Modular Total Synthesis of the 5/5-Spirocyclic Spiroindimicins.

Total syntheses of the 5/5-spirocyclic indoline alkaloids (±)-spiroindimicins B, C, D, E, F, and G have been achieved via a modular approach. Our route features direct coupling of halogenated pyrrolemetal and isatin partners, Suzuki coupling to append the indole unit, Lewis acid-mediated spirocyclization, and divergent functionalization to give various family members. These syntheses are concise (six or seven steps from commercial materials) and highly amenable to analogue synthesis.

Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome.

Background Right ventricular failure is a life-threatening postoperative complication after pericardiectomy. We conducted a retrospective study with a special emphasis on right ventricular failure. Methods Between June 1997 and September 2011, 69 patients underwent surgical pericardiectomy at our center. Mean age was 59 ( ± 15.5) years, and 49 (71%) patients were male. Causes of constrictive pericarditis included idiopathic (52%, n = 36), tuberculosis (9%, n = 6), postcardiotomy (12%, n = 8), radiation (4%, n = 3), renal insufficiency (12%, n = 8), and autoimmune disease (12%, n = 8). Concomitant cardiac surgery was performed in 33 (48%) patients. Results In-hospital mortality rate was 14% (10/69 patients). Extracorporeal membrane oxygenation (ECMO) was necessary in 8 (12%) cases because of right (n = 7) or biventricular (n = 1) failure. Statistical analysis showed a significant correlation between early mortality and the following preoperative variables: postcardiotomy (p = 0.049), radiation (p = 0.009), pleural effusion (p = 0.012), ascites (p = 0.039), hepatic congestion (p = 0.023), absence of calcification on X-ray (p = 0.041), tricuspid valve insufficiency (TI, p < 0.001), and low cardiac index (p = 0.003). Diuretic usage (p = 0.044), peripheral edema (p = 0.050), low voltage (p = 0.027), dip-plateau sign (p = 0.027), elevated GGT (p < 0.001), and decreased serum protein (p < 0.001) correlated with ECMO implantation. Binary logistic regression identified pleural effusion (OR = 16.2, 95% CI = 1.4-191.5), moderate/severe TI (OR = 28.8, 95% CI = 2.7-306.8) and low cardiac index (OR = 25.3, 95% CI = 2.0-315.6) as preoperative independent risk factors for early mortality, whereas elevated GGT (OR = 28.3, 95% CI = 2.4-329.2) and decreased protein (OR = 24.7, 95% CI = 1.8-343.7) could predict right ventricular failure with the need for ECMO. Conclusion We recommend nondelayed ECMO support in case of significant postoperative right-sided heart failure. High-risk patients might benefit from elective pre- or intraoperative ECMO implantation.

Simulated car driving in fMRI--Cerebral activation patterns driving an unfamiliar and a familiar route.

Understanding the neuronal underpinnings of cognitive processes during car driving is essential to understanding the origin of automobile accidents. Using fMRI we aimed to reveal differences in activation distribution contrasting passively observing an unfamiliar versus a familiar route to analyse the importance of the degree of familiarity of a route on attention process. We developed a special driving simulation software known as "Mechanics & Traffic", which focuses on the physical properties of driving. Sixteen male police-academy students with special driving training were examined while passively watching the car on an unfamiliar route, following a training-period outside the scanner, and passively watching the car on the now familiar route. The driving task revealed activations in frontal, parietal, temporal, occipital lobes, the thalamus, and cerebellum. Direct comparison revealed significant activation for the unfamiliar route in the middle temporal and occipital cortex and in the cerebellum. Correlating activations with the influencing covariates of driving experience, the activation pattern was confirmed and an additional activation for the unfamiliar route was found in the inferior frontal and parahippocampal gyrus. The results give further evidence that driving a car is a complex cognitive skill. A training-period and a familiar, monotonous route seem to lead to a reduction in attention and perception processes which might be associated with a danger for commuters, even in specially trained drivers.