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Fine and ultra-fine particulate matter (PM) are major constituents of urban air pollution and recognized risk factors for cardiovascular diseases. This review examined the effects of PM exposure on vascular tissue. Specific mechanisms by which PM affects the vasculature include inflammation, oxidative stress, actions on vascular tone and vasomotor responses, as well as atherosclerotic plaque formation. Further, there appears to be a greater PM exposure effect on susceptible individuals with pre-existing cardiovascular conditions.

Introduction Posterior cervical foraminotomy and anterior cervical discectomy and fusion (ACDF) are the mainstay treatments for cervical radiculopathy. A recent alternative or adjunct involves the placement of interfacet spacers, which promote indirect decompression by increasing foraminal height. Cervical interfacet spacers have been shown to be safe options for indirect decompression and improve short-term clinical outcomes in patients with cervical spine pathologies. However, no previous data regarding malpositioned spacers and their management have been reported. Given this paucity of data, we aim to present examples of malpositioned interfacet spacers and their management. Methods This was a retrospective single-center review. Results Twenty-five patients were identified in which interfacet spacers were used at a single level in 19 cases, two levels in five cases, and three levels in one case. The cohort had a mean follow-up of 14.4 months. Among 60 total spacers placed, two required repositioning (3.3%). The first underwent bilateral placement at C4/5 and developed a unilateral deltoid palsy postoperatively. She was taken back to the operating room the same day for implant removal. A second patient underwent removal after a malpositioned implant at C4/5 was identified on an intraoperative CT scan. A third patient had spacers placed at a referring hospital and presented with progressive neck pain and radiculopathy. She underwent successful removal with a resolution of her symptoms. Conclusions Interfacet spacers represent a novel technique for the treatment of cervical radiculopathy, however, there are limited data on their utilization. We present the first reports of malpositioned spacers and their management. Patients with small facet joints and lateral masses may be at increased risk for malposition, and intraoperative fluoroscopy may not adequately confirm implant placement. Surgeons should use caution when implementing new technology with a low threshold for intraoperative CT to confirm the appropriate placement of these devices.

Exposure to ambient air pollution particulate matter (PM) is associated with increased risk of dementia and accelerated cognitive loss. Vascular contributions to cognitive impairment are well recognized. Chronic cerebral hypoperfusion (CCH) promotes neuroinflammation and blood-brain barrier weakening, which may augment neurotoxic effects of PM.This study examined interactions of nanoscale particulate matter (nPM; fine particulate matter with aerodynamic diameternPM was collected using a particle sampler near a Los Angeles, California, freeway. Mice were exposed to 10 wk of reaerosolized nPM or filtered air (FA) for 150 h. CCH was induced by BCAS surgery. Mice (C57BL/6J males) were randomized to four exposure paradigms:The jointOur data suggest that nPM and CCH contribute to white matter injury in a synergistic manner in a mouse model. Adverse neurological effects may be aggravated in a susceptible population exposed to air pollution. https://doi.org/10.1289/EHP8792.

Background Ventricular shunting is one of the primary modalities for addressing hydrocephalus in both children and adults. Despite advances in shunt technology and surgical practices, shunt failure is a persistent challenge for neurosurgeons, and shunt revisions account for a substantial proportion of all shunt-related procedures. There are a wealth of studies elucidating failure patterns and patient demographics in pediatric cohorts; however, data in adults are less uniform. We sought to determine the rates of all-cause and shunt failure readmission in adults who underwent the insertion of a ventricular shunt. Methods We queried the Nationwide Readmissions Database from 2010 to 2014 to evaluate new ventricular shunts placed in adults with hydrocephalus. We sought to determine the rates of all-cause and shunt revision-related readmissions and to characterize factors associated with readmissions. We analyzed predictors including patient demographics, hospital characteristics, shunt type, and hydrocephalus cause. Results Analysis included 24,492 initial admissions for shunt placement in patients with hydrocephalus. Of patients, 9.17% required a shunt revision within the first 6 months; half of all revisions occurred within the first 41 days. There were 4044 (16.50%) 30-day and 5758 (28.8%) 90-day all-cause readmissions. In multivariable analysis, patients with a ventriculopleural shunt, Medicare insurance, and younger age had increased likelihood for shunt revision. Notable predictors for all-cause readmission were insurance type, length of hospitalization, age, comorbidities, and hydrocephalus cause. Conclusions Most shunt revisions occurred during the first 2 months. Readmissions occurred frequently. We identified patient factors that were associated with all-cause and shunt failure readmissions.

