Intranasal inoculation of an MVA-based vaccine induces IgA and protects the respiratory tract of hACE2 mice from SARS-CoV-2 infection.

Current vaccines have greatly diminished the severity of the COVID-19 pandemic, even though they do not entirely prevent infection and transmission, likely due to insufficient immunity in the upper respiratory tract. Here, we compare intramuscular and intranasal administration of a live, replication-deficient modified vaccinia virus Ankara (MVA)-based Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike (S) vaccine to raise protective immune responses in the K18-hACE2 mouse model. Using a recombinant MVA expressing firefly luciferase for tracking, live imaging revealed luminescence of the respiratory tract of mice within 6 h and persisting for 3 d following intranasal inoculation, whereas luminescence remained at the site of intramuscular vaccination. Intramuscular vaccination induced S-binding-Immunoglobulin G (IgG) and neutralizing antibodies in the lungs, whereas intranasal vaccination also induced Immunoglobulin A (IgA) and higher levels of antigen-specific CD3+CD8+IFN-γ+ T cells. Similarly, IgG and neutralizing antibodies were present in the blood of mice immunized intranasally and intramuscularly, but IgA was detected only after intranasal inoculation. Intranasal boosting increased IgA after intranasal or intramuscular priming. While intramuscular vaccination prevented morbidity and cleared SARS-CoV-2 from the respiratory tract within several days after challenge, intranasal vaccination was more effective as neither infectious virus nor viral messenger (m)RNAs were detected in the nasal turbinates or lungs as early as 2 d after challenge, indicating prevention or rapid elimination of SARS-CoV-2 infection. Additionally, we determined that neutralizing antibody persisted for more than 6 mo and that serum induced to the Wuhan S protein neutralized pseudoviruses expressing the S proteins of variants, although with less potency, particularly for Beta and Omicron.

Enhanced recovery after surgery in patients after hip and knee arthroplasty: a systematic review and meta-analysis.

PURPOSE: Enhanced recovery after surgery (ERAS) was characterized as patient-centered, evidence-based, multidisciplinary team-developed routes for a surgical speciality and institution to improve postoperative recovery and attenuate the surgical stress response. However, evidence of their effectiveness in osteoarthroplasty remains sparse. This study aimed to develop an ERAS standard and evaluate the significance of ERAS interventions for postoperative outcomes after primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). METHODS: We searched Medline, Embase, Cochrane databases, and Clinicaltrials.gov for randomized controlled trials, cohort studies, and case-control studies until 24 February 2023. All relevant data were collected from studies meeting the inclusion criteria. Two reviewers independently assessed the risk of bias and extracted data. The primary outcome was the length of stay (LOS), postoperative complications, and readmission rate. The secondary outcomes included transfusion rate, mortality rate, visual analog score (VAS), the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), Short Form 36 (SF-36) bodily pain (SF-36 BP), SF-36 physical function (SF-36 PF), oxford knee score, and range of motion (ROM). RESULTS: A total of 47 studies involving 76 971 patients (ERAS group: 29 702, control group: 47 269) met the inclusion criteria and were included in the meta-analysis. The result showed that ERAS could significantly shorten the LOS (WMD = -2.65, P < .001), reduce transfusion rate (OR = 0.40, P < .001), and lower 30-day postoperative mortality (OR = 0.46, P = .01) without increasing postoperative complications or readmission rate. Apart from that, ERAS may decrease patients' VAS (WMD = -0.88, P = .01) while improving their ROM (WMD = 6.65, P = .004), SF-36 BP (WMD = 4.49, P < .001), and SF-36 PF (WMD = 3.64, P < .001) scores. However, there was no significant difference in WOMAC, oxford knee score between the ERAS and control groups.Furthermore, we determined that the following seven components of the ERAS program are highly advised: avoid bowel preparation, PONV prophylaxis, standardized anesthesia, use of local anesthetics for infiltration analgesia and nerve blocks, tranexamic acid, prevent hypothermia, and early mobilization. CONCLUSION: Our meta-analysis suggested that the ERAS could significantly shorten the LOS, reduce transfusion rate, and lower 30-day postoperative mortality without increasing postoperative complications or readmission rate after THA and TKA. Meanwhile, ERAS could decrease the VAS of patients while improving their ROM, SF-36 BP, and SF-36 PF scores. Finally, we expect future studies to utilize the seven ERAS elements proposed in our meta-analysis to prevent increased readmission rate for patients with THA or TKA.

