Potential Cross-Links of Inflammation With Schizophreniform and Affective Symptoms: A Review and Outlook on Autoimmune Encephalitis and COVID-19

Based on current implications of the SARS-CoV-2 pandemic with regards to mental health, we show that biological links exist between inflammation and mental illness in addition to psychoreactive effects. We describe key principles of the biological interaction of the immune system and the mind, as well as the possible routes of viral entry into the brain. In addition, we provide a stepwise scheme for the diagnosis and therapy of autoimmune-encephalitis with schizophrenia-like symptomatology as a general guide for clinical practice and in the specialized scenario of infections, such as those caused by the SARS-CoV-2 virus.

Body Movin’: Ecocritical and Postcolonial Readings of the Travelling Body in the Tomb Raider Series

When Lara Croft travels, she travels light – sans suitcase, but in most cases with enough firepower to take opposing forces ranging from dinosaurs to bloodthirsty locals. However, her big guns seems often unnecessary titillation, for she can manage very well without them thanks to her exquisite acrobatic and hand-to-hand combat skills. She will vault over any obstacle, swim across rapid flowing rivers and abseil the steepest ravines. Lara Croft’s travels are often as physical as the virtual world would allow. That physicality returns our attention to the oft forgotten aspect of travelling namely the body of the traveller, not only defined by its position in space, but also by the ordinary and extraordinary circumstances of its biological interaction with the surrounding environment.In this paper I would like to explore the interplay between the body of the traveller and contexts it is located in. These contexts range from the narrative and gameplay aspects of the Tomb Raider series, but also go beyond the border of the game and are realised in the transformative and reflective cultural milieu of the game. In particular I want to focus on the representations of Lara Croft as an archetypal “action girl” and “adventurer archaeologist” and how these representations are realised in reference to the changing (maturing?) video game environments. In the framework of postcolonial and ecocritical theories I want to explore the dyads of body/the purported exotic, body/natural environment, as well as physical/mental aspects of travelling.

The interaction effect between comorbidity and venous thromboembolism on mortality rates after venous thromboembolism: A 5-year cohort study

Background: Comorbidity influences venous thromboembolism (VTE) mortality, but it is unknown whether this is due to comorbidity alone or whether biological interaction exists. Objectives: We examined whether comorbidity and VTE interact to increase VTE mortality beyond their individual effects. Methods: This register-based 5-year cohort study included all VTE patients ≥18 years during 2000–2016, and an age-, sex-, and comorbidity-matched comparison cohort of individuals without VTE. We computed age-standardized mortality rates and examined interaction on the additive scale via interaction contrasts (difference in rate differences). Results: After 30-day follow-up, the mortality rate per 1000 person-years among individuals with no comorbidity was 419 (95% confidence interval [CI]: 391–447) in the VTE and 16 (95% CI: 13–18) in the comparison cohort (rate difference: 403). The corresponding mortality rate increased to 591 (95% CI: 539–643) in the VTE cohort and 38 (95% CI: 33–44) in the comparison cohort among individuals with low comorbidity (rate difference: 553). The interaction contrast (150) showed that 25% (150/591) of mortality was explained by the interaction in individuals with low comorbidity. This percentage increased to 56% for moderate and 63% for severe comorbidity. Interaction effects were largest within 30-day follow-up, for provoked VTE, and in young individuals. Dose-response patterns between comorbidity and interaction effects were also observed after 31–365-day and >1–5-year follow-up (p<0.0001). Interaction effects varied between individual comorbidities. Conclusion: Biological interaction between comorbidity and VTE explains a substantial proportion of VTE mortality, and this interaction effect increases with comorbidity burden.