BackgroundStroke systems of care employ a hub-and-spoke model, with fewer centers performing mechanical thrombectomy (MT) compared with stroke-receiving centers, where a higher number offer high-level, centralized treatment to a large number of patients.ObjectiveTo characterize rates and outcomes of readmission to index and non-index hospitals for patients with ischemic stroke who underwent MT.MethodsThis study leveraged a population-based, nationally representative sample of patients with stroke undergoing MT from the Nationwide Readmissions Database between 2010 and 2014. Descriptive, logistic regression analyses, and univariate and multivariate logistic regression models were carried out to determine patient- and hospital-level factors, mortality, complications, and subsequent readmissions associated with index and non-index hospitals' 90-day readmissions.ResultsIn the study, 2111 patients with a stroke were treated with MT, of whom 534 were readmitted within 90 days. The most common reasons for readmission were: septicemia (5.9%), atrial fibrillation (4.8%), and cerebral artery occlusion with infarct (4.8%). Among readmitted patients, 387 (74%) were readmitted to index and 136 (26%) to non-index hospitals. On multivariable logistic regression analysis, non-index hospital readmission was not independently associated with major complications (p=0.09), mortality (p=0.34), neurological complications (p=0.47), or second readmission (p=0.92).ConclusionOne-quarter of patients with a stroke treated with MT were readmitted within 90 days, and one quarter of these patients were readmitted to non-index hospitals. Readmission to a non-index hospital was not associated with mortality or increased complication rates. In a hub-and-spoke model it is important that follow-up care for a specialized procedure can be performed effectively at a vast number of non-index hospitals covering a large geographic area.

STUDY DESIGN Retrospective analysis of a prospective registry. OBJECTIVE We utilized the Quality Outcomes Database (QOD) registry to investigate the "July Effect" at QOD spondylolisthesis module sites with residency trainees. SUMMARY OF BACKGROUND DATA There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data. METHODS This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups. RESULTS Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9-449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons). CONCLUSION Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes.Level of Evidence: 3.

OBJECTIVE Cerebrospinal fluid diversion via ventricular shunting is a common surgical treatment for hydrocephalus in the pediatric population. No longitudinal follow-up data for a multistate population-based cohort of pediatric patients undergoing ventricular shunting in the United States have been published. In the current review of a nationwide population-based data set, the authors aimed to assess rates of shunt failure and hospital readmission in pediatric patients undergoing new ventricular shunt placement. They also review patient- and hospital-level factors associated with shunt failure and readmission. METHODS Included in this study was a population-based sample of pediatric patients with hydrocephalus who, in 2010–2014, had undergone new ventricular shunt placement and had sufficient follow-up, as recorded in the Nationwide Readmissions Database. The authors analyzed the rate of revision within 6 months, readmission rates at 30 and 90 days, and potential factors associated with shunt failure including patient- and hospital-level variables and type of hydrocephalus. RESULTS A total of 3520 pediatric patients had undergone initial ventriculoperitoneal shunt placement for hydrocephalus at an index admission. Twenty percent of these patients underwent shunt revision within 6 months. The median time to revision was 44.5 days. Eighteen percent of the patients were readmitted within 30 days and 31% were readmitted within 90 days. Different-hospital readmissions were rare, occurring in ≤ 6% of readmissions. Increased hospital volume was not protective against readmission or shunt revision. Patients with grade 3 or 4 intraventricular hemorrhage were more likely to have shunt malfunctions. Patients who had private insurance and who were treated at a large hospital were less likely to be readmitted. CONCLUSIONS In a nationwide, population-based database with longitudinal follow-up, shunt failure and readmission were common. Although patient and hospital factors were associated with readmission and shunt failure, system-wide phenomena such as insufficient centralization of care and fragmentation of care were not observed. Efforts to reduce readmissions in pediatric patients undergoing ventricular shunt procedures should focus on coordinating care in patients with complex neurological diseases and on reducing healthcare disparities associated with readmission.

