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Systemic lupus erythematosus (SLE) is a chronic inflammatory disease caused by autoantibodies. Serum samples from patients with SLE ( n = 10) were compared with those from normal controls (NCs, n = 5) using 21K protein chip analysis to identify a biomarker for SLE, revealing 63 SLE-specific autoantibodies. The anti-chaperonin-containing t-complex polypeptide-1 (TCP1) antibody exhibited higher expression in patients with SLE than in NCs. To validate the specificity of the anti-TCP1 antibody in SLE, dot blot analysis was conducted using sera from patients with SLE ( n = 100), rheumatoid arthritis (RA; n = 25), Behçet's disease (BD; n = 28), and systemic sclerosis (SSc; n = 30) and NCs ( n = 50). The results confirmed the detection of anti-TCP1 antibodies in 79 of 100 patients with SLE, with substantially elevated expression compared to both NCs and patients with other autoimmune diseases. We performed an enzyme-linked immunosorbent assay to determine the relative amounts of anti-TCP1 antibodies; markedly elevated anti-TCP1 antibody levels were detected in the sera of patients with SLE (50.1 ± 17.3 arbitrary unit (AU), n = 251) compared to those in NCs (33.9 ± 9.3 AU), RA (35 ± 8.7 AU), BD (37.5 ± 11.6 AU), and SSc (43 ± 11.9 AU). These data suggest that the anti-TCP1 antibody is a potential diagnostic biomarker for SLE.

Introduction: This study aimed to demonstrate the potential of activated leukocyte cell adhesion molecule (ALCAM), hemopexin (HPX), and peroxiredoxin 6 (PRDX6) as urine biomarkers for systemic lupus erythematosus (SLE)., Methods: Urine samples were collected from 138 Korean patients with SLE from the Ajou Lupus Cohort and 39 healthy controls (HC). The concentrations of urine biomarkers were analyzed using enzyme-linked immunosorbent assay kits specific for ALCAM, HPX, and PRDX6, respectively. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic utility, and Pearson's correlation analysis was conducted to assess the relationships between the disease activity and urine biomarkers., Results: Patients with SLE and patients with lupus nephritis (LN) showed significantly elevated ALCAM, HPX, and PRDX6 levels compared with HCs. ALCAM, HPX, and PRDX6 showed significant diagnostic values, especially for lupus nephritis (LN), with areas under the receiver operating characteristic curve for LN was 0.850 for ALCAM (95% CI, 0.778-0.921), 0.781 for HPX (95% CI, 0.695-0.867), and 0.714 for PRDX6 (95% CI, 0.617-0.812). Correlation analysis revealed that all proteins were significantly associated with anti-double stranded DNA antibody (ALCAM, r = 0.350, p < 0.001; HPX, r = 0.346, p < 0.001; PRDX6, r = 0.191, p = 0.026) and SLEDAI (ALCAM, r = 0.526, p < 0.001; HPX, r = 0.479, p < 0.001; PRDX6, r = 0.262, p = 0.002). Results from the follow-up of the three biomarker levels in these patients revealed a significant decrease, showing a positive correlation with changes in SLEDAI-2k scores (ALCAM, r = 0.502, p < 0.001; HPX, r = 0.475, p < 0.001; PRDX6, r = 0.245, p = 0.026), indicating their potential as indicators for tracking disease activity., Discussions: Urinary ALCAM, HPX, and PRDX6 levels have diagnostic value and reflect disease activity in Korean patients with SLE, emphasizing their potential for non-invasive monitoring and treatment response evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Kim, Baek, Jung, Kim, Lee and Suh.)

