Body, brain, life for cognitive decline (BBL-CD): Protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment

This is the final version. Available from Dove Medical Press via the DOI in this record. Background: With no cure for dementia and the number of people living with the condition predicted to rapidly rise, there is an urgent need for dementia risk reduction and prevention interventions. Modifiable lifestyle risk factors have been identified as playing a major role in the development of dementia; hence, interventions addressing these risk factors represent a significant opportunity to reduce the number of people developing dementia. Relatively few interventions have been trialed in older participants with cognitive decline (secondary prevention). Objectives: This study evaluates the efficacy and feasibility of a multidomain lifestyle risk reduction intervention for people with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: This study is an 8-week, two-arm, single-blind, randomized controlled trial (RCT) of a lifestyle modification program to reduce dementia risk. The active control group receives the following four online educational modules: dementia literacy and lifestyle risk, Mediterranean diet (MeDi), cognitive engagement and physical activity. The intervention group also completes the same educational modules but receives additional practical components including sessions with a dietitian, online brain training and sessions with an exercise physiologist to assist with lifestyle modification. Results: Primary outcome measures are cognition (The Alzheimer’s Disease Assessment Scale-Cognitive-Plus [ADAS-Cog-Plus]) and a composite lifestyle risk factor score for Alzheimer’s disease (Australian National University – Alzheimer’s Disease Risk Index [ANU-ADRI]). Secondary outcome measures are motivation to change lifestyle (Motivation to Change Lifestyle and Health Behaviour for Dementia Risk Reduction [MCLHB-DRR]) and health-related quality of life (36-item Short Form Health Survey [SF-36]). Feasibility will be determined through adherence to diet (Mediterranean Diet Adherence Screener [MEDAS] and Australian Recommended Food Score [ARFS]), cognitive engagement (BrainHQ-derived statistics) and physical activity interventions (physical activity calendars). Outcomes are measured at baseline, immediately post-intervention and at 3-and 6-month follow-up by researchers blind to group allocation. Discussion: If successful and feasible, secondary prevention lifestyle interventions could provide a targeted, cost-effective way to reduce the number of people with cognitive decline going on to develop Alzheimer’s disease (AD) and other dementias.Dementia Australia Research FoundationAustralian National UniversityDementia Collaborative Research CentreNHMRC Centre for Research Excellence in Cognitive Health, the Australian National UniversityNeuroscience Research Australia, University of New South WalesRoyal Commonwealth Societ

Genetic diversity and population structure among six cattle breeds in South Africa using a whole genome SNP panel

Information about genetic diversity and population structure among cattle breeds is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of cattle breeds. This study investigated genetic diversity and the population structure among six cattle breeds in South African (SA) including Afrikaner (n=44), Nguni (n=54), Drakensberger (n=47), Bonsmara (n=44), Angus (n=31) and Holstein (n=29). Genetic diversity within cattle breeds was analyzed using three measures of genetic diversity namely allelic richness (AR), expected heterozygosity (He) and inbreeding coefficient (f). Genetic distances between breed pairs were evaluated using Nei’s genetic distance. Population structure was assessed using model-based clustering (ADMIXTURE). Results of this study revealed that the allelic richness ranged from 1.88 (Afrikaner) to 1.73 (Nguni). Afrikaner cattle had the lowest level of genetic diversity (He=0.24) and the Drakensberger cattle (He=0.30) had the highest level of genetic variation among indigenous and locally-developed cattle breeds. The level of inbreeding was lower across the studied cattle breeds. As expected the average genetic distance was the greatest between indigenous cattle breeds and Bos taurus cattle breeds but the lowest among indigenous and locally-developed breeds. Model-based clustering revealed some level of admixture among indigenous and locally-developed breeds and supported the clustering of the breeds according to their history of origin. The results of this study provided useful insight regarding genetic structure of South African cattle breeds

Examining variation across treatment clinics in cancer patients' psychological outcomes: results of a cross sectional survey

Published online: 4 April 2018Purpose: The majority of research on psychological outcomes for cancer patients has focussed on the role of individual characteristics, and disease and treatment factors. There has been very little exploration of the potential contribution of the treatment clinic to these outcomes. This study explored whether there is variation among clinics in cancer patients’ psychological outcomes. Methods: Cancer outpatients were recruited from 22 medical oncology and haematology clinics in Australia. Participants completed a pen and paper survey including the Hospital Anxiety and Depression Scale (HADS), as well as sociodemographic, disease and treatment characteristics. Results: Of those eligible to participate, 4233 (82%) consented and 2811 (81% of consenters) returned the completed survey. There was no statistically significant variation in HADS depression scores across clinics. Some difference in anxiety scores derived from the HADS questionnaire between clinics (p = 0.03) was found with the percentage of between-clinic variation estimated to be 1.11%. However, once all demographic, disease and treatment predictors were adjusted for there was no statistical differences between clinics (percent of between-clinic variation = 0.53%; p = 0.1415). Conclusions: Psychological outcomes were not found to vary between clinics. Other sources of variation including patient characteristics may over-ride between-clinic variability, if it exists.Mariko Carey, Robert Sanson-Fisher, Tara Clinton-McHarg, Allison Boyes, Ian Olver, Christopher Oldmeadow, Christine Paul, Catherine D'Este, Frans Hensken

