Reduction of femoral fractures in long-term care facilities: the Bavarian fracture prevention study

Background

Hip fractures are a major public health burden. In industrialized countries about 20% of all femoral fractures occur in care dependent persons living in nursing care and assisted living facilities. Preventive strategies for these groups are needed as the access to medical services differs from independent home dwelling older persons at risk of osteoporotic fractures. It was the objective of the study to evaluate the effect of a fall and fracture prevention program on the incidence of femoral fracture in nursing homes in Bavaria, Germany.

Methods

In a translational intervention study a fall prevention program was introduced in 256 nursing homes with 13,653 residents. The control group consisted of 893 nursing homes with 31,668 residents. The intervention consisted of staff education on fall and fracture prevention strategies, progressive strength and balance training, and on institutional advice on environmental adaptations. Incident femoral fractures served as outcome measure.

Results

In the years before the intervention risk of a femoral fracture did not differ between the intervention group (IG) and control group (CG). During the one-year intervention period femoral fracture rates were 33.6 (IG) and 41.0/1000 person years (CG), respectively. The adjusted relative risk of a femoral fracture was 0.82 (95% CI 0.72-0.93) in residents exposed to the fall and fracture prevention program compared to residents from CG.

Conclusions

The state-wide dissemination of a multi-factorial fall and fracture prevention program was able to reduce femoral fractures in residents of nursing homes.     

The Impact of Bdnf Gene Deficiency to the Memory Impairment and Brain Pathology of APPswe/PS1dE9 Mouse Model of Alzheimer’s Disease

Brain-derived neurotrophic factor (BDNF) importantly regulates learning and memory and supports the survival of injured neurons. Reduced BDNF levels have been detected in the brains of Alzheimer’s disease (AD) patients but the exact role of BDNF in the pathophysiology of the disorder remains obscure. We have recently shown that reduced signaling of BDNF receptor TrkB aggravates memory impairment in APPswe/PS1dE9 (APdE9) mice, a model of AD. The present study examined the influence of Bdnf gene deficiency (heterozygous knockout) on spatial learning, spontaneous exploratory activity and motor coordination/balance in middle-aged male and female APdE9 mice. We also studied brain BDNF protein levels in APdE9 mice in different ages showing progressive amyloid pathology. Both APdE9 and Bdnf mutations impaired spatial learning in males and showed a similar trend in females. Importantly, the effect was additive, so that double mutant mice performed the worst. However, APdE9 and Bdnf mutations influenced spontaneous locomotion in contrasting ways, such that locomotor hyperactivity observed in APdE9 mice was normalized by Bdnf deficiency. Obesity associated with Bdnf deficiency did not account for the reduced hyperactivity in double mutant mice. Bdnf deficiency did not alter amyloid plaque formation in APdE9 mice. Before plaque formation (3 months), BDNF protein levels where either reduced (female) or unaltered (male) in the APdE9 mouse cortex. Unexpectedly, this was followed by an age-dependent increase in mature BDNF protein. Bdnf mRNA and phospho-TrkB levels remained unaltered in the cortical tissue samples of middle-aged APdE9 mice. Immunohistological studies revealed increased BDNF immunoreactivity around amyloid plaques indicating that the plaques may sequester BDNF protein and prevent it from activating TrkB. If similar BDNF accumulation happens in human AD brains, it would suggest that functional BDNF levels in the AD brains are even lower than reported, which could partially contribute to learning and memory problems of AD patients.     

Quick start guide to soil methods for ecologists

Increasingly biologists and ecologists are becoming aware of the vital importance of soil to processes observed aboveground and are incorporating soil analyses into their research. Because of the dynamic and heterogeneous nature of soil, proper incorporation of soil analysis into ecological studies requires knowledge and planning. Unfortunately, many ecologists may not be current (or trained at all) in soil science. We provide this review, based on our cumulative >60 years of work in soil science, to help familiarize researchers with essential information to appropriately incorporate soil analyses into ecological studies. Specifically, we provide a brief introduction into soils and then discuss issues related to soil sterilization, choosing a soil for a greenhouse project, sampling soils, and soil analyses.     

