Neurobiology, empathy and social cognition: the potential benefits of theatre in traumatised communities

Includes abstract.Includes bibliographical references.The ubiquity of technology enables unprecedented contact between people, yet it neglects essential face-to-face communion; e-mail, text-messaging and even social media strip away the metadata of our interpersonal communications; the emotional cues and clues that are a necessary part of everyday social interaction. At the same time, the relentless densification of urban populations enforces proximity among strangers, with routine encounters increasingly bereft of emotional nourishment. The affective numbing that ensues shares many characteristics of post-traumatic stress disorder. The current study explores how exposure to theatre may help to maintain the emotional health of individuals alienated by the stresses of 21st century urban living; moreover, it examines how performance is able to facilitate emotional and social healing in post-conflict communities

Self-force via Green functions and worldline integration

A compact object moving in curved spacetime interacts with its own gravitational field. This leads to both dissipative and conservative corrections to the motion, which can be interpreted as a self-force acting on the object. The original formalism describing this self-force relied heavily on the Green function of the linear differential operator that governs gravitational perturbations. However, because the global calculation of Green functions in non-trivial black hole spacetimes has been an open problem until recently, alternative methods were established to calculate self-force effects using sophisticated regularization techniques that avoid the computation of the global Green function. We present a method for calculating the self-force that employs the global Green function and is therefore closely modeled after the original self-force expressions. Our quantitative method involves two stages: (i) numerical approximation of the retarded Green function in the background spacetime; (ii) evaluation of convolution integrals along the worldline of the object. This novel approach can be used along arbitrary worldlines, including those currently inaccessible to more established computational techniques. Furthermore, it yields geometrical insight into the contributions to self-interaction from curved geometry (back-scattering) and trapping of null geodesics. We demonstrate the method on the motion of a scalar charge in Schwarzschild spacetime. This toy model retains the physical history-dependence of the self-force but avoids gauge issues and allows us to focus on basic principles. We compute the self-field and self-force for many worldlines including accelerated circular orbits, eccentric orbits at the separatrix, and radial infall. This method, closely modeled after the original formalism, provides a promising complementary approach to the self-force problem.Comment: 18 pages, 9 figure

Substrate and Stereochemical Control of Peptidoglycan Cross-Linking by Transpeptidation by Escherichia coli PBP1B

Penicillin binding proteins (PBPs) catalyzing transpeptidation reactions that stabilize the peptidoglycan component of the bacterial cell wall are the targets of β-lactams, the most clinically successful antibiotics to date. However, PBP-transpeptidation enzymology has evaded detailed analysis, because of the historical unavailability of kinetically competent assays with physiologically relevant substrates and the previously unappreciated contribution of protein cofactors to PBP activity. By re-engineering peptidoglycan synthesis, we have constructed a continuous spectrophotometric assay for transpeptidation of native or near native peptidoglycan precursors and fragments by Escherichia coli PBP1B, allowing us to (a) identify recognition elements of transpeptidase substrates, (b) reveal a novel mechanism of stereochemical editing within peptidoglycan transpeptidation, (c) assess the impact of peptidoglycan substrates on β-lactam targeting of transpeptidation, and (d) demonstrate that both substrates have to be bound before transpeptidation occurs. The results allow characterization of high molecular weight PBPs as enzymes and not merely the targets of β-lactam acylation

Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity

The rapid rise of multi-drug-resistant bacteria is a global healthcare crisis, and new antibiotics are urgently required, especially those with modes of action that have low-resistance potential. One promising lead is the liposaccharide antibiotic moenomycin that inhibits bacterial glycosyltransferases, which are essential for peptidoglycan polymerization, while displaying a low rate of resistance. Unfortunately, the lipophilicity of moenomycin leads to unfavourable pharmacokinetic properties that render it unsuitable for systemic administration. In this study, we show that using moenomycin and other glycosyltransferase inhibitors as templates, we were able to synthesize compound libraries based on novel pyranose scaffold chemistry, with moenomycin-like activity, but with improved drug-like properties. The novel compounds exhibit in vitro inhibition comparable to moenomycin, with low toxicity and good efficacy in several in vivo models of infection. This approach based on non-planar carbohydrate scaffolds provides a new opportunity to develop new antibiotics with low propensity for resistance induction