One or two injections of MVA-vectored vaccine shields hACE2 transgenic mice from SARS-CoV-2 upper and lower respiratory tract infection.

Modified vaccinia virus Ankara (MVA) is a replication-restricted smallpox vaccine, and numerous clinical studies of recombinant MVAs (rMVAs) as vectors for prevention of other infectious diseases, including COVID-19, are in progress. Here, we characterize rMVAs expressing the S protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Modifications of full-length S individually or in combination included two proline substitutions, mutations of the furin recognition site, and deletion of the endoplasmic retrieval signal. Another rMVA in which the receptor binding domain (RBD) is flanked by the signal peptide and transmembrane domains of S was also constructed. Each modified S protein was displayed on the surface of rMVA-infected cells and was recognized by anti-RBD antibody and soluble hACE2 receptor. Intramuscular injection of mice with the rMVAs induced antibodies, which neutralized a pseudovirus in vitro and, upon passive transfer, protected hACE2 transgenic mice from lethal infection with SARS-CoV-2, as well as S-specific CD3+CD8+IFNγ+ T cells. Antibody boosting occurred following a second rMVA or adjuvanted purified RBD protein. Immunity conferred by a single vaccination of hACE2 mice prevented morbidity and weight loss upon intranasal infection with SARS-CoV-2 3 wk or 7 wk later. One or two rMVA vaccinations also prevented detection of infectious SARS-CoV-2 and subgenomic viral mRNAs in the lungs and greatly reduced induction of cytokine and chemokine mRNAs. A low amount of virus was found in the nasal turbinates of only one of eight rMVA-vaccinated mice on day 2 and none later. Detection of low levels of subgenomic mRNAs in turbinates indicated that replication was aborted in immunized animals.

Legg-Calvé-Perthes Disease: Diagnosis, Decision Making, and Outcome.

ABSTRACT: Legg-Calvé-Perthes disease (LCPD), or idiopathic avascular necrosis of the proximal capital femoral epiphysis in children, has a variable presentation and can result in significant femoral head deformity that can lead to long-term functional deficits. Plain radiographic imaging is crucial in diagnosing LCPD and guiding treatment. Although the etiology of LCPD remains unknown, the evolution of the disease has been well characterized to include the phases of ischemia, revascularization, and reossification. The mechanical weakening during these phases of healing place the femoral head at high risk of deformity. Treatment of LCPD, therefore, focuses on minimizing deformity through operative and nonoperative strategies to reduce the risk of premature osteoarthritis. Advanced imaging using perfusion MRI may refine surgical decision making in the future, and biological treatments to improve femoral head healing are on the horizon.

A Combination of Ilizarov Frame, Externalized Locking Plate and Tibia Bridging for an Adult with Large Tibial Defect and Severe Varus Deformity Due to Chronic Osteomyelitis in Childhood: A Case Report.

Background: Various techniques have been reported to treat large, segmental tibial defects, such as autogenous bone graft, vascularized free fibula transfer and bone transport. We present a case of a 24-year-old male with a 17-year history of chronic osteomyelitis with obvious lower limb length discrepancy and severe varus deformity of the tibia secondary to osteomyelitis in childhood. Aim: The aim of this work is to provide an alternative choice for treating patients in developing countries with severe lower limb deformity caused by chronic osteomyelitis. Case Presentations: Without surgical intervention for a prolonged period of time, the patient was admitted in our institute for corrective surgery. Corrective surgery consisted of three stages: lengthening with Ilizarov frame, removal of Ilizarov frame and fixation with externalized locking plate, and removal of externalized locking plate. Tibia bridging was achieved at the distal and proximal junction. The range of motion (ROM) of the knee joint was nearly normal, but the stiffness of the ankle joint was noticeable. The remaining leg discrepancy of 0.1 cm required no application of a shoe lift. Moreover, the patient could engage in daily activities without noted limping. Conclusions: Distraction-compression osteogenesis using the Ilizarov apparatus is a powerful tool to lengthen the shortened long bone and adjust the deformity of the lower limbs. Externalized locking plates provide an alternative to the traditional bulky external fixator, as its low profile makes it more acceptable to patients without compromising axial and torsional stiffness. In all, a combination of Ilizarov frame, externalized locking plate and tibia bridging is an alternative for patients in similar conditions.

