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Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.

Background The ideal method of administering tranexamic acid (TXA) for reverse total shoulder arthroplasty (RTSA) remains unknown. We aimed to evaluate TXA efficacy according to 3 administration methods after RTSA. Methods Overall, 102 patients who underwent RTSA using a single implant between September 2016 and November 2018 were randomized to the following groups according to the TXA administration method: intravenous (n = 34; 1 g + 0.9% normal saline 100 mL), topical (n = 33; 2 g + 0.9% normal saline 50 mL), and combined groups (n = 34). Patients were enrolled in 4 tertial referral hospitals for prospective multicenter studies. The primary outcome was a hemoglobin decrease in 24 hours postoperatively; secondary outcomes were total drain volume, transfusion rate, and calculated total blood loss. Results Demographic data, including preoperative hemoglobin levels, were not different among the 3 groups, but the average age was higher in the combined group (P = .038). Hemoglobin decrease (1.8 ± 1.1 vs. 1.8 ± 1.0 vs. 2.0 ± 1.1 g/dL, P = .769), total drain volume (209.2 ± 147.6 vs. 167.2 ± 102.0 vs. 166.0 ± 118.7, P = .270), and total blood loss (701.1 ± 352.3 vs. 656.5 ± 285.6 vs. 699.0 ± 248.7 mL, P = .810) were not significantly different among the 3 groups (all P > .05). The transfusion rate was higher in the intravenous group (n = 4), whereas only 1 patient had transfusion in the topical group and none in the combined group, although the difference was not statistically significant (P = .084). Conclusion Blood loss did not differ among TXA administration methods after RTSA. However, considering the risk of complication in intravenous TXA, topical TXA after RTSA may be safer, even for patients with normal risk for venous thromboembolic complication.

Background Hidradenitis suppurativa (HS) is a devastating chronic inflammatory skin disease with frequent recurrences. Various systemic treatments and procedures have been used but the efficacy of fractional microneedling radiofrequency (FMR) has not been reported. Aim To evaluate the clinical and histological efficacy of FMR in the treatment of HS lesions. Methods An 8-week, prospective, split-body, unblinded study was conducted, which enrolled 10 adult patients with mild to moderate HS to receive 3 sessions of FMR treatment biweekly. HS severity was assessed using the number and type of lesions, HS Physician Global Assessment (HS-PGA) and the modified Sartorius score (mSS). Skin biopsies were performed on participants to assess change in inflammation before and after FMR. Results Severity of HS was significantly reduced on the FMR-treated side of the body, but not on the control side. Inflammatory HS lesions were significantly reduced after 4 weeks, while HS-PGA and mSS were significantly decreased after 6 weeks. Immunohistochemistry staining showed decreased expression of inflammatory markers including neutrophil elastases, interleukin (IL)-8 and IL-17, tumour necrosis factor-α, transforming growth factor-β1 and matrix metalloproteinases. Conclusion FMR may be a viable treatment option for mild to moderate HS.

Background: The inflammatory lesions of acne leave scars which greatly affect patients’ quality of life. Treatment options targeting both acne and acne scars are still lacking. Objectives: To evaluate the clinical efficacy of epidermal growth factor ointment (EGFO) on acne and acne scars. Methods: The study design was 12-week, prospective, split-face, single-blinded. The 36 patients with mild to moderate acne vulgaris applied EGFO on one side of the face and the vehicle ointment on the other side twice daily. The patients were assessed every 4 weeks by acne lesion and scar counts, investigator’s global assessment for acne (IGA) and scar (SGA), and the ECCA scar grading scale. Biopsies were performed before and after treatment. Results: Acne and acne scars were significantly improved on EGFO-treated sides, while control sides were not. Acne lesion and scar counts were significantly reduced after 4 weeks, while IGA, SGA, and ECCA grade significantly decreased after 8 weeks. Immunohistochemistry showed decreased expression of keratin 16, NF-κB p65, IL-1α, and IL-8, and increased expression of TGF-β1, elastin, and collagen type 1, 3 after treatment. Conclusions: EGFO can be a treatment option targeting acne and acne scars.

Herbal extracts with fewer adverse effects can be an alternative to these drugs because they can target various molecular pathways of acne pathogenesis.To evaluate the clinical efficacy of herbal extracts (mangosteen,Sixty patients were randomized in a 1:1 ratio to receive blinded treatment with herbal extracts or vehicle for 8 weeks. Inflammatory and non-inflammatory acne lesion counts, Investigator's Global Assessment, patient's satisfaction and safety profiles were assessed. We also performed skin biopsy at baseline and week 8 to confirm immunological changes with immunohistochemistry staining.By the end of the study period, both inflammatory and non-inflammatory acne lesion counts were significantly decreased in herbal extracts group (This herbal extracts can be a new therapeutic option for patients with mild to moderate acne vulgaris who are reluctant to use drugs.

Objective Odontoblast differentiation from dental pulp stem cells (DPSCs) is involved in a cascade of key biological events for maintaining pulp-dentin homeostasis, repair and regeneration. A pulp regeneration biomaterial (mineral trioxide aggregate (MTA)) increased intracellular reactive oxygen species (ROS) levels during differentiation, ameliorating the differentiating of DPSCs into odontoblasts. Here, ceria nanoparticles (CNP) were incorporated as an insoluble antioxidant into commercially available MTA (CMTA), and the odontoblastic differentiation of human DPSCs was investigated. Methods The CMTA was fabricated from MTA and CNP conjugation up to 4 wt%, and the compressive strength, surface morphology after setting and setting time were investigated. Furthermore, the alkaline phosphatase (ALP) assay, Alizarin Red staining (ARS) and quantitative real-time polymerase chain reaction (qPCR) were performed to evaluate odontoblastic differentiation in an indirect co-culture system using inserts with pores. To reveal the underlying mechanism, the ROS levels and ion release were measured. Statistical analysis was performed by one-way analysis of variance with a Tukey post hoc test (P Results CMTA significantly elevated the odontoblastic differentiation of hDPSCs measured by ALP activity, ARS, and odontoblastic gene expression, whereas the other physico-mechanical properties were relatively maintained. Upregulation of gene expression from CMTA was reversed with hydrogen peroxide. CMTA could reduce the increased intracellular ROS levels of hDPSCs by approximately 70% during differentiation, similar to when an antioxidant was used, without changing the ion release and pH of the media. Significance CMTA could be useful dental materials for regenerating dentin-pulp complexes by instructing intracellular ROS during differentiation to achieve beneficial biological functions. This study suggests a new direction of dental nanomaterials in treating pulp-dentin complexes.

BACKGROUND: Preterm labor is a leading risk factor for neonatal death and long-term impairment and linked closely with inflammation. Non-obstetric surgery is occasionally needed during pregnancy and the anesthetic drugs or surgery itself can give rise to inflammation. Here, we examined the influence of propofol pretreatment on the expression of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) after lipopolysaccharide (LPS) stimulation. In addition, we evaluated the expression of pro-inflammatory cytokines and nuclear factor kappa B (NF-κB). METHODS: Human amnion-derived WISH cells were used to investigate the effect of propofol on the LPS-induced expression of inflammatory substances involved in preterm labor. For the experiment, WISH cells were pretreated with various concentrations propofol (0.01–10 μg/ml) for 1 h and then treated with LPS (1 μg/ml) for 24 h. Cytotoxicity was evaluated using MTT assay. PGE(2) concentration was assessed by ELISA. Protein expressions of COX-2, PGE(2) and NF-κB were analyzed by western blotting analysis. RT-PCR was used for analysis of mRNA expression of COX-2, PGE(2), interlukin (IL)-1β and tumor necrosis factor (TNF)-α. RESULTS: Propofol showed no cytotoxicity on the WISH cells. LPS-induced PGE(2) production and COX-2 and PGE(2) expression were decreased after propofol pretreatment. Propofol also attenuated the LPS-induced mRNA expression of IL-1β and TNF-α. Moreover, the activation of NF-κB was inhibited by propofol pretreatment on LPS-stimulated WISH cells. CONCLUSION: We demonstrated that propofol suppresses the expression of inflammatory substances enhanced by LPS stimulation. Furthermore, this inhibitory effect of propofol on the inflammatory substance expression is mediated by suppression of NF-κB activation.

