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Thiocyanate (SCN) is used by the innate immune system, but less is known about its impact on inflammation and oxidative stress. Granulocytes oxidize SCN to evolve the bactericidal hypothiocyanous acid, which we previously demonstrated is metabolized by mammalian, but not bacterial, thioredoxin reductase (TrxR). There is also evidence that SCN is dysregulated in cystic fibrosis (CF), a disease marked by chronic infection and airway inflammation. To investigate antiinflammatory effects of SCN, we administered nebulized SCN or saline to β epithelial sodium channel (βENaC) mice, a phenotypic CF model. SCN significantly decreased airway neutrophil infiltrate and restored the redox ratio of glutathione in lung tissue and airway epithelial lining fluid to levels comparable to wild type. Furthermore, in Pseudomonas aeruginosa–infected βENaC and wild-type mice, SCN decreased inflammation, proinflammatory cytokines, and bacterial load. SCN also decreased airway neutrophil chemokine keratinocyte chemoattractant (also known as C-X-C motif chemokine ligand 1) and glutathione sulfonamide, a biomarker of granulocyte oxidative activity, in uninfected βENaC mice. Lung tissue TrxR activity and expression increased in inflamed lung tissue, providing in vivo evidence for the link between hypothiocyanous acid metabolism by TrxR and the promotion of selective biocide of pathogens. SCN treatment both suppressed inflammation and improved host defense, suggesting that nebulized SCN may have important therapeutic utility in diseases of both chronic airway inflammation and persistent bacterial infection, such as CF.

Periodic breathing (PB), regular cycles of short apneic pauses and breaths, is common in newborn infants. To characterize normal and potentially pathologic PB, we used our automated apnea detection system and developed a novel method for quantifying PB. We identified a preterm infant who died of sudden infant death syndrome (SIDS) and who, on review of her breathing pattern while in the neonatal intensive care unit (NICU), had exaggerated PB.We analyzed the chest impedance signal for short apneic pauses and developed a wavelet transform method to identify repetitive 10-40 second cycles of apnea/breathing. Clinical validation was performed to distinguish PB from apnea clusters and determine the wavelet coefficient cutoff having optimum diagnostic utility. We applied this method to analyze the chest impedance signals throughout the entire NICU stays of all 70 infants born at 32 weeks' gestation admitted over a two-and-a-half year period. This group includes an infant who died of SIDS and her twin.For infants of 32 weeks' gestation, the fraction of time spent in PB peaks 7-14 d after birth at 6.5%. During that time the infant that died of SIDS spent 40% of each day in PB and her twin spent 15% of each day in PB.This wavelet transform method allows quantification of normal and potentially pathologic PB in NICU patients.

Metabolic alterations have been implicated in the etiology of temporal lobe epilepsy (TLE), but whether or not they have a functional impact on cellular energy producing pathways (glycolysis and/or oxidative phosphorylation) is unknown. The goal of this study was to determine if alterations in cellular bioenergetics occur using real-time analysis of mitochondrial oxygen consumption and glycolytic rates in an animal model of TLE. We hypothesized that increased steady-state levels of reactive oxygen species (ROS) initiated by epileptogenic injury result in impaired mitochondrial respiration. We established methodology for assessment of bioenergetic parameters in isolated synaptosomes from the hippocampus of Sprague-Dawley rats at various times in the kainate (KA) model of TLE. Deficits in indices of mitochondrial respiration were observed at time points corresponding with the acute and chronic phases of epileptogenesis. We asked if mitochondrial bioenergetic dysfunction occurred as a result of increased mitochondrial ROS and if it could be attenuated in the KA model by pharmacologically scavenging ROS. Increased steady-state ROS in mice with forebrain-specific conditional deletion of manganese superoxide dismutase (Sod2(fl/fl)NEX(Cre/Cre)) in mice resulted in profound deficits in mitochondrial oxygen consumption. Pharmacological scavenging of ROS with a catalytic antioxidant restored mitochondrial respiration deficits in the KA model of TLE. Together, these results demonstrate that mitochondrial respiration deficits occur in experimental TLE and ROS mechanistically contribute to these deficits. Furthermore, this study provides novel methodology for assessing cellular metabolism during the entire time course of disease development.

Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcitabine-resistant (GR) and gemcitabine-sensitive (GS) PanC cells and underlying molecular mechanisms, together with efficacy of a natural agent bitter melon juice (BMJ). GR PanC cells showed distinct morphological features including spindle-shaped morphology and a decrease in E-cadherin expression. GR cells also showed higher ATP production with an increase in oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Molecular studies showed higher expression of glucose transporters (GLUT1 and 4) suggesting an increase in glucose uptake by GR cells. Importantly, GR cells showed a significant increase in Akt and ERK1/2 phosphorylation and their inhibition decreased cell viability, suggesting their role in survival and drug resistance of these cells. Recently, we reported strong efficacy of BMJ against a panel of GS cells in culture and nude mice, which we expanded here and found that BMJ was also effective in decreasing both Akt and ERK1/2 phosphorylation and viability of GR PanC cells. Overall, we have identified novel mechanisms of gemcitabine resistance in PanC cells which are targeted by BMJ. Considering the short survival in PanC patients, our findings could have high translational potential in controlling this deadly malignancy.

Head and neck squamous cell carcinoma (HNSCC) is a major killer worldwide and innovative measures are urgently warranted to lower the morbidity and mortality caused by this malignancy. Aberrant redox and metabolic status in HNSCC cells offer a unique opportunity to specifically target cancer cells. Therefore, we investigated the efficacy of grape seed extract (GSE) to target the redox and bioenergetic alterations in HNSCC cells. GSE treatment decreased the mitochondrial electron transport chain complex III activity, increased the mitochondrial superoxide levels and depleted the levels of cellular antioxidant (glutathione), thus resulting in the loss of mitochondrial membrane potential in human HNSCC Detroit 562 and FaDu cells. Polyethylene glycol-SOD addition reversed the GSE-mediated apoptosis without restoring complex III activity. Along with redox changes, GSE inhibited the extracellular acidification rate (representing glycolysis) and oxygen consumption rate (indicating oxidative phosphorylation) leading to metabolic stress in HNSCC cells. Molecular studies revealed that GSE activated AMP-activated protein kinase (AMPK), and suppressed Akt/mTOR/4E-BP1/S6K signaling in both Detroit 562 and FaDu cells. Interestingly, GSE increased the autophagic load specifically in FaDu cells, and autophagy inhibition significantly augmented the apoptosis in these cells. Consistent with in vitro results, in vivo analyses also showed that GSE feeding in nude mice activated AMPK and induced-autophagy in FaDu xenograft tumor tissues. Overall, these findings are innovative as we for the first time showed that GSE targets ETC complex III and induces oxidative and metabolic stress, thereby, causing autophagy and apoptotic death in HNSCC cells.

