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Atrial fibrillation is the most common type of cardiac arrhythmias in humans, mostly caused by hyper excitation of specific areas in the atrium resulting in dyssynchronous atrial contractions, leading to severe consequences such as heart failure and stroke. Current therapeutics aim to target this condition through both pharmacological and non-pharmacological approaches. To test and validate any of these treatments, an appropriate preclinical model must be carefully chosen to refine and optimise the therapy features to correctly reverse this condition. A broad range of preclinical models have been developed over the years, with specific features and advantages to closely mimic the pathophysiology of atrial fibrillation. In this review, currently available models are described, from traditional animal models and in vitro cell cultures to state-of-the-art organoids and organs-on-a-chip. The advantages, applications and limitations of each model are discussed, providing the information to select the appropriate model for each research application. [ABSTRACT FROM AUTHOR]

Neurodegeneration is hallmarked by the progressive loss of dopaminergic neurons and/or a significant increase in protein aggregates in the brain. Neurodegenerative diseases are a leading cause of death worldwide with over 15 million people currently suffering from either Parkinson's disease (PD) or Alzheimer's disease (AD). PD is often characterized by both motor and non-motor symptoms, including muscle rigidity, tremors and bradykinesia, with AD displaying symptoms of confusion and dementia. The current mainstay of therapeutics includes pharmacological approaches such as levodopa to replace dopamine in PD patients, deep brain stimulation in affected regions of the brain and physical therapy. However, these treatments are typically not disease-modifying, though they do help at least for some time with symptom management. These treatments often also fail due to their inability to cross the blood–brain barrier. There is a need to develop new strategies to target neurodegeneration in an ever-ageing population. First, we review the current PD and AD treatments and their limitations. Second, we review the current use of extracellular vesicles (EVs), cell-penetrating peptides (CPPs) and miRNAs as neuroprotective agents. Finally, we discuss the possibility of exploiting these as a combinatory therapeutic, alongside some potential drawbacks. [ABSTRACT FROM AUTHOR]

Background: Irreversible electroporation has emerged as a new modality to overcome issues associated with other energy sources for cardiac ablation. Strong evidence on the optimal, effective, and selective voltage threshold is lacking for both in vitro and preclinical in vivo studies. The aim of this study is to examine the optimal threshold for selective cell ablation on cardiac associated cell types. Methods: Conventional monophasic and biphasic pulses of different field strength were delivered in a monolayer culture system of cardiomyocytes, neurons, and adipocytes. The dynamics of cell death mechanisms were examined at different time points. Results: Neurons exhibit higher susceptibility to electroporation and cell death at higher field strength of 1250 V/cm in comparison to cardiomyocytes. Cardiac adipocytes showed lower susceptibility to electroporation in comparison to other cell types. A significant proportion of cardiomyocytes recovered after 24 h postelectroporation, while neuronal cell death remained consistent but with a significant delayed cell death at a higher voltage threshold. Caspase 3/7 activity was observed in both cardiomyocytes and neurons, with a higher level of activity in cardiomyocytes in response to electroporation. Biphasic and monophasic pulses showed no significant difference in both cell types, and significantly lower cell death in neurons when inter pulse interval was reduced. Conclusions: This study presents important findings on the differences in the susceptibility of neurons and cardiomyocytes to irreversible electroporation. Cell type alone yielded selective and different dynamics in terms of the evolution and signaling mechanism of cell death in response to electroporation. [ABSTRACT FROM AUTHOR]

Diet behaviour is influenced by the interplay of the physical and social environment as well as macro-level and individual factors. In this study, we focus on diet behaviour at an individual level and describe the design of a behaviour change artefact to support diet behaviour change in persons with type 2 diabetes. This artefact was designed using a human-centred design methodology and the Behaviour Change Wheel framework. The designed artefact sought to support diet behaviour change through the addition of healthy foods and the reduction or removal of unhealthy foods over a 12-week period. These targeted behaviours were supported by the enabling behaviours of water consumption and mindfulness practice. The artefact created was a behaviour change planner in calendar format, that incorporated behaviour change techniques and which focused on changing diet behaviour gradually over the 12-week period. The behaviour change planner forms part of a behaviour change intervention which also includes a preparatory workbook exercise and one-to-one action planning sessions and can be customised for each participant. [ABSTRACT FROM AUTHOR]

