CFHealthHub: Complex intervention to support adherence to treatment in adults with cystic fibrosis: external pilot trial

E-Poster Session

A collagen-hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates.

An emerging paradigm in orthopedics is that a bone-healing outcome is the product of the anabolic (bone-forming) and catabolic (bone-resorbing) outcomes. Recently, surgical and tissue engineering strategies have emerged that combine recombinant human bone morphogenetic proteins (rhBMPs) and bisphosphonates (BPs) in order to maximize anabolism and minimize catabolism. Collagen-based scaffolds that are the current surgical standard can bind rhBMPs, but not BPs. We hypothesized that a biomimetic collagen-hydroxyapatite (CHA) scaffold would bind both agents and produce superior in vivo outcomes. Consistent with this concept, in vitro elution studies utilizing rhBMP-2 ELISA assays and scintillation counting of (14)C-radiolabeled zoledronic acid (ZA) confirmed delayed release of both agents from the CHA scaffold. Next, scaffolds were tested for their capacity to form ectopic bone after surgical implantation into the rat hind limb. Using CHA, a significant 6-fold increase in bone volume was seen in rhBMP-2/ZA groups compared to rhBMP-2 alone, confirming the ability of ZA to enhance rhBMP-2 bone formation. CHA scaffolds were found to be capable of generating mineralized tissue in the absence of rhBMP-2. This study has implications for future clinical treatments of critical bone defects. It demonstrates the relative advantages of co-delivering anabolic and anti-catabolic agents using a multicomponent scaffold system

Spatial control of bone formation using a porous polymer scaffold co-delivering anabolic RHBMP-2 and anti-resorptive agents

Current clinical delivery of recombinant human bone morphogenetic proteins (rhBMPs) utilises freeze-dried collagen. Despite effective new bone generation, rhBMP via collagen can be limited by significant complications due to inflammation and uncontrolled bone formation. This study aimed to produce an alternative rhBMP local delivery system to permit more controllable and superior rhBMP-induced bone formation. Cylindrical porous poly(lactic-co-glycolic acid) (PLGA) scaffolds were manufactured by thermally-induced phase separation. Scaffolds were encapsulated with anabolic rhBMP-2 (20 μg) ± anti-resorptive agents: zoledronic acid (5 μg ZA), ZA pre-adsorbed onto hydroxyapatite microparticles, (5 μg ZA/2 % HA) or IkappaB kinase (IKK) inhibitor (10 μg PS-1145). Scaffolds were inserted in a 6-mm critical-sized femoral defect in Wistar rats, and compared against rhBMP-2 via collagen. The regenerate region was examined at 6 weeks by 3D microCT and descriptive histology. MicroCT and histology revealed rhBMP-induced bone was more restricted in the PLGA scaffolds than collagen scaffolds (-92.3 % TV, p < 0.01). The regenerate formed by PLGA + rhBMP-2/ZA/HA showed comparable bone volume to rhBMP-2 via collagen, and bone mineral density was +9.1 % higher (p < 0.01). Local adjunct ZA/HA or PS-1145 significantly enhanced PLGA + rhBMP-induced bone formation by +78.2 % and +52.0 %, respectively (p ≤ 0.01). Mechanistically, MG-63 human osteoblast-like cells showed cellular invasion and proliferation within PLGA scaffolds. In conclusion, PLGA scaffolds enabled superior spatial control of rhBMP-induced bone formation over clinically-used collagen. The PLGA scaffold has the potential to avoid uncontrollable bone formation-related safety issues and to customise bone shape by scaffold design. Moreover, local treatment with anti-resorptive agents incorporated within the scaffold further augmented rhBMP-induced bone formation

Health care system planning for and response to a nuclear detonation

The hallmark of a successful response to a nuclear detonation will be the resilience of the community, region, and nation. An incident of this magnitude will rapidly become a national incident; however, the initial critical steps to reduce lives lost, save the lives that can be saved with the resources available, and understand and apply resources available to a complex and dynamic situation will be the responsibility of the local and regional responders and planners. Expectations of the public health and health care systems will be met to the extent possible by coordination, cooperation, and an effort to produce as consistent a response as possible for the victims. Responders will face extraordinarily stressful situations, and their own physical and psychological health is of great importance to optimizing the response. This article illustrates through vignettes and supporting text how the incident may unfold for the various components of the health and medical systems and provides additional context for the discipline-related actions outlined in the state and local planners’ playbook

