rudyvdbrink/CitationDatabase huggingface dataset:
Pur-alpha functionally interacts with FUS carrying ALS-associated mutations.
Cell death & disease, 2015

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to motor neuron loss. Fused in sarcoma (FUS) protein carrying ALS-associated mutations localizes to stress granules and causes their coalescence into larger aggregates. Here we show that Pur-alpha physically interacts with mutated FUS in an RNA-dependent manner. Pur-alpha colocalizes with FUS carrying mutations in stress granules of motoneuronal cells differentiated from induced pluripotent stem cells and that are derived from ALS patients. We observe that both Pur-alpha and mutated FUS upregulate phosphorylation of the translation initiation factor eukaryotic translation initiation factor 2 alpha and consistently inhibit global protein synthesis. In vivo expression of Pur-alpha in different Drosophila tissues significatively exacerbates the neurodegeneration caused by mutated FUS. Conversely, the downregulation of Pur-alpha in neurons expressing mutated FUS significatively improves fly climbing activity. All these findings suggest that Pur-alpha, through the control of mRNA translation, might be involved in the pathogenesis of ALS associated with the mutation of FUS, and that an alteration of protein synthesis may be directly implicated in the disease. Finally, in vivo RNAi-mediated ablation of Pur-alpha produced locomotion defects in Drosophila, indicating a pivotal role for this protein in the motoneuronal function.
Cardiometabolic Risks in Schizophrenia and Directions for Intervention, 2: Nonpharmacological Interventions.
The Journal of clinical psychiatry, 2016

Patients with schizophrenia have increased prevalence rates for many cardiometabolic risks, including the metabolic syndrome, and an increased risk of adverse cardiovascular events, including mortality. Behavioral interventions such as diet and exercise (separately and together) improve physical health outcomes in the general population. There are no studies on dietary guidance as a sole behavioral intervention for patients with schizophrenia. A meta-analysis found that exercise as a sole behavioral intervention does not result in meaningful physical or mental health gains in patients with major mental illness. Another meta-analysis found that combined diet and exercise, along with other behavioral elements, was associated with statistically significant but modest weight reduction (mean = 3.14 kg) in the short to intermediate term, but with no other cardiometabolic risk factor benefits. A large, well-supervised, pragmatic, 1-year randomized controlled trial found that behavioral interventions were not associated with health gains on a 10-year cardiovascular risk index, or on a large range of indices of physical and mental health. An added concern is that patients with schizophrenia are poorly motivated for behavioral interventions and show poor participation in such interventions. Barriers, and means of overcoming these barriers, have been identified for the implementation of behavioral programs to improve physical health in patients with serious mental illness. It remains to be demonstrated, however, that behavioral intervention programs consistently improve cardiovascular health indices in patients with schizophrenia and other major mental illnesses.
Autism and the environment: challenges and opportunities for research.
Pediatrics, 2008

Autism spectrum disorder is a complex developmental disorder that dramatically affects the lives of patients and their families and the broader community. The causes of autism are unknown; however, evidence increasingly suggests that a complex interplay among environmental stressors, genetic mutations, and other biological factors likely plays a significant role in the development and/or progression of autism spectrum disorder. On April 18 and 19, 2007, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders hosted a workshop to provide a venue to bring together scientists; major sponsors of autism-related research; and members of the autism patient, family, and advocacy community to discuss the most promising and urgent scientific questions and opportunities. Broad participation by the autism community enriched the meeting significantly by contributing a valuable and personal perspective that is often missing from scientific meetings. It also began a much improved public-private partnership in which all stakeholders are represented. On the basis of the presentations and the discussions that followed, an array of important scientific opportunities were identified in 5 general categories: (1) opportunities to advance clinical research; (2) opportunities to enhance epidemiologic studies; (3) opportunities to improve the understanding of autism's pathology and etiology; (4) tools and infrastructure needs; and (5) opportunities for public-private partnerships. This workshop demonstrated that full public engagement can greatly enhance activities such as this workshop and its outcomes. Furthermore, we expect that this listing of scientific challenges, needs, and opportunities will help to frame a more comprehensive research agenda.
Salvage of Dental Implant Located in Mandibular Odontogenic Cyst. A Conservative Surgical Treatment Proposal.
Dentistry journal, 2020

