Validation of a novel robotic-assisted partial nephrectomy surgical training model

What's known on the subject? and What does the study add? One area of particular growth for robotic surgery has been partial nephrectomy. Despite a perceived notion that robotic-assisted partial nephrectomy is more easily adaptable compared to laparoscopic partial nephrectomy, there is nonetheless an associated learning curve. Validated training models with a corresponding assessment method for robotic-assisted partial nephrectomy were previously unavailable. We have designed and validated a RAPN surgical model appropriate for resident and fellow training.

Debulking surgery in the setting of very high-risk prostate cancer scenarios

What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential.

Stem Cells From Umbilical Cord Wharton's Jelly From Preterm Birth Have Neuroglial Differentiation Potential

Objective:The aim of the study is to determine the neuroglial differentiation potential of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from preterm birth when compared to term delivery.Study Design:The WJ-MSCs from umbilical cords of preterm birth and term controls were isolated and induced into neural progenitors. The cells were analyzed for neuroglial markers by flow cytometry, real-time polymerase chain reaction, and immunocytochemistry. Results:Independent of gestational age, a subset of WJ-MSC displayed the neural progenitor cell markers Nestin and Musashi-1 and the mature neural markers microtubule-associated protein 2, glial fibrillary acidic protein, and myelin basic protein. Neuroglial induction of WJ-MSCs from term and preterm birth resulted in the enhanced transcription of Nestin and Musashi-1.Conclusions:Undifferentiated WJ-MSCs from preterm birth express neuroglial markers and can be successfully induced into neural progenitors similar to term controls. Their potential use as cellular graft in neuroregenerative therapy for peripartum brain injury in preterm birth has to be tested.

The chironomid-temperature relationship: expression in nature and palaeoenvironmental implications

Fossils of chironomid larvae (non-biting midges) preserved in lake sediments are well-established palaeotemperature indicators which, with the aid of numerical chironomid-based inference models (transfer functions), can provide quantitative estimates of past temperature change. This approach to temperature reconstruction relies on the strong relationship between air and lake surface water temperature and the distribution of individual chironomid taxa (species, species groups, genera) that has been observed in different climate regions (arctic, subarctic, temperate and tropical) in both the Northern and Southern hemisphere. A major complicating factor for the use of chironomids for palaeoclimate reconstruction which increases the uncertainty associated with chironomid-based temperature estimates is that the exact nature of the mechanism responsible for the strong relationship between temperature and chironomid assemblages in lakes remains uncertain. While a number of authors have provided state of the art overviews of fossil chironomid palaeoecology and the use of chironomids for temperature reconstruction, few have focused on examining the ecological basis for this approach. Here, we review the nature of the relationship between chironomids and temperature based on the available ecological evidence. After discussing many of the surveys describing the distribution of chironomid taxa in lake surface sediments in relation to temperature, we also examine evidence from laboratory and field studies exploring the effects of temperature on chironomid physiology, life cycles and behaviour. We show that, even though a direct influence of water temperature on chironomid development, growth and survival is well described, chironomid palaeoclimatology is presently faced with the paradoxical situation that the relationship between chironomid distribution and temperature seems strongest in relatively deep, thermally stratified lakes in temperate and subarctic regions in which the benthic chironomid fauna lives largely decoupled from the direct influence of air and surface water temperature. This finding suggests that indirect effects of temperature on physical and chemical characteristics of lakes play an important role in determining the distribution of lake-living chironomid larvae. However, we also demonstrate that no single indirect mechanism has been identified that can explain the strong relationship between chironomid distribution and temperature in all regions and datasets presently available. This observation contrasts with the previously published hypothesis that climatic effects on lake nutrient status and productivity may be largely responsible for the apparent correlation between chironomid assemblage distribution and temperature. We conclude our review by summarizing the implications of our findings for chironomid-based palaeoclimatology and by pointing towards further avenues of research necessary to improve our mechanistic understanding of the chironomid-temperature relationship.

