Claudin-1 expression decreases with increasing pathological grade in actinic keratosis and may be a marker of high-risk actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common sun-induced skin disorder that can progress to invasive squamous cell carcinoma. However, there is still no reliable method to predict high-risk AK. AIM: To identify markers that reflect the biological behaviour of AK and to understand the pathogenesis of AK. METHODS: In total, 52 patients with AK and 17 site-matched healthy controls (HCs) were enrolled. We evaluated solar elastosis and immunohistochemical features using antibodies to p53, vitamin D receptor (VDR), claudin-1 and Langerin (CD207). Comparisons between AK and HC skin were performed and analyses carried out according to the pathological grade of AK. RESULTS: We found that in both patients and HCs, solar elastosis increased and Langerhans cell (LC) density decreased with ageing. Solar elastosis and p53 expression were higher and VDR expression was lower in patients than in HCs; however, there was no statistical difference between them in relation to the pathological grade of AK. Claudin-1 expression gradually decreased from HC skin to severe AK, and particularly decreased in areas with epidermal atypia. LC density in severe AK was significantly lower than in HC skin and mild AK, while there was no difference in LC density between HC skin, mild AK and moderate AK. CONCLUSIONS: Claudin-1 could be a useful marker of the pathological severity of AK. In addition, p53 increases and VDR decreases in AK, not in a gradual manner but in the early steps of carcinogenesis. LC density is relatively maintained in AK until it reaches severe dysplasia.

The quality of reporting randomized controlled trials in the dermatology literature in an era where the CONSORT statement is a standard.

BACKGROUND: The quality of reporting randomized controlled trials (RCTs) in the dermatology literature has not received much consideration since the late 2000s. OBJECTIVES: We aimed to assess the quality of recently reported RCTs published in dermatology journals, focusing on randomization processes, blinding and trial registration. METHODS: We reviewed 2042 original articles and identified 141 primary reports of RCTs in four dermatology journals (Journal of the American Academy of Dermatology, JAMA Dermatology, Journal of Investigative Dermatology and British Journal of Dermatology) from January 2015 to December 2017. Details were extracted from articles, supplements and public trial registries. A multivariable logistic regression analysis was conducted to identify factors associated with optimal reporting quality. RESULTS: Among the 141 RCTs, 99 (70·2%), 82 (58·2%) and 69 (48·9%) described methods used for randomization, allocation concealment and implementation, respectively. Most trials (126, 89·4%) reported blinding status; however, one-third did not state the similarity of the intervention. Furthermore, 52 RCTs (36·9%) were not registered prospectively. Trials published in the British Journal of Dermatology and using central randomization were significantly associated with optimal reporting quality after adjusting for covariates. CONCLUSIONS: Several critical items in reporting RCTs, including allocation concealment, similarity of interventions in blinded trials and prospective trial registration, have remained unsatisfactory in the recent dermatology literature.

CD34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea.

BACKGROUND: Fibrosis is thought to be the main pathophysiology of scleroderma, and myofibroblasts play the main role in abnormal fibrotic pathologies. Altered distribution of dermal dendritic cells (DDCs) and vascular abnormalities has been reported to relate to the pathogenesis of scleroderma. OBJECTIVE: To investigate fibrotic pathogenesis of morphea (localized scleroderma) by demonstrating the relative expression and distribution of DDCs and myofibroblasts, we performed immunohistochemical stains using several relevant antibodies. METHODS: Skin lesions of 50 patients with morphea and age-, sex- and site-matched normal skin of 50 subjects were evaluated for the following antibodies: CD34, factor XIIIa (FXIIIa), smooth muscle actin (SMA), CD31 and vascular cell adhesion molecule-1 (VCAM-1). RESULTS: CD34 stromal stain was significantly lower in patients than controls (P = 0.000), while FXIIIa, SMA and VCAM-1 stains were significantly higher in patients than controls (P = 0.043, P = 0.000 and P = 0.027, respectively). In subtype analysis within patients, CD34 stromal stain showed decreasing trends with increasing disease extent and increasing fibrosis, respectively. CD34 stromal stain showed an inverse correlation and mutually exclusive spatial expression pattern with SMA stain (r = -0.286, P = 0.044). The inverse relationship was maintained in each dermal layer analysis, upper and lower dermis (r = -0.397, P = 0.004 and r = -0.281, P = 0.048, respectively). CONCLUSIONS: Mutually exclusive staining patterns of CD34 stromal and SMA stains suggest a phenotypic change of CD34+ DDCs into SMA+ myofibroblasts with increasing disease extent and fibrosis in morphea. Degree of loss of CD34+ DDCs can be a useful marker in predicting the extent and severity of morphea.

