Non-invasive transcriptomic analysis using mRNAs in skin surface lipids obtained from children with mild-to-moderate atopic dermatitis.

BACKGROUND: Specimens for analysing the molecular pathology of skin disease are generally obtained through invasive methods, such as biopsy. However, less burdensome methods are desirable for paediatric patients. We recently established a method that comprehensively analyses RNA present in sebum (skin surface lipid-RNAs: SSL-RNAs) using a next-generation sequencer. Using this method, biological information can be obtained from the skin in a completely non-invasive manner. OBJECTIVES: To verify the applicability of the SSL-RNA method for analysis of paediatric skin and analyse the molecular pathology of mild-to-moderate atopic dermatitis (AD) in children. METHODS: We collected sebum specimens from the whole faces of 23 healthy children and 16 children with mild-to-moderate AD (eczema area and severity index (EASI) score: 5.9 ± 2.6) ranging in age from 6 months to 5 years, using an oil-blotting film. We then extracted SSL-RNAs from the samples and performed an AmpliSeq transcriptomic analysis. RESULTS: The expressions of genes related to keratinization (LCE, PSORS1C2, IVL and KRT17), triglyceride synthesis and storage (PLIN2, DGAT2 and CIDEA), wax synthesis (FAR2), ceramide synthesis (GBA2, SMPD3 and SPTLC3), antimicrobial peptides (DEFB1) and intercellular adhesion (CDSN), all of which are related to the skin barrier, are lower in children with AD than in healthy children. The children with AD also have higher expression of CCL17, a Th2-cytokine and an increased Th2-immune response as demonstrated by a gene set variation analysis. Moreover, KRT17 and CCL17 expression levels are significantly correlated with the EASI score. CONCLUSIONS: Molecular changes associated with abnormal immune responses and the epidermal barrier in children with mild-to-moderate AD can be determined using the SSL-RNA method. This non-invasive method could therefore be a useful means for understanding the molecular pathology of paediatric AD.

Interaction between sodium dodecylsulfate (SDS) and pluronic L61 in aqueous medium: assessment of the nature and morphology of the formed mixed aggregates by NMR, EPR, SANS and FF-TEM measurements.

The interaction of copolymer L61 i.e., (EO)2(PO)32(EO)2 (where EO and PO are ethylene and propylene oxides, respectively) with surfactant SDS (sodium dodecylsulfate) in relation to their self-aggregation, dynamics and microstructures has been physicochemically studied in detail employing the Nuclear Magnetic Resonance (NMR), Electron Paramagnetic Resonance (EPR), Small-Angle Neutron Scattering (SANS), and Freeze-Fracture Transmission Electron Microscopy (FF-TEM) methods. The NMR self-diffusion study indicated a synergistic interaction between SDS and L61 forming L61-SDS mixed complex aggregates, and deuterium (2H) NMR pointed out the nonspherical nature of these aggregates with increasing [L61]. EPR spectral analysis of the motional parameters of 5-doxyl steraric acid (5-DSA) as a spin probe provided information on the microviscosity of the local environment of the L61-SDS complex aggregates. SANS probed the geometrical aspects of the SDS-L61 assemblies as a function of both [L61] and [SDS]. Progressive evolution of the mixed-aggregate geometries from globular to prolate ellipsoids with axial ratios ranging from 2 to 10 with increasing [L61] was found. Such morphological changes were further corroborated with the results of 2H NMR and FF-TEM measurements. The strategy of the measurements, and data analysis for a concerted conclusion have been presented.

Practices and perspectives of primary care physicians in Japan and the United States about diagnosing dementia: a qualitative study.

BACKGROUND: While dementia is a common problem in Japan and the US, primary care physicians' practices and perspectives about diagnosing dementia in these different healthcare systems are unknown. METHODS: Qualitative research was conducted in an ethnographic tradition using semi-structured interviews and thematic analysis in primary care settings across Japan and in the Midwest State of Michigan, US. Participants were a total of 48 primary care physicians, 24 each from Japan and the US participated. Both groups contained a mixture of geographic areas (rural/urban), gender, age, and years of experience as primary care physicians. RESULTS: Participants in Japan and the US voiced similar practices for making the diagnosis of dementia and held similar views about the desired benefits of diagnosing dementia. Differences were found in attitudes about the appropriate timing of formally diagnosing dementia. Japanese physicians tended to make a formal diagnosis when problems that would benefit from long-term care services emerged for family members. US physicians were more proactive in diagnosing dementia in the early stages by screening for dementia in health check-ups and promoting advance directives when the patients were still capable of decision-making. Views about appropriate timing of diagnostic testing for dementia in the two systems reflect what medical or nursing care services physicians can use to support dementia patients and caregivers. CONCLUSIONS: Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US. Testing to establish an early diagnosis of dementia by primary care physicians only partly relates to testing and treatment options available. Benefits of making the diagnosis included the need to activate the long-term care services in Japan and for early intervention and authoring advance directives in the US.