The epilepsies are a heterogeneous group of disorders characterized by the propensity to experience spontaneous recurrent seizures. Epilepsies can be genetic or acquired, and the underlying mechanisms of seizure initiation, seizure propagation, and comorbid conditions are incompletely understood. Metabolic changes including the production of reactive species are known to result from prolonged seizures and may also contribute to epilepsy development. In this review, we focus on the evidence that metabolic and redox disruption is both cause and consequence of epileptic seizures. Additionally, we discuss the promise of targeting redox processes as a therapeutic option in epilepsy.

Background Several clusters of serogroup C meningococcal disease among men who have sex with men (MSM) have been reported in the United States in recent years. The epidemiology and risk of meningococcal disease among MSM is not well described. Methods All meningococcal disease cases among men aged 18-64 years reported to the National Notifiable Disease Surveillance System between January 2012 and June 2015 were reviewed. Characteristics of meningococcal disease cases among MSM and men not known to be MSM (non-MSM) were described. Annualized incidence rates among MSM and non-MSM were compared through calculation of the relative risk and 95% confidence intervals. Isolates from meningococcal disease cases among MSM were characterized using standard microbiological methods and whole-genome sequencing. Results Seventy-four cases of meningococcal disease were reported among MSM and 453 among non-MSM. Annualized incidence of meningococcal disease among MSM was 0.56 cases per 100000 population, compared to 0.14 among non-MSM, for a relative risk of 4.0 (95% confidence interval [CI], 3.1-5.1). Among the 64 MSM with known status, 38 (59%) were infected with human immunodeficiency virus (HIV). HIV-infected MSM had 10.1 times (95% CI, 6.1-16.6) the risk of HIV-uninfected MSM. All isolates from cluster-associated cases were serogroup C sequence type 11. Conclusions MSM are at increased risk for meningococcal disease, although the incidence of disease remains low. HIV infection may be an important factor for this increased risk. Routine vaccination of HIV-infected persons with a quadrivalent meningococcal conjugate vaccine in accordance with Advisory Committee on Immunization Practices recommendations should be encouraged.

An analysis on numerous researches on MIMO STBC system so as to achieve the higher system performance is standard that the performance of the wireless communication systems can be enhanced by utilization multiple transmit and receive antennas (MIMO), that is typically supposed because the MIMO technique, and has been included. The reference system cryptography (STBC) may be a promising thanks to notice the gain within the wireless communications system exploitation MIMO. To extend the code rate and also the output of the orthogonal area time block code for over 2 transmit antennas is analyzed. The designed system is outperformed once imposed with 16-PSK modulation. The system organized and tested for 4×M and 2×M, wherever M is variety of receiver antennas.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders where oxidative stress and mitochondrial dysfunction have been implicated as etiological factors. Mitochondria are the major producers of reactive oxygen species (ROS) that can have damaging effects to cellular macromolecules leading to neurodegeneration. The most compelling evidence for the role of mitochondria in the pathogenesis of PD has been derived from toxicant-induced models of parkinsonism. Over the years, epidemiological studies have suggested a link between exposure to environmental toxins such as pesticides and the risk of developing PD. Data from human and experimental studies involving the use of chemical agents like paraquat, diquat, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and maneb have provided valuable insight into the underlying mitochondrial mechanisms contributing to PD and associated neurodegeneration. In this review, we have discussed the role of mitochondrial ROS and dysfunction in the pathogenesis of PD with a special focus on environmental agent-induced parkinsonism. We have described the various mitochondrial mechanisms by which such chemicals exert neurotoxicity, highlighting some landmark epidemiological and experimental studies that support the role of mitochondrial ROS and oxidative stress in contributing to these effects. Finally, we have discussed the significance of these studies in understanding the mechanistic underpinnings of PD-related dopaminergic neurodegeneration.

Objective Multi-sequence sagittal magnetic resonance imaging (MRI) of the entire spine is performed in patients with known single level spondylodiscitis. Our objective is to determine the frequency of multifocal infection. Methods After IRB approval, a retrospective five-year review of all patients with spondylodiscitis was performed. Results MRI identified 82 patients with single-level infection. All 82 had entire spine imaging performed within 72 h of admission, showing additional non-continuous sites of infection in 19 patients (23%). Remote levels of spondylodiscitis were present in 11 patients (13%). Conclusion Multi-sequence sagittal MRI of the entire spine may be helpful in patients with known single-level spine infection.

Status epilepticus is a common manifestation of nerve agent toxicity and represents a serious medical emergency with high rates of mortality and neurologic injury in those that survive. The aim of the current study was to determine if targeting oxidative stress with the catalytic antioxidant, AEOL10150, would reduce pilocarpine-induced mortality and attenuate neuronal death and neuroinflammation. We found that treatment with AEOL10150 in conjunction with scopolamine and diazepam following pilocarpine-induced SE was able to significantly reduce mortality compared to treatment with just scopolamine and diazepam. Mortality was further reduced when AEOL10150 was used in conjunction with atropine and diazepam which is considered the standard of care for nerve agent exposures. Both treatment paradigms offered significant protection against SE-induced oxidative stress. Additionally, treatment with scopolamine, AEOL10150 and diazepam attenuated SE-induced neuronal loss and neuroinflammation. Taken together, the data suggest that pharmacological targeting of oxidative stress can improve survival and attenuate secondary neurological damage following SE induced by the nerve agent surrogate pilocarpine.

