In vivo imaging of tau pathology using multi-parametric quantitative MRI

As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention

Should patients with hip joint prosthesis receive antibiotic prophylaxis before dental treatment?

The safety committee of the American Academy of Orthopedic Surgeons (AAOS) recommended in 2009 that clinicians should consider antibiotic prophylaxis for all patients with total joint replacement before any invasive procedure that may cause bacteremia. This has aroused confusion and anger among dentists asking for the evidence. The present review deals with different aspects of the rationale for this recommendation giving attention to views both in favor of and against it

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research