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Contact with nature can contribute to health and wellbeing, but knowledge gaps persist regarding the environmental characteristics that promote these benefits. Understanding and maximising these benefits is particularly important in urban areas, where opportunities for such contact is limited. At the same time, we are facing climate and ecological crises which require policy and practice to support ecosystem functioning. Policies are increasingly being oriented towards delivering benefits for people and nature simultaneously. However, different disciplinary understandings of environments and environmental quality present challenges to this agenda. This paper highlights key knowledge gaps concerning linkages between nature and health. It then describes two perspectives on environmental quality, based respectively in environmental sciences and social sciences. It argues that understanding the linkages between these perspectives is vital to enable urban environments to be planned, designed and managed for the benefit of both environmental functioning and human health. Finally, it identifies key challenges and priorities for integrating these different disciplinary perspectives., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Independent organisations monitor the safety and governance of clinical services but do not assess specialist expertise. Peer review can assess service capability but is resource-intense and infeasible., The Problem: How can you ensure a service provides safe, effective rehabilitation? You ask them to provide data as evidence that they can be trusted to do so. This article suggests a structured approach to providing data on entrustability., An Analogy: How is the specialist skill of a doctor in training established? They provide evidence about high-level outcomes (capabilities in practice) related to their speciality. An educational supervisor assesses whether they can be trusted to perform safely and effectively without supervision. The capabilities in practice define their expertise., The Solution: A service can use seven high-level rehabilitation service capabilities, based on the clinical capabilities associated with medical training, with observable indicative descriptors, to collect evidence of their rehabilitation approach. A service must also select four to eight high-level competencies indicating they can rehabilitate their patient caseload safely and effectively. These competencies also need indicative descriptors as evidence of their performance in the service; 11 examples are given., Capabilities.: The seven rehabilitation capabilities are: using the biopsychosocial model, having a multi-professional team, making a person-centred rehabilitation plan, working collaboratively across all boundaries, tailoring treatments to the patient's needs, ensuring staff have specific competencies required for their caseload, and acknowledging and managing uncertainty and complexity., Conclusion.: Service providers could use this structured approach to develop and provide users with evidence of their rehabilitation expertise., Competing Interests: Declaration of conflicting interestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period., Methods: We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose-response, using data assembled for a recent systematic review., Results: There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect., Conclusions: There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Acute lymphocytic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) are among the commonest types of childhood cancer. Some previous studies suggested that elevated ultraviolet radiation (UVR) exposures increase ALL risk; many more indicate NHL risk is reduced., Methods: We assessed age<20 ALL/NHL incidence in Surveillance, Epidemiology and End Results data using AVGLO-derived UVR irradiance/cumulative radiant exposure measures, using quasi-likelihood models accounting for underdispersion, adjusted for age, sex, racial/ethnic group and other county-level socioeconomic variables., Results: There were 30,349 cases of ALL and 8062 of NHL, with significant increasing trends of ALL with UVR irradiance (relative risk (RR) = 1.200/mW/cm 2 (95% CI 1.060, 1.359, p = 0.0040)), but significant decreasing trends for NHL (RR = 0.646/mW/cm 2 (95% CI 0.512, 0.816, p = 0.0002)). There was a borderline-significant increasing trend of ALL with UVR cumulative radiant exposure (RR = 1.444/MJ/cm 2 (95% CI 0.949, 2.197, p = 0.0865)), and significant decreasing trends for NHL (RR = 0.284/MJ/cm 2 (95% CI 0.166, 0.485, p < 0.0001)). ALL and NHL trend RR is substantially increased among those aged 0-3. All-age trend RRs are most extreme (increasing for ALL, decreasing for NHL) for Hispanics for both UVR measures., Conclusions: Our more novel finding, of excess UVR-related ALL risk, is consistent with some previous studies, but is not clear-cut, and in need of replication., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

