Distinct B-cell lineage commitment distinguishes adult bone marrow hematopoietic stem cells

The question of whether a single hematopoietic stem cell (HSC) gives rise to all of the B-cell subsets [B-1a, B-1b, B-2, and marginal zone (MZ) B cells] in the mouse has been discussed for many years without resolution. Studies here finally demonstrate that individual HSCs sorted from adult bone marrow and transferred to lethally irradiated recipients clearly give rise to B-2, MZ B, and B-1b, but does not detectably reconstitute B-1a cells. These findings place B-2, MZ, and B-1b in a single adult developmental lineage and place B-1a in a separate lineage derived from HSCs that are rare or missing in adults. We discuss these findings with respect to known developmental heterogeneity in other HSC-derived lymphoid, myeloid, and erythroid lineages, and how HSC developmental heterogeneity conforms to the layered model of the evolution of the immune system that we proposed some years ago. In addition, of importance to contemporary medicine, we consider the implications that HSC developmental heterogeneity may have for selecting HSC sources for human transplantation.     

Antigen-specific memory in B-1a and its relationship to natural immunity

In the companion article by Yang and colleagues [Yang Y, et al. (2012) Proc Natl Acad Sci USA, 109, 10.1073/pnas.1121631109], we have shown that priming with glycolipid (FtL) from Francisella tularensis live-vaccine strain (i) induces FtL-specific B-1a to produce robust primary responses (IgM >IgG); (ii) establishes persistent long-term production of serum IgM and IgG anti-FtL at natural antibody levels; and (iii) elicits FtL-specific B-1a memory cells that arise in spleen but rapidly migrate to the peritoneal cavity, where they persist indefinitely but divide only rarely. Here, we show that FtL rechallenge alone induces these PerC B-1a memory cells to divide extensively and to express a unique activation signature. However, FtL rechallenge in the context of a Toll-like receptor 4 agonist-stimulated inflammatory response readily induces these memory cells to migrate to spleen and initiate production of dominant IgM anti-FtL secondary responses. Thus, studies here reveal unique mechanisms that govern B-1a memory development and expression, and introduce B-1a memory as an active participant in immune defenses. In addition, at a practical level, these studies suggest previously unexplored vaccination strategies for pathogen-associated antigens that target the B-1a repertoire.     

Epidemiology of risks and child maltreatment in early childhood: a pilot study

There is a lack of prevalence data of child maltreatment and neglect in German speaking countries. The aim of this pilot study was to develop a questionnaire as a generally useable method for surveys of early child maltreatment and to test its feasibility and usefulness. The pilot study of this methodology would also give a first indication of the prevalence of risk factors and of child maltreatment itself. The study was carried out in 21 day-care centres in Vorarlberg, Austria. The questionnaire was judged as very user-friendly and useable. Prevalence was 5.3 % for neglect and 1.2 % for abuse in the study sample. The results demonstrate that systematic data collection in the field of youth welfare is practicable in German speaking countries. In addition, day-care centres allow easy access to data collection. Further psychometric testing of the questionnaire with normative data samples and across different professional groups is required.     

Management of osteoporosis-related bone fractures: an integrated concept of care

Introduction

Multidisciplinary medical management of osteoporosis and osteoporosis-related fractures is still an important treatment issue today. In view of ethiopathology of osteoporosis and the future demographic development an increasing socioeconomic burden has to be estimated. A prerequisite for an effective secondary prophylaxis of osteoporotic fractures is the implementation of a treatment network, with inclusion of all partners involved in patient’s care. Therefore, special attention should be paid to formation and establishment of centres with multidisciplinary and integrated treatment concepts. This paper outlines the concept of a clinical centre for diagnosis and therapy of osteoporosis established 4 years ago. Furthermore, a concept of integrated care of osteoporosis-related fractures is introduced and the obtained data of a 2-year follow-up analysis will be presented.

Methods

The establishment of an osteoporosis centre at a university teaching hospital as well as certification according to the Dachverband Osteologie (DVO) guidelines were necessary. Recruitment of contract partners on both sides, health insurances and outpatient general practitioners as well as specialist doctors, was also essential. The implementation of an osteoporosis coordinator was a step to put the treatment concept into practice.

Results and discussion

Based on the recommendations of DVO guidelines, all diagnostic and therapeutic requirements of osteoporosis can be met by the team of consultant specialists at a clinical osteoporosis centre. In the described treatment concept of integrated care, 44 patients suffering of osteoporosis with a consecutive fracture could be included. Mean age was 77. Inclusion criteria were spinal fractures (61%), proximal femoral fractures (27%) and peripheral fractures (12%). Fifty percent of patients included into the contract had not received previous osteoporosis medication. Sixty-eight patients who met the inclusion criteria could not be included due to the lack of compliance (42%), patients’ disapproval (34%) or incomplete treatment and documentation algorithm (24%). Special attention should focus on the completion of standardised diagnosis and documentation. The high amount of time and personnel required has proven the importance of the introduction of an osteoporosis coordinator to be essential.     

A new variant of MYCN gene as a cause of Feingold syndrome

Feingold syndrome 1 (FS1) is a rare disorder that is inherited in autosomal dominant manner with full penetrance but with variable expressivity. The most common phenotypical features described are finger and toe anomalies, microcephaly, short stature, and intestinal atresia. Dysmorphic features, intellectual disability and other organ anomalies are less frequently described. Here, we present a 7‐year‐old boy with severe intellectual disability who is diagnosed with FS1 syndrome caused by a new heterozygous variant of MYCN gene