Apolipoprotein E (APOE) modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In the present study, we analyzed multi-omic association patterns across APOE genotypes, sex, and biological age (BA) axes in 2,229 community dwelling individuals. Our analysis, supported by validation in an independent cohort, identified diacylglycerols as the top APOE-associated plasma metabolites. However, despite the known opposing aging effects of the allele variants, both ε2- and ε4-carriers showed higher diacylglycerols compared to ε3-homozygotes. 'Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites. These results demonstrate the context-dependence of the influence of APOE, with ε2 potentially strengthening insulin resistance-like pathways in the decades prior to imparting its longevity benefits. Additionally, they provide an atlas of APOE-related 'omic associations and support the involvement of bioenergetic pathways in mediating the impact of APOE on aging.

Modern health care faces several serious challenges, including an ageing population and its inherent burden of chronic diseases, rising costs and marginal quality metrics. By assessing and optimizing the health trajectory of each individual using a data-driven personalized approach that reflects their genetics, behaviour and environment, we can start to address these challenges. This assessment includes longitudinal phenome measures, such as the blood proteome and metabolome, gut microbiome composition and function, and lifestyle and behaviour through wearables and questionnaires. Here, we review ongoing large-scale genomics and longitudinal phenomics efforts and the powerful insights they provide into wellness. We describe our vision for the transformation of the current health care from disease-oriented to data-driven, wellness-oriented and personalized population health.

The media has been used to disseminate public information amid the Covid-19 pandemic. However, the Covid-19 news has triggered emotional responses in people that have impacted their mental well-being and led to news avoidance. To understand the emotional response to the Covid-19 news, we study user comments on the news published on Twitter by 37 media outlets in 11 countries from January 2020 to December 2022. We employ a deep-learning-based model to identify one of the 6 Ekman's basic emotions, or the absence of emotional expression, in comments to the Covid-19 news, and an implementation of Latent Dirichlet Allocation (LDA) to identify 12 different topics in the news messages. Our analysis finds that while nearly half of the user comments show no significant emotions, negative emotions are more common. Anger is the most common emotion, particularly in the media and comments about political responses and governmental actions in the United States. Joy, on the other hand, is mainly linked to media outlets from the Philippines and news on vaccination. Over time, anger is consistently the most prevalent emotion, with fear being most prevalent at the start of the pandemic but decreasing and occasionally spiking with news of Covid-19 variants, cases, and deaths. Emotions also vary across media outlets, with Fox News having the highest level of disgust, the second-highest level of anger, and the lowest level of fear. Sadness is highest at Citizen TV, SABC, and Nation Africa, all three African media outlets. Also, fear is most evident in the comments to the news from The Times of India.

Abstract P4 medicine will employ longitudinal, high-dimensional analyses of individuals, integrating molecular, digital, electronic health record, and self-monitoring data. This will classify patients, diseases, and drugs, and continually convert data into knowledge through iterative hypothesis testing to inform systems approaches to both wellness and disease. Two preliminary trials have been carried out to validate this approach, one involving 100 individuals over nine months in 2014 and a second recruiting 5,000 individuals over four years from 2015 until 2019. These trials (i) validated scientific (quantitative) wellness, using personal, high-dimensional data to improve one’s wellness, and (ii) demonstrated the power of longitudinal data clouds to bring fundamental new insights into wellness and disease. These led to a vision of 21st century n = 1 medicine which optimizes the health trajectories of each individual. Each health trajectory has three states: (1) a wellness state that will be extended and optimized through scientific wellness and healthy ageing; (2) a wellness-to-disease transition state where early biomarkers will be identified and used to design therapies employing the identification of the earliest disease-perturbed networks to reverse disease before it manifests as a clinical entity; and (3) a progressive disease state for which physicians and scientists will use data-driven systems approaches to find therapies that ameliorate or reverse disease. This chapter discusses the promotion of a million person genome/phenome project with a major healthcare system to initiate the implementation of 21st century medicine in the US healthcare system. The challenges and opportunities associated with the realization of 21st century medicine are also discussed.

