Search

Light use is rising steeply, mainly because of the advent of light-emitting diode (LED) devices. LEDs are frequently blue-enriched light sources and may have different impacts on the non-image forming (NIF) system, which is maximally sensitive to blue-wavelength light. Most importantly, the timing of LED device use is widespread, leading to novel light exposure patterns on the NIF system. The goal of this narrative review is to discuss the multiple aspects that we think should be accounted for when attempting to predict how this situation will affect the NIF impact of light on brain functions. We first cover both the image-forming and NIF pathways of the brain. We then detail our current understanding of the impact of light on human cognition, sleep, alertness, and mood. Finally, we discuss questions concerning the adoption of LED lighting and screens, which offer new opportunities to improve well-being, but also raise concerns about increasing light exposure, which may be detrimental to health, particularly in the evening.

The Mousepost 1.0 online search tool, launched in 2017, allowed to search for variations in all protein-coding gene sequences of 36 sequenced mouse inbred strains, compared to the reference strain C57BL/6J, which could be linked to strain-specific phenotypes and modifier effects. Because recently these genome sequences have been significantly updated and sequences of 16 extra strains added by the Mouse Genomes Project, a profound update, correction and expansion of the Mousepost 1.0 database has been performed and is reported here. Moreover, we have added a new class of protein disturbing sequence polymorphisms (besides stop codon losses, stop codon gains, small insertions and deletions, and missense mutations), namely start codon mutations. The current version, Mousepost 2.0 (https://mousepost.be), therefore is a significantly updated and invaluable tool available to the community and is described here and foreseen by multiple examples.

Whether treatment response in patients with Parkinson disease depends on brain atrophy is insufficiently understood. The goal of this study is to identify specific atrophy patterns associated with response to dopaminergic therapy and deep brain stimulation.In this study, we analyzed the association of gray matter brain atrophy patterns, as identified by voxel-based morphometry, with acute response to levodopa (N = 118) and subthalamic nucleus deep brain stimulation (N = 39). Motor status was measured as a change in points on the Unified Parkinson's Disease Rating Scale III score. Baseline values were obtained before surgery, after cessation of dopaminergic medication for at least 12 hours; response to medication was assessed after administration of a standardized dose of levodopa. Response to deep brain stimulation was measured three months after surgery in the clinical condition after withdrawal of dopaminergic medication.Although frontoparietal brain gray matter loss was associated with subpar response to deep brain stimulation, there was no significant link between brain atrophy and response to levodopa.We conclude that response to deep brain stimulation relies on gray matter integrity; hence, gray matter loss may present a risk factor for poor response to deep brain stimulation and may be considered when making decision regarding clinical practice.

International audience; Background The identification of patients at high risk of a disabling disease course would be invaluable in guiding initial therapy in Crohn’s disease (CD). Our objective was to evaluate a combination of clinical, serological, and genetic factors to predict complicated disease course in pediatric-onset CD. Methods Data for pediatric-onset CD patients, diagnosed before 17 years of age between 1988 and 2004 and followed more than 5 years, were extracted from the population-based EPIMAD registry. The main outcome was defined by the occurrence of complicated behavior (stricturing or penetrating) and/or intestinal resection within the 5 years following diagnosis. Lasso logistic regression models were used to build a predictive model based on clinical data at diagnosis, serological data (ASCA, pANCA, anti-OmpC, anti-Cbir1, anti-Fla2, anti-Flax), and 369 candidate single nucleotide polymorphisms. Results In total, 156 children with an inflammatory (B1) disease at diagnosis were included. Among them, 35% (n = 54) progressed to a complicated behavior or an intestinal resection within the 5 years following diagnosis. The best predictive model (PREDICT-EPIMAD) included the location at diagnosis, pANCA, and 6 single nucleotide polymorphisms. This model showed good discrimination and good calibration, with an area under the curve of 0.80 after correction for optimism bias (sensitivity, 79%, specificity, 74%, positive predictive value, 61%, negative predictive value, 87%). Decision curve analysis confirmed the clinical utility of the model. Conclusions A combination of clinical, serotypic, and genotypic variables can predict disease progression in this population-based pediatric-onset CD cohort. Independent validation is needed before it can be used in clinical practice.

