Effects of smoking on clinical treatment outcomes amongst patients with chronic inflammatory diseases initiating biologics: secondary analyses of the prospective BELIEVE cohort study.

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs.

FcRn overexpression in human cancer drives albumin recycling and cell growth; a mechanistic basis for exploitation in targeted albumin-drug designs.

Albumin accumulation in tumours could reflect a role of albumin in transport of endogenous nutrient cargos required for cellular growth and not just a suggested source of amino acids; a role driven by albumin engagement with its cognate cellular recycling neonatal Fc receptor. We investigate the hypothesis that albumin cellular recruitment is increased by higher human FcRn (hFcRn) expression in human cancer tissue that provides the mechanistic basis for exploitation in albumin-based drug designs engineered to optimise this process. Eight out of ten different human cancer tissue types screened for hFcRn expression by immunohistochemistry (310 samples) exhibited significantly higher hFcRn expression compared to healthy tissues.

Cellular recycling-driven in vivo half-life extension using recombinant albumin fusions tuned for neonatal Fc receptor (FcRn) engagement.

Recombinant albumin-drug genetic fusions are an effective technology to prolong the serum half-life of therapeutics that has resulted in marketed products. Indirect evidence suggests albumin fusions' long circulation is controlled by engagement with the cellular recycling neonatal Fc receptor (FcRn) in addition to reduced kidney filtration. In this work, we have used a panel of recombinant fusions, engineered with different human FcRn (hFcRn) affinity, including a novel high binding albumin variant (HBII), to directly define and importantly, control the intracellular mechanism as a half-life extension tuning method.

An Albumin-Oligonucleotide Assembly for Potential Combinatorial Drug Delivery and Half-Life Extension Applications.

The long blood circulatory property of human serum albumin, due to engagement with the cellular recycling neonatal Fc receptor (FcRn), is an attractive drug half-life extension enabling technology. This work describes a novel site-specific albumin double-stranded (ds) DNA assembly approach, in which the 3' or 5' end maleimide-derivatized oligodeoxynucleotides are conjugated to albumin cysteine at position 34 (cys34) and annealed with complementary strands to allow single site-specific protein modification with functionalized ds oligodeoxynucleotides. Electrophoretic gel shift assays demonstrated successful annealing of complementary strands bearing Atto488, 6-carboxyfluorescein (6-FAM), or a factor IXa aptamer to the albumin-oligodeoxynucleotide conjugate.

Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter.

The human serotonin transporter is the primary target of several antidepressant drugs, and the importance of a primary, high affinity binding site (S1) for antidepressant binding is well documented. The existence of a lower affinity, secondary binding site (S2) has, however, been debated. Herein we report the synthesis of 3-position coupled imipramine ligands from clomipramine using a copper free Sonogashira reaction.

Albumin-based drug delivery: harnessing nature to cure disease.

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association.

Intersectoral action for health: the experience of a Danish municipality.

Background: The aim was to build up evidence on intersectoral action for health at local government level by identifying both challenges and facilitating factors in collaboration between sectors when developing and implementing an intersectoral health policy in Varde, Denmark.

Methods: The study was carried out in 2011 using the case-study method. Approximately 500 pages of documents from the period 2007-2011 were analysed, and semi-structured interviews were carried out with nine key informants.

Assessing public health intervention practices in a Danish municipality: applying criteria based on the European Community Health Promotion Indicator Development (EUHPID) model.

Aim: To develop a set of assessment criteria and assess public health interventions at municipal level in Denmark using the European Community Health Promotion Indicator Development (EUHPID) model to support more effective planning and funding allocation in public health.

Methods: Based on knowledge synthesis, a set of assessment criteria were developed to classify interventions into the four types of public health provided by the EUHPID model: health promotion, health protection, disease prevention, and health care. Information was then collected on all current public health interventions in Varde Municipality within a 3-month period in spring 2009.

Basic N-interlinked imipramines show apoptotic activity against malignant cells including Burkitt's lymphoma.

We here report the synthesis of ethylene glycol N-interlinked imipramine dimers of various lengths from the tricyclic antidepressant desipramine via an amide coupling reaction followed by reduction with lithium aluminium hydride. The target molecules were found to be potent inhibitors of cellular viability while inducing cell type specific death mechanisms in three cancer cell lines including a highly chemoresistant Burkitt's lymphoma cell line. Basic amine analogues were found to be important for increased potency.

Use of evidence in local public health work in Denmark.

Objective: The aim was to investigate how and on which level evidence is used in policy processes related to local public health work in Denmark.

Method: A survey was carried out in municipalities in Denmark (n = 98, response rate 81%) with health managers as respondents.

Results: A large variation in understanding of the concept of evidence was found.

[Good experiences with collaboration between research and practice in public health].

In order to evaluate the first year of collaboration between Unit for Health Promotion Research (SDU) and three municipalities a survey was completed with respondents from municipalities. The evaluation showed gains: increased use of research-based working methods, image lift, concrete products delivered, and support in project development. Challenges experienced: different working traditions, translating research into practical know-how, and lack of capacity for knowledge exchange.

[New European model for cross-sectorial health initiatives].

Over the last years EU have been working on the development of a common classification system for health indicators. In connection with prevention and health promotion, a classification system has now been developed: the European Health Promotion Indicator Development, EUHPID. The purpose has been to establish a system of indicators to advance the focus on health promotion.

[Evidence-based treatment of mentally ill homeless persons].

A systematic review of the literature shows that it is possible to reduce homelessness among mentally ill homeless persons, partly by offering access to housing and partly by providing intensive care through Assertive Community Treatment. Assertive Community Treatment can, to some extent, decrease psychiatric symptoms and increase quality of life. It is evident that by offering housing, homelessness may be reduced, but the comparison of independent housing and group living did not reveal big differences.