The Ins and Outs of miRNA-Mediated Gene Silencing during Neuronal Synaptic Plasticity

Neuronal connections through specialized junctions, known as synapses, create circuits that underlie brain function. Synaptic plasticity, i.e., structural and functional changes to synapses, occurs in response to neuronal activity and is a critical regulator of various nervous system functions, including long-term memory formation. The discovery of mRNAs, miRNAs, ncRNAs, ribosomes, translational repressors, and other RNA binding proteins in dendritic spines allows individual synapses to alter their synaptic strength rapidly through regulation of local protein synthesis in response to different physiological stimuli. In this review, we discuss our understanding of a number of miRNAs, ncRNAs, and RNA binding proteins that are emerging as important regulators of synaptic plasticity, which play a critical role in memory, learning, and diseases that arise when neuronal circuits are impaired

Laparoscopic Appendectomy Outcomes on the Weekend and During the Week are no Different: A National Study of 151,774 Patients

Background: The "weekend effect” is defined as increased morbidity and mortality for patients admitted on weekends compared with weekdays. It has been observed for several diseases, including myocardial infarction and renal insufficiency; however, it has not yet been investigated for laparoscopic appendectomy in acute appendicitis—one of the most prevalent surgical diagnoses. Methods: The present study is based on the Nationwide Inpatient Sample (NIS) from 1999 to 2008. The following outcomes were compared between patients undergoing laparoscopic appendectomy for acute appendicitis admitted on weekdays versus weekends: severity of appendicitis, intraoperative and postoperative complications, conversion rate, in-hospital mortality, and length of hospital stay. Unadjusted and risk-adjusted generalized linear regression analyses were performed. Results: Overall, 151,774 patients were included, mean age was 39.6years, 52.6% (n=79,801) were male, and 25.3% (n=38,317) were admitted on weekends. After risk adjustment, the conversion rate was lower [odds ratio (OR): 0.94, p=0.004, number needed to harm (NNH): 244], whereas pulmonary complications (OR: 1.12, p=0.028, NNH: 649) and reoperations (OR: 1.21, p=0.013, NNH: 1,028) were slightly higher on weekends than on weekdays. Overall postoperative complications (OR: 1.03, p=0.24), mortality (OR: 1.37, p=0.075) and length of hospital stay (mean on weekday: 2.00days, weekends: 2.01days, p=0.29) were not statistically different. Conclusions: The present investigation provides evidence that no clinically significant "weekend effect” for patients undergoing laparoscopic appendectomy exists. Therefore, hospital or staffing policy changes are not justified based on the findings from this large national stud

Cholecystectomy Concomitant with Laparoscopic Gastric Bypass: A Trend Analysis of the Nationwide Inpatient Sample from 2001 to 2008

Background: Gallstone formation is common in obese patients, particularly during rapid weight loss. Whether a concomitant cholecystectomy should be performed during laparoscopic gastric bypass surgery is still contentious. We aimed to analyze trends in concomitant cholecystectomy and laparoscopic gastric bypass surgery (2001-2008), to identify factors associated with concomitant cholecystectomy, and to compare short-term outcomes after laparoscopic gastric bypass with and without concomitant cholecystectomy. Methods: We used data from adults undergoing laparoscopic gastric bypass for obesity from the Nationwide Inpatient Sample. The Cochran-Armitage trend test was used to assess changes over time. Unadjusted and risk-adjusted generalized linear models were performed to assess predictors of concomitant cholecystectomy and to assess postoperative short-term outcomes. Results: A total of 70,287 patients were included: mean age was 43.1years and 81.6% were female. Concomitant cholecystectomy was performed in 6,402 (9.1%) patients. The proportion of patients undergoing concomitant cholecystectomy decreased significantly from 26.3% in 2001 to 3.7% in 2008 (p for trend < 0.001). Patients who underwent concomitant cholecystectomy had higher rates of mortality (unadjusted odds ratios [OR], 2.16; p = 0.012), overall postoperative complications (risk-adjusted OR, 1.59; p = 0.001), and reinterventions (risk-adjusted OR, 3.83; p < 0.001), less frequent routine discharge (risk-adjusted OR, 0.70; p = 0.05), and longer adjusted hospital stay (median difference, 0.4days; p < 0.001). Conclusions: Concomitant cholecystectomy and laparoscopic gastric bypass surgery have decreased significantly over the last decade. Given the higher rates of postoperative complications, reinterventions, mortality, as well as longer hospital stay, concomitant cholecystectomy should only be considered in patients with symptomatic gallbladder diseas

Cost performance and risk in the construction of offshore and onshore wind farms

This article investigates the risk of cost overruns and underruns occurring in the construction of 51 onshore and offshore wind farms commissioned between 2000 and 2015 in 13 countries. In total, these projects required about $39 billion in investment and reached about 11 GW of installed capacity. We use this original dataset to test six hypotheses about construction cost overruns related to (i) technological learning, (ii) fiscal control, (iii) economies of scale, (iv) configuration, (v) regulation and markets and (vi) manufacturing experience. We find that across the entire dataset, the mean cost escalation per project is 6.5$63 million per windfarm, although 20 projects within the sample (39%) did not exhibit cost overruns. The majority of onshore wind farms exhibit cost underruns while for offshore wind farms the results have a larger spread. Interestingly, no significant relationship exists between the size (in total MWor per individual turbine capacity) of a windfarm and the severity of a cost overrun. Nonetheless, there is an indication that the risk increases for larger wind farms at greater distances offshore using new types of turbines and foundations. Overall, the mean cost escalation for onshore projects is 1.7% and 9.6% for offshore projects, amounts much lower than those for other energy infrastructure

Mouse models of nesprin-related diseases

Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression. Over 80 disease-related variants have been identified in SYNE-1/2 (nesprin-1/2) genes, which result in muscular or central nervous system disorders including autosomal dominant Emery–Dreifuss muscular dystrophy, dilated cardiomyopathy and autosomal recessive cerebellar ataxia type 1. To date, 17 different nesprin mouse lines have been established to mimic these nesprin-related human diseases, which have provided valuable insights into the roles of nesprin and its scaffold LINC complex in a tissue-specific manner. In this review, we summarise the existing nesprin mouse models, compare their phenotypes and discuss the potential mechanisms underlying nesprin-associated diseases