National and regional systems of stroke care are designed to provide patients with widespread access to hospitals with thrombolytic capabilities. However, such triaging systems may contribute to fragmentation of care. This study aims to compare rates of readmission and outcomes between index and non-index hospitals for stroke patients following intravenous thrombolytic therapy (IVT). This study utilized a nationally representative sample of stroke patients with IVT from the Nationwide Readmissions Database from 2010 to 2014. Descriptive and regression analyses were performed for patient and hospital level factors that influenced 90-day readmissions and regression models were used to identify differences in mortality, complications, and repeat readmissions between patients readmitted to index (facility where IVT was administered) and non-index hospitals. In the study, 49415 stroke patients were treated with IVT, of whom 21.7% were readmitted within 90 days. Among readmissions, 79.4% of patients were readmitted to index hospitals and 20.6% to non-index hospitals. On multivariate logistic regression analysis, index hospital readmission was independently associated with lower frequency of second readmissions (non-index OR 1.09, 95%CI 1.07-1.11, p

Author(s): Winkler, Ethan A; Lu, Alex; Morshed, Ramin A; Yue, John K; Rutledge, W Caleb; Burkhardt, Jan-Karl; Patel, Arati B; Ammanuel, Simon G; Braunstein, Steve; Fox, Christine K; Fullerton, Heather J; Kim, Helen; Cooke, Daniel; Hetts, Steven W; Lawton, Michael T; Abla, Adib A; Gupta, Nalin | Abstract: OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs.

INTRODUCTION: Successful endovascular management of aneurysmal subarachnoid hemorrhage (aSAH) requires timely access to significant resources. Prior studies suggest an association between time to treatment and patient outcome. Patients treated at safety- net hospitals are thought to be particularly vulnerable to disparities in access to interventions that require substantial technological resources. We hypothesize that patients treated at safety-net hospitals are at greater risk for delayed access to endovascular treatment. MATERIALS AND METHODS: Adults undergoing endovascular coiling procedures between 2002–2011 in the Nationwide Inpatient Sample were included. Hospitals in the quartile with the highest proportion of Medicaid or uninsured patients were defined as safety-net hospitals. A multivariable model including patient and hospital-level factors was constructed to permit analysis of delays in endovascular treatment (defined as time to treatment greater than 3 days). RESULTS: Analysis included 7,109 discharges of patients with aSAH undergoing endovascular coil embolization procedures from 2002–2011. The median time to coil embolization in all patients was 1 day; 10.1% of patients waited more than three days until treatment. In multivariable analysis, patients treated at safety-net hospitals were more likely to have a prolonged time to coil embolization (OR 1.32, p

Clinical outcomes in the surgical management of severe traumatic brain injury (TBI) have been shown to vary across different hospital institutions. The effect of the safety-net burden on postoperative mortality, complication rates, and failure to rescue rates is unclear. We evaluated the relationship of the safety-net burden with outcomes in the treatment of patients with severe TBI undergoing neurosurgery.The hospitals were grouped according to their safety-net burden, defined as the proportion of Medicaid and uninsured patient charges for all hospitalizations during that time. Multivariate analyses were performed to examine significant associations with the degree of safety-net burden while controlling for potential confounders.Data from 20,989 encounters in 788 hospitals were included. Compared with low-burden hospitals (LBHs), high-burden hospitals (HBHs; odds ratio [OR], 1.48; 95% confidence interval [CI], 1.04-2.12; P = 0.03) had greater mortality rates. Major complications were more likely to occur at HBHs (OR, 1.44; 95% CI, 1.12-1.84; P0.01) compared with LBHs. The failure to rescue rates were similar among all safety-net burden hospital groups. Patients at HBHs also had an increased likelihood of an extended length of stay (OR, 1.92; 95% CI, 1.12-3.29; P = 0.02) and receiving a tracheostomy or gastrostomy (OR, 1.99; 95% CI, 1.36-2.89; P0.01) compared with patients at LBHs.The present study found that a greater hospital safety-net burden was independently associated with greater rates of mortality and major complications in the treatment of patients with severe TBI undergoing neurosurgery. Further research in evaluating the cause of disparities in mortality outcomes at high safety-burden hospitals is needed.

