School socioeconomic status and psychological complaints among adolescents in 44 countries: The mediating role of schoolwork pressure and classmate support and the moderating role of family SES and country-level income inequality.

Previous research has reported both positive and negative associations between school socioeconomic status (SES) and internalizing problems among adolescents. Little is known about cross-national differences in this association, as well as potential mediators and moderators. Therefore, this study investigated this association using representative cross-national samples of adolescents whilst exploring the mediating role of schoolwork pressure and classmate support, and the moderating role of family SES and country-level income inequality.

The impact of residential environment on older people's capabilities to live independently: a survey in Beijing.

Background: Studies have shown how environmental factors influence older people's health and functional limitations, which are crucial for achieving healthy aging. However, such a healthy aging model has been criticized for defining health as an absence of disease, because chronic conditions cannot be reversed through medical treatments. In response to such critiques, this study refers to Huber's positive health definition, arguing that health should not be defined as the absence of disease but as the ability to adapt and self-manage in the face of social, physical, and emotional challenges.

Smartphone-delivered approach bias modification for reducing harmful drinking amongst middle-older age adults: Secondary analyses of a single-arm pilot study.

Introduction: Novel, scalable, low-cost interventions are needed to reduce harmful drinking amongst middle-older adults. Approach bias modification (ApBM) is a promising form of cognitive training for preventing/reducing alcohol use that can be delivered via smartphone. This study explored the acceptability and preliminary effectiveness of smartphone delivered and personalised ApBM amongst Australians ≥55 years, an age cohort at risk of alcohol-related harms.

Predictors of cognitive functioning in presentations to a community-based specialist addiction neuropsychology service.

Introduction: Cognitive impairment is common in individuals presenting to alcohol and other drug (AOD) settings and the presence of biopsychosocial complexity and health inequities can complicate the experience of symptoms and access to treatment services. A challenge for neuropsychologists in these settings is to evaluate the likely individual contribution of these factors to cognition when providing an opinion regarding diagnoses such as acquired brain injury (ABI). This study therefore aimed to identify predictors of cognitive functioning in AOD clients attending for neuropsychological assessment.

'A circuit breaker' - Interrupting the alcohol autopilot: A qualitative exploration of participants' experiences of a personalised mHealth approach bias modification intervention for alcohol use.

Objective: There is a need for low-cost, wide-reaching interventions to enhance accessibility of support for people with hazardous alcohol consumption. We assessed participant experiences of using a novel, personalised mHealth intervention offering approach bias modification (ApBM) for alcohol use in a community sample drinking at harmful levels to enable a deeper understanding of the end user and engagement.

Methods: Eighteen semi-structured telephone interviews were conducted with adults in the community drinking at harmful/hazardous levels.

Maybe It's Not the Meth: Considering Biopsychosocial Contributors to Cognitive Impairment in Methamphetamine Polydrug Use.

Objective: In considering the cognitive harms of methamphetamine (MA) use, there is currently a limited appreciation of the profile of pre-existing, comorbid, or modifiable risk factors for cognitive impairment in individuals with MA-polydrug use who present to clinical services. This is in contrast to the well-recognized evidence in alcohol use groups. The aim of this study was to investigate the biopsychosocial and neuropsychological profiles of MA-polysubstance using individuals reporting cognitive impairment in comparison to an alcohol-using group.

Independent associations between residential neighbourhood and school characteristics and adolescent mental health in the Netherlands.

This study examined associations between characteristics of the residential neighbourhood and the school and adolescent mental health, including the moderating role of family socioeconomic status (SES) and family support. Nationally representative Dutch data from adolescents aged 12-16 (N = 6422) were analysed through cross-classified multilevel models. Findings showed that school characteristics are more strongly linked to adolescent mental health than residential neighbourhood characteristics.

Neighbourhood deprivation effects on young people's mental health and well-being: A systematic review of the literature.

Since the growth of research into neighbourhood effects on young people's health in the 1980s, there have been major societal changes and scientific methodological advancements. In this systematic review we will, therefore, discuss the recent (>2009) literature on the association between neighbourhood deprivation and young people's (0-19 years old) mental health and well-being. We focus on whether neighbourhood deprivation effects exist, and how and for whom the neighbourhood matters.

Interaction Between the a3 Region of Factor VIII and the TIL'E' Domains of the von Willebrand Factor.

The von Willebrand factor (VWF) and coagulation factor VIII (FVIII) are intricately involved in hemostasis. A tight, noncovalent complex between VWF and FVIII prolongs the half-life of FVIII in plasma, and failure to form this complex leads to rapid clearance of FVIII and bleeding diatheses such as hemophilia A and von Willebrand disease (VWD) type 2N. High-resolution insight into the complex between VWF and FVIII has so far been strikingly lacking.

Factor VIII with a 237 amino acid B-domain has an extended half-life in F8-knockout mice.

Essentials Factor (F)VIII with an intermediate-length B-domain showed higher levels in murine gene therapy. FVIII with different B-domain lengths were analysed. FVIII variants with B-domains between 186 and 240 amino acids (aa) have extended half-life in mice.