We report the detection of 5-vinyluridine (5-VUrd) in RNA at single nucleotide resolution via mutational profiling.

While multi-drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used for other indications could provide a novel approach to improve the therapeutic efficacy of standard multiple myeloma treatments. Here, we assessed the anti-tumor effects of cardiac drugs called β-blockers as a single agent and in combination with commonly used anti-myeloma therapies. Expression of the β 2-adrenergic receptor correlated with poor survival outcomes in patients with multiple myeloma. Targeting the β 2-adrenergic receptor (β 2AR) using either selective or non-selective β-blockers reduced multiple myeloma cell viability, and induced apoptosis and autophagy. Blockade of the β 2AR modulated cancer cell metabolism by reducing the mitochondrial respiration as well as the glycolytic activity. These effects were not observed by blockade of β 1-adrenergic receptors. Combining β 2AR blockade with the chemotherapy drug melphalan or the proteasome inhibitor bortezomib significantly increased apoptosis in multiple myeloma cells. These data identify the therapeutic potential of β 2AR-blockers as a complementary or additive approach in multiple myeloma treatment and support the future clinical evaluation of non-selective β-blockers in a randomized controlled trial.

BACKGROUND: Deep brain stimulation (DBS) has been increasingly used in the management of dyskinetic cerebral palsy (DCP). Data on long-term effects and the safety profile are rare. OBJECTIVES: We assessed the efficacy and safety of pallidal DBS in pediatric patients with DCP. METHODS: The STIM-CP trial was a prospective, single-arm, multicenter study in which patients from the parental trial agreed to be followed-up for up to 36 months. Assessments included motor and non-motor domains. RESULTS: Of the 16 patients included initially, 14 (mean inclusion age 14 years) were assessed. There was a significant change in the (blinded) ratings of the total Dyskinesia Impairment Scale at 36 months. Twelve serious adverse events (possibly) related to treatment were documented. CONCLUSION: DBS significantly improved dyskinesia, but other outcome parameters did not change significantly. Investigations of larger homogeneous cohorts are needed to further ascertain the impact of DBS and guide treatment decisions in DCP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. ispartof: Mov Disord ispartof: location:United States status: Published online

Sleep has been suggested to contribute to myelinogenesis and associated structural changes in the brain. As a principal hallmark of sleep, slow-wave activity (SWA) is homeostatically regulated but also differs between indi-viduals. Besides its homeostatic function, SWA topography is suggested to reflect processes of brain maturation. Here, we assessed whether interindividual differences in sleep SWA and its homeostatic response to sleep manip-ulations are associated with in-vivo myelin estimates in a sample of healthy young men. Two hundred twenty-six participants (18-31 y.) underwent an in-lab protocol in which SWA was assessed at baseline (BAS), after sleep deprivation (high homeostatic sleep pressure, HSP) and after sleep saturation (low homeostatic sleep pressure, LSP). Early-night frontal SWA, the frontal-occipital SWA ratio, as well as the overnight exponential SWA decay were computed over sleep conditions. Semi-quantitative magnetization transfer saturation maps (MTsat), provid-ing markers for myelin content, were acquired during a separate laboratory visit. Early-night frontal SWA was negatively associated with regional myelin estimates in the temporal portion of the inferior longitudinal fasci-culus. By contrast, neither the responsiveness of SWA to sleep saturation or deprivation, its overnight dynamics, nor the frontal/occipital SWA ratio were associated with brain structural indices. Our results indicate that frontal SWA generation tracks inter-individual differences in continued structural brain re-organization during early adulthood. This stage of life is not only characterized by ongoing region-specific changes in myelin content, but also by a sharp decrease and a shift towards frontal predominance in SWA generation.

