Effect of ultra-high-density polyethylene microplastic on the sorption and biodegradation of organic micropollutants.

Microplastics and organic micropollutants are two emerging contaminants that interact with each other in environmental and engineered systems. Sorption of organic micropollutants, such as pharmaceuticals, pesticides and industrial compounds, to microplastics can modify their bioavailability and biodegradation. The present study investigated the capacity of ultra-high density polyethylene particles (125 µm in diameter), before and after aging, to sorb 21 organic micropollutants at different environmentally relevant concentration. Furthermore, the biodegradation of these organic micropollutants by a biofilm microbial community growing on the microplastic surface was compared with the biodegradation by a microbial community originating from activated sludge. Among all tested organic micropollutants, propranolol (70%), trimethoprim (25%) and sotalol (15%) were sorbed in the presence of polyethylene particles. Growth of a biofilm on the polyethylene particles had a beneficial effect on the sorption of bromoxynil, caffeine and chloridazon and on the biodegradation of irbesartan, atenolol and benzotriazole. On the other hand, the biofilm limited the sorption of trimethoprim, propranolol, sotalol and benzotriazole and the biodegradation of 2,4-D. These results showed that ultra-high density polyethylene particles can affect both in a positive and negative way for the abiotic and biotic removal of organic micropollutants in wastewater. This project highlights the need for further investigation regarding the interaction between microplastics and organic micropollutants in the aquatic environment.

Potential and limitations for monitoring of pesticide biodegradation at trace concentrations in water and soil.

Pesticides application on agricultural fields results in pesticides being released into the environment, reaching soil, surface water and groundwater. Pesticides fate and transformation in the environment depend on environmental conditions as well as physical, chemical and biological degradation processes. Monitoring pesticides biodegradation in the environment is challenging, considering that traditional indicators, such as changes in pesticides concentration or identification of pesticide metabolites, are not suitable for many pesticides in anaerobic environments. Furthermore, those indicators cannot distinguish between biotic and abiotic pesticide degradation processes. For that reason, the use of molecular tools is important to monitor pesticide biodegradation-related genes or microorganisms in the environment. The development of targeted molecular (e.g., qPCR) tools, although laborious, allowed biodegradation monitoring by targeting the presence and expression of known catabolic genes of popular pesticides. Explorative molecular tools (i.e., metagenomics & metatranscriptomics), while requiring extensive data analysis, proved to have potential for screening the biodegradation potential and activity of more than one compound at the time. The application of molecular tools developed in laboratory and validated under controlled environments, face challenges when applied in the field due to the heterogeneity in pesticides distribution as well as natural environmental differences. However, for monitoring pesticides biodegradation in the field, the use of molecular tools combined with metadata is an important tool for understanding fate and transformation of the different pesticides present in the environment.

Biodegradation of metformin and its transformation product, guanylurea, by natural and exposed microbial communities.

Metformin (MET) is a pharmaceutical product mostly biotransformed in the environment to a transformation product, guanylurea (GUA). In ready biodegradability tests (RBTs), however, contrasting results have been observed for metformin. The objective of this study was to measure the biodegradation of MET and GUA in RBTs, using activated sludge from the local wastewater treatment plant, either directly or after pre-exposure to MET, in a chemostat. The activated sludge community was cultivated in chemostats, in presence or absence of MET, for a period of nine months, and was used in RBT after one, three and nine months. The results of this study showed that the original activated sludge was able to completely remove MET (15 mg/l) and the newly produced GUA (50% of C0MET) under the test conditions. Inoculation of the chemostat led to a rapid shift in the community composition and abundance. The community exposed to 1.5 mg/l of MET was still able to completely consume MET in the RBTs after one-month exposure, but three- and nine-months exposure resulted in reduced removal of MET in the RBTs. The ability of the activated sludge community to degrade MET and GUA is the result of environmental exposure to these chemicals as well as of conditions that could not be reproduced in the laboratory system. A MET-degrading strain belonging to the genus Aminobacter has been isolated from the chemostat community. This strain was able to completely consume 15 mg/l of MET within three days in the test. However, community analysis revealed that the fluctuation in relative abundance of this genus (<1%) could not be correlated to the fluctuation in biodegradation capacity of the chemostat community.

Prion propagation and toxicity occur in vitro with two-phase kinetics specific to strain and neuronal type.

