Teacher emotions and the emotional labour of modern language (ML) teachers working in UK secondary schools.

The present paper seeks to explore the contextual factors shaping the emotional labour experiences of secondary school teachers and explain the ways these educators manage their emotions. Data were generated through a series of 20 in-depth, semi-structured interviews with modern language (ML) teachers in the UK. The findings showed that teachers experienced primarily negative forms of emotional labour and these experiences were driven by five interrelated contextual factors: the lack of institutional support, heavy workload, low perceived status of MLs, students' lack of motivation, and classroom misbehaviour. To manage their emotions, the study reveals that teachers used a wide range of coping mechanisms such as suppression, venting, social support, positive reframing, and the development of positive student-teacher relationships. In light of our results, we call for the emotional dimension of teaching to be better integrated into training programmes, an improvement in working conditions and better support mechanisms for teachers.

Locking mixed-lineage kinase domain-like protein in its auto-inhibited state prevents necroptosis.

As an alternative pathway of controlled cell death, necroptosis can be triggered by tumor necrosis factor via the kinases RIPK1/RIPK3 and the effector protein mixed-lineage kinase domain-like protein (MLKL). Upon activation, MLKL oligomerizes and integrates into the plasma membrane via its executioner domain. Here, we present the X-ray and NMR costructures of the human MLKL executioner domain covalently bound via Cys86 to a xanthine class inhibitor. The structures reveal that the compound stabilizes the interaction between the auto-inhibitory brace helix α6 and the four-helix bundle by stacking to Phe148. An NMR-based functional assay observing the conformation of this helix showed that the F148A mutant is unresponsive to the compound, providing further evidence for the importance of this interaction. Real-time and diffusion NMR studies demonstrate that xanthine derivatives inhibit MLKL oligomerization. Finally, we show that the other well-known MLKL inhibitor Necrosulfonamide, which also covalently modifies Cys86, must employ a different mode of action.

Recapitulation of NOD/RIPK2 signaling in iPSC-derived macrophages.

Human induced pluripotent stem cell (iPSC)-derived macrophages (IDMs) present a valuable substitute for monocyte-derived macrophages (MDMs) in order to study inflammation pathways in vitro. Through optimization of an IDM differentiation protocol, a six-fold increase in the production yield of myeloid progenitors was achieved. The derived IDMs were further characterized with respect to nucleotide-binding oligomerization domain (NOD) and receptor-interacting serine/threonine-protein kinase 2 (RIPK2) signaling, a key regulatory pathway for autoimmune diseases. The IDM cells recapitulated MDM biology with respect to the proinflammatory chemokine and inflammatory cytokine fingerprint more closely than THP-1 cells. When assessing RIPK2 modulation effect on tumor necrosis factor α (TNF-α), a cardinal mediator of inflammation, a similar pharmacological effect of RIPK2 inhibitors was observed in IDMs and MDMs. Additionally, IDMs and MDMs displayed a similar transcription and pathway profile in response to NOD1/2 stimulation and pharmacological inhibition of RIPK2. In summary, the enhanced myeloid production yield in the improved IDM differentiation protocol offers new opportunities for utilizing physiologically relevant macrophage models in the context of inflammatory diseases.

Discovery and Structure-Based Optimization of Fragments Binding the Mixed Lineage Kinase Domain-like Protein Executioner Domain.

Necroptosis is a form of programmed cell death that in case of misregulation can lead to inflammatory diseases. Mixed lineage kinase domain-like protein (MLKL), the effector protein in the canonical necroptosis signaling pathway, becomes activated by phosphorylation. Here, we report the identification of novel reversible binders of the MLKL executioner domain by a protein NMR-detected fragment-based screen. Determination of protein fragment costructures using NMR spectroscopy revealed a small molecule binding site that is distinct from the previously identified binding site of covalent MLKL inhibitors. Affinity optimization of the initially prioritized hit with millimolar affinity was achieved by NMR-guided structure-based design and yielded fragment-like molecules with a KD of 50 µM. Furthermore, we demonstrate that the improved fragment competes for the same binding site as nonyl-maltoside, a detergent that in conjunction with phytic acid activates the MLKL executioner domain.

Hardwood tree survival in heavy ground cover on reclaimed land in West Virginia: mowing and ripping effects.

Current West Virginia coal mining regulations emphasize reforestation as a preferred postmining land use on surface mined areas. Some mined sites reclaimed to pasture are being converted to forests. In the spring of 2001, we compared the establishment and growth of five hardwood tree species on a reclaimed West Virginaia surface mine with compacted soils and a heavy grass groundcover. We planted 1-yr-old seedlings of five species (black cherry [Prunus serotina Ehrh.], red oak [Quercus rubra L.], yellow poplar [Liriodendron tulipifera L.], black walnut [Juglans nigra L.], and white ash [Fraxinus americana L.]) into sites that were mowed and unmowed on north- and south-facing aspects. We applied a ripping treatment, which loosened the compacted soils and disturbed the heavy ground cover. First year results showed >80% survival for all species. After 7 yr black cherry survival averaged 36%, red oak 47%, yellow poplar 66%, black walnut 80%, and white ash 98% across all sites and treatments. Seedling survival was best on north, unmowed, and ripped areas. Average growth (height x diameter(2)) of trees after 7 yr was greatest with white ash (434 cm(3)), followed by yellow poplar (256 cm(3)) and black walnut (138 cm(3)), then by black cherry (31 cm(3)) and red oak (27 cm(3)). Browsing by wildlife had a negative impact on tree growth especially on south aspect sites. Overall, mowing reduced survival of black cherry, red oak, and yellow poplar, but not for black walnut and white ash. Ripping increased survival of black cherry, red oak, and yellow poplar. Growth of all species was improved with ripping. Using inverse linear-quadratic plateau models, the time required for tree survival to stabilize varied from 1 yr for white ash to 6 to 9 yr for the other species.

