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We report on the present status of the Lawrence Livermore AMS spectrometer, including sample throughput and progress towards routine 1% measurement capability for 14C, first results on other isotopes and experience with a multisample high-intensity ion source.

Background: High doses and prolonged duration of opioids are associated with tolerance, dependence, and increased mortality. Unfortunately, despite recent efforts to curb outpatient opioid prescribing because of the ongoing epidemic, utilization remains high in the intensive care setting, with intubated patients commonly receiving infusions with a potency much higher than doses required to achieve pain control. We attempted to use implementation science techniques to monitor and reduce excessive opioid prescribing in ventilated patients in our surgical intensive care unit (SICU)., Methods: We conducted a prospective study investigating opioid administration in a closed SICU at an academic medical center over 18 months. Commonly accepted conversions were used to aggregate daily patient opioid use. Patients with a history of chronic opioid use and those being treated with an intracranial pressure monitor/drain, neuromuscular blocker, or extracorporeal membrane oxygenation were excluded. If the patient spent a portion of a day on a ventilator, that day's total was included in the "vent group." morphine milligram equivalents per patient were collected for each patient and assigned to the on-call intensivist. Intensivists were blinded to the data for the first 7 months. They were then provided with academic detailing followed by audit and feedback over the subsequent 11 months, demonstrating how opioid utilization during their time in the SICU compared with the unit average and a blinded list of the other attendings. Student's t tests were performed to compare opioid utilization before and after initiation of academic detailing and audit and feedback., Results: Opioid utilization in patients on a ventilator decreased by 20.1% during the feedback period, including less variation among all intensivists and a 30.9% reduction by the highest prescribers., Conclusion: Implementation science approaches can effectively reduce variation in opioid prescribing, especially for high outliers in a SICU. These interventions may reduce the risks associated with prolonged use of high-dose opioids., Level of Evidence: Therapeutic/Care Management; Level II., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Simulation offers a mechanism for scaffolded learning in a safe environment and affords opportunities for students to integrate nursing knowledge, skills, and behaviors into patient care activities. Faculty applied a structured change model and utilized simulation theory and the AACN Essentials framework for competency-based education to integrate simulation across the pre-licensure curriculum at a large school of nursing. A series of clinical learning activities were implemented including one revised scenario, a computer-based simulation adapted from an existing manikin-based activity, and a multi-patient simulation developed by modifying three textbook publisher simulation resources. Students were provided with opportunities to develop competencies across multiple Essentials domains, and congruence between course and simulation objectives was achieved. The purpose of this article is to describe the processes and outcomes of a faculty-driven effort to advance competency-based education in baccalaureate nursing curricula., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Arterioles are key determinants of the total peripheral vascular resistance, which, in turn, is a key determinant of arterial blood pressure. However, the amount of protein available from one isolated human arteriole may be less than 5 μg, making proteomic analysis challenging. In addition, obtaining human arterioles requires manual dissection of unfrozen clinical specimens. This limits its feasibility, especially for powerful multicenter clinical studies in which clinical specimens need to be shipped overnight to a research laboratory for arteriole isolation. We performed a study to address low-input, test overnight tissue storage and develop a reference human arteriolar proteomic profile. In tandem mass tag proteomics, use of a booster channel consisting of human induced pluripotent stem cell-derived endothelial and vascular smooth muscle cells (1:5 ratio) increased the number of proteins detected in a human arteriole segment with a false discovery rate of <0.01 from 1051 to more than 3000. The correlation coefficient of proteomic profile was similar between replicate arterioles isolated freshly, following cold storage, or before and after the cold storage (1-way analysis of variance; P = .60). We built a human arteriolar proteomic profile consisting of 3832 proteins based on the analysis of 12 arteriole samples from 3 subjects. Of 1945 blood pressure-relevant proteins that we curated, 476 (12.5%) were detected in the arteriolar proteome, which was a significant overrepresentation (χ 2 test; P < .05). These findings demonstrate that proteomic analysis is feasible with arterioles isolated from human adipose tissue following cold overnight storage and provide a reference human arteriolar proteome profile highly valuable for studies of arteriole-related traits., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Empathy is a desired characteristic in nurses, but its development is often overlooked in nursing simulation., Purpose: This study evaluated the effect of a storytelling and empathy training intervention to enhance empathy development in simulation-based learning., Methods: A quasi-experimental control group design was used to evaluate differences in self-perceived and observed empathy in undergraduate nursing students (N = 71). Relationships between self-perceived and observed empathy were also assessed., Results: Repeated-measures analysis of variance revealed a statistically significant increase in self-perceived empathy, and higher, but nonstatistically significant differences in observed empathy for subjects in the treatment condition. No relationship between self-perceived and observed empathy was observed., Conclusions: Storytelling and empathy training may augment simulation-based learning experiences to promote empathy development in undergraduate nursing students., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest Archer Kilbourne Martin, MD, serves on the Scientific Advisory Board of Attgeno AB, a privately held pharmaceutical company.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Competing Interests: The authors declare no conflicts of interest.

