Human monoclonal antibodies against Ross River virus target epitopes within the E2 protein and protect against disease

Ross River fever is a mosquito-transmitted viral disease that is endemic to Australia and the surrounding Pacific Islands. Ross River virus (RRV) belongs to the arthritogenic group of alphaviruses, which largely cause disease characterized by debilitating polyarthritis, rash, and fever. There is no specific treatment or licensed vaccine available, and the mechanisms of protective humoral immunity in humans are poorly understood. Here, we describe naturally occurring human mAbs specific to RRV, isolated from subjects with a prior natural infection. These mAbs potently neutralize RRV infectivity in cell culture and block infection through multiple mechanisms, including prevention of viral attachment, entry, and fusion. Some of the most potently neutralizing mAbs inhibited binding of RRV to Mxra8, a recently discovered alpahvirus receptor. Epitope mapping studies identified the A and B domains of the RRV E2 protein as the major antigenic sites for the human neutralizing antibody response. In experiments in mice, these mAbs were protective against cinical disease and reduced viral burden in multiple tissues, suggesting a potential therapeutic use for humans

Cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in progressive neurodegenerative conditions: a scoping review

BACKGROUND: Despite their potentially significant impact, cognitive disability may be overlooked in a number of progressive neurodegenerative conditions, as other difficulties dominate the clinical picture. OBJECTIVE: We examined the extent, nature and range of the research evidence relating to cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in Parkinsonian disorders, multiple sclerosis (MS), frontotemporal dementias (FTD), motor neuron disease and Huntington’s disease. METHODS: Scoping review based on searches of MEDLINE and CINAHL up to 15 March 2016. RESULTS: We included 140 eligible papers. Over half of the studies, and almost all the randomised controlled trials, related to MS, while a number of single case studies described interventions for people with FTD. CR interventions addressed functional ability, communication and interaction, behaviour or memory. The majority of psychotherapy interventions involved cognitive behavioural therapy for depression or anxiety. Self-management interventions were mainly available for people with MS. There were few reports of interventions specific to caregivers. Numerous methodological challenges were identified. CONCLUSIONS: The limited range of studies for all conditions except MS suggests a need firstly to synthesise systematically the available evidence across conditions and secondly to develop well-designed studies to provide evidence about the effectiveness of CR and other psychological interventions

The clinical toxicology of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4-butanediol

International audienc

Poisoning due to water hemlock

Introduction. Water hemlock, which encompasses a range of species divided across two genera (Cicuta and Oenanthe), are regarded as being among the most poisonous plants both in North America and in the United Kingdom. Despite their toxicity, the literature consists almost entirely of case reports.  Aim. The aim of this review is to summarize this literature by covering all aspects of taxonomy and botanical characterization, principal toxins, basic pharmacology including mechanisms of toxicity, and the clinical features, diagnosis, and management of poisoning. Mechanisms of toxicity. The principal toxins, cicutoxin and oenanthotoxin, belong to a group of C17 conjugated polyacetylenes. They act as (noncompetitive) gamma-aminobutyric acid antagonists in the central nervous system (CNS), resulting in unabated neuronal depolarization that can lead to seizures. Ingestion of even a small amount of plant matter may result in severe intoxication.  Features. After ingestion, the patient is most likely to experience CNS stimulatory effects including seizures that, in the absence of aggressive supportive care, can result in death. Other features include nausea, vomiting, diarrhea, tachycardia, mydriasis, rhabdomyolysis, renal failure, coma, respiratory impairment, and cardiac dysrhythmias.  Management. Treatment consists mainly of prompt airway management and seizure control, plus decontamination if achieved early and after stabilization. In the event of renal failure, the use of hemodialysis has been employed successfully.  Conclusions.  The ingestion of water hemlock can lead to serious complications that may be fatal. Prognosis is good, however, if prompt supportive care is provided

Reliability and validity assessment of the observation of human-animal interaction for research (OHAIRE) behavior coding tool

The Observation of Human-Animal Interaction for Research (OHAIRE) is a coding tool developed to capture the behavior of children when interacting with social partners and animals in naturalistic settings. The OHAIRE behavioral categories of focus are emotional displays, social communication behaviors toward adults and peers, behaviors directed toward animals or experimental control objects, and interfering behaviors. To date, the OHAIRE has been used by 14 coders to code 2,732 min of video across four studies with a total of 201 participants ages 5 to 18 years (M = 10.1, SD = 2.5). Studies involved animal-assisted intervention with three species (i.e., dogs, horses, and guinea pigs) and three populations (i.e., autism spectrum disorder, attention-deficit hyperactivity disorder, and typically developing children) in a school, a therapeutic horseback riding program, a group therapy program, and the hospital setting. We explored the psychometric properties of the OHAIRE through analyses of its inter-rater reliability, intra-rater reliability, convergent and divergent validity, and internal structure, using data from these four human-animal interaction studies. The average inter-rater reliability was excellent (kappa = 0.81), with good reliability in most of the behavioral categories coded. Intra-rater reliability was consistently excellent (0.87 ≤ kappa ≤0.96). Internal structure analyses with Cronbach's alpha supported the exploratory use of subscales to measure social communication behaviors toward peers (α = 0.638) and adults (α = 0.605), and interactions experimental control objects (α = 0.589), and the use of a subscale to measure interactions with animals (α = 0.773). Correlation analyses with multiple questionnaires showed a convergence between positive emotional display and social behaviors as assessed by the OHAIRE and social skills as assessed by the Social Skills Rating System (SSRS) and the Social Communication Questionnaires (SCQ). Little concordance was found between the OHAIRE and the Social Responsiveness Scale (SRS) or the Aberrant Behavior Checklist-Community (ABC). The OHAIRE shows promise for wider use in the field of Human-Animal Interaction, with a need for generalization across more settings and ages