rudyvdbrink/CitationDatabase huggingface dataset:
Remission from antipsychotic treatment in first episode psychosis related to longitudinal changes in brain glutamate.
NPJ schizophrenia, 2019

Neuroimaging studies in schizophrenia have linked elevated glutamate metabolite levels to non-remission following antipsychotic treatment, and also indicate that antipsychotics can reduce glutamate metabolite levels. However, the relationship between symptomatic reduction and change in glutamate during initial antipsychotic treatment is unclear. Here we report proton magnetic resonance spectroscopy (1H-MRS) measurements of Glx and glutamate in the anterior cingulate cortex (ACC) and thalamus in patients with first episode psychosis (n = 23) at clinical presentation, and after 6 weeks and 9 months of treatment with antipsychotic medication. At 9 months, patients were classified into Remission (n = 12) and Non-Remission (n = 11) subgroups. Healthy volunteers (n = 15) were scanned at the same three time-points. In the thalamus, Glx varied over time according to remission status (P = 0.020). This reflected an increase in Glx between 6 weeks and 9 months in the Non-Remission subgroup that was not evident in the Remission subgroup (P = 0.031). In addition, the change in Glx in the thalamus over the 9 months of treatment was positively correlated with the change in the severity of Positive and Negative Syndrome Scale (PANSS) positive, total and general symptoms (P<0.05). There were no significant effects of group or time on glutamate metabolites in the ACC, and no differences between either patient subgroup and healthy volunteers. These data suggest that the nature of the response to antipsychotic medication may be related to the pattern of changes in glutamatergic metabolite levels over the course of treatment. Specifically, longitudinal reductions in thalamic Glx levels following antipsychotic treatment are associated with symptomatic improvement.
Prevalence of age-related macular degeneration in an elderly UK Caucasian population-The Bridlington Eye Assessment Project: a cross-sectional study.
Eye (London, England), 2017

ImportanceThere is paucity of data on prevalence and disease asymmetry of age-related macular degeneration (AMD), particularly the earlier stages, in the UK population.Objective and PurposeTo determine the prevalence of age-related macular degeneration in an elderly Caucasian UK population.DesignCross-sectional population study, 2002-2006.ParticipantsResidents in the study area of Bridlington aged 65 years and older.MethodsFull-ophthalmic examination was undertaken in 3549 participants, of eligible 6319 Caucasian population (response rate of 56%). Non-stereoscopic Colour fundus photographs (30°) were graded masked using a modified Rotterdam Classification for 3475 (98%) participants with gradable images. Prevalence for different AMD grades were calculated. Demographic details were analysed then integrated with the AMD gradings for full analysis. Prevalence rates for the different AMD Grades were calculated, as well as the age-specific prevalences.ResultsAMD prevalence in the worst eye were 38.5% grade 0, 41.4% grade 1, 12.8% grade 2, 2.8% grade 3, and 4.6% grade 4. Geographic atrophy (grade 4a) occurred in 2.5%, and neovascular AMD (grade 4b) in 1.8%. Prevalence increased with age such that grade 4 (advanced) AMD was 2.2% in the 65-69 years group, 15.8% for the 85-90, and 21.2% for over 90 years. There was significant asymmetry between the two eyes of individuals with advanced AMD (P<0.001), such that vision loss was unilateral. Persons with more advanced AMD grades were more likely to be dissatisfied with their vision.ConclusionsAdvanced AMD occurs more commonly in the UK Caucasian population than previously reported. Significant asymmetry between the two eyes occurs in individuals with unilateral advanced AMD so that visual impairment statistics do not represent true prevalence of advanced AMD. Persons with more advanced AMD were more likely to be dissatisfied with their vision.
Stress disrupts response memory retrieval.
Psychoneuroendocrinology, 2013

Stress effects on memory are well-known. Most studies, however, focused on the impact of stress on hippocampus-dependent 'declarative' memory processes. Less is known about whether stress influences also striatum-based memory processes, such as stimulus-response (S-R) memory. First evidence from rodent experiments shows that glucocorticoid stress hormones may enhance the consolidation of S-R memories. Whether stress affects also S-R memory retrieval remains largely elusive. Therefore, we tested in the present experiment in humans the effect of stress on the retrieval of S-R memories. Healthy men and women were trained to locate three objects in an S-R version of a virtual eight-arm radial maze. One week later, participants underwent a stressor or a control condition before their memory of the S-R task was tested. Our results showed that participants (n=43) who were exposed to the stressor before retention testing made significantly more errors in this test trial, suggesting that stress impaired S-R memory retrieval. Moreover, high cortisol concentrations were associated with reduced S-R memory. These findings indicate that stress may affect memory retrieval processes in humans beyond hippocampal 'declarative' memory.
mGluR5-dependent modulation of dendritic excitability in CA1 pyramidal neurons mediated by enhancement of persistent Na
The Journal of physiology, 2018