In New Jersey, a statewide nurse residency program was implemented using an apprenticeship model. The pandemic created disruption to registered nurse residency programs. This included rapid restructuring of program delivery to online methods and a need to adapt curricula to reflect changing practice and guidelines. As a result of the pandemic, new graduates had educational gaps and nurse leaders experienced staffing shortages. First year program outcomes demonstrated a 90% retention of new graduates and financial benefits for organizations participating in the statewide nurse residency program., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Many schools of nursing were not prepared to transition to remote instruction during the COVID-19 pandemic. Virtual and computer-based simulation can offer a substitution for in-person clinical learning. This article describes the use of storyboards, created by faculty, to provide context during remote clinical experiences. The theoretical basis for the design and implementation of the activity is discussed. Faculty observations of student behaviors (i.e., clinical decision-making, reflection on performance, and engagement) were consistent between computer-based and laboratory-based simulation settings., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2021 National League for Nursing.)

Background: Epigenetic marks (eg, DNA methylation) may capture the effect of gene-environment interactions. DNA methylation is involved in blood pressure (BP) regulation and hypertension development; however, no studies have evaluated its relationship with 24-hour BP phenotypes (daytime, nighttime, and 24-hour average BPs)., Methods: We examined the association of whole blood DNA methylation with 24-hour BP phenotypes and clinic BPs in a discovery cohort of 281 Blacks participants using reduced representation bisulfite sequencing. We developed a deep and region-specific methylation sequencing method, Bisulfite ULtrapLEx Targeted Sequencing and utilized it to validate our findings in a separate validation cohort (n=117)., Results: Analysis of 38 215 DNA methylation regions (MRs), derived from 1 549 368 CpG sites across the genome, identified up to 72 regions that were significantly associated with 24-hour BP phenotypes. No MR was significantly associated with clinic BP. Two to 3 MRs were significantly associated with various 24-hour BP phenotypes after adjustment for age, sex, and body mass index. Together, these MRs explained up to 16.5% of the variance of 24-hour average BP, while age, sex, and BMI explained up to 11.0% of the variance. Analysis of one of the MRs in an independent cohort using Bisulfite ULtrapLEx Targeted Sequencing confirmed its association with 24-hour average BP phenotype., Conclusions: We identified several MRs that explain a substantial portion of variances in 24-hour BP phenotypes, which might be excellent markers of cumulative effect of factors influencing 24-hour BP levels. The Bisulfite ULtrapLEx Targeted Sequencing workflow has potential to be suitable for clinical testing and population screenings on a large scale.

The Institute of Medicine recommends residency programs be implemented for new graduates across all settings, yet hospitals have not consistently hardwired this into their organizations. The value proposition is in recruitment, retention, and the conservation of resources. New Jersey's experiences using the US Department of Labor apprenticeship model for nurse residency programs provides a strategy that can be implemented on a statewide basis., Competing Interests: Funding was provided by the New Jersey Department of Labor and Workforce Development, Office of Apprenticeship, Growing Apprenticeships in Nontraditional Sectors (GAINS) grant, March 14, 2020, to August 31, 2021. E.O. is employed by Vizient, Inc., and owner of Vizient/AACN Nurse Residency Program. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

[Figure: see text].

