Editorial board members

Publication date: April–June 2017
Source:Mutation Research/Reviews in Mutation Research, Volume 772





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Rapid Web-Based Platform for Assessment of Orthopedic Surgery Patient Care Milestones: A 2-Year Validation

Publication date: Available online 18 May 2017
Source:Journal of Surgical Education
Author(s): Kenneth R. Gundle, Dayne T. Mickelson, Arien Cherones, Jason Black, Doug P. Hanel
ObjectiveTo determine the validity, feasibility, and responsiveness of a new web-based platform for rapid milestone-based evaluations of orthopedic surgery residents.SettingSingle academic medical center, including a trauma center and pediatrics tertiary hospital.ParticipantsForty residents (PG1-5) in an orthopedic residency program and their faculty evaluators.MethodsResidents and faculty were trained and supported in the use of a novel trainee-initiated web-based evaluation system. Residents were encouraged to use the system to track progress on patient care subcompetencies. Two years of prospectively collected data were reviewed from residents at an academic program. The primary outcome was Spearman's rank correlation between postgraduate year (PGY) and competency level achieved as a measure of validity. Secondary outcomes assessed feasibility, resident self-evaluation versus faculty evaluation, the distributions among subcompetencies, and responsiveness over time.ResultsBetween February 2014 and February 2016, 856 orthopedic surgery patient care subcompetency evaluations were completed (1.2 evaluations per day). Residents promptly requested feedback after a procedure (median = 0 days, interquartile range: 0-2), and faculty responded within 2 days in 51% (median = 2 days, interquartile range: 0-13). Primary outcome showed a correlation between PGY and competency level (r = 0.78, p < 0.001), with significant differences in competency among PGYs (p < 0.001 by Kruskal-Wallis rank sum test). Self-evaluations by residents substantially agreed with faculty-assigned competency level (weighted Cohen's κ = 0.72, p < 0.001). Resident classes beginning the study as PGY1, 2, and 3 separately demonstrated gains in competency over time (Spearman's rank correlation 0.39, 0.60, 0.59, respectively, each p < 0.001). There was significant variance in the number of evaluations submitted per subcompetency (median = 43, range: 6-113) and competency level assigned (p < 0.01).ConclusionsRapid tracking of trainee competency with milestone-based evaluations in a learner-centered mobile platform demonstrated validity, feasibility, and responsiveness. Next Accreditation System-mandated data may be efficiently collected and used for trainee and program self-study.



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The Usage of Mock Oral Examinations for Program Improvement

Publication date: Available online 18 May 2017
Source:Journal of Surgical Education
Author(s): Shari L. Meyerson, Stuart Lipnick, Edward Hollinger
ObjectiveMock oral examinations are often used to prepare residents for the American Board of Surgery certifying examination. Another potential use of these examinations is to identify programmatic weaknesses. Results from a multi-institutional mock oral examination were evaluated to determine if specific areas of weakness within each of the participating programs could be identified to facilitate program development.DesignA mock oral examination was administered annually consisting of 3 examination rooms per resident with 3 cases in each room. Case categories included core general surgery and subspecialties and cases were changed yearly. Each case included facets of patient management from history and physical examination, and differential diagnosis to postoperative care and professional behaviors.SettingGeneral Surgery programs at 3 academic medical centers—Northwestern University, Rush University, and University of Illinois at Chicago.ParticipantsA total of 259 resident examinations of fourth- and fifth-year general surgery residents over a 7-year period.ResultsA total of 2331 individual resident cases were evaluated with an overall case pass rate of 50.2% across all 3 programs. The weakest case category for each program was different (A = vascular 40.0% pass, B = trauma 41.4% pass, and C = breast 30.0% pass). All programs scored above their mean in gastrointestinal and abdominal surgery and below their mean in vascular surgery. Within vascular surgery, the weakest facet of patient management also differed between programs (A = select tests 44.3% pass, B = complications 57.0% pass, and C = history and physical 55.4% pass).ConclusionsA standardized mock oral examination is able to identify topic areas of relative strength and weakness that differ between programs. These results can be used to define focused areas for improvement within training programs, guide rotation schedules, and improve didactic curricula.



