Workplace learning and career progression: qualitative perspectives of UK dietitians.

BACKGROUND: Post-graduate education and continuous professional development (CPD) within dietetics lack clearly defined pathways. The current literature primarily focuses on new graduate perceptions of workplace learning (WPL). The present study raises issues of how CPD is sustained throughout a National Health Service (NHS) career, how informal learning might be made more visible and whether the workplace withholds learning opportunities. METHODS: Qualified dietitians participated in focus groups (n = 32) and a nominal group technique (n = 24). Data from audio recordings were transcribed and triangulated. Thematic analysis took an interpretative approach. RESULTS: One size for WPL for dietetics and, likely, other allied health professionals (AHPs) did not meet the learning needs of everyone. The informal implicit learning affordances often went unrecognised. A greater emphasis on teaching, picking up on the strong preference for discussion with others voiced in the present study, may improve recognition of all WPL opportunities. Better scaffolding or guided support of entry level dietitians may ease the transition from study to workplace and challenge any perception of 'clipped wings'. Where development and career progression proves difficult for experienced dietitians, mentoring or stepping outside the NHS may revitalise by providing new communities of practice. CONCLUSIONS: WPL cannot be understood as a unitary concept. Dietitians engage with WPL differently across their careers. Future visions of WPL, especially explicit post-graduate career and education frameworks, must accommodate these differences to retain the highest calibre dietitians. The implications of a period of learning 'maintenance' rather than CPD among experienced dietitians offers a topic for further research, particularly as the workforce ages.

Does bariatric surgery improve adipose tissue function?

Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.

Recombinant vascular endothelial growth factor165 gene therapy improves anastomotic healing in an animal model of ischemic esophagogastrostomy.

Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal-gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid-based nonviral delivery system. Twenty-nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low- and high-dose VEGF groups; however, the high-dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.

Hypoxia-induced inflammatory cytokine secretion in human adipose tissue stromovascular cells.

AIMS: Hypoxia has been implicated as a cause of adipose tissue inflammation in obesity, although the inflammatory response of human adipose tissue to hypoxia is not well understood. The goal of this study was to define in vitro inflammatory responses of human adipose tissue to hypoxia and identify molecular mechanisms of hypoxia-induced inflammation. METHODS: The inflammatory milieu and responses of visceral (VAT) and subcutaneous (SAT) adipose tissue explants and purified stromovascular cells (SVFs) from obese and lean humans were studied in an in vitro hypoxic culture system using quantitative real-time PCR, ELISA, western blotting, immunofluorescence microscopy, flow cytometry and immunohistochemistry. RESULTS: Human adipose tissue in obesity demonstrates an increased leucocyte infiltrate that is greater in VAT than SAT and involves macrophages, T cells and natural killer (NK) cells. Hypoxic culture regulates inflammatory cytokine secretion and transcription of metabolic stress response genes in human adipose tissue SVF. Adipocyte diameter is increased and adipose tissue capillary density is decreased in obese participants. Inhibition of c-Jun terminal kinase (JNK) or p38 significantly attenuates hypoxia-induced SVF inflammatory responses. Hypoxia induces phosphorylation of p38 in adipose tissue. CONCLUSIONS: Human adipose tissue in obesity is characterised by a depot-specific inflammatory cell infiltrate that involves not only macrophages, but also T cells and NK cells. Hypoxia induces inflammatory cytokine secretion by human adipose tissue SVF, the primary source of which is adipose tissue macrophages. These data implicate p38 in the regulation of hypoxia-induced inflammation and suggest that alterations in adipocyte diameter and adipose tissue capillary density may be potential underlying causes of adipose tissue hypoxia.

Trends in the management of esophageal carcinoma based on provider volume: treatment practices of 618 esophageal surgeons.

Controversy exists regarding optimal treatment practices for esophageal cancer. Esophagectomy has received focus as one of the index procedures for both hospital and surgical quality despite a relative paucity of controlled trials to define best practices. A survey was created to determine the degree of heterogeneity in the treatment of esophageal cancer among a diverse group of surgeons and to use high-volume (HV) (>/=15 cases/year) and low-volume (LV) (<15 cases/year) designations to discern specific differences in the management of esophageal cancer from the surgeon's perspective. Based on society rosters, surgeons (n = 4000) in the USA and 15 countries were contacted via mail and queried regarding their treatment practices for esophageal cancer using a 50-item survey instrument addressing demographics, utilization of neoadjuvant chemoradiotherapy, and choice of surgical approach for esophageal resection and palliation. There were 618 esophageal surgeons among respondents (n = 1447), of which 77 (12.5%) were considered HV. The majority of HV surgeons (87%) practiced in an academic setting and had cardiothoracic training, while most LV surgeons were general surgeons in private practice (52.3%). Both HV and LV surgeons favored the hand-sewn cervical anastomosis and the stomach conduit. Minimally invasive esophagectomy is performed more frequently by HV surgeons when compared with LV surgeons (P = 0.045). Most HV surgeons use neoadjuvant therapy for patients with nodal involvement, while LV surgeons are more likely to leave the decision to the oncologist. With a few notable exceptions, substantial heterogeneity exists among surgeons' management strategies for esophageal cancer, particularly when grouped and analyzed by case volume. These results highlight the need for controlled trials to determine best practices in the treatment of this complex patient population.

Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue.

BACKGROUND: Adipose tissue is a primary in vivo site of inflammation in obesity. Excess visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), imparts an increased risk of obesity-related comorbidities and mortality, and exhibits differences in inflammation. Defining depot-specific differences in inflammatory function may reveal underlying mechanisms of adipose-tissue-based inflammation. METHODS: Stromovascular cell fractions (SVFs) from VAT and SAT from obese humans undergoing bariatric surgery were studied in an in vitro culture system with transcriptional profiling, flow cytometric phenotyping, enzyme-linked immunosorbent assay and intracellular cytokine staining. RESULTS: Transcriptional profiling of SVF revealed differences in inflammatory transcript levels in VAT relative to SAT, including elevated interferon-gamma (IFN-gamma) transcript levels. VAT demonstrated a broad leukocytosis relative to SAT that included macrophages, T cells and natural killer (NK) cells. IFN-gamma induced a proinflammatory cytokine expression pattern in SVF and adipose tissue macrophages (ATM). NK cells, which constitutively expressed IFN-gamma, were present at higher frequency in VAT relative to SAT. Both T and NK cells from SVF expressed IFN-gamma on activation, which was associated with tumor necrosis factor-alpha expression in macrophages. CONCLUSION: These data suggest involvement of NK cells and IFN-gamma in regulating ATM phenotype and function in human obesity and a potential mechanism for the adverse physiologic effects of VAT.

Psychiatric illness delays diagnosis of esophageal cancer.

Evidence suggests that patients with psychiatric illnesses may be more likely to experience a delay in diagnosis of coexisting cancer. The association between psychiatric illness and timely diagnosis and survival in patients with esophageal cancer has not been studied. The specific aim of this retrospective cohort study was to determine the impact of coexisting psychiatric illness on time to diagnosis, disease stage and survival in patients with esophageal cancer. All patients with a diagnosis of esophageal cancer between 1989 and 2003 at the Portland Veteran's Administration hospital were identified by ICD-9 code. One hundred and sixty patients were identified: 52 patients had one or more DSM-IV diagnoses, and 108 patients had no DSM-IV diagnosis. Electronic charts were reviewed beginning from the first recorded encounter for all patients and clinical and demographic data were collected. The association between psychiatric illness and time to diagnosis of esophageal cancer and survival was studied using Cox proportional hazard models. Groups were similar in age, ethnicity, body mass index, and history of tobacco and alcohol use. Psychiatric illness was associated with delayed diagnosis (median time from alarm symptoms to diagnosis 90 days vs. 35 days in patients with and without psychiatric illness, respectively, P < 0.001) and the presence of advanced disease at the time of diagnosis (37% vs. 18% of patients with and without psychiatric illness, respectively, P= 0.009). In multivariate analysis, psychiatric illness and depression were independent predictors for delayed diagnosis (hazard ratios 0.605 and 0.622, respectively, hazard ratio < 1 indicating longer time to diagnosis). Dementia was an independent risk factor for worse survival (hazard ratio 2.984). Finally, psychiatric illness was associated with a decreased likelihood of receiving surgical therapy. Psychiatric illness is a risk factor for delayed diagnosis, a diagnosis of advanced cancer, and a lower likelihood of receiving surgical therapy in patients with esophageal cancer. Dementia is associated with worse survival in these patients. These findings emphasize the importance of prompt evaluation of foregut symptoms in patients with psychiatric illness.

Erdheim-Chester disease: a rare cause of acute renal failure.

Erdheim-Chester disease (ECD) is a rare systemic histiocytic infiltrative disease of unknown aetiology. In radiology it is characterized by symmetrical sclerotic bone lesions predominantly affecting the diaphyses and metaphyses of long bones. Perivascular fibrosis has been reported in the literature as being a feature of this disease and we report one such case that presented with an encased aorta and renal arteries leading to acute renal failure. The diagnosis of ECD was delayed until a biopsy of the retroperitoneal infiltrate was performed. Further imaging with fluorine 18 deoxyglucose positron emission tomography, bone scintigraphy, plain films of the long bones and CT of the chest, abdomen and pelvis were performed to assess the extent of the patient's systemic disease involvement. To our knowledge, this is the first reported case of ECD presenting with acute renal failure secondary to bilateral occlusion of the renal arteries.