Purpose: With the revision of the Organ and Transplantation Act in 2018, the hand has become legal as an area of transplantable organs in Korea. In January 2021, the first hand allotransplantation since legalization was successfully performed, and we have performed a total of three successful hand transplantation since then. By comparing and incorporating our experiences, this study aimed to provide a comprehensive reconstructive solution for hand amputation in Korea., Materials and Methods: Recipients were selected through a structured preoperative evaluation, and hand transplantations were performed at the distal forearm level. Postoperatively, patients were treated with three-drug immunosuppressive regimen, and functional outcomes were monitored., Results: The hand transplantations were performed without intraoperative complications. All patients had partial skin necrosis and underwent additional surgical procedures in 2 months after transplantation. After additional operations, no further severe complications were observed. Also, patients developed acute rejection within 3 months of surgery, but all resolved within 2 weeks after steroid pulse therapy. Motor and sensory function improved dramatically, and patients were very satisfied with the appearance and function of their transplanted hands., Conclusion: Hand transplantation is a viable reconstructive option, and patients have shown positive functional and psychological outcomes. Although this study has limitations, such as the small number of patients and short follow-up period, we should focus on continued recovery of hand function, and be careful not to develop side effects from immunosuppressive drugs. Through the present study, we will continue to strive for a bright future regarding hand transplantation in Korea., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Background: Seasonal variation and sunlight exposure can impact serum vitamin D levels, potentially influencing lupus symptoms. We investigated seasonal vitamin D levels and their correlation with clinical manifestations and disease activity in systemic lupus erythematosus (SLE)., Methods: Serum 25(OH) vitamin D3 (25(OH)D3) levels were categorised as deficient (25(OH)D3 < 10 ng/mL), insufficient (10-30 ng/mL) and sufficiency (>30 ng/mL) in participants analysed in winter (n = 407) and summer (n = 377). Logistic regression analysis was performed to assess the impact of vitamin D levels on achieving a lupus low disease activity state (LLDAS), stratified by season., Results: The mean serum 25(OH)D3 levels differed significantly between the winter and summer measurement groups (22.4 vs. 24.2 ng/mL; p = .018). The prevalences of vitamin D deficiency, insufficiency and sufficiency in the winter group were 12.8%, 66.6% and 20.6%, respectively, compared with 4.5%, 67.9% and 27.6% in the summer group. Achieving LLDAS was highest in the vitamin D sufficiency group (winter: 56.6%, summer: 55%) and lowest in the vitamin D deficiency group (winter: 15.4%, summer: 13.6%), with significant differences (all p < .001). Multivariate analysis identified SLE disease activity index ≤4, normal anti-double-stranded DNA and vitamin D sufficiency as significant factors for achieving LLDAS in both seasons., Conclusions: Sufficient vitamin D levels are important for achieving LLDAS in patients with SLE during winter and summer. Therefore, physicians should pay attention to the adequacy of vitamin D levels and consider recommending vitamin D supplementation for patients with vitamin D insufficiency., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Since the first description of the keystone perforator island flap (KPIF) in 2003, several modifications have been suggested to enhance its coverage ability. However, locoregional flaps have limited its use in chronic wounds due to decreased elasticity around the defect. We investigated the use of a bipedicled KPIF (bKPIF), which covers a defect while completely elevating the median part of the flap from the fascia. A retrospective chart review of 20 consecutive patients who underwent classical type I KPIF (n = 10) or bKPIF (n = 10) reconstruction from June 2020 to December 2022 was performed. Baseline characteristics, indications, operative details, healing time, and complications were analyzed and compared between the two groups. The average defect size was 30 cm 2 in type I KPIF and 36.6 cm 2 in bKPIF, and an average flap size of 86.5 cm 2 was covered in type I KPIF, larger than bKPIF at 73.8 cm 2 . The flap/defect ratio was significantly lower in the bKPIF group (p < 0.02), with an average of only 55% pedicular area. The average advancement distance in the bKPIF group was 1.85 cm (standard deviation 0.78) greater than that in the type 1 KPIF group. There was no significant difference between the groups in terms of operation time, complete healing time, and complications. All ten bKPIFs were successful without any flap necrosis. Even though the mean pedicular area in the bKPIF group was nearly half compared with that in the type I KPIF group, it was sufficient to perfuse the entire flap without any major complications. This novel technique using bKPIF has potential clinical relevance, as evidenced by the enhanced ability to cover chronic defects with severe scarring. Lateralizing the hotspots to the bilateral corners of the flap is the mechanism that facilitates this potential., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The revision of the Korea Organ Transplantation Act (KOTA) in 2018 included hand/arm among the organs that can be transplanted. The first hand transplantation since the revision of KOTA took place in January 2021. A 62-year-old male patient experienced hand amputation on July 13, 2018, by a catapult injury. The patient first visited our institute 3 months after the injury. After serial interviews and an overall evaluation, the patient was registered on the hand transplantation waiting list in January 2020. On January 9, 2021, the patient underwent hand transplantation at the right distal forearm level. The total operation time was 17 hours 15 minutes, and the cold ischemic time was 4 hours 9 minutes. Postoperative immunosuppression was administered based on the protocol used for kidney transplantation. Two acute rejection episodes occurred, on postoperative days 33 and 41. Both rejection episodes were reversible with rescue therapy of a higher tacrolimus trough level, steroid pulse therapy, and topical immunosuppressants. Controlled passive range of motion exercise was started on postoperative day 10. Dynamic splint was applied on postoperative day 18. At 1 year, graft maintenance and functional improvement were satisfactory, and the patient showed a Disabilities of Arm, Shoulder and Hand score of 25.8. We successfully performed the first hand transplantation surgery under the KOTA amendment. It came from the organic and effective cooperation of plastic, orthopaedic, and transplantation departments and we believe it will guarantee the future ongoing success., Competing Interests: Conflict of Interest W.J.L. is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by the production of autoantibodies and high cholesterol levels. HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors have exhibited anti-inflammatory effects in several clinical trials. We conducted this study to evaluate the effect of rosuvastatin on inflammatory responses in lupus-prone mice., Methods: MRL/ lpr mice were intraperitoneally injected with rosuvastatin (10 mg/kg, n=4) or vehicle (2% dimethyl sulfoxide, n=4) five times a week from 13 to 17 weeks of age. The serum levels of low-density lipoprotein (LDL) cholesterol and autoantibodies were measured, as well as the urine levels of albumin. Renal tissues were stained for histopathological analysis. Concentrations of key inflammatory cytokines were measured in the serum, and messenger RNA (mRNA) levels in target organs (kidney, spleen, and lymph nodes) were evaluated., Results: Rosuvastatin treatment significantly decreased serum LDL cholesterol concentration in MRL/ lpr mice. However, the clinical manifestations and autoantibody titres did not improve with rosuvastatin treatment. In addition, serum inflammatory cytokines and proteinuria did not change. Histopathological analysis of the kidneys revealed no improvement. When assessing the expression of mRNA, treatment with rosuvastatin decreased tumor necrosis alpha and interleukin-17 concentration in spleen and kidney tissue and in the kidneys and lymph nodes of MRL/ lpr mice, respectively., Conclusion: Although it can decrease inflammatory cytokines in the lymphoid organs and kidneys of MRL/ lpr mice, treatment with rosuvastatin is insufficient to alleviate SLE., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean College of Rheumatology. All rights reserved.)

Immunoglobulin gamma-3 chain C (IGHG3) levels have been detected in the blood and tissue of patients with systemic lupus erythematosus (SLE). This study aims to assess its clinical value by measuring and comparing levels of IGHG3 in different body fluids in patients with SLE. The levels of IGHG3 in saliva, serum, and urine from 181 patients with SLE and 99 healthy controls were measured and analyzed. In patients with SLE and healthy controls, salivary IGHG3 levels were 3078.9 ± 2473.8 and 1413.6 ± 1075.3 ng/mL, serum IGHG3 levels were 478.1 ± 160.9 and 364.4 ± 97.9 μg/mL, and urine IGHG3 levels were 64.0 ± 74.5 and 27.1 ± 16.2 ng/mL, respectively (all p < 0.001). Salivary IGHG3 was correlated with ESR (correlation coefficient [r], 0.173; p = 0.024). Serum IGHG3 was correlated with leukocyte count (r, -0.219; p = 0.003), lymphocyte count (r, 0.22; p = 0.03), anti-dsDNA antibody positivity (r, 0.22; p = 0.003), and C3 levels (r, -0.23; p = 0.002). Urinary IGHG3 was correlated with hemoglobin level (r, -0.183; p = 0.021), ESR (r, 0.204; p = 0.01), anti-dsDNA antibody positivity (r, 0.262; p = 0.001), C3 levels (r, -0.202; p = 0.011), and SLE disease activity index (r, 0.332; p = 0.01). Urinary IGHG3 was higher in patients with nephritis than in those without (119.5 ± 110.0 vs. 49.8 ± 54.4 ng/mL; p < 0.01). IGHG3 was increased in the saliva, serum, and urine of patients with SLE. While salivary IGHG3 was not identified to be specific to SLE disease activity, serum IGHG3 showed correlations with clinical characteristics. Urinary IGHG3 levels were associated with disease activity and renal involvement in SLE.

Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS., Approach and Results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001)., Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of American Association for the Study of Liver Diseases.)