For many cancer sites low-dose risks are not known and must be extrapolated from those observed in groups exposed at much higher levels of dose. Measurement error can substantially alter the dose-response shape and hence the extrapolated risk. Even in studies with direct measurement of low-dose exposures measurement error could be substantial in relation to the size of the dose estimates and thereby distort population risk estimates. Recently, there has been considerable attention paid to methods of dealing with shared errors, which are common in many datasets, and particularly important in occupational and environmental settings. In this paper we test Bayesian model averaging (BMA) and frequentist model averaging (FMA) methods, the first of these similar to the so-called Bayesian two-dimensional Monte Carlo (2DMC) method, and both fairly recently proposed, against a very newly proposed modification of the regression calibration method, the extended regression calibration (ERC) method, which is particularly suited to studies in which there is a substantial amount of shared error, and in which there may also be curvature in the true dose response. The quasi-2DMC with BMA method performs well when a linear model is assumed, but very poorly when a linear-quadratic model is assumed, with coverage probabilities both for the linear and quadratic dose coefficients that are under 5% when the magnitude of shared Berkson error is large (50%). For the linear model the bias is generally under 10%. However, using a linear-quadratic model it produces substantially biased (by a factor of 10) estimates of both the linear and quadratic coefficients, with the linear coefficient overestimated and the quadratic coefficient underestimated. FMA performs as well as quasi-2DMC with BMA when a linear model is assumed, and generally much better with a linear-quadratic model, although the coverage probability for the quadratic coefficient is uniformly too high. However both linear and quadratic coefficients have pronounced upward bias, particularly when Berkson error is large. By comparison ERC yields coverage probabilities that are too low when shared and unshared Berkson errors are both large (50%), although otherwise it performs well, and coverage is generally better than the quasi-2DMC with BMA or FMA methods, particularly for the linear-quadratic model. The bias of the predicted relative risk at a variety of doses is generally smallest for ERC, and largest for the quasi-2DMC with BMA and FMA methods (apart from unadjusted regression), with standard regression calibration and Monte Carlo maximum likelihood exhibiting bias in predicted relative risk generally somewhat intermediate between ERC and the other two methods. In general ERC performs best in the scenarios presented, and should be the method of choice in situations where there may be substantial shared error, or suspected curvature in the dose response., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: In estimating radiation-associated cancer risks a fixed period for the minimum latency is often assumed. Two empirical latency functions have been used to model latency, continuously increasing from 0. A stochastic biologically-based approach yields a still more plausible way of describing latency and can be directly estimated from clinical data., Methods: We derived the parameters for a stochastic biologically-based model from tumour growth data for various cancers, and least-squares fitted the two types of empirical latency function to the stochastic model-predicted cumulative probability., Results: There is wide variation in growth rates among tumours, particularly slow for prostate and thyroid cancer and particularly fast for leukaemia. The slow growth rate for prostate and thyroid tumours implies that the number of tumour cells required for clinical detection cannot greatly exceed 10 6 . For all tumours, both empirical latency functions closely approximated the predicted biological model cumulative probability., Conclusions: Our results, illustrating use of a stochastic biologically-based model using clinical data not tied to any particular carcinogen, have implications for estimating latency associated with any mutagen. They apply to tumour growth in general, and may be useful for example, in planning screenings for cancer using imaging techniques., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aims: Acute myocardial infarction rapidly increases blood neutrophils (<2 h). Release from bone marrow, in response to chemokine elevation, has been considered their source, but chemokine levels peak up to 24 h after injury, and after neutrophil elevation. This suggests that additional non-chemokine-dependent processes may be involved. Endothelial cell (EC) activation promotes the rapid (<30 min) release of extracellular vesicles (EVs), which have emerged as an important means of cell-cell signalling and are thus a potential mechanism for communicating with remote tissues., Methods and Results: Here, we show that injury to the myocardium rapidly mobilizes neutrophils from the spleen to peripheral blood and induces their transcriptional activation prior to arrival at the injured tissue. Time course analysis of plasma-EV composition revealed a rapid and selective increase in EVs bearing VCAM-1. These EVs, which were also enriched for miRNA-126, accumulated preferentially in the spleen where they induced local inflammatory gene and chemokine protein expression, and mobilized splenic-neutrophils to peripheral blood. Using CRISPR/Cas9 genome editing, we generated VCAM-1-deficient EC-EVs and showed that its deletion removed the ability of EC-EVs to provoke the mobilization of neutrophils. Furthermore, inhibition of miRNA-126 in vivo reduced myocardial infarction size in a mouse model., Conclusions: Our findings show a novel EV-dependent mechanism for the rapid mobilization of neutrophils to peripheral blood from a splenic reserve and establish a proof of concept for functional manipulation of EV-communications through genetic alteration of parent cells., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The coexistence of different mating strategies, whereby a species can reproduce both by selfing and outcrossing, is an evolutionary enigma. Theory predicts two predominant stable mating states: outcrossing with strong inbreeding depression or selfing with weak inbreeding depression. As these two mating strategies are subject to opposing selective forces, mixed breeding systems are thought to be a rare transitory state yet can persist even after multiple speciation events. We hypothesise that if each mating strategy plays a distinctive role during some part of the species life history, opposing selective pressures could be balanced, permitting the stable co-existence of selfing and outcrossing sexual morphs. In this scenario, we would expect each morph to be specialised in their respective roles. Here we show, using behavioural, physiological and gene expression studies, that the selfing (hermaphrodite) and outcrossing (female) sexual morphs of the trioecious nematode Auanema freiburgensis have distinct adaptations optimised for their different roles during the life cycle. A. freiburgensis hermaphrodites are known to be produced under stressful conditions and are specialised for dispersal to new habitat patches. Here we show that they exhibit metabolic and intestinal changes enabling them to meet the cost of dispersal and reproduction. In contrast, A. freiburgensis females are produced in favourable conditions and facilitate rapid population growth. We found that females compensate for the lack of reproductive assurance by reallocating resources from intestinal development to mate-finding behaviour. The specialisation of each mating system for its role in the life cycle could balance opposing selective forces allowing the stable maintenance of both mating systems in A. freiburgensis., (© 2022. The Author(s).)