Central nervous system infection can induce epilepsy that is often refractory to established antiseizure drugs. Previous studies in the Theiler’s murine encephalomyelitis virus (TMEV)-induced mouse model of limbic epilepsy have demonstrated the importance of inflammation, especially that mediated by tumor necrosis factor-α (TNFα), in the development of acute seizures. TNFα modulates glutamate receptor trafficking via TNF receptor 1 (TNFR1) to cause increased excitatory synaptic transmission. Therefore, we hypothesized that an increase in TNFα signaling after TMEV infection might contribute to acute seizures. We found a significant increase in both mRNA and protein levels of TNFα and the protein expression ratio of TNF receptors (TNFR1:TNFR2) in the hippocampus, a brain region most likely involved in seizure initiation, after TMEV infection, which suggests that TNFα signaling, predominantly through TNFR1, may contribute to limbic hyperexcitability. An increase in hippocampal cell-surface glutamate receptor expression was also observed during acute seizures. Although pharmacological inhibition of TNFR1-mediated signaling had no effect on acute seizures, several lines of genetically modified animals deficient in either TNFα or TNFRs had robust changes in seizure incidence and severity after TMEV infection. TNFR2–/–mice were highly susceptible to developing acute seizures, suggesting that TNFR2-mediated signaling may provide beneficial effects during the acute seizure period. Taken together, the present results suggest that inflammation in the hippocampus, caused predominantly by TNFα signaling, contributes to hyperexcitability and acute seizures after TMEV infection. Pharmacotherapies designed to suppress TNFR1-mediated or augment TNFR2-mediated effects of TNFα may provide antiseizure and disease-modifying effects after central nervous system infection.

OBJECTIVE: To assess the safety of meningococcal group B (MenB)-4C vaccine. PARTICIPANTS: Undergraduates, dormitory residents, and persons with high-risk medical conditions received the MenB-4C vaccine two-dose series during mass vaccination clinics from 12/2013 through 11/2014. METHODS: Adverse events (AEs) were identified by 15 minutes of observation postvaccination, spontaneous reports, surveys, and hospital surveillance. Causality was assessed for serious adverse events (SAEs). RESULTS: 16,974 persons received 31,313 MenB-4C doses. The incidence of syncope during the 15-minutes post-dose 1 was 0.88/1000 persons. 2% of participants spontaneously reported an AE (most common were arm pain and fever). 3 SAEs were suspected of being caused by the vaccine, including one case of anaphylaxis. CONCLUSIONS: Most AEs reported were nonserious and consistent with previous clinical trial findings. Measures to prevent injury from syncope and to treat anaphylaxis should be available wherever vaccines are administered. Our safety evaluation supports the use of MenB-4C in response to outbreaks.

Inflammation has been identified as an important mediator of seizures and epileptogenesis. Understanding the mechanisms underlying seizure-induced neuroinflammation could lead to the development of novel therapies for the epilepsies. Reactive oxygen species (ROS) are recognized as mediators of seizure-induced neuronal damage and are known to increase in models of epilepsies. ROS are also known to contribute to inflammation in several disease states. We hypothesized that ROS are key modulators of neuroinflammation i.e. pro-inflammatory cytokine production and microglial activation in acquired epilepsy. The role of ROS in modulating seizure-induced neuroinflammation was investigated in the pilocarpine model of temporal lobe epilepsy (TLE). Pilocarpine-induced status epilepticus (SE) resulted in a time-dependent increase in pro-inflammatory cytokine production in the hippocampus and piriform cortex. Scavenging ROS with a small-molecule catalytic antioxidant decreased SE-induced pro-inflammatory cytokine production and microglial activation, suggesting that ROS contribute to SE-induced neuroinflammation. Scavenging ROS also attenuated phosphorylation of ribosomal protein S6, the downstream target of the mammalian target of rapamycin (mTOR) pathway indicating that this pathway might provide one mechanistic link between SE-induced ROS production and inflammation. Together, these results demonstrate that ROS contribute to SE-induced cytokine production and antioxidant treatment may offer a novel approach to control neuroinflammation in epilepsy.

In 1988, the World Health Assembly resolved to eradicate poliomyelitis (polio). Since then, wild poliovirus (WPV) cases have declined by >99.9%, from an estimated 350,000 cases of polio each year to 74 cases in two countries in 2015 (1). This decrease was achieved primarily through the use of trivalent oral poliovirus vaccine (tOPV), which contains types 1, 2, and 3 live, attenuated polioviruses. Since 2000, the United States has exclusively used inactivated polio vaccine (IPV), which contains all three poliovirus types (2,3). In 2013, the World Health Organization (WHO) set a target of a polio-free world by 2018 (4). Of the three WPV types, type 2 was declared eradicated in September 2015. To remove the risk for infection with circulating type 2 vaccine-derived polioviruses (cVDPV), which can lead to paralysis similar to that caused by WPV, all OPV-using countries simultaneously switched in April 2016 from tOPV to bivalent OPV (bOPV), which contains only types 1 and 3 polioviruses (5). This report summarizes current Advisory Committee on Immunization Practices (ACIP) recommendations for poliovirus vaccination and provides CDC guidance, in the context of the switch from tOPV to bOPV, regarding assessment of vaccination status and vaccination of children who might have received poliovirus vaccine outside the United States, to ensure that children living in the United States (including immigrants and refugees) are protected against all three poliovirus types. This guidance is not new policy and does not change the recommendations of ACIP for poliovirus vaccination in the United States. Children living in the United States who might have received poliovirus vaccination outside the United States should meet ACIP recommendations for poliovirus vaccination, which require protection against all three poliovirus types by age-appropriate vaccination with IPV or tOPV. In the absence of vaccination records indicating receipt of these vaccines, only vaccination or revaccination in accordance with the age-appropriate U.S. IPV schedule is recommended. Serology to assess immunity for children with no or questionable documentation of poliovirus vaccination will no longer be an available option and therefore is no longer recommended, because of increasingly limited availability of antibody testing against type 2 poliovirus.

Current antiseizure therapy is ineffective in approximately one third of people with epilepsy and is often associated with substantial side effects. In addition, most current therapeutic paradigms offer treatment, but not cure, and no therapies are able to modify the underlying disease, that is, can prevent or halt the process of epileptogenesis or alleviate the cognitive and psychiatric comorbidities. Preclinical research in the field of epilepsy has been extensive, but unfortunately, not all the animal models being used have been validated for their predictive value. The overall goal of TASK2 of the AES/ILAE Translational Task Force is to organize and coordinate systematic reviews on selected topics regarding animal research in epilepsy. Herein we describe our strategy. In the first part of the paper we provide an overview of the usefulness of systematic reviews and meta-analysis for preclinical research and explain the essentials for their conduct. Then we describe in detail the protocol for a first systematic review, which will focus on the identification and characterization of outcome measures reported in animal models of epilepsy. The specific goals of this study are to define systematically the phenotypic characteristics of the most commonly used animal models, and to effectively compare these with the manifestations of human epilepsy. This will provide epilepsy researchers with detailed information on the strengths and weaknesses of epilepsy models, facilitating their refinement and future research. Ultimately, this could lead to a refined use of relevant models for understanding the mechanism(s) of the epilepsies and developing novel therapies.