OBJECTIVE There is a learning curve for surgeons performing “awake” spinal surgery. No comprehensive guidelines have been proposed for the selection of ideal candidates for awake spinal fusion or decompression. The authors sought to formulate an algorithm to aid in patient selection for surgeons who are in the startup phase of awake spinal surgery. METHODS The authors developed an algorithm for selecting patients appropriate for awake spinal fusion or decompression using spinal anesthesia supplemented with mild sedation and local analgesia. The anesthetic protocol that was used has previously been reported in the literature. This algorithm was formulated based on a multidisciplinary team meeting and used in the first 15 patients who underwent awake lumbar surgery at a single institution. RESULTS A total of 15 patients who underwent decompression or lumbar fusion using the awake protocol were reviewed. The mean patient age was 61 ± 12 years, with a median BMI of 25.3 (IQR 2.7) and a mean Charlson Comorbidity Index of 2.1 ± 1.7; 7 patients (47%) were female. Key patient inclusion criteria were no history of anxiety, 1 to 2 levels of lumbar pathology, moderate stenosis and/or grade I spondylolisthesis, and no prior lumbar surgery at the level where the needle is introduced for anesthesia. Key exclusion criteria included severe and critical central canal stenosis or patients who did not meet the inclusion criteria. Using the novel algorithm, 14 patients (93%) successfully underwent awake spinal surgery without conversion to general anesthesia. One patient (7%) was converted to general anesthesia due to insufficient analgesia from spinal anesthesia. Overall, 93% (n = 14) of the patients were assessed as American Society of Anesthesiologists class II, with 1 patient (7%) as class III. The mean operative time was 115 minutes (± 60 minutes) with a mean estimated blood loss of 46 ± 39 mL. The median hospital length of stay was 1.3 days (IQR 0.1 days). No patients developed postoperative complications and only 1 patient (7%) required reoperation. The mean Oswestry Disability Index score decreased following operative intervention by 5.1 ± 10.8. CONCLUSIONS The authors propose an easy-to-use patient selection algorithm with the aim of assisting surgeons with patient selection for awake spinal surgery while considering BMI, patient anxiety, levels of surgery, and the extent of stenosis. The algorithm is specifically intended to assist surgeons who are in the learning curve of their first awake spinal surgery cases.

Inpatient hospital stays for patients with epilepsy represent a significant burden on patients and society. Identifying factors that contribute to such costs aides in developing effective strategies to address this burden. July admissions have been associated with higher rates of complications and worse outcomes, attributed to the presence of new physicians. This study aims to evaluate whether epilepsy patients admitted in July have higher preventable complication rates and mortality than during the rest of the year.Data was derived from the Nationwide Inpatient Sample (NIS) for epilepsy admissions for the years 2000-2010. Multivariable analyses assessed the effect of July against non-July admission on "hospital acquired complications" (HAC), which are complications identified as owing to preventable causes and mortality. Additionally, the total adjusted charges and prolonged length of stay (pLOS) for July admissions were compared to the 50th percentile.A total of 12,997,181 admissions for epilepsy were identified with 993,619 (8%) occurring in July, 10,810,900 (83%) were non-July months, and 1,192,662 (9%) were missing data. Patients admitted in July showed an increased association for HAC events (RR=1.02, [1.01,1.03], p0.01), but a decrease in mortality (RR=0.96, [0.95,0.97], p0.01). There was no difference in rates of higher total adjusted charges for July admissions (RR=1.00, [1.00,1.00], p0.01) and a decrease in rates of pLOS (RR=0.99, [0.98,0.99], p0.01).In the epilepsy population, although July admissions were associated with a slight increase in HAC events, there was a non-significant or decreased rate of mortality, LOS, and total charge. Our results suggest that although complications were increased in July, possibly due to new staff, supervision is sufficient to prevent significant burden on patients and hospitals.

The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer’s and Parkinson’s Diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health.

Chronic cerebral hypoperfusion (CCH) can result in vascular dementia and small vessel white matter ischemic injury. These findings have previously been demonstrated in a murine experimental model of CCH secondary to bilateral common carotid artery stenosis (BCAS). This study sought to elucidate the effects of CCH on recognition memory as assessed by the novel object recognition (NOR) test and histological analysis of the hippocampus and perirhinal cortex.Studies were performed on ten-week-old male mice using bilateral 0.18 mm microcoils to narrow the carotid arteries in accordance with prior publications. Following surgery, BCAS (n = 6) and sham (n = 6) mice were evaluated using NOR and 8-arm radial maze testing paradigms. Tissue damage was assessed using HE staining on a parallel cohort of mice (n = 6 BCAS, n = 7 sham).In the NOR paradigm, BCAS mice demonstrated significant deficits in short-term memory. Consistent with prior studies, BCAS mice also performed significantly worse on 8-arm radial maze testing. BCAS mice exhibited significantly more neuronal injury in the perirhinal cortex when compared to sham-operated mice. However, no significant differences in neuronal damage were observed in the CA1 region of the hippocampus.Experimental CCH secondary to BCAS results in recognition memory deficits on NOR testing. Damage to the perirhinal cortex, rather than to the hippocampus, may underlie this impairment.

