The perceptions and experiences of North Korean refugee doctors concerning the burden of non-communicable diseases in North Korea.

BACKGROUND: Non-communicable diseases (NCDs) are a major challenge to health and social development in the 21st century, and North Korea is no exception. However, there is a lack of information concerning NCDs in North Korea, and a different approach is needed to understand the NCDs burden there. This study examines the perceptions and experiences of refugee doctors from North Korea concerning the NCDs burden in North Korea. METHODS: Focus group discussions were conducted with 10 refugee doctors from North Korea who had been recruited through snowball sampling. RESULTS: North Korean refugee doctors participating in this study indicated that NCDs are the highest priority diseases, that North Koreans did not appear to have a high level of understanding and knowledge of NCDs, that economic breakdown was the primary cause of the NCDs burden, and that a high priority should be assigned to targeting NCDs in North Korea. DISCUSSION: Although the North Korean refugee doctors were medical professionals, they faced serious challenges accessing and managing patients with NCDs. South Korea needs to prepare for a potentially large number of people with NCDs should a freer movement of peoples occur between the two countries.

The diagnostic thresholds for synovial fluid analysis in late periprosthetic infection of the hip depend on the duration of symptoms.

AIMS: We hypothesised that the synovial white blood cell (WBC) count in patients with a late periprosthetic joint infection (PJI) of the hip would depend on the duration of a patient's symptoms, and that the optimal diagnostic threshold would also depend on this period of time. PATIENTS AND METHODS: The synovial WBC count and percentage of polymorphonuclear cells (%PMN), and the serum CRP and ESR levels obtained > six weeks after primary THA were compared between 50 infected and 88 non-infected THAs, and in patients with symptoms for more than or less than two weeks. Diagnostic thresholds for the synovial WBC count were calculated using area under the curve calculation. RESULTS: The synovial WBC count was significantly higher in patients with symptoms for ≤ two weeks compared with those with symptoms for > two weeks (p = 0.03). The optimal threshold for diagnosing PJI for the synovial WBC count was 5750 cells/µL (sensitivity 94; specificity 100; PPV 100%; NPV 89%; AUC 99%) and 1556 cells/µL (sensitivity 91; specificity 94; PPV 87% and NPV 97%; AUC 95%), respectively. The thresholds for the cut-offs based on duration of symptoms improved the diagnostic performance of this test. CONCLUSION: This study shows that the diagnostic thresholds for synovial fluid analysis in late periprosthetic infection following THA may depend on duration of symptoms. Cite this article: Bone Joint J 2016;98-B:1355-9.

Disulfanyl peptide decreases melanin synthesis via receptor-mediated ERK activation and the subsequent downregulation of MITF and tyrosinase.

OBJECTIVE: Bioactive peptides are commonly used in cosmeceutical purpose. This study was performed to search for an effective and short hypopigmenting peptide using normal human melanocytes as a screening model. A peptide that exhibits multitarget activities will be a promising peptide. METHODS: Depigmenting effects were tested in normal human melanocytes. One peptide was selected, and signalling mechanism was investigated by Western blotting and immunofluorescent microscopic examination. RESULTS: A novel hypopigmenting peptide (dSHP) has been found to inhibit the production of melanin. This peptide significantly decreases tyrosinase activity but was not effective in a direct in vitro assay. It also induces the prolonged activation of ERK, and subsequently downregulates the levels of MITF. PD98059 abolished the dSHP-induced downregulation of MITF. These findings indicate that the dSHP-induced activation of ERK contributes to a reduced melanin synthesis via the downregulation of MITF. Fluorescent microscopic studies were consistent with such findings. Pertussis toxin reverses the downregulation of MITF, which means that the receptor-mediated ERK activation is involved. Moreover, it was also found that downregulation of MITF was clearly inhibited by lysosomal inhibitor (chloroquine). CONCLUSION: Novel tetrapeptide dSHP reduces the melanin synthesis by a receptor-mediated pathway. Furthermore, dSHP works by ERK activation and key transcription factor MITF degradation. Thus, it may be a good candidate as an effective hypopigmenting cosmetic agent.

Immediate induction of heat shock proteins is not protective against cryopreservation in normal human fibroblasts.

