those with acute anterior talofibular ligament injury. In addition, we asked: (2) What is the expression level of apoptotic enzymes such as caspases 3, 7, 8, and 9 and cytochrome c in each patient group? (3) Is there a correlation between apoptotic activities and the symptom duration period of chronic lateral ankle instability? METHODS: Between March 2019 and February 2021, 50 patients were prospectively enrolled in this study. Anterior talofibular ligament tissues were harvested from patients who were divided into two groups: the chronic lateral ankle instability group and the acute anterior talofibular ligament injury group. Patients with insufficient remaining ligaments were excluded from the chronic lateral ankle instability group, and cases in which the tissue was severely damaged or the quality of collected tissue was insufficient because of severe impingement into the fracture site were excluded from the acute anterior talofibular ligament injury group. Tissues were collected from 21 patients (11 males and 10 females) in the chronic lateral ankle instability group with a mean age of 37 ± 14 years and from 17 patients (6 males and 11 females) in the acute anterior talofibular ligament injury group with a mean age of 49 ± 17 years. To investigate our first purpose, apoptotic cells were counted using a TUNEL assay. To answer our second question, Western blotting for apoptotic enzymes such as caspases 3, 7, 8, and 9 and cytochrome c was performed to investigate apoptotic activity. Immunohistochemistry was also used to detect apoptotic enzymes. To answer our third question, the time elapsed after the first symptom related to chronic lateral ankle instability occurred and the expression level of each enzyme was investigated. RESULTS: More apoptotic cells were observed in the chronic lateral ankle instability group than in the acute anterior talofibular ligament injury group in the TUNEL assay. Western blotting revealed that the apoptotic activities of the chronic lateral ankle instability group were higher than those of the acute anterior talofibular ligament injury group: caspase 3 was 117 in the chronic lateral ankle instability group and 59 in the acute anterior talofibular ligament injury group (mean difference 58 [95% confidence interval (CI) 31 to 86]; p < 0.001), caspase 7 was 138 in the chronic lateral ankle instability group and 45 in the acute anterior talofibular ligament injury group (mean difference 93 [95% CI 58 to 128]; p < 0.001), caspase 8 was 126 in the chronic lateral ankle instability group and 68 in the acute anterior talofibular ligament injury group (mean difference 58 [95% CI 29 to 89]; p < 0.001), caspase 9 was 128 in the chronic lateral ankle instability group and 54 in the acute anterior talofibular ligament injury group (mean difference 74 [95% CI 44 to 104]; p < 0.001), and cytochrome c was 139 in the chronic lateral ankle instability group and 51 in the acute anterior talofibular ligament injury group (mean difference 88 [95% CI 46 to 129]; p < 0.001). Immunohistochemistry revealed higher expression of caspases 3, 7, 8, and 9 and cytochrome c in the chronic lateral ankle instability group compared with those in the acute anterior talofibular ligament injury group. Caspases 3, 7, and 9 showed no correlation with duration of chronic lateral ankle instability symptoms: the Pearson correlation coefficient was 0.22 [95% CI -0.25 to 0.69] for caspase 3 (p = 0.36), 0.29 [95% CI -0.16 to 0.74] for caspase 7 (p = 0.23), and 0.29 [95% CI -0.16 to 0.74] for caspase 9 (p = 0.23). CONCLUSION: In chronic lateral ankle instability, apoptotic activity in the anterior talofibular ligament was higher than in acute anterior talofibular ligament injury. CLINICAL RELEVANCE: Apoptosis occurs more in chronic injured ligaments than in acutely injured ligaments. Although urgent surgical repair is not required for acute anterior talofibular ligament injury, chronic lateral ankle instability may progress if the nonoperative treatment is not successful. Further research should focus not only on timing of apoptotic progression, but also on biological augmentation to reverse or prevent apoptosis within the anterior talofibular ligament.