Intracerebral hemorrhage and, more specifically, intraparenchymal hemorrhage, are devastating disease processes with poor clinical outcomes. Primary injury to the brain results from initial hematoma expansion while secondary hemorrhagic injury occurs from blood-derived products such as hemoglobin, heme, iron, and coagulation factors that overwhelm the brains natural defenses. Novel neuroprotective treatments have emerged that target primary and secondary mechanisms of injury. Nonetheless, translational application of neuroprotectants from preclinical to clinical studies has yet to show beneficial clinical outcomes. This review summarizes therapeutic agents and neuroprotectants in ongoing clinical trials aimed at targeting primary and secondary mechanisms of injury after intraparenchymal hemorrhage.

Background: The hallmark of inflammation is activation of the immune system, recruitment of leukocytes and induction of proinflammatory cytokines. Air pollution induced nano-size particulate matter (nPM) from vehicular exhaust is a potent environmental source of inflammation. The carotid arteries, a principle source of blood flow to the brain, are susceptible to inflammatory changes. Objective: To examine the effects of nano-size particulate matter (nPM) exposure on vascular tissue inflammation in the common carotid artery in mice. Methods: Particulate Matter was collected from an urban area in central Los Angeles, transferred to aqueous suspension by vortexing and sonication and reaerosolized for animal exposure. Mice were exposed to filtered air (n=7) or nPM (n=7) for a duration of 10 weeks, 3 days a week for 5 hours. Following the exposure period, animals were sacrificed and common carotid arteries were extracted, frozen, cut axially at 20um, and mounted on slides. Immunohistochemical analysis was performed. Staining was analyzed for presence of Intercellular Adhesion Molecule 1 (ICAM-1), endothelial surface adhesion molecule activated by leukocytes, and leukocyte antigen 6G precursor (Ly6g), a maker for monocytes and neutrophils. Results: An average of 5 axial sections were taken from carotid arteries of 14 mice (Filter n=7, nPM =7). Mean ICAM-1 values were computed for each carotid artery. Group averages were compared between cohorts of mice exposed to filtered air and nPM. Semiquantitative immunohistochemical analysis of the intimal and medial layers of the common carotid arteries demonstrated increased ICAM-1 in mice exposed to nPM (filter 15.6 SD +/-1.7 vs nPM 19.7 SD +/-3.4, p=0.01), but did not demonstrate differences in Ly6g values (filter mean 19.4, SD +/-3.9 vs nPM mean 16.1, SD +/-2.7, p=0.1) Conclusion: Higher ICAM-1 concentrations on carotid arteries exposed to nano-size particulate matter indicates inflammatory upregulation of adhesion molecules. However, there is no clear increase in circulating leucocytes within the vessel wall.

22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.

Background Overshunting of cerebrospinal fluid may lead to intracranial hypotension and dilation of spinal epidural veins. Radiculopathy may rarely occur secondary to engorged spinal epidural veins. In addition, the cause of radiculopathy may be obscured by concomitant spinal degenerative changes. We present a case and review the pathogenesis as well as the current clinical literature. Case Description A 29-year-old woman presented with positional headaches from intracranial hypotension in the setting of cerebrospinal fluid overshunting. The patient also had back pain and lumbar radiculopathy, which became more severe after lumboperitoneal shunt placement. On radiographic work-up, there was evidence of right L5 nerve root impingement secondary to a disc bulge and an engorged lumbar epidural venous plexus secondary to overshunting. The patient underwent surgery for a planned L4-5 decompression with a transforaminal lumbar interbody fusion. The operation was complicated by rapid blood loss originating from the epidural venous plexus, and we were unable to safely place the interbody graft. Conclusions Spinal surgeons need to be aware of the rare diagnosis of radiculopathy secondary to epidural venous plexus engorgement, as it may change the treatment approach or lead to deleterious intraoperative consequences, such as hemorrhage.

Background: Clinical and epidemiologic studies suggest a relationship between long-term nano-particulate matter (nPM) exposure and white matter injury 1 . Accumulating laboratory evidence suggests that nPM exposure causes inflammation in multiple brain regions 2 . Objective: We sought to study the effects nano-particulate matter exposure on microglia activation and complement upregulation within the corpus callosum in a murine model. Methods: C57 black 6J mice were randomized to re-aerosolized nPM (n=18, nPM Results: There were significant differences in IBA-1 cell count staining between the groups (filtered air- 94.7± 18.87; nPM- 158.5 ± 41.69, p Conclusion: Chronic particulate matter exposure is associated with white matter changes in a murine model. Regional increases in microglia number and C5α deposition suggest an inflammatory mechanism. References: 1. Calderon-Garciduenas L, Mora-Tiscareno A, Ontiveros E, Gomez-Garza G, Barragan-Mejia G, Broadway J, Chapman S, Valencia-Salazar G, Jewells V, Maronpot RR, Henriquez-Roldan C, Perez-Guille B, Torres-Jardon R, Herrit L, Brooks D, Osnaya-Brizuela N, Monroy ME, Gonzalez-Maciel A, Reynoso-Robles R, Villarreal-Calderon R, Solt AC, Engle RW. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn. 2008;68(2):117-27. 2. Block, M. L., & Calderón-Garcidueñas, L. (2009). Air pollution: mechanisms of neuroinflammation and CNS disease. Trends in neurosciences , 32 (9), 506-516.

Background Individuals with 22q11.2 microdeletion syndrome (22q11DS) have elevated rates of autism spectrum disorder (ASD), although the diagnosis is controversial. To determine whether there is a biological substrate of ASD in patients with 22q11DS, we examined neurocognitive and structural neuroanatomic differences between those with 22q11DS and an ASD diagnosis (22q11DS-ASD + ) and those with 22q11DS without ASD (22q11DS-ASD − ). We then determined whether these differences were better characterized within a categorical or dimensional framework. Methods We collected multiple neurocognitive measures and high-resolution T1-weighted magnetic resonance imaging scans from 116 individuals (29 patients who were 22q11DS-ASD + , 32 patients who were 22q11DS-ASD − , and 55 typically developing controls) who were between 6 and 26 years of age. Measures of subcortical volume, cortical thickness (CT), and surface area were extracted using the FreeSurfer image analysis software. Group differences in neurocognitive and neuroanatomic measures were assessed; regression analyses were then performed to determine whether a categorical or dimensional measure of ASD was a better predictor of neurocognitive impairment or neuroanatomic abnormalities observed in patients with 22q11DS-ASD + . Results In comparison to 22q11DS-ASD – individuals, 22q11DS-ASD + participants had decreased bilateral parahippocampal CT and decreased right amygdala volumes. Those with 22q11DS-ASD + also showed slowed processing speed and impairments in visuospatial and facial memory. Neurocognitive impairments fit a dimensional model of ASD, whereas reductions in parahippocampal CT were best explained by a categorical measure of ASD. Conclusions A combination of categorical and dimensional measures of ASD may provide the most comprehensive understanding of ASDs in individuals with 22q11DS.

The role of mobile genetic elements in imparting multiple drug resistance to a clinical isolate of Vibrio fluvialis (BD146) was investigated. This isolate showed complete or intermediate resistance to all of the 14 antibiotics tested. Polymerase chain reaction (PCR) revealed the presence of a class 1 integron and the absence of the SXT element in this isolate. The strain harboured a 7.5 kb plasmid and a very low copy number plasmid of unknown molecular size. Transformation of Escherichia coli with plasmid(s) from BD146 generated two kinds of transformants, one that harboured both of these plasmids and the other that harboured only the low copy number plasmid. PCR and antibiogram analysis indicated the association of the class 1 integron with the low copy number plasmid, which also conferred all the transferable resistance traits except trimethoprim to the parent strain. A BLAST search with the sequence of the 7.5kb plasmid showed that it was 99% identical to plasmid pVN84 from Vibrio cholerae O1 in Vietnam, indicating that these two plasmids are probably one and the same. To the best of our knowledge, this is the first report of horizontal transfer of a plasmid between V. fluvialis and V. cholerae.

