Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes

A Cell-Free Microtiter Plate Screen for Improved [FeFe] Hydrogenases

, a potential renewable fuel. Attempts to exploit these catalysts in engineered systems have been hindered by the biotechnologically inconvenient properties of the natural enzymes, including their extreme oxygen sensitivity. Directed evolution has been used to improve the characteristics of a range of natural catalysts, but has been largely unsuccessful for [FeFe] hydrogenases because of a lack of convenient screening platforms. [FeFe] hydrogenase HydA1 with a specific activity ∼4 times that of the wild-type enzyme. cell extracts, which allows unhindered access to the protein maturation and assay environment

Achieving Education for Sustainable Development (ESD) in Early Childhood Education Through Critical Reflection in Transformative Learning

The central role of education in creating a more sustainable future has been already recognized by educators and policy-makers alike. This chapter argues that this can only be truly achieved through the efforts of teachers in implementing an “education of a different kind,” a general educational shift that seeks to encompass a converging transformation of the priorities and mindsets of education professionals. In this regard, the professional preparation of teachers, as the leading actors in shaping children’s learning processes, and their continuous professional development are vital considerations for Education for Sustainable Development (ESD) to be successfully achieved. Linking transformative learning and ESD has emerged as a distinct and useful pedagogy because they both support the process of critically examining habits of mind, then revising these habits and acting upon the revised point of view. This study aims to describe and evaluate the potential of transformative learning in innovating mainstream education toward sustainability by focusing on the role of critical reflection in a capacity building research project realized in Turkey. The data was gathered from 24 early childhood educators using a mixed-method research design involving learning diaries, a learning activities survey, and follow-up interviews. This chapter identified content, context, and application method of the in-service training as factors that have contributed to the reflective practices of the participants. In addition, presenting the implications regarding the individual differences in how learners engage in critical reflection practices, this research offers a framework for a content- and process-based approach derived from Mezirow’s conception of critical reflection

A blinded, controlled trial of objective measurement in Parkinson's disease

Medical conditions with effective therapies are usually managed with objective measurement and therapeutic targets. Parkinson's disease has effective therapies, but continuous objective measurement has only recently become available. This blinded, controlled study examined whether management of Parkinson's disease was improved when clinical assessment and therapeutic decisions were aided by objective measurement. The primary endpoint was improvement in the Movement Disorder Society-United Parkinson's Disease Rating Scale's (MDS-UPDRS) Total Score. In one arm, objective measurement assisted doctors to alter therapy over successive visits until objective measurement scores were in target. Patients in the other arm were conventionally assessed and therapies were changed until judged optimal. There were 75 subjects in the objective measurement arm and 79 in the arm with conventional assessment and treatment. There were statistically significant improvements in the moderate clinically meaningful range in the MDS-UPDRS Total, III, IV scales in the arm using objective measurement, but not in the conventionally treated arm. These findings show that global motor and non-motor disability is improved when management of Parkinson's disease is assisted by objective measurement

Playing at the edge of criticality: Expanded whole-brain repertoire of connectome-harmonics

In order for us to survive, our behaviour has to be perched somewhere between stability and flexibility, or between exploitation and exploration of available resources. This requires the underlying spatiotemporal brain dynamics to be delicately balanced between order and disorder, drawing upon a large repertoire of available brain states. Beyond survival, in order to thrive the brain has to be sufficiently flexible to be able to seek novel trajectories and expand the dynamical repertoire. Here we propose that a key ingredient could be play, the active exploration of novelty beyond exploiting existing potentially scarce resources. Using a novel analysis method called ‘connectome harmonics’ we not only demonstrate that brain activity resides close to criticality—at the delicate balance between order (stability) and disorder (flexibility)—but this whole-brain criticality is also intrinsically linked to oscillatory brain dynamics. We show that compared to wakefulness, other conscious states are related to different connectome-harmonic repertoires and differ in their proximity to criticality, where the critical regime may enhance the ability to flexibly seek new brain states. In particular, we propose that these brain dynamics may underlie the creative process found in play and improvisation, and as such may shed new light on discovering how the brain optimizes the balance between exploitation and exploration needed for behavioural flexibility