rudyvdbrink/CitationDatabase huggingface dataset:
The sterol regulatory element-binding protein 2 is dysregulated by tau alterations in Alzheimer disease.
Brain pathology (Zurich, Switzerland), 2019

Disturbed neuronal cholesterol homeostasis has been observed in Alzheimer disease (AD) and contributes to the pathogenesis of AD. As the master switch of cholesterol biosynthesis, the sterol regulatory element-binding protein 2 (SREBP-2) translocates to the nucleus after cleavage/activation, but its expression and activation have not been studied in AD which is the focus of the current study. We found both a significant decrease in the nuclear translocation of N-terminal SREBP-2 accompanied by a significant accumulation of C-terminal SREBP-2 in NFT-containing pyramidal neurons in AD. N-terminal- SREBP-2 is also found in dystrophic neurites around plaques in AD brain. Western blot confirmed a significantly reduced nuclear translocation of mature SREBP-2 (mSREBP-2) in AD brain. Interestingly, reduced nuclear mSREBP-2 was only found in animal models of tauopathies such as 3XTg AD mice and P301L Tau Tg mice but not in CRND8 APP transgenic mice, suggesting that tau alterations likely are involved in the changes of mSREBP-2 distribution and activation in AD. Altogether, our study demonstrated disturbed SREBP-2 signaling in AD and related models, and proved for the first time that tau alterations contribute to disturbed cholesterol homeostasis in AD likely through modulation of nuclear mSREBP-2 translocation.
A cell fitness selection model for neuronal survival during development.
Nature communications, 2019

Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.
Comparison between Ischemic and Hemorrhagic Strokes in Functional Outcome at Discharge from an Intensive Rehabilitation Hospital.
Diagnostics (Basel, Switzerland), 2020

Comparison studies on recovery outcomes in ischemic (IS) and hemorrhagic strokes (HS) have yielded mixed results. In this retrospective observational study of consecutive IS and HS patients, we aimed at evaluating functional outcomes at discharge from an intensive rehabilitation hospital, comparing IS vs. HS, analyzing possible predictors. Modified Rankin Scale (mRS) at discharge was the main outcome. Out of the 229 patients included (mean age 72.9 ± 13.9 years, 48% males), 81 had HS (35%). Compared with IS (
Longitudinal association between housing accessibility and activities of daily living: the role of self-efficacy and control in people ageing with Parkinson's disease.
BMC geriatrics, 2020

External housing-related control beliefs (HCB) and general self-efficacy (GSE) influence different health outcomes in the general ageing population, but there is no information of their role in people ageing with Parkinson's disease (PD). This study aimed to longitudinally assess the role of external HCB and GSE on the association between housing accessibility and activities of daily living (ADL) among people ageing with PD.
Mechanical and physiological effects of varying pole weights during Nordic walking compared to walking.
European journal of applied physiology, 2011

The study investigated the effect of varying pole weights on energy expenditure, upper limb muscle activation and on forces transmitted to the poles during Nordic walking (NW). Twelve women [age = 21 (2) years, body mass = 60.8 (6) kg, height = 1.71 (0.06) m] participated in five 7-min walking tests randomly chosen without poles (W), with normal NW poles (NW) or with added masses of 0.5 kg (NW + 0.5) 1.0 kg (NW + 1.0) or 1.5 kg (NW + 1.5) at a speed of 2 m s(-1). Heart rate (HR), relative oxygen uptake ([Formula: see text]), blood lactate (La) and rate of perceived exertion (RPE) were registered along with surface EMG (SEMG) from biceps brachii, triceps brachii, trapecius and deltoideus muscles. Inbuilt force transducers measured reaction forces along the long axes of the poles. NW + 0.5 and NW + 1.5 showed significant increases for [Formula: see text] and RPE compared with W (p < 0.05) but with no respective differences within NW. SEMG revealed higher activation of biceps brachii for all NW tests plus added masses compared to W (p < 0.05). Additionally the activation of biceps brachii was higher for NW + 1.5 compared to NW (p < 0.05). The contribution to overall activation duration of triceps brachii became lower but increased for biceps brachii with heavier poles. The increased energy expenditure during NW can be attributed to intensified muscle activation during forward swing of the poles. Heavier poles have no effect on energy expenditure compared to NW with usual poles but enhance muscular activity. Since there are no benefits concerning physiological and biomechanical parameters we do not recommend the use of heavier NW poles.
Gambling with Rose-Tinted Glasses on: Use of Emotion-Regulation Strategies Correlates with Dysfunctional Cognitions in Gambling Disorder Patients.
Journal of behavioral addictions, 2016

Background and aims Existing research shows that gambling disorder patients (GDPs) process gambling outcomes abnormally when compared against healthy controls (HCs). These anomalies present the form of exaggerated or distorted beliefs regarding the expected utility of outcomes and one's ability to predict or control gains and losses, as well as retrospective reinterpretations of what caused them. This study explores the possibility that the emotional regulation strategies GDPs use to cope with aversive events are linked to these cognitions. Methods 41 GDPs and 45 HCs, matched in sociodemographic variables, were assessed in gambling severity, emotion-regulation strategies (cognitive emotion-regulation questionnaire, CERQ), and gambling-related cognitions (gambling-related cognitions scale, GRCS). Results GDPs showed higher scores in all gambling-related cognition dimensions. Regarding emotion regulation, GDPs were observed to use self-blame and catastrophizing, but also positive refocusing, more often than controls. Additionally, in GDPs, putatively adaptive CERQ strategies shared a significant portion of variance with South Oaks gambling screen severity and GRCS beliefs. Shared variability was mostly attributable to the roles of refocusing on planning and putting into perspective at positively predicting severity and the interpretative bias (GDPs propensity to reframe losses in a more benign way), respectively. Discussion and conclusions Results show links between emotion-regulation strategies and problematic gambling-related behaviors and cognitions. The pattern of those links supports the idea that GDPs use emotion-regulation strategies, customarily regarded as adaptive, to cope with negative emotions, so that the motivational and cognitive processing of gambling outcomes becomes less effective in shaping gambling-related behavior.
Protracted development of executive and mnemonic brain systems underlying working memory in adolescence: A longitudinal fMRI study.
NeuroImage, 2017

Working memory (WM), the ability to hold information on-line to guide planned behavior, improves through adolescence in parallel with continued maturation of critical brain systems supporting cognitive control. Initial developmental neuroimaging studies with one or two timepoints have provided important though varied results limiting our understanding of which and how neural systems change during this transition into mature WM. In this study, we leverage functional magnetic resonance imaging (fMRI) longitudinal data spanning up to 9 years in 129 normally developing individuals to identify which systems demonstrate growth changes that accompany improvements in WM performance. We used a memory guided saccade task that allowed us to probe encoding, pure maintenance, and retrieval neural processes of WM. Consistent with prior research, we found that WM performance continued to improve into the early 20's. fMRI region of interest (ROI) analyses revealed developmental (1) increases in sensorimotor-related (encoding/retrieval) activity in visual cortex from childhood through early adulthood that were associated with WM accuracy and (2) decreases in sustained (maintenance) activity in executive regions from childhood through mid-adolescence that were associated with response latency in childhood and early adolescence. Together these results provide compelling evidence that underlying the maturation of WM is a transition from reliance on executive systems to specialized regions related to the domain of mnemonic requirements of the task leading to optimal performance.
Prevalence and disability of comorbid social phobia and obsessive-compulsive disorder in patients with panic disorder and generalized anxiety disorder.
International journal of psychiatry in clinical practice, 2014

Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive-compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58).
Movement goals encoded within the cortex and muscle synergies to reduce redundancy pre and post-stroke. The relevance for gait rehabilitation and the prescription of walking-aids. A literature review and scholarly discussion.
Physiotherapy theory and practice, 2019

Current knowledge of neural and neuromuscular processes controlling gait and movement as well as an understanding of how these mechanisms change following stroke is an important basis for the development of effective rehabilitation interventions. To support the translation of findings from basic research into useful treatments in clinical practice, up-to-date neuroscience should be presented in forms accessible to all members of the multidisciplinary team. In this review we discuss aspects of cortical control of gait and movement, muscle synergies as a way of translating cortical commands into specific muscle activity and as an efficient means of reducing neural and musculoskeletal redundancy. We discuss how these mechanisms change following stroke, potential consequences for gait rehabilitation, and the prescription and use of walking-aids as well as areas requiring further research.
Effect of androgen supplementation on 24-hour activity-rest patterns of aged male rhesus macaques.
Neurobiology of aging, 2017

Like elderly men, old male rhesus macaques show attenuated circulating levels of testosterone and dehydroepiandrosterone sulfate, and many of them also show reduced levels of daytime activity. It is unclear, however, if this age-associated behavioral change is causally related to the underlying decrease in circulating androgen levels. To test this possibility, old male rhesus macaques were given daily supplements of testosterone and DHEA for 6 months, designed to mimic the mean 24-hour circulating hormone patterns of young adults. Compared with the young adults, the old controls showed attenuated daytime activity levels. However, there was no difference between the androgen-supplemented old animals and the aged-matched controls, even after 6 months of treatment. The data suggest that age-associated decreases in circulating androgen levels are unlikely to be a primary reason for altered activity-rest patterns in elderly men, and that androgen supplementation paradigms might not provide any obvious therapeutic benefit.
Recommended Strategies for Physician Burnout, a Well-Recognized Escalating Global Crisis Among Neurologists.
Journal of clinical neurology (Seoul, Korea), 2020

Several indexes are used to classify physician burnout, with the Maslach Burnout Inventory currently being the most widely accepted. This index measures physician burnout based on emotional exhaustion, detachment from work, and lack of personal achievement. The overall percentage of physicians with burnout is estimated to be around 40%, but the proportion varies between specialties. Neurology currently has the second-highest rate of burnout and is projected to eventually take the top position. The purpose of this review is to provide a comprehensive overview focusing on the causes and ramifications of burnout and possible strategies for addressing the crisis. Several factors contribute to burnout among neurologist, including psychological trauma associated with patient care and a lack of respect compared to other specialties. Various interventions have been proposed for reducing burnout, and this article explores the feasibility of some of them. Burnout not only impacts the physician but also has adverse effects on the overall quality of patient care and places a strain on the health-care system. Burnout has only recently been recognized and accepted as a health crisis globally, and hence most of the proposed action plans have not been validated. More studies are needed to evaluate the long-term effects of such interventions.
Loss of IGF1R in Human Astrocytes Alters Complex I Activity and Support for Neurons.
Neuroscience, 2018

The insulin/insulin-like growth factor 1 (IGF1) signaling pathways are implicated in longevity and in progression of Alzheimer's disease. Previously, we showed that insulin-like growth factor 1 receptor (IGF1R) and downstream signaling transcripts are reduced in astrocytes in human brain with progression of Alzheimer's neuropathology and developed a model of IGF1 signaling impairment in human astrocytes using an IGF1R-specific monoclonal antibody, MAB391. Here, we have established a novel human astrocyte-neuron co-culture system to determine whether loss of astrocytic IGF1R affects their support for neurons. Astrocyte-neuron co-cultures were developed using human primary astrocytes and differentiated Lund Human Mesencephalic Cells (LUHMES). Neurite outgrowth assays, performed to measure astrocytic support for neurons, showed astrocytes provided contact-mediated support for neurite outgrowth. Loss of IGF1R did not affect neurite outgrowth under control conditions but when challenged with hydrogen peroxide IGF1R-impaired astrocytes were less able to protect LUHMES. To determine how loss of IGF1R affects neuronal support MAB391-treated astrocytes were FACS sorted from GFP-LUHMES and their transcriptomic profile was investigated using microarrays. Changes in transcripts involved in astrocyte energy metabolism were identified, particularly NDUFA2 and NDUFB6, which are related to complex I assembly. Loss of complex I activity in MAB391-treated astrocytes validated these findings. In conclusion, reduced IGF1 signaling in astrocytes impairs their support for neurons under conditions of stress and this is associated with defects in the mitochondrial respiratory chain in astrocytes.
Age-dependent uncoupling of mitochondria from Ca2⁺ release units in skeletal muscle.
Oncotarget, 2015

Calcium release units (CRUs) and mitochondria control myoplasmic [Ca2+] levels and ATP production in muscle, respectively. We recently reported that these two organelles are structurally connected by tethers, which promote proximity and proper Ca2+ signaling.Here we show that disposition, ultrastructure, and density of CRUs and mitochondria and their reciprocal association are compromised in muscle from aged mice. Specifically, the density of CRUs and mitochondria is decreased in muscle fibers from aged (>24 months) vs. adult (3-12 months), with an increased percentage of mitochondria being damaged and misplaced from their normal triadic position. A significant reduction in tether (13.8 ± 0.4 vs. 5.5 ± 0.3 tethers/100 µm2) and CRU-mitochondrial pair density (37.4 ± 0.8 vs. 27.0 ± 0.7 pairs/100 µm2) was also observed in aged mice. In addition, myoplasmic Ca2+ transient (1.68 ± 0.08 vs 1.37 ± 0.03) and mitochondrial Ca2+ uptake (9.6 ± 0.050 vs 6.58 ± 0.54) during repetitive high frequency tetanic stimulation were significantly decreased. Finally oxidative stress, assessed from levels of 3-nitrotyrosine (3-NT), Cu/Zn superoxide-dismutase (SOD1) and Mn superoxide dismutase (SOD2) expression, were significantly increased in aged mice. The reduced association between CRUs and mitochondria with aging may contribute to impaired cross-talk between the two organelles, possibly resulting in reduced efficiency in activity-dependent ATP production and, thus, to age-dependent decline of skeletal muscle performance.
Inflammatory insults and mental health consequences: does timing matter when it comes to depression?
Psychological medicine, 2016

It has become widely accepted that the immune system, and specifically increased levels of inflammation, play a role in the development of depression. However, not everyone with increased inflammation develops depression, and as with all other diseases, there are risk factors that may contribute to an increased vulnerability in certain individuals. One such risk factor could be the timing of an inflammatory exposure. Here, using a combination of PubMed, EMBASE, Ovid Medline and PsycINFO, we systematically reviewed whether exposure to medically related inflammation in utero, in childhood, and in adolescence, increases the risk for depression in adulthood. Moreover, we tried to determine whether there was sufficient evidence to identify a particular time point during the developmental trajectory in which an immune insult could be more damaging. While animal research shows that early life exposure to inflammation increases susceptibility to anxiety- and depressive-like behaviour, human studies surprisingly find little evidence to support the notion that medically related inflammation in utero and in adolescence contributes to an increased risk of developing depression in later life. However, we did find an association between childhood inflammation and later life depression, with most studies reporting a significantly increased risk of depression in adults who were exposed to inflammation as children. More robust clinical research, measuring direct markers of inflammation throughout the life course, is greatly needed to expand on, and definitively address, the important research questions raised in this review.
Clinical presentation of young people (10-24 years old) with brain tumors: results from the international MOBI-Kids study.
Journal of neuro-oncology, 2020

We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24).
Validating biomarkers of treatable mechanisms in irritable bowel syndrome.
Neurogastroenterology and motility, 2014

A valid biomarker is 'an indicator of normal biologic or pathogenic processes, or pharmacological responses to a therapeutic intervention'. There is no validated biomarker for irritable bowel syndrome (IBS). The aim of the study was to assess ability of three quantitative traits to identify treatable processes to discriminate between IBS-diarrhea (IBS-D) patients, IBS-constipation (IBS-C) patients and healthy volunteers (HV).
Holistic versus feature-based binding in the medial temporal lobe.
Cortex; a journal devoted to the study of the nervous system and behavior, 2017

A central question for cognitive neuroscience is how feature-combinations that give rise to episodic/source memories are encoded in the brain. Although there is much evidence that the hippocampus (HIP) is involved in feature binding, and some evidence that other brain regions are as well, there is relatively little evidence about the nature of the resulting representations in different brain regions. We used multivoxel pattern analysis (MVPA) to investigate how feature combinations might be represented, contrasting two possibilities, feature-based versus holistic. Participants viewed stimuli that were composed of three source features - a person (face or body), a scene (indoor or outdoor), and an object (bike or luggage) - which were combined to make eight unique stimulus identities. We reasoned that regions that can classify the eight identities (a multiclass classification) but not the individual features (a binary classification) likely have a holistic representation of each identity. In contrast, regions that can classify the eight identities and can classify each feature are likely to contain feature-based representations of these identities. To further probe the extent of feature-based or holistic classification in each region, we developed and validated a novel approach that directly compares binary and multiclass classification. We found clear evidence for holistic representation in the parahippocampal cortex (PHC), consistent with theories that posit that pattern-separation-like binding mechanisms are not unique to the HIP. Further clarifying the mechanisms of feature binding should benefit from systematic comparisons of multi-feature representations and whether they vary with task, type of stimulus, and/or experience.
Effect of fatigue-related group III/IV afferent firing on intracortical inhibition and facilitation in hand muscles.
Journal of applied physiology (Bethesda, Md. : 1985), 2020

Fatiguing exercise causes a reduction in motor drive to the muscle. Group III/IV muscle afferent firing is thought to contribute to this process; however, the effect on corticospinal and intracortical networks is poorly understood. In two experiments, participants performed sustained maximal isometric finger abductions of the first dorsal interosseous (FDI) muscle, with postexercise blood flow occlusion (OCC) to maintain the firing of group III/IV afferents or without occlusion (control; CON). Before and after exercise, single- and paired-pulse transcranial magnetic stimulation (TMS) tested motor evoked potentials (MEPs), intracortical facilitation [ICF (12 ms)], and short-interval intracortical inhibition [SICI