OBJECTIVE The treatment of symptomatic, progressive or recurrent acquired intracerebral cysts is challenging, especially when they are localized in eloquent structures. In addition to resection, endoscopic fenestration, or stereotactic puncture, the implantation of a cystoventricular shunt by stereotactic guidance (SCVS) has been reported as a minimally invasive procedure; however, only scarce data are available regarding its feasibility and efficacy. Here, the authors evaluated the feasibility and efficacy of frame-based SCVS in patients with acquired intracranial cysts. METHODS In this single-center retrospective analysis, the authors included all patients with acquired intracerebral cysts treated by SCVS following a standardized prospective protocol between 2012 and 2020. They analyzed clinical symptoms, complications, and radiological outcome with regard to cyst volume reduction by 3D volumetry. RESULTS Thirty-four patients (17 females and 17 males; median age 44 years, range 5–77 years) were identified. The median initial cyst volume was 11.5 cm3 (range 1.6–71.6 cm3), and the mean follow-up was 20 months (range 1–82 months). At the last follow-up, 27 of 34 patients (79%) showed a cyst volume reduction of more than 50%. Initial symptoms improved or resolved in 74% (n = 25) and remained stable in 24% (n = 8). No permanent clinical deterioration after treatment was observed. The total complication rate was 5.9%, comprising transient neurological deterioration (n = 1) and ventriculitis (n = 1). There were no deaths. The overall recurrence rate was 11.8%. CONCLUSIONS In this study, SCVS proved to be a safe, minimally invasive, and effective treatment with reliable long-term volume reduction, resulting in clinical improvement and a minor complication rate.

The genetic characteristics of neutral loci in natural populations are shaped by the interplay between genetic drift and gene flow that themselves result from key ecological and evolutionary processes. Because of their influence on population size, habitats characteristics may influence substantially populations' genetic characteristics. However, past studies focused primarily on variables related to habitat quantity while habitat quality was largely overlooked. We therefore combined genetic data to detailed habitat descriptions of three sympatric butterfly species having different ecological needs to quantify the relative contribution of geographic distance and habitat quality/quantity on their genetic characteristics. In all species, the genetic diversity was greater in larger and good quality patches. The genetic differentiation of Lycaena helle (specialist species with limited dispersal) was mostly explained by geographical distances. This effect was dampened by habitat quality as populations inhabiting low quality patches had higher genetic differentiations indicating that the constraints set by local environmental factors increased genetic drift. In Boloria eunomia (specialist species with greater dispersal), the genetic differentiation was only influenced by geographic distance. Finally, in Brenthis ino (more generalist species with greater dispersal), isolation-by-distance was weak and habitat characteristics were unrelated to genetic differentiation. The different effect of habitat quality on these species' genetic characteristics suggests that fundamental ecological traits underpin their response to habitat degradation. In L. helle, a species with major conservation concerns, these results show that preserving habitat quality and connectivity among populations' are important to ensure the maintenance of fully functional metapopulations.

The Couffo basin is not well known, and neither are its aquatic living resources, such as fish fauna, which are subjected to high exploitation rates. The objectives of this study were to establish length-weight ratios (LWRs) and length-length ratios (LLRs) for the most important species in the catches and those of certain economic value. A total of 12,191 specimens belonging to 40 commercial species of actinopterygian fishes were caught with several fishing gears and methods between February 2018 and March 2021. Allometric coefficient b of the LWRs (BW = a × TL b ) ranged from 2.194 for Enteromius callipterus to 3.673 for Protopterus annectens with a mean of 2.902 ± 0.315. The growth of thirteen species was isometric, that of fourteen species was negatively allometric, and that of the remaining thirteen species was positively allometric. Coefficient of determination r2 for the LLRs of 39 of the 40 selected species mentioned above was significant and ranged from 0.781 in Gobionellus occidentalis to 0.997 in Elops senegalensis with a mean value of 0.951 ± 0.049. The results will be useful for further studies on assessments of population dynamics and the sustainable conservation of the already limited fish stocks in the Couffo River basin.

