rudyvdbrink/CitationDatabase huggingface dataset:
COVID-19 and stroke-Understanding the relationship and adapting services. A global World Stroke Organisation perspective.
International journal of stroke : official journal of the International Stroke Society, 2021

A year ago the World Stroke Organisation (WSO) highlighted the enormous global impact of the COVID-19 pandemic on stroke care. In this review, we consider a year later where we are now, what the future holds, and what the long-term effects of the pandemic will be on stroke. Stroke occurs in about 1.4% of patients hospitalized with COVID-19 infection, who show an excess of large vessel occlusion and increased mortality. Despite this association, stroke presentations fell dramatically during the pandemic, although emerging data suggest that total stroke mortality may have risen with increased stroke deaths at home and in care homes. Strategies and guidelines have been developed to adapt stroke services worldwide, and protect healthcare workers. Adaptations include increasing use of telemedicine for all aspects of stroke care. The pandemic is exacerbating already marked global inequalities in stroke incidence and mortality. Lastly, the pandemic has had a major impact on stroke research and funding, although it has also emphasized the importance of large scale collaborative research initiatives.
Psychiatrists and neuroscientists of Indian origin in Canada: Glimpses.
Indian journal of psychiatry, 2010

Psychiatrists of Indian origin are popular in Canada, being firmly rooted in the Canadian mental health system, and they have been making considerable contributions internationally. The Indian Psychiatric Society has long been collaborating with and inviting contributions from overseas Indian psychiatrists, particularly those in academics, and this collaboration has fructified well. There are several different challenges these psychiatrists have had to face in their own specialty work, with having to adjust to a new culture, new ways of living, and new ways of work. Our colleagues of Indian origin have demonstrated excellence in almost all fields of mental health and neurosciences. There are many popular teachers, outstanding researchers, and psychiatrists in community practice and community development. The Early Psychosis Program, Mood and Anxiety Program, Perinatal Psychiatry, Women's Mental Health, and Postpartum Mental Health are some of their key areas of research. Our basic scientists are involved in experimental design, neurochemistry, imaging, and genetics, where they have made their mark with acclaim. This article highlights some of the achievements of a few members and is by no means completely representative of the entire work that psychiatrists of Indian origin are doing in Canada, providing readers with a glimpse of our labors away from home.
Stuck in the past: neural events that predict intrusions from prior trials.
Psychological science, 2013

Neurologically intact adults perseverate in immediate serial recall, intruding items from a previous trial into the current response. We applied the electroencephalogram/event-related-potential subsequent-memory paradigm to immediate serial recall to investigate the causes of these errors. In line with previous studies using this paradigm, results revealed that words that were correctly recalled elicited a greater frontal positivity during encoding when compared with words that were either perseverated over or not produced for some other reason. More surprisingly, differences were also found at encoding between the words perseverated into the subsequent response and words that were not perseverated. These findings support a theory stating that abnormalities in both how the current target and the previous trial are processed can contribute to perseveration errors. These results inform existing theories of immediate serial recall and theories of the control of irrelevant information.
Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.
Annual review of pharmacology and toxicology, 2021

This review explores how different classes of drugs, including those with therapeutic and abuse potential, alter brain functions and behavior via the epigenome. Epigenetics, in its simplest interpretation, is the study of the regulation of a genes' transcriptional potential. The epigenome is established during development but is malleable throughout life by a wide variety of drugs, with both clinical utility and abuse potential. An epigenetic effect can be central to the drug's therapeutic or abuse potential, or it can be independent from the main effect but nevertheless produce beneficial or adverse side effects. Here, I discuss the various epigenetic effects of main pharmacological drug classes, including antidepressants, antiepileptics, and drugs of abuse.
"MAPseq"-uencing Long-Range Neuronal Projections.
Neuron, 2016

Kebschull et al. (2016a) describe "MAPseq," which tags individual neurons from a specific brain region with individual mRNA barcodes and sequences these barcodes in other brain regions. This allows the simultaneous mapping of long-range neuronal projections at single-cell resolution.
ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks.
Nature communications, 2019

Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. To explore genetic resistance mechanisms, we performed genome-wide CRISPR-Cas9 screens in cells treated with the DNA topoisomerase I inhibitor topotecan. Thus, we here establish that inactivating terminal components of the non-homologous end-joining (NHEJ) machinery or of the BRCA1-A complex specifically confer topotecan resistance to ATM-deficient cells. We show that hypersensitivity of ATM-mutant cells to topotecan or the poly-(ADP-ribose) polymerase (PARP) inhibitor olaparib reflects delayed engagement of homologous recombination at DNA-replication-fork associated single-ended double-strand breaks (DSBs), allowing some to be subject to toxic NHEJ. Preventing DSB ligation by NHEJ, or enhancing homologous recombination by BRCA1-A complex disruption, suppresses this toxicity, highlighting a crucial role for ATM in preventing toxic LIG4-mediated chromosome fusions. Notably, suppressor mutations in ATM-mutant backgrounds are different to those in BRCA1-mutant scenarios, suggesting new opportunities for patient stratification and additional therapeutic vulnerabilities for clinical exploitation.
Helmets improve estimations of depth and visual angle to safe targets.
Attention, perception & psychophysics, 2018

Egocentric distance estimation has been shown to depend on wearing safety gear, which promotes compensatory behavior, and on target type, which regulates fight-or-flight responses. We hypothesized that the two factors interact, possibly in asymmetric fashion, and set out to uncover the limits of this interaction in a perceptual task where individuals wearing helmets or baseball caps estimated egocentric distance to non-threatening and threatening animals depicted on cards (i.e., safe and unsafe targets). We found that, compared to participants wearing caps, participants wearing helmets overshoot distance estimations and were able to distinguish not only between targets situated at two depth levels as participants wearing caps could, but also between safe targets situated at wide and narrow visual angles. Our findings help define the interaction between safety devices and target type, thereby contributing to the debate between advocates of prevention models and those who maintain that these are offset by compensatory strategies.
Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial.
Psychopharmacology, 2021

Suicidality is a major public health concern with limited treatment options. Accordingly, there is a need for innovative interventions for suicidality. Preliminary evidence indicates that treatment with the psychedelic ayahuasca may lead to decreases in depressive symptoms among individuals with major depressive disorder (MDD). However, there remains limited understanding of whether ayahuasca also leads to reductions in suicidality.
Age-related hearing loss: Why we need to think about sex as a biological variable.
Journal of neuroscience research, 2020

It has long been known that age-related hearing loss (ARHL) is more common, more severe, and with an earlier onset in men compared to women. Even in the absence of confounding factors such as noise exposure, these sexdifferences in susceptibility to ARHL remain. In the last decade, insight into the pleiotrophic nature by which estrogen signaling can impact multiple signaling mechanisms to mediate downstream changes in gene expression and/or elicit rapid changes in cellular function has rapidly gathered pace, and a role for estrogen signaling in the biological pathways that confer neuroprotection is becoming undeniable. Here I review the evidence why we need to consider sex as a biological variable (SABV) when investigating the etiology of ARHL. Loss of auditory function with aging is frequency-specific and modulated by SABV. Evidence also suggests that differences in cochlear physiology between women and men are already present from birth. Understanding the molecular basis of these sex differences in ARHL will accelerate the development of precision medicine therapies for ARHL.
Identification of high-impact gene-drug pairs for pharmacogenetic testing in Alberta, Canada.
Pharmacogenetics and genomics, 2021

To facilitate decision-making and priority-setting related to Alberta's Pharmacogenomics (PGx) testing implementation strategy by identifying gene-drug pairs with the highest potential impact on prescribing practices in Alberta.
Psychological and neurobiological mechanisms underlying the decline of maternal behavior.
Neuroscience and biobehavioral reviews, 2020