Epidemiological Investigation of Pediatric Fractures-A Retrospective Cohort Study of 1129 Patients.

Background and Objectives: Fractures are common in pediatric trauma, and they are caused by a broad spectrum of factors. Only a few studies have discussed the mechanisms of injury and their relationships to different types of fractures. The most frequent type of fractures in different age groups remains unclear. Therefore, we aim to summarize the epidemiological characteristics of pediatric fractures in a medical center in Zhuhai, China from 2006 to 2021 and analyze the causes of fractures with the highest frequency in different age groups. Materials and Methods: We extracted the information from the Zhuhai Center for Maternal and Child Health Care of those under 14 years old who had fractures from 2006 to 2021. Results: We reviewed the information of 1145 children. The number of patients increased during the 15 years (p < 0.0001). The number of patients was significantly different between genders after Y2 (p = 0.014). In addition, more than two-thirds of patients (71.3%) had upper limb fractures, and all types of falls were the most common cause of fractures (83.6%). The incidence demonstrated an insignificant difference in age groups except for the fractures of humerus and radius. Moreover, we discovered that the prevalence of fall-related injuries decreased with age, while that of sports-related injuries increased with age. Conclusions: Our study demonstrates that the prevalence of fall-related injuries decreases with age, and that of sports-related injuries increases with age. Most patients have upper limb fractures, and all types of falls are the most common cause of fractures. Fracture types with the highest frequency differ in each age group. These findings might supplement current epidemiological knowledge of childhood fracture and provide references for decision-making in children's health policies.

SalterHarris fractures in paediatric skiers and snowboarders.

The incidence of paediatric fractures among winter sport athletes is not adequately studied. Our objective was to categorize fractures that occurred in paediatric skiers and snowboarders at a single ski resort. X-rays of 756 skiers/snowboarders aged 3-17 diagnosed with a fracture were categorized using the Salter-Harris (SH) classification. SH fractures were seen in 158 (21%) patients, with 123 (77%) being Type II. There were no significant differences between patients with a SH fracture and patients with a non-SH fracture for age, sex, snowboarding or skiing, mechanism of injury, terrain or the resort conditions on the day of injury. The most common mechanism of injury was falling onto snow while collisions resulted in more severe injuries. Compared to fractures without growth plate involvement, a higher proportion of SH fractures were seen in the humerus, radius, fibula and thumb; a lower proportion of SH fractures were observed at the tibia and clavicle.

Glenohumeral joint dislocation is rare in children with proximal humeral fractures: a descriptive study and literature review.

BACKGROUND: Glenohumeral dislocation combined with fracture of the proximal humerus is extremely rare in children, and this study aims to investigate its incidence in the pediatric population and review the treatment strategy for this condition. METHODS: Between Jan 2014 and Jan 2019, 280 patients with unilateral proximal humeral fractures were retrospectively reviewed. Imaging and follow-up notes were reviewed for patients with a predilection for glenohumeral joint dislocation. Six (2.14%) patients between the ages of 5 and 10 years were confirmed as glenohumeral joint dislocation and included in the study. All these patients underwent closed reduction and external fixation under general anesthesia. RESULTS: Out of 280 patients with proximal humeral fractures, only 6 patients, including 4 males and 2 females, were confirmed as glenohumeral joint dislocation. ROM was normal compared with the contralateral shoulder in every patient at the last follow-up. There was no case of radiological abnormality, including avascular necrosis or devascularization of the humeral head. CONCLUSIONS: Glenohumeral dislocation is a rare entity associated with the proximal humerus fracture in children, with an overall incidence in our case series was 2.14%. Reduction and stabilization of such injury using an external fixator is a suitable choice for pediatric patients that failed closed reduction.

Plating versus elastic stable intramedullary nailing for displaced pediatric midshaft clavicular fractures.

