ABSTRACT
Cerebrovascular Reactivity (CVR) refers to the ability of cerebral blood vessels to dilate or constrict under the effect of vasoactive substances and can be estimated using functional Magnetic Resonance Imaging (fMRI). Computation of CVR maps is relevant in various brain diseases and requires specialized data processing. We introduce CVRmap, an opensource software that automates the computation of CVR map. The toolbox complies with the Brain Imaging Data Structure (BIDS) standards.
Subject(s)
Brain Diseases , Cerebrovascular Circulation , Humans , Magnetic Resonance Imaging/methods , Angiography , Head , Brain/diagnostic imaging , Brain/blood supply , Brain MappingABSTRACT
There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.
Subject(s)
Heart Failure , Myocardial Infarction , Rats , Mice , Humans , Animals , Swine , Myocardial Infarction/pathology , Myocardial Infarction/therapy , Heart Failure/metabolism , Myocytes, Cardiac/metabolism , Ventricular Function, Left , Macrophages/metabolismABSTRACT
State modeling of whole-brain electroencephalography (EEG) or magnetoencephalography (MEG) allows to investigate transient, recurring neurodynamical events. Two widely-used techniques are the microstate analysis of EEG signals and hidden Markov modeling (HMM) of MEG power envelopes. Both reportedly lead to similar state lifetimes on the 100 ms timescale, suggesting a common neural basis. To investigate whether microstates and power envelope HMM states describe the same neural dynamics, we used simultaneous MEG/EEG recordings at rest and compared the spatial signature and temporal activation dynamics of microstates and power envelope HMM states obtained separately from EEG and MEG. Results showed that microstates and power envelope HMM states differ both spatially and temporally. Microstates reflect sharp events of neural synchronization, whereas power envelope HMM states disclose network-level activity with 100-200 ms lifetimes. Further, MEG microstates do not correspond to the canonical EEG microstates but are better interpreted as split HMM states. On the other hand, both MEG and EEG HMM states involve the (de)activation of similar functional networks. Microstate analysis and power envelope HMM thus appear sensitive to neural events occurring over different spatial and temporal scales. As such, they represent complementary approaches to explore the fast, sub-second scale bursting electrophysiological dynamics in spontaneous human brain activity.
Subject(s)
Brain/physiology , Electroencephalography/methods , Magnetoencephalography/methods , Adolescent , Adult , Female , Healthy Volunteers , Humans , Male , Markov Chains , RestABSTRACT
A 73-year-old man with a history of marginal zone lymphoma was admitted to the emergency room for diplopia and ipsilateral headache. The Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated intense and symmetrical hypermetabolism of the cavernous sinuses, and hypermetabolic lesions diffusely in the lymph nodes and bones. The diagnosis of high-grade relapse of lymphomatous disease was made. In this context, the homogenous and symmetric lesion of the cavernous sinuses, without any other encephalic or meningeal lesions, raised the hypothesis of a paraneoplastic origin. A plausible paraneoplastic link between the neuro-ophthalmological lesion and the malignant disorder is IgG4-related disease, a condition that may be associated with lymphoma. As in our case, this diagnosis is often presumptive because histopathological confirmation is difficult to obtain.
