rudyvdbrink/CitationDatabase huggingface dataset:
Evaluation of attention in APP/PS1 mice shows impulsive and compulsive behaviours.
Genes, brain, and behavior, 2021

While Alzheimer's disease (AD) is traditionally associated with deficits in episodic memory, early changes in other cognitive domains, such as attention, have been gaining interest. In line with clinical observations, some animal models of AD have been shown to develop attentional deficits, but this is not consistent across all models. The APPswe/PS1ΔE9 (APP/PS1) mouse is one of the most commonly used AD models and attention has not yet been scrutinised in this model. We set out to assess attention using the 5-choice serial reaction time task (5CSRTT) early in the progression of cognitive symptoms in APP/PS1 mice, using clinically translatable touchscreen chambers. APP/PS1 mice showed no attentional changes across 5CSRTT training or any probes from 9 to 11 months of age. Interestingly, APP/PS1 mice showed increased impulsive and compulsive responding when task difficulty was high. This suggests that while the APP/PS1 mouse model may not be a good model of attentional changes in AD, it may be useful to study the early changes in impulsive and compulsive behaviour that have been identified in patient studies. As these changes have not previously been reported without attentional deficits in the clinic, the APP/PS1 mouse model may provide a unique opportunity to study these specific behavioural changes seen in AD, including their mechanistic underpinnings and therapeutic implications.
Cortical layer 6 control of sensory responses in higher-order thalamus.
The Journal of physiology, 2020

Thalamic activity is regulated by corticothalamic feedback from layers 5B and 6. To selectively study the importance of the layer 6 corticothalamic (L6 CT) projection, a transgenic mouse line was used in which layer 6 cells projecting to posterior medial thalamus (POm) were targeted for expression of channelrhodopsin-2. Repetitive optogenetic stimulation of this sub-type of L6 cells caused a rapid adaptation in POm spiking output, but had little effect on the spiking activity in the other cortical layers. L6 photoactivation increased POm spiking to the first, but not to subsequent whisker deflections in a 4 Hz train. A sub-population of L6 CT cells that can cause an initial increase in POm activity, that is not sustained with repetitive stimulation, could indicate that this L6 projection does not modulate ongoing sensory processing, but rather serves to briefly increase POm activity in specific behavioural contexts.
Genome-wide association study and polygenic risk score analysis of esketamine treatment response.
Scientific reports, 2020

To elucidate the genetic underpinnings of the antidepressant efficacy of S-ketamine (esketamine) nasal spray in major depressive disorder (MDD), we performed a genome-wide association study (GWAS) in cohorts of European ancestry (n = 527). This analysis was followed by a polygenic risk score approach to test for associations between genetic loading for psychiatric conditions, symptom profiles and esketamine efficacy. We identified a genome-wide significant locus in IRAK3 (p = 3.57 × 10
Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.
Journal of clinical medicine, 2021

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.
Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets.
JAMA neurology, 2021

Substantial genome-wide association study (GWAS) work in Parkinson disease (PD) has led to the discovery of an increasing number of loci shown reliably to be associated with increased risk of disease. Improved understanding of the underlying genes and mechanisms at these loci will be key to understanding the pathogenesis of PD.
Extended Reality for the Clinical, Affective, and Social Neurosciences.
Brain sciences, 2020

Brain science research often involves the use of low-dimensional tools and stimuli that lack several of the potentially valuable features of everyday activities and interactions. Although this research has provided important information about cognitive, affective, and social processes for both clinical and nonclinical populations, there is growing interest in high-dimensional simulations that extend reality. These high-dimensional simulations involve dynamic stimuli presented serially or concurrently to permit the assessment and training of perceivers' integrative processes over time. Moreover, high-dimensional simulation platforms can contextually restrain interpretations of cues about a target's internal states. Extended reality environments extend assessment and training platforms that balance experimental control with emotionally engaging background narratives aimed at extending the affective experience and social interactions. Herein, we highlight the promise of extended reality platforms for greater ecological validity in the clinical, affective, and social neurosciences.
The Perplexity Surrounding Chiari Malformations - Are We Any Wiser Now?
AJNR. American journal of neuroradiology, 2020

Chiari malformations are a diverse group of abnormalities of the brain, craniovertebral junction, and the spine. Chiari 0, I, and 1.5 malformations, likely a spectrum of the same malformation with increasing severity, are due to the inadequacy of the para-axial mesoderm, which leads to insufficient development of occipital somites. Chiari II malformation is possibly due to nonclosure of the caudal end of the neuropore, with similar pathogenesis in the rostral end, which causes a Chiari III malformation. There have been significant developments in the understanding of this complex entity owing to insights into the pathogenesis and advancements in imaging modalities and neurosurgical techniques. This article aims to review the different types and pathophysiology of the Chiari malformations, along with a description of the various associated abnormalities. We also highlight the role of ante- and postnatal imaging, with a focus on the newer techniques in the presurgical evaluation, with a brief mention of the surgical procedures and the associated postsurgical complications.
Adolescent Characters and Alcohol Use Scenes in Brazilian Movies, 2000-2008.
International quarterly of community health education, 2016

