Effect of 24-h severe energy restriction on appetite regulation and ad libitum energy intake in lean men and women

Background: Intermittent severe energy restriction (SER) can induce substantial weight loss, but the appetite regulatory responses to SER are unknown and may dictate long-term dietary adherence. Objective: We determined the effect of 24-h SER on appetite regulation, metabolism, and energy intake. Design: Eighteen lean men and women completed two 3-d trials in randomized, counterbalanced order. On day 1 subjects consumed standardized diets containing 100% (mean 6 SD: 9.3 6 1.3 MJ; energy balance) or 25% [2.3 6 0.3 MJ; energy restriction (ER)] of energy requirements. On day 2, a standardized breakfast was consumed, with plasma concentrations of acylated ghrelin, glucagon-like peptide 1, insulin, glucose, and nonesterified fatty acids determined for 4 h. Ad libitum energy intake was assessed at lunch and dinner with subjective appetite and resting metabolism assessed throughout. On day 3, ad libitum energy intake was assessed at breakfast and by weighed food records. Results: Energy intake was 7% greater on day 2 (P<0.05) during ER but not significantly different on day 3 (P=0.557). Subjective appetite was greater during ER on the morning of day 2 (P<0.05) but was not significantly different thereafter (P<0.145). During ER, postprandial concentrations of acylated ghrelin were lower (P<0.05), whereas glucose (P<0.05) and nonesterified fatty acids (P<0.0001) were higher. Postprandial glucagon-like peptide 17–36 (P=0.784) and insulin (P=0.06) concentrations were not significantly different between trials. Energy expenditure was lower during ER in the morning (P<0.01). Conclusions: In lean young adults, 24-h SER transiently elevated subjective appetite and marginally increased energy intake, but hormonal appetite markers did not respond in a manner indicative of hyperphagia. These results suggest that intermittent SER might be useful to attenuate energy intake and control body weight in this population. This trial was registered at www.clinicaltrials.gov.uk as NCT02696772

Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease

BACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer’s Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer’s Disease in individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer’s Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada. SETTING: Multi-center genetics study. PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment. MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years

‘I think I'm more free with them'—Conflict, Negotiation and Change in Intergenerational Relations in African Families Living in Britain

While the family is increasingly being recognised as pivotal to migration, there remain too few studies examining how migration impacts on intergenerational relationships. Although traditional intergenerational gaps are intensified by migration, arguably there has been an over-emphasis on the divisions between ‘traditional’ parents and ‘modern’ children at the expense of examining the ways in which both generations adapt. As Foner and Dreby [2011. “Relations Between the Generations in Immigrant Families.” Annual Review of Sociology 37: 545–564] stress, the reality of post-migration intergenerational relations is inevitably more complex, requiring the examination of both conflict and cooperation. This article contributes to this growing literature by discussing British data from comparative projects on intergenerational relations in African families (in Britain, France and South Africa). It argues that particular understandings can be gained from examining the adaptation of parents and parenting strategies post-migration and how the reconfiguration of family relations can contribute to settlement. By focusing on how both parent and child generations engage in conflict and negotiation to redefine their relationships and expectations, it offers insight into how families navigate and integrate the values of two cultures. In doing so, it argues that the reconfiguration of gender roles as a result of migration offers families the space to renegotiate their relationships and make choices about what they transmit to the next generation

Impact of Short-Term Computerized Cognitive Training on Cognition in Older Adults With and Without Genetic Risk of Alzheimer's Disease: Outcomes From the START Randomized Controlled Trial

This paper represents independent research partly funded by the National Institute of Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The paper was also supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South-West Peninsula. The funders did not have any input into the design of the study, interpretation of results, writing of the manuscript, or decision to publish. No funding has been provided by a pharmaceutical company or other agency to write this article. Authors have not been precluded from accessing data, and all authors accept responsibility for publication.Objectives: To establish the impact of a 3-minute computerized cognitive training program (START) on cognition in older adults with and without genetic risk of Alzheimer's disease. Design: Two-arm randomized controlled trial of the START program. Setting and Participants: Remote online trial in adults older than 50 taking part from home. Methods: The trial compared the START program with placebo in 6544 people older than 50. Primary outcome was executive function measured through Trailmaking B, with other secondary cognitive measures. Genetic risk profile and ApoE4 status were determined by Illumina Array. Results: START conferred benefit to executive function, attention, memory, and a composite measure, including in people with the ApoE4 genotype. Conclusions and Implications: The 3-minute START task offers a means of supporting cognitive health in older adults and could be used at scale and within a precision medicine approach to reduce risk of cognitive decline in a targeted way.This work was funded in part through the MRC Proximity to Discovery: Industry Engagement Fund (External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2) ref. MC_PC_17189) awarded to B.C