ABSTRACT
OBJECTIVE: Joint injury-induced perturbations to the endocannabinoid system (ECS), a regulator of both inflammation and nociception, remain largely uncharacterized. We employed a mouse model of ACL rupture to assess alterations to nociception, inflammation, and the ECS while using in vitro models to determine whether CB2 agonism can mitigate inflammatory signaling in macrophages and fibroblast-like synoviocytes (FLS). DESIGN: Mice underwent noninvasive ACL rupture (ACLR) via tibial compression-based loading. Nociception was measured longitudinally using mechanical allodynia and knee hyperalgesia testing. Synovitis was assessed using histological scoring and histomorphometry. Gene and protein markers of inflammation were characterized in whole joints and synovium. Immunohistochemistry assessed injury-induced alterations to CB1+, CB2+, and F4/80+ cells in synovium. To assess whether CB2 agonism can inhibit pro-inflammatory macrophage polarization, murine bone marrow-derived macrophages (mBMDM) were stimulated with IL-1ß or conditioned medium from IL-1ß-treated FLS and treated with vehicle (DMSO), the CB2 agonist HU308, or cannabidiol (CBD). Macrophage polarization was assessed as the ratio of M1-associated (IL1b, MMP1b, and IL6) to M2-associated (IL10, IL4, and CD206) gene expression. Human FLS (hFLS) isolated from synovial tissue of OA patients were treated with vehicle (DMSO) or HU308 following TNF-α or IL-1ß stimulation to assess inhibition of catabolic/inflammatory gene expression. RESULTS: ACLR induces synovitis, progressively-worsening PTOA severity, and an immediate and sustained increase in both mechanical allodynia and knee hyperalgesia, which persist beyond the resolution of molecular inflammation. Enrichment of CB2, but not CB1, was observed in ACLR synovium at 3d, 14d, and 28d, and CB2 was found to be associated with F4/80 (+) cells, which are increased in number in ACLR synovium at all time points. The CB2 agonist HU308 strongly inhibited mBMDM M1-type polarization following stimulation with either IL-1ß or conditioned medium from IL-1ß-treated mFLS, which was characterized by reductions in Il1b, Mmp1b, and Il6 and increases in Cd206 gene expression. Cannabidiol similarly inhibited IL-1ß-induced mBMDM M1 polarization via a reduction in Il1b and an increase in Cd206 and Il4 gene expression. Lastly, in OA hFLS, HU308 treatment inhibited IL-1ß-induced CCL2, MMP1, MMP3, and IL6 expression and further inhibited TNF-α-induced CCL2, MMP1, and GMCSF expression, demonstrating human OA-relevant anti-inflammatory effects by targeting CB2. CONCLUSIONS: Joint injury perturbs the intra-articular ECS, characterized by an increase in synovial F4/80(+) cells, which express CB2, but not CB1. Targeting CB2 in murine macrophages and human FLS induced potent anti-inflammatory and anti-catabolic effects, which indicates that the CB2 receptor plays a key role in regulating inflammatory signaling in the two primary effector cells in the synovium. The intraarticular ECS is therefore a potential therapeutic target for blocking pathological inflammation in future disease-modifying PTOA treatments.
Subject(s)
Anterior Cruciate Ligament Injuries , Fibroblasts/metabolism , Macrophages/metabolism , Receptor, Cannabinoid, CB2/metabolism , Up-Regulation , Animals , Cannabidiol/pharmacology , Cannabinoid Receptor Agonists/pharmacology , Cannabinoids/pharmacology , Disease Models, Animal , Fibroblasts/drug effects , Interleukin-1beta/pharmacology , Macrophages/drug effects , Mice, Inbred C57BL , Synovial MembraneABSTRACT
OBJECTIVE: Modified natural cycles for frozen embryo transfer utilize an ovulation trigger which assists in embryo transfer scheduling and simplifies cycle monitoring. There have been conflicting results with this protocol and modifications may be sought. We wanted to ascertain whether a modified natural protocol for frozen embryo transfer without triggered ovulation but with luteal progesterone support disconnecting the timing of embryo transfer from the timing of the LH surge can achieve a high pregnancy rate. STUDY DESIGN: Candidates for frozen embryo transfer of 48-h cleavage cell embryos were recruited from May 2016 to April 2018. The patients were monitored for endometrial growth, follicle formation and estradiol, progesterone, and LH hormone levels. After meeting the predetermined criteria, embryo transfer was scheduled. The patients began progesterone treatment 48 h before embryo transfer, regardless of identification of the LH surge if ovulation had not commenced. The predetermined primary outcome was the biochemical pregnancy rate while the secondary outcome included the clinical pregnancy rate and the ongoing pregnancy rate. Patients were monitored to the eighth week of pregnancy, but data was collected from the medical records to provide the live birth rate as well. RESULTS: Fifty-six women were screened. Eleven women declined or did not meet the inclusion criteria. Three had anovulatory cycles and were excluded. Forty-two women were included in the statistical analysis. The implantation rate was 42.9 % [95 %CI 29.3 %-56.4 %). Of the 42 participants, 25 (59.5 %) conceived [95 % CI 44.0 %-75 %]. Two pregnancies ended in first trimester miscarriage leaving 23 (54.7 %) ongoing pregnancies [95 % CI 39.1 %-70.5 %]. One patient experienced a late abortion such that the live birth rate was 22 of 42 patients or 52.4 % [95 % CI 36.4 %-68.0 %]. CONCLUSION: The proposed modified natural protocol which utilizes progesterone luteal support but does not trigger ovulation, maintains a high pregnancy rate while providing flexibility regarding the day of transfer disconnected from the day of the LH surge. This was a prospective, proof of concept study. This protocol may be suitable for smaller or public in-vitro fertility units whose resources are limited and facilities are not available daily. The high pregnancy and live birth rate that we found provides confidence that this protocol can be part of the armament of protocols the clinician may offer to his patients. Larger studies should confirm these findings.
