Organic electrochemical transistors with PVA hydrogels/PEDOT:PSS channel

Most organic electrochemical transistor (OECT)-based biosensors currently rely solely on the generation of electronic signals upon sensor-analyte interaction which has limited the range of analytes to those with distinct electronic properties or those that rely on specific biological materials with poor environmental stability, such as redox enzymes and antibodies. The development of durable stimuli-responsive hydrogels, which exhibit changes in ionic conductivity upon interacting with specific analytes, has significantly expanded the potential for ionic-based sensing as an alternative to electronic-based sensing. Although OECTs are suitable for measuring ionic signals, there have been only a few instances where these materials have been utilized within an OECT platform. This study investigates the applicability of OECTs for ionic-based sensing using poly(vinyl alcohol) (PVA) hydrogels and PEDOT:PSS based OECTs. Through varying macromer percentage alone, a set of hydrogels was fabricated that mimics the network properties seen in complex analyte-responsive systems. These hydrogels offer a cheap alternative, without the use of biorecognition elements, for probing OECT sensitivity to ionic signals. A system based on four electrode impedance spectroscopy was also developed to independently measure their ionic conductivity, with preliminary results consistent with values reported in literature. To enhance device reproducibility and improve compatibility with hydrogel deposition, a novel OECT geometry was designed. This involved incorporating larger features such as wider channels and thicker electrode contacts to minimize fabrication artifacts which ultimately improved OECT transconductance. Additionally, the impact of 3 direct polymerization of hydrogels on PEDOT:PSS was explored using Raman spectroscopy. The findings revealed that a high degree of adherence between the hydrogel and PEDOT:PSS may significantly reduce the dedoping capacity of PEDOT:PSS. Overall, this work represents a valuable first step in exploring the suitability of OECTs to ionic flow based sensing using hydrogels.Open Acces

Neighbourhood drivability: environmental and individual characteristics associated with car use across Europe

Background: Car driving is a form of passive transportation associated with higher sedentary behaviour, which is associated with morbidity. The decision to drive a car is likely to be influenced by the ‘drivability’ of the built environment, but there is lack of scientific evidence regarding the relative contribution of environmental characteristics of car driving in Europe, compared to individual characteristics. This study aimed to determine which neighbourhood- and individual-level characteristics were associated with car driving in adults of five urban areas across Europe. Second, the study aimed to determine the percentage of variance in car driving explained by individual- and neighbourhood-level characteristics. Methods: Neighbourhood environment characteristics potentially related to car use were identified from the literature. These characteristics were subsequently assessed using a Google Street View audit and available GIS databases, in 59 administrative residential neighbourhoods in five European urban areas. Car driving (min/week) and individual level characteristics were self-reported by study participants (analytic sample n = 4258). We used linear multilevel regression analyses to assess cross-sectional associations of individual and neighbourhood-level characteristics with weekly minutes of car driving, and assessed explained variance at each level and for the total model. Results: Higher residential density (β:-2.61, 95%CI: − 4.99; -0.22) and higher land-use mix (β:-3.73, 95%CI: − 5.61; -1.86) were significantly associated with fewer weekly minutes of car driving. At the individual level, higher age (β: 1.47, 95%CI: 0.60; 2.33), male sex (β: 43.2, 95%CI:24.7; 61.7), being employed (β:80.1, 95%CI: 53.6; 106.5) and ≥ 3 person household composition (β: 47.4, 95%CI: 20.6; 74.2) were associated with higher weekly minutes of car driving. Individual and neighbourhood characteristics contributed about equally to explained variance in minutes of weekly car driving, with 2 and 3% respectively, but total explained variance remained low. Conclusions: Residential density and land-use mix were neighbourhood characteristics consistently associated with minutes of weekly car driving, besides age, sex, employment and household composition. Although total explained variance was low, both individual- and neighbourhood-level characteristics were similarly important in their associations with car use in five European urban areas. This study suggests that more, higher quality, and longitudinal data are needed to increase our understanding of car use and its effects on determinants of health

Correction: Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue.

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances

Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances

Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

The Use and Effects of an App-Based Physical Activity Intervention “Active2Gether” in Young Adults: Quasi-Experimental Trial

Background: Insufficient physical activity (PA) is highly prevalent and associated with adverse health conditions and the risk of noncommunicable diseases. To increase levels of PA, effective interventions to promote PA are needed. Present-day technologies such as smartphones, smartphone apps, and activity trackers offer several possibilities in health promotion. Objective: This study aimed to explore the use and short-term effects of an app-based intervention (Active2Gether) to increase the levels of PA in young adults. Methods: Young adults aged 18-30 years were recruited (N=104) using diverse recruitment strategies. The participants were allocated to the Active2Gether-Full condition (tailored coaching messages, self-monitoring, and social comparison), Active2Gether-Light condition (self-monitoring and social comparison), and the Fitbit-only control condition (self-monitoring). All participants received a Fitbit One activity tracker, which could be synchronized with the intervention apps, to monitor PA behavior. A 12-week quasi-experimental trial was conducted to explore the intervention effects on weekly moderate-to-vigorous PA (MVPA) and relevant behavioral determinants (ie, self-efficacy, outcome expectations, social norm, intentions, satisfaction, perceived barriers, and long-term goals). The ActiGraph wGT3XBT and GT3X+ were used to assess baseline and postintervention follow-up PA. Results: Compared with the Fitbit condition, the Active2Gether-Light condition showed larger effect sizes for minutes of MVPA per day (regression coefficient B=3.1; 95% CI −6.7 to 12.9), and comparatively smaller effect sizes were seen for the Active2Gether-Full condition (B=1.2; 95% CI −8.7 to 11.1). Linear and logistic regression analyses for the intervention effects on the behavioral determinants at postintervention follow-up showed no significant intervention effects of the Active2Gether-Full and Active2Gether-Light conditions. The overall engagement with the Fitbit activity tracker was high (median 88% (74/84) of the days), but lower in the Fitbit condition. Participants in the Active2Gether conditions reported more technical problems than those in the Fitbit condition. Conclusions: This study showed no statistically significant differences in MVPA or determinants of MVPA after exposure to the Active2Gether-Full condition compared with the Active2Gether-Light or Fitbit condition. This might partly be explained by the small sample size and the low rates of satisfaction in the participants in the two Active2Gether conditions that might be because of the high rates of technical problems

Mutant and idiopathic PD occipital cortex samples used in this study.

<p>Mutant and idiopathic PD occipital cortex samples used in this study.</p