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BACKGROUND: Polymorphisms in TMEM106B, a gene on chromosome 7p21.3 involved in lysosomal trafficking, correlates to worse neuropathological and clinical outcomes in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) with TDP-43 inclusions. In a small cohort of C9orf72 expansion carriers, we previously found an atypical, neuroglial tauopathy in cases harboring a TMEM106B rs1990622 A/A genotype. AIMS: To test whether TMEM106B genotype affects the risk of developing atypical tauopathy under a recessive genotype model (presence versus absence of two major alleles: A/A vs. A/G and G/G). METHODS: We characterized the atypical tauopathy neuropathologically and determined its frequency by TMEM106B rs1990622 genotypes in 90 postmortem cases with a primary diagnosis of FTLD/ALS-TDP [mean age at death 65.5 years (±8.1),40% female]. We investigated the effect of this new atypical tauopathy on demographics and clinical and neuropsychological metrics. We also genotyped TMEM106B in an independent series with phenotypically similar cases. RESULTS: Sixteen cases (16/90, 17.7 %) showed the temporal-predominant neuro-astroglial tauopathy, and 93.7% of them carried an A/A genotype (vs. ~35% in a population cohort). The odds ratio of FTLD/ALS-TDP individuals with the A/A genotype showing neuro-astroglial tauopathy was 13.9. Individuals with this tauopathy were older at onset (p=0.01). The validation cohort had a similarly high proportion of rs1990622 A/A genotype. TDP-43 and tau changes co-occur in a subset of neurons. CONCLUSIONS: Our data add to the growing body of evidence that TMEM106B polymorphisms may modulate neurodegeneration. A distinctive medial temporal predominant, 4-repeat, neuro-astroglial tauopathy strongly correlates to TMEM106B A/A genotype in FTLD/ALS-TDP cases.

Given that injuries to children during periods of hospitalization can lead to more serious health conditions in vulnerable children, preventing pediatric inpatient injuries should be a priority for the pediatric health care profession. This study was conducted to develop a conceptual model of factors affecting pediatric inpatient safety, including all injuries, not just fall injuries, in pediatric units. An explorative sequential mixed methods design was used. Qualitative interviews were conducted with 13 nurses working in pediatrics units and 17 parents of hospitalized children, and then 200 nurses in pediatrics units and parents of hospitalized children completed a self-report questionnaire. Based on the integration of both qualitative and quantitative data using building and weaving narrative integration, the Pediatric Inpatient Safety Accidents (PISA) model was proposed. The PISA model contains two main domains, the immediate and mediating domain and encompasses the six factors explain of the elements affecting the occurrence and prevention of pediatric inpatient safety accidents. The PISA model can serve as a model to understand child accidents in hospitals as well as to plan customized nursing interventions to prevent child accidents.

Background Previous studies have demonstrated increased pore size and darkening skin color with total sleep deprivation. There are many studies of skin characteristics with short-term sleep restriction, but there are few studies on skin characteristics when sleep is restricted more than three consecutive days. This study evaluated skin changes with sleep limited to 4 hours per night for six nights. Materials and methods The study included 32 Korean women in their 40s. Skin hydration, desquamation, barrier recovery, texture, gloss, transparency, elasticity, crow's feet, frown lines, and color were measured. Individual sleep time was monitored by smartwatches. Subjects slept 8 hours per night for six nights in week one and 4 hours per night for six nights in week two. Results Skin hydration was significantly reduced after 1 day of sleep deprivation, and it continued to decrease. Skin gloss, desquamation, transparency, elasticity, and wrinkles were significantly aggravated after 1 day of sleep deprivation. Skin texture was significantly aggravated on the fourth day of sleep restriction. Elasticity was most affected by reduced sleep, with a standardized coefficient of -.320, indicating a significant decrease over time as compared to other characteristics. Conclusion Skin hydration was gradually decreased with sleep restriction. Skin texture did not change after only 1 day of sleep restriction. It is a new finding that elasticity decreases more than other skin characteristics with prolonged sleep restriction.

Background Transparent-looking skin is an objective of facial makeup products. However, this effect of makeup products has not been investigated to Korean women's faces. Materials and methods We investigated the perception of blue light on women's faces using the blue pearl pigment. We compared colors and/or spectra of naked skin, standard makeup powder foundation (standard foundation), and test makeup powder foundations containing the blue pearl pigment 10% (w/w) (pearl foundation) or (ultramarine blue) blue pigment 0.2% (w/w) (pigment foundation) on real women's faces (n = 6) using spectrophotometry and facial image analysis. A self-administered questionnaire showed facial images (n = 3) with applied makeup powder foundations on computer monitor (n = 35); evaluated items were blooming, transparency, smoothness, gloss, and vitality. Results In vivo, the pearl foundation showed significantly lower b* values (degree of yellowness) than did naked skin, and pigment foundation and the samples also showed significantly higher reflection of blue light (410-490 nm) than did naked skin, standard foundation, or pigment foundation. In image analysis, the image with the pearl foundation showed significantly lower quasi-b* value. On the self-administered questionnaire, the results showed that the pearl foundation had a significantly higher grade than did naked skin, standard foundation, or pigment foundation at all evaluation items: blooming, transparency, smoothness, gloss, and vitality. Conclusion Blue pearl pigment creates the perception of blue light effect, including transparency and gloss in Korean women.