Media has played an important role in public information on COVID-19. But distressing news, e.g., COVID-19 death tolls, may trigger negative emotions in public, discouraging them from following the news, which, in turn, can limit the effectiveness of the media. To understand people’s emotional response to the COVID-19 news, we have investigated the prevalence of basic human emotions in around 19 million user responses to 1.7 million COVID-19 news posts on Twitter from (English-speaking) media across 12 countries from January 2020 to April 2021. We have used Latent Dirichlet Allocation (LDA) to identify news themes on Twitter. Also, the Robustly Optimized BERT Pretraining Approach (RoBERTa) model was used to identify emotions in the tweets. Our analysis of the Twitter data revealed that anger was the most prevalent emotion in user responses to the news coverage of COVID-19. That was followed by sadness, optimism, and joy, steadily over the period of the study. The prevalence of anger (in user responses) was higher for the news about authorities and politics while optimism and joy were more prevalent for the news about vaccination and educational impacts of COVID-19 respectively. The prevalence of sadness in user responses, however, was the highest for the news about COVID-19 cases and deaths and the impacts on the families, mental health, jails, and nursing homes. We also observed a higher level of anger in the user responses to the (COVID-19) news posted by the USA media accounts (e.g., CNN Politics, Fox News, MSNBC). Optimism, on the other hand, was found to be the highest for Filipino media accounts.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

We have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8–94.7%) and specificity of 92.4% (95% CI 83.2–97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance.

Background: Patient and public involvement (PPI) plays a crucial role in ensuring research is carried out in conjunction with the people that it will impact upon. In this article, we present our experiences and reflections from working collaboratively with patients and public through the lifetime of an National Institute for Health Research (NIHR) programme grant; the Chronic Headache Education and Self-management Study (CHESS) which took place between 2015 and 2020. PPI over the course of CHESS: We worked closely with three leading UK migraine charities and a lay advisory group throughout the programme. We followed NIHR standards and used the Guidance for Reporting Involvement of Patients and the Public checklist. We consulted our PPI contacts using a variety of methods depending on the phase of the study and the nature of the request. This included emails, discussions, and face-to-face contact. PPI members contributed throughout the study in the programme development, in the grant application, ethics documentation, and trial oversight. During the feasibility study; in supporting the development of a classification interview for chronic headache by participating in a headache classification conference, assessing the relevance, and acceptability of patient-reported outcome measures by helping to analyse cognitive interview data, and testing the smartphone application making suggestions on how best to present the summary of data collected for participants. Due to PPI contribution, the content and duration of the study intervention were adapted and a Delphi study with consensus meeting developed a core outcome set for migraine studies. Conclusions: The involvement of the public and patients in CHESS has allowed us to shape its overall design, intervention development, and establish a core outcome set for future migraine studies. We have reflected on many learning points for the future application of PPI.

The COVID-19 pandemic and the consequent restrictions imposed by governments worldwide have had profound social and psychological effects, particularly for young adults. This study used longitudinal data to characterise effects on mental health and behaviour in a UK student sample, measuring sleep quality and diurnal preference, depression and anxiety symptoms, wellbeing and loneliness, and alcohol use. Self-report data was collected from 254 undergraduates (219 females) at a UK university at two-time points: autumn 2019 (baseline, pre-pandemic) and April/May 2020 (under ?lockdown? conditions). Longitudinal analyses showed a significant rise in depression symptoms and a reduction in wellbeing at lockdown. Over a third of the sample could be classed as clinically depressed at lockdown compared to 15% at baseline. Sleep quality was not affected across the sample as a whole. The increase in depression symptoms was highly correlated with worsened sleep quality. A reduction in alcohol use, and a significant shift towards an ?evening? diurnal preference, were also observed. Levels of worry surrounding contracting COVID-19 were high. Results highlight the urgent need for strategies to support young people?s mental health: alleviating worries around contracting COVID, and supporting good sleep quality, could benefit young adults? mental health as the COVID-19 crisis unfolds.