Lipid profile in patients with androgenetic alopecia: a meta-analysis.

BACKGROUND: Many studies have reported that androgenetic alopecia (AGA) might be a risk factor for cardiovascular disorders, and the association of AGA with dyslipidaemia has been studied. However, the results were controversial and previous meta-analyses had several critical limitations. OBJECTIVE: We performed a meta-analysis to clarify whether AGA patients have abnormal lipid profiles. METHODS: A literature search was performed using the MEDLINE, EMBASE, The Cochrane Library and KOREA MED databases. RESULTS: We pooled 19 observational studies and performed a meta-analysis to compare serum total cholesterol, serum triglyceride (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) and the cholesterol levels between AGA and control groups. The serum total cholesterol, TG and LDL cholesterol levels were significantly higher in the AGA group than in the control group, and the standardized mean differences were 0.377 (95% confidence interval [CI]: 0.182-0.572, P < 0.001), 0.426 (95% CI: 0.164-0.688, P = 0.001) and 0.450 (95% CI: 0.171-0.728, P = 0.002) respectively. In addition, HDL cholesterol level was significantly lower in the AGA group than in the control group, and the standardized mean difference was -0.248 (95% CI: -0.472 to -0.023, P = 0.030). CONCLUSIONS: AGA patients showed statistically significant abnormal lipid profiles, and this might partly explain the association between AGA and cardiovascular diseases.

A case of perforating dermatofibroma with floret-like giant cells.

Dermatofibromas are slow-growing solitary nodules, composed mostly of a dermal proliferation of spindle cells and epithelioid cells. Some dermatofibromas present with multinucleated giant cells, such as Touton, foreign body, and osteoclast-like cells. We report a case of dermatofibroma containing both Touton giant cells and floret-type cells. A 12-year-old boy presented with a 6-mm, firm, nontender, dusky-red to greyish dermal nodule on his left popliteal fossa. As suggested clinically by the central opening, perforation of the epidermis with partial extrusion of the dermal components, including macrophages and vertically oriented collagen bundles, via transepidermal elimination, were detected. In the upper dermis, collagen trapping and mostly epithelioid cells with many giant cells were seen, while the lower part contained mainly spindle cells in a storiform pattern. Multinucleated giant cells scattered in the upper dermis were mainly floret-type multinucleated giant cells with star-shaped cytoplasmic projections, associated with some Touton giant cells. To our knowledge, this is the first report of a perforating dermatofibroma with floret-type multinucleated giant cells.

Psoriasis concurrent with inflammatory bowel disease.

BACKGROUND: Previous studies have indicated an association between psoriasis and inflammatory bowel disease (IBD), and the concurrence of the two diseases reportedly has higher morbidities in Caucasian populations. However, reports on the concurrence of psoriasis with IBD in the Asian population in the literature are scarce. Objective To analyse the characteristics of psoriasis concurrent with IBD and investigate the associated morbidity in the Asian population. METHODS: We retrospectively examined the medical records of 15 patients with a confirmed diagnosis of both psoriasis and IBD. Sixty age-, gender-, and ethnicity-matched patients with a confirmed diagnosis of only psoriasis were included as controls. Both cases and controls had visited the Seoul National University Hospital or Seoul National University Boramae Hospital between 1990 and 2012. The characteristics of psoriasis, presence of comorbidity and laboratory parameters were compared between the two groups. RESULTS: Compared to controls with psoriasis only, cases of psoriasis concurrent with IBD had a younger age of onset, longer duration of psoriasis and a higher Psoriasis Area Severity Index (PASI) score. A larger proportion of cases was treated with phototherapy, systemic therapy and biologics. However, all these differences above were not statistically significant. Cases of psoriasis with concurrent IBD showed higher erythrocyte sedimentation rate and C-reactive protein levels compared with the controls (both P = 0.000). Furthermore, this case group had a higher proportion of patients with psoriatic arthritis and with more than one autoimmune disease as compared with the control group (P = 0.007 and 0.005 respectively). CONCLUSION: Asian patients having psoriasis concurrent with IBD exhibited different characteristics as compared with those having psoriasis only, particularly in terms of psoriasis severity, risk of psoriatic arthritis, systemic inflammatory parameters and presence of autoimmune comorbidity. However, further studies elucidating the exact pathogenesis and including a larger number of patients are required.

