In Vitro Antiviral Activity of Hyperbranched Poly-L-Lysine Modified by L-Arginine against Different SARS-CoV-2 Variants.

The emergence of SARS-CoV-2 variants requires close monitoring to prevent the reoccurrence of a new pandemic in the near future. The Omicron variant, in particular, is one of the fastest-spreading viruses, showing a high ability to infect people and evade neutralization by antibodies elicited upon infection or vaccination. Therefore, the search for broad-spectrum antivirals that can inhibit the infectious capacity of SARS-CoV-2 is still the focus of intense research. In the present work, hyperbranched poly-L-lysine nanopolymers, which have shown an excellent ability to block the original strain of SARS-CoV-2 infection, were modified with L-arginine. A thermal reaction at 240 °C catalyzed by boric acid yielded Lys-Arg hyperbranched nanopolymers. The ability of these nanopolymers to inhibit viral replication were assessed for the original, Delta, and Omicron strains of SARS-CoV-2 together with their cytotoxicity. A reliable indication of the safety profile and effectiveness of the various polymeric compositions in inhibiting or suppressing viral infection was obtained by the evaluation of the therapeutic index in an in vitro prevention model. The hyperbranched L-arginine-modified nanopolymers exhibited a twelve-fold greater therapeutic index when tested with the original strain. The nanopolymers could also effectively limit the replication of the Omicron strain in a cell culture.

Suicidality Treatment Occurring in Paediatrics (STOP) Medication Suicidality Side Effects Scale in young people in two cohorts across Europe.

OBJECTIVES: As part of the 'Suicidality: Treatment Occurring in Paediatrics (STOP)' study, we developed and performed psychometric validation of an electronic-clinical-outcome-assessment (eCOA), which included a patient-reported-outcome (ePRO), an observer-rated-outcome (eObsRO) for parents/carers and a clinician-reported-outcome (eClinRO) that allows identification and monitoring of medication-related suicidality (MRS) in adolescents. DESIGN: STOP: Prospective study: A two phase validation study to assess the impact of medication on suicidal ideations. SETTING: Six participating countries: Netherlands, UK, Germany, France, Spain and Italy that were part of the Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 261411. PARTICIPANTS: Cohort 1 consisted of 41 adolescent-completions, 50 parent-completions and 56 clinician-completions. Cohort 2 consisted of 244 adolescent-completions, 198 parent-completions and 240 clinician-completions from across the six countries. The scale was administered only to participants who have screened positive for the STOP-Suicidality Assessment Scale (STOP-SAS). RESULTS: A total of 24 items for the development of the STOP-Medication Suicidality Side Effects Scale (STOP-MS3) were identified and three versions (for patients, parents and clinicians) of the STOP-MS3 were developed and validated in two separate study cohorts comprising of adolescents, their parents and clinicians. Cronbach's α coefficients were above 0.85 for all domains. The inter-rater reliability of the STOP-MS3 was good and significant for the adolescent (ePRO), clinician (eClinRO) (r=0.613), parent (eObsRO) versions of the scale (r=0.394) and parent and clinician (r=0.347). Exploratory factor analysis identified a 3-factor model across 24 items for the adolescent and parent version of the scale: (1) Emotional Dysregulation, (2) Somatic Dysregulation and (3) Behavioural Dysregulation. For the clinician version, a 4-factor model defined the scale structure: (1) Somatic Dysregulation, (2) Emotional Dysregulation, (3) Behavioural Dysregulation and (4) Mood Dysregulation. CONCLUSION: These findings suggest that the STOP-MS3 scale, a web-based eCOA, allows identification and monitoring of MRS in the adolescent population and shows good reliability and validity.

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.

BACKGROUND/OBJECTIVES: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. SUBJECTS/METHODS: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. RESULTS: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS -0.03 cm (-0.05 to -0.008); PW -0.03 cm (-0.05 to -0.01); RWT -0.02 cm (-0.04 to -0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. CONCLUSIONS: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

Development and Psychometric Properties of the Multi-System Profile of Symptoms Scale in Patients with Rett Syndrome.

