Aneurysm of the Artery of Wollschlaeger and Wollschlaeger.

The Artery of Wollschlaeger and Wollschlaeger (AWW) is a non-eloquent, tentorial branch of the superior cerebellar artery (SCA). Coursing posteriorly from an intradural origin, the AWW passes through the ambient cistern and supplies the medial tentorium. Due to its small diameter, the AWW is often only identified in the context of secondary dilation from pathologies such as dural arteriovenous fistulas (DAVF). Herein, we report the first case, to our knowledge, of an aneurysm of the AWW associated with a posterior fossa DAVF Swift identification and diagnosis followed by cautious treatment of both the aneurysm and fistula were critical to avert rupture and optimize outcomes, avoiding potential hemorrhagic complications.

Evaluation of valganciclovir's neutropenia risk in pediatric solid organ transplant recipients utilizing two dosing regimens.

BACKGROUND: Valganciclovir is approved for cytomegalovirus prophylaxis in pediatrics using the Pescovitz algorithm. There are reports of valganciclovir overdoses in children with low body surface area and overestimated creatinine clearance utilizing this algorithm. This study compared the incidence of neutropenia and cytomegalovirus infection between the Pescovitz and weight-based dosing algorithms. METHODS: A single-center retrospective chart review from January 2010 to September 2018 was performed on pediatric heart, liver, and kidney transplant recipients, who received valganciclovir. Data were collected from the initiation of valganciclovir prophylaxis to 30 days after discontinuation. The primary objective was the incidence of neutropenia in patients receiving valganciclovir dosed by the Pescovitz versus weight-based dosing algorithms. RESULTS: This study included 187 pediatric transplant recipients who received valganciclovir dosed via the Pescovitz (62 recipients) or weight-based dosing algorithms (125 recipients). The incidence of neutropenia was higher in the Pescovitz (69.4%) compared to the weight-based dosing group (53.6%; p = .04) including moderate and severe neutropenia. Cytomegalovirus viremia was not significantly different between the two groups and occurred in 4.8% of the Pescovitz group compared to 2.4% of the weight-based group (p = .4). CONCLUSIONS: The incidence of neutropenia was greater in recipients receiving valganciclovir dosed via the Pescovitz algorithm compared to the weight-based dosing. There were no significant differences in regard to cytomegalovirus viremia or disease between the two groups.

Multimodal single-neuron, intracranial EEG, and fMRI brain responses during movie watching in human patients.

We present a multimodal dataset of intracranial recordings, fMRI, and eye tracking in 20 participants during movie watching. Recordings consist of single neurons, local field potential, and intracranial EEG activity acquired from depth electrodes targeting the amygdala, hippocampus, and medial frontal cortex implanted for monitoring of epileptic seizures. Participants watched an 8-min long excerpt from the video "Bang! You're Dead" and performed a recognition memory test for movie content. 3 T fMRI activity was recorded prior to surgery in 11 of these participants while performing the same task. This NWB- and BIDS-formatted dataset includes spike times, field potential activity, behavior, eye tracking, electrode locations, demographics, and functional and structural MRI scans. For technical validation, we provide signal quality metrics, assess eye tracking quality, behavior, the tuning of cells and high-frequency broadband power field potentials to familiarity and event boundaries, and show brain-wide inter-subject correlations for fMRI. This dataset will facilitate the investigation of brain activity during movie watching, recognition memory, and the neural basis of the fMRI-BOLD signal.

A Systematic Review and Meta-Analysis of Drug Eluting Stents for Safety and Efficacy in Intracranial Atherosclerotic Disease.

BACKGROUND: Advancements in arterial stenting technology have challenged prior notions favoring medical management for intracranial atherosclerotic disease (ICAD). Where previous conclusions were drawn from bare metal stent (BMS) technology, recent studies suggest drug-eluting stents (DES) are favorable due to their anti-proliferative effect, which reduces vascular remodeling. METHODS: We conducted a systematic review and meta-analysis of the literature prior to August 2023 reviewing all reports of ICAD treated with DES. Our target outcomes were incidence of any stroke, transient ischemic attack (TIA), or death within 30 days (postprocedural complications), ischemic stroke in the territory of the qualifying artery beyond 30 days (long-term complications), radiographically detected in-stent restenosis rate (ISR), and symptomatic ISR during follow-up. A subgroup analysis further stratified preprocedural mean stenosis above and below 70% into severe and moderate cohorts, respectively. RESULTS: PubMed, Web of Science, Cochrane and EMBASE query identified 527 candidate articles, from which 14 studies met inclusion criteria for a total of 607 patients and 640 ICAD lesions. Incidence of postprocedural complications was 7.3% (95% CI 3.9-11.7%) with subgroup analysis demonstrating significantly higher incidence in the severely stenotic group [9.0% (95% CI 4.7-14.5%)] than the moderately stenotic group [3.0% (95% CI 0.7-6.8%)]. Long-term complications were 1.2% (95% CI 0.4-2.3%). Radiographic ISR was 3.5% (95% CI 1.4-6.3%) and symptomatic ISR was 0.3% (95% CI 0.0-1.5%). CONCLUSIONS: Our systematic review and meta-analysis suggest that DES can effectively reduce the risk of ISR and may be a viable treatment modality to reduce long-term complications in refractory ICAD patients.