Metabolic syndrome and sex-specific socio-economic disparities in childhood and adulthood: the Korea National Health and Nutrition Examination Surveys.

AIMS: To examine whether adulthood and/or childhood sex-specific socio-economic disparities are associated with metabolic syndrome and its components in a developed non-Western setting. METHODS: Based on the Fourth Korea National Health and Nutrition Examination Surveys, 14 888 people aged ≥ 20 years were analysed to evaluate the effect of adult and childhood socio-economic status on metabolic syndrome. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Logistic regression analyses were conducted to calculate the odds ratios for metabolic syndrome and each component of metabolic syndrome in later life. RESULTS: The age-standardized prevalence of metabolic syndrome was 26.6% for men and 21.3% for women. Compared with the highest level of education, men with the lowest education level were significantly less likely to have metabolic syndrome (odds ratio 0.76, 95% CI 0.60-0.96), whereas the opposite association was found in women (odds ratio 3.29, 95% CI 2.45-4.42). Men who were manual labourers and economically inactive had a lower prevalence of metabolic syndrome compared with those with non-manual jobs (odds ratio 0.82, 95% CI 0.69-0.98 and odds ratio 0.79, 95% CI 0.64-0.99, respectively), but the reverse association was observed in women (odds ratio 1.34, 95% CI 1.04-1.73 and odds ratio 1.40, 95% CI 1.09-1.81, respectively). A significant interaction between combined adulthood and childhood socio-economic status on the presence of metabolic syndrome was observed (P < 0.05). CONCLUSIONS: Our findings suggest that sex-specific socio-economic disparities in childhood and adulthood have differential effects on the prevalence of metabolic syndrome and its individual components in Korea.

Emergence of Enterococcus species in the infectious microorganisms cultured from patients with endophthalmitis in South Korea.

PURPOSE: To investigate the microorganisms in culture-proven endophthalmitis and their susceptibilities to antimicrobial agents commonly used in South Korea. METHODS: Medical records of consecutive patients with culture-proven endophthalmitis at eight institutions between 1 January 2004 and 31 July 31 2010 were reviewed. Four categories of endophthalmitis were studied: postoperative, posttraumatic, endogenous, and unspecified. Outcome measures were culture-proven infectious organisms, antimicrobial susceptibilities, and final visual acuity in the patients. RESULTS: A total of 93 microorganisms were identified from 103 patients during the study period. The positive culture rate was 59.2 % (103/174). The most common organisms identified were Enterococcus faecalis (in 20.8 % of patients, 20/96), Staphylococcus epidermidis (18.8 %, 18/96), other coagulase-negative staphylococci (10.4 %, 10/96), Pseudomonas aeruginosa (6.3 %, 6/96), and Klebsiella pneumoniae (6.3 %, 6/96). Two cases of Enterococcus faecium (2.1 %) were recognized. Overall, 70 of 96 (73.0 %) isolates were Gram-positive bacteria, 22 (23.0 %) were Gram-negative bacteria, and 4 (4.2 %) were fungi. The most common organisms resulting in reduced light perception were E. faecalis and K. pneumoniae. CONCLUSIONS: The emergence of E. faecalis in endophthalmitis is mainly caused by the high incidence of E. faecalis in postoperative endophthalmitis. This increase also impacts the final visual acuity of the patients.

Additional surgical factors affecting the recurrence of hallux valgus after Ludloff osteotomy.

