Clinical Pharmacology & Therapeutics: Past, Present, and Future.

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare

Health Care Evolves From Reactive to Proactive.

Decoding health and disease pathways drives healthcare evolution. Historically, therapeutic paradigms have relied on interventions that mitigate symptoms of established diseases. Increasingly, molecular insights into pathophysiology now provide unprecedented opportunities to offer curative solutions or even prevent disease and thereby secure longitudinal wellness. These opportunities extend past individual patients to entire populations and geographies. Moreover, they optimize prospective healthspan across lifespan. Linking discovery science and its translatable innovations beyond reactive disease intervention to proactive prevention will maximize society’s returns creating the greatest benefit for the greatest number of people globally

Process Improvement for Maximized Therapeutic Innovation Outcome.

Deconvoluting key biological mechanisms forms the framework for therapeutic discovery. Strategies that enable effective translation of those insights along the development and regulatory path ultimately drive validated clinical application in patients and populations. Accordingly, parity in What vs. How we transform novel mechanistic insights into therapeutic paradigms is essential in achieving success. Aligning molecular discovery with innovations in structures and processes along the discovery-development-regulation-utilization continuum maximizes the return on public and private investments for next-generation solutions in managing health and disease

The Guanylate Cyclase C-cGMP Signaling Axis Opposes Intestinal Epithelial Injury and Neoplasia.

Guanylate cyclase C (GUCY2C) is a transmembrane receptor expressed on the luminal aspect of the intestinal epithelium. Its ligands include bacterial heat-stable enterotoxins responsible for traveler\u27s diarrhea, the endogenous peptide hormones uroguanylin and guanylin, and the synthetic agents, linaclotide, plecanatide, and dolcanatide. Ligand-activated GUCY2C catalyzes the synthesis of intracellular cyclic GMP (cGMP), initiating signaling cascades underlying homeostasis of the intestinal epithelium. Mouse models of GUCY2C ablation, and recently, human populations harboring GUCY2C mutations, have revealed the diverse contributions of this signaling axis to epithelial health, including regulating fluid secretion, microbiome composition, intestinal barrier integrity, epithelial renewal, cell cycle progression, responses to DNA damage, epithelial-mesenchymal cross-talk, cell migration, and cellular metabolic status. Because of these wide-ranging roles, dysregulation of the GUCY2C-cGMP signaling axis has been implicated in the pathogenesis of bowel transit disorders, inflammatory bowel disease, and colorectal cancer. This review explores the current understanding of cGMP signaling in the intestinal epithelium and mechanisms by which it opposes intestinal injury. Particular focus will be applied to its emerging role in tumor suppression. In colorectal tumors, endogenous GUCY2C ligand expression is lost by a yet undefined mechanism conserved in mice and humans. Further, reconstitution of GUCY2C signaling through genetic or oral ligand replacement opposes tumorigenesis in mice. Taken together, these findings suggest an intriguing hypothesis that colorectal cancer arises in a microenvironment of functional GUCY2C inactivation, which can be repaired by oral ligand replacement. Hence, the GUCY2C signaling axis represents a novel therapeutic target for preventing colorectal cancer

Peer Review Certifies Quality and Innovation in Clinical Pharmacology & Therapeutics.

Clinical Pharmacology & Therapeutics (CPT) is an established voice of the discipline, a trusted source of new knowledge showcasing discovery, translation, and application of novel therapeutic paradigms to advance the management of patients and populations. Identifying, evaluating, prioritizing, and disseminating the best science along the discovery-development-regulatory-utilization continuum are responsibilities shared through peer review. To enhance the uniformity of this essential component of quality assurance and innovation, and maximize the value of the journal and its contents to authors, reviewers, and the readership, we review key concepts concerning peer review as it specifically relates to CPT

The utilization of eye movement desensitization reprocessing as a therapeutic tool

Eye Movement Desensitization and Reprocessing, EMDR, is a new clinical treatment shown to be effective for victims of trauma. EMDR is a time efficient, comprehensive methodology backed by positive, controlled research, for the treatment of disturbing experiences that underlie many pathologies. An eight phase treatment approach that includes using eye movements or other left-right stimulation, EMDR helps victims of trauma reprocess disturbing thoughts and memories. The purpose of this research project was to describe and explore the utilization of EMDR by licensed clinical social workers who were registered as members of the National Association of Social Workers

Household Demand for Broadband Internet Service

As part of the Federal Communications Commission (“FCC”) National Broadband Report to Congress, we have been asked to conduct a survey to help determine consumer valuations of different aspects of broadband Internet service. This report details our methodology, sample and preliminary results. We do not provide policy recommendations. This draft report uses data obtained from a nationwide survey during late December 2009 and early January 2010 to estimate household demand for broadband Internet service. The report combines household data, obtained from choices in a real market and an experimental setting, with a discrete-choice model to estimate the marginal willingness-to-pay (WTP) for improvements in eight Internet service characteristics.

ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice.

There is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents

Building spelling power: word analysis lessons for grade 2.

Thesis (Ed.M.)--Boston Universit

Year in Review

If examination of journal performance is a surrogate for the vitality of a discipline, the continued ascension of Clinical Pharmacology and Therapeutics (CPT) bodes well for the evolution and practice of human therapeutics in this decade. CPT has excelled as the authoritative, cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy and evaluation of therapeutics in humans. Building on a foundation that established the core tenets, and a framework providing the structural integrity for the field, CPT was conceived by visionary precedent editors and editorial teams who were themselves leaders of this discipline. Today, CPT is regarded as the premier international forum for the intersection of diverse communities of practice enriching the discovery and application of therapeutics in this new era of molecular science and translational medicine