Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1ß, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

Comparative study of lung toxicity of E-cigarette ingredients to investigate E-cigarette or vaping product associated lung injury.

No comparative study has yet been performed on the respiratory effects of individual E-cigarette ingredients. Here, lung toxicity of individual ingredients of E-cigarette products containing nicotine or tetrahydrocannabinol was investigated. Mice were intratracheally administered propylene glycol (PG), vegetable glycerin (VG), vitamin E acetate (VEA), or nicotine individually for two weeks. Cytological and histological changes were noticed in PG- and VEA-treated mice that exhibited pathophysiological changes which were associated with symptoms seen in patients with symptoms of E-cigarette or Vaping Use-Associated Lung Injuries (EVALI) or E-cigarette users. Compared to potential human exposure situations, while the VEA exposure condition was similar to the dose equivalent of VEA content in E-cigarettes, the PG condition was about 47-137 times higher than the dose equivalent of the daily PG intake of E-cigarette users. These results reveal that VEA exposure is much more likely to cause problems related to EVALI in humans than PG. Transcriptomic analysis revealed that PG exposure was associated with fibrotic lung injury via the AKT signaling pathway and M2 macrophage polarization, and VEA exposure was associated with asthmatic airway inflammation via the mitogen-activated protein kinase signaling pathway. This study provides novel insights into the pathophysiological effects of individual ingredients of E-cigarettes.

Risk factors for residual popliteal cyst after arthroscopic decompression and cystectomy: Associated with degenerative cartilage lesions.

BACKGROUND: In previous studies, good results have been reported after arthroscopic treatment of popliteal cysts and concomitant intra-articular pathology. However, only a few studies have reported the associated factors with residual popliteal cysts. The aim of this study was to examine the clinical and radiographic outcomes and investigate the factors associated with the recurrence of popliteal cyst after arthroscopic cyst decompression and cyst wall resection. HYPOTHESIS: The authors hypothesized that residual popliteal cyst after arthroscopic decompression and cystectomy would be associated with degenerative cartilage lesions. PATIENTS AND METHODS: From December 2010 to December 2018, 54 patients with popliteal cysts were treated with arthroscopic decompression and cyst wall resection through an additional posteromedial cystic portal. Magnetic resonance imaging (MRI) or ultrasonography was used to observe whether the popliteal cyst had disappeared or decreased. The maximum diameter of the popliteal cyst was measured after surgery. The patients were classified into the disappeared and reduced groups according to the treatment outcome. Age, sex, symptom duration, preoperative degenerative changes based on the Kellgren-Lawrence (K-L) grade, cartilage lesions according to the International Cartilage Repair Society (ICRS) grades, synovitis, functional outcomes, and associated intra-articular lesions were compared between the two groups. The functional outcome was evaluated on the basis of the Rauschning and Lindgren knee score. The study included 22 men and 32 women, with mean age of 49.6 years (range, 5-82 years). According to the ICRS grade system, 28 (51.8%) patients had grade 0 to II, 26 (48.2%) patients had grade III to IV. RESULTS: Follow-up radiographic evaluation revealed that the cyst had completely disappeared in 20 patients (37%) and reduced in size in 34 (63%). The mean cyst size was decreased significantly from 5.7cm (range, 1.7-15cm) to 1.7cm (range, 0-6.4cm), and the Rauschning and Lindgren knee score showed improved clinical features in all the patients. Between the disappeared and reduced groups, the presence of degenerative cartilage lesions (p=0.022, odds ratio 8.702, 95% confidence interval: 1.368-55.362) showed statistically significant differences. DISCUSSION: Through the posteromedial cystic portal, cysts were completely removed in approximately 40% of patients, and the size was reduced in 60% of patients. Presence of degenerative cartilage lesion represents an associated risk factor for residual popliteal cyst. These findings could be helpful in ensuring explaining poor prognostic factors. LEVEL OF EVIDENCE: IIIb; retrospective cohort study.

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

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

Chromosome Damage in Relation to Recent Radiation Exposure and Radiation Quality in Nuclear Power Plant Workers.