Geographical partitioning of goat diversity in Europe and the Middle East

Thirty microsatellite markers were analysed in 1426 goats from 45 traditional or rare breeds in 15 European and Middle Eastern countries. In all populations inbreeding was indicated by heterozygosity deficiency (mean FIS = 0.10). Genetic differentiation between breeds was moderate with a mean FST value of 0.07, but for most (c. 71%) northern and central European breeds, individuals could be assigned to their breeds with a success rate of more than 80%. Bayesian-based clustering analysis of allele frequencies and multivariate analysis revealed at least four discrete clusters: eastern Mediterranean (Middle East), central Mediterranean, western Mediterranean and central/northern Europe. About 41% of the genetic variability among the breeds could be explained by their geographical origin. A decrease in genetic diversity from the south-east to the north-west was accompanied by an increase in the level of differentiation at the breed level. These observations support the hypothesis that domestic livestock migrated from the Middle East towards western and northern Europe and indicate that breed formation was more systematic in north-central Europe than in the Middle East. We propose that breed differentiation and molecular diversity are independent criteria for conservation.

Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study

OBJECTIVE: Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. METHODS: All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. RESULTS: Overall, 8,033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10-20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. CONCLUSION: During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol.

Hepatitis C virus and non-Hodgkin's lymphoma: Findings from the Swiss HIV Cohort Study

Infections with hepatitis C virus (HCV) and, possibly, hepatitis B virus (HBV) are associated with an increased risk of non-Hodgkin's lymphoma (NHL) in the general population, but little information is available on the relationship between hepatitis viruses and NHL among people with HIV (PHIV). We conducted a matched case-control study nested in the Swiss HIV Cohort Study (SHCS). Two hundred and ninety-eight NHL cases and 889 control subjects were matched by SHCS centre, gender, age group, CD4+ count at enrollment, and length of follow-up. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using logistic regression to evaluate the association between NHL and seropositivity for antibodies against HCV (anti-HCV) and hepatitis B core antigen (anti-HBc), and for hepatitis B surface antigen (HBsAg). Anti-HCV was not associated with increased NHL risk overall (OR = 1.05; 95% CI: 0.63-1.75), or in different strata of CD4+ count, age or gender. Only among men having sex with men was an association with anti-HCV found (OR = 2.37; 95% CI: 1.03-5.43). No relationships between NHL risk and anti-HBc or HBsAg emerged. Coinfection with HIV and HCV or HBV did not increase NHL risk compared to HIV alone in the SHCS.

Induction of apoptosis and enhancement of chemosensitivity in human prostate cancer LNCaP cells using bispecific antisense oligonucleotide targeting Bcl-2 and Bcl-xL genes

OBJECTIVE: To determine whether a specifically designed bispecific (Bcl-2/Bcl-xL) antisense oligonucleotide (ASO) induces apoptosis and enhances chemosensitivity in human prostate cancer LNCaP cells, as Bcl-2 and Bcl-xL are both anti-apoptotic genes associated with treatment resistance and tumour progression in many malignancies, including prostate cancer. MATERIALS AND METHODS: Inhibition of Bcl-2 and Bcl-xL expression by the bispecific ASO was evaluated using real-time reverse transcription-polymerase chain reaction and Western blotting, while growth inhibition and induction of apoptosis were analysed by a crystal violet assay, flow cytometry and Western blotting of apoptosis-relevant proteins. The effect of combined treatment with bispecific ASO and chemotherapy or small-interference RNA (siRNA) targeting the clusterin gene was also investigated. RESULTS: Bispecific ASO reduced Bcl-2 and Bcl-xL expression in LNCaP cells in a dose-dependent manner. There was cell growth inhibition, increases in the sub-G0-G1 fraction, and cleavage of caspase-3 and poly(ADP-Ribose) polymerase proteins in LNCaP cells after bispecific ASO treatment. Interestingly, Bcl-2/Bcl-xL bispecific ASO treatment also resulted in the down-regulation of Mcl-1 and up-regulation of Bax. The sensitivity of LNCaP cells to mitoxantrone, docetaxel or paclitaxel was significantly increased, reducing the 50% inhibitory concentration by 45%, 80% or 90%, respectively. Furthermore, the apoptotic induction by Bcl-2/Bcl-xL bispecific ASO was synergistically enhanced by siRNA-mediated inhibition of clusterin, a cytoprotective chaperone that interacts with and inhibits activated Bax. CONCLUSIONS: These findings support the concept of the targeted suppression of Bcl-2 anti-apoptotic family members using multitarget inhibition strategies for prostate cancer, through the effective induction of apoptosis.

