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Patients who are oral hygiene noncompliant (OHNC) are more likely to lose teeth after radiation therapy (RT) for head and neck cancer (HNC), which increases the risk of developing osteoradionecrosis. A previous study revealed that patients who were OHNC at baseline (BL) who became oral hygiene compliant during follow-up had the best tooth-failure outcomes. The purpose of this study was to identify factors associated with oral hygiene compliance (OHC), overall, and among those who were BL OHNC.

ObjectiveThe effectiveness of µ-opioid receptor (MOPr) agonists for treatment of visceral pain is compromised by constipation, respiratory depression, sedation and addiction. We investigated whether a fentanyl analogue, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), which preferentially activates MOPr in acidified diseased tissues, would inhibit pain in a preclinical model of inflammatory bowel disease (IBD) without side effects in healthy tissues.DesignAntinociceptive actions of NFEPP and fentanyl were compared in control mice and mice with dextran sodium sulfate colitis by measuring visceromotor responses to colorectal distension. Patch clamp and extracellular recordings were used to assess nociceptor activation. Defecation, respiration and locomotion were assessed. Colonic migrating motor complexes were assessed by spatiotemporal mapping of isolated tissue. NFEPP-induced MOPr signalling and trafficking were studied in human embryonic kidney 293 cells.ResultsNFEPP inhibited visceromotor responses to colorectal distension in mice with colitis but not in control mice, consistent with acidification of the inflamed colon. Fentanyl inhibited responses in both groups. NFEPP inhibited the excitability of dorsal root ganglion neurons and suppressed mechanical sensitivity of colonic afferent fibres in acidified but not physiological conditions. Whereas fentanyl decreased defecation and caused respiratory depression and hyperactivity in mice with colitis, NFEPP was devoid of these effects. NFEPP did not affect colonic migrating motor complexes at physiological pH. NFEPP preferentially activated MOPr in acidified extracellular conditions to inhibit cAMP formation, recruit β-arrestins and evoke MOPr endocytosis.ConclusionIn a preclinical IBD model, NFEPP preferentially activates MOPr in acidified microenvironments of inflamed tissues to induce antinociception without causing respiratory depression, constipation and hyperactivity.

This phase is also when to identify training needs (Tn) in terms of the number of trainees, their educational and professional background, their present level of competence, and the desired behavior or skill level acquired upon training completion. From test tube to results (Training and knowledge transfer) The Training and Knowledge Transfer Workstream is where you will start creating a reaction, and training is the element that makes that happen. Periodic Table of Change Management Strategy & Alignment Leader Readiness Communications & Engagement Training & Knowledge Transfer Foundational Roadblocks Sa Stakeholder Analysis Or Orientation Pm Project Management Le Leader List Lc Leader Coalitions Sp Sponsorship Cp Communications Plan Km Key Messages KPI Performance Indicators Aa Audience Analysis Tp Training Plan Lo Learning Outcomes En Environments Tc Time Constraints Bc Budget Constraints Rc Resource Constraints Mm Meeting Matrix Se Stakeholder Engagement Cs Communications Strategy Sg Steering & Governance Ap Action Plans Ad Active Advocacy ME WIIFM Sd Sender Ot Course Outlines At Authoring Tools Lms Learning Mgmt System Ll Lessons Learned UAT User-Acceptance Testing Cf Change Fatigue C Confusion Fe Fear Rp Resistance Plan Rm Readiness Measures Tn Training Needs Gs Go-Live Strategy Rf Reinforcement Co Coaching Be Branding Ws Website Cc Communications Collaboration Se Sponsorship Engagement Te Training Environment T3 Train the Trainer Ts Training Strategy Sp Support Ct Cutover Plan Bi Buy-in Ho Hand-Off Plan Ci Change Impact Up Updates Wt Workforce Transition Dc Direct Communications Ep Employee Presence Cn Change Network Cm Communications Modality Kt Knowledge Transfer Dm Delivery Modalities In Incentives Cb Collaboration Er Employee Resistance Ri Risks DIAGRAM: Elements of Change DIAGRAM: Elements of Change PHOTO (COLOR). [Extracted from the article]