Subject(s)
Embryo Transfer , Progesterone , Cryopreservation , Female , Humans , Live Birth , Ovulation Induction , Pregnancy , Pregnancy Rate , Proof of Concept Study , Prospective StudiesABSTRACT
Human brain activity is intrinsically organized into resting-state networks (RSNs) that transiently activate or deactivate at the sub-second timescale. Few neuroimaging studies have addressed how Alzheimer's disease (AD) affects these fast temporal brain dynamics, and how they relate to the cognitive, structural and metabolic abnormalities characterizing AD. We aimed at closing this gap by investigating both brain structure and function using magnetoencephalography (MEG) and hybrid positron emission tomography-magnetic resonance (PET/MR) in 10 healthy elders, 10 patients with subjective cognitive decline (SCD), 10 patients with amnestic mild cognitive impairment (aMCI) and 10 patients with typical Alzheimer's disease with dementia (AD). The fast activation/deactivation state dynamics of RSNs were assessed using hidden Markov modeling (HMM) of power envelope fluctuations at rest measured with MEG. Correlations were sought between temporal properties of HMM states and participants' cognitive test scores, whole hippocampal grey matter volume and regional brain glucose metabolism. The posterior default-mode network (DMN) was less often activated and for shorter durations in AD patients than matched healthy elders. No significant difference was found in patients with SCD or aMCI. The time spent by participants in the activated posterior DMN state did not correlate significantly with cognitive scores, nor with the whole hippocampal volume. However, it correlated positively with the regional glucose consumption in the right dorsolateral prefrontal cortex (DLPFC). AD patients present alterations of posterior DMN power activation dynamics at rest that identify an additional electrophysiological correlate of AD-related synaptic and neural dysfunction. The right DLPFC may play a causal role in the activation of the posterior DMN, possibly linked to the occurrence of mind wandering episodes. As such, these data might suggest a neural correlate of the decrease in mind wandering episodes reported in pathological aging.
Subject(s)
Alzheimer Disease/physiopathology , Nerve Net/physiopathology , Rest/physiology , Aged , Brain/metabolism , Brain/pathology , Brain/physiopathology , Brain Mapping , Cognition , Female , Humans , Magnetoencephalography , Male , Time FactorsABSTRACT
This magnetoencephalography study aimed at characterizing age-related changes in resting-state functional brain organization from mid-childhood to late adulthood. We investigated neuromagnetic brain activity at rest in 105 participants divided into three age groups: children (6-9 years), young adults (18-34 years) and healthy elders (53-78 years). The effects of age on static resting-state functional brain integration were assessed using band-limited power envelope correlation, whereas those on transient functional brain dynamics were disclosed using hidden Markov modeling of power envelope activity. Brain development from childhood to adulthood came with (1) a strengthening of functional integration within and between resting-state networks and (2) an increased temporal stability of transient (100-300 ms lifetime) and recurrent states of network activation or deactivation mainly encompassing lateral or medial associative neocortical areas. Healthy aging was characterized by decreased static resting-state functional integration and dynamic stability within the primary visual network. These results based on electrophysiological measurements free of neurovascular biases suggest that functional brain integration mainly evolves during brain development, with limited changes in healthy aging. These novel electrophysiological insights into human brain functional architecture across the lifespan pave the way for future clinical studies investigating how brain disorders affect brain development or healthy aging.