As breast conserving surgery increases in the surgical treatment of breast cancer, partial mastectomy is also increasing. Polycaprolactone (PCL) is a polymer that is used as an artifact in various parts of the human body based on the biocompatibility and mechanical properties of PCL. Here, we hypothesized that a PCL scaffold can be utilized for the restoration of breast tissue after a partial mastectomy. To demonstrate the hypothesis, a PCL scaffold was fabricated by 3D printing and three types of spherical PCL scaffold including PCL scaffold, PCL scaffold with collagen, and the PCL scaffold with breast tissue fragment were implanted in the rat breast defect model. After 6 months of implantation, the restoration of breast tissue was observed in the PCL scaffold and the expression of collagen in the PCL scaffold with collagen was seen. The expression of TNF-α was significantly increased in the PCL scaffold, but the expression of IL-6 showed no significant difference in all groups. Through this, it showed the possibility of using it as a method to conveniently repair tissue defects after partial mastectomy of the human body.

Purpose: Robotic head and neck surgery is widespread nowadays. However, in the reconstruction field, the use of robotic operations is not. This article aimed to examine methodologies for conventional head and neck reconstruction after robotic tumor surgery in an effort to obtain further options for future reconstruction manipulations., Materials and Methods: A retrospective review of all patients who received head and neck robot surgery and conventional reconstructive surgery between October 2016 and September 2021., Results: In total, 53 cases were performed. 67.9% of the tumors were greater than 4 cm. Regarding defect size, 47.2% of the lesions were greater than 8 cm. In terms of TNM stage, stage 3 disease was recorded in 26.4% and stage 4 in 52.8%. To make a deep and narrow field wider, we changed the patient's posture in pre-op field, additional dissection was done. We used radial forearm flap mostly (62.2%)., Conclusion: Conventional head and neck reconstruction after robotic ENT cancer surgery is possible. One key step is to secure additional space in the deep and narrow space left after robotic surgery. For this, we opted for a radial forearm flap mostly. This can be performed as a bridgehead to perform robotic head and neck reconstruction., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Objectives: This study aimed to elucidate the potential of serum, urine, and saliva S100 calcium-binding protein A8 protein (S100A8) levels as biomarkers for systemic lupus erythematosus (SLE)., Methods: Serum, urine, and saliva samples were obtained from 249 patients with SLE from the Ajou lupus cohort and 52 age- and sex-matched healthy controls (HCs). The concentrations of S100A8 were quantified using an ELISA, and a receiver operating characteristic curve was used to analyze whether they may be used as biomarkers for diagnosing SLE., Results: Among 249 SLE patients included in our study, the mean SLE disease activity index (SLEDAI)-2K was 7.16 ± 5.61, and the number of patients with lupus flare was 11. Patients with SLE showed a 2.7-fold increase in serum S100A8 levels compared with that in HCs (1,890.6 vs. 709 pg/ml, p < 0.001). In urine and saliva, the average S100A8 levels were significantly higher in patients with SLE compared with those in HCs (urine, 2,029.4 vs. 1,096.7 pg/ml, p = 0.001; saliva, 290,496.3 vs. 47,742 pg/ml, p < 0.001). For SLE diagnosis, the area under the receiver operating characteristic curve was 0.831 for serum S100A8 (95% CI, 0.765-0.897), 0.751 for urine S100A8 (95% CI, 0.648-0.854), and 0.729 for salivary S100A8 (95% CI, 0.646-0.812). Pearson's correlation analysis showed that S100A8 in serum, urine, and saliva was significantly associated with the SLEDAI (r = 0.267, p < 0.001; r = 0.274, p < 0.001; and r = 0.629, p < 0.001, respectively). Among the clinical manifestations, nephritis was the most influential factor related to SLE in the concentration of S100A8 in serum, urine, and saliva., Conclusion: This is the first study to show that the expression of S100A8 in serum, urine, and saliva is significantly higher in patients with SLE than in HCs and is associated with disease activity markers. Therefore, we suggest that S100A8 protein could be a potential biomarker for SLE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Jung, Lee, Baek, Kim and Suh.)

Introduction: Presently, super-thin ALT flap, which is elevated above the superficial fascial plane, is gaining popularity. Although there is a huge demand for thin flaps for various types of extremity reconstruction, the technique for ALT flap thinning remains controversial. In this study, we investigated the distance and vector between penetrating points of perforators in deep and superficial fascia using color duplex and clinical measurement to suggest a reliable super-thin flap elevation technique., Materials and Methods: From June 2018 to February 2020, 44 patients with various types of defects who were treated using super-thin ALT flaps were enrolled; 69 surgically detected perforators were analyzed. All patients' flap outcomes and characteristics of the perforators were analyzed. In addition, the effects of patients' body mass index (BMI) and thickness of super-thin flap were evaluated., Results: The average traveling length of perforator at the deep adipofascial layer (DAL) was 2.43 cm, and the vector of traveling was randomly arranged. The mean thickness of super-thin ALT flap was 6.8 mm. The thickness of super-thin flap was not significantly correlated with patients' BMI (ranged from 17.4 to 34.2 kg/m 2 ; p = 0.183)., Conclusion: The novel elevation technique for super-thin ALT might be useful, as evidenced by perforator traveling distance and vector in DAL. Preoperative color duplex ultrasonography is helpful to detect the running course of the perforators during elevating the flap. This anatomic concept must be considered to obtain the reliability of the super-thin ALT flap., Competing Interests: Conflict of Interest The authors have nothing to disclose., (Copyright © 2021 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Toll-like receptors (TLRs) play a major role in the innate immune system. Several studies have shown the regulatory effects of TLR-mediated pathways on immune and inflammatory diseases. Dysregulated functions of TLRs within the endosomal compartment, including TLR7/9 trafficking, may cause systemic lupus erythematosus (SLE). TLR signaling pathways are fine-tuned by Toll/interleukin-1 receptor (TIR) domain-containing adapters, leading to interferon (IFN)-α production. This study describes a TLR inhibitor peptide 1 (TIP1) that primarily suppresses the downstream signaling mediated by TIR domain-containing adapters in an animal model of lupus and patients with SLE. The expression of most downstream proteins of the TLR7/9/myeloid differentiation factor 88 (MyD88)/IFN regulatory factor 7 signaling was downregulated in major tissues such as the kidney, spleen, and lymph nodes of treated mice. Furthermore, the pathological analysis of the kidney tissue confirmed that TIP1 could improve inflammation in MRL/ lpr mice. TIP1 treatment downregulated many downstream proteins associated with TLR signaling, such as MyD88, interleukin-1 receptor-associated kinase, tumor necrosis factor receptor-associated factor 6, and IFN-α, in the peripheral blood mononuclear cells of patients with SLE. In conclusion, our data suggest that TIP1 can serve as a potential candidate for the treatment of SLE.