Cross-genotype protection of live-attenuated vaccine candidate for severe fever with thrombocytopenia syndrome virus in a ferret model.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus classified within the Banyangvirus genus. SFTS disease has been reported throughout East Asia since 2009 and is characterized by high fever, thrombocytopenia, and leukopenia and has a 12 to 30% case fatality rate. Due to the recent emergence of SFTSV, there has been little time to conduct research into preventative measures aimed at combatting the virus. SFTSV is listed as one of the World Health Organization's Prioritized Pathogens for research into antiviral therapeutics and vaccine development. Here, we report 2 attenuated recombinant SFTS viruses that induce a humoral immune response in immunized ferrets and confer complete cross-genotype protection to lethal challenge. Animals infected with rHB29NSsP102A or rHB2912aaNSs (both genotype D) had a reduced viral load in both serum and tissues and presented without high fever, thrombocytopenia, or mortality associated with infection. rHB29NSsP102A- or rHB2912aaNSs-immunized animals developed a robust anti-SFTSV immune response against cross-genotype isolates of SFTSV. This immune response was capable of neutralizing live virus in a focus-reduction neutralization test (FRNT) and was 100% protective against a cross-genotype lethal challenge with the CB1/2014 strain of SFTSV (genotype B). Thus, using our midsized, aged ferret infection model, we demonstrate 2 live attenuated vaccine candidates against the emerging pathogen SFTSV.

Severe Fever with Thrombocytopenia Syndrome Virus NSs Interacts with TRIM21 To Activate the p62-Keap1-Nrf2 Pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) dissociates from its inhibitor, Keap1, upon stress signals and subsequently induces an antioxidant response that critically controls the viral life cycle and pathogenesis. Besides intracellular Fc receptor function, tripartite motif 21 (TRIM21) E3 ligase plays an essential role in the p62-Keap1-Nrf2 axis pathway for redox homeostasis. Specifically, TRIM21-mediated p62 ubiquitination abrogates p62 oligomerization and sequestration activity and negatively regulates the Keap1-Nrf2-mediated antioxidant response. A number of viruses target the Nrf2-mediated antioxidant response to generate an optimal environment for their life cycle. Here we report that a nonstructural protein (NSs) of severe fever with thrombocytopenia syndrome virus (SFTSV) interacts with and inhibits TRIM21 to activate the Nrf2 antioxidant signal pathway. Mass spectrometry identified TRIM21 to be a binding protein for NSs. NSs bound to the carboxyl-terminal SPRY subdomain of TRIM21, enhancing p62 stability and oligomerization. This facilitated p62-mediated Keap1 sequestration and ultimately increased Nrf2-mediated transcriptional activation of antioxidant genes, including those for heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and CD36. Mutational analysis found that the NSs-A46 mutant, which no longer interacted with TRIM21, was unable to increase Nrf2-mediated transcriptional activation. Functionally, the NS wild type (WT), but not the NSs-A46 mutant, increased the surface expression of the CD36 scavenger receptor, resulting in an increase in phagocytosis and lipid uptake. A combination of reverse genetics and assays with Ifnar-/- mouse models revealed that while the SFTSV-A46 mutant replicated similarly to wild-type SFTSV (SFTSV-WT), it showed weaker pathogenic activity than SFTSV-WT. These data suggest that the activation of the p62-Keap1-Nrf2 antioxidant response induced by the NSs-TRIM21 interaction contributes to the development of an optimal environment for the SFTSV life cycle and efficient pathogenesis.IMPORTANCE Tick-borne diseases have become a growing threat to public health. SFTSV, listed by the World Health Organization as a prioritized pathogen, is an emerging phlebovirus, and fatality rates among those infected with this virus are high. Infected Haemaphysalis longicornis ticks are the major source of human SFTSV infection. In particular, the recent spread of this tick to over 12 states in the United States has increased the potential for outbreaks of this disease beyond Far East Asia. Due to the lack of therapies and vaccines against SFTSV infection, there is a pressing need to understand SFTSV pathogenesis. As the Nrf2-mediated antioxidant response affects viral life cycles, a number of viruses deregulate Nrf2 pathways. Here we demonstrate that the SFTSV NSs inhibits the TRIM21 function to upregulate the p62-Keap1-Nrf2 antioxidant pathway for efficient viral pathogenesis. This study not only demonstrates the critical role of SFTSV NSs in viral pathogenesis but also suggests potential future therapeutic approaches to treat SFTSV-infected patients.

Arthroscopic repair of large to massive rotator cuff tears in patients younger than 60 years.

