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Members of NDCN were successful in two categories of these awards, which celebrate the digital at the University of Oxford
A cross-sectional investigation of the ophthalmological impact of loiasis in Cameroon, Central Africa
Background Current knowledge of ocular manifestations of loiasis is limited to the transient subconjunctival passage of the adult filaria and anecdotal reports of posterior segment lesions. Therefore, the ocular burden of loiasis is likely underestimated since it has never been systematically assessed at the population level. We aimed to evaluate the relationship of Loa loa microfilaremia and recent eye worm passage with chronic ocular lesions identified through comprehensive ophthalmological assessment in an endemic area. Methodology/principal findings Subjects aged ≥ 15 years, residing in Akonolinga for ≥ 5 years, without filaricidal treatment for ≥3 years, were screened for filariases. After excluding participants with onchocerciasis lesions, a subset of randomly selected participants was assessed by ophthalmologists blinded to blood test results then allocated to four groups defined by microfilarial load (MFL) on calibrated thick blood film: G1 (Loa MFL = 0), G2 (MFL < 8000/mL), G3 (MFL ≥ 8000/mL), G4 (co-infestation with Mansonella MFL > 100/mL). The ophthalmological assessment comprised distance visual acuity, examination of the anterior segment with a slit lamp, and fundoscopy. The primary analysis consisted of univariable comparisons of the frequency of abnormal findings across four groups (G1 – 4) or two groups defined by history of eye worm passage. The secondary analysis consisted of a multivariable logistic regression analysis of the relationship of high Loa MFL (≥8000/mL) with chorioretinitis and eye worm passage with unilateral ametropia, adjusting for confounders. Of 1511 subjects screened, 200 underwent ophthalmological assessment, including 65, 69, 35, and 16 in G1 to 4. History of eye worm passage in the previous year was reported by 121 participants (65.4%). Unilateral ametropia was more prevalent in people with history of eye worm passage in the previous year (26.5% versus 10.9%, p = 0.014). Chorioretinitis was the most frequent posterior segment lesion (n = 11, 6.1%) and was most prevalent in G3 (14.3%). The frequency of chorioretinitis was higher in participants with moderate-to-severe visual impairment (27.3% versus 4.4%, p = 0.002). High Loa MFL was an independent predictor of chorioretinitis (adjusted OR=5.28; p = 0.01). History of eye worm passage in the previous year was independently associated with unilateral ametropia (adjusted OR=3.27, p = 0.0088). Conclusions/significance This study has, for the first time, provided evidence of independent association between history of eye worm passage and unilateral ametropia, and between high Loa MFL and severe chorioretinal lesions. This suggests that loiasis should be classified as a neglected tropical disease.
Academia in the throes of faceless bureaucracy
Pansieri et al. argue that bureaucracy is suffocating research, as an ever increasing administrative burden consumes researchers’ time and diverts focus from discovery to compliance. They highlight ways in which red tape delays progress, wastes funding, and drives researchers out of academia, and call for systemic change.
Submaximal 2-day cardiopulmonary exercise testing to assess exercise capacity and post-exertional symptom exacerbation in people with long COVID.