Objective: Systemic lupus erythematosus (SLE) is a common chronic autoimmune inflammatory disease According to recent studies, signaling through Toll-like receptor (TLR) protein, which promotes the production of inflammatory cytokines, leads to the development of SLE TLR-inhibitory peptide 1 (TIP1) has been newly identified for the treatment of autoimmune diseases., Methods: The effect of TIP1 was analyzed in an SLE mouse model (MRL/ lpr ) The mice in the control treatment group (n=5) were administered an intravenous injection of phosphate-buffered saline twice weekly, whereas the mice in the TIP1 treatment group (n=6) were administered an intravenous injection of TIP1 (1 nmol/g) twice weekly MRL/ mpj mice (n=5) were selected as normal controls The mice were injected for 4 weeks between 14 and 18 weeks of age, followed by assays of their spleen, kidneys, lymph nodes, serum, and urine., Results: The antinuclear antibody and inflammatory cytokine (interferon-α) in the serum as well as levels of albumin in the urine of the mice in the TIP1 treatment group had decreased when compared to those of mice in the control treatment group Kidney inflammation in mice in the TIP1 treatment group was alleviated The mRNA expression levels of TLR7- or TLR9-related downstream signaling molecules also decreased in all organs of the mice in the TIP1 treatment group., Conclusion: Intravenous treatment with TIP1 reduces symptoms and markers of inflammation in MRL/ lpr mice Hence, TIP1 is a promising medication for the treatment of SLE., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported., (Copyright © 2021 by The Korean College of Rheumatology. All rights reserved.)

We aimed to characterize the salivary protein components and identify biomarkers in patients with systemic lupus erythematosus (SLE). A proteomic analysis using two-dimensional gel electrophoresis and mass spectrometry was performed to determine the alterations of salivary proteins between patients with SLE and healthy controls, and the concentrations of the candidate proteins were measured through Western blot analysis and the enzyme-linked immunosorbent assay. The 10 differentially expressed protein spots were immunoglobulin gamma-3 chain C region (IGHG3), immunoglobulin alpha-1 chain C region, protein S100A8, lactoferrin, leukemia-associated protein 7, and 8-oxoguanine DNA glycosylase. The patients with SLE exhibited enhanced salivary IGHG3 (3.9 ± 2.15 pg/mL) and lactoferrin (4.7 ± 1.8 pg/mL) levels compared to patients with rheumatoid arthritis (1.8 ± 1.01 pg/mL and 3.2 ± 1.6 pg/mL, respectively; p < 0.001 for both) or healthy controls (2.2 ± 1.64 pg/mL and 2.2 ± 1.7 pg/mL, respectively; p < 0.001 for both). The salivary IGHG3 levels correlated with the erythrocyte sedimentation rate ( r = 0.26, p = 0.01), anti-double-stranded DNA (dsDNA) antibody levels ( r = 0.25, p = 0.01), and nephritis ( r = 0.28, p = 0.01). The proteomic analysis revealed that the salivary IGHG3 levels were associated with SLE and lupus disease activity, suggesting that salivary IGHG3 may be a promising noninvasive biomarker for SLE.

Purpose: To retrospectively evaluate the chest computed tomography (CT) findings of coronavirus disease 2019 (COVID-19) in patients with mild clinical symptoms at a single hospital in South Korea., Materials and Methods: CT scans of 87 COVID-19 patients [43 men and 44 women; median age: 41 years (interquartile range: 26.1-51.0 years)] with mild clinical symptoms (fever < 38℃ and no dyspnea) were evaluated., Results: CT findings were normal in 39 (44.8%) and abnormal in 48 (55.2%) patients. Among the 48 patients with lung opacities, 17 (35.4%) had unilateral disease and 31 (64.6%) had bilateral disease. One (2.1%) patient showed subpleural distribution, 9 (18.8%) showed peribronchovascular distribution, and 38 (79.2%) showed subpleural and peribronchovascular distributions. Twenty-two (45.8%) patients had pure ground-glass opacities (GGOs) with no consolidation, 17 (35.4%) had mixed opacities dominated by GGOs, and 9 (18.8%) had mixed opacities dominated by consolidation. No patients demonstrated consolidation without GGOs., Conclusion: The most common CT finding of COVID-19 in patients with mild clinical symptoms was bilateral multiple GGO-dominant lesions with subpleural and peribronchovascular distribution and lower lung predilection. The initial chest CT of almost half of COVID-19 patients with mild clinical symptoms showed no lung parenchymal lesions. Compared to relatively severe cases, mild cases were more likely to manifest as unilateral disease with pure GGOs or GGO-dominant mixed opacities and less likely to show air bronchogram., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)

The stopping power of liquid water was measured for carbon ions with energies in the Bragg peak region using the inverted Doppler shift attenuation method. Among the semiempirical data, the results of this work agree best with the data recommended in the Errata and Addendum of ICRU Report No. 73, which is based on an I value of 78 eV for water. The agreement was worse when the present results were compared to the newer recommendation of the ICRU published in ICRU Report No. 90. The srim code seems to slightly overestimate the stopping power of water for carbon ions above 3 MeV. A semiexperimental stopping power of water for α particles was derived from the present results using the theoretical ratio between the stopping powers of water for carbon ions and α particles computed by means of the casp code. These values agree well with the experimental data for α particles within the uncertainties.

Critics argue that service firms should pay more attention to human resource management's psychological and voluntary aspects to contribute to overall organizational development. The purpose of this study was to investigate the effects of physical self-efficacy on the psychological well-being and organizational citizenship behavior among hotel employees and the moderating effects of leisure-time physical activity on the relationships between the previously mentioned variables. To achieve the research purpose, 346 hotel employees working at the room, food, beverage, and kitchen departments of 10 hotels located in Seoul, South Korea, participated in the study. The researchers visited their department meetings and provided a brief description of the present study and informed consent forms to participate in the study. After obtaining written informed consent forms, the researchers distributed the surveys and asked participants to complete them. Several statistical analyses, including descriptive statistics, confirmatory factor analysis (CFA) for examining the hypothesized model's psychometric properties, and structural equation modeling (SEM) for testing the hypotheses were conducted using SPSS Ver. 23.0 and AMOS 23.0. Results revealed that perceived physical ability and self-presentation confidence, and psychological well-being positively affected organizational citizenship behavior. Perceived physical ability also had a positive effect on psychological well-being. Lastly, leisure-time physical activity had a partial moderating role in the relationships between the variables mentioned above. This study suggests that promoting employees' participation in leisure-time physical activity is needed to improve service workers' organizational citizenship behavior via physical self-efficacy and psychological well-being enhancement.

