A comparison of the kinematics and kinetics of barefoot and shod running in children with cerebral palsy.

BACKGROUND: The biomechanics of barefoot and shod running are different for typically developing children but unknown for children with cerebral palsy (CP). Such differences may have implications for injury and performance. AIMS: The primary aims of this study were to compare the lower limb biomechanics of barefoot and shod running in children with CP, and to determine whether any differences were the same in GMFCS levels I and II. METHODS: This cross-sectional study examined 38 children with CP (n = 24 (GMFCS) level I; n = 14 GMFCS II), running overground at 3 speeds (jog, run, sprint) in barefoot and shod conditions. Marker trajectories and force plate data were recorded, and lower limb kinematics, kinetics and spatiotemporal variables were derived. Differences between barefoot and shod running were analysed using linear mixed models. RESULTS: For both GMFCS levels, barefoot running resulted in higher loading rates, but smaller impact peaks at all speeds. Barefoot running was associated with greater hip and knee power; less ankle dorsiflexion and hip flexion at initial contact, and less ankle and knee range of motion during stance, compared to shod running, at all speeds. Barefoot stride length was shortened, and cadence increased compared to shod during jogging and running but not sprinting. For GMFCS level I only, barefoot running involved a higher incidence of forefoot strike, greater ankle power generation and less hip range of motion during stance. SIGNIFICANCE: Running barefoot may facilitate running performance by increasing power generation at the ankle in children with CP, GMFCS level I. Higher barefoot loading rates may have implications for performance and injury.

Interactive learning and action: realizing the promise of synthetic biology for global health.

The emerging field of synthetic biology has the potential to improve global health. For example, synthetic biology could contribute to efforts at vaccine development in a context in which vaccines and immunization have been identified by the international community as being crucial to international development efforts and, in particular, the millennium development goals. However, past experience with innovations shows that realizing a technology's potential can be difficult and complex. To achieve better societal embedding of synthetic biology and to make sure it reaches its potential, science and technology development should be made more inclusive and interactive. Responsible research and innovation is based on the premise that a broad range of stakeholders with different views, needs and ideas should have a voice in the technological development and deployment process. The interactive learning and action (ILA) approach has been developed as a methodology to bring societal stakeholders into a science and technology development process. This paper proposes an ILA in five phases for an international effort, with national case studies, to develop socially robust applications of synthetic biology for global health, based on the example of vaccine development. The design is based on results of a recently initiated ILA project on synthetic biology; results from other interactive initiatives described in the literature; and examples of possible applications of synthetic biology for global health that are currently being developed.

Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met.

The vasoactive amine histamine is found at high concentrations in the immune and inflammatory tissues. Earlier studies have revealed that histamine regulates the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent formation of oxygen radicals by phagocytic cells. However, the effects of histamine on intracellular signal transduction mechanisms of relevance to oxidase regulation remain controversial. For this study, we investigated the effects of histamine on NADPH oxidase activity in human neutrophil granulocytes triggered by a lipoxin A4 receptor agonist [the hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), a formyl peptide receptor (FPR) agonist (the chemotactic tripeptide formylmethionyl-leucyl-phenylalanine (fMLF)) and an activator of protein kinase C (phorbol myristate acetate (PMA)]. We report that histamine, acting via H2-type histamine receptors (H2R), suppresses NADPH oxidase-dependent formation of oxygen radicals induced by WKYMVM and fMLF but not that induced by PMA. Peptide-induced mobilization of granule-localized complement receptor 3 (CR3) was unaffected by histamine suggesting that the inhibition specifically affected NADPH oxidase activation. Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation.

Histamine protects T cells and natural killer cells against oxidative stress.

Oxidative stress inflicted by monocytes/macrophages (MO) is recognized as an important immunosuppressive mechanism in human neoplastic disease. We report that two types of lymphocytes of relevance for protection against malignant cells, T cells and natural killer (NK) cells, became anergic to the T cell and NK cell activator interleukin-2 (IL-2) after exposure to MO-derived reactive oxygen metabolites and subsequently acquired features characteristic of apoptosis. The MO-induced anergy and apoptosis in T cells and NK cells were reversed by histamine, an inhibitor of reactive oxygen metabolite synthesis in MO. We propose that strategies to circumvent oxidative inhibition of lymphocytes may be of benefit in immunotherapy of neoplastic disease.