Background: NRXN1 deletions are identified as one of major rare risk factors for autism spectrum disorder (ASD) and other neurodevelopmental disorders. ASD has 30% co-morbidity with epilepsy, and the latter is associated with excessive neuronal firing. NRXN1 encodes hundreds of presynaptic neuro-adhesion proteins categorized as NRXN1α/β/γ. Previous studies on cultured cells show that the short NRXN1β primarily exerts excitation effect, whereas the long NRXN1α which is more commonly deleted in patients involves in both excitation and inhibition. However, patient-derived models are essential for understanding functional consequences of NRXN1α deletions in human neurons. We recently derived induced pluripotent stem cells (iPSCs) from five controls and three ASD patients carrying NRXN1α+/- and showed increased calcium transients in patient neurons.Methods: In this study we investigated the electrophysiological properties of iPSC-derived cortical neurons in control and ASD patients carrying NRXN1α+/- using patch clamping. Whole genome RNA sequencing was carried out to further understand the potential underlying molecular mechanism.Results: NRXN1α+/- cortical neurons were shown to display larger sodium currents, higher AP amplitude and accelerated depolarization time. RNASeq analyses revealed transcriptomic changes with significant upregulation glutamatergic synapse and ion channels/transporter activity including voltage-gated potassium channels (GRIN1, GRIN3B, SLC17A6, CACNG3, CACNA1A, SHANK1), which are likely to couple with the increased excitability in NRXN1α+/- cortical neurons.Conclusions: Together with recent evidence of increased calcium transients, our results showed that human NRXN1α+/- isoform deletions altered neuronal excitability and non-synaptic function, and NRXN1α+/- patient iPSCs may be used as an ASD model for therapeutic development with calcium transients and excitability as readouts. [ABSTRACT FROM AUTHOR]

Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1α+/− deletions. Seven control and six NRXN1α+/− iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca2+) imaging was performed using Fluo4-AM, and the properties of Ca2+ transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1α+/− neurons. Results: NRXN1α+/− neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca2+ transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1α+/− neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1α+/− neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca2+ transients, which may facilitate the development of drug screening assays for the treatment of ASD. [ABSTRACT FROM AUTHOR]

Introduction. Freezing of gait (FoG) is a movement abnormality that presents with advancing Parkinson’s disease (PD) and is one of the most debilitating symptoms of the disease. The mainstay of nonpharmacological management of FoG is typically through external cueing techniques designed to relieve or prevent the freezing episode. Previous work shows that electrical stimulation may prove useful as a gait guidance technique, but further evidence is required. The main objective of this study was to determine whether a “fixed” rhythmic sensory electrical stimulation (sES) cueing strategy would significantly (i) reduce the time taken to complete a walking task and (ii) reduce the number of FoG episodes occurring when performing the task. Methods. 9 participants with idiopathic PD performed a self-identified walking task during both control (no cue) and cueing conditions. The self-identified walking task was a home-based daily walking activity, which was known to result in FoG for that person. A trained physiotherapist recorded the time taken to complete the walking task and the number of FoG episodes which occurred during the task. Data were analyzed by paired t-tests for both the time to complete a walking task and the number of FoG episodes occurring. Results. sES cueing resulted in a reduction in the time taken to complete a walking task and in the number of FoG episodes occurring during performance of this task by 14.23 ± 11.15% (p=0.009) and 58.28 ± 33.89% (p=0.002), respectively. Conclusions. This study shows a positive effect of “fixed” rhythmic sES on the time taken to complete a walking task and on the number of FoG episodes occurring during the task. Our results provide evidence that sES cueing delivered in a “fixed” rhythmic manner has the potential to be an effective cueing mechanism for FoG prevention. [ABSTRACT FROM AUTHOR]

