Background and Hypothesis: Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to... Show moreBackground and Hypothesis: Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Study Design: Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Results: Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. Conclusions: These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species. Show less
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been... Show moreThe number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sezary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies. Show less
Brysbaert, M.; Bakk, Z.; Buchanan, E.M.; Drieghe, D.; Frey, A.; Kim, E.; ... ; Yap, M. 2022
Neurosurgery as a distinct speciality has been around for 100 years. Some of the earliest women neurosurgeons were European, emerging from the 19200s onwards. Here we detail the rise of women in... Show moreNeurosurgery as a distinct speciality has been around for 100 years. Some of the earliest women neurosurgeons were European, emerging from the 19200s onwards. Here we detail the rise of women in neurosurgery across Europe with a decade by decade account of big events and firsts across the continent. The emerging themes are seen in stories of pioneers with enormous resilience, camaraderie, trailblazing and triumphing in a system with great obstacles and challenges. Our journey through this chronology brings us to the modern day, where most European countries have or have had a woman neurosurgeon and the future for women in neurosurgery in the continent is very bright. (C) 2021 Published by Elsevier Ltd. Show less
Murphy, M.; Hernandez-Duran, S.; Kim, E.; Al-Shehhi, N.; Broekman, M.; Praeter, M. de; ... ; Rosseau, G. 2021
A collaborative global working group of women neurosurgeons in multiple countries at different stages of their neurosurgical careers undertook the task of researching the history of European women... Show moreA collaborative global working group of women neurosurgeons in multiple countries at different stages of their neurosurgical careers undertook the task of researching the history of European women in neurosurgery. While doing so, we happened upon many remarkable female neurosurgeons who overcame great adversity, made tremendous contributions to society and institutional neurosurgery, and displayed numerous talents beyond the operating room. In the first part of this paper, we recounted a chronology of female neurosurgeons in Europe, highlighting the most remarkable achievements of women in every decade, from the 1920 & rsquo;s to 2020. In this paper, we honor fascinating women in European neurosurgery, both historical characters and living legends. These women have overcome great adversity and have also excelled in a huge variety of pursuits. While some were themselves refugees, we also have uncovered noteworthy examples of women who immersed themselves in humanitarian missions and who tried to better the world through political action. There are stories of women beating the odds, taking on biased institutions and proving their worth, in spite of the prevailing system. Most inspirational, we have discovered through our comprehensive research on the history of women in European neurosurgery that the future is increasingly female.CO 2021 Elsevier Ltd. All rights reserved. Show less
Zhang, Y.C.; Yang, Y.; Jiang, M.; Huang, S.X.; Zhang, W.W.; Alam, D. al; ... ; Que, J.W. 2018
Sm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for... Show moreSm-p80-based vaccine efficacy for Schistosoma mansoni was evaluated in a baboon model of infection and disease. The study was designed to replicate a human vaccine implementation scenario for endemic regions in which vaccine would be administered following drug treatment of infected individuals. In our study, the Sm-p80-based vaccine reduced principal pathology producing hepatic egg burdens by 38.0% and egg load in small and large intestines by 72.2% and 49.4%, respectively, in baboons. Notably, hatching rates of eggs recovered from liver and small and large intestine of vaccinated animals were significantly reduced, by 60.4%, 48.6%, and 82.3%, respectively. Observed reduction in egg maturation/hatching rates was supported by immunofluorescence and confocal microscopy showing unique differences in Sm-p80 expression in worms of both sexes and matured eggs. Vaccinated baboons had a 64.5% reduction in urine schistosome circulating anodic antigen, a parameter that reflects worm numbers/health status in infected hosts. Preliminary analyses of RNA sequencing revealed unique genes and canonical pathways associated with establishment of chronic disease, praziquantel-mediated parasite killing, and Sm-p80-mediated protection in vaccinated baboons. Overall, our study demonstrated efficacy of the Sm-p80 vaccine and provides insight into some of the epistatic interactions associated with protection. Show less