Ionizing radiation is a well-known carcinogen that causes genomic instability. However, the biological and carcinogenetic effects of occupational radiation exposure at low doses have not been extensively studied. The aim of this study was to assess chromosomal instability in power plant workers exposed to occupational radiation at low doses in South Korea. Chromosomal aberrations in the lymphocytes of 201 nuclear power plant workers and 59 sex-matched controls were measured. Chromosomal aberrations in the lymphocytes of 201 nuclear power plant workers (mean age: 41.4 ± 10.0 years) and 59 sex-matched controls (mean age: 47.2 ± 6.0 years) were measured. A total of 500 metaphases for each subject were scored randomly. The means of recent 1.5-year, recent 5.5-year, and cumulative exposed radiation doses among workers were 8.22 ± 7.0 mSv, 30.7 ± 22.0 mSv, and 158.8 ± 86.1 mSv, respectively. The frequency of chromosome-type and chromatid-type aberrations was significantly higher in workers than that in the control group (p < 0.001), and the frequency of chromosome-type aberrations among workers increased in a radiation dose-dependent manner (τ = 0.16, p = 0.005). Poisson regression analyses revealed that chromosome-type aberrations were significantly associated with recent 1.5-year dose after adjusting for confounding variables such as age, smoking, and alcohol intake, even when only the exposed worker was considered. Frequency of multi-aberrant cells (two or more chromosome aberrations within a cell) increased according to cumulative neutron exposure. Our study demonstrates that chromosome damage can be induced in nuclear power plant workers occupationally exposed to ionizing radiation at low doses below the occupational permissible dose limit. Furthermore, an increase in multi-aberrant cells may provide evidence for chronic neutron exposure in nuclear power plant workers. This study was performed to obtain baseline data for a surveillance program of workers occupationally exposed to ionizing radiation long-term.

Diesel Exhaust Particles Impair Therapeutic Effect of Human Wharton's Jelly-Derived Mesenchymal Stem Cells against Experimental Colitis through ROS/ERK/cFos Signaling Pathway.

Background and Objectives: Epidemiological investigations have shown positive correlations between increased diesel exhaust particles (DEP) in ambient air and adverse health outcomes. DEP are the major constituent of particulate atmospheric pollution and have been shown to induce proinflammatory responses both in the lung and systemically. Here, we report the effects of DEP exposure on the properties of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs), including stemness, regeneration, and immunomodulation. Methods and Results: Non-apoptotic concentrations of DEP (10 µg/ml) inhibited the migration and osteogenic differentiation capacity of WJ-MSCs. Gene expression profiling showed that DEP increased intracellular reactive oxygen species (ROS) and expression of pro-inflammatory and metabolic-process-related genes including cFos. Furthermore, WJ-MSCs cultured with DEP showed impaired suppression of T cell proliferation that was reversed by inhibition of ROS or knockdown of cFos. ERK inhibition assay revealed that DEP-induced ROS regulated cFos through activation of ERK but not NF-κB signaling. Overall, low concentrations of DEP (10 µg/ml) significantly suppressed the stemness and immunomodulatory properties of WJ-MSCs through ROS/ERK/cFos signaling pathways. Furthermore, WJ-MSCs cultured with DEP impaired the therapeutic effect of WJ-MSCs in experimental colitis mice, but was partly reversed by inhibition of ROS. Conclusions: Taken together, these results indicate that exposure to DEP enhances the expression of pro-inflammatory cytokines and immune responses through a mechanism involving the ROS/ERK/cFos pathway in WJ-MSCs, and that DEP-induced ROS damage impairs the therapeutic effect of WJ-MSCs in colitis. Our results suggest that modulation of ROS/ERK/cFos signaling pathways in WJ-MSCs might be a novel therapeutic strategy for DEP-induced diseases.

Steep posterior lateral tibial slope, bone contusion on lateral compartments and combined medial collateral ligament injury are associated with the increased risk of lateral meniscal tear.

