BackgroundSystemic inflammation associated with sepsis can induce neuronal hyperexcitability, leading to enhanced seizure predisposition and occurrence. Brain microglia are rapidly activated in response to systemic inflammation and, in this activated state, release multiple cytokines and signaling factors that amplify the inflammatory response and increase neuronal excitability. NADPH oxidase (NOX) enzymes promote microglial activation through the generation of reactive oxygen species (ROS), such as superoxide anion. We hypothesized that NOX isoforms, particularly NOX2, are potential targets for prevention of sepsis-associated seizures.MethodsTo reduce NADPH oxidase 2-derived ROS production, mice with deficits of NOX regulatory subunit/NOX2 organizer p47phox (p47phox−/−) or NOX2 major subunit gp91phox (gp91phox−/−) were used or the NOX2-selective inhibitor diphenyleneiodonium (DPI) was used to treat wild-type (WT) mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). Seizure susceptibility was compared among mouse groups in response to intraperitoneal injection of pentylenetetrazole (PTZ). Brain tissues were assayed for proinflammatory gene and protein expression, and immunofluorescence staining was used to estimate the proportion of activated microglia.ResultsIncreased susceptibility to PTZ-induced seizures following sepsis was significantly attenuated in gp91phox−/− and p47phox−/− mice compared with WT mice. Both gp91phox−/− and p47phox−/− mice exhibited reduced microglia activation and lower brain induction of multiple proconvulsive cytokines, including TNFα, IL-1β, IL-6, and CCL2, compared with WT mice. Administration of DPI following LPS injection significantly attenuated the increased susceptibility to PTZ-induced seizures and reduced both microglia activation and brain proconvulsive cytokine concentrations compared with vehicle-treated controls. DPI also inhibited the upregulation of gp91phox transcripts following LPS injection.ConclusionsOur results indicate that NADPH oxidases contribute to the development of increased seizure susceptibility in mice after sepsis. Pharmacologic inhibition of NOX may be a promising therapeutic approach to reducing sepsis-associated neuroinflammation, neuronal hyperexcitability, and seizures.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1186-5) contains supplementary material, which is available to authorized users.
BackgroundSalmonella meningitis remains a threat to children below two years of age in both developing and developed countries. However, information on such infections has not been well characterized. We analyzed data related to twelve years of experience in order to clarify the comprehensive features of Salmonella meningitis in our patients, including admission characteristics, acute complications, and long-term outcome.MethodsThe records of patients with spontaneous Salmonella meningitis from 1982 to 1994 were retrospectively reviewed. The long-term outcome was prospectively determined for survivors at school age by the developmental milestones reported by their parents and detailed neurological evaluation along with intelligence, hearing, visual, speech and language assessments.ResultsOf the twenty-four patients, seizures were noted in fifteen (63%) before admission and thirteen (54%) during hospitalization. Acute complications mainly included hydrocephalus (50%), subdural collection (42%), cerebral infarction (33%), ventriculitis (25%), empyema (13%), intracranial abscess (8%), and cranial nerve palsy (8%). Three patients (13%) died during the acute phase of Salmonella meningitis. The twenty-one survivors, on whom we followed up at school age, have sequelae consisting of language disorder (52%), motor disability (48%), intelligence quotient < 80 (43%), epilepsy (33%), sensorineural hearing loss (17%), visual deficits (10%), abducens nerve palsy (5%), microcephaly (5%), and hydrocephalus (5%). Overall, good outcome was noted in six (28.6%) of twenty-one survivors, mild sequelae in three (14.2%), moderate in six (28.6%), and severe in six (28.6%).ConclusionSalmonella meningitis in neonates and infants had a wide spectrum of morbidity and acute complications, leading to a complicated hospital course and subsequently a high prevalence of permanent adverse outcome. Thus, early recognition of acute complications of Salmonella meningitis and a follow-up plan for early developmental assessment of survivors are vital.
Blue, green, and yellow phosphors are obtained in the Sr1−xY0.98+xCe0.02Si4N7−xCx system (x=0→1). Decreases in thermal quenching barrier height with x result from a dominant neighboring‐cation effect, through which the replacement of Sr2+ by Y3+ reduces the covalency of CeN bonding. Green emission is observed from a cation‐segregated nanostructure of SrYSi4N7 and Y2Si4N6C domains in x=0.2–0.6 samples.
Purpose Based on the institutional background of mandatory requirement of performance-based executive equity incentives, this paper aims to investigate the impacts of executive equity incentives, vesting periods and vesting performance conditions on corporate innovation. Design/methodology/approach The empirical analysis is based on the detailed data of equity incentives in China’s listed companies from 2006 to 2014, the Tobit method is implemented to estimate the regression coefficients, and the instrumental variable (IV) approach, Heckman two stage regression, propensity score matching and difference-in-difference models are adopted to solve the problem of endogeneity in several robust tests. Findings This paper documents that equity incentives and vesting periods are significantly and positively related to corporate innovation measured by R&D investment and patent applications, yet requirements on vesting performance impede corporate innovative activities. Specifically, compared with non-equity incentive companies, the R&D investment and the number of patent applications of equity incentive companies are 40 and 46.2 per cent higher, respectively. A one year increase in equity incentive duration can correspondingly increase the R&D investment by 15 per cent and the patent applications by 18.3 per cent. However, a one standard deviation increase in industry-adjusted ROE target reduces corporate R&D investment by 5 per cent and the patent applications by 8.39 per cent. The main empirical findings still hold after several robust tests. Research limitations/implications This paper confirms that the impact of performance-based compensation system on corporate innovation depends on its structure. Specifically, the empirical findings suggest that equity incentive plans being correctly designed can enhance corporate innovative activities, but myopic managers will damage the corporate innovation. Originality/value This paper investigates the influence of equity incentive structure on equity incentive effect based on the institutional background of mandatory requirement of performance-based executive equity incentives. It provides an opportunity to understand the mystery of equity incentives, which helps to enrich the structure of equity incentive theoretically. The empirical evidence confirms the importance of tolerating short-term failure and extending the horizon of managerial decision-making on promoting innovation. Overall, the research indicates that only well-designed equity incentive plans can promote innovation, which contributes to regulators and practitioners to form a rational understanding of the premise of equity incentives in promoting innovation and provides a reference for their decision-making.
Stock market has been associated with economic growth through its role as a source of new private capital. On the other hand, economic growth may be the catalyst for stock market growth. The purpose of this paper is to investigate the efficiency of the two official stock markets in China. The sample includes the daily closing prices of A-share and B-share indexes in both the Shanghai and Shenzhen stock exchanges for the period of January 1st, 2006 to December 31st, 2010. Three different approaches are employed; namely, serial correlation test, runs test and variance ratio test. Statistical evidence from serial correlation test shows that returns are correlated in both Shanghai and Shenzhen indexes and therefore the markets are weak-form efficiency. JEL Classification: G15
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