Subject(s)
Brain Mapping/methods , Brain/growth & development , Magnetoencephalography/methods , Rest/physiology , Adult , Age Distribution , Aged , Brain/physiology , Brain Waves , Child , Female , Humans , Magnetic Resonance Imaging , Male , Markov Chains , Middle Aged , Young AdultSubject(s)
Cerebral Cortex/physiopathology , Proprioception/physiology , Somatosensory Disorders/physiopathology , Spastic Paraplegia, Hereditary/physiopathology , Adolescent , Adult , Biomechanical Phenomena/physiology , Female , Humans , Magnetoencephalography , Male , Neural Conduction/physiology , Neural Pathways/physiopathology , Young AdultABSTRACT
PURPOSE: The small bites surgical technique supported by the STITCH trial has been touted as a strategy for preventing early laparotomy dehiscence through greater force distribution at the suture-tissue interface. However, this hernia prevention strategy requires an alteration in the standard closure technique that has not been widely adopted in the USA. This study seeks to determine whether incorporating a mid-weight polypropylene mesh material into a hollow-bore surgical suture material will effectively increase the force distribution at the suture-tissue interface and potentially help prevent early laparotomy dehiscence in an ex vivo model. METHODS: A cyclic stress ball-burst model was used to compare suturable mesh (0 DuraMesh™) to conventional suture. After midline laparotomy, 28 porcine abdominal wall specimens were closed with either 0 DuraMesh™ or #1 polydioxanone double-loop suture. A custom 3D-printed ball-burst test apparatus was used to fatigue the repair on a MTS Bionix Load Frame. The tissue was repetitively stressed at a physiological force of 15-120 N cycled at a rate of 0.25 Hz for a total of 1000 repetitions, followed by a load to failure, and the maximal force was recorded. RESULTS: The mean maximal force at suture pull-through was significantly higher (p < 0.0095) in the 0 DuraMesh suture group (mean: 850.1 N) compared to the 1 PDS group (mean: 714.7 N). CONCLUSION: This ex vivo study suggests that using rational suture design to improve force distribution at the suture-tissue interface may be a viable strategy for preventing the suture pull-through that drives incisional hernia.
Subject(s)
Abdominal Wound Closure Techniques , Hernia/prevention & control , Laparotomy , Surgical Wound Dehiscence/prevention & control , Suture Techniques , Sutures , Abdominal Wall/physiopathology , Abdominal Wall/surgery , Abdominal Wound Closure Techniques/instrumentation , Animals , Biocompatible Materials , Biomechanical Phenomena , Hernia/etiology , Hernia/physiopathology , Hernia, Abdominal/etiology , Hernia, Abdominal/prevention & control , Incisional Hernia/etiology , Incisional Hernia/physiopathology , Incisional Hernia/prevention & control , Laparotomy/adverse effects , Laparotomy/methods , Polypropylenes , Prosthesis Failure , Stress, Mechanical , Surgical Mesh , Surgical Wound Dehiscence/etiology , Surgical Wound Dehiscence/physiopathology , SwineABSTRACT
Magnetoencephalography (MEG) has been used in conjunction with resting-state functional connectivity (rsFC) based on band-limited power envelope correlation to study the intrinsic human brain network organization into resting-state networks (RSNs). However, the limited availability of current MEG systems hampers the clinical applications of electrophysiological rsFC. Here, we directly compared well-known RSNs as well as the whole-brain rsFC connectome together with its state dynamics, obtained from simultaneously-recorded MEG and high-density scalp electroencephalography (EEG) resting-state data. We also examined the impact of head model precision on EEG rsFC estimation, by comparing results obtained with boundary and finite element head models. Results showed that most RSN topographies obtained with MEG and EEG are similar, except for the fronto-parietal network. At the connectome level, sensitivity was lower to frontal rsFC and higher to parieto-occipital rsFC with MEG compared to EEG. This was mostly due to inhomogeneity of MEG sensor locations relative to the scalp and significant MEG-EEG differences disappeared when taking relative MEG-EEG sensor locations into account. The default-mode network was the only RSN requiring advanced head modeling in EEG, in which gray and white matter are distinguished. Importantly, comparison of rsFC state dynamics evidenced a poor correspondence between MEG and scalp EEG, suggesting sensitivity to different components of transient neural functional integration. This study therefore shows that the investigation of static rsFC based on the human brain connectome can be performed with scalp EEG in a similar way than with MEG, opening the avenue to widespread clinical applications of rsFC analyses.