Purpose of Review: Cardiovascular toxicity is a leading cause of mortality among cancer survivors and has become increasingly prevalent due to improved cancer survival rates. In this review, we synthesize evidence illustrating how common cancer therapeutic agents, such as anthracyclines, human epidermal growth factors receptors (HER2) monoclonal antibodies, and tyrosine kinase inhibitors (TKIs), have been evaluated in cardiomyocytes (CMs) derived from human-induced pluripotent stem cells (hiPSCs) to understand the underlying mechanisms of cardiovascular toxicity. We place this in the context of precision cardio-oncology, an emerging concept for personalizing the prevention and management of cardiovascular toxicities from cancer therapies, accounting for each individual patient's unique factors. We outline steps that will need to be addressed by multidisciplinary teams of cardiologists and oncologists in partnership with regulators to implement future applications of hiPSCs in precision cardio-oncology., Recent Findings: Current prevention of cardiovascular toxicity involves routine screenings and management of modifiable risk factors for cancer patients, as well as the initiation of cardioprotective medications. Despite recent advancements in precision cardio-oncology, knowledge gaps remain and limit our ability to appropriately predict with precision which patients will develop cardiovascular toxicity. Investigations using patient-specific CMs facilitate pharmacological discovery, mechanistic toxicity studies, and the identification of cardioprotective pathways. Studies with hiPSCs demonstrate that patients with comorbidities have more frequent adverse responses, compared to their counterparts without cardiac disease. Further studies utilizing hiPSC modeling should be considered, to evaluate the impact and mitigation of known cardiovascular risk factors, including blood pressure, body mass index (BMI), smoking status, diabetes, and physical activity in their role in cardiovascular toxicity after cancer therapy. Future real-world applications will depend on understanding the current use of hiPSC modeling in order for oncologists and cardiologists together to inform their potential to improve our clinical collaborative practice in cardio-oncology. When applying such in vitro characterization, it is hypothesized that a safety score can be assigned to each individual to determine who has a greater probability of developing cardiovascular toxicity. Using hiPSCs to create personalized models and ultimately evaluate the cardiovascular toxicity of individuals' treatments may one day lead to more patient-specific treatment plans in precision cardio-oncology while reducing cardiovascular disease (CVD) morbidity and mortality.

Background: Serum bile acids (SBAs) are frequently measured in dogs. However, there is limited data comparing SBAs in different liver diseases diagnosed according to standardized histological criteria., Objectives: To compare resting and postprandial SBAs, and determine their sensitivity and specificity, for various liver diseases in dogs., Animals: Three hundred and forty-one client-owned dogs with suspected liver disease that had a liver biopsy and SBAs measured., Methods: Multicenter retrospective study. Cases were classified according to standardized histological criteria. The sensitivity and specificity of resting and postprandial SBAs for the diagnosis of each liver disease, and all liver diseases combined, were calculated., Results: The median resting SBAs were highest in dogs with cirrhosis (98.8 μmol/L; range, 6-135) and congenital circulatory anomalies (CCa; 79.45 μmol/L; 0.3-705). The highest median postprandial concentrations were found in CCa (126 μmol/L; 0-726) and chronic hepatitis (CH; 54.3 μmol/L; 0-260). Using the cut-off value of 10 μmol/L, the highest sensitivities of resting SBAs were recorded in dogs with CCa (87.5%; 95% confidence interval, 76.8-94.4) and CH (81.1%; 71.5-88.6). The sensitivities of postprandial SBAs were the highest in cholangitis (100%; 47.8-100.0) and CCa (91.1%; 78.8-97.5). The specificities of resting and postprandial SBAs for all diseases were 49.3% (37.6-61.1) and 29.7% (15.9-47.0), respectively., Conclusions and Clinical Importance: Postprandial SBAs are more sensitive but less specific than resting SBAs for the diagnosis of liver disease. There were dogs in all categories of liver disease with resting SBAs <10 and >90 μmol/L. Therefore, careful interpretation of both normal and elevated values is required., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: This study was designed to investigate whether cerebral oxygen desaturations during thoracic surgery are predictive of patients' quality of recovery. As a secondary aim, the authors investigated the relationship among cerebral desaturations and postoperative delirium and hospital length of stay., Design: This study was a prospective observational cohort study., Setting: A single tertiary-care medical center from September 2012 through March 2014., Patients: Adult patients scheduled for elective pulmonary surgery requiring one-lung ventilation., Interventions: All patients were monitored with the ForeSight cerebral oximeter., Measurements and Main Results: The primary assessment tool was the Postoperative Quality of Recovery Scale. Delirium was assessed using the Confusion Assessment Method. Of the 117 patients analyzed in the study, 60 of the patients desaturated below a cerebral oximetry level of 65% for a minimum of 3 minutes (51.3%). Patients who desaturated were significantly less likely to have cognitive recovery in the immediate postoperative period (p = 0.012), which did not persist in the postoperative period beyond day 0. Patients who desaturated also were more likely to have delirium (p = 0.048, odds ratio 2.81 [95% CI 1.01-7.79]) and longer length of stay (relative duration 1.35, 95% CI 1.05-1.73; p = 0.020)., Conclusions: Intraoperative cerebral oxygen desaturations, frequent during one-lung ventilation, are associated significantly with worse early cognitive recovery, high risk of postoperative delirium, and prolonged length of stay. Large interventional studies on cerebral oximetry in the thoracic operating room are warranted., (Published by Elsevier Inc.)

