Genome-wide admixture and association study of serum iron, ferritin, transferrin saturation and total iron binding capacity in African Americans

Iron is an essential component of many important proteins and enzymes, including hemoglobin, which is responsible for carrying oxygen to the cells. African Americans (AAs) have a greater prevalence of iron deficiency compared with European Americans. We conducted genome-wide admixture-mapping and association studies for serum iron, serum ferritin, transferrin saturation (SAT) and total iron binding capacity (TIBC) in 2347 AAs participating in the Jackson Heart Study (JHS). Follow-up replication analyses for JHS iron-trait associated SNPs were conducted in 329 AA participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study (HANDLS). Higher estimated proportions of global African ancestry were significantly associated with lower levels of iron (P = 2.4 × 10−5), SAT (P = 0.0019) and TIBC (P = 0.042). We observed significant associations (P < 5 × 10−8) between serum TIBC levels and two independent SNPs around TF on chromosome 3, the first report of a genome-wide significant second independent signal in this region, and SNPs near two novel genes: HDGFL1 on chromosome 6 and MAF on chromosome 16. We also observed significant associations between ferritin levels and SNPs near GAB3 on chromosome X. We replicated our two independent associations at TF and our association at GAB3 in HANDLS. Our study provides evidence for both shared and unique genetic risk factors that are associated with iron-related measures in AAs. The top two variants in TF explain 11.2% of the total variation in TIBC levels in AAs after accounting for age, gender, body mass index and background ancestry

The low frequency radio emission and spectrum of the extended SNR W44: new VLA observations at 74 and 324 MHz

We present new Very Large Array (VLA) radio images at 74 and 324 MHz of the SNR W44. The VLA images, obtained with unprecedented angular resolution and sensitivity for such low frequencies have been used in combination with existing 1442 MHz radio data, Spitzer IR data, and ROSAT and Chandra X-ray data to investigate morphological and spectral properties of this SNR. The spatially resolved spectral index study revealed that the bright filaments, both around and across the SNR, have a straight spectrum between 74 and 1442 MHz, with alpha ~ -0.5, with two clear exceptions: a short portion of the SNR limb to the southeast, with alpha varying between 0 and +0.4 and a bright arc to the west where the spectrum breaks around 300 MHz and looks concave down. We conclude that at the shell and along the internal filaments, the electrons responsible for the synchrotron emission were accelerated at the shock according to a simple diffusive shock model; the positive spectrum corresponds to a location where the SN shock is running into a molecular cloud and where the line of sight intersects the photo dissociation region of an HII region and a young stellar object is present. The curved spectrum on the westernmost bright arc is explained as the consequence of strong post-shock densities and enhanced magnetic fields after the interaction of the SN shock with a collindant molecular cloud.Comment: After language edited, 16 pages, 12 figures (3 in color). Figures degraded to reduce file size. Accepted 01/03/2007 for publicaion in A&

Global Position Statement: Religion and Spirituality in Mental Health Care

Careif is an international mental health charity that works towards protecting and promoting mental health and resilience, to eliminate inequalities and strengthen social justice. Our principles include working creatively with humility and dignity, and with balanced partnerships in order to ensure all cultures and societies play their part in our mission of protecting and promoting mental health and wellbeing. We do this by respecting the traditions of all world societies, whilst believing traditions can evolve, for even greater benefit to individuals and society. Careif believes that knowledge should not only be available to those with wealth or those who live in urban and industrialised parts of the world. It considers knowledge sharing to be a basic human right, particularly where this knowledge can change lives and help realise true human potential. Furthermore, there is substantial knowledge to be found in low and middle income countries and within rural and poorer areas of the world and this knowledge is just as valuable to the wellbeing of people in areas which are wealthier. This Position Statement aims to highlight the current position and need for understanding the role of culture, spirituality and religion in the diagnosis and treatment of mental illness. Globalisation has created culturally rich and diverse societies. During the past several decades, there has been a steadily increasing recognition of the importance of cultural influences on life and health. Societies are becoming multi-ethnic and poly-cultural in nature worldwide, where different groups enrich each other's lives with their unique culture/s. Cultural transition and acculturation is often discussed as relevant to migrants and the need to integrate, when in fact it is of relevance to all cultures in an ever-interconnected world. It is indeed necessary to be equipped with knowledge about cultures and their influence on mental health and illness. Until the early 19th century, psychiatry and religion were closely connected. Religious institutions were responsible for the care of the mentally ill. A major change occurred when Charcot and his pupil Freud associated religion with hysteria and neurosis. This created a divide between religion and mental health care, which has continued until recently. Psychiatry has a long tradition of dismissing and attacking religious experience. Religion has often been seen by mental health professionals in Western societies as irrational, outdated, and dependency forming and has sometimes been viewed as resulting in emotional instability

Global Position Statement: Stigma, Mental Illness and Diversity

Careif is an international mental health charity that works towards protecting and promoting mental health, wellbeing, resilience and resourcefulness with a special focus towards eliminating inequalities and strengthening social justice. Our principles include working creatively with humility, dignity and balanced partnerships in order to ensure that all cultures and societies play their part in our mission of protecting and promoting mental health and wellbeing. We do this by respecting the traditions of all world societies, whilst believing that culture and traditions can evolve for even greater benefit to individuals and society. Globalisation has created culturally rich and diverse societies. During the past several decades, there has been a steadily increasing recognition of the importance of societal and cultural influences on life and health. Societies are becoming multi-ethnic and poly-cultural in nature worldwide, where different groups enrich each other's lives with their unique culture/s. Cultural transition and acculturation is often discussed as relevant to migrants and mentions the need to integrate, when in fact it is of relevance to all cultures in an ever interconnecting world. It is indeed necessary to be equipped with knowledge about cultures and their influence on mental health and illness. Culturally informed mental health care is rapidly moving from an attitudinal orientation to an evidence-based approach, therefore understanding culture and mental health care becomes greater than a health care issue