Cell reprogramming can satisfy the demands of obtaining specific cell types for applications such as tissue regeneration and disease modeling. Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized nodules. Bulk and single-cell RNA sequencing identified a distinct ciOG population. ciOG formed mineralized tissue in an ectopic site of immunodeficiency mice, unlike the original fibroblasts. Osteogenic reprogramming was modulated under engineered culture substrates. When generated on a nanofiber substrate ciOG accelerated bone matrix formation in a calvarial defect, indicating that the engineered biomaterial promotes the osteogenic capacity of ciOG in vivo. Furthermore, the ciOG platform recapitulated the genetic bone diseases Proteus syndrome and osteogenesis imperfecta, allowing candidate drug testing. The reprogramming of human fibroblasts into osteogenic cells with a chemical cocktail thus provides a source of specialized cells for use in bone tissue engineering and disease modeling.

Background Teres minor (TM) muscle hypertrophy in large to massive rotator cuff tears (RCTs) has been considered a compensatory change to atrophy of the infraspinatus (ISP). However, few reports have assessed its relation to the prognosis after rotator cuff repair. Methods A total of 139 patients who underwent arthroscopic repair of large to massive RCTs involving the ISP between January 2013 and December 2015 were retrospectively investigated. Occupational ratios of the ISP (OR_ISP) and TM (OR_TM) were measured by sagittal magnetic resonance imaging (MRI). Rotator cuff healing was evaluated by MRI 1 year postoperatively, and functional outcomes using the Simple Shoulder Test (SST) and Constant score and external rotator (ER) strength by isokinetic muscle performance test (IMPT) were measured. Results A total of 116 patients completed the MRI and IMPT at 1 year postoperatively, and functional scores were measured at least 2 years postoperatively. Of these, the repaired tendon had not healed in 34 patients (29%). There was a highly negative correlation between OR_ISP and OR_TM both pre- and postoperatively (Pearson correlation = –0.52 and –0.54, respectively). Preoperative OR_ISP was significantly higher in the healed than in the healing failure group (0.47 ± 0.10 vs. 0.41 ± 0.12, P = .02); however, postoperative OR_ISP and pre- and postoperative OR_TM were not. The preoperative OR_ISP cutoff value for healing was 0.46. For functional outcomes, only postoperative OR_ISP showed a statistical correlation with SST, Constant score (P = .04 and .03, respectively), and ER strength (P = .02). Conclusion TM muscle hypertrophy in large to massive RCT appears to be a compensatory change in the progression of atrophy of the ISP muscle and was not a significant indicator of either better healing of the repaired rotator cuff tendon or better function. Only preoperative OR_ISP was an independent prognostic factor affecting rotator cuff healing after repair of large to massive RCTs.

The last few decades have seen an increased interest in ‘Mental Health Literacy (MHL)’ which addresses knowledge and beliefs relating to mental health problems and is likely to hinder treatment-seeking behaviors. Although MHL research to date has explored various mental disorders, far too little attention has been paid to Internet Gaming Disorder (IGD) and Problematic Smartphone use (PSU). The objective of this study is to develop an MHL questionnaire for IGD and PSU by adopting the MHL approach in the previous literature and examine MHL of IGD and PSU in Korean teenagers by focusing on their ability to recognize addictions, and perceptions and help-seeking attitudes towards a person with addictions. The current study also aimed to compare Korean teenagers’ MHL depending on low- and high-risk of IGD and PSU. A total of 169 teenagers aged 10 and 16 years were recruited from schools and children’s centers in Seoul and completed the newly developed MHL questionnaire and screening questionnaires for IGD and PSU. The MHL questionnaire for IGD and PSU was designed as a vignette-based questionnaire that depicted behavioral characteristics of a severe problem with Internet and smartphone usage. Korean teenagers had a poor ability to recognize IGD and PSU and were more prone to seek parental help than professional help. The current study also showed that teenagers had better recognition of IGD than PSU and perceived that a person with IGD has a more difficult life than a person with PSU. Furthermore, a low-risk or high-risk group of IGD or PSU showed minimal differences in MHL. The current study provided empirical evidence to support a need to develop educational programs to improve Korean teenagers’ MHL for both IGD and PSU.

O-GlcNAc transferase (OGT) is an enzyme that catalyzes the O-GlcNAc modification of nucleocytoplasmic proteins and is highly expressed in many types of cancer. However, the mechanism regulating its expression in cancer cells is not well understood. This study shows that OGT is a substrate of the E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) which plays an important role in cancer pathogenesis. Although LSD2 histone demethylase has already been reported as an E3 ubiquitin ligase in lung cancer cells, we identified XIAP as the main E3 ubiquitin ligase in colon cancer cells. Interestingly, OGT catalyzes the O-GlcNAc modification of XIAP at serine 406 and this modification is required for the E3 ubiquitin ligase activity of XIAP toward specifically OGT. Moreover, O-GlcNAcylation of XIAP suppresses colon cancer cell growth and invasion by promoting the proteasomal degradation of OGT. Therefore, our findings regarding the reciprocal regulation of OGT and XIAP provide a novel molecular mechanism for controlling cancer growth and invasion regulated by OGT and O-GlcNAc modification.

BACKGROUND A decreased acromiohumeral distance (AHD) is commonly detected in patients with massive rotator cuff tears (mRCTs). Most studies evaluating fixed humeral elevation have used preoperative or postoperative standardized radiography and not stress radiography. This study aimed to evaluate the predictive role of the preoperative AHD measured using stress radiography (AHD_stress) in rotator cuff healing and function after arthroscopic repair of mRCTs. METHODS The data of 113 patients who underwent arthroscopic repair of mRCTs were analyzed. Postoperative cuff integrity was evaluated using magnetic resonance imaging at 1 year, and shoulder function was evaluated at a mean of 34.9 ± 17.8 months (range, 24-92 months) postoperatively. Forty-seven patients showed healing failure. Propensity score matching (1-1) was performed between the healed group and healing failure group. Thirty-eight patients in each group were matched in the final analysis. The AHD and AHD_stress were defined as the shortest distances from the inferior acromion to the superior humerus on standard anteroposterior radiography and stress radiography (5.4-kg weight applied inferiorly in a neutral position), respectively. The AHD difference (AHD_diff) was defined as the difference between the AHD and AHD_stress values. Receiver operating characteristic curve analysis was performed to determine cutoff values for significant variables. RESULTS No difference in the mean preoperative AHD was found between the healed group (7.5 ± 2.0 mm) and healing failure group (6.9 ± 2.2 mm, P = .234). The AHD_diff value was significantly higher in the healed group (4.4 ± 2.1 mm) than in the healing failure group (3.0 ± 2.0 mm, P = .002; cutoff, 3.2 mm). Patients with an AHD_diff value ≥ 3.2 mm showed a lower healing failure rate (28.9% vs. 71.1%, P < .001) and higher functional scores than patients with an AHD_diff value < 3.2 mm. The AHD_diff value was higher in patients with an American Shoulder and Elbow Surgeons (ASES) score ≥ 80 (4.9 ± 1.9 mm) than in those with an ASES score < 80 (3.1 ± 2.1 mm, P = .024). Among patients with healing failure, only the postoperative AHD showed a significant difference between those with an ASES score ≥ 80 (7.0 ± 2.5 mm) and those with an ASES score < 80 (4.8 ± 2.1 mm, P = .009; cutoff, 4.8 mm). CONCLUSION A reducible AHD, which increased by ≥ 3.2 mm under stress radiography, can be a favorable predictor of rotator cuff healing and function after arthroscopic repair of mRCTs. Our findings suggest that this new and simple radiologic parameter should be considered preoperatively and would be helpful to determine appropriate treatment strategies.

