Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINA1 (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children.

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor which is present in foods such as milk and beer. It was reported that NR can prevent obesity, increase longevity, and promote liver regeneration. However, whether NR can prevent ethanol-induced liver injuries is not known. This study aimed to explore the effect of NR on ethanol induced liver injuries and the underlying mechanisms.

This study aims to evaluate the associations between genetic polymorphisms and the effect of sodium valproate (VPA) therapy in children with generalized seizures.

Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use.

Short tandem repeats on the male-specific region of the Y chromosome (Y-STRs) are permanently linked as haplotypes, and therefore Y-STR sequence diversity can be considered within the robust framework of a phylogeny of haplogroups defined by single nucleotide polymorphisms (SNPs). Here we use massively parallel sequencing (MPS) to analyse the 23 Y-STRs in Promega's prototype PowerSeq™ Auto/Mito/Y System kit (containing the markers of the PowerPlex® Y23 [PPY23] System) in a set of 100 diverse Y chromosomes whose phylogenetic relationships are known from previous megabase-scale resequencing. Including allele duplications and alleles resulting from likely somatic mutation, we characterised 2311 alleles, demonstrating 99.83% concordance with capillary electrophoresis (CE) data on the same sample set. The set contains 267 distinct sequence-based alleles (an increase of 58% compared to the 169 detectable by CE), including 60 novel Y-STR variants phased with their flanking sequences which have not been reported previously to our knowledge. Variation includes 46 distinct alleles containing non-reference variants of SNPs/indels in both repeat and flanking regions, and 145 distinct alleles containing repeat pattern variants (RPV). For DYS385a,b, DYS481 and DYS390 we observed repeat count variation in short flanking segments previously considered invariable, and suggest new MPS-based structural designations based on these. We considered the observed variation in the context of the Y phylogeny: several specific haplogroup associations were observed for SNPs and indels, reflecting the low mutation rates of such variant types; however, RPVs showed less phylogenetic coherence and more recurrence, reflecting their relatively high mutation rates. In conclusion, our study reveals considerable additional diversity at the Y-STRs of the PPY23 set via MPS analysis, demonstrates high concordance with CE data, facilitates nomenclature standardisation, and places Y-STR sequence variants in their phylogenetic context.

ROS and their downstream molecules such as oxidized phospholipids (OxPL) and 4‐hydroxynonenal activate TRPA1 and TRPV1 (vanilloid 1) cation channels in vivo and in vitro shaping thermal and mechanical hypersensitivity in inflammatory pain. E06/T15 is a monoclonal autoantibody against oxidized phosphatidylcholine (OxPC) used in diagnostics in arteriosclerosis. Recently, we provided evidence that E06 also ameliorates inflammatory pain. Here, we studied E06 for local treatment against hypersensitivity evoked by endogenous and exogenous agonists of TRPA1 or TRPV1 channels.

Hatching is crucial for mammalian embryo implantation, since difficulties during this process can lead to implantation failure, ectopic pregnancy and consequent infertility. Despite years of intensive researches, how internal and external factors affecting embryo hatch are still largely unclear.

Size and shape have progressively appeared as some of the key factors influencing the properties of nanosized drug delivery systems. In particular, elongated materials are thought to interact differently with cells and therefore may allow alterations of in vivo fate without changes in chemical composition. A challenge, however, remains the creation of stable self-assembled materials with anisotropic shape for delivery applications that still feature the ability to disassemble, avoiding organ accumulation and facilitating clearance from the system. In this context, we report on cyclic peptide-polymer conjugates that self-assemble into supramolecular nanotubes, as confirmed by SANS and SLS. Their behaviour ex and in vivo was studied: the nanostructures are non-toxic up to a concentration of 0.5 g L-1 and cell uptake studies revealed that the pathway of entry was energy-dependent. Pharmacokinetic studies following intravenous injection of the peptide-polymer conjugates and a control polymer to rats showed that the larger size of the nanotubes formed by the conjugates reduced renal clearance and elongated systemic circulation. Importantly, the ability to slowly disassemble into small units allowed effective clearance of the conjugates and reduced organ accumulation, making these materials interesting candidates in the search for effective drug carriers.