ObjectiveThis study aims to shed light on structural networks associated with stimulation-induced dysarthria (SID) and to derive a data-driven model to predict SID in patients with Parkinson’s Disease (PD) and deep brain stimulation (DBS) of the subthalamic nucleus (STN).MethodsRandomized, double-blinded monopolar reviews determining SID thresholds were conducted in 25 patients with PD and STN-DBS. A fiber-based mapping approach, based on the calculation of fiber-wise Odds Ratios for SID, was employed to identify the distributional pattern of SID in the STN’s vicinity. The ability of the data-driven model to classify stimulation volumes as “causing SID” or “not causing SID” was validated by calculating receiver operating characteristics (ROC) in an independent out-of-sample cohort comprising 14 patients with PD and STN-DBS.ResultsLocal fiber-based stimulation maps showed an involvement of fibers running lateral and postero-medial to the STN in the pathogenesis of SID, independent of the investigated hemisphere. ROC-analysis in the independent out-of-sample cohort resulted in a good fit of the data-driven model for both hemispheres (AUCleft= 0.88, AUCright= 0.88).InterpretationThis study reveals an involvement of both, cerebello-thalamic fibers, as well as the pyramidal tract, in the pathogenesis of SID in STN-DBS. The results may impact future postoperative programming strategies to avoid SID in patients with PD and STN-DBS.

thersites. Journal for Transcultural Presences & Diachronic Identities from Antiquity to Date, Vol. 16 (2023)

Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects the crosstalk between brain areas to trigger this stimulating effect is not established. We recorded the brain activity of 19 healthy young participants (24.05±2.63; 12 women) while they completed an auditory attentional task in darkness or under an active (blue-enriched) or a control (orange) light, in an ultra-high-field 7 Tesla MRI scanner. We tested if light modulated the effective connectivity between an area of the posterior associative thalamus, encompassing the pulvinar, and the intraparietal sulcus (IPS), key areas in the regulation of attention. We found that only the blue-enriched light strengthened the connection from the posterior thalamus to the IPS. Our results provide the first empirical data supporting that blue wavelength light affects ongoing non-visual cognitive activity by modulating task-dependent information flow from subcortical to cortical areas.

Light triggers numerous non-image forming (NIF), or non-visual, biological effects. The brain correlates of these NIF effects have been investigated, notably using Magnetic Resonance Imaging (MRI) and short light exposures varying in irradiance and spectral quality. However, it is not clear whether having light in subsequent blocks may induce carry over effects of one light block onto the next, thus biasing the study. We reasoned that pupil light reflex (PLR) was an easy readout of one of the NIF effects of light that could be used to address this issue. We characterized the sustained PLR in 13 to 16 healthy young individuals under short light exposures during three distinct cognitive processes (executive, emotional and attentional). Light conditions pseudo-randomly alternated between monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (mel EDI) lux] and polychromatic blue-enriched white light of three different levels [37, 92, 190 mel EDI lux]. As expected, higher melanopic irradiance was associated with larger sustained PLR in each cognitive domain. This result was stable over the light block sequence under higher melanopic irradiance levels as compared to lower ones. Exploratory frequency-domain analyses further revealed that PLR was more variable within a light block under lower melanopic irradiance levels. Importantly, PLR varied across tasks independently of the light condition pointing to a potential impact of the light history and/or cognitive context on PLR. Together, our results emphasize that the distinct contribution and adaptation of the different retinal photoreceptors influence the NIF effects of light and therefore potentially their brain correlates.

Light has many non-image-forming functions including modulation of pupil size and stimulation of alertness and cognition. Part of these non-image-forming effects may be mediated by the brainstem locus coeruleus. The processing of sensory inputs can be associated with a transient pupil dilation that is likely driven in part by the phasic activity of the locus coeruleus. Here, we aimed to characterise the task-evoked pupil response associated with auditory inputs under different light levels and across two cognitive tasks. We continuously monitored the pupil of 20 young healthy participants (24.05y ±4.0; 14 women) while they completed an attentional and an emotional auditory task whilst exposed to repeated 30-to-40s-blocks of light interleaved with darkness periods. Blocks could either consist of monochromatic orange light [0.16 melanopic Equivalent Daylight Illuminance (EDI) lux] or blue-enriched white light of three different levels [37, 92, 190 melanopic EDI lux; 6500K]. For the analysis 15 and then 14 participants were included in the attentional and emotional tasks respectively. Generalized Linear Mixed Models showed a significant main effect of light level on the task-evoked pupil responses triggered by the attentional and emotional tasks (p≤.0001). The impact of light was different for the target vs. non-target stimulus of the attentional task but was not different for the emotional and neutral stimulus of the emotional task. Despite a smaller sustained pupil size during brighter light blocks, a higher light level triggers a stronger task-evoked pupil response to auditory stimulation, presumably through the recruitment of the locus coeruleus.

During historical and contemporary crises in the U.S., Blacks and other marginalized groups experience an increased risk for adverse health, social, and economic outcomes. These outcomes are driven by structural factors, such as poverty, racial residential segregation, and racial discrimination. These factors affect communities’ exposure to risk and ability to recover from disasters, such as pandemics. This study examines whether areas where descendants of enslaved Africans and other Blacks lived in Chicago were vulnerable to excess death during the 1918 influenza pandemic and whether these disparities persisted in the same areas during the COVID-19 pandemic. To examine disparities, demographic data and influenza and pneumonia deaths were digitized from historic weekly paper maps from the week ending on 5 October 1918 to the week ending on 16 November 1918. Census tracts were labeled predominantly Black or white if the population threshold for the group in a census tract was 40% or higher for only one group. Historic neighborhood boundaries were used to aggregate census tract data. The 1918 spatial distribution of influenza and pneumonia mortality rates and cases in Chicago was then compared to the spatial distribution of COVID-19 mortality rates and cases using publicly available datasets. The results show that during the 1918 pandemic, mortality rates in white, immigrant and Black neighborhoods near industrial areas were highest. Pneumonia mortality rates in both Black and immigrant white neighborhoods near industrial areas were approximately double the rates of neighborhoods with predominantly US-born whites. Pneumonia mortality in Black and immigrant white neighborhoods, far away from industrial areas, was also higher (40% more) than in US-born white neighborhoods. Around 100 years later, COVID-19 mortality was high in areas with high concentrations of Blacks based on zip code analysis, even though the proportion of the Black population with COVID was similar or lower than other racial and immigrant groups. These findings highlight the continued cost of racial disparities in American society in the form of avoidable high rates of Black death during pandemics.

IntroductionPolymicrobial sepsis causes acute anorexia (loss of appetite), leading to lipolysis in white adipose tissue and proteolysis in muscle, and thus release of free fatty acids (FFAs), glycerol and gluconeogenic amino acids. Since hepatic peroxisome proliferator-activated receptor alpha (PPARα) and glucocorticoid receptor (GR) quickly lose function in sepsis, these metabolites accumulate (causing toxicity) and fail to yield energy-rich molecules such as ketone bodies (KBs) and glucose. The mechanism of PPARα and GR dysfunction is not known.Methods & resultsWe investigated the hypothesis that hypoxia and/or activation of hypoxia inducible factors (HIFs) might play a role in these issues with PPARα and GR. After cecal ligation and puncture (CLP) in mice, leading to lethal polymicrobial sepsis, bulk liver RNA sequencing illustrated the induction of the genes encoding HIF1α and HIF2α, and an enrichment of HIF-dependent gene signatures. Therefore, we generated hepatocyte-specific knock-out mice for HIF1α, HIF2α or both, and a new HRE-luciferase reporter mouse line. After CLP, these HRE-luciferase reporter mice show signals in several tissues, including the liver. Hydrodynamic injection of an HRE-luciferase reporter plasmid also led to (liver-specific) signals in hypoxia and CLP. Despite these encouraging data, however, hepatocyte-specific HIF1α and/or HIF2α knock-out mice suggest that survival after CLP was not dependent on the hepatocyte-specific presence of HIF proteins, which was supported by measuring blood levels of glucose, FFAs, and KBs. The HIF proteins were also irrelevant in the CLP-induced glucocorticoid resistance, but we found indications that the absence of HIF1α in hepatocytes causes less inactivation of PPARα transcriptional function.ConclusionWe conclude that HIF1α and HIF2α are activated in hepatocytes in sepsis, but their contribution to the mechanisms leading to lethality are minimal.

