Application of IgG-Derived Natural Treg Epitopes (IgG Tregitopes) to Antigen-Specific Tolerance Induction in a Murine Model of Type 1 Diabetes

HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigens ex vivo and on the modulation of type 1 diabetes (T1D) in a murine model in vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+ T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. In ex vivo studies of human T cells, peripheral blood mononuclear cells’ (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopes ex vivo by Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management

Coupling sensitive \u3cem\u3ein vitro\u3c/em\u3e and in silico techniques to assess cross-reactive CD4\u3csup\u3e+\u3c/sup\u3e T cells against the swine-origin H1N1 influenza virus

The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role in protecting against the pandemic H1N1 in the absence of cross-reactive humoral immunity. In a published study, we used an immunoinformatics approach to predict a number of CD4+ T cell epitopes are conserved between the 2008–2009 seasonal H1N1 vaccine strain and pandemic H1N1 (A/California/04/2009) hemagglutinin proteins. Here, we provide results from biological studies using PBMCs from human donors not exposed to the pandemic virus to demonstrate that pre-existing CD4+ T cells can elicit cross-reactive effector responses against the pandemic H1N1 virus. As well, we show our computational tools were 80–90% accurate in predicting CD4+ T cell epitopes and their HLA-DRB1-dependent response profiles in donors that were chosen at random for HLA haplotype. Combined, these results confirm the power of coupling immunoinformatics to define broadly reactive CD4+ T cell epitopes with highly sensitive in vitro biological assays to verify these in silico predictions as a means to understand human cellular immunity, including cross-protective responses, and to define CD4+ T cell epitopes for potential vaccination efforts against future influenza viruses and other pathogens

Reducing anxiety for dental visits

This work addresses children’s (under 6 years of age) fear and apprehension to visit dental clinics. We present a bespoke interactive Virtual Reality reproduction of the physical dental clinic, augmented with virtual characters and enriched with gamification style information for a richer user experience. The experience allows the user to navigate and familiarise themselves with the location and the procedures they will undertake before visiting the clinic. The experience is now being piloted at the Dental Public Health at the University Hospital of Wales

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients

Short-Latency, Goal-Directed Movements of the Pinnae to Sounds That Produce Auditory Spatial Illusions

The precedence effect (PE) is an auditory spatial illusion whereby two identical sounds presented from two separate locations with a delay between them are perceived as a fused single sound source whose position depends on the value of the delay. By training cats using operant conditioning to look at sound sources, we have previously shown that cats experience the PE similarly to humans. For delays less than ±400 μs, cats exhibit summing localization, the perception of a “phantom” sound located between the sources. Consistent with localization dominance, for delays from 400 μs to ∼10 ms, cats orient toward the leading source location only, with little influence of the lagging source. Finally, echo threshold was reached for delays >10 ms, where cats first began to orient to the lagging source. It has been hypothesized by some that the neural mechanisms that produce facets of the PE, such as localization dominance and echo threshold, must likely occur at cortical levels. To test this hypothesis, we measured both pinnae position, which were not under any behavioral constraint, and eye position in cats and found that the pinnae orientations to stimuli that produce each of the three phases of the PE illusion was similar to the gaze responses. Although both eye and pinnae movements behaved in a manner that reflected the PE, because the pinnae moved with strikingly short latencies (∼30 ms), these data suggest a subcortical basis for the PE and that the cortex is not likely to be directly involved

Patient and Provider Perspectives on Symptom Monitoring During Outpatient Chemotherapy: Interview Study

BackgroundFluctuating symptoms and side effects are common during outpatient cancer treatment, and approaches to monitoring symptoms vary widely across providers, patients, and clinical settings. To design a remote symptom monitoring system that patients and providers find to be useful, it may be helpful to understand current clinical approaches to monitoring and managing chemotherapy-related symptoms among patients and providers and assess how more frequent and systematic assessment and sharing of data could improve patient and provider experiences. ObjectiveThe goals of this study were to learn about patient and provider perspectives on monitoring symptoms during chemotherapy, understand barriers and challenges to effective symptom monitoring at one institution, and explore the potential value of remote symptom monitoring between provider visits. MethodsA total of 15 patients who were currently undergoing or had recently completed chemotherapy and 7 oncology providers participated in semistructured interviews. Interviews were transcribed and coded using an iterative thematic analysis approach. The study was conducted at a National Cancer Institute–Designated Comprehensive Cancer Center. ResultsFour main themes were discussed by patients and providers: (1) asynchronous nature of current methods for tracking and managing symptoms, (2) variability in reported symptoms due to patient factors, (3) limitations of existing communication channels, and (4) potential value of real-time remote symptom monitoring during chemotherapy. Current asynchronous methods and existing communication channels resulted in a disconnect between when symptoms are most severe and when conversations about symptoms happen, a situation further complicated by memory impairments during chemotherapy. Patients and providers both highlighted improvements in patient-provider communication as a potential benefit of remote real-time symptom monitoring. Providers also emphasized the value of temporal data regarding when symptoms first emerge and how they progress over time, as well as the potential value of concurrent activity or other data about daily activities and functioning. Patients noted that symptom monitoring could result in better preparation for subsequent treatment cycles. ConclusionsBoth patients and providers highlighted significant challenges of asynchronous, patient-initiated, phone-dependent symptom monitoring and management. Oncology patients and providers reported that more routine remote monitoring of symptoms between visits could improve patient-provider communication, prepare patients for subsequent chemotherapy cycles, and facilitate provider insight and clinical decision-making with regard to symptom management

Behavioral and neural identification of birdsong under several masking conditions

Many animals are adept at identifying communication calls in the presence of competing sounds, from human listeners communicating in a cocktail party to penguins locating their kin amongst the thousands of conspecifics in their colony. The kind of perceptual interference in such settings differs from th