Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs

Objectives This study’s aim was to investigate the safety and performance of a self-assembling peptide matrix (SAPM) P11-4 for the treatment of periodontal disease in a controlled pre-clinical study. Materials and methods Acute buccal bony dehiscence defects (LxW: 5 × 3 mm) were surgically created on the distal root of four teeth on one mandible side of 7 beagle dogs followed by another identical surgery 8 weeks later on the contralateral side. SAPM P11-4 (with and without root conditioning with 24% EDTA (T1, T2)), Emdogain® (C) and a sham intervention (S) were randomly applied on the four defects at each time point. Four weeks after the second surgery and treatment, the animals were sacrificed, the mandibles measured by micro-computed tomography (µ-CT) and sections of the tissue were stained and evaluated histologically. Results Clinically and histologically, no safety concerns or pathological issues due to the treatments were observed in any of the study groups at any time point. All groups showed overall similar results after 4 and 12 weeks of healing regarding new cementum, functionality of newly formed periodontal ligament and recovery of height and volume of the new alveolar bone and mineral density. Conclusion A controlled clinical study in humans should be performed in a next step as no adverse effects or safety issues, which might affect clinical usage of the product, were observed. Clinical relevance The synthetic SAPM P11-4 may offer an alternative to the animal-derived product Emdogain® in the future.

The Role of RIPC in Preventing Organ Damage, Inflammation, and Oxidative Stress during Lower Limb DSA: A Randomised Controlled Trial

Objective. Diagnostic digital subtraction angiography (DSA) and DSA with percutaneous transluminal angioplasty (DSA-PTA) are common procedures for diagnosing and treating symptomatic lower extremity arterial disease (LEAD). However, organ damage following DSA and DSA-PTA is often underrecognised and hence undiagnosed. To reduce the risk induced by invasive procedures in symptomatic LEAD patients, the method of remote ischemic preconditioning (RIPC) has been suggested. The aim of the current study was to assess the effect of RIPC intervention on the organ damage markers profile, oxidative stress, and inflammation biomarkers in LEAD patients undergoing DSA and DSA-PTA procedure. Methods. The RIPC intervention was performed by inflating a standard blood pressure cuff on the patient’s upper arm to 200 mmHg for 5 minutes four times with 5-minute perfusion between each cycle. The sham intervention was performed similarly, but the cuff was inflated to 20 mmHg. Changes in the cardiac and renal damage biomarkers’ profile, oxidative stress, and inflammation biomarkers were recorded before and 24 hours after DSA or DSA-PTA. Results. A total of 111 (RIPC 54, sham 57) patients with symptomatic LEAD scheduled for endovascular procedure were randomised, and 102 patients (RIPC 47, sham 55) completed the study protocol. RIPC significantly limited the increase of adiponectine levels after DSA and DSA-PTA, compared to sham intervention ( p = 0.020 ), but CK-MB levels were markedly lower in the sham group ( p = 0.047 ) after procedure. There was no significant difference between the RIPC and the sham group in mean changes in hs-troponin-T ( p = 0.25 ), NT-proBNP ( p = 0.24 ), creatinine ( p = 0.76 ), eGFR ( p = 0.61 ), urea ( p = 0.95 ), beta-2-microglobuline ( p = 0.34 ), or cystatine C ( p = 0.24 ) levels. Conclusion. In this controlled clinical study, RIPC failed to improve the profile of renal and cardiac biomarkers in patients with LEAD periprocedurally. RIPC significantly limits the rise in adiponectin levels and may influence the decrease of CK-MB levels 24 hours after endovascular procedure.

Development and Validation of a Cloak-Shaped Device for Sham Pediatric Tuina: a Randomized Controlled Study

Background: To date, no well-recognized placebo device or procedure for pediatric Tuina (PT) has been reported. We developed a cloak-shaped device and designed an RCT to detect whether the device is effective as a placebo in PT research.Methods: It was a two-arm, parallel-group RCT design. Children were randomly assigned to the genuine Tuina or sham Tuina group at a 1:1 ratio. The genuine and sham Tuina interventions were delivered using the same standardized procedure by adopting a cloak-shaped device. The primary outcomes were the judgement rates of the type of Tuina that participants received based on caregivers’ and observers’evaluations. The analysis explored whether parents' attitude towards PT was related to their judgment rate.Results: A total of 60 participants were enrolled (37 boys [61.7%]; 16.0[2.3] months). Thirty children received genuine PT, and 30 received sham PT. There was no significant difference in parents' judgment of the interventions received between the two groups (χ2=0.65,P=0.421) or based on observers' judgments (χ2=0.07, P=0.795). In terms of parents' attitude towards PT or compliance with PT, parents whose children were in the genuine Tuina group were not significantly different from those in the sham group(z=0.01, P=0.99; z=0.34, P=0.73). Of the participants in the sham group, none of their parents recorded receiving the sham intervention.Conclusions: The placebo device for sham PT was found to be a credible control for PT. This study supports its use in prospective, sham-controlled, randomized trials.Trial registration: ClinicalTrials.gov, NCT03474172. Registered in March 2018.