Purpose: To explore the extent to which musculoskeletal (MSK) complications have been reported following critical illness, identifying evidence gaps and providing recommendations for future research., Materials and Methods: We searched five databases from January 1st 2000 to March 31st 2021. We included published original research reporting MSK complications in patients discharged from hospital following an admission to an intensive care unit (ICU). Two reviewers independently screened English language articles for eligibility. Data extracted included the MSK area of investigation and MSK outcome measures. The overall quality of study was evaluated against standardised reporting guidelines., Results: 4512 titles were screened, and 32 met the inclusion criteria. Only one study included was interventional, with the majority being prospective cohort studies (n = 22). MSK complications identified included: muscle weakness or atrophy, chronic pain, neuromuscular dysfunction, peripheral joint impairment and fracture risk. The quality of the overall reporting in the studies was deemed adequate., Conclusions: We identified a heterogenous body of literature reporting a high prevalence of a variety of MSK complications extending beyond muscle weakness, therefore future investigation should include evaluations of more than one MSK area. Further investigation of MSK complications could inform the development of future post critical illness rehabilitation programs., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2 -/- ) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression., (© 2021. Crown.)

Purpose: Plant-based proteins may have the potential to improve glycaemic and gastrointestinal hormone responses to foods and beverages. The aim of this study was to investigate the effect of two doses of pea protein on postprandial glycaemic, insulinaemic, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) response following a high-carbohydrate beverage intake in healthy individuals., Methods: In a single-blind, randomised, controlled, repeat measure, crossover design trial, thirty-one participants were randomly assigned to ingest 50 g glucose (Control), 50 g glucose with 25 g pea protein (Test 1) and 50 g glucose with 50 g pea protein (Test 2) on three separate days. Capillary blood samples (blood glucose and plasma insulin measurements) and venous blood samples (GIP and GLP-1 concentrations) were taken before each test and at fixed intervals for 180 min. The data were compared using repeated-measures ANOVA or the Friedman test., Results: Glucose incremental Area under the Curve (iAUC180) was significantly lower (p < 0.001) after Test 2 compared with Control (- 53%), after Test 1 compared with Control (- 31%) and after Test 2 compared with Test 1 (-32%). Insulin iAUC 180 was significantly higher (p < 0.001) for Test 1 (+ 28%) and Test 2 (+ 40%) compared with Control and for Test 2 (+ 17%) compared with Test 1 (p = 0.003). GIP and GLP-1 release showed no clear difference between Control and Pea protein drinks., Conclusion: The consumption of pea protein reduced postprandial glycaemia and stimulated insulin release in healthy adults with a dose-response effect, supporting its role in regulating glycaemic and insulinaemic responses., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Background: There is a strong policy impetus for the One Health cross-sectoral approach to address the complex challenge of zoonotic diseases, particularly in low/lower middle income countries (LMICs). Yet the implementation of this approach in LMIC contexts such as India has proven challenging, due partly to the relatively limited practical guidance and understanding on how to foster and sustain cross-sector collaborations. This study addresses this gap by exploring the facilitators of and barriers to successful convergence between the human, animal and environmental health sectors in India., Methods: A mixed methods study was conducted using a detailed content review of national policy documents and in-depth semi-structured interview data on zoonotic disease management in India. In total, 29 policy documents were reviewed and 15 key informant interviews were undertaken with national and state level policymakers, disease managers and experts operating within the human-animal-environment interface of zoonotic disease control., Results: Our findings suggest that there is limited policy visibility of zoonotic diseases, although global zoonoses, especially those identified to be of pandemic potential by international organisations (e.g. CDC, WHO and OIE) rather than local, high burden endemic diseases, have high recognition in the existing policy agenda setting. Despite the widespread acknowledgement of the importance of cross-sectoral collaboration, a myriad of factors operated to either constrain or facilitate the success of cross-sectoral convergence at different stages (i.e. information-sharing, undertaking common activities and merging resources and infrastructure) of cross-sectoral action. Importantly, participants identified the lack of supportive policies, conflicting departmental priorities and limited institutional capacities as major barriers that hamper effective cross-sectoral collaboration on zoonotic disease control. Building on existing informal inter-personal relationships and collaboration platforms were suggested by participants as the way forward., Conclusion: Our findings point to the importance of strengthening existing national policy frameworks as a first step for leveraging cross-sectoral capacity for improved disease surveillance and interventions. This requires the contextual adaptation of the One Health approach in a manner that is sensitive to the underlying socio-political, institutional and cultural context that determines and shapes outcomes of cross-sector collaborative arrangements., (© 2021. The Author(s).)