Background: Rett Syndrome (RTT) is a rare, neurodevelopmental disorder characterised by a range of problematic symptoms. There is yet to be a robust instrument to adequately capture the range of disease severity across the lifespan. In this study, we aimed to develop and assess the validity of an RTT-specific electronic Observer Reported Outcome (eObsRO), the Multi-System Profile of Symptoms Scale (MPSS). Methods: The study was conducted in two phases. Phase 1 consisted of a systematic literature review, focus groups, expert feedback, and a pilot test of the new scale. Modifications were made based on preliminary analysis and feedback collected in the pilot phase. Phase 2 consisted of the validation of the questionnaire based on two samples (Sample 1, n = 18; Sample 2, n = 106). Participants were all parents or caregivers of individuals with RTT. Results: The MPSS consists of 12 validated sub-scales (mental health problems, autonomic problems, cardiac problems, communication problems, problems in social behaviour, problems in engagement, gastrointestinal problems, problems in motor skills, neurological problems, orofacial problems, respiratory problems, and sleep problems), which explore symptom frequency in the past month and a supplement to the scale consisting of five sub-scales (sensory problems, immune dysfunction and infection, endocrine problems, skeletal problems, and dermatological problems), which is designed to capture symptom changes over a longer time period. The frequency of symptoms was rated on a 10-point slider scale, which then was automatically transformed into a 0 to 5 Likert score. All 12 sub-scales showed strong internal consistency (α ≥ 0.700) and good stability, ranging from 0.707 to 0.913. Pearson's correlation showed a statistically significant (r = 0.649) correlation between the MPSS and the Rett Syndrome Behaviour Questionnaire (RSBQ) total score and significant correlations between sub-scales with items that were presented in both the MPSS and RSBQ. Conclusions: The MPSS is a psychometrically validated eObsRO using the HealthTrackerTM platform and has the potential to be used in clinical trials.

An Observational Study of Heart Rate Variability Using Wearable Sensors Provides a Target for Therapeutic Monitoring of Autonomic Dysregulation in Patients with Rett Syndrome.

Rett Syndrome (RTT) is a complex neurodevelopmental disorder that has multi-system involvement with co-occurring epilepsy, breathing problems and autonomic dysregulation. Autonomic dysregulation can increase the risk of cardiorespiratory vulnerability in this patient group. Assessment of heart rate variability (HRV) provides an overview of autonomic health in RTT and offers insight into how the sympathetic and parasympathetic components of the nervous system function. However, to our knowledge, no study has evaluated HRV in Rett patients to assess how the dynamics of autonomic function vary with age and changes during the day and/or night. Using non-invasive wearable sensors, we measured HRV in 45 patients with RTT and examined the time and frequency domain sympathetic and parasympathetic indices. Among the HRV indices assessed, heart rate decreases with age and is lower in the night across all ages studied. The sympathetic index (SDNN) and the parasympathetic indices (RMSSD and pNN50) are not seen to change with age. Nevertheless, these indices were all higher during the day when compared to the night. Our findings appear to show that Rett patients are less adaptable to autonomic changes during the night. In the clinical setting, this might be more relevant for patients with severe psychopathology.

Highly Photostable Carbon Dots from Citric Acid for Bioimaging.

Bioimaging supported by nanoparticles requires low cost, highly emissive and photostable systems with low cytotoxicity. Carbon dots (C-dots) offer a possible solution, even if controlling their properties is not always straightforward, not to mention their potentially simple synthesis and the fact that they do not exhibit long-term photostability in general. In the present work, we synthesized two C-dots starting from citric acid and tris (hydroxymethyl)-aminomethane (tris) or arginine methyl ester dihydrochloride. Cellular uptake and bioimaging were tested in vitro using murine neuroblastoma and ovine fibroblast cells. The C-dots are highly biocompatible, and after 24 h of incubation with the cells, 100% viability was still observed. Furthermore, the C-dots synthesized using tris have an average dimension of 2 nm, a quantum yield of 37%, high photostability and a zeta potential (ζ) around -12 mV. These properties favor cellular uptake without damaging cells and allow for very effective bioimaging.

Cohort profile: demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe.

PURPOSE: The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. PARTICIPANTS: Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. FINDINGS TO DATE: This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. FUTURE PLANS: Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. TRIAL REGISTRATION NUMBER: NCT03013595.

Emotional Behavioural and Autonomic Dysregulation (EBAD) in Rett Syndrome - EDA and HRV monitoring using wearable sensor technology.