Esophageal motility disorders after gastric banding.

The long-term effects of gastric banding on esophageal function are not well described. This report describes a 28-year-old woman who developed signs and symptoms of abnormal esophageal motility and lower esophageal sphincter hypotension after gastric banding for morbid obesity. The current literature addressing the effects of gastric banding on esophageal function in light of this case report is discussed.

Serum leptin levels, hepatic leptin receptor transcription, and clinical predictors of non-alcoholic steatohepatitis in obese bariatric surgery patients.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a major cause of liver disease in morbidly obese patients. Clinical predictors of NASH remain elusive, as do molecular mechanisms of pathogenesis. METHODS: A series of 35 morbidly obese patients undergoing bariatric surgery had a liver biopsy performed for standard histologic analysis. In addition, RNA was obtained from liver tissue and analyzed for leptin receptor gene expression. Regression analysis was used to correlate clinical variables, including serum leptin levels and hepatic leptin receptor gene expression, with the presence of histologically confirmed NASH. RESULTS: Of the 35 subjects enrolled, 29% had steatosis only, 60% had NASH, and 11% had normal liver histology. Among the clinical variables studied, only diabetes mellitus was an independent predictor of NASH. There was a trend toward lower levels of mRNA encoding the long form of the leptin receptor in hepatic tissue from patients with NASH compared to those with steatosis only. CONCLUSIONS: Diabetes mellitus is associated with an increased risk of NASH in obese patients. Downregulation of hepatic leptin receptor may play a role in the pathogenesis of NASH.

Alterations in peripheral blood lymphocyte cytokine expression in obesity.

Obesity is characterized by alterations in immune and inflammatory function. In order to evaluate the potential role of cytokine expression by peripheral blood mononuclear cells (PBMC) in obesity-associated inflammation, we studied serum protein levels and mRNA levels in PBMC of interleukin (IL)-6, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1Ra in nine lean and 10 obese subjects. Serum IL-1beta was undetectable, IL-1Ra serum levels were elevated, serum levels of TNF-alpha were decreased and serum levels of IL-6 were similar in obese subjects compared to lean subjects, while transcript levels of IL-6, IL-1beta and TNF-alpha, but not IL-1Ra, were decreased in PBMC from obese subjects. PBMC from obese subjects did, however, up-regulate cytokine expression in response to leptin. Thus, obesity-associated changes in IL-1Ra serum levels and IL-6 mRNA levels were not correlated with changes in cognate mRNA and serum levels, respectively, while TNF-alpha serum levels and PBMC mRNA levels were both decreased in obese patients. While immune alterations in obesity are manifest in peripheral blood lymphocytes, the general lack of correlation between altered serum levels and altered PBMC gene expression suggests that PBMC may not be the source of aberrant serum cytokine levels in obesity.

Transthoracic hepatic radiofrequency ablation.

BACKGROUND: Radiofrequency ablation (RFA) is an alternative for the treatment of unresectable hepatic tumors. Tumors beneath the diaphragmatic dome may be difficult to access by laparoscopy. In these cases, a transthoracic transdiaphragmatic approach for delivering RFA can be used. METHODS: Three patients with hepatic metastatic disease were treated using a transthoracic transdiaphragmatic approach to deliver RFA therapy for tumors in liver segments 7 and 8. The patients underwent thoracoscopy. The tumors were identified using transdiaphragmatic ultrasound, and transthoracic transdiaphragmatic RFA (TTRFA) was performed. RESULTS: In three patients, TTRFA was successfully used to ablate five lesions. There were no perioperative complications, blood loss was minimal,and postoperative hospital stays ranged from 2 to 8 days. There were no recurrences during a follow-up period of 4 to 20 months. CONCLUSIONS: TTRFA is a viable alternative for hepatic tumors located beneath the dome of the diaphragm that are difficult to access by laparoscopy.

Laparoscopic radiofrequency ablation and hepatic artery infusion pump placement in the evolving treatment of colorectal hepatic metastases.