IL-1-dependent electrophysiological changes and cardiac neural remodeling in a mouse model of Kawasaki disease vasculitis.

Kawasaki disease (KD) is the leading cause of acquired heart disease in children. In addition to coronary artery abnormalities, aneurysms and myocarditis, acute KD is also associated with echocardiogram (ECG) abnormalities in 40-80% of patients. Here, we show that these ECG changes are recapitulated in the Lactobacillus casei cell wall extract (LCWE)-induced KD vasculitis mouse model. LCWE-injected mice developed elevated heart rate and decreased R wave amplitude, with significant differences in prolonged ventricular repolarization. LCWE-injected mice developed cardiac ganglion inflammation, that may affect the impulse-conducting system in the myocardium. Furthermore, serum nerve growth factor (NGF) was significantly elevated in LCWE-injected mice, similar to children with KD vasculitis, associated with increased neural remodeling of the myocardium. ECG abnormalities were prevented by blocking interleukin (IL)-1 signaling with anakinra, and the increase in serum NGF and cardiac neural remodeling were similarly blocked in Il1r1-/- mice and in wild-type mice treated with anakinra. Thus, similar to clinical KD, the LCWE-induced KD vasculitis mouse model also exhibits electrophysiological abnormalities and cardiac neuronal remodeling, and these changes can be prevented by blocking IL-1 signaling. These data support the acceleration of anti-IL-1 therapy trials to benefit KD patients.

Shoe-Integrated, Force Sensor Design for Continuous Body Weight Monitoring.

Traditional pedobarography methods use direct force sensor placement in the shoe insole to record pressure patterns. One problem with such methods is that they tap only a few points on the flat sole under the foot and, therefore, do not account for the total ground reaction force. As a result, body weight tends to be under-estimated. This disadvantage has made it more difficult for pedobarography to be used to monitor many diseases, especially when their symptoms include body weight changes. In this paper, the problem of pedobarographic body weight measurement is addressed using a novel ergonomic shoe-integrated sensor array architecture based on concentrating the applied force via three-layered structures that we call Sandwiched Sensor Force Consolidators (SSFC). A shoe prototype is designed with the proposed sensors and shown to accurately measure body weight with an achievable relative accuracy greater than 99%, even in the presence of motion. The achieved relative accuracy is at least 4X better than the existing state of the art. The SSFC shoe prototype is built using readily available soccer shoes and piezoresistive FlexiForce sensors. To improve the wearability and comfort of the instrumented shoe, a semi-computational sensor design methodology is developed based on an equivalent-area concept that can accurately account for SSFC's with arbitrary shapes. The search space of the optimal SSFC design is shown to be combinatorial, and a high-performance computing (HPC) framework based on OpenMP parallel programming is proposed to accelerate the design optimization process. An optimal sensor design speedup of up to 22X is shown to be achievable using the HPC implementation.

In vivo anti-ageing activity of cream containing niosomes loaded with purple glutinous rice (Oryza sativa Linn.) extract.