The SS (Dahl salt sensitive) rat is an established model of hypertension and renal damage that is accompanied with immune system activation in response to a high-salt diet. Investigations into the effects of sodium-independent and dependent components of the diet were shown to affect the disease phenotype with SS/MCW (JrHsdMcwi) rats maintained on a purified diet (AIN-76A) presenting with a more severe phenotype relative to grain-fed SS/CRL (JrHsdMcwiCrl) rats. Since contributions of the immune system, environment, and diet are documented to alter this phenotype, this present study examined the epigenetic profile of T cells isolated from the periphery and the kidney from these colonies. T cells isolated from kidneys of the 2 colonies revealed that transcriptomic and functional differences may contribute to the susceptibility of hypertension and renal damage. In response to high-salt challenge, the methylome of T cells isolated from the kidney of SS/MCW exhibit a significant increase in differentially methylated regions with a preference for hypermethylation compared with the SS/CRL kidney T cells. Circulating T cells exhibited similar methylation profiles between colonies. Utilizing transcriptomic data from T cells isolated from the same animals upon which the DNA methylation analysis was performed, a predominant negative correlation was observed between gene expression and DNA methylation in all groups. Lastly, inhibition of DNA methyltransferases blunted salt-induced hypertension and renal damage in the SS/MCW rats providing a functional role for methylation. This study demonstrated the influence of epigenetic modifications to immune cell function, highlighting the need for further investigations.

The Dahl salt-sensitive (SS) rat is an established model of SS hypertension and renal damage. In addition to salt, other dietary components were shown to be important determinants of hypertension in SS rats. With previous work eliminating the involvement of genetic differences, grain-fed SS rats from Charles River Laboratories (SS/CRL; 5L2F/5L79) were less susceptible to salt-induced hypertension and renal damage compared with purified diet-fed SS rats bred at the Medical College of Wisconsin (SS/MCW; 0.4% NaCl, AIN-76A). With the known role of immunity in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys via flow cytometry and RNA sequencing in T-cells isolated from the blood and kidneys of rats maintained on their respective parental diet or on 3 weeks of high salt (4.0% NaCl, AIN-76A). SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 versus 141.9±14.4 mm Hg), albuminuria (21.7±3.5 versus 162.9±22.2 mg/d), and renal immune cell infiltration compared with SS/MCW. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney, regardless of colony or chow. Pathway analysis of significantly differentially expressed genes between low and high salt conditions demonstrated changes related to inflammation in SS/MCW renal T-cells compared with metabolism-related pathways in SS/CRL renal T-cells. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that dietary components in addition to salt may influence immunity and the infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.