Acne vulgaris is a universal skin disease and it may leave a scar when the original skin lesion disappears. These scars can cause cosmetic problems and psychological burden, leading to poor quality of life of patients. Acne scars are classified into atrophic scars and hypertrophic scars. As most of the acne scars are atrophic, many studies have been conducted focusing on the treatment of atrophic lesions. This study was conducted to investigate the underlying pathogenesis of acne hypertrophic scars by identifying roles of fibrogenetic and inflammatory markers. Skin biopsy samples were obtained from hypertrophic scars of face and back and from adjacent normal tissues as control group. Some samples from back were immature hypertrophic scars and the other samples were in mature stages. Immunohistochemistry staining and quantitative PCR were performed for fibrogenetic and inflammatory markers. Both in mature and immature hypertrophic scars, vimentin and α-SMA were increased. Production of TGF-β3 protein as well as transcription of TGF-β3 was also significantly elevated. In contrast, expression of TGF-β1 showed no increase. Instead, expression levels of SMAD2 and SMAD4 were increased. Elevations of CD45RO, TNF-α and IL-4 and reduction of IL-10 were observed. In immature hypertrophic scars, IGF-1R and insulin-degrading enzyme expression were increased. Increased apoptosis was observed in immature stages of hypertrophic scars but not in mature stages. Elevations of TGF-β3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.

Excess reactive oxygen species are detrimental to wound repair. Remifentanil decreases reactive oxygen species generation and inflammatory response; however, its effects on oxidative cell injury are not completely understood. Therefore, we investigated the effects of remifentanil on human keratinocytes under hydrogen peroxide-induced oxidative stress and the correlation of these effects with autophagy.Human keratinocytes (HaCaT cell line) were randomly assigned to four groups: control, hydrogen peroxide, remifentanil pretreatment + hydrogen peroxide, and 3-methyladenine + remifentanil pretreatment + hydrogen peroxide. The MTT assay was performed to analyze cell viability. Apoptotic cell death was measured by Hoechst staining. A scratch assay was used to measure cell migration. The role of autophagy was ascertained by autophagosome staining and western blot analysis of autophagy-related proteins.Compared with the control group, the hydrogen peroxide group showed decreased cell viability, which was improved by remifentanil pretreatment. Hydrogen peroxide-induced apoptotic cell death and delayed cell migration were also improved by remifentanil pretreatment. Western blot analysis showed that the expression of autophagy-related proteins significantly increased in the remifentanil pretreatment + hydrogen peroxide group compared with that in the hydrogen peroxide group.This study demonstrated that remifentanil pretreatment ameliorates hydrogen peroxide-induced oxidative injury in human keratinocytes. In addition, our results show that the antioxidative effect of remifentanil against hydrogen peroxide-induced oxidative injury was mediated by autophagy.

We performed a nationwide, population-based cohort study to investigate the risk of osteoporosis in patients with peptic ulcer disease in South Korea and concluded that peptic ulcer disease is associated with an increased risk of osteoporosis. This study aimed to evaluate the association between peptic ulcer disease (PUD) and the occurrence of osteoporosis using a national sample cohort from South Korea. Using the national cohort study from the Korean National Health Insurance Service, we extracted data for patients with PUD (n = 50,002) and for 1:1 matched control participants (n = 50,002); we then analyzed the occurrence of osteoporosis from 2002 to 2013. The patients were matched according to age, sex, income, region of residence, and past medical history. A stratified Cox proportional hazards model was used to analyze the hazard ratios (HRs) and the 95% confidence intervals (CIs). Subgroup analyses were performed based on age and sex. The adjusted HR for osteoporosis was 1.36 (95% CI = 1.33–1.40, P < 0.001) in the PUD group. In the subgroup analysis based on age and sex, the respective adjusted HRs of PUD for osteoporosis were 1.33 (95% CI = 1.21–1.47) in the < 65-year-old group of men and 1.42 (95% CI = 1.30–1.56) in the ≥ 65-year-old group of men (each P < 0.001). The respective adjusted HRs of PUD for osteoporosis were 1.34 (95% CI = 1.29–1.39) in the < 65-year-old group of women and 1.38 (95% CI = 1.33–1.47) in the ≥ 65-year-old group of women (each P < 0.001). In the current nationwide cohort study, we found that PUD is associated with an increased risk of osteoporosis regardless of sex.

Post-inflammatory erythema is a common result of acne inflammation and is cosmetically unacceptable without effective treatment. Fractional microneedling radiofrequency (FMR) has potential for treatment of post-inflammatory erythema. The aim of this study was to evaluate the efficacy and safety of this treatment. A retrospective chart review was undertaken of 25 patients treated with 2 sessions of radiofrequency at 4-week intervals and 27 patients treated with oral antibiotics and/or topical agents. Efficacy was assessed through an investigator's global assessment of photographs, and the analysis of erythema with image analysis software and photometric devices. Histological changes resulting from the treatment were evaluated by skin biopsy. FMR treatment resulted in significant improvements in erythema with no severe adverse effects. Histological study revealed a reduction in vascular markers and inflammation. FMR is a safe and effective treatment for post-inflammatory erythema, with potential anti-inflammatory and anti-angiogenetic properties.

Fractional microneedling radiofrequency (FMR) is one of the promising methods in acne treatment. Moreover, bipolar radiofrequency (BR) generates heat thereby which induces neocollagenosis. FMR may have the potential to be a safe and effective treatment for the patients both with acne and acne scar. This study was performed to compare the efficacy and safety of FMR and BR in acne and acne scar treatment. Furthermore, mechanism of the FMR treatment was investigated through skin tissues obtained from subjects. Twenty subjects with mild-to-moderate acne and acne scars were treated in a split-face manner with FMR and BR. Two sessions of treatment was done 4 weeks apart in a total 12-week prospective single-blind, randomized clinical trial. Clinical assessment and sebum measurement were carried out for the evaluation of efficacy and safety. Skin tissues were acquired for investigation of molecular changes. FMR was more effective for acne scar especially in icepick and boxcar scar compared to BR. Both inflammatory and non-inflammatory acne lesions decreased by 80 and 65 % in the FMR-treated side at the final visit of 12 weeks, respectively. FMR treatment resulted in significant reduction of sebum excretion. Both treatments showed no severe adverse effects other than erythema. The FMR showed superior efficacy in acne and acne scar compared with BR. Increased expression of TGFβ and collagen I and decreased expression of NF-κB, IL-8 are suggested to involve in the improvement of acne scar and acne lesion by FMR.

