BACKGROUND: In order to meet the needs of therapy of multiple sclerosis (MS) new immune therapies with a user-friendly application and better effectiveness together with good tolerability are necessary. COMPASSIONATE USE: With respect to its potential to improve MS therapy, patients with a high medical need were given access to ...

Modelling survival data from long-term follow-up studies presents challenges. The commonly used proportional hazards model should be extended to account for dynamic behaviour of the effects of fixed covariates. This work illustrates the use of reduced rank models in survival data, where some of the covariate effects are allowed to ...

ABSTRACT: BACKGROUND: Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles ...

The impact of low vitamin D status on asthma development is unclear. The authors investigated the relation between the baseline serum 25-hydroxyvitamin D (25(OH)D) level and incident asthma in adults, including possible effect modification by allergy status, using allergic rhinitis as a proxy measure. A cohort of 25,616 Norwegian adults ...

Introduction: HIV-1 infected patients have an increased risk of osteoporosis and fractures. The main objective of this study was to evaluate the bone metabolism in HIV-1 infected patients exposed to calcitriol and cholecalciferol. We also investigated the relationship between T cells and bone markers. Methods: We conducted a placebo controlled ...

Aims Melanoma is the most aggressive type of malignant skin cancer derived from uncontrolled proliferation of melanocytes. Melanoma cells possess a high potential to metastasize and the prognosis for advanced melanoma is rather poor due to its strong resistance to conventional chemotherapeutics. Nanomaterials are at the cutting edge of the ...

Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the ...

Lung transplantation has become a viable treatment therapy for end-stage lung disease patients. The most common etiologies of end-stage lung disease, which can require a transplant are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and pulmonary fibrosis (PF). Listing criteria are institution and program ...

ABSTRACT: BACKGROUND: Few investigations have been done to analyze the level of evidence in journals related to hand surgery, compared to other related research fields. The objective of this study was to assess the level of evidence of the clinical research papers published in the Ibero-american (RICMA), the European (JHSE) ...

Two-dimensional (2D) atomic crystals, such as graphene and transition-metal dichalcogenides, have emerged as a new class of materials with remarkable physical properties. In contrast to graphene, monolayer MoS(2) is a non-centrosymmetric material with a direct energy gap. Strong photoluminescence, a current on/off ratio exceeding 10(8) in field-effect transistors, and efficient ...

ABSTRACT: Despite the protection provided by several factors, including maternal antibodies, the burden of malaria in young infants may be higher than previously thought. Infants with congenital or neonatal malaria may have a different clinical presentation than older children, and diagnosis may be confused with other neonatal diseases due to ...

AIM: Sickle-cell disease (SCD) is more prevalent in Australia due to increased migration; however, the Australian paediatric SCD population has not been previously described. This study aimed to identify the demographic features of and quantify the hospital resource utilisation in the SCD population at The Royal Children's Hospital in Victoria. ...

ABSTRACT: BACKGROUND: Docosahexaenoic acid (DHA) and DHA-derived lipid mediators have recently been shown to possess anti-inflammatory and pro-resolving properties. In fact, DHA can down-regulate lipolysaccharide (LPS)-induced activation of NF-kappaB via a PPARgamma-dependent pathway. We sought to investigate the effects of the novel DHA-derived mediator resolvin D1 (RvD1) on LPS-induced acute ...

Measles virus is a major public health concern worldwide. Three measles virus cell receptors have been identified so far, and the structures of the first two in complex with measles virus hemagglutinin (MV-H) have been reported. Nectin-4 is the most recently identified receptor in epithelial cells, and its binding mode ...

Significance: Selenium is utilized in the methionine sulfoxide reduction system that occurs in most organisms. Methionine sulfoxide reductases (Msrs), MsrA and MsrB, are the enzymes responsible for this system. Msrs repair oxidatively damaged proteins, protect against oxidative stress, and regulate protein function and have also been implicated in the aging ...

Abstract OBJECTIVES: Anterior cruciate ligament (ACL) reconstruction with the hamstring tendon graft takes a long time as the tendon graft needs to heal at the site of the bone tendon integration in the created bone tunnels. Several reports have shown the therapeutic effects of simvastatin on bone formation with neovascularization. ...

Electric arc furnace steel slag (EAF-slag) and basic oxygen furnace steel slag (BOF-slag) were used as filter substrates in two horizontal sub-surface flow filters (6 m3 each) designed to remove phosphorus (P) from the effluent of a constructed wetland. The influences of slag composition, void hydraulic retention time (HRTv), temperature, ...

