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Carboxysomes are bacterial microcompartments encapsulating Rubisco and carbonic anhydrase for carbon fixation. Here, authors determine the organization of Rubisco and its interaction with the linker protein CsoS2 within two distant α-carboxysomes.

Decompressive craniectomies are a neurosurgical operation aimed at normalizing intracranial pressure (ICP). Occasionally, there is delayed replacement of the skull resulting in an acquired skull defect. When managing laboring patients with an acquired skull defect there is often fear associated with traditional labor involving the Valsalva maneuver and with neuraxial anesthesia. These fears typically stem from potential ICP changes and risk of herniation. In reviewing the literature, only 15 cases are described detailing labor management after decompressive craniectomy (DC), mostly with incomplete labor histories. We aim to expand that literature by reporting two cases of safe labor with epidural anesthesia in patients with large skull defects. The first described patient underwent a cranioplasty during pregnancy because of trauma. Later, because of concerns for pre‐eclampsia, induction of labor was initiated and she received neuraxial anesthesia via epidural. The patient ultimately underwent cesarean delivery 48 h after induction began due to nonreassuring fetal heart tones. The second patient underwent a cranioplasty because of infection prior to pregnancy. Once in labor, she was cleared by neurosurgery and the anesthesia team placed her epidural. She later underwent an uncomplicated standard vaginal delivery. The existing literature on labor following DC is sparse. Retrospective review of case reports can advance discussion and standardization regarding care for laboring women with a history of DC. We advocate that the Valsalva maneuver and epidural anesthesia is safe for pregnant women who are neurologically asymptomatic. [ABSTRACT FROM AUTHOR]

Ruptured intracranial aneurysms lead to significant mortality and morbidity. Recent advancements have suggested staged coiling with subsequent flow diverter stent placement may reduce the risk of hemorrhage with dual antiplatelet therapy (DAPT) or stent thrombosis in the acute inflammatory phase after aneurysm rupture while still appropriately mitigating risk of aneurysmal rehemorrhage.A systematic review and single-arm meta-analysis was conducted. Studies reporting patients receiving coiling followed by delayed flow diverter placement on a separate day were included.Five studies, comprising 94 patients, were included for meta-analysis. Average time between procedures ranged from 9.8 to 169 days; 24% (95% CI: 10–41%) of patients had a poor functional neurologic outcome (modified Rankin Scale > 2) at discharge compared to 4% (0–11%) at last follow-up. There was one incidence of rehemorrhage between treatments, 0% (0–4%). Vasospasm after coiling was the most common adverse event, 16% (1–41%). There was low risk of ischemic complications [1% (0–8%) with coil placement and 5% (1–11%) with stent placement]. Intraprocedural intracranial hemorrhage was also rare (two patients during coil placement; no cases during stent placement). There were no significant differences if flow diversion was performed less than or greater than 100 days from coiling.Our study highlights the benefit of primary coiling with staged flow diversion for the management of ruptured intracranial aneurysms with a low risk for complications. Namely, the rate of rebleeding between treatments was exceptionally low. We advocate for the greater consideration of this treatment combination in the treatment of ruptured intracranial aneurysms. [ABSTRACT FROM AUTHOR]