Previously, we reported that piperine, one of the major pungent components in black pepper, attenuates adipogenesis by repressing PPARγ activity in 3T3-L1 preadipocytes. However, the epigenetic mechanisms underlying this activity remain unexplored. Here, gene set enrichment analysis using microarray data indicated that there was significant downregulation of adipogenesis-associated and PPARγ target genes and upregulation of genes bound with H3K27me3 in response to piperine. As shown by Gene Ontology analysis, the upregulated genes are related to lipid oxidation and polycomb repressive complex 2 (PRC2). Chromatin immunoprecipitation assays revealed that PPARγ (and its coactivators), H3K4me3, and H3K9ac were less enriched at the PPAR response element of three adipogenic genes, whereas increased accumulation of H3K9me2, H3K27me3, and Ezh2 was found, which likely led to the reduced gene expression. Further analysis using three lipolytic genes revealed the opposite enrichment pattern of H3K4me3 and H3K27me3 at the Ezh2 binding site. Treatment with GSK343, an Ezh2 inhibitor, elevated lipolytic gene expression by decreasing the enrichment of H3K27me3 during adipogenesis, which confirms that Ezh2 plays a repressive role in lipolysis. Overall, these results suggest that piperine regulates the expression of adipogenic and lipolytic genes by dynamic regulation of histone modifications, leading to the repression of adipocyte differentiation.