Predicting seizurogenic properties of pharmacologically active compounds is difficult due to the complex nature of the mechanisms involved and because of the low sensitivity and high variability associated with current behavioral-based methods. To identify early neuronal signaling events predictive of seizure, we exposed transgenic NF-κB/EGFP reporter mice to multiple low doses of kainic acid (KA), postulating that activation of the stress-responsive NF-κB pathway could be a sensitive indicator of seizurogenic potential. The sub-threshold dose level proximal to the induction of seizure was determined as 2.5 mg/Kg KA, using video EEG monitoring. Subsequent analysis of reporter expression demonstrated significant increases in NF-κB activation in the CA3 and CA1 regions of the hippocampus 24 hrs after a single dose of 2.5 mg/Kg KA. This response was primarily observed in pyramidal neurons with little non-neuronal expression. Neuronal NF-κB/EGFP expression was observed in the absence of glial activation, indicating a lack of neurodegeneration-induced neuroinflammation. Protein expression of the immediate-early gene, Nurr1, increased in neurons in parallel to NF-κB activation, supporting that the sub-threshold doses of KA employed directly caused neuronal stress. Lastly, KA also stimulated NF-κB activation in organotypic hippocampal slice cultures established from NF-κB/EGFP reporter mice. Collectively, these data demonstrate the potential advantages of using genetically encoded stress pathway reporter models in the screening of seizurogenic properties of new pharamacologically active compounds.

Cognitive impairment is a common comorbidity in patients with Temporal Lobe Epilepsy (TLE). Learning and memory impairments can be recapitulated in animal models, particularly those using chemoconvulsants. Here, we used two relatively low-stress behavioral paradigms, the novel object recognition task (NOR) and a spatial variation, the novel placement recognition task (NPR) to reveal deficits in short and long term memory, in both kainic acid (KA) and pilocarpine (Pilo) treated animals. We found that both KA- and Pilo-induced significant deficits in long term recognition memory but not short term recognition memory. Additionally, KA significantly impaired spatial memory as detected by both NPR and Morris water maze. These deficits were present one week after SE. The characterization of memory performance of two chemoconvulsant- models, one of which is considered a surrogate organophosphate, provides an avenue for which targeted cognitive therapeutics can be tested.

a b s t r a c t Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria tox- oid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time- points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concen- trations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ≥8 by chi-square. Pre-vaccination rSBA GMT was

Steady-state levels of reactive oxygen species (ROS) and oxidative damage to cellular macromolecules are increased in the rodent hippocampus during epileptogenesis. However, the role of reactive nitrogen species (RNS) in epileptogenesis remains to be explored. The goal of this study was to determine the spatial and temporal occurrence of RNS i.e. nitric oxide levels in a rat model of temporal lobe epilepsy (TLE). Rats were injected with a single high dose of kainate and monitored by video for behavioral seizures for 6 weeks to determine the onset and severity of chronic seizures. RNS and tissue/mitochondrial redox status (glutathione redox couple and coenzyme A:glutathione redox couple) were measured in the hippocampus at 8 h, 24 h, 48 h, 1 wk, 3 wk and 6 wk following kainate to assess the level of reactive species in subcellular compartments. We observed a biphasic increase in RNS levels with a return to control values at the 48 h time point. However, both tissue and mitochondrial redox status showed permanent and significant decreases during the entire time course of epilepsy development. 3 nitrotyrosine (3NT) protein adducts were found to gradually increase throughout epileptogenesis, conceivably as a result of the local environment under oxidative and nitrosative stress. Colocalization of 3NT immunostaining with neuron- or astrocyte-specific markers revealed neuron-specific localization of 3NT in hippocampal principal neurons. Persistent and concurrent glutathione oxidation and nitrosative stress occur during epileptogenesis suggesting a favorable environment for posttranslational modifications.

Kathryn Firth, Chief of Design at the London Legacy Development Corporation (LLDC), and Manisha Patel, a director at PRP Architects, describe how the London 2012 bid's promise to promote wellbeing and social inclusion in the Stratford area of East London is now being borne out in urban design and housing that meet ‘the evolving needs and desires of people throughout their lifetimes’. A key scheme is PRP Architects' design for multi-generation houses at Chobham Manor, on the eastern side of the Queen Elizabeth Olympic Park.

Epilepsy therapy is based on antiseizure drugs that treat the symptom, seizures, rather than the disease and are ineffective in up to 30% of patients. There are no treatments for modifying the disease—preventing seizure onset, reducing severity or improving prognosis. Among the potential molecular targets for attaining these unmet therapeutic needs, we focused on oxidative stress since it is a pathophysiological process commonly occurring in experimental epileptogenesis and observed in human epilepsy. Using a rat model of acquired epilepsy induced by electrical status epilepticus, we show that oxidative stress occurs in both neurons and astrocytes during epileptogenesis, as assessed by measuring biochemical and histological markers. This evidence was validated in the hippocampus of humans who died following status epilepticus. Oxidative stress was reduced in animals undergoing epileptogenesis by a transient treatment with N-acetylcysteine and sulforaphane, which act to increase glutathione levels through complementary mechanisms. These antioxidant drugs are already used in humans for other therapeutic indications. This drug combination transiently administered for 2 weeks during epileptogenesis inhibited oxidative stress more efficiently than either drug alone. The drug combination significantly delayed the onset of epilepsy, blocked disease progression between 2 and 5 months post-status epilepticus and drastically reduced the frequency of spontaneous seizures measured at 5 months without modifying the average seizure duration or the incidence of epilepsy in animals. Treatment also decreased hippocampal neuron loss and rescued cognitive deficits. Oxidative stress during epileptogenesis was associated with de novo brain and blood generation of high mobility group box 1 (HMGB1), a neuroinflammatory molecule implicated in seizure mechanisms. Drug-induced reduction of oxidative stress prevented HMGB1 generation, thus highlighting a potential novel mechanism contributing to therapeutic effects. Our data show that targeting oxidative stress with clinically used drugs for a limited time window starting early after injury significantly improves long-term disease outcomes. This intervention may be considered for patients exposed to potential epileptogenic insults.

