SIAIP position paper: provocation challenge to antibiotics and non-steroidal anti-inflammatory drugs in children

Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents

Post-transcriptional regulation of satellite cell quiescence by TTP-mediated mRNA decay.

Skeletal muscle satellite cells in their niche are quiescent and upon muscle injury, exit quiescence, proliferate to repair muscle tissue, and self-renew to replenish the satellite cell population. To understand the mechanisms involved in maintaining satellite cell quiescence, we identified gene transcripts that were differentially expressed during satellite cell activation following muscle injury. Transcripts encoding RNA binding proteins were among the most significantly changed and included the mRNA decay factor Tristetraprolin. Tristetraprolin promotes the decay of MyoD mRNA, which encodes a transcriptional regulator of myogenic commitment, via binding to the MyoD mRNA 3' untranslated region. Upon satellite cell activation, p38α/β MAPK phosphorylates MAPKAP2 and inactivates Tristetraprolin, stabilizing MyoD mRNA. Satellite cell specific knockdown of Tristetraprolin precociously activates satellite cells in vivo, enabling MyoD accumulation, differentiation and cell fusion into myofibers. Regulation of mRNAs by Tristetraprolin appears to function as one of several critical post-transcriptional regulatory mechanisms controlling satellite cell homeostasis

The cytolytic T lymphocyte response to the murine cytomegalovirus

During the acute cytolytic T lymphocyte (CTL) response of mice to infection with the murine cytomegalovirus two independent populations of activated interleukin-receptive CTL precursors can be demonstrated. One population is specific for cell membrane-incorporated viral structural antigens, whereas the second population detects an antigen, whose appearance is correlated with the synthesis of viral immediate early proteins. Since this new type of antigen is only defined by lymphocyte recognition, it is referred to as the lymphocyte-detected immediate early antigen (LYDIEA). Expression of immediate early antigen precedes the production of viral progeny and, therefore, it is possible that LYDIEA-specific CTL could serve as indicator cells for the very first activities of the viral genome, even during nonproductive infection

Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms

Investigating the physiological underpinnings of proactive and reactive behavioural types in grey seals (Halichoerus grypus): Trial deployment of a minimally invasive data logger for recording heart rate and heart rate variability in a wild free-ranging breeding pinniped species

Individuals differ non-randomly in their responses to stressors, exhibiting consistent individual differences (CIDs) in behavioural and physiological coping mechanisms commonly referred to as coping styles. Grey seals (Halichoerus grypus) are one of the few mammal species in which CIDs in stress responses have been documented in wild populations, though evidence thus far has been purely behavioural. Physiologically, coping styles can be distinguished by differences in the autonomic regulation of cardiac activity, which can be measured using heart rate variability (HRV). The objectives of this study were two-fold. First, to assess the suitability of Polar® RS800CX monitors and H2/H3 sensors for conducting HRV analyses in grey seals. Second, to quantify inter-individual variation, repeatability, and reproductive performance correlates of baseline HRV. Polar® devices were deployed successfully during the 2013 breeding season on female grey seals (N = 15) on the Isle of May, Scotland, and were capable of recording HR patterns that characterise phocid seals at rest on land. However, artefacts were widespread and biased HRV metrics. Filtration and correction protocols were able to counteract the effects of artefacts, but severely limited the amount of data available for analysis. There were significant inter-individual differences in baseline HRV, which could not be explained by factors associated with the breeding season (e.g. percentage mass loss, day of lactation), diurnal rhythms (e.g. time of day), or stressors (e.g. days since capture). These differences in baseline HRV showed consistency across early and late lactation. Individuals appeared to separate into two groups: those with consistently lower or higher baseline HRV, characteristic of proactive and reactive coping styles, respectively. Furthermore, females with lower baseline HRV showed greater maternal transfer efficiency – though there were no associations between baseline HRV and maternal expenditure (i.e. maternal mass loss, kgday–1) or fitness outcomes (i.e. pup mass gain, kgday–1). These findings build upon previous studies on behavioural CIDs in female grey seals by providing the first preliminary evidence for physiological CIDs that are associated with maternal investment. However, due to small sample sizes, further studies are required to determine whether these findings are truly indicative of coping styles. In their current form, the use of Polar® devices requires several caveats and further studies are needed to fully realise their potential. Future research should focus on validation against simultaneously recorded ECGs to improve artefact detection and correction, and modification to minimise the occurrence of artefacts. Despite their limitations, Polar® devices have immense potential as a minimally invasive research tool for conducting HRV analyses in the field