Pseudomonas aeruginosa is an opportunist pathogen that causes purulent inflammation in the skin and in the ears of dogs. Among the various virulence factors of P. aeruginosa, biofilms have been reported to result in antibiotic resistance, leading to therapeutic limitations. Cold atmospheric microwave plasma (CAMP) is known to have a high antimicrobial effect, which causes physical cell wall rupture and DNA damage.The objective of this study was to evaluate the antibacterial and antibiofilm effects of CAMP against planktonic bacteria and the biofilm of P. aeruginosa.The antibacterial effect of CAMP against P. aeruginosa ATCC10145 and clinical isolates (n = 30) was evaluated using the colony count method. We also assessed the effect of CAMP on biofilm of P. aeruginosa ATCC strain by the colony count method, water-soluble tetrazolium salt (WST) assay and confocal laser scanning microscopy (CLSM).The complete eradication of P. aeruginosa (ATCC strain and clinical isolates) was achieved within 120 s at 50 W, and clinical isolates required 60 s shorter than the ATCC strain for complete eradication at 50 W. We also confirmed the time-dependent bactericidal effect of CAMP at 50 W against ATCC strain biofilm.CAMP was effective against both planktonic bacteria and biofilm formation of P. aeruginosa. However, further studies on in vivo efficacy and safety in canine skin and ears are necessary to fully validate its clinical application.背景-铜绿假单胞菌是一种条件致病菌, 可引起犬皮肤和耳部化脓性炎症。在铜绿假单胞菌的各种毒力因子中, 有报道生物膜导致抗生素耐药, 限制了疗效。已知冷大气微波等离子体(CAMP)具有较高的抗菌作用, 从而引起物理细胞壁破裂和DNA损伤。 假设/目的-本研究的目的是评价CAMP对浮游细菌和铜绿假单胞菌生物膜的抗菌和抗生物膜作用。 方法和材料-使用菌落计数法评价CAMP对铜绿假单胞菌ATCC10145和临床分离株(n = 30)的抗菌作用。我们还通过菌落计数法、水溶性四唑盐(WST)试验和激光共聚焦显微镜(CLSM)评估了CAMP对铜绿假单胞菌ATCC菌株生物膜的影响。 结果-铜绿假单胞菌 (ATCC菌株和临床分离株) 在50 W下120 s内完全根除, 在50 W下,临床分离株完全根除所需时间比ATCC菌株短60 s。我们还证实了50 WCAMP对ATCC菌株生物膜的时间依赖性杀菌作用。 结论和临床重要性-CAMP对抑制浮游细菌和铜绿假单胞菌生物膜形成均有效。但有必要对犬皮肤和耳部的体内疗效和安全性进行进一步研究, 以充分验证其临床应用。.Pseudomonas aeruginosa est un pathogène opportuniste qui provoque une inflammation purulente de la peau et des oreilles des chiens. Parmi les différents facteurs de virulence de P. aeruginosa, il a été rapporté que les biofilms entraînent une résistance aux antibiotiques, entraînant des limitations thérapeutiques. Le CAMP (Cold atmospheric microwave plasma) est connu pour avoir un effet antimicrobien élevé, ce qui provoque une rupture physique de la paroi cellulaire et des dommages à l'ADN. HYPOTHÈSE/OBJECTIFS: L'objectif de cette étude était d'évaluer les effets antibactériens et antibiofilm du CAMP contre les bactéries planctoniques et le biofilm de P. aeruginosa. MÉTHODES ET MATÉRIEL: L'effet antibactérien du CAMP contre P. aeruginosa ATCC10145 et les isolats cliniques (n = 30) a été évalué à l'aide de la méthode de comptage des colonies. Nous avons également évalué l'effet du CAMP sur le biofilm de la souche ATCC de P. aeruginosa par la méthode de comptage des colonies, le dosage du sel de tétrazolium hydrosoluble (WST) et la microscopie confocale à balayage laser (CLSM). RÉSULTATS: L'éradication complète de P. aeruginosa (souche ATCC et isolats cliniques) a été réalisée en 120 s à 50 W, et les isolats cliniques ont nécessité 60 s de moins que la souche ATCC pour une éradication complète à 50 W. Nous avons également confirmé l’effet bactéricide temps dépendant du CAMP à 50 W contre le biofilm de la souche ATCC.CAMP était efficace contre les bactéries planctoniques et la formation de biofilm de P. aeruginosa. Cependant, d'autres études sur l'efficacité et l'innocuité in vivo dans la peau et les oreilles canines sont nécessaires pour valider pleinement son application clinique.Pseudomonas aeruginosa ist ein opportunistisches Pathogen, welches eine eitrige Entzündung in der Haut und in den Ohren von Hunden verursacht. Unter den verschiedenen Virulenzfaktoren von P. aeruginosa wird ein Biofilm beschrieben, welcher zu antibiotischer Resistenz führt, was wiederum zu therapeutischen Limitierungen führt. Kaltes atmosphärisches Mikrowellenplasma (CAMP) ist bekannt für eine starke antimikrobielle Wirkung, die eine physische Zellwandruptur und eine Schädigung der DNA verursacht.Das Ziel dieser Studie war eine Evaluierung der antibakteriellen und Antibiofilm Wirksamkeiten von CAMP gegenüber planktonischen Bakterien und dem Biofilm von P. aeruginosa.Die antibakterielle Wirkung von CAMP gegenüber P. aeruginosa ATCC10145 und klinischen Isolaten (n = 30) wurde mittels Koloniezählungsmethode evaluiert. Wir untersuchten auch die Auswirkung von CAMP auf den Biofilm von P. aeruginosa ATCC Stamm mittels Koloniezählungsmethode, wasserlöslichem Tetrazolium Salz (WST) Assay und konfokaler Laserscanmikroskopie (CLSM).Die gänzliche Auslöschung von P. aeruginosa (ATCC Stamm und klinische Isolate) wurde innerhalb von 120s bei 50 W erzielt, klinische Isolate benötigten 60s weniger als die ATCC Stämme für eine komplette Auslöschung bei 50 W. Wir bestätigten auch eine Zeit-abhängige bakterizide Wirkung von CAMP bei 50 W gegenüber dem Biofilm von ATCC Stämmen.CAMP war gegenüber planktonischen Bakterien sowie Biofilmbildung von P. aeruginosa wirksam. Es sind jedoch weitere Studien nötig, um die in vivo Wirksamkeit und Sicherheit auf der Haut und in den Ohren des Hundes zu untersuchen, um die klinische Applikation vollständig zu validieren.背景-Pseudomonas aeruginosaは、犬の皮膚や耳に膿性の炎症を引き起こす日和見病原体である。P. aeruginosaの様々な病原因子の中でも、バイオフィルムは抗生物質耐性をもたらすことが報告されており、治療の限界につながっている。冷気マイクロ波プラズマ (CAMP) は高い抗菌効果を持つことが知られており、物理的な細胞壁の破壊及びDNAの損傷を引き起こす。 仮説・目的-本研究の目的は、浮遊性細菌およびP. aeruginosaのバイオフィルムに対するCAMPの抗菌・抗バイオフィルム効果を評価することであった。 材料と方法 - P. aeruginosa ATCC10145および臨床分離株 (n = 30) に対するCAMPの抗菌効果をコロニーカウント法で評価した。また、P. aeruginosa ATCC株のバイオフィルムに対するCAMPの効果をコロニーカウント法、水溶性テトラゾリウム塩 (WST) アッセイ法、共焦点レーザー走査型顕微鏡 (CLSM) で評価した。 結果 - P. aeruginosa(ATCC株および臨床分離株) の完全な根絶は50Wで120秒以内に達成され、臨床分離株は50Wでの完全な根絶にATCC株よりも60秒短い時間を必要とした。また、ATCC株のバイオフィルムに対するCAMPの50Wでの時間依存的な殺菌効果を確認した。 結論と臨床上の重要性 - CAMPは、浮遊性細菌及びP. aeruginosaのバイオフィルム形成の両方に対して有効であった。しかし、その臨床応用を完全に検証するためには、犬の皮膚や耳におけるin vivoの有効性及び安全性に関するさらなる研究が必要である。.Pseudomonas aeruginosa é um patógeno oportunista que causa inflamação purulenta na pele e orelhas de cães. Dentre os fatores de virulência de P. aeruginosa, os biofilmes têm sido relatados como causadores de resistência a antimicrobianos, levando a limitações terapêuticas. O plasma atmosférico frio (CAMP) é conhecido por apresentar elevada ação antimicrobiana, que causa ruptura física da parede celular e dano ao DNA. HIPÓTESE/OBJETIVOS: O objetivo deste estudo foi avaliar os efeitos antibacterianos e antibiofilme do CAMP contra bactérias P. aeruginosa nas formas planctônica e biofilme. MÉTODOS E MATERIAIS: O efeito antibacteriano de CAMP contra P. aeruginosa ATCC10145 e isolados clínicos (n = 30) foi avaliado utilizando o método de contagem de colônias. Nós também avaliamos o efeito de CAMP no biofilme de P. aeruginosa cepa ATCC pelo método de contagem de colônias, ensaio de sal de tetrazólio solúvel em água (WST) e microscopia confocal de varredura a laser (CLSM).A erradicação completa de P. aeruginosa (cepa ATCC e isolados clínicos) foi obtida dentro de 120 s a 50 W, e os isolados clínicos precisaram de 60 s a menos que a cepa ATCC para completar a erradicação a 50 W. Nós também confirmamos o efeito bactericida tempo-dependente do CAMP a 50 W contra o biofilme da cepa ATCC. CONCLUSÕES E IMPORTÂNCIA CLÍNICA: O CAMP foi eficaz contra bactérias planctônicas e formação de biofilme de P. aeruginosa. Entretanto, mais estudos sobre a eficácia in vivo e a segurança na pele canina e orelhas são necessários para validar a sua aplicação clínica.INTRODUCCIÓN: Pseudomonas aeruginosa es un patógeno oportunista que causa inflamación purulenta en la piel y en los oídos de los perros. Entre los diversos factores de virulencia de P. aeruginosa, se ha informado que la formación de biopelículas da lugar a resistencia a los antibióticos, lo que genera limitaciones terapéuticas. Se sabe que el plasma de microondas atmosférico frío (CAMP) tiene un alto efecto antimicrobiano, que provoca la ruptura física de la pared celular y daño al DNA bacteriano. HIPÓTESIS/OBJETIVOS: El objetivo de este estudio fue evaluar los efectos antibacterianos y antipelículas biológicas de CAMP contra bacterias planctónicas y el biofilm de P. aeruginosa. MÉTODOS Y MATERIALES: Se evaluó el efecto antibacteriano de CAMP contra P. aeruginosa ATCC10145 y aislados clínicos (n = 30) utilizando el método de recuento de colonias. También evaluamos el efecto de CAMP sobre la biopelícula de la cepa ATCC de P. aeruginosa mediante el método de recuento de colonias, el ensayo de sal de tetrazolio soluble en agua (WST) y la microscopía de barrido láser confocal (CLSM). RESULTADOS: la eleiminación completa de P. aeruginosa (cepa ATCC y aislados clínicos) se logró con 120s a 50 W, y los aislados clínicos requirieron 60s menos que la cepa ATCC para la eliminación completa a 50 W. También confirmamos efecto bactericida dependiente de tiempo de CAMP a 50 W contra la biopelícula de la cepa ATCC. CONCLUSIONES E IMPORTANCIA CLÍNICA: CAMP fue eficaz tanto contra las bacterias planctónicas como contra la formación de biopelículas de P. aeruginosa. Sin embargo, son necesarios más estudios sobre la eficacia y seguridad in vivo en piel y oídos caninos para validar completamente su aplicación clínica. CONCLUSIONS AND CLINICAL IMPORTANCE: CAMP was effective against both planktonic bacteria and biofilm formation of P. aeruginosa. However, further studies on in vivo efficacy and safety in canine skin and ears are necessary to fully validate its clinical application.

