Increasing Medical Trainees’ Empathy Through Volunteerism and Mentorship

Background: Within medical education, there have been recent calls for increased understanding and exposure to poverty to increase trainees’ empathy toward the underserved. Students participating in Michigan Cardiovascular Outcomes Research and Reporting Program research program volunteered at World Medical Relief (WMR) in Detroit, Michigan, a nonprofit organization which recycles medical equipment for developing countries and within greater Detroit. Participants’ perceptions of the underserved were measured before and after the experience. Methods: Preliminary questionnaires were given to participants prior to and after exposures at WMR. Questionnaires examined participants’ attitudes toward the underserved, knowledge of medical supply reuse, and their perceived ability to impact change. P values of 4× more likely than previously to have knowledge of the variety of recycled medical supplies at WMR. Prior to volunteering, 48.7% of participants gave little thought to how excess medical supplies could be collected versus 0% after exposure. Participants were 1.5× more likely to agree that the experience was enhanced working with their peers and 2.7× more likely to consider starting their own organization/intervention for medical supply donations. Those participants that never previously volunteered were 1.3× more likely to do so with encouragement from a mentor. Conclusions: Encouraging exposure to such service programs resulted in enhanced knowledge of community resources and increased motivation to participate in outreach and belief of individual responsibility to care for the underserved. Incorporating volunteerism into traditional education programs offers the opportunity to build awareness and interest in students reaching out to the underserved

Immunodominant conformational and linear IgE epitopes lie in a single segment of Ara h 2

International audienceBackground: Contribution of conformational epitopes to the IgE reactivity of peanut allergens Ara h 2 and Ara h 6 is at least as important as that of the linear epitopes. However, little is known about these conformational IgE-binding epitopes.Objective: We investigated the distribution of conformational epitopes on chimeric 2S-albumins.Methods: Recombinant chimeras were generated by exchanging structural segments between Ara h 2 and Ara h 6. Well-refolded chimeras, as verified by circular dichroism analysis, were then used to determine the epitope specificity of mAbs by performing competitive inhibition of IgG binding. Furthermore, we delineated the contribution of each segment to the overall IgE reactivity of both 2S-albumins by measuring the chimeras' IgE-binding capacity with sera from 21 patients allergic to peanut. We finally assessed chimeras' capacity to trigger mast cell degranulation.Results: Configuration of the conformational epitopes was preserved in the chimeras. Mouse IgG mAbs, raised against natural Ara h 6, and polyclonal human IgE antibodies recognized different conformational epitopes distributed all along Ara h 6. In contrast, we identified human IgG mAbs specific to different Ara h 2 linear or conformational epitopes located in all segments except the C-terminal one. The major conformational IgE-binding epitope of Ara h 2 was located in a segment located between residues 33 and 81 that also contains the major linear hydroxyproline-containing epitope. Accordingly, this segment is critical for the capacity of Ara h 2 to induce mast cell degranulation.Conclusions: Chimeric 2S-albumins provide new insights on the conformational IgE-binding epitopes of Ara h 2 and Ara h 6. Proximity of the immunodominant linear and conformational IgE-binding epitopes probably contributes to the high allergenic potency of Ara h 2

Immunotherapy-induced neutralizing antibodies disrupt allergen binding and sustain allergen tolerance in peanut allergy

International audienceIn IgE-mediated food allergies, exposure to the allergen activates systemic allergic responses. Oral immunotherapy (OIT) treats food allergies through incremental increases in oral allergen exposure. However, OIT only induces sustained clinical tolerance and decreased basophil sensitivity in a subset of individuals despite increases in circulating allergen-specific IgG in all treated individuals. Therefore, we examined the allergen-specific antibodies from 2 OIT cohorts of patients with sustained and transient responses. Here, we compared antibodies from individuals with sustained or transient responses and discovered specific tolerance-associated conformational epitopes of the immunodominant allergen Ara h 2 recognized by neutralizing antibodies. First, we identified what we believe to be previously unknown conformational, intrahelical epitopes using x-ray crystallography with recombinant antibodies. We then identified epitopes only recognized in sustained tolerance. Finally, antibodies recognizing tolerance-associated epitopes effectively neutralized allergen to suppress IgE-mediated effector cell activation. Our results demonstrate the molecular basis of antibody-mediated protection in IgE-mediated food allergy, by defining how these antibodies disrupt IgE-allergen interactions to prevent allergic reactions. Our approach to studying the structural and functional basis for neutralizing antibodies demonstrates the clinical relevance of specific antibody clones in antibody-mediated tolerance. We anticipate that our findings will form the foundation for treatments of peanut allergy using neutralizing antibodies and hypoallergens

Executive Functions in Children and Adolescents with Turner Syndrome: A Systematic Review and Meta-Analysis

International audienceTurner syndrome (TS) is a genetic disorder, affecting 1/2500 to 1/3000 live female births, induced by partial or total deletion of one X chromosome. The neurocognitive profile of girls with TS is characterized by a normal Verbal IQ and weaknesses in visual-spatial, mathematics, and social cognitive domains. Executive functions (EFs) impairments have also been reported in these young patients. However, methodological differences across studies do not allow determination of which EFs are impaired and what is the magnitude of these impairments. The aim of this review was to clarify the EF profile of children and adolescents with TS. Sixteen samples, from thirteen studies, were included in the current meta-analysis. EFs measures used in these studies were classified into working memory, inhibitory control, cognitive flexibility, or higher-order EFs tasks in accordance with Diamond’s model, Annual Review of Psychology, 64, 135–168 (2013). Results confirmed that girls with TS had significant executive impairments with effect sizes varying from small (inhibitory control) to medium (cognitive flexibility) and large (working memory, higher-order EFs). Analyses by task revealed that cognitive inhibition may be more impaired than the other inhibitory control abilities. Heterogeneity across cognitive flexibility measures was also highlighted. Between-sample heterogeneity was observed for three tasks and the impact of participants’ characteristics on EFs was discussed. This meta-analysis confirms the necessity to assess, in patients living with TS, each EF by combining both visual and verbal tasks. Results also underline that, when studying girls with TS’ executive profile, it is important to explore the impact of moderator variables, such as IQ, parental socio-economic status, TS karyotype, psychiatric comorbidities, and hormonal treatment status