Background: Increasingly, states are legalizing cannabis for recreational use. Improved accessibility may allow adults with pain to use cannabis more liberally. Greater understanding is needed about how adults with pain perceive the effects of cannabis, particularly those who also use opioid analgesics., Purpose: To examine the perceived effects of cannabis among adults who have been prescribed opioids for persistent pain., Methods: A survey-based study was conducted on 150 adults with persistent pain. Data from two open-ended questions were analyzed using a qualitative descriptive approach and content analysis., Findings: Data analysis led to identification of two main categories and five subcategories: (a) cannabis benefits with two subcategories of "physiological" and "mental health"; (b) adverse effects with three subcategories of "physiological," "mental health," and "social and economic concerns.", Discussion: Both positive and negative effects of cannabis were described. Nursing practice, including open communication with patients, can be guided by patient perspectives surrounding benefits and adverse effects of cannabis use., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Lubricating agents facilitate effective harvesting of split-thickness skin grafts. Multiple agents, including water-based gel, mineral oil, glycerin, and poloxamer 188, have been utilized in this capacity. The agent selected is typically at the discretion of the provider and institution, as a single "ideal" lubricant remains to be objectively established. Furthermore, a recent discontinuation of Shur-Clens® Skin Wound Cleanser1 (a wound cleansing solution consisting of the surfactant poloxamer 188) has prompted the search for a suitable substitute for many providers. The purpose of this study is to directly compare five lubricants (including a novel surgical lubricant-based solution) to select a preferred agent. Four practitioners blindly tested five lubricants while harvesting a split-thickness skin graft on a porcine skin model (glycerin, mineral oil, saline, poloxamer 188, and a novel lubricant solution created with surgical lube and sterile water). The results were recorded on a Likert scale where 1 indicated poor performance and 5 indicated excellent performance. Data were pooled, and means were compared with analysis of variance and post hoc Tukey test. The cost of each lubricating solution was also reported. Mean scores for each of the solutions were as follows: dry control = 1.1 ± 0.1; glycerin = 2.62 ± 1.02, saline = 3.88 ± 0.81, mineral oil = 3.75 ± 1.00, novel water-based lubricant solution = 4.63 ± 0.71, and poloxamer 188 = 3.88 ± 0.81. All solutions were superior to dry control (P < .01). Glycerin was noted to have statistically lower scores than all of the other solutions (P < .01). The novel water-based surgical lubricant solution had significantly higher mean scores than both glycerin (P < .01) and mineral oil (P < .05). Each solution was compared according to dollars per 100cc with glycerin and Shur-Clens® representing the most expensive options at almost $3/100cc and saline the least expensive at less than $0.15/100cc. In a porcine skin model, the novel water-based surgical lubricant solution had the best performance. It was statistically superior to glycerin and mineral oil and was also found to be the most cost-effective option in terms of overall performance compared with relative cost. Glycerin had the worst performance with statistically lower scores than all other solutions. Glycerin was also found to be the least cost-effective due to a large discrepancy between high cost and low overall performance. Saline performed better than expected. These results may be skewed due to the inherently greasy nature of the butcher shop porcine skin, creating limitations and decreasing the fidelity of the model. In a search for the "ideal" lubricant, other models should be further studied., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Case Summary: A 4-month-old neutered male Russian Blue kitten had a 4 week history of hypersalivation and failure to thrive. In addition, there was a 2 week history of soft tissue swelling on the ventral abdomen, which had failed to improve with antimicrobial therapy. There were no significant physical examination or neurological deficits on examination; however, the cat had a quiet demeanour for its age. Postprandial bile acids were increased (32 µmol/l; reference interval <25 µmol/l). An abdominal CT scan revealed changes consistent with an extrahepatic portosystemic shunt and inflammation of fat of the ventral abdominal body wall. Surgical biopsy and culture of the subcutaneous swelling identified non-infectious steatitis. Ten weeks following initial presentation, surgical exploration, liver biopsy and ligation of the portosystemic shunt were performed. Liver biopsy was submitted to the Anatomical Pathology Laboratory of Cornell University Animal Health Diagnostic Center, New York, USA. Histopathology revealed a ductal plate malformation (Caroli's type), as well as changes consistent with a portosystemic shunt., Relevance and Novel Information: Ductal plate malformations are rarely described in the veterinary literature. To our knowledge this is the first reported case of Caroli's-type malformation in a cat. There are no biochemical changes that allow for differentiation of ductal plate malformations from other hepatopathies. Liver biopsy is required for a definitive diagnosis., Competing Interests: Conflict of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Object  Primary closure of posterior fossa dura can be challenging, and postoperative cerebrospinal fluid (CSF) leaks continue to represent a common complication of the retrosigmoid approach. We describe a simple technique to allow for primary closure of the dura following retrosigmoid approaches. The incidence of CSF leaks using this method is reported. Methods  A retrospective chart review was conducted on all cases of retrosigmoid craniotomies performed by the senior surgeon from February 2009 to February 2015. The primary outcome was development of postoperative CSF leak or pseudomeningocele. Length of stay, lesion type, and other surgical complications were also reported. Results  Eighty-six patients underwent a retrosigmoid craniotomy during the study period. The most common indications for retrosigmoid craniotomy were microvascular decompression (58%) and tumor resection (36%). No allo- or autografts to repair the dural defect were needed, and no lumbar drains were used. No patients developed CSF otorrhea, rhinorrhea, or incisional leak postoperatively. Conclusion  Primary dural closure is possible in retrosigmoid approaches without the use of allo- or autografts and may prevent postoperative CSF leaks when combined with other posterior fossa closure techniques. Careful attention to the handling of the dural flap is necessary to achieve this.