OBJECTIVE: To evaluate the anti-ageing activity of cream containing the methanolic purple glutinous rice extract loaded in niosomes. METHODS: The in vitro biological activities of the purple glutinous rice extracted by methanol maceration were determined. The extract loaded in niosomes and the cream containing the niosomes were developed. The in vivo anti-ageing activity in 20 human volunteers including skin hydration, pigmentation, roughness and elasticity after daily application for 28 days compared to at initial was evaluated by Corneometer, Mexameter, Visiometer and Cutometer, respectively. RESULTS: The purple glutinous rice extract showed free radical scavenging (SC50 ), lipid peroxidation inhibition (IPC50 ), metal ion chelating (CC50 ) and tyrosinase inhibition (IC50 ) values at 32.31 ± 1.28, 57.40 ± 2.12, 85.05 ± 5.43 and 43.89 ± 2.14 mg/mL which were 0.00031, 0.011, 0.0078 and 0.0016 times of the standards (0.01 ± 0.00, 0.62 ± 0.14, 0.66 ± 0.05 and 0.07 ± 0.01), respectively. The purple glutinous rice extract contained 0.35 µg of anthocyanin/1 mg of the extract determined by HPLC. After loaded in niosomes, the solubility of the extract was not only increased in various solvents, but also the chemical stability in different environments (weak base, reducing agent and acid salt) was improved. The cream formulation containing niosomes loaded with 1%w/v of the purple glutinous rice extract indicated the anthocyanin remaining percentages after 6 cycles of heating and cooling test at 52.28% of the initial. For in vivo anti-ageing activities, cream containing niosomes loaded with the extract gave significant decreased melanin index and skin roughness reduction of -14.05 and -9.95% of the initial, respectively. The % changes of the increased skin hydration, skin elastic extension and skin elastic recovery when applied on human volunteers' skin with this formulation were +48.73, -24.51 and +35.98%, respectively. CONCLUSION: The cream containing niosomes loaded with the 1%w/v methanolic purple glutinous rice extract gave not only the suitable in vitro antioxidant activity and physical stability of the active anthocyanin, but also the superior in vivo anti-ageing activity on human skin compared to the cream base and before application which can be further developed as a novel anti-ageing cosmeceutical product.

OBJECTIF: Evaluer l'activité anti-âge d'une crème contenant de l'extrait de riz gluant violet méthanolique chargé en niosomes. MÉTHODES: Les activités biologiques in vitro de l'extrait du riz gluant violet par macération au méthanol ont été déterminées. L'extrait chargé en niosomes et la crème contenant les niosomes ont été développés. L'activité anti-âge in vivo sur 20 volontaires humains, y compris de l'hydratation de la peau, la pigmentation, la rugosité et l'élasticité après une application quotidienne pendant 28 jours a été évaluée par comparaison avec T0 par cornéomètre, mexamètre, visiomètre et cutomètre, respectivement. RÉSULTATS: L'extrait de riz gluant violet a montré des valeurs de piégeage des radicaux libres (SC50), d'inhibition de la peroxydation lipidique (IPC50), de chélation des ions métalliques (CC50) et d'inhibition de la tyrosinase (IC50) à 32,31 ± 1,28, 57,40 ± 2,12, 85,05 ± 5,43 et 43,89 ± 2,14 mg / ml qui étaient 0,00031, 0,011, 0,0078 et 0,0016 fois des standards respectivement (0,01 ± 0,00, 0,62 ± 0,14, 0,66 ± 0,05 et 0,07 ± 0,01). L'extrait de riz gluant violet contenait 0.35 pg d'anthocyanine / 1 mg de l'extrait déterminé par HPLC. Après avoir été chargé dans les niosomes, la solubilité de l'extrait a non seulement été augmentée dans divers solvants, mais aussi la stabilité chimique dans différents environnements (base faible, agent réducteur et sel d'acide) a été améliorée. La formulation de crème contenant des niosomes chargés avec 1% p / v de l'extrait de riz gluant violet a indiqué les pourcentages d'anthocyanine restants après 6 cycles de test de chauffage et de refroidissement à 52,28% de la valeur initiale. Pour les activités anti-âge in vivo, la crème contenant des niosomes chargés de l'extrait a donné une réduction significative de l'indice de mélanine et de la rugosité cutanée de -14,05 et -9,95% de la valeur initiale, respectivement. Les pourcentages de variation de l'hydratation accrue de la peau, de l'extension élastique de la peau et de la récupération de l'élasticité de la peau lors de l'application sur la peau de volontaires humains avec cette formulation étaient respectivement de +48,73, -24,51 et + 35,98%. CONCLUSION: La crème contenant des niosomes chargée avec l'extrait de riz gluant violet méthanolique à 1% p / v a donné non seulement une activité antioxydante in vitro appropriée et une stabilité physique de l'anthocyanine active, mais également une activité anti-vieillissement in vivo supérieure sur la peau humaine par rapport à la base de la crème et avant application, qui peut être développée en tant que nouveau produit cosméceutique anti-âge. Mots clés: riz gluant violet, niosomes, antioxydant, inhibition de la tyrosinase, efficacité anti-âge in vivo, produit cosméceutique.