Background: Csd6 is one of the cell shape-determining proteins in H. pylori. Results: The active site of Csd6 is tailored to function as an l,d-carboxypeptidase in the peptidoglycan-trimming process. Conclusion: Csd6 constitutes a new family of l,d-carboxypeptidase. Significance: The substrate limitation of Csd6 is a strategy that H. pylori uses to regulate its helical cell shape and motility., Helicobacter pylori causes gastrointestinal diseases, including gastric cancer. Its high motility in the viscous gastric mucosa facilitates colonization of the human stomach and depends on the helical cell shape and the flagella. In H. pylori, Csd6 is one of the cell shape-determining proteins that play key roles in alteration of cross-linking or by trimming of peptidoglycan muropeptides. Csd6 is also involved in deglycosylation of the flagellar protein FlaA. To better understand its function, biochemical, biophysical, and structural characterizations were carried out. We show that Csd6 has a three-domain architecture and exists as a dimer in solution. The N-terminal domain plays a key role in dimerization. The middle catalytic domain resembles those of l,d-transpeptidases, but its pocket-shaped active site is uniquely defined by the four loops I to IV, among which loops I and III show the most distinct variations from the known l,d-transpeptidases. Mass analyses confirm that Csd6 functions only as an l,d-carboxypeptidase and not as an l,d-transpeptidase. The d-Ala-complexed structure suggests possible binding modes of both the substrate and product to the catalytic domain. The C-terminal nuclear transport factor 2-like domain possesses a deep pocket for possible binding of pseudaminic acid, and in silico docking supports its role in deglycosylation of flagellin. On the basis of these findings, it is proposed that H. pylori Csd6 and its homologs constitute a new family of l,d-carboxypeptidase. This work provides insights into the function of Csd6 in regulating the helical cell shape and motility of H. pylori.

Fixed-dose combination adapalene 0.1% and benzoyl peroxide 2.5% gel (A-BPO) has rarely been studied for Asian acne patients, while they have complained of local irritations more often when applying individual components. In this study, we compared A-BPO gel with benzoyl peroxide (BPO) in terms of efficacy and tolerability in Korean patients first, and assessed the clinical benefit of a dermatological tutorial on application technique in reducing irritations for A-BPO. This study was conducted as a single-blind controlled split-face trial for a 12-week period. Each half facial side of 85 patients was randomly assigned to either A-BPO or BPO. Success rate, lesion counts and safety profiles were evaluated (analysis I). During initial assignment, all patients were further randomized to either dermatological tutorial (DT) or non-tutorial (NT) subgroups depending on the presence of dermatologists' tutorials for application methods to their A-BPO sides. Clinical data of the A-BPO side was compared between two subgroups (analysis II). As a result, A-BPO gel outperformed BPO, demonstrating better efficacy in success rates and lesion counts as early as 1 week. However, A-BPO proved significantly less tolerable compared with both BPO and previous A-BPO data from Caucasians. Bioengineering measurements further confirmed clinical data (analysis I). The DT subgroup achieved much better tolerability with comparable therapeutic efficacies compared with the NT subgroup (analysis II). In conclusion, A-BPO demonstrated higher efficacies in acne compared with BPO in Korean patients, while skin irritation levels were notable concurrently. Dermatologists' education for application methods would significantly decrease these side-effects, maintaining superior efficacy levels.

Background/Aims: Interval gastric cancer (IGC) is defined as cancer that is diagnosed between the time of screening and postscreening esophagogastroduodenoscopy (EGD). Un-fortunately, little is known about the characteristics of IGC in Korea, a country with a high incidence of gastric cancer. The aim of this study was to evaluate the clinicopathologic char-acteristics of IGCs in Korea. Methods: From January 2006 to July 2011, a total of 81,762 subjects underwent screening EGD at Yonsei University Health Promotion Center, Seoul, Ko-rea. We defined missed cancer as cancer diagnosed within 1 year of screening EGD and latent cancer as cancer diagnosed more than 1 year after EGD. Results: A total of 16 IGC patients (17 lesions; three missed cancers and 14 latent can-cers) were identified, with a mean age of 60.68 years and a mean interval time of 19.64 months. IGCs tended to be undifferentiated (12/17, 70.6%), located in the lower body of the stomach (12/17, 70.6%) and exhibited flat/depressed endoscopic morphology (11/17, 64.7%). The patients with missed cancer were generally younger than the patients with latent cancer (51.3 years vs 62.8 years, p=0.037), and the patients with undifferentiated cancer were significantly younger than those with differentiated cancer (57.0 years vs 68.8 years, p=0.008). Conclusions: IGCs tended to be undifferentiated, located in the lower body of the stomach, and exhibited flat/depressed endoscopic morphology. (Gut Liver, 2015;9:167-173)

Background: Ischemia-reperfusion of bone occurs in a variety of clinical conditions, such as orthopedic arthroplasty, plastic gnathoplasty, spinal surgery, and amputation. Usually, cellular models of hypoxia-reoxygenation reflect in vivo models of ischemia-reperfusion. With respect to hypoxia-reoxygenation conditions, the effects of remifentanil on osteogenesis have received little attention. Therefore, we investigated the effects of remifentanil on the proliferation and differentiation of osteoblasts during hypoxic-reoxygenation. Methods: After remifentanil (0.1, 1 ng/mL) preconditioning for 2 hours, human osteoblasts were cultured under 1% oxygen tension for 24 hours. Thereafter, the cells were reoxygenated for 12 hours at 37 °C. The naloxone groups were treated with naloxone for 30 minutes before remifentanil treatment. We measured cell viability via MTT assay. Osteoblast maturation was determined by assay of bone nodular mineralization. Quantitative PCR and western blot methods were used to determine BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-β1, HIF-1α, and RUNX2 expression levels. Results: Osteoblast viability and bone nodular mineralization by osteoblasts is recovered by remifentanil preconditioning from hypoxia-reoxygenation insult. During hypoxic-reoxygenation condition, remifentanil preconditioning induced the expression of BMP-2, osteocalcin, Akt, type I collagen, osterix, TGF-β1, HIF-1α, and RUNX2 in osteoblasts. Conclusions: Under hypoxia-reoxygenation conditions, remifentanil preconditioning enhanced the cell viability and maturation of osteoblasts, and stimulated the expression of proteins associated with osteoblast proliferation and differentiation of the osteoblast. Our results suggest that remifentanil may help in the treatment of bone stress injuries.

Platelet-rich plasma (PRP) which contains large amounts of growth factors has been tried to enhance therapeutic efficacy of laser treatment for acne scar with unknown underlying mechanism.The present study was conducted to investigate the molecular mechanism of increased clinical efficacy of PRP when combined with fractional laser treatment for treating acne scars.Subjects with mild to moderate acne scars were treated with two sessions of fractional COThe PRP treatment increased clinical efficacy with decreased severity of adverse effects such as erythema, swelling and oozing. Productions of TGFβ1 and TGFβ3 proteins were more highly elevated on the PRP-treated side of the face compared to the control side at day 28. Furthermore, PRP-treated side showed significant increase of c-myc, TIMP, and HGF expression. Experimental fibroblast culture model was also used. PRP administration after laser irradiation increased expressions of p-Akt, TGFβ1, TGFβ3, β-catenin, collagen 1, and collagen 3 in both dose-dependent and time dependent manners in fibroblast. Moreover, we acquired clinical and histological data through randomized control clinical trial.Taken together with human study results combined with the data from cell experiments we suggest that PRP treatment increased fibrogenetic molecules induced by fractional CO