Carboxysomes are a family of bacterial microcompartments in cyanobacteria and chemoautotrophs. They encapsulate Ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase catalyzing carbon fixation inside a proteinaceous shell. How Rubisco complexes pack within the carboxysomes is unknown. Using cryo-electron tomography, we determine the distinct 3D organization of Rubisco inside two distant α-carboxysomes from a marine α-cyanobacterium Cyanobium sp. PCC 7001 where Rubiscos are organized in three concentric layers, and from a chemoautotrophic bacterium Halothiobacillus neapolitanus where they form intertwining spirals. We further resolve the structures of native Rubisco as well as its higher-order assembly at near-atomic resolutions by subtomogram averaging. The structures surprisingly reveal that the authentic intrinsically disordered linker protein CsoS2 interacts with Rubiscos in native carboxysomes but functions distinctively in the two α-carboxysomes. In contrast to the uniform Rubisco-CsoS2 association in the Cyanobium α-carboxysome, CsoS2 binds only to the Rubiscos close to the shell in the Halo α-carboxysome. Our findings provide critical knowledge of the assembly principles of α-carboxysomes, which may aid in the rational design and repurposing of carboxysome structures for new functions. Carboxysomes are bacterial microcompartments encapsulating Rubisco and carbonic anhydrase for carbon fixation. Here, authors determine the organization of Rubisco and its interaction with the linker protein CsoS2 within two distant α-carboxysomes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate whether application of bipolar galvanic vestibular stimulation (GVS) would influence the common modulation of motor unit discharge rate in bilateral soleus muscles during quiet standing. Soleus motor unit activity was recorded with fine wire electrodes in each leg. Subjects stood, with eyes closed, on two adjacent force platforms to record postural sway with the head facing straight ahead, turned to right, or turned left. Subjects also swayed voluntarily without GVS to the same position as evoked during the GVS. There was no difference in the common drive to bilateral soleus motoneurons during quiet standing and voluntary sway tasks. Common drive was significantly lower during right cathode GVS with the head straight or turned to the right. These results demonstrate that manipulation of vestibular afferent input influences the common modulation of bilateral soleus motor unit pairs during quiet standing. [ABSTRACT FROM AUTHOR]

- The evolution of a collagen/vicryl composite membrane designed as a prosthetic material for use in urinary tract surgery is described. The early experiments in which collagen film alone was used to repair experimental ureterotomies are reviewed together with our first experiments with the collagen/vicryl prosthesis in the repair of partial nephrectomies and of full thickness defects created in the urinary bladder of experimental rabbits. These early results led to the preparation of a composite using a more highly purified collagen and employing a method of sterilisation (gamma irradiation) which would be acceptable for regular use in medical products. The results of a further series of partial nephrectomy and full thickness bladder repairs show that irradiation does not compromise the efficacy of the collagen/vicryl composite in vivo. [ABSTRACT FROM AUTHOR]

- One hundred and fifty children with proven urinary tract infection who were assessed by renal ultrasound (U/S), intravenous urography (IVU) and dimercaptosuccinic acid (M99mTc DMSA) scan, were studied to identify the sensitivity of each examination and the pick-up rate of renal scarring secondary to vesicoureteric reflux. Sixty-three of these children who had the examinations carried out within a 6-month period were assessed in detail. A scan is the most accurate method of detecting early renal scars in the young age group (0-2 and 2-5 years), followed by ultrasound. The examinations are equally sensitive over the age of 5. A new grading system of the severity of renal scarring is presented. [ABSTRACT FROM AUTHOR]

Describes a procedure that communication departments, advisors and graduate students can utilize to help students cope with the task and social pressures that accompany working on a dissertation. Written from the phenomenological perspective of two recent PhDs who went through the process of completing their dissertations together. All but dissertation (ABD); Formal support for individuals of ABD status; Functions of dissertation partner; More.