PURPOSE: To determine the risk factors for lateral meniscus and root tears in patients with acute anterior cruciate ligament (ACL) injuries. METHODS: A total of 226 patients undergoing acute ACL reconstruction were included in the study sample. Exclusion criteria were revisions, fractures, chronic cases, and multiple ligament injuries, with the exception of medial collateral ligament (MCL) injuries. The patients were divided into groups based on the presence of lateral meniscus and root tears by arthroscopy. Binary logistic regression was used to analyze risk factors including age, sex, body mass index (BMI), injury mechanism (contact/non-contact), Segond fracture, side-to-side laxity, location of bone contusion, medial and lateral tibial and meniscal slope, mechanical axis angle, and grade of pivot shift. RESULTS: Overall lateral meniscus (LM) tears were identified in 97 patients (42.9%), and LM root tears were found in 22 patients (9.7%). The risk of an LM tear in ACL-injured knees increased with bone contusion on LTP (odds ratio [OR], 3.5; 95% confidence interval [CI] 1.419-8.634; P = 0.007), steeper lateral tibial slope (OR, 1.133; 95% CI 1.003-1.28; P = 0.045), MCL injury (OR, 2.618; 95% CI 1.444-4.746; P = 0.002), and non-contact injury mechanism (OR, 3.132; 95% CI 1.446-6.785; P = 0.004) in logistic regression analysis. The risk of LM root tear in ACL-injured knees increased with high-grade pivot shift (OR, 9.127; 95% CI 2.821-29.525; P = 0.000) and steeper lateral tibial slope (OR, 1.293; 95% CI 1.061-1.576; P = 0.011). CONCLUSION: The increased risk of LM lesions in acute ACL-injured knees should be considered if significant risk factors including bone contusion on lateral compartments, MCL injury, and a steeper lateral tibial slope are present. Moreover, high-grade rotational injury with steeper lateral tibial slope are also significant risk factors for LM root tears, and therefore care should be taken by clinicians not to miss such lesions. LEVEL OF EVIDENCE: III.

The impact of fine particulate matter (PM) on various beneficial functions of human endometrial stem cells through its key regulator SERPINB2.

Fine particulate matter (PM) has a small diameter but a large surface area; thus, it may have broad toxic effects that subsequently damage many tissues of the human body. Interestingly, many studies have suggested that the recent decline in female fertility could be associated with increased PM exposure. However, the precise mechanisms underlying the negative effects of PM exposure on female fertility are still a matter of debate. A previous study demonstrated that resident stem cell deficiency limits the cyclic regenerative capacity of the endometrium and subsequently increases the pregnancy failure rate. Therefore, we hypothesized that PM exposure induces endometrial tissue damage and subsequently reduces the pregnancy rate by inhibiting various beneficial functions of local endometrial stem cells. Consistent with our hypothesis, we showed for the first time that PM exposure significantly inhibits various beneficial functions of endometrial stem cells, such as their self-renewal, transdifferentiation, and migratory capacities, in vitro and in vivo through the PM target gene SERPINB2, which has recently been shown to be involved in multiple stem cell functions. In addition, the PM-induced inhibitory effects on the beneficial functions of endometrial stem cells were significantly diminished by SERPINB2 depletion. Our findings may facilitate the development of promising therapeutic strategies for improving reproductive outcomes in infertile women.

Age and Gender Effects on Genotoxicity in Diesel Exhaust Particles Exposed C57BL/6 Mice.

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM2.5) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM2.5 induced genomic damage. Here, we assessed the DNA damage potency of PM2.5 using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks. Mice were intratracheally instilled with diesel exhaust PM2.5 (DEP, NIST SRM 1650b), twice a week for 4 weeks. Exposure to DEP was not associated with an increase in the frequency of micronucleated polychromatic erythrocytes and did not induce a systemic genotoxic effect in the bone marrow. Meanwhile, the results from the comet assay showed a significant increase in DNA damage in DEP exposed mouse lung specimens. The positive relationship between DEP exposure and DNA damage is stronger in the older than in the younger group. Statistical analysis showed that there was a modifying effect of age on the association between PM2.5 exposure and DNA damage. Our results suggest that the age factor should be considered to better understand the cellular adverse effects of PM2.5.

Determination of Genotoxicity Attributed to Diesel Exhaust Particles in Normal Human Embryonic Lung Cell (WI-38) Line.

Several epidemiological studies concluded that inhalation of diesel exhaust particles (DEP) is associated with an increase in the relative risk of lung cancer. In vitro research evaluating the genetic damage and/or changes in gene expression have been attempted to explain the relationship between DEP exposure and carcinogenicity. However, to date, investigations have been largely confined to studies in immortalized or tumorigenic epithelial cell models. Few studies have investigated damage at the chromosomal level to DEP exposure in normal cell lines. Here, we present the genotoxic effects of DEP in normal cells (embryonic human lung fibroblasts) by conventional genotoxicity testing (micronuclei (MN) and comet assay). We show the differentially expressed genes and enriched pathways in DEP-exposed WI-38 cells using RNA sequencing data. We observed a significant increase in single-strand DNA breaks and the frequency of MN in DEP-exposed cells in a dose-dependent manner. The differentially expressed genes following DEP exposure were significantly enriched in the pathway for responding to xenobiotics and DNA damage. Taken together, these results show that DEP exposure induced DNA damage at the chromosomal level in normal human lung cells and provide information on the expression of genes associated with genotoxic stress.