Subject(s)
Cerebral Cortex/physiology , Electroencephalography/standards , Functional Neuroimaging/standards , Magnetoencephalography/standards , Nerve Net/physiology , Adult , Cerebral Cortex/diagnostic imaging , Female , Humans , Male , Nerve Net/diagnostic imaging , Sensitivity and Specificity , Young AdultSubject(s)
Friedreich Ataxia/physiopathology , Proprioception , Sensorimotor Cortex/physiopathology , Adolescent , Adult , Biomechanical Phenomena , Evoked Potentials , Female , Humans , Male , MovementABSTRACT
Assessing energy intake (EI) in children and adolescents is essential for monitoring population nutrition trends and interpreting clinical outcomes. The aim of this review was to examine the validity of dietary assessment methods for estimating EI in children and adolescents when compared with total energy expenditure (TEE) measured using doubly labelled water (DLW). Six online databases were searched to identify articles published in English. Studies were included if they were conducted in participants aged ≤18 years, if they estimated EI via a dietary assessment method, and if they compared this estimate to TEE measured using the DLW method. The search strategy identified 345 articles, of which 13 articles (12 studies) (n = 306 children) met the selection criteria. Five studies were carried out in children aged 5-11 years with dietary intake of children reported by parents/caregivers. The most common dietary assessment methods used were food frequency questionnaires (n = 5) and weighed food records (n = 4). All methods were found to have some level of misreporting. Child characteristics including weight status, age, and sex were not found to consistently influence the accuracy of reported EI. Five studies employing technology-assisted approaches for assessing dietary intake in children were identified and reported mixed findings. Validity studies using DLW remain sparse in the literature. Studies including participants less than 5 years or older than 11 years, and from diverse ethnicities and socioeconomic backgrounds are warranted to explore other demographic differences that may affect the accuracy of dietary assessment methods. While reported in few studies, technology-assisted methods were found to perform equally well in estimating intakes when compared to DLW and other traditional forms of dietary assessment.
Subject(s)
Diet Records , Diet/statistics & numerical data , Energy Intake , Nutrition Assessment , Water/analysis , Child , Humans , Reproducibility of ResultsABSTRACT
First clinical indications of positron emission tomography (PET) were in the fields of neurology and cardiology, but oncology is the domain in which PET got its recognition as an essential diagnostic tool. Its fast diffusion as an imaging method for diagnosis and follow-up of cancer has been facilitated by the existence of a single tracer for all kinds of oncological PET explorations. Nowadays, this tracer, fluorodeoxyglucose (FDG), is so largely distributed that non oncological PET indications have emerged. For instance, PET with FDG has totally supplanted gallium-67 for the evaluation of inflammatory conditions. Another non oncological domain in which PET with FDG has kept an important clinical role is neurology. The strong local relationship between neuronal activity and cerebral glucose uptake confers to PET with FDG a primordial role in neurological conditions in which structural changes are insufficient to establish a firm diagnosis. This is the case for focal epilepsy that remains an undisputed indication of PET with FDG, and for neurodegenerative disorders, in particular those that lead to dementia for which tracers detecting amyloid and tau depositions are now available. New tracers have enlarged PET indications in oncology, in particular for cancers that are not well evaluated with FDG. Since the early clinical PET introduction, patients with brain tumours are benefiting from PET exploration with amino-acid tracers, in particular for therapeutic tumour targeting. The recent development of tracers for neuroendocrine and prostatic cancers has opened a new field of applications for PET, linked to innovative radiotherapeutic approaches.
La tomographie par émission de positons (TEP) a connu ses premières indications dans le domaine des affections neurologiques et cardiaques, mais c'est en oncologie que cette méthode va s'implanter comme un outil diagnostique essentiel. Sa diffusion rapide en imagerie oncologique a été facilitée par le fait qu'un unique traceur permet de pratiquer la très grande majorité des explorations. Ce traceur, le fluoro-désoxyglucose (FDG), est aujourd'hui distribué de façon très large de sorte que les indications non oncologiques de la TEP se sont également développées. La TEP au FDG a ainsi totalement supplanté la scintigraphie au citrate de gallium-67 pour l'évaluation des affections inflammatoires. La neurologie est restée un autre champ d'application non oncologique de la TEP au FDG. La relation qui lie l'activité neuronale locale à la consommation de glucose confère à la TEP au FDG un rôle déterminant pour l'évaluation de maladies du cerveau dans lesquelles les modifications structurelles sont insuffisantes pour établir un diagnostic. C'est le cas de l'épilepsie focale et des maladies neurodégénératives, principalement les démences pour lesquelles de nouveaux traceurs ciblant les dépôts amyloïdes ou de protéines tau, sont apparus. S'agissant de nouveaux traceurs, notons que certains ont étendu l'usage de la TEP à des cancers mal évalués par le FDG. Les cancers cérébraux bénéficient depuis longtemps de l'utilisation en TEP d'acides aminés marqués, en particulier pour le ciblage thérapeutique des tumeurs. L'apparition de traceurs des cancers neuroendocrines et prostatiques a ouvert un nouveau champ d'indications de la TEP, en lien avec de nouvelles approches radiothérapeutiques.
