A review of the basic science of the diabetic foot and its complications

Challenges and opportunities of electronic publishing

IntroductionMany medical and allied health institutions are moving away from the traditional lecture‐based approaches. Instead, students are educated through other models including case‐based collaborative learning and team‐based learning where students can apply and integrate their newly acquired basic and clinical science through small group activities. Substantial challenges for educators using these learning approaches include: delivering new and engaging activities, effective integration of content from basic and clinical disciplines, efficient use of class time, and scaling the activity to the level of the learner. Here we designed an exciting and innovative game activity to integrate clinically‐focused anatomy with other disciplines and to mitigate student disengagement.AimTo deliver a challenging and engaging classroom activity that integrates different basic and clinical science disciplines, allowing students to apply and assess their knowledge of a body system or region.MethodsIn this IRB approved study, first year medical students participated in a board game (Fig. 1) consisting of 30 challenges related to the gastrointestinal system. The board game activity was developed by experts from microbiology/immunology, anatomy, surgery, pathology, pharmacology, pathophysiology, and physiology. It was one of eleven case‐based basic science sessions that were included in a 6 week long course focused on the gastrointestinal system. The goal was to create single or integrated discipline challenges that took on a variety of formats. Using a game board and points system, student teams completed 30 challenges (Table 1) by applying high yield content while accumulating points as they progressed through the gastrointestinal tract. Students then evaluated the success of the session through a survey.Results100% of students (n=133) who participated in the board game activity completed the survey. Overall, 84.3% of students endorsed that the learning objectives for this module were met (27.6% strongly agree) and 81.5% endorsed that the overall quality of this session was excellent (33.3% strongly agree). On average, the overall quality rating of the session was 4.66(+/− 0.8) out of a 6 point Likert scale, a score that was higher than all 11 sessions in this course, and well above the mean satisfaction rating of 3.77 +/− 0.7 for all 11 sessions in this course.117 of 133 students left a narrative evaluation of the self‐study materials, activity, or their experience with their classroom facilitator. Of the 75 comments directly related to the activity, 34 stated the activity was “awesome”, “good”, or “best of the year so far”, 12 remarked that the activity was highly engaging and/or interactive, and 11 stated the activity was fun. The most commonly received negative comment was that the activity too long.DiscussionThis game‐format activity provides an engaging review of basic science and clinical disciplines that can be scaled to the ability of the learner and adapted to accommodate different disciplines. It can be easily developed by content experts and deployed with minimal faculty training, contributing to the collection of in‐class activities for health science curricula.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Commonly used isotonic arthroscopic irrigation fluids, such as normal saline or lactated Ringer's, were initially formulated for intravenous administration so they do not replicate the physiologic properties of healthy synovial fluid. Synovial fluid plays an important role in regulating joint homeostasis such that even transient disruptions in its composition and physiology can be detrimental. Previous studies suggest that hyperosmolar solutions may be a promising alternative to traditional isotonic fluids. This manuscript sought to systematically review and synthesize previously published basic science, translational, and clinical studies on the use of hyperosmolar arthroscopic irrigation fluids to delineate the optimal fluid for clinical use. A systematic literature search of MEDLINE/PubMed and Embase databases was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) guidelines. The search phrases were: ("cartilage" AND "hyperosmolar"); ("arthroscopy" OR "arthroscopic" AND "hyperosmolar"). The titles, abstracts, and full texts were screened for studies on hyperosmolar solutions and articular cartilage. Study quality was assessed, and relevant data were collected. A meta-analysis was not performed due to study heterogeneity. A risk of bias assessment was performed on the included translational and clinical studies. There were 10 basic science studies, 2 studies performed in translational animal models, and 2 clinical studies included in this review. Of the basic science studies, 7 utilized a mechanical injury model. The translational studies were carried out in the canine shoulder and equine stifle (knee) joint. Clinical studies were performed in the shoulder and knee. Multiple basic science, translational, and clinical studies highlight the short-term safety, cost-effectiveness, and potential benefits associated with use of hyperosmolar solutions for arthroscopic irrigation. Further work is needed to develop and validate the ideal formulation for a hyperosmolar irrigation solution with proven long-term benefits for patients undergoing arthroscopic surgeries.

Oral health

Objective:To develop a postoperative rehabilitation protocol for patients receiving autologous-chondrocyte implantation (ACI) to repair articular-cartilage defects of the knee.Data Sources:careful review of both basic science and clinical literature, personal communication with colleagues dealing with similar cases, and the authors’ experience and expertise in rehabilitating numerous patients with knee pathologies, injuries, and trauma.Data Synthesis:Postoperative rehabilitation of the ACI patient plays a critical role in the outcome of the procedure. The goals are to improve function and reduce discomfort by focusing on 3 key elements: weight bearing, range of motion, and strengthening.Conclusions:The authors present 2 flexible postoperative protocols to rehabilitate patients after an ACI procedure to the knee.

