The transforming growth factor-beta (TGF-beta) superfamily comprises nearly 30 growth and differentiation factors that include TGF-betas, activins, inhibins, and bone morphogenetic proteins (BMPs). Multiple members of the TGF-beta superfamily serve key roles in stem cell fate commitment. The various members of the family can exhibit disparate roles in regulating the biology of embryonic stem (ES) cells and tumor suppression. For example, TGF-beta inhibits proliferation of multipotent hematopoietic progenitors, promotes lineage commitment of neural precursors, and suppresses epithelial tumors. BMPs block neural differentiation of mouse and human ES cells, contribute to self-renewal of mouse ES cells, and also suppress tumorigenesis. ES cells and tumors may be exposed to multiple TGF-beta members, and it is likely that the combination of growth factors and cross-talk among the intracellular signaling pathways is what precisely defines stem cell fate commitment. This Connections Map Pathway in the Database of Cell Signaling integrates signaling not only from TGF-beta and BMP but also from the ligands nodal and activin, and describes the role of the signaling pathways activated by these ligands in mammalian development. Much of the evidence for the connections shown comes from studies on mouse and human ES cells or mouse knockouts. This pathway is important for understanding not only stem cell biology, but also the molecular effectors of TGF-beta and BMP signaling that may contribute to cancer suppression or progression and thus are potential targets for therapeutic intervention.

Prevention can help older adults avoid illness by identifying and addressing conditions before they cause symptoms, but prevention can also harm older adults if conditions that are unlikely to cause symptoms in the individual's lifetime are identified and treated. To identify older adults who preventive interventions are most likely to benefit (and most likely to harm), we propose a framework that compares an individual's life expectancy (LE) with the time to benefit (TTB) for an intervention. If LE is less than the TTB, the individual is unlikely to benefit but is exposed to the risks of the intervention, and the intervention should generally NOT be recommended. If LE is longer than the TTB, the individual could benefit, and the intervention should generally be recommended. If LE is similar to the TTB, the individual's values and preferences should be the major determinant of the decision. To facilitate the use of this framework in routine clinical care, we explored ways to estimate LE, identified the TTB for common preventive interventions, and developed strategies for communicating with individuals. We have synthesized these strategies and demonstrate how they can be used to individualize prevention for a hypothetical beneficiary in the setting of a Medicare annual wellness visit. Finally, we place prevention in the context of curative and symptom-oriented care and outline how prevention should be focused on healthier older adults, whereas symptom-oriented care should predominate in sicker older adults.

Purpose of review-Microbiome refers to the genetic potential of resident microorganisms that inhabit a given niche. The exact role of the microbiome and its relation to chronic disease processes remains largely unknown, although various associations have been observed. We reviewed current literature investigating the microbiome of the upper airway by subsite (nasal cavity, sinus cavities, nasopharynx, and larynx) and its relation to chronic inflammatory disease processes. Recent findings-The disruption of indigenous microbiota at a specific subsite may lead to pathogen overgrowth and increased susceptibility to infection. This has previously been demonstrated in the gastrointestinal tract and lower airways. The role of the microbiome and its relation to pathogenesis of disease in the upper airway, however, is less clearly understood. The present review discusses the recent studies that appear to link dysbiosis to upper airway chronic inflammatory diseases. Summary-Despite mounting research, the role of microbiota in the upper airway remains poorly understood. Based on review of the current literature comparing healthy versus diseased patients with site-specific inflammatory conditions, a complex consortium of microbial communities inhabits the upper airway. Fluctuations in the baseline microbiome may contribute to disease pathogenesis, and improved understanding of the dynamics between shifting microbiota may be critical to guiding future medical therapy.

Introduction The role of conventionally fractionated radiation therapy in the management of unresectable pancreatic cancer is controversial. One concern about concurrent chemoradiation relates to the timing of chemotherapy. In contrast to conventional radiation therapy, SBRT delivers high doses in a shorter duration resulting in minimal disruption in chemotherapy. Here we report our results of patients treated with SBRT and chemotherapy for inoperable pancreatic cancer. Methods Thirty-eight consecutive patients treated with SBRT and chemotherapy for locally advanced, borderline resectable, and medically inoperable at our institution from January 2008 to December 2012 were included in this retrospective analysis. Treatment was delivered in 5 fractions of 5 or 6 Gy per fraction over five days. Median time from diagnosis to SBRT was 1.9 months. Toxicities were scored using the CTCAE v.3. Survival was calculated using the Kaplan-Meier method. Results The median age was 70 years (range 45 – 90). ECOG performance status ranged from 0 – 3. Thirty-four patients received concurrent chemotherapy. Four other patients received sequential chemotherapy. Median OS was 14.3 months and median PFS was 9.2 months from diagnosis. From radiation, OS and PFS were 12.3 months and 6.8 months, respectively. The overall local control rate was 79%. Acute toxicity was minimal. Severe late SBRT-related toxicities included one grade 3 gastric outlet obstruction, one grade 4 biliary stricture and a grade 5 gastric hemorrhage. Conclusions SBRT combined with chemotherapy for unresectable pancreatic cancer is convenient, feasible and generally well tolerated. The outcomes of SBRT combined with chemotherapy compare favorably to the results of treatment with chemotherapy and conventional radiation therapy.