Many genes are recruited to the nuclear periphery upon transcriptional activation in Saccharomyces cerevisiae. We have identified two Gene Recruitment Sequences (GRS I and II) from the promoter of the INO1 gene that target the gene to the nuclear periphery. These GRSs function as DNA zip codes; they are sufficient to target a nucleoplasmic locus to the nuclear periphery. Targeting requires components of the nuclear pore complex (NPC) and a GRS is sufficient to confer a physical interaction with the NPC. GRS I elements are enriched in promoters of genes that interact with the NPC and genes that are induced by protein folding stress. Full transcriptional activation of INO1 and another GRS-containing gene requires GRS-mediated targeting of the promoter to the nuclear periphery. Finally, GRS I also functions as a DNA zip code in Schizosaccharomyces pombe, suggesting that this mechanism of targeting to the nuclear periphery has been conserved over approximately one billion years of evolution.

Cement augmentation is a controversial treatment for painful vertebral compression fractures (VCF). Our research questions for the meta-analysis were: Is there a clinical and statistical difference in pain relief, functional improvement, and quality of life between conservative care and cement augmentation for VCF and, if so, are they maintained at longer time points? We conducted a search of MEDLINE from January 1980 to July 2011 using PubMed, Cochrane Database of Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Searches were performed from Medical Subject Headings. Terms ''vertebroplasty'' and ''compression fracture'' were used. The outcome variables of pain, functional measures, health-related quality of life (HRQOL), and new fracture risk were analyzed. A random effects model was chosen. Continuous variables were calculated using the standardized mean difference comparing improvement from baseline of the experimental group with the control group. New vertebral fracture risk was calculated using log odds ratio. Six studies met the criteria. The pain visual analog scale (VAS) mean difference was 0.73 (confidence interval [CI] 0.35, 1.10) for early (<12 weeks) and 0.58 (CI 0.19, 0.97) for late time points (6 to 12 months), favoring vertebroplasty (p < 0.001). The functional outcomes at early and late time points were statistically significant with 1.08 (CI 0.33, 1.82) and 1.16 (CI 0.14, 2.18), respectively. The HRQOL showed superior results of vertebroplasty compared with conservative care at early and late time points of 0.39 (CI 0.16, 0.62) and 0.33 (CI 0.16, 0.51), respectively. Secondary fractures were not statistically different between the groups, 0.065 (CI À0.57, 0.70). This meta-analysis showed greater pain relief, functional recovery, and health-related quality of life with cement augmentation compared with controls. Cement augmentation results were significant in the early (<12 weeks) and the late time points (6 to 12 months). This meta-analysis provides strong evidence in favor of cement augmentation in the treatment of symptomatic

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Use of spinal anesthesia (SA) in children may address concerns about potential neurocognitive effects of general anesthesia. We used near-infrared spectroscopy (NIRS) to assess the effects of SA on cerebral and tissue oxygenation in 19 patients aged 7 ± 3 months. Prior to SA placement, NIRS monitors were placed on the forehead (cerebral) and the thigh (tissue). Intraoperative cerebral and tissue saturation were 73 ± 7 and 80 ± 11%, respectively, before SA placement. NIRS measurements were monitored every minute for 30 min after SA placement and modeled using mixed-effects linear regression. Regression estimates showed that cerebral saturation remained stable from 67% [95% confidence interval (CI) 63, 71%] after SA placement to 68% (95% CI 65, 72%) at the conclusion of monitoring. After SA placement, tissue saturation was elevated compared to baseline values; but further change [from 91% (95% CI 89, 93%) to 93% (95% CI 91, 95%) at the end of monitoring] was clinically non-significant. All patients breathed spontaneously on room air without changes in oxygen saturation. Blood pressure and heart rate decreased after SA placement, but no changes in hemodynamic parameters required treatment. These data provide further evidence of the neutral effect of SA on cerebral oxygenation 30 min after block placement.