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A National Cross-Sectional Study of Surgery Residents Who Underreport Duty Hours

Publication date: Available online 18 May 2017
Source:Journal of Surgical Education
Author(s): Christopher L. Bennett, David A. McDonald, Yuchiao Chang, Alex Finch, Kimmy Vuong, Stuart Rennie, Eric S. Nadel
ObjectivePrevious work demonstrates that many surgery residents underreport duty hours. The purpose of this study was to identify characteristics of these residents and better understand why they exceed duty hours.DesignDuring the winter of 2015 we conducted an anonymous cross-sectional survey of Accreditation Council for Graduate Medical Education accredited general surgery programs.SettingA total of 101 general surgery residency programs across the United States.ParticipantsA total of 1003 general surgery residents across the United States. Respondents' mean age was 29.9 ± 3.0 years; 53% were male.ResultsStudy response rate was 31.9%. Residents age <30 were more likely to exceed duty hours to complete charting/documentation (68% vs. 54%, p < 0.001). Females more often cited guilt about leaving the hospital (32% vs. 24%, p = 0.014) as to why they exceed duty hours. Programs with >40 residents had the highest rates of underreporting (82% vs. 67% in other groups p < 0.001) and residents who worked >90 hours on an average week more frequently cited external pressure (p = 0.0001), guilt (p = 0.006), and feeling it was expected of them (p < 0.0001) as reasons why they underreport compared to those who worked fewer hours.ConclusionsUnderreporting and duty-hour violations are a complex issue influenced by many variables including age, sex, and internal and external pressures.



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Dedicated Research Time During Surgery Residency Leads to a Significant Decline In Self-Assessed Clinical Aptitude and Surgical Skills

Publication date: Available online 19 May 2017
Source:Journal of Surgical Education
Author(s): Monica M. Grova, Anthony D. Yang, Misty D. Humphries, Joseph M. Galante, Edgardo S. Salcedo
ObjectiveThe surgical community commonly perceives a decline in surgical and patient care skills among residents who take dedicated time away from clinical activity to engage in research. We hypothesize that residents perceive a decline in their skills because of dedicated research time.SettingUC Davis Medical Center, Sacramento, CA, an institutional tertiary care center.ParticipantsGeneral surgery residents and graduates from UC Davis general surgery residency training program, who had completed at least 1 year of research during their training. A total of 35 people were asked to complete the survey, and 19 people submitted a completed survey.DesignParticipants were invited to complete an online survey. Factors associated with the decline in skills following their research years were examined. All statistical analyses were performed with IBM SPSS Statistics software.ResultsA total of 19 current or former general surgery residents responded to the survey (54% response rate). Overall, 42% described their research as "basic science." Thirteen residents (68%) dedicated 1 year to research, while the remainder spent 2 or more years. Basic science researchers were significantly more likely to report a decrease in clinical judgment (75% vs. 22%, p = 0.013) as well as a decrease in patient care skills (63% vs. 0%, p = 0.002). Residents who dedicated at least 2 years to research were more likely to perceive a decline in overall aptitude and surgical skills (100% vs. 46%, p = 0.02), and a decline in patient care skills (67% vs. 8%, p = 0.007).ConclusionsMost residents who dedicate time for research perceive a decline in their overall clinical aptitude and surgical skills. This can have a dramatic effect on the confidence of these residents in caring for patients and leading a care team once they re-enter clinical training. Residents who engaged in 2 or more years of research were significantly more likely to perceive these problems. Further research should determine how to keep residents who are interested in academics from losing ground clinically while they are pursuing research training.