INTRODUCTION: Traditionally, operative treatment for displaced midshaft clavicle fractures in adolescents has been achieved by using a plate and screws. However, a minimally invasive trend has led surgeons to use the elastic stable intramedullary nail (ESIN) for displaced midshaft clavicle fractures. This study aims to compare the clinical outcomes of adolescent patients who were operated on with an ESIN vs. a plate. METHODS: All patients aged between 10 and 14 years with displaced midshaft clavicle fractures who were operated on at our institute between January 2014 and January 2018 were reviewed retrospectively. The preoperative data, including baseline information on the patients, and types of surgical procedure were collected from the hospital database. The postoperative data, including clinical outcome and complications, were collected during the follow-up visits. Clinical outcome was evaluated during outpatient visits using the American Shoulder and Elbow Surgeons (ASES) score. The scar problem was evaluated according to the Scar Cosmesis Assessment and Rating (SCAR) scale. RESULTS: A total of 73 patients were included. Patients were categorized into two groups: ESIN (n = 45; 27 males, 18 females) and plate (n = 28; 17 males, 11 females), according to surgical technique. The average age of the patients in the ESIN group was 12.2 ± 1.5 years, and that in the plate group was 12.2 ± 1.4 years. The ESIN group presented significantly less operative time (31.1 vs. 59.8 min), a shorter hospital stay (1.5 vs. 2.5 days), and a smaller incision (2.4 vs. 5.4 cm) as compared to the plate group (P < .001). The rate of scar concern was much higher in the plate group (71.4%) than the ESIN group (22.2%) (P < .001). There was no statistically significant difference in shoulder function between the ESIN group and the plate group at different time points. CONCLUSION: A conservative approach remains the first choice for a pediatric clavicle fracture. Both the ESIN and the plate are safe and effective treatment methods for displaced midshaft clavicle fractures in adolescents. The ESIN is superior to the plate given its shorter operative time, shorter hospital stay, lower rate of scar concern, and easier implant removal. LEVEL OF EVIDENCE: III, retrospective observational study.

SPI-1 is a missing host-range factor required for replication of the attenuated modified vaccinia Ankara (MVA) vaccine vector in human cells.

Modified vaccinia virus Ankara (MVA) is the leading poxvirus vector for development of vaccines against diverse infectious diseases. This distinction is based on high expression of proteins and good immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety. Nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s). The search for host-range factors is exacerbated by the large number of deletions, truncations and mutations that occurred during the long passage history of MVA in chicken embryo fibroblasts. By whole genome sequencing of a panel of recombinant host-range extended (HRE) MVAs generated by marker rescue with 40 kbp segments of vaccinia virus DNA, we identified serine protease inhibitor 1 (SPI-1) as one of several candidate host-range factors present in those viruses that gained the ability to replicate in human cells. Electron microscopy revealed that the interruption of morphogenesis in human cells infected with MVA occurred at a similar stage as that of a vaccinia virus strain WR SPI-1 deletion mutant. Moreover, the introduction of the SPI-1 gene into the MVA genome led to more than a 2-log enhancement of virus spread in human diploid MRC-5 cells, whereas deletion of the gene diminished the spread of HRE viruses by similar extents. Furthermore, MRC-5 cells stably expressing SPI-1 also enhanced replication of MVA. A role for additional host range genes was suggested by the restoration of MVA replication to a lower level relative to HRE viruses, particularly in other human cell lines. Although multiple sequence alignments revealed genetic changes in addition to SPI-1 common to the HRE MVAs, no evidence for their host-range function was found by analysis thus far. Our finding that SPI-1 is host range factor for MVA should simplify use of high throughput RNAi or CRISPR/Cas single gene methods to identify additional viral and human restriction elements.

Prevalence of shoulder labral abnormalities on MRI in a non-athletic asymptomatic young adult population.