Heat shock proteins (HSPs) were first identified as proteins whose synthesis was enhanced by stresses, such as increased temperature. HSPs can protect cells from various cytotoxic factors by stabilizing proteins. Thus, it could be hypothesized that heat induced HSPs can provide protective effects against cryopreservation-induced cell death. The aim of this study was to determine whether induction of HSPs can increase the cell viability of normal human fibroblasts after cryopreservation. Cytotoxic effects of heat treatment were tested and the induction of HSPs was assessed by examining time-dependent HSP expression. A cell counting method using fluorescence microscopy was used to determine the viability of cells. In addition, the effects of geranylgeranylacetone were evaluated in terms of HSP expression and cytoskeleton changes. The results of this study showed that immediate induction of HSPs does not protect normal human fibroblasts against cryopreservation-induced cell death possibly by inducing cytoskeleton changes.

Cervi cornus Colla (deer antler glue) induce epidermal differentiation in the reconstruction of skin equivalents.

In the reconstruction of skin equivalents (SEs), keratinocyte differentiation is important because epidermal differentiation is closely related with barrier function. The aim of this study was to investigate the effects of Cervi cornus Colla (CCC) on the stem cell activity and epidermal differentiation in the reconstruction of skin equivalent. Four different models were constructed according to different composition of dermal substitute. Results showed similar morphologic findings when hyaluronic acid (HA) and/or CCC was added. But, immunohistochemical staining showed that p63 was significantly increased by addition of HA and/or CCC. Increased staining of integrin α6 and ß1 was variably observed when HA and/or CCC was added to make dermal substitute. These finding showed that addition of HA and/or CCC may affect the stem cell activity in the reconstruction of skin. Furthermore, filaggrin expression was much increased when CCC was added. It showed that epidermal differentiation was significantly improved by addition of CCC. In conclusion, simultaneous presence of HA and CCC contributed to the stem cell activity and epidermal differentiation in the reconstruction of SE. Legislation in the EU prohibits marketing cosmetics and personal care products that contain constituents that have been examined through animal experiments. To avoid these limitations, SEs can be used for testing the safety or the efficacy of cosmetic ingredients. Therefore, our results showed that combined use of HA and CCC can be helpful for the reconstruction of SE with good stem cell activity and epidermal differentiation.

Effect of tranexamic acid on melasma: a clinical trial with histological evaluation.

BACKGROUND: Melasma is associated with epidermal hyperpigmentation, weak basement membrane, vascular proliferation and increased numbers of mast cell. Tranexamic acid (TXA), a plasmin inhibitor, is reported to improve melasma when injected locally. However, the effects of oral and topical TXA on melasma have not been well studied and the underlying mechanism remains unclear. OBJECTIVES: To elucidate the effects of oral and topical TXA on melasma. METHODS: A clinical study was conducted with 25 women for 8 weeks from March to July 2010. Volunteers were instructed to take two TXA tablets three times a day and apply a TXA topical agent twice a day for 8 weeks. Skin pigmentation and erythema was measured using a Mexameter(®) during each visit and skin biopsies were collected from eight subjects before and 8 weeks after treatment. Fontana-Masson, anti-CD31, antitryptase and antitype IV collagen staining was performed. RESULTS: Twenty-two subjects completed the study and no serious adverse events occurred during the study period. The mean lesional melanin index (MI) scores decreased significantly. Interestingly, the MI scores for the perilesional skin increased. The erythema index scores of lesional and perilesional skin also showed a similar pattern. Histological analysis showed significant reduction of epidermal pigmentation, vessel numbers and mast cell counts. Type IV collagen staining was not observed in all specimens. CONCLUSION: TXA decreased epidermal pigmentation associated with melasma and also reversed melasma-related dermal changes, such as vessel number and increased numbers of mast cells.

Optimization of mechanical performance of oxidative nano-particle electrode nitrile butadiene rubber conducting polymer actuator.

Present work delivers a systematical evaluation of actuation efficiency of a nano-particle electrode conducting polymer actuator fabricated based on Nitrile Butadiene Rubber (NBR). Attempts are made for maximizing mechanical functionality of the nano-particle electrode conducting polymer actuator that can be driven in the air. As the conducting polymer polypyrrole of the actuator is to be fabricated through a chemical oxidation polymerization process that may impose certain limitations on both electrical and mechanical functionality of the actuator, a coordinated study for optimization process of the actuator is necessary for maximizing its performance. In this article actuation behaviors of the nano-particle electrode polypyrrole conducting polymer is studied and an optimization process for the mechanical performance maximization is performed.

On the role of major vault protein in the resistance of senescent human diploid fibroblasts to apoptosis.