High-frequency stimulation (HFS) of the Schaffer collateral pathway activates metabotropic glutamate receptor 5 (mGluR5) signalling in the proximal apical dendrites of CA1 pyramidal neurons. The synaptic activation of mGluR5-mediated calcium signalling causes a significant increase in persistent sodium current (I
Cortical morphometric correlational networks associated with cognitive deficits in first episode schizophrenia.
Schizophrenia research, 2021

Schizophrenia (SCZ) is a chronic cognitive and behavioral disorder associated with abnormal cortical activity during information processing. Several brain structures associated with the seven performance domains evaluated using the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) have shown cortical volume loss in first episode schizophrenia (FES) patients. However, the relationship between morphological organization and MCCB performance remains unclear. Therefore, in the current observational study, high-resolution structural MRI scans were collected from 50 FES patients, and the morphometric correlation network (MCN) using cortical volume was established to characterize the cortical pattern associated with poorer MCCB performance. We also investigated topological properties, such as the modularity, the degree and the betweenness centrality. Our findings show structural volume was directly and strongly associated with the cognitive deficits of FES patients in the precuneus, anterior cingulate, and fusiform gyrus, as well as the prefrontal, parietal, and sensorimotor cortices. The medial orbitofrontal, fusiform, and superior frontal gyri were not only identified as the predominant nodes with high degree and betweenness centrality in the MCN, but they were also found to be critical in performance in several of the MCCB domains. Together, these results suggest a widespread cortical network is altered in FES patients and that performance on the MCCB domains is associated with the core pathophysiology of SCZ.
Watching what's coming near increases tactile sensitivity: An experimental investigation.
Behavioural brain research, 2016

During medical examinations, doctors regularly investigate a patient's somatosensory system by approaching the patient with a medical device (e.g. Von Frey hairs, algometer) or with their hands. It is assumed that the obtained results reflect the true capacities of the somatosensory system. However, evidence from crossmodal spatial research suggests that sensory experiences in one modality (e.g. touch) can be influenced by concurrent information from other modalities (e.g. vision), especially near the body (i.e. in peripersonal space). Hence, we hypothesized that seeing someone approaching your body could alter tactile sensitivity in that body-part. In the In Vivo Approaching Object (IVAO) paradigm, participants detected and localized threshold-level vibrotactile stimuli administered on the left of right hand (=tactile targets). In Experiment 1, this was always preceded by the experimenter approaching the same (congruent trials) or the other (incongruent trials) hand with a pen (=visual cue). In Experiment 2, a condition was added in which a point further away from the hands (also left vs. right) was approached. Response Accuracy was calculated for congruent and incongruent trials (Experiment 1 & 2) and compared between the close and far condition (Experiment 2). As expected, Response Accuracy was higher in congruent trials compared to incongruent trials, but only near the body. As a result, evidence was found for a crossmodal interaction effect between visual and tactile information in peripersonal space. These results suggest that somatosensory evaluations-both medical or research-based-may be biased by viewing an object approaching the body.
Longitudinal Maintenance of Cognitive Health in Centenarians in the 100-plus Study.
JAMA network open, 2020

Some individuals who reach ages beyond 100 years in good cognitive health may be resilient against risk factors associated with cognitive decline. Exploring the processes underlying resilience may contribute to the development of therapeutic strategies that help to maintain cognitive health while aging.
Restoration of direct pathway glycogen synthesis flux in the STZ-diabetes rat model by insulin administration.
American journal of physiology. Endocrinology and metabolism, 2012

Type 1 diabetes subjects are characterized by impaired direct pathway synthesis of hepatic glycogen that is unresponsive to insulin therapy. Since it is not known whether this is an irreversible defect of insulin-dependent diabetes, direct and indirect pathway glycogen fluxes were quantified in streptozotocin (STZ)-induced diabetic rats and compared with STZ rats that received subcutaneous or intraperitoneal insulin (I-SC or I-IP). Three groups of STZ rats were studied at 18 days post-STZ treatment. One group was administered I-SC and another I-IP as two daily injections of short-acting insulin at the start of each light and dark period for days 9-18. A third group did not receive any insulin, and a fourth group of nondiabetic rats was used as control. Glycogen synthesis via direct and indirect pathways, de novo lipogenesis, and gluconeogenesis were determined over the nocturnal feeding period using deuterated water. Direct pathway was residual in STZ rats, and glucokinase activity was also reduced significantly from control levels. Insulin administration restored both net glycogen synthesis via the direct pathway and glucokinase activity to nondiabetic control levels and improved the lipogenic pathway despite an inefficient normalization of the gluconeogenic pathway. We conclude that the reduced direct pathway flux is not an irreversible defect of insulin-dependent diabetes.
Exploring Risk and Resilient Profiles for Functional Impairment and Baseline Predictors in a 2-Year Follow-Up First-Episode Psychosis Cohort Using Latent Class Growth Analysis.
Journal of clinical medicine, 2020