Background: Psychological safety-speaking up about ideas and concerns, free from interpersonal risk-are essential to the high-risk environment, such as healthcare settings. Psychologically safe working is particularly important in mental health where recovery-oriented approaches rely on collaborative efforts of interprofessional teams to make complex decisions. Much research focuses on antecedents and outcomes associated with psychological safety, but little focus on the practical steps for how to increase psychological safety across and at different levels of a healthcare organisation., Aims: We explore how a mental health organisation creates an organisation-wide plan for building the foundations of mental health and how to enhance psychological safety., Methods: This review encompasses strategies across psychological safety and organisational culture change to increase psychological safety at an individual, team and organisational level. We set out a comprehensive overview of the types of strategies and interventions for increasing the ethos of psychological safety and setting the foundations for delivering an organisation-wide programme on this topic. We also provide a list of key targeted areas in mental health that would maximally benefit from increasing psychological safety-both in clinical and non-clinical settings., Conclusions: Psychological safety is a crucial determinant of safe and effective patient care in mental health services. This paper provides the key steps and considerations, creating a large-scale programme in psychological safety with a focus on mental health and drawing from the current literature, providing concrete steps for how our current understanding of psychological safety into practice.

A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labeled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939, and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, P = 1 × 10-6; AVI/AAV, P = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (P = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = -0.256, P = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs. 12.6 ± 0.5%TEI, P = 0.047) warranting further exploration in a larger cohort., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Quercus suber (cork oak) is an evergreen tree native to the Mediterranean basin, which plays a key role in the ecology and economy of this area. Over the last decades, this species has gone through an observable decline, mostly due to environmental factors. Deciphering the mechanisms of cork oak's response to the environment and getting a deep insight into its biology are crucial to counteract biotic and abiotic stresses compromising the stability of a unique ecosystem. In the light of these setbacks, the publication of the genome in 2018 was a major step towards understanding the genetic make-up of this species. In an effort to integrate this information in a comprehensive, accessible and intuitive format, we have developed The Cork Oak Genome Database Portal (CorkOakDB). The CorkOakDB is supported by the BioData.pt e-infrastructure, the Portuguese ELIXIR node for biological data. The portal gives public access to search and explore the curated genomic and transcriptomic data on this species. Moreover, CorkOakDB provides a user-friendly interface and functional tools to help the research community take advantage of the increased accessibility to genomic information. A study case is provided to highlight the functionalities of the portal. CorkOakDB guarantees the update, curation and data collection, aiming to collect data besides the genetic/genomic information, in order to become the main repository in cork oak research. Database URL: http://corkoakdb.org/., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Pupils in secondary schools do not meet the targets for physical activity levels during physical education (PE) sessions, and there is a lack of data on the vigorous physical activity domain (VPA) in PE known to be positively associated with cardio metabolic health While PE session intensity depends on a variety of factors, the large majority of studies investigating these factors have not taken into account the nested structure of this type of data set. Therefore, the aim of this study was to investigate the relationship between various factors (gender, activity type, class location and class composition) and various activity levels during PE classes in secondary schools, using a multi-level statistical approach., Methods: Year eight (12-13 years old) adolescents (201 boys and 106 girls) from six schools were fitted with accelerometers during one PE session each, to determine the percentage (%) of the PE session time spent in sedentary (SPA), light (LPA), moderate (MPA), vigorous (VPA) and moderate-to-vigorous (MVPA) intensity levels. Two- and three-level (pupils, n = 307; classes, n = 13, schools, n = 6) mixed-effect models were used to assess the relationship between accelerometer-measured physical activity levels (% of class time spent in various activity levels) and gender, activity type, class location and composition., Results: Participants engaged in MVPA and VPA for 30.7 ± 1.2% and 11.5 ± 0.8% of PE classes, respectively. Overall, no significant association between gender or class composition and PA was shown. A significant relationship between activity type and PA was observed, with Artistic classes significantly less active than Fitness classes for VPA (5.4 ± 4.5 vs. 12.5 ± 7.1%, p = 0.043, d:1.19). We also found a significant association between class location and PA, with significantly less time spent in SPA (24.8 ± 4.8% vs. 30.0 ± 3.4%, p = 0.042, d:0.77) and significantly more time spent in VPA (12.4 ± 3.7% vs. 7.6 ± 2.0%, p = 0.022, d:1.93) and MVPA (32.3 ± 6.7% vs.24.8 ± 3.8%, p = 0.024, d:1.33) in outdoors vs. indoors classes., Conclusions: The results suggest that class location and activity type could be associated with the intensity of PA in PE. It is essential to take into account the clustered nature of this type of data in similar studies if the sample size allows it.

