Effect of Corticosteroid Use on the Occurrence and Progression of Osteonecrosis of the Femoral Head: A nationwide Nested Case-Control Study.

BACKGROUND: Although it is very well known that corticosteroids cause osteonecrosis of the femoral head (ONFH), it is unclear as to which patients develop ONFH. Additionally, there are no studies on the association between corticosteroid use and femoral head collapse in ONFH patients. We aimed to investigate the association between corticosteroid use and the risk of ONFH among the general population and what factors affect ONFH occurrence. Additionally, we aimed to demonstrate which factors affect femoral head collapse and total hip arthroplasty (THA) after ONFH occurrence. METHODS: A nationwide, nested case-control study was conducted with data from the National Health Insurance Service Physical Health Examination Cohort (2002 to 2019) in the Republic of Korea. We defined ONFH (N = 3,500) using diagnosis and treatment codes. Patients who had ONFH were matched 1:5 to form a control group based on the variables of birth year, sex, and follow-up duration. Additionally, in patients who have ONFH, we looked for risk factors for progression to THA. RESULTS: Compared with the control group, ONFH patients had a low household income and had more diabetes, hypertension, dyslipidemia, and heavy alcohol use (drinking more than 3 to 7 drinks per week). Systemic corticosteroid use (≥ 1,800 mg) was significantly associated with an increased risk of ONFH incidence. However, lipid profiles, corticosteroid prescription, and cumulative doses of corticosteroid did not affect the progression to THA. CONCLUSION: The ONFH risk increased rapidly when cumulative prednisolone use was ≥ 1,800 mg. However, oral or high-dose intravenous corticosteroid use and cumulative dose did not affect the prognosis of ONFH. Since the occurrence and prognosis of ONFH are complex and multifactorial processes, further study is needed.

Impact of IL-1ß on lung pathology caused by Mycobacterium abscessus infection and its association with IL-17 production.

Mycobacterium abscessus (MAB), a non-tuberculous mycobacterium (NTM), causes chronic pulmonary inflammation in humans. The NLRP3 inflammasome is a multi-protein complex that triggers IL-1ß maturation and pyroptosis through the cleavage of caspase-1. In this study, we investigated the roles of NLRP3 and IL-1ß in the host's defense against MAB. The IL-1ß production by MAB was completely abolished in NLRP3, but not NLRC4, deficient macrophages. The NLRP3 inflammasome components, which are ASC and caspase-1 were also found to be essential for IL-1ß production in response to MAB. NLRP3 and IL-1ß deficiency did not affect the intracellular growth of MAB in macrophages, and the bacterial burden in lungs of NLRP3- and IL-1ß-deficient mice was also comparable to the burden observed in WT mice. In contrast, IL-1ß deficiency ameliorated lung pathology in MAB-infected mice. Notably, the lung homogenates of IL-1ß-deficient mice had reduced levels of IL-17, but not IFN-γ and IL-4 when compared with WT counterparts. Furthermore, in vitro co-culture analysis showed that IL-1ß signaling was essential for IL-17 production in response to MAB. Finally, we observed that the anti-IL-17 antibody administration moderately mitigated MAB-induced lung pathology. These findings indicated that IL-1ß production contribute to MAB-induced lung pathology via the elevation of IL-17 production.

Evaluating Pain Management from Peripheral Nerve Block for Geriatric Patients following Bipolar Hemiarthroplasty for Displaced Femoral-Neck Fracture.