Introduction 22q11.2 deletion syndrome (22q11DS) represents one of the largest known genetic risk factors for psychosis, yet the neurobiological mechanisms underlying symptom development are not well understood. Here we conducted a cross-sectional study of 22q11DS to decompose cortical volume into its constituent parts, cortical thickness (CT) and surface area (SA), which are believed to have distinct neurodevelopmental origins. Methods High-resolution T1-weighted scans were collected on 65 participants (31 22q11DS, 34 demographically comparable typically developing controls, 10–25 years old). Measures of cortical volume, CT, and SA were extracted from regions of interest using the FreeSurfer image analysis suite. Group differences and age-related trajectories in these structures, as well as their association with psychotic symptomatology, were assessed. Results Relative to controls, 22q11DS participants showed bilateral volumetric reductions in the inferior temporal cortex, fusiform gyrus, anterior cingulate, superior parietal cortex, and cuneus, which were driven by decreased SA in these regions. 22q11DS participants also had increased volumes, driven by increased CT, in bilateral insula regions. 22q11DS youth had increased CT in frontal regions, particularly middle frontal and medial orbitofrontal cortices. A pattern of age-associated cortical thinning was observed in typically developing controls in brain regions associated with visual and sensory information-processing (i.e., left pericalcarine cortex and fusiform gyrus, right lingual and postcentral cortices). However, this relationship was disrupted in 22q11DS participants. Finally, correlational analyses revealed that increased CT in right medial orbitofrontal cortex was associated with increased positive symptom severity in 22q11DS. Conclusion Differential disruptions of CT and SA in distinct cortical regions in 22q11DS may indicate abnormalities in distinct developmental neural processes. Further, neuroanatomic abnormalities in medial frontal brain structures disproportionately affected in idiopathic schizophrenia were associated with psychotic symptom severity in 22q11DS youth, suggesting that disrupted biological processes in these cortical regions may underlie development of psychotic symptoms, both in 22q11DS and in the broader population., Highlights • 22q11DS offers a valuable model for neurobiological mechanisms of psychosis. • First study of multiple structural MRI indices in 22q11DS. • Reduced surface area in multiple neuroanatomic regions in 22q11DS. • Increased cortical thickness in multiple frontal regions and insula in 22q11DS. • Orbitofrontal abnormalities associated with positive symptom severity in 22q11DS.

This study examines the effects of nano-size particulate matter (nPM) exposure in the setting of murine reperfused stroke. Particulate matter is a potent source of inflammation and oxidative stress. These processes are known to influence stroke progression through recruitment of marginally viable penumbral tissue into the ischemic core. nPM was collected in an urban area in central Los Angeles, impacted primarily by traffic emissions. Re-aerosolized nPM or filtered air was then administered to mice through whole body exposure chambers for forty-five cumulative hours. Exposed mice then underwent middle cerebral artery occlusion/ reperfusion. Following cerebral ischemia/ reperfusion, mice exposed to nPM exhibited significantly larger infarct volumes and less favorable neurological deficit scores when compared to mice exposed to filtered air. Mice exposed to nPM also demonstrated increases in markers of inflammation and oxidative stress in the region of the ischemic core. The findings suggest a detrimental effect of urban airborne particulate matter exposure in the setting of acute ischemic stroke.

Resistance profiles and their correlation with genetic factors were investigated in 12 isolates of Vibrio fluvialis obtained from hospitalized patients in Kolkata, India, in 2006. All the strains displayed drug resistance with varying antibiograms. However, resistance to ampicillin and neomycin was common to all of them. Three isolates harboured plasmids carrying drug-resistance genes that could be transferred to recipient strains by conjugation and transformation. PCR results indicated the absence of class 1 integrons and SXT elements in these isolates. A mutation in gyrase A (serine 83→isoleucine) and the presence of the qnrVC-like [corrected] gene were found to contribute towards quinolone resistance. In the 12 isolates, the qnrVC-like [corrected] gene was associated only with two plasmid-bearing isolates, L10734 and L9978, which displayed resistance to quinolones. The gene was transferable during transformation and conjugation, indicating that it was plasmid-borne. Taken together, these data indicate that plasmids, the qnrVC-like [corrected] gene and a mutation in gyrase A were responsible for the observed drug resistance in these strains. To the best of our knowledge, this is the first report of the presence of the qnrVC-like [corrected] allele in V. fluvialis isolates from India.