Abstract: Physicochemical modification of implantable electrode systems is recognized as a viable strategy to enhance tissue/electrode integration and electrode performance in situ. In this work, a bench‐top electrochemical process to formulate anodized indium tin oxide (ITO) films with altered roughness, conducting profiles, and thickness is explored. In addition, the influence of these anodized films on neural cell adhesion, proliferation, and function indicates that anodized ITO film cytocompatibility can be altered by varying the anodization current density. Furthermore, ITO‐anodized films formed with a current density of 0.4 mA cm−2 show important primary neural cell survival, modulation of glial scar formation, and promotion of neural network activity. [ABSTRACT FROM AUTHOR]

Objective: Dietary behavior is closely connected to type 2 diabetes. The purpose of this meta-analysis was to identify behavior change techniques (BCTs) and specific components of dietary interventions for patients with type 2 diabetes associated with changes in HbA1c and body weight.Research Design and Methods: The Cochrane Library, CINAHL, Embase, PubMed, PsycINFO, and Scopus databases were searched. Reports of randomized controlled trials published during 1975-2017 that focused on changing dietary behavior were selected, and methodological rigor, use of BCTs, and fidelity and intervention features were evaluated.Results: In total, 54 studies were included, with 42 different BCTs applied and an average of 7 BCTs used per study. Four BCTs-"problem solving," "feedback on behavior," "adding objects to the environment," and "social comparison"-and the intervention feature "use of theory" were associated with >0.3% (3.3 mmol/mol) reduction in HbA1c. Meta-analysis revealed that studies that aimed to control or change the environment showed a greater reduction in HbA1c of 0.5% (5.5 mmol/mol) (95% CI -0.65, -0.34), compared with 0.32% (3.5 mmol/mol) (95% CI -0.40, -0.23) for studies that aimed to change behavior. Limitations of our study were the heterogeneity of dietary interventions and poor quality of reporting of BCTs.Conclusions: This study provides evidence that changing the dietary environment may have more of an effect on HbA1c in adults with type 2 diabetes than changing dietary behavior. Diet interventions achieved clinically significant reductions in HbA1c, although initial reductions in body weight diminished over time. If appropriate BCTs and theory are applied, dietary interventions may result in better glucose control. [ABSTRACT FROM AUTHOR]

Among Parkinson’s disease (PD) symptoms, freezing of gait (FoG) is one of the most debilitating. To assess FoG, current clinical practice mostly employs repeated evaluations over weeks and months based on questionnaires, which may not accurately map the severity of this symptom. The use of a non-invasive system to monitor the activities of daily living (ADL) and the PD symptoms experienced by patients throughout the day could provide a more accurate and objective evaluation of FoG in order to better understand the evolution of the disease and allow for a more informed decision-making process in making adjustments to the patient’s treatment plan. This paper presents a new algorithm to detect FoG with a machine learning approach based on Support Vector Machines (SVM) and a single tri-axial accelerometer worn at the waist. The method is evaluated through the acceleration signals in an outpatient setting gathered from 21 PD patients at their home and evaluated under two different conditions: first, a generic model is tested by using a leave-one-out approach and, second, a personalised model that also uses part of the dataset from each patient. Results show a significant improvement in the accuracy of the personalised model compared to the generic model, showing enhancement in the specificity and sensitivity geometric mean (GM) of 7.2%. Furthermore, the SVM approach adopted has been compared to the most comprehensive FoG detection method currently in use (referred to as MBFA in this paper). Results of our novel generic method provide an enhancement of 11.2% in the GM compared to the MBFA generic model and, in the case of the personalised model, a 10% of improvement with respect to the MBFA personalised model. Thus, our results show that a machine learning approach can be used to monitor FoG during the daily life of PD patients and, furthermore, personalised models for FoG detection can be used to improve monitoring accuracy. [ABSTRACT FROM AUTHOR]

