Glioblastoma remodelling of human neural circuits decreases survival.

Gliomas synaptically integrate into neural circuits1,2. Previous research has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth1-4 and gliomas increasing neuronal excitability2,5-8. Here we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumour tissue biopsies and cell biology experiments, we find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumour-infiltrated cortex well beyond the cortical regions that are normally recruited in the healthy brain. Site-directed biopsies from regions within the tumour that exhibit high functional connectivity between the tumour and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumour cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumour regions compared with tumour regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 using the FDA-approved drug gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively affects both patient survival and performance in language tasks. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumour progression and impairs cognition.

Implementing a Trauma-Informed Approach at a Student-Run Clinic for Individuals Seeking Asylum.

PROBLEM: Health care professionals complete forensic medical evaluations (FMEs) to corroborate evidence of persecution among individuals seeking asylum. Many FMEs are conducted at student-run clinics for individuals seeking asylum (or student-run asylum clinics; SRACs). Trauma-informed care (TIC) recognizes that trauma is pervasive and seeks to mitigate reexposure to trauma in health care interactions. Given that FMEs involve recalling trauma, TIC is an ideal model for supporting the individuals involved in an FME. APPROACH: The authors operationalized TIC principles in an SRAC model (the Human Rights Cooperative) at the University of California, San Francisco. Between April 2019 and April 2022, the SRAC provided 3 to 10 pro bono FMEs per month, as well as community referrals for individuals seeking asylum, clinician and medical student training on FMEs and TIC, and research on FMEs. This report describes the SRAC operations, organized by the 10 implementation domains of the Substance Abuse and Mental Health Services Administration guidance to organizations for implementing a trauma-informed approach. OUTCOMES: Between April 2019 and April 2022, the SRAC completed 160 FMEs. Sixty-nine clinicians performed FMEs, and 119 first-year medical students participated in the accompanying elective. Qualitative survey responses by clinicians, lawyers, students, and clients (individuals seeking asylum) highlighted the trauma-informed principles of safety; trustworthiness and transparency; empowerment, voice, and choice; peer support; collaboration and mutuality; and cultural, historical, and gender issues. All students who acted as leaders sustained their engagement with the SRAC over time. NEXT STEPS: Future research should use validated tools to assess secondary trauma and resilience within SRACs. The SRAC concept, which engages medical students and experienced clinicians in learning skills that can be used in the pursuit of health justice and equity, should be expanded and supported in U.S. medical schools across the country, which is facing unprecedented levels of migration.

Asylum seeker trauma in a student-run clinic: reducing barriers to forensic medical evaluations.

Introduction This research, through the analysis of the case-law of the Inter-American Court of Human Rights (IACtHR), seeks to shed light on the nexus between families of the missing' claims, their agency and State compliance with reparations. The IACtHR has a unique follow-up system in the area of reparations, where victims can directly address the judges during hearings. This paper suggests that victims' participation - before and after the judgment- pervades the legal rigidity of international jurisdictions and contributes to a better understanding of reparations. INTRODUCTION: The number of forcibly displaced immigrants seeking asylum in the United States continues to rapidly increase. Movement from Latin America to the United States was the third-largest migration worldwide in 2017 (Leyva-Flores et al., 2019). As migration patterns change, understanding the background and trauma profile of newly displaced populations is essential to meet their health needs and aid successful resettlement. University-affiliated student-run asylum clinics conduct a growing number of forensic medical evaluations of asylum seekers and provide a vital lens to study changes in this population's profile over time. METHODS: A retrospective review was conducted of the first 102 asylum seekers receiving forensic medical evaluations between 2019 and 2021 at a university-affiliated student- run clinic, reporting demographics; trauma, medical, and mental health histories; referral patterns; and legal outcomes. Bivariate statistics were used to investigate the relationship between past trauma and mental health outcomes. RESULTS: Clients reported an average of 4.4 different types of physical, psychological, and sexual ill-treatment per person. The current mental health burden was extensive with 86.9 percent of clients reporting symptoms of PTSD and/or depression. Clinician-student teams evaluated clients within a clinic structure deploying a continuous improvement model to reduce common barriers to forensic evaluations and promote longitudinal follow- up and referrals. DISCUSSION: This study demonstrates the complexity of trauma exposure reported by asylum seekers, contributes to the evidence on how trauma results in mental health outcomes, and describes trauma-centred clinic adaptations that reduce barriers to forensic evaluations known to improve the rates of legal protection.

Systematic morphological and morphometric analysis of identified olfactory receptor neurons in Drosophila melanogaster.

The biophysical properties of sensory neurons are influenced by their morphometric and morphological features, whose precise measurements require high-quality volume electron microscopy (EM). However, systematic surveys of nanoscale characteristics for identified neurons are scarce. Here, we characterize the morphology of Drosophila olfactory receptor neurons (ORNs) across the majority of genetically identified sensory hairs. By analyzing serial block-face electron microscopy images of cryofixed antennal tissues, we compile an extensive morphometric data set based on 122 reconstructed 3D models for 33 of the 40 identified antennal ORN types. Additionally, we observe multiple novel features-including extracellular vacuoles within sensillum lumen, intricate dendritic branching, mitochondria enrichment in select ORNs, novel sensillum types, and empty sensilla containing no neurons-which raise new questions pertinent to cell biology and sensory neurobiology. Our systematic survey is critical for future investigations into how the size and shape of sensory neurons influence their responses, sensitivity, and circuit function.

An ammonium transporter is a non-canonical olfactory receptor for ammonia.

Numerous hematophagous insects are attracted to ammonia, a volatile released in human sweat and breath.1-3 Low levels of ammonia also attract non-biting insects such as the genetic model organism Drosophila melanogaster and several species of agricultural pests.4,5 Two families of ligand-gated ion channels function as olfactory receptors in insects,6-10 and studies have linked ammonia sensitivity to a particular olfactory receptor in Drosophila.5,11,12 Given the widespread importance of ammonia to insect behavior, it is surprising that the genomes of most insects lack an ortholog of this gene.6 Here, we show that canonical olfactory receptors are not necessary for responses to ammonia in Drosophila. Instead, we demonstrate that a member of the ancient electrogenic ammonium transporter family, Amt, is likely a new type of olfactory receptor. We report two hitherto unidentified olfactory neuron populations that mediate neuronal and behavioral responses to ammonia in Drosophila. Their endogenous ammonia responses are lost in Amt mutant flies, and ectopic expression of either Drosophila or Anopheles Amt confers ammonia sensitivity. These results suggest that Amt is the first transporter known to function as an olfactory receptor in animals and that its function may be conserved across insect species.