Toll-like receptors (TLRs) play a fundamental role in the inflammatory response against invading pathogens. However, the dysregulation of TLR-signaling pathways is implicated in several autoimmune/inflammatory diseases. Here, we show that a novel small molecule TLR-inhibitor (TAC5) and its derivatives TAC5-a, TAC5-c, TAC5-d, and TAC5-e predominantly antagonized poly(I:C) (TLR3)-, imiquimod (TLR7)-, TL8-506 (TLR8)-, and CpG-oligodeoxynucleotide (TLR9)-induced signaling pathways. TAC5 and TAC5-a significantly hindered the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), reduced the phosphorylation of mitogen-activated protein kinases, and inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6. Besides, TAC5-a prevented the progression of psoriasis and systemic lupus erythematosus (SLE) in mice. Interestingly, TAC5 and TAC5-a did not affect Pam 3 CSK 4 (TLR1/2)-, FSL-1 (TLR2/6)-, or lipopolysaccharide (TLR4)-induced TNF-α secretion, indicating their specificity towards endosomal TLRs (TLR3/7/8/9). Collectively, our data suggest that the TAC5 series of compounds are potential candidates for treating autoimmune diseases such as psoriasis or SLE.

Despite being crucial for combating microbes, paradoxical Toll-like receptors (TLRs) signaling have been associated with the aggravation of multiple immune disorders such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, and nonalcoholic steatohepatitis. The stoichiometry and precise arrangement of the interaction of adapters (via their Toll/interleukin-1 receptor [TIR] domains) are indispensable for the activation of TLRs and of downstream signaling cascades. Among adapters, plasma membrane-anchored MyD88 adaptor-like (MAL) has the potential for BB-loop-mediated self-oligomerization and interacts with other TIR domain-containing adaptors through αC and αD helices. Here, we used information on the MAL-αC interface to exploit its pharmacophores and to design a decoy peptide (MIP2) with broad-range TLR-inhibitory abilities. MIP2 abrogated MyD88- and TRIF-dependent lipopolysaccharide (LPS)-induced TLR4 signaling in murine and human cell lines and manifested a therapeutic potential in models of psoriasis, systemic lupus erythematosus, nonalcoholic steatohepatitis, and sepsis. Levels of hallmark serological and histological biomarkers were significantly restored and the disease symptoms were substantially ameliorated by MIP2 treatment of the animals. Collectively, our biophysical, in vitro, and in vivo findings suggest that MIP2 has broad specificity for TLRs and may be effective in modulating autoimmune complications caused by microbial or environmental factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: TLRs are some of the actively pursued drug-targets in immune disorders. Owing to a recent surge in the cognizance of TLR structural biology and signalling pathways, numerous therapeutic modulators, ranging from low-molecular-weight organic compounds to polypeptides and nucleic acid agents have been developed., Methods: A penetratin-conjugated small peptide (TIP3), derived from the core β-sheet of TIRAP, was evaluated in vitro by monitoring the TLR-mediated cytokine induction and quantifying the protein expression using western blot. The therapeutic potential of TIP3 was further evaluated in TLR-dependent in vivo disease models., Findings: TIP3 blocks the TLR4-mediated cytokine production through both the MyD88- and TRIF-dependent pathways. A similar inhibitory-effect was exhibited for TLR3 but not on other TLRs. A profound therapeutic effect was observed in vivo, where TIP3 successfully alleviated the inflammatory response in mice model of collagen-induced arthritis and ameliorated the disease symptoms in psoriasis and SLE models., Interpretation: Our data suggest that TIP3 may be a potential lead candidate for the development of effective therapeutics against TLR-mediated autoimmune disorders., Funding: This work was supported by the National Research Foundation of Korea (NRF-2019M3A9A8065098, 2019M3D1A1078940 and 2019R1A6A1A11051471). The funders did not have any role in the design of the present study, data collection, data analysis, interpretation, or the writing of the manuscript., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Progress in the field of ionising radiation (IR) metrology achieved in the BioQuaRT project raised the question to what extent radiobiological investigations would benefit from metrological support of the applied methodologies. A panel of experts from the medical field, fundamental research and radiation protection attended a workshop at Physikalisch-Technische Bundesanstalt to consult on metrology needs related to biological radiation effects. The panel identified a number of metrological needs including the further development of experimental and computational techniques for micro- and nanodosimetry, together with the determination of related fundamental material properties and the establishment of rigorous uncertainty budgets. In addition to this, a call to develop a metrology support for assisting quality assurance of radiobiology experiments was expressed. Conclusions from the workshop were presented at several international conferences for further discussion with the scientific community and stakeholder groups that led to an initiative within the metrology community to establish a European Metrology Network on biological effects of IR., (© The Author(s) 2019. Published by Oxford University Press.)

Systemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

In recent years, several approaches have been proposed to provide an understanding of the enhanced relative biological effectiveness of ion beams based on multi-scale models of their radiation effects. Among these, the BioQuaRT project was the only one which focused on developing metrology for a multi-scale characterization of particle track structure. The progress made within the BioQuaRT project has motivated the formation of a department 'Radiation Effects' at PTB dedicated to metrological research on ionizing radiation effects. This paper gives an overview of the department's present research directions and shortly discusses ideas for the future development of metrology related to biological effects of ion beams that are based on a stakeholder consultation., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Liver X receptors (LXRs) have emerged as important regulators of inflammatory gene expression. Previously, we had reported that an LXR α gene promoter polymorphism (-1830 T > C) is associated with systemic lupus erythematosus (SLE). Therefore, we assessed cytokine expression in relation to LXR α polymorphism in monocyte-derived macrophages from patients with SLE. Macrophages were obtained after 72 hours of culture of human monocytes supplemented with phorbol 12-myristate 13-acetate. Cells were transfected with LXR α promoter constructs. Additionally, peripheral blood mononuclear cell- (PBMC-) derived macrophages from the patients were evaluated for proinflammatory cytokines in relation to the genotypes of LXR α -1830 T > C. The expression of LXR α was increased in macrophages; levels of proinflammatory cytokines were decreased with LXR α expression. Production of proinflammatory cytokines varied depending on LXR α -1830 T > C genotype. In particular, expression of LXR α was decreased and that of proinflammatory cytokines was increased for LXR α -1830 TC genotype compared to that for TT genotype. The data were consistent in PBMC-derived macrophages from patients with SLE. Increased proinflammatory cytokines is related to TLR7 and TLR9 expression. These data suggest that the expression levels of LXR α , according to LXR α -1830 T > C genotype, may contribute to the inflammatory response by induction of inflammatory cytokines in SLE.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with various clinical manifestations and serologic markers. In this study, we analyzed nine polyamine (PA) profiles of plasma from patients with SLE and healthy controls (HCs), and the relationship between the PA profiles and disease activity. PA alterations in plasma of 44 patients with SLE and fever were investigated using gas chromatography mass spectrometry (GC-MS) in selected ion monitoring mode using N-ethoxycarbonyl/ N-pentafluoropropionyl derivatives, and compared with those of 43 HCs. Patients with SLE and HCs showed differences in five of nine PA profiles. Among five changed PA levels, four PAs, namely N 1 -acetylcadaverine, spermidine, N 1 -acetylspermidine, and spermine, were dramatically decreased. However, the level of cadaverine was increased in patients with SLE. In the partial correlation with PA profiles and disease activity markers of SLE, several disease activity markers and nutritional markers were correlated with cadaverine, spermidine, and N 8 -acetylspermidine. Thus, our results provide a comprehensive understanding of the relationship between PA metabolomics and disease activity markers in patients with SLE.

