Mice Knocked Out for the Primary Brain Calcification–Associated Gene Slc20a2 Show Unimpaired Prenatal Survival but Retarded Growth and Nodules in the Brain that Grow and Calcify Over Time

Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by pre- and post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with pre-diagnosed PAVMs on contrast-enhanced MRA underwent embolization therapy. The number of PAVMs treated in each patient ranged from 1–8 PAVMs. Depending on the size and localization of the feeding arteries, either Nester-Coils or Amplatzer vascular plugs were used for embolization therapy. cMRI was performed immediately before, and at the 4 h and 3-month post-embolization therapy. Detection of peri-interventional cerebral emboli was performed via T2w and DWI sequences using three different b-values, with calculation of ADC maps. Results Embolization did not show any post-/peri-interventional, newly developed ischemic lesions in the brain. Only one patient who underwent re-embolization and was previously treated with tungsten coils that corroded over time showed newly developed, small, diffuse emboli in the post-interventional DWI sequence. This patient already had several episodes of brain emboli before re-treatment due to the corroded coils, and during treatment, when passing the corroded coils, experienced additional small, clinically inconspicuous brain emboli. However, this complication was anticipated but accepted, since the vessel had to be occluded distally. Conclusion Catheter-based embolization of PAVMs is a safe method for treatment and does not result in clinically inconspicuous cerebral ischemia, which was not demonstrated previously.

Download Full-text

What is special about L3 processing?

Bilingualism Language and Cognition ◽

10.1017/s1366728913000448 ◽

2013 ◽

Vol 18 (2) ◽

pp. 130-144 ◽

Cited By ~ 36

Author(s):

KEES DE BOT ◽

CAROL JAENSCH

Keyword(s):

Second Language ◽

Language Processing ◽

Language Use ◽

Fundamental Question ◽

Third Language ◽

The Core ◽

Dynamic Perspective ◽

Core Issue ◽

The Brain ◽

Over Time

While research on third language (L3) and multilingualism has recently shown remarkable growth, the fundamental question of what makes trilingualism special compared to bilingualism, and indeed monolingualism, continues to be evaded. In this contribution we consider whether there is such a thing as a true monolingual, and if there is a difference between dialects, styles, registers and languages. While linguistic and psycholinguistic studies suggest differences in the processing of a third, compared to the first or second language, neurolinguistic research has shown that generally the same areas of the brain are activated during language use in proficient multilinguals. It is concluded that while from traditional linguistic and psycholinguistic perspectives there are grounds to differentiate monolingual, bilingual and multilingual processing, a more dynamic perspective on language processing in which development over time is the core issue, leads to a questioning of the notion of languages as separate entities in the brain.

Download Full-text

GROUP 6 year outcome data in relation to antipsychotic medication

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.917 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S50-S50

Author(s):

W. Cahn ◽

Keyword(s):

Metabolic Syndrome ◽

Cohort Study ◽

Psychotic Disorders ◽

Medication Use ◽

Mood Stabilizer ◽

Outcome Data ◽

Longitudinal Cohort Study ◽

Longitudinal Cohort ◽

The Brain ◽

Over Time

ObjectiveGenetic risk and outcome of psychoses (GROUP) is a 6 year longitudinal cohort study that focus on gene–environment vulnerability and resilience in patients with psychotic disorders, their unaffected family members and non-related controls. Its main aim is to elucidate etiological and pathogenetic factors that influence the onset and course of psychotic disorders. In this substudy, we will examine medication use over time, its relation with (the change in) metabolic syndrome status and effects on the brain.MethodsA consortium of four university psychiatric centers and their affiliated mental health care institutions, conducted the GROUP study. At baseline, 1120 patients, 1057 siblings, 919 parents and 590 healthy controls were included. After inclusion, participants, except parents, were evaluated again after three and six years of follow-up. Extensive assessment of genetic factors, environmental factors, medication use, metabolic parameters and outcome were performed. Moreover, brain imaging was performed in a subset of participants, using a 1.5 Tesla MRI scanner.ResultsAt baseline 65% of patients used atypical antipsychotics, 16% used conventional antipsychotics and 19% used clozapine. Siblings and controls used no antipsychotics. Forty-three percent of patients, 21.3% of siblings and 9.1% of controls used antidepressants; 43.9% of patients, 2.1% of siblings and none of the controls used a mood stabilizer. We are currently analyzing the medication data over time in relation to (change in) metabolic syndrome status and the effects on the brain.ConclusionGROUP is a longitudinal cohort study in patients with psychotic disorders, their healthy siblings and controls without psychosis. This naturalistic substudy examines medication use, its association with (change of) metabolic status and effects on the brain in subjects with (high risk of) psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Download Full-text

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

Trends in Psychiatry and Psychotherapy ◽

10.1590/2237-6089-2016-0075 ◽

2017 ◽

Vol 39 (2) ◽

pp. 98-105 ◽

Cited By ~ 4

Author(s):

Paula Madeira Fortes ◽

Lucas Albrechet-Souza ◽

Mailton Vasconcelos ◽

Bruna Maria Ascoli ◽

Ana Paula Menegolla ◽

...