Prion diseases, or transmissible spongiform encephalopathies (TSEs), are fatal neurodegenerative disorders that occur in humans and animals. The neuropathological hallmarks of TSEs are spongiosis, glial proliferation, and neuronal loss. The only known specific molecular marker of TSEs is the abnormal isoform (PrP(Sc)) of the host-encoded prion protein (PrP(C)), which accumulates in the brain of infected subjects and forms infectious prion particles. Although this transmissible agent lacks a specific nucleic acid component, several prion strains have been isolated. Prion strains are characterized by differences in disease outcome, PrP(Sc) distribution patterns, and brain lesion profiles at the terminal stage of the disease. The molecular factors and cellular mechanisms involved in strain-specific neuronal tropism and toxicity remain largely unknown. Currently, no cellular model exists to facilitate in vitro studies of these processes. A few cultured cell lines that maintain persistent scrapie infections have been developed, but only two of them have shown the cytotoxic effects associated with prion propagation. In this study, we have developed primary neuronal cultures to assess in vitro neuronal tropism and toxicity of different prion strains (scrapie strains 139A, ME7, and 22L). We have tested primary neuronal cultures enriched in cerebellar granular, striatal, or cortical neurons. Our results showed that (i) a strain-specific neuronal tropism operated in vitro; (ii) the cytotoxic effect varied among strains and neuronal cell types; (iii) prion propagation and toxicity occurred in two kinetic phases, a replicative phase followed by a toxic phase; and (iv) neurotoxicity peaked when abnormal PrP accumulation reached a plateau.

Unravelling the mechanisms of organic micropollutant removal in bio-electrochemical systems: Insights into sorption, electrochemical degradation, and biodegradation processes.

Bio-electrochemical systems (BESs) have recently been proposed as an efficient treatment technology to remove organic micropollutants from water treatment plants. In this study, we aimed to differentiate between sorption, electrochemical transport/degradation, and biodegradation. Using electro-active microorganisms and electrodes, we investigated organic micropollutant removal at environmentally relevant concentrations, clarifying the roles of sorption and electrochemical and biological degradation. The role of anodic biofilms on the removal of 10 relevant organic micropollutants was studied by performing separate sorption experiments on carbon-based electrodes (graphite felt, graphite rod, graphite granules, and granular activated carbon) and electrochemical degradation experiments at two different electrode potentials (-0.3 and 0 V). Granular activated carbon showed the highest sorption of micropollutants; applying a potential to graphite felt electrodes increased organic micropollutant removal. Removal efficiencies >80 % were obtained for all micropollutants at high anode potentials (+0.955 V), indicating that the studied compounds were more susceptible to oxidation than to reduction. All organic micropollutants showed removal when under bio-electrochemical conditions, ranging from low (e.g. metformin, 9.3 %) to exceptionally high removal efficiencies (e.g. sulfamethoxazole, 99.5 %). The lower removal observed under bio-electrochemical conditions when compared to only electrochemical conditions indicated that sorption to the electrode is key to guarantee high electrochemical degradation. The detection of transformation products of chloridazon and metformin indicated that (bio)-electrochemical degradation occurred. This study confirms that BES can treat some organic micropollutants through several mechanisms, which merits further investigation.

The abiotic removal of organic micropollutants with iron and manganese oxides in rapid sand filters for groundwater treatment.

Rapid sand filters (RSFs) have shown potential for removing organic micropollutants (OMPs) from groundwater. However, the abiotic removal mechanisms are not well understood. In this study, we collect sand from two field RSFs that are operated in series. The sand from the primary filter abiotically removes 87.5% of salicylic acid, 81.4% of paracetamol, and 80.2% of benzotriazole, while the sand from the secondary filter only removes paracetamol (84.6%). The field collected sand is coated by a blend of iron oxides (FeOx) and manganese oxides (MnOx) combined with organic matter, phosphate, and calcium. FeOx adsorbs salicylic acid via bonding of carboxyl group with FeOx. The desorption of salicylic acid from field sand indicates that salicylic acid is not oxidized by FeOx. MnOx adsorbs paracetamol through electrostatic interactions, and further transforms it into p-benzoquinone imine through hydrolysis-oxidation. FeOx significantly adsorbs organic matter, calcium, and phosphate, which in turn influences OMP removal. Organic matter on field sand surfaces limits OMP removal by blocking sorption sites on the oxides. However, calcium and phosphate on field sand support benzotriazole removal via surface complexation and hydrogen bonding. This paper provides further insight into the abiotic removal mechanisms of OMPs in field RSFs.

