Dnmt3a regulates myeloproliferation and liver-specific expansion of hematopoietic stem and progenitor cells.

DNA methyltransferase 3A (DNMT3A) mutations are observed in myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Transplantation studies have elucidated an important role for Dnmt3a in stem cell self-renewal and in myeloid differentiation. Here, we investigated the impact of conditional hematopoietic Dnmt3a loss on disease phenotype in primary mice. Mx1-Cre-mediated Dnmt3a ablation led to the development of a lethal, fully penetrant MPN with myelodysplasia (MDS/MPN) characterized by peripheral cytopenias and by marked, progressive hepatomegaly. We detected expanded stem/progenitor populations in the liver of Dnmt3a-ablated mice. The MDS/MPN induced by Dnmt3a ablation was transplantable, including the marked hepatomegaly. Homing studies showed that Dnmt3a-deleted bone marrow cells preferentially migrated to the liver. Gene expression and DNA methylation analyses of progenitor cell populations identified differential regulation of hematopoietic regulatory pathways, including fetal liver hematopoiesis transcriptional programs. These data demonstrate that Dnmt3a ablation in the hematopoietic system leads to myeloid transformation in vivo, with cell-autonomous aberrant tissue tropism and marked extramedullary hematopoiesis (EMH) with liver involvement. Hence, in addition to the established role of Dnmt3a in regulating self-renewal, Dnmt3a regulates tissue tropism and limits myeloid progenitor expansion in vivo.

Stress, disease, and dentistry.

There is increasing evidence that chronic stress, by suppressing the immune system, can lead to physical illnesses and, in turn, impact dental outcomes. Often, how patients cope with chronic stress is a common underlying factor in the outcome of both dental and systemic illnesses. Integrative dental medicine emphasizes an understanding of how dental diseases and systemic diseases interrelate. By developing positive coping strategies, raising self-awareness, and establishing a state of emotional balance, we can learn to identify the stressors in our lives and cope with them in more effective ways.

Esthetic applications of restorative materials and techniques in the anterior dentition.

The esthetic expectations of our patients can be met by doing a thorough initial examination with emphasis on periodontal health, caries incidence, occlusion, possible orthodontic corrections, esthetic needs, and economic concerns. Through proper communication with the patient, a written treatment plan can be developed that uses the various techniques of bleaching, cosmetic recontouring, direct resin bonding, porcelain veneering, or crowning to meet the patient's restorative needs. The most conservative noninvasive techniques should be evaluated first. Often, bleaching and partial direct bonding are all that is needed. If the dentition is badly worn or discolored, then more extensive treatment is indicated. Patients frequently have concerns about longevity of restorations or require very high levels of esthetic correction, which can only be accomplished with more invasive techniques. When patients understand what can be accomplished and are involved in the treatment decision, then successful results are assured. Esthetic restorative dentistry is probably the most rewarding aspect of practice today, but it is also the most challenging. New materials appear and techniques change so rapidly that it is sometimes difficult to keep up. Practitioners should acquire a thorough knowledge of available methods and materials, learn the limitations of these materials and techniques, and master skills through continuing education (courses, journals, and newsletters) as well as chairside repetition as new procedures become available.

Bleaching, bonding, and veneering: a rationale for material and technique choice.

A vast number of materials and multiple choice treatment options are available for dental corrections, ranging from conservative bleaching to more extensive veneering and crowning. Thus, the choice of the proper technique and materials is a challenge for dentists faced with performing aesthetic dental corrections.

Anterior composite resins and veneers: treatment planning, preparation, and finishing.

Today's esthetic dental restorations are limited only by the practitioner's artistic ability and imagination. Less invasive procedures such as bleaching, bonding, and veneer placement are useful adjuncts and economic alternatives to more extensive procedures such as crown placement, orthodontic treatment, and orthognathic surgery. In addition to a discussion of the considerations when planning esthetic restorative treatment, technique and material selection, tooth preparation, material placement, and finishing are presented.