Metabolic control of epilepsy is recognized in part due to the efficacy of ketogenic diets, which provide alternate fuels rather than glucose for neuronal activity. It is documented that glycolytic rates are acutely increased during epileptic seizures and inhibition of glycolysis with 2-deoxyglucose (2-DG) has anti-seizure effects. Work from our laboratory has shown that seizure activity increases the steady-state levels of reactive oxygen species (ROS) production and causes mitochondrial dysfunction. Here we determined the relationship between glycolysis, ROS production and neuronal excitability. Mixed rat primary cortical cultures treated with 4-Aminopyridine (4-AP), a potassium channel blocker, showed an increase in a) Extracellular Acidification Rate (ECAR) levels (measure of glycolytic rate in the Seahorse XF analyzer), b) ROS production, measured by Amplex Red and c) increased neuronal excitability, assessed by a multiple electrode array system (Axion Biosystems). Pre-treatment of mixed primary cortical cultures with compounds like 2-DG, Bromopyruvic acid (3BP), palmitate - an anaplerotic substrate (along with glycogenic substrate limitation), nicotinamide riboside (NR) – an NAD+ precursor, oxaloacetate (OA) - a TCA cycle intermediate, and mTOR inhibitor rapamycin decreased ECAR rates and neuronal hyperexcitability induced by 4-AP. Pre-treatment with a reduced B-nicotinamide adenine dinucleotide (NADH), Thiazolidinediones – an acute specific inhibitor of the mitochondrial pyruvate carrier, PI3K inhibitor wortmannin decreased 4-AP induced increase in glycolysis, without significantly altering neuronal hyperexcitability. Lastly, 2-DG also reversed ROS production produced by 4-AP. Taken together, these results suggest that glycolysis contributes to ROS production, which in turn increases neuronal hyperexcitability.

Background Numerous mumps outbreaks occurred in the United States over the last decade, with outbreaks affecting young adults on college campuses being among the largest and most widely publicized. However, at least half of mumps cases and outbreaks occurred in other age-groups and settings. We describe reported mumps cases among children and adolescents during 2015 through 2017. Methods The Centers for Disease Control and Prevention (CDC) analyzed reports of confirmed and probable mumps cases in persons aged ≤18 years (defined here as pediatric mumps) transmitted electronically through the Nationally Notifiable Diseases Surveillance System (NNDSS) by the 52 reporting jurisdictions. Results Between January 1, 2015 and December 31, 2017, 49 jurisdictions reported 4,886 pediatric mumps cases (35% of all US reported cases, 13,807); 8 jurisdictions reported >100 cases each, representing 82% of all pediatric cases. Overall, 29 (1%) cases were in infants Conclusion About one-third of cases reported during the recent US mumps resurgence were in children and adolescents. The low rate of mumps complications compared with previous studies suggests mumps complications may not be adequately captured in national surveillance or identified by providers. Providers should remain vigilant that mumps can still occur among fully vaccinated pediatric patients, even those recently vaccinated. Disclosures All authors: No reported disclosures.

Background The United States is experiencing the largest measles outbreak since elimination was declared in 2000, with the majority of cases in NYS reported in undervaccinated communities. The objective of this evaluation was to describe adult measles cases in the NYS measles outbreak outside of New York City (NYC). Methods We included all confirmed cases aged ≥18 years in NYS residents (excluding NYC) during October 1, 2018–July 25, 2019 that met the CSTE measles case definition. We defined measles cases attributable to adults as the sum of measles cases among adults and children who contracted disease directly from adults. Results Among 371 confirmed measles cases, the median age was 5.5 years (range: 1 day to 64 years); 79 (21%) were in adults, 4 (5%) of whom were born before 1957 (3 unvaccinated and 1 with unknown vaccine status). Among the 75 cases born during or after 1957, 65 (87%) were unvaccinated or had unknown vaccine status, while 3 had one dose and 7 had 2 doses of measles vaccine. Notably, 5 of 11 internationally imported measles cases were adults, and all were unvaccinated or had unknown vaccine status. During the first month of the outbreak, 26 of the 51 (51%) cases were attributable to adults; of the 26, 15 (58%) were in adults and 11 (42%) were in children who acquired infection from adults (Figure 3). Conclusion The majority of measles cases occurred in unvaccinated children emphasizing the importance of ongoing and focused efforts on pediatric vaccination. However, measles cases in unvaccinated adults played an important role in both importations and disease transmission early in the outbreak. These data strongly support current recommendations of 1 dose of measles, mumps, rubella vaccine (MMR) for most adults and 2 doses of MMR for adults traveling internationally and at high-risk such as those in outbreak areas, as determined by local/state public health. Disclosures Kirsten St. George, MAppSc, PhD, Akonni Biosystems (Other Financial or Material Support), ThermoFisher (Grant/Research Support), Zeptometrix (Other Financial or Material Support, royalty generating collaborative agreement). .

Background Measles, a vaccine-preventable viral illness that can cause serious complications, was declared eliminated from the United States in 2000 because of a successful measles vaccination program. Recent years have seen an increase in the number of measles cases and outbreaks. We summarized measles epidemiology in the United States during 2017–2019. Methods We reviewed US national surveillance data on confirmed measles cases reported to the Centers for Disease Control and Prevention during January 1, 2017–April 26, 2019. We describe the demographic characteristics, vaccination status, and disease epidemiology of measles cases. Results During 2017–April 2019, 1,196 measles cases were reported in 37 US States and Washington DC, including 146 (12%) importations from 37 countries; 108 (74%) of importations were US residents returning from travel abroad, of which 60 (56%) were unvaccinated and 31 (29%) had unknown vaccinations status. Among 1,148 cases who were US-residents, the highest incidence of measles was among infants and children aged 6–11 and 12–15 months (112 cases [19 cases/million person-years] and 106 cases [27 cases/million person-years], respectively). Among US-resident cases, 846 (74%) were unvaccinated and 163 (14%) had unknown vaccination status; 777 (68%) were considered to have preventable measles (i.e., were eligible for vaccination but unvaccinated). Among the 1,196 cases, 85 were single cases, and the remaining 1,111 represented 19 two-case chains and 34 outbreaks of 3 or more cases linked epidemiologically; the median outbreak size and duration was 6 cases (range, 3 to 452 cases) and 19.5 days (range, 5 to 205 days). A total of 934 (78%) of the 1196 cases and 13 (38%) of the 34 outbreaks occurred in under-immunized close-knit communities; eight outbreaks are ongoing. Conclusion Outbreaks of measles in the United States result from recurring measles introductions and subsequent measles spread, especially in under-immunized close-knit communities. To sustain measles elimination, it will be necessary to maintain timely routine high coverage with MMR vaccine, improve implementation of pretravel recommendations to minimize importations, and close immunity gaps in communities of US residents who remain unvaccinated. Disclosures All Authors: No reported Disclosures.