Chronic pain is a hallmark of functional disorders, inflammatory diseases and cancer of the digestive system. The mechanisms that initiate and sustain chronic pain are incompletely understood, and available therapies are inadequate. This review highlights recent advances in the structure and function of pronociceptive and antinociceptive G protein-coupled receptors (GPCRs) that provide insights into the mechanisms and treatment of chronic pain. This knowledge, derived from studies of somatic pain, can guide research into visceral pain. Mediators from injured tissues transiently activate GPCRs at the plasma membrane of neurons, leading to sensitisation of ion channels and acute hyperexcitability and nociception. Sustained agonist release evokes GPCR redistribution to endosomes, where persistent signalling regulates activity of channels and genes that control chronic hyperexcitability and nociception. Endosomally targeted GPCR antagonists provide superior pain relief in preclinical models. Biased agonists stabilise GPCR conformations that favour signalling of beneficial actions at the expense of detrimental side effects. Biased agonists of µ-opioid receptors (MOPrs) can provide analgesia without addiction, respiratory depression and constipation. Opioids that preferentially bind to MOPrs in the acidic microenvironment of diseased tissues produce analgesia without side effects. Allosteric modulators of GPCRs fine-tune actions of endogenous ligands, offering the prospect of refined pain control. GPCR dimers might function as distinct therapeutic targets for nociception. The discovery that GPCRs that control itch also mediate irritant sensation in the colon has revealed new targets. A deeper understanding of GPCR structure and function in different microenvironments offers the potential of developing superior treatments for GI pain.

AbstractWhile all of the social sciences have been interested in theory, the disciplinary history of International Relations (IR) has been, in many ways, a story of a continuous, yet frustrating, attempt to formulate an all-encompassing theory of international. This attempt formed a crucial context for the recently rediscovered the Council on Foreign Relations Study Group on the Theory of International Relations 1953–1954. This article reconstruct the post-World War Two disciplinary history of International Relations. In the 1940s, the field faced a profound identity crisis. It was in this context that interest began to be directed at developing a theory of international politics. Increasingly, theory was viewed as the solution to the problems that the field was facing. The article describes these developments and relates them to the deliberations of the Council on Foreign Relations Study Group.

Aims/Hypothesis: Diabetic foot complications remain very prevalent in the US and worldwide, and a major risk for devastating amputations. We evaluated the impact of establishing a fully integrated and specialized Podiatry service into a large tertiary academic health system to implement structured and targeted preventative foot care on limb salvage rates. Methods: Cross-sectional cohorts’ data mining analysis was conducted of all encounters for diabetes and any foot complications between 2000-2005 and 2010-2015, preceding and after full implementation of podiatry service, respectively. The primary outcome was the change in major non-traumatic lower extremity amputations. Secondary outcomes included minor non-traumatic lower extremity amputations, other diabetic foot complications, limb salvage procedures as documented by procedural coding, and location (outpatient, inpatient, ED) of service rendered. Results: We analyzed 100 million patient encounters that met the above criteria. Compared with the initial cohort, integration of specialized podiatry services resulted in a significant decrease in the number of major amputations from 127 to 85/year (p<0.05), and halved the amputations rate from 0.004% to 0.002% (p<0.05). Rates of minor lower extremity amputations remained unchanged (p>0.10), while the rates of preventative procedures including foot ulcer debridement doubled (0.0002% to 0.0004% ; p<0.03). Diagnoses of diabetic foot complications increased significantly (p<0.05) and shifted toward the outpatient setting. Conclusion: Full integration of specialized Podiatry service led to a significant decrease in major amputation rates, supporting teamwork between podiatry and diabetes health-care providers is essential to performing timely diabetic foot complications management, preventative procedures leading to limb salvage, and a shift in the care location.

The complex interplay between microbiota and immunity is important to human health. To explore how altered adaptive immunity influences the microbiome, we characterize skin, nares, and gut microbiota of patients with recombination-activating gene (RAG) deficiency—a rare genetically defined inborn error of immunity (IEI) that results in a broad spectrum of clinical phenotypes. Integrating de novoassembly of metagenomes from RAG-deficient patients with reference genome catalogs provides an expansive multi-kingdom view of microbial diversity. RAG-deficient patient microbiomes exhibit inter-individual variation, including expansion of opportunistic pathogens (e.g., Corynebacterium bovis, Haemophilus influenzae), and a relative loss of body site specificity. We identify 35 and 27 bacterial species derived from skin/nares and gut microbiomes, respectively, which are distinct to RAG-deficient patients compared to healthy individuals. Underscoring IEI patients as potential reservoirs for viral persistence and evolution, we further characterize the colonization of eukaryotic RNA viruses (e.g., Coronavirus 229E, Norovirus GII) in this patient population.