Understanding the relationships between accumulated metal speciation in cells and tissues of ecologically significant taxa such as earthworms will improve risk assessments. Synchrotron-based µ-focus X-ray spectroscopy was used to detect, localize, and determine ligand-speciation of Zn and Pb in thin sections of two epigeic earthworm species collected from a Pb/Zn-mine ...

Aim: Platelet derivatives serve as an efficient source of natural growth factors. In the current study, α-granules were incorporated into coaxial nanofibers. Materials & methods: A nanofiber scaffold containing α-granules was prepared by coaxial electrospinning. The biological potential of the nanofiber scaffold was evaluated in chondrocyte and mesenchymal stem cell ...

Controlling the speed at which systems evolve is a challenge shared by all disciplines, and otherwise unrelated areas use common theoretical frameworks towards this goal. A particularly widespread model is Glauber dynamics, which describes the time evolution of the Ising model and can be applied to any binary system. Here ...

ABSTRACT: BACKGROUND: The aim of this study was to optimize quantitative (real-time) polymerase chain reaction (qPCR) assays for 8 major periodontal pathogens, i.e. Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Parvimonas micros, Porphyromonas gingivalis, Prevotella intermedia, Tanerella forsythia and Treponema denticola, and of the caries pathogen Streptococcus mutans. RESULTS: Eighteen different primer pairs ...

The shortage of oil resources, the steadily rising oil prices and the impact of its use on the environment evokes an increasing political, industrial and technical interest for development of safe and efficient processes for the production of chemicals from renewable biomass. Thus, microbial fermentation of renewable feedstocks found its ...

SCOPE: Recent data suggest that gut microbiota contributes to the regulation of host lipid metabolism. We report how fermentable dietary fructo-oligosaccharides (FOS) control hepatic steatosis induced by n-3 PUFA depletion, which leads to hepatic alterations similar to those observed in non-alcoholic fatty liver disease patients. METHODS AND RESULTS: C57Bl/6J mice ...

This review presents clinical pearls for initiating liraglutide (Victoza®, Novo Nordisk Inc) therapy for the management of type 2 diabetes and selecting patients who will benefit from liraglutide therapy. Liraglutide, a once-daily glucagon-like peptide 1 receptor agonist, is Food and Drug Administration approved as an adjunct to diet and exercise ...

Electrons in semiconductors usually behave like a gas-as independent particles. However, when confined to two dimensions under a perpendicular magnetic field at low temperatures, they condense into an incompressible quantum liquid. This phenomenon, known as the fractional quantum Hall (FQH) effect, is a quantum-mechanical manifestation of the macroscopic behaviour of ...

ABSTRACT: BACKGROUND: The objective of this study was to examine the threshold fibre length for the onset of pulmonary inflammation after aspiration exposure in mice to four different lengths of silver nanowires (AgNW). We further examined the effect of fibre length on macrophage locomotion in an in vitro wound healing ...

ABSTRACT: The global demand for artemisinin-based combination therapy (ACT) has grown sharply since its recommendation by the World Health Organization in 2002. However, a combination of financing and programmatic uncertainties, limited suppliers of finished products, information opacity across the different tiers in the supply chain, and widespread fluctuations in raw ...

ABSTRACT: Background It is desirable in genomic studies to select biomarkers that differentiate between normal and diseased populations based on related data sets from different platforms, including microarray expression and proteomic data. Most recently developed integration methods focus on correlation analyses between gene and protein expression profiles. The correlation methods ...

Significance The thioredoxin and glutathione pathways are universally conserved thiol-reductase systems that drive an array of cellular functions involving reversible disulfide formation. Here we consider these pathways in S. cerevisiae, focusing on their cell compartments-specific functions, as well as the mechanisms that explain extreme differences of redox states between compartments. ...

The vascular endothelial growth factor A (VEGFA) is among the most significant stimulators of angiogenesis. Its effect on cardiovascular diseases and on the variation of related risk factors such as lipid parameters is considered important, although unclear yet. Recently, we identified four common variants (rs6921438, rs4416670, rs6993770, and rs10738760) explaining ...

OBJECTIVE: The health status and psychosocial well-being of multiple primary cancer (MPC) survivors are under-researched. METHODS: In total, 3615 survivors identified from the Eindhoven Cancer Registry between 2008 and 2009 were assessed. About one in six survivors had survived MPC (n = 556). All survivors completed questionnaires on health status (SF-36/European Organization ...

Lineage conversion of one somatic cell type to another is an attractive approach for generating specific human cell types. Lineage conversion can be direct, in the absence of proliferation and multipotent progenitor generation, or indirect, by the generation of expandable multipotent progenitor states. We report the development of a reprogramming ...