Long COVID has a complex pathology and a heterogeneous symptom profile that impacts quality of life and functional status. Post-exertional symptom exacerbation (PESE) affects one-third of people living with long COVID, but the physiological basis of impaired physical function remains poorly understood. Sixty-eight people (age (mean ± SD): 50 ± 11 years, 46 females (68%)) were screened for severity of PESE and completed two submaximal cardiopulmonary exercise tests separated by 24 h. Work rate was stratified relative to functional status and was set at 10, 20 or 30 W, increasing by 5 W/min for a maximum of 12 min. At the first ventilatory threshold (VT1), V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ was 0.73 ± 0.16 L/min on Day 1 and decreased on Day 2 (0.68 ± 0.16 L/min; P = 0.003). Work rate at VT1 was lower on Day 2 (Day 1 vs. Day 2; 28 ± 13 vs. 24 ± 12 W; P = 0.004). Oxygen pulse on Day 1 at VT1 was 8.2 ± 2.2 mL/beat and was reduced on Day 2 (7.5 ± 1.8 mL/beat; P = 0.002). The partial pressure of end tidal carbon dioxide was reduced on Day 2 (Day 1 vs. Day 2; 38 ± 3.8 vs. 37 ± 3.2 mmHg; P = 0.010). Impaired V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ is indicative of reduced transport and/or utilisation of oxygen. V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ at VT1 was impaired on Day 2, highlighting worsened function in the 24 h after submaximal exercise. The data suggest multiple contributing physiological mechanisms across different systems and further research is needed to investigate these areas.
Prior Expectations of Volatility Following Psychotherapy for Delusions: A Randomized Clinical Trial.
IMPORTANCE: Persecutory delusions are common, distressing, and difficult to treat. Testing computational neuroscience models of delusions can identify new therapeutic targets. OBJECTIVE: To determine whether change in delusion severity is associated with a corresponding change in volatility priors and brain activation estimated during a belief updating task. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted from April 9, 2021, to December 5, 2023, within the Vanderbilt University Medical Center Psychiatric Hospital and at a community mental health center in Nashville, Tennessee. Participants were adults (aged between 18 and 65 years) with schizophrenia spectrum or delusional disorder and an active, persistent (≥3 months) persecutory delusion with strong conviction (>50%). Participants were randomly assigned 1:1 to either cognitive behavioral therapy for psychosis (CBTp)-based intervention or befriending therapy. Intention-to-treat analysis was performed from June 1 to October 31, 2024. INTERVENTION: The CBTp was a manualized intervention targeting persecutory delusions. The befriending therapy involved engaging in conversations and activities focused on neutral topics. Both interventions were provided in person, lasted for 8 weeks, and included standard care. Standard care consisted of medication management and ancillary services. MAIN OUTCOMES AND MEASURES: Primary outcomes were volatility priors (ie, prior expectations of volatility) derived from a 3-option probabilistic reversal learning task; persecutory delusion severity measured by the Psychotic Symptom Rating Scales (PSYRATS delusion subscale; score range: 0-16, with the highest score indicating severe preoccupation, distress, conviction, and functioning impact); and brain activation in the striatum and prefrontal cortex measured by blood oxygenation level-dependent signal change. Associations between volatility priors, clinical improvement, and change in neural activation were examined. RESULTS: Sixty-two participants (median [range] age, 31 [19-63] years; 38 males [61%]) were randomly assigned to the CBTp (n = 32) or befriending therapy (n = 30) arms. A subgroup of 35 participants (57%) completed functional magnetic resonance imaging. Volatility priors decreased following treatment (F1,112 = 7.7 [P = .006]; Cohen d = 0.52 [95% CI, 0.15-0.90]), as did delusion severity (F1,112 = 59.7 [P
Validation of the “Patient‐Acceptable Symptom State” Question as Outcome Measure in AChR Myasthenia Gravis: A Multicentre, Prospective Study
ABSTRACTIntroductionPatient Acceptable Symptom State (PASS) is emerging as a valuable subjective measure of the overall myasthenia gravis (MG)‐related burden. This study aimed at identifying PASS‐positive thresholds for the most used clinical scales, investigating whether PASS and MGFA post‐intervention status capture different aspects of the disease outcome, and identifying clinical variables associated with PASS=YES response.MethodsAdult AChR‐MG patients were prospectively enrolled at two Italian Centres (Rome: index cohort; Florence: validation cohort). PASS thresholds for MG‐ADL, QMG, and MG‐QOL15r were defined in the index cohort by ROC analysis and validated in the validation cohort; predictors of favorable PASS were identified by multivariable analysis.ResultsThis study included 173 patients (44% females, median age at onset: 53 years). PASS=YES patients had significantly lower median MG‐ADL, QMG, and MG‐QOL15r scores, with the following thresholds for PASS=YES: MG ADL ≤ 2, QMG ≤ 8 and MG‐QOL15r ≤ 6. The MG‐ADL (OR = 0.46, 95% CI = 0.36–0.60, p < 0.001), QMG (OR = 0.72, 95% CI = 0.64–0.81, p < 0.001) and MG‐QOL15r (OR = 0.76, 95% CI = 0.70–0.84, p < 0.001), were independently associated with a favorable PASS. The degree of ocular involvement in each scale was the strongest negative determinant of PASS=YES.ConclusionsThis study validates the PASS question and highlights the relevance of ocular complaints in patients' perception of MG burden.