Glycoprotein inhibitors as a first line rescue treatment after unsuccessful recanalization of endovascular thrombectomy: A systematic review and meta-analysis.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a major cause of stroke with a high rate of re-occlusion following mechanical thrombectomy (MT). Among the available rescue options, glycoprotein IIb/IIIa inhibitors (GPI) have shown promise as a potential therapeutic strategy. This systematic review and meta-analysis examine studies exploring the use of glycoprotein inhibitors as a first-line treatment for refractory occlusion or high-grade stenosis following EVT in the setting of ICAD. METHODS: A systematic review and meta-analysis were performed. Studies using GPI as the first-line rescue treatment (GPI-rt) after failed thrombectomy or in the setting with high-grade stenosis (>50%) were included. The primary outcome of interest was good clinical outcomes (defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days). Secondary outcomes of interest were successful recanalization (TICI 2b-3), symptomatic intracranial hemorrhage (sICH), and mortality by 90 days. RESULTS: Our study processed 2111 articles, which yielded eight relevant studies for review, four single and four double arm. These studies comprised 763 patients, divided into GPI-rt (535 patients) and non-GPI-rt (228 patients) cohorts. The GPI-rt group had higher rates of mRS ≤ 2 at 90 days (58.5% vs 38.9%, p = 0.002) and lower mortality rates (7.8% vs 17.5%, p = 0.04) compared to the non-GPI-rt cohort. mTICI 2b-3 rates and rates of sICH were not significantly different between the cohorts. CONCLUSIONS: First line GPI-rt demonstrates significant clinical benefit and significantly lower mortality without a rise in rates of sICH. GPI are a potential first line rescue treatment of ICAD.

Endovascular thrombectomy for posterior cerebral artery strokes in the national inpatient sample (EaT PeCANpIeS) study.

BACKGROUND: Posterior cerebral arteries with acute ischemic strokes (PCA-AISs) comprise around 2% of all acute ischemic strokes and may result in significant long-term deficits. Current guidance regarding endovascular thrombectomy (EVT) for PCA-AIS is insufficient as no published randomized trials exist. METHODS: An analysis of the National Inpatient Sample database compared medical management versus EVT for PCA-AIS. Propensity score matching was applied to adjust for nonrandomization. RESULTS: The study included 19,655 patients. Before matching, the EVT cohort had significantly higher National Institutes of Health Stroke Scale (NIHSS) (10.21 vs. 4.67, p < 0.001), had lower rates of favorable functional outcomes, functional independence, and higher rates of intracranial hemorrhage (ICH) and inpatient mortality. After matching, no differences in functional outcomes were identified, but revealed a higher proportion of ICH in the EVT group (17.45% vs. 8.98%, p < 0.001). However, NIHSS subgroup analysis identified improved functional outcomes associated with the EVT group who presented with an NIHSS between 10 and 19 both in terms of rates of favorable functional outcomes (35.56% vs. 12.09%, p < 0.001) and rates of functional independence (26.67% vs. 9.34%, p < 0.01). On further investigation, the clinical benefit, in the NIHSS 10-19 subgroup, was driven by patients receiving EVT in combination with intravenous thrombolysis (IVT). CONCLUSIONS: This analysis shows that current national practices utilize EVT for more severe PCA strokes. Clinical benefit was only detected in patients with moderate stroke severity (NIHSS 10-19) who were treated with combined EVT and IVT. Further work is needed to investigate the features of PCA-AIS that might benefit from EVT the most.

ß-tubulin functions in spermatogenesis in Lygus hesperus Knight.

Lygus hesperus Knight is an important insect pest of crops across western North America, with field management heavily reliant on the use of chemical insecticides. Because of the evolution of resistance to these insecticides, effective and environmentally benign pest management strategies are needed. Traditional sterile insect technique (SIT) has been successfully employed to manage or eradicate some insect pests but involves introducing irradiated insects with random mutations into field populations. New genetically-driven SIT techniques are a safer alternative, causing fixed mutations that manipulate individual genes in target pests to produce sterile individuals for release. Here, we identified seven ß-tubulin coding genes from L. hesperus and show that Lhßtub2 is critical in male sperm production and fertility. Lhßtub2 is expressed primarily in the male testes and targeting of this gene by RNA interference or gene editing leads to male sterility.

