Citations

AbstractHigh stress is a prevalent problem in the worksite. To reduce stress, improve productivity, reduce absenteeism, and lower healthcare costs, many companies offer exercise classes or stress management programmes. Although physical activity is an important component of stress management, few worksites have integrated physical activity into their comprehensive stress reduction programmes. The purpose of this single‐arm pilot project was to examine the potential effectiveness of an integrated exercise (studio cycling) and cognitive–behavioural stress management programme. Eighty‐four adults, 75% female, mostly aged 40+ years, participated in an integrated 12‐week cycling studio and cognitive–behavioural stress management programme. Participants experienced a significant and clinically meaningful reduction on the Perceived Stress Scale (p < 0.01), rating of current stress level and confidence to manage stress at the programme's end and at a 1‐month follow‐up. Participants also reported having significantly improved overall health, improved nutritional habits, higher physical activity level, greater confidence in their ability to follow a healthy diet, higher spiritual well‐being, improved sleep, receiving more support for maintaining healthy living and improved quality of life at the completion of the 12‐week programme and 1‐month follow‐up. These findings provide further support for an integrated exercise and stress management programme. Copyright © 2013 John Wiley & Sons, Ltd.

Background HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. Methods and Results Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti‐Retroviral Therapy ( SMART ) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy ( ART ) treatment versus the untreated state ( HIV replication) via 3 separate analyses: (1) a cross‐sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short‐term increases in some procoagulants (eg, 15% to 23% higher FVIII ; P <0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [ AT ] and 6% to 10% lower protein C; P <0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P <0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. Conclusions HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV ‐related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation. Clinical Trial Registration URL: ClinicalTrials.gov . Unique identifier: NCT 00027352.

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare variant of hepatocellular carcinoma (HCC) that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

Outcomes of external beam radiotherapy (EBRT) in advanced medullary thyroid carcinoma (MTC) are largely unknown. Retrospective review of data from patients with MTC, diagnosed from June 1, 1970, through December 31, 2007. Overall survival and locoregional tumor control rates were calculated. Seventeen patients had adjuvant or palliative EBRT delivered to 41 sites. Six patients initially had adjuvant EBRT (median, 60.80 Gy); none had relapse in the treated area. Five patients with locoregional recurrence after surgery were treated (median, 59.40 Gy), and durable disease control was achieved in 3. Twelve patients received palliative EBRT to 29 sites of metastatic disease (median, 30.00 Gy), which provided sustained symptom relief at 45% of sites. Five- and ten-year overall survival rates were 44% and 19%, respectively. Adjuvant EBRT may be most effective for prevention of locoregional recurrence. EBRT may provide sustained control of advanced, metastatic disease in select patients.

Key Points Treatment response criteria for MF must capture drug benefit in terms of symptom burden. The current document includes stricter definitions of red cell transfusion need and independence.

Summary Streptozotocin (STZ), a glucosamine-nitrosourea compound, has potent genotoxic effects on pancreatic β-cells and is frequently used to induce diabetes in experimental animals. Glucagon-like peptide-1 (GLP-1) has β-cell protective effects and is known to preserve β-cells from STZ treatment. In this study, we analyzed the mechanisms of STZ-induced diabetes and GLP-1-mediated β-cell protection in STZ-treated mice. At 1 week after multiple low-dose STZ administrations, pancreatic β-cells showed impaired insulin expression, while maintaining expression of nuclear Nkx6.1. This was accompanied by significant upregulation of p53-responsive genes in islets, including a mediator of cell cycle arrest, p21 (also known as Waf1 and Cip1). STZ treatment also suppressed expression of a wide range of genes linked with key β-cell functions or diabetes development, such as G6pc2, Slc2a2 (Glut2), Slc30a8, Neurod1, Ucn3, Gad1, Isl1, Foxa2, Vdr, Pdx1, Fkbp1b and Abcc8, suggesting global β-cell defects in STZ-treated islets. The Tmem229B, Prss53 and Ttc28 genes were highly expressed in untreated islets and strongly suppressed by STZ, suggesting their potential roles in β-cell function. When a pancreas-targeted adeno-associated virus (AAV) vector was employed for long-term Glp-1 gene delivery, pancreatic GLP-1 expression protected mice from STZ-induced diabetes through preservation of the β-cell mass. Despite its potent β-cell protective effects, however, pancreatic GLP-1 overexpression showed limited effects on the global gene expression profiles in the islets. Network analysis identified the programmed-cell-death-associated pathways as the most relevant network in Glp-1 gene therapy. Upon pancreatic GLP-1 expression, upregulation of Cxcl13 and Nptx2 was observed in STZ-damaged islets, but not in untreated normal islets. Given the pro-β-cell-survival effects of Cxcl12 (Sdf-1) in inducing GLP-1 production in α-cells, pancreatic GLP-1-mediated Cxcl13 induction might also play a crucial role in maintaining the integrity of β-cells in damaged islets.

AbstractBackgroundVirtual microscopy is increasingly being used in dermatopathology educational settings.ObjectiveThe objective is to evaluate diagnostic accuracy and attitudes between virtual microscopy and traditional glass slide microscopy among dermatology residents.MethodsA 48‐question dermatopathology examination was administered to 35 dermatology residents at three different dermatology residency training sites during the 2011–2012 academic year with half (n = 24) of the questions using the gold standard of glass slide microscopy and half (n = 24) using whole, scanned virtual slides. Correct number of questions using glass slides and virtual slides was evaluated. Participants were surveyed regarding previous experience with digital slide imaging; quality, ease of use, and speed of slide review; and overall microscopy preferences.ResultsOverall, diagnostic accuracy was better with glass slides than virtual slides (p = 0.01). However, no statistically significant difference was found in diagnostic accuracy of first‐year trainees (p > 0.99) or trainees with exposure to virtual microscopy greater than two times per month (p = 0.27). There was no overall personal preference for glass slide vs. virtual microscopy.LimitationsDifferent cases and questions were used for glass slides and virtual microscopy.ConclusionsDiagnostic accuracy with virtual microscopy is dependent on year of residency training and prior experience with virtual microscopy.