Background: Generalized Structured Component Analysis (GSCA) is a component-based alternative to traditional covariance-based structural equation modelling. This method has previously been applied to test for association between candidate genes and clinical phenotypes, contrasting with traditional genetic association analyses that adopt univariate testing of many individual single nucleotide polymorphisms (SNPs) with correction for multiple testing. Methods: We first evaluate the ability of the GSCA method to replicate two previous findings from a genetics association study of developmental language disorders. We then present the results of a simulation study to test the validity of the GSCA method under more restrictive data conditions, using smaller sample sizes and larger numbers of SNPs than have previously been investigated. Finally, we compare GSCA performance against univariate association analysis conducted using PLINK v1.9. Results: Results from simulations show that power to detect effects depends not just on sample size, but also on the ratio of SNPs with effect to number of SNPs tested within a gene. Inclusion of many SNPs in a model dilutes true effects. Conclusions: We propose that GSCA is a useful method for replication studies, when candidate SNPs have been identified, but should not be used for exploratory analysis., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Thompson PA et al.)

Considering that neurogenic oropharyngeal dysphagia is a prevalent condition with or without cardiac disease we should contemplate issues surrounding cardiovascular difficulties during rehabilitation. This study aims to evaluate the effects of effortful swallowing maneuver (ESM) on heart rate variability (HRV) in subjects with neurogenic oropharyngeal dysphagia. We studied 22 individuals [8 Stroke and 14 Parkinson Disease (PD) subjects aged between 41 and 75 years old] with neurogenic oropharyngeal dysphagia regardless of gender. HRV was assessed under two circumstances: spontaneous swallowing versus ESM. Surface electromyography of the suprahyoid muscles was undertaken to measure the swallowing muscle excitation, which then confirmed higher muscle activity during ESM. We attained no changes in HRV between the two swallowing events [HR: spontaneous swallowing 78.68 ± 13.91 bpm vs. ESM 102.57 ± 107.81 bpm, p = 0.201; RMSSD (root-mean square of differences between adjacent normal RR intervals in a time interval): spontaneous swallowing 16.99 ± 15.65 ms vs. ESM 44.74 ± 138.85 ms, p = 0.312; HF (high frequency): spontaneous swallowing 119.35 ± 273 ms 2 vs. ESM 99.83 ± 194.58 ms 2 , p = 0.301; SD1 (standard deviation of the instantaneous variability of the beat-to-beat heart rate): spontaneous swallowing 12.02 ± 1.07 ms vs. ESM 31.66 ± 98.25 ms, p = 0.301]. The effortful swallowing maneuver did not cause clinically significant changes in autonomic control of HR in this group of subjects with oropharyngeal dysphagia.

Background: Generalized Structured Component Analysis (GSCA) is a component-based alternative to traditional covariance-based structural equation modelling. This method has previously been applied to test for association between candidate genes and clinical phenotypes, contrasting with traditional genetic association analyses that adopt univariate testing of many individual single nucleotide polymorphisms (SNPs) with correction for multiple testing. Methods: We first evaluate the ability of the GSCA method to replicate two previous findings from a genetics association study of developmental language disorders. We then present the results of a simulation study to test the validity of the GSCA method under more restrictive data conditions, using smaller sample sizes and larger numbers of SNPs than have previously been investigated. Finally, we compare GSCA performance against univariate association analysis conducted using PLINK v1.9. Results: Results from simulations show that power to detect effects depends not just on sample size, but also on the ratio of SNPs with effect to number of SNPs tested within a gene. Inclusion of many SNPs in a model dilutes true effects. Conclusions: We propose that GSCA is a useful method for replication studies, when candidate SNPs have been identified, but should not be used for exploratory analysis., Competing Interests: No competing interests were disclosed., (Copyright: © 2019 Thompson PA et al.)