BACKGROUND: The incidence of rotator cuff tears in young patients has increased recently with the increase in sports and recreation activities, however, few studies have reported clinical outcomes after arthroscopic repair of large to massive rotator cuff tears in young patients. This study aimed to evaluate preoperative characteristics and postoperative outcomes after arthroscopic repair of large to massive rotator cuff tears in patients younger than 60 years, and to compare these results with those of tear size-matched patients older than 60 years. METHODS: Forty-eight patients who underwent arthroscopic repair for large to massive rotator cuff tears were included. Group I (n = 24) consisted of patients younger than 60 years, while tear size-matched patients older than 60 years were assigned to group II (n = 24). Clinical outcomes were evaluated preoperatively and at 3, 6, and 12 months postoperatively, and at the final visit. All patients underwent magnetic resonance imaging (MRI) preoperatively and at 3 and 12 months postoperatively to evaluate repair integrity. RESULTS: The mean patient age was 53.4 ± 4.2 years in group I and 67.4 ± 4.5 in group II (P = 0.001). At the last visit, there were no significant differences in postoperative clinical scores or passive range of motion between two groups. However, young patients complained of shoulder pain less frequently than elderly patients (visual analog scale for pain at last visit: 0.8 ± 0.3 in group I, 2.4 ± 1.9 in group II, P = 0.04). Elderly patients showed more advanced fatty infiltration preoperatively than young patients and advanced fatty infiltration was correlated with postoperative repair integrity (r = 0.83, P = 0.001). Postoperative re-tear rate was 12.5% in group I, and 33.3% in group II (P = 0.08). CONCLUSION: More satisfactory clinical and structural outcomes followed by less advanced preoperative fatty infiltration can be expected in younger patients compared with patients older than 60 years, based on large to massive rotator cuff tear treatment outcomes.

Plasmid-encoded MCP is involved in virulence, motility, and biofilm formation of Cronobacter sakazakii ATCC 29544.

The aim of this study was to elucidate the function of the plasmid-borne mcp (methyl-accepting chemotaxis protein) gene, which plays pleiotropic roles in Cronobacter sakazakii ATCC 29544. By searching for virulence factors using a random transposon insertion mutant library, we identified and sequenced a new plasmid, pCSA2, in C. sakazakii ATCC 29544. An in silico analysis of pCSA2 revealed that it included six putative open reading frames, and one of them was mcp. The mcp mutant was defective for invasion into and adhesion to epithelial cells, and the virulence of the mcp mutant was attenuated in rat pups. In addition, we demonstrated that putative MCP regulates the motility of C. sakazakii, and the expression of the flagellar genes was enhanced in the absence of a functional mcp gene. Furthermore, a lack of the mcp gene also impaired the ability of C. sakazakii to form a biofilm. Our results demonstrate a regulatory role for MCP in diverse biological processes, including the virulence of C. sakazakii ATCC 29544. To the best of our knowledge, this study is the first to elucidate a potential function of a plasmid-encoded MCP homolog in the C. sakazakii sequence type 8 (ST8) lineage.

Putative Inv is essential for basolateral invasion of Caco-2 cells and acts synergistically with OmpA to affect in vitro and in vivo virulence of Cronobacter sakazakii ATCC 29544.

Cronobacter sakazakii is an opportunistic pathogen that causes neonatal meningitis and necrotizing enterocolitis. Its interaction with intestinal epithelium is important in the pathogenesis of enteric infections. In this study, we investigated the involvement of the inv gene in the virulence of C. sakazakii ATCC 29544 in vitro and in vivo. Sequence analysis of C. sakazakii ATCC 29544 inv revealed that it is different from other C. sakazakii isolates. In various cell culture models, an Δinv deletion mutant showed significantly lowered invasion efficiency, which was restored upon genetic complementation. Studying invasion potentials using tight-junction-disrupted Caco-2 cells suggested that the inv gene product mediates basolateral invasion of C. sakazakii ATCC 29544. In addition, comparison of invasion potentials of double mutant (ΔompA Δinv) and single mutants (ΔompA and Δinv) provided evidence for an additive effect of the two putative outer membrane proteins. Finally, the importance of inv and the additive effect of putative Inv and OmpA were also proven in an in vivo rat pup model. This report is the first to demonstrate two proteins working synergistically in vitro, as well as in vivo in C. sakazakii pathogenesis.

Complete genome sequence of Cronobacter sakazakii temperate bacteriophage phiES15.

While most phage genome studies have been focused on the virulent phages, the inducible temperate bacteriophage genome study provides more detailed information about the interaction between the host strain and the phage. To study this interaction in detail, UV-induced phiES15 bacteriophage was isolated from the host strain Cronobacter sakazakii ES15 and its genome was completely sequenced. Here we announce the genome sequence of phiES15 and report major findings from the annotation.

Identification and characterization of a novel flagellum-dependent Salmonella-infecting bacteriophage, iEPS5.