The Korean subclade of subtype B (KSB) is the most prevalent HIV-1 strain found in Korea. To date, only 2 near full-length HIV-1 sequences from Korean patients have been reported. Here, we analyzed a total of 24 near full-length genomes of HIV-1 strains that were isolated from 17 antiretroviral therapy ...

The incorporation of Quality by Design (QbD) principles in tissue engineering bioprocess development towards clinical use will ensure that manufactured constructs possess prerequisite quality characteristics addressing emerging regulatory requirements and ensuring functional in-vivo behavior. In this work QbD principles were applied on a manufacturing process step for the in vitro ...

Aim: We hypothesized that liposomes modified with lysosomotropic octadecyl-rhodamine B (Rh) and loaded with therapeutic glucocerebroside velaglucerase alfa (VPRIV™) will improve lysosomal delivery of the enzyme into Gaucher's cells. Materials & methods: Confocal microscopy and flow cytometry were used to evaluate the ability of Rh-modified liposomes loaded with VPRIV to ...

Aim: This work aimed to determine if the treatment outcomes of bladder cancer could be improved by targeting micelles that are decorated with bladder cancer-specific ligands on the surface and loaded with the chemotherapeutic drug paclitaxel. Materials & methods: Targeting efficacy and specificity was determined with cell lines. An in ...

Significance: In this review the dual nature of both iron and reactive oxygen species (ROS) will be explored in normal and cancer cell metabolism. Although iron and ROS play important roles in cellular homeostasis, they may also contribute to carcinogenesis. On the other hand, many studies have indicated that abrogation ...

AIM: The study aims to analyse clinical data and outcome in Aboriginal and non-Aboriginal children with cancer. METHODS: This is a retrospective case-note review of biological features, treatment outcome and survival in Aboriginal and non-Aboriginal children with a malignancy who were treated at the Women's and Children's Hospital, a tertiary ...

The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to ...

Aims: To predict the deposition of nanoparticles in a patient-specific arterial tree as a function of the vascular architecture, flow conditions, receptor surface density and nanoparticle properties. Materials & methods: The patient-specific vascular geometry is reconstructed from computed tomography angiography images. The isogeometric analysis framework integrated with a special boundary ...

Skeletal muscle atrophy occurs in aging and pathological conditions, including cancer, diabetes and AIDS. Treatment of atrophy is based on either preventing protein-degradation pathways, which are activated during atrophy, or activating protein-synthesis pathways, which induce muscle hypertrophy. Here we show that neuronal nitric oxide synthase (nNOS) regulates load-induced hypertrophy by ...

Studies for assessing non-inferiority or superiority of a new diagnostic or screening test relative to a standard test use a complete matched-pairs design in which results for both tests are obtained for all subjects. We present alternative tests for the situation where results on the standard test are obtained for ...

Several prebiotics, such as inulin, fructo-oligosaccharides and galacto-oligosaccharides, are widely used commercially in foods and there is convincing evidence, in particular for galacto-oligosaccharides, that prebiotics can modulate the microbiota and promote bifidobacterial growth in the intestinal tract of infants and adults. In this study we describe the identification and functional ...

Metamaterials are artificial substances that are structurally engineered to have properties not typically found in nature. To date, almost all metamaterials have been made from inorganic materials such as silicon and copper, which have unusual electromagnetic or acoustic properties that allow them to be used, for example, as invisible cloaks, ...

ABSTRACT: BACKGROUND: Urinary Ca2+ excretion increases with dietary NaCl. NaCl-induced calciuria may be associated with hypertension, urinary stone formation and osteoporosis, but its mechanism and long-term effects are not fully understood. This study examined alterations in the expressions of renal Ca2+ transporters, channels and claudins upon salt loading to better ...

ABSTRACT: BACKGROUND: The evidence on the agreement between self-reported health resource use and administrative records is mixed and no gold standard exists. The objective of this study was to assess self-reported general practitioner (GP) and specialist doctor visits, as well as medication use via telephone interview against national insurance administrative ...

The autophagy factor ATG12~ATG5 conjugate exhibits E3 ligase-like activity which facilitates the lipidation of members of the LC3 family. The crystal structure of the human ATG12~ATG5 conjugate bound to the N-terminal region of ATG16L1, the factor that recruits the conjugate to autophagosomal membranes, reveals an integrated architecture in which ATG12 ...

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle-specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype ...

AIM: Subjects who did not respond to an invitation to participate in a community-based randomised controlled trial for childhood obesity in Melbourne, Australia were approached to investigate reasons for non-participation. METHODS: Between January and September 2007, 305 families were sent a brief questionnaire and invited to take part in the ...

Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers data interpretation, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons ...