IMPORTANCEOxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.OBJECTIVE To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men. DESIGN, SETTING, AND PARTICIPANTSThe Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms. INTERVENTIONSParticipants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment.MAIN OUTCOMES AND MEASURES Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen. RESULTSThe mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo.CONCLUSIONS AND RELEVANCE Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.

One hundred and one new dinucleotide repeat polymorphisms specific for the canine genome have been identified and characterized. Screening of both primary libraries and marker-selected libraries enriched for simple sequence repeats led to the isolation of large numbers of genomic clones that contained (CA)n repeats. Over 200 of these clones were sequenced, and PCR primers that bracket the repeat were developed for those that contained ten or more continuous (CA)n units. This effort led to the production of 101 polymorphic markers, which were assigned to one of four categories depending on their degree of polymorphism. Fifty-four markers were found to be highly or very highly polymorphic as they had four or more alleles when tested on a panel of unrelated dogs. This group of markers will be useful for following inheritance of traits in crosses between dogs.

the co-occurrence of Geobacter and Methanosarcinales is often used as a proxy for the manifestation of direct interspecies electron transfer (Diet) in the environment. Here we tested eleven new coculture combinations between methanogens and electrogens. previously, only the most electrogenic Geobacter paired by Diet with Methanosarcinales methanogens, namely G. metallireducens and G. hydrogenophilus. Here we provide additional support, and show that five additional Methanosarcinales paired with G. metallireducens, while a strict hydrogenotroph could not. We also show that G. hydrogenophilus, which is incapable to grow with a strict hydrogenotrophic methanogen, could pair with a strict non-hydrogenotrophic Methanosarcinales. Likewise, an electrogen outside the Geobacter cluster (Rhodoferrax ferrireducens) paired with Methanosarcinales but not with strict hydrogenotrophic methanogens. the ability to interact with electrogens appears to be conserved among Methanosarcinales, the only methanogens with c-type cytochromes, including multihemes (MHc). nonetheless, MHc, which are often linked to extracellular electron transfer, were neither unique nor universal to Methanosarcinales and only two of seven Methanosarcinales tested had MHc. of these two, one strain had an MHc-deletion knockout available, which we hereby show is still capable to retrieve extracellular electrons from G. metallireducens or an electrode suggesting an MHcindependent strategy for extracellular electron uptake.Direct interspecies electron transfer (DIET) was discovered in an artificial co-culture of an ethanol-oxidizing Geobacter metallireducens with a fumarate-reducing Geobacter sulfurreducens where the possibility of hydrogen gas (H 2 ) or formate transfer was invalidated through genetic studies 1,2 . Gene deletions rendering H 2 and formate transfer impossible resulted in active co-cultures 1,2 , whereas deletion of genes for extracellular electron transfer proteins (EET) such as pili, and multiheme c-type cytochromes made the interspecies interaction impossible 1,3 . Remarkably, a deletion mutant lacking an outer membrane multiheme c-type cytochrome (OmcS) could be rescued by the addition of extracellular conductive particles, whereas a pili knock-out strain could not be rescued by conductive particles 4 . Additionally, previous studies have shown that G. metallireducens is also highly effective as an anode-respiring bacteria (ARB) generating some of the highest current densities of all Geobacter tested 5 . During DIET with G. sulfurreducens, G. metallireducens requires pili and certain multiheme c-type cytochromes 3 , which were also required during anode respiration 6,7 .G. metallireducens is a strict respiratory microorganism unable to ferment its substrates to produce H 2 for interspecies H 2 -transfer 8,9 . Consequently, G. metallireducens could not provide reducing equivalents for strict hydrogenotrophic methanogens (Methanospirilum hungatei and Methanobacterium formicicum) 10,11 . However, G. metallireducens did interact syntrophically wi...

GAC or electrodes). A comparison of functional gene categories between the two Methanosarcina showed differences regarding energy metabolism, which could explain dissimilarities concerning electromethanogenesis at fixed potentials. We suggest that these dissimilarities are minimized in the presence of an electrogenic DIET partner (e.g., Geobacter), which can modulate its surface redox potentials by adjusting the expression of electroactive surface proteins.