INTRODUCTION: The purpose of this study was to evaluate peripheral nerve block (PNB) effectiveness in postoperative pain management and surgical outcomes for displaced femoral-neck fracture in geriatric patients (>70 years) who underwent bipolar hemiarthroplasty (BHA). METHODS: From January 2017 to December 2021, 231 geriatric patients with displaced femoral-neck fracture who consecutively underwent BHA were retrospectively reviewed. Patients were divided into two groups: the patient-controlled analgesia (PCA) group (n = 132) who received only intravenous (IV) PCA for postoperative pain management, and all others who received PNB with IV PCA (PNB+PCA) such as femoral nerve block or fascia iliaca compartment block after surgery (n = 99). Primary outcomes were postoperative visual analog scale (VAS) at rest and during activity at 6, 24, and 48 h postoperatively. Secondary outcomes were postoperative complications, changes in hemoglobin, length of hospital stay, and total morphine usage after surgery. RESULTS: Postoperative resting VAS at 6 h and 48 h was significantly lower in the PNB+PCA group compared with the PCA group (p = 0.075, p = 0.0318, respectively). However, there was no significant difference in either resting VAS at 24 h or active VAS. Complications of pneumonia and delirium until 1 month postoperative were significantly lower in the PNB + PCA group than the PCA group (p = 0.0022, p = 0.0055, respectively). CONCLUSION: PNB with IV PCA seems to have a beneficial effect on geriatric femoral-neck patients who underwent BHA with postoperative analgesia for reducing postoperative resting pain and complications, especially pneumonia and delirium.

A Randomized Controlled Trial to Evaluate the Analgesic Effectiveness of Periarticular Injections and Pericapsular Nerve Group Block for Patients Undergoing Total Hip Arthroplasty.

Pericapsular nerve group (PENG) block and periarticular injection (PAI) provide motor-sparing analgesia following hip surgery. We hypothesized that PAI offers non-inferior pain relief compared with PENG block in patients undergoing primary total hip arthroplasty (THA). In this randomized trial, 66 patients who underwent primary THA under spinal anesthesia were assigned to the PENG or PAI groups. The primary endpoint was the resting pain score 24 h postoperatively. The secondary endpoints included pain scores at rest and during movement at 6 and 48 h postoperatively, quadriceps strength at 24 h postoperatively, and opioid consumption at 24 and 48 h postoperatively. The mean difference in pain scores at rest between the two groups was 0.30 (95% confidence interval [CI], -0.78 to 1.39) at 24 h postoperatively. The upper 95% CI was lower than the non-inferiority margin, indicating non-inferior performance. No significant between-group differences were observed in the pain scores at 6 and 48 h postoperatively. Additionally, no significant differences in quadriceps strength and opioid consumption were observed between the two groups. The PAI and PENG blocks provided comparable postoperative analgesia during the first 48 h after primary THA. Further investigation is required to determine the optimal PAI technique and local anesthetic mixture.

Water Extract of Desalted Salicornia europaea Inhibits RANKL-Induced Osteoclast Differentiation and Prevents Bone Loss in Ovariectomized Mice.

Osteoporosis, which is often associated with increased osteoclast activity due to menopause or aging, was the main focus of this study. We investigated the inhibitory effects of water extract of desalted Salicornia europaea L. (WSE) on osteoclast differentiation and bone loss in ovariectomized mice. Our findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as demonstrated by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. The expression levels of genes related to osteoclast differentiation, including NFATc1, ACP5, Ctsk, and DCSTAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoylquinic acids (DCQAs) and saponins were detected in WSE, with 3,4-DCQA, 3,5-DCQA, and 4,5-DCQA being isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQAs, as preventive or therapeutic agents against osteoporosis and related conditions.

Could We Expect Postoperative Cup Anteversion after Total Hip Arthroplasty Using Postoperative Plain Anteroposterior and Lateral Radiograph? A Three-Dimensional Experimental Operation Study.