IL-1 receptor antagonist, anakinra, prevents myocardial dysfunction in a mouse model of Kawasaki disease vasculitis and myocarditis.

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Erratum: Mercury Monohalides: Suitability for Electron Electric Dipole Moment Searches [Phys. Rev. Lett. 114, 183001 (2015)].

This corrects the article DOI: 10.1103/PhysRevLett.114.183001.

Investigation of SO3 absorption line for in situ gas detection inside combustion plants using a 4-µm-band laser source.

We have investigated 4-µm-band SO3 absorption lines for in situSO3 detection using a mid-infrared laser source based on difference frequency generation in a quasi-phase-matched LiNbO3 waveguide. In the wavelength range of 4.09400-4.10600 µm, there were strong SO3 absorption lines. The maximum absorption coefficient at a concentration of 170 ppmv was estimated to be about 3.2×10-5 cm-1 at a gas temperature of 190°C. In coexistence with H2O, the reduction of the SO3 absorption peak height was observed, which was caused by sulfuric acid formation. We discuss a method of using an SO3 equilibrium curve to derive the total SO3 molecule concentration.

Mercury monohalides: suitability for electron electric dipole moment searches.

Heavy polar diatomic molecules are the primary tools for searching for the T-violating permanent electric dipole moment of the electron (eEDM). Valence electrons in some molecules experience extremely large effective electric fields due to relativistic interactions. These large effective electric fields are crucial to the success of polar-molecule-based eEDM search experiments. Here we report on the results of relativistic ab initio calculations of the effective electric fields in a series of molecules that are highly sensitive to an eEDM, the mercury monohalides (HgF, HgCl, HgBr, and HgI). We study the influence of the halide anions on E_{eff}, and identify HgBr and HgI as attractive candidates for future electric dipole moment search experiments.

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. OBJECTIVES: To determine the 16-week efficacy and safety of two oral tofacitinib doses vs. placebo in patients with moderate-to-severe chronic plaque psoriasis. METHODS: Patients in two similarly designed phase III studies (OPT Pivotal 1, NCT01276639, n = 901; OPT Pivotal 2, NCT01309737, n = 960) were initially randomized 2 : 2 : 1 to tofacitinib 10 or 5 mg or placebo, twice daily. Coprimary efficacy end points (week 16) included the proportion of patients achieving Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) and the proportion achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75). RESULTS: Across OPT Pivotal 1 and OPT Pivotal 2, 745 patients received tofacitinib 5 mg, 741 received tofacitinib 10 mg and 373 received placebo. At week 16, a greater proportion of patients achieved PGA responses with tofacitinib 5 and 10 mg twice daily vs. placebo (OPT Pivotal 1, 41·9% and 59·2% vs. 9·0%; OPT Pivotal 2, 46·0% and 59·1% vs. 10·9%; all P < 0·001). Higher PASI 75 rates were observed with tofacitinib vs. placebo (OPT Pivotal 1, 39·9%, 59·2% and 6·2%, respectively, for tofacitinib 5 and 10 mg twice daily and placebo; OPT Pivotal 2, 46·0%, 59·6% and 11·4%; all P < 0·001 vs. placebo). Adverse event (AE) rates appeared generally similar across groups; rates of serious AEs, infections, malignancies and discontinuations due to AEs were low. Twelve patients reported herpes zoster across the tofacitinib treatment groups in both studies vs. none in the respective placebo groups. The most common AE across groups was nasopharyngitis. CONCLUSIONS: Oral tofacitinib demonstrated significant efficacy vs. placebo during the initial 16 weeks of treatment in patients with moderate-to-severe psoriasis. Safety findings were consistent with prior studies.

Leptin improves fatty liver independently of insulin sensitization and appetite suppression in hepatocyte-specific Pten-deficient mice with insulin hypersensitivity.