Background Visual impairment is a common comorbidity in people living with dementia. Addressing sources of visual difficulties can have a significant impact on the quality of life for people living with dementia and their caregivers. Depth perception problems are purportedly common in dementia and also contribute to falls, visuomotor task difficulties, and poorer psychosocial well-being. However, depth perception and binocular vision are rarely assessed in dementia research. Sleep fragmentation is also common for people living with dementia, and binocular cooperation for depth perception can be affected by fatigue. Pupillary responses under cognitive load also have the potential to be a risk marker for cognitive decline in people living with dementia and can be combined with the above measures for a comprehensive evaluation of clinical visual changes in people living with dementia and their relation to changes in cognitive status, sleep quality, and cortical structure or function. Objective This study aims to characterize the nature of clinical visual changes and altered task-evoked pupillary responses that may occur in people living with dementia and evaluate whether these responses relate to changes in cognitive status (standardized Mini Mental State Examination [MMSE] score), Pittsburgh sleep quality index, and cortical structure or function. Methods This proposed exploratory observational study will enroll ≤210 people with recently diagnosed dementia (within the last 24 months). The following parameters will be assessed on 3 occasions, 4 months apart (plus or minus 2 weeks): visual function (visual acuity and contrast sensitivity), binocular function (motor fusion and stereopsis), task-evoked pupillary responses (minimum and maximum pupil size, time to maximum dilation, and dilation velocity), cognitive status (MMSE score), and sleep quality (Pittsburgh Sleep Quality Index). A subset of patients (n=30) with Alzheimer disease will undergo structural and functional magnetic resonance imaging at first and third visits, completing a 10-day consensus sleep diary to monitor sleep quality, verified by sleep actimetry. Results This research was funded in February 2018 and received National Health Service Research Ethics Committee approval in September 2018. The data collection period was from October 1, 2018, to November 30, 2019. A total of 24 participants were recruited for the study. The data analysis is complete, with results expected to be published before the end of 2020. Conclusions Findings will demonstrate how often people with dementia experience binocular vision problems. If frequent, diagnosing and treating them could improve quality of life by reducing the risk of falls and fine visuomotor task impairment and by relieving psychosocial anxiety. This research will also demonstrate whether changes in depth perception, pupillary responses, and quality of vision relate to changes in memory or sleep quality and brain structure or function. If related, these quick and noninvasive eye tests help monitor dementia. This would help justify whether binocular vision and pupillary response testing should be included in dementia-friendly eye-testing guidelines. International Registered Report Identifier (IRRID) RR1-10.2196/16089

PurposeThis paper explores residents' perceptions and experiences of extra care housing as an integrated model of housing with care.Design/methodology/approachData were collected in a longitudinal qualitative study based on four extra care housing schemes. Data from interviews with residents, care workers, managers and local commissioners were analysed thematically.FindingsThe integration of housing with care enabled many older people to manage their care proactively. However, the increasing number of residents with complex health and care needs, including chronic illness, led some residents to question the ability of the model to support residents to live independently.Research limitations/implicationsThe study struggled to recruit sufficient residents from the specialist dementia setting who were able to communicate their consent to take part in the research. In addition, the quality of qualitative data collected in interviews with participants at this setting reduced over successive rounds of interviews.Practical implicationsThe study suggests the need to ensure that residents are fully informed about levels of care and support is available when considering a move into extra care housing.Originality/valueThis paper provides a timely opportunity to consider extra care housing as an example of an integrated housing service, particularly in light of the current challenges facing the sector.

Existing models of Borderline Personality Disorder (BPD) suggest that a combination of genetic vulnerability, childhood trauma, and disrupted attachment can lead to the marked emotional lability, impulsivity and interpersonal difficulties observed clinically. Brain structural differences in frontal, limbic and hippocampal regions have been reported in BPD. Less clear is how specific psychological factors relate to these structural differences, and how consistently this is found across studies. This was the focus of the present review. Eighteen studies published between 2004 and 2018 met inclusion criteria encompassing 990 participants. Study quality was assessed using the Nottingham-Ottawa Scale. We also introduce a newly devised scale to assess MRI reporting quality. The most frequently investigated psychological variable were impulsivity (9 studies), depression (8), trauma (6), aggression (6), severity of symptoms (3), global functioning, abuse and dissociation (2). Study quality varied, however, a trend was observed where newer studies were higher in reporting quality. Impulsivity demonstrated greater association with frontal structures, trauma related to the hypothalamus and limbic systems, and aggression with hippocampal and frontal structures. The present review recommends greater exploration of neurocognitive and psychosis-related features such as delusions, paranoia and voice-hearing in future studies, and to investigate cortical changes in longitudinal designs.

