Radiation from the equine perineal region is low compared with the elbow and head 24 hours after bone scintigraphic examination.

The timing of follow-up radiography and ultrasound in horses that undergo skeletal scintigraphy for lameness investigation varies internationally and between equine hospitals. The prospective, one-group, pretest, posttest study aimed to estimate radiation levels from horses three and 24 h after injection of hydroxydiphosphonate labeled with metastable technetium (99mTc-HDP) and investigate which anatomical locations of the horse had higher radiation levels. Included were 46 horses referred for lameness investigation between June and December 2021. Radiation levels from the horse surface were measured using an electronic device from six anatomical locations (head, elbow, dorsum, ventrum, stifle, and perineum) at two time points and adjusted to three and 24 h after injection of 99mTc-HDP using the radioactive decay law. The radiation measured was significantly different in the various locations of the horses for both time points. At 3 h after injection of 99mTc-HDP, the ventrum had the highest radiation dose. At 24 h, the radiation emitted from the perineal region was significantly lower (P < .0001) than from the elbow and head, which had the highest values. There was a negative correlation between age and the radiation detected at 24 h postinjection (P = .02). Radiation from the perineal region was low compared with other regions of the horse 24 h postscintigraphy. Additional care should be taken around the ventrum area during the scintigraphy examination and around the elbow and head at 24 h postscintigraphy to minimize radiation to personnel.

Intervention to reduce sedentary behaviour and improve outcomes after stroke (Get Set Go): a study protocol for the process evaluation of a pilot cluster randomised controlled trial (RECREATE).

INTRODUCTION: Stroke survivors spend long periods of time engaging in sedentary behaviour (SB) even when their functional recovery is good. In the RECREATE programme, an intervention aimed at reducing SB ('Get Set Go') will be implemented and evaluated in a pragmatic external pilot cluster randomised controlled trial with embedded process and economic evaluations. We report the protocol for the process evaluation which will address the following objectives: (1) describe and clarify causal assumptions about the intervention, and its mechanisms of impact; (2) assess implementation fidelity; (3) explore views, perceptions and acceptability of the intervention to staff, stroke survivors and their carers; (4) establish the contextual factors that influence implementation, intervention mechanisms and outcomes. METHODS AND ANALYSIS: This pilot trial will be conducted in 15 UK-based National Health Service stroke services. This process evaluation study, underpinned by the Medical Research Council guidance, will be undertaken in six of the randomised services (four intervention, two control). Data collection includes the following: observations of staff training sessions, non-participant observations in inpatient and community settings, semi-structured interviews with staff, patients and carers, and documentary analysis of key intervention components. Additional quantitative implementation data will be collected in all sites. Training observations and documentary analysis data will be summarised, with other observational and interview data analysed using thematic analysis. Relevant theories will be used to interpret the findings, including the theoretical domains framework, normalisation process theory and the theoretical framework of acceptability. Anticipated outputs include the following: recommendations for intervention refinements (both content and implementation); a revised implementation plan and a refined logic model. ETHICS AND DISSEMINATION: The study was approved by Yorkshire & The Humber - Bradford Leeds Research Ethics Committee (REC reference: 19/YH/0403). Findings will be disseminated via peer review publications, and national and international conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN82280581.

RECREATE: a study protocol for a multicentre pilot cluster randomised controlled trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations.

INTRODUCTION: Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention ('Get Set Go') was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation. METHODS AND ANALYSIS: This study is a pragmatic, multicentre, two-arm, external pilot cluster randomised controlled trial with embedded process and economic evaluations. UK-based stroke services will be randomised 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300-400 stroke inpatient and carer participants, with follow-up at 6, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living scale at 12 months. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability and how it can be optimised. ETHICS AND DISSEMINATION: The study has been approved by Yorkshire and The Humber - Bradford-Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations. TRIAL REGISTRATION NUMBER: This trial was registered prospectively on 01 April 2020 (ISRCTN ref: ISRCTN82280581).

The role of the healthcare assistant on a stroke unit: A scoping review.