MRI of complex regional pain syndrome in the foot

PURPOSE To evaluate the diagnostic potential of MRI in patients with suspected CRPS (complex regional pain syndrome). METHOD A retrospective health-record search was conducted for patients with suspected CRPS (foot). Fifty patients with initially suspected CRPS were included (37 females (51 ± 13 years) and 13 males (44 ± 15 years)). All patients underwent MRI. Two radiologists assessed skin, bone, and soft tissue parameters on MRI. The final diagnosis was CRPS (Gold standard: Budapest criteria) or non-CRPS. MRI parameters were compared between CRPS patients and non-CRPS patients. RESULTS CRPS was diagnosed in 22/50(44 %) patients. Skin thickness (1.9 ± 0.5 mm vs. 1.7 ± 0.3 mm, p = 0.399), enhancement, and subcutaneous edema showed no differences between CRPS and non-CRPS patients. Bone marrow edema presence and pattern were not different between groups. Up to 50 % of CRPS patients showed no bone marrow edema. Subcortical enhancement and periosteal enhancement were not different between groups. For reader 1, muscle edema score was higher in the non-CRPS group compared to the CRPS group (0.1 ± 0.2 vs. 0.6 ± 1.0, p = 0.008), but not different for reader 2 (0.1 ± 0.5 vs. 0.2 ± 0.8, p = 0.819). Perfusion pattern was more extensive in non-CRPS patients for reader 1 (p = 0.048), but not for reader 2 (p = 0.157). Joint effusions showed no difference between groups. CONCLUSIONS MRI cannot distinguish between CRPS and non-CRPS patients. The role of MR imaging in patients with suspected CRPS is to exclude alternative diagnoses that would better explain patients' symptoms

Risk assessment and risk management : developing a model of shared learning in clinical practice

The symposium provided an opportunity for clinicians to critically present and discuss risk assessment and risk management practices in an endeavour to develop a systematic approach to the effective assessment and management of suicide, aggression and violence in a range of mental health settings. Key findings from the symposium are discussed against a backdrop of contemporary literature in the field and form a practical framework for the assessment and management of risk regarding suicide, aggression and violence.

Lactobacillus reuteri in its biofilm state promotes neurodevelopment after experimental necrotizing enterocolitis in rats

Necrotizing enterocolitis (NEC) is a devastating disease affecting premature newborns with no known cure. Up to half of survivors subsequently exhibit cognitive impairment and neurodevelopmental defects. We created a novel probiotics delivery system in which the probiotic Lactobacillus reuteri (Lr) was induced to form a biofilm [Lr (biofilm)] by incubation with dextranomer microspheres loaded with maltose (Lr-DM-maltose). We have previously demonstrated that a single dose of the probiotic Lr administered in its biofilm state significantly reduces the incidence of NEC and decreases inflammatory cytokine production in an animal model of the disease. The aim of our current study was to determine whether a single dose of the probiotic Lr administered in its biofilm state protects the brain after experimental NEC. We found that rat pups exposed to NEC reached developmental milestones significantly slower than breast fed pups, with mild improvement with Lr (biofilm) treatment. Exposure to NEC had a negative effect on cognitive behavior, which was prevented by Lr (biofilm) treatment. Lr administration also reduced anxiety-like behavior in NEC-exposed rats. The behavioral effects of NEC were associated with increased numbers of activated microglia, decreased myelin basic protein (MBP), and decreased neurotrophic gene expression, which were prevented by administration of Lr (biofilm). Our data indicate early enteral treatment with Lr in its biofilm state prevented the deleterious effects of NEC on developmental impairments