Citations

Laparoendoscopic single-site surgery (LESS) is a new minimally invasive surgical technique that presents physical and mental challenges to surgeons. Currently, LESS procedures are commonly performed using surgical instruments designed for traditional multi-incision laparoscopic surgery. A pilot study was conducted to determine which laparoscopic instruments were the most efficient for LESS procedures. In a LESS surgical trainer, 24 novice users completed a simple surgical task using standard (non-articulating) straight laparoscopic graspers and two different articulating instruments. Task performance was scored based on completion time and the number of errors. Analyses showed that the use of the simpler straight instruments produced significantly faster times (p = 0.004 and p = 0.014) and higher task scores (p = 0.005 and p = 0.021) than the articulating instruments. These results suggest that standard laparoscopic hand instruments enable better novice performance for a basic LESS task.

The importance of portal insulin delivery in the regulation of postprandial carbohydrate metabolism is uncertain. To address this question, three groups of dogs were studied: one group in which pancreatic venous drainage was transected and reanastomosed (portal insulin delivery), one in which the pancreatic drainage was transected and anastomosed to the inferior vena cava (peripheral insulin delivery), and one that received only a sham operation. Plasma insulin was greater (P < 0.05) during peripheral insulin delivery than in either the portal or sham groups, respectively, before and after meal ingestion. On the other hand, C-peptide concentrations did not differ between groups, resulting in a higher (P < 0.001) insulin to C-peptide ratio in the peripheral group. This indicated that the hyperinsulinemia in the peripheral group was due to decreased insulin clearance rather than increased insulin secretion. Isotopically determined splanchnic uptake of ingested glucose, postprandial suppression of hepatic glucose release, incorporation of CO2 into glucose (a qualitative measure of gluconeogenesis), and total-body glucose uptake were virtually identical in all groups. Similarly, plasma lipid, β-hydroxybutyrate, and lactate concentrations did not differ between groups. Our data indicate that, despite differences in systemic insulin concentration, portal and peripheral insulin delivery comparably regulate hepatic and extrahepatic carbohydrate metabolism after meal ingestion.

The use of charged-particle radiation therapy (CPRT) is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields (radiation oncology, medical physics, radiobiology, research ethics and methodology), including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research.

Objective Although the majority of high altitude studies have used doubly labeled water to assess energy expenditure (EE), minimal research has examined variation in intensity levels while participating in such an expedition. The purpose of this study was to use ambulatory monitoring technology to assess EE and time spent in moderate (3.0–6.0 METS), vigorous (6.0–9.0 METS), and very vigorous (>9.0 METS) intensities during an expedition to summit a 6170-m peak in Northern Pakistan. Methods Twelve men and 2 women were studied. Their EE was determined from galvanic skin response, heat flux, and biaxial accelerometry using a multisensor armband. Lake Louise Scores for altitude illness assessment were obtained each morning. Results Average daily total EE and number of steps taken was 4173 ± 848 kcal/d (range, 3332 to 4838 kcal/d) and 26,232 ± 7210 steps/d (range, 11,788 to 34,979 steps/d), respectively. On average, subjects spent approximately 7.7 h/d performing physical activity (>3.0 METS). Of this, subjects spent 399 ± 107, 61 ± 77, and 3 ± 10 min/d at moderate, vigorous, and very vigorous intensity levels, respectively, corresponding to 88%, 11%, and 1% of total physical activity time. During summit day, subjects climbed at an intensity equivalent to approximately 42% of their high altitude predicted maximal oxygen consumption at 5100 m). Conclusions During a high altitude expedition, subjects predominantly exercise at a moderate intensity, with limited time spent at higher intensity levels. Use of accelerometer-based technology may provide more cost-effective and logistically easier means of assessing EE in extreme environments.

The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD+/+) and manganese SOD heterozygous haploinsufficient (MnSOD+/−) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression. Haploinsufficiency of MnSOD did not alter antioxidant expression in aorta, but increased expression of Nox2. When compared with that of aorta, age-associated reductions in antioxidant expression were larger in aortic valves from wild-type and MnSOD haploinsufficient mice, although Nox2 expression was unchanged. Similarly, sirtuin expression was relatively well-preserved in aorta from both genotypes, whereas expression of SIRT1, SIRT2, SIRT3, SIRT4, and SIRT6 were significantly reduced in the aortic valve. Expression of p16ink4a, a marker of cellular senescence, was profoundly increased in both aorta and aortic valve from MnSOD+/+ and MnSOD+/− mice. Functionally, we observed comparable age-associated reductions in endothelial function in aorta from both MnSOD+/+ and MnSOD+/− mice. Interestingly, inhibition of NAD(P)H oxidase with apocynin or gp91ds-tat improved endothelial function in MnSOD+/+ mice but significantly impaired endothelial function in MnSOD+/− mice at both ages. Aortic valve function was not impaired by aging or MnSOD haploinsufficiency. Changes in antioxidant and sirtuin gene expression with aging differ dramatically between aorta and aortic valve. Furthermore, although MnSOD does not result in overt cardiovascular dysfunction with aging, compensatory transcriptional responses to MnSOD deficiency appear to be tissue specific.

ObjectiveTo identify new genetic associations with juvenile and adult dermatomyositis (DM).MethodsWe performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.ResultsCompared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.ConclusionOur findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.