BACKGROUND: A postoperative radiograph in total hip arthroplasty (THA) is usually obtained to evaluate the inclination and anteversion of the acetabular components. However, there is no gold-standard method for calculating the exact inclination and anteversion of the acetabular components on post-THA radiographs. We aimed to measure the actual anteversion of the acetabular component on postoperative radiographs by obtaining correlation data between the virtual and actual acetabular component positioning using virtual three-dimensional (3D) surgery. METHODS: A total of 64 hip scans of 32 patients who underwent lower-extremity computed tomography (CT) were retrospectively reviewed. We reconstructed 3D models of the 64 hips using customized computer software (Mimics). Furthermore, to identify the safe zone of acetabular component position in THA, we performed virtual 3D surgery simulations for five anteversion (-10°, 0°, 10°, 20°, and 30°) and five inclination (20°, 30°, 40°, 50°, and 60°) types. We analyzed the acetabular anatomy using 3D models to measure the radiographic, anatomical, and operative anteversion (RA, AA, OA) and inclination (RI, AI, OI) angles. Additionally, we used the Woo-Morrey (WM) method to calculate the anteversion angle in the reconstructed cross-table lateral (CL) radiographs and determined the correlation between these measurements. RESULTS: The safe zone of the acetabular component was visualized on post-THA CL radiographs using the WM method of anteversion measurement based on the different anteversions and inclinations of the acetabular component. The AA, RA, OA, OI, and WM differed significantly between males and females (p value < 0.05). As the anatomical inclination or anteversion increased, the WM anteversion measurements also increased. The radiographic anteversion measurement best matched the WM method of measurement, followed by anatomical and operative methods. CONCLUSIONS: The actual anteversion of the acetabular component after THA can be measured on CL radiographs with the WM method using a 3D virtual program, with good reproducibility.

Peripheral Nerve Blockade in Total Hip Arthroplasty: A Retrospective Study with Propensity Score Matching.

The effect of peripheral nerve block (PNB) according to leg lengthening following total hip arthroplasty (THA) has not been studied yet. The purpose of this study was to investigate the effect of PNB according to the change in leg length after THA. From January 2016 to August 2021, 353 patients who underwent unilateral THA for osteonecrosis of the femoral head or osteoarthritis of the hip joint were retrospectively reviewed. The patients were divided into two groups for comparison: 217 patients who controlled postoperative pain using only intravenous venous patient-controlled analgesia (IV PCA) (PCA group) and 136 patients who controlled postoperative pain using PNB and IV PCA (PCA + PNB group). We further divided the patients into two groups (leg lengthening after surgery < 10 mm and >10 mm) and compared them. After propensity score matching, the PCA and PCA + PNB groups, with 134 patients each, were compared and analyzed. The pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 6, 24, and 48 h (p = 0.0001, 0.0009, and <0.0001, respectively). In the subgroup analysis, for patients whose limb lengthening was less than 10 mm after THA, the pain intensity at rest was significantly lower in the PCA + PNB group compared with that in the PCA group at postoperative 24 and 48 h (p = 0.0165 and 0.0015, respectively). However, in patients whose limb lengthening was more than 10 mm after THA, there was no significant difference between the pain intensity at activity and rest in the two groups at postoperative 6, 24, and 48 h (p > 0.05). PNB did not show superiority in terms of pain reduction in patients whose limb lengthening was more than 10 mm after THA. Further investigations on methods for reducing pain in patients whose leg length is increased by more than 10 mm are needed.

Oral Administration of Lactobacillus sakei CVL-001 Improves Recovery from Dextran Sulfate Sodium-Induced Colitis in Mice by Microbiota Modulation.

Inflammatory bowel disease (IBD) is an intestinal chronic inflammatory disease, and its incidence is steadily increasing. IBD is closely related to the intestinal microbiota, and probiotics are known to be a potential therapeutic agent for IBD. In our study, we evaluated the protective effect of Lactobacillus sakei CVL-001, isolated from Baechu kimchi, on dextran sulfated sodium (DSS)-induced colitis in mice. The oral administration of L. sakei CVL-001 according to the experimental schedule alleviated weight loss and disease activity in the mice with colitis. Furthermore, the length and histopathology of the colon improved. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß genes decreased in the colons of mice that were administered L. sakei CVL-001, whereas that of IL-10 increased. The expressions of genes coding for E-cadherin, claudin3, occludin, and mucin were also restored. In co-housed conditions, L. sakei CVL-001 administration did not improve disease activity, colon length, and histopathology. Microbiota analysis revealed that L. sakei CVL-001 administration increased the abundance of microbiota and altered Firmicutes/Bacteroidetes ratio, and decreased Proteobacteria. In conclusion, L. sakei CVL-001 administration protects mice from DSS-induced colitis by regulating immune response and intestinal integrity via gut microbiota modulation.

