The effect of three-dimensional visualisation on performance in endoscopic sinus surgery:A clinical training study using surgical navigation for movement analysis in a randomised crossover design

Objectives: Endoscopic imaging techniques and endoscopic endonasal surgery (EES) expertise have evolved rapidly. Only few studies have assessed the effect of three-dimensional (3D) endoscopy on endoscopic sinus surgery (ESS). The present study aimed to objectively and subjectively assess the additional value of 3D high-definition (HD) endoscopy in ESS. Design: A randomized crossover study of endoscopic surgery performance, using five ESS tasks of varying complexity, performed on Thiel embalmed human specimens. Setting: Simulated surgical environment. Participants: Thirty participants, inexperienced in ESS. Main outcome measures: Performance was assessed using video imaging, surgical navigation and questionnaires. Main outcome measures were as follows: efficiency (defined by time to task completion), distance covered inside the nose, average velocity towards target, accuracy (measured by error rate), and subjective assessment of endoscope characteristics. Results: During ESS tasks, both efficiency and accuracy did not differ significantly between 2D HD and 3D HD endoscopy. Subjectively, imaging characteristics of the 3D HD endoscope were rated significantly better. Conclusions: ESS performance of inexperienced participants was not significantly improved by the use of 3D HD endoscopy during ESS tasks, although imaging characteristics of the 3D HD endoscope were rated significantly better. Surgical field characteristics and surgical techniques are likely to influence any additional value of 3D HD endoscopy

Characterization of the role of the Rab GTPase-activating protein AS160 in insulin-regulated GLUT4 trafficking

Insulin stimulates the translocation of the glucose transporter GLUT4 from intracellular vesicles to the plasma membrane. In the present study we have conducted a comprehensive proteomic analysis of affinity-purified GLUT4 vesicles from 3T3-L1 adipocytes to discover potential regulators of GLUT4 trafficking. In addition to previously identified components of GLUT4 storage vesicles including the insulin-regulated aminopeptidase insulin-regulated aminopeptidase and the vesicle soluble N-ethylmaleimide factor attachment protein (v-SNARE) VAMP2, we have identified three new Rab proteins, Rab10, Rab11, and Rab14, on GLUT4 vesicles. We have also found that the putative Rab GTPase-activating protein AS160 (Akt substrate of 160 kDa) is associated with GLUT4 vesicles in the basal state and dissociates in response to insulin. This association is likely to be mediated by the cytosolic tail of insulin-regulated aminopeptidase, which interacted both in vitro and in vivo with AS160. Consistent with an inhibitory role of AS160 in the basal state, reduced expression of AS160 in adipocytes using short hairpin RNA increased plasma membrane levels of GLUT4 in an insulin-independent manner. These findings support an important role for AS160 in the insulin regulated trafficking of GLUT4

Mitochondrial mutations and metabolic adaptation in pancreatic cancer.

BACKGROUND: Pancreatic cancer has a five-year survival rate of ~8%, with characteristic molecular heterogeneity and restricted treatment options. Targeting metabolism has emerged as a potentially effective therapeutic strategy for cancers such as pancreatic cancer, which are driven by genetic alterations that are not tractable drug targets. Although somatic mitochondrial genome (mtDNA) mutations have been observed in various tumors types, understanding of metabolic genotype-phenotype relationships is limited. METHODS: We deployed an integrated approach combining genomics, metabolomics, and phenotypic analysis on a unique cohort of patient-derived pancreatic cancer cell lines (PDCLs). Genome analysis was performed via targeted sequencing of the mitochondrial genome (mtDNA) and nuclear genes encoding mitochondrial components and metabolic genes. Phenotypic characterization of PDCLs included measurement of cellular oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using a Seahorse XF extracellular flux analyser, targeted metabolomics and pathway profiling, and radiolabelled glutamine tracing. RESULTS: We identified 24 somatic mutations in the mtDNA of 12 patient-derived pancreatic cancer cell lines (PDCLs). A further 18 mutations were identified in a targeted study of ~1000 nuclear genes important for mitochondrial function and metabolism. Comparison with reference datasets indicated a strong selection bias for non-synonymous mutants with predicted functional effects. Phenotypic analysis showed metabolic changes consistent with mitochondrial dysfunction, including reduced oxygen consumption and increased glycolysis. Metabolomics and radiolabeled substrate tracing indicated the initiation of reductive glutamine metabolism and lipid synthesis in tumours. CONCLUSIONS: The heterogeneous genomic landscape of pancreatic tumours may converge on a common metabolic phenotype, with individual tumours adapting to increased anabolic demands via different genetic mechanisms. Targeting resulting metabolic phenotypes may be a productive therapeutic strategy

Reproducibility of goniometric measurement of the knee in the in-hospital phase following total knee arthroplasty

