Robotic surgery training: construct validity of Global Evaluative Assessment of Robotic Skills (GEARS)

The objective of this study is to determine the ability of the GEARS scale (Global Evaluative Assessment of Robotic Skills) to differentiate individuals with different levels of experience in robotic surgery, as a fundamental validation. This is a cross-sectional study that included three groups of individuals with different levels of experience in robotic surgery (expert, intermediate, novice) their performance were assessed by GEARS applied by two reviewers. The difference between groups was determined by Mann–Whitney test and the consistency between the reviewers was studied by Kendall W coefficient. The agreement between the reviewers of the scale GEARS was 0.96. The score was 29.8 ± 0.4 to experts, 24 ± 2.8 to intermediates and 16 ± 3 to novices, with a statistically significant difference between all of them (p < 0.05). All parameters from the scale allow discriminating between different levels of experience, with exception of the depth perception item. We conclude that the scale GEARS was able to differentiate between individuals with different levels of experience in robotic surgery and, therefore, is a validated and useful tool to evaluate surgeons in training.     

The Seventh Report of the Joint National Committee on Prevention,Detection, Evaluation,and Treatment of High Blood Pressure: the JNC 7 report

"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.     

Human monocytic ehrlichiosis

John H. Stone, MD, MPH; Kerry Dierberg; Ghazaleh Aram, MD; J. Stephen Dumler, MD

JAMA. 2004;292:2263-2270.

A 56-year-old man with a history of Wegener granulomatosis presented with 6 days of sinus congestion, fever, malaise, myalgias, episcleritis, and a morbilliform rash. An exacerbation of Wegener granulomatosis was the principal concern because of the frequency of flares in that disease. The patient developed acute renal failure, thrombocytopenia, transaminitis, and, finally, severe myocarditis that led to congestive heart failure. Additional history-taking and the evolution of his clinical features led to empirical treatment with doxycycline for human monocytic ehrlichiosis (HME). The diagnosis of HME was confirmed by both a polymerase chain reaction assay for Ehrlichia chaffeensis and by the demonstration of morulae within peripheral blood mononuclear cells. The patient improved promptly following institution of doxycycline, and his cardiac function returned to normal over a period of 4 months.

     

A lysolecithin/fatty acid mixture promotes and then blocks neurotransmitter release at the Drosophila melanogaster larval neuromuscular junction

The study of the effect of snake presynaptic neurotoxins with phospholipase A2 activity on nerve terminals has recently unveiled the inhibitory action of a lysophosphatidylcholine (LysoPC)/fatty acid mixture. We report here that these neurotoxins have no activity on Drosophila melanogaster nerve terminals. However, a 1:1 mixture of LysoPC and oleic acid induces an early increase, followed by an inhibition of both evoked and spontaneous neurotransmitter release. This effect is also induced by LysoPC alone. The present findings provide an indirect evidence that the lipid hemifusion-to-pore transition is a key event in neuroexocytosis in Drosophila. Moreover, these findings substantiate the use of LysoPC as a general agonist of membrane fusion at nerve terminals. This novel tool could contribute to the unraveling of the molecular steps involved in neuroexocytosis, particularly in Drosophila, where it is straightforward to combine it with electrophysiology and genetics.     

Enhanced Cellular Uptake of Oligonucleotides by EGF Receptor-Mediated Endocytosis in A549 Cells

Purpose. The goal of this study was to investigate the feasibility of utilizing epidermal growth factor (EGF) receptor-mediated endocytosis to enhance cellular uptake and targeting of oligonucleotides in epithelial cancer cells. To overcome the problem of endosomal entrappment associated with receptor-mediated delivery, we also examined the effects of two fusogenic peptides, polymyxin B and influenza HA2 peptide, for their capability to promote cytoplasmic delivery of oligonucleotides. Methods. A molecular conjugate consisting of EGF and poly-L-lysine (PL) was synthesized and complexed with 5′ fluorescently-labeled oligonucleotide. Cellular uptake of the complex in presence or absence of the fusogenic peptides was monitored fluorometrically. Microscopic studies were performed to visualize the intracellular distribution of the oligonucleotide. Results. Cells treated with the complex exhibited intracellular fluorescence intensity significantly enhanced over free oligonucleotide-treated controls. The uptake of the complex was shown to occur via the EGF receptor-mediated pathway. Fluorescence microscopic studies revealed cellular internalization of the complex, however, the complex appeared to be accumulated in endocytic vesicles. Exposure of the cells to complex in presence of HA2 peptide and polymyxin B resulted in a more diffused intracellular fluorescence pattern and a corresponding increase in fluorescence intensity. These results are consistent with the known fusion and destabilizing activities of the peptides. Conclusions. Since EGF receptors are overexpressed in many cancer cell types, the EGF-PL conjugate may potentially be used as an effective and selective delivery system to enhance uptake of oligonucleotides into cancer cells.     

Characteristics and anti-proliferative activity of azelaic acid and its derivatives entrapped in bilayer vesicles in cancer cell lines

The hydrophilicity and lipophilicity of azelaic acid (AA) were modified to diethyl azelate (DA) which was synthesized by Fisher esterification reaction and identified by IR, MS and ¹H NMR and to azelaic acid-β-cyclodextrin complex (AACD) which was prepared by inclusion complexation and identified by IR, DSC and XRD respectively. AA, DA and AACD were entrapped in liposomes and niosomes comprising of l-α-dipalmitoyl phosphatidylcholine (DPPC)/cholesterol at 7:3 molar ratio and Tween61/cholesterol at 1:1 molar ratio, respectively, using a thin-film hydration method with sonication. The size and morphology of these bilayer vesicles were determined by optical and transmission electron microscopy. The particle size was found to be in the range of 90–190 nm. The entrapment efficiency of AA, DA and AACD in all vesicular formulations was more than 80%, as analyzed by HPLC for AA and AACD, and GC for DA. Anti-proliferative activity of AA and its derivatives (DA and AACD) both entrapped and not entrapped in bilayer vesicles, using MTT assay in three cancer cell lines (HeLa, KB and B₁₆F₁₀) comparing with vincristine, were investigated. AACD showed the highest potency comparing to AA in HeLa, KB and B₁₆F₁₀ of 1.48, 1.6 and 1.5 times, respectively. AA entrapped in liposomes was about 90 times more potent than the free AA, and about 1.5 times less potent than vincristine. When entrapped in bilayer vesicles, DA and AACD were more effective than AA in killing cancer cells. AACD entrapped in liposomes gave the highest anti-proliferation activity in HeLa cell lines with the IC₅₀ of 2.3 and 327 times more potent than vincristine and AA, respectively. DA in liposomes demonstrated the IC₅₀ of 0.03 times less potent than vincristine in KB cell lines, while in B₁₆F₁₀ AACD in niosomes showed the IC₅₀ of 0.05 times less potent than vincristine. This study has suggested that the modification of AA by derivatization and complexation as well as the entrapment in bilayer vesicles can enhance its therapeutic efficacy.     

Suprapubic Fat Pad Excision with Simultaneous Placement of Inflatable Penile Prosthesis

Introduction

Many men suffering from erectile dysfunction are overweight with generous suprapubic fat pads, which often contribute to a decrease in visible exophytic phallic length.