IntroductionDeep brain stimulation (DBS) is an established treatment in patients with pharmaco-resistant neurological disorders of different ages. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures and on electrode connectivity to a specific distributed pattern of brain networks. Such information is usually collected using group-level analysis which relies on the availability normative imaging-resources (atlases and connectomes). To this end, analyzing DBS data of children with debilitating neurological disorders like dystonia would make benefit from such resources, especially given the developmental differences between adults and children neuroimaging data. We assembled pediatric, normative neuroimaging-resources from open-access neuroimaging datasets and illustrated their utility on a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources.MethodsA pediatric average brain template was implemented and used to localize DBS electrodes of twenty patients of the GEPESTIM registry cohort. Next, a pediatric subcortical atlas was also employed to highlight anatomical structures of interest. Local pallidal sweetspot was modeled and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcome. Additionally, a pediatric functional connectome of neurotypical subjects was built to allow network-based analyses and decipher a connectivity fingerprint responsible for clinical improvement in our cohort.ResultsWe successfully implemented a pediatric neuroimaging dataset that will be made available to public use as a tool for DBS-analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46,permuted p= 0.019). Functional connectivity fingerprint of DBS-outcome was determined as a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30,permuted p= 0.003).ConclusionsLocal sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcome in dystonia using pediatric neuroimaging surrogate data. The current implementation of pediatric neuroimaging dataset might help improving the practice of DBS-neuroimaging analyses in pediatric patients.

The locus coeruleus (LC) is the primary source of norepinephrine (NE) in the brain, and the LC-NE system is involved in regulating arousal and sleep. It plays key roles in the transition between sleep and wakefulness, and between slow wave sleep (SWS) and rapid eye movement sleep (REMS). However, it is not clear whether the LC activity during the day predicts sleep quality and sleep properties during the night, and how this varies as a function of age. Here, we used 7 Tesla functional Magnetic Resonance Imaging (7T fMRI), sleep electroencephalography (EEG) and a sleep questionnaire to test whether the LC activity during wakefulness was associated with sleep quality in 52 healthy younger (N=33; ~22y; 28 women) and older (N=19; ~61y; 14 women) individuals. We find that, in older, but not in younger participants, higher LC activity, as probed during an auditory mismatch negativity task, is associated with worse subjective sleep quality and with lower power over the EEG theta band during REMS (4-8Hz), which are two sleep parameters significantly correlated in our sample of older individuals. The results remain robust even when accounting for the age-related changes in the integrity of the LC. These findings suggest that the activity of the LC may contribute to the perception of the sleep quality and to an essential oscillatory mode of REMS, and that the LC may be an important target in the treatment of sleep disorders and age-related diseases.

International audience; The recurrent admissions of elderly people at hospital can be modeled by a censored counting process. The intensity of this processe can be specified as functions of covariates as in the Andersen-Gill model. However, accounting for these covariates is often not sufficient to explain the observed inter-patient heterogeneity. We propose a mixture model (also called a latent class model) which takes into account this heterogenity and allows to perform the patients' clustering. Within each cluster, the recurrent events process intensity is modeled by a parametric baseline intensity (Weibull) adjusted by the effect of the covariates. The model parameters are estimated by maximum likelihood using the EM algorithm, and the BIC criterion is adopted to choose the optimal numbers of clusters. The behaviour of the model is studied on simulated data. The analysis of two real datasets is also performed. The first one (PAERPA cohort) contains administrative data on hospital admission dates, death and basic clinical/demographic variables for over 35000 older persons. The second one (DAMAGE cohort) contains more detailed data on over 3500 older persons: dates of hospital admissions, clinical, biological, socio-demographic variables.

