Bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations assessed by magnetic resonance imaging

Sleep-disordered breathing, including habitual snoring, is a major health problem. Treatment of primary habitual snoring should be individualized using both conservative and active treatment methods. Active surgical interventions are, however, associated with significant morbidity. Therefore, procedures causing far less morbidity should be preferred. Our aim was to assess the efficacy and acceptability of bipolar radiofrequency thermal ablation of the soft palate in habitual snorers without significant desaturations associated with excessive daytime sleepiness. We treated 20 nonobese habitual snorers (median age, 43 years, range 35-63). All the patients had the major site of obstruction at the level of the soft palate, and they were treated on an outpatient basis in two treatment sessions separated by 1 week. The pretreatment and post-treatment symptoms and findings as well as the overall efficacy of the procedure were evaluated by questionnaires, visual analogue scales, and magnetic resonance imaging. All the questionnaires showed a statistically significant change, indicating decreased snoring and daytime sleepiness. The magnetic resonance studies showed that the procedure induced notable T1-signal alterations in the treated tissue, and when compared with the pretreatment images, certain dimensions of the soft palate were significantly changed. Bipolar radiofrequency thermal ablation of the soft palate seems to be well tolerated and effective regarding primary habitual snorers without significant desaturations associated with excessive daytime sleepiness.     

Engraftment of human HSCs in nonirradiated newborn NOD-scid IL2rγ null mice is enhanced by transgenic expression of membrane-bound human SCF

Immunodeficient mice engrafted with human HSCs support multidisciplinary translational experimentation, including the study of human hematopoiesis. Heightened levels of human HSC engraftment are observed in immunodeficient mice expressing mutations in the IL2-receptor common γ chain (IL2rg) gene, including NOD-scid IL2rγ(null) (NSG) mice. Engraftment of human HSC requires preconditioning of immunodeficient recipients, usually with irradiation. Such preconditioning increases the expression of stem cell factor (SCF), which is critical for HSC engraftment, proliferation, and survival. We hypothesized that transgenic expression of human membrane-bound stem cell factor Tg(hu-mSCF)] would increase levels of human HSC engraftment in nonirradiated NSG mice and eliminate complications associated with irradiation. Surprisingly, detectable levels of human CD45(+) cell chimerism were observed after transplantation of cord blood-derived human HSCs into nonirradiated adult as well as newborn NSG mice. However, transgenic expression of human mSCF enabled heightened levels of human hematopoietic cell chimerism in the absence of irradiation. Moreover, nonirradiated NSG-Tg(hu-mSCF) mice engrafted as newborns with human HSCs rejected human skin grafts from a histoincompatible donor, indicating the development of a functional human immune system. These data provide a new immunodeficient mouse model that does not require irradiation preconditioning for human HSC engraftment and immune system development.     

Clonal competition with alternating dominance in multiple myeloma

Emerging evidence indicates that tumors can follow several evolutionary paths over a patient's disease course. With the use of serial genomic analysis of samples collected at different points during the disease course of 28 patients with multiple myeloma, we found that the genomes of standard-risk patients show few changes over time, whereas those of cytogenetically high-risk patients show significantly more changes over time. The results indicate the existence of 3 temporal tumor types, which can either be genetically stable, linearly evolving, or heterogeneous clonal mixtures with shifting predominant clones. A detailed analysis of one high-risk patient sampled at 7 time points over the entire disease course identified 2 competing subclones that alternate in a back and forth manner for dominance with therapy until one clone underwent a dramatic linear evolution. With the use of the Vk*MYC genetically engineered mouse model of myeloma we modeled this competition between subclones for predominance occurring spontaneously and with therapeutic selection.