Background: Transmitted HIV-1 drug resistance can compromise initial antiretroviral therapy (ART); therefore, its detection is important for patient management. The absence of drug-associated selection pressure in treatment-naïve persons can cause drug-resistant viruses to decline to levels undetectable by conventional bulk sequencing (minority drug-resistant variants). We used sensitive and simple tests to investigate evidence of transmitted drug resistance in antiretroviral drug-naïve persons and assess the clinical implications of minority drug-resistant variants.Methods and Findings: We performed a cross-sectional analysis of transmitted HIV-1 drug resistance and a case-control study of the impact of minority drug resistance on treatment response. For the cross-sectional analysis, we examined viral RNA from newly diagnosed ART-naïve persons in the US and Canada who had no detectable (wild type, n = 205) or one or more resistance-related mutations (n = 303) by conventional sequencing. Eight validated real-time PCR-based assays were used to test for minority drug resistance mutations (protease L90M and reverse transcriptase M41L, K70R, K103N, Y181C, M184V, and T215F/Y) above naturally occurring frequencies. The sensitive real-time PCR testing identified one to three minority drug resistance mutation(s) in 34/205 (17%) newly diagnosed persons who had wild-type virus by conventional genotyping; four (2%) individuals had mutations associated with resistance to two drug classes. Among 30/303 (10%) samples with bulk genotype resistance mutations we found at least one minority variant with a different drug resistance mutation. For the case-control study, we assessed the impact of three treatment-relevant drug resistance mutations at baseline from a separate group of 316 previously ART-naïve persons with no evidence of drug resistance on bulk genotype testing who were placed on efavirenz-based regimens. We found that 7/95 (7%) persons who experienced virologic failure had minority drug resistance mutations at baseline; however, minority resistance was found in only 2/221 (0.9%) treatment successes (Fisher exact test, p = 0.0038).Conclusions: These data suggest that a considerable proportion of transmitted HIV-1 drug resistance is undetected by conventional genotyping and that minority mutations can have clinical consequences. With no treatment history to help guide therapies for drug-naïve persons, the findings suggest an important role for sensitive baseline drug resistance testing. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective review., Objective: We sought to characterize complications associated with anterior column release (ACR)., Summary of Background Data: Correction of positive sagittal imbalance was traditionally completed with anterior column grafts or posterior osteotomies. ACR is a minimally invasive technique for addressing sagittal plane deformity by restoring lumbar lordosis., Methods: We conducted a retrospective review of consecutive patients who underwent ACR in a prospectively kept database at a tertiary care academic center from January 2012 to December 2018. The prespecified complications were hardware failure (rod fracture, hardware loosening, or screw fracture), proximal junctional kyphosis, ipsilateral thigh numbness, ipsilateral femoral nerve weakness, arterial injury requiring blood transfusion, bowel injury, and abdominal pseudohernia., Results: Thirty-eight patients were identified. Thirty-five patients had ACR at L3-4, 1 had ACR at L4-5, and 1 patient had ACR at L2-3 and L3-4. Eighteen patients (47.4%) had one of the prespecified complications (10 patients had multiple). Ten patients developed hardware failure (26.3%); 8 patients (21.1%) had rod fracture, 4 (10.5%) had screw fracture, and 1 (2.6%) had screw loosening. At discharge, rates of ipsilateral thigh numbness (37.8%) and hip flexor (37.8%)/quadriceps weakness (29.7%) were the highest. At follow-up, 6 patients (16.2%) had ipsilateral anterolateral thigh numbness, 5 (13.5%) suffered from ipsilateral hip flexion weakness, and 3 patients (5.4%) from ipsilateral quadriceps weakness. Arterial injury occurred in 1 patient (2.7%). Abdominal pseudohernia occurred in 1 patient (2.7%). There were no bowel injuries observed., Conclusions: ACR is associated with a higher than initially anticipated risk of neurological complications, hardware failure, and proximal junctional kyphosis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Chiari malformations (CM) are often diagnosed in childhood and younger adults, with an incidence of only 0.77% in adult populations. Patients with CM may develop syringomyelia and increased intracranial pressure (ICP) due to cerebrospinal fluid (CSF) obstruction and altered fluid dynamics at the cervicomedullary junction. We describe the case of a 65-year-old female presenting with an angionegative subarachnoid hemorrhage (SAH) with concomitant new diagnosis of CM type I with syringomyelia. After ruling out any aneurysm or vascular malformations, she underwent a suboccipital craniectomy for a Chiari decompression with a C1 laminectomy. There were no complications with the surgery and her symptoms improved. This case report highlights the unusual presentation of a CM., (Copyright © 2024 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To examine claims for reversible prescription contraceptives and chlamydia and gonorrhea testing among commercially and Medicaid-insured adolescent and young adult (AYA) females in the United States. Methods: Using IBM MarketScan Research Databases, we identified sexually active, nonpregnant AYA (15- to 24-year-old) females enrolled in 2018. We examined claims for reversible prescription contraceptives and chlamydia and gonorrhea testing, using drug names and diagnosis/procedure codes, by age-group in commercially and Medicaid-insured separately and by race/ethnicity in Medicaid-insured. Results: Among 15- to 19-year-old and 20- to 24-year-old females, 67.2% and 67.9% of commercially insured and 57.3% and 54.0% of Medicaid-insured, respectively, had claims for reversible prescription contraceptives in 2018. Across insurance types among both age-groups, the most common claim for contraceptives was prescription for combined oral contraceptives. Among Medicaid-insured 15- to 19-year-olds, claims for contraceptives ranged from 42.6% for Hispanic females to 63.4% for non-Hispanic White females; among Medicaid-insured 20- to 24-year-olds, claims ranged from 50.4% for non-Hispanic Black females to 57.0% for non-Hispanic White females. Approximately half of the commercially and Medicaid-insured females had claims for chlamydia and gonorrhea testing. Non-Hispanic Black females had the highest percentages of claims for chlamydia testing (56.3% among 15- to 19-year-olds and 61.1% among 20- to 24-year-olds) and gonorrhea testing (61.6% among 15- to 19-year-olds and 64.9% among 20- to 24-year-olds). Conclusion: Approximately, two-thirds of commercially insured and more than half of Medicaid-insured, sexually active, nonpregnant AYA females had claims for reversible prescription contraceptives. Race/ethnicity data were available for Medicaid-insured females, and there were differences in claims for contraceptives and chlamydia and gonorrhea testing by race/ethnicity. Half of the AYA females had claims for chlamydia and gonorrhea testing suggesting missed opportunities.