<p>Abstract</p> <p>Background</p> <p>The objective of the present study was to assess interobserver reproducibility (in terms of reliability and agreement) of active and passive measurements of knee RoM using a long arm goniometer, performed by trained physical therapists in a clinical setting in total knee arthroplasty patients, within the first four days after surgery.</p> <p>Methods</p> <p>Test-retest analysis</p> <p>Setting: University hospital departments of orthopaedics and physical therapy</p> <p>Participants: Two experienced physical therapists assessed 30 patients, three days after total knee arthroplasty.</p> <p>Main outcome measure: RoM measurement using a long-arm (50 cm) goniometer</p> <p>Agreement was calculated as the mean difference between observers ± 95% CI of this mean difference. The intraclass correlation coefficient (ICC) was calculated as a measure of reliability, based on two-way random effects analysis of variance.</p> <p>Results</p> <p>The lowest level of agreement was that for measurement of passive flexion with the patient in supine position (mean difference 1.4°; limits of agreement 16.2° to 19° for the difference between the two observers. The highest levels of agreement were found for measurement of passive flexion with the patient in sitting position and for measurement of passive extension (mean difference 2.7°; limits of agreement -6.7 to 12.1 and mean difference 2.2°; limits of agreement -6.2 to 10.6 degrees, respectively). The ability to differentiate between subjects ranged from 0.62 for measurement of passive extension to 0.89 for measurements of active flexion (ICC values).</p> <p>Conclusion</p> <p>Interobserver agreement for flexion as well as extension was only fair. When two different observers assess the same patients in the acute phase after total knee arthroplasty using a long arm goniometer, differences in RoM of less than eight degrees cannot be distinguished from measurement error. Reliability was found to be acceptable for comparison on group level, but poor for individual comparisons over time.</p

Influence of Calendar Period on the Association Between BMI and Coronary Heart Disease: A Meta-Analysis of 31 Cohorts

Objective: The association between obesity and coronary heart disease (CHD) may have changed over time, for example due to improved pharmacological treatment of CHD risk factors. This meta-analysis of 31 prospective cohort studies explores the influence of calendar period on CHD risk associated with body mass index (BMI). Design and Methods: The relative risks (RRs) of CHD for a five-BMI-unit increment and BMI categories were pooled by means of random effects models. Meta-regression analysis was used to examine the influence of calendar period (>1985 v 1985) in univariate and multivariate analyses (including mean population age as a covariate). Results: The age, sex, and smoking adjusted RR (95% confidence intervals) of CHD for a five-BMI-unit increment was 1.28(1.22:1.34). For underweight, overweight and obesity, the RRs (compared to normal weight) were 1.11(0.91:1.36), 1.31(1.22:1.41), and 1.78(1.55:2.04), respectively. The univariate analysis indicated 31% (95%CI: 56:0) lower RR of CHD associated with a five-BMI-unit increment and a 51% (95%CI: 78: 14)) lower RR associated with obesity in studies starting after 1985 (n ¼ 15 and 10, respectively) compared to studies starting in or before 1985 (n ¼ 16 and 10). However, in the multivariate analysis, only mean population age was independently associated with the RRs for a five-BMI-unit increment and obesity ( 29(95%CI: 55: 5)) and 31(95%CI: 66:3), respectively) per 10-year increment in mean age). Conclusion: This study provides no consistent evidence for a difference in the association between BMI and CHD by calendar period. The mean population age seems to be the most important factor that modifies the association between the risk of CHD and BMI, in which the RR decreases with increasing age

Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

Genetic loci for body mass index (BMI) in adolescence and young adulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10−8) near FTO (P = 3.72 × 10−23), TMEM18 (P = 3.24 × 10−17), MC4R (P = 4.41 × 10−17), TNNI3K (P = 4.32 × 10−11), SEC16B (P = 6.24 × 10−9), GNPDA2 (P = 1.11 × 10−8) and POMC (P = 4.94 × 10−8) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10−5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different age

Green consumer segmentation: managerial and environmental implications from the perspective of business strategies and practices

With the new millennium, environmental concern entered a new phase, with stricter governmental regulations and incentives. Currently, within environmental issues, there is a broader challenge to commitment with economic and social goals. This is motivating companies and organizations to participate in transformation processes with the aim of minimizing the negative impacts of their activities. Within this context, new business philosophies, emerged empowering organizations to consider sustainability issues that have come to be viewed as an innovative and differentiating factor, providing competitive advantages (Fraj-Andres, MartinezSalinas, & Matute-Vallejo. Journal of Business Ethics, 88,263-286, 2009; Leipziger. The corporate responsibility code book. Greenleaf Publishing Limited, 2016; Leipziger. The corporate responsibility code book. Greenleaf Publishing Limited, 2016). Therefore, organizations have begun incorporating these concerns in their processes, adopting green management policies, and including green marketing strategies in order to remain competitive (Straughan & Roberts. Journal of Consumer Marketing, 16(6), 558-575, 1999; Rivera-Camino. European Journal of Marketing, 41, 1328-1358, 2007). From the marketing perspective, the importance of understanding green consumer behaviour in order to develop better segmentation and targeting strategies is highlighted. Green consumers are changing significantly. Consumers, although with some reluctance, are moving to greener products. The Mintel organization reported that the number of consumers buying green has tripled in recent years. Furthermore, it found that the number of consumers that never bought green products have decreased. These results show that widespread environmental awareness had an important role in purchasing behaviour, with more consumers considering the environmental impact of their buying decisions and looking for a greener alternative to their conventional purchasing options. The existing literature suggests that previous research regarding the green consumer profile has different perspectives. The first group of researchers attempted to characterize green consumer profile using sociodemographic variables such as age, gender, education, income and occupation. In tum, the second group of researchers used psychographic variables instead of sociodemographic ones (Mainieri, Barnett, Valdero, Unipan, & Oskamp. Journal of Social Psychology, 137(2), 189-204, 1997). This chapter aims to better explore the importance of green consumer segmentation and its implications from a management point of view. More specifically, the aim is to analyze which variables better characterize green consumers (sociodemographic and psychographic). At the end, a theoretical framework is proposed to enable and support organizations to better understand green consumer profile. It also enables managers and marketers to target and develop better marketing strategies for these segments.info:eu-repo/semantics/publishedVersio