Background: Changing diet and physical activity behaviour is one of the cornerstones of type 2 diabetes treatment, but changing behaviour is challenging. The objective of this study was to identify behaviour change techniques (BCTs) and intervention features of dietary and physical activity interventions for patients with type 2 diabetes that are associated with changes in HbA1c and body weight. Methods: We performed a systematic review of papers published between 1975-2015 describing randomised controlled trials (RCTs) that focused exclusively on both diet and physical activity. The constituent BCTs, intervention features and methodological rigour of these interventions were evaluated. Changes in HbA1c and body weight were meta-analysed and examined in relation to use of BCTs. Results: Thirteen RCTs were identified. Meta-analyses revealed reductions in HbA1c at 3, 6, 12 and 24 months of -1. 11 % (12 mmol/mol), -0.67 % (7 mmol/mol), -0.28 % (3 mmol/mol) and -0.26 % (2 mmol/mol) with an overall reduction of -0.53 % (6 mmol/mol [95 % CI -0.74 to -0.32, < 0.00001]) in intervention groups compared to control P groups. Meta-analyses also showed a reduction in body weight of -2.7 kg, -3.64 kg, -3.77 kg and -3.18 kg at 3, 6, 12 and 24 months, overall reduction was -3.73 kg (95 % CI -6.09 to -1.37 kg, = 0.002). P Four of 46 BCTs identified were associated with >0.3 % reduction in HbA1c: 'instruction on how to perform a behaviour', 'behavioural practice/rehearsal', 'demonstration of the behaviour' and 'action planning', as were intervention features 'supervised physical activity', 'group sessions', 'contact with an exercise physiologist', 'contact with an exercise physiologist and a dietitian', 'baseline HbA1c >8 %' and interventions of greater frequency and intensity. Conclusions: Diet and physical activity interventions achieved clinically significant reductions in HbA1c at three and six months, but not at 12 and 24 months. Specific BCTs and intervention features identified may inform more effective structured lifestyle intervention treatment strategies for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: The study aims were to evaluate the validity of two commercially available swimming activity monitors for quantifying temporal and kinematic swimming variables. Methods: Ten national level swimmers (5 male, 5 female; 15.3±1.3years; 164.8±12.9cm; 62.4±11.1kg; 425±66 FINA points) completed a set protocol comprising 1,500m of swimming involving all four competitive swimming strokes. Swimmers wore the Finis Swimsense and the Garmin Swim activity monitors throughout. The devices automatically identified stroke type, swim distance, lap time, stroke count, stroke rate, stroke length and average speed. Video recordings were also obtained and used as a criterion measure to evaluate performance. Results: A significant positive correlation was found between the monitors and video for the identification of each of the four swim strokes (Garmin: X2 (3) = 31.292, p<0.05; Finis:X2 (3) = 33.004, p<0.05). No significant differences were found for swim distance measurements. Swimming laps performed in the middle of a swimming interval showed no significant difference from the criterion (Garmin: bias -0.065, 95% confidence intervals -3.828–6.920; Finis bias -0.02, 95% confidence intervals -3.095–3.142). However laps performed at the beginning and end of an interval were not as accurately timed. Additionally, a statistical difference was found for stroke count measurements in all but two occasions (p<0.05). These differences affect the accuracy of stroke rate, stroke length and average speed scores reported by the monitors, as all of these are derived from lap times and stroke counts. Conclusions: Both monitors were found to operate with a relatively similar performance level and appear suited for recreational use. However, issues with feature detection accuracy may be related to individual variances in stroke technique. It is reasonable to expect that this level of error would increase when the devices are used by recreational swimmers rather than elite swimmers. Further development to improve accuracy of feature detection algorithms, specifically for lap time and stroke count, would also increase their suitability within competitive settings. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity is an essential aspect of a healthy lifestyle for both physical and mental health states. As step count is one of the most utilized measures for quantifying physical activity it is important that activity-monitoring devices be both sensitive and specific in recording actual steps taken and disregard non-stepping body movements. The objective of this study was to assess the specificity of five activity monitors during a variety of prescribed non-stepping activities. Methods: Participants wore five activity monitors simultaneously for a variety of prescribed activities including deskwork, taking an elevator, taking a bus journey, automobile driving, washing and drying dishes; functional reaching task; indoor cycling; outdoor cycling; and indoor rowing. Each task was carried out for either a specific duration of time or over a specific distance. Activity monitors tested were the ActivPAL micro™, NL-2000™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2)™, Fitbit One™ and Jawbone UP™. Participants were video-recorded while carrying out the prescribed activities and the false positive step count registered on each activity monitor was obtained and compared to the video. Results: All activity monitors registered a significant number of false positive steps per minute during one or more of the prescribed activities. The Withings™ activity performed best, registering a significant number of false positive steps per minute during the outdoor cycling activity only (P = 0.025). The Jawbone™ registered a significant number of false positive steps during the functional reaching task and while washing and drying dishes, which involved arm and hand movement (P < 0.01 for both). The ActivPAL™ registered a significant number of false positive steps during the cycling exercises (P < 0.001 for both). Conclusion: As a number of false positive steps were registered on the activity monitors during the non-stepping activities, the authors conclude that non-stepping physical activities can result in the false detection of steps. This can negatively affect the quantification of physical activity with regard to step count as an output. The Withings™ activity monitor performed best with regard to specificity during the activities of daily living tested. [ABSTRACT FROM AUTHOR]