Objectives To characterise the behavioural and neuropsychiatric disturbances of patients with three clinical subtypes of frontotemporal dementia (FTD): behavioural variant FTD (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Methods Consecutive series of 66 patients with bvFTD, 58 patients with SD and 21 patients with PNFA were compared using the Frontal Behavioural Inventory (FBI) and the Neuropsychiatric Inventory (NPI). Results Patients with bvFTD had more behavioural and neuropsychiatric disturbances than patients with PNFA based on the total scores of FBI and NPI. When comparing subtotal and item scores of FBI and NPI, there were some significant differences among three clinical subtypes of FTD. Conclusion There are some distinct patterns of behavioural and neuropsychiatric disturbance among three clinical subtypes of FTD.

Aim Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. Methods This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Results Factor analyses showed two symptom clusters: factor A – aggressive agitated behaviors – versus factor B – non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. Conclusions In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494–499.

Elevated expression and aberrant activation of Ras have been implicated in breast cancer aggressiveness. H-Ras, but not N-Ras, induces breast cell invasion. A crucial link between lipid rafts and H-Ras function has been suggested. This study sought to identify the lipid raft protein(s) responsible for H-Ras-induced tumorigenicity and invasiveness of breast cancer. We conducted a comparative proteomic analysis of lipid raft proteins from invasive MCF10A human breast epithelial cells engineered to express active H-Ras and non-invasive cells expressing active N-Ras. Here, we identified a lipid raft protein flotillin-1 as an important regulator of H-Ras activation and breast cell invasion. Flotillin-1 was required for epidermal growth factor-induced activation of H-Ras, but not that of N-Ras, in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Flotillin-1 knockdown inhibited the invasiveness of MDA-MB-231 and Hs578T TNBC cells in vitro and in vivo. In xenograft mouse tumor models of these TNBC cell lines, we showed that flotillin-1 played a critical role in tumor growth. Using human breast cancer samples, we provided clinical evidence for the metastatic potential of flotillin-1. Membrane staining of flotillin-1 was positively correlated with metastatic spread (p = 0.013) and inversely correlated with patient disease-free survival rates (p = 0.005). Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p

Background and purpose Patients with the cerebellar variant of multiple system atrophy (MSA-C) often show cognitive deficits in various cognitive domains. The association between morphometric changes in cortical and subcortical structures and cognitive impairments in MSA-C were investigated to explore the neural correlates responsible for cognitive deficits in MSA-C patients. Methods Using surface-based morphometry, region-of-interest cortical thickness and the volumes and shapes of subcortical structures were examined in 18 patients who fulfilled the criteria of probable MSA-C and were compared to 50 healthy controls. The association between regional changes and cognitive functions in MSA-C were investigated by applying linear regression analyses after controlling for confounding factors. Results Compared with controls, the patients with MSA-C showed significant cortical thinning in the fronto-temporo-parietal regions and volume reduction in subcortical structures with shape changes. Cerebellar volume had no significant effect on cortical and subcortical volumes. The severity of atrophic changes in the bilateral thalamus, the left cerebellum and the left pericalcarine gyrus were significantly correlated with attentional, executive and visuospatial dysfunctions. Conclusion Cognitive impairment in MSA-C might result from functional disruption of the corticostriatal and pontocerebellar circuit mediated by primary cortical, cerebellar or thalamic pathology.