Subject(s)
Positron-Emission Tomography , Brain Diseases/diagnostic imaging , Forecasting , Humans , Neoplasms/diagnostic imaging , Positron-Emission Tomography/trendsABSTRACT
This magnetoencephalography (MEG) study aims at characterizing the coupling between cerebellar activity and the kinematics of repetitive self-paced finger movements. Neuromagnetic signals were recorded in 11 right-handed healthy adults while they performed repetitive flexion-extensions of right-hand fingers at three different movement rates: slow (~ 1 Hz), medium (~ 2 Hz), and fast (~ 3 Hz). Right index finger acceleration was monitored with an accelerometer. Coherence analysis was used to index the coupling between right index finger acceleration and neuromagnetic signals. Dynamic imaging of coherent sources was used to locate coherent sources. Coupling directionality between primary sensorimotor (SM1), cerebellar, and accelerometer signals was assessed with renormalized partial directed coherence. Permutation-based statistics coupled with maximum statistic over the entire brain volume or restricted to the cerebellum were used. At all movement rates, maximum coherence peaked at SM1 cortex contralateral to finger movements at movement frequency (F0) and its first harmonic (F1). Significant (statistics restricted to the cerebellum) coherence consistently peaked at the right posterior lobe of the cerebellum at F0 with no influence of movement rate. Coupling between Acc and cerebellar signals was significantly stronger in the afferent than in the efferent direction with no effective contribution of cortico-cerebellar or cerebello-cortical pathways. This study demonstrates the existence of significant coupling between finger movement kinematics and neuromagnetic activity at the posterior cerebellar lobe ipsilateral to finger movement at F0. This coupling is mainly driven by spinocerebellar, presumably proprioceptive, afferences.
Subject(s)
Cerebellum/physiology , Fingers/physiology , Motor Skills/physiology , Accelerometry , Adult , Biomechanical Phenomena , Female , Functional Laterality , Humans , Magnetoencephalography , Male , Sensorimotor Cortex/physiology , Signal Processing, Computer-Assisted , Young AdultABSTRACT
OBJECTIVES: Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. METHODS: We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. RESULTS: Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. CONCLUSIONS: We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Infections/drug therapy , Clinical Trials, Phase III as Topic , Databases, Factual , Publishing , Registries , Humans , PublicationsABSTRACT
This study investigates whether movement kinematics modulates similarly the rolandic α and ß rhythm amplitude during executed and observed goal-directed hand movements. It also assesses if this modulation relates to the corticokinematic coherence (CKC), which is the coupling observed between cortical activity and movement kinematics during such motor actions. Magnetoencephalography (MEG) signals were recorded from 11 right-handed healthy subjects while they performed or observed an actor performing the same repetitive hand pinching action. Subjects' and actor's forefinger movements were monitored with an accelerometer. Coherence was computed between acceleration signals and the amplitude of α (8-12 Hz) or ß (15-25 Hz) oscillations. The coherence was also evaluated between source-projected MEG signals and their ß amplitude. Coherence was mainly observed between acceleration and the amplitude of ß oscillations at movement frequency within bilateral primary sensorimotor (SM1) cortex with no difference between executed and observed movements. Cross-correlation between the amplitude of ß oscillations at the SM1 cortex and movement acceleration was maximal when acceleration was delayed by ~ 100 ms, both during movement execution and observation. Coherence between source-projected MEG signals and their ß amplitude during movement observation and execution was not significantly different from that during rest. This study shows that observing others' actions engages in the viewer's brain similar dynamic modulations of SM1 cortex ß rhythm as during action execution. Results support the view that different neural mechanisms might account for this modulation and CKC. These two kinematic-related phenomena might help humans to understand how observed motor actions are actually performed.