Quantitative structured assessment of 193 scenes depicting substance use from a convenience sample of 50 Brazilian movies was performed. Logistic regression and analysis of variance or multivariate analysis of variance models were employed to test for two different types of outcome regarding alcohol appearance: The mean length of alcohol scenes in seconds and the prevalence of alcohol use scenes. The presence of adolescent characters was associated with a higher prevalence of alcohol use scenes compared to nonalcohol use scenes. The presence of adolescents was also associated with a higher than average length of alcohol use scenes compared to the nonalcohol use scenes. Alcohol use was negatively associated with cannabis, cocaine, and other drugs use. However, when the use of cannabis, cocaine, or other drugs was present in the alcohol use scenes, a higher average length was found. This may mean that most vulnerable group may see drinking as a more attractive option leading to higher alcohol use.
Characterization of focused ultrasound-mediated brainstem delivery of intranasally administered agents.
Journal of controlled release : official journal of the Controlled Release Society, 2020

Focused ultrasound-mediated intranasal (FUSIN) delivery is a recently proposed technique that bypasses the blood-brain barrier to achieve noninvasive and localized brain drug delivery. The goal of this study was to characterize FUSIN drug delivery outcome in mice with regard to its dependency on several critical experimental factors, including the time interval between IN administration and FUS sonication (T
Persistence of Antipsychotic Use After Clozapine Discontinuation: A Real-World Study Across Antipsychotics.
Clinical and translational science, 2020

Although clozapine treatment is often discontinued due to limited efficacy or low tolerability, there is a lack of guidelines and evidence on treatment options after discontinuation of clozapine in patients with schizophrenia. Persistence has proven to be an adequate indicator for treatment effectiveness in patients with schizophrenia. The aim of this study was, therefore, to compare persistence of antipsychotic use between antipsychotic treatment options in patients after stopping clozapine treatment. Registry data from a prescription database representative of the Dutch population (1996-2017) was collected to investigate persistence in patients with schizophrenia who had been using clozapine for ≥ 90 days. Persistence with antipsychotics after clozapine discontinuation was analyzed using Cox-proportional hazard regression models. Our study population consisted of 321 participants, of whom 138 re-initiated clozapine and 183 started some other antipsychotic in the year after clozapine discontinuation (N = 518 antipsychotic use periods, N = 9,178 months). Second-generation antipsychotics (SGAs) as a group were associated with better persistence compared to first-generation antipsychotics (adjusted hazard ratio (aHR), 0.73; 95% confidence interval (CI) 0.57-0.93; P = 0.011). Compared with other antipsychotics, the following oral monotherapy antipsychotics were associated with significantly better persistence: restarting clozapine (aHR 0.48; 95% CI 0.32-0.71; P < 0.001) and switching to risperidone (aHR 0.52; 95% CI 0.32-0.84; P = 0.008) or olanzapine (aHR 0.55; 95% CI 0.35-0.87; P = 0.010). Sensitivity analyses confirmed the results. In conclusion, oral SGAs are associated with better persistence than alternative antipsychotic treatment options in patients discontinuing clozapine for undefined reasons. Especially clozapine (except in those with previous serious adverse reactions to clozapine), olanzapine and risperidone should be considered as oral monotherapy for these patients.
Stalling for Time: It's Not the Magnitude, but the Way Neurons Fire that Matters.
Neuron, 2017

In this issue of Neuron, Stavisky et al. (2017) demonstrate that visual feedback in M1 during reaching initially reflects a specific pattern of neural activity that does not generate motor output and then is altered to a pattern that does generate motor output. This switch likely provides time for the motor system to consider various behavioral factors when specifying the appropriate motor response during voluntary motor actions.
The Demands of Geometry on Color Vision.
Vision (Basel, Switzerland), 2017

While studies of human color vision have made enormous strides, an overarching rationale for the circular sense of color relationships generated by two classes of color opponent neurons and three cone types is still lacking. Here we suggest that color circularity, color opponency and trichromacy may have arisen, at least in part, because of the geometrical requirements needed to unambiguously distinguish all possible spectrally different regions on a plane.
Mitophagy coordination with retrograde transport ensures the integrity of synaptic mitochondria.
Autophagy, 2020