BACKGROUND: Rett syndrome (RTT) is a severe genetic neurodevelopmental disorder. Emotional, Behavioural and Autonomic Dysregulation (EBAD), is frequent in RTT and is associated with multiple impairments. There are major challenges in the clinical assessment of emotions, behaviours, and autonomic function in RTT patients that limit the management of symptoms. METHODS: Web-based technology (HealthTracker™) to measure the phenotype, and non-invasive, wearable sensor technology to evaluate autonomic function through Electrodermal Activity (EDA) and Heart Rate Variability (HRV) in 10 RTT patients was used, and treatment response of EBAD symptoms was monitored after different pharmacological treatments. RESULTS: and discussion: 4 patients received buspirone, 2 sertraline, 1 gabapentin and 3 were not started on medications. Buspirone normalized the EDA in 3 patients with associated improvement in EBAD, whilst another patient only improved marginally. Both patients treated with sertraline (including one with normal EDA) significantly improved symptomatically. The patients on unchanged regimens showed no change in symptoms and autonomic function. Within 24 h of our assessment, one patient required intensive inpatient care due to septicaemia - this patient had been on gabapentin and showed a sharp and sustained EDA increase without obvious worsening of emotional and behavioural symptoms. Unlike the EDA, the analyses of HRV metrics did not reveal patterns that were associated with clinical outcomes. Our findings suggest a reasonable association of EDA normalization and symptomatic improvement in RTT subjects with EBAD treated with buspirone and point out its potential application as a measure of dysautonomia in RTT. Very high and sustained EDA levels may be a biomarker for concurrent serious physical illness in RTT.

Development and Psychometric Properties of a New Questionnaire to Assess Mental Health and Concerning Behaviors in Children and Young People with Autism Spectrum Disorder (ASD): The Assessment of Concerning Behavior (ACB) Scale.

Although 70% of autistic children and young people meet criteria for co-occurring psychiatric conditions, there are few screening measures specifically for autistic individuals. We describe the development and validation of the Assessment of Concerning Behavior (ACB), an instrument co-developed with the autistic community to assess mental health and problematic/risky behaviors. Items include descriptions to facilitate symptom recognition by autistic people, and carers/professionals. The ACB was completed by 255 parents, 149 autistic children and young people and 30 teachers. Internal consistency, stability and validity was assessed. The ACB parent-version fit a two-factor model (internalizing and externalizing problems) and showed adequate test-retest reliability, internal consistency and construct validity. The ACB is a promising new measure for research and clinical use in autism.

Surgical treatment of diastasis recti: the importance of an overall view of the problem.

PURPOSE: Diastasis recti (DR) is characterized by an alteration of the linea alba with increased inter-recti distance (IRD). It is more frequent in females, and when symptomatic or associated with midline hernia it needs to be surgically repaired. This retrospective study aims to demonstrate how an overall approach to DR leads to good results in terms of functional and morphological outcomes and quality of life (QoL). METHODS: From January 2018 to December 2019, 94 patients were operated for DR > 50 mm, with or without midline hernias. Three different surgical approaches were used: complete laparoabdominoplasty, laparominiabdominoplasty and minimally invasive (endoscopic) technique. QoL was assessed with the EuraHS-QoL tool. RESULTS: All patients were female except two males. We performed 26 endoscopic treatments (27.7%), 39 laparoabdominoplasties (41.5%) and 29 laparominiabdominoplasties (umbilical float procedure) (30.9%). The total median operative time was 160 min. No intraoperative complications were registered. In three (4.2%) cases, major surgical complications occurred, all after open operations. In 13 open surgery cases, vacuum-assisted closure (VAC) therapy was used to repair the cutaneous ischemic defect. No recurrence was registered to date. Minimally invasive surgery showed fewer complications and lower hospital stay than the open approach. The QoL was significantly improved. CONCLUSION: Our experience shows the importance of an overall view of the functional and cosmetic impairment created by DR. The surgeon should obtain an optimal repair of the function, by open or minimally invasive surgery, also considering the morphological aspects, which are very important for the patients in terms of QoL.

Differentiating Females with Rett Syndrome and Those with Multi-Comorbid Autism Spectrum Disorder Using Physiological Biomarkers: A Novel Approach.

This study explored the use of wearable sensor technology to investigate autonomic function in children with autism spectrum disorder (ASD) and Rett syndrome (RTT). We aimed to identify autonomic biomarkers that can correctly differentiate females with ASD and Rett Syndrome using an innovative methodology that applies machine learning approaches. Our findings suggest that we can predict (95%) the status of ASD/Rett. We conclude that physiological biomarkers may be able to assist in the differentiation between patients with RTT and ASD and could allow the development of timely therapeutic strategies.