Silicone ring tourniquet could be a substitute for a conventional tourniquet in total knee arthroplasty with a longer surgical field: a prospective comparative study in simultaneous total knee arthroplasty.

INTRODUCTION: This study aimed to compare the clinical outcomes of silicon ring tourniquets and conventional pneumatic tourniquets in total knee arthroplasty (TKA). The study compared the operation time, total bleeding amount, length from the tourniquet distal end to the patella superior pole (L_TP), and complications related to the two tourniquet application methods and attempted to determine whether the silicon ring tourniquet has advantages over conventional pneumatic tourniquets. MATERIALS AND METHODS: This prospective comparative study included 30 patients who underwent bilateral simultaneous TKA for degenerative osteoarthritis in August to December 2021. All patients underwent TKA on one side with a conventional pneumatic tourniquet, while TKA on the other side with a silicon ring tourniquet. The primary outcomes were the L_TP, operation time, tourniquet time, total bleeding amount, total drainage amount, and postoperative visual analog scale (VAS) score of the tourniquet applied site at 6, 24, and 48 h postoperatively. The secondary outcome was tourniquet-related complications in both groups. RESULTS: L_TP was significantly longer in the silicon ring tourniquet group compared with that in the pneumatic tourniquet group (20.22 ± 2.74 cm versus 15.12 ± 2.40, p < 0.001). No significant difference was found in other results. The tourniquet applied site pain was less in the silicon ring tourniquet group (p = 0.037). CONCLUSIONS: Silicon ring tourniquet application resulted in better clinical outcomes than conventional pneumatic tourniquets in TKA. Because we can obtain a wider surgical field using silicon ring tourniquets without complications, silicon ring tourniquets could be a substitute for conventional pneumatic tourniquets in total knee arthroplasty or distal femoral surgeries.

D-galactose Intake Alleviates Atopic Dermatitis in Mice by Modulating Intestinal Microbiota.

Atopic dermatitis (AD) is one of the most prevalent, chronic and persistent inflammatory skin diseases closely associated with intestinal microbiota. To evaluate the effect of D-galactose intake on AD, we orally administered D-galactose to BALB/c mice whose ears and skin were treated with 2,4-dinitrochlorobenzene (DNCB). D-galactose alleviated DNCB-induced AD-like phenotypes such as redness, scaling/dryness and excoriation. Ear thickness was also decreased by D-galactose administration. Histopathological analysis revealed decreased epidermal thickening, infiltration of immune cells, especially mast cells, in the dermis. Total levels of serum IgE representing the immunological response of AD were decreased by D-galactose administration. Microbiota analysis showed that D-galactose administration restored gut microbiota profiles, which were altered in AD mice, characterized by increased abundance of Bacteroidetes and decreased abundance of Firmicutes. The increased abundance of Bacteroides and the decreased abundance of Prevotella and Ruminococcus were reversed by D-galactose treatment, following improvement of AD. Our results suggest the possible use of D-galactose as a prebiotic to alleviate AD by altering gut microbiota.

Improved analog switching characteristics of Ta2O5-based memristor using indium tin oxide buffer layer for neuromorphic computing.