Being able to predict functional outcomes after First-Episode Psychosis (FEP) is a major goal in psychiatry. Thus, we aimed to identify trajectories of psychosocial functioning in a FEP cohort followed-up for 2 years in order to find premorbid/baseline predictors for each trajectory. Additionally, we explored diagnosis distribution within the different trajectories. A total of 261 adults with FEP were included. Latent class growth analysis identified four distinct trajectories: Mild impairment-Improving trajectory (Mi-I) (38.31% of the sample), Moderate impairment-Stable trajectory (Mo-S) (18.39%), Severe impairment-Improving trajectory (Se-I) (12.26%), and Severe impairment-Stable trajectory (Se-S) (31.03%). Participants in the Mi-I trajectory were more likely to have higher parental socioeconomic status, less severe baseline depressive and negative symptoms, and better premorbid adjustment than individuals in the Se-S trajectory. Participants in the Se-I trajectory were more likely to have better baseline verbal learning and memory and better premorbid adjustment than those in the Se-S trajectory. Lower baseline positive symptoms predicted a Mo-S trajectory vs. Se-S trajectory. Diagnoses of Bipolar disorder and Other psychoses were more prevalent among individuals falling into Mi-I trajectory. Our findings suggest four distinct trajectories of psychosocial functioning after FEP. We also identified social, clinical, and cognitive factors associated with more resilient trajectories, thus providing insights for early interventions targeting psychosocial functioning.
Visual orientation and directional selectivity through thalamic synchrony.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Thalamic neurons respond to visual scenes by generating synchronous spike trains on the timescale of 10-20 ms that are very effective at driving cortical targets. Here we demonstrate that this synchronous activity contains unexpectedly rich information about fundamental properties of visual stimuli. We report that the occurrence of synchronous firing of cat thalamic cells with highly overlapping receptive fields is strongly sensitive to the orientation and the direction of motion of the visual stimulus. We show that this stimulus selectivity is robust, remaining relatively unchanged under different contrasts and temporal frequencies (stimulus velocities). A computational analysis based on an integrate-and-fire model of the direct thalamic input to a layer 4 cortical cell reveals a strong correlation between the degree of thalamic synchrony and the nonlinear relationship between cortical membrane potential and the resultant firing rate. Together, these findings suggest a novel population code in the synchronous firing of neurons in the early visual pathway that could serve as the substrate for establishing cortical representations of the visual scene.
fMRI activation during failures to respond key to understanding performance changes with sleep deprivation.
Behavioural brain research, 2011

During sleep deprivation (SD), failures to respond (FR) increase across a variety of tasks. This is the first systematic investigation of neural correlates of FR during SD. We use multivariate analysis to model neural activation separately for FR and responses (R) at each trial phase.
Evaluation of nutritional status in non-small-cell lung cancer: screening, assessment and correlation with treatment outcome.
ESMO open, 2020

BackgroundNutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients.MethodsData regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016-October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan-Meier curves were compared with log-rank test.ResultsThirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002 <3 had significantly longer 1-year PFS (85.7% vs 19.4%, p=0.02) and higher ORR (66.7%
Precise small-molecule recognition of a toxic CUG RNA repeat expansion.
Nature chemical biology, 2017

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)
Patient Expectancy as a Mediator of Placebo Effects in Antidepressant Clinical Trials.
The American journal of psychiatry, 2017

Causes of placebo effects in antidepressant trials have been inferred from observational studies and meta-analyses, but their mechanisms have not been directly established. The goal of this study was to examine in a prospective, randomized controlled trial whether patient expectancy mediates placebo effects in antidepressant studies.
The inner ear is involved in the aggravation of nociceptive behavior induced by lowering barometric pressure of nerve injured rats.
European journal of pain (London, England), 2010

Patients suffering from neuropathic pain often complain of pain aggravation when the weather is changing. The exact mechanism for weather change-induced pain has not been clarified. We have previously demonstrated that experimentally lowering barometric pressure (LP) intensifies pain-related behaviors in rats with chronic constriction injury (CCI). In the present experiment we examined whether this pain aggravating effect of LP exposure in nerve injured rats is still present after lesioning of the inner ear. We used both CCI and spinal nerve ligation (SNL) models for this study. We injected into the middle ear sodium arsanilate solution (100mg/ml, 50microl/ear), which is known to degenerate vestibular hair cells, under anesthesia the day before surgery. Rats were exposed to LP (27hPa decrease over 8min) 7-9 days after CCI or 5-8 days after SNL surgery, and pain-related behavior (number of paw lifts induced by von Frey hair stimuli) was measured. When the inner ear lesioned SNL or CCI rats were exposed to LP, they showed no augmentation of pain-related behavior. On the other hand, the pain aggravating effect of a temperature decrease (from 24 to 17 degrees C) was maintained in both SNL and CCI rats. These results suggest that the barometric sensor/sensing system influencing nociceptive behavior during LP in rats is located in the inner ear.
TAG-1-assisted progenitor elongation streamlines nuclear migration to optimize subapical crowding.
Nature neuroscience, 2013