Background and purpose A common single nucleotide polymorphism, Val66Met, in the human brain-derived neurotrophic factor (BDNF) gene has a potential role in the pathogenesis and treatment of stroke. The relevance of the BDNF Val66Met polymorphism to long-term stroke outcomes was examined, specifically with respect to changes in corticospinal integrity. Methods Thirty-five stroke patients with unilateral motor weakness were genotyped within 2 weeks after onset (T1), and changes in the integrity of the ipsilesional corticospinal tract (CST) as well as alterations in motor function at 1 month (T2) and 3 months after onset (T3) were tracked. Results On the basis of the Fugl−Meyer assessment upper extremity score, carriers of the Met allele (Val/Met and Met/Met) showed poorer motor outcomes at T2 and T3 compared to carriers of only the Val allele (Val/Val). For both BDNF allele types, patients exhibited characteristic degeneration of the CST compared to healthy controls. There were no differences between the two genotypes with respect to time-dependent changes in diffusion-tensor-imaging-derived parameters of the CST. However, the two groups showed different relationships between motor outcomes and directional diffusivities according to the elapsed time after onset. Poorer motor function was associated with lower axial diffusivity values for the Val/Val genotype group in the sub-acute phase (T1 and T2) but with higher radial diffusivity values for the Val/Met and Met/Met genotype group in the early chronic phase (T3). Conclusions Motor recovery in stroke patients may be affected by the BDNF Val66Met polymorphism, possibly through its effects on distinct pathological processes underlying corticospinal degeneration.

Background/purpose This study was conducted to define yellowish skin color, which is a major concern of Asian women, and to develop a 3D skin-pigment color model. Methods A total of 22 Korean females were enrolled in this study. These women were asked to use a functional cosmetic product with whitening agents for 8 weeks. We photographed the subsurface reflection of each subject's face using polarized light. The color of the subsurface reflection is a result of diffusive light transports that are attenuated by various skin pigments such as melanin, hemoglobin, and skin base colors. In this subsurface photo image, we eliminated the color effects of melanin and hemoglobin distribution by skin color analysis resulting in skin base color. Based on a variety of observed skin base colors from which the melanin and hemoglobin pigments have been removed, we defined a standard skin color for the entire subject group, and then, we gained a particular yellowish skin color by excluding the standard skin color from the skin base color again. Results After applying whitening cosmetic products, the amount of melanin and hemoglobin was reduced by 7.3% and 18.6%, respectively. Also, through using our new analysis method, yellowish skin color has been improved by 2.8%. We showed the improvement on 3D Skin Chroma Diagram™ three-dimensionally. Conclusion It became possible to diagnose yellowish color on human skin and to analyze the improvement in skin tone both quantitatively and visually.

Objectives The aim of this study was to describe the current state of home visit nursing services in the Korean context and to suggest future policy directions. Design First, the three home visit nursing services that have developed in Korea are compared using the analytic framework provided by Gilbert and Terrell in 2012. The framework is based on four dimensions of social welfare: users, services, source of funds, and service delivery process. Second, we perform a strength, weakness, opportunity, and threat analysis to suggest comprehensive and constructive home visit nursing service policies for the future. Results Specifically, we advocate the creation of an organization that steers the central government to operate an integrated management organization to distribute services and reduce redundancy for preventing the waste of both medical and state financial resources. This study also recommends the development of educational programs to improve the quality of services and service evaluation criteria for the objective assessment of those services. Conclusions These policy guidelines may prove useful both for Korea and for other countries that intend to prepare or revise their home visit nursing service systems.

Background There are many reports on regional variations in skin bio-mechanical properties, but few studies have been performed on the neck. The neck is sun-exposed and continues to move so the neck skin can be more apt to aging. Methods The skin properties of the neck, cheek, and ventral forearm of 58 Korean female volunteers in good health (25–64 years old, 42.3 ± 11.7) were assessed non-invasively with skin measuring devices, and the correlation with age and wrinkles was analyzed. Results Neck skin was more extensible, elastic and visco-elastic than the cheek. The dermal layer for the neck skin was thinner and more intense than the cheek, but the results were opposite when compared with the skin of the forearm. We could observe that the subcutaneous layer was divided by the fascia with regard to the neck skin, and this thickness increased BMI-dependently. The neck skin had the correlation between R0, R3, and dermal thickness. The correlation coefficient of elasticity on the neck with ages was −0.550 and the elasticity on the neck skin was highly negatively correlated with age than any other sites. Therefore, this bio-mechanical property was important for determining the aging. TEWL was correlated with ages for only neck skin(R = 0.368). We found that the wrinkles on the neck were correlated with age, the elasticity, skin color (L*), TEWL. Conclusion The biomechanical properties of the neck skin were highly correlated with age than skin parameters of other sites. These results were influenced by constant movement and sun-exposure, and therefore, the neck wrinkles were apt to form.

Aim Patients with Alzheimer's disease (AD) and cerebrovascular disease (CVD) show greater attentional deficits compared with AD patients without CVD. The aim of the present study was to investigate the effect of galantamine on attention in AD patients with CVD. Methods In this open trial, 1512 patients with AD and CVD were recruited from 71 nationwide hospitals. The patients were given galantamine for 16 weeks. The primary outcome measure was the score on the Attention Questionnaire Scale (AQS), which measures the patients’ attention in their daily lives. The secondary outcome measures were the scores on the Korean Mini-Mental State Examination, the Clinical Dementia Rating scale and the Global Deterioration Scale. Efficacy measures were calculated both at baseline and at the end of the treatment (week 16). Results The responders rate on the AQS (change of the AQS from baseline >0) was 60.6% in AD patients with CVD. At the end of the treatment, both the AQS (15.0 ± 5.7 vs 16.3 ± 5.8, P