We reviewed 91 patients (103 feet) who underwent a Ludloff osteotomy combined with additional procedures. According to the combined procedures performed, patients were divided into Group I (31 feet; first web space release), Group II (35 feet; Akin osteotomy and trans-articular release), or Group III (37 feet; Akin osteotomy, supplementary axial Kirschner (K-) wire fixation, and trans-articular release). Each group was then further subdivided into severe and moderate deformities. The mean hallux valgus angle correction of Group II was significantly greater than that of Group I (p = 0.001). The mean intermetatarsal angle correction of Group III was significantly greater than that of Group II (p < 0.001). In severe deformities, post-operative incongruity of the first metatarsophalangeal joint was least common in Group I (p = 0.026). Akin osteotomy significantly increased correction of the hallux valgus angle, while a supplementary K-wire significantly reduced the later loss of intermetatarsal angle correction. First web space release can be recommended for severe deformity. Additionally, K-wire fixation (odds ratio (OR) 5.05 (95% confidence interval (CI) 1.21 to 24.39); p = 0.032) and the pre-operative hallux valgus angle (OR 2.20 (95% CI 1.11 to 4.73); p = 0.001) were shown to be factors affecting recurrence of hallux valgus after Ludloff osteotomy.

Modulation of the murine microbiome with a concomitant anti-obesity effect by Lactobacillus rhamnosus GG and Lactobacillus sakei NR28.

The microbiota of the gastrointestinal tract (GIT) constitutes the major part of the total human microbiome and is considered to be an important regulator of human health and host metabolism. Numerous investigations in recent years have focused on the connection between the human microbiota and metabolic diseases such as obesity, type II diabetes and atherosclerosis. Yet, little is known about the impact of probiotic consumption on the GIT microbial population and the potential effect on chronic diseases. In this study, the modulation of the microbial community in the murine small intestine resulting from probiotic feeding was investigated and was found to be associated with an anti-obesity effect. Changes in the microbiota of the mouse faeces and small intestine were monitored using quantitative real-time PCR and by following the mRNA expression levels of various obesity-related biomarkers following probiotic feeding in a mouse model. Lactobacillus rhamnosus GG and Lactobacillus sakei NR28 (a putative probiotic strain isolated from kimchi) were administered at a daily level of approximately 1×10(8) viable bacteria per mouse (C57BL/6J mice) for up to three weeks. Feeding these strains resulted in a significant reduction of epididymal fat mass, as well as obesity-related biomarkers like acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 in the liver. The total number and ratio of the microbial groups, i.e. Firmicutes, Bacteroidetes, Clostridium cluster I and XIVab, and Lactobacillus spp. were modulated in the small intestine, and the Firmicutes:Bacteroidetes ratio was decreased. In contrast, no noticeable effect of probiotic feeding could be detected on the faecal microbiota, neither quantitatively, nor with regard to the bacterial groups (Firmicutes, Bacteroidetes, Clostridium cluster I and XIVab, and Lactobacillus spp.) studied.

External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long-chain triglyceride emulsion propofol in beagle dogs.

This study aimed at assessing the predictive performance of a target-controlled infusion (TCI) system, which incorporates canine PK-PD models for microemulsion and long-chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7-day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: -0.8 to 4.9), 18.1% (15.6-20.5), 1.9%/h, 7.3% (5.4-9.3), and -0.5% (-2.6 to 1.6), 8.7% (7.3-10.1), 2.5%/h, 6.0% (4.1-7.2) for microemulsion propofol, and -9.3% (-11.6 to -6.9), 20.1% (18.2-22.0), 5.1%/h, 7.6% (6.1-9.1) and 5.6% (4.1-7.1), 8.0% (6.9-9.3), 4.7%/h, 4.1% (3.1-5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK-PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.

Role of FK506 binding proteins in neurodegenerative disorders.