Neural progenitors exhibit cell cycle-dependent interkinetic nuclear migration (INM) along the apicobasal axis. Despite recent advances in understanding its underlying molecular mechanisms, the processes to which INM contributes mechanically and the regulation of INM by the apicobasally elongated morphology of progenitors remain unclear. We found that knockdown of the cell-surface molecule TAG-1 resulted in retraction of neocortical progenitors' basal processes. Highly shortened stem-like progenitors failed to undergo basalward INM and became overcrowded in the periventricular (subapical) space. Surprisingly, the overcrowded progenitors left the apical surface and migrated into basal neuronal territories. These observations, together with the results of in toto imaging and physical tests, suggest that progenitors may sense and respond to excessive mechanical stress. Although, unexpectedly, the heterotopic progenitors remained stem-like and continued to sequentially produce neurons until the late embryonic period, histogenesis was severely disrupted. Thus, INM is essential for preventing overcrowding of nuclei and their somata, thereby ensuring normal brain histogenesis.
Outcomes of endovascular treatment for acute large-vessel ischaemic stroke more than 6 h after symptom onset.
Journal of internal medicine, 2017

Benefit from endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) acute ischaemic stroke (AIS) is well demonstrated. Furthermore, emerging evidence supports efficacy in appropriately selected patients treated beyond current recommendations of 6 h. We evaluated clinical outcomes in patients undergoing late EVT at our institution.
Properties of short-latency responses in the upper limbs evoked by axial impulses during leaning: evidence for reticulospinal projections.
Experimental brain research, 2018

We studied the short-latency (SL) effects of postural perturbations produced by impulses applied over the spine of the C7 vertebra or the sternum ("axial impulses") in 12 healthy subjects. EMG recordings were made bilaterally from the triceps brachii, biceps brachii, soleus, and tibialis anterior muscles, and unilaterally from the deltoid, forearm flexors, forearm extensors, and first dorsal interosseous (FDI) muscles. Sternal impulses evoked short-latency responses in the biceps when subjects leaned posteriorly to support approximately 12% of their body weight with the arms, but these responses were only modestly larger than for isometric contraction of the arms (26.3 vs. 14.7%). In contrast, clear excitatory responses could be evoked in the deltoid, triceps, forearm muscles, and FDI when leaning anteriorly to support similar amounts of body weight. These responses were significantly larger than during isometric contraction. The deltoid (42.5%) and triceps (44.7%) had the largest responses in supported anterior lean and onset latencies increased distally in this condition (mean 31.8 ms in deltoid to 53.7 ms in FDI). There was a disproportionate delay between the forearm muscles and FDI. For both directions of lean, postural reflex responses normally present in the legs were severely attenuated. SL upper limb excitatory responses were bigger in proximal muscles as well as larger and more widespread for anterior axial perturbations compared to posterior axial perturbations when using the arms to support body weight. Our findings also provide further evidence of a role for reticulospinal pathways in mediating these rapid postural responses to accelerations of the trunk.
Movement disorders in adult surviving patients with maple syrup urine disease.
Movement disorders : official journal of the Movement Disorder Society, 2011

Maple syrup urine disease is a rare metabolic disorder caused by mutations in the branched-chain α-keto acid dehydrogenase complex gene. Patients generally present early in life with a toxic encephalopathy because of the accumulation of the branched-chain amino acids leucine, isoleucine, and valine and the corresponding ketoacids. Movement disorders in maple syrup urine disease have typically been described during decompensation episodes or at presentation in the context of a toxic encephalopathy, with complete resolution after appropriate dietary treatment. Movement disorders in patients surviving childhood are not well documented. We assessed 17 adult patients with maple syrup urine disease (mean age, 27.5 years) with a special focus on movement disorders. Twelve (70.6%) had a movement disorder on clinical examination, mainly tremor and dystonia or a combination of both. Parkinsonism and simple motor tics were also observed. Pyramidal signs were present in 11 patients (64.7%), and a spastic-dystonic gait was observed in 6 patients (35.2%). In summary, movement disorders are common in treated adult patients with maple syrup urine disease, and careful neurological examination is advisable to identify those who may benefit from specific therapy. © 2011 Movement Disorder Society.