Doppler coherence imaging and tomography of flows in tokamak plasmas

This article describes the results of spatial heterodyne Doppler "coherence imaging" of carbon ion flows in the divertor region of the DIII-D tokamak. Spatially encoded interferometric projections of doubly ionized carbon emission at 465 nm have been demodulated and tomographically inverted to obtain the spatial distribution of the carbon ion parallel flow and emissivity. The operating principles of the new instruments are described, and the link between measured properties and line integrals of the flow field are established. An iterative simultaneous arithmetic reconstruction procedure is applied to invert the interferometric phase shift projections, and the reconstructed parallel flow field amplitudes are found to be in reasonable agreement with UEDGE modeling

Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness.

In the fourth article of a five-part series providing a global perspective on integrating mental health, Sylvia Kaaya and colleagues discuss the importance of integrating mental health interventions into HIV prevention and treatment platforms. Please see later in the article for the Editors' Summary

Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease

This is the final version. Available on open access from Springer Nature via the DOI in this recordBACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer’s Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer’s Disease in individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aẞ1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer’s Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada SETTING: Multi-center genetics study PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aẞ1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four yearsNational Institutes of Health (NIH)Department of DefenseInnovate U

The relationship between playing musical instruments and cognitive trajectories: Analysis from a UK ageing cohort

Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.Copyright © 2024 The Authors. Background: The accumulation of age-associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. Objectives: Explore the relationship between musicality and cognitive function in a large cohort of older adults. Methods: This was a nested study within the PROTECT-UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT-UK. Results: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. Conclusions: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health.NIHR Exeter BRC; NIHR Maudsley Biomedical Research Centre; National Institute for Health Research Applied Research Collaboration South West Peninsula

The development and use of the Assessment of Dementia Awareness and Person-centred Care Training (ADAPT) tool in long-term care

Policy and practice guidelines recommend person-centred care (PCC) to support people to live well with dementia in long-term care (LTC). Therefore, staff working in LTC settings need to be trained in dementia awareness and PCC. However, the access to, content of and reach of training across LTC settings can be varied. Data on current and ongoing access to PCC training can form and important component of data gathered on usual care (UC) in research studies, in particular clinical trials within LTC. However, no suitable assessment tools are available to measure dementia awareness and PCC training availability, content and reach. This paper describes the development of a training audit tool to meet this need for a UC measure of dementia awareness and PCC training. The ‘Assessment of Dementia Awareness and Person-centred care Training’ (ADAPT) tool was based on a review of published PCC literature and consultation with dementia and aged care experts. The ADAPT tool was piloted in 13 LTC facilities the UK and Australia, before being used to assess the content of dementia and PCC awareness training in 50 UK settings in a randomized controlled trial (RCT) as part of a UC recording. Following pilot testing, modifications to the ADAPT tool’s wording were made to enhance item clarity. When implemented in the RCT, pre-baseline training assessment data showed that the ADAPT tool was able to differentiate between LTC and identify settings where further dementia awareness training was required. ADAPT was then used as a method of recording data on dementia awareness and PCC training as part of UC data collection. The ADAPT tool is suitable for use by researchers to establish the availability, content and reach of dementia and PCC awareness training to staff within research studies

Whole transcriptome in silico screening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side effects

Background: Stroke/thromboembolic events, infections, and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events. Methods: Whole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic analysis was performed that scored the association between antipsychotic signatures and expression data from 415,252 samples in the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) repository. Results: Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (eg, brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor [PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta, selenoamino acid metabolism, and influenza infection). Conclusions: These findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This work was generously supported by the Wellcome Trust Institu tional Strategic Support Award (204909/Z/16/Z) and in part through the MRC Proximity to Discovery: Industry Engagement Fund (External Collaboration, Innovation and Entrepreneurism: Translational Medicine in Exeter 2 (EXCITEME2) ref. MC_PC_16072.published version, accepted version (12 month embargo), submitted versio