A ten-year follow-up cohort study of childhood epilepsy: Changes in epilepsy diagnosis with age

Publication date: Available online 12 November 2016
Source:Brain and Development
Author(s): Yoshiyuki Hanaoka, Harumi Yoshinaga, Katsuhiro Kobayashi
ObjectiveTo elucidate all of the characteristics of childhood epilepsy, we performed a long-term follow-up study on the patients who visited Okayama University Hospital.Subjects and methodsWe retrospectively investigated the patients who were involved in the previous epidemiological study and visited Okayama University Hospital for a period of 10years after December 31, 1999.ResultsOverall, there were 350 patients' medical records that were evaluated, and 258 patients with complete clinical information available for a 10-year period were enrolled. Ten patients died and the remaining 82 were lost to follow-up. Of 258 patients with complete information, 153 (59.3%) were seizure-free for at least 5years. One hundred thirty (50.4%) had intellectual disabilities and 77 (29.8%) had motor disabilities, including 75 (29.1%) with both disabilities on December 31, 2009. Thirty-four patients of 350 (9.7%) changed the epilepsy classification during follow-up. With regard to ten patients who died, nine of them had symptomatic epilepsy, particularly those with severe underlying disorders with an onset during the first year of life.ConclusionClinical status considerably changed during the decade-long follow-up period in childhood epilepsy. Changes in the epilepsy diagnosis are especially important and should be taken into account in the long-term care of children with epilepsy.



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Enhanced protective efficacy against tuberculosis provided by a recombinant urease deficient BCG expressing heat shock protein 70-major membrane protein-II having PEST sequence

Publication date: Available online 12 November 2016
Source:Vaccine
Author(s): Yumiko Tsukamoto, Yumi Maeda, Toshiki Tamura, Tetsu Mukai, Satoshi Mitarai, Saburo Yamamoto, Masahiko Makino
Enhancement of the T cell-stimulating ability of Mycobacterium bovis BCG (BCG) is necessary to develop an effective tuberculosis vaccine. For this purpose, we introduced the PEST-HSP70-major membrane protein-II (MMPII)-PEST fusion gene into ureC-gene depleted recombinant (r) BCG to produce BCG-PEST. The PEST sequence is involved in the proteasomal processing of antigens. BCG-PEST secreted the PEST-HSP70-MMPII-PEST fusion protein and more efficiently activated human monocyte-derived dendritic cells (DCs) in terms of phenotypic changes and cytokine productions than an empty-vector-introduced BCG or HSP70-MMPII gene-introduced ureC gene-depleted BCG (BCG-DHTM). Autologous human naïve CD8⁺ T cells and naïve CD4⁺ T cells were effectively activated by BCG-PEST and produced IFN-γ in an antigen-specific manner through DCs. These T cell activations were closely associated with phagosomal maturation and intraproteasomal protein degradation in antigen-presenting cells. Furthermore, BCG-PEST produced long-lasting memory-type T cells in C57BL/6 mice more efficiently than control rBCGs. Moreover, a single subcutaneous injection of BCG-PEST more effectively reduced the multiplication of subsequent aerosol-challenged Mycobacterium tuberculosis of the standard H37Rv strain and clinically isolated Beijing strain in the lungs than control rBCGs. The vaccination effect of BCG-PEST lasted for at least 6months. These results indicate that BCG-PEST may be able to efficiently control the spread of tuberculosis in human.



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Protective efficacy of a novel alpha hemolysin subunit vaccine (AT62) against Staphylococcus aureus skin and soft tissue infections

Publication date: Available online 12 November 2016
Source:Vaccine
Author(s): Rajan P. Adhikari, Christopher D. Thompson, M. Javad Aman, Jean C. Lee
Alpha hemolysin (Hla) is a pore-forming toxin produced by most Staphylococcus aureus isolates. Hla is reported to play a key role in the pathogenesis of staphylococcal infections, such as skin and soft tissue infection, pneumonia, and lethal peritonitis. This study makes use of a novel recombinant subunit vaccine candidate (AT62) that was rationally designed based on the Hla heptameric crystal structure. AT62 comprises a critical structural domain at the N terminus of Hla, and it has no inherent toxic properties. We evaluated the efficacy of AT62 in protection against surgical wound infection and skin and soft tissue infection. Mice were vaccinated on days 0, 14, and 28 with 20μg AT62 or bovine serum albumin (BSA) mixed with Sigma adjuvant system®. Mice immunized with AT62 produced a robust antibody response against native Hla. In the surgical wound infection model, mice immunized with AT62 and challenged with a USA300 S. aureus strain showed a significantly reduced bacterial burden in the infected tissue compared to animals given BSA. Similarly, mice passively immunized with rabbit IgG to AT62 showed reduced wound infection and tissue damage. Subcutaneous abscess formation was not prevented by immunization with AT62. However, in a skin necrosis infection model, immunization with the AT62 vaccine resulted in smaller lesions and reduced mouse weight loss compared to controls. Although AT62 immunization reduced tissue necrosis, it did not reduce the bacterial burdens in the lesions compared to controls. Our data indicate that AT62 may be a valuable component of a multivalent vaccine against S. aureus.