A dominant inhibitory mutant of the type II transforming growth factor beta receptor in the malignant progression of a cutaneous T-cell lymphoma.

In many cancers, inactivating mutations in both alleles of the transforming growth factor beta (TGF-beta) type 11 receptor (TbetaRII) gene occur and correlate with loss of sensitivity to TGF-beta. Here we describe a novel mechanism for loss of sensitivity to growth inhibition by TGF-beta in tumor development. Mac-1 cells, isolated from the blood of a patient with an indolent form of cutaneous T-cell lymphoma, express wild-type TbetaRII and are sensitive to TGF-beta. Mac-2A cells, clonally related to Mac-1 and isolated from a skin nodule of the same patient at a later, clinically aggressive stage of lymphoma, are resistant to TGF-beta. They express both the wild-type TbetaRII and a receptor with a single point mutation (Asp-404-Gly [D404G]) in the kinase domain (D404G-->TbetaRII); no TbetaRI or TbetaRII is found on the plasma membrane, suggesting that D404G-TbetaRII dominantly inhibits the function of the wild-type receptor by inhibiting its appearance on the plasma membrane. Indeed, inducible expression, under control of a tetracycline-regulated promoter, of D404G-TbetaRII in TGF-beta- sensitive Mac-1 cells as well as in Hep3B hepatoma cells results in resistance to TGF-beta and disappearance of cell surface TbetaRI and TbetaRII. Overexpression of wild-type TbetaRII in Mac-2A cells restores cell surface TbetaRI and TbetaRH and sensitivity to TGF-beta. The ability of the D404G-TbetaRH to dominantly inhibit function of wild-type TGF-beta receptors represents a new mechanism for loss of sensitivity to the growth-inhibitory functions of TGF-beta in tumor development.     

Radiosynthesis and in vivo evaluation of a fluorine-18 labeled pyrazine based radioligand for PET imaging of the adenosine A2B receptor

On the basis of a pyrazine core structure, three new adenosine A_2B receptor ligands (7a–c) were synthesized containing a 2-fluoropyridine moiety suitable for ¹⁸F-labeling. Compound 7a was docked into a homology model of the A_2B receptor based on X-ray structures of the related A_2A receptor, and its interactions with the adenosine binding site were rationalized. Binding affinity data were determined at the four human adenosine receptor subtypes. Despite a rather low selectivity regarding the A₁ receptor, 7a was radiolabeled as the most suitable candidate (K_i(A_2B)?=?4.24?nM) in order to perform in vivo studies in mice with the aim to estimate fundamental pharmacokinetic characteristics of the compound class. Organ distribution studies and a single PET study demonstrated brain uptake of [¹⁸F]7a with a standardized uptake value (SUV) of ≈1 at 5?min post injection followed by a fast wash out. Metabolism studies of [¹⁸F]7a in mice revealed the formation of a blood–brain barrier penetrable radiometabolite, which could be structurally identified. The results of this study provide an important basis for the design of new derivatives with improved binding properties and metabolic stability in vivo.     

Layer-by-layer Synthesis and Transfer of Freestanding Conjugated Microporous Polymer Nanomembranes

CMP as large surface area materials have attracted growing interest recently, due to their high variability in the incorporation of functional groups in combination with their outstanding thermal and chemical stability, and low densities. However, their insoluble nature causes problems in their processing since usually applied techniques such as spin coating are not available. Especially for membrane applications, where the processing of CMP as thin films is desirable, the processing problems have hindered their commercial application.Here we describe the interfacial synthesis of CMP thin films on functionalized substrates via molecular layer-by-layer (l-b-l) synthesis. This process allows the preparation of films with desired thickness and composition and even desired composition gradients.The use of sacrificial supports allows the preparation of freestanding membranes by dissolution of the support after the synthesis. To handle such ultra-thin freestanding membranes the protection with sacrificial coatings showed great promise, to avoid rupture of the nanomembranes. To transfer the nanomembranes to the desired substrate, the coated membranes are upfloated at the air-liquid interface and then transferred via dip coating.