Keyword(s):

Aggressive Behavior ◽

Physiological Responses ◽

Plasma Corticosterone ◽

Corticotropin Releasing Factor ◽

Brain Areas ◽

Social Stressors ◽

Swiss Mice ◽

The Brain ◽

Over Time ◽

Resident Intruder

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Download Full-text

Leukocyte dynamics after intracerebral hemorrhage in a living patient reveal rapid adaptations to tissue milieu

10.1101/2020.11.10.375675 ◽

2020 ◽

Author(s):

Brittany A. Goods ◽

Michael H. Askenase ◽

Erica Markarian ◽

Hannah E. Beatty ◽

Riley Drake ◽

...

Keyword(s):

Intracerebral Hemorrhage ◽

Single Cell ◽

Brain Tissue ◽

Cellular Response ◽

Tissue Injury ◽

Brain Inflammation ◽

Therapeutic Interventions ◽

Acute Injury ◽

The Brain ◽

Over Time

ABSTRACTIntracerebral hemorrhage (ICH) is a devastating form of stroke with a high mortality rate and few treatment options. Discovery of therapeutic interventions has been slow given the challenges associated with studying acute injury, particularly over time, in the human brain. Inflammation induced by exposure of brain tissue to blood appears to be a major part of brain tissue injury. Here we longitudinally profiled blood and cerebral hematoma effluent from a patient enrolled in the Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIEIII) trial, offering a rare window into the local and systemic immune responses to acute brain injury. Using single-cell RNA-sequencing, we characterized the local cellular response during ICH in the brain of a living patient at single-cell resolution for the first time. Our analysis revealed rapid shifts in the activation states of myeloid and T cells in the brain over time, suggesting that leukocyte responses are dynamically reshaped by the hematoma microenvironment. Interestingly, the patient had an asymptomatic re-bleed (second local exposure to blood) that our transcriptional data indicated occurred more than 30 hours prior to detection by CT scan. This case highlights the rapid immune dynamics in the brain after ICH and suggests that sensitive methods like scRNA-seq can inform our understanding of complex intracerebral events.

Download Full-text

Moving beyond the distinction between concrete and abstract concepts

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2017.0144 ◽

2018 ◽

Vol 373 (1752) ◽

pp. 20170144 ◽

Cited By ~ 27

Author(s):

Lawrence W. Barsalou ◽

Léo Dutriaux ◽

Christoph Scheepers

Keyword(s):

Conceptual System ◽

Frequent Patterns ◽

Abstract Concepts ◽

Theme Issue ◽

Situated Action ◽

Conceptual Processing ◽

Individual Concepts ◽

Directed Action ◽

The Brain ◽

Over Time

From the perspective of the situated conceptualization framework, the primary purpose of concepts is for categorizing and integrating elements of situations to support goal-directed action (including communication and social interaction). To the extent that important situational elements are categorized and integrated properly, effective goal-directed action follows. Over time, frequent patterns of co-occurring concepts within situations become established in memory as situated conceptualizations, conditioning the conceptual system and producing habitual patterns of conceptual processing. As a consequence, individual concepts are most basically represented within patterns of concepts that become entrained with specific kinds of physical situations. In this framework, the concrete versus abstract distinction between concepts is no longer useful, with two other distinctions becoming important instead: (i) external versus internal situational elements, (ii) situational elements versus situational integrations. Whereas concepts for situational elements originate in distributed neural networks that provide continual feeds about components of situations, concepts for situational integrations originate in association areas that establish temporal co-occurrence relations between situational elements, both external and internal. We propose that studying concepts in the context of situated action is necessary for establishing complete accounts of them, and that continuing to study concepts in isolation is likely to provide relatively incomplete and distorted accounts. This article is part of the theme issue ‘Varieties of abstract concepts: development, use and representation in the brain’.

Download Full-text

Resilience

Genes, brain, and emotions ◽

10.1093/oso/9780198793014.003.0020 ◽

2019 ◽

pp. 286-303 ◽

Cited By ~ 1

Author(s):

Rebecca Alexander ◽

Justine Megan Gatt

Keyword(s):

Well Being ◽

Neural Systems ◽

Dynamic Interactions ◽

Control Networks ◽

Effective Interventions ◽

Adaptive Recovery ◽

The Brain ◽

Insight Into ◽

Over Time

Resilience refers to the process of adaptive recovery following adversity or trauma. It is likely to include an intertwined series of dynamic interactions between neural, developmental, environmental, genetic, and epigenetic factors over time. Neuroscientific research suggests the potential role of the brain’s threat and reward systems, as well as executive control networks. Developmental research provides insight into how the environment may affect these neural systems across the lifespan towards greater risk or resilience to stress. Genetic work has revealed numerous targets that alter key neurochemical systems in the brain to influence mental health. Current challenges include ambiguities in the definition and measurement of resilience and a simplified focus on resilience as the absence of psychopathology, irrespective of levels of positive mental functioning. Greater emphasis on understanding the protective aspects of resilience and related well-being outcomes are important to delineate the unique neurobiological factors that underpin this process, so that effective interventions can be developed to assist vulnerable populations and resilience promotion.