Validation of the Transition Readiness and Appropriateness Measure (TRAM) for the Managing the Link and Strengthening Transition from Child to Adult Mental Healthcare in Europe (MILESTONE) study.

OBJECTIVE: Young people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16-18 years of age in Europe). The objective of this study was to develop and validate the Transition Readiness and Appropriateness Measure (TRAM) for assessing a young person's readiness for transition, and their outcomes at the transfer boundary. DESIGN: MILESTONE prospective study. SETTING: Eight European Union (EU) countries participating in the EU-funded MILESTONE study. PARTICIPANTS: The first phase (MILESTONE validation study) involved 100 adolescents (pre-transition), young adults (post-transition), parents/carers and both CAMHS and AMHS clinicians. The second phase (MILESTONE cohort study and nested cluster randomised trial) involved over 1000 young people. RESULTS: The development of the TRAM began with a literature review on transitioning and a review of important items regarding transition by a panel of 34 mental health experts. A list of 64 items of potential importance were identified, which together comprised the TRAM. The psychometric properties of the different versions of the TRAM were evaluated and showed that the TRAM had good reliability for all versions and low-to-moderate correlations when compared with other established instruments and a well-defined factor structure. The main results of the cohort study with the nested cluster randomised trial are not reported. CONCLUSION: The TRAM is a reliable instrument for assessing transition readiness and appropriateness. It highlighted the barriers to a successful transition and informed clinicians, identifying areas which clinicians on both sides of the transfer boundary can work on to ease the transition for the young person. TRIAL REGISTRATION NUMBER: ISRCTN83240263 (Registered 23 July 2015), NCT03013595 (Registered 6 January 2017); Pre-results.

A structured medication review tool to promote psychotropic medication optimisation for adults with intellectual disability: feasibility study.

OBJECTIVES: To investigate the feasibility of delivering structured psychotropic medication review in community services for adults with intellectual disability (ID). DESIGN: Single-arm feasibility study conducted over a 6-month period. SETTING: Specialist community ID teams in England. PARTICIPANTS: Psychiatrists working with adults with ID and adults with ID who had been prescribed psychotropic medication. INTERVENTION: A structured web-based psychotropic medication review tool (the HealthTracker-based structured medication review) comprising measures of therapeutic benefit and adverse side-effects was made available for use by psychiatrists in routine clinic appointments. A summary measure of medication effectiveness was graphically presented to aid discussion and decision-making. MAIN OUTCOME MEASURES: Feasibility metrics including number of people with ID referred, eligible and recruited, and uptake of the medication review tool in naturalistic clinical settings. Psychiatrist and patient feedback was collected to assess acceptability of the intervention and suggestions for development. RESULTS: Fifteen psychiatrists from five clinical teams took part. In total 94 potentially eligible people with ID were referred, of whom 79 (84%) were recruited and together underwent 97 medication reviews over the 6-month study period. Feedback from participants with ID was favourable. Psychiatrists indicated that the HealthTracker-based structured medication review was broadly acceptable and suggested adaptations to improve integration with existing information technology systems and to enhance patient involvement in the review. CONCLUSIONS: Structured psychotropic medication review can be used in community services for adults with ID as part of a programme of medication optimisation. It would be feasible to test clinical and patient outcomes of the HealthTracker-based medication review in a randomised clinical trial.

Totally Endoscopic Sublay Anterior Repair for Ventral and Incisional Hernias.

BACKGROUND: Endoscopic technique is a valid and safe approach for the treatment of abdominal wall defects. To combine the advantages of complete endoscopic extraperitoneal surgery with those of sublay mesh repair we propose Totally Endoscopic Sublay Anterior Repair (TESAR) a safe and feasible approach for the treatment of ventral and incisional midline hernias. METHODS: From May to November 2018, 12 patients were referred to our unit for clinical and radiological diagnosis of midline ventral or incisional hernia and selected for TESAR. Exclusion criteria were: complicated ventral or incisional hernia (i.e., incarcerated hernia), maximum defect width >7 cm, and contraindications to general anesthesia. RESULTS: All procedures were completed with endoscopic approach, with no conversion to laparoscopy or open surgery. No intraoperative complications were registered. Total mean operative time was 148 ± 18.5 minutes. No postoperative major complications were registered. Only one subcutaneous seroma was registered (8.3%) and treated conservatively. The mean postoperative stay was 2.6 ± 0.6 days. CONCLUSIONS: TESAR is a safe and feasible technique for the extraperitoneal sublay repair of ventral hernias with a totally endoscopic approach. It provides accurate hernia repair with good outcomes in terms of resolution of symptoms and postoperative complications.

