Obesity and Surgical Wound Healing: A Current Review

Objective. The correlation between obesity and deficient wound healing has long been established. This review examines the current literature on the mechanisms involved in obesity-related perioperative morbidity. Methods. A literature search was performed using Medline, PubMed, Cochrane Library, and Internet searches. Keywords used include obesity, wound healing, adipose healing, and bariatric and surgical complications. Results. Substantial evidence exists demonstrating that obesity is associated with a number of postoperative complications. Specifically in relation to wound healing, explanations include inherent anatomic features of adipose tissue, vascular insufficiencies, cellular and composition modifications, oxidative stress, alterations in immune mediators, and nutritional deficiencies. Most recently, advances made in the field of gene array have allowed researchers to determine a few plausible alterations and deficiencies in obese individuals that contribute to their increased risk of morbidity and mortality, especially wound complications. Conclusion. While the literature discusses how obesity may negatively affect health on various of medical fronts, there is yet to be a comprehensive study detailing all the mechanisms involved in obesity-related morbidities in their entirety. Improved knowledge and understanding of obesity-induced physiological, cellular, molecular, and chemical changes will facilitate better assessments of surgical risks and outcomes and create efficient treatment protocols for improved patient care of the obese patient population

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: the Sun Exposure and Vitamin D Supplementation (SEDS) Study

BACKGROUND Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. METHODS/DESIGN The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. DISCUSSION This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013

Conference report:Improving outcomes for gastrointestinal cancer in the UK

Substantial steps are being made towards early diagnosis. A range of tools are available to help GPs appropriately categorise early symptoms during routine consultations. Various promising new tests and devices are being explored, especially for cancers that frequently present at late stages. The continuing increase in demand on endoscopy services is a major concern, not least because of the shortage of trained practitioners and other healthcare staff. However, screening and collaborative streamlining initiatives might help to improve the relevance of referrals. The question posed in the title of the conference was rhetorical, but a positive answer seems potentially achievable, even in austere times, through facilitating uptake of screening, working to develop the primary-secondary care interface, educating the public and by protecting funds for research.</p

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Contains reports on six research projects.U.S. Air Force - Office of Scientific Research (Contract F49620-84-C-0004)Analog Devices, Inc.Defense Advanced Research Projects Agency (Contract N00014-80-C-0622)National Science Foundation (Grant ECS83-10941

Deletion of the mRNA Stability Factor ELAVL1 (HuR) In Pancreatic Cancer Cells Disrupts the Tumor Microenvironment Integrity

Stromal cells promote extensive fibrosis in pancreatic ductal adenocarcinoma (PDAC), which is associated with poor prognosis and therapeutic resistance. We report here for the first time that loss of the RNA-binding protein human antigen R (HuR, ELAVL1) in PDAC cells leads to reprogramming of the tumor microenvironment. In multiple in vivo models, CRISPR deletion of ELAVL1 in PDAC cells resulted in a decrease of collagen deposition, accompanied by a decrease of stromal markers (i.e. podoplanin, αsmooth muscle actin, desmin). RNA-sequencing data showed that HuR plays a role in cell–cell communication. Accordingly, cytokine arrays identified that HuR regulates the secretion of signaling molecules involved in stromal activation and extracellular matrix organization [i.e. platelet-derived growth factor AA (PDGFAA) and pentraxin 3]. Ribonucleoprotein immunoprecipitation analysis and transcription inhibition studies validated PDGFA mRNA as a novel HuR target. These data suggest that tumor-intrinsic HuR supports extrinsic activation of the stroma to produce collagen and desmoplasia through regulating signaling molecules (e.g. PDGFAA). HuR-deficient PDAC in vivo tumors with an altered tumor microenvironment are more sensitive to the standard of care gemcitabine, as compared to HuR-proficient tumors. Taken together, we identified a novel role of tumor-intrinsic HuR in its ability to modify the surrounding tumor microenvironment and regulate PDGFAA

Up-regulated expression of LAMP2 and autophagy activity during neuroendocrine differentiation of prostate cancer LNCaP cells

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer

Comparing the effects of sun exposure and vitamin D supplementation on vitamin D insufficiency, and immune and cardio-metabolic function: The Sun Exposure and Vitamin D Supplementation (SEDS) Study

Background: Adults living in the sunny Australian climate are at high risk of skin cancer, but vitamin D deficiency (defined here as a serum 25-hydroxyvitamin D (25(OH)D) concentration of less than 50 nmol/L) is also common. Vitamin D deficiency may be a risk factor for a range of diseases. However, the optimal strategies to achieve and maintain vitamin D adequacy (sun exposure, vitamin D supplementation or both), and whether sun exposure itself has benefits over and above initiating synthesis of vitamin D, remain unclear. The Sun Exposure and Vitamin D Supplementation (SEDS) Study aims to compare the effectiveness of sun exposure and vitamin D supplementation for the management of vitamin D insufficiency, and to test whether these management strategies differentially affect markers of immune and cardio-metabolic function. Methods/Design: The SEDS Study is a multi-centre, randomised controlled trial of two different daily doses of vitamin D supplementation, and placebo, in conjunction with guidance on two different patterns of sun exposure. Participants recruited from across Australia are aged 18-64 years and have a recent vitamin D test result showing a serum 25(OH)D level of 40-60 nmol/L. Discussion: This paper discusses the rationale behind the study design, and considers the challenges but necessity of data collection within a non-institutionalised adult population, in order to address the study aims. We also discuss the challenges of participant recruitment and retention, ongoing engagement of referring medical practitioners and address issues of compliance and participant retention. Trial registration: Australia New Zealand Clinical Trials Registry: ACTRN12613000290796 Registered 14 March 2013

Custom Integrated Circuits

Contains table of contents for Part III, table of contents for Section 1 and reports on eleven research projects.IBM CorporationMIT School of EngineeringNational Science Foundation Grant MIP 94-23221Defense Advanced Research Projects Agency/U.S. Army Intelligence Center Contract DABT63-94-C-0053Mitsubishi CorporationNational Science Foundation Young Investigator Award Fellowship MIP 92-58376Joint Industry Program on Offshore Structure AnalysisAnalog DevicesDefense Advanced Research Projects AgencyCadence Design SystemsMAFET ConsortiumConsortium for Superconducting ElectronicsNational Defense Science and Engineering Graduate FellowshipDigital Equipment CorporationMIT Lincoln LaboratorySemiconductor Research CorporationMultiuniversity Research IntiativeNational Science Foundatio