Nonalcoholic fatty liver disease (NAFLD) is recognized as the hepatic component of the metabolic syndrome. Although NAFLD is a major cause of cirrhosis and cancer of the liver of unknown cause, no established pharmacological treatment for NAFLD has been established yet. It has been reported that leptin treatment improved fatty liver dramatically as well as insulin resistance and hyperphagia in patients with lipodystrophy. However, it is unclear whether leptin improves fatty liver independently of these metabolic improvements. We investigated the liver effect of leptin independently of insulin sensitization and appetite suppression using hepatocyte-specific Pten-deficient (AlbCrePtenff) mouse, a model of severe fatty liver with insulin hypersensitivity. Male AlbCrePtenff mice were infused subcutaneously with leptin (20 ng/g/h) for 2 weeks using osmotic minipumps. Leptin infusion effectively reduced liver weight, liver triglyceride content, and glutamate pyruvate transaminase (GPT) concentrations as well as food intake and body weight without the change of plasma insulin concentration in AlbCrePtenff mice. Pair-feeding also reduced body weight but not liver triglyceride content. Pair feeding reduced α1 and α2 AMP-activated protein kinase (AMPK) activities and PGC1α gene expression in the liver, while leptin infusion unchanged them. The present study clearly demonstrated that leptin improve fatty liver independently of insulin sensitization and suppression of food intake. It was suggested that leptin improves fatty liver by stimulation of ß-oxidation in the liver. The present study might provide a further understanding on the mechanism of metabolic effect of leptin.

Effects of biosurfactants, mannosylerythritol lipids, on the hydrophobicity of solid surfaces and infection behaviours of plant pathogenic fungi.

AIMS: To investigate the effects of mannosylerythritol lipids (MELs) on the hydrophobicity of solid surfaces, their suppressive activity against the early infection behaviours of several phytopathogenic fungal conidia, and their suppressive activity against disease occurrences on fungal host plant leaves. METHODS AND RESULTS: The changes in the hydrophobicity of plastic film surfaces resulting from treatments with MEL solutions (MEL-A, MEL-B, MEL-C and isoMEL-B) and synthetic surfactant solutions were evaluated based on the changes in contact angles of water droplets placed on the surfaces. The droplet angles on surfaces treated with MELs were verified to decrease within 100 s after placement, with contact angles similar to those observed on Tween 20-treated surfaces, indicating decreases in surface hydrophobicity after MEL treatments. Next, conidial germination, germ tube elongation and the formation of appressorium of Blumeria graminis f. sp. tritici, Colletotrichum dematium, Glomerella cingulata and Magnaporthe grisea were evaluated on plastic surfaces that were pretreated with surfactant solutions. On the surfaces of MEL-treated plastic film, inhibition of conidial germination, germ tube elongation, and suppression of appressoria formation tended to be observed, although the level of effect was dependent on the combination of fungal species and type of MEL. Inoculation tests revealed that the powdery mildew symptom caused by B. graminis f. sp. tritici was significantly suppressed on wheat leaf segments treated with MELs. CONCLUSIONS: MELs exhibited superior abilities in reducing the hydrophobicity of solid surfaces, and have the potential to suppress powdery mildew in wheat plants, presumably due to the inhibition of conidial germination. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides significant evidence of the potential for MELs to be used as novel agricultural chemical pesticides.

A comparative study of ibuprofen and ketoprofen glass-forming liquids by molecular dynamics simulations.

In this paper, structural and dynamical properties of ibuprofen and ketoprofen glass-forming liquids have been investigated by means of molecular dynamics simulations. Molecular mobility of both materials is analyzed with respect to the different inter-molecular linear/cyclic hydrogen bonding associations. For ibuprofen, the dominant organization is found to be composed of small hydrogen bonding aggregates corresponding to cyclic dimers through the carboxyl group. For ketoprofen, the propensity of cyclic dimers is significantly reduced by the formation of hydrogen bonds with the ketone oxygen of the molecule altering the hydrogen bond (HB) associating structures that can be formed and thus molecular dynamics. The issue of the presence/absence of the peculiar low frequency Debye-type process in dielectric relaxation spectroscopy (DRS) data in these materials is addressed. Results obtained from simulations confirm that the Debye process originates from the internal cis-trans conversion of the -COOH carboxyl group. It is shown that the specific intermolecular HB structures associated to a given profen control the main dynamical features of this conversion, in particular its separation from the α-process, which make it detectable or not from DRS. For ibuprofen, the possible role of the -CCCO torsion motion, more "local" than the -COOH motion since it is less influenced by the intermolecular HBs, is suggested in the microscopic origin of the quite intense secondary γ-relaxation process detected from DRS.