Stem-like CD4+ T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis.

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4+ T cell population with stem cell-like features. CD4+ T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES)+ cytotoxic T cells and B cell lymphoma 6 (BCL6)+ T follicular helper-like cells. TCF1hiCD4+ T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1hiCD4+ T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4+ T cells instead of only effector T cells.

A review of the top 100 most influential articles on basilar artery aneurysms.

Basilar artery aneurysms account for approximately 5% of all intracranial aneurysms. This bibliometric analysis summarizes the most-cited articles on basilar artery aneurysms and highlights the contributing articles to today's evidence-based practice. In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "basilar artery aneurysm" or "basilar aneurysm" was used. Our results were arranged in descending order based on the article's citation count. The 100 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact Per Paper (SNIP), and Hirsch index. The keyword-based search showed that 699 articles were published between 1888 and 2022. The top 100 articles were published between 1961 and 2019. The top 100 most cited articles collected a total of 8869 citations with an average of 89 citations per paper. The rate of self-citations accounted for an average of 4.85% of the total number of citations. The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in basilar artery aneurysms by finding the top 100 most cited papers.

Endovascular Management of Pediatric Traumatic Intracranial Pseudoaneurysms: A Systematic Review and Case Series.

OBJECTIVE: This study aims to systematically review the management and outcomes of pediatric patients who develop intracranial pseudoaneurysm (IPA) following head trauma or iatrogenic injury. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Additionally, a retrospective analysis was conducted on pediatric patients who underwent evaluation and endovascular treatment for IPA originating from head trauma or iatrogenic injury at a single institution. RESULTS: Two hundred twenty-one articles in the original literature search. Fifty-one met inclusion criteria resulting in a total of 87 patients with 88 IPAs including our institution. Patients ranged in age from 0.5 months to 18 years. Parent vessel reconstruction was used as first-line treatment in 43 cases, parent vessel occlusion in 26, and direct aneurysm embolization (DAE) in 19. Intraoperative complications were observed in 3.00% of procedures. Complete aneurysm occlusion was achieved in 89.61% of cases. 85.54% of cases resulted in favorable clinical outcomes. The mortality rate after treatment was 3.61%. The DAE group had higher rates of aneurysm recurrence than other treatment strategies (P = 0.009). Patients with SAH had overall worse outcomes compared to patients who did not (P = 0.024). There were no differences in favorable clinical outcomes (P = 0.274) or complete aneurysm occlusion (P = 0.13) between primary treatment strategies. CONCLUSIONS: IPAs were successfully obliterated, and favorable neurological outcomes were achieved at a high rate regardless of primary treatment strategy. DAE had a higher rate of recurrence than the other treatment groups. Each described treatment method in our review is safe and viable for the treatment of IPAs in pediatric patients.

Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses.

To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding the protective potential of epitopes conserved across SARS-CoV-2 variants and coronavirus lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in the prefusion core of ß-coronaviruses: SARS-CoV-2 S2 apex residues 980-1006 in the flexible hinge. Antibody RAY53 binds the native hinge in MERS-CoV and SARS-CoV-2 spikes on the surface of mammalian cells and mediates antibody-dependent cellular phagocytosis and cytotoxicity against SARS-CoV-2 spike in vitro. Hinge epitope mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere that affect spike opening dynamics, including those found in Omicron BA.1, occlude the epitope and may evade pre-existing serum antibodies targeting the S2 core. This work defines a third class of S2 antibody while providing insights into the potency and limitations of S2 core epitope targeting.

A Bibliometric Analysis of the Top 50 Most Influential Articles on External Ventricular Drains.

OBJECTIVE: External ventricular drains (EVDs) are commonly used to remove cerebrospinal fluid and monitor intracranial pressure in patients with neurological dysfunction. Often the first invasive procedure learned in training, ventricular drain placement is the quintessential neurosurgical procedure. This bibliometric analysis highlights the top contributing EVD articles in current evidence-based practice. METHODS: The Scopus database was used to perform a title-specific, keyword-based search for all publications until September 2022. The keywords "external ventricular drain" or "EVD" or "external ventriculostomy" were used. The 50 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index. RESULTS: The keyword-based search showed that 8464 articles on EVDs were published between 1991 and 2022. The top 50 articles were published between 1999 and 2019. The top 50 articles acquired a total of 3343 citations with an average of 66.86 citations per paper. The rate of self-citations accounted for an average of 5.16% of the total number of citations. A majority of the top 50 articles focused on EVD infection and placement accuracy. The first and second most cited papers were authored by Zabramski et al and Fried et al, respectively. CONCLUSIONS: The bibliometric analysis provides a quantitative overview of how topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in EVDs by analyzing the top 50 most cited papers.