Clinical Outcomes of Arthroscopic Notchplasty and Partial Resection for Mucoid Degeneration of the Anterior Cruciate Ligament.

BACKGROUND: Mucoid degeneration of the anterior cruciate ligament (MD-ACL) is a chronic degenerative process involving a hypertrophied ACL, which may lead to notch impingement syndrome. As a treatment method, there is consensus regarding arthroscopic resection for MD-ACL resulting in good clinical outcomes; however, additional notchplasty remains controversial. The purpose of this study was to investigate clinical outcomes after arthroscopic partial resection of the ACL and additional notchplasty performed to minimize volume reduction of the ACL. STUDY DESIGN: Level IIIb retrospective cohort study. METHODS: Of 1810 individuals who underwent knee arthroscopic surgery performed by the same surgeon between July 2011 and October 2020, 52 were included, while 10 were excluded due to a follow-up period of <1 year. Clinical data including pain location, terminal flexion or extension pain, range of motion (ROM), Lysholm knee score, and Hospital for Special Surgery (HSS) knee score were assessed pre- and postoperatively. Additionally, according to the resected volume of the ACL, patients were classified into two groups: <25% (Group 1), and 25-50% (Group 2). Clinical outcomes were compared between the two groups. RESULTS: There were 17 (40.5%) men and 25 (59.5%) women with a mean age of 53.9 years (range, 16-81 years) at the time of surgery. The mean duration of symptoms before surgery was 14.4 months (range, 3-66 months). Arthroscopic partial resection of the MD-ACL was performed in all patients, and concomitant notchplasty was performed in 36 (81.8%). All clinical scores improved postoperatively, and were statistically significant (p < 0.01). However, there was no significant difference in clinical outcomes between groups 1 and 2 classified according to the resected ACL volume. Recurrence of MD-ACL was recorded in only one patient, 11 months after arthroscopic treatment. No patients underwent ACL reconstruction because of symptoms of anterior instability. CONCLUSION: Arthroscopic partial resection of the ACL and concomitant notchplasty yielded satisfactory outcomes for the treatment of MD-ACL. Notchplasty may be an alternative procedure to avoid total ACL resection and postoperative instability.

Can an injured discoid lateral meniscus be returned to the correct anatomic position and size of the native lateral meniscus after surgery?

BACKGROUND: No previous studies have compared the position and size of the remaining discoid lateral meniscus (DLM) with that of a normal lateral meniscus. This study aimed to evaluate the postoperative position and size of DLM compared with that of normal controls using magnetic resonance imaging (MRI). METHODS: This retrospective study involved 52 symptomatic complete type DLMs (discoid group) who underwent arthroscopic surgery and 50 normal controls (control group). Pre- and postoperative MRI evaluations, height, width, and relative percentage of extrusion (RPE) were assessed. Sagittal position parameters, including distances from articular cartilage center to anterior meniscus (CAMD) and from anterior articular cartilage margin to anterior horn (ACMD), were also assessed. Logistic regression analysis was performed to find factors with extrusion of remaining DLM. RESULTS: The height of the discoid group was significantly lower than that of the control group (P = 0.000). RPE in the discoid group was significantly larger than in the control group (P = 0.005). Only CAMD and ACMD in the discoid group were different (positioned more anteriorly) from the control group (P = 0.000). Preoperative meniscal shift (odds ratio (OR): 12.448; P = 0.003) and operative technique, especially partial meniscectomy with repair (OR: 19.125; P = 0.000), were the major factors associated with extrusion. CONCLUSION: The width of remaining DLM was comparable to that of normal controls, but the position was found to be more anterior and lateral than that of normal controls. Preoperative meniscal shift and combined meniscus repair were the major factors for smaller width and greater extrusion; thus, surgeons should address and counsel these factors before surgery.

Radiographic findings for surgery-related complications after pedicle subtraction osteotomy for thoracolumbar kyphosis in 230 patients with ankylosing spondylitis.

