NF-E2-related factor 2 activation boosts antioxidant defenses and ameliorates inflammatory and amyloid properties in human Presenilin-1 mutated Alzheimer's disease astrocytes

Alzheimer's disease (AD) is a common dementia affecting a vast number of individuals and significantly impairing quality of life. Despite extensive research in animal models and numerous promising treatment trials, there is still no curative treatment for AD. Astrocytes, the most common cell type of the central nervous system, have been shown to play a role in the major AD pathologies, including accumulation of amyloid plaques, neuroinflammation, and oxidative stress. Here, we show that inflammatory stimulation leads to metabolic activation of human astrocytes and reduces amyloid secretion. On the other hand, the activation of oxidative metabolism leads to increased reactive oxygen species production especially in AD astrocytes. While healthy astrocytes increase glutathione (GSH) release to protect the cells, Presenilin-1-mutated AD patient astrocytes do not. Thus, chronic inflammation is likely to induce oxidative damage in AD astrocytes. Activation of NRF2, the major regulator of cellular antioxidant defenses, encoded by the NFE2L2 gene, poses several beneficial effects on AD astrocytes. We report here that the activation of NRF2 pathway reduces amyloid secretion, normalizes cytokine release, and increases GSH secretion in AD astrocytes. NRF2 induction also activates the metabolism of astrocytes and increases the utilization of glycolysis. Taken together, targeting NRF2 in astrocytes could be a potent therapeutic strategy in AD.     

Taxonomic Characterization and Secondary Metabolite Profiling of Aspergillus Section Aspergillus Contaminating Feeds and Feedstuffs

Xerophilic fungal species of the genus Aspergillus are economically highly relevant due to their ability to grow on low water activity substrates causing spoilage of stored goods and animal feeds. These fungi can synthesize a variety of secondary metabolites, many of which show animal toxicity, creating a health risk for food production animals and to humans as final consumers, respectively. Animal feeds used for rabbit, chinchilla and rainbow trout production in Argentina were analysed for the presence of xerophilic Aspergillus section Aspergillus species. High isolation frequencies (>60%) were detected in all the studied rabbit and chinchilla feeds, while the rainbow trout feeds showed lower fungal charge (25%). These section Aspergillus contaminations comprised predominantly five taxa. Twenty isolates were subjected to taxonomic characterization using both ascospore SEM micromorphology and two independent DNA loci sequencing. The secondary metabolite profiles of the isolates were determined qualitatively by HPLC-MS. All the isolates produced neoechinulin A, 17 isolates were positive for cladosporin and echinulin, and 18 were positive for neoechinulin B. Physcion and preechinulin were detected in a minor proportion of the isolates. This is the first report describing the detailed species composition and the secondary metabolite profiles of Aspergillus section Aspergillus contaminating animal feeds.     

The incidence of pelvic fractures and related surgery in the Finnish adult population: a nationwide study of 33,469 patients between 1997 and 2014

Background and purpose — Information on the epidemiological trends of pelvic fractures and fracture surgery in the general population is limited. We therefore determined the incidence of pelvic fractures in the Finnish adult population between 1997 and 2014 and assessed the incidence and trends of fracture surgery.Patients and methods — We used data from the Finnish National Discharge Register (NHDR) to calculate the incidence of pelvic fractures and fracture surgery. All patients 18 years of age or older were included in the study. The NHDR covers the whole Finnish population and gives information on health care services and the surgical procedures performed.Results and interpretation — We found that in Finnish adults the overall incidence of hospitalization for a pelvic fracture increased from 34 to 56/100,000 person-years between 1997 and 2014. This increase was most apparent for the low-energy fragility fractures of the elderly female population. The ageing of the population is likely therefore to partly explain this increase. The annual number and incidence of pelvic fracture surgery also rose between 1997 and 2014, from 118 (number) and 3.0 (incidence) in 1997 to 187 and 4.3 in 2014, respectively. The increasing number and incidence of pelvic fractures in the elderly population will increase the need for social and healthcare services. The main focus should be on fracture prevention.

Pelvic fractures range from minor to major trauma and constitute about 3% to 8% of all fractures treated in hospitals (Court-Brown and Caesar 2006). The incidence of pelvic fractures has varied from 17 to 364/100,000 person-years (Melton et al. 1981, Ragnarsson and Jacobsson 1992, Lüthje et al. 1995, Kannus et al. 2000, Balogh et al. 2007, Andrich et al. 2015, Kannus et al. 2015, Verbeek et al. 2017). This wide range in incidence rates can be explained by different study populations with varying age, and by variations in study designs and follow-up periods. In previous studies, the incidence (n/100,000 person-years) of pelvic fractures was in the United States 37 between 1968 and 1977 (Melton et al. 1981), in Sweden 20 between 1976 and 1985 (Ragnarsson and Jacobsson 1992), in Finland 24 in 1988 (Lüthje et al. 1995), in the Finnish population aged 60 years or older 20 in 1970 and 92 in 1997 (Kannus et al. 2000), in Australia 23 between 2005 and 2006 (Balogh et al. 2007), in the German population aged 60 years or older 22 between 2008 and 2011 (Andrich et al. 2015), in the Finnish population aged 80 years or older 73 in 1971 and 364 in 2013 (Kannus et al. 2015) and in the Netherlands 14 between 2008 and 2012 (Verbeek et al. 2017).In the 80 years and older population, the incidence of low-energy pelvic fractures seems to be increasing (Kannus et al. 2015). Indeed, between 1997 and 2014, the incidence of acetabular fractures, especially low-energy acetabular fractures, rose in Finland (Rinne et al. 2017), whereas the incidence of high-energy acetabular fractures remained at the same level. Notably, since 1997, the incidence of many other fall-related low-energy fractures, such as hip fractures, has decreased in Finland (Korhonen et al. 2013, Kannus et al. 2018).Most pelvic fracture studies concentrate on surgical treatment, even though the majority of these fractures can be treated nonoperatively (Osterhoff et al. 2019, Tornetta et al. 2019). Unstable and dislocated pelvic fractures often need surgery, while stable, non-displaced, or minimally displaced fractures, mostly occurring in elderly people after a simple fall, can usually be treated nonsurgically. At present, however, there is only limited information available regarding the incidence and trends of pelvic fracture surgery in the general population.We assessed the incidence of pelvic fractures in the Finnish adult population between 1997 and 2014 and the incidence and trends of pelvic fracture surgery.