Coupling is the process that links bone resorption to bone formation in a temporally and spatially coordinated manner within the remodeling cycle. Several lines of evidence point to the critical roles of osteoclast-derived coupling factors in the regulation of osteoblast performance. Here, we used a fractionated secretomic approach and identified the axon-guidance molecule SLIT3 as a clastokine that stimulated osteoblast migration and proliferation by activating β-catenin. SLIT3 also inhibited bone resorption by suppressing osteoclast differentiation in an autocrine manner. Mice deficient in Slit3 or its receptor, Robo1, exhibited osteopenic phenotypes due to a decrease in bone formation and increase in bone resorption. Mice lacking Slit3 specifically in osteoclasts had low bone mass, whereas mice with either neuron-specific Slit3 deletion or osteoblast-specific Slit3 deletion had normal bone mass, thereby indicating the importance of SLIT3 as a local determinant of bone metabolism. In postmenopausal women, higher circulating SLIT3 levels were associated with increased bone mass. Notably, injection of a truncated recombinant SLIT3 markedly rescued bone loss after an ovariectomy. Thus, these results indicate that SLIT3 plays an osteoprotective role by synchronously stimulating bone formation and inhibiting bone resorption, making it a potential therapeutic target for metabolic bone diseases.

Introduction: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with heterogeneous clinical manifestations mediated by immune dysregulation., Objectives: We aimed to analyze the metabolomic differences in free fatty acids (FFAs) between patients with SLE and healthy controls (HCs)., Methods: In this study, the levels of 24 FFAs, as their tert-butyldimethylsilyl derivatives, in the plasma of 41 patients with SLE and 41 HCs, were investigated using gas chromatography with mass spectrometry in selected-ion monitoring mode., Results: The results showed that patients with SLE and HCs had significantly different levels of 13 of the 24 FFAs. The levels of myristic, palmitoleic, oleic, and eicosenoic acids were significantly higher, whereas the levels of caproic, caprylic, linoleic, stearic, arachidonic, eicosanoic, behenic, lignoceric, and hexacosanoic acids were significantly lower in patients with SLE, than in the HCs. In the partial-correlation analysis of the FFA profiles and markers of disease activity of SLE, several metabolic markers correlated with SLE disease activity., Conclusions: Our results provide a comprehensive understanding of the relationship between FFAs and markers of SLE disease activity. Thus, this approach has promising potential for the discovery of metabolic biomarkers of SLE.

Purpose: Posttraumatic edema in facial bone fracture patients may interfere with the operation field and delay the schedule. Thus, swiftly reducing the edema alleviates patient discomfort and advances the operation date. Ice packing and compression bandages are often used for such a purpose, but such methods are often inconvenient for the face. In this study, we aim to analyze the effect of light-emitting diode (LED) (590/830 nm)-based low-level laser therapy (LLLT) in posttraumatic edema in facial bone fracture patients., Materials and Methods: We conducted a prospective cohort study of 40 patients who were admitted to a single institution for facial bone fracture. The patients were divided into two groups of 20 each, treated either with LLLT or with sham treatment light. We used an LLLT device that consists of planar LED-based arrays with double wavelengths 590 nm and 830 nm. The patients were treated with either true or sham light from posttraumatic day 1-5, twice a day. After each treatment, the volume of a patient's face was measured with a 3-dimensional camera. We analyzed and compared the changes in facial edema. The Wilcoxon rank sum test was conducted for statistical comparison of the two groups, and significance was set to the level of p < 0.05., Results: The sex ratio and mean age of the two groups were of little difference. The fracture sites included the nasal bone, orbital wall, zygomaticomaxillary bone, mandible, and frontal sinus. Mechanisms of injury included fall, assault, traffic accident, sports, and gunshot. The total operation rate of both groups was equal to 85%. Our analysis showed a 16.5% reduction of edema in the LLLT group and 7.3% in the sham light group. The edema reduction was statistically significantly greater in the LLLT group than in the sham light group (p < 0.047)., Conclusion: LED-based LLLT is recently receiving attention worldwide for its cost-effectiveness and large coverage area compared to traditional laser therapy. Recent studies support its effectiveness in various areas such as wound healing, skin rejuvenation, and pain alleviation. In this study, we treated facial bone fracture patients with LED-based LLLT, and showed its effectiveness in reducing posttraumatic edema., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Understanding the anatomy of the muscles and other structures of the chest is of great importance in breast surgery. We have conducted the first analysis of the overall variations and relationships among the pectoralis major (PM), inframammary fold (IMF), and pectoralis minor (Pm). We studied 30 patients and 10 cadavers, leading to a total of 50 breasts. Preoperatively, the breast width was measured, and the costal origin of the lowest IMF point was marked. Intraoperatively, we recorded the costal origins of the PM and IMF, PM width, the distance between the PM and IMF, and the relationship and distance between the PM and Pm. Among the patients, PMs originated from the sixth rib in 80% and above the IMF in 66.67%. The mean distances between the PM and IMF were 10.5 mm in the patients and 16 mm in the cadavers. The mean PM/breast width ratio was 0.82 in the patients and 0.85 in the cadavers. The PM and Pm mostly crossed on the fourth or fifth rib, and the average angles between the two muscles were 23.5° and 21.4° in the patients and cadavers, respectively. This study is the first to analyze the anatomical variations of the PM, IMF, and Pm simultaneously. We also examined the differences between Western and Asian populations. Understanding the anatomy is undoubtedly crucial for breast surgery, and here we provide a firm guide to the variations to be expected during operations, which can lead to successful outcomes. Clin. Anat. 30:357-361, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Purpose: Breast volume assessment is one of the most important steps during implant-based breast reconstruction because it is critical in selecting implant size. According to previous studies, there is a close relationship between the mastectomy specimen weight and resected breast volume. The aim of this study was to evaluate long-term patient satisfaction with implant-based breast reconstruction guided by the ratio of implant volume to mastectomy specimen weight. In doing so, we describe the ideal ratio for patient satisfaction., Methods: A total of 84 patients who underwent implant-based breast reconstruction for breast cancer were included in this study. The patients were grouped by the ratio of implant size to mastectomy specimen weight (group 1, <65%; group 2, 65%-75%; and group 3, >75%). Outcome analysis was performed using a questionnaire of patient satisfaction and the desired implant size., Results: Patient satisfaction scores concerning the postoperative body image, size, and position of the reconstructed breast were significantly higher in group 2. The average ratio of the ideal implant volume to mastectomy specimen weight for each group was 71.9% (range, 54.5%-96.7%), with the differences across the three groups being not significant ( p =0.244)., Conclusion: Since there is an increase in breast reconstruction, selecting the appropriate breast implant is undoubtedly important. Our novel technique using the ratio of implant volume to mastectomy specimen weight provides physicians a firm guide to intraoperative selection of the proper implant in reconstructive breast surgery., Competing Interests: CONFLICT OF INTEREST: The authors declare that they have no competing interests.