Cyclophilin C-associated protein (CyCAP) knock-out mice spontaneously develop colonic mucosal hyperplasia and exaggerated tumorigenesis after treatment with carcinogen azoxymethane1

<p>Abstract</p> <p>Background</p> <p>The discovery of a "serrated neoplasia pathway" has highlighted the role of hyperplastic lesions of the colon as the significant precursor of colorectal adenocarcinoma. In mice, hyperplasia of the colonic mucosa is a regular phenomenon after a challenge with colonic carcinogens indicating that mucosal hyperproliferation and thickening, even without cytological dysplasia, represents an early pre-malignant change. Cyclophilin C-associated protein (CyCAP) has been described to down-modulate endotoxin signaling in colorectal murine mucosa and is a murine orthologue of the tumor-associated antigen 90 K (TAA90K)/mac-2-binding protein.</p> <p>Methods</p> <p>Female Balb/c wild-type (WT) and CyCAP knock-out (KO) mice (6–8 weeks old) were administered 2 or 6 weekly subcutaneous injections of azoxymethane. The animals were evaluated post-injection at six weeks for aberrant crypt foci (ACF) study and at five months for colon tumor measurement. The thickness of the colon crypts was measured in microns and the number of colonocytes per crypt was also determined in well-oriented crypts. Morphometric analyses of the colon mucosa were also performed in untreated 6–8 weeks old KO and WT animals. Formalin-fixed/paraffin-embedded colon sections were also studied by immunohistochemistry to determine the Ki-67 proliferation fraction of the colon mucosa, β-catenin cellular localization, cyclin D1, c-myc, and lysozyme in Paneth cells.</p> <p>Results</p> <p>Cyclophilin C-associated protein (CyCAP)^-/-mice, spontaneously developed colonic mucosal hyperplasia early in life compared to wild-type mice (WT) (p < 0.0001, T-test) and crypts of colonic mucosa of the (CyCAP)^-/-mice show higher proliferation rate (p = 0.039, Mann-Whitney Test) and larger number of cyclin D1-positive cells (p < 0.0001, Mann-Whitney Test). Proliferation fraction and cyclin D1 expression showed positive linear association (p = 0.019, Linear-by-Linear Association). The hyperplasia was even more pronounced in CyCAP^-/-mice than in WT after challenge with azoxymethane (p = 0.005, T-test). The length of the crypts (r = 0.723, p = 0.018, Spearman Correlation) and the number of colonocytes per crypt (r = 0.863, p = 0.001, Spearman Correlation) in non-tumorous areas were positively associated with azoxymethane-induced number of tumors. CyCAP^-/-developed larger numbers of tumors than WT animals (p = 0.003, T-Test) as well as overall larger tumor mass (p = 0.016, T-Test). Membranous β-catenin was focally overexpressed in KO mice including proliferative zone of the crypts.</p> <p>Conclusion</p> <p>CyCAP^-/-represent the first described model of spontaneous colonic mucosal hyperplasia. We conclude that CyCAP-deficient mice spontaneously and after challenge with carcinogen develop significantly more colorectal mucosal hyperplasia, an early stage in murine colonic carcinogenesis.</p

Study protocol for the recreational stimulation for elders as a vehicle to resolve delirium superimposed on dementia (Reserve For DSD) trial

<p>Abstract</p> <p>Background</p> <p>Delirium is a state of confusion characterized by an acute and fluctuating decline in cognitive functioning. Delirium is common and deadly in older adults with dementia, and is often referred to as delirium superimposed on dementia, or DSD. Interventions that treat DSD are not well-developed because the mechanisms involved in its etiology are not completely understood. We have developed a theory-based intervention for DSD that is derived from the literature on cognitive reserve and based on our prior interdisciplinary work on delirium, recreational activities, and cognitive stimulation in people with dementia. Our preliminary work indicate that use of simple, cognitively stimulating activities may help resolve delirium by helping to focus inattention, the primary neuropsychological deficit in delirium. Our primary aim in this trial is to test the efficacy of Recreational Stimulation for Elders as a Vehicle to resolve DSD (RESERVE- DSD).</p> <p>Methods/Design</p> <p>This randomized repeated measures clinical trial will involve participants being recruited and enrolled at the time of admission to post acute care. We will randomize 256 subjects to intervention (RESERVE-DSD) or control (usual care). Intervention subjects will receive 30-minute sessions of tailored cognitively stimulating recreational activities for up to 30 days. We hypothesize that subjects who receive RESERVE-DSD will have: decreased severity and duration of delirium; greater gains in attention, orientation, memory, abstract thinking, and executive functioning; and greater gains in physical function compared to subjects with DSD who receive usual care. We will also evaluate potential moderators of intervention efficacy (lifetime of complex mental activities and APOE status). Our secondary aim is to describe the costs associated with RESERVE-DSD.</p> <p>Discussion</p> <p>Our theory-based intervention, which uses simple, inexpensive recreational activities for delivering cognitive stimulation, is innovative because, to our knowledge it has not been tested as a treatment for DSD. This novel intervention for DSD builds on our prior delirium, recreational activity and cognitive stimulation research, and draws support from cognitive reserve theory.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267682">NCT01267682</a></p