Dental caries characterized by acid damage of tooth enamel is a persistent disease that begins with the formation of biofilms on the tooth surface. The secreted glucosyltransferases enable Streptococcus mutans to synthesize extracellular glucan polymers using ingested starch within the oral cavity, which eventually results in the production of acid, a contributing factor to cariogenesis. In this paper, we report the cloning, expression, purification, crystallization, and preliminary X-ray diffraction characterization of glucosyltransferase B.

The solid-liquid interface of Bi (1-x) Sb(x) crystal growth is most favorable for investigation of electron and phonon phenomena. Bismuth is a semimetal with high electron and hole mobility. Interest in Bi-Sb material system has recently been stimulated by promise of a new generation of thermoelectric materials based on these alloy. The crystals were grown using zone melting method with 1.0 and 1.5 cm/hour growth velocity and temperature gradient 650C/cm. The surface was determinal on the basis of growth feature profiles under optical microscope. The features observed on the top-free surface of as-grown crystals have also been discussed. The crystals have been characterized by using the powder XRD technique. The optical absorption was measured in the wave number range 510 cm-1 to 4000 cm-1. From the optical absorption through direct inter band transition.The results are reported and discussed in detailed.

A similarity analysis of non-Newtonian fluid flow past an accelerated vertical infinite plate in the presence of free convection current is carried out. A group theoretic generalized dimensional analysis is employed to achieve the governing non-linear ordinary differential equations in the most general form. Numerical solutions of these equations are given with the plot of their velocity profiles with the effects of Pr-Prandtl number and Gr-Grashof number

Depletion of glutathione has been shown to occur in autopsied brains of patients with Parkinson's disease (PD) and in animal models of PD. The goal of this study was to determine whether chronic glutathione (GSH) deficiency per se resulted in complex I inhibition and/or dopamine depletion and whether these indices were further potentiated by aging or administration of paraquat, a redox-cycling herbicide that produces a PD-like neurodegeneration model in rodents (Brooks, A. I., Chadwick, C. A., Gelbard, H. A., Cory-Slechta, D. A., and Federoff, H. J. [1999]. Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res. 823, 1-10; McCormack, A. L., Thiruchelvam, M., Manning-Bog, A. B., Thiffault, C., Langston, J. W., Cory-Slechta, D. A., and Di Monte, D. A. [2002]. Environmental risk factors and Parkinson's disease: Selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol. Dis. 10, 119-127.) Deletion of the rate-limiting GSH synthesis gene, glutamate-cysteine ligase modifier subunit (Gclm), leads to significantly lower GSH concentrations in all tissues including brain. Gclm null (Gclm (-/-)) mice provide a model of prolonged GSH depletion to explore the relationship between GSH, complex I inhibition, and dopamine loss in vivo. Despite ~60% depletion of brain GSH in Gclm (-/-) mice of ages 3-5 or 14-16 months, striatal complex I activity, dopamine levels, 3-nitrotyroine/tyrosine ratios, aconitase activity, and CoASH remained unchanged. Administration of paraquat (10mg/kg, twice/week, 3 weeks) to 3- to 5-month-old Gclm (-/-) mice resulted in significantly decreased aconitase activity, complex I activity, and dopamine levels but not in 3- to 5-month-old Gclm (+/+) mice. Furthermore, paraquat-induced inhibition of complex I and aconitase activities in Gclm (-/-) mice was observed in the striatum but not in the cortex. The results suggest that chronic deficiency of GSH in Gclm (-/-) mice was not sufficient to result in complex I inhibition or dopamine depletion perhaps due to homeostatic mechanisms but required an additional oxidative stress insult as shown with paraquat exposure.

Objective Brain abscesses cause substantial morbidity and mortality even after appropriate therapy, and no underlying cause is found in 25% of cases. We investigated the added utility of contrast-enhanced chest computed tomography (CT) in the diagnostic work-up of patients presenting with cerebral abscesses and no history or prior trauma or cranial surgery. Methods All patients presenting to a single institution with a surgically proven brain abscess were reviewed. Concurrent contrast-enhanced chest CT imaging results were reviewed when available to identify treatable predisposing causes of intracranial suppuration. Results This study included 31 patients with biopsy-proven abscesses. Multiple abscesses were present in 8 patients (26%). Contrast-enhanced CT was performed in 15 patients (48%). Of these 15 patients, 2 had pulmonary arteriovenous malformations, 1 had an intrapulmonary shunt, and 3 had empyemas. Definitive therapy for the chest findings was provided to 6 of the 15 patients (40%). In the remaining 9 patients, 3 had pulmonary abscesses, for which diagnostic aspiration was requested. Another patient had an incidental pulmonary embolism, resulting in same-day placement of an inferior vena caval filter (not included in chest analysis, given that the finding was incidental). Conclusions Contrast-enhanced chest CT is useful for identifying treatable causes of cerebral abscesses in patients with a cerebral abscess and no history of surgery or trauma.

Currently, no reliable markers are available to evaluate the epileptogenic potential of a brain injury. The electroencephalogram is the standard method of diagnosis of epilepsy; however, it is not used to predict the risk of developing epilepsy. Biomarkers that indicate an individual’s risk to develop epilepsy, especially those measurable in the periphery are urgently needed. Temporal lobe epilepsy (TLE), the most common form of acquired epilepsy, is characterized by spontaneous recurrent seizures following brain injury and a seizure-free “latent” period. Elucidation of mechanisms at play during epilepsy development (epileptogenesis) in animal models of TLE could enable the identification of predictive biomarkers. Our pilot study using liquid chromatography-mass spectrometry metabolomics analysis revealed changes (p-value ≤ 0.05, ≥1.5-fold change) in lipid, purine, and sterol metabolism in rat plasma and hippocampus during epileptogenesis and chronic epilepsy in the kainic acid model of TLE. Notably, disease development was associated with dysregulation of vitamin D3 metabolism at all stages and plasma 25-hydroxyvitamin D3 depletion in the acute and latent phase of injury-induced epileptogenesis. These data suggest that plasma VD3 metabolites reflect the severity of an epileptogenic insult and that a panel of plasma VD3 metabolites may be able to serve as a marker of epileptogenesis.

International audience; Peripheral biomarkers have myriad potential uses for treatment, prediction, prognostication, and pharmacovigilance in epilepsy. To date, no single peripheral biomarker has demonstrated proven effectiveness, although multiple candidates are in development. In this review, we discuss the major areas of focus including inflammation, blood-brain barrier dysfunction, redox alterations, metabolism, hormones and growth factors.