A novel flagellatropic phage of Salmonella enterica serovar Typhimurium, called iEPS5, was isolated and characterized. iEPS5 has an icosahedral head and a long noncontractile tail with a tail fiber. Genome sequencing revealed a double-stranded DNA of 59,254 bp having 73 open reading frames (ORFs). To identify the receptor for iEPS5, Tn5 transposon insertion mutants of S. Typhimurium SL1344 that were resistant to the phage were isolated. All of the phage-resistant mutants were found to have mutations in genes involved in flagellar formation, suggesting that the flagellum is the adsorption target of this phage. Analysis of phage infection using the ΔmotA mutant, which is flagellated but nonmotile, demonstrated the requirement of flagellar rotation for iEPS5 infection. Further analysis of phage infection using the ΔcheY mutant revealed that iEPS5 could infect host bacteria only when the flagellum is rotating counterclockwise (CCW). These results suggested that the CCW-rotating flagellar filament is essential for phage adsorption and required for successful infection by iEPS5. In contrast to the well-studied flagellatropic phage Chi, iEPS5 cannot infect the ΔfliK mutant that makes a polyhook without a flagellar filament, suggesting that these two flagellatropic phages utilize different infection mechanisms. Here, we present evidence that iEPS5 injects its DNA into the flagellar filament for infection by assessing DNA transfer from SYBR gold-labeled iEPS5 to the host bacteria.

Complete genome sequence analysis of bacterial-flagellum-targeting bacteriophage chi.

Bacteriophage chi is a well-known phage that infects pathogens such as E. coli, Salmonella, and Serratia via bacterial flagella. To further understand its host-phage interaction and infection mechanism via host flagella, the genome was completely sequenced and analyzed. The phage genome contains 59,407-bp-length DNA with a GC content of 56.51 %, containing 75 open reading frames (ORFs) with no tRNA genes. Its annotation and functional analysis revealed that chi is evolutionarily very closely related to Enterobacter phage Enc34 and Providencia phage Redjac. However, most of the annotated genes encode hypothetical proteins, indicating that further genomic study of phage chi is required to elucidate the bacterial-flagellum-targeting infection mechanism of phage chi.

Anterior operation for unstable thoracolumbar and lumbar burst fractures: tricortical autogenous iliac bone versus titanium mesh cage.

STUDY DESIGN: We retrospectively compared 25 cases that used the autogenous iliac bone grafting with 18 cases that used a titanium mesh cage for reconstruction of the vertebral body. OBJECTIVE: To analyze clinical and radiographic results of the autogenous iliac bone and a titanium mesh cage used to reconstruct the vertebral body. SUMMARY OF BACKGROUND DATA: Grafting of the autogenous iliac bone as a strut bone has been traditionally applied for reconstruction of the spine using anterior approach. Although grafting the autogenous iliac bone as a strut bone achieves a high bone fusion rate, it has reported complications in the donor site. For this reason, bone fusion with a mesh cage has been introduced. METHODS: Between March 2000 and December 2010, 43 cases that underwent decompression and instrumented fusion for unstable burst fractures using the anterior approach were enrolled. Levels of injury were T12 in 8 cases, L1 in 19 cases, L2 in 11 cases, and L3 in 5 cases. The mean follow-up period was 64.5 months (range, 14-129 mo). RESULTS: The local kyphotic angle in the group that used the tricortical autogenous iliac bone (group A) was measured 24.81±2.27 degrees preoperatively and 4.95±0.61 degrees at the last follow-up. The angle in the group that used a titanium mesh cage (group B) was 25.21±1.55 degrees preoperatively and 3.9±0.43 degrees at the last follow-up. Both groups obtained bone fusion of grade I and II by Bridwell fusion criteria. The operation site visual analog scale and Korean Oswestry disability index did not differ significantly between 2 groups. Donor site visual analog scale and the operation time was significantly in favor of group B (P<0.05). CONCLUSIONS: Titanium mesh cage filled with the autogenous cancellous bone shortened operation time and reduced the risk of complications in the donor site compared with the group that used the tricortical iliac bone.

Simple curettage and allogeneic cancellous bone chip impaction grafting in solitary enchondroma of the short tubular bones of the hand.