OBJECTIVE: The purpose of this study was to investigate the rate of and the risk factors for surgery-related complications demonstrated on radiography after pedicle subtraction osteotomy (PSO) for thoracolumbar kyphosis in patients with ankylosing spondylitis (AS). METHODS: The authors retrospectively reviewed the medical records of 230 consecutive patients with thoracolumbar kyphosis due to AS who had undergone 1-level PSO at a single institution in the period from 2010 to 2017. The causes of surgery-related complications were divided into two types: surgical/technical failure and mechanical failure. RESULTS: The patients consisted of 20 women and 210 men, with an average age of 43.4 years. The average follow-up period was 39.0 months. The preoperative sagittal vertical axis was 18.5 ± 69.3 cm, which improved to 4.9 ± 4.6 cm after PSO. Of the 77 patients (33.5%) who experienced minor or major surgery-related complications, 56 had complications related to surgical/technical failure (overall incidence 24.3%) and 21 had complications related to mechanical failure (overall incidence 9.1%). Fourteen patients (6.1%) underwent reoperation. However, among the 77 patients with complications, the rate of revision surgery was 18.2%. The most common radiological complications were as follows: sagittal translation in 24 patients, coronal imbalance in 20, under-correction in 8, delayed union in 8, and distal junctional failure and kyphosis in 8. The most common causes of reoperation were coronal imbalance in 4 patients, symptomatic malposition of pedicle screws in 3, and distal junctional failure in 3. Delayed union was statistically correlated with posterior sagittal translation (p = 0.007). CONCLUSIONS: PSO can provide acceptable radiographic outcomes for the correction of thoracolumbar kyphosis in patients with AS. However, a high incidence of surgery-related complications related to mechanical failure and surgical technique can develop. Thorough radiographic investigation before and during surgery is needed to determine whether complete ossification occurs along the anterior and posterior longitudinal ligaments of the spine.

Staged Revision of Infected-hip Arthroplasty Using an Antibiotics-loaded Intra-articular Cement Spacer: Impact on Cemented and Cementless Stem Retention.

PURPOSE: Currently, standard management of a peri-prosthetic infection is a two-stage revision precedure. However, removal of well-fixed cement is technically demanding and associated with numerous potential complications. For theses reasons, two-stage revision with preservation of the original femoral stem can be considered and several previous studies have achieved successful results. While most prior studies used cemented stems, the use of cementless stems during arthroplasty has been gradually increasing; this study aims to assess the comparative effectiveness of a two-stage revision of infected hip arthroplasties at preserving cemented and cementless stems. MATERIALS AND METHODS: Between December 2001 and February 2017, Inje University Sanggye Paik Hospital treated 45 cases of deep infections following hip arthroplasty with a two stage revisional arthroplasty using antibiotics-loaded cement spacers. This approach was applied in an effort to preserve the previously implanted femoral stem. Of these 45 cases, 20 were followed-up for at least two years and included in this analysis. Perioperative clinical symptoms, radiological findings, function and complications during insertion of an antibiotics-loaded cement spacer were analyzed in this study. RESULTS: Peri-prothetic infections were controlled in 19 of the 20 included cases. Clinical outcomes, as assessed using the Harris hip score, Western Ontario and McMaster University score, also improved. Importantly, similarly improved outcomes were achieved for both cemented and cementless femoral stems. CONCLUSION: In cases of deep infection following hip arthroplasty, two-stage revision arthroplasty to preserve the previously implanted femoral stem (cemented or cementless) effectively controls infections and preserves joint function.

Factors associated with bilateral discoid lateral meniscus tear in patients with symptomatic discoid lateral meniscus tear using MRI and X-ray.