High-affinity von Willebrand factor binding does not affect the anatomical or hepatocellular distribution of factor VIII in rats.

Unlabelled: Essentials Von Willebrand factor (VWF) stabilizes factor VIII (FVIII) and prevents its premature clearance. Rat anatomical and hepatocellular distribution studies assessed the VWF effect on FVIII clearance. Hepatocytes and liver sinusoidal endothelial cells play a key role in FVIII clearance.

Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule.

Turoctocog alfa (NovoEight) is a third-generation recombinant factor VIII (rFVIII) with a truncated B-domain that is manufactured in Chinese hamster ovary cells. No human or animal-derived materials are used in the process. The aim of this study is to describe the molecular design and purification process for turoctocog alfa.

Deep sequencing reveals different compositions of mRNA transcribed from the F8 gene in a panel of FVIII-producing CHO cell lines.

Coagulation factor VIII (FVIII) is one of the most complex biopharmaceuticals due to the large size, poor protein stability and extensive post-translational modifications. As a consequence, efficient production of FVIII in mammalian cells poses a major challenge, with typical yields two to three orders of magnitude lower than for antibodies. In the present study we investigated CHO DXB11 cells transfected with a plasmid encoding human coagulation factor VIII.

N-glycosylation increases the circulatory half-life of human growth hormone.

Therapeutic use of recombinant GH typically involves daily sc injections. We examined the possibilities for prolonging the in vivo circulation of GH by introducing N-glycans. Human GH variants with a single potential N-glycosylation site (N-X-S/T) introduced by site-directed mutagenesis were expressed in HEK293 cells.

Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent.

Recombinant factor VIIa (rFVIIa, NovoSeven) is currently the only bypassing agent produced by recombinant technology for the treatment of haemophiliacs whose disease is complicated by inhibitory antibodies. In addition, recombinant production of FVIIa has made it widely available for a variety of purposes and accelerated the growth of our knowledge about FVIIa by generating an abundance of clinical and biochemical data. This fascinating molecule has turned out to be a safe haemostatic agent with great potential in the clinic and has inspired the generation of improved variants currently in (pre-)clinical testing.

Purification and characterization of a new recombinant factor VIII (N8).

A new recombinant factor VIII (FVIII), N8, has been produced in Chinese hamster ovary (CHO) cells. The molecule consists of a heavy chain of 88 kDa including a 21 amino acid residue truncated B-domain and a light chain of 79 kDa. The two chains are held together by non-covalent interactions.

More than one intracellular processing bottleneck delays the secretion of coagulation factor VII.

Coagulation factor VII (FVII) is a vitamin K-dependent glycoprotein that undergoes extensive post-translational modification prior to secretion. Secretion of FVII proteins from producer cells is a slow process. To identify bottlenecks for the transport of FVII through the secretory pathway of FVII-producing cells, we analysed the processing of intracellular FVII by pulse-chase of FVII producing CHO cells followed by radioimmuno precipitation, SDS-PAGE, and autoradiography.

Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity.

The intrinsic activity of coagulation factor VIIa (FVIIa) is dependent on Ca(2+) binding to a loop (residues 210-220) in the protease domain. Structural analysis revealed that Ca(2+) may enhance the activity by attenuating electrostatic repulsion of Glu(296) and/or by facilitating interactions between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity.

All post-translational modifications except propeptide cleavage are required for optimal secretion of coagulation factor VII.

Human coagulation factor VII (FVII) has two N-glycosylation sites (N145 and N322) and two O-glycosylation sites (S52 and S60). In transiently transfected COS-7 cells, all combinations of N- and O-glycosylation knock-out mutations reduced the release of FVII to the medium. Pulse-chase analysis of CHO-K1 cell lines expressing recombinant FVII demonstrated that virtually all wild-type FVII synthesized was secreted from the cells, whereas both N- and O-glycosylation knock-out mutations induced partial intracellular degradation of the synthesized FVII.

Posttranslational N-glycosylation takes place during the normal processing of human coagulation factor VII.

N-glycosylation is normally a cotranslational process that occurs during translocation of the nascent protein to the endoplasmic reticulum. In the present study, however, we demonstrate posttranslational N-glycosylation of recombinant human coagulation factor VII (FVII) in CHO-K1 and 293A cells. Human FVII has two N-glycosylation sites (N145 and N322).

Changes in the receptorbinding haemagglutinin protein of wild-type morbilliviruses are not required for adaptation to Vero cells.

We examined the consequences of isolation and adaptation to Vero cells for the receptorbinding haemagglutinin (H) gene of four syncytia-forming isolates of canine distemper virus (CDV) and of a dolphin morbillivirus isolate. A Vero-adapted CDV isolate exhibited biased hypermutation, since 11 out of 12 nucleotide differences to other isolates from the same epidemic were U-C transitions. Most of these transitions appeared to have taken place during in vitro cultivation.

Measles virus-induced modulation of host-cell gene expression.

The influence of measles virus (MV) infection on gene expression by human peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays. The mRNA levels of more than 3000 cellular genes were compared between uninfected PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV isolate. The MV-induced upregulation of individual genes identified by microarray analyses was confirmed by RT-PCR.