Mitochondria sustain various essential functions at synaptic terminals. Synaptic mitochondria deficits have been implicated in early Alzheimer disease (AD) pathophysiology. Mitophagy, a selective autophagy for removal of damaged mitochondria, plays a key role in mitochondrial quality control in neurons. However, fundamental questions remain unanswered as to whether mitophagy regulates synaptic mitochondrial integrity and whether AD-associated early deficits in synaptic mitochondria are attributed to mitophagy failure. We have recently revealed that the integrity of synaptic mitochondria is maintained by a coordination of RHEB-mediated mitophagy with dynein- and SNAPIN-driven retrograde transport. We demonstrate that increased mitophagy initiation, coupled with defective retrograde transport, triggers mitophagy stress at AD synapses. Excitingly, SNAPIN-enhanced retrograde transport reduces synaptic mitophagy stress and ameliorates mitochondrial deficits, thereby counteracting synaptic damage in AD mouse brains. Therefore, our study provides new mechanistic insights into how mitophagy facilitates synaptic mitochondrial maintenance and how mitophagy failure exacerbates AD-linked mitochondrial defects and synaptic degeneration. Abbreviation: AD: Alzheimer disease; Aβ: amyloid-β; APP: amyloid beta precursor protein; CCCP: carbonyl cyanide
Exosome-Shuttled circSHOC2 from IPASs Regulates Neuronal Autophagy and Ameliorates Ischemic Brain Injury via the miR-7670-3p/SIRT1 Axis.
Molecular therapy. Nucleic acids, 2020

The aim of the present study was to investigate the neuroprotective roles and mechanisms of the circular RNA circSHOC2 in ischemic-preconditioned astrocyte-derived exosomes (IPAS-EXOs) against ischemic stroke. We established an ischemia model based on oxygen glucose deprivation (OGD)
Mechanisms and mode of action of spinal cord stimulation in chronic neuropathic pain.
Postgraduate medicine, 2020

Tonic spinal cord stimulation (SCS) has been used as a treatment for chronic neuropathic pain ever since its discovery in late 1960s. Despite its clinical successes in a subset of chronic neuropathic pain syndromes, several limitations such as insufficient pain relief and uncomfortable paresthesias have led to the development of new targets, the dorsal root ganglion, and new stimulation waveforms, such as burst and high frequency. The aim of this review is to provide a brief overview of the main mechanisms behind the mode of action of the different SCS paradigms. Tonic SCS mainly acts via a segmental spinal mechanism where it induces GABA-release from inhibitory interneurons in the spinal dorsal horn. Tonic SCS concurrently initiates neuropathic pain modulation through a supraspinal-spinal feedback loop and serotonergic descending fibers. Mechanisms of stimulation of the DRG as well as those related to new SCS paradigms are now under investigation, where it seems that burst SCS not only stimulates sensory, discriminative aspects of pain (like Tonic SCS) but also emotional, affective, and motivational aspects of pain. Initial long-term study results on closed-loop SCS systems hold promise for improvement of future SCS treatment.
Developing an instrument for an early prediction model of long-term functional outcomes in people with acquired injuries of the central nervous system: protocol and methodological aspects.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2021

Severe acquired brain injury (ABI) is a major cause of long-term disability and is the main determinant of health and societal costs. Early identification of favourable long-term recovery would allow personalized rehabilitative programs and better health care resources allocation. In light of the higher survival rate from intensive care units (ICU) in recent years, there is a growing need for early prognostication markers of functional recovery; to date, these data have been mainly collected at rehabilitation unit admission and not during the acute phase. We present the protocol and methodology to develop prediction models in people with severe acquired brain injury (GCS at admission to ICU < 8) for the functional and cognitive outcome at 12 months from the event. Predictors will be collected during the acute stage. Participants will be recruited within the first 72 h from the event in the ICUs of two teaching hospitals (Padova and Treviso). Participants will be followed up at discharge from ICU, admission and discharge from Neurorehabilitation and after 12 months from the event. Clinical and functional scales, electroencephalography, evoked potentials, magnetic resonance imaging and serological markers will be entered into a digital registry. Survival will be estimated using the Cox proportional hazard model. A multivariate prediction model will be developed for each of the functional and cognitive outcomes at 12 months from the event.
Effect of subthalamic nucleus stimulation on severe striatal hand deformity in Parkinson's disease: a case report.
Neuromodulation : journal of the International Neuromodulation Society, 2008

Striatal hand is a deformity encountered in Parkinson's disease and other parkinsonisms. It is characterized by extension that occurs at all the interphalangeal joints, flexion at the metacarpophalangeal joints, and ulnar deviation. It can be differentiated from levodopa-induced dystonia and primary dystonia, since the deformity exists continuously even during sleep. We experienced a case of Parkinson's disease with severe striatal hand deformity which was successfully treated by deep brain stimulation of the subthalamic nucleus (STN-DBS). Although the precise mechanism remains unclear, rigidity is assumed to contribute to the limb deformities. Based on our experience, it seems possible therefore that the effect of STN-DBS on the hand deformity was a secondary effect on muscular rigidity. STN-DBS is assumed to represent a useful treatment option for striatal hand deformity.
Microglia dynamics in sleep/wake states and in response to sleep loss.
Neurochemistry international, 2021