BACKGROUND: The incidence of bilateral discoid lateral meniscus (DLM) is as high as 73 to 85%, and associated contralateral meniscus tears ranged from 4 to 33% in symptomatic surgical DLM. The goal of the study was analyzing the factors that predict contralateral presence and tearing of DLM in patients who underwent surgery for symptomatic DLM. Our hypothesis was that there is a significant correlation between operative DLM properties and the incidence of bilateral DLM with associated contralateral meniscus tears. These properties include tear patterns, younger patient age, and characteristic X-ray findings. PATIENTS AND METHODS: This prospective study included 76 patients who underwent arthroscopic surgery for symptomatic DLM. The contralateral knees were evaluated with X-ray and MRI. Based on the MRI findings, DLM was categorized into three types, and tear patterns were analyzed. The characteristic X-ray findings were evaluated as follows: (1) high fibular head, (2) squared-off appearance of the lateral femoral condyle, (3) cupping of the lateral tibial plateau, (4) widened femorotibial joint space, (5) hypoplasia of the lateral intercondylar spine, (6) notching of the LFC. The number of characteristic X-ray findings (0/1/more than 2) was noted. Binary logistic analysis was performed to find the factors that predict the presence and tear of contralateral DLM. RESULTS: MRI of contralateral knees revealed 43 cases (57%) of complete DLM, 25 cases (33%) of incomplete DLM, and 8 cases (11%) of normal meniscus. Meniscus tears were found in 29 cases (38%) in the contralateral knee. X-ray of the contralateral knee revealed that 27 patients (36%) had one and 24 patients (32%) had two or more characteristic X-ray findings. On logistic regression analysis, the associations between contralateral knee meniscal tear and the presence of one or more than two characteristic X-ray findings were statistically significant (OR: 16.5, p=0.028; OR: 264.0, p=0.000, respectively). DISCUSSION: The number of characteristic X-ray findings in the contralateral knee is a significant predictive factor for contralateral DLM type and/or tear. Symptomatic DLM patients with characteristic X-ray findings should be carefully evaluated for contralateral DLM and meniscal tears. LEVEL OF EVIDENCE: III, prospective diagnostic study of consecutive patients.

How to Avoid Distal Adding-on Phenomenon for Rigid Curves in Major Thoracolumbar and Lumbar Adolescent Idiopathic Scoliosis? Identifying the Incidence of Distal Adding-on by Selection of Lowest Instrumented Vertebra.

OBJECTIVE: We sought to compare the radiologic outcomes for different distal fusion levels in a rigid curve with major thoracolumbar and lumbar (TL/L) adolescent idiopathic scoliosis (AIS) using rod derotation (RD) with direct vertebral rotation (DVR) after pedicle screw instrumentation (PSI). METHODS: This study finally enrolled 28 patients who were diagnosed with AIS in rigid curve with major TL/L curves, treated by PSI with RD and DVR and with a minimum 2-year follow-up. Patients were divided into 2 groups, L3 and L4, on the basis of the distal fusion level at the lowest instrumented vertebra (LIV) of L3 or L4. RESULTS: There was no significant difference in TL/L curve, thoracic (minor), and compensatory (caudal) curves between the L3 and L4 groups either postoperatively (P = 0.162, 0.426, and 0.762, respectively) or at the last follow-up (P = 0.952, 0.620, and 0.562, respectively). The overall prevalence of unsatisfactory results was 42.9% (12/28 patients). The prevalence of unsatisfactory results was 61.1% (11/18) in the L3 group and 10% (1/10) in the L4 group, which was significantly different (P < 0.05). CONCLUSIONS: Unsatisfactory results occurred more often in the L3 group than in the L4 group, and unsatisfactory results had significant influence on progression of TL/L and distal compensatory curves. Such progression was closely correlated with deteriorating LIV disk angle in the L3 group. Therefore if the curve is rigid, LIV should be extended to L4 to avoid the adding-on phenomenon in the treatment of major TL/L AIS using RD with DVR after PSI.

Cytology smears for DNA extraction: Practical approach for selecting the best slide.

BACKGROUND: Next generation sequencing (NGS) to detect actionable genetic abnormalities is standard of care in advanced stage lung adenocarcinoma. Many studies have shown that the molecular results obtained from fine needle aspiration cytology material are comparable to those obtained from formalin-fixed tissue samples. We undertook this study to validate DNA extraction from cytology material for molecular studies and to find any correlation between DNA yield, pattern of tumour cells and tumour fraction. METHODS: DNA was extracted from 34 cytology slides of pulmonary adenocarcinoma cases with predetermined EGFR mutation status. Cytology slides were reviewed for pattern of tumour distribution and tumour fraction. NGS was performed on five slides with variable DNA and compared with original results. RESULTS: There were 14 alcohol-fixed and 20 air-dried smears. The mean DNA yield was 1.74 µg and median of 0.4 µg (range, 0.02-21 µg). Tumour fractions varied from 10% to 90%. No correlation was found between tumour fraction and DNA yield (P = 0.14). The mean DNA yield was high in slides with tumour throughout the slide (sheets or scattered clusters) as compared to rare scattered clusters and/or single cells. EGFR mutation was found in four of the five cases sent for NGS lung panel while one case revealed BRAF mutation. CONCLUSIONS: DNA with good quantity and quality can be extracted from the cytology slides for NGS irrespective of type of fixation. DNA yield has better correlation with distribution pattern of tumour cells on the slides rather than tumour fraction.

