New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The geochemical evolution of brines from phosphogypsum deposits in Huelva (SW Spain) and its environmental implications

The present study focuses on the geochemistry of large phosphogypsum deposits in Huelva (SW Spain). Phosphogypsum slurry waste from fertiliser production was disposed in large ponds containing aqueous waste (i.e. brines) and exposed to weathering. These evaporation ponds were found to be dynamic environments far from attaining steady state conditions where a number of trace pollutants are subjected to temporal variations in response to changing environmental conditions. Chemical, mineralogical and morphological data were used to improve our understanding on the dynamics of a large number of elements in the phosphogypsum-brine-evaporation deposits system. Weekly sampling of brines over the course of 1 yr indicated a substantial enrichment in potentially harmful elements (e.g. As, Cr, Cu, F, Ni, U, V, Zn) present in time-dependent concentrations. The evaporation deposits formed multi-layered precipitates of chlorides, sulphates, phosphates and fluorides containing a large number of pollutants in readily soluble forms. The precipitation sequence revealed a time-dependent composition reflecting alternating precipitation and re-dissolution processes associated with seasonal changes in the local weather conditions. Concatenation of precipitation/re-dissolution stages was found to progressively enrich the brines in pollutants. These findings were supported by the observations from a tank experiment simulating the phosphogypsum-brine-evaporation deposits system under laboratory conditions. Given the substantially high concentrations of pollutants present in mobile forms in the brine-salt system, actions to abate these compounds should be implemented.This study was supported by the Spanish Autonomous Government and the Ministry of Economy and Competitiveness of Spain (Project CGL2014-54637-P; BES-2015-071239). We would like to thank the analytical staff at IDAEA-CSIC for their assistance. We would also like to acknowledge the Generalitat de Catalunya (AGAUR 2015 SGR33) for its support

A randomised, double blind, placebo-controlled study to determine the efficacy of immune modulation therapy in the treatment of patients suffering from peripheral arterial occlusive disease with intermittent claudication

AbstractObjectives: this study examined the effect of immune modulation therapy (IMT) on claudication distancesMaterials and methods: a double-blind placebo controlled trial was performed on patients with disabling intermittent claudication with randomisation stratified for short and long distance IC. For IMT, following exposure to UV light, oxidisation and 42.5°C, 10ml of citrated autologous blood was administered by intra-muscular injection. One course consisted of 6 injections in 3-weeks followed by 3-weeks rest. Patients received 2, 3 or 4 courses depending on response. The primary end-point was the number of responders (>50% increase in initial claudication distance (ICD)) in each group. Secondary end-points included percentage changes in ICD and change in quality of life.Results: at week 24, there were more responders in the IMT group (20/31, 65%) compared to placebo (16/39, 41%) (p=0.06). In the subgroup of short distance claudicants this difference reached significance (IMT 17/26, 65%) (Placebo12/33, 36%) (p=0.04). The median increase in ICD was significantly greater in the IMT group (81%) compared to placebo (44%, p=0.04). These results were supported by quality of life measurements.Conclusions: IMT is a safe and apparently effective treatment for patients with short distance claudication