The maternal behavior decline is important for the normal development of the young and the wellbeing of the mother. This paper reviews limited research on the factors and mechanisms involved in the rat maternal behavior decline and proposes a multi-level model. Framed in the parent-offspring conflict theory (an ultimate cause) and the approach-withdrawal model (a proximate cause), the maternal behavior decline is viewed as an active and effortful process, reflecting the dynamic interplay between the mother and her offspring. It is instigated by the waning of maternal motivation, coupled with the increased maternal aversion by the mother in responding to the changing sensory and motoric patterns of pup stimuli. In the decline phase, the neural circuit that mediates the inhibitory ("withdrawal") responses starts to increase activity and gain control of behavioral outputs, while the excitatory ("approach") maternal neural circuit is being inhibited or reorganized. Various hormones and certain monoamines may play a critical role in tipping the balance between the excitatory and inhibitory neural circuits to synchronize the mother-infant interaction.
Neuronal NADPH oxidase 2 regulates growth cone guidance downstream of slit2/robo2.
Developmental neurobiology, 2021

NADPH oxidases (Nox) are membrane-bound multi-subunit protein complexes producing reactive oxygen species (ROS) that regulate many cellular processes. Emerging evidence suggests that Nox-derived ROS also control neuronal development and axonal outgrowth. However, whether Nox act downstream of receptors for axonal growth and guidance cues is presently unknown. To answer this question, we cultured retinal ganglion cells (RGCs) derived from zebrafish embryos and exposed these neurons to netrin-1, slit2, and brain-derived neurotrophic factor (BDNF). To test the role of Nox in cue-mediated growth and guidance, we either pharmacologically inhibited Nox or investigated neurons from mutant fish that are deficient in Nox2. We found that slit2-mediated growth cone collapse, and axonal retraction were eliminated by Nox inhibition. Though we did not see an effect of either BDNF or netrin-1 on growth rates, growth in the presence of netrin-1 was reduced by Nox inhibition. Furthermore, attractive and repulsive growth cone turning in response to gradients of BDNF, netrin-1, and slit2, respectively, were eliminated when Nox was inhibited in vitro. ROS biosensor imaging showed that slit2 treatment increased growth cone hydrogen peroxide levels via mechanisms involving Nox2 activation. We also investigated the possible relationship between Nox2 and slit2/Robo2 signaling in vivo. astray/nox2 double heterozygote larvae exhibited decreased area of tectal innervation as compared to individual heterozygotes, suggesting both Nox2 and Robo2 are required for establishment of retinotectal connections. Our results provide evidence that Nox2 acts downstream of slit2/Robo2 by mediating growth and guidance of developing zebrafish RGC neurons.
Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.
Journal of neurology, neurosurgery, and psychiatry, 2021

The ever-growing availability of imaging led to increasing incidentally discovered unruptured intracranial aneurysms (UIAs). We leveraged machine-learning techniques and advanced statistical methods to provide new insights into rupture intracranial aneurysm (RIA) risks.
Acute activation of bronchopulmonary vagal nociceptors by type I interferons.
The Journal of physiology, 2020

