A novel tDCS sham approach based on model-driven controlled shunting

BackgroundTranscranial direct current stimulation (tDCS), a non-invasive brain stimulation technique able to transiently modulate brain activity, is surging as one of the most promising therapeutic solutions in many neurological and psychiatric disorders. However, profound limitations exist in current placebo (sham) protocols that limit single- and double-blinding, especially in non-naïve subjects.ObjectiveTo ensure better blinding and strengthen reliability of tDCS studies and trials, we tested a new optimization algorithm aimed at creating an “active” sham tDCS condition (ActiSham hereafter) capable of inducing the same scalp sensations perceived during real stimulation while preventing currents from reaching the cortex and cause changes in brain excitability.MethodsA novel model-based multielectrode technique — optimizing the location and currents of a set of small electrodes placed on the scalp — was used to control the relative amount of current delivered transcranially in real and placebo multichannel tDCS conditions. The presence, intensity and localization of scalp sensations during tDCS was evaluated by means of a specifically designed questionnaire administered to the participants. We compared blinding ratings by directly addressing subjects’ ability to discriminate across conditions for both traditional (Bifocal-tDCS and Sham, using sponge electrodes) and our novel multifocal approach (both real Multifocal-tDCS and ActiSham). Changes in corticospinal excitability were monitored based on Motor Evoked Potentials (MEPs) recorded via concurrent Transcranial Magnetic Stimulation (TMS) and electromyography (EMG).ResultsParticipants perceived Multifocal-tDCS and ActiSham similarly in terms of both localization and intensity of scalp sensations, whereas traditional Bifocal stimulation was rated as more painful and annoying compared to its Sham counterpart. Additionally, differences in scalp localization were reported for active/sham Bifocal-tDCS, with Sham tDCS inducing more widespread itching and burning sensations. As for MEPs amplitude, a main effect of stimulation was found when comparing Bifocal-Sham and ActiSham (F_(1,13) = 6.67, p = .023), with higher MEPs amplitudes after the application of Bifocal-Sham.ConclusionsCompared to traditional Bifocal-tDCS, ActiSham offers better participants’ blinding by inducing very similar scalp sensations to those of real Multifocal tDCS both in terms of intensity and localization, while not affecting corticospinal excitability.     

Mimengosides J and K: two new neuroprotective triterpenoids from the fruits of Buddleja lindleyana

Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP⁺) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.

     

Weight-bearing in ankle fractures: An audit of UK practice

IntroductionThe purpose of this national study was to audit the weight-bearing practice of orthopaedic services in the National Health Service (NHS) in the treatment of operatively and non-operatively treated ankle fractures.MethodsA multicentre prospective two-week audit of all adult ankle fractures was conducted between July 3rd 2017 and July 17th 2017. Fractures were classified using the AO/OTA classification. Fractures fixed with syndesmosis screws or unstable fractures (>1 malleolus fractured or talar shift present) treated conservatively were excluded. No outcome data were collected. In line with NICE (The National Institute for Health and Care Excellence) criteria, “early” weight-bearing was defined as unrestricted weight-bearing on the affected leg within 3 weeks of injury or surgery and “delayed” weight-bearing as unrestricted weight-bearing permitted after 3 weeks.Results251 collaborators from 81 NHS hospitals collected data: 531 patients were managed non-operatively and 276 operatively. The mean age was 52.6 years and 50.5 respectively. 81% of non-operatively managed patients were instructed for early weight-bearing as recommended by NICE. In contrast, only 21% of operatively managed patients were instructed for early weight-bearing.DiscussionThe majority of patients with uni-malleolar ankle fractures which are managed non-operatively are treated in accordance with NICE guidance. There is notable variability amongst and within NHS hospitals in the weight-bearing instructions given to patients with operatively managed ankle fractures.ConclusionThis study demonstrates community equipoise and suggests that the randomized study to determine the most effective strategy for postoperative weight-bearing in ankle fractures described in the NICE research recommendation is feasible.     

Moving Toward Empirically Based Standardization in the Diagnosis of Delayed Ejaculation

BackgroundCriteria for delayed ejaculation (DE) rely on a long ejaculation latency (EL) time, lack of control/advancement regarding ejaculation, and associated bother/distress; yet, few studies have investigated these criteria in men who indicate the desire to ejaculate sooner during partnered sex.AimTo help standardize criteria for DE by better understanding characteristics of men who desire to ejaculate sooner during partnered sex in terms of their EL, reported ejaculatory control, and level of bother/distress, as well as their perceptions of typical and ideal ELs for men in general and of ELs for men with premature ejaculation (PE).MethodsA total of 572 men recruited through social media responded to an online survey regarding their EL, as well as typical, ideal, and PE ELs of men in general. They also rated (i) their ability to control and/or advance ejaculation and (ii) their level of associated bother/distress. 4 comparison groups were then established: men with probable DE (with [DE1] and without [DE2] ejaculatory control issues), a reference group with no ejaculatory disorders, and men who identified as having PE.OutcomesTo demonstrate differences in EL, ejaculatory control, and bother/distress between men with delayed ejaculation and the control and PE reference groups.ResultsELs for men with probable DE were twice as long as those with no ejaculatory disorders. When probable DE men were further subdivided into DE2 and DE1, differences were greater for the DE2 group. DE2 men also differed significantly from the reference group on ejaculatory control/advancement but not on bother/distress. Both DE and reference groups differed from the PE group.Clinical ImplicationsUsing both EL and ejaculatory control are useful in distinguishing men with delayed ejaculation from men without delayed ejaculation.Strengths & LimitationsA sizable sample drawn from a multinational population powered the study, whereas the use of social media for recruitment limited the generalizability of findings.ConclusionBoth EL and ejaculatory control differentiate men with probable DE from a control reference group having no ejaculatory disorders. Differences in bother/distress did not emerge as significant. Implications for diagnosing men with DE are presented.Rowland DL, Cote-Leger P. Moving Toward Empirically Based Standardization in the Diagnosis of Delayed Ejaculation. J Sex Med 2020;17:1896–1902.     

An Environmental Scan of the National and Provincial Diagnostic Reference Levels in Canada for Common Adult Computed Tomography Scans

Several regulatory bodies have agreed that low-dose radiation used in medical imaging is a weak carcinogen that follows a linear, non-threshold model of cancer risk. While avoiding radiation is the best course of action to mitigate risk, computed tomography (CT) scans are often critical for diagnosis. In addition to the as low as reasonably achievable principle, a more concrete method of dose reduction for common CT imaging exams is the use of a diagnostic reference level (DRL). This paper examines Canada's national DRL values from the recent CT survey and compares it to published provincial DRLs as well as the DRLs in the United Kingdom and the United States of America for the 3 most common CT exams: head, chest, and abdomen/pelvis. Canada compares well on the international scale, but it should consider using more electronic dose monitoring solutions to create a culture of dose optimization.     

Meta-analysis of the effects of transcranial direct current stimulation on inhibitory control

BackgroundInhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders.ObjectiveThe primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.MethodsA comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies.ResultsResults of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.ConclusionBased on the studies included, our meta-analytic approach substantiates previously observed differences between brain regions, i.e., involvement of the right inferior frontal gyrus (rIFG) vs. the right dorsolateral prefrontal cortex (rDLPFC) in inhibitory control. Results indicate a small moderating effect of tDCS on inhibitory control in single-session studies and highlight the relevance of technical and behavioral parameters.