Definitions and outcome measures for bullous pemphigoid: Recommendations by an international panel of experts

Our scientific knowledge of bullous pemphigoid (BP) has dramatically progressed in recent years. However, despite the availability of various therapeutic options for the treatment of inflammatory diseases, only a few multicenter controlled trials have helped to define effective therapies in BP. A major obstacle in sharing multicenter-based evidences for therapeutic efforts is the lack of generally accepted definitions for the clinical evaluation of patients with BP. Common terms and end points of BP are needed so that experts in the field can accurately measure and assess disease extent, activity, severity, and therapeutic response, and thus facilitate and advance clinical trials. These recommendations from the International Pemphigoid Committee represent 2 years of collaborative efforts to attain mutually acceptable common definitions for BP and proposes a disease extent score, the BP Disease Area Index. These items should assist in the development of consistent reporting of outcomes in future BP reports and studies. © 2011 by the American Academy of Dermatology, Inc

Voice complaints, risk factors for voice problems and history of voice problems in relation to puberty in female student teachers.

Item does not contain fulltextThe aim of the study was to estimate voice complaints, risk factors for voice complaints and history of voice problems in student teachers before they embarked on their professional teaching career. A cross-sectional questionnaire survey was performed among female student teachers. The response rate was 72% and 457 questionnaires were analyzed. Voice complaints at the moment and/or during the past year were reported by 39.6% subjects. Subjects with voice complaints had significantly higher VHI scores than subjects without voice complaints. In comparison to subjects without voice complaints, overall, subjects with voice complaints reported more frequently that vocal loading factors, physical factors, environmental factors and psychological factors had a negative influence on their voice. Subjects with voice complaints reported more frequently a history of voice complaints during puberty and before puberty in comparison to subjects without voice complaints. Voice complaints in student teachers apparently had a multifactorial genesis and with roots during puberty or before puberty. Logistic regression analysis revealed that intensive voice use, emotions and history of voice complaints during puberty were the most discriminating set of risk factors for voice complaints. Subjects with voice complaints in comparison to those without voice complaints reported more frequently that they would develop a voice problem due to future teaching and that future teaching would have a negative influence on their voice. Around three quarters of subjects with and without voice complaints reported that attention paid to their voice during their training was sufficient. However, subjects with voice complaints were observed to report the need for a refresher course on voice use more frequently than those without voice complaints. The findings call for more intensive voice training for student teachers to cope with the vocal, physical and psychological demands of the teaching profession. Authorities should take responsibility to monitor and improve working conditions of student teachers and teachers

Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance

We previously reported that some of the rare broadly reactive, HIV-1 neutralizing antibodies are polyreactive, leading to the hypothesis that induction of these types of neutralizing antibody may be limited by immunologic tolerance. However, the notion that such antibodies are sufficiently autoreactive to trigger B cell tolerance is controversial. To test directly whether rare neutralizing HIV-1 antibodies can activate immunologic tolerance mechanisms, we generated a knock-in mouse in which the Ig heavy chain (HC) variable region rearrangement (VHDJH) from the polyreactive and broadly neutralizing human monoclonal antibody 2F5 was targeted into the mouse Igh locus. In vitro, this insertion resulted in chimeric human/mouse 2F5 antibodies that were functionally similar to the human 2F5 antibody, including comparable reactivity to human and murine self-antigens. In vivo, the 2F5 VHDJH insertion supported development of large- and small pre-B cells that expressed the chimeric human/mouse Igμ chain but not the production of immature B cells expressing membrane IgM. The developmental arrest exhibited in 2F5 VHDJH knock-in mice is characteristic of other knock-in strains that express the Ig HC variable region of autoreactive antibodies and is consistent with the loss of immature B cells bearing 2F5 chimeric antibodies to central tolerance mechanisms. Moreover, homozygous 2F5 VHDJH knock-in mice support reduced numbers of residual splenic B cells with low surface IgM density, severely diminished serum IgM levels, but normal to elevated quantities of serum IgGs that did not react with autoantigens. These features are consistent with elimination of 2F5 HC autoreactivity by additional negative selection mechanism(s) in the periphery