The aim of this case report was to evaluate the use of Partsch I cystotomy in order to preserve a dental implant located in an odontogenic cyst extended from 3.2 to 4.4. A 50 year-old woman showed a circular, well-defined unilocular radiolucent area, Ø2.5 cm, in the right mandibular region with an oral implant intruding inside it. The overdenture in the mandibular right site showed no clinical mobility. The authors decided to perform a surgical treatment aimed to preserve the implant. The patient underwent Partsch I surgery followed by iodoform gauze insertion replaced weekly for one month, revision of the previous orthograde endodontic treatments, and an acrylic resin obturator prosthesis application for the following two months. The twelve month follow-up showed no clinical mobility of the right lateral mandibular implant prostheses. Radiographical analysis revealed cystic lesion healing and perimplant bone regeneration. This report highlights the opportunity to apply cystotomy when the cyst involves a dental implant and undermines its stability. This possibility is offered by the peculiar clinical scenario where the implant was stabilized by the presence of a previous prosthetic fixation. Our study led to the application of an operative protocol that allowed for the preservation of the implant.
Cilostazol improves hippocampus-dependent long-term memory in mice.
Psychopharmacology, 2014

Phosphodiesterases (PDEs) play an important role in the regulation of intracellular signaling mediated by cyclic adenosine monophosphate (cAMP). Recently, several PDE inhibitors were assessed for their possible cognitive enhancing properties. However, little is known about the effect of PDE3 inhibitors on memory function.
Regulation of voltage-gated sodium channel expression in cancer: hormones, growth factors and auto-regulation.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2014

Although ion channels are increasingly being discovered in cancer cells in vitro and in vivo, and shown to contribute to different aspects and stages of the cancer process, much less is known about the mechanisms controlling their expression. Here, we focus on voltage-gated Na(+) channels (VGSCs) which are upregulated in many types of carcinomas where their activity potentiates cell behaviours integral to the metastatic cascade. Regulation of VGSCs occurs at a hierarchy of levels from transcription to post-translation. Importantly, mainstream cancer mechanisms, especially hormones and growth factors, play a significant role in the regulation. On the whole, in major hormone-sensitive cancers, such as breast and prostate cancer, there is a negative association between genomic steroid hormone sensitivity and functional VGSC expression. Activity-dependent regulation by positive feedback has been demonstrated in strongly metastatic cells whereby the VGSC is self-sustaining, with its activity promoting further functional channel expression. Such auto-regulation is unlike normal cells in which activity-dependent regulation occurs mostly via negative feedback. Throughout, we highlight the possible clinical implications of functional VGSC expression and regulation in cancer.
A quarter century of decline of autopsies in the Netherlands.
European journal of epidemiology, 2019

Autopsy rates have been declining worldwide. The present study reports the outcome of a retrospective analysis of all non-forensic autopsies in the Netherlands over a course of 25 years, and compares these with the most recent Dutch study.
Advance care planning in Australia during the COVID-19 outbreak: now more important than ever.
Internal medicine journal, 2020

The novel Coronavirus disease 2019 (COVID-19) outbreak has led to rapid and profound changes in healthcare system delivery and society more broadly. Older adults, and those living with chronic or life-limiting conditions, are at increased risk of experiencing severe or critical symptoms associated with COVID-19 infection and are more likely to die. They may also experience non-COVID-19 related deterioration in their health status during this period. Advance care planning (ACP) is critical for this cohort, yet there is no coordinated strategy for increasing the low rates of ACP uptake in these groups, or more broadly. This paper outlines a number of key reasons why ACP is an urgent priority, and should form a part of the health system's COVID-19 response strategy. These include reducing the need for rationing, planning for surges in healthcare demand, respecting human rights, enabling proactive care coordination and leveraging societal change. We conclude with key recommendations for policy and practice in the system-wide implementation of ACP, to enable a more ethical, coordinated and person-centred response in the COVID-19 context.
tDCS Effects on Verbal Fluency: A Response to Vannorsdall et al (2016).
Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology, 2016

In a prior study (Cattaneo et al, 2011. Neuroscience. 183:64-70), we demonstrated that anodal transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus enhanced verbal fluency in healthy young adults. Although our data are in line with the results of other published studies, another research group recently failed to report anodal tDCS effects on verbal fluency using a paradigm similar to ours (Vannorsdall et al, 2016. Cogn Behav Neurol. 29:11-17). Here we discuss aspects of study design and interpretation of results that should be considered in replications, focusing particularly on homogeneity of procedures. Notwithstanding the possibility that our study may indeed not be replicable, we hypothesize that Vannorsdall et al found an interesting modifier of the tDCS effects on verbal production by introducing a critical methodologic difference from our original study. We demonstrate this difference by presenting the results of an additional experiment. We believe that the sharing of data between research groups and constructive debate on possible differences in results should be encouraged because they help define the boundaries of applicability of an experimental paradigm. This is even more important for research findings that may have clinical implications, as is the case here.
Transcranial direct current stimulation for the treatment of tinnitus: a review of clinical trials and mechanisms of action.
BMC neuroscience, 2018