Pedunculated Epipericardial Fat Torsion: A Subtle Clinical and Radiological Mimicker.

Teaching Point: Epipericardial fat torsion is a little-known and uncommon condition with sometimes subtle findings making general awareness essential for detection and for confident diagnosis.

The impact of wait time on patient outcomes in knee and hip replacement surgery: a scoping review protocol.

BACKGROUND: Total hip and total knee replacement surgery are in high demand, leading to long wait times for many patients. While on the waiting list, patients may experience worsening pain, reduced mobility, and deteriorating health. Given that long wait times are common for lower joint replacement surgery, it is important to understand how patient health changes during the wait period and whether this impacts patient outcomes after surgery. The aim of this scoping review will be to identify and describe the evidence regarding the impact of wait time on patient outcomes for patients who undergo total knee and total hip replacement surgery. METHODS: This scoping review was designed with guidance from the Joanna Briggs Institute Manual for Evidence Synthesis, and results will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. EMBASE, Medline, PubMed, Scopus, CINAHL, and Cochrane electronic databases will be searched for English language articles published after 1999. Studies of adult patients with osteoarthritis undergoing primary knee or hip replacement surgery, which measure patient outcomes over the wait period for surgery, will be included. Two independent reviewers will screen titles and abstracts followed by full article review. Data will be extracted by two reviewers using a standardized form. Outcomes assessed during the wait period will be identified and described in tables. Factors associated with changes in health status during the wait period will be qualitatively described. DISCUSSION: This review will map the evidence regarding wait times for lower extremity joint replacement surgery. Better understanding of how the impact of wait times on patient health status is measured over the perioperative period will inform future research on wait times. SCOPING REVIEW REGISTRATION: Registered with Open Science Framework, Feb 14, 2021 DOI: https://doi.org/10.17605/OSF.IO/MV4FS.

Unravelling the contribution of nitrifying and methanotrophic bacteria to micropollutant co-metabolism in rapid sand filters.

The presence of organic micropollutant (OMP) in groundwater threatens drinking water quality and public health. Rapid sand filter (RSF) rely on biofilms with nitrifying and methanotrophic bacteria to remove ammonia and methane during drinking water production. Previous research observed the partial removal of OMPs with active nitrification and methane oxidation due to co-metabolic conversion of OMPs. However, the contribution of indigenous nitrifying and methanotrophic communities from RSF has yet to be fully explored. Accordingly, experiments were carried out with biofilm-covered sand collected from field-scale RSF, to assess the removal of nine OMPs by nitrifying and methanotrophic bacteria. Results indicated that stimulating nitrification resulted in significantly more removal of caffeine, 2,4-dichlorophenoxyacetic acid and bentazone. Stimulating methanotrophic conditions enhanced the removal of caffeine, benzotriazole, 2,4-dichlorophenoxyacetic acid and bentazone. Microbial community analysis based on 16 S rRNA gene sequencing revealed Nitrosomonas and Nitrospira are the dominant genus in the community under nitrifying conditions. The three genera Methylobacter, Methylomonas and Methylotenera were enriched under methanotrophic conditions. This study highlights that nitrifying and methanotrophic bacteria play important roles during OMP removal in field RSF. Furthermore, results suggest that bioaugmentation with an enriched nitrifying and methanotrophic culture is a promising approach to improve OMP removal in RSF.

Exploring organic micropollutant biodegradation under dynamic substrate loading in rapid sand filters.