A Method for Detecting the Deterioration in the Shock Absorption Capability of Mouthguards.

Objective methods for mechanical assessment of mouthguards used for a prolonged period of time are currently unavailable. The aim of this experimental study was to establish a quantitative method for assessing the preventive effect of mouthguards. 10 participants volunteered for this study. Impact loads were simulated by dropping a 250-g steel rod from a height of 100 mm onto upper front teeth of 10 custom ethylene vinyl acetate mouthguards fixed to a steel receiving rod. The mean output from load cells equilaterally placed between plates at the base of the apparatus was measured as the impact pressure (N). Its attenuation ratio (%) was calculated as the ratio of the difference in impact pressures without and with a mouthguard to impact pressure without a mouthguard. Impact pressure with mouthguard was approximately 60% of that without mouthguard in all cases. Intraclass correlations showed excellent intra-rater and inter-rater reliability for attenuation ratio (0.98 and 0.94, respectively). Bland-Altman plots indicated lack of systematic bias. The results suggest that attenuation ratio of impact pressure calculated by the proposed method is a valid criterion for assessing the preventive effect of mouthguards. The method may enable early detection of mouthguard deterioration and their timely replacement.

Statins inhibit tumor progression via an enhancer of zeste homolog 2-mediated epigenetic alteration in colorectal cancer.

While statin intake has been proven to reduce the risk of colorectal cancer (CRC), the mechanism of antitumor effects and clinical significance in survival benefits remain unclear. Statin-induced antiproliferative effects and its underlying mechanism were examined using six CRC cell lines. Statins except pravastatin showed antiproliferative effects (simvastatin ≥ fluvastatin > atorvastatin) even though both of simvastatin and pravastatin could activate mevalonate pathways, suggesting the statin-mediated antiproliferative effects depended on non-mevalonate pathway. Indeed, statin induced p27(KIP1) expression by downregulation of histone methyltransferase enhancer of zeste homolog 2 (EZH2), which acts as an epigenetic gene silencer. Additionally, the use of simvastatin plus classII histone deacetylase (HDAC) inhibitor (MC1568) induced further overexpression of p27(KIP1) by inhibiting HDAC5 induction originated from downregulated EZH2 in CRC cells and synergistically led to considerable antiproliferative effects. In the clinical setting, Statin intake (except pravastatin) displayed the downregulated EZH2 expression and inversely upregulated p27(KIP1) expression in the resected CRC by immunohistochemical staining and resulted in the significantly better prognoses both in overall survival (p = 0.02) and disease free survival (p < 0.01) compared to patients without statin intake. Statins may inhibit tumor progression via an EZH2-mediated epigenetic alteration, which results in survival benefits after resected CRC. Furthermore, statin plus classII HDAC inhibitor could be a novel anticancer therapy by their synergistic effects in CRC.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model.

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis.

Missense variants of the alanine: glyoxylate aminotransferase 2 gene correlated with carotid atherosclerosis in the Japanese population.

Alanine:glyoxylate aminotransferase 2 (AGXT2; EC 2.6.1.44) degrades asymmetric dimethylarginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Increased ADMA, reduced NO, and hypertension are shown in Agxt2 knockout mice. There are four single nucleotide polymorphisms (rs37370, rs37369, rs180749, and rs16899974) with which AGXT2 activity changes in humans and may be related to vulnerability of vascular sclerosis. To examine the relationship between them, we studied the functional haplotypes of the AGXT2 gene and decided their relationship with arteriosclerotic changes via carotid intima-media thickness (carotid IMT) in Japanese subjects. Genotyping of those polymorphisms and the carotid IMT in 1,426 Japanese subjects were then evaluated. Subjects with C-A-A-A haplotype (rs37370, rs37369, rs180749, rs16899974) showed low AGXT2 activity (P<0.0001; Pearson’s correlation coefficients: 0.497). The C-A-A-A haplotype was significantly associated with mean carotid IMT (P=0.049) and max carotid IMT (P=0.004). Subjects with two C-A-A-A haplotypes exhibited thicker mean carotid IMT (P=0.022) and maximum carotid IMT (P=0.001). In multiple regression analysis, subjects with two C-A-A-A haplotypes were independently and positively associated with mean carotid IMT (P=0.02) and maximum IMT (P=0.005) after correction. There was a significant correlation between the functional variants in the AGXT2 gene and carotid IMT in Japanese. The AGXT2 genotype may be an important factor underlying atherosclerosis.