Postural sway variability in young adults presents higher complexity during morning compared to evening hours while in older adults remains the same
Human movement variability reflects the adaptive capacity of the nervous system, yet how it is influenced by aging and circadian rhythms remain unclear. Therefore, the purpose of this study was to investigate postural sway variability as a function of aging and time of day. Nineteen young and nineteen older adults completed one 60-s quite stance trial with eyes open while standing on a force platform, at 12 p.m. and 12 a.m. Postural sway variability was evaluated regarding both its magnitude (total travel distance and interquartile range) and the complexity (a exponent using Detrended Fluctuation Analysis) of its temporal structure using the center of pressure time series. A two-way ANOVA (2 age groups × 2 times of day) was used. Correlation analysis was also performed to further investigate the relationship between circadian regulation and postural sway complexity. Complexity was higher for the young compared to the older group independently of the time of day. Furthermore, young adults presented higher values during the morning as compared to evening, while older adults did not reveal significant differences within the day. Finally, a strong correlation was found but only for young adults. In general, our results suggested that complexity of postural sway variability is affected both by age and time of day. Aging impacts postural control by reducing the complexity of sway variability and diminishing its sensitivity to circadian influences. Future work will address the effect of chronotype, sleep, and arousal levels on these novel findings and assess their impact on overall health.
Sleep-related hypermotor epilepsy in a patient with myelin-oligodendrocyte-glycoprotein antibody disease
Unusual seizure phenotypes in myelin-oligodendrocyte-glycoprotein (MOG) seropositive patients have previously been reported, although so far, no cases of sleep-related hypermotor epilepsy (SHE). In our case, a patient with a diagnosis of MOG antibody-associated disease (MOGAD) began reporting unusual sleep disturbances; video-audio documentation was in keeping with the clinical diagnosis of SHE. MRI brain was normal at the time of the assessment for seizures. Symptoms responded to antiepileptic drugs (AEDs). These unusual seizure events were thought to be indicative of the underlying autoimmune condition, suggesting that the clinical spectrum of MOGAD is wider than previously thought.
The relationship between TMS measures of functional properties and DTI measures of microstructure of the corticospinal tract
Background: Recently, a link between resting motor threshold (RMT) and local tissue microstructure, as indexed by fractional anisotropy (FA), was demonstrated in large parts of white matter. However, regions showing such correlations were generally found outside of the corticospinal tract (CST). Therefore, the question arises whether other electrophysiologic measurements could be more locally related to microstructural properties of the CST. In this study, we explored the relationship between such measurements and regional FA in a group of healthy volunteers. Objective/Hypothesis: We hypothesized that RMT might be more related to an overall susceptibility of white matter to TMS, whereas other electrophysiologic markers might be more specifically related to properties of the CST only. Methods: Thirty-seven subjects were included. We studied RMT, active motor threshold (AMT), intensity to evoke a motor-evoked potential (MEP) of 1 mV (S1mV), MEP input-output curve (IO-curve), and central motor conduction time (CMCT) using transcranial magnetic stimulation, and FA of the corticospinal tract using diffusion tensor magnetic resonance imaging. We performed voxel-wise and TBSS correlation analysis between these electrophysiologic measurements and FA. In addition, we tested for significant correlation between these parameters and mean diffusivity (MD). Results: On voxel-wise analysis, we did not detect significant correlations between any electrophysiologic parameter (RMT, AMT, S1mV, IO curve slope, CMCT) and FA. With TBSS, we detected correlations between FA and bilateral AMT, as well as left-hemispheric S1mV, but these correlations were found in locations unlikely to contribute to motor pathways. Conclusions: Although a relationship between structure and function has been shown in many other regions of the brain, it seems to be much more challenging to demonstrate such a relationship in the CST of healthy subjects. © 2012 Elsevier Inc. All rights reserved.