BACKGROUND: Laparoscopic radiofrequency ablation (LRFA) and laparoscopic hepatic artery infusion pump (LHAIP) placement are new treatment options for patients with colorectal liver metastases. This study investigates the selection criteria, safety, efficacy, and preliminary outcomes of patients treated with LRFA and LHAIP placement. METHODS: Fourty five patients with colorectal metastases confined to the liver, 37 of whom had failed systemic chemotherapy, were treated with LRFA and/or LHAIP between September 1996 and December 2001. Treatment selection was individualized, based on each patient's general health, liver function, and tumor size, number, location, and distribution. RESULTS: Twenty patients (44%) had LRFA alone, 10 (22%) had LHAIP placement alone, and 15 (33%) patients had combined LRFA and LHAIP therapy. The LRFA group had a significantly shorter mean operative time and blood loss (p <0.05), but hospital stays were similar when compared to patients receiving LRFA + LHAIP or LHAIP alone. Tumor characteristics were worse in both LHAIP groups, with a higher incidence of tumors >or=4 cm, major vascular involvement, diffuse tumor pattern, bilobar distribution, and involvement of more than three segments. During a mean follow-up period of 11.5 +/- 7.8 months (range, 1-38), the actuarial survival was 70%, 67%, and 50% for LRFA, LRFA + LHAIP, and LHAIP, respectively. LHAIP only patients had the shortest estimated mean survival time of the three groups by Kaplan-Meier survival curves (p = 0.001). CONCLUSION: LRFA and/or LHAIP placement are safe and feasible treatment options for the treatment of colorectal hepatic metastases. The choice of treatment for patients should be based primarily on tumor characteristics. Long-term studies, which will elucidate the role of these evolving treatments, are now under way.

A novel assay for fungal ketol-isomerase activity.

2-Deoxy-D-glucose-6-phosphate ketol-isomerase (EC 2.6.1.16) forms glucosamine-6-phosphate and glutamate from fructose-6-phosphate and glutamine and plays an important role in chitin synthesis in fungi. We have established a new assay for fungal ketol-isomerase activity that is amenable to high throughput screening to identify enzyme inhibitors. Aspergillus fumigatus crude lysate was incubated with substrates and after incubation, reactions were terminated. Glutamate dehydrogenase, nitro blue tetrazolium chloride, phenazine methosulfate and beta-NAD were added and the amount of glutamate formed by ketol-isomerase activity was determined by measuring OD585nm. A feedback inhibitor, UDP-N-acetylglucosamine, of fungal ketol-isomerase was successfully detected by this assay (IC50=0.48 mM). In a pilot scale screening, an active extract from an extremophilic bacterium was found, and the extract showed antifungal activity against A. fumigatus, Candida albicans and C. glabrata.

Calculation of lung flow differential after single-lung transplantation: a transesophageal echocardiographic study.

Single-lung transplantation (SLT) is a viable option for patients with end-stage pulmonary disease. After successful SLT, pulmonary blood flow is preferentially shifted to the transplanted lung, creating a flow differential. Lack of flow differential may be indicative of potential vascular complications such as anastomotic stenosis or thrombosis. To assess the ability of transesophageal echocardiography (TEE) in estimating lung flow differential in patients undergoing SLT, biplane TEE was prospectively performed in 18 consecutive patients undergoing SLT early (24 to 72 hours), and in 10 of them late (3 to 6 months) after surgery. Right and left pulmonary vein flow were calculated as Qnu=A. VTI, where A, the pulmonary vein area, was derived as pi.(D/2)(2) and VTI is the velocity time integral of the pulmonary vein spectral display. Lung flow differential was calculated as the ratio of right (RQnu) or left (LQnu) pulmonary vein flow to total pulmonary venous flow (RQnu + LQnu). Lung perfusion imaging scintigraphy (technetium-99m) was used for comparison. Pulmonary vein velocity time integral of transplanted lung was significantly greater than that of native lung (34 +/- 9 vs 18 +/- 8 cm, p <0.001). Percent differential lung flow derived by perfusion imaging scintigraphy and by TEE showed a good correlation (r = 0.67, p <0.001). Pulmonary artery anastomoses were seen in all 12 right-lung recipients, and in 4 of the 6 left-lung recipients; no significant stenosis was noted in the arteries visualized. The pulmonary venous anastomoses were imaged in all patients. Small, nonocclusive pulmonary vein thrombi were seen in 1 patient. In conclusion, TEE is a useful method for calculating lung flow differential in patients undergoing SLT. In addition, TEE provides superb direct visualization of the venous and arterial anastomoses in most patients. Contrary to previous reports, the overall incidence of anastomotic complications is relatively low.

Zeamatin inhibits trypsin and alpha-amylase activities.

Zeamatin is a 22-kDa protein isolated from Zea mays that has antifungal activity against human and plant pathogens. Unlike other pathogenesis-related group 5 proteins, zeamatin inhibits insect alpha-amylase and mammalian trypsin activities. It is of clinical significance that zeamatin did not inhibit human alpha-amylase activity and inhibited mammalian trypsin activity only at high molar concentrations.