Coronary artery stent geometry and in-stent contrast attenuation with 64-slice computed tomography

We aimed at assessing stent geometry and in-stent contrast attenuation with 64-slice CT in patients with various coronary stents. Twenty-nine patients (mean age 60 +/- 11 years; 24 men) with 50 stents underwent CT within 2 weeks after stent placement. Mean in-stent luminal diameter and reference vessel diameter proximal and distal to the stent were assessed with CT, and compared to quantitative coronary angiography (QCA). Stent length was also compared to the manufacturer's values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f) kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter was systematically underestimated with CT compared to QCA (1.60 +/- 0.39 mm versus 2.49 +/- 0.45 mm; P < 0.0001), resulting in a modest correlation of QCA versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was 18.2 +/- 6.2 mm, correlating well with CT (18.5 +/- 5.7 mm; r = 0.95; P < 0.0001) and QCA (17.4 +/- 5.6 mm; r = 0.87; P < 0.0001). Proximal and distal reference vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f kernel images showed higher image noise (P < 0.05) and lower in-stent CT attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64-slice CT allows measurement of coronary artery in-stent density, and significantly underestimates the true in-stent diameter compared to QCA.

Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women

AIMS: We sought to determine whether fasting or post-challenge glucose were associated with progression of coronary atherosclerosis in non-diabetic women. METHODS: We performed a post-hoc analysis of 132 non-diabetic women who underwent 75-g oral glucose tolerance testing. The primary outcome of interest was progression of atherosclerosis determined by baseline and follow-up coronary angiography, a mean of 3.1 +/- 0.9 years apart. We analysed the association of change in minimal vessel diameter (DeltaMD) by quartile of fasting and post-challenge glucose using mixed models that included adjustment for age, systolic blood pressure, total : high-density lipoprotein cholesterol ratio, current smoking, lipid-lowering and anti-hypertensive medication use and other covariates. RESULTS: At baseline, participants had a mean age of 65.7 +/- 6.7 years and a mean body mass index of 27.9 +/- 8.5 kg/m(2). Although there were no significant differences in atherosclerotic progression by fasting glucose category (P for trend across quartiles = 0.99), there was a significant inverse association between post-challenge glucose and DeltaMD (in mm) (Q1 : 0.01 +/- 0.03; Q2 : 0.08 +/- 0.03; Q3 : 0.13 +/- 0.03; Q4 : 0.11 +/- 0.03; P for trend = 0.02). CONCLUSIONS: In post-menopausal women without diabetes, post-challenge glucose predicts angiographic disease progression. These findings suggest that even modest post-challenge hyperglycaemia influences the pathogenesis of atherosclerotic progression.

Liver enzyme elevation after lamivudine withdrawal in HIV-hepatitis B virus co-infected patients: the Swiss HIV Cohort Study

Background The principal causes of liver enzyme elevation among HIV-hepatitis B virus (HBV) co-infected patients are the hepatotoxic effects of antiretroviral therapy (ART), alcohol abuse, ART-induced immune reconstitution and the exacerbation of chronic HBV infection. Objectives To investigate the incidence and severity of liver enzyme elevation, liver failure and death following lamivudine (3TC) withdrawal in HIV-HBV co-infected patients. Methods Retrospective analysis of the Swiss HIV Cohort Study database to assess the clinical and biological consequences of the discontinuation of 3TC. Variables considered for analysis included liver enzyme, HIV virological and immunological parameters, and medication prescribed during a 6-month period following 3TC withdrawal. Results 3TC was discontinued in 255 patients on 363 occasions. On 147 occasions (109 patients), a follow-up visit within 6 months following 3TC withdrawal was recorded. Among these patients, liver enzyme elevation occurred on 42 occasions (29%), three of them (2%) with severity grade III and five of them (3.4%) with severity grade IV elevations (as defined by the AIDS Clinical Trials Group). Three patients presented with fulminant hepatitis. One death (0.7%) was recorded. Conclusions HBV reactivation leading to liver dysfunction may be an under-reported consequence of 3TC withdrawal in HIV-HBV co-infected patients. Regular monitoring of HBV markers is warranted if active therapy against HBV is discontinued.