The gut hormone oxyntomodulin (OXM) causes weight loss by reducing appetite and increasing energy expenditure. Several analogues are being developed to treat obesity. Exactly how oxyntomodulin works, however, remains controversial. OXM can activate both glucagon and GLP-1 receptors but no specific receptor has been identified. It is thought that the anorectic effect occurs predominantly through GLP-1 receptor activation but, to date, it has not been formally confirmed which receptor is responsible for the increased energy expenditure. We developed OX-SR, a sustained-release OXM analogue. It produces a significant and sustained increase in energy expenditure in rats as measured by indirect calorimetry. We now show that this increase in energy expenditure occurs via activation of the glucagon receptor. Blockade of the GLP-1 receptor with Exendin 9-39 does not block the increase in oxygen consumption caused by OX-SR. However, when activity at the glucagon receptor is lost, there is no increase in energy expenditure. Glucagon receptor activity therefore appears to be essential for OX-SR's effects on energy expenditure. The development of future 'dual agonist' analogues will require careful balancing of GLP-1 and glucagon receptor activities to obtain optimal effects.

Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10. Moreover, in pre-established humanized mouse AA lesions, hair regrowth is promoted by α-GalCer treatment through a process requiring both effector-memory iNKT cells, which can interact directly with CD8+/NKG2D+ T cells, and IL-10. This provides the first in vivo evidence in a humanized model of autoimmune disease that iNKT10 cells are key disease-protective lymphocytes. Since these regulatory NKT cells can both prevent the development of AA lesions and promote hair re-growth in established AA lesions, targeting iNKT10 cells may have preventive and therapeutic potential also in other autoimmune disorders related to AA.

Silicosis is the most common occupational lung disease in China, and is associated with a variety of complications, many of which are poorly understood. For example, recent data indicate that silicosis associates with the development of osteopenia, and in some cases this bone loss is severe, meeting criteria for osteoporosis. Although many factors are likely to contribute to this relationship, including a sedentary lifestyle in patients with advanced silicotic lung disease, we hypothesized that silica might directly reduce bone mineral density. In the present study, six Wistar rats were exposed to silica for 24 weeks in order to induce pulmonary silicosis and examine the relationship to bone mineral density. As expected, all rats exposed to silica developed severe pulmonary fibrosis, as manifested by the formation of innumerable silicotic nodules and the deposition of large amounts of interstitial collagen. Moreover, micro-CT results showed that bone mineral density (BMD) was also significantly reduced in rats exposed to silica when compared control animals and this associated with a modest reduction in serum calcium and 25-hydroxyvitamin D levels. In addition, we found that decreased BMD was also linked to increased osteoclast activity as well as fibrosis-like changes, and to the deposition of silica within bone marrow. In summary, our findings support the hypothesis that silicosis reduces bone mineral density and provide support for ongoing investigations into the mechanisms causing osteopenia in silicosis patients.

Methionine aminopeptidase 2 (MAP2) is a principal regulator of apoptosis for Leishmania donovani and a potential candidate for the design and synthesis of novel antileishmanials. The LdMAP2 gene was cloned in pET28a(+)-SUMO vector, expressed in E. coli and then purified by chromatographic methods. It was found to be a monomer and required divalent metal ion for its activity against synthetic substrates with Co(II), Mg(II), Mn(II) and Ni(II) being the major activators. Moreover, Ca(II) showed the tightest binding with Km value of 124.7 ± 9.2 μM, while Co(II) proved most efficient for catalysis with kcat value of 128.1 ± 4 min-1. The naturally occurring aminopeptidase B inhibitor bestatin was found to be a potent inhibitor of LdMAP2 with a Ki value of 0.86 μM. Further, structural studies with circular dichroism (CD) showed an increase in the α-helical and β-sheet contents and a decrease in random coils in LdMAP2 upon interactions with both bestatin and fluorogenic substrates. Finally, structural studies pointed out key differences in the structure of LdMAP2 and HsMAP2 and their interactions with inhibitor bestatin, Ala-AMC, Leu-AMC and Met-AMC. The structural differences of two orthologs and different binding modes with bestatin can be crucial for the development of novel and specific inhibitor against leishmaniasis.

