Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia.
To determine if antioxidant supplements (vitamin E or selenium) used ...alone or in combination can prevent dementia in asymptomatic older men.
The 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.
Participants 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.
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.
The 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.
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.
Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear ...injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.
Endovascular treatments of Stanford type B aortic dissection may help to promote aortic remodeling and reduce the incidence of aortic-related complications. The aim of this study was to review ...published literature describing aortic remodeling after endovascular treatment of aortic dissection.
A systematic review of the literature was performed which was compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The type of aortic morphology measurements made and the methods used to make them were characterized. The endpoints of interest were the change in these measurements over time.
After initial screening, 77 articles were identified; 16 of which met the inclusion criteria. Few studies used three-dimensional reconstruction software and none had validated their measurement protocol. True lumen (TL) and false lumen (FL) diameters, areas, and in some cases volumes were measured. Studies assessed the aorta at a variety of different levels and over different periods of follow-up. Acute dissection patients displayed more consistent degree of remodeling (thoracic FL thrombosis in 80% to 90%) than chronic dissection patients (38% to 91%). Less remodeling was seen below the diaphragm in both groups.
Aortic remodeling after treatment for dissection is described in a highly heterogeneous manner. Despite this there appears to be a greater degree of complete FL resolution in patients with acute dissection than chronic. Factors such as length of aortic coverage and timing of treatment may explain the variation seen in the chronic dissection group. Consensus-based reporting standards are required to synthesize evidence and inform clinical decisions regarding patient selection and operative timing.
As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform ...typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones.
This paper reviews current literature on the projected effects of climate change on marine fish and shellfish, their fisheries, and fishery-dependent communities throughout the northern hemisphere. ...The review addresses the following issues: (i) expected impacts on ecosystem productivity and habitat quantity and quality; (ii) impacts of changes in production and habitat on marine fish and shellfish species including effects on the community species composition, spatial distributions, interactions, and vital rates of fish and shellfish; (iii) impacts on fisheries and their associated communities; (iv) implications for food security and associated changes; and (v) uncertainty and modelling skill assessment. Climate change will impact fish and shellfish, their fisheries, and fishery-dependent communities through a complex suite of linked processes. Integrated interdisciplinary research teams are forming in many regions to project these complex responses. National and international marine research organizations serve a key role in the coordination and integration of research to accelerate the production of projections of the effects of climate change on marine ecosystems and to move towards a future where relative impacts by region could be compared on a hemispheric or global level. Eight research foci were identified that will improve the projections of climate impacts on fish, fisheries, and fishery-dependent communities.
Cognitively intact elderly research volunteers at the University of Kentucky have been recruited, followed longitudinally, and autopsied with extensive neuropathological evaluations since 1989. To ...date, the cohort has recruited 1,030 individuals with 552 participants being actively followed, 363 deceased, and 273 autopsied. An extensive database has been constructed with continuous updates that include textured clinical, neuropsychological, neuroimaging, and pathological information. The history, demographics, clinical observations, and pathological features of this research cohort are described. We also explain some of the evolving methodologies and the academic contributions that have been made due to this motivated group of older Kentuckians.
Global climate change will increase outdoor and indoor heat loads, and may impair health and productivity for millions of working people. This study applies physiological evidence about effects of ...heat, climate guidelines for safe work environments, climate modeling, and global distributions of working populations to estimate the impact of 2 climate scenarios on future labor productivity. In most regions, climate change will decrease labor productivity, under the simple assumption of no specific adaptation. By the 2080s, the greatest absolute losses of population-based labor work capacity (in the range 11% to 27%) are seen under the A2 scenario in Southeast Asia, Andean and Central America, and the Caribbean. Increased occupational heat exposure due to climate change may significantly impact on labor productivity and costs unless preventive measures are implemented. Workers may need to work longer hours, or more workers may be required, to achieve the same output and there will be economic costs of lost production and/or occupational health interventions against heat exposures.
Malignant mesothelioma (MM) is an aggressive cancer of the pleural and peritoneal cavities caused by exposure to asbestos. Asbestos-induced mesotheliomas in wild-type mice have been used extensively ...as a preclinical model because they are phenotypically identical to their human counterpart. However, it is not known if the genetic lesions in these mice tumours are similar to in the human disease, a prerequisite for any new preclinical studies that target genetic abnormalities.
We performed whole exome sequencing of fifteen asbestos-induced murine MM tumour cell lines from BALB/c, CBA and C57BL/6 mouse strains and compared the somatic mutations and copy number variations with those recurrently reported in human MM. We then catalogued and characterised the mutational landscape of the wild-type murine MM tumours. Quantitative RT-PCR was used to interrogate the expression of key MM genes of interest in the mRNA.
Consistent with human MM tumours, we identified homozygous loss of the tumour suppressor Cdkn2a in 14/15 tumours. One tumour retained the first exon of both of the p16INK4a and p19ARF isoforms though this tumour also contained genetic amplification of Myc resulting in increased expression of the c-Myc proto-oncogene in the mRNA. There were no chromosomal losses in either the Bap1 or Nf2 regions. One tumour harbored homozygous loss of Trp53 in the DNA. Mutation rates were similar in tumours generated in the CBA and C57BL/6 strains when compared to human MM. Interestingly, all BALB/c tumour lines displayed high mutational loads, consistent with the known mutator phenotype of the host strain. The Wnt, MAPK and Jak-STAT signaling pathways were found to be the most commonly affected biological pathways. Mutations and copy number deletions also occurred in the Hedgehog and Hippo pathways.
These data suggest that in the wild-type murine model asbestos causes mesotheliomas in a similar way to in human MM. This further supports the notion that the murine model of MM represents a genuine homologue of the human disease, something uncommon in cancer, and is thus a valuable tool to provide insight into MM tumour development and to aide the search for novel therapeutic strategies.
Hermaphroditism, associated with territoriality and dominance behavior, is common in the marine environment. While male sex-specific coloration patterns have been documented in groupers, particularly ...during the spawning season, few data regarding social structure and the context for these color displays are available. In the present study, we define the social structure and male typical behavior of rock hind (Epinephelus adscensionis) in the wild. In addition, we detail the captive conditions and time period necessary to induce the onset of the sex-specific coloration and sexual change. At six oil production platform locations in the Gulf of Mexico, rock hind social group size and typical male rock hind social behavior were documented. We observed a rapid temporary color display in rock hind that could be turned on and off within three seconds and was used for confronting territory intruders and displays of aggression towards females. The male-specific "tuxedo" pattern consists of a bright yellow tail, a body with alternating dark brown and white patches and a dark bar extending from the upper mandible to the operculum. Identification and size ranges of male, female and intersex fish collected from oil platforms were determined in conjunction with gonadal histology. Rock hind social order is haremic with one dominant male defending a territory and a linear dominance hierarchy among individuals. In five captive experiments, the largest remaining female rock hind displayed the male specific color pattern within 32d after dominant male removal from the social group. To our knowledge, this is the first evidence in a grouper species of color patterning used to display territoriality and dominance outside of spawning aggregations. The behavioral paradigm described here is a key advance that will enable mechanistic studies of this complex sex change process.
PDF