Microbial removal of trace organic micropollutants (OMPs) from drinking water sources remains challenging. Nitrifying and heterotrophic bacteria in rapid sand filters (RSFs) are capable of biodegrading OMPs while growing on ammonia and dissolved organic matter (DOM). The loading patterns of ammonia and DOM may therefore affect microbial activities as well as OMP biodegradation. So far, there is very limited information on the effect of substrate loading on OMP biodegradation at environmentally relevant concentrations (∼ 1 µg/L) in RSFs. We investigated the biodegradation rates of 16 OMPs at various substrate loading rates and/or empty bed contact times (EBCT). The presence of DOM improved the biodegradation of paracetamol (41.8%) by functioning as supplementary carbon source for the heterotrophic degrader, while hindering the biodegradation of 2,4-D, mecoprop and benzotriazole due to substrate competition. Lower loading ratios of DOM/benzotriazole benefited benzotriazole biodegradation by reducing substrate competition. Higher ammonia loading rates enhanced benzotriazole removal by stimulating nitrification-based co-metabolism. However, stimulating nitrification inhibited heterotrophic activity, which in turn inhibited the biodegradation of paracetamol, 2,4-D and mecoprop. A longer EBCT promoted metformin biodegradation as it is a slowly biodegradable compound, but suppressed the biodegradation of paracetamol and benzotriazole due to limited substrate supply. Therefore, the optimal substrate loading pattern is contingent on the type of OMP, which can be chosen based on the priority compounds in practice. The overall results contribute to understanding OMP biodegradation mechanisms at trace concentrations and offer a step towards enhancing microbial removal of OMPs from drinking water by optimally using RSFs.

The sympathetic nervous system is involved in variant Creutzfeldt-Jakob disease.

Prion epizoonoses spread from animals consumed by humans raise the question of which pathways lead to prion neuroinvasion after oral exposure of humans. Here we show that neurons of sympathetic ganglia of patients with variant Creutzfeldt-Jakob disease (vCJD) accumulate the abnormal isoform of the protein prion. This observation shows the involvement of the sympathetic nervous system in the pathogenesis of vCJD and suggests a role for GUT-associated sympathetic neurons in prion propagation in humans after oral contamination.

Bathroom contamination by antibiotic-resistant Enterobacterales (ESBLPE and CPE): an experimental study.

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacterales (ESBLPE) and carbapenemase-producing Enterobacterales (CPE) cause serious infections. Their presence in urine may lead to environmental contamination potentially responsible for cross-transmission. AIM: To evaluate the level of spraying and contamination after emptying urine in the toilet and rinsing in the sink, a common practice in the healthcare setting. METHODS: For each test, the procedure was similar: seat raised, emptying urinal bottle into the toilet at the height of the bowl, rinsing in the sink and flushing. To study splash-drops, water and fluorescein were mixed in the urinal bottle. In each area, the splash-drops frequency and level were assessed with UV. To study contamination, three ESBLPE and one CPE were diluted in saline, 106/mL. Contamination was assessed by sampling before, immediately after and 3 h after the test. The swabs were cultured and the colonies counted and identified. FINDINGS: The areas at the highest risk of spraying were the toilet bowl contour (N = 36/36), the underside of the toilet seat (N = 34) and the inside of the sink (N = 34). Except for gloves (N = 14), there was low clothing contamination. The most frequently contaminated areas were inside the sink (40/48), where the highest levels of contamination were found (14/48). CONCLUSION: Emptying the urinal bottles in the toilet followed by sink rinsing is associated with a significant risk of projection and contamination, depending on the area (highest risk at the sink), but the bacteria did not survive beyond 3 h. This practice, which carries a risk of cross-transmission, should be reviewed.

Long-term exposure of activated sludge in chemostats leads to changes in microbial communities composition and enhanced biodegradation of 4-chloroaniline and N-methylpiperazine.

Exposure history and adaptation of the inoculum to chemicals have been shown to influence the outcome of ready biodegradability tests. However, there is a lack of information about the mechanisms involved in microbial adaptation and the implication thereof for the tests. In the present study, we investigated the impact of a long-term exposure to N-methylpiperazine (NMP) and 4-chloroaniline (4CA) of an activated sludge microbial community using chemostat systems. The objective was to characterize the influence of adaptation to the chemicals on an enhanced biodegradation testing, following the OECD 310 guideline. Cultures were used to inoculate the enhanced biodegradability tests, in batch, before and after exposure to each chemical independently in chemostat culture. Composition and diversity of the microbial communities were characterised by 16s rRNA gene amplicon sequencing. Using freshly sampled activated sludge, NMP was not degraded within the 28 d frame of the test while 4CA was completely eliminated. However, after one month of exposure, the community exposed to NMP was adapted and could completely degrade it. This result was in complete contrast with that from the culture exposed for 3 months to 4CA. Long term incubation in the chemostat system led to a progressive loss of the initial biodegradation capacity of the community, as a consequence of the loss of key degrading microorganisms. This study highlights the potential of chemostat systems to induce adaptation to a specific chemical, ultimately resulting in its biodegradation. At the same time, one should be critical of these observations as the dynamics of a microbial community are difficult to maintain in chemostat, as the loss of 4CA biodegradation capacity demonstrates.

