In the Wake of the Storm: Environment, Disaster, and Race After Katrina

Studies evidence of environmental disparities by which poor and minority communities are disproportionately exposed to disasters, are less prepared, and have less access to relief agencies. Makes recommendations for preparedness and environmental justice

Enhanced Proteolysis of β-Amyloid in APP Transgenic Mice Prevents Plaque Formation, Secondary Pathology, and Premature Death

AbstractConverging evidence suggests that the accumulation of cerebral amyloid β-protein (Aβ) in Alzheimer's disease (AD) reflects an imbalance between the production and degradation of this self-aggregating peptide. Upregulation of proteases that degrade Aβ thus represents a novel therapeutic approach to lowering steady-state Aβ levels, but the consequences of sustained upregulation in vivo have not been studied. Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Aβ levels, retards or completely prevents amyloid plaque formation and its associated cytopathology, and rescues the premature lethality present in amyloid precursor protein (APP) transgenic mice. Our findings demonstrate that chronic upregulation of Aβ-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo

Correction to: Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation

No abstract was provided by the editors of this work

Air pollution, methane super-emitters, and oil and gas wells in Northern California: the relationship with migraine headache prevalence and exacerbation

Background Migraine–an episodic disorder characterized by severe headache that can lead to disability–affects over 1 billion people worldwide. Prior studies have found that short-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone increases risk of migraine-related emergency department (ED) visits. Our objective was to characterize the association between long-term exposure to sources of harmful emissions and common air pollutants with both migraine headache and, among patients with migraine, headache severity. Methods From the Sutter Health electronic health record database, we identified 89,575 prevalent migraine cases between 2014 and 2018 using a migraine probability algorithm (MPA) score and 270,564 frequency-matched controls. Sutter Health delivers care to 3.5 million patients annually in Northern California. Exposures included 2015 annual average block group-level PM2.5 and NO2 concentrations, inverse-distance weighted (IDW) methane emissions from 60 super-emitters located within 10 km of participant residence between 2016 and 2018, and IDW active oil and gas wells in 2015 within 10 km of each participant. We used logistic and negative binomial mixed models to evaluate the association between environmental exposures and (1) migraine case status; and (2) migraine severity (i.e., MPA score > 100, triptan prescriptions, neurology visits, urgent care migraine visits, and ED migraine visits per person-year). Models controlled for age, sex, race/ethnicity, Medicaid use, primary care visits, and block group-level population density and poverty. Results In adjusted analyses, for each 5 ppb increase in NO2, we observed 2% increased odds of migraine case status (95% CI: 1.00, 1.05) and for each 100,000 kg/hour increase in IDW methane emissions, the odds of case status also increased (OR = 1.04, 95% CI: 1.00, 1.08). We found no association between PM2.5 or oil and gas wells and migraine case status. PM2.5 was linearly associated with neurology visits, migraine-specific urgent care visits, and MPA score > 100, but not triptans or ED visits. NO2 was associated with migraine-specific urgent care and ED visits, but not other severity measures. We observed limited or null associations between continuous measures of methane emissions and proximity to oil and gas wells and migraine severity. Conclusions Our findings illustrate the potential role of long-term exposure to multiple ambient air pollutants for prevalent migraine and migraine severity

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexnucleotide repeat expansion

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA binding protein of 43kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n=14), with the major allele correlated with later age at death (p=0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n=75), again finding that the major allele associates with later age at death (p=0.016), as well as later age at onset (p=0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions

Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease

Sequential osseointegration from osseohealing to osseoremodeling - Histomorphological comparison of novel 3D porous and solid Ti-6Al-4V titanium implants

In the present study, we analyzed the histological characteristics of osseointegration of an open-porous Ti-6Al-4V material that was produced in a space holder method creating a 3-D through-pores trabecular design that mimics the inhomogeneity and size relationships of trabecular bone in macro- as well as microstructure. Pairs of cylindrical implants with a porosity of 49% and an average pore diameter of 400 µm (PI) or equal sized solid, corundum blasted devices (SI) as reference were bilaterally implanted press fit in the lateral condyles of 16 rabbits. Histological examination was performed after 4 weeks of short-term osseohealing and 12 weeks of mid-term osseoremodeling and we summarized the criteria for sequential osseointegration. After 4 weeks, osteoid had already been largely replaced by mineralized woven bone in both types of implants but was only represented to a greater extent in the deeper pores of PI. The cortical as well as trabecular region showed regular osseohealing with excessive and spatially undirected formation of immature woven bone. A dense bone mass was found in the cortical area, while in the trabecular region the bone mass was reduced distinctly, presenting large lacuna-like recesses and a demarcating trabecular structure. The pores near the implant surface contained more mineralized woven bone than the deeper pores. After 12 weeks, the osseoremodeling was largely completed with a physiological maturation to lamellar bone. The newly formed bone mass increased for PI and SI compared to the 4-week group and osteoid was only detectable in the deeper pores. The inhomogeneous trabecular design of the pores enables an excellent ingrowth of mineralized lamellar bone after remodeling to a pore depth of 1800 µm, which proves a functional load transfer from the surrounding bone into the implant. According to the concept of osseointegration by Branemark and Albrektsson, the histological evaluation confirms a successful, superior osseointegration of the presented porous properties improving long-term implant stability. The presented study protocol allows an excellent evaluation and comparison of the sequential osseointegration from short-term osseohealing to midterm osseoremodeling

Osseointegration of a novel 3D porous Ti-6Al-4V implant material – Histomorphometric analysis in rabbits

Porous structure properties are known to conduct initial and long-term stability of titanium alloy implants. This study aims to assess the histomorphometric effect of a 3-D porosity in Ti-6Al-4V implants (PI) on osseointegration in comparison to solid Ti-6Al-4V implants (SI). The PI was produced in a spaceholder method and sintering and has a pore size of mean 400 µm (50 µm to 500 µm) and mimics human trabecular bone. Pairs of PI and equal sized SI as reference were bilaterally implanted at random in the lateral femoral condyle of 16 Chinchilla-Bastard rabbits. The animals were sacrificed after 4 and 12 weeks for histomorphometric analysis. The histomorphometric evaluation confirmed a successful short-term osseohealing (4 weeks) and mid-term osseoremodeling (12 weeks) for both types of implants. The total newly formed bone area was larger for PI than for SI after 4 and 12 weeks, with the intraporous bone area being accountable for the significant difference (p<0.05). A more detailed observation of bone area distribution revealed a bony accumulation in a radius of ±500 µm around the implant surface after remodeling. The boneto-implant contact (BIC) increased significantly (p<0.05) from 4 to 12 weeks (PI 26.23% to 42.68%; SI 28.44% to 47.47%) for both types of implants. Due to different surface properties, however, PI had a significant (p<0.05) larger absolute osseous contact (mm) to the implant circumference compared to the SI (4 weeks: 7.46 mm vs 5.72 mm; 12 weeks: 11.57 mm vs 9.52 mm [PI vs. SI]). The regional influences (trabecular vs. cortical) on bone formation and the intraporous distribution were also presented. Conclusively, the porous structure and surface properties of PI enable a successful and regular osseointegration and enhance the bony fixation compared to solid implants under experimental conditions