A memristor is defined as a non-volatile memory switching two-terminal resistor, and a memristor with digital switching characteristics is widely studied as a next-generation non-volatile memory because of its simple structure, high integration density, and low power consumption. Recently, analog memristors with gradual resistance switching (RS) characteristics have garnered great attention because of their potential to implement artificial synapses that can emulate the brain functions. Transition metal oxides are thought to be strong candidate materials for the RS. In particular, tantalum oxide (TaOx)-based memristive devices provide stable and durable switching characteristics. TaOx-based memristors utilize analog switching characteristics and have excellent durability and reliability, so they can be applied as artificial synaptic device. In this study, the characteristics of analog RS using Ta2O5-based memristive devices were investigated. The current level of the Pt/Ta2O5/Pt memristors was improved by adjusting the thickness of Ta2O5. In particular, when an indium-tin-oxide (ITO) buffer layer was added to Ta2O5forming a Pt/ITO/Ta2O5/Pt heterostructured double-layer device, it showed more symmetrical potentiation and depression characteristics under both polarities than a single-layer device without ITO layer. The symmetrical and linear potentiation and depression characteristics are essential for the development of efficient memristor-based neuromorphic systems. Insertion of the ITO buffer layer improves linearity, symmetry, and stability of the analog RS properties of Ta2O5-based memristors to artificial synapses.

Type I Interferons Are Involved in the Intracellular Growth Control of Mycobacterium abscessus by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages.

Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-ß treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/ß receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-ß treatment enhanced the expression of iNOS gene and protein, and NO production in response to MAB. We also found that NO is essential for the intracellular growth control of MAB within macrophages in an inhibitor assay using iNOS-deficient cells. In addition, pretreatment of rIFN-ß before MAB infection in mice increased production of NO in the lungs at day 1 after infection and promoted the bacterial clearance at day 5. However, when alveolar macrophages were depleted by treatment of clodronate liposome, rIFN-ß did not promote the bacterial clearance in the lungs. Moreover, we found that a cytosolic receptor nucleotide-binding oligomerization domain 2 (NOD2) is required for MAB-induced TANK binding kinase 1 (TBK1) phosphorylation and IFN-ß gene expression in macrophages. Finally, increase in the bacterial loads caused by reduction of NO levels was reversed by rIFN-ß treatment in the lungs of NOD2-deficient mice. Collectively, our findings suggest that type I IFNs act as an intermediator of NOD2-induced NO production in macrophages and thus contribute to host defense against MAB infection.

Receptor-interacting protein kinase 2 contributes to host innate immune responses against Fusobacterium nucleatum in macrophages and decidual stromal cells.

PROBLEM: Chorioamnionitis is caused by a bacterial infection that ascends from the vagina and can cause adverse pregnancy outcomes (APOs). Fusobacterium nucleatum (F. nucleatum) is a periodontal pathogen associated with the occurrence of APOs. In this study, we evaluated whether receptor-interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide-binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against F. nucleatum. METHOD OF STUDY: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and Ripk2-deficient mice and hDSCs were cultured with F. nucleatum (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme-linked immunosorbent assay, Western blot analysis, real-time PCR, and nitrite assay. RESULTS: Fusobacterium nucleatum-induced production of IL-6, but not of TNF-α and IL-10, was lower in Ripk2-deficient BMDMs than in WT cells. Western blotting revealed a decrease in F. nucleatum-induced p65 phosphorylation in Ripk2-deficient macrophages, whereas mitogen-activated protein kinases activation was comparable between WT and Ripk2-deficient cells. The production of nitric oxide (NO) in response to F. nucleatum and the gene and protein expression of inducible NO synthase was impaired in Ripk2-deficient BMDMs. In hDSCs, F. nucleatum upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time-dependent manner. F. nucleatum also increased the production of IL-6, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2. CONCLUSIONS: In conclusion, Ripk2 signaling appears to contribute to the F. nucleatum-induced immune response and can be a preventive and therapeutic target against APOs.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Contouring the Mandible for Aesthetic Enhancement in Asian Patients.