Loss of cerebellar granule neurons is associated with punctate but not with large focal deposits of prion protein in Creutzfeldt-Jakob disease.

Whether aggregates of prion protein (PrP) reflect neurotoxicity or are neuroprotective in prion diseases is unclear. To address this question, we performed a clinicopathologic study of cerebellar granular neurons in 100 patients affected with sporadic Creutzfeldt-Jakob disease (CJD). There was significant loss of these neurons in the subset of cases with Val/Val genotype at PRNP Codon 129 and Molecular Isotype 2 of abnormal PrP (sporadic CJD-VV2) (n=32) compared with both the other CJD subtypes and to controls. Pathological PrP deposits of the punctate-type (synaptic-type) in this subgroup correlated with neuronal loss and proliferation of astrocytes and microglia. By contrast, the numbers of large deposits (5- to 50-microm-diameter) and numbers of amyloid plaques did not correlate with neuronal loss. These findings are consistent with the view that large aggregates may protect neurons by sequestering neurotoxic PrP oligomers, whereas punctate deposits may indicate the location of neuronal death processes in CJD.

Treatment of hepatitis C infection for current or former substance abusers in a community setting.

Substance abusers account for the largest number of hepatitis C infected cases in developed countries. We describe a care model for treating current or former substance abusers with antiviral therapy for hepatitis C virus (HCV) infection. The care model involved hepatitis nurses, a psychologist, infectious disease specialist and primary care physicians. Clients met selection criteria including regular attendance at clinic appointments and social stability. Use of alcohol and illicit substances was monitored with urine toxicology screens. The association between substance use, rates of completion of therapy and rates of response were assessed using multivariable regression analyses. A total of 109 clients (75 with genotype 1/4 and 34 with genotype 2/3) received at least one injection with pegylated interferon between November 2002 and January 2006. Treatment completion rates of 61 and 74% were achieved for genotypes 1/4 and 2/3, respectively. Treatment response rates in an intention to treat analysis were 51% for genotypes 1/4 and 68% for genotypes 2/3. A positive urine toxicology screen indicating use of illicit substances 6 months prior to initiating therapy was significantly associated with lower rates of treatment completion but not lower rates of sustained virological response. A positive urine screen indicating use of alcohol prior to therapy was significantly associated with lower rates of completion and lower rates of response. Rates of completion and response are comparable to non-substance abusing populations. Antiviral therapy for HCV infection can be successful within the context of ongoing care for substance abuse for carefully selected patients.

Biomechanical evaluation of injury severity associated with patient falls from bed.

This study investigated the severity of injuries associated with falling from bed and the effectiveness of injury-prevention strategies. Injury criteria were calculated for head- and feet-first falls from six bed heights onto a tiled surface and floor mat. These values indicated a 25% chance of experiencing a serious head injury as a result of falling feet-first from a bed height of 97.5 cm onto a tiled surface. Risk of injury increased to 40% when extrapolated for the height added by bedrails. Using a floor mat decreased this risk to less than 1% for bedrail height for feet-first falls. Calculated impact forces indicated a risk of skull fracture when hitting the tiled surface. Floor mats and height-adjustable beds positioned to the lowest height should be used to decrease the risk of injury associated with falling from bed.

Trends in hepatitis B and hepatitis C seroprevalence among blood donors - Haiti, 2005-2014.