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Macrophages produce IL-33 by activating MAPK signaling pathway during RSV infection

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Feifei Qi, Song Bai, Dandan Wang, Lei Xu, Haiyan Hu, Sheng Zeng, Ruonan Chai, Beixing Liu
It has been reported that RSV infection can enhance IL-33 production in lung macrophages. However, little is known about specific signaling pathways for activation of macrophages during RSV infection. In the present study, by using real-time RT-PCR as well as western blot assay, it became clear that RSV infection can enhance not only the expression of mRNAs for MAPK molecules (including p38, JNK1/2, and ERK1/2), but also the levels of MAPK proteins in lung macrophages as well as RAW264.7 cells. Furthermore, infection with RSV resulted in an increased level of phosphorylated MAPK proteins in RAW264.7 cells, suggesting that MAPK signaling pathway may participate in the process of RSV-induced IL-33 secretion by macrophages. In fact, the elevated production of IL-33 in RAW264.7 was attenuated significantly by pretreatment of the cells with special MAPK inhibitor before RSV infection, further confirming the function of MAPKs pathway in RSV-induced IL-33 production in macrophages. In contrast, the expression of NF-κB mRNA as well as the production of NF-κB protein in lung macrophages and RAW264.7 cells was not enhanced markedly after RSV infection. Moreover, RSV infection failed to induce the phosphorylation of NF-κB in RAW264.7 cells, suggesting that NF-κB signaling pathway may be not involved in RSV-induced IL-33 production in macrophages. Conclusion, these results indicate that RSV-induced production of IL-33 in macrophages is dependent on the activation of MAPK signaling pathway.



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Gayle & Richard Olson prize pages

Publication date: May 2017
Source:Peptides, Volume 91





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The evidence of apelin has the bidirectional effects on feeding regulation in Siberian sturgeon (Acipenser baerii)

Publication date: Available online 19 May 2017
Source:Peptides
Author(s): Jin Hao, Qing Liu, Xin Zhang, Yuanbing Wu, Jieyao Zhu, Jinwen Qi, Ni Tang, Shuyao Wang, Hong Wang, Defang Chen, Zhiqiong Li
Apelin is a peptide, mainly produced in the brain, which participates in several physiologic effects. However, knowledge about the mechanism of appetite regulation in teleosts, including the role of apelin is not well understood. The aim of this study is to explore the effect of feeding status on the expression of apelin mRNA in the whole brain and the effects of injection of apelin on food intake in Siberian sturgeon (Acipenser baerii). In this study, we first cloned the apelin cDNA sequence of the Siberian sturgeon. We obtained a 1046-bp cDNA fragment, including a 237-bp open reading frame (ORF) that encoded 77 amino acids. Apelin was widely distributed in 11 tissues related to feeding regulation, with the highest expression in thewhole brain, followed by the spleen and trunk kidney. In addition, we measured the effects of periprandial (preprandial and postprandial) change, fasting and re-feeding on apelin mRNA expression in whole brain. The level of apelin mRNA was significantly decreased 1h after feeding. The results of the fasting experiment showed that the expression of apelin mRNA in the brain was significantly elevated after 1day of fasting but consistently increased throughout the 15-day food deprivation period. When the 15-day fasted fish were re-fed, apelin mRNA expression in the brain was significantly increased as compared to that of the control. These results suggest that apelin may play a bidirectional role in the regulation of food intake in the Siberian sturgeon. In order to further examine the effect of apelin on feeding regulation in Siberian sturgeons, acute and chronic intraperitoneal (i.p.) injection experiments were performed and food intakes were recorded. Results showed that acute i.p. injection of apelin-13 reduced food intake, however, chronic i.p. injection apelin-13 increased the food intake for 7days in Siberian sturgeons. In conclusion, our results show that apelin has a bidirectional effect on feeding regulation in Siberian sturgeons by acting as a satiety factor in short-term feeding regulation and a starvation factor in long-term feeding regulation.



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The International Neuropeptide society pages

Publication date: May 2017
Source:Peptides, Volume 91





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IFC (editorial board)

Publication date: May 2017
Source:Peptides, Volume 91





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Molecular species of prostaglandins involved in modulating luteinizing hormone pulses of female rats under infectious stress conditions