Perfect facial and body symmetry is an important aesthetic concept which is very difficult, if not impossible, to achieve. Yet, facial asymmetries are commonly encountered by plastic and reconstructive surgeons. Here, we present a case of posttraumatic facial asymmetry successfully treated with a unique concept of facial flap repositioning. A 25-year-old male patient visited our department with severe posttraumatic facial asymmetry. There was deviated nasal bone and implant to the right, and the actual facial appearance asymmetry was much more severe compared to the computed tomography, generally shifted to the right. After corrective rhinoplasty, we approached through intraoral incision, and much adhesion from previous surgeries was noted. We meticulously elevated the facial flap of both sides, mainly involving the cheeks. The elevated facial flap was shifted to the left, and after finding the appropriate location, we sutured the middle portion of the flap to the periosteum of anterior nasal spine for fixation. We successfully freed the deviated facial tissues and repositioned it to improve symmetry in a single stage operation. We conclude that facial flap repositioning is an effective technique for patients with multiple operation history, and such method can successfully apply to other body parts with decreased tissue laxity., Competing Interests: No potential conflict of interest relevant to this article was reported.

For track structure simulations in the Bragg peak region, measured electron emission cross sections of DNA constituents are required as input for developing parameterized model functions representing the scattering probabilities. In the present work, double differential cross sections were measured for the electron emission from vapor-phase pyrimidine, tetrahydrofuran, and trimethyl phosphate that are structural analogues to the base, the sugar, and the phosphate residue of the DNA, respectively. The range of proton energies was from 75 keV to 135 keV, the angles ranged from 15° to 135°, and the electron energies were measured from 10 eV to 200 eV. Single differential and total electron emission cross sections are derived by integration over angle and electron energy and compared to the semi-empirical Hansen-Kocbach-Stolterfoht (HKS) model and a quantum mechanical calculation employing the first Born approximation with corrected boundary conditions (CB1). The CB1 provides the best prediction of double and single differential cross section, while total cross sections can be fitted with semi-empirical models. The cross sections of the three samples are proportional to their total number of valence electrons.

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4(-/-)) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1(Tg+)) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4(-/-) and fat-1(Tg+) mice over two generations to generate four genotypes of mice littermates: Ffar4(+/+);fat-1(Tg-), Ffar4(+/+);fat-1(Tg+), Ffar4(-/-);fat-1(Tg-), and Ffar4(-/-);fat-1(Tg+). Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1(Tg+) mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In a high-fat diet-fed model, male fat-1(Tg+) mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

The ionization and fragmentation of methane induced by low-energy (E0 = 66 eV) electron-impact is investigated using a reaction microscope. The momentum vectors of all three charged final state particles, two outgoing electrons, and one fragment ion, are detected in coincidence. Compared to the earlier study [Xu et al., J. Chem. Phys. 138, 134307 (2013)], considerable improvements to the instrumental mass and energy resolutions have been achieved. The fragment products CH4 (+), CH3 (+), CH2 (+), CH(+), and C(+) are clearly resolved. The binding energy resolution of ΔE = 2.0 eV is a factor of three better than in the earlier measurements. The fragmentation channels are investigated by measuring the ion kinetic energy distributions and the binding energy spectra. While being mostly in consistence with existing photoionization studies the results show differences including missing fragmentation channels and previously unseen channels.

Background: Rupture is an important complication of breast implants. Before cohesive gel silicone implants, rupture rates of both saline and silicone breast implants were over 10%. Through an analysis of ruptured implants, we can determine the various factors related to ruptured implants., Methods: We performed a retrospective review of 72 implants that were removed for implant rupture between 2005 and 2014 at a single institution. The following data were collected: type of implants (saline or silicone), duration of implantation, type of implant shell, degree of capsular contracture, associated symptoms, cause of rupture, diagnostic tools, and management., Results: Forty-five Saline implants and 27 silicone implants were used. Rupture was diagnosed at a mean of 5.6 and 12 years after insertion of saline and silicone implants, respectively. There was no association between shell type and risk of rupture. Spontaneous was the most common reason for the rupture. Rupture management was implant change (39 case), microfat graft (2 case), removal only (14 case), and follow-up loss (17 case)., Conclusions: Saline implants have a shorter average duration of rupture, but diagnosis is easier and safer, leading to fewer complications. Previous-generation silicone implants required frequent follow-up observation, and it is recommended that they be changed to a cohesive gel implant before hidden rupture occurs.

We study the low-energy (E0 = 26 eV) electron-impact induced ionization and fragmentation of tetrahydrofuran using a reaction microscope. All three final-state charged particles, i.e., two outgoing electrons and one fragment ion, are detected in triple coincidence such that the momentum vectors and, consequently, the kinetic energies for charged reaction products are determined. The ionic fragments are clearly identified in the experiment with a mass resolution of 1 amu. The fragmentation pathways of tetrahydrofuran are investigated by measuring the ion kinetic energy spectra and the binding energy spectra where an energy resolution of 1.5 eV has been achieved using the recently developed photoemission electron source. Here, we will discuss the fragmentation reactions for the cations C4H8O(+), C4H7O(+), C2H3O(+), C3H6(+), C3H5(+), C3H3(+), CH3O(+), CHO(+), and C2H3(+).