OBJECTIVE: To determine the prevalence of shoulder (specifically labral) abnormalities on MRI in a young non-athletic asymptomatic cohort. We hypothesize that this population will have fewer labral abnormalities than an athletic population. MATERIALS AND METHODS: In this cross-sectional study, non-athletic young adults age 18-29 with no history of shoulder pain received bilateral shoulder MRIs. A total of 58 total shoulder MRIs were completed on a 3-T MRI scanner (PRISMA-Fit Siemens Medical). MRIs were read by two board-certified fellowship-trained musculoskeletal radiologists at two time points 3 months apart to determine prevalence of labral and other shoulder anatomy abnormalities. Kappa statistics and the associated 95% confidence intervals were computed for inter/intra-reader reliability. Fisher's exact test was used to compare rates of abnormalities in our study with a similarly designed study involving ice hockey athletes. RESULTS: Prevalence of labral abnormalities was 9% (5/58). Kappa coefficient was 1.0 for both readers for intra-reader reliability and 0.57 for inter-reader reliability of labral abnormalities. We further compared our results in asymptomatic athletes with previously published work using the same protocol at our institution. The prevalence of labral abnormalities on MRI in asymptomatic professional and collegiate ice hockey players (49 imaged shoulders) was 24%, which demonstrated a statistically significant (p value < 0.05) difference compared with our data with a p value of 0.03. CONCLUSIONS: Non-athletic young adults with no history of shoulder pain/injury had an overall prevalence of shoulder MRI abnormalities less than asymptomatic professional and collegiate ice hockey players in a similarly designed study.

Discrepancies in child and parent reporting of concussion symptoms.

Objective: To assess discrepancies between child and parent symptom reports following concussion.Methods: Prospective cohort study involving 61 patients, age 7-21 years, diagnosed with a concussion within the previous 14 days. Children/parents completed the Child SCAT-3 symptom inventory at enrollment and 4 weeks post-injury. A within-subjects t-test was used to compare differences in child/parent response for each of 20 individual symptoms, 4 symptom domains, and total symptom severity. Pearson correlations were used to measure agreement between child/parent responses. A repeated measures analysis of variance assessed the effect of time on child/parent symptom discrepancy.Results: At enrollment, children reported higher symptom severity for 'distracted easily' (adj. p = .015) and 'confused' (adj. p = .015). There was moderate-to-high (r > 0.3) agreement between children and parents for more individual symptoms at enrollment (18/20) than at 4 weeks post-injury (14/20). Age had no effect (p > .05) on the discrepancy between child/parent reports.Conclusions: Although there was moderate-to-strong agreement between child/parent reports of concussion symptoms, discrepancies in individual cognitive symptom reports exist, in both children and adolescents. Therefore, collection of parent scales may provide useful information when tracking cognitive symptoms in adolescent patients, who may under-report or under-recognize cognitive deficits.

Musculoskeletal and Sports Medicine Curriculum Guidelines for Pediatric Residents.

ABSTRACT: Musculoskeletal (MSK) and sports-related conditions are relatively common in the pediatric population. Pediatric residencies should provide residents with the knowledge and skills to assess and manage both acute and chronic MSK and sports injuries and complaints. Residents should develop the competencies and attitudes to safeguard and promote a healthy and active lifestyle for youth. Programs can use a variety of educational tools, both in the clinic and on the field, to provide a well-rounded MSK curriculum throughout the residency years. This article provides a review of general pediatric sports medicine curriculum guidelines and suggested implementation strategies.

Pediatric physeal slide-traction plate fixation for pathological distal femoral fracture caused by unicameral bone cyst in adolescents.

BACKGROUND: Most patients suffering from distal femoral unicameral bone cysts (UBCs) are adolescents that require an early return to normal activities, including school attendance and sports exercises. However, the optimal choice of implants for such patients remains controversial. This study evaluated the application of pediatric physeal slide-traction plate (PPSP) in the treatment of pathological distal femoral fracture caused by UBCs. METHODS: Between Jan 2014 and Jan 2016, 11 (male = 6, female = 5) patients were reviewed retrospectively. Age, sex, operative time, limb-length discrepancy (LLD), and valgus angulation were all recorded for every patient. RESULTS: The average age of 11 patients was 12.2 ± 1.1 years. The operating time was 94.8 ± 7.8 min. The postoperative hospital stay was 5 to 7 days. The epiphyseal morphology in the operative leg was nearly normal. The plate was removed in an average of 19.5 ± 3.1 months. The knee range of motion (ROM) was normal in 9 patients, whereas 2 female patients reported a loss of less than 10 degrees of ROM as compared to the contralateral knee joint. Breakage of plates or refracture did not occur in our cases. All patients had a follow-up of at least 24 months. At the latest follow-up visit, all patients walked without a limp. None of the patients manifested obvious LLD and valgus deformity. CONCLUSION: PPSP combined with curettage and bone grafting allows early mobilization and produces satisfactory outcomes for pathological fracture of distal femur secondary to UBCs in adolescents.