Background and purpose: Reports describing functional neuroimaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), in sporadic Creutzfeldt–Jakob disease (sCJD) have consistently suggested that these tools are sensitive for the identification of areas of hypoperfusion or hypometabolism, even in the early stages of sCJD. However, there are few reports on the use of [18F]fluoro-2-deoxy-D-glucose (FDG) PET in sCJD, and most of them are single case reports. Only two small cohort studies based on visual inspection or a region of interest method have been published to date. Using a statistical parametric mapping (SPM) analysis of 18F-FDG PET, we investigated whether there are brain regions preferentially affected in sCJD. Methods: After controlling for age and gender, using SPM 2, we compared the glucose metabolism between (i) 11 patients with sCJD and 35 controls and (ii) the subset of five patients with the Heidenhain variant of sCJD and 35 controls. Results: The patients with sCJD showed decreased glucose metabolism in bilateral parietal, frontal and occipital cortices. The Heidenhain variant of sCJD showed glucose hypometabolism mainly in bilateral occipital areas. Conclusions: Glucose hypometabolism in sCJD was detected in extensive cortical regions; however, it was not found in the basal ganglia or thalamus, which are frequently reported to be affected on diffusion-weighted images. The medial temporal area, which is possibly resistant to the prion deposits, was also less involved in sCJD.

Aims and objectives. The purpose of this study was to assess the level of anxiety and uncertainty in Korean mothers of children with febrile convulsion and to indentify factors associated with maternal anxiety. Background. In general, febrile convulsions are harmless to the child, but parents perceive the convulsion as frightening. Previous authors of a few studies suggested that providing information was helpful for parents’ knowledge, attitude and fear about a febrile convulsion. Design. This was a descriptive, cross-sectional survey. Methods. The sample comprised 102 mothers whose children had been diagnosed with a febrile convulsion and admitted to paediatric wards in five general hospitals in South Korea. The researchers gave the questionnaires to nursing departments for distribution and collection by paediatric nurses. To test differences in anxiety and uncertainty by participants’ characteristics, t-tests and anova were conducted. Linear regression was used to identify factors associated with maternal state anxiety. Statistical significance level was set at 0·05. Results. A multiple linear regression of maternal anxiety showed that four statistically significant predictors explained 56% of the total variations of maternal anxiety. The significant predictors were uncertainty, frequency of febrile convulsion, income and information about febrile convulsion. Among the significant variables, uncertainty was the dominant contributing factor (p

Polystyrene-block-poly(2-vinyl pyridine) (PS-b-P2VP) block copolymer photonic gels are fabricated that exhibit controllable optical hysteresis in response to a cyclic pH sweep. The optical hysteresis is tuned by controlling the ion-pairing affinity between various anions and the protonated pyridinium ions on the P2VP block, which is highly dependent on the hydration energy of the ions, the dielectric constant of the solvent, and the ionic strength of the medium. The pH coercivity defining the magnitude of hysteresis of the photonic gels could be varied from 0.26 to 7.4. Photonic gel films with strong optical hysteresis can serve as wet photonic memory films where information can be cyclically recorded and erased at least 15 times and maintained for at least 96 h. The memory colors can be further tuned by selection of the copolymer molecular weight.

Lapatinib is one of several tyrosine kinase inhibitors used against solid tumour cancers such as breast and lung cancer. Although lapatinib is associated with a risk of QT prolongation, the effects of the drug on cellular cardiac electrical properties and on action potential duration (APD) have not been studied. To evaluate the potential effects of lapatinib on cardiac repolarization, we investigated its electrophysiological effects using a whole-cell patch-clamp technique in transiently transfected HEK293 cells expressing human ether-a-go-go (hERG; to examine the rapidly activating delayed rectifier K(+) current, I(Kr)), KCNQ1/KCNE1 (to examine the slowly activating delayed rectifier K(+) current, I(Ks)), KCNJ2 (to examine the inwardly rectifying K(+) current, I(K1)), or SCN5A (to examine the inward Na(+) current, I(Na)) and in rat cardiac myocytes (to examine the inward Ca(2+) current, I(Ca)). We also examined its effects on the APD at 90% (APD(90)) in isolated rabbit Purkinje fibres. In ion channel studies, lapatinib inhibited the hERG current in a concentration-dependent manner, with a half-maximum inhibition concentration (IC(50)) of 0.8 +/- 0.09 microm. In contrast, at concentrations up to 3 microm, lapatinib did not significantly reduce the I(Na), I(K1) or I(Ca) amplitudes; at 3 microm, it did slightly inhibit the I(Ks) amplitude (by 19.4 +/- 4.7%; p < 0.05). At 5 microm, lapatinib induced prolongation of APD(90) by 16.1% (p < 0.05). These results suggest that the APD(90)-prolonging effect of lapatinib on rabbit Purkinje fibres is primarily a result of inhibition of the hERG current and I(Ks), but not I(Na), I(K1) or I(Ca).

In this paper we propose an efficient method to reconstruct a small inclusion buried inside a body using the perturbation of modal parameters measured on the boundary of the body. We design a reconstruction algorithm based on the asymptotic expansions of the eigenvalue perturbations obtained by Ammari and Moskow (Math. Meth. Appl. Sci. 2003; 26:67–75). We then implement this algorithm and demonstrate its viability and limitations. Copyright © 2008 John Wiley & Sons, Ltd.