A prominent mandible that gives a squared face in Asians is considered unattractive as it imparts a coarse and masculine image. Mandibular contouring surgery allows slender oval faces. The purpose of conventional mandible reduction is to make the lower face appear slim in frontal view and to have a smooth contour in lateral view. As shaping the lateral contour of the mandible alone may result in minimal improvement in the frontal view, surgical techniques to reduce the width of the lower face through narrowing genioplasty (i.e., the "V-line" surgery) and sagittal resection of the lateral cortex should be combined. Examination of the shape and symmetry, the relationship between the maxilla and the mandible, understanding overlying soft tissue contribution, and understanding the overall balance of the face are mandatory. An important factor influencing ideal facial shape is patient's personal preference, which is often influenced by his/her ethnic and cultural background. Especially when consulting patients of different nationalities or ethnic backgrounds, careful attention should be paid to the patient's aesthetic sensibility regarding the ideal or desirable facial shape. Narrowing the chin and modification of chin shape can be accomplished by narrowing genioplasty with central strip resection. This midsymphyseal sectioning procedure yields safe and very satisfactory results. This procedure not only augments the narrowing effect by leaving soft tissues attached to the bone but also enables modification of chin shape by altering the shape of resection. The surgeon should customize the surgery based on a comprehensive assessment of the patient's preoperative chin and mandible morphology complemented by an assessment of their aesthetic goals.

Cathelicidin-related Antimicrobial Peptide Contributes to Host Immune Responses Against Pulmonary Infection with Acinetobacter baumannii in Mice.

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP-/- mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP-/- mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP-/- neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP-/- neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

Comparison of the Prevalence of Low Back Pain and Related Spinal Diseases among Smokers and Nonsmokers: Using Korean National Health Insurance Database.

BACKGROUD: To compare the risk of low back pain (LBP) and related spinal diseases between smokers (exposure group) and nonsmokers (non-exposure group). No large registry study has so far investigated the association between smoking and LBP-related spinal diseases such as intervertebral disc disease, spinal stenosis, spinal instability, and spondylolisthesis. METHODS: A random sample was taken from the Korean National Health Insurance Research Database. In total, 204,066 men (160,105 smokers, 43,961 nonsmokers) who were followed up between 2002 and 2013 were included in the analysis. Patients with previous back pain or spinal disease in 2003 and 2004, patients with inappropriate data, and women (due to the lower percentage of smokers) were excluded. The Cox proportional hazard model was used to investigate the risk of LBP and related spinal diseases associated with smoking, while adjusting for demographic, clinical, and socioeconomic factors. RESULTS: The overall median follow-up period was 5.6 years (interquartile range, 3.48-8.43 years). Compared to the nonsmoker group, the smoker group had a higher incidence of LBP (p = 0.01), intervertebral disc disease (p < 0.001), spinal stenosis (p = 0.004), spinal instability (p < 0.001), and spondylolisthesis (p = 0.023). Compared to the nonsmoker group, the smoker group had a higher adjusted hazard ratio (HR) per year of LBP (HR, 1.18; 95% confidence interval [CI], 1.15 to 1.21), intervertebral disc disease (HR, 1.25; 95% CI, 1.21 to 1.30), spinal stenosis (HR, 1.52; 95% CI, 1.41 to 1.64), spinal instability (HR, 1.33; 95% CI, 1.24 to 1.44), and spondylolisthesis (HR, 1.49; 95% CI, 1.23 to 1.80). CONCLUSIONS: Smokers in male samples were at higher risk for LBP and related spinal diseases than nonsmokers.

Unveiling the Crucial Role of Type IV Secretion System and Motility of Helicobacter pylori in IL-1ß Production via NLRP3 Inflammasome Activation in Neutrophils.