Tactile distance illusions reflect a coherent stretch of tactile space.

Illusions of the perception of distance between two touches on the skin have been described since the classic work of Weber in the 19th century. The perceptual mechanisms underlying such spatial distortions, however, remain poorly understood. One potential interpretation is that the representational space of touch is related to the true structure of the skin by a geometrically simple stretch. If distortions of tactile distance perception reflect a simple stretch of tactile space, perceived distance should vary predictably as a function of the orientation of the stimulus on the skin, showing a sinusoidal pattern. Here, we tested this prediction by obtained judgments of perceived tactile distance for pairs of touches aligned with eight orientations on the skin. Across four experiments, the results were highly consistent with this prediction, showing no apparent deviation from a model of simple stretch of tactile space. Similar results were apparent on both the dorsum and palm of the hand, as well as the forehead. These results show that spatial distortions of touch are well characterized by a geometrically simple stretch of tactile space.

Development of the Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database and the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire.

INTRODUCTION: Rett syndrome (RTT) is a pervasive neurodevelopmental disorder that presents with deficits in brain functioning leading to language and learning regression, characteristic hand stereotypies and developmental delay. Different mutations in the gene implicated in RTT-methyl-CpG-binding protein 2 (MECP2) establishes RTT as a disorder with divergent symptomatology ranging from individuals with severe to milder phenotypes. A reliable and single multidimensional questionnaire is needed that can embrace all symptoms, and the relationships between them, and can map clinically meaningful data to symptomatology across the lifespan in patients with RTT. As part of the HealthTracker-based Tailored Rett Intervention and Assessment Longitudinal (TRIAL) database, the Rett Evaluation of Symptoms and Treatments (REST) Questionnaire will be able to marry with the physiological aspects of the disease obtained using wearable sensor technology, along with genetic and psychosocial data to stratify patients. Taken together, the web-based TRIAL database will empower clinicians and researchers with the confidence to delineate between different aspects of disorder symptomatology to streamline care pathways for individuals or for those patients entering clinical trials. This protocol describes the anticipated development of the REST questionnaire and the TRIAL database which links with the outcomes of the wearable sensor technology, and will serve as a barometer for longitudinal patient monitoring in patients with RTT. METHODS AND ANALYSIS: The US Food and Drug Administration Guidance for Patient-Reported Outcome Measures will be used as a template to inform the methodology of the study. It will follow an iterative framework that will include item/concept identification, item/concept elicitation in parent/carer-mediated focus groups, expert clinician feedback, web-based presentation of questionnaires, initial scale development, instrument refinement and instrument validation. ETHICS AND DISSEMINATION: The study has received favourable opinion from the National Health Service (NHS) Research Ethics Committee (REC): NHS Research Ethics Committee (REC)-London, Bromley Research Ethics Committee (reference: 15/LO/1772).

Pediatric Antipsychotic Use and Outcomes Monitoring.

Antipsychotic (ATP) prescription rates have increased in children and adolescents despite concern regarding the safety and effectiveness of ATP usage in community populations. Rising safety concerns and uncertainty regarding ATP effectiveness in children stress the need for improvement in routine clinical outcome monitoring and research. Due to the growing number of children exposed to atypical ATPs, studies assessing the risk/benefit ratio of administering ATPs in this age group-especially in off-label conditions-become of high importance. The Centre for Interventional Pediatric Psychopharmacology and Rare Diseases (CIPPRD) uses a suite of instruments to monitor outcomes using the web-based HealthTracker™, a health monitoring platform. The HealthTracker allows for capture of symptoms, side effects, quality of life, patient experience, and lifetime response to individualized treatments using a multi-informant multimodal methodology. It enables the tracking of ongoing medical treatments and assists in shared treatment decision-making, longitudinal patient centered outcome monitoring, and helps optimize care. An example of its use in the CIPPRD is provided to demonstrate how it can be used for ATP-related outcome monitoring in complex neurodisability within routine clinical practice.

Development and psychometric properties of the parent version of the Profile of Neuropsychiatric Symptoms (PONS) in children and adolescents.