Clinical and Radiological Outcomes of Modified Phemister Operation with Coracoclavicular Ligament Augmentation Using Suture Anchor for Acute Acromioclavicular Joint Dislocation.

BACKGROUND: Modified Phemister operation has been widely used for the treatment of acute acromioclavicular (AC) joint dislocation. Additionally, the use of suture anchor for coracoclavicular (CC) fixation has been reported to provide CC stability. This study was conducted to evaluate the clinical and radiological results of a modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation. METHODS: Seventy-four patients underwent the modified Phemister operation with CC ligament augmentation using suture anchor for acute AC joint dislocation and were followed-up for an average of 12.3 months. The visual analogue scale (VAS), range of motion, Constant score, and Korean shoulder scoring system (KSS) were used for clinical assessment. Acromioclavicular interval (ACI), coracoclavicular distance (CCD), and acromioclavicular distance (ACD) were obtained to evaluate the radiological assessments. RESULTS: At the last follow-up, the mean VAS Score was 1.7 points, the mean joint range of the forward flexion was 164.6°, external rotation at the side was 61.2°, and internal rotation to the posterior was a level of T12. The mean Constant score and the mean KSS was 82.7 points and 84.2 points, respectively. At the mean ACI, CCD, and ACD, significant differences were found preoperatively and at the last follow-up. When the ACI, CCD, and ACD were compared with the contralateral unaffected shoulder at the last follow-up, the affected shoulders had significantly higher values. CONCLUSIONS: The modified Phemister operation with CC ligament augmentation using suture anchor is clinically and radiologically effective at acute AC joint dislocation.

Structure and function of the yeast listerin (Ltn1) conserved N-terminal domain in binding to stalled 60S ribosomal subunits.

The Ltn1 E3 ligase (listerin in mammals) has emerged as a paradigm for understanding ribosome-associated ubiquitylation. Ltn1 binds to 60S ribosomal subunits to ubiquitylate nascent polypeptides that become stalled during synthesis; among Ltn1's substrates are aberrant products of mRNA lacking stop codons [nonstop translation products (NSPs)]. Here, we report the reconstitution of NSP ubiquitylation in Neurospora crassa cell extracts. Upon translation in vitro, ribosome-stalled NSPs were ubiquitylated in an Ltn1-dependent manner, while still ribosome-associated. Furthermore, we provide biochemical evidence that the conserved N-terminal domain (NTD) plays a significant role in the binding of Ltn1 to 60S ribosomal subunits and that NTD mutations causing defective 60S binding also lead to defective NSP ubiquitylation, without affecting Ltn1's intrinsic E3 ligase activity. Finally, we report the crystal structure of the Ltn1 NTD at 2.4-Å resolution. The structure, combined with additional mutational studies, provides insight to NTD's role in binding stalled 60S subunits. Our findings show that Neurospora extracts can be used as a tool to dissect mechanisms underlying ribosome-associated protein quality control and are consistent with a model in which Ltn1 uses 60S subunits as adapters, at least in part via its NTD, to target stalled NSPs for ubiquitylation.

Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development.

Asbestos in combination with tobacco smoke exposure reportedly leads to more severe physiological consequences than asbestos alone; limited data also show an increased disease risk due to environmental tobacco smoke (ETS) exposure. Environmental influences during gestation and early lung development can result in physiological changes that alter risk for disease development throughout an individual's lifetime. Therefore, maternal lifestyle may impact the ability of offspring to subsequently respond to environmental insults and alter overall disease susceptibility. In this study, we examined the effects of exposure to ETS in utero and during early postnatal development on asbestos-related inflammation and disease in adulthood. ETS exposure in utero appeared to shift inflammation towards a Th2 phenotype, via suppression of Th1 inflammatory cytokine production. This effect was further pronounced in mice exposed to ETS in utero and during early postnatal development. In utero ETS exposure led to increased collagen deposition, a marker of fibrotic disease, when the offspring was later exposed to asbestos, which was further increased with additional ETS exposure during early postnatal development. These data suggest that ETS exposure in utero alters the immune responses and leads to greater disease development after asbestos exposure, which is further exacerbated when exposure to ETS continues during early postnatal development.