Sleep has an essential role for optimal brain function, but the cellular substrates for sleep regulation are not fully understood. Microglia, the immune cells of the brain, have gained increasingly more attention over the last two decades for their important roles in various brain functions that extend beyond their well-known immune function, including brain development, neuronal protection, and synaptic plasticity. Here we review recent advances in understanding: i) morphological and phenotypic dynamics of microglia including process motility/growth and gene/protein expression, and ii) microglia-neuron interactions including phagocytosis and contact at synapses which alters neuronal circuit activity, both under physiological state in the adult brain. We discuss how the microglia-neuron interactions particularly at synapses could influence microglia and neuronal activities across circadian cycles and sleep/wake states. We also review recent findings on how microglia respond to sleep loss. We conclude by pointing out key questions and proposing suggestions for future research to better understand the role of microglia in sleep regulation, sleep homeostasis, and the function of sleep.
Family-Based Treatment for Pediatric Obesity: Case Study of an Adaptation for a Non-Psychiatric Adolescent Population.
Journal of contemporary psychotherapy, 2019

Pediatric overweight and obesity, a highly prevalent condition posing risks extending into adulthood, is considered a major public health concern. Findings from the pediatric obesity treatment literature support the efficacy of parental involvement across multiple formats. Family-based treatment is an outpatient intervention for adolescents with eating disorders that enlists parents as the primary agents of symptom management during the acute stages of illness, titrating down their involvement as severity of the disorder decreases. We adapted family-based treatment for pediatric obesity, modifying the original model to recognize that children and adolescents with obesity do not exhibit the developmental regression seen in eating disorders and to reflect the non-psychiatric nature of obesity. Thus, family-based treatment for pediatric obesity modulates the degree of parental involvement as a function of chronological developmental stage, not severity of the condition. To illustrate the implementation of this treatment, we present a case report of a 15-year old with an eight-year history of overweight and a greater than 30-pound weight gain prior to treatment. Through this case study, the three phases of family-based treatment for pediatric obesity and six-month post treatment follow-up results are presented through the lens of response from this adolescent and her family. We present this case report to illustrate the implementation of the intervention's adolescent module, and the potential impact of the approach in the treatment of adolescents with obesity and their families.
Evolution of TLR4 role in mediating the hepatoprotective effects of estradiol after traumatic brain injury in male rats.
Biochemical pharmacology, 2020

Several studies have shown that 17β-estradiol (E2) exerted beneficial effects on liver disease, and it has a protective impact on brain damage after traumatic brain injury (TBI). TBI-induced liver injury is associated with the activation of TLR4. However, it remains unknown whether E2 can modulate TBI-induced liver injury through TLR4. The objective of this study was to determine the role of TLR4 in hepatoprotective mechanisms of E2 after TBI. Diffuse TBI induced by the Marmarou model in male rats. TAK-242 as a selective antagonist of TLR4 (3 mg/kg) and E2 (33.3 μg/kg) were injected (i.p) respectively 30 min before and 30 min after TBI. The results showed that E2 and TAK-242 markedly inhibited TBI-induced liver injury, which was characterized by decreased aminotransferase activities, inhibition of the oxidative stress, and reduced levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and IL-17 in the liver. We also found that TBI induced significant upregulation of TLR4 in the liver, with peak expression occurring 24 h after TBI, and that treatment with E2 significantly inhibited the upregulation of TLR4. Also, both classic [Estrogen receptors alpha (ERα) and beta (ERβ)] and non-classic (G protein-coupled estrogen receptor GPER) E2 receptors are involved in modulating the expression of TLR4. These results suggested that the hepatoprotective effects of estradiol after TBI may be mediated via the downregulation expression of TLR4.
Dietary and Pharmacological Interventions That Inhibit Mammalian Target of Rapamycin Activity Alter the Brain Expression Levels of Neurogenic and Glial Markers in an Age-and Treatment-Dependent Manner.
Rejuvenation research, 2020

Intermittent fasting (IF) and its mimetic, rapamycin extend lifespan and healthspan through mechanisms that are not fully understood. We investigated different short-term durations of IF and rapamycin on cellular and molecular changes in the brains of young (6-10 months) and old (26-31 months) zebrafish. Interestingly, our results showed that IF significantly lowered glucose levels while increasing DCAMKL1 in both young and old animals. This proliferative effect of IF was supported by the upregulation of