In utero alcohol exposure can cause fetal alcohol spectrum disorders (FASD), characterized by structural brain abnormalities and long-lasting behavioral and cognitive dysfunction. Neuronal plasticity is affected by in utero alcohol exposure and can be modulated by extracellular proteolysis. Plasmin is a major extracellular serine-protease whose activation is tightly regulated by the plasminogen activator (PA) system. In the present study we explored the effect of ethanol on the expression of the main components of the brain PA system in sex-specific cortical astrocyte primary cultures in vitro and in the cortex and hippocampus of post-natal day (PD) 9 male and female rats. We find that ethanol alters the PA system in astrocytes and in the developing brain. In particular, the expression of tissue-type PA (tPA), encoded by the gene Plat, is consistently upregulated by ethanol in astrocytes in vitro and in the cortex and hippocampus in vivo. Astrocytes exhibit endogenous plasmin activity that is increased by ethanol and recombinant tPA and inhibited by tPA silencing. We also find that tPA is expressed by astrocytes of the developing cortex and hippocampus in vivo. All components of the PA system investigated, with the exception of Neuroserpin/Serpini1, are expressed at higher levels in astrocyte cultures than in the developing brain, suggesting that astrocytes are major producers of these proteins in the brain. In conclusion, astrocyte PA system may play a major role in the modulation of neuronal plasticity; ethanol-induced upregulation of tPA levels and plasmin activity may be responsible for altered neuronal plasticity in FASD., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To test whether DNA samples stored for a prolonged period (20 years) under various storage conditions could be used for comparative methylation studies using reduced representation bisulfite sequencing., Patients & Methods: Five groups of human blood DNA samples (n = 5-6/group) were compared. The groupings were based on the anticoagulant used and storage temperature and duration., Results: Methylation profiles of defined genomic regions in the DNA or blood samples archived for 20 years were similar across all storage temperatures, including 4°C. The level of intersample similarity in archived samples was not significantly different than that in recently collected samples., Conclusion: Archived samples, including DNA stored at 4°C for 20 years, are suitable for comparative studies of DNA methylation.

Some of the neurobehavioral deficits identified in children with Fetal Alcohol Spectrum Disorders (FASDs) have been recapitulated in a binge model of gestational third trimester-equivalent ethanol (EtOH) exposure, in which Sprague-Dawley rats are intragastrically intubated between post-natal day (PD) 4 and PD9 with high doses of EtOH. In this model, the ameliorating effects of choline (Chol) administration on hippocampus-dependent behaviors altered by EtOH have also been extensively documented. In the present study, we investigated the effects of EtOH (5 g/kg/day) and/or Chol (100 mg/kg/day) on morphometric parameters of CA1 pyramidal neurons by Golgi-Cox staining followed by Neurolucida tracing and analysis. We found that EtOH increased apical dendrite complexity in male and female pups neonatally exposed to EtOH. EtOH did not significantly affect basal dendrite parameters in female and male rats. Interestingly, Chol treatments decreased basal dendrites' length, number, and maximal terminal distance in male pups. When pups were co-treated with EtOH and Chol, Chol did not rescue the effect of EtOH. In conclusion, EtOH increases while Chol decreases dendritic length and arborization of hippocampal CA1 neurons in PD9 rats. We hypothesize that developmental EtOH exposure induces a premature maturation of neurons, leading to early restriction of neuronal plasticity while Chol treatments delay the normal program of neuronal maturation and therefore prolong the window of maximal plasticity. Chol does not prevent the effects of developmental alcohol exposure on hippocampal pyramidal neurons' morphology characterized in the present study, although whether prolonged Chol administration after developmental EtOH exposure rectifies EtOH damage remains to be assessed., (Published by Elsevier Ltd.)

