Although simvastatin (SIM) has been proven to be a powerful agent against myocardial ischemia/reperfusion (MI/R) injury, poor water solubility, short half-life, and low bioavailability have made it futile while using conventional drug delivery system. Hence, this study aims to investigate therapeutic efficacy of SIM-loaded nano-niosomes on MI/R injury. Surface active agent film hydration method was used to synthesize nano-niosomes. The physicochemical properties of nano-niosomes were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, niosomes were characterized in entrapment efficiency (EE) and releasing pattern. Male Wistar rats were assigned into five groups (sham, MI/R, SIM, nano-niosomes, and SIM-loaded nano-niosomes). To induce MI/R, left thoracotomy was performed along mid-axillary line. The LAD ligation lasted for 45 min. A single dose (3 mg/kg) of drug formulations was injected into myocardial. Echocardiography was performed to evaluate cardiac function. The expression of the necroptosis markers was evaluated using western blot assay. Particle size of only nano-niosomes was about 137 nm, whereas a shift to 163 nm was observed in nano-niosomes containing SIM. Optimized niosomes were achieved by span 80, drug to cholesterol ratio of 0.4 with 7-min sonication time. EE of optimized nano-niosomes containing SIM was 98.21%. The effects of nano-niosomes containing on improving cardiac function and inhibiting necroptosis pathway was more efficient than the SIM group. Our findings have suggested that nano-niosomes can be applied as a notable drug delivery method to augment stability, bioavailability, and therapeutic efficacy of SIM, when it used against myocardial I/R injury.Radiofrequency ablation (RFA) has emerged as a new treatment for primary aldosteronism owing to aldosterone-producing adenoma (APA). We aimed to compare the perioperative outcomes and safety of RFA and laparoscopic adrenalectomy (LA) for patients with APA. We searched PubMed, EMBASE, and the Cochrane Library for all literatures published from January 2001 to September 2020 to compare RFA with LA for APA. PRT543 research buy After data extraction and quality assessments, we used Review Manager 5.4.1 and STATA 14.0 to pool the data. Four retrospective studies consisting of 170 patients were obtained. Patients who underwent RFA were associated with shorter operative time (standard mean difference (SMD) -1.98, 95% confidence interval (CI) -3.86 to 0.11, P = 0.04), less intraoperative blood loss (SMD -0.61, 95% CI -0.96 to -0.26, P = 0.0007), and shorter hospital stay (weight mean difference (WMD) -1.40, 95% CI -1.71 to -1.10, P  less then  0.00001) than those who underwent LA. No significant differences were found in the complication rate (odds ratio (OR) 0.67, 95% CI 0.27-1.68, P = 0.39), the incidence of hypertensive crisis (OR 3.16, 95% CI 0.36-27.94, P = 0.30), the conversion rate (OR 0.44, 95% CI 0.04-4.32, P = 0.48) or the treatment success rate (OR 0.72, 95% CI 0.22-2.39, P = 0.59) between the two groups. RFA could achieve clinical outcomes that approach LA for patients with APA but result in shorter operative time, less intraoperative blood loss, and shorter hospital stay. However, RFA does not appear to be able to replace the LA. Future prospective randomized trials are needed to validate these results.The National Institutes of Health Stroke Scale (NIHSS) is commonly used to evaluate stroke neurological deficits and to predict the patient's outcome. Neurological instability (NI), defined as the variation of the NIHSS in the first 48 h, is a simple clinical metric that reflects dynamic changes in the area of the brain affected by the ischemia. We hypothesize that NI may represent areas of cerebral instability known as penumbra, which could expand or reduce brain injury and its associated neurological sequels. In this work, our aim was to analyze the association of NI with the functional outcome at 3 months and to study clinical biomarkers associated to NI as surrogate biomarkers of ischemic and inflammatory penumbrae in ischemic stroke (IS) patients. We included 663 IS patients in a retrospective observational study. Neutral NI was defined as a variation in the NI scale between - 5 and 5% (37.1%). Positive NI is attributed to patients with an improvement of > 5% NI after 48 h (48.9%), while negative NI is aency times, decreasing at higher latency times. An opposite trend was observed for inflammation, and IL6 levels were similar in patients with positive and negative NI in the first 6 h and then higher in patients with negative NI. These results support NI as a prognosis factor in IS and the hypothesis of the existence of a delayed inflammatory penumbra, opening up the possibility of extending the therapeutic window for IS.Because of enhanced life expectancy due to medical and surgical therapeutic advances, it is estimated that there are more adults than children living with Down syndrome (DS), or trisomy 21, in the United States. Therefore, DS can no longer be considered a syndrome limited to the pediatric population. These patients are presenting for surgery and anesthesia in adult care settings, where anesthesiologists will encounter these patients more frequently. As these patients age, their commonly associated co-morbidities not only progress, but they also develop other cardiac, respiratory, gastrointestinal, and neurologic conditions. The manifestations and consequences of chronic disease can present new challenges for the anesthesiologist and require expertise and judgement to minimize patient risk. The purpose of this narrative review is to describe the common pediatric co-morbidities associated with DS and discuss the age-acquired manifestations. Additionally, considerations for anesthetic care of the adult with DS will be presented, including the preoperative assessment, intraoperative management, and postoperative care.Presence of pseudogenes is a dreadful issue in next generation sequencing (NGS), because their contamination can interfere with the detection of variants in the genuine gene and generate false positive and false negative variants.In this chapter we focus on issues related to the application of NGS strategies for analysis of genes with pseudogenes in a clinical setting. The degree to which a pseudogene impacts the ability to accurately detect and map variants in its parent gene depends on the degree of similarity (homology) with the parent gene itself. Hereby, target enrichment and mapping strategies are crucial factors to avoid "contaminating" pseudogene sequences. For target enrichment, we describe advantages and disadvantages of PCR- and capture-based strategies. For mapping strategies, we discuss crucial parameters that need to be considered to accurately distinguish sequences of functional genes from pseudogenic sequences. Finally, we discuss some examples of genes associated with Mendelian disorders, for which interesting NGS approaches are described to avoid interference with pseudogene sequences.