Purpose A novel disposable endovascular chemotherapy filter (CF) device was developed to remove excess doxorubicin (Dox) from the blood during intra-arterial chemotherapy delivery to prevent systemic toxicities. Previous proof-of-concept established the capacity of the filter to bind Dox in swine serum in vitro. In this study, CF navigation, deployment and in vivo Dox binding was evaluated in the porcine inferior vena cava (IVC). Materials and methods An 18 Fr CF device was constructed with an ion-exchange membrane attached to an expandable 28 mm diameter Nitinol frame. Under X-ray fluoroscopy and contrast venography, the CF was percutaneously introduced via the internal jugular vein and deployed in the porcine infrarenal IVC. 50 mg of Dox (2 mg/ml) was injected over 10 min in the IVC below the CF device. Venous catheters with tips proximal and distal to the CF device in the infrarenal IVC obtained pressures and blood samples for Dox concentrations over 90 min across the CF device membrane. Results The CF device was successfully introduced and deployed in the infrarenal IVC in vivo. Visualization under X-ray fluoroscopy verified the proper placement and mechanical expansion of the Nitinol framework. In a 90 min study, the device was biocompatible, not leading to hemodynamic disturbances: pressure measurements taken throughout the experiment yielded a max gradient of 17 mmHg across the CF membrane. Venography demonstrated non-flow-limiting thrombus associated with the CF device after 90 min of deployment (swine were not heparinized). Significant Dox binding was noted with an 85%, 74%, and 83% decrease in relative pre- versus post-filter Dox concentrations at times 3, 10, and 30 min, respectively after Dox injection. Conclusion: We developed a biocompatible CF device that can be safely introduced, deployed, and removed from the IVC in vivo. The CF device demonstrated significant Dox binding, and could serve as a platform technology in drug therapy to allow for higher regional doses of drug while limiting systemic toxicity. In future in vivo experiments, animals or the CF device itself may be heparinized in order to prevent thrombosis. When fully developed, indications for this device could include head and neck cancer, with the device deployed in the superior vena cava or internal jugular veins during selective IA chemotherapy. Disclosures A. Patel: 1; C; NIH-NCI. 4; C; ChemoFilter. A. Chin: 1; C; NIH-NCI. 4; C; ChemoFilter. J. Yang: None. B. Thorne: None. M. Saeed: None. M. Wilson: 1; C; NIH-NIBIB, NIH-NCI. 4; C; ChemoFilter. S. Hetts: 1; C; NIH-NIBIB, NIH-NCI, Siemens, Covidien. 2; C; Stryker, Penumbra, Silk Road Medical, Medina Medical. 4; C; ChemoFilter, Medina Medical, DriftCoast.

Background The study seeks to understand the role of efflux pumps in multidrug resistance displayed by the clinical isolates of Vibrio fluvialis, a pathogen known to cause cholera-like diarrhoea. Methodology Two putative MATE family efflux pumps (H- and D-type) were PCR amplified from clinical isolates of V. fluvialis obtained from Kolkata, India, in 2006 and sequenced. Bioinformatic analysis of these proteins was done to predict protein structures. Subsequently, the genes were cloned and expressed in a drug hypersusceptible Escherichia coli strain KAM32 using the vector pBR322. The recombinant clones were tested for the functionality of the efflux pump proteins by MIC determination and drug transport assays using fluorimeter. Results The sequences of the genes were found to be around 99% identical to their counterparts in V. cholerae. Protein structure predicting servers TMHMM and I-TASSER depicted ten-twelve membrane helical structures for both type of pumps. Real time PCR showed that these genes were expressed in the native V. fluvialis isolates. In the drug transport assays, the V. fluvialis clinical isolates as well as recombinant E. coli harbouring the efflux pump genes showed the energy-dependent and sodium ion-dependent drug transport activity. KAM32 cells harbouring the recombinant plasmids showed elevated MIC to the fluoroquinolones, norfloxacin and ciprofloxacin but H-type pumps VCH and VFH from V. cholerae and V. fluvialis respectively, showed decreased MIC to aminoglycosides like gentamicin, kanamycin and streptomycin. Decrease in MIC was also observed for acriflavin, ethidium bromide, safranin and nalidixic acid. Significance Increased resistance towards fluoroquinolones exhibited due to these efflux pumps from multidrug resistant clinical isolates of V. fluvialis implies that treatment procedure may become more elaborate for this simple but highly infectious disease. To the best of our knowledge, this is the first report of cloning and characterization of efflux pumps from multidrug resistant clinical isolates of V. fluvialis.