Background: Early adolescence is a period of dynamic neurobiological change. Converging lines of research suggest that regular physical activity (PA) and improved aerobic fitness have the potential to stimulate positive brain changes, improve cognitive function and boost academic attainment in this age group, but high-quality studies are needed to substantiate these findings. The primary aim of the Fit to Study trial is to investigate whether short infusions of vigorous PA (VPA) delivered during secondary school physical education (PE) can improve attainment in maths, as described in a protocol published by NatCen Social Research. The present protocol concerns the trial's secondary outcome measures, which are variables thought to moderate or mediate the relationship between PA and attainment, including the effect of the intervention on cardiorespiratory fitness, cognitive performance, mental health and brain structure and function., Method: The Fit to Study project is a cluster-randomised controlled trial that includes Year 8 pupils (aged 12-13) from secondary state schools in South/Mid-England. Schools were randomised into an intervention condition in which PE teachers delivered an additional 10 min of VPA per PE lesson for one academic year, or a 'PE as usual' control condition. Intervention and control groups were stratified according to whether schools were single-sex or co-educational. Assessments take place at baseline (end of Year 7, aged 11-12) and after 12 months (Year 8). Secondary outcomes are cardiorespiratory fitness, objective PA during PE, cognitive performance and mental health. The study also includes exploratory measures of daytime sleepiness, attitudes towards daily PA and PE enjoyment. A sub-set of pupils from a sub-set of schools will also take part in a brain imaging sub-study, which is embedded in the trial., Discussion: The Fit to Study trial could advance our understanding of the complex relationships between PA and aerobic fitness, the brain, cognitive performance, mental health and academic attainment during adolescence. Further, it will add to our understanding of whether school PE is an effective setting to increase VPA and fitness, which could inform future PA interventions and education policy., Trial Registration: ClinicalTrials.gov, NCT03286725 . Retrospectively registered on 18 September 2017. ClinicalTrials.gov, NCT03593863 . Retrospectively registered on 19 July 2018.

Knowledge of protein signalling pathways in the working cell is seen as a primary route to identifying and developing targeted medicines. In recent years there has been a growing awareness of the importance of the mTOR pathway, making it an attractive target for therapeutic intervention in several diseases. Within this pathway we have focused on S6 kinase 1 (S6K1), the downstream phosphorylation substrate of mTORC1, and specifically identify its juxtaposition with mTORC1. When S6K1 is co-expressed with raptor we show that S6K1 is translocated from the nucleus to the cytoplasm. By developing a novel biosensor we demonstrate in real-time, that phosphorylation and de-phosphorylation of S6K1 occurs mainly in the cytoplasm of living cells. Furthermore, we show that the scaffold protein raptor, that typically recruits mTOR substrates, is not always involved in S6K1 phosphorylation. Overall, we demonstrate how FRET-FLIM imaging technology can be used to show localisation of S6K1 phosphorylation in living cells and hence a key site of action of inhibitors targeting mTOR phosphorylation.

Background: Amyotrophic Lateral Sclerosis (ALS) is a rapid progressive neurodegenerative disease, characterized by a selective loss of motor neurons, brain stem and spinal cord which leads to deterioration of motor abilities. Devices that promote interaction with tasks on computers can enhance performance and lead to greater independence and utilization of technology., Objective: To evaluate performance on a computer task in individuals with ALS using three different commonly used non-immersive devices., Method: Thirty individuals with ALS (18 men and 12 women, mean age 59 years, range 44-74 years) with a mean score of 26, (minimum score of 14 and maximum 41) on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and 30 healthy controls matched for age and gender, participated. All participants were randomly divided into three groups, each using a different device system (motion tracking, finger motion control or touchscreen) to perform three task phases (acquisition, retention and transfer)., Results: Both the ALS and control group (CG) showed better performance on the computer task when using the touchscreen device, but there was limited transfer of performance onto the task performed on the Finger Motion control or motion tracking. However, we found that using the motion tracking device led to transfer of performance to the touchscreen., Conclusion: This study presents novel and important findings when selecting interaction devices for individuals with ALS to access technology by demonstrating immediate performance benefits of using a touchscreen device, such as improvement of motor skills. There were possible transferable skills obtained when using virtual systems which may allow flexibility and enable individuals to maintain performance overtime., Trial Registration: Registration name: Virtual Task in Amyotrophic Lateral Sclerosis; Registration number: NCT03113630 ; retrospectively registered on 04/13/2017. Date of enrolment of the first participant to the trial: 02/02/2016.