Non-Invasive Brain Stimulation Modulates GABAergic Activity In Neurofibromatosis 1

BackgroundNeurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates how inter-individual differences in GABA relate to working memory and whether application of anodal transcranial direct current stimulation (atDCS) can modulate of GABA and working memory.Methods31 adolescents with NF1 were recruited to a single-blind, sham-controlled cross-over trial. Baseline assessments included detailed working memory tests and parent reported measures. Each participant had two study visits, one with atDCS and another with sham intervention applied to the left Dorsolateral Prefrontal Cortex (DLPFC) inside the scanner. Magnetic Resonance Spectroscopy was collected before and after aTDCS/sham intervention in the left DLPFC and occipital cortex.ResultsHigher baseline GABA was associated with faster response times (RT) on verbal and visuospatial working memory measures. No correlation was observed between baseline GABA and working memory accuracy. AtDCS was associated with significantly greater reduction in GABA, as compared to sham in the left DLPFC. There was no effect of atDCS on Glx in left DLPFC and no significant effect of atDCS on GABA or Glx in the occipital cortex. There was no effect of atDCS on behavioural measures of working memory.LimitationsLimitations of this study include use of brief behavioural outcome measures post tDCS chosen to reduce participant burden and the lack of a healthy control group. The GABA levels measured in this study will contain contributions from co-edited macromolecule signal (so-called GABA+), but the relative contribution of these macromolecular signals are thought to be constant unlikely to account for within participant/session GABA changes. ConclusionsThis first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. This focussed mechanism trial presents a highly promising approach to understanding complex neural pathology in neurodevelopmental disorders. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising novel therapeutic approach. ClinicalTrials.gov Identifier: NCT0499142. Registered 5th August 2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428

Six-week behaviour change intervention to reduce sedentary behaviour in people with chronic obstructive pulmonary disease: a randomised controlled trial

IntroductionThis study aimed to determine whether a 6-week behaviour change intervention was more effective than a sham intervention for reducing sedentary behaviour (SB) in people with chronic obstructive pulmonary disease (COPD).MethodsPeople with stable COPD on the waitlist for entry into pulmonary rehabilitation were recruited to this multicentre trial with randomisation (independent, concealed allocation) to either an intervention group or sham group, assessor blinding and intention-to-treat (ITT) analysis. The behaviour change intervention consisted of once weekly sessions for 6 weeks with a physiotherapist to reduce SB through education, guided goals setting and real-time feedback on SB. The sham intervention consisted of once weekly phone calls for 6 weeks to monitor health status. SB was measured continuously over 7 days using thigh-worn accelerometry (activPAL3 micro). The primary outcome was time spent in SB. Participants with at least 4 days of ≥10 hours waking wear time were included in the ITT analysis and those who reported achieving ≥70% of goals to reduce SB or who completed all sham calls were included in a per-protocol analysis.Results70 participants were recruited and 65 completed the study (mean±SD age 74±9 years, mean FEV1 55%±19% predicted, 49% male). At 6 weeks, no between-group differences in time spent in SB were observed in the ITT analysis (mean difference 5 min/day, 95% CI −38 to 48) or per-protocol analysis (−16 min/day, 95% CI −80 to 48).DiscussionA 6-week behaviour change intervention did not reduce time in SB compared with a sham intervention in people with stable moderate-to-severe COPD prior to pulmonary rehabilitation.

Does ischemic preconditioning really improve performance or it is just a placebo effect?