Abstract

Mammalian reproductive function is controlled by the hypothalamus-pituitary-gonadal (HPG) axis, which is suppressed under infectious stress conditions. We have previously demonstrated, by analyzing the pulsatility of luteinizing hormone (LH), that prostaglandins (PGs) in the central nervous system (CNS) mediate infectious stress to suppress the activity of the HPG axis. The aim of the present study is to characterize the types of PGs responsible for suppression of the HPG axis. We focused on 3 major types of PGs, i.e., PGE₂, PGD₂, and PGF_2α. We used female rats overiectomized bilaterally 1 week before the experiments. Lipopolysaccharide (LPS, 100 μg/kg) suppressed LH pulses while enhancing the concentration of all 3 PGs in the CSF, which was restored by indomethacin (10 mg/kg). Subsequently, we observed LH pulsatility after a single injection of each PG and after co-injection of PGE₂ with PGF_2α into the third cerebral ventricle. A single injection of PGE₂ dose-dependently induced a transient increase in mean LH concentration and LH pulse amplitude, and PGD₂ significantly increased the amplitude of LH pulses, while PGF_2α did not affect LH pulsatility. On the other hand, co-injection of PGE₂ and PGF_2α induced significant suppression of both frequency and amplitude of LH pulses. These results suggest that PGE₂ and PGF_2α can be one of the mediators that suppress the HPG axis in situations of infectious stress. Moreover, they imply that there are 2 contradictory effects of PGE₂ on LH pulsatility: enhancive when working alone while suppressive when working together with PGF_2α. (244/250)

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Nanodiamond-based injectable hydrogel for sustained growth factor release: preparation, characterization and in vitro analysis

Publication date: Available online 19 May 2017
Source:Acta Biomaterialia
Author(s): Settimio Pacelli, Francisca Acosta, Aparna R. Chakravarti, Saheli G. Samanta, Jonathan Whitlow, Saman Modaresi, Rafeeq P.H. Ahmed, Johnson Rajasingh, Arghya Paul
Nanodiamonds (NDs) represent an emerging class of carbon nanomaterials that possess favorable physical and chemical properties to be used as multifunctional carriers for a variety of bioactive molecules. Here we report the synthesis and characterization of a new injectable ND-based nanocomposite hydrogel which facilitates a controlled release of therapeutic molecules for regenerative applications. In particular, we have formulated a thermosensitive hydrogel using gelatin, chitosan and NDs that provides a sustained release of exogenous human vascular endothelial growth factor (VEGF) for wound healing applications. Addition of NDs improved the mechanical properties of the injectable hydrogels without affecting its thermosensitive gelation properties. Biocompatibility of the generated hydrogel was verified by in vitro assessment of apoptotic gene expressions and anti-inflammatory interleukin productions. NDs were complexed with VEGF and the inclusion of this complex in the hydrogel network enabled the sustained release of the angiogenic growth factor. These results suggest for the first time that NDs can be used to formulate a biocompatible, thermosensitive and multifunctional hydrogel platform that can function both as a filling agent to modulate hydrogel properties, as well as a delivery platform for the controlled release of bioactive molecules and growth factors.Statement of significanceOne of the major drawbacks associated with the use of conventional hydrogels as carriers of growth factors is their inability to control the release kinetics of the loaded molecules. In fact, in most cases, a burst release is inevitable leading to diminished therapeutic effects and unsuccessful therapies. As a potential solution to this issue, we hereby propose a strategy of incorporating ND complexes within an injectable hydrogel matrix. The functional groups on the surface of the NDs can establish interactions with the model growth factor VEGF and promote a prolonged release from the polymer network, therefore, providing a longer therapeutic effect. Our strategy demonstrates the efficacy of using NDs as an essential component for the design of a novel injectable nanocomposite system with improved release capabilities.

Graphical abstract

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The Role of PYY in Pancreatic Islet Physiology and Surgical Control of Diabetes

Publication date: Available online 19 May 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Claudia Guida, Sam Stephen, Romain Guitton, Reshma D. Ramracheya
Bariatric surgery in obese individuals leads to rapid and lasting remission of type 2 diabetes (T2D). This phenomenon occurs independently of weight loss possibly via a combination of factors. The incretin hormone GLP-1 has so far been recognised as a critical factor. However, recent data have indicated that elevation in another gut hormone, peptide tyrosine tyrosine (PYY), may drive the beneficial effects of surgery. Here we discuss recent findings on PYY-mediated control of glucose homeostasis and its role in diabetes, in the context of what is known for GLP-1. Identification of factors that increase the expression of PYY following bariatric surgery and elucidation of its role in diabetes reversal may have clinical relevance as a nonsurgical therapy for T2D.



