Depressed Mood and the Incidence of Alzheimer's Disease in the Elderly Living in the Community

BACKGROUND: It remains unclear whether depression increases the risk for dementia in the elderly. We evaluated the relationship between depressed mood at baseline and the incidence of dementia, particularly Alzheimer's disease, in the elderly living in the community. METHODS: A total of 1070 elderly individuals, aged 60 years or older, were identified as part of a registry for dementia in the Washington Heights community of North Manhattan, NY. In a prospective, longitudinal design with follow-up for 1 to 5 years, annual physician evaluation and neuropsychological testing were used to assess levels of cognitive impairment and to diagnose dementia. Depressive symptoms were evaluated with the 17-item Hamilton Rating Scale for Depression. Based on clinical considerations and a validity study, a positive score for the depressed mood item was used in statistical analyses. To confirm the results, the total Hamilton Rating Scale for Depression score was also evaluated as the "depression" variable. RESULTS: Of the 1070 subjects, 218 met criteria for dementia at baseline evaluation. In the 852 subjects without dementia, depressed mood was more common in individuals with greater cognitive impairment. In a follow-up study of 478 of these subjects without dementia (mean +/- SD, 2.54 +/- 1.12 years of follow-up), the effect of baseline depressed mood on the end- point diagnosis of dementia (93% had possible or probable Alzheimer's disease) was evaluated in a Cox proportional hazards model. Depressed mood at baseline was associated with an increased risk of incident dementia (relative risk, 2.94; 95% confidence interval, 1.76 to 4.91; P .001). This effect remained after adjustment for age, gender, education, language of assessment, Blessed Memory Information and Concentration test scores, and Blessed Functional Activity Scale scores (relative risk, 2.05; 95% confidence interval, 1.16 to 3.62; P .02). Similar results were obtained when the total Hamilton Rating Scale for Depression score was used as the depression variable, with the use of the same covariates (relative risk, 1.07 per point interval; 95% confidence interval, 1.02 to 1.11; P .01). CONCLUSIONS: Depressed mood moderately increased the risk of developing dementia, primarily Alzheimer's disease. Whether depressed mood is a very early manifestation of Alzheimer's disease, or increases susceptibility through another mechanism, remains to be determined

Musculoskeletal mass and shape are correlated with competitive ability in male house mice (Mus musculus)

Intense physical competition between males for mating opportunities is widespread among mammals. In such agonistic encounters, males with combinations of morphological, physiological, and behavioral characters that allow them to dominate an opponent have greater fitness. However, the specific physical traits associated with competitive ability are poorly understood. Larger body size is often correlated with fitness in mammals. Interestingly, fitness is maximized at intermediate body masses in male house mice (Mus musculus), a species with a polygynous mating system in which males compete physically for access to reproductive resources. Here, we used competition trials in semi-natural, mixed-sex population enclosures to directly measure competitive ability in male house mice based on control of a preferred nesting site. We tested the hypothesis that the musculoskeletal systems of male mice demonstrating high competitive ability are more specialized for competition by comparing the masses of 10 major muscle groups and eight bones as well as a set of 12 skeletal shape indices associated with anatomical specialization for fighting performance in a set of nine winners and 20 losers. Winning males possessed several traits hypothesized to enhance performance in male-male contests: relatively greater mass in several muscle groups and bones of the fore- and hindlimb and larger scapular surface area. Unexpectedly, no measurements of the head and neck differed significantly between winners and losers. These results identify musculoskeletal traits associated with competitive ability in male house mice and suggest that our current understanding of mammalian fighting performance is incomplete and more nuanced than previously considered

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.We thank members of the Cambridge BioResource Scientific Advisory Board and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. K.D. is funded as a HSST trainee by NHS Health Education England. M.F. is funded from the BLUEPRINT Grant Code HEALTH-F5-2011-282510 and the BHF Cambridge Centre of Excellence [RE/13/6/30180]. J.R.S. is funded by a MRC CASE Industrial studentship, co-funded by Pfizer. J.D. is a British Heart Foundation Professor, European Research Council Senior Investigator, and National Institute for Health Research (NIHR) Senior Investigator. S.M., S.T, M.H, K.M. and L.D. are supported by the NIHR BioResource-Rare Diseases, which is funded by NIHR. Research in the Ouwehand laboratory is supported by program grants from the NIHR to W.H.O., the European Commission (HEALTH-F2-2012-279233), the British Heart Foundation (BHF) to W.J.A. and D.R. under numbers RP-PG-0310-1002 and RG/09/12/28096 and Bristol Myers-Squibb; the laboratory also receives funding from NHSBT. W.H.O is a NIHR Senior Investigator. The INTERVAL academic coordinating centre receives core support from the UK Medical Research Council (G0800270), the BHF (SP/09/002), the NIHR and Cambridge Biomedical Research Centre, as well as grants from the European Research Council (268834), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), Merck and Pfizer. DJR and DA were supported by the NIHR Programme ‘Erythropoiesis in Health and Disease’ (Ref. NIHR-RP-PG-0310-1004). N.S. is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510). The INTERVAL study is funded by NHSBT and has been supported by the NIHR-BTRU in Donor Health and Genomics at the University of Cambridge in partnership with NHSBT. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health of England or NHSBT. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Transition from school to adult services for young people with severe or profound intellectual disability: A systematic review utilizing framework synthesis

Background The transition to adulthood has been described as a difficult time in the lives of young people with intellectual disability. There has been little emphasis on young people with severe or profound intellectual disability specifically, even though their pathways may differ, due to greater support needs across the life course. Methods A systematic review was conducted utilising Bronfenbrenner's ecological model to inform framework analysis to synthesise qualitative findings. Results Taking an ecological perspective proved valuable. The transition process was described as stressful and barriers were identified across the ecological levels. Parents accounted for the majority of participants in studies, and the needs of young people and their parents emerged as highly interdependent. Conclusion Themes reflect the complex nature of the question what adulthood should look like for individuals with severe or profound intellectual disability. There is a lack of involvement of multiple stakeholders and young people themselves within studies

Thermal and noise level characteristics of hard dental tissue ablation with 350-fs pulse laser

In spite of intensive research, lasers have not replaced conventional tools in many hard tissue applications. Low removal rates, loud operation noise, and mechanical and thermal damage are among the main obstacles to successful application of lasers. Ultrashort pulse lasers offer several advantages in their high per-pulse-efficiency, negligible thermal and mechanical damage and low noise operation. Practical applications of these devices, however, depends critically on sufficiently high volume removal which should match or even exceed the high speed drill. In our study, acoustical output of the USPL is compared to the low and high speed dental drill, Er:YAG, and Ho:YSGG lasers. Noise levels of the USPL are shown to be negligible in comparison with all other tested system. In addition, thermal characteristics of hard dental tissue ablation by ultrashort pulse laser of low and high pulse repetition rates are presented. Encouraging results showing temperatures increases smaller than 10°C even at the highest pulse repetition rates (1 KHz) are presented. A simple model for heat diffusion is discussed