Enhanced recovery care versus traditional non-ERAS care following osteotomies in developmental dysplasia of the hip in children: a retrospective case-cohort study.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been shown to shorten the length of hospital stay and reduce the incidence of perioperative complications in many surgical fields. However, there has been a paucity of research examining the application of ERAS in major pediatric orthopaedic surgeries. This study aims to compare the perioperative complications and length of hospital stay after osteotomies in children with developmental dysplasia of the hip (DDH) between ERAS and traditional non-ERAS group. METHODS: The ERAS group consisted of 86 patients included in the ERAS program from January 2016 to December 2017. The Control group consisted of 82 DDH patients who received osteotomies from January 2014 to December 2015. Length of hospital stay, physiological function, postoperative visual analogue scale (VAS) score, and postoperative complications were compared between the two groups. RESULTS: The mean duration of hospital stay was significantly reduced from 10.0 ± 3.1 in the traditional care group to 6.0 ± 0.8 days in the ERAS(P < 0.001). The average VAS score in the first 3 days was significantly lower in the ERAS group (2.9 ± 0.8) than the traditional non-ERAS group (4.0 ± 0.8) (P < 0.001). However, there was no significant difference in the frequency of break-out pain (VAS > 4) between two groups (29.5 ± 6.3 times vs.30.6 ± 6.5 times, P = 0.276). The frequency of postoperative fever was lower in the ERAS group. The frequency of urinary tract infection in both groups were not noticeable because the catheter was removed promptly after the surgery. CONCLUSION: The ERAS protocol is both safe and feasible for pediatric DDH patients undergoing osteotomies, and it can shorten the length of hospital stay without increasing the risk of perioperative complications.

Fixation of delayed distal radial fracture involving metaphyseal diaphyseal junction in adolescents: a comparative study of crossed Kirschner-wiring and non-bridging external fixator.

BACKGROUND: Conservative treatment remains the preferred choice for distal radius fracture in children. However, loss of reduction is problematic, especially in an older child. Crossed Kirschner-wires is widely used to treat distal radius fracture in adolescents. This study aimed to compare the application of crossed Kirschner-wiring (KW) and non-bridging external fixator (EF) for the treatment of delayed distal radial fracture involving metaphyseal diaphyseal junction (MDJ) in adolescents. METHODS: Between January 2012 to January 2017, 146 (male = 101, female = 45) patients in EF group and 117 (male = 76, female = 41) in KW group, were reviewed retrospectively. Preoperative data were collected from the hospital database, and postoperative clinical outcomes data were collected during the follow-up visits. We used SPSS for data analysis. RESULTS: There existed no significant difference between EF and KW regarding sex, body weight, fracture side, duration from injury to surgery. The duration of surgery was significantly shorter in EF (30.5 ± 6.1 min) than the KW group (44.6 ± 9.4 min), P < 0.001. The number of intraoperative X-ray images was significantly lower in EF (6.5 ± 1.1) than KW (11.8 ± 2.3), P < 0.001. The incidence of tendon irritation is significantly higher in the KW (19.7%) than the EF group (0%), P < 0.001. The residual angulation on the AP view was higher in KW (3.8 ± 2.3, degrees) than the EF group (2.5 ± 1.6, degrees), P < 0.001. The volar tilting is better in EF (6.6 ± 1.1, degrees) than the KW group (1.0 ± 1.5, degrees), P < 0.001. However, the functional outcomes of the wrist showed no significant difference between EF and KW group, P = 0.086. CONCLUSION: The EF was superior to KW in the treatment of radial MDJ fractures in adolescents. The EF displayed shorter duration of surgery, less tendon irritation, and better radiographic outcomes than the KW. However, the cost-effect analysis remains to be investigated, because the EF is more expensive than KW.

Biodegradable pins for lateral condylar fracture of the humerus with an early delayed presentation in children: a retrospective study of biodegradable pin vs. Kirschner wire.