The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.

<p>Currently there is a growing interest in the study of intervertebral discs due to loss of manpower brought to society by low back and neck pains. These papers seek to delineate the difference between normal aging and disc degeneration, trying to understand what factor would be determining for the second condition. Thus, the morphology field was expanded and knowledge on the structure of intervertebral discs currently uses the research field of cell and molecular biology, and genetics. The results indicate that regardless of age or condition, the intervertebral disc undergoes long and extensive remodeling of its constituents, which are influenced by several factors: environmental, soluble, cell growth and extracellular matrix. In this literature review we describe the biological characteristics of the cervical and lumbar intervertebral disc with a focus on basic science of aging and degeneration, selecting the latest findings and discussions of the area, which influence future research and clinical thoughts.</p>

Over the past decade, a new discipline in biomedical research has emerged. Translational science, as it has been termed, is concerned with the application of laboratory or “bench” science to the diagnosis and treatment of human diseases. The importance and potential impact of this new discipline for collaboration, education, funding and public interest have been widely discussed.1 Moreover; the role of well-informed clinicians, invested in promoting as well as utilizing new research, is clearly recognized as crucial for the communal advancement of medicine and continued support of basic science.2 To meet these emergent objectives for vision scientists, Journal of Ophthalmic and Vision Research is establishing a new section entitled Translational Eye Research, to stimulate communication between basic scientists and clinicians. Basic research is expanding scientific knowledge at a phenomenal rate through in vitro experiments, investigations of model organisms and using cross-discipline methodologies. Yet, the development of improved clinical applications utilizing this information is complex and unpredictable. Progress does occur via studies designed to understand a specific disease or treatments developed according to defined strategies. Often, however, novel concepts arise in ways not readily connected to an obvious clinical problem. The language and ideas, not to mention the methods of investigation, can be foreign and impenetrable to those not yet experienced with the diverse experimental and biological systems in use today. The fact that many breakthroughs occur outside the realms of visual system research presents a severe and mounting challenge for ophthalmologists. This new section will meet the needs for the vision community by presenting up to date reviews in translational science. The articles will have two goals: first, to review an area of basic research at a level accessible to clinicians and second, to highlight clinical applications in ophthalmology. The ultimate goal is to present concepts and methods that may have applications not yet realized for treating patients. We hope to draw attention to basic science areas with potential for further development or exploration in the eye and ocular diseases. The goal is to stimulate the clinical audience to investigate unexpected avenues for possible applications in their own specialty and to expose basic researchers to opportunities for applying their expertise to clinical problems.

Autologous fat is considered the ideal material for soft-tissue augmentation in plastic and reconstructive surgery. The primary drawback of autologous fat grafting is the high resorption rate. The isolation of mesenchymal stem cells from adipose tissue inevitably led to research focusing on the study of combined transplantation of autologous fat and adipose derived stem cells (ADSCs) and introduced the theory of ‘cell-assisted lipotransfer’. Transplantation of ADSCs is a promising strategy, due to the high proliferative capacity of stem cells, their potential to induce paracrine signalling and ability to differentiate into adipocytes and vascular cells. The current study examined the literature for clinical and experimental studies on cell-assisted lipotransfer to assess the efficacy of this novel technique when compared with traditional fat grafting. A total of 30 studies were included in the present review. The current study demonstrates that cell-assisted lipotransfer has improved efficacy compared with conventional fat grafting. Despite relatively positive outcomes, further investigation is required to establish a consensus in cell-assisted lipotransfer.

Vitamin D deficiency is commonly diagnosed among patients with inflammatory bowel disease (IBD). Patients with IBD are at risk of low bone density and increased fractures due to low vitamin D levels, long standing disease, and frequent steroid exposures; as a result, it is well established that vitamin D supplementation in this population is important. There is increasing support for the role of vitamin D in strengthening the innate immune system by acting as an immunomodulator and reducing inflammation in experimental and human IBD. The active form of vitamin D, 1,25(OH)D3, acts on T cells to promote T helper (Th)2/regulatory T responses over Th1/Th17 responses; suppresses dendritic cell inflammatory activity; induces antibacterial activity; and regulates cytokine production in favor of an anti-inflammatory response. Murine and human IBD studies support a therapeutic role of vitamin D in IBD. Risk factors for vitamin D deficiency in this population include decreased sunlight exposure, disease duration, smoking, and genetics. Vitamin D normalization is associated with reduced risk of relapse, reduced risk of IBD-related surgeries, and improvement in quality of life. Vitamin D is an inexpensive supplement which has been shown to improve IBD outcomes. However, further research is required to determine optimal serum vitamin D levels which will achieve beneficial immune effects, and stronger evidence is needed to support the role of vitamin D in inducing disease response and remission, as well as maintaining this improvement in patients' disease states.