Background: Factors that contribute to student success in accelerated degree nursing programs are poorly understood and may vary by gender., Purpose: Examine associations between satisfaction with peer and mentor support, gender, and academic outcomes among students in accelerated degree nursing programs., Methods: We used data (demographic variables, satisfaction with peer and mentor support, graduation, and attempts of National Council Licensure Examination for Registered Nurses) from the American Association of Colleges of Nursing and Robert Wood Johnson Foundation's New Career in Nursing Program. Multivariable mixed effects regression models were used to examine associations among gender, satisfaction with support, and academic outcomes., Findings: Males had an increased probability of reporting high satisfaction with peer support. Both males and females who were very dissatisfied with peer support were less likely to graduate than students who were very satisfied with peer support. Gender did not moderate the relationships between satisfaction with peer and mentor support and academic outcomes., Conclusion: Peer support is an important aspect of graduation among students in accelerated degree nursing programs. Continuous quality improvement strategies to improve student peer support may be warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Synthetic promoters have been developed in a number of different organisms and are capable of mediating specific and enhanced levels of gene expression. Typically, cis-regulatory regions from a few genes are randomly combined to generate a synthetic promoter library, and the sequences with the highest activity are selected for in target cell lines. Here we describe a novel approach that can be employed in the construction of synthetic promoters . Specifically, we use gene expression profiles obtained from microarray datasets to select the cis-regulatory elements that comprise the synthetic promoter library. By adopting this approach, we were able to construct several promoters that could specifically mediate gene expression in colorectal cancer cells. We develop a new selection criteria based on the observed transcriptome of target cells, the frequency that identified cis-regulatory sequences occur in identified gene modules, and the length of identified cis-regulatory regions. Our method allows for the generation of synthetic promoter libraries with increased level of specificity and facilitates the selection of promoters that are highly active only under predefined gene expression profiles.

Background: Many rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. A highly homologous amino acid sequence (663YLCM KTLLL671) is present in the ligand-binding domain of hGRα, suggesting that hGRα might also undergo S-palmitoylation., Aim: To investigate the role of the motif 663YLCMKTLLL671 in membrane localization of the hGRα and in mediating rapid nongenomic glucocorticoid signaling., Methods and Results: We showed that the mutant receptors hGRαY663A, hGRαC665A and hGRαLL670/671AA, and the addition of the palmitoylation inhibitor 2-bromopalmitate did not prevent membrane localization of hGRα and co-localization with caveolin-1, and did not influence the biphasic activation of mitogen-activated protein kinase (MAPK) signaling pathway in the early time points. Finally, the hGRα was not shown to undergo S-palmitoylation., Conclusions: The motif 663YLCMKTLLL671 does not play a role in membrane localization of hGRα and does not mediate the nongenomic glucocorticoid actions., Competing Interests: Conflicts of interest None.