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Impact of a maternal immunization program against pertussis in a developing country

Publication date: Available online 12 November 2016
Source:Vaccine
Author(s): Carla Vizzotti, Maria V. Juarez, Eduardo Bergel, Viviana Romanin, Gloria Califano, Sandra Sagradini, Carolina Rancaño, Analía Aquino, Romina Libster, Fernando P Polack, Juan Manzur
BackgroundPertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20weeks of gestation with the intent of reducing morbidity and mortality in young infants.MethodsMaternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program.FindingsWe observed a relative reduction of 51% (95% CI [−67%, −35%]; p=0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [−66%, −24%]; p=0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013.InterpretationWe show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.



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Association of serum bactericidal antibody and opsonic antibody levels after Neisseria meningitidis serogroup C conjugate vaccine in Brazilian children and adolescents infected or not infected with HIV

Publication date: Available online 12 November 2016
Source:Vaccine
Author(s): Wânia F. Pereira-Manfro, Raquel M. Alvino, Aline C. Cruz, Giselle P. Silva, Raquel B.N. Castro, Bianca Ferreira, Daniella M. Barreto, Ana Cristina C. Frota, Cristina B. Hofer, Lucimar G. Milagres
Neisseria meningitidis serogroup C (MenC) is the main causative agent of meningitis in Brazil. HIV infection affects the quality of the immune system. HIV⁺ children have an increased risk of infection to encapsulated bacteria such as N. meningitidis. We evaluated the opsonic antibody (OPA) levels and its correlation with serum bactericidal antibody (SBA) levels induced by one and two doses of a MenC conjugate vaccine in children and adolescents HIV⁺ and HIV-exposed but uninfected children (HEU) group. Overall the data show the importance of two doses of vaccine for HIV⁺ individuals. About 79% and 58% of HIV⁺ patients showed SBA and OPA positive response after two doses of vaccine, respectively. For HEU group, 62% and 41% of patients showed SBA and OPA positive response after one dose of vaccine, respectively. A positive and significant association between SBA and OPA levels was seen after two doses of vaccine in HIV⁺ patients.



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The role of white matter microstructure in inhibitory deficits in patients with schizophrenia

Publication date: Available online 12 November 2016
Source:Brain Stimulation
Author(s): Xiaoming Du, Peter Kochunov, Ann Summerfelt, Joshua Chiappelli, Fow-Sen Choa, L. Elliot Hong
BackgroundInhibitory-excitatory (I-E) imbalance has increasingly been proposed as a fundamental mechanism giving rise to many schizophrenia-related pathophysiology. The integrity of I-E functions should require precise and rapid electrical signal transmission.Objective/HypothesisWe hypothesized that part of the I-E abnormality in schizophrenia may originate from their known abnormal white matter connectivity that may interfere the I-E functions.MethodsWe test this using short-interval intracortical inhibition (SICI) vs. intracortical facilitation (ICF) which is a non-invasive measurement of I-E signaling. SICI-ICF from left motor cortex and white matter microstructure were assessed in schizophrenia patients and healthy controls.ResultsSchizophrenia patients showed significantly reduced SICI but not ICF. White matter microstructure as measured by fraction anisotropy (FA) in diffusion tensor imaging had a significant effect on SICI in patients, such that weaker SICI was associated with lower FA in several white matter tracts, most strongly with left corona radiata (r = −0.68, p = 0.0002) that contains the fibers connecting with left motor cortex. Left corticospinal tract, which carries the motor fibers to peripheral muscular output, also showed significant correlation with SICI (r = −0.54, p = 0.005). Mediation analysis revealed that much of the schizophrenia disease effect on SICI can be accounted for by mediation through left corona radiata. SICI was also significantly associated with the performance of processing speed in patients.ConclusionThis study demonstrated the importance of structural circuitry integrity in inhibitory signaling in schizophrenia, and encouraged modeling the I-E dysfunction in schizophrenia from a circuitry perspective.



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Short Takes

Publication date: Available online 12 November 2016
Source:Pediatric Neurology
Author(s): Steven G. Pavlakis




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