BACKGROUND: The clinical outcome of open reduction and internal fixation (ORIF) for delayed lateral condylar fracture of the humerus (LCFH) varies in different studies, but ORIF for LCFH with an early-delayed presentation usually resulted in significant improvement of elbow function. Early delayed presentation is defined as a period of 3 to 12 weeks from the injury. This study aims to compare the clinical outcomes of biodegradable pin (BP) vs. Kirschner wire (KW) in the treatment of LCFH with an early delayed presentation. METHODS: LCFH with an early-delayed presentation treated with KW or BP were retrospectively reviewed in our hospital. The patients were divided into two groups KW (n = 17) and BP group (n = 26). Baseline information, including sex, age, operative side, duration from injury to surgery, and implant choice, was reviewed. Radiographs and medical records were collected from the Hospital Database. RESULTS: In all, 17 patients (male/female, 9/8) in KW and 26 patients (male/female,13/13) in the BP group were included. The age showed no statistically significant difference between the KW (52.3 ± 10.2, month) and the BP (56.1 ± 10.7, month), (P = 0.258). At the last follow-up, there existed no statistically significant difference between the two groups concerning Baumann's angle (P = 0.272) and carrying angle (P = 0.911). The MEPS at the last follow-up was better in the KW group (91.1 ± 2.7) than the BP group (89.2 ± 3.0), (P = 0.048). There was no case of nonunion or malunion in both groups. The incidence of fishtail deformity was (8/17, 47.1%) in KW and (13/26, 50%) in the BP group. The incidence of lateral prominence was (5/17, 29.4%) in the KW and (7/26, 26.9%) in the BP group. Furthermore, the incidence of implant prominence was higher in KW (12/17, 70.6%) than BP (0) (P <  0.001). CONCLUSION: Open reduction and internal fixation for LCFH with an early-delayed presentation produced satisfactory outcomes. Biodegradable pin is a good alternative to Kirschner wire, with comparable clinical outcomes.

Vaccinia Virus C9 Ankyrin Repeat/F-Box Protein Is a Newly Identified Antagonist of the Type I Interferon-Induced Antiviral State.

Type I interferons (IFNs) induce expression of more than 300 cellular genes that provide protection against viruses and other pathogens. For survival, viruses evolved defenses to prevent the IFN response or counteract the IFN-induced antiviral state. However, because viruses and cells coevolved, the dynamic relationship between virus and host is difficult to discern. In the present study, we demonstrated that vaccinia virus with a large deletion near the left end of the genome had a diminished ability to replicate in cells that had been pretreated with beta interferon (IFN-ß), suggesting that one or more of the missing 17 open reading frames (ORFs) encode an antagonist of the IFN-induced antiviral state. By systematically deleting groups of ORFs and then individual ORFs, the C9L gene was shown to be required for IFN resistance. Replication of the C9L deletion mutant (vΔC9) was impaired in human cells that had been pretreated with IFN-ß. Expression of viral early genes occurred, but subsequent events, including genome uncoating, genome replication, and postreplicative gene expression, were inhibited. Expression of the C9 protein occurred prior to genome replication, consistent with an early role in counteracting the IFN-induced antiviral state. C9 contains six ankyrin repeat motifs and a near C-terminal F-box. Mass spectrometry and immunoblotting identified host proteins that copurified with a functional epitope-tagged C9. The most abundant proteins were components of the SCF (CUL1, SKP1, F-box) and signalosome/deneddylation complexes, which interact with each other, suggesting a possible role in proteolysis of one or more interferon-induced proteins.IMPORTANCE Poxviruses comprise a family of large DNA viruses that replicate in the cytoplasm of vertebrate and insect hosts and cause human and zoonotic diseases. In most cases the primary infection is moderated by innate immune defenses. Vertebrates, including fish, amphibians, reptiles, birds, and mammals, all produce type I interferon homologs. In humans, interferon stimulates the synthesis of more than 300 proteins thought to have roles in host defense. Conversely, viruses have evolved means to thwart the host defenses. We are attempting to deconstruct the established virus-host relationship in order to better understand the molecular mechanisms involved. In the present study, we identified a vaccinia virus gene that prevents interferon-mediated inhibition of very early stages of viral replication and is conserved in orthopoxviruses. The viral protein was shown to interact with host proteins involved in proteolysis, suggesting that vaccinia virus may subvert the cellular apparatus for its own defense.