Chronic myeloid leukemia (CML) is one of the most commonly found types of myeloproliferative neoplasms, characterized by increased proliferation of granulocytic cells without losing their differentiation ability. Imatinib, a tyrosine kinase inhibitor (TKI), can be effectively used as therapy for CML. However, Imatinib can affect bone turnover thus having clinical implications on the bones of CML patients undergoing long-term Imatinib therapy. However, parameters that can accurately describe the bone condition in CML patients receiving Imatinib still need further study. A combination of imaging techniques such as bone mineral density (BMD) and bone turnover activity markers such as C-terminal telopeptide of type I collagen (CTX-1) and osteocalcin has the potential to be used as monitoring parameters for bone density abnormalities in CML patients receiving Imatinib. This article explains the rationale for using BMD, CTX-1, and osteocalcin as monitoring parameters of bone remodeling in CML patients receiving Imatinib. First, the physiological process of bone turnover will be explained. Then, we describe the role of tyrosine kinase in bone metabolism. Next, the impact of Imatinib on BMD, CTX-1, and osteocalcin will be explained. The assessment of bone health of CML patients on Imatinib should include both BMD tests and bone turnover marker assays such as CTX-1 and osteocalcin.

ABSTRACTBackground: Glucagon-like peptide-1 (GLP‑1) and glucose-dependent insulinotropic polypeptide (GIP) are hormones secreted by the enteroendocrine cells of the gut in response to the ingestion of nutrients. These incretin hormones, so called because they increase insulin secretion, are key modulators of pancreatic islet hormone secretion and, thus, glucose homeostasis. The glucoregulatory effects of incretins are the basis for new therapies currently being developed for the treatment of type 2 diabetes mellitus (T2DM). Drugs that inhibit dipeptidyl peptidase-4 (DPP‑4), a ubiquitous enzyme that rapidly inactivates both GLP-1 and GIP, increase active levels of these hormones and, in doing so, improve islet function and glycemic control in T2DM.Scope: In this review, we briefly describe (1) the role of pancreatic islet dysfunction in the onset and progression of T2DM, (2) the rationale for developing drugs that enhance incretin activity, (3) the evidence that inhibition of DPP‑4 is effective in ameliorating islet dysfunction and improving glycemic control in T2DM, (4) the efficacy, safety, and tolerability of DPP‑4 inhibitors as monotherapy and in combination with other antidiabetic agents, and (5) the potential utility of DPP‑4 inhibitors relative to existing oral antidiabetic agents and newer antidiabetic drugs in the pipeline. The review is based upon MEDLINE literature searches (1966–August 2006) and abstracts and presentations from the American Diabetes Association Scientific Sessions (2002–2006) and the European Association for the Study of Diabetes Annual Meetings (1998–2006). Basic science, preclinical, and clinical studies and review articles published in the English language were evaluated and selected based upon consideration of their originality, relevance, and frequency of citation.Findings: DPP‑4 inhibitors are a new class of antidiabetogenic drugs that provide comparable efficacy to current treatments. They are effective as monotherapy in patients inadequately controlled with diet and exercise and as add-on therapy in combination with metformin, thiazolidinediones, and insulin. The DPP‑4 inhibitors are well tolerated, carry a low risk of producing hypoglycemia, and are weight-neutral. The long-term durability of effect on glycemic control and β‑cell morphology and function remain to be established.Conclusions: Islet cell dysfunction is central to the pathogenesis of T2DM. Incretin-based therapies, including GLP-1 analogues and DPP‑4 inhibitors, have been shown to restore glucose homeostasis and improve glycemic control. The DPP‑4 inhibitors, which can be used as monotherapy or in combination with other antidiabetic drugs, are a promising new treatment option, especially for patients with early-stage T2DM and more severe hyperglycemia.

14 - Deep Venous Thrombosis and Pulmonary Embolism

Thrombin, thrombomodulin and the control of hemostasis

Modulation of the kappa and mu opioid axis for the treatment of chronic pruritus: A review of basic science and clinical implications