Comparative study of autofluorescence in flat and tapered optical fibers towards application in depth-resolved fluorescence lifetime photometry in brain tissue

As the scientific community seeks efficient optical neural interfaces with sub-cortical structures of the mouse brain, a wide set of technologies and methods is being developed to monitor cellular events through fluorescence signals generated by genetically encoded molecules. Among these technologies, tapered optical fibers (TFs) take advantage of the modal properties of narrowing waveguides to enable both depth-resolved and wide-volume light collection from scattering tissue, with minimized invasiveness with respect to standard flat fiber stubs (FFs). However, light guided in patch cords as well as in FFs and TFs can result in autofluorescence (AF) signal, which can act as a source of time-variable noise and limit their application to probe fluorescence lifetime in vivo. In this work, we compare the AF signal of FFs and TFs, highlighting the influence of the cladding composition on AF generation. We show that the autofluorescence signal generated in TFs has a peculiar coupling pattern with guided modes, and that far-field detection can be exploited to separate functional fluorescence from AF. On these bases, we provide evidence that TFs can be employed to implement depth-resolved fluorescence lifetime photometry, potentially enabling the extraction of a new set of information from deep brain regions, as time-correlating single photon counting starts to be applied in freely-moving animals to monitor the intracellular biochemical state of neurons.     

Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database

STUDY OBJECTIVES: To determine the effect of age and type of surgery on long-term survival in patients with early-stage non-small cell lung cancer (NSCLC). DESIGN AND PATIENTS: A total of 14,555 patients who were > or = 20 years of age with stage I or II primary NSCLC and had been registered in the Surveillance, Epidemiology, and End Results Database from 1992 to 1997 were analyzed. Age was grouped into the following three categories: < 65 years (n = 5,057; 35%); 65 to 74 years (n = 6,073; 42%); and > or = 75 years (n = 3,425; 23%). Log-rank tests and Cox regression models were used for crude and adjusted survival analyses. MEASUREMENTS AND RESULTS: A total of 8,080 men (55%) and 6,475 women (mean [+/- SD] age, 67.3 +/- 9.8 years) with stage I NSCLC (83%) or stage II NSCLC were analyzed. Curative surgery was performed in 4,669 patients (92%) who were < 65 years of age (youngest), 5,219 patients (86%) who were 65 to 74 years of age (intermediate age), and 2,382 patients (70%) who were > or = 75 years of age (elderly) [p < 0.0001]. Thirty percent of the elderly patients were denied surgery or were offered only palliative surgery, in contrast with 8% among the youngest patients (p < 0.0001). Limited resections increased from 8% in young patients to 17% in the elderly (p < 0.0001). Survival decreased with age. The median survival times were 71, 47, and 28 months, respectively, for patients < 65, 65 to 74, and > or = 75 years of age (p < 0.0001). The results were unchanged after adjusting for sex, type of surgery, histology, and stage of disease. For the young patients, lobectomies conferred better survival times than limited resections after 2 years. However, there was no difference in survival between lobectomies and limited resections in terms of survival time for the elderly patients. The statistical difference in long-term survival between those patients undergoing lobectomies and those undergoing limited resections disappeared at 71 years. CONCLUSIONS: Age is an independent predictor of postsurgical survival in NSCLC patients, even after adjustment for significant covariates. Curative surgery is performed less frequently in elderly patients. Among younger patients undergoing curative surgery, lobectomies are more commonly performed and confer a significant survival benefit over limited resections. This benefit, however, is not evident for patients > 71 years of age.     