The vibration behavior of structures can be characterized in terms of resonance frequencies and mode shapes which describe properties of the tested object in a global way but do not in general provide information about structural details. Following an asymptotic formalism, in much the same spirit as the work in [3] and recent text [1], we develop a simple method to address the inverse problem of identifying an internal corrosive part of small Hausdorfi measure in a two-dimensional structure by vibration analysis. The viability of our reconstruction method is documented by a variety of numerical results from synthetic, noiseless and noisy data.

Activation-induced upregulation of inhibitory killer Ig-like receptor (KIR) is regulated by protein kinase Cs (PKCs). Conventional PKCs increase KIR expression on the post-transcriptional level by increasing the recycling of surface molecules and endoplasmic reticulum (ER)-Golgi processing. PKCdelta plays a role in the secretion of cytoplasmic KIR through lytic granules. In this study, we identified amino acid sequence motifs associated with PKC-mediated KIR membrane trafficking by systematic mutagenesis. Mutations of Y(398) and HLWC(364) completely inhibited the PMA-induced increase of KIR molecules at surface as well as total protein levels, indicating that these are associated with ER-Golgi processing and sorting to plasma membrane through lytic granules. Mutations of Y-based motif, including Y(398), acidic region (PE(394)), dileucine motif-like region (IL(423)) and PKC-phosphorylatable S(415) caused a blockade of surface KIR endocytosis after PKC stimulation. Mutation of T(145) caused an accumulation of mutant proteins in late endosomes and lysosomes after PKC activation, suggesting that T(145) might be related to the recovery of endocytosed KIR to the surface membrane. We also demonstrated that PKCs could directly phosphorylate the KIR cytoplasmic tail by means of western blot and in vitro kinase assay, implying that phosphorylation status of KIR cytoplasmic tail can direct the fate of surface KIR molecules. Taken together, various sequence motifs are implicated in the PKC-mediated post-transcriptional upregulation of KIR, and each of these motifs work in different steps after PKC activation.

A number of clinically used drugs block delayed rectifier K+ channels and prolong the duration of cardiac action potentials associated with long QT syndrome. This study investigated the molecular mechanisms of voltage-dependent inhibition of human ether-a-go-go-related gene (HERG) delayed rectifier K+ channels expressed in HEK-293 cells by brompheniramine, an antihistamine. Brompheniramine inhibited HERG current in a concentration-dependent manner with the half-maximal inhibitory concentration (IC50) value of 1.7 microm at 0 mV. A block of HERG current by brompheniramine was enhanced by progressive membrane depolarization and showed significantly negative shift in voltage-dependence of channel activation. Inhibition of HERG current by brompheniramine showed time-dependence. The S6 residue HERG mutant Y652A and F656C largely reduced the blocking potency of HERG current. These results indicate that brompheniramine mainly inhibited the HERG potassium channel through the residue Y652 and F656 and these residues may be an obligatory determinant in inhibition of HERG current for brompheniramine.

The purpose of this study is to investigate the optimum combination of polyols and oils in moisturizing cosmetic products to improve the human skin moisturization and skin surface roughness. Polyols and oils are essential ingredients in skin care products, but it is still not understood how their concentrations affect their efficacy and sensory properties on human skin. We investigated the effect of polyol and oil concentration on skin properties by noninvasive methods.The polyols consisted of glycerin and butylenes glycol in a ratio of 1:1 and the oils consisted of equal parts of hydrogenated polydecene, cethyl ethylhexanoate and pentaerythrityl tetraethylhexanoate. All cosmetic products were made in O/W emulsions in concentrations ranging from 0% to 30% for polyols and from 0% to 35% for oils. We investigated the effect on water content and skin surface roughness on the forearm after application of the cosmetic products. The skin water contents were measured by a Corneometer CM825 and the skin surface roughness by visual coring of skin surface biopsies in the scanning electron micrographs.In the first study, we found that the water content of the skin correlated highly with the polyol (up to 30%) and oil (up to 12%) concentrations, respectively. At two hours after application, the correlation coefficients were 0.971 and 0.985, respectively (P0.01). Skin surface roughness not only showed a strong concentration dependence on polyols and oils (up to 6%). In the second study, we investigated the optimum combination of polyols and oils to improve the skin moisturization and skin surface roughness by the Response surface methodology. The water content of the skin surface was high in the ratio of polyol to oil (30:12 and 25:30). The skin surface roughness was improved considerably in the ratio of polyols to oil (30:6 and 30:35).Our results indicated that the skin surface properties were improved in the different ratios of their concentrations because they are influenced by not one ingredient but the interaction between polyols and oils. In this study, we could recommend the optimum concentration of polyols and oils to improve the skin surface properties. Further studies will be performed with other ingredients such as surfactants, lipids and so on.

We isolated MED25, which associates with retinoic acid (RA)-bound retinoic acid receptor (RAR) through the C-terminal nuclear hormone receptor (NR) box/LxxLL motif, and increases RAR/RXR-mediated transcription. When tethered to a promoter, MED25 showed intrinsic transcriptional activity in its PTOV domain, which is likely accomplished by direct association with CBP. Reporter assays using dominant negatives of MED25 demonstrated the importance of the N-terminal Mediator-binding and C-terminal domains in CBP and RAR/RXR binding, which affect MED25 activity. Downregulation of MED25 specifically reduced RAR but not thyroid hormone receptor (TR) activity. Stimulation of RAR by MED25 was correlated with enhanced RA cytotoxicity in vivo. Chromatin immunoprecipitation (ChIP) assays revealed the RA-dependent recruitment of MED25 to the RARbeta2 promoter. Recruitment of CBP and TRAP220 was diminished by the overexpression of a MED25 NR box deletion mutant, and by treatment with MED25 siRNA. Time-course ChIP assays indicated that CBP, together with RAR and MED25, is recruited early, whereas TRAP220 is recruited later to the promoter. Our data suggest that MED25, in cooperation with CBP and Mediators through its distinct domains, imposes a selective advantage on RAR/RXR activation.