This study examined the effects of a simultaneous ischemic preconditioning (IPC) and SHAM intervention to reduce the placebo effect due to a priori expectation on the performance of knee extension resistance exercise. Nine moderately trained men were tested in three different occasions. Following the baseline tests, subjects performed a first set of leg extension tests after the IPC (3 X 5 min 50 mmHg above systolic blood pressure) on right thigh and the SHAM (same as IPC, but 20 mmHg) on left thigh. After 48 hours, the subjects performed another set of tests with the opposite applications. Number of repetitions, maximal voluntary isometric contraction (MVIC) and perceptual indicators were analyzed. After IPC and SHAM intervention performed at the same time, similar results were observed for the number of repetitions, with no significant differences between conditions (baseline x IPC x SHAM) for either left (p = 0.274) or right thigh (p = 0.242). The fatigue index and volume load did not show significant effect size after IPC and SHAM maneuvers. In contrast, significant reduction on left tight MVIC was observed (p = 0.001) in SHAM and IPC compared to baseline, but not for right thigh (p = 0.106). Results from the current study may indicate that applying IPC prior to a set of leg extension does not result in ergogenic effects. The placebo effect seems to be related to this technique and its dissociation seems unlikely, therefore including a SHAM or placebo group in IPC studies is strongly recommended.

Evaluation of a Web-Based ADHD Awareness Training in Primary Care: Pilot Randomized Controlled Trial With Nested Interviews

Background Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5% of children and adults. Undiagnosed and untreated ADHD can result in adverse long-term health, educational, and social impacts for affected individuals. Therefore, it is important to identify this disorder as early as possible. General practitioners (GPs) frequently play a gatekeeper role in access to specialist services in charge of diagnosis and treatment. Studies have shown that their lack of knowledge and understanding about ADHD can create barriers to care. Objective This pilot randomized controlled trial assesses the efficacy of a web-based psychoeducation program on ADHD tailored for GPs. Methods A total of 221 participants were randomized to either a sham intervention control or an awareness training intervention and they completed questionnaires on ADHD knowledge, confidence, and attitude at 3 time points (preintervention, postintervention, and 2-week follow-up). Participants in the intervention arm were invited to participate in a survey and follow-up interview between 3 and 6 months after the intervention. Results The responses of 109 GPs were included in the analysis. The knowledge (P<.001) and confidence (P<.001) of the GPs increased after the intervention, whereas misconceptions decreased (P=.04); this was maintained at the 2-week follow-up (knowledge, P<.001; confidence, P<.001; misconceptions, P=.03). Interviews and surveys also confirmed a change in practice over time. Conclusions These findings demonstrate that a short web-based intervention can increase GPs’ understanding, attitude, and practice toward ADHD, potentially improving patients’ access to care. Trial Registration International Standard Randomized Controlled Trial Number ISRCTN45400501; http://www.isrctn.com/ISRCTN45400501.

A Diffusion Model Approach for Understanding the Impact of 17 Interventions on the Race Implicit Association Test

<p>Performance on implicit measures reflects construct-specific and non-construct-specific processes. This creates an interpretive issue for understanding interventions to change implicit measures: change in performance could reflect changes in the constructs-of-interest or changes in other mental processes. We re-analyzed data from six studies (<i>N</i> = 23,342) to examine the process-level effects of 17 interventions and one sham intervention to change race Implicit Association Test (IAT) performance. Diffusion models decompose overall IAT performance (<i>D</i>-scores) into construct-specific (ease of decision-making), and non-construct-specific processes (speed-accuracy tradeoffs, non-decision-related processes like motor execution). Interventions that effectively reduced <i>D-</i>scores changed ease of decision-making on compatible and incompatible trials. They also eliminated differences in speed-accuracy tradeoffs between compatible and incompatible trials. Non-decision-related processes were impacted by two interventions only. There was little evidence that interventions had any long-term effects. These findings highlight the value of diffusion modeling for understanding the mechanisms by which interventions affect implicit measure performance.</p>

A Diffusion Model Approach for Understanding the Impact of 17 Interventions on the Race Implicit Association Test

<p>Performance on implicit measures reflects construct-specific and non-construct-specific processes. This creates an interpretive issue for understanding interventions to change implicit measures: change in performance could reflect changes in the constructs-of-interest or changes in other mental processes. We re-analyzed data from six studies (<i>N</i> = 23,342) to examine the process-level effects of 17 interventions and one sham intervention to change race Implicit Association Test (IAT) performance. Diffusion models decompose overall IAT performance (<i>D</i>-scores) into construct-specific (ease of decision-making), and non-construct-specific processes (speed-accuracy tradeoffs, non-decision-related processes like motor execution). Interventions that effectively reduced <i>D-</i>scores changed ease of decision-making on compatible and incompatible trials. They also eliminated differences in speed-accuracy tradeoffs between compatible and incompatible trials. Non-decision-related processes were impacted by two interventions only. There was little evidence that interventions had any long-term effects. These findings highlight the value of diffusion modeling for understanding the mechanisms by which interventions affect implicit measure performance.</p>