Aim: Medium chain length-polyhydroxyalkanoate/multi-walled carbon nanotube (MWCNTs) nanocomposites with a range of mechanical and electrochemical properties were fabricated via assisted dispersion and solvent casting, and their suitability as neural interface biomaterials was investigated. Materials & methods: Mechanical and electrical properties of medium chain length-polyhydroxyalkanoate/MWCNTs nanocomposite films were evaluated by tensile test and electrical impedance spectroscopy, respectively. Primary rat mesencephalic cells were seeded on the composites and quantitative immunostaining of relevant neural biomarkers, and electrical stimulation studies were performed. Results: Incorporation of MWCNTs to the polymeric matrix modulated the mechanical and electrical properties of resulting composites, and promoted differential cell viability, morphology and function as a function of MWCNT concentration. Conclusion: This study demonstrates the feasibility of a green thermoplastic MWCNTs nanocomposite for potential use in neural interfacing applications. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity is a vitally important part of a healthy lifestyle, and is of major benefit to both physical and mental health. A daily step count of 10,000 steps is recommended globally to achieve an appropriate level of physical activity. Accurate quantification of physical activity during conditions reflecting those needed to achieve the recommended daily step count of 10,000 steps is essential. As such, we aimed to assess four commercial activity monitors for their sensitivity/accuracy in a prescribed walking route that reflects a range of surfaces that would typically be used to achieve the recommended daily step count, in two types of footwear expected to be used throughout the day when aiming to achieve the recommended daily step count, and in a timeframe required to do so. Methods: Four commercial activity monitors were worn simultaneously by participants (n = 15) during a prescribed walking route reflective of surfaces typically encountered while achieving the daily recommended 10,000 steps. Activity monitors tested were the Garmin Vivofit ™, New Lifestyles’ NL-2000 ™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2) ™, and Fitbit One ™. Results: All activity monitors tested were accurate in their step detection over the variety of different surfaces tested (natural lawn grass, gravel, ceramic tile, tarmacadam/asphalt, linoleum), when wearing both running shoes and hard-soled dress shoes. Conclusion: All activity monitors tested were accurate in their step detection sensitivity and are valid monitors for physical activity quantification over the variety of different surfaces tested, when wearing both running shoes and hard-soled dress shoes, and over a timeframe necessary for accumulating the recommended daily step count of 10,000 steps. However, it is important to consider the accuracy of activity monitors, particularly when physical activity in the form of stepping activities is prescribed as an intervention in the treatment or prevention of a disease state. [ABSTRACT FROM AUTHOR]

Technical evaluation of swimming performance is an essential factor of elite athletic preparation. Novel methods of analysis, incorporating body worn inertial sensors ( i.e. , Microelectromechanical systems, or MEMS, accelerometers and gyroscopes), have received much attention recently from both research and commercial communities as an alternative to video-based approaches. This technology may allow for improved analysis of stroke mechanics, race performance and energy expenditure, as well as real-time feedback to the coach, potentially enabling more efficient, competitive and quantitative coaching. The aim of this paper is to provide a systematic review of the literature related to the use of inertial sensors for the technical analysis of swimming performance. This paper focuses on providing an evaluation of the accuracy of different feature detection algorithms described in the literature for the analysis of different phases of swimming, specifically starts, turns and free-swimming. The consequences associated with different sensor attachment locations are also considered for both single and multiple sensor configurations. Additional information such as this should help practitioners to select the most appropriate systems and methods for extracting the key performance related parameters that are important to them for analysing their swimmers’ performance and may serve to inform both applied and research practices. [ABSTRACT FROM AUTHOR]