A randomized, placebo-controlled trial of prednisone in early Henoch Schönlein Purpura [ISRCTN85109383].

BACKGROUND: Henoch Schönlein Purpura (HSP) is the most common systemic vasculitis of childhood. There is considerable controversy over whether children with HSP should be treated with corticosteroids. The goal of this study was to investigate whether early corticosteroid administration could reduce the rate of renal or gastrointestinal complications in children with HSP. METHODS: Forty children with HSP, seen in the emergency room of a tertiary-care, paediatric centre, entered a randomized, double-blind, placebo controlled study. The treatment group (n = 21) received oral prednisone, 2 mg/kg/day for one week, with weaning over a second week, while the placebo group (n = 19) received an identical appearing placebo. Co-primary outcomes were the rate of renal involvement at one year and the rate of acute gastrointestinal complications. Co-primary outcomes were analysed using Fisher's Exact test. RESULTS: At one year, there was no difference in the rate of renal involvement (3/21 prednisone group vs. 2/19 placebo group, P = 1.0). There was also no statistically significant difference in the rate of acute gastrointestinal complications (2/21 prednisone group vs. 3/19 placebo group, P = 0.7). Two children in the placebo group did experience intussusceptions compared with none in the prednisone group (P = 0.2). CONCLUSIONS: Early prednisone therapy in HSP does not appear to reduce the risk of renal involvement at one year, or the risk of acute gastrointestinal complications. There may be a reduced risk of intussusception. The routine, early use of prednisone in uncomplicated HSP cannot be recommended at this time.

Head injury secondary to suspected child maltreatment: results of a prospective Canadian national surveillance program.

OBJECTIVE: We sought to determine the incidence, clinical features, and demographic profile of head injury secondary to suspected child maltreatment (abuse or neglect) in Canada to help inform the development and evaluation of prevention programs for abusive head injuries. METHODS: From March 1, 2005 to February 28, 2008, an average of 2,545 paediatricians and paediatric subspecialists were surveyed monthly through the established network of the Canadian Paediatric Surveillance Program. We calculated incidence rates using the number of confirmed cases over the product of the duration of the study (3 years) and population estimates by age group. RESULTS: There were 220 confirmed cases of head injury from suspected child maltreatment. The annual incidence rate was 14.1 per 100,000 for children less than 1 year of age and 1.4 per 100,000 for those less than 15 years. Seventy three percent (141) of cases involved infants less than 12 months of age and 52% (100) of cases involved infants less than 6 months of age. Seventy-five percent (165) of cases presented to the emergency room. With regard to outcome, 12% (27) of cases resulted in death and 45% (75) of survivors had neurological sequelae at discharge. Thirty percent (67) of all cases, as well as 30% (8) of deaths were previously known to child welfare authorities. CONCLUSION: This study provides an estimate of the rate of head injury secondary to suspected child maltreatment in Canada. The young age and poor medical outcomes of those involved highlights the need for prevention efforts that are implemented early in life. Given that a significant percentage of injured infants and children were already known to child welfare authorities, the study also highlights the need to establish and evaluate additional preventive efforts for parents and caregivers already in the child welfare system.

Parents are reluctant to use technological means of communication in pediatric day care.

PURPOSE: We hypothesized that advanced information and communication technology (ICT) would be acceptable to parents in a pediatric surgical, and diagnostic imaging day care setting. METHODS: After Ethics Committee approval, we distributed surveys, over a one-month period, to parents of children arriving for day care surgery or diagnostic imaging. Parents indicated their acceptance of various proposed modes of postoperative discussion of healthcare i.e.; face-to-face, videophone, or telephone. Parents were also asked to describe their receptiveness to scheduling non-emergency hospital appointments online and to receiving electronic media describing their child's surgery and postoperative management. Parental education, income, and familiarity with the Internet were also assessed. RESULTS: A total of 451 surveys (84% response rate) were returned. Most parents (95%) had access to the Internet and 70% did their banking online. Forty-two percent of the parents had at least a university education and 63% had an annual family income > $50,000 Canadian. The majority of parents (98%) accepted face-to-face interaction, while only 35% and 37% of parents were receptive to videophone and telephone interviews, respectively. Computer availability (P = 0.001) and online banking (P = 0.011) were the only variables that predicted those parents who were in favour of using videophone technology. Parents were receptive to instruction electronic media (80%) and booking appointments online (61%). CONCLUSIONS: A well-educated and technologically sophisticated parent population does not favour advanced communication technologies over simple, face-to-face interaction in an in-hospital setting. These parents are prepared to receive technology-based information about their child's surgery and to schedule non-emergency hospital appointments online.