The majority of colon tumors are triggered by aberrant Wnt signaling in intestinal stem cells, which is an extremely efficient route towards initiating intestinal cancer. Curcumin, a component of t...

Fenretinide, 4-(N-hydroxyphenyl) retinamide (4-HPR), has demonstrated anticancer activity associated with a favorable toxicity profile and is now being investigated in several clinical trials. However, its plasma levels in patients have been far lower than the effective concentration required to induce apoptosis (usually 10 μM). This result has led to the synthesis of derivatives with better efficacy. Sodium butyrate's potential as an anticancer agent prompted us to synthesize a butanoate derivative of 4-HPR, 5-hydroxyphenyl butanoate retinamide (5-HPBR) and compare it to the parent compound for antitumor potential in vitro. The cytotoxicity of 5-HPBR was 2- to 6-fold greater than that of 4-HPR against cancer cell lines derived from various tissues. In premalignant bronchial cells (BEAS2B), 5-HPBR exhibited about a 10-fold stronger cytotoxicity than did 4-HPR. Normal CHANG liver cells were unaffected by either 4-HPR or 5-HPBR. Subsequent assays using DNA fragmentation, DAPI staining, FACS and Western blotting suggested that the potent inhibitory effect of 5-HPBR is mediated by apoptosis; the exact mechanism appears to differ among cancer cell types. In transcription assays with COS-1 cells, 5-HPBR selectively activated RARβ and RARγ but was a weaker ligand for all 3 subtypes of RAR than either all-trans retinoic acid or 4-HPR. Overall, these data suggest that 4-BHPR may be a promising retinoid with enhanced antitumor activity and reduced toxicity. © 2003 Wiley-Liss, Inc.

Interferon-gamma (IFN-gamma), as one of interferon family that regulates antiviral, antiproliferative, and immunomodulatory responses, has been implicated for the growth regulation of ovarian cancer cells. However, the molecular mechanisms are not yet fully defined. To analyze detailed mechanisms, the ovarian cancer cell lines (2774, PA-1, OVCAR-3, and SKOV-3) were treated with IFN-gamma. The growth of 2774 was most effectively suppressed than that of other cells in both time-course and dose-dependent experiments. The order of sensitivity in other cells was PA-1 >> OVCAR-3 > SKOV-3 (not responded at all). The DNA fragmentation and DAPI staining assays suggested that the IFN-gamma-mediated cytotoxicity could be triggered by apoptosis. The treatment induced IFN regulatory factor-1 (IRF-1) in two IFN-gamma-sensitive cells (2774, PA-1), whereas IRF-1 was not induced in two IFN-gamma-resistant cells (OVCAR-3, SKOV-3). The levels of p53 and p21WAF1 were not strikingly changed in all four cells. Interestingly, the expression of interleukin-converting enzyme (ICE, or caspase-1) was increased by the treatment in a kinetically consistent manner to the induction of IRF-1. However, CD95 (Fas/APO-1) was not changed. Apoptosis was greatly induced, when IRF-1 was transiently expressed in PA-1 without the treatment of IFN-gamma. However, it was repressed when IRF-1 together with IRF-2, an antagonist of IRF-1, were coexpressed. In addition, the effect of IFN-gamma was reduced in the 2774 and PA-1 cells stably expressing either IRF-1 antisense or IRF-2 sense, as shown by the cytotoxicity and FACS analysis. Furthermore, the IFN-gamma-induced apoptosis was greatly reduced, when inhibitors of ICE were treated into PA-1 cells. Taken together, these results suggest that IRF-1 directly mediates the IFN-gamma-induced apoptosis via the activation of caspase-1 gene expression in IFN-gamma-sensitive ovarian cancer cells.

Furthermore, an observational study shows that greater cardiorespiratory fitness is associated with slowed progression of dementia and brain atrophy in patientswithAD.Objectivewas to assess the influence of physical activity and cognition on ADL.Methods: In the present study, data from the " Preserving quality of life, physical health and functional ability in A lzheimer’s d isease: The effect of physical ex ercise (ADEX) study" a randomized controlled multicentre study, was used. Baseline data from 166 patients with AD (age (mean 6SD): 70,9 67,5; gender (f/m): 72/94; Mini-Mental State Examination (MMSE)(mean 6SD): 24,1 63,6) were included.ADL was assessed by the Alzheimer’s Disease Co-operative Study Activities of Daily Living (ADCSADL) scale and physical activity by the Physical Activity Scale for the Elderly (PASE) (caregiver interview).Furthermore, global cognitive function and mental speed/attention was assessed by the MMSE and Symbol Digit Modalities Test (SDMT), respectively. Two linear regression models were performed to investigate the impact of SDMT and PASE on ADCS-ADL. Covariates were PASE, age, gender and MMSE. In the second model, PASE was replaced by SDMT. Results: A significant association between ADL and PASE was found and between ADL and SDMT (B: 0,06; (SE: 6 0,02); b:0,27; and B: 0,06 (SE: 6 0,06); b:0,09, respectively).Conclusions:Bothmental speed/attention (SDMT) and physical activity (PASE) had a significant but modest association with ADL. There was a tendency that low physical activity was associated with impairedADL to a greater extent than mental speed/attention. Future studies should to clarify if improving physical activity may supplement pharmacotherapy in postponing the decline in ADL in patients with AD.