Genomic selection signatures in autism spectrum disorder identifies cognitive genomic tradeoff and its relevance in paradoxical phenotypes of deficits versus potentialities

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by paradoxical phenotypes of deficits as well as gain in brain function. To address this a genomic tradeoff hypothesis was tested and followed up with the biological interaction and evolutionary significance of positively selected ASD risk genes. SFARI database was used to retrieve the ASD risk genes while for population datasets 1000 genome data was used. Common risk SNPs were subjected to machine learning as well as independent tests for selection, followed by Bayesian analysis to identify the cumulative effect of selection on risk SNPs. Functional implication of these positively selected risk SNPs was assessed and subjected to ontology analysis, pertaining to their interaction and enrichment of biological and cellular functions. This was followed by comparative analysis with the ancient genomes to identify their evolutionary patterns. Our results identified significant positive selection signals in 18 ASD risk SNPs. Functional and ontology analysis indicate the role of biological and cellular processes associated with various brain functions. The core of the biological interaction network constitutes genes for cognition and learning while genes in the periphery of the network had direct or indirect impact on brain function. Ancient genome analysis identified de novo and conserved evolutionary selection clusters. The de-novo evolutionary cluster represented genes involved in cognitive function. Relative enrichment of the ASD risk SNPs from the respective evolutionary cluster or biological interaction networks may help in addressing the phenotypic diversity in ASD. This cognitive genomic tradeoff signatures impacting the biological networks can explain the paradoxical phenotypes in ASD.

O27 Frailty and co-morbidity in people with osteoarthritis and rheumatoid arthritis

Background/Aims People with osteoarthritis (OA) and rheumatoid arthritis (RA) are at increased risk of frailty, though the role of co-morbidities in contributing to frailty risk in these arthritides is uncertain. The aim of this study was i) to determine the association between common co-morbidities and frailty in OA and RA; and ii) to determine whether co-morbidities interact synergistically with OA and RA to increase the likelihood of frailty. Methods A cross-sectional analysis of the UK Biobank data was carried out. In this national cohort of participants aged 40-69 years, self-reported physician-diagnosed diseases including OA, RA, and common co-morbidities (including hypertension, coronary heart disease, diabetes, stroke/TIA, chronic obstructive pulmonary disease (COPD), and depression) were recorded. Frailty was assessed using a modification of the frailty phenotype (FP), comprising five components: self-reported weight loss, exhaustion, low physical activity (international activity questionnaire), slow walking speed, and low hand-grip strength. Pre-frailty and frailty, was identified based on the presence of 1-2 and ≥3 of these components, respectively. Among participants with OA and RA at baseline, the likelihood of being pre-frail or frail (vs not frail) at baseline among people with (vs without) each of the co-morbidities was assessed using multinomial logistic regression. To determine whether co-morbidities interact synergistically with OA and RA to increase the likelihood of frailty, deviation from additivity of risk was estimated by calculating the attributable proportion (AP) of risk due to biological interaction. An AP &gt; 0 indicates positive (synergistic) biological interaction. Analyses were adjusted for age, sex, smoking status, BMI, and deprivation. Results In total, 457,561 people were included in the analysis; 35,884 (7.8%) had OA and 4,894 (1.1%) had RA. Overall, the mean (SD) age was 56.5 (8.1) years and 54% were female. The overall prevalence of frailty was 3.4%. The prevalence of frailty was higher among those with OA (10.0%) and RA (18.6%). Each of the co-morbidities considered was associated with increased relative risk of pre-frailty and frailty particularly COPD in OA, relative risk ratio (95%CI): pre-frailty, 2.09 (1.80, 2.42) and frailty, 4.45 (3.71, 5.33) and stroke/TIA in RA: pre-frailty, 1.97 (1.18, 3.29) and frailty, 3.64 (2.11, 6.29). Most of the co-morbidities considered interacted synergistically with OA and RA to increase the risk of pre-frailty and frailty, particularly diabetes in OA, AP (95% CI): pre-frailty, 0.13 (0.04, 0.23) and frailty, 0.49 (0.42, 0.55) and stroke/TIA in RA: pre-frailty, 0.34 (0.003, 0.68) and frailty 0.60 (0.38, 0.82). Conclusion Co-morbidity is associated with an increased occurrence of pre-frailty and frailty among people with OA and RA and interacts synergistically with OA and RA to increase the likelihood of pre-frailty and frailty. Disclosure M.J. Cook: None. M. Lunt: None. S.M.M. Verstappen: None. T.W. O'Neill: None.