Trichloroethylene (TCE) is one of the industrial toxic byproducts that now persist in the air, soil, and water. Several studies have already illustrated the toxic effect of high doses of TCE on the biological functions of several organs. This study aims to highlight the toxic impact of a low dose of TCE (1 μmol/L) on the development of rat neural stem cells (NSCs). The subventricular zones (SVZ) of rat pup's brains were collected and minced, and the harvested cells were cultured in the presence of neural growth factors B27/N2 to develop neurospheres. The cells were then exposed to a dose of 1 μmol/L TCE for 1 or 2 weeks. The outcomes indicated a remarkable inhibitory effect of TCE on the differentiation capacity of NSCs, which was confirmed by down-regulation of the astrocyte marker GFAP The inhibitory effect of TCE on the proliferation of NSCs was identified by the reductions in neurosphere diameter, Ki67 expression, and cell cycle arrest at the G1/S phase. Immunolabelling with annexin V indicated the proapoptotic effect of TCE exposure. PCR results revealed a TCE-mediated suppression of the expression of the antioxidant enzyme SOD1. This paper illustrates, for the first time, a detailed examination of the toxic effects of an environmentally low dose of TCE on NCSs at the transcriptional, translational, and functional levels.

The analysis of nuclear envelope components and their function has recently been progressed by the use of computational methods of analysis. The methods in this chapter provided by members of the International Plant Nucleus Consortium address the identification of novel nuclear envelope proteins and the study of structure and mobility of the nucleus. DORY2 is an upgrade of the KASH-finder DORY, and NucleusJ is used to characterize the three-dimensional structure of the nucleus in light microscope images. Finally, a method is provided for analysis of the migration of the nucleus, a key technique for exploring the function of plant nuclear proteins.

The shape and form of protozoan parasites are inextricably linked to their pathogenicity. The evolutionary pressure associated with establishing and maintaining an infection and transmission to vector or host has shaped parasite morphology. However, there is not a 'one size fits all' morphological solution to these different pressures, and parasites exhibit a range of different morphologies, reflecting the diversity of their complex life cycles. In this review, we will focus on the shape and form of Leishmania spp., a group of very successful protozoan parasites that cause a range of diseases from self-healing cutaneous leishmaniasis to visceral leishmaniasis, which is fatal if left untreated., (© 2017 The Authors.)

In plant cells, molecular connections link the cell wall-plasma membrane-actin cytoskeleton to form a continuum. It is hypothesized that the cell wall provides stable anchor points around which the actin cytoskeleton remodels. Here we use live cell imaging of fluorescently labelled marker proteins to quantify the organization and dynamics of the actin cytoskeleton and to determine the impact of disrupting connections within the continuum. Labelling of the actin cytoskeleton with green fluorescent protein (GFP)-fimbrin actin-binding domain 2 (FABD2) resulted in a network composed of fine filaments and thicker bundles that appeared as a highly dynamic remodelling meshwork. This differed substantially from the GFP-Lifeact-labelled network that appeared much more sparse with thick bundles that underwent 'simple movement', in which the bundles slightly change position, but in such a manner that the structure of the network was not substantially altered during the time of observation. Label-dependent differences in actin network morphology and remodelling necessitated development of two new image analysis techniques. The first of these, 'pairwise image subtraction', was applied to measurement of the more rapidly remodelling actin network labelled with GFP-FABD2, while the second, 'cumulative fluorescence intensity', was used to measure bulk remodelling of the actin cytoskeleton when labelled with GFP-Lifeact. In each case, these analysis techniques show that the actin cytoskeleton has a decreased rate of bulk remodelling when the cell wall-plasma membrane-actin continuum is disrupted either by plasmolysis or with isoxaben, a drug that specifically inhibits cellulose deposition. Changes in the rate of actin remodelling also affect its functionality, as observed by alteration in Golgi body motility., (© The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The use of suspension cultures synchronised by aphidicolin provides a method to study cell division in living plant cells. This chapter describes the use of this technique in tobacco suspension cultures expressing nuclear and nuclear envelope proteins that have been fused to fluorescent proteins. The protocol provides advice on optimizing synchrony and on real-time imaging by confocal microscopy.