ZusammenfassungAufgrund steigender Fallzahlen der Alzheimer-Erkrankung und bislang eher mäßigem Erfolg der verfügbaren symptomatischen und kausalen pharmakologischen Therapien besteht ein erheblicher Bedarf, nicht-pharmakologische Behandlungsmöglichkeiten zu erforschen. Im Bereich der nicht-invasiven Hirnstimulation (non-invasive brain stimulation; NIBS) wurden verschiedene Verfahren untersucht, insbesondere die transkranielle Magnetstimulation und die transkranielle elektrische Stimulation. Zusätzlich wird derzeit die Tiefe Hirnstimulation (deep brain stimulation; DBS) als innovatives Verfahren zur gezielten Neuromodulation erforscht. Nicht-invasiven und invasiven Ansätzen gemein ist der Versuch, neuronale Aktivität zu modulieren und kognitiv-mnestische Funktionen zu verbessern. Durch sekundäre Mechanismen wie die Langzeit-Potenzierung bei NIBS oder Neurogenese bei DBS könnten auch längerfristige positive Effekte erzielt werden. Präklinische und klinische Studien ergaben bereits vielversprechende Ergebnisse bei Patientinnen und Patienten in frühen Stadien der Alzheimer-Erkrankung. Inkonsistente Studien- und Stimulationsprotokolle sowie kleine Stichproben erschweren jedoch die Bewertung der Wirksamkeit. Weitere Forschungsbemühungen sind angebracht, um einen zeitnahen Einzug nicht-invasiver oder invasiver neuromodulatorischer Ansätze in die klinische Praxis zu ermöglichen.

OBJECTIVE To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data was used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement greater than 50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural-connectivity-based cerebello-thalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a greater than 50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION Our multicentre ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of deep brain stimulation in the future. This article is protected by copyright. All rights reserved.

BACKGROUND: The majority of opioid overdose admissions in pediatric patients are associated with prescription opioids. Post-operative prescriptions are an addressable source of opioids in the household. This study aims to assess for sustained reduction in opioid prescribing after implementation of provider-based education at nine centers. METHODS: Opioid prescribing information was collected for pediatric patients undergoing umbilical hernia repair at nine centers between December 2018 and January 2019, one year after the start of an education intervention. This was compared to prescribing patterns in the immediate pre- and post-intervention periods at each of the nine centers. RESULTS: In the current study period, 29/127 (22.8%) patients received opioid prescriptions (median 8 doses) following surgery. There were no medication refills, emergency department returns or readmissions related to the procedure. There was sustained reduction in opioid prescribing compared to pre-intervention (22.8% vs 75.8% of patients, p

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

We investigate the parameter estimation of regression models with fixed group effects, when the group variable is missing while group related variables are available. This problem involves clustering to infer the missing group variable based on the group related variables, and regression to build a model on the target variable given the group and eventually additional variables. Thus, this problem can be formulated as the joint distribution modeling of the target and of the group related variables. The usual parameter estimation strategy for this joint model is a two-step approach starting by learning the group variable (clustering step) and then plugging in its estimator for fitting the regression model (regression step). However, this approach is suboptimal (providing in particular biased regression estimates) since it does not make use of the target variable for clustering. Thus, we claim for a simultaneous estimation approach of both clustering and regression, in a semi-parametric framework. Numerical experiments illustrate the benefits of our proposition by considering wide ranges of distributions and regression models. The relevance of our new method is illustrated on real data dealing with problems associated with high blood pressure prevention.