Surpass Flow Diverter in the Treatment of Intracranial Aneurysms: A Prospective Multicenter Study

BACKGROUND AND PURPOSE:Incomplete occlusion and recanalization of large and wide-neck brain aneurysms treated by endovascular therapy remains a challenge. We present preliminary clinical and angiographic results of an experimentally optimized Surpass flow diverter for treatment of intracranial aneurysms in a prospective, multicenter, nonrandomized, single-arm study.MATERIALS AND METHODS:At 24 centers, 165 patients with 190 intracranial aneurysms of the anterior and posterior circulations were enrolled. The primary efficacy end point was the percentage of intracranial aneurysms with 100% occlusion on 6-month DSA. The primary safety end point was neurologic death and any stroke through a minimum follow-up of 6 months.RESULTS:Successful flow-diverter delivery was achieved in 161 patients with 186 aneurysms (98%); the mean number of devices used per aneurysm was 1.05. Clinical follow-up (median, 6 months) of 150 patients (93.2%), showed that the primary safety end point occurred in 18 subjects. Permanent neurologic morbidity and mortality were 6% and 2.7%, respectively. Morbidity occurred in 4% and 7.4% of patients treated for aneurysms of the anterior and posterior circulation, respectively. Neurologic death during follow-up was observed in 1.6% and 7.4% of patients with treated intracranial aneurysms of the anterior and posterior circulation, respectively. Ischemic stroke at ≤30 days, SAH at ≤7 days, and intraparenchymal hemorrhage at ≤7 days were encountered in 3.7%, 2.5%, and 2.5% of subjects, respectively. No disabling ischemic strokes at >30 days or SAH at >7 days occurred. New or worsening cranial nerve deficit was observed in 2.7%. Follow-up angiography available in 158 (86.8%) intracranial aneurysms showed 100% occlusion in 75%.CONCLUSIONS:Clinical outcomes of the Surpass flow diverter in the treatment of intracranial aneurysms show a safety profile that is comparable with that of stent-assisted coil embolization. Angiographic results showed a high rate of intracranial aneurysm occlusion.

Previous in vivo and in vitro hemodynamic experimental studies showed that optimization is required to balance the porosity (metal-free/metal area) and pore or mesh density (number of pores/mm²) of flow diverters (FDs) to optimize the effect on flow reduction within the aneurysm sac while keeping the side branches (perforators) patent.^1–6 We evaluated, in a multicenter, prospective, nonrandomized study, our hypothesis that a single optimized FD would suffice to obliterate a variety of aneurysms located in the anterior and posterior circulation without occluding perforators.     

Pharmacological characterization of mechanisms involved in the vasorelaxation produced by rosuvastatin in aortic rings from rats with a cafeteria‐style diet

The present study aimed to investigate the possible influence of several inhibitors and blockers on the vascular effect produced by the acute in vitro application of rosuvastatin to phenylephrine‐precontracted aortic rings from rats with a semi‐solid, cafeteria‐style (CAF) diet. It also aimed to examine the effects of rosuvastatin on the expression of endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase in aortic rings from rats with a CAF diet. From comparisons of the effect on phenylephrine‐precontracted aortic rings extracted from rats with two different diets (a standard and a CAF diet), it was found that 10^?9–10^?5‐mol/L rosuvastatin produced lower concentration‐dependent vasorelaxation on rings from the CAF diet group. The vasorelaxant effect was unaffected by the vehicle, but it was significantly attenuated by 10^?5‐mol/L N^G‐nitro‐l ‐arginine methyl ester, 10^?2‐mol/L tetraethylammonium, 10^?3‐mol/L 4‐aminopyridine, 10^?7‐mol/L apamin plus 10^?7‐mol/L charybdotoxin, 10^?5‐mol/L indomethacin, or 10^?5‐mol/L cycloheximide. Moreover, in aortic rings from rats with a CAF diet, rosuvastatin enhanced the expression of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase. The acute in vitro application of rosuvastatin to phenylephrine‐precontracted aortic rings from rats with a CAF diet had a vasorelaxant effect. Overall, the present results suggest that the stimulation of eNOS, the opening of Ca²⁺‐activated and voltage‐activated K⁺ channels, the stimulation of prostaglandin synthesis and enhanced protein levels of eNOS, inducible nitric oxide synthase, constitutive cyclooxygenase, and inducible cyclooxygenase are involved in this relaxant effect.     

Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial.

OBJECTIVES: This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Randomized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infarction in patients with stable angina during elective PCI; however, this therapy has not been tested in patients with ACS. METHODS: A total of 171 patients with non-ST-segment elevation ACS were randomized to pretreatment with atorvastatin (80 mg 12 h before PCI, with a further 40-mg preprocedure dose [n = 86]) or placebo (n = 85). All patients were given a clopidogrel 600-mg loading dose. All patients received long-term atorvastatin treatment thereafter (40 mg/day). The main end point of the trial was a 30-day incidence of major adverse cardiac events (death, myocardial infarction, or unplanned revascularization). RESULTS: The primary end point occurred in 5% of patients in the atorvastatin arm and in 17% of those in the placebo arm (p = 0.01); this difference was mostly driven by reduction of myocardial infarction incidence (5% vs. 15%; p = 0.04). Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group (7% vs. 27%, p = 0.001 and 41% vs. 58%, p = 0.039, respectively). At multivariable analysis, pretreatment with atorvastatin conferred an 88% risk reduction of 30-day major adverse cardiac events (odds ratio 0.12, 95% confidence interval 0.05 to 0.50; p = 0.004). CONCLUSIONS: The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy. These findings may support routine use of high-dose statins before intervention in patients with ACS.     

Cardiovascular mortality in Hispanics compared to non-Hispanic whites: A systematic review and meta-analysis of the Hispanic paradox

BackgroundHispanics, the largest minority in the U.S., have a higher prevalence of several cardiovascular (CV) risk factors than non-Hispanic whites (NHW). However, some studies have shown a paradoxical lower rate of CV events among Hispanics than NHW.ObjectiveTo perform a systematic review and a meta-analysis of cohort studies comparing CV mortality and all-cause mortality between Hispanic and NHW populations in the U.S.MethodsWe searched EMBASE, MEDLINE, Web of Science, and Scopus databases from 1950 through May 2013, using terms related to Hispanic ethnicity, CV diseases and cohort studies. We pooled risk estimates using the least and most adjusted models of each publication.ResultsWe found 341 publications of which 17 fulfilled the inclusion criteria; data represent 22,340,554 Hispanics and 88,824,618 NHW, collected from 1950 to 2009. Twelve of the studies stratified the analysis by gender, and one study stratified people by place of birth (e.g. U.S.-born, Mexican-born, and Central/South American-born). There was a statistically significant association between Hispanic ethnicity and lower CV mortality (OR 0.67; 95% CI, 0.57–0.78; p < 0.001), and lower all-cause mortality (0.72; 95% CI, 0.63–0.82; p < 0.001). A subanalysis including only studies that reported prevalence of CV risk factors found similar results. OR for CV mortality among Hispanics was 0.49; 95% CI 0.30–0.80; p-value < 0.01; and OR for all-cause mortality was 0.66; 95% CI 0.43–1.02; p-value 0.06.ConclusionThese results confirm the existence of a Hispanic paradox regarding CV mortality. Further studies are needed to identify the mechanisms mediating this protective CV effect in Hispanics.     

视黄醛联合透明质酸抗皮肤老化功效及安全性评价

目的:观察外用0.05%视黄醛联合0.5%及1%透明质酸片段对中国人面部皮肤抗老化的功效性和安全性.方法:采用多中心研究.将受试者分为3组,分别于整个面部使用含0.05%视黄醛+0.5%透明质酸片段制剂;于深皱纹区域使用含O.05%视黄醛+1%透明质酸片段制剂及两种制剂联合应用.经90d观察期,评估包括照片分级评分、面部肤色均匀度、皮肤干燥度、色素沉着、皮肤弹性及局部皱纹程度等多项老化指标,对2种外用制剂进行耐受性评估.结果:3组老化指标均有改善.照片分级评分降低,面部肤色均匀度改善,皮肤干燥度、色素沉着、皮肤弹性等皮肤老化体征均有改善.除1组受试者眉间纹外局部深皱纹程度均有改善.不良反应轻微.结论:视黄醛联合透明质酸片段外用可改善多种皮肤老化征象,安全有效.