Template-Directed Olefin Cross Metathesis

A template containing two secondary dialkylammonium ion recognition sites for encirclement by olefin-bearing dibenzo[24]crown-8 derivatives has been used to promote olefin cross metatheses with ruthenium-alkylidene catalysts. For monoolefin monomers, the rates of metatheses and yields of the dimers are both amplified in the presence of the template. Likewise, for a diolefin monomer, the yield of the dimer is enhanced in the presence of the template under conditions where higher oligomers are not formed

Dynamic Mechanically Interlocked Dendrimers: Amplification in Dendritic Dynamic Combinatorial Libraries

In the context of constructing nonclassical mechanically interlocked dendrimers by employing a convergent templation procedure, the “clipping” thermodynamic approach has been explored to introduce sterically bulky Fre´chet-type dendrons with successive generations [G0] to [G3] onto a trivalent ammonium ion core using a seven-component self-assembly via imine bond formation. Four generations of mechanically interlocked dendrimers up to a molecular weight over 8800 Da were synthesized in a one-pot reaction by simply mixing the seven components together. The dendrimers form in excellent yield (>90%). The mechanically interlocked core of the [G0]-[G2] dendrimers can be modified and transformed into kinetically stable dendrimers by reduction of the imine bonds with borane-tetrahydrofuran complex. Moreover, the dynamic nature of the thermodynamically controlled self-assembly process is employed to obtain three dynamic combinatorial libraries of dendrimers by the treatment of the dendrons [G0]-[G3] with the complementary components in one pot. The inherent modularity of the overall process should allow for the rapid and straightforward access to many other analogues of mechanically interlocked systems for which either the branched core or the dendritic periphery can be modified to suit the needs of any potential application of these molecules

Middle Miocene to Pliocene History of Antarctica and the Southern Ocean

This chapter explores the Middle Miocene to Pliocene terrestrial and marine records of Antarctica and the Southern Ocean. The structure of the chapter makes a clear distinction between terrestrial and marine records as well as proximal (on or around Antarctica) and more distal records (Southern Ocean). Particular geographical regions are identified that reflect the areas for which the majority of palaeoenvironmental and palaeoclimatic information exist. Specifically, the chapter addresses the terrestrial sedimentary and fjordal environments of the Transantarctic Mountains and Lambert Glacier region, the terrestrial fossil record of Antarctic climate, terrestrial environments of West Antarctica, and the marine records of the East Antarctic Ice Sheet (EAIS), the West Antarctic Ice Sheet (WAIS) and the Antarctic Peninsula Ice Sheet (APIS), as well as the marine record of the Southern Ocean. Previous and current studies focusing on modelling Middle Miocene to Pliocene climate, environments and ice sheets are discussed.Published401-4631.8. Osservazioni di geofisica ambientale3.8. Geofisica per l'ambientereserve

WHICH TESTOSTERONE REPLACEMENT THERAPY?

SUMMARY Three different forms of testosterone (T) replacement therapy were compared; they were the intramuscular injection of mixed testosterone esters 250 mg; the subcutaneous implantation of 6 x 100 mg pellets of fused testosterone; and the oral administration of testosterone undecanoate (TU) 80 mg twice daily. Six hypogonadal males were treated with oral TU for an eight week period, during which time serial serum hormonal estimations were performed over 10 h at the initiation and after four and eight weeks of therapy. Serum T levels showed marked variability both between subjects and within the same subject on different occasions. We attribute this to variability in absorption of TU, which is formulated in oleic acid. The overall mean T level calculated from the areas under the profiles of TU was 12.0 nmol/l. Hormone responses to injected T esters were studied in nine hypogonadal males. Serum T rose to supraphysiological peak concentrations (mean 71 nmol/l) 24-48 h after an injection, followed by an exponential decay to reach baseline concentrations after 2-3 weeks. The overall calculated mean T level in subjects receiving testosterone esters 250 mgevery three weeks was 27.7 nmol/l. Subcutaneous implantation of testosterone in six hypogonadal men produced a gradual rise in serum T followed by a slow decline, with T levels remaining within the normal range for 4-5 months. The calculated overall mean T level over 21 weeks after implantation was 17.0 nmol/l. Serum oestradiol (Ez) levels remained within the normal male range throughout the study periods on both TU and T implant therapy but showed a supraphysiological peak (mean 347 pmol/l) 24-48 h after a T injection. Sa-dihydrotestosterone (DHT) levels appeared to parallel those of T on the three forms of therapy, with DHT:T ratios being highest for TU therapy. This was also true for the target organ metabolite 5a-androstane-3a, 17B-diol. At the doses studied drug costs were similar for T implantation (every 5 months) and Tester injections (every 3 weeks), but were 7-8 times higher for TU (80 mg twice a day). We conclude that T implantation remains overall the most physiological form of androgen replace