About females and males: continuity and discontinuity in flies

Through the decades of relentless and dedicated studies in Drosophila melanogaster, the pathway that governs sexual development has been elucidated in great detail and has become a paradigm in understanding fundamental cell-fate decisions. However, recent phylogenetic studies show that the molecular strategy used in Drosophila deviates in some important aspects from those found in other dipteran flies and suggest that the Drosophila pathway is likely to be a derivative of a simpler and more common principle. In this essay, I will discuss the evolutionary plasticity of the sex-determining pathway based on studies in the common housefly, Musca domestica. Diversification appears to primarily arise from subtle differences in the regulation of the key switch gene transformer at the top of the pathway. On the basis of these findings I propose a new idea on how the Drosophila pathway may have evolved from a more archetypal system such as in M. domestica. In essence, the arrival of an X counting mechanism mediated by Sex-lethal to compensate for X linked gene dose differences set the stage for an intimate coupling of the two pathways. Its precedent recruitment to the dosage compensation pathway allowed for an intervention in the regulation of transformer where it gradually and eventually' completely substituted for a need of transformer autoregulation

Efficacy, Stability, and Biosafety of Sifuvirtide Gel as a Microbicide Candidate against HIV-1

Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission

Africa in the click stream: audience metrics and foreign correspondents in africa

Digital technologies have transformed the relationship between news outlets, journalists and their audiences. Notably, editors can now monitor their websites and discern the exact news preferences of their readers. Research suggests that some editors are using this data to help them produce more popular, ‘click friendly’ content. To date, research on this phenomenon has focused on journalists working within newsrooms. This article adds to the literature by exploring the relationship of foreign correspondents in Africa with their audiences, and asks whether readership metrics are influencing the journalists’ selection and development of news stories. Drawing on 67 interviews with foreign correspondents in East and West Africa, the article identifies three different approaches to audience metrics: correspondents who are 1) data-driven; 2) data informed; and 3) data denialists. The article discusses the implications of these approaches for the media image of Africa that is distributed around the globe

Teaching computer-assisted qualitative data analysis to a large cohort of undergraduate students

Qualitative research is increasingly being conducted with the support of computer-assisted qualitative data analysis software (CAQDAS), yet limited research has been conducted on integrating the teaching of CAQDAS packages within qualitative methods university courses. Existing research typically focuses on teaching NVivo to small groups of postgraduate (primarily doctoral) students and mostly take the form of reflections of the trainers. In 2011, we implemented the teaching and use of a CAQDAS package, NVivo, within a large third-year undergraduate psychology research methods unit. Sixty-seven students participated in an online survey evaluating the use of NVivo in the unit. In this paper, we present quantitative and qualitative findings related to students' perceptions of the resources provided, their confidence in using NVivo, their satisfaction with the teaching and their intentions to use CAQDAS in the future. Student evaluations were generally positive, but highlighted the need for both increased class time and greater access to the CAQDAS program outside of class time to enhance opportunities for learning

The SR-BI Partner PDZK1 Facilitates Hepatitis C Virus Entry

Entry of hepatitis C virus (HCV) into hepatocytes is a multi-step process that involves a number of different host cell factors. Following initial engagement with glycosaminoglycans and the low-density lipoprotein receptor, it is thought that HCV entry proceeds via interactions with the tetraspanin CD81, scavenger receptor class B type I (SR-BI), and the tight-junction proteins claudin-1 (CLDN1) and occludin (OCLN), culminating in clathrin-dependent endocytosis of HCV particles and their pH-dependent fusion with endosomal membranes. Physiologically, SR-BI is the major receptor for high-density lipoproteins (HDL) in the liver, where its expression is primarily controlled at the post-transcriptional level by its interaction with the scaffold protein PDZK1. However, the importance of interaction with PDZK1 to the involvement of SR-BI in HCV entry is unclear. Here we demonstrate that stable shRNA-knockdown of PDZK1 expression in human hepatoma cells significantly reduces their susceptibility to HCV infection, and that this effect can be reversed by overexpression of full length PDZK1 but not the first PDZ domain of PDZK1 alone. Furthermore, we found that overexpression of a green fluorescent protein chimera of the cytoplasmic carboxy-terminus of SR-BI (amino acids 479–509) in Huh-7 cells resulted in its interaction with PDZK1 and a reduced susceptibility to HCV infection. In contrast a similar chimera lacking the final amino acid of SR-BI (amino acids 479–508) failed to interact with PDZK1 and did not inhibit HCV infection. Taken together these results indicate an indirect involvement of PDZK1 in HCV entry via its ability to interact with SR-BI and enhance its activity as an HCV entry factor

CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development