Protein misfolding has been implicated in the pathophysiology of several neurodegenerative 'amyloidoses' that includes Alzheimer's, Parkinson's, Huntington's disease, frontotemporal dementia and amyotrophic lateral sclerosis. Accumulation of misfolded proteins into ordered fibrillar intra- or extracellular amyloids results in brain lesions that in turn lead to injury and neuronal loss. The appearance of protein aggregates in the diseased brain hints at an inability of cellular chaperones to properly assist folding of client proteins. Not surprisingly, studies involving cell-based and animal models of the neurodegenerative diseases have shown that overexpression of molecular chaperones can provide neuroprotection. Together with identification of new targets for symptomatic relief of motor and non-motor defects in neurodegenerative disorders, there is a critical unmet clinical need for the development of novel neuroprotective molecules. One such promising class of compounds are neuroimmunophilin ligands (NILs). Derived from FK506 (tacrolimus), NILs have been shown to be efficacious in a number of neurodegenerative disorders. The ability of these nonimmunosuppressive NILs to protect neurons is modulated, in part, by a large family of co-chaperone proteins called the FK506 binding proteins (FKBPs). This review focuses on the roles of FKBPs in neurodegenerative disorders with an emphasis on the cellular mechanisms responsible for their neuroprotective and neurotrophic activities. We discuss the structural features of FKBPs and the mode of action of NILs. For brevity, we limit our discussion to those FKBPs that are particularly enriched in the nervous system. We hope that such information will aid in the rational design of new and improved NILs for ameliorating neurodegenerative disorders.

Degradation of organic dye using zero-valent iron prepared from by-product of pickling line.

In this study, zero-valent iron (ZVI) was produced using iron oxide that is a by-product of a pickling line at a steel works. The reaction activity of the produced ZVI was evaluated through a series of decomposition experiments of Orange II aqueous solution. The size of ZVI particles increased with reduction temperature due to coalescence. Correspondingly, the specific surface area of ZVI decreased with increasing reduction temperature. The decomposition efficiency of synthesized ZVI particles was higher at a lower pH. In particular, no significant decomposition reaction was observed at pH of 4 and higher. The rate of the ZVI-assisted decomposition of Orange II was increased by addition of H2O2 at pH of 3, whereas it was reduced by addition of H2O2 at a higher pH of 6. Nevertheless, simultaneous use of ZVI, UV and H2O2 led to a considerable increase in the decomposition rate even at a high pH condition (pH = 6).

A tunable 3D optofluidic waveguide dye laser via two centrifugal Dean flow streams.

This paper presents a tunable optofluidic waveguide dye laser utilizing two centrifugal Dean flows. The centrifugal Dean flow increases the light confinement of the dye laser by shaping a three-dimensional (3D) liquid waveguide from curved microchannels. The active medium with the laser dye is dissolved in the liquid core and pumped with an external pump laser to produce stimulated emission. The laser's Fabry-Pérot microcavity is formed with a pair of aligned gold-coated fiber facets to amplify the fluorescent emission. The advantage of the 3D optofluidic waveguide dye laser is its higher efficiency, thus to obtain lasing at a reduced threshold (60%) with higher output energy. The demonstrated slope efficiency is at least 3-fold higher than its traditional two-dimensional equivalent. In addition, the laser output energy can be varied on demand by tuning the flow rates of the two flows. This technique provides a versatile platform for high potential applications microfluidic biosensor and bioanalysis.

High-concentration all-trans retinoic acid induces dermal inflammation and reduces the accumulation of type I procollagen in human skin in vivo.

BACKGROUND: Because inflammation is a factor promoting ageing, all-trans retinoic acid (RA)-induced irritation may have a negative influence on collagen accumulation in human skin despite its stimulation of collagen production. OBJECTIVES: To determine whether RA-induced irritation detrimentally affects RA efficacy as represented by new collagen synthesis. METHODS: Retinoic acid (0·01%, 0·025% or 0·05%) or vehicle was applied to the buttock skin of elderly male volunteers three times a week for 8 weeks under continuous occlusion. Every 2 weeks, biopsy specimens were obtained and immunohistochemical analysis was performed to determine levels of type I procollagen expression and inflammatory cell infiltration. RESULTS: Topical RA regardless of concentration increased type I procollagen expression in human skin in vivo after 2 weeks. However, only 0·01% RA continuously increased type I procollagen expression up to 8 weeks. After 4 weeks, significant infiltrations of macrophages and neutrophils were observed in 0·025% and 0·05% RA-treated skin, and procollagen expression had returned to baseline. CONCLUSIONS: Excessive RA-induced inflammation might prevent collagen accumulation in aged skin despite the positive effect of RA on collagen production.