Patients with Duchenne muscular dystrophy (DMD) often have systemic manifestations with comorbid involvement of the cardiac and respiratory systems that increase the risk of anesthetic and perioperative morbidity. These patients frequently develop progressive myocardial involvement with cardiomyopathy, depressed cardiac function, and arrhythmias. The latter may necessitate the placement of an automatic implantable cardioverter defibrillator (AICD) insertion. As a means of avoiding the need for general anesthesia and its inherent potential of morbidity, regional anesthesia may be used in specific cases. We present two cases of successful AICD insertion in patients with DMD using unilateral pectoralis and intercostal nerve blocks supplemented with intravenous sedation. Relevant anatomy for this regional anesthetic technique is reviewed and benefits of this anesthetic technique compared to general anesthesia are discussed.

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IntroductionEpidural anesthesia is frequently used to provide postoperative analgesia following major surgical procedures. Secure fixation of the epidural catheter is necessary to prevent premature dislodgment and loss of epidural analgesia. Using an in vitro model, the current prospective study evaluates different types of dressings for securement of an epidural catheter by quantifying the force in Newtons (N) required for dislodgment using a digital force gage.MethodsFour methods of epidural catheter securement were used on a simulator mannequin: 1) Suresite® Window Clear Dressing, 2) Op-Site Post-Op® Visible Dressing, 3) Steri-Strips® and Suresite Window Clear Dressing, and 4) Steri-Strips and Op-Site Post-Op Visible Dressing. Each method of securement was assessed 10 times to calculate the mean force required to dislodge the catheter. Mean force of dislodgment for each method was compared using parametric tests.ResultsThe force (mean ± SD) required for catheter dislodgment for the four methods was 14.0±2.9, 2, 10.7±1.5, 8.6±2.3, and 9.6±2.2 N, respectively. The pairwise difference showed that the Suresite Window Clear Dressing was the best securement method when compared with other methods.ConclusionOur study demonstrates the advantage of the Suresite Window Clear Dressing in securing the epidural catheter. Future clinical trials are needed to validate these findings.

Background Niemann‐Pick disease type C is an autosomal‐recessive, lysosomal storage disorder with variable age of onset and a heterogeneous clinical presentation that includes neurological, psychiatric, and visceral findings. Serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin are being evaluated as a treatment modality for Niemann‐Pick disease type C with a subset of patients requiring anesthesia for this procedure. Aims The aim of this study was to evaluate the safety of anesthesia provided for patients undergoing intrathecal injection of 2‐hydroxypropyl‐beta‐cyclodextrin. Methods A retrospective review of pediatric patients who received serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin with anesthesia at two tertiary care centers was conducted from December 2015 through April 2019. Data were extracted for analysis included preoperative comorbidities, demographics, vital signs, intraoperative anesthesia course, airway management technique, venous access, postoperative course, and perioperative complications. In total, 19 patients were identified and a total of 394 anesthetic encounters were included in this study. Results All 394 2‐hydroxypropyl‐beta‐cyclodextrin administration procedures were successfully performed, and there were no changes made in the anesthetic plan during the anesthesia encounters. Three hundred forty‐nine anesthetics were performed utilizing inhalation induction and mask maintenance, and 45 anesthetics were performed with placement of a supraglottic airway device due to patient body habitus and provider preference. The incidence of a major adverse event (aspirations, arterial desaturation) was 5/394 (1.3%, 95% CI 0.05%‐3.1%). Minor adverse events (emesis, delirium, hypotension, seizure, and airway obstruction) were observed in 19/394 encounters (4.8%, 95% CI 3.0%‐7.5%). Conclusions Our findings suggest that general anesthesia induced via inhalation induction and maintained with volatile anesthetic via mask or supraglottic airway is a safe and effective option for pediatric patients with Niemann‐Pick disease type C undergoing serial intrathecal injections of 2‐hydroxypropyl‐beta‐cyclodextrin, supporting this technique as a viable option for anesthetic care in these patients.