Spatiotemporal dynamics of bimanual integration in human somatosensory cortex and their relevance to bimanual object manipulation
Little is known about the spatiotemporal dynamics of cortical responses that integrate slightly asynchronous somatosensory inputs from both hands. This study aimed to clarify the timing and magnitude of interhemispheric interactions during early integration of bimanual somatosensory information in different somatosensory regions and their relevance for bimanual object manipulation and exploration. Using multi-fiber probabilistic diffusion tractography and MEG source analysis of conditioning-test (C-T) median nerve somatosensory evoked fields in healthy human subjects, we sought to extract measures of structural and effective callosal connectivity between different somatosensory cortical regions and correlated them with bimanual tactile task performance. Neuromagnetic responses were found in major somatosensory regions, i.e., primary somatosensory cortex SI, secondary somatosensory cortex SII, posterior parietal cortex, and premotor cortex. Contralateral to the test stimulus, SII activity was maximally suppressed by 51% at C-T intervals of 40 and 60 ms. This interhemispheric inhibition of the contralateral SII source activity correlated directly and topographically specifically with the fractional anisotropy of callosal fibers interconnecting SII. Thus, the putative pathway that mediated inhibitory interhemispheric interactions in SII was a transcallosal route from ipsilateral to contralateral SII. Moreover, interhemispheric inhibition of SII source activity correlated directly with bimanual tactile task performance. These findings were exclusive to SII. Our data suggest that early interhemispheric somatosensory integration primarily occurs in SII, is mediated by callosal fibers that interconnect homologous SII areas, and has behavioral importance for bimanual object manipulation and exploration. © 2012 the authors.
The tremor network targeted by successful VIM deep brain stimulation in humans
Objective: Deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM) is a treatment option in medically intractable tremor, such as essential tremor or tremor-dominant Parkinson disease (PD). Although functional studies demonstrated modulation of remote regions, the structural network supporting this is as yet unknown. In this observational study, we analyzed the network mediating clinical tremor modulation. Methods: We studied 12 patients undergoing VIM stimulation for debilitating tremor. We initiated noninvasive diffusion tractography from tremor-suppressive VIM electrode contacts. Moreover, we tested for the contribution of primary motor projections in this structural correlate of a functional tremor network, comparing the connectivity of effective DBS contacts with those of adjacent, but clinically ineffective, stimulation sites. Results: VIM stimulation resulted in decrease of tremor and improvement in quality of life. Tractography initiated from the effective stimulation site reconstructed a highly reproducible network of structural connectivity comprising motor cortical, subcortical, and cerebellar sites and the brainstem, forming the anatomic basis for remote effects of VIM stimulation. This network is congruent with functional imaging studies in humans and with thalamic projections found in the animal literature. Connectivity to the primary motor cortex seemed to play a key role in successful stimulation. Conclusions: Patients undergoing DBS provide a unique opportunity to assess an electrophysiologically defined seed region in human thalamus, a technique that is usually restricted to animal research. In the future, preoperative tractography could aid with stereotactic planning of individual subcortical target points for stimulation in tremor and in other disease entities. Copyright © 2012 by AAN Enterprises, Inc.