Insulin signaling and pharmacology in humans and in corals.

Once thought to be a unique capability of the Langerhans islets in the pancreas of mammals, insulin (INS) signaling is now recognized as an evolutionarily ancient function going back to prokaryotes. INS is ubiquitously present not only in humans but also in unicellular eukaryotes, fungi, worms, and Drosophila. Remote homologue identification also supports the presence of INS and INS receptor in corals where the availability of glucose is largely dependent on the photosynthetic activity of the symbiotic algae. The cnidarian animal host of corals operates together with a 20,000-sized microbiome, in direct analogy to the human gut microbiome. In humans, aberrant INS signaling is the hallmark of metabolic disease, and is thought to play a major role in aging, and age-related diseases, such as Alzheimer's disease. We here would like to argue that a broader view of INS beyond its human homeostasis function may help us understand other organisms, and in turn, studying those non-model organisms may enable a novel view of the human INS signaling system. To this end, we here review INS signaling from a new angle, by drawing analogies between humans and corals at the molecular level.

Novel Non-Cyclooxygenase Inhibitory Derivative of Sulindac Inhibits Breast Cancer Cell Growth In Vitro and Reduces Mammary Tumorigenesis in Rats.

The nonsteroidal anti-inflammatory drug (NSAID) sulindac demonstrates attractive anticancer activity, but the toxicity resulting from cyclooxygenase (COX) inhibition and the suppression of physiologically important prostaglandins precludes its long-term, high dose use in the clinic for cancer prevention or treatment. While inflammation is a known tumorigenic driver, evidence suggests that sulindac's antineoplastic activity is partially or fully independent of its COX inhibitory activity. One COX-independent target proposed for sulindac is cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) isozymes. Sulindac metabolites, i.e., sulfide and sulfone, inhibit cGMP PDE enzymatic activity at concentrations comparable with those associated with cancer cell growth inhibitory activity. Additionally, the cGMP PDE isozymes PDE5 and PDE10 are overexpressed during the early stages of carcinogenesis and appear essential for cancer cell proliferation and survival based on gene silencing experiments. Here, we describe a novel amide derivative of sulindac, sulindac sulfide amide (SSA), which was rationally designed to eliminate COX-inhibitory activity while enhancing cGMP PDE inhibitory activity. SSA was 68-fold and 10-fold less potent than sulindac sulfide (SS) in inhibiting COX-1 and COX-2, respectively, but 10-fold more potent in inhibiting growth and inducing apoptosis in breast cancer cells. The pro-apoptotic activity of SSA was associated with inhibition of cGMP PDE activity, elevation of intracellular cGMP levels, and activation of cGMP-dependent protein kinase (PKG) signaling, as well as the inhibition of ß-catenin/Tcf transcriptional activity. SSA displayed promising in vivo anticancer activity, resulting in a 57% reduction in the incidence and a 62% reduction in the multiplicity of tumors in the N-methyl-N-nitrosourea (MNU)-induced model of breast carcinogenesis. These findings provide strong evidence for cGMP/PKG signaling as a target for breast cancer prevention or treatment and the COX-independent anticancer properties of sulindac. Furthermore, this study validates the approach of optimizing off-target effects by reducing the COX-inhibitory activity of sulindac for future targeted drug discovery efforts to enhance both safety and efficacy.

Introducing IJTMB's Trigger Points: Topical Dialogue amongst Therapeutic Massage & Bodywork Practitioners and Educators.