BACKGROUND:Numerous reports have described increased rates of exposure to Toxoplasma gondii levels in individuals with a history of suicide attempts in comparison with well controls, or psychiatrically ill individuals, with no suicide attempt history. Such findings suggest that the behavioral effects this parasite exerts on rodent hosts extends to humans though few studies have searched for underlying mechanisms.METHODS:The present study compared 96 patients with an active depressive disorder and a history of at least two suicide attempts to 126 depressed patients with no history of suicide attempts by IgG and IgM levels of Toxoplasma gondii and cytomegalovirus (CMV). The groups were also compared by IL_1b, TNF-alpha, CRP, IL_6, and IL_1ra titers.RESULTS:Toxoplasma gondii IgM levels were higher, and seropositivity more likely, in the suicide attempt group. CMV IgG levels were also higher among suicide attempters. Several of these immunoglobulin measures were more robustly associated with the number of suicide attempts than with the dichotomy of suicide attempter and non-attempter. These two antibody levels were also additive in their association with suicide attempter status. IL_1a levels were lower in suicide attempters and correlated negatively with levels of antibodies to Toxoplasma gondii and CMV.LIMITATIONS:These include a sample size insufficient to explore differences across mood disorder diagnoses or demographic groupings.CONCLUSIONS:These results indicate that exposure to common infectious agents such as Toxoplasma gondii and CMV are associated with increased risk of suicide attempts but the mechanism of association does not appear to involve the activation of cytokines. Elucidation of the mechanisms which define the relationship between infections and suicide attempts may lead to new methods for the prediction and prevention of suicide attempts.

Context Metabolic syndrome (MetS) is a complex condition comprising a ‘clustering’ of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation. Objective We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil. Methods Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted. Results Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants. Conclusions The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies.

PurposeThe purpose this paper is to explore walking with purpose in extra care, retirement and domestic housing settings to better understand and support people living with dementia in these settings, develop recommendations and inform practice.Design/methodology/approachA mixed-methods study was used: scoping literature review; online survey of extra care and retirement housing managers in the UK; case studies involving interviews with staff and family carers (n= 14) of ten individuals who engaged in walking with purpose in the different housing settings.FindingsAlthough residents who walk with purpose constitute a minority (0–2 residents), managing walking with purpose can be challenging and time consuming. Distraction or redirection was the most common response. Other strategies included identifying the resident’s motivations and accommodating their wishes or walking with them. Culture of care, staff training and dementia-friendly design are keys to effective support for safe walking with purpose. Responses to walking with purpose in the domestic housing settings have raised serious deprivation of liberty issues.Research limitations/implicationsThis study had a number of limitations. The completed survey questionnaires represent a self-selected sample of extra care and retirement housing settings, and responses are based on the perceptions of the staff members completing the survey. There were a relatively small number of case study sites (three extra care housing and three retirement housing), and it was not possible to interview family members for all of the residents who walked with purpose.Originality/valueThis study provides unique data on walking with purpose in extra care and retirement housing setting in the UK.

