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Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort
No full textWe aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10-8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the "irritable"nociceptor profile to those with a "nonirritable"nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10-8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.</p
Variation of subclinical psychosis as a function of population density across different European settings:Findings from the multi-national EU-GEI study
No full textBackground: Urbanicity is a well-established risk factor for psychosis. Our recent multi-national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North-western Europe countries than in Southern Europe ones. Methods: We recruited 1080 individuals representative of the populations aged 18–64 of 14 different sites within 5 countries, classified as either North-western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy-Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi-level regression analysis. To test the differential effect of urbanicity between North-western and Southern European, we added an interaction term between population density and region of recruitment. Results: Population density was associated with schizotypy (β = 0.248,95%CI = 0.122–0.375;p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio:χ 2 = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North-western Europe (β = 0.620,95%CI = 0.362–0.877;p < 0.001) compared with Southern Europe (β = 0.190,95%CI = 0.083–0.297;p = 0.001). Conclusions: The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context-specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship.</p
The perceived quality of life in adult patients with inherited ichthyosis:a qualitative interview study
No full textThis qualitative interview study aimed to gain insight into the perceived impact of ichthyosis on the biopsychosocial quality of life of adult patients. Fifteen patients [with a diagnosis of autosomal recessive congenital ichthyosis (n = 10), X-linked ichthyosis (n = 3) and epidermolytic hyperkeratosis (n = 2)] highlighted the multifaceted impact of growing older with ichthyosis within the biologic (e.g. excessive scaling and overheating), psychological (e.g. low self-esteem and complex reproductive decision-making) and social domains (e.g. limited career options and being bullied). Suggestions for healthcare improvements include long-term management of ichthyosis, psychological support, societal awareness, medication reimbursement and research into reproductive and age-related issues
Can Offset Analgesia Magnitude Provide Additional Information About Endogenous Pain Modulation in People With Knee Osteoarthritis?:An Experimental Study
No full textObjectives: To investigate the relationship between offset analgesia magnitude and the responsiveness to conditioned pain modulation (CPM), temporal summation of (second) pain (TSP), and clinical pain severity in people with knee osteoarthritis (KOA). Methods: Electrical stimuli were applied to 88 participants with KOA to measure offset analgesia at the volar forearm of the dominant hand, and CPM and TSP at the most symptomatic knee and ipsilateral volar wrist. Clinical pain severity was assessed using the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOSPAIN). Linear mixed effects models evaluated pain modulatory effects across all tests, and Spearman's partial correlations assessed associations between offset analgesia, CPM, TSP, and KOOSPAIN while accounting for covariates of interest. Participants unable to validly finish all psychophysical tests were excluded from effect and correlation analyses but were evaluated for predictors of non-valid completion using bivariate Stochastic Search Variable Selection. Results: Significant pain modulation was observed across all psychophysical tests (P < 0.05) and no meaningful predictors of non-valid test completion were found. Offset analgesia magnitude did not significantly correlate with CPM, TSP, or KOOSPAIN (p ≥ 0.05), with a maximum partial correlation coefficient of ρ = 0.21. Discussion: Offset analgesia was not associated with CPM, TSP, or KOOSPAIN in people with KOA. Despite the lack of case-control studies comparing offset analgesia between people with KOA and healthy controls, these findings suggest that offset analgesia may provide information about endogenous pain modulation beyond CPM and TSP, though its clinical translation remains uncertain.</p
Which Characteristics are Associated With Going Outside for People Living With Dementia in Nursing Homes? A Cross-Sectional Study
No full textThis cross-sectional study explores the frequency of going outside and characteristics that are associated with going outside for people living with dementia in nursing homes in the Netherlands. A subsample of a national survey in 353 nursing homes was used (N = 693). Two-thirds (66.5%) go outside often. Compared to those who rarely or never go outside, participants who go outside often receive visits more often (odds ratio (OR) 1.68, 95% confidence interval (CI) 1.02-2.75), have less severe physical impairments (severe vs. mild: OR 0.17, 95% CI 0.04-0.73; very severe vs. mild: OR 0.11, 95% CI 0.03-0.49), use less pain medication (OR 0.61, 95% CI 0.38-0.98), experience higher positive affect (OR 1.10, 95% CI 1.03-1.17), and feel less at home (OR 0.86, 95% CI 0.76-0.97). These findings are the first step in developing effective interventions that will contribute to people living with dementia going outside more often
Giving serious thought to bad policy and the state of democracy
No full textThis chapter aims to make explicit what is at stake when ineffective policy emerges. It situates ineffective policy within the workings of Western democratic systems and outlines to what extent and how the effects of such policies may extend beyond the sole remit of these policies and onto the quality of democratic systems themselves. We draw upon research on (patterns of) democratic backsliding to conceptualise the relationship between ineffective policy and democracy in settings of democratic failings. We argue that ineffective policy is necessarily relational to the democratic environment within which it emerges and structure our argument about the relationality of ineffective policy to democratic regression around three vectors: the role of interests, ideas, and values in policymaking; institutional contexts; and temporality. Ineffective policy, we argue, weakens democracy, yet also reflects a weakened democratic space. The weakening of democratic safeguards, in turn, can generate space for ineffective policy to flourish
Authoritarian Algorithmic Publics:Conceptualising the Nexus of Authoritarianism and Digital Innovation Uptake in Russian News Media
No full textScholarship on digital innovation uptake in journalism has expanded to include hybrid and authoritarian regimes. However, the intersection of digital innovation and algorithmisation with restricted media freedom remains undertheorised. This article introduces the concept of authoritarian algorithmic publics (AAP), building upon “authoritarian publics-at-large” (Toepfl) and “algorithmic publics” (Christen), and applies it to Russia. Based on in-depth interviews with media professionals in Russian media (N = 51) we elucidate how media professionals’ perceptions of advanced digital technologies, rooted in a journalistic culture shaped by the conditions of authoritarianism, affect the development of digital journalism in autocracies. Contrary to politically-determined perspectives on media development in autocracies, our findings suggest that political loyalty is a poor explanatory factor of digital innovation uptake. By examining three media outlets – RT, RBC, and Meduza – we illustrate digital innovation across the political spectrum, revealing a complexity of digital authoritarianism better captured by AAP. Both pro-state media, forming a non-critical public, and oppositional media, creating a leadership-critical public, may use similar technologies and practices for optimization. However, their different perceptions and tailored use of these tools lead to the production of distinct algorithmic publics
Climate change, development interventions and (im)mobility in Ethiopia:the perceived role of climate development interventions on aspirations and capabilities
No full textAccording to the Intergovernmental Panel on Climate Change’s Sixth Assessment Report 2023, 3.6 billion people worldwide live in areas increasingly vulnerable to climate change. By enhancing people’s resilience to climate change, the EU Commission aims to address the root causes of irregular migration in countries of origin and manage migration. But how exactly does climate change influence migration? Will a better resilience to withstand climate shocks help people to stay where they are, as expected by the EU and other donors? To contribute new evidence to the outlined research gap, this dissertation qualitatively explores the role of an EU-funded climate development intervention for the aspirations and perceived capabilities of supported farmers, pastoralists and youths to migrate or stay. Between 2021 and 2023, several rounds of in-depth interviews, focus group discussions and key informant interviews with approximately 200 research participants were conducted in two different research areas of southern Ethiopia, that are affected by climate change