Computed tomography of the thorax in calves from birth to 105 days of age.

The present study was undertaken to provide computed tomographic (CT) reference values for structures in the thorax of the calf. Six clinically healthy Holstein-Friesian calves were anaesthetized. Transverse pre- and postcontrast images with a reconstructed 1.5-mm slice thickness were obtained using a multislice-CT scanner at 6 different time points from birth to 105 days of age. Absolute and relative measurements of the trachea, heart, cranial and caudal vena cava, thoracic aorta, right and left principal bronchi, right and left caudal lobar bronchi and the accompanying branches of the right and left pulmonary artery and vein, thoracic lymph nodes and lung density were taken for every time point. All animals were euthanized after the last CT scan, and 4 calves were frozen to generate an atlas comparing gross anatomy with CT. During the study, 4 animals temporarily showed coughing and mucopurulent nasal discharge, and mild to moderate bronchopneumonia and pleuritis were diagnosed using CT. Animals recovered with treatment; however, mild to moderate CT changes remained throughout the study. Even in the 2 clinically normal animals, mild bronchopneumonia was diagnosed on CT.

Dans ce travail, on a relevé les valeurs normales de tomodensitométrie pour les structures thoraciques de veaux. Six veaux holstein-friesian en bonne santé ont pour cela été examinés sous narcose à six reprises, de leur naissance à l'âge de 105 jours, au moyen d'un scanner multi-barrettes sous forme native et en angiographie. On a reconstruit des images avec une épaisseur de coupe de 1.5 mm. On a effectué à chaque fois des mesures absolues et relatives du cœur, de la trachée, de l'aorte thoracique, de la veine cave crâniale et caudale, des bronches principales, des bronches lobaires avec les rameaux des artères et des veines pulmonaires, des ganglions lymphatiques ainsi que de la densité pulmonaire. Tous les animaux ont été euthanasiés à l'issue du sixième examen et quatre d'entre eux ont été congelés pour permettre une comparaison entre les images obtenues et des coupes anatomiques. Durant l'étude, quatre veaux ont présenté de la toux et un écoulement nasal. La tomodensitométrie a permis de diagnostiquer une bronchopneumonie légère à moyenne ainsi qu'une pleurésie. Bien que les animaux aient, après traitement, complètement guéri, des modifications légères à moyennes des images tomodensitométriques ont persistés jusqu'à la fin de l'étude. Une légère broncho-pneumonie a même été diagnostiquée chez les deux animaux ne présentant pas de symptômes cliniques.

Community health nurses' HIV health promotion and education programmes: a qualitative study.

BACKGROUND: Globally, nurses practice in many settings with people with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), taking an increasing share of the professional burden of care and helping to reduce morbidity and mortality. International literature is sparse about Thai community nurses providing primary healthcare programmes for people with HIV. AIM: This study aimed to describe background, experiences and strategies of community nurses regarding their design and delivery of programmes for people living with HIV and AIDS in Chiang Mai Province, Thailand. DESIGN: This study used a qualitative mixed-methods study employing a qualitative survey and in-depth interviews. METHODS: Twenty community health nurses from 18 small community hospitals completed a survey comprising demographic data and 13 open-ended questions. Four of them later engaged in in-depth interviews using the same questions. Survey, interview data and field notes were analysed using interpretive content analysis. FINDINGS: Four themes and six sub-themes portrayed participants' rich experiences and knowledge of HIV health promotion and education; challenges of daily work, discrimination and ethical issues; success through programme diversity comprising promotion of community volunteerism, networking and relationships; and holistic connections with Thai cultural traditions and Buddhism. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings help to recognize the diversity, uniqueness and contributions of Thai community nurses regarding culturally appropriate health promotion and education programmes for people living with HIV and AIDS. Findings inform nurses and health officials in and outside of the country to complement innovation in future HIV health promotion and education programmes. LIMITATIONS: Our sample came from one province of Thailand. Findings might not be reflective of nurses elsewhere. IMPLICATIONS FOR HEALTH AND NURSING POLICY: Three decades of collective experience in providing holistic and multifaceted HIV and AIDS nursing care, education and health promotion by community health nurses have the potential to effect new and existing policies and protocols on HIV community care in Thailand, but more research is required for this.