Adverse reactions to foods and adverse drug reactions are inherent in product defects, medication errors, and differences in individual drug exposure. Pharmacogenetics is the study of genetic causes of individual variations in drug response and pharmacogenomics more broadly involves genome-wide analysis of the genetic determinants of drug efficacy and toxicity. The similarity of nutritional genomics and pharmacogenomics stems from the innate goal to identify genetic variants associated with metabolism and disease. Thus, nutrigenomics can be thought of as encompassing gene-diet interactions involving diverse compounds that are present in even the simplest foods. The advances in the knowledge base of the complex interactions among genotype, diet, lifestyle, and environment is the cornerstone that continues to elicit changes in current medical practice to ultimately yield personalized nutrition recommendations for health and risk assessment. This information could be used to understand how foods and dietary supplements uniquely affect the health of individuals and, hence, wellness. The individual's gut microbiota is not only paramount but pivotal in embracing the multiple-functional relationships with complex metabolic mechanisms involved in maintaining cellular homeostasis. The genetic revolution has ushered in an exciting era, one in which many new opportunities are expected for nutrition professionals with expertise in nutritional genomics. The American College of Nutrition's conference focused on "Personalized Nutrition: Translating the Science of NutriGenomics Into Practice" was designed to help to provide the education needed for the professional engagement of providers in the personalized medicine era.

The majority of people with dementia live in their own homes, often supported by a family member. While this is the preferred option for most, they often face multiple challenges due to a deterioration in their physical and cognitive abilities. This paper reports on a pilot study that aimed to explore the impacts of aids and adaptations on the wellbeing of people with dementia and their families living at home. Quantitative data were collected using established measures of wellbeing at baseline, 3 months and 9 months. In-depth case studies were carried out with a sample of participants. Findings from the pilot suggest that relatively inexpensive aids can contribute towards the maintenance of wellbeing for people with dementia in domestic settings. The project also increased the skills and confidence of professionals involved in the project and strengthened partnerships between the collaborating organisations across health, housing and social care. Providing aids that can help people with dementia to remain living at home with a good quality of life, often with the support of a family member, is an important element in the development of age-friendly communities.

Metacognition is the ability to be aware of own mental activities. Metacognitive deficits are reliably reported in schizophrenia and metacognitive ability has been strongly linked to functional capacity. However, the neural correlates of metacognitive ability in schizophrenia is uncertain, although some evidence implicates the hippocampus as a critical structure in this group. We explored neural correlates of perceptual metacognitive accuracy in first episode psychosis (FEP) and healthy controls, hypothesizing that lower hippocampal volume would correlate with poorer metacognition in FEP only. 31 patients with FEP (9 female, aged between 19 and 39, mean age 25.95) and eighteen age, gender and education matched healthy controls (6 female, aged between 18 and 38, mean age 24.43) took part in the study. Brain structural T1s were acquired using MRI and all participants completed a perceptual metacognitive accuracy task outside of the scanner. Gray matter volumes for cortical and subcortical regions were calculated using Freesurfer’s “recon-all” pipeline (http://surfer.nmr.mgh.harvard.edu). Regions of interest (ROI) included prefrontal and hippocampal structures, as implicated in previous studies on metacognition. Comparisons between FEP and control groups were performed using t-tests for continuous variables (ROI volumes, metacognitive accuracy). Correlational analyses than explored relationships between ROI and metacognitive accuracy, by group. In the FEP group, metacognitive accuracy was significantly impaired compared to controls. There was no difference between groups on any of the ROI volume measures. Metacognitive accuracy in the FEP group correlated with total hippocampal volumes both in left hemisphere (r=.429, p=.016), and right hemisphere r=.487, p=.005). These relationships were localized to specific hippocampal subfields (left hippocampal head; r=.376, p=.037, left hippocampal body; r=.462, p=.009; right hippocampal head; r=.475, p=.007, right hippocampal body; r=.516, p=.003). In contrast, there were no statistically significant relationships between metacognitive accuracy and hippocampal volume in the control group (left hippocampus: r=-0.046, p=0.855, right hippocampus: r=.056, p=.826). Results of this study provide evidence of a positive relationship between hippocampal volumes and metacognitive accuracy in FEP only. This points to possible differences in the neural substrates of metacognition in schizophrenia, with hippocampus contributing to the poorer metacognitive performance frequently observed in patients. Metacognitive ability has important consequences for functional capacity, and these results are consistent with the suggestion that hippocampal pathophysiology might be central to cognitive deficit in schizophrenia.