Enchondroma is the most common bone tumor in the hand. While standard surgical procedure is intra-lesional excision and bone grafting, there is a dispute between allogeneic bone, autogenous bone, and synthetic bone substitute grafting. Diverse adjuvant treatments have been introduced to reduce recurrence, but results are mixed with controversies. Meanwhile, whether existing descriptive classification could predict treatment outcome remains unclear. Thus, we reviewed patients with solitary enchondroma of the hand who underwent simple curettage followed by allogeneic cancellous bone chip impaction grafting. Eighty-eight patients with more than 5 years of follow-up were enrolled. Demographic data, local recurrence, and complications were reviewed. Duration of consolidation and the difference according to Takigawa classification were assessed. Range of motion (ROM), and functional scores were also evaluated. There were 51 women and 37 men, with a mean age of 37.9 years. Mean follow-up was 10.2 years. Recurrence occurred only in one patient. There was no complication. Mean postoperative total active motions of fingers and thumb were 239° and 132.9°. Mean modified Disabilities of the Arm, Shoulder, Hand score, and Musculoskeletal Tumor Society Score were 1.63, and 99.2 at the last follow-up. Consolidation, ROM, and functional scores according to Takigawa classification showed no significant differences. This study suggests that simple curettage with impaction grafting of allogeneic cancellous bone chip is a feasible method for treating solitary enchondromas involving short tubular bone of the hand with good long-term outcomes. Postoperative recurrence and complication rates were very low. Radiographic and clinical results were good regardless of the previous radiological classification.

Association of general and central obesity, and their changes with risk of knee osteoarthritis: a nationwide population-based cohort study.

In this study, we aimed to evaluate the association between general and central obesity, and their changes with risk of knee osteoarthritis (OA) using retrospective cohort data collected from the Korean National Health Insurance Service. We studied 1,139,463 people aged 50 and over who received a health examination in 2009. To evaluate the association between general and/or central obesity and knee OA risk, a Cox proportional hazard models were used. Additionally, we investigate knee OA risk according to the change in obesity status over 2 years for subjects who had undergone health examinations for 2 consecutive years. General obesity without central obesity (HR 1.281, 95% CI 1.270-1.292) and central obesity without general obesity (HR 1.167, 95% CI 1.150-1.184) were associated with increased knee OA risk than the comparison group. Individuals with both general with central obesity had the highest risk (HR 1.418, 95% CI 1.406-1.429). This association was more pronounced in women and younger age group. Remarkably, the remission of general or central obesity over two years was associated with decreased knee OA risk (HR 0.884; 95% CI 0.867-0.902; HR 0.900; 95% CI 0.884-0.916, respectively). The present study found that both general and central obesity were associated with increased risk of knee OA and the risk was highest when the two types of obesity were accompanied. Changes in obesity status have been confirmed to alter the risk of knee OA.

Association between knee osteoarthritis and the risk of cardiovascular disease and the synergistic adverse effects of lack of exercise.

We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15-1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00-1.44), and stroke (HR 1.29, 95% CI 1.16-1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11-1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96-1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.

Self-assembling Gn head ferritin nanoparticle vaccine provides full protection from lethal challenge of Dabie Bandavirus in aged ferrets.

Dabie Bandavirus (DBV), previously known as Severe Fever with Thrombocytopenia Syndrome (SFTS) Virus, induces a characteristic thrombocytopenia with a mortality rate ranging from 12% to as high as 30%. The sero-prevalence of DBV in healthy people is not significantly different among age groups, but clinically diagnosed SFTS patients are older than ~50 years, suggesting that age is the critical risk factor for SFTS morbidity and mortality. Accordingly, our immune-competent ferret model demonstrates an age (>4 years old)-dependent DBV infection and pathogenesis that fully recapitulates human clinical manifestation. To protect the aged population from DBV-induced SFTS, vaccine should carry robust immunogenicity with high safety profile. Previous studies have shown that glycoproteins Gn/Gc are the most effective antigens for inducing both neutralizing antibody (NAb)- and T cell-mediated immunity and, thereby, protection. Here, we report the development of a protein subunit vaccine with 24-mer self-assembling ferritin (FT) nanoparticle to present DBV Gn head region (GnH) for enhanced immunogenicity. Anion exchange chromatography and size exclusion chromatography readily purified the GnH-FT nanoparticles to homogeneity with structural integrity. Mice immunized with GnH-FT nanoparticles induced robust NAb response and T-cell immunity against DBV Gn. Furthermore, aged ferrets immunized with GnH-FT nanoparticles were fully protected from DBV challenge without SFTS symptoms such as body weight loss, thrombocytopenia, leukopenia, and fatality. This study demonstrates that DBV GnH-FT nanoparticles provide an efficient vaccine efficacy in mouse and aged ferret models and should be an outstanding vaccine candidate targeted for the aged population against fatal DBV infection.