Background Botulinum toxins have been widely used in cosmetic dermatology. Neurotoxin from the CBFC26 strain (NTC) is a recently developed botulinum toxin type A product manufactured through refined procedures. Objective A double-blinded, randomized, multicentre-designed, phase III trial to investigate the non-inferiority of NTC to existing botulinum toxin A, onabotulinumtoxin A in the treatment of moderate to severe glabellar lines. Methods A total of 272 subjects were randomized in a 1 : 1 ratio to receive 20 U of NTC or onabotulinumtoxin A. The primary endpoint was the response rate of physicians' assessment (PA) using the Facial Wrinkle Scale at week 4. The secondary endpoints included the response rate of PA at weeks 8, 12 and 16, and photographic assessment at weeks 4, 8, 12 and 16. Subjects' improvement assessment and subjective self-satisfaction levels were also investigated. Results Response rates for maximum frown were 89.3% in the NTC group and 81.9% in the onabotulinumtoxin A group at week 4. NTC also resulted in comparable results for both the response rates of the other evaluation points and incidence of adverse events compared to those of onabotulinumtoxin A. In subjects' improvement assessment and photographic evaluations, NTC even demonstrated better results compared with onabotulinumtoxin A in the early phase after treatment. Analysis of these results strongly supports the non-inferiority of NTC to onabotulinumtoxin A in the efficacy and safety. Conclusion NTC is as effective as onabotulinumtoxin A in the treatment of glabellar lines, and both products were well tolerated.

This study was undertaken to evaluate the clinical efficacy, safety, and histological changes induced by dietary omega-3 fatty acid and γ-linoleic acid in acne vulgaris. A 10-week, randomised, controlled parallel dietary intervention study was performed in 45 participants with mild to moderate acne, which were allocated to either an omega-3 fatty acid group (2,000 mg of eicosapentaenoic acid and docosahexaenoic acid), a γ-linoleic acid group (borage oil containing 400 mg γ-linoleic acid), or a control group. After 10 weeks of omega-3 fatty acid or γ-linoleic acid supplementation, inflammatory and non-inflammatory acne lesions decreased significantly. Patient subjective assessment of improvement showed a similar result. Heamatoxylin & eosin staining of acne lesions demonstrated reductions in inflammation and immunohistochemical staining intensity for interleukin-8. No severe adverse effect was reported. This study shows for the first time that omega-3 fatty acid and γ-linoleic acid could be used as adjuvant treatments for acne patients.

Background and Objective Fractional Er:YAG minimizes the risk associated with skin ablation. Infrared diode laser and radiofrequency have suggested comparable improvements in acne scar. We compared the clinical efficacy of Er:YAG laser and bipolar radiofrequency combined with diode laser (BRDL) for the treatment of acne scars. Moreover, acute molecular changes of cytokine profile associated with wound healing have been evaluated to suggest mechanisms of improvement of acne scar. Study Design Twenty-four subjects with mild-to-moderate acne scars were treated in a split-face manner with Er:YAG and BRDL, with two treatment sessions, 4 weeks apart. Objective and subjective assessments were done at baseline, 1, 3, 7 days after each treatment and 4 weeks after last treatment. Skin biopsy specimens were obtained at baseline, 1, 3, 7, 28 days after one session of treatment for investigation of molecular profile of acute skin changes by laser treatment. Results Investigator's Global Assessment representing the improvement degree shows 2.1 (50%) in fractional Er:YAG and 1.2 (25%) in BRDL. Er:YAG induced the later and higher peak expression of TGFβs and collagenases, whereas BRDL induced earlier and lower expression of TGFβ and collagenases, relatively. PPARγ dropped rapidly after a peak in Er:YAG-treated side, which is associated with tissue inhibitor of metalloproteinase (TIMP) expression. We observed higher expression of TIMP after Er:YAG treatment compared with BRDL by immunohistochemistry, which may be associated with the expression of upregulation of collagen fibers. Conclusion The superior efficacy of Er:YAG to BRDL in the treatment of acne scars may be associated with higher expression of collagen which is associated with differential expression of TGFβs, collagenases, PPARγ, and TIMP. Lasers Surg. Med. 49:341–347, 2017. © 2016 Wiley Periodicals, Inc.

Background Fractional microneedling radiofrequency (FMR) is an emerging treatment modality, but its effect on rosacea has not been studied yet. Objective To investigate the potential impact of FMR treatment on clinical improvement and histologic changes in rosacea patients. Materials and methods A 12-week, prospective, randomized, split-face clinical trial was conducted. Two sessions of FMR were performed on one side of the cheeks with 4-week interval and the other side remained untreated. Erythema index from DermaSpectrometer and a* value from Spectrophotometer CM-2002 were measured at each visit for the objective measurement of erythema. Histologic analysis of skin samples was also carried out. Results Clinical evaluation and photometric measurement revealed the reduction of redness in the treated side compared with untreated side and baseline. Erythema index decreased 13.6% and a* value decreased 6.8% at Week 12 compared with baseline. Reduced expression of markers related to inflammation, innate immunity, and angiogenesis was observed in immunohistochemical staining of tissue obtained after FMR treatment. Conclusion Fractional microneedling radiofrequency treatment showed modest clinical and histologic improvement of rosacea, and it might be used as an alternative or in combination with other treatment methods.

Ginsenoside Rc (Rc) is a major ginsenoside isolated from Panax ginseng, and has exhibited pharmacological effects on skin cells. The present study aimed to investigate the putative skin‑protective properties of Rc, including its anti‑photoaging and barrier function‑protective effects, in human HaCaT keratinocytes exposed to UVB radiation. The protective properties of Rc were evaluated through the assessment of keratinocyte viability, reactive oxygen species (ROS) production, total glutathione (GSH) and superoxide dismutase (SOD) activity, caspase‑14, matrix metalloproteinase (MMP)‑2 and ‑9 activity, and MMP‑2, MMP‑9 and filament aggregating protein (filaggrin) expression following UVB irradiation. Treatment with Rc was revealed to prevent the UVB‑induced increase in ROS production and pro‑MMP‑2 and ‑9 levels in HaCaT keratinocytes. In addition, treatment with Rc resulted in enriched GSH contents and enhanced SOD activity following exposure to UVB radiation. Furthermore, Rc treatment enhanced caspase‑14 activity and counteracted the UVB‑induced downregulation in filaggrin expression. However, no significant difference was identified between Rc‑treated and normal groups in terms of keratinocyte viability, regardless of exposure to radiation. The present findings suggested that Rc may exert anti‑photoaging and barrier function‑protective effects in keratinocytes, and thus protect the skin against photooxidative stress induced by exposure to UV radiation.

We report on three cases of longstanding pulmonary tuberculosis patients with coronary to bronchial artery fistula (CBF) who presented with recurrent massive hemoptysis. The first and second patients died because of decreased functional pulmonary volume plus massive hemoptysis and cannulation failure of CBF due to hypovolemic vasospasm, respectively. When recurrent hemoptysis occurs despite successful embolization treatment, CBF should be considered as a potential bleeding source. Moreover, a coronary angiography should be performed, especially in patients with longstanding cardiopulmonary disease such as pulmonary tuberculosis.

There has been considerable interest in virulence genes in the plasticity region of Helicobacter pylori , but little is known about many of these genes. JHP940, one of the virulence factors encoded by the plasticity region of H. pylori strain J99, is a proinflammatory protein that induces tumor necrosis factor-alpha and interleukin-8 secretion as well as enhanced translocation of NF-κB in cultured macrophages. Here we have characterized the structure and function of JHP940 to provide the framework for better understanding its role in inflammation by H. pylori . Our work demonstrates that JHP940 is the first example of a eukaryotic-type Ser/Thr kinase from H. pylori . We show that JHP940 is catalytically active as a protein kinase and translocates into cultured human cells. Furthermore, the kinase activity is indispensable for indirectly up-regulating phosphorylation of NF-κB p65 at Ser276. Our results, taken together, contribute significantly to understanding the molecular basis of the role of JHP940 in inflammation and subsequent pathogenesis caused by H. pylori . We propose to rename the jhp940 gene as ctkA ( c ell t ranslocating k inase A ).

