SynopsisThe Mini-Mental State Examination was administered to 1865 general-practice patients aged 75 years and over. Even when demented cases were removed from analysis, respondents with relatively little education, together with those in social classes Ill-manual and below, were significantly more likely to score below the cut-off point used in North American community surveys to denote ‘cognitive impairment’. Education and social class influenced scores on all sections within the MMSE with the exception of registration. Sex influenced scores on tests of calculation and spelling backwards but had no effect on total scores. These findings emphasize the importance of investigating low scorers in more detail before making a diagnosis of dementia.

Background The Vaxxas high-density microarray patch (HD-MAP) consists of a high density of microprojections coated with vaccine for delivery into the skin. Microarray patches (MAPs) offer the possibility of improved vaccine thermostability as well as the potential to be safer, more acceptable, easier to use, and more cost-effective for the administration of vaccines than injection by needle and syringe (N&S). Here, we report a phase I trial using the Vaxxas HD-MAP to deliver a monovalent influenza vaccine that was to the best of our knowledge the first clinical trial to evaluate the safety, tolerability, and immunogenicity of lower doses of influenza vaccine delivered by MAPs. Methods and findings HD-MAPs were coated with a monovalent, split inactivated influenza virus vaccine containing A/Singapore/GP1908/2015 H1N1 haemagglutinin (HA). Between February 2018 and March 2018, 60 healthy adults (age 18-35 years) in Melbourne, Australia were enrolled into part A of the study and vaccinated with either: HD-MAPs delivering 15 μg of A/Singapore/ GP1908/2015 H1N1 HA antigen (A-Sing) to the volar forearm (FA); uncoated HD-MAPs; intramuscular (IM) injection of commercially available quadrivalent influenza vaccine (QIV) containing A/Singapore/GP1908/2015 H1N1 HA (15 μg/dose); or IM injection of H1N1 HA antigen (15 μg/dose). After 22 days' follow-up and assessment of the safety data, a further 150 healthy adults were enrolled and randomly assigned to 1 of 9 treatment groups.

Lentiviral vectors based on equine infectious anemia virus (EIAV) stably integrate into dividing and nondividing cells such as neurons, conferring long-term expression of their transgene. The integration profile of an EIAV vector was analyzed in dividing HEK293T cells, alongside an HIV-1 vector as a control, and compared to a random dataset generated in silico. A multivariate regression model was generated and the influence of the following parameters on integration site selection determined: (a) within/not within a gene, (b) GC content within 20 kb, (c) within 10 kb of a CpG island, (d) gene density within a 2-Mb window, and (e) chromosome number. The majority of the EIAV integration sites (68%; n = 458) and HIV-1 integration sites (72%; n = 162) were within a gene, and both vectors favored AT-rich regions. Sites within genes were examined using a second model to determine the influence of the gene-specific parameters, gene region, and transcriptional activity. Both EIAV and HIV-1 vectors preferentially integrated within active genes. Unlike the gammaretrovirus MLV, EIAV and HIV-1 vectors do not integrate preferentially into the promoter region or the 5' end of the transcription unit.

The potentiating factor remains unknown: if dietary fat has any effect on NMSC, it is not apparent when basal cell tumours are considered. There was no evidence of a generalized healthy eating effect. A substantial protective effect was found in exploratory analyses for the fat soluble antioxidant vitamin E.

SYNOPSISWe have reported previously that poorly educated elderly people and those of low social class were at much increased risk of scoring below the customary cut-point on the Mini-Mental State Examination, a widely-used, brief cognitive screening test. As part of the same study, subjects who scored 23 or less on the MMSE out of a maximum of 30 points, and a sample of those who scored 24 or 25 points, were assessed by psychiatrists using a structured, diagnostic interview. Assuming that persons who scored 26 points or above were cognitively intact (our data suggest that 2% or less were not), neither educational attainment nor social class had any influence on the likelihood that subjects would be diagnosed as demented. Our data suggest that social and psychological factors contribute substantially to cognitive test scores and serve to emphasize the importance of detailed assessment procedures in epidemiological surveys of dementia.