Organophosphate nerve agents exert their toxicity through inhibition of acetylcholinesterase. The excessive stimulation of cholinergic receptors rapidly causes neuronal damage, seizures, death, and long-term neurological impairment in those that survive. Owing to the lethality of organophosphorus agents and the growing risk they pose, medical interventions that prevent organophosphate toxicity and the delayed injury response are much needed. Studies have shown that oxidative stress occurs in models of subacute, acute, and chronic exposure to organophosphate agents. Key findings of these studies include alterations in mitochondrial function and increased free radical–mediated injury, such as lipid peroxidation. This review focuses on the role of reactive oxygen species in organophosphate neurotoxicity and its dependence on seizure activity. Understanding the sources, mechanisms, and pathological consequences of organophosphate-induced oxidative stress can lead to the development of rational therapies for treating toxic exposures.

Altered metabolism is an important feature of many epileptic syndromes but has not been reported in Dravet syndrome (DS), a catastrophic childhood epilepsy associated with mutations in a voltage-activated sodium channel, Nav1.1 (SCN1A). To address this, we developed novel methodology to assess real-time changes in bioenergetics in zebrafish larvae between 4 and 6 d postfertilization (dpf). Baseline and 4-aminopyridine (4-AP) stimulated glycolytic flux and mitochondrial respiration were simultaneously assessed using a Seahorse Biosciences extracellular flux analyzer.Scn1Labmutant zebrafish showed a decrease in baseline glycolytic rate and oxygen consumption rate (OCR) compared to controls. A ketogenic diet formulation rescued mutant zebrafish metabolism to control levels. Increasing neuronal excitability with 4-AP resulted in an immediate increase in glycolytic rates in wild-type zebrafish, whereas mitochondrial OCR increased slightly and quickly recovered to baseline values. In contrast,scn1Labmutant zebrafish showed a significantly slower and exaggerated increase of both glycolytic rates and OCR after 4-AP. The underlying mechanism of decreased baseline OCR inscn1Labmutants was not because of altered mitochondrial DNA content or dysfunction of enzymes in the electron transport chain or tricarboxylic acid cycle. Examination of glucose metabolism using a PCR array identified five glycolytic genes that were downregulated inscn1Labmutant zebrafish. Our findings inscn1Labmutant zebrafish suggest that glucose and mitochondrial hypometabolism contribute to the pathophysiology of DS.

The ketogenic diet (KD) is a high-fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. The broad efficacy of the KD in diverse epilepsies coupled with its profound influence on metabolism suggests that mitochondrial functions may be critical in its mechanism(s) of seizure control. Mitochondria subserve important cellular functions that include the production of cellular ATP, control of apoptosis, maintenance of calcium homeostasis and the production and elimination of reactive oxygen species (ROS). This review will focus on recent literature reporting the regulation of mitochondrial functions and redox signaling by the KD. The review highlights a potential mechanism of the KD involving the production of low levels of redox signaling molecules such as H(2)O(2) and electrophiles e.g. 4-hydroxynonenal (4-HNE), which in turn activate adaptive pathways such as the protective transcription factor, NF E2-related factor 2 (Nrf2). This can ultimately result in increased production of antioxidants (e.g. GSH) and detoxification enzymes which may be critical in mediating the protective effects of the KD.

To determine the influence of drug physicochemical properties on brain mitochondrial delivery of 20 drugs at physiological pH.The delivery of 8 cationic drugs (beta-blockers), 6 neutral drugs (corticosteroids), and 6 anionic drugs (non-steroidal anti-inflammatory drugs, NSAIDs) to isolated rat brain mitochondria was determined with and without membrane depolarization. Multiple linear regression was used to determine whether lipophilicity (Log D), charge, polarizability, polar surface area (PSA), and molecular weight influence mitochondrial delivery.The Log D for beta-blockers, corticosteroids, and NSAIDs was in the range of -1.41 to 1.37, 0.72 to 2.97, and -0.98 to 2, respectively. The % mitochondrial uptake increased exponentially with an increase in Log D for each class of drugs, with the uptake at a given lipophilicity obeying the rank order cationicanionicneutral. Valinomycin reduced membrane potential and the delivery of positively charged propranolol and betaxolol. The best equation for the combined data set was Log % Uptake = 0.333 Log D + 0.157 Charge - 0.887 Log PSA + 2.032 (R(2) = 0.738).Drug lipopohilicity, charge, and polar surface area and membrane potential influence mitochondrial drug delivery, with the uptake of positively charged, lipophilic molecules being the most efficient.

CMI responses, combined with quantification of CMV DNA (DNAemia), may identify transplantation recipients at risk for invasive disease. PBMC were collected in pediatric transplantation candidates at one, three, and six months post-transplant in 10 subjects (six renal, three cardiac, one stem cell) and at single time points in eight HC and 14 children greater than one yr post-transplant (LTTx). Cells were stimulated with anti-CD3mAb or CMV pp65 peptide pools and responses assessed by IFNG enzyme-linked immunosorbent spot assay and cytokine secretion. IFNG responses to anti-CD3mAb were significantly lower pretransplant relative to HC and were further decreased at one and three months post-transplant, but recovered to levels comparable to HC by six months. Responses to pp65 among CMV-seropositive recipients followed a similar pattern but recovered by three months. CMV-seropositive LTTx and HC showed a Th1 cytokine response to pp65 stimulation. Three LTTx subjects developed CMV DNAemia; two demonstrated decreased responses to anti-CD3mAB (and pp65 in the CMV seropositive subject) at the onset of DNAemia, which recovered as DNAemia resolved. Monitoring CMI in children is feasible and may provide an adjunct biomarker to predict CMV progression and recovery.

J. Neurochem. (2011) 10.1111/j.1471-4159.2011.07290.x Abstract Mitochondrial oxidative stress is a contributing factor in the etiology of numerous neuronal disorders. However, the precise mechanism(s) by which mitochondrial reactive oxygen species modify cellular targets to induce neurotoxicity remains unknown. In this study, we determined the role of mitochondrial aconitase (m-aconitase) in neurotoxicity by decreasing its expression. Incubation of the rat dopaminergic cell line, N27, with paraquat (PQ2+) resulted in aconitase inactivation, increased hydrogen peroxide (H2O2) and increased ferrous iron (Fe2+) at times preceding cell death. To confirm the role of m-aconitase in dopaminergic cell death, we knocked down m-aconitase expression via RNA interference. Incubation of m-aconitase knockdown N27 cells with PQ2+ resulted in decreased H2O2 production, Fe2+ accumulation, and cell death compared with cells expressing basal levels of m-aconitase. To determine the metabolic role of m-aconitase in mediating neuroprotection, we conducted a complete bioenergetic profile. m-Aconitase knockdown N27 cells showed a global decrease in metabolism (glycolysis and oxygen consumption rates) which blocked PQ2+-induced H+ leak and respiratory capacity deficiency. These findings suggest that dopaminergic cells are protected from death by decreasing release of H2O2 and Fe2+ in addition to decreased cellular metabolism.