Purpose: Three-column osteotomies (TCOs) and minimally invasive techniques such as anterior column realignment (ACR) are powerful tools used to restore lumbar lordosis and sagittal alignment. We aimed to appraise the differences in construct and global spinal stability between TCOs and ACRs in long constructs., Methods: We identified consecutive patients who underwent a long construct lumbar or thoracolumbar fusion between January 2016 and November 2021. "Long construct" was any construct where the uppermost instrumented vertebra (UIV) was L2 or higher and the lowermost instrumented vertebra (LIV) was in the sacrum or ileum., Results: We identified 69 patients; 14 (20.3%) developed PJK throughout follow-up (mean 838 days). Female patients were less likely to suffer PJK (p = 0.009). TCO was more associated with open (versus minimally invasive) screw/rod placement, greater number of levels, higher UIV, greater rate of instrumentation to the ilium, and posterior (versus anterior) L5-S1 interbody placement versus the ACR cohort (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.005, respectively). Patients who developed PJK were more likely to have undergone ACR (12 (32.4%) versus 2 (6.3%, p = 0.007)). The TCO cohort had better improvement of lumbar lordosis despite similar preoperative measurements (ACR: 16.8 ± 3.78°, TCO: 23.0 ± 5.02°, p = 0.046). Pelvic incidence-lumbar lordosis mismatch had greater improvement after TCO (ACR: 14.8 ± 4.02°, TCO: 21.5 ± 5.10°, p = 0.042). By multivariate analysis, ACR increased odds of PJK by 6.1-times (95% confidence interval: 1.20-31.2, p = 0.29)., Conclusion: In patients with long constructs who undergo ACR or TCO, we experienced a 20% rate of PJK. TCO decreased PJK 6.1-times compared to ACR. TCO demonstrated greater improvement of some spinopelvic parameters., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The role of resting state functional MRI (rsfMRI) is increasing in the field of epilepsy surgery because it is possible to interpolate network connectivity patterns across the brain with a high degree of spatial resolution. Prior studies have shown that by rsfMRI with scalp electroencephalography (EEG), an epileptogenic network can be modeled and visualized with characteristic patterns of connectivity that are relevant to both seizure-related and neuropsychological outcomes after surgery. The aim of this study is to show that a 5-min acquisition time provides reproducible results related to the relevant connectivity metrics when compared to a separately acquired 5-min scan. Fourteen separate rsfMRI sessions from ten different patients were used for comparison, comprised of patients with temporal lobe epilepsy both pre- and post-operation. Results showed that there was no significant difference in any of the connectivity metrics when comparing both 5-min scans to each other. These data support the continued use of a 5-min scan for epileptogenic network modeling in future studies because the inter-scan variability is sufficiently low as not to alter the output metrics characterizing the network connectivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Neal, Schimmel, George, Monsour, Alayli, Lockard, Piper, Maciver, Vale and Bezchlibnyk.)

Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year. 1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules. 14 ., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurological disease characterized by upper and lower motor neuron degeneration. Though typically idiopathic, familial forms of ALS are commonly comprised of a superoxide dismutase 1 (SOD1) mutation. Basic science frequently utilizes SOD1 models in vitro and in vivo to replicate ALS conditions. Therapies are sparse; those that exist on the market extend life minimally, thus driving the demand for research to identify novel therapeutics. Transplantation of stem cells is a promising approach for many diseases and has shown efficacy in SOD1 models and clinical trials. The underlying mechanism for stem cell therapy presents an exciting venue for research investigations. Most notably, the paracrine actions of stem cell-derived extracellular vesicles (EVs) have been suggested as a potent mitigating factor. This literature review focuses on the most recent preclinical research investigating cell-free methods for treating ALS. Various avenues are being explored, differing on the EV contents (protein, microRNA, etc.) and on the cell target (astrocyte, endothelial cell, motor neuron-like cells, etc.), and both molecular and behavioral outcomes are being examined. Unfortunately, EVs may also play a role in propagating ALS pathology. Nonetheless, the overarching goal remains clear; to identify efficient cell-free techniques to attenuate the deadly consequences of ALS., Competing Interests: Conflicts of interest S.G.-D. and C.V.B. declared leadership positions with the University of South Florida, patents and patent applications on stem cell biology and its therapeutic applications, consultant to a number of stem cell-based companies, and research funding from the NIH. All of the other authors declared no potential conflicts of interest.

Competing Interests: None

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: None

Introduction: Lesions affecting the anterior skull base and involving the paranasal sinuses (PNS), nasal cavity (NC), and orbit are infrequent and include predominantly a wide variety of sinonasal malignancies. Less than 3% of intracranial meningiomas extend extracranially and involve PNS and NC. Given their relatively low incidence, little is known about the treatment outcome of this subset of meningiomas., Methods: Systematic literature and retrospective review of own institutional series of midline anterior skull base meningiomas with significant PNS and NC involvement were performed., Results: Overall, 21 patients-16 in the literature review group and 5 of our institutional series-were included. Eleven (52.4%) patients had had a prior surgery for midline anterior skull base meningioma. Of patients having reported WHO grade, two were WHO II. Gross total resection was achieved in 16 (76.2%) of patients, utilizing solely transcranial approach in 15 patients, combined endoscopic and transcranial in five patients and purely endoscopic in one patient. Postoperative radiotherapy was administered in three (14.3%) patients, all after total resection via transcranial route, without a history of prior treatment. A postoperative cerebrospinal fluid leak was reported in four (10%) patients, requiring surgical repair in two. There were no reports of postoperative meningitis. No neurological complications were observed except of a reported worsening of vision in one patient., Conclusion: Midline anterior skull base meningiomas infrequently extend significantly into the PNS and NC. Despite their significant involvement, along with concomitant involvement of orbit, gross total resection is possible in the majority of cases with low morbidity using either purely transcranial or combined endoscopic/transcranial approach., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Carboxysomes are proteinaceous bacterial microcompartments that sequester the key enzymes for carbon fixation in cyanobacteria and some proteobacteria. They consist of a virus-like icosahedral shell, encapsulating several enzymes, including ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), responsible for the first step of the Calvin-Benson-Bassham cycle. Despite their significance in carbon fixation and great bioengineering potentials, the structural understanding of native carboxysomes is currently limited to low-resolution studies. Here, we report the characterization of a native α-carboxysome from a marine cyanobacterium by single-particle cryoelectron microscopy (cryo-EM). We have determined the structure of its RuBisCO enzyme, and obtained low-resolution maps of its icosahedral shell, and of its concentric interior organization. Using integrative modeling approaches, we have proposed a complete atomic model of an intact carboxysome, providing insight into its organization and assembly. This is critical for a better understanding of the carbon fixation mechanism and toward repurposing carboxysomes in synthetic biology for biotechnological applications., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke., Discussion: Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke. Additionally, hyperglycemic conditions may play a significant role in worsening stroke outcomes due to microbiome dysbiosis., Conclusion: Recent research has illuminated the vital role of the GBA in propagating poor clinical outcomes, such as hemorrhagic transformation, following ischemic stroke. Considering this detrimental consequence of stroke, and the apparent role of the GBA role, future therapeutics should aim to mitigate this peripheral contribution to stroke complications., (© 2022 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to the brain. To this end, peripheral inflammation has emerged as an equally potent contributor to the onset and progression of stroke secondary cell death. Here, we review novel concepts on peripheral organs displaying robust inflammatory response to stroke. These inflammation-plagued organs include the spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, and adrenal glands, likely converging their inflammatory effects through B and T-cells. Recognizing the significant impact of this systemic inflammation, we also discuss innovative stroke therapeutics directed at sequestration of peripheral inflammation. This review paper challenges the paradigm of a brain-centered disease pathology and treatment and offers a peripheral approach to our stroke understanding.