Wearable electronics are gaining widespread use as enabling technologies, monitoring human physical activity and behavior as part of connected health infrastructures. Attention to human factors and comfort of these devices can greatly positively influence user experience, with a subsequently higher likelihood of user acceptance and lower levels of device rejection. Here, we employ a human factors and comfort assessment methodology grounded in the principles of human-centered design to influence and enhance the design of an instrumented insole. A use case was developed and interrogated by stakeholders, experts, and end users, capturing the context of use and user characteristics for the instrumented insole. This use case informed all stages of the design process through two full design cycles, leading to the development of an initial version 1 and a later version 2 prototype. Each version of the prototype was subjected to an expert human factors inspection and controlled comfort assessment using human volunteers. Structured feedback from the first cycle of testing was the driver of design changes implemented in the version 2 prototype. This prototype was found to have significantly improved human factors and comfort characteristics over the first version of the prototype. Expert inspection found that many of the original problems in the first prototype had been resolved in the second prototype. Furthermore, a comfort assessment of this prototype with a group of young healthy adults showed it to be indistinguishable from their normal footwear. This study demonstrates the power and effectiveness of human factors and comfort assessment methodologies in influencing and improving the design of wearable devices. [ABSTRACT FROM AUTHOR]

Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications. [ABSTRACT FROM AUTHOR]

Aims: Irreversible electroporation is an ablation technique being adapted for the treatment of atrial fibrillation. Currently, there are many differences reported in the in vitro and pre-clinical literature for the effective voltage threshold for ablation. The aim of this study is a direct comparison of different cell types within the cardiovascular system and identification of optimal voltage thresholds for selective cell ablation. Methods: Monophasic voltage pulses were delivered in a cuvette suspension model. Cell viability and live–dead measurements of three different neuronal lines, cardiomyocytes, and cardiac fibroblasts were assessed under different voltage conditions. The immediate effects of voltage and the evolution of cell death was measured at three different time points post ablation. Results: All neuronal and atrial cardiomyocyte lines showed cell viability of less than 20% at an electric field of 1000 V/cm when at least 30 pulses were applied with no significant difference amongst them. In contrast, cardiac fibroblasts showed an optimal threshold at 1250 V/cm with a minimum of 50 pulses. Cell death overtime showed an immediate or delayed cell death with a proportion of cell membranes re-sealing after three hours but no significant difference was observed between treatments after 24 h. Conclusions: The present data suggest that understanding the optimal threshold of irreversible electroporation is vital for achieving a safe ablation modality without any side-effect in nearby cells. Moreover, the evolution of cell death post electroporation is key to obtaining a full understanding of the effects of IRE and selection of an optimal ablation threshold. [ABSTRACT FROM AUTHOR]

Chronic discogenic back pain is associated with increased inflammatory cytokine levels that can influence the proximal peripheral nervous system, namely the dorsal root ganglion (DRG). However, transition to chronic pain is widely thought to involve glial activation in the spinal cord. In this study, an in vitro model was used to evaluate the communication between DRG and spinal cord glia. Primary neonatal rat DRG cells were treated with/without inflammatory cytokines (TNF-α, IL-1β, and IL-6). The conditioned media were collected at two time points (12 and 24 h) and applied to spinal cord mixed glial culture (MGC) for 24 h. Adult bovine DRG and spinal cord cell cultures were also tested, as an alternative large animal model, and results were compared with the neonatal rat findings. Compared with untreated DRG-conditioned medium, the second cytokine-treated DRG-conditioned medium (following medium change, thus containing solely DRG-derived molecules) elevated CD11b expression and calcium signal in neonatal rat microglia and enhanced Iba1 expression in adult bovine microglia. Cytokine treatment induced a DRG-mediated microgliosis. The described in vitro model allows the use of cells from large species and may represent an alternative to animal pain models (3R principles). [ABSTRACT FROM AUTHOR]