BACKGROUND: The use of neuropsychiatric Patient Centred Outcome Measures (PCOMs) in routine child mental health and paediatric services is very time consuming and often requires multiple scales being completed as no single scale covers all areas of psychopathology. The use of a web-based programme can overcome these problems and contribute to improved use of PCOMs in clinical practice. We aim to develop a web-based scale (using HealthTracker™) to screen and identify young people with significant neuropsychiatric symptoms to enable early intervention. METHODS: Qualitative development of the Profile of Neuropsychiatric Symptoms (PONS) and quantitative evaluation of the psychometric properties of the PONS scale (parent version). Parents of 929 from the general population and 147 with neuropsychiatric disorders (5-18 years old) completed the PONS online. In addition, those children with neuropsychiatric disorders were assessed for the presence of current and lifetime psychiatric disorders using the Development and Well-Being Assessment (DAWBA). RESULTS: The PONS scale (parent version) consists of 30 symptom domains rated on a 7-point scale for both frequency and impairment. We found an intra-class correlation coefficient for single measures was 0.44 (0.42-0.46 95 % CI, F = 22.84, p ≤ 0.0001) and for average measures was 0.96 (0.95-0.96 95 % CI, F = 22.84, p ≤ 0.0001). The factor analysis showed a 4-factor model: Neurodevelopmental Disability; Behavioural and Emotional Dysregulation; Psychoses and Personality Dysfunction; and Anxiety and Depression. The receiver operating characteristic area for the 4-factors was 0.96 (SE = 0.006; 0.95-0.97 95 % CI). CONCLUSIONS: The PONS scale (parent version) is a web-based PCOM on the HealthTracker™ system that is a rapid, engaging measure that has excellent reliability and validity. The system allows for automated scoring and immediate feedback of statistical cut-off points and assists clinicians with diagnostic decision-making and optimises use of clinician time.

Motor imagery in spinal cord injury patients: moving makes the difference.

Both real action control and execution and motor imagery abilities require knowledge of the spatial location of body parts, in other words efference copy information and feedbacks from the sensory system (Frith et al., 2000, Philos. Trans. R. Soc. Lond. B. Biol. Sci., 355, 1771). Spinal cord injuries induce severe motor disability, due to a damage of the descending motor pathways (Cramer et al., 2007, Exp. Brain. Res., 177, 233). Patients' motor imagery competences are variably reported as either normal or defective (Decety & Boisson, 1990, Eur. Arch. Psychiatry Clin. Neurosci., 240, 39; Lacourse et al., 1999, Behav. Brain Sci., 104, 73). We explored biomechanical constraint effects in Spinal Cord Injury (SCI) patients, as they are considered the most reliable indexes of motor imagery abilities (Parsons, 1987b, Cogn. Psychol., 19, 178). Sixteen spinal cord injuries patients and 16 neurologically unimpaired subjects have been administered with (1) the Hand Laterality Task (HLT), in which subjects were asked to judge the laterality of a rotated hand; and (2) the Mirror Letter Discrimination Task (MLD), in which subjects were asked to judge if a rotated character was in its correct upright position or mirror-reversed form. Our patients did not present the effect of stimulus orientation, neither did they show any effect related to biomechanical constraints. Based on these data, the hypothesis is that SCI patients' performance may be ascribed to the use of a different strategy to solve the tasks, based on memory rather than on mental rotation.

Vestibular modulation of spatial perception.

Vestibular inputs make a key contribution to the sense of one's own spatial location. While the effects of vestibular stimulation on visuo-spatial processing in neurological patients have been extensively described, the normal contribution of vestibular inputs to spatial perception remains unclear. To address this issue, we used a line bisection task to investigate the effects of galvanic vestibular stimulation (GVS) on spatial perception, and on the transition between near and far space. Brief left-anodal and right-cathodal GVS or right-anodal and left-cathodal GVS were delivered. A sham stimulation condition was also included. Participants bisected lines of different lengths at six distances from the body using a laser pointer. Consistent with previous results, our data showed an overall shift in the bisection bias from left to right as viewing distance increased. This pattern suggests leftward bias in near space, and rightward bias in far space. GVS induced strong polarity dependent effects in spatial perception, broadly consistent with those previously reported in patients: left-anodal and right-cathodal GVS induced a leftward bisection bias, while right-anodal and left-cathodal GVS reversed this effect, and produced bisection bias toward the right side of the space. Interestingly, the effects of GVS were comparable in near and far space. We speculate that vestibular-induced biases in space perception may optimize gathering of information from different parts of the environment.