An Analysis of Landmark Articles Regarding Aneurysms of the Middle Cerebral Artery.

OBJECTIVE: Aneurysms located on the middle cerebral artery (MCA) range from 22% to 31.5% in prevalence of all aneurysms in the anterior cerebral circulation. This bibliometric analysis summarizes the most cited articles on MCA aneurysms and highlights the landmark publications that contributed to evidence-based practice. METHODS: In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until August 2022. The keyword "(middle cerebral artery OR MCA) AND aneurysm" was used. Our results were arranged in descending order based on the citation count of the article. The 100 most cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index. RESULTS: The keyword-based search showed that 1206 articles on MCA aneurysms were published up to August 2022. The top 100 articles were published between 1940 and 2019. The top 100 most cited articles collected a total of 6232 citations with an average of 62.3 citations per article. The rate of self-citations accounted for an average of 5.75% of the total number of citations. CONCLUSIONS: The bibliometric analysis provides a quantitative overview of how medical literature and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in research regarding MCA aneurysms by finding the top 100 most cited articles.

Wait times and patient throughput after the implementation of a novel model of virtual care in an outpatient neurology clinic: A retrospective analysis.

INTRODUCTION: Neurology wait times - from referral to consultation - continue to grow, leading to various adverse effects on patient outcomes. Key elements of virtual care can be leveraged to improve efficiency. This study examines the implementation of a novel virtual care model - Virtual Rapid Access Clinics - at the Neurology Centre of Toronto. The model employs a patient-centred care workflow, involving multidisciplinary staff and online administrative tools that are synthesized to expedite care and maintain quality. METHODS: Virtual Rapid Access Clinic efficacy was studied by determining average wait times and patient throughput, calculated from anonymous data that was extracted from the clinic patient database (n = 1542). Comparative analysis focused on new patient consultations during the 12-month periods prior to (pre-Virtual Rapid Access Clinic, n = 456) and following (post-Virtual Rapid Access Clinic, n = 1086) Virtual Rapid Access Clinic implementation. RESULTS: After Virtual Rapid Access Clinic implementation, there was a mean 15-day wait time reduction, and a monthly average 52-patient increase in patient throughput. Wait time reductions and increased patient throughput were observed in all three Virtual Rapid Access Clinic sub-clinics - epilepsy, headache and concussion. Respectively, average wait times reduced significantly by 26.4 and 18.9 days and insignificantly by 1.1 days; monthly average patient throughputs increased by 235%, 95% and 161%. DISCUSSION: These findings demonstrated that the Virtual Rapid Access Clinic model of care is effective at reducing patient wait times and increasing patient throughput. While the Virtual Rapid Access Clinic presents a feasible model both during and after pandemic restrictions, further research exploring its scalability in other care contexts, potential changes in care quality and efficiency outside of pandemic restrictions must be performed.

A Systematic Review of Adherence to Immunosuppression among Pediatric Heart Transplant Patients.

After pediatric heart transplant, commitment to lifelong immunosuppression is crucial to maintaining graft health. However, a review of the current literature surrounding adherence to immunosuppression in pediatric heart transplant patients is lacking. This systematic review aims to summarize the current landscape of adherence to immunosuppression in pediatric heart transplant patients. We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence to immunosuppression and the measurement of adherence was performed with an objective or otherwise validated measure of adherence (e.g., drug levels, adherence questionnaires). The titles/abstracts of 880 articles were reviewed. After initial screening, 106 articles underwent full text review. As such, 14 articles were included in the final review. Baseline adherence estimates varied greatly, with most values between 40% and 70%. Nonadherence to immunosuppression is associated with worse outcomes (rejection, hospitalization, mortality), impaired quality of life, and mental health concerns in pediatric heart transplant patients. As nonadherence to immunosuppression is common and associated with worse outcomes, there is a need for further development and evaluation of interventions in this space.

In vivo overexpression of frataxin causes toxicity mediated by iron-sulfur cluster deficiency.

Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, a mitochondrial protein implicated in the synthesis of iron-sulfur clusters. Preclinical studies in mice have shown that gene therapy is a promising approach to treat individuals with Friedreich's ataxia. However, a recent report provided evidence that AAVrh10-mediated overexpression of frataxin could lead to cardiotoxicity associated with mitochondrial dysfunction. While evaluating an AAV9-based frataxin gene therapy using a chicken ß-actin promoter, we showed that toxic overexpression of frataxin could be reached in mouse liver and heart with doses between 1 × 1013 and 1 × 1014 vg/kg. In a mouse model of cardiac disease, these doses only corrected cardiac dysfunction partially and transiently and led to adverse findings associated with iron-sulfur cluster deficiency in liver. We demonstrated that toxicity required frataxin's primary function by using a frataxin construct bearing the N146K mutation, which impairs binding to the iron-sulfur cluster core complex. At the lowest tested dose, we observed moderate liver toxicity that was accompanied by progressive loss of transgene expression and liver regeneration. Together, our data provide insights into the toxicity of frataxin overexpression that should be considered in the development of a gene therapy approach for Friedreich's ataxia.

CRISPR-mediated knockout of cardinal and cinnabar eye pigmentation genes in the western tarnished plant bug.

The western tarnished plant bug, Lygus hesperus, is a key hemipteran pest of numerous agricultural, horticultural, and industrial crops in the western United States and Mexico. A lack of genetic tools in L. hesperus hinders progress in functional genomics and in developing innovative pest control methods such as gene drive. Here, using RNA interference (RNAi) against cardinal (LhCd), cinnabar (LhCn), and white (LhW), we showed that knockdown of LhW was lethal to developing embryos, while knockdown of LhCd or LhCn produced bright red eye phenotypes, in contrast to wild-type brown eyes. We further used CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated) genome editing to generate germline knockouts of both LhCd (Card) and LhCn (Cinn), producing separate strains of L. hesperus characterized by mutant eye phenotypes. Although the cardinal knockout strain Card exhibited a gradual darkening of the eyes to brown typical of the wild-type line later in nymphal development, we observed bright red eyes throughout all life stages in the cinnabar knockout strain Cinn, making it a viable marker for tracking gene editing in L. hesperus. These results provide evidence that CRISPR/Cas9 gene editing functions in L. hesperus and that eye pigmentation genes are useful for tracking the successful genetic manipulation of this insect.

Expression and characterization of SARS-CoV-2 spike proteins.

The severe acute respiratory syndrome coronavirus 2 spike protein is a critical component of coronavirus disease 2019 vaccines and diagnostics and is also a therapeutic target. However, the spike protein is difficult to produce recombinantly because it is a large trimeric class I fusion membrane protein that is metastable and heavily glycosylated. We recently developed a prefusion-stabilized spike variant, termed HexaPro for six stabilizing proline substitutions, that can be expressed with a yield of >30 mg/L in ExpiCHO cells. This protocol describes an optimized workflow for expressing and biophysically characterizing rationally engineered spike proteins in Freestyle 293 and ExpiCHO cell lines. Although we focus on HexaPro, this protocol has been used to purify over a hundred different spike variants in our laboratories. We also provide guidance on expression quality control, long-term storage, and uses in enzyme-linked immunosorbent assays. The entire protocol, from transfection to biophysical characterization, can be completed in 7 d by researchers with basic tissue cell culture and protein purification expertise.

Schizophrenia-associated SLC39A8 polymorphism is a loss-of-function allele altering glutamate receptor and innate immune signaling.

Schizophrenia is a complex and heterogenous disease that presents with abnormalities in glutamate signaling and altered immune and inflammatory signals. Genome-wide association studies have indicated specific genes and pathways that may contribute to schizophrenia. We assessed the impact of the functional missense variant SLC39A8 (ZIP8)-A391T (ZIP8A391T) on zinc transport, glutamate signaling, and the neuroinflammatory response. The ZIP8A391T mutation resulted in reduced zinc transport into the cell, suggesting a loss in the tight control of zinc in the synaptic cleft. Electrophysiological recordings from perturbed neurons revealed a significant reduction in NMDA- and AMPA-mediated spontaneous EPSCs (sEPSCs) and a reduction in GluN2A and GluA1/2/3 receptor surface expression. All phenotypes were rescued by re-expression of wild-type ZIP8 (ZIP8WT) or application of the membrane-impermeable zinc chelator ZX1. ZIP8 reduction also resulted in decreased BBB integrity, increased IL-6/IL-1ß protein expression, and increased NFκB following TNFα stimulation, indicating that ZIP8 loss-of-function may exacerbate immune and inflammatory signals. Together, our findings demonstrate that the A391T missense mutation results in alterations in glutamate and immune function and provide novel therapeutic targets relevant to schizophrenia.