We present a case of combined general anesthesia with muscle relaxant and epidural analgesia for hemicolectomy in a 56-year-old woman with Pompe disease. Progressive pulmonary function loss predisposes Pompe disease patients to an increased risk of aspiration pneumonia, atelectasis, and all pulmonary infections. Given the impaired cough resulting from abdominal muscle weakness, patients with Pompe disease who undergo abdominal major surgery are prone to great risks of postoperative pulmonary complications. In our case, to optimize the patient's pulmonary toilet during the postoperative period, epidural block was provided as well as general anesthesia. Although she had a severe scoliotic spine and a worst pulmonary function test, the attempt of epidural block provided excellent pain control and pulmonary toilet care.

Background: Percutaneous injection of bone cement (acrylic cement) during percutaneous kyphoplasty and vertebroplasty can cause symptomatic or asymptomatic complications due to leakage, extravasation or vascular migration of cement. Purpose: To investigate and to compare the incidence and site of local leakage or complications of bone cement after percutaneous kyphoplasty and vertebroplasty using bone cement. Material and Methods: We retrospectively reviewed 473 cases of percutaneous kyphoplasty or vertebroplasty performed under fluoroscopic guidance. Of the 473 cases, follow-up CT scans that covered the treated bones were available for 83 cases (59 kyphoplasty and 24 vertebroplasty). Results: The rate of local leakage of bone cement was 87.5% (21/24) for percutaneous vertebroplasty and 49.2% (29/59) for kyphoplasty. The most common site of local leakage was perivertebral soft tissue ( n=8, 38.1%) for vertebroplasty. The most common site of local leakage was a perivertebral vein ( n=7, 24.1%) for kyphoplasty. Two cases of pulmonary cement embolism developed: one case after kyphoplasty and one case after vertebroplasty. Conclusion: Local leakage of bone cement was more common for percutaneous vertebroplasty compared with kyphoplasty ( P

Various strategies have been studied to reduce the discomfort of rocuronium injection. This study was designed to determine the effect-site target concentration (Ce) of remifentanil at which there was a 50% probability of preventing movement from pain in response to the injection of rocuronium (EC(50)).Anesthesia was induced with a propofol target-controlled infusion (TCI, Marsh model) and remifentanil TCI (Minto model). Effect-site target concentration of propofol was 3 microg/ml. Ce of remifentanil for the first patient started at 2.0 ng/ml. Ce of remifentanil for each subsequent patient was determined by the response of the previous patient by the Dixon up-and-down method with an interval of 0.5 ng/ml. After both drugs reached target concentration, rocuronium 0.8 mg/kg was administered, and the pain response was observed.The EC(50) of remifentanil was 1.5 +/- 0.45 ng/ml by Dixon's up-and-down method. From probit analysis, the EC(50) of remifentanil was 1.37 ng/ml (95% confidence limits, 0.69-2.15 ng/ml), and the EC(95) was 3.19 ng/ml (95% confidence limits, 2.31-11.24 ng/ml).The EC(50) of remifentanil to blunt the withdrawal responses to rocuronium injection was 1.37-1.5 ng/ml during 3 microg/ml propofol TCI anesthesia.

Percutaneous vertebroplasty (PVP) of the axis (C2) is less aggressive than any surgical stabilizing procedure for the upper cervical spine, and it does not restrict the mobility of the upper cervical joints. Disruption of the weight-bearing unit of the second cervical (C2) vertebral body causes excessive load at the relatively small adjacent upper cervical joints. Upper cervical joint block before or after PVP at the C2 level has not been reported thus far. A 67-year-old man was referred to a pain clinic with a 6-month history of increasing neck pain without focal neurologic symptoms. Studies revealed a compression fracture of the C2 vertebral body and invasion of the adjacent soft tissue. To treat the mechanical component of the symptoms, anterolateral PVP at C2 was successfully performed, but the residual suboccipital headache was alleviated only after upper cervical joint block was performed. Thus, upper cervical joint block can be performed to treat the residual suboccipital headache after PVP at C2.

Systematic investigations of clinical manifestation and factors associated with the severity of seborrheic dermatitis (SD) have rarely been reported in Asia. We investigated the clinical manifestation and associated factors of SD. Patients were asked to fill a self-questionnaire including symptom severity and aggravating factors. We evaluated objective severity and involved sites of SD. Patients were categorized into three groups; young age group (age30), middle age group (30≤ age60), and old age group (age ≥60) and we compared clinical features among them.Among 253 patients included, scalp was the most frequently involved site and the most frequently reported aggravating factor was psychological stress. Different age groups have distinct clinical features and severity. Severity of SD decreased with age and patients in the old age group had less frequent involvement of the lower face. Risk factors of scalp involvement were male gender, disease duration ≥7 years and a history of acne. We investigated associated factors of SD and observed different clinical features between the age groups. We suggest that the adult form of SD can be categorized into three groups; young age SD, middle age SD and old age SD.

The yeast protein Dom34 is a key component of no-go decay, by which mRNAs with translational stalls are endonucleolytically cleaved and subsequently degraded. However, the identity of the endoribonuclease is unknown. Homologs of Dom34, called Pelota, are broadly conserved in eukaryotes and archaea. To gain insights into the structure and function of Dom34/Pelota, we have determined the structure of Pelota from Thermoplasma acidophilum (Ta Pelota) and investigated the ribonuclease activity of Dom34/Pelota. The structure of Ta Pelota is tripartite, and its domain 1 has the RNA-binding Sm fold. We have discovered that Ta Pelota has a ribonuclease activity and that its domain 1 is sufficient for the catalytic activity. We also demonstrate that domain 1 of Dom34 has an endoribonuclease activity against defined RNA substrates containing a stem loop, which supports a direct catalytic role of yeast Dom34 in no-go mRNA decay.

Introduction We investigated the inflammatory potential of O-linked N-acetylglucosamine glycosylation (O-GlcNAcylation) of p65 in rheumatoid arthritis (RA). Methods Fibroblast-like synoviocytes (FLS) and MH7A cells were treated with synthetic ThiaMet-G (200 μM), an O-GlcNAcase (OGA) inhibitor, followed by tumor necrosis factor (TNF)-α (10 μg/mL). Proliferation of synovial cells was measured by MTT assay, and the levels of mRNAs encoding pro-inflammatory molecules were quantitated by RT-PCR. The nuclear localization of O-GlcNAcylated of p65 and its DNA binding affinity and transcriptional activity were assessed. The severity assessment of arthritis and a histopathological examination were done in mice with collagen induced arthritis (CIA). ThiaMet-G (20 mg/kg) intraperitoneal injection was done every other day for 26 days. Fluorescence-activated cell sorting (FACS) analysis of T cells was performed. Results Hyper-O-GlcNAcylation increased the proliferation and mRNA expression of pro-inflammatory genes in synoviocytes stimulated by TNF-α. Moreover, O-GlcNAcylation of p65 enhanced its proportion of nuclear localization, DNA binding affinity and transcriptional activity. In CIA mice, ThiaMet-G significantly aggravated the severity of arthritis clinically and histologically, and it also increased CD4 + IFN-γ + T cells and CD4 + IL-17+ T cells. Conclusions O-GlcNAcylation of p65 increased the effects of TNF-α-mediated inflammation both in vitro (in synovial cells) and in vivo (in mice with CIA). Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0762-7) contains supplementary material, which is available to authorized users.