OBJECTIVE: This scoping review explores the role of a healthcare assistant on a stroke unit, potential barriers to role fulfilment and whether stroke-specific training could enhance rehabilitative practice. DATA SOURCES: Searches were conducted on CINAHL, MEDLINE and APA PsycInfo in May 2021 and repeated in September 2022. METHODS: This scoping review was guided by Arksey and O'Malley's framework. Article selection and data extraction were conducted by one researcher using a structured proforma. A narrative approach to data synthesis was undertaken following the research questions. RESULTS: From a combined total of 533 articles, sixty-six full-text articles were assessed for eligibility. Sixteen full articles were included in this review. A healthcare assistants' role was viewed as caring directly for patients - some individuals felt they contributed to rehabilitation during these tasks, and that they could be undervalued by multidisciplinary team members, patients and their families. The barriers identified to healthcare assistants' role fulfilment were lack of time, training and staffing shortages. Training was perceived to improve healthcare assistants' communication, confidence and knowledge but training needed to be flexible, ward based and accommodate staffing shortages. However, it is unclear whether training has any clinical benefit for patients. CONCLUSION: Healthcare assistants are well placed to enhance rehabilitative practice with patients; however, there are clear perceived barriers to this occurring. Future research should aim to define the role of healthcare assistants and explore whether further stroke-specific training could cause clinical benefits for patients.

Systematic review of process evaluations of interventions in trials investigating sedentary behaviour in adults.

OBJECTIVES: To systematically review and synthesise findings from process evaluations of interventions in trials which measured sedentary behaviour as an outcome in adults to explore: (1) how intervention content, implementation, mechanisms of impact and context influence outcomes and (2) how these interventions are experienced from different perspectives (participants, carers, staff). DESIGN: Systematic review and narrative synthesis underpinned by the Medical Research Council process evaluation framework. DATA SOURCES: Databases searches were conducted in March 2019 then updated in May 2020 and October 2021 in: CINAHL, SPORTDiscus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, AMED; EMBASE, PsycINFO, MEDLINE, Web of Science and ProQuest Dissertations & Theses. ELIGIBILITY CRITERIA: We included: Process evaluations of trials including interventions where sedentary behaviour was measured as an outcome in adults aged 16 or over from clinical or non-clinical populations. We excluded studies if interventions were delivered in educational or workplace settings, or if they were laboratory studies focused on immediate effects of breaking sitting. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted and coded data into a framework and assessed the quality of studies using the Mixed Methods Appraisal Tool. We synthesised findings using a narrative approach. RESULTS: 17 process evaluations were included. Five interventions focused on reducing sedentary behaviour or sitting time, 12 aimed to increase physical activity or promote healthier lifestyles. Process evaluations indicated changes in sedentary behaviour outcomes were shaped by numerous factors including: barriers (eg, staffing difficulties and scheduling problems) and facilitators (eg, allowing for flexibility) to intervention delivery; contextual factors (eg, usual lifestyle and religious events) and individual factors (eg, pain, tiredness, illness, age and individual preferences). DISCUSSION: Intervention requires careful consideration of different factors that could influence changes in sedentary behaviour outcomes to ensure that interventions can be tailored to suit different individuals and groups. PROSPERO REGISTRATION NUMBER: CRD42018087403.

Proinflammatory Cytokines and Oxidative Stress Decrease the Transport of Dopamine Precursor Tyrosine in Human Fibroblasts.

BACKGROUND: Proinflammatory cytokines and oxidative stress responses have been extensively implicated in the pathophysiology of neuropsychiatric disorders over the past 2 decades. Moreover, disturbed transport of the dopamine precursor (i.e., the amino acid tyrosine) has been demonstrated, in different studies, across fibroblast cell membranes obtained from neuropsychiatric patients. However, the role and influences of proinflammatory cytokines and oxidative stress, and the reasons for disturbed tyrosine transport in neuropsychiatric disorders, are still not evaluated. AIMS: The present study aimed to assess the role of proinflammatory cytokines and oxidative stress, indicated in many neuropsychiatric disorders, in tyrosine transportation, by using human skin-derived fibroblasts. METHODS: Fibroblasts obtained from a healthy control were used in this study. Fibroblasts were treated with proinflammatory cytokines (IL-1ß, IFN-γ, IL-6, TNF-α), their combinations, and oxidative stress, optimized for concentrations and incubation time, to analyze the uptake of 14C-tyrosine compared to untreated controls. RESULTS AND CONCLUSION: This study demonstrates that proinflammatory cytokines and oxidative stress decrease the transport of tyrosine (47% and 33%, respectively), which can alter dopamine synthesis. The functionality of the tyrosine transporter could be a new potential biomarker to target for discovering new drugs to counteract the effects of proinflammatory cytokines and oxidative stress in the pathophysiology of neuropsychiatric disorders.

Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia.

Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.

Decreased binding capacity (Bmax) of muscarinic acetylcholine receptors in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD).

Monoaminergic dysregulation is implicated in attention-deficit/hyperactivity disorder (ADHD), and methylphenidate and amphetamines are the most frequently prescribed pharmacological agents for treating ADHD. However, it has recently been proposed that the core symptoms of the disorder might be due to an imbalance between monoaminergic and cholinergic systems. In this study, we used fibroblast cell homogenates from boys with and without ADHD as an extraneural cell model to examine the cholinergic receptor density, that is, muscarinic acetylcholine receptors (mAChRs). We found that the binding capacity (Bmax) of [³H] Quinuclidinyl benzilate (³H-QNB) to mAChRs was decreased by almost 50 % in the children with ADHD (mean = 30.6 fmol/mg protein, SD = 25.6) in comparison with controls [mean = 63.1 fmol/mg protein, SD = 20.5, p ≤ 0.01 (Student's unpaired t test)]. The decreased Bmax indicates a reduced cholinergic receptor density, which might constitute a biomarker for ADHD. However, these preliminary findings need to be replicated in larger ADHD and comparison cohorts.

Polycyclic aromatic hydrocarbons (PAHs) reduce hepatic ß-oxidation of fatty acids in chick embryos.

Polycyclic aromatic hydrocarbons (PAHs) are widespread fused-ring contaminants formed during incomplete combustion of almost all kind of organic materials from both natural and anthropogenic sources. Some PAHs have been shown to be carcinogenic to humans, and a wide range of PAHs are found in wildlife all around the globe including avian species. The purpose of this project was to assess the effects of a standard mixture of 16 PAHs (United States Environmental Protection Agency) on the hepatic fatty acid ß-oxidation in chicken embryos (Gallus gallus domesticus) exposed in ovo. The hepatic ß-oxidation was measured using a tritium release assay with [9,10-(3)H]-palmitic acid (16:0) as substrate. Treated groups were divided into groups of 0.05, 0.1, 0.3, 0.5, and 0.8 mg PAHs/kg egg weight. The hepatic ß-oxidation was reduced after exposure in ovo to the 16 PAHs mixture compared to control. The mechanisms causing reduced fatty acid oxidation in the present study are unclear, however may be due to deficient membrane structure, the functionality of enzymes controlling the rate of fatty acid entering into the mitochondria, or complex pathways connected to endocrine disruption. To the best of our knowledge, this is the first time a PAH-caused reduction of hepatic ß-oxidation of fatty acids in avian embryos has been observed. The implication of this finding on risk assessment of PAH exposure in avian wildlife remains to be determined.

Tryptophan transport in human fibroblast cells-a functional characterization.

There are indications that serotonergic neurotransmission is disturbed in several psychiatric disorders. One explanation may be disturbed transport of tryptophan (precursor for serotonin synthesis) across cell membranes. Human fibroblast cells offer an advantageous model to study the transport of amino acids across cell membranes, since they are easy to propagate and the environmental factors can be controlled. The aim of this study was to functionally characterize tryptophan transport and to identify the main transporters of tryptophan in fibroblast cell lines from healthy controls.Tryptophan kinetic parameters (V(max) and K(m)) at low and high concentrations were measured in fibroblasts using the cluster tray method. Uptake of (3)H (5)-L-tryptophan at different concentrations in the presence and absence of excess concentrations of inhibitors or combinations of inhibitors of amino acid transporters were also measured. Tryptophan transport at high concentration (0.5 mM) had low affinity and high V(max) and the LAT1 isoform of system-L was responsible for approximately 40% of the total uptake of tryptophan. In comparison, tryptophan transport at low concentration (50 nM) had higher affinity, lower V(max) and approximately 80% of tryptophan uptake was transported by system-L with LAT1 as the major isoform. The uptake of tryptophan at the low concentration was mainly sodium (Na(+)) dependent, while uptake at high substrate concentration was mainly Na(+) independent. A series of different transporter inhibitors had varying inhibitory effects on tryptophan uptake.This study indicates that tryptophan is transported by multiple transporters that are active at different substrate concentrations in human fibroblast cells. The tryptophan transport trough system-L was mainly facilitated by the LAT1 isoform, at both low and high substrate concentrations of tryptophan.