Vehicle Logo Recognition Based on Enhanced Matching for Small Objects, Constrained Region and SSFPD Network.

Vehicle Logo Recognition (VLR) is an important part of vehicle behavior analysis and can provide supplementary information for vehicle identification, which is an essential research topic in robotic systems. However, the inaccurate extraction of vehicle logo candidate regions will affect the accuracy of logo recognition. Additionally, the existing methods have low recognition rate for most small vehicle logos and poor performance under complicated environments. A VLR method based on enhanced matching, constrained region extraction and SSFPD network is proposed in this paper to solve the aforementioned problems. A constrained region extraction method based on segmentation of the car head and car tail is proposed to accurately extract the candidate region of logo. An enhanced matching method is proposed to improve the detection performance of small objects, which augment each of training images by copy-pasting small objects many times in the unconstrained region. A single deep neural network based on a reduced ResNeXt model and Feature Pyramid Networks is proposed in this paper, which is named as Single Shot Feature Pyramid Detector (SSFPD). The SSFPD uses the reduced ResNeXt to improve classification performance of the network and retain more detailed information for small-sized vehicle logo detection. Additionally, it uses the Feature Pyramid Networks module to bring in more semantic context information to build several high-level semantic feature maps, which effectively improves recognition performance. Extensive evaluations have been made on self-collected and public vehicle logo datasets. The proposed method achieved 93.79% accuracy on the Common Vehicle Logos Dataset and 99.52% accuracy on another public dataset, respectively, outperforming the existing methods.

Opposing Roles of Double-Stranded RNA Effector Pathways and Viral Defense Proteins Revealed with CRISPR-Cas9 Knockout Cell Lines and Vaccinia Virus Mutants.

UNLABELLED: Vaccinia virus (VACV) decapping enzymes and cellular exoribonuclease Xrn1 catalyze successive steps in mRNA degradation and prevent double-stranded RNA (dsRNA) accumulation, whereas the viral E3 protein can bind dsRNA. We showed that dsRNA and E3 colocalized within cytoplasmic viral factories in cells infected with a decapping enzyme mutant as well as with wild-type VACV and that they coprecipitated with antibody. An E3 deletion mutant induced protein kinase R (PKR) and eukaryotic translation initiation factor alpha (eIF2α) phosphorylation earlier and more strongly than a decapping enzyme mutant even though less dsRNA was made, leading to more profound effects on viral gene expression. Human HAP1 and A549 cells were genetically modified by clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) to determine whether the same pathways restrict E3 and decapping mutants. The E3 mutant replicated in PKR knockout (KO) HAP1 cells in which RNase L is intrinsically inactive but only with a double knockout (DKO) of PKR and RNase L in A549 cells, indicating that both pathways decreased replication equivalently and that no additional dsRNA pathway was crucial. In contrast, replication of the decapping enzyme mutant increased significantly (though less than that of wild-type virus) in DKO A549 cells but not in DKO HAP1 cells where a smaller increase in viral protein synthesis occurred. Xrn1 KO A549 cells were viable but nonpermissive for VACV; however, wild-type and mutant viruses replicated in triple-KO cells in which RNase L and PKR were also inactivated. Since KO of PKR and RNase L was sufficient to enable VACV replication in the absence of E3 or Xrn1, the poor replication of the decapping mutant, particularly in HAP1 DKO, cells indicated additional translational defects. IMPORTANCE: Viruses have evolved ways of preventing or counteracting the cascade of antiviral responses that double-stranded RNA (dsRNA) triggers in host cells. We showed that the dsRNA produced in excess in cells infected with a vaccinia virus (VACV) decapping enzyme mutant and by wild-type virus colocalized with the viral E3 protein in cytoplasmic viral factories. Novel human cell lines defective in either or both protein kinase R and RNase L dsRNA effector pathways and/or the cellular 5' exonuclease Xrn1 were prepared by CRISPR-Cas9 gene editing. Inactivation of both pathways was necessary and sufficient to allow full replication of the E3 mutant and reverse the defect cause by inactivation of Xrn1, whereas the decapping enzyme mutant still exhibited defects in gene expression. The study provided new insights into functions of the VACV proteins, and the well-characterized panel of CRISPR-Cas9-modified human cell lines should have broad applicability for studying innate dsRNA pathways.