Background: We recently performed a comprehensive bibliometric analysis of 103 U.S. neurosurgical departments and found the ih(5)-index as meaningful and reproducible using public data. The present report expands this analysis by adding 14 Canadian and 2 additional U.S. programs., Methods: Departments were included if listed in the American Association of Neurological Surgeons Residency Directory. Each institution was considered a single entity, and original research articles with authors who were neurosurgeon faculty were counted only once per institution, although a single article may have been credited toward multiple institutions, if applicable. The following bibliometric indices were calculated and used to rank departments: ih(5), ig(5), ie(5), and i10(5). In addition, intradepartmental comparison of productivity among faculty members was analyzed by computing Gini coefficients for publications and citations., Results: The top 5 most academically productive North American neurosurgical programs based on ih(5)-index were found to be the University of Toronto, University of California at San Francisco, University of California at Los Angeles, University of Pittsburgh, and Brigham and Women's Hospital. The top 5 Canadian programs were the University of Toronto, University of Calgary, McGill University, University of Sherbrooke, and University of British Columbia. The median ih(5)-index for U.S. and Canadian programs was 12 and 10.5, respectively., Conclusions: This is the most accurate comprehensive analysis to date of contemporary bibliometrics among North American neurosurgery departments. Using the ih(5)-index for institutional ranking allows for informative comparison of recent scholarly efforts., (Copyright © 2016 Elsevier Inc. All rights reserved.)

OBJECTIVE Shunt surgery consumes a large amount of pediatric neurosurgical health care resources. Although many studies have sought to identify risk factors for shunt failure, there is no consensus within the literature on variables that are predictive or protective. In this era of "quality outcome measures," some authors have proposed various metrics to assess quality outcomes for shunt surgery. In this paper, the Preventable Shunt Revision Rate (PSRR) is proposed as a novel quality metric. METHODS An institutional shunt database was queried to identify all shunt surgeries performed from January 1, 2010, to December 31, 2014, at Le Bonheur Children's Hospital. Patients' records were reviewed for 90 days following each "index" shunt surgery to identify those patients who required a return to the operating room. Clinical, demographic, and radiological factors were reviewed for each index operation, and each failure was analyzed for potentially preventable causes. RESULTS During the study period, there were 927 de novo or revision shunt operations in 525 patients. A return to the operating room occurred 202 times within 90 days of shunt surgery in 927 index surgeries (21.8%). In 67 cases (33% of failures), the revision surgery was due to potentially preventable causes, defined as inaccurate proximal or distal catheter placement, infection, or inadequately secured or assembled shunt apparatus. Comparing cases in which failure was due to preventable causes and those in which it was due to nonpreventable causes showed that in cases in which failure was due to preventable causes, the patients were significantly younger (median 3.1 vs 6.7 years, p = 0.01) and the failure was more likely to occur within 30 days of the index surgery (80.6% vs 64.4% of cases, p = 0.02). The most common causes of preventable shunt failure were inaccurate proximal catheter placement (33 [49.3%] of 67 cases) and infection (28 [41.8%] of 67 cases). No variables were found to be predictive of preventable shunt failure with multivariate logistic regression. CONCLUSIONS With economic and governmental pressures to identify and implement "quality measures" for shunt surgery, pediatric neurosurgeons and hospital administrators must be careful to avoid linking all shunt revisions with "poor" or less-than-optimal quality care. To date, many of the purported risk factors for shunt failure and causes of shunt revision surgery are beyond the influence and control of the surgeon. We propose the PSRR as a specific, meaningful, measurable, and-hopefully-modifiable quality metric for shunt surgery in children.

Chronic alcohol abuse is associated with brain damage in a sex-specific fashion, but the mechanisms involved are poorly described and remain controversial. Previous results have suggested that astrocyte gene expression is influenced by ethanol intoxication and during abstinence in vivo. Here, bioinformatic analysis of astrocyte-enriched ethanol-regulated genes in vivo revealed ubiquitin pathways as an ethanol target, but with sexually dimorphic cytokine signaling and changes associated with brain aging in females and not males. Consistent with this result, astrocyte activation was observed after exposure in female but not male animals, with reduced S100β levels in the anterior cingulate cortex and increased GFAP(+) cells in the hippocampus. In primary culture, the direct effects of chronic ethanol exposure followed by recovery on sex-specific astrocyte function were examined. Male astrocyte responses were consistent with astrocyte deactivation with reduced GFAP expression during ethanol exposure. In contrast, female astrocytes exhibited increased expression of Tnf, reduced expression of the neuroprotective cytokine Tgfb1, disrupted bioenergetics and reduced excitatory amino acid uptake following exposure or recovery. These results indicate widespread astrocyte dysfunction in ethanol-exposed females and suggest a mechanism that may underlie increased vulnerability to ethanol-induced neurotoxicity in females., (© 2015 International Society of Neuropathology.)