Monte Carlo simulations of the particle track structure require accurate ion- and electron-impact cross-section data of the medium. These data are scarce and often inconsistent when measured by different groups. In this work, literature data on ionisation cross sections (CSs) of nitrogen and propane for protons with energies 0.1-10 MeV are reviewed and implemented in the code PTra. Methane data were used to obtain proton-impact CSs of propane due to their absence in the literature. PTra is benchmarked by comparing simulated particle-track parameters to experimental results, measured with an ion-counting nanodosemeter., (© The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The stopping power of liquid water was measured for the first time for carbon ions in the energy range between 1 and 6 MeV using the inverted Doppler shift attenuation method. The feasibility study carried out within the scope of the present work shows that this method is well suited for the quantification of the controversial condensed phased effect in the stopping power for heavy ions in the intermediate energy range. The preliminary results of this work indicate that the stopping power of water for carbon ions with energies prevailing in the Bragg-peak region is significantly lower than that of water vapor. In view of the relatively high uncertainty of the present results, a new experiment with uncertainties less than the predicted difference between the stopping powers of both water phases is planned.

Background: Recent research has shown that reactive oxygen species (ROS) play a significant role in the development and persistence of neuropathic pain through central sensitization via N-methyl-D-aspartate (NMDA) receptor activation. In the present study, we examined whether the intraperitoneal administration of vitamins C and E alone or together could alleviate mechanical allodynia in a chronic post-ischemia pain (CPIP) rat model., Methods: Vitamins C and E were administered intraperitoneally to 48 male Sprague Dawley rats once per day for 3 days before hindpaw ischemia-reperfusion (I/R) injury was induced. On the third day, the CPIP rat model was produced by inducing ischemia in the left hindpaw by applying an O-ring for 3 h, followed by reperfusion. Three days after reperfusion, hindpaw mechanical allodynia was assessed by measuring the withdrawal response to von Frey filament stimulation. The rats were sacrificed immediately after behavioral testing to determine the phosphorylated NMDA receptor subunit 1 (pNR1) and extracellular-signal-regulated kinases (pERK) levels in the spinal cord., Results: When the antioxidant vitamins C and E were administered intraperitoneally to CPIP rats, I/R injury-induced mechanical allodynia was attenuated, and pNR1 and pERK levels were decreased in the rat spinal cord. Additionally, the co-administration of both vitamins had an increased antiallodynic effect., Conclusions: The reduced phosphorylated NR1 and ERK levels indicate that vitamins C and E inhibit the modulation of spinal cord neuropathic pain processing. Co-administration of vitamins C and E had a greater antiallodynic effect.

Track structure Monte Carlo simulations are frequently applied in micro- and nanodosimetry to calculate the radiation transport in detail. The use of a well-validated set of cross section data in such simulation codes ensures accurate calculations of transport parameters, such as ionization yields. These cross section data are, however, scarce and often discrepant when measured by different groups. This work surveys literature data on ionization and charge-transfer cross sections of nitrogen, methane, and propane for electrons, protons, and helium particles, focusing on the energy range between 100 keV and 20 MeV. Based on the evaluated data, different models for the parametrization of the cross section data are implemented in the code ptra, developed for simulating proton and alpha particle transport in an ion-counting nanodosimeter. The suitability of the cross section data is investigated by comparing the calculated mean ionization cluster size and energy loss with experimental results in either nitrogen or propane. For protons, generally good agreement between measured and simulated data is found when the Rudd model is used in ptra. For alpha particles, however, a considerable influence of different parametrizations of cross sections for ionization and charge transfer is observed. The ptra code using the charge-transfer data is, nevertheless, successfully benchmarked by the experimental data for the calculation of nanodosimetric quantities, but remaining discrepancies still have to be further investigated (up to 13% lower energy loss and 19% lower mean ionization cluster size than in the experiment). A continuation of this work should investigate data for the energy loss per interaction as well as differential cross section data of nitrogen and propane. Interpolation models for ionization and charge-transfer data are proposed. The Barkas model, frequently used for a determination of the effective charge in the ionization cross section, significantly underestimates both the energy loss (by up to 19%) and the mean ionization cluster size (up to 65%) for alpha particles. It is, therefore, not recommended for particle-track simulations.

Farnesoid X receptor (FXR) is a nuclear receptor that functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR(-/-) ) in vivo resulted in a significant reduction in bone mineral density by 4.3% to 6.6% in mice 8 to 20 weeks of age compared with FXR(+/+) mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, tartrate-resistant acid phosphatase (TRACP) staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR(-/-) mice compared with FXR(+/+) mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR(-/-) mice compared with FXR(+/+) mice in concert with a significant reduction in type I collagen a1(Col1a1), ALP, and runt-related transcription factor 2 (Runx2) gene expressions. Cultures of bone marrow-derived macrophages from FXR(-/-) mice exhibited an increased number of osteoclast formations and protein expression of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). In female FXR(-/-) mice, although bone mineral density (BMD) was not significantly different from that in FXR(+/+) mice, bone loss was accelerated after an ovariectomy compared with FXR(+/+) mice. In vitro, activation of FXR by bile acids (chenodeoxycholic acid [CDCA] or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced extracellular signal-regulated kinase (ERK) and β-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol (FOH 1%) diet marginally prevented ovariectomy (OVX)-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways; ie, bone formation and resorption., (© 2013 American Society for Bone and Mineral Research.)

Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx knockout show a complete absence of bone formation, whereas Osx conditional knockout in osteoblasts produce an osteopenic phenotype after birth. Here, we questioned whether Osx has a potential role in regulating physiological homeostasis. In Osx heterozygotes expressing low levels of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly elevated, indicating that reduced Osx expression may reflect an inflammatory-prone state. In particular, the expression of interleukin-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressing osteoblasts, and transcriptionally down-regulated by Osx. Although no significant differences were revealed in renal morphology and function between Osx heterozygotes and wild-type under normoxic conditions, recovery of kidneys after ischemic damage was remarkably delayed in Osx heterozygotes, as indicated by elevated blood urea nitrogen and creatinine levels, and by morphological alterations consistent with acute tubular necrosis. Eventually, protracted low Osx expression level caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury and the delayed renal repair after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important in terms of preventing the onset of an inflammatory-prone state.