Background: Existing literature suggests differences in face scanning in individuals with different socio-behavioural characteristics. Cornelia de Lange syndrome (CdLS) and Rubinstein-Taybi syndrome (RTS) are two genetically defined neurodevelopmental disorders with unique profiles of social behaviour., Methods: Here, we examine eye gaze to the eye and mouth regions of neutrally expressive faces, as well as the spontaneous visual preference for happy and disgusted facial expressions compared to neutral faces, in individuals with CdLS versus RTS., Results: Results indicate that the amount of time spent looking at the eye and mouth regions of faces was similar in 15 individuals with CdLS and 17 individuals with RTS. Both participant groups also showed a similar pattern of spontaneous visual preference for emotions., Conclusions: These results provide insight into two rare, genetically defined neurodevelopmental disorders that have been reported to exhibit contrasting socio-behavioural characteristics and suggest that differences in social behaviour may not be sufficient to predict attention to the eye region of faces. These results also suggest that differences in the social behaviours of these two groups may be cognitively mediated rather than subcortically mediated.

At any given moment, our awareness of what we 'see' before us seems to be rather limited. If, for instance, a display containing multiple objects is shown (red or green disks), when one object is suddenly covered at random, observers are often little better than chance in reporting about its colour (Wolfe, Reinecke, & Brawn, Visual Cognition, 14, 749-780, 2006). We tested whether, when object attributes (such as colour) are unknown, observers still retain any knowledge of the presence of that object at a display location. Experiments 1-3 involved a task requiring two-alternative (yes/no) responses about the presence or absence of a colour-defined object at a probed location. On this task, if participants knew about the presence of an object at a location, responses indicated that they also knew about its colour. A fourth experiment presented the same displays but required a three-alternative response. This task did result in a data pattern consistent with participants' knowing more about the locations of objects within a display than about their individual colours. However, this location advantage, while highly significant, was rather small in magnitude. Results are compared with those of Huang (Journal of Vision, 10(10, Art. 24), 1-17, 2010), who also reported an advantage for object locations, but under quite different task conditions.

The biogenesis and positioning of organelles involves complex interacting processes and precise control. Progress in our understanding is being made rapidly as advances in analysing the nuclear and organellar genome and proteome combine with developments in live-cell microscopy and manipulation at the subcellular level. This paper introduces the collected papers resulting from Organelle Biogenesis and Positioning in Plants, the 2009 Biochemical Society Annual Symposium. Including papers on the nuclear envelope and all major organelles, it considers current knowledge and progress towards unifying themes that will elucidate the mechanisms by which cells generate the correct complement of organelles and adapt and change it in response to environmental and developmental signals.

Controlled movement of the nucleus is important in a wide variety of plant cellular events. Positioning involving intact nuclei occurs in cell division, development, tip growing systems such as the root hair and in response to stimuli, including light, touch and infection. Positioning is also essential in the division and replication of nuclear components, ranging from chromosome attachment to the breakdown and reformation of the nuclear envelope. Although description and understanding of the processes involved have advanced rapidly in recent years, significant gaps remain in our knowledge, especially concerning nuclear proteins involved in anchoring and interacting with cytoskeletal and nucleoskeletal elements involved in movement. In the present review, processes involving the movement and positioning of nuclei and nuclear components are described together with novel proteins implicated in nucleoskeletal and cytoskeletal interactions.

Recent progress in understanding the plant NE (nuclear envelope) has resulted from significant advances in identifying and characterizing the protein constituents of the membranes and nuclear pores. Here, we review recent findings on the membrane integral and membrane-associated proteins of the key domains of the NE, the pore domain and inner and outer NEs, together with information on protein targeting and NE function.

Sad1/UNC-84 (SUN)-domain proteins are inner nuclear membrane (INM) proteins that are part of bridging complexes linking cytoskeletal elements with the nucleoskeleton, and have been shown to be conserved in non-plant systems. In this paper, we report the presence of members of this family in the plant kingdom, and investigate the two Arabidopsis SUN-domain proteins, AtSUN1 and AtSUN2. Our results indicate they contain the highly conserved C-terminal SUN domain, and share similar structural features with animal and fungal SUN-domain proteins including a functional coiled-coil domain and nuclear localization signal. Both are expressed in various tissues with AtSUN2 expression levels relatively low but upregulated in proliferating tissues. Further, we found AtSUN1 and AtSUN2 expressed as fluorescent protein fusions, to localize to and show low mobility in the nuclear envelope (NE), particularly in the INM. Deletion of various functional domains including the N terminus and coiled-coil domain affect the localization and increase the mobility of AtSUN1 and AtSUN2. Finally, we present evidence that AtSUN1 and AtSUN2 are present as homomers and heteromers in vivo, and that the coiled-coil domains are required for this. The study provides evidence suggesting the existence of cytoskeletal-nucleoskeletal bridging complexes at the plant NE.