Major vault protein (MVP), the main component of vault complex, is overexpressed in many multidrug-resistant cancer cell lines, suggesting a possible role for MVP in cell signaling and survival. In this study, we have found that MVP is markedly increased in senescent human diploid fibroblasts (HDFs) as well as in aged organs. We examined whether MVP expression might be affected by apoptotic stress in an aging-dependent manner. We treated young and senescent HDFs with apoptosis-inducing agents such as H(2)O(2), staurosporine and thapsigargin, and monitored MVP expression. We found that MVP expression is markedly reduced in young HDFs but not in senescent HDFs, in response to apoptotic stresses. Downregulation of MVP increased the sensitivity of senescent HDFs to apoptosis. Also, the level of antiapoptotic B-cell lymphoma protein-2 (Bcl-2) was significantly reduced and the accumulation of c-Jun increased in MVP knocked-down senescent HDFs. Moreover, treatment of MVP knocked-down senescent HDFs with SP600125, a specific c-Jun NH(2)-terminal kinase (JNK) inhibitor, restored the level of Bcl-2 protein. Taken together, these results suggest that MVP is important in the resistance of senescent HDFs to apoptosis by modulation of Bcl-2 expression by JNK pathway.

Upregulation of heme oxygenase-1 in oral epithelial dysplasias.

The expression of heme oxygenase-1 (HO-1), stress-related enzyme, is induced in leukaemia and some cancer tissues, but relatively little is known about the differential pattern of HO-1 expression and proliferation in premalignant lesions of the epithelial oral mucosa. The purpose of this study was to evaluate whether HO-1 expression and proliferation were increased in preneoplastic lesions compared to normal and oral cancer tissues. Immunohistochemical staining was used to examine the expression patterns of HO-1 and proliferating cell nuclear antigen (PCNA) in a series of normal mucosa and mild-to-severe cases of oral epithelial dysplasia (OED) and oral squamous cell carcinoma. Both HO-1 and PCNA are expressed in the basal cells of normal oral mucosa. In patients with OED and carcinoma in situ, immunostaining for PCNA and HO-1 was more intense, and gradually extended into the superficial layers of the mucosa. HO-1 and PCNA expression was correlated with the degree of epithelial dysplasia. Oral squamous cell carcinoma also showed elevated expression of HO-1, but this level was not higher than in severe OED or carcinoma in situ. These results suggest that the up-regulation of HO-1 in premalignant oral lesions is part of an early cytoprotection mechanism against carcinogenesis in the oral mucosa.

Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents.

The isolation of human epidermal stem cells is critical for their clinical applications. In the present study, we isolated three populations of epidermal keratinocytes according to their ability to adhere to collagen type IV: i.e., rapidly adhering (RA), slowly adhering (SA), and non-adhering (NA) cells. The aim of this study was to characterize RA cells and to investigate the possibility of using these cells for epidermis reconstruction. To identify RA cells, flow cytometric analysis was performed using anti-alpha(6) integrin and anti-CD71 antibodies. RA cells express high levels of alpha(6) integrin and low levels of CD71, which are considered as markers of an epidermal stem cell nature. Furthermore, electron microscopy showed that RA cells are small and have a high nuclear to cytoplasmic ratio, whereas SA and NA cells have well-developed cellular organelles and abundant tonofilaments. Western blot analysis showed that RA cells are slow cycling and express p63, a putative epidermal stem cell marker, whereas SA and NA cells express c-Myc, which is known to regulate stem cell fate. To compare epidermal regenerative abilities, skin equivalents (SEs) were made using RA, SA, and NA cells. The epidermis constructed from RA cells was well formed compared to those formed from SA or NA cells. In addition, only SEs with RA cells expressed alpha(6) integrin and beta(1) integrin at the basal layer. These results indicate that RA cells represent epidermal stem cells and are predominately comprised of stem cells. Therefore, the isolation of RA cells using a simple technique offers a potential route to their clinical application, because they are easily isolated and provide a high yield of epidermal stem cells.

Modulation of skin collagen metabolism in aged and photoaged human skin in vivo.

To the best of our knowledge, no study has been conducted to date to directly compare the collagen metabolism of photoaged and naturally aged human skin. In this study, we compared collagen synthesis, matrix metalloproteinase-1 levels, and gelatinase activity of sun-exposed and sun-protected skin of both young and old subjects. Using northern blot analysis, immunohistochemical stain, and Western blot analysis, we demonstrated that the levels of procollagen type I mRNA and protein in photoaged and naturally aged human skin in vivo are significantly lower than those of young skin. Furthermore, we demonstrated, by northern blot analysis, that the procollagen alpha1(I) mRNA expression of photoaged skin is much greater than that of sun-protected skin in the same individual. In situ hybridization and immunohistochemical stain were used to show that the expression of type I procollagen mRNA and protein in the fibroblasts of photoaged skin is greater than for naturally aged skin. In addition, it was found, by Western blot analysis using protein extracted from the dermal tissues, that the level of procollagen type I protein in photoaged skin is lower than that of naturally aged skin. The level of matrix metalloproteinase-1 protein and the activity of matrix metalloproteinase-2 were higher in the dermis of photoaged skin than in naturally aged skin. Our results suggest that the natural aging process decreases collagen synthesis and increases the expression of matrix metalloproteinases, whereas photoaging results in an increase of collagen synthesis and greater matrix metalloproteinase expression in human skin in vivo. Thus, the balance between collagen synthesis and degradation leading to collagen deficiency is different in photoaged and naturally aged skin.