A drug delivery system to the inner ear using nanoparticles consisting of oligoarginine peptide (Arg8) conjugated to poly(amino acid) (poly(2-hydroxyethyl L-aspartamide; PHEA) was investigated to determine whether the limitations of low drug transport levels across the round window membrane (RWM) and poor transport into inner ear target cells, including hair cells and spiral ganglion, could be overcome. Three types of carrier materials, PHEA-g-C18, PHEA-g-Arg8, and PHEA-g-C18-Arg8, were synthesized to examine the effects of oligoarginine and morphology of the synthesized carriers. Nile red (NR) was used as a fluorescent indicator as well as to model a hydrophobic drug. Compared with PHEA-g-C18-NR nanoparticles, the oligoarginine-conjugated nanoparticles of PHEA-g-C18-Arg8-NR and PHEA-g-Arg8-NR entered into HEI-OC1 cells at significant levels. Furthermore, the strongest fluorescence intensity was observed in nuclei when PHEA-g-C18-Arg8 nanoparticles were used. The high uptake rates of PHEA-g-C18 and PHEA-g-C18-Arg8 nanoparticles were observed in ex vivo experiments using hair cells. After the delivery of PHEA-g-C18-Arg8 nanoparticles with reporter gene transfer, EGFP (enhanced green fluorescent protein) expression was monitored as an indicator of gene delivery. In the inner ear cells, PHEA-g-C18-Arg8 nanoparticles showed comparable or better transfection capabilities than the commercially available Lipofectamine reagent. PHEA-g-C18-Arg8 penetrated in vivo across the RWM of C57/BL6 mice with Nile red staining and GFP expression in various inner ear tissues. In conclusion, PHEA-g-C18-Arg8 nanoparticles were successfully transported into the inner ear through the intratympanic route and are proposed as promising candidates as delivery carriers to address inner ear diseases.

While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5-aminolevulinate (ALA)-ester, 1.5% 3-butenyl ALA-bu gel, using daylight only as the potential visible light source. Forty-six acne patients were randomly assigned to either ALA-bu or vehicle application group in a double-blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non-inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA-bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin-8, interleukin-1β, matrix metalloproteinase-9 and phosphorylated nuclear factor-κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy.

SummaryBackground The epidemiology of acne vulgaris appears to be evolving, with an increasingly earlier onset seen in childhood. Relevant studies have been rarely performed in Asia. Aim We sought to estimate the prevalence and clinical characteristics of acne among schoolchildren, and its association with treatment-seeking behaviour, body mass index (BMI), nutritional habits and other lifestyle elements. Methods A cross-sectional study was conducted with elementary schoolchildren aged 7–12 years. Children were interviewed by self-administered questionnaires, and were subsequently evaluated by dermatologists. Results Of 693 children enrolled, 36.2% were diagnosed with acne, and the prevalence increased with age. Additionally, clinical characteristics including severity, duration of disease and lesion distribution were significantly different between the lower (aged 7–9 years) and the higher (aged 10–12 years) grades. Subjective features including recognition about acne and treatment-seeking behaviours were also different between the two groups. Overweight or obesity (BMI ≥ 25 kg/m2 at 18 years of age; OR = 2.7) and consumption of chocolates/sweets (OR = 1.6) were significant risk factors for acne. Conclusions In the current study, the prevalence of acne among elementary schoolchildren was high, but only a few children had received treatment. Physicians should be attentive to childhood acne, and educate patients and their parents about the need to treat it.

The proliferation, differentiation, and migration of keratinocytes are essential in the early stages of wound healing. Hypoxia-Reoxygenation (H/R) injury to keratinocytes can occur in various stressful environments such as surgery, trauma, and various forms of ulcers. The effects of remifentanil on human keratinocytes under hypoxia-reoxygenation have not been fully studied. Therefore, we investigated the effects of remifentanil on the proliferation, apoptosis, and autophagic activation of human keratinocytes during hypoxic-reoxygenation. Human keratinocytes were cultured under 1% oxygen tension for 24 h. The cells were then treated with various concentrations of remifentanil (0.01, 0.1, 0.5, and 1 ng/mL) for 2 h. Thereafter, the cells were reoxygenated for 12 h at 37°C. We measured cell viability via MTT assay. Using quantitative real-time PCR and western blot analysis, we measured the expression levels of proteins associated with apoptosis and autophagy. Quantification of apoptotic cells was performed using flow cytometer analysis and autophagic vacuoles were observed under a fluorescence microscope. Remifentanil treatment brought about an increase in the proliferation of human keratinocytes damaged by hypoxia-reoxygenation and decreased the apoptotic cell death, enhancing autophagic activity. However, the autophagy pathway inhibitor 3-MA inhibited the protective effect of remifentanil in hypoxia-reoxygenation injury. In conclusion, the current study demonstrated that remifentanil treatment stimulated autophagy and reduced apoptotic cell death in a hypoxia-reoxygenation model of human keratinocytes. Our results provide additional insights into the relationship between apoptosis and autophagy.

H. pylori Csd3 (HP0506), together with other peptidoglycan hydrolases, plays an important role in determining cell shape. Its crystal structure in the latent state is reported., Helicobacter pylori is associated with various gastrointestinal diseases such as gastritis, ulcers and gastric cancer. Its colonization of the human gastric mucosa requires high motility, which depends on its helical cell shape. Seven cell shape-determining genes (csd1, csd2, csd3/hdpA, ccmA, csd4, csd5 and csd6) have been identified in H. pylori. Their proteins play key roles in determining the cell shape through modifications of the cell-wall peptidoglycan by the alteration of cross-linking or by the trimming of peptidoglycan muropeptides. Among them, Csd3 (also known as HdpA) is a bifunctional enzyme. Its d,d-endopeptidase activity cleaves the d-Ala4-mDAP3 peptide bond between cross-linked muramyl tetrapeptides and pentapeptides. It is also a d,d-carboxypeptidase that cleaves off the terminal d-Ala5 from the muramyl pentapeptide. Here, the crystal structure of this protein has been determined, revealing the organization of its three domains in a latent and inactive state. The N-terminal domain 1 and the core of domain 2 share the same fold despite a very low level of sequence identity, and their surface-charge distributions are different. The C-terminal LytM domain contains the catalytic site with a Zn2+ ion, like the similar domains of other M23 metallopeptidases. Domain 1 occludes the active site of the LytM domain. The core of domain 2 is held against the LytM domain by the C-terminal tail region that protrudes from the LytM domain.

A 58-year-old woman presenting with atypical chest pain showed a turbulent color Doppler signal at the interatrial septum on a transthoracic echocardiography and was found to have a huge coronary arteriovenous fistula originating from the middle right coronary artery and draining into right atrium with a very tortuous course using cardiac multidetector CT. A trivial echocardiographic finding should not be overlooked and could be evaluated thoroughly and noninvasively by multidetector CT.

Acne vulgaris is a nearly universal cutaneous disease characterized by multifactorial pathogenic processes. Because current acne medications have various side effects, investigating new pharmacologically active molecules is important for treating acne. As natural products generally provide various classes of relatively safe compounds with medicinal potentials, we performed activity-guided purification after a series of screenings from the extracts of five medicinal plants to explore alternative acne medications. Lupeol, a pentacyclic triterpene, from the hexane extract of Solanum melongena L. (SM) was identified after instrumental analysis. Lupeol targeted most of the major pathogenic features of acne with desired physicochemical traits. It strongly suppressed lipogenesis by modulating the IGF-1R/phosphatidylinositide 3 kinase (PI3K)/Akt/sterol response element-binding protein-1 (SREBP-1) signaling pathway in SEB-1 sebocytes, and reduced inflammation by suppressing the NF-κB pathway in SEB-1 sebocytes and HaCaT keratinocytes. Lupeol exhibited a marginal effect on cell viability and may have modulated dyskeratosis of the epidermis. Subsequently, histopathological analysis of human patients' acne tissues after applying lupeol for 4 weeks demonstrated that lupeol markedly attenuated the levels of both the number of infiltrated cells and major pathogenic proteins examined in vitro around comedones or sebaceous glands, providing solid evidence for suggested therapeutic mechanisms. These results demonstrate the clinical feasibility of applying lupeol for the treatment of acne.

We report the case of a 46-year-old woman presenting with postoperative bilateral cerebral visual loss that was initially misinterpreted as an irreversible ischemic event. Magnetic resonance imaging of the brain showed high signal intensity on T2-weighted and fluid-attenuated inversion recovery images and normal signal intensity on diffusion-weighted images of the posterior lobe, which mostly disappeared with the improvement of clinical symptoms. Subsequent diagnosis revealed posterior reversible encephalopathy syndrome (PRES). Recognition of PRES as the correct diagnosis led to the appropriate management strategy and the recovery of normal vision. Differentiation from acute cerebral ischemia is important in order to prevent permanent vision loss due to delay in initiating prompt and vigorous treatment of exacerbating factors, such as intermittent hypertension. We believe that it is important for anesthesiologists and critical care physicians to accurately diagnose PRES in view of the key differences in the management of similarly presenting conditions.

AIM: To determine whether there is a correlation between the location of the lesion and endoscopic submucosal dissection (ESD) outcome. METHODS: From January 2008 to December 2010, ESD of 1443 gastric tumors was performed. En bloc resection rate, complete resection rate, procedure time and complication rate were analyzed according to the tumor location. RESULTS: The rates of en bloc resection and complete resection were 91% (1318/1443) and 89% (1287/1443), respectively. The post-ESD bleeding rate was 4.3%, and perforation rate was 2.7%. Tumors located in the upper third of the stomach were associated with a longer procedure time and significantly higher rates of incomplete resection, piecemeal resection, and perforation than tumors below the upper third of the stomach. Posterior wall lesions had significantly longer procedure times and higher rates of incomplete resection and piecemeal resection than lesions in other locations. In multivariate analysis, posterior wall lesions and upper third lesions were significantly associated with incomplete resection and perforation, respectively. In post-ESD bleeding analysis, location was not a significant related factor. CONCLUSION: More advanced endoscopic techniques are required during ESD for lesions located in the upper third or posterior wall of the stomach to decrease complications and improve therapeutic outcomes.

Background: Screening of natural compounds for the development of anti-acne therapeutic agents has been steadily required considering various side effects of acne medications. However, previous studies have mainly focused on experimental tests without clinical trials and histopathological analysis. Objectives: To compare the clinical efficacy, safety and histopathological changes between Lactobacillus-fermented Chamaecyparis obtusa (LFCO) and existing tea tree oil (TTO). Methods: A total of 34 patients were instructed to apply 5% LFCO to the involved areas of a randomly allocated side and 5% TTO extract to the other side for 8 weeks in a double-blind split-face clinical trial. Results: After 8 weeks, inflammatory acne lesions were reduced by 65.3% on the LFCO side and by 38.2% on the TTO side. LFCO was also superior to TTO in the onset time of efficacy (p < 0.05). The LFCO side further demonstrated improvement for non-inflammatory lesions (52.6%, p < 0.05), decreased size of sebaceous glands and sebum output reductions. Patients' subjective satisfaction was also higher without severe adverse reactions. Protein expressions of nuclear factor κB decreased earlier on the LFCO side, and those of interleukin-1a (IL-1a), IL-8, insulin-like growth factor 1 receptor and sterol regulatory element-binding protein 1 decreased subsequently. Ultra-performance liquid chromatography/high-resolution mass spectrometry further demonstrated that the contents of dihydroxybenzoic acid, taxifolin and quercetin were increased in LFCO after fermentation. Conclusions: LFCO treatment was rapid and effective for treating acne lesions compared to TTO. Histopathological findings correlated well with the clinical acne grade and treatment response. This novel natural compound appears to be effective and safe for acne treatment.

Bovine amniotic membrane (BAM) has been regarded as an ideal dressing material because it accelerates epithelization and has anti-inflammatory, anti-angiogenic, and strong analgesic effects. To evaluate the clinical effects of BAM and compare them to that of hydrocolloid dressings on wounds created by ablative laser treatments, 49 subjects with nevi or scars requiring ablative laser treatment were evaluated. To compare efficacy, we divided the body into six areas and included patients with two or more similar skin lesions in the same body area. After ablative laser treatments, BAM and hydrocolloid dressing were applied to the wounds with random allocation. Clinical assessments were performed at baseline, 1, 4, 6, 8, 11, and 13 days after treatment. Histologic changes were assessed by skin biopsy. BAM treatment induced faster epithelization than hydrocolloid treatment (6.7 vs. 9.2 days). Erythema and oozing faded more quickly, and the satisfaction score was higher in BAM-treated sites than it was in hydrocolloid-treated sites, without severe adverse effects. Histologic analysis confirmed epithelization and immunohistochemistry revealed different growth factor profiles between the two treatment modalities. BAM benefits wound healing following ablative laser treatment.

Acne vulgaris is a highly prevalent skin disorder characterized by hyperseborrhea, inflammation, and Propionibacterium acnes overgrowth. Only isotretinoin and hormonal therapy reduce sebum production. To identify a new drug candidate that modulates sebum, we examined the effects of EGCG, the major polyphenol in green tea, on human SEB-1 sebocytes and in patients with acne. In SEB-1 sebocytes, we found that EGCG reduced sebum by modulating the AMPK–SREBP-1 signaling pathway. EGCG also reduces inflammation by suppressing the NF-κB and AP-1 pathways. EGCG also induces cytotoxicity of SEB-1 sebocytes via apoptosis and decreases the viability of P. acnes, thus targeting almost all the pathogenic features of acne. Finally, and most importantly, EGCG significantly improved acne in an 8-week randomized, split-face, clinical trial, and was well tolerated. Our data provide a therapeutic rationale for the use of EGCG in acne.

Various methods of photodynamic therapy (PDT) for acne have been introduced. However, comparative studies among them are still needed. We performed this study to compare the effect of methyl aminolevulinate (MAL) PDT for acne between red light and intense pulsed light (IPL). Twenty patients were enrolled in this eight-week, prospective, split-face study. We applied MAL cream over the whole face with a three-hour incubation time. Then patients were irradiated with 22 J/cm(2) of red light on one-half of the face and 8-10 J/cm(2) of IPL on the other half during each treatment session. We performed three treatment sessions at two-week intervals and followed-up patients until four weeks after the last session. Inflammatory and non-inflammatory acne lesions were reduced significantly on both sides. The red light side showed a better response than the IPL side after the first treatment. Serious adverse effects after treatment were not observed. MAL-PDT with red light and IPL are both an effective and safe modality in acne treatment. Red light showed a faster response time than IPL. After multiple sessions, both light sources demonstrated satisfactory results. We suggest that reducing the total dose of red light is desirable when performing MAL-PDT in Asian patients with acne compared with Caucasians.