Download Full-text

Pharmacodynamics of Isavuconazole in a Rabbit Model of Cryptococcal Meningoencephalitis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00546-19 ◽

2019 ◽

Vol 63 (9) ◽

Cited By ~ 4

Author(s):

Laura L. Kovanda ◽

Charles Giamberardino ◽

Laura McEntee ◽

Dena L. Toffaletti ◽

Kelly S. Franke ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Fungal Pathogens ◽

Rabbit Model ◽

Response Relationship ◽

Fungal Burden ◽

Cryptococcal Meningoencephalitis ◽

Exposure Response ◽

Dose Dependent ◽

The Brain ◽

Over Time

ABSTRACT Cryptococcus spp., important fungal pathogens, are the leading cause of fungus-related mortality in human immunodeficiency virus-infected patients, and new therapeutic options are desperately needed. Isavuconazonium sulfate, a newer triazole antifungal agent, was studied to characterize the exposure-response relationship in a rabbit model of cryptococcal meningoencephalitis. Rabbits treated with isavuconazonium sulfate were compared with those treated with fluconazole and untreated controls. The fungal burden in the cerebrospinal fluid was measured serially over time, while the yeast concentrations in the brain and the eye (aqueous humor) were determined at the end of therapy. The exposure impact of isavuconazonium sulfate dosing in the rabbit was linked using mathematical modeling. Similar significant reductions in the fungal burden in the brain and cerebrospinal fluid in rabbits treated with isavuconazonium sulfate and fluconazole compared with that in the untreated controls were observed. No dose-dependent response was demonstrated with isavuconazonium sulfate treatment in this study. The treatment of cryptococcal meningoencephalitis with isavuconazonium sulfate was similar to that with fluconazole. Dose-dependent reductions in yeast over time were not demonstrated, which limited our ability to estimate the pharmacodynamic target. Further nonclinical and clinical studies are needed in order to characterize the extent of the exposure-response relationship in cryptococcal meningoencephalitis. However, this study suggests that isavuconazonium sulfate, like fluconazole, could be beneficial in the setting of consolidation and maintenance therapy, rather than induction monotherapy, in high-burden cryptococcal meningoencephalitis.

Download Full-text

A Design Tool for Distributed Concept Development

Volume 9: Engineering Education and Professional Development ◽

10.1115/imece2008-67751 ◽

2008 ◽

Author(s):

Kate Nordland ◽

Edward Hensel

Keyword(s):

Design Space ◽

Concept Development ◽

Design Tool ◽

Design Environment ◽

Weighted Voting ◽

Design Intent ◽

Morphological Chart ◽

The Brain ◽

Over Time

This paper provides an overview of a database tool to support collaborative concept development in an asynchronous, distributed design environment. This paper will illustrate how an ideation method, such as as brainstorming, can be applied to a desired set of functions for a new design. The result of the brain-storming session for each articulated function can then be used in conjunction with a collaborative weighted voting tool to develop a rank-ordered morphological chart of the design space. A case study will be presented to illustrate how the information and knowledge generated in a prior working session by a design group can be introduced into a subsequent design session. The case study will illustrate how knowledge can be effectively transferred from one design project to the next, and preserve design intent over time.

Download Full-text

Using surgical and oncology workload to plan brain tumour trial recruitment in England

Neuro-Oncology ◽

10.1093/neuonc/noz167.047 ◽

2019 ◽

Vol 21 (Supplement_4) ◽

pp. iv11-iv12

Author(s):

Kerlann Le Calvez ◽

Peter Treasure ◽

Matt Williams

Keyword(s):

Clinical Trials ◽

Brain Tumour ◽

Brain Tumours ◽

Adult Patients ◽

Trial Recruitment ◽

Trade Off ◽

Primary Brain Tumour ◽

Rational Planning ◽

The Brain ◽

Over Time

Abstract Introduction Access to clinical trials is a common request for patients with brain tumours. However, opening clinical trials requires additional work per centre opened. We have previously shown that surgical and oncology workload varies between centres, and fluctuates over time. There is a trade-off between offering access to clinical trials and increasing costs associated with opening trials in centres that treat few patients. Methods We used two separate datasets from England covering 3 years – one for neurosurgical workload and one for radiotherapy. We only included adult patients and calculated cumulative proportions of the malignant primary brain tumour population (C71) by number of centres. We investigated stability by checking how many patients would have to be added/ removed from a centre to change their rank. Results There were 7061 surgical and 5060 radiotherapy patients. To capture 25% of patients, we would need to open trials in 4 surgical/5 radiotherapy centres; for 50%, 9 surgical/ 13 radiotherapy centres; for 75%, 16 surgical/ 24 radiotherapy centres. Centre rank was fluid: adding 16 surgical/9 radiotherapy patients would change the rank of a centre. Discussion These are the first data to allow for rational planning of trials in brain tumour patients. We have shown that we can reach 75% of the brain tumour population by opening trials in ~50% of surgical and radiotherapy centres. Centre rank alters over year, so we should be cautious about being too prescriptive. Nonetheless, these data should allow some rational planning of trial centre inclusion.

Download Full-text