This report focusses on the modification of physical structure and chemical properties of a bentonite clay from the Hammam Boughrara region of the Maghnia district in western Algeria to maximize its adsorption capacity. The purified bentonite clay (called B) was modified, either by acid activation with 1M sulfuric acid (B-Act), or by intercalation with the cationic surfactant cetytrimethyl ammonium bromide (CTAB), applying a cation exchange capacity (CEC) of 100% (called B-CTAB). Modification of B was also introduced by combining these two steps consecutively, i.e., at first acid activation of B, followed by intercalation with CTAB (B-Act-CTAB). The B-Act-CTAB was obtained by H2SO4 (1M) acid activation, followed by co-adsorption of CTAB with 100% and 300% of the CEC of B-Act as precursor. In particular, a strong increase of surface area and pore volume of the modified bentonites was observed for B-Act (469.83 m²/g and 0.401 cm3g−1), B-Act-CTAB100 (267.72 m²/g and 0.316 cm3 g−1) and B-Act-CTAB300 (111.15 m²/g and 0.171 cm3g−1), compared to B (31.79 m²/g and 0.074 cm3 g−1) and B-CTAB (3.79 m²/g and 0.034 cm3 g−1), respectively. The bentonite-based adsorbents were then used to evaluate the removal efficiency of an organic molecule, the azo dye Orange G (OG), as a model for a Persistent Organic Pollutant. Freundlich, Langmuir and Sips (Langmuir–Freundlich) models were applied to analyze equilibrium isotherms, showing a good correlation between experimental data and the Freundlich model. A good agreement was obtained between experimentally obtained kinetic adsorption data and the pseudo-second-order model, allowing to evaluate rate constants. B-Act-CTAB300 can be applied as a low-cost material for removal of azo dyes, since its adsorption capacity towards OG (102.80 mg/g) exceeds largely that of B-CTAB (31.49 mg/g) and B-Act-CTAB100 (12.77 mg/g).

The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine to potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast. We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals. Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Critically, while the LC contrast was higher in older individuals, the functional response of the LC was not associated with its contrast. These findings show that the age-related alterations of the LC structural integrity may not necessarily be related to changes in its functional response. The results further indicate that LC responses could remain stable in healthy individuals aged 20 to 70.

This study investigates players’ perceived realism of historical video games. Perceived realism is understood as a multidimensional concept, going beyond the more traditional use of ‘realism’ in historical game studies, where it often refers to the plausibility or accuracy of historical reconstructions. The study further examines how perceived realism relates to players’ enjoyment of historical games. Specifically, this study analyses Assassin's Creed, Assassin's Creed Unity and Assassin's Creed Odyssey. Through an online survey among 1,317 respondents, this study found that the five-dimensional structure of perceived realism holds for historical games. The three games differed in their perceptions of social realism, perceptual pervasiveness, freedom of choice and enjoyment. Finally, perceptual pervasiveness and character involvement were identified as strong predictors of enjoyment in historical games. This study contributes towards further validation of the perceived realism scale across game genres and pleads for a systematic use of the multidimensional term ‘realism’ in historical game research.

Introduction: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD.Methods: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests.Results: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores.Conclusions: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.Keywords: Deep brain stimulation; Nonmotor symptoms; Postural instability and gait difficulty; Quality of life; Tremor-dominant.

Characterization refers to the process of attributing character traits to narrative entities called 'characters'. While there is a long tradition of characterization theory in literary studies, the topic has not been examined extensively in game research. Based on insights from literary, film, and game studies, this article creates a theoretical model of how 'character,' or character traits, can be attributed in video games, and offers a methodological vocabulary for further character(ization) research. First, this paper synthesizes the tradition of characterization research in literary studies. Second, it identifies three participants in video game characterization (developers, actors, and players) and introduces the concept of ergodic characterization to describe those instances in which players produce nontrivial characterization efforts. Finally, the framework itself is presented through application to various game titles, and several answers to methodological problems within game characterization analysis are suggested.

In the framework of model-based clustering, a model, called multi-partitions clustering, allowing several latent class variables has been proposed. This model assumes that the distribution of the observed data can be factorized into several independent blocks of variables, each block following its own mixture model. In this paper, we assume that each block follows a non parametric latent class model, {\it i.e.} independence of the variables in each component of the mixture with no parametric assumption on their class conditional distribution. The purpose is to deduce, from the observation of a sample, the number of blocks, the partition of the variables into the blocks and the number of components in each block, which characterise the proposed model. By following recent literature on model and variable selection in non-parametric mixture models, we propose to discretize the data into bins. This permits to apply the classical multi-partition clustering procedure for parametric multinomials, which are based on a penalized likelihood method (\emph{e.g.} BIC). The consistency of the procedure is obtained and an efficient optimization is proposed. The performances of the model are investigated on simulated data.

Purpose This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). Design Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. Outcomes The primary outcome was the mean change of “intra-patient” composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. Methods The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from − 5 to − 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. Results The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. Conclusions This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients.