An 18 year old male with an incompletely healed clavicle fracture presented with unexplained syncope. Subsequent investigations were consistent with a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). A subcutaneous implantable cardioverter-defibrillator (S-ICD) was successfully implanted and defibrillation threshold (DFT) testing performed as per standard protocol. Shortly following the procedure, the patient complained of pain and swelling over the left clavicle. A radiograph revealed aggravation and displacement of the underlying clavicle fracture. Surgical reduction and internal fixation was performed one week later. OBJECTIVES Comparison of outcomes, device deployment time (DT), and total time (TT) using a single tapered Coons dilator versus sequential serial dilation for implantation of the Micra leadless pacemaker. BACKGROUND Micra leadless pacemaker placement requires a 23 French Micra introducer sheath (MIS) for percutaneous delivery. We sought to evaluate outcomes with use of a single tapered Coons dilator (CD) versus sequential serial dilatation (SD) method to facilitate insertion of the Micra introducer sheath. METHODS 35 patients were included in the SD arm and 49 in the CD arm. DT and TT were recorded in minutes and cost in dollars. Analysis was performed using independent t-test between two groups and one-way ANOVA to evaluate inter-operator variability in the CD arm. RESULTS Both DT and TT were significantly lower for the CD arm (15.1 ± 5.1 vs 23.5 ± 9.3, p  less then  0.0005 and 29.9 ± 14 vs 39.3 ± 13.5 min, p = 0.000374; respectively). The cost was also significantly lower using a CD versus SD. There was no inter-operator variability in the CD arm between 6 operators (p = 0.177 for DT and p = 0.304 for TT). No complications occurred in the SD arm. There were 3 vascular access site complications in the CD arm, all of which occurred early in the operator’s experience. CONCLUSION Coons dilator is an efficient and cost-effective method for vascular dilatation to facilitate Micra leadless pacemaker insertion. Rate of complications is low and expected to improve with greater experience. Pesticides are widely-used chemicals commonly applied in agriculture for the protection of crops from pests. Selleck Linrodostat Depending on the class of pesticides, the specific substances may have a specific set of adverse effects on humans, especially in cases of acute poisoning. In past years, evidence regarding sequelae of chronic, low-level exposure has been accumulating. Cognitive impairment and dementia heavily affect a person’s quality of life and scientific data has been hinting towards an association between them and antecedent chronic pesticide exposure. Here, we reviewed animal and human studies exploring the association between pesticide exposure, cognition and dementia. Additionally, we present potential mechanisms through which pesticides may act neurotoxically and lead to neurodegeneration. Study designs rarely presented homogeneity and the estimation of the exposure to pesticides has been most frequently performed without measuring the synergic effects and the possible interactions between the toxicants within mixtures, and also overlooking low exposures to environmental toxicants. It is possible that a Real-Life Risk Simulation approach would represent a robust alternative for future studies, so that the safe exposure limits and the net risk that pesticides confer to impaired cognitive function can be examined. Previous studies that evaluated the effect of low dose chronic exposure to mixtures of pesticides and other chemicals intending to simulate real life exposure scenarios showed that hormetic neurobehavioral effects can appear after mixture exposure at doses considered safe for individual compounds and these effects can be exacerbated by a coexistence with specific conditions such as vitamin deficiency. However, there is an overall indication, derived from both epidemiologic and laboratory evidence, supporting an association between exposure to neurotoxic pesticides and cognitive dysfunction, dementia and Alzheimer’s disease. Ethylene oxide (EO), a carcinogenic chemical used as an industrial intermediate and sterilant, forms covalent adducts with DNA and proteins. The adduct with N-terminal valine [N-(2-hydroxyethyl)-l-valine, HEV] in blood protein globin has been employed as a principal biomarker of cumulative exposures to EO. However, as sampling of blood is inconvenient in routine occupational health practice, a non-invasive alternative to globin analysis has been investigated. Following identification of N-(2-hydroxyethyl)-l-valyl-l-leucine (HEVL) as ultimate cleavage product of EO-adducted globin excreted in the rat urine, here we report for the first time on the presence of HEVL in the urine of humans. In 18 sterilization workers, urinary HEVL ranged from 0.67 to 11.98 μg/g creatinine (mean ± SD 5.04 ± 3.14 μg/g creat) and correlated with HEV HEVL (μg/g creat) = 0.833 HEV (nmol/g globin) + 1.19 (R2 = 0.45). As unexpectedly high levels of urinary HEVL were found also in controls (mean ± SD 0.97 ± 0.37 μg/g creat, n = 32), HEVL is not proposed for the accurate assessment of sub-ppm exposures to EO. On the other hand, non-invasive sampling and facile work-up procedure predetermine HEVL for screening purposes to identify subjects approaching to or exceeding occupational exposure limit for EO (1.8 mg/m3) to be re-examined by the more sensitive reference analysis for HEV. Infantile hemangioma is one of the most common vascular tumors, which might result in morbidity and mortality without timely intervention. Propranolol is currently the first-line therapy for hemangiomas, but its potential side effects and high frequency of administration make it urgent to develop a suitable drug delivery system for propranolol. In the present study, we formulated a propranolol delivery system based on mesoporous silica nanoparticles (PRN@MSN) and investigated the interplay between autophagic activities mediated by nanoparticles and improved therapeutic efficacy of PRN@MSN. The results showed that PRN@MSN nanoparticles exhibited higher cytotoxicity compared with free propranolol in vitro and in vivo, which could induce excessive autophagosome accumulation through increased autophagosome formation and impaired autophagic degradation. Inhibition of autophagy in the early stage could attenuate the cytotoxicity of PRN@MSN. ROS generation was essential for nanoparticle-mediated autophagy and cytotoxicity, and PRN@MSN-induced autophagy dysfunction could enhance endoplasmic reticulum (ER) stress in hemangioma stem cells.