Steady two dimensional MHD stagnation point flow of a power law fluid over a stretching surface is investigated when the surface is stretched in its own plane with a velocity proportional to the distance from the stagnation point. The fluid impinges on the surface is considered orthogonally. Numerical and analytical solutions are obtained for different cases.

Mitochondrial dysfunction and oxidative stress contribute to several neurologic disorders and have recently been implicated in acquired epilepsies such as temporal lobe epilepsy (TLE). Acquired epilepsy is typically initiated by a brain injury followed by a “latent period” whereby molecular, biochemical and other cellular alterations occur in the brain leading to chronic epilepsy. Mitochondrial dysfunction and oxidative stress are emerging as factors that not only occur acutely as a result of precipitating injuries such as status epilepticus (SE), but may also contribute to epileptogenesis and chronic epilepsy. Mitochondria are the primary site of reactive oxygen species (ROS) making them uniquely vulnerable to oxidative damage that may affect neuronal excitability and seizure susceptibility. This mini-review provides an overview of evidence suggesting the role of mitochondrial dysfunction and oxidative stress as acute consequences of injuries that are known to incite chronic epilepsy and their involvement in the chronic stages of acquired epilepsy.

OBJECTIVE: To assess the current medical school training of internal medicine and pediatric residents in transitioning youth with special health care needs from child-oriented to adult-oriented health care. METHODS: We surveyed internal medicine and pediatric residents to assess their preparedness to transition youth with special health care needs to adult-oriented health care. RESULTS: The survey results demonstrated that internal medicine residents felt unprepared to care for most patients with chronic childhood-onset illness; however, most pediatric residents were comfortable caring for such patients. CONCLUSION: Training in chronic childhood-onset illness should be included in internal medicine training programs.

Background During the 2016–2017 school year, the largest mumps outbreak in the United States since 2006 occurred in Arkansas with nearly 3,000 cases. As part of outbreak response, a third dose of measles–mumps–rubella vaccine (MMR3) was offered at 27 schools with mumps attack rates ≥5 cases/1,000 students. We compared attack rates after vaccination clinics among students who received MMR3 and students with 2 MMR vaccine doses. Methods We obtained information on school enrollment and student immunization status from school registries, and mumps case status from Arkansas’s National Electronic Disease Surveillance System database. We included students aged 6–21 years who had previously received ≥2 doses of MMR vaccine. We used Arkansas’s Immunization Information System to identify students who received MMR3. We included schools with at least 1 mumps case after their vaccination clinic. We calculated mumps attack rates by 2- and 3-dose MMR vaccine recipients. Observation time started 14 days after each clinic to allow for development of an immune response to MMR3, and continued to the end of the 2016–2017 school year. Observation time varied by school as schools held clinics on different dates. Results A total of 18 schools (10 elementary, 8 middle/junior high) with 10,275 students who had previously received ≥2 doses of MMR (85% of total enrolled) met inclusion criteria. Median number of students per school was 553. Median student age was 11 years (range, 6–18) and 1,525 students received MMR3. MMR3 uptake varied by school (median, 12%; range, 2–33%; interquartile range, 7–22%). A total of 12 mumps cases occurred among MMR3 recipients and 122 cases among 2-dose recipients. School-specific attack rates ranged from 0 to 23 cases/1,000 students among 3-dose recipients, and 2–41 cases/1,000 students among 2-dose recipients. Mumps attack rates within each school were lower for 3-dose recipients vs. 2-dose recipients in all but one school (P < .05). The differences in attack rates between 2- and 2-dose recipients ranged from −5 to 23 cases/1,000 students (median, 5/1,000). Conclusion Mumps attack rates were lower in 3-dose vs. 2-dose MMR vaccine recipients after MMR3 vaccination clinics, supporting a benefit of MMR3 for persons in outbreak settings. Further analysis is needed to determine impact of MMR3 on duration and size of mumps outbreaks. Disclosures All authors: No reported disclosures.

Background Since 2012, there has been a steady increase in the number of reported mumps cases and outbreaks in the United States, primarily affecting young, two-dose vaccinated adults. We analyzed epidemiologic characteristics of mumps cases reported nationally from 2016 to 2018. Methods We included confirmed and probable mumps cases transmitted from January 2016 to April 2018 by 52 health department jurisdictions (50 states, DC and NYC) that report cases to the National Notifiable Diseases Surveillance System (NNDSS). We calculated overall and age-specific incidence rates (IR) by dividing the annual number of mumps cases by the corresponding US Census Bureau’s Bridged Race population estimates. Cases were reported as outbreak-related or non-related in NNDSS by the submitting jurisdiction. Results Between January 1, 2016–April 21, 2018, 13,348 mumps cases (n = 6,369 in 2016, n = 6,056 in 2017 and n = 923 in 2018) were reported to NNDSS. IRs were 20, 19, and 2.9/million population in 2016, 2017, and January–April 2018, respectively. Young adults (18–22 years) had the highest IR: 88, 76, and 7.3/million population in 2016, 2017, and 2018, respectively. During January–April timeframe, 348 more cases were reported in 2016 (IR = 3.8/million) and almost four times as many cases were reported in 2017 (n = 3,376, IR = 10.5/million) compared with 2018 (P < 0.0001). The number of jurisdictions that reported cases in the first 4 months of each year was 39, 44, and 47 in 2016, 2017, and 2018, respectively. During the same timeframe, the number of outbreak-related cases reported was lower in 2018 (n = 523) vs. 2017 (n = 2,350) and 2016 (n = 1,271) (P < 0.0001), and the number of jurisdictions reporting outbreak-related cases was lower in 2018 (n = 16) vs. 2017 (n = 32, P = 0.002) and 2016 (n = 22, P = 0.23). Conclusion Preliminary data suggest that the overall and outbreak-related mumps cases may be decreasing in 2018 after 2 years of increased reports. However, the number of jurisdictions reporting mumps cases has not decreased. Thorough investigations of sporadic cases may lead to improved identification of epidemiologic linkages and earlier identification of outbreaks. Disclosures All authors: No reported disclosures.