Type I interferon receptors are expressed by the majority of vagal C-fibre neurons innervating the respiratory tract Interferon alpha and beta acutely and directly activate vagal C-fibers in the airways. The interferon-induced activation of C-fibers occurs secondary to stimulation of type 1 interferon receptors Type 1 interferons may contribute to the symptoms as well as the spread of respiratory viral infections by causing coughing and other defensive reflexes associated with vagal C-fibre activation ABSTRACT: We evaluated the ability of type I interferons to acutely activate airway vagal afferent nerve terminals in mouse lungs. Using single cell RT-PCR of lung-specific vagal neurons we found that IFNAR1 and IFNAR2 were expressed in 70% of the TRPV1-positive neurons (a marker for vagal C-fibre neurons) and 44% of TRPV1-negative neurons. We employed an ex vivo vagal innervated mouse trachea-lung preparation to evaluate the effect of interferons in directly activating airway nerves. Utilizing 2-photon microscopy of the nodose ganglion neurons from Pirt-Cre;R26-GCaMP6s mice we found that applying IFNα or IFNβ to the lungs acutely activated the majority of vagal afferent nerve terminals. When the type 1 interferon receptor, IFNAR1, was blocked with a blocking antibody the response to IFNβ was largely inhibited. The type 2 interferon, IFNγ, also activated airway nerves and this was not inhibited by the IFNAR1 blocking antibody. The Janus kinase inhibitor GLPG0634 (1 μm) virtually abolished the nerve activation caused by IFNβ. Consistent with the activation of vagal afferent C-fibers, infusing IFNβ into the mouse trachea led to defensive breathing reflexes including apneas and gasping. These reflexes were prevented by pretreatment with an IFN type-1 receptor blocking antibody. Finally, using whole cell patch-clamp electrophysiology of lung-specific neurons we found that IFNβ (1000 U ml
Effects of gastric inhibitory polypeptide (GIP) immunoneutralization on mouse motor coordination and memory.
Peptides, 2020

Gastric inhibitory polypeptide (GIP) is a regulatory peptide expressed in the mammalian upper small intestine, and both GIP and its receptor (GIPR) are expressed in the cortex and hippocampus regions of the brain as well. While learning and memory deficits have been observed in GIPR
Clients' Preferences for Family Involvement and Subsequent Family Contact Patterns Within OnTrackNY Early Psychosis Services.
Psychiatric services (Washington, D.C.), 2021

Little is known about clients' preferences for family involvement and subsequent family contact in naturalistic, community-based coordinated specialty care (CSC) settings. The study's primary goal was to characterize clients' preferences and longitudinal patterns of family contact with providers across the OnTrackNY network in New York.
Sequence heterochrony led to a gain of functionality in an immature stage of the central complex: A fly-beetle insight.
PLoS biology, 2020

Animal behavior is guided by the brain. Therefore, adaptations of brain structure and function are essential for animal survival, and each species differs in such adaptations. The brain of one individual may even differ between life stages, for instance, as adaptation to the divergent needs of larval and adult life of holometabolous insects. All such differences emerge during development, but the cellular mechanisms behind the diversification of brains between taxa and life stages remain enigmatic. In this study, we investigated holometabolous insects in which larvae differ dramatically from the adult in both behavior and morphology. As a consequence, the central complex, mainly responsible for spatial orientation, is conserved between species at the adult stage but differs between larvae and adults of one species as well as between larvae of different taxa. We used genome editing and established transgenic lines to visualize cells expressing the conserved transcription factor retinal homeobox, thereby marking homologous genetic neural lineages in both the fly Drosophila melanogaster and the beetle Tribolium castaneum. This approach allowed us for the first time to compare the development of homologous neural cells between taxa from embryo to the adult. We found complex heterochronic changes including shifts of developmental events between embryonic and pupal stages. Further, we provide, to our knowledge, the first example of sequence heterochrony in brain development, where certain developmental steps changed their position within the ontogenetic progression. We show that through this sequence heterochrony, an immature developmental stage of the central complex gains functionality in Tribolium larvae.
Unraveling neurological diseases: the contribution of neuroimaging.
Expert review of neurotherapeutics, 2011

The 21st Meeting of the European Neurological Society (ENS) was held on 28-31 May 2011 in Lisbon, Portugal. Over 3400 participants attained the meeting. The ENS meeting is an international event, which offers an exclusive opportunity for excellent continuous education, as well as an update of cutting-edge research in all fields of neurology. Among the key themes of this year's conference, the contribution of magnetic resonance-based techniques to unravel the physiopathology of neurological diseases and improve our knowledge of the way they progress was highlighted in several sessions. This article summarizes the major neuroimaging findings of the 21st ENS Meeting.
p-Aminobenzoic acid as an alternative chemical biopsy agent for human hepatic UDP-glucose.
Analytical biochemistry, 2020

p-Aminobenzoic acid (PABA) was evaluated for noninvasive sampling of UDP-glucose in the liver. Six healthy subjects ingested 550 mg PABA during a breakfast meal. Urine was collected 0-2 and 2-4 h after PABA ingestion. N-acetyl PABA glucuronide (NAPG) was identified with 522 ± 212 μmol recovered in the 2-4 h urines. One of the subjects ingested 2 g of 98% [U-
Regulation of risky decision making by gonadal hormones in males and females.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021

Psychiatric diseases characterized by dysregulated risky decision making are differentially represented in males and females. The factors that govern such sex differences, however, remain poorly understood. Using a task in which rats make discrete trial choices between a small, "safe" food reward and a large food reward accompanied by varying probabilities of footshock punishment, we recently showed that females are more risk averse than males. The objective of the current experiments was to test the extent to which these sex differences in risky decision making are mediated by gonadal hormones. Male and female rats were trained in the risky decision-making task, followed by ovariectomy (OVX), orchiectomy (ORX), or sham surgery. Rats were then retested in the task, under both baseline conditions and following administration of estradiol and/or testosterone. OVX increased choice of the large, risky reward (increased risky choice), an effect that was attenuated by estradiol administration. In contrast, ORX decreased risky choice, but testosterone administration was without effect in either ORX or sham males. Estradiol, however, decreased risky choice in both groups of males. Importantly, none of the effects of hormonal manipulation on risky choice were due to altered shock sensitivity or food motivation. These data show that gonadal hormones are required for maintaining sex-typical profiles of risk-taking behavior in both males and females, and that estradiol is sufficient to promote risk aversion in both sexes. The findings provide novel information about the mechanisms supporting sex differences in risk taking and may prove useful in understanding sex differences in the prevalence of psychiatric diseases associated with altered risk taking.
Psychosocial factors associated with pain and sexual function in women with Vulvodynia: A systematic review.
European journal of pain (London, England), 2021

Vulvodynia is a prevalent chronic vulval pain condition affecting 10%-28% of women, and significantly impacting their health and quality of life. It is currently poorly understood and biomedical treatments achieve only modest benefits for pain and sexual functioning. A wider psychosocial conceptualization of this condition may improve outcomes. There is currently no coherent understanding of how psychosocial factors may contribute to outcomes in Vulvodynia. The aim of this review is to identify and systematically review psychosocial factors associated with pain and sexual outcomes and to inform a psychosocial model of Vulvodynia.
Resting fMRI-guided TMS results in subcortical and brain network modulation indexed by interleaved TMS/fMRI.
Experimental brain research, 2021

Traditional non-invasive imaging methods describe statistical associations of functional co-activation over time. They cannot easily establish hierarchies in communication as done in non-human animals using invasive methods. Here, we interleaved functional MRI (fMRI) recordings with non-invasive transcranial magnetic stimulation (TMS) to map causal communication between the frontal cortex and subcortical target structures including the subgenual anterior cingulate cortex (sgACC) and the amygdala. Seed-based correlation maps from each participant's resting fMRI scan determined individual stimulation sites with high temporal correlation to targets for the subsequent TMS/fMRI session(s). The resulting TMS/fMRI images were transformed to quantile responses, so that regions of high-/low-quantile response corresponded to the areas of the brain with the most positive/negative evoked response relative to the global brain response. We then modeled the average quantile response for a given region (e.g., structure or network) to determine whether TMS was effective in the relative engagement of the downstream targets. Both the sgACC and amygdala were differentially influenced by TMS. Furthermore, we found that the sgACC distributed brain network was modulated in response to fMRI-guided TMS. The amygdala, but not its distributed network, also responded to TMS. Our findings suggest that individual targeting and brain response measurements reflect causal circuit mapping to the sgACC and amygdala in humans. These results set the stage to further map circuits in the brain and link circuit pathway integrity to clinical intervention outcomes, especially when the intervention targets specific pathways and networks as is possible with TMS.