Subject(s)
Alpha Rhythm/physiology , Beta Rhythm/physiology , Brain/physiology , Goals , Movement/physiology , Adult , Biomechanical Phenomena/physiology , Female , Fingers , Humans , Magnetoencephalography/methods , MaleABSTRACT
The mismatch negativity (MMN) reflects the early detection of changes in sensory stimuli at the cortical level. The mechanisms underlying its genesis remain debated. This magnetoencephalography study investigates the spatio-temporal dynamics and the neural mechanisms of the magnetic somatosensory MMN. Somatosensory evoked magnetic fields elicited by tactile stimulation of the right fingertip (Single), tactile stimulation of the right middle phalanx and fingertip (Double) or omissions (Omitted) of tactile stimuli were studied in different paradigms: in oddballs where Double/Omitted followed a sequence of four Single, in sequences of two stimuli where Double occurred after one Single, and in random presentation of Double only. The predictability of Double occurrence in oddballs was also manipulated. Cortical sources of evoked responses were identified using equivalent current dipole modeling. Evoked responses elicited by Double were significantly different from those elicited by Single at the contralateral secondary somatosensory (cSII) cortex. Double elicited higher cSII cortex responses than Single when preceded by a sequence of four Single, compared to when they were preceded by one Single. Double elicited higher cSII cortex response when presented alone compared to when Double were preceded by one or a sequence of Single. Omitted elicited similar cSII cortex response than Single. Double in oddballs led to higher cSII cortex responses when less predictable. These data suggest that early tactile change detection involves mainly cSII cortex. The predictive coding framework probably accounts for the SII cortex response features observed in the different tactile paradigms.
Subject(s)
Evoked Potentials, Somatosensory/physiology , Magnetoencephalography , Somatosensory Cortex/physiology , Touch Perception/physiology , Touch/physiology , Adult , Brain Mapping , Female , Fingers/physiology , Humans , Male , Somatosensory Cortex/diagnostic imagingABSTRACT
Functional magnetic resonance imaging (fMRI) studies report age-related changes in resting-state functional connectivity (rsFC), suggesting altered or reorganized connectivity patterns with age. However, age-related changes in neurovascular coupling might also partially account for altered connectivity patterns. Here, we used resting-state magnetoencephalography (MEG) and a connectome approach in carefully selected healthy young adults and elders. The MEG connectome was estimated as rsFC matrices involving forty nodes from six major resting-state networks. Source-level rsFC maps were computed in relevant frequency bands using leakage-corrected envelope correlations. Group differences were statistically assessed using non-parametric permutation tests. Our results failed to evidence significant age-related differences after correction for multiple comparisons in the α and the ß bands both for static and dynamic rsFC, suggesting that the electrophysiological connectome is maintained in healthy ageing. Further studies should compare the evolution of the human brain connectome as estimated using fMRI and MEG in same healthy young and elder adults, as well as in ageing conditions associated with cognitive decline. At present, our results are in agreement with the brain maintenance theory for successful aging as they suggest that preserved intrinsic functional brain integration contributes to preserved cognitive functioning in healthy elders.
Subject(s)
Brain/physiology , Cognitive Dysfunction/physiopathology , Connectome , Electrophysiological Phenomena , Magnetoencephalography/methods , Nerve Net/physiology , Rest/physiology , Adult , Aged , Female , Humans , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging , Male , Young AdultABSTRACT
INTRODUCTION: Grade II intramedullary astrocytomas are rare tumors. Despite a well-defined role of adjuvant temozolomide chemotherapy for brain gliomas, the contribution of this therapy for intramedullary gliomas is not yet clearly defined. METHOD: We retrospectively analyzed the data of 5 adult patients treated with temozolomide between 2008 and 2015 for a grade II intramedullary astrocytoma with progression after surgery. RESULTS: Five patients from 19 to 70 years of age (median, 37years) underwent a second surgery for the progression of a grade II intramedullary astrocytoma (median progression-free survival 26months [8-90]). All tumors remained grade II. Due to a second clinical or/and radiological tumor progression, the patients were treated with temozolomide after a 37months median progression-free survival (5-66). All patients received at minimum 12 cycles (mean 14 ± 5; range 12-24) of temozolomide (150-200mg/m2/day, 5days/28days). All patients were alive after a 10-year median follow-up after diagnosis (6-13). All patients were able to walk except one, who was previously in McCormick autonomy grade IV before chemotherapy. The McCormick autonomy rating after temozolomide was stable for 4 patients and improved for 1 patient. The treatment was delayed once for hematological toxicity. CONCLUSION: Temozolomide stabilized all 5 patients without any major toxicity. Based on this experience that needs to be confirmed, we consider that temozolomide should be envisaged within the therapeutic arsenal for progressive intramedullary grade II astrocytomas.