Objective: Vein of Galen Malformations (VoGM) are rare vascular malformations, typically seen in pediatric age groups. Even more rarely, VoGM's may be seen later in adulthood. In this case report and systematic review, we provide a thorough description of the current literature as well as provide a case example exploring the diagnosis, imaging, treatment, and management of VoGM in adults., Methods: In accordance with PRISMA guidelines, we performed a systematic literature search for all relevant cases and case series of VoGM in adult patients. The reference list of all articles were reviewed for additional relevant cases. Articles were included if they described a VoGM of a patient over the age of 18 years old and published in English. 149 articles were originally identified and 26 described cases met our inclusion criteria., Results: In our literature review we found 26 patients that met our inclusion criteria. We found 14 male patients and 12 female patients. The mean age at presentation was 37.2 years (median=34 years, SD= 13.6 years). The most common presenting symptoms of patient were headache (n = 9), seizure (n = 6), and vomiting (n = 4). Of the 12 cases which clearly reported the subtype of VoGM, the choroidal type was more frequently seen (n = 10) compared to the mural type (n = 2). In 3 patients, the VoGM was thrombosed at time of diagnosis. Of the 26 patients, endovascular treatment was performed most frequently (n = 8) but some received microsurgical treatment (n = 4) or were treated conservatively (n = 6). Other treatment modalities included (ventriculoperitoneal shunt, ventriculostomy) (n = 5). In 3 cases treatment was not specified. In comparison to VoGM seen in pediatric or neonatal populations, VoGM in adults generally resulted in more favorable outcomes with only 2 patients reported to have passed away following treatment., Conclusion: VoGM remains a rare finding amongst the adult population. Hence, we described the clinical presentation, treatment modalities, and outcomes of the cases described in the English literature. Perhaps due to the rate of thrombosis and the unique angioarchitecture seen in adult VoGM patients, outcomes were generally more favorable than those described in the literature in pediatric or neonate VoGM patients., Competing Interests: Competing Interests No competing interests to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Although the US infant mortality rate reached a record low in 2020, the sudden infant death syndrome (SIDS) rate increased from 2019. To understand if the increase was related to changing death certification practices or the coronavirus disease 2019 (COVID-19) pandemic, we examined sudden unexpected infant death (SUID) rates as a group, by cause, and by race and ethnicity., Methods: We estimated SUID rates during 2015 to 2020 using US period-linked birth and death data. SUID included SIDS, unknown cause, and accidental suffocation and strangulation in bed. We examined changes in rates from 2019 to 2020 and assessed linear trends during prepandemic (2015-2019) using weighted least squares regression. We also assessed race and ethnicity trends and quantified COVID-19-related SUID., Results: Although the SIDS rate increased significantly from 2019 to 2020 (P < .001), the overall SUID rate did not (P = .24). The increased SIDS rate followed a declining linear trend in SIDS during 2015 to 2019 (P < .001). Other SUID causes did not change significantly. Our race and ethnicity analysis showed SUID rates increased significantly for non-Hispanic Black infants from 2019 to 2020, widening the disparities between these two groups during 2017 to 2019. In 2020, <10 of the 3328 SUID had a COVID-19 code., Conclusions: Diagnositic shifting likely explained the increased SIDS rate in 2020. Why the SUID rate increased for non-Hispanic Black infants is unknown, but warrants continued monitoring. Interventions are needed to address persistent racial and ethnic disparities in SUID., (Copyright © 2023 by the American Academy of Pediatrics.)

Transfer of healthy mitochondria from mesenchymal stem cells (MSCs) to ischemic neurons represents a potent stroke therapeutic. MSCs were grown under ambient conditions (nMSCs) or a metabolic switching paradigm by alternating galactose and glucose in medium (sMSCs) and then assayed for oxygen consumption rates using the Seahorse technology. Subsequently, primary neurons were subjected to oxygen glucose deprivation (OGD) and then co-cultured with either nMSCs or sMSCs. Compared to nMSCs, sMSCs displayed higher basal energy production, larger spare respiratory capacity, greater ATP production, and decreased proton leak. Co-culture of OGD-exposed neurons with sMSCs conferred greater cell viability, enhanced cell metabolism, reduced mitochondrial reactive oxidative species mRNA, and elevated mitochondria ATP mRNA than those cultured with nMSCs. Metabolic switching produces "super" mitochondria that may underlie the therapeutic benefit of using sMSCs to treat ischemic cells., (© 2022. The Author(s).)

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Despite a relatively developed understanding of the pathophysiology underlying primary and secondary mechanisms of cell death after ischemic injury, there are few established treatments to improve stroke prognoses. A major contributor to secondary cell death is mitochondrial dysfunction. Recent advancements in cell-based therapies suggest that stem cells may be revolutionary for treating stroke, and the reestablishment of mitochondrial integrity may underlie these therapeutic benefits. In fact, functioning mitochondria are imperative for reducing oxidative damage and neuroinflammation following stroke and reperfusion injury. In this review, we will discuss the role of mitochondria in establishing the anti-oxidative effects of stem cell therapies for stroke.

Objective(s): To understand how contraception method use differed between women prescribed and not prescribed medications for opioid use disorder (MOUD) among commercially-insured and Medicaid-insured women., Study Design: IBM Watson Health MarketScan Commercial Claims and Encounters database and the Multi-State Medicaid database were used to calculate the (1) crude prevalence, and (2) adjusted odds ratios (adjusted for demographic characteristics) of using long-acting reversible or short-acting hormonal contraception methods or female sterilization compared with none of these methods (no method) in 2018 by MOUD status among women with OUD, aged 20 to 49 years, with continuous health insurance coverage through commercial insurance or Medicaid for ≥6 years. Claims data was used to define contraception use. Fisher exact test or χ 2 test with a P-value ≤ 0.0001, based on the Holm-Bonferroni method, and 95% confidence intervals were used to determine statistically significant differences for prevalence estimates and adjusted odds ratios, respectively., Results: Only 41% of commercially-insured and Medicaid-insured women with OUD were prescribed MOUD. Medicaid-insured women with OUD prescribed MOUD had a significantly lower crude prevalence of using no method (71.1% vs 79.0%) and higher odds of using female sterilization (aOR, 1.33; 95% CI: 1.06-1.67 vs no method) than those not prescribed MOUD. Among commercially-insured women there were no differences in contraceptive use by MOUD status and 66% used no method., Conclusions: Among women with ≥ 6 years of continuous insurance coverage, contraceptive use differed by MOUD status and insurance. Prescribing MOUD for women with OUD can be improved to ensure quality care., Implications: Only two in five women with OUD had evidence of being prescribed MOUD, and majority did not use prescription contraception or female sterilization. Our findings support opportunities to improve prescribing for MOUD and integrate contraception and MOUD services to improve clinical care among women with OUD., (Published by Elsevier Inc.)

The field of stem cell therapy is growing rapidly and hopes to offer an alternative solution to diseases that are historically treated medically or surgically. One such focus of research is the treatment of medically refractory epilepsy, which is traditionally approached from a surgical or interventional standpoint. Research shows that stem cell transplantation has potential to offer significant benefits to the epilepsy patient by reducing seizure frequency, intensity, and neurological deficits that often result from the condition. This review explores the basic science progress made on the topic of stem cells and epilepsy by focusing on experiments using animal models and highlighting the most recent developments from the last 4 years.

Objective: Thoracolumbar lateral interbody fusions (tLLIF) are one tool in the spine surgeon's toolbox to indirectly decompress neuroforamina while also improving segmental lordosis in a biomechanically distinct manner from posterior fusions. When part of a concomitant posterior construct, hardware failure (HF), sometimes requiring revision surgery, can occur. We sought to study the relationship between tLLIF and HF., Methods: We conducted a retrospective study on consecutive patents who underwent tLLIF at a single academic center between January 2012 and December 2021 by seven unique neurosurgeons. Patients were excluded if they had no posterior instrumentation within their construct or if they had less than six months of follow-up. Hardware failure was defined as screw breakage or rod fracture seen on postoperative imaging., Results: 232 patients were identified; 6 (2.6 %) developed HF throughout a mean follow-up of 1182 days (range =748-1647 days). Adjacent segment disease was the most common pathology addressed (75 patients (32.3 %)). The amount of posterior instrumentation both in the surgery in question and in the total construct were significantly higher in the HF cohort (4.33 ± 1.52 levels, 5.83 ± 3.36 levels) versus the non-HF cohort (2.08 ± 0.296 levels, p = 0.014; 2.86 ± 0.316 levels, p = 0.003, respectively). The number of interbody devices added in the index surgery and in the entire construct were both significantly higher in the HF cohort (3.33 ± 0.666 interbody devices, 3.33 ± 0.666 devices) than in the non-HF cohort (1.88 ± 0.152 interbody devices, p = 0.002; 2.31 ± 0.158 devices, p = 0.036, respectively). Higher amounts of lateral levels of fusion approached significance for association with HF (HF: 2.67 ± 0.844 levels, no HF: 1.73 ± 1.26 levels, p = 0.076). On multivariate analysis, only the number of interbody devices added in the index surgery was predictive of HF (Odds ratio=2.3, 95 % confidence interval=1.25-4.23, p = 0.007)., Conclusion: Greater levels of posterior fusion, and greater numbers of interbody devices in an index surgery and in a construct as a whole, were associated with higher rates of HF in our cohort of patients with tLLIF. Greater numbers of lateral segments fused in this population may also be related to HF., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The immense neuroinflammation induced by multiple sclerosis (MS) promotes a favorable environment for ischemic stroke (IS) development, making IS a deadly complication of MS. The overlapping inflammation in MS and IS is a prelude to the vascular pathology, and an inherent cell death mechanism that exacerbates neurovascular unit (NVU) impairment in the disease progression. Despite this consequence, no therapies focus on reducing IS incidence in patients with MS. To this end, the preclinical and clinical evidence we review here argues for cell-based regenerative medicine that will augment the NVU dysfunction and inflammation to ameliorate IS risk.

Amyotrophic lateral sclerosis (ALS) is a debilitating disease with poor prognosis. The pathophysiology of ALS is commonly debated, with theories involving inflammation, glutamate excitotoxity, oxidative stress, mitochondria malfunction, neurofilament accumulation, inadequate nutrients or growth factors, and changes in glial support predominating. These underlying pathological mechanisms, however, act together to weaken the blood brain barrier and blood spinal cord barrier, collectively considered as the blood central nervous system barrier (BCNSB). Altering the impermeability of the BCNSB impairs the neurovascular unit, or interdependent relationship between the brain and advances the concept that ALS is has a significant neurovascular component contributing to its degenerative presentation. This unique categorization of ALS opens a variety of treatment options targeting the reestablishment of BCNSB integrity. This review will critically assess the evidence implicating the significant neurovascular components of ALS pathophysiology, while also offering an in-depth discussion regarding the use of stem cells to repair these pathological changes within the neurovascular unit., (© The Author(s) 2022. Published by Oxford University Press.)