Targeted cellular ablation is being increasingly used in the treatment of arrhythmias and structural heart disease. Catheter-based ablation for atrial fibrillation (AF) is considered a safe and effective approach for patients who are medication refractory. Electroporation (EPo) employs electrical energy to disrupt cell membranes which has a minimally thermal effect. The nanopores that arise from EPo can be temporary or permanent. Reversible electroporation is transitory in nature and cell viability is maintained, whereas irreversible electroporation causes permanent pore formation, leading to loss of cellular homeostasis and cell death. Several studies report that EPo displays a degree of specificity in terms of the lethal threshold required to induce cell death in different tissues. However, significantly more research is required to scope the profile of EPo thresholds for specific cell types within complex tissues. Irreversible electroporation (IRE) as an ablative approach appears to overcome the significant negative effects associated with thermal based techniques, particularly collateral damage to surrounding structures. With further fine-tuning of parameters and longer and larger clinical trials, EPo may lead the way of adapting a safer and efficient ablation modality for the treatment of persistent AF. [ABSTRACT FROM AUTHOR]

Parkinson's Disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms, among which are bradykinesia, rigidity, tremor as well as mental symptoms such as dementia. The underlying cause of Parkinson disease is degeneration of dopaminergic neurons. It has been challenging to develop an efficient animal model to accurately represent the complex phenotypes found with PD. However, it has become possible to recapitulate the myriad of phenotypes underlying the PD pathology by using human induced pluripotent stem cell (iPSC) technology. Patient-specific iPSC-derived dopaminergic neurons are available and present an opportunity to study many aspects of the PD phenotypes in a dish. In this review, we report the available data on iPSC-derived neurons derived from PD patients with identified gene mutations. Specifically, we will report on the key phenotypes of the generated iPSC-derived neurons from PD patients with different genetic background. Furthermore, we discuss the relationship these cellular phenotypes have to PD pathology and future challenges and prospects for iPSC modelling and understanding of the pathogenesis of PD. [ABSTRACT FROM AUTHOR]

Treatment of Type 2 Diabetes (T2D) typically involves pharmacological methods and adjunct behavioural modifications, focused on changing diet and physical activity (PA) behaviours. Changing diet and physical activity behaviours is complex and any behavioural intervention in T2D, to be successful, must use an appropriate suite of behaviour change techniques (BCTs). In this study, we sought to understand the perceived barriers and facilitators to diet and PA behaviour change in persons with T2D, with a view to creating artefacts to facilitate the required behaviour changes. The Design Probe was chosen as the most appropriate design research instrument to capture the required data, as it enabled participants to reflect and self-document, over an extended period of time, on their daily lived experiences and, following this reflection, to identify their barriers and facilitators to diet and PA behaviour change. Design Probes were sent to 21 participants and 13 were fully completed. A reflective thematic analysis was carried out on the data, which identified themes of food environment, mental health, work schedule, planning, social support, cravings, economic circumstances and energy associated with diet behaviour. Similar themes were identified for PA as well as themes of physical health, weather, motivation and the physical environment. [ABSTRACT FROM AUTHOR]

Aims: To examine the effect of three commercial intravesical formulations of glycosaminoglycan on in vitro inflammatory models of IC/BPS to better understand there effect on specific markers of disease. Methods: Human urothelial cells (HTB-4) were cultured under four conditions in the presence or absence of commercial GAG formulations. Cells were cultured under a basal condition or pre-treated with protamine sulfate (100 ng/ml) (damages the endogenous glycosaminoglycan layer), hydrogen peroxide (1%) (a metabolic stressor) or TNFα (10 ng/ml) (creating an inflammatory environment). Each of these four culture conditions was then treated with one of three GAG formulations, CystistatⓇ, iAluRilⓇ and HyacystⓇ. Assays were then performed to examine the effect of the exogenous GAGs on cell viability, cell migration, sGAG production, cytokine and gene expression. Results: All GAG formulations were well tolerated by the HTB-4 cells and supported cell growth and migration. iAluRilⓇ was most effective at stimulating endogenous sGAG production under all conditions, increasing sGAGs by up to 15-fold. All GAG formulations significantly reduced the production of the pro-inflammatory cytokine IL-8 under basal conditions, while no GAG treatment suppressed cytokine production under any other condition. Only CystistatⓇ had a significant effect on HA receptor expression, significantly increasing ICAM-1 expression at 3 h that returned to basal levels at 24 h. No GAG treatment significantly changed the expression of GAG synthesis enzymes (CSGALNACT1, CSGALNACT2) or markers of tissue remodeling (MMP2, TIMP1) and pain (COX-1/PTGS-1, NGF). Conclusions: The data presented in this study reveal that commercial intravesical formulation support cell viability and migration. In addition, the commercial GAG formulations have a mild anti-inflammatory effect in the in vitro model of interstitial cystitis/bladder pain syndrome. [ABSTRACT FROM AUTHOR]