Peroxynitrite scavenging and cytoprotective activity of 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether from the marine alga Symphyocladia latiuscula.

Peroxynitrite (ONOO(-)), formed from the reaction of superoxide (O(2)*(-)) and nitric oxide (*NO), is a cytotoxic species that can oxidize several cellular components such as proteins, lipids, and DNA. It has been implicated in diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, and atherosclerosis. Due to the lack of endogenous enzymes responsible for ONOO(-) inactivation, developing a specific ONOO(-) scavenger is of considerable importance. The aim of this study was to evaluate the ability of marine natural products to scavenge ONOO(-) and to protect cells against ONOO(-). Methanolic extracts of 17 marine alga were tested for their ONOO(-) scavenging activity. Among them, Symphyocladia latiuscula showed the potent scavenging activity. CH(2)CH(2) fraction was partitioned with CH(2)CH(2) following n-hexanal extraction from the methanol extract of S. latiuscula. It was highly effective for ONOO(-) scavenging activity. Further analysis of the active fractionated extract identified 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) as a potent ONOO(-) scavenger. The data demonstrated that TDB led to decreased ONOO(-)-mediated nitration of tyrosine through electron donation. TDB showed significant inhibition on nitration of bovine serum albumin and low-density lipoprotein by ONOO(-) in a dose-dependent manner. It also provided cytoprotection from cell damage induced by ONOO(-). TDB can be developed as an effective peroxynitrite scavenger for the prevention of the involved diseases.

Ultraviolet radiation increases tropoelastin mRNA expression in the epidermis of human skin in vivo.

Photoaged skin contains elastotic materials in the upper reticular dermis. This phenomenon is commonly known as solar elastosis. Little is known about the mechanisms leading to the accumulation of elastotic materials in photoaged skin, however. In this study, it was demonstrated that ultraviolet irradiation induced tropoelastin mRNA expression in the keratinocytes of human skin in vivo and also in cultured human keratinocytes by in situ hybridization and reverse transcriptase polymerase chain reaction. It was also shown by northern blot analysis (n = 5) that there were increased tropoelastin mRNA levels in the forearm (sun-exposed) skin of elderly persons, compared with upper-inner arm (sun-protected) skin of the same individuals. As demonstrated by in situ hybridization compared to sun-protected skin (upper-inner arm) (n = 5), tropoelastin mRNA expression in photoaged skin was higher in keratinocytes as well as in fibroblasts. Therefore, our results suggest that keratinocytes are another source of tropoelastin production after acute and chronic ultraviolet irradiation in human skin in vivo.

High tibial osteotomy for varus gonarthrosis: a 10- to 24-year follow-up study.

From January 1976 to December 1990, 66 high tibial osteotomies for medial gonarthrosis were performed in 59 patients. Thirty knees of 26 patients (18 women and 8 men) were reviewed after a mean follow-up period of 15.3 years (range, 10-24 years). The mean age of these 26 patients was 59 years at the time of operation and 75.5 years at the latest follow-up. The average femoro-tibial angle changed, from 187 degrees before surgery to 170 degrees after surgery, and to 174 degrees at the latest follow-up. Progression of osteoarthritic changes was observed in 87% for the medial and in 90% for the lateral compartment of the knee. Clinical results, assessed according to the Japanese Orthopaedic Association (JOA) knee score, showed improvement with a score of 65 points before surgery, and a score of 81 points at the latest follow-up. The overall clinical results were satisfactory for 60% of the knees. The results of this long-term follow-up study show that high tibial osteotomy for medial compartment osteoarthritis can be effective for as long as 15 years.

Site-specific effect of testosterone on bone mineral density in male hypogonadism.