Altered tryptophan and alanine transport in fibroblasts from boys with attention-deficit/hyperactivity disorder (ADHD): an in vitro study.

BACKGROUND: The catecholaminergic and serotonergic neurotransmitter systems are implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). The amino acid tyrosine is the precursor for synthesis of the catecholamines dopamine and norepinephrine, while tryptophan is the precursor of serotonin. A disturbed transport of tyrosine, as well as other amino acids, has been found in a number of other psychiatric disorders, such as schizophrenia, bipolar disorder and autism, when using the fibroblast cell model. Hence, the aim of this study was to explore whether children with ADHD may have disturbed amino acid transport. METHODS: Fibroblast cells were cultured from skin biopsies obtained from 14 boys diagnosed with ADHD and from 13 matching boys without a diagnosis of a developmental disorder. Transport of the amino acids tyrosine, tryptophan and alanine across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (V(max)) and affinity constant (K(m)) were determined. Any difference between the two groups was analyzed by Student's unpaired t-test or the Mann Whitney U test. RESULTS: The ADHD group had significantly decreased V(max) (p = 0.039) and K(m) (increased affinity) (p = 0.010) of tryptophan transport in comparison to controls. They also had a significantly higher V(max)of alanine transport (p = 0.031), but the Km of alanine transport did not differ significantly. There were no significant differences in any of the kinetic parameters regarding tyrosine transport in fibroblasts for the ADHD group. CONCLUSIONS: Tryptophan uses the same transport systems in both fibroblasts and at the blood brain barrier (BBB). Hence, a decreased transport capacity of tryptophan implies that less tryptophan is being transported across the BBB in the ADHD group. This could lead to deficient serotonin access in the brain that might cause disturbances in both the serotonergic and the catecholaminergic neurotransmitter systems, since these systems are highly interconnected. The physiological importance of an elevated transport capacity of alanine to the brain is not known to date.

Numbers, biomass and cultivable diversity of microbial populations relate to depth and borehole-specific conditions in groundwater from depths of 4-450 m in Olkiluoto, Finland.

Microbiology, chemistry and dissolved gas in groundwater from Olkiluoto, Finland, were analysed over 3 years; samples came from 16 shallow observation tubes and boreholes from depths of 3.9-16.2 m and 14 deep boreholes from depths of 35-742 m. The average total number of cells (TNC) was 3.9 x 10(5) cells per ml in the shallow groundwater and 5.7 x 10(4) cells per ml in the deep groundwater. There was a significant correlation between the amount of biomass, analysed as ATP concentration, and TNC. ATP concentration also correlated with the stacked output of anaerobic most probable number cultivations of nitrate-, iron-, manganese- and sulphate-reducing bacteria, and acetogenic bacteria and methanogens. The numbers and biomass varied at most by approximately three orders of magnitude between boreholes, and TNC and ATP were positively related to the concentration of dissolved organic carbon. Two depth zones were found where the numbers, biomass and diversity of the microbial populations peaked. Shallow groundwater down to a depth of 16.2 m on average contained more biomass and cultivable microorganisms than did deep groundwater, except in a zone at a depth of approximately 300 m where the average biomass and number of cultivable microorganisms approached those of shallow groundwater. Starting at a depth of approximately 300 m, there were steep gradients of decreasing sulphate and increasing methane concentrations with depth; together with the peaks in biomass and sulphide concentration at this depth, these suggest that anaerobic methane oxidation may be a significant process at depth in Olkiluoto.