Currently, 1% of the population of the Western world suffers from venous leg ulcers as a result of chronic venous insufficiency. Current treatment involves the use of moist wound healing, compression bandages, and intermittent pneumatic compression. Neuromuscular electrical stimulation is a novel potential new therapeutic method for the promotion of increased lower limb hemodynamics. The aim of this study was to measure the hemodynamic changes in the lower limb with the use of two neuromuscular electrical stimulation devices. Twelve healthy volunteers received two neuromuscular stimulation device interventions. The GekoTM and National University of Ireland (NUI) Galway neuromuscular electrical stimulation devices were randomized between dominant and non-dominant legs. Hemodynamic measurements of peak venous velocity (cm/s), the time average mean velocity (TAMEAN) (cm/s), and ejected volume (mL) of blood were recorded. Peak venous velocity was significantly increased by the GekoTM and the NUI Galway device compared to baseline blood flow (p < 0.0001), while only the voluntary contraction produced significant increases in TAMEAN and ejected volume (both p < 0.05). Neuromuscular muscular electrical stimulation can produce adequate increases in lower limb hemodynamics sufficient to prevent venous stasis. Greater use of neuromuscular stimulation devices could be considered in the treatment of conditions related to chronic venous insufficiency but requires further research. [ABSTRACT FROM AUTHOR]

Freezing of Gait (FoG) is one of the most debilitating symptoms of Parkinson's disease and is an important contributor to falls. When the management of freezing episodes cannot be achieved through medication or surgery, non-pharmacological methods, such as cueing, have emerged as effective techniques, which ameliorates FoG. The use of On-Demand cueing systems (systems that only provide cueing stimuli during a FoG episode) has received attention in recent years. For such systems, the most common method of triggering the onset of cueing stimuli, utilize autonomous real-time FoG detection algorithms. In this article, we assessed the potential of a simple double-tap gesture interaction to trigger the onset of cueing stimuli. The intended purpose of our study was to validate the use of double-tap gesture interaction to facilitate Self-activated On-Demand cueing. We present analyses that assess if PwP can perform a double-tap gesture, if the gesture can be detected using an accelerometer's embedded gestural interaction recognition function and if the action of performing the gesture aggravates FoG episodes. Our results demonstrate that a double-tap gesture may provide an effective actuation method for triggering On-Demand cueing. This opens up the potential future development of self-activated cueing devices as a method of On-Demand cueing for PwP and others. [ABSTRACT FROM AUTHOR]

Our research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson's disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson's patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient's activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician's assessment and the sensor output was analyzed with the Spearman's correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33–0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76–0.97: p < 0.001). The conclusion is that the magnitude of dyskinesia, as measured by the tested device, presented good correlation with that observed by a physician. [ABSTRACT FROM AUTHOR]

Freezing of gait is one of the most debilitating symptoms of Parkinson's disease and is an important contributor to falls, leading to it being a major cause of hospitalization and nursing home admissions. When the management of freezing episodes cannot be achieved through medication or surgery, non-pharmacological methods such as cueing have received attention in recent years. Novel cueing systems were developed over the last decade and have been evaluated predominantly in laboratory settings. However, to provide benefit to people with Parkinson's and improve their quality of life, these systems must have the potential to be used at home as a self-administer intervention. This paper aims to provide a technological review of the literature related to wearable cueing systems and it focuses on current auditory, visual and somatosensory cueing systems, which may provide a suitable intervention for use in home-based environments. The paper describes the technical operation and effectiveness of the different cueing systems in overcoming freezing of gait. The "What Works Clearinghouse (WWC)" tool was used to assess the quality of each study described. The paper findings should prove instructive for further researchers looking to enhance the effectiveness of future cueing systems. [ABSTRACT FROM AUTHOR]