To assess the correlation between the remaining serum testosterone and bone mineral density(BMD), and to determine the effect of exogenous testosterone on BMD in subjects with male hypogonadism, we evaluated the serum testosterone levels and BMDs of the femur neck, Ward's triangle and the spine(L1-4) in 20 subjects with Klinefelter's syndrome and 7 with hypogonadotropic hypogonadism before and after testosterone replacement. BMDs of the femur neck, Ward's triangle and the spine were below the age-matched normal mean at 77.8%(21/20), 74.1%(20/27) and 88.9%(24/27), respectively. There were significant differences in serum testosterone levels and the spinal BMD between the two groups and the BMD of the spine closely correlated with the serum testosterone level (R = 0.63, p < 0.001). Following a mean 11.8 +/- 4.9 months of testosterone replacement, the BMD at all sites increased significantly and the pretreatment difference in spinal BMD between the two groups disappeared. We conclude that, although testosterone may increases the bone density, it has a site-specific effect of maintaining and increasing the bone mass especially at the spine in male hypogonadism.

Testosterone productivity and histostructural changes of autotransplanted rat Leydig cells.

To investigate the possibility of in vivo transplantation of Leydig cells as a new biologic androgen replacement therapy, the Leydig cells procured from 6 week-old male Sprague-Dawley rats were autotransplanted, and the level of testosterone secretion and histostructural changes were observed. The renal subcapsular and intraperitoneal transplant showed higher levels of testosterone compared to subcutaneous or scrotal counterparts, and the number of transplanted cells was correlated with the level of measured testosterone. Furthermore, if the Leydig cells were transplanted intraperitoneally after the uptake on synthetic collagen, testosterone levels were higher than the ones simply transplanted without synthetic collagen uptake, resulting in 27 fold increase at 3 months. The activity of 125I-hCG decreased 20 to 40% at each month after transplantation compared to the normal levels, but no statistical significance was noted among different periods. The histologic examination revealed neovascularized capillaries and well demarcated sheet-like group of eosinophilic Leydig cells were observed at 4 weeks. But the evidence of destructive changes such as a focal inflammation with central dystropic ossification could be noted after 3 month. On electron microscopy, the marked indentation of nucleus and presence of lipochrome pigment were seen, and the number and size of smooth endoplasmic reticulum and mitochondria were reduced after 3 month. In conclusion, testosterone output could be increased to the physiologic range by increasing the number of transplant cells or utilizing collagen uptake but further effort is necessary on delaying or preventing the structural and functional decrement of Leydig cells.

Paraffinoma of the penis.

Augmentation of the body contour by localized injection of hard and soft paraffin rose to a zenith of popularity in the early 1900s, whereafter the severe destructive consequences of such injections became widely recognized. However in Korea, these injections are still performed much by nonmedical person. Paraffin or other mineral oil injection into body is no more a useful method to change body contour. We reviewed 26 cases of sclerosing lipogranuloma of penis with complications in recent 13 years after mean 18.5 months from previous injection of paraffin or vaseline. We conclude that the public should be informed of detrimental effects of paraffin injections and that the best treatment of penile paraffinoma is complete excision and appropriate penoplasty.

Treatment response with transurethral radiofrequency thermotherapy for symptomatic benign prostatic hyperplasia.

One hundred and two patients with benign prostatic hyperplasia were treated by transurethral radio-frequency thermotherapy (TURT) device (Thermex-II, Direx, Israel) with 47.5 degrees C in single session for 2 hours and 30 minutes from November 1992 to October 1993. Among them, 83 patients, who were followed up for more than 3 months were included in this study. Twenty-seven (32.5%) patients had a history of acute retention. Pretreated values of the mean Madsen-Iversen symptom score, maximum urine flow rate, postvoiding residual urine volume, prostate volume and prostate specific antigen (PSA) were 15.4, 6.5 ml/sec, 61.3ml, 43.2ml and 0.77 ng/ml respectively. Madsen-Iversen symptom score, maximum urine flow rate were measured at 2 weeks, 1, 3 and 6 months after TURT. The residual urine volume, prostate volume and PSA level were measured at 3 and 6 months after TURT. During the follow up, the symptom score started to decrease significantly at 1 month (9.9, p < 0.01) after TURT, and gradually decreased up to 6.9 at 3 months. The maximum flow rate showed initial significant improvement at 2 weeks (8.1 ml/sec., p < 0.01), but no significant interval change was observed thereafter. The residual volume decreased significantly at 3 months (41.3 ml, p < 0.01) and no decrement was noted until 6 months. Neither the prostate volume nor PSA value changed significantly at 3 or 6 months after TURT. The improvement, which was defined as a change of 50% or more in at least one of subjective or objective symptoms showed in 63.9% (53/83) at 3 months and 57.1% (32/56) at 6 months. Both subjective and objective improvements at 3 and 6 months after treatment showed in 24.1% and 19.6%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)