The International Journal of Therapeutic Massage and Bodywork (IJTMB) has as its core a key interest in and mission to develop the practice of therapeutic massage and bodywork by contributing to the field's body of knowledge. The IJTMB Editorial Board understands that one's daily practice provides the initial testing ground for the development of practice-based knowledge and, ultimately, expertise. Consequently, this practice-based knowledge and experience provides fertile ground for research ideas that further refine our understanding and come full circle to enhance clinical efficacy. Ultimately, without discourse and knowledge transference, the possibility of growing the body of knowledge for therapeutic massage and bodywork or stimulating research in the field is lost. To facilitate discourse and transference of knowledge within the field of therapeutic massage and bodywork, the IJTMB is launching a new journal component entitled Trigger Points: Topical Dialogue amongst Therapeutic Massage & Bodywork Practitioners and Educators. The purpose of IJTMB's Trigger Points is to "trigger" the sharing and discussion of knowledge and expertise among therapeutic massage and bodywork practitioners, educators, and researchers about different approaches to treating specific conditions or addressing specific population issues. Each IJTMB issue, starting with this issue, will include a call for responses to the next Trigger Points topic. Publication of the results for each topic will be in the second issue after the initial call for submissions. With your participation, these IJTMB Trigger Points columns will spark dynamic dialogue, perhaps even collaborations, in the therapeutic massage and bodywork field across practitioners, educators, and researchers.

It's Only a Matter of Time: Clock Hours vs. Competency.

What does it mean to be competent and why is this so important? While there is no generally accepted definition of competency, there are key components that should guide the emerging movement of competency-based education (CBE). In addition, entry-level massage curricula typically run from approximately 500 clock hours to 3000 hours or more. This discrepancy demonstrates markedly divergent opinions on what constitutes the required amount of time (content) for entry-level massage and bodywork curriculum. Some programs have begun using competency models, but there is no broad implementation of CBE. A first step is to come to some agreement on what competencies are actually needed for an entry-level massage therapist. A current effort is underway in the United States that should lay essential groundwork for greater adoption of CBE models.

Is the Sun Setting on Lecture-based Education?

Lecture-based instructional models have been the mainstay of education for centuries. They excel primarily at delivering information from the one to the many. Educators refer to this model as "the sage on the stage". Clearly there are educators who relish this role and are strongly opposed to moving away from it. Yet, educational research and new innovative technologies are suggesting that lecture-based classes may no longer be the most effective teaching method for many situations, especially clinical practice.

Suggested variations on standard carpal tunnel syndrome assessment tests.

Carpal tunnel syndrome is a highly prevalent peripheral neuropathy and manual therapy practitioners are likely to have clients presenting with this condition. There are no definitive diagnostic procedures that have shown a high degree of accuracy in identifying carpal tunnel syndrome. In addition, manual therapy practitioners do not have access to high-tech diagnostic procedures and therefore rely on physical examination methods to identify peripheral neuropathies like carpal tunnel syndrome. Several special orthopedic testing procedures have shown value in predicting the presence of carpal tunnel syndrome. Combining these standard testing procedures with neurodynamic principles allows for modifications to these tests making them more sensitive in identifying median nerve compression neuropathy in the carpal tunnel.

Steps toward massage therapy guidelines: a first report to the profession.

The massage profession has grown rapidly since the late 1980s. As with business startups that begin informally and successfully mature into larger enterprises, growth brings new organizational challenges, together with greater visibility and opportunity. The maturation of massage as a health care profession increases the need for a process to formalize the synthesis of massage therapy knowledge from clinical experience and research-to collect what we know and to make such baseline knowledge widely available to practitioners, consumers, and other health care stakeholders. In short, we need to create a process for setting guidelines.The present paper lays out the motivations and framework for creating massage therapy guidelines that are informed both by research and by clinical experience. It also acts as a report to the massage therapy profession and to other stakeholders about the work of the Best Practices Committee of the Massage Therapy Foundation since 2006. And it has the additional goal of providing a health care literature basis for future academic discussions of massage.The discussion here is based on a definition from the Institute of Medicine and on research into the nature of expertise. Guidelines are targeted for submission to the National Guideline Clearinghouse. Challenges in creating guidelines for massage therapy are discussed. Various stakeholders are considered. Current literature from the wider scope of health care is extensively reviewed. Topics addressed include guideline creation, credentialing of complementary and alternative medicine practitioners, definition of competence, and the increasing role of technology (that is, informatics) in managing training and task-necessary competencies. Finally, a process for creation of massage therapy guidelines is proposed. A central feature of the proposal is the use of a "World Café" symposium to elicit knowledge and solutions from diverse experts. The role of transparency and broad and open peer review is emphasized as essential to the usability and credibility of guidelines.