Single photon emission computed tomography ventilation/perfusion (SPECT V/Q) imaging has many proponents within the nuclear medicine community and has already largely replaced planar V/Q scintigraphy in daily practice for the diagnosis of pulmonary embolism (PE). However, the test is still described in clinical guidelines as an experimental test because of insufficient evidence.

Periodontitis is a chronic disease that due to an intense inflammatory response triggers systemic changes such as hepatic alterations. This study aimed to compare hepatic damage in rats that received experimental periodontitis at one or two periodontal sites with ligatures.

Aim of this study was to investigate the association of the time under immunosuppression and different immunosuppressive medication on periodontal parameters and selected periodontal pathogenic bacteria of immunosuppressed patients after solid organ transplantation (SOT).

BACKGROUND Insulin-degrading enzyme (IDE) is an important regulator for Ab clearance and diabetes. Although it is indispensable in removing plaques related to onset Alzheimer's disease (AD) and in degrading insulin related to diabetes, there have been few studies on the dynamic level of IDE in different stages of AD. MATERIAL AND METHODS The present study explored the level IDE protein in different stages of APPswe/PS1dE9 mice and their correlations with cognitive decline. The 4-month-old, 10-month-old, and 18-month-old mice were used as the different age stages of mice. Cognitive function was evaluated using the Morris water maze test. We also observed the level of Ab plaques in brain regions of different stages. RESULTS The data revealed that the expression of IDE was dramatically higher than in age-matched wild mice at the age of 10 months and 18 months. In terms of distribution, Aβ plaques were deposited mostly in the cortex and hippocampus, especially in 10-month-old and 18-month-old APPswe/PS1dE9 mice. The cognitive function of 4-month-old APPswe/PS1dE9 mice was not significantly differ in spatial learning. However, the cognitive function, both spatial learning and spatial memory, was dramatically lower in 10-month-old and 18-month-old groups. CONCLUSIONS There was a positive correlation between the expression of IDE and spatial memory in 10-month-old and 18-month-old APPswe/PS1dE9 mice. The study of this protein may provide reference values for the further study of IDE in Alzheimer's disease.

Greater body mass index (BMI) has been associated with increased risk of psoriasis in case-control and cross-sectional studies, however, the evidence from prospective studies has been limited. We conducted a systematic review and dose-response meta-analysis of different adiposity measures and the risk of psoriasis to provide a more robust summary of the evidence based on data from prospective studies. PubMed and Embase databases were searched for relevant studies up to August 8th 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model. The summary relative risk (RR) for a 5 unit increment in BMI was 1.19 (95% CI 1.10-1.28, I2 = 83%, n = 7). The association appeared to be stronger at higher compared to lower levels of BMI, pnonlinearity < 0.0001, and the lowest risk was observed at a BMI around 20. The summary RR was 1.24 (95% CI 1.17-1.31, I2 = 0%, pheterogeneity = 0.72, n = 3) per 10 cm increase in waist circumference, 1.37 (95% CI 1.23-1.53, I2 = 0%, pheterogeneity = 0.93, n = 3) per 0.1 unit increase in waist-to-hip ratio, and 1.11 (95% CI 1.07-1.16, I2 = 47%, pheterogeneity = 0.15, n = 3) per 5 kg of weight gain. Adiposity as measured by BMI, waist circumference, waist-to-hip ratio, and weight gain is associated with increased risk of psoriasis.

 The International Medical Informatics Association (IMIA) Open Source Working Group (OSWG) initiated a group discussion to discuss current privacy and security issues in the open data movement in the healthcare domain from the perspective of the OSWG membership.

A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials.

Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) and tissue tracking strain analyses are proposed as non-invasive methods for quantifying myocardial fibrosis and deformation. This study sought (1) to histologically validate myocardial ECV against the collagen volume fraction (CVF) measured from tissue samples of patients undergoing heart transplantation and (2) to detect the correlations between myocardial systolic strain and the myocardial ECV and histological CVF in patients undergoing heart transplantation.