Background and Objectives: Data on the seroprevalence of viral hepatitis are limited in Haiti; consequently, the epidemiology is poorly described. This study aims to provide a descriptive analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) seroprevalence of blood donations in Haiti. Materials and Methods: Using Haiti's National Blood Safety Program and Haitian Red Cross reports from 2005 to 2014, we analysed the results of screening tests of donor serum samples to assess HBV and HCV seroprevalence among adults aged 17 to 65 years. Results: A total of 198 758 donor samples were screened from 2005 to 2014, of which 0·56% were positive for antibody to hepatitis C virus (anti-HCV) and 3·80% were positive for hepatitis B surface antigen. Over the 10-year study period, anti-HCV seroprevalence among blood donors increased by 31% from 0.66% to 0.86% (95% CI: 1·01-1·70); however, this trend was not uniform over time, with a significant decrease from 0·66% in 2005 to 0·39% in 2009 (95% CI: 0·43- 0·82) and 0·43% in 2012 (95% CI: 0·50-0·90). Conversely, HBV decreased significantly by 13% from 3·95% in 2005 to 3·42% in 2014 (95% CI: 0·77-0·97), a trend that was also observed in 2012 and 2013. Conclusion: The significant, uniform decrease in HBV seroprevalence in more recent years may represent the positive impact of public health interventions in preventing the transmission of blood-borne infections. More research is needed to understand why the trends in HCV transmission are non-uniform and to investigate the significant increase in more recent years.

Geographic distribution of blood collections in Haiti before and after the 2010 earthquake.

BACKGROUND: The January 2010 Haiti earthquake destroyed the National Blood Transfusion Center and reduced monthly national blood collections by > 46%. Efforts to rapidly scale-up blood collections outside of the earthquake-affected region were investigated. STUDY DESIGN AND METHODS: Blood collection data for 2004-2014 from Haiti's 10 administrative departments were grouped into four regions: Northern, Central, Port-au-Prince and Southern. Analyses compared regional collection totals during the study period. RESULTS: Collections in Port-au-Prince accounted for 52% of Haiti's blood supply in 2009, but fell 96% in February 2010. Haiti subsequently increased blood collections in the North, Central and Southern regions to compensate. By May 2010, national blood collections were only 10·9% lower than in May 2009, with 70% of collections coming from outside of Port-au-Prince. By 2013 national collections (27 478 units) had surpassed 2009 levels by 30%, and Port-au-Prince collections had recovered (from 11 074 units in 2009 to 11 670 units in 2013). CONCLUSION: Haiti's National Blood Safety Program managed a rapid expansion of collections outside of Port-au-Prince following the earthquake. Annual collections exceeded pre-earthquake levels by 2012 and continued rising annually. Increased regional collections provided a greater share of the national blood supply, reducing dependence on Port-au-Prince for collections.

Comparing surgical trays with redundant instruments with trays with reduced instruments: a cost analysis.

BACKGROUND: When prearranged standard surgical trays contain instruments that are repeatedly unused, the redundancy can result in unnecessary health care costs. Our objective was to estimate potential savings by performing an economic evaluation comparing the cost of surgical trays with redundant instruments with surgical trays with reduced instruments ("reduced trays"). METHODS: We performed a cost-analysis from the hospital perspective over a 1-year period. Using a mathematical model, we compared the direct costs of trays containing redundant instruments to reduced trays for 5 otolaryngology procedures. We incorporated data from several sources including local hospital data on surgical volume, the number of instruments on redundant and reduced trays, wages of personnel and time required to pack instruments. From the literature, we incorporated instrument depreciation costs and the time required to decontaminate an instrument. We performed 1-way sensitivity analyses on all variables, including surgical volume. Costs were estimated in 2013 Canadian dollars. RESULTS: The cost of redundant trays was $21 806 and the cost of reduced trays was $8803, for a 1-year cost saving of $13 003. In sensitivity analyses, cost savings ranged from $3262 to $21 395, based on the surgical volume at the institution. Variation in surgical volume resulted in a wider range of estimates, with a minimum of $3253 for low-volume to a maximum of $52 012 for high-volume institutions. INTERPRETATION: Our study suggests moderate savings may be achieved by reducing surgical tray redundancy and, if applied to other surgical specialties, may result in savings to Canadian health care systems.

The N-terminal cleavage of cellular prion protein in the human brain.

Human brain cellular prion protein (PrP(c)) is cleaved within its highly conserved domain at amino acid 110/111/112. This cleavage generates a highly stable C-terminal fragment (C1). We examined the relative abundance of holo- and truncated PrP(c) in human cerebral cortex and we found important inter-individual variations in the proportion of C1. Neither age nor postmortem interval explain the large variability observed in C1 amount. Interestingly, our results show that high levels of C1 are associated with the presence of the active ADAM 10 suggesting this zinc metalloprotease as a candidate for the cleavage of PrP(c) in the human brain.