Tinnitus is the perception of sound in the absence of any external acoustic stimulation. Transcranial direct current stimulation (tDCS) has shown promising though heterogeneous therapeutic outcomes for tinnitus. The present study aims to review the recent advances in applications of tDCS for tinnitus treatment. In addition, the clinical efficacy and main mechanisms of action of tDCS on suppressing tinnitus are discussed.
Importance of the commissural nucleus of the solitary tract in renovascular hypertension.
Hypertension research : official journal of the Japanese Society of Hypertension, 2019

The rodent renovascular hypertension model has been used to investigate the mechanisms promoting hypertension. The importance of the carotid body for renovascular hypertension has been demonstrated. As the commissural NTS (cNTS) is the first synaptic site in the central nervous system that receives information from carotid body chemoreceptors, we evaluated the contribution of cNTS to renovascular hypertension in the present study. Normotensive male Holtzman rats were implanted with a silver clip around the left renal artery to induce two-kidney, one-clip (2K1C) hypertension. Six weeks later, isoguvacine (a GABA
In a rat model of panic, corticotropin responses to dorsal periaqueductal gray stimulation depend on physical exertion.
Psychoneuroendocrinology, 2015

Panic disorder patients are exquisitely and specifically sensitive to hypercapnia. The demonstration that carbon dioxide provokes panic in fear-unresponsive amygdala-calcified Urbach-Wiethe patients emphasizes that panic is not fear nor does it require the activation of the amygdala. This is consonant with increasing evidence suggesting that panic is mediated caudally at midbrain's dorsal periaqueductal gray matter (DPAG). Another startling feature of the apparently spontaneous clinical panic is the counterintuitive lack of increments in corticotropin, cortisol and prolactin, generally considered 'stress hormones'. Here we show that the stress hormones are not changed during DPAG-evoked panic when escape is prevented by stimulating the rat in a small compartment. Neither did the corticotropin increase when physical exertion was statistically adjusted to the same degree as non-stimulated controls, as measured by lactate plasma levels. Conversely, neuroendocrine responses to foot-shocks were independent from muscular effort. Data are consonant with DPAG mediation of panic attacks.
Understanding the need for assistance with survey completion in people with Huntington disease.
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, 2018

In Huntington disease (HD), motor, cognitive, and psychiatric changes can have a detrimental impact on health-related quality of life (HRQOL). The purpose of this paper is to describe the extent and type of assistance needed to complete online HRQOL surveys, and the impact of assistance on HRQOL scores.
Effects of a single interprofessional simulation session on medical and nursing students' attitudes toward interprofessional learning and professional identity: a questionnaire study.
BMC medical education, 2020

Participation in simulation-based interprofessional education (sim-IPE) may affect students' attitudes towards interprofessional learning (through gaining experience with others) and their professional identity (by increasing the 'fit' of group membership). We examined this in two questionnaire studies involving students from four universities in two areas of the UK.
Drug attitude and other predictors of medication adherence in schizophrenia: 12 months of electronic monitoring (MEMS(®)) in the Swedish COAST-study.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 2013

The aim was to investigate clinical predictors of adherence to antipsychotics. Medication use was electronically monitored with a Medication Event Monitoring System (MEMS(®)) for 12 months in 112 outpatients with schizophrenia and schizophrenia-like psychosis according to DSM-IV. Symptom burden, insight, psychosocial function (PSP) and side effects were rated at baseline. A comprehensive neuropsychological test battery was administered and a global composite score was calculated. The Drug Attitude Inventory (DAI-10) was filled in. A slightly modified DAI-10 version for informants was distributed as a postal questionnaire. Non-adherence (MEMS(®) adherence ≤0.80) was observed in 27%. In univariate regression models low scores on DAI-10 and DAI-10 informant, higher positive symptom burden, poor function, psychiatric side effects and lack of insight predicted non-adherence. No association was observed with global cognitive function. In multivariate regression models, low patient-rated DAI-10 and PSP scores emerged as predictors of non-adherence. A ROC analysis showed that DAI-10 had a moderate ability to correctly identify non-adherent patients (AUC=0.73, p<0.001). At the most "optimal" cut-off of 4, one-third of the adherent would falsely be identified as non-adherent. A somewhat larger AUC (0.78, p<0.001) was observed when the ROC procedure was applied to the final regression model including DAI-10 and PSP. For the subgroup with informant data, the AUC for the DAI-10 informant version was 0.68 (p=0.021). Non-adherence cannot be properly predicted in the clinical setting on the basis of these instruments alone. The DAI-10 informant questionnaire needs further testing.
Positron Emission Tomographic Imaging in Stroke: Cross-Sectional and Follow-Up Assessment of Amyloid in Ischemic Stroke.
Stroke, 2016

Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time.
Stepwise impairment of neural stem cell proliferation and neurogenesis concomitant with disruption of blood-brain barrier in recurrent ischemic stroke.
Neurobiology of disease, 2018

Stroke patients are at increased risk for recurrent stroke and development of post-stroke dementia. In this study, we investigated the effects of recurrent stroke on adult brain neurogenesis using a novel rat model of recurrent middle cerebral artery occlusion (MCAO) developed in our laboratory. Using BrdU incorporation, activation and depletion of stem cells in the subgranular zone (SGZ) and subventricular zone (SVZ) were assessed in control rats and rats after one or two strokes. In vitro neurosphere assay was used to assess the effects of plasma from normal and stroke rats. Also, EM and permeability studies were used to evaluate changes in the blood-brain-barrier (BBB) of the SGZ after recurrent stroke. We found that proliferation and neurogenesis was activated 14 days after MCAO. This was correlated with increased permeability in the BBB to factors which increase proliferation in a neurosphere assay. However, with each stroke, there was a stepwise decrease of proliferating stem cells and impaired neurogenesis on the ipsilateral side. On the contralateral side, this process stabilized after a first stroke. These studies indicate that stem cells are activated after MCAO, possibly after increased access to systemic stroke-related factors through a leaky BBB. However, the recruitment of stem cells for neurogenesis after stroke results in a stepwise ipsilateral decline with each ischemic event, which could contribute to post-stroke dementia.
A novel anti-inflammatory role of NCAM-derived mimetic peptide, FGL.
Neurobiology of aging, 2010

Age-related cognitive deficits in hippocampus are correlated with neuroinflammatory changes, typified by increased pro-inflammatory cytokine production and microglial activation. We provide evidence that the neural cell adhesion molecule (NCAM)-derived mimetic peptide, FG loop (FGL), acts as a novel anti-inflammatory agent. Administration of FGL to aged rats attenuated the increased expression of markers of activated microglia, the increase in pro-inflammatory interleukin-1beta (IL-1beta) and the impairment in long-term potentiation (LTP). We report that the age-related increase in microglial activation was accompanied by decreased expression of neuronal CD200, and suggest that the proclivity of FGL to suppress microglial activation is due to its stimulatory effect on neuronal CD200. We demonstrate that FGL enhanced interleukin-4 (IL-4) release from glial cells and IL-4 in turn enhanced neuronal CD200 in vitro. We provide evidence that the increase in CD200 is reliant on IL-4-induced extracellular signal-regulated kinase (ERK) signal transduction. These findings provide the first evidence of a role for FGL as an anti-inflammatory agent and identify a mechanism by which FGL controls microglial activation.
Fine Astrocyte Processes Contain Very Small Mitochondria: Glial Oxidative Capability May Fuel Transmitter Metabolism.
Neurochemical research, 2015

The peripheral astrocyte process (PAP) is the glial compartment largely handling inactivation of transmitter glutamate, and supplying glutamate to the axon terminal. It is not clear how these energy demanding processes are fueled, and whether the PAP exhibits oxidative capability. Whereas the GFAP-positive perinuclear cytoplasm and stem process are rich in mitochondria, the PAP is often considered too narrow to contain mitochondria and might thus not rely on oxidative metabolism. Applying high resolution light microscopy, we investigate here the presence of mitochondria in the PAPs of freshly dissociated, isolated astrocytes. We provide an overview of the subcellular distribution and the approximate size of astrocytic mitochondria. A substantial proportion of the astrocyte's mitochondria are contained in the PAPs and, on the average, they are smaller there than in the stem processes. The majority of mitochondria in the stem and peripheral processes are surprisingly small (0.2-0.4 µm), spherical and not elongate, or tubular, which is supported by electron microscopy. The density of mitochondria is two to several times lower in the PAPs than in the stem processes. Thus, PAPs do not constitute a mitochondria free glial compartment but contain mitochondria in large numbers. No juxtaposition of mitochondria-containing PAPs and glutamatergic synapses has been reported. However, the issue of sufficient ATP concentrations in perisynaptic PAPs can be seen in the light of (1) the rapid, activity dependent PAP motility, and (2) the recently reported activity-dependent mitochondrial transport and immobilization leading to spatial, subcellular organisation of glutamate uptake and oxidative metabolism.