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Cyclooxygenases mediate early induction of interleukin-6 expression by solar ultraviolet irradiation in human skin

Publication date: Available online 19 May 2017
Source:Journal of Dermatological Science
Author(s): Peiru Wang, Min Sun, John J. Voorhees, Gary J. Fisher, Yong Li




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Altered expression of epidermal lipid bio-synthesis enzymes in atopic dermatitis skin is accompanied by changes in stratum corneum lipid composition

Publication date: Available online 18 May 2017
Source:Journal of Dermatological Science
Author(s): M.O. Danso, W. Boiten, V. van Drongelen, K.M. Gmelig, G. Gooris, A. El Ghalbzouri, S. Absalah, R. Vreeken, S. Kezic, J. van Smeden, A.P.M. Lavrijsen, J.A. Bouwstra
BackgroundThe barrier dysfunction in atopic dermatitis (AD) skin correlates with stratum corneum (SC) lipid abnormalities including reduction of global lipid content, shorter ceramide (CER) as well as free fatty acid (FFA) chain length and altered CER subclass levels. However, the underlying cause of these changes in lipid composition has not been fully investigated.AimWe investigated whether the expression of CER and FFA biosynthesis enzymes are altered in AD skin compared with control skin and determine whether changes in enzyme expression can be related with changes in lipid composition.MethodsIn AD patients and controls the expression of enzymes involved in the biosynthesis of FFAs and CERs was analyzed in relation to the SC lipid composition. These enzymes include stearoyl CoA desaturase (SCD), elongase 1 (ELOVL1) and ELOVL6 involved in FFA synthesis and β-glucocerebrosidase (GBA), acid-sphingomyelinase (aSmase), ceramide synthase 3 (CerS3) involved in CER synthesis. In TH2 treated human skin equivalents (AD HSEs) mimicking lesional AD skin, the mRNA expression of these enzymes was investigated.ResultsThe results reveal an altered expression of SCD and ELOVL1 in AD lesional skin. This was accompanied by functional changes displayed by increased unsaturated FFAs (SCD) and reduced FFA C22-C28 (ELOVL1) in AD lesional skin. The expression of GBA, aSmase and CerS3 were also altered in lesional skin. The CER composition in AD lesional skin showed corresponding changes such as increased CER AS and NS (aSmase) and decreased esterified ω-hydroxy CERs (CerS3). In support of the results from AD skin, the AD HSEs showed reduced mRNA ELOVL1, GBA and a Smase levels.ConclusionThis study shows that alterations in the expression of key enzymes involved in SC lipid synthesis contribute to changes in the lipid composition in AD skin and inflammation may influence expression of these enzymes.



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Keap1 knockdown in melanocytes induces cell proliferation and survival via HO-1-associated β-catenin signaling

Publication date: Available online 18 May 2017
Source:Journal of Dermatological Science
Author(s): Ji Young Kim, Hemin Lee, Eun Jung Lee, Mikyoung Kim, Tae-Gyun Kim, Hyoung-Pyo Kim, Sang Ho Oh
BackgroundNrf2-Keap1 signaling pathway protects cells against photo-oxidative stress. Yet in recent works, its role in melanogenesis together with cell protection functions against oxidative stress has been gaining interest. However, its effect on melanogenesis still has contradictory results from different studies.ObjectiveThe aims of our study were to investigate the effect of Keap1 silencing in melanocyte on melanogenesis and its associated mechanism.MethodsPrimary human epidermal melanocytes and melan-a cell line were used for this experiment. RNA sequencing was done to identify genes involved in melanocyte biology using Keap1 knockdown through siRNA techniques. And melanogenesis and the expression of melanogenesis-associated molecules were evaluated in Keap1 silenced melanocyte to examine the effects of Keap1 on melanogenesis, melanocyte growth, and related pathways.ResultsRNA-sequencing data revealed that Keap1 knockdown in primary human epidermal melanocytes (PHEMs) induced cell survival-related gene expression. Additionally, siRNA-mediated inhibition of Keap1 led to upregulation of MITF and melanogenesis-associated molecules along with Nrf2 activation in PHEMs. HO-1, a major gene that is upregulated in RNA-sequencing using Keap1-silenced PHEMs, protected melanocytes against H2O2-induced cell death and upregulated MITF and β-catenin expression. Further, increased expression of melanogenesis-associated molecules after Keap1 silencing was validated to occur through HO-1-associated β-catenin activation in a Keap1 and HO-1 double knockdown experiment.ConclusionThis work suggests that Keap1 silencing in melanocytes induced melanogenesis and the expression of melanogenesis-associated molecules through HO-1-associated β-catenin activation. Keap1 downregulation in melanocytes is important for cell proliferation and survival.