Helicobacter pylori is a gram-negative, microaerophilic, and spiral-shaped bacterium and causes gastrointestinal diseases in human. IL-1ß is a representative cytokine produced in innate immune cells and is considered to be a key factor in the development of gastrointestinal malignancies. However, the mechanism of IL-1ß production by neutrophils during H. pylori infection is still unknown. We designed this study to identify host and bacterial factors involved in regulation of H. pylori-induced IL-1ß production in neutrophils. We found that H. pylori-induced IL-1ß production is abolished in NLRP3-, ASC-, and caspase-1/11-deficient neutrophils, suggesting essential role for NLRP3 inflammasome in IL-1ß response against H. pylori. Host TLR2, but not TLR4 and Nod2, was also required for transcription of NLRP3 and IL-1ß as well as secretion of IL-1ß. H. pylori lacking cagL, a key component of the type IV secretion system (T4SS), induced less IL-1ß production in neutrophils than did its isogenic WT strain, whereas vacA and ureA were dispensable. Moreover, T4SS was involved in caspase-1 activation and IL-1ß maturation in H. pylori-infected neutrophils. We also found that FlaA is essential for H. pylori-mediated IL-1ß production in neutrophils, but not dendritic cells. TLR5 and NLRC4 were not required for H. pylori-induced IL-1ß production in neutrophils. Instead, bacterial motility is essential for the production of IL-1ß in response to H. pylori. In conclusion, our study shows that host TLR2 and NLRP3 inflammasome and bacterial T4SS and motility are essential factors for IL-1ß production by neutrophils in response to H. pylori.

IL-10 Protects Mice From the Lung Infection of Acinetobacter baumannii and Contributes to Bacterial Clearance by Regulating STAT3-Mediated MARCO Expression in Macrophages.

Interleukin-10 plays important, yet contrasting, roles in host protection against bacterial infections and in the septic response. To determine the role of IL-10 in the host defense against Acinetobacter baumannii infection, wild-type (WT) and IL-10-deficient mice were infected intranasally with the bacteria. IL-10-deficient mice exhibited increased mortality, severe pathology, and excess production of proinflammatory cytokines and chemokines in the lungs, and increased bacterial burdens in bronchoalveolar lavage (BAL) fluids and lung homogenates after A. baumannii infection, compared to WT mice. Intranasal administration of recombinant IL-10 rescued mice from the lethality of the bacterial infection by promoting bacterial clearance and reducing production of cytokines and chemokines in the lungs. In vitro experiments revealed that IL-10 enhanced phagocytosis and bacterial killing by macrophages by upregulating the macrophage receptor with collagenous structure (MARCO). In addition, A. baumannii-induced activation of STAT3 was impaired in IL-10-deficient macrophages, which was essential for expression of MARCO. Intranasal adoptive transfer of WT macrophages resulted in significant increases in mice survival and bacterial clearance in IL-10-deficient mice infected with A. baumannii. Our results show that IL-10 played an important role in the host defense against pulmonary infection of A. baumannii by promoting the antibacterial function of macrophages by regulating MARCO expression through the STAT3-mediated pathway.

Clockwise Rotation of the Occlusal Plane for Aesthetic Purposes by Double Jaw Surgery without Orthodontic Treatment.

The occlusal plane angle is an important factor in lateral facial aesthetics. Low occlusal plane facial profiles appear planar and long-faced, whereas high occlusal plane facial profiles are considered more attractive, especially in Asian regions. Clockwise rotation of the occlusal plane for truly aesthetic purposes can be accomplished with double jaw surgery, without need for orthodontic treatments. Patients with normal occlusion who desired to improve their lateral facial aesthetics were included in this study. A conventional Le Fort I osteotomy was followed by a sagittal split ramus osteotomy under general anesthesia. The movement of the maxillomandibular complex was determined in accord with a preoperative analysis. From 2015 to 2017, 43 patients with normal occlusion underwent double jaw surgery without orthodontic treatment. Whereas all patients were subjectively satisfied with the surgery, two underwent orthodontic treatment to correct mild occlusal discrepancies noticed after surgery. There were no delayed occlusal problems or relapses reported during the study. For patients who desired to improve their lateral facial aesthetics but had normal occlusion, orthognathic surgery without orthodontic treatment can be effective. Clockwise rotation of the occlusal plane by double jaw surgery without orthodontic treatment resulted in satisfactory aesthetic outcomes with stable and reliable long-term results. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.