Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart.

Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process

Indications for implant removal after fracture healing: a review of the literature

Introduction: The aim of this review was to collect and summarize published data on the indications for implant removal after fracture healing, since these are not well defined and guidelines hardly exist. Methods: A literature search was performed. Results: Though there are several presumed benefits of implant removal, such as functional improvement and pain relief, the surgical procedure can be very challenging and may lead to complications or even worsening of the complaints. Research has focused on the safety of metal implants (e.g., risk of corrosion, allergy, and carcinogenesis). For these reasons, implants have been removed routinely for decades. Along with the introduction of titanium alloy implants, the need for implant removal became a subject of debate in view of potential (dis)advantages since, in general, implants made of titanium alloys are more difficult to remove. Currently, the main indications for removal from both the upper and lower extremity are mostly 'relative' and patient-driven, such as pain, prominent material, or simply the request for removal. True medical indications like infection or intra-articular material are minor reasons. Conclusion: This review illustrates the great variety of view points in the literature, with large differences in opinions and practices about the indications for implant removal after fracture healing. Since some studies have described asymptomatic patients developing complaints after removal, the general advice nowadays is to remove implants after fracture healing only in symptomatic patients and after a proper informed consent. Well-designed prospective studies on this subject are urgently needed in order to form guidelines based on scientific evidence

Advances in Understanding Environmental Risks of Red Mud After the Ajka Spill, Hungary

In the 5 years since the 2010 Ajka red mud spill (Hungary), there have been 46 scientific studies assessing the key risks and impacts associated with the largest single release of bauxite-processing residue (red mud) to the environment. These studies have provided insight into the main environmental concerns, as well as the effectiveness of remedial efforts that can inform future management of red mud elsewhere. The key immediate risks after the spill were associated with the highly caustic nature of the red mud slurry and fine particle size, which once desiccated, could generate fugitive dust. Studies on affected populations showed no major hazards identified beyond caustic exposure, while red mud dust risks were considered equal to or lesser than those provided by urban dusts of similar particle size distribution. The longer-term environmental risks were related to the saline nature of the spill material (salinization of inundated soils) and the release and the potential cycling of oxyanion-forming metals and metalloids (e.g., Al, As, Cr, Mo, and V) in the soil–water environment. Of these, those that are soluble at high pH, inefficiently removed from solution during dilution and likely to be exchangeable at ambient pH are of chief concern (e.g., Mo and V). Various ecotoxicological studies have identified negative impacts of red mud-amended soils and sediments at high volumes (typically [5 %) on different test organisms, with some evidence of molecularlevel impacts at high dose (e.g., genotoxic effects on plants and mice). These data provide a valuable database to inform future toxicological studies for red mud. However, extensive management efforts in the aftermath of the spill greatly limited these exposure risks through leachate neutralization and red mud recovery from the affected land. Monitoring of affected soils, stream sediments, waters and aquatic biota (fungi, invertebrates and fish) have all shown a very rapid recovery toward prespill conditions. The accident also prompted research that has also highlighted potential benefits of red mud use for critical raw material recovery (e.g., Ga, Co, V, rare earths, inform), carbon sequestration, biofuel crop production, and use as a soil ameliorant