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Evaluation of alternative monomers to HEMA for dental applications

Publication date: Available online 18 May 2017
Source:Dental Materials
Author(s): Sven Tauscher, Jörg Angermann, Yohann Catel, Norbert Moszner
ObjectiveThe objective of this work is to find potential alternative monomers to 2-hydroxyethyl methacrylate (HEMA) for dental materials (self-etch adhesives and luting composites).MethodsMonomers 1–9 were tested as potential HEMA substitutes. Methacrylates 4, 5 and 6 and (N-methyl)acrylamides 7–9 were synthesized and characterized by ¹H NMR spectroscopy. The reactivity of each monomer was studied using photo-DSC. Mixtures of monomers 1–9 with the urethane dimethacrylate UDMA (1/1: wt/wt) were formulated and cured. The water sorption and solubility of these materials were determined according to ISO 4049. Luting composites based on monomers 1–9 or on HEMA were formulated. The flexural strength and modulus of elasticity were measured using a three-point bending setup, according to ISO 4049. Self-etch adhesives containing monomers 1–9 or HEMA were prepared and used to mediate a bond between the dental composite Tetric EvoCeram^® and both dentin and enamel. The shear bond strength (SBS) was measured using a Zwick universal testing machine.ResultsPolymerizable diols 3 and 4 as well as (N-methyl)acrylamides 7–9 were found to be significantly more reactive than HEMA. Resins based on the hydrophilic monomers 3, 7 and 8 exhibited a significantly higher water sorption than the corresponding HEMA-containing material. Luting composites containing monomers 2, 3, 6 and 7 showed similar or even improved mechanical properties compared to the reference material containing HEMA. Self-etch adhesives containing monomers 4 and 9 provided significantly higher dentin SBS than the reference material.SignificanceSome of the evaluated monomers are promising candidates for the development of HEMA-free dental materials.



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Diabetic Peripheral Neuropathy and Associated Pain: Emerging and Updated Research

Publication date: Available online 18 May 2017
Source:Clinical Therapeutics
Author(s): John G. Ryan




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Qualitative agreement and diagnostic performance of arterial spin labelling MRI and FDG PET-CT in suspected early-stage dementia

Publication date: Available online 19 May 2017
Source:Clinical Imaging
Author(s): K. Weyts, M.W. Vernooij, R.M.E. Steketee, R. Valkema, M. Smits
18FDG PET-CT is useful for early and differential diagnosis of dementia.ASL-MRI seems an attractive alternative.Visual agreement was calculated in 21 brain regions bilaterally in 9/11 patients with suspected early-stage dementia, excluding 2 patients due to ASL-MRI motion artefacts. Overall gross agreement was almost perfect and identical between and within modalities (κ=0.85–0.86, p<0.05).Intermodality regional agreement was variable, moderate (κ=0,56 in posterior cingulate) to perfect (including in precuneus), not different from intramodality agreement.Diagnostic accuracy was 5/9 (56%) for ASL-MRI and 7/9 (78%) for FDG PETCT.(p=0.31).Clinical experience and optimisation may further improve ASL-MRI's performance.



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Salvage-Radiotherapie mit antiandrogener Therapie nach Prostatektomie

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