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Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center

Fri, 06/30/2017 - 1:52pm

OBJECTIVE: The Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) system aims to stratify threatened limbs according to their anticipated natural history and estimate the likelihood of benefit from revascularization, but whether it accurately stratifies outcomes in limbs undergoing aggressive treatment for limb salvage is unknown. We investigated whether the WIfI stage correlated with the intensity of limb treatment required and patient-centered outcomes.

METHODS: We stratified limbs from a prospectively maintained database of consecutive patients referred to a limb preservation center according to WIfI stage (October 2013-May 2015). Comorbidities, multimodal limb treatment, including foot operations and revascularization, and patient-centered outcomes (wound healing, limb salvage, amputation-free survival, maintenance of ambulatory and independent living status, and mortality) were compared among WIfI stages. Multivariate analysis was performed to identify predictors of wound healing and limb salvage.

RESULTS: We identified 280 threatened limbs encompassing all WIfI stages in 257 consecutive patients: stage 1, 48 (17%); stage 2, 67 (24%); stage 3, 64 (23%); stage 4, 83 (30%); and stage 5 (unsalvageable), 18 (6%). Operative foot debridement, minor amputation, and use of revascularization increased with increasing WIfI stage (P

CONCLUSIONS: In patients treated aggressively for limb salvage, WIfI stage correlated with intensity of multimodal limb treatment and with limb salvage and patient-centered outcomes at 1 year. Revascularization improved limb salvage in severe ischemia. These data support the Society for Vascular Surgery WIfI system as a powerful tool to risk-stratify patients with threatened limbs and guide treatment.

A School-Based Program for Overweight and Obese Adolescents: A Randomized Controlled Trial

Fri, 06/30/2017 - 1:52pm

BACKGROUND: Given the dramatic increase in adolescent overweight and obesity, models are needed for implementing weight management treatment through readily accessible venues. We evaluated the acceptability and efficacy of a school-based intervention consisting of school nurse-delivered counseling and an afterschool exercise program in improving diet, activity, and body mass index (BMI) among overweight and obese adolescents.

METHODS: A pair-matched cluster-randomized controlled school-based trial was conducted in which 8 public high schools were randomized to either a 12-session school nurse-delivered cognitive-behavioral counseling intervention plus school-based after school exercise program, or 12-session nurse contact with weight management information (control). Overweight or obese adolescents (N = 126) completed anthropometric and behavioral assessments at baseline and 8-month follow-up. Main outcome measures included diet, activity, and BMI. Mixed effects regression models were conducted to examine differences at follow-up.

RESULTS: At follow-up, students in intervention compared with control schools were not different in BMI, percent body fat, and waist circumference. Students reported eating breakfast (adjusted mean difference 0.81 days; 95% confidence interval [CI] 0.11-1.52) on more days/week; there were no differences in other behaviors targeted by the intervention.

CONCLUSIONS: While a school-based intervention including counseling and access to an after-school exercise program is theoretically promising with public health potential, it was not effective in reducing BMI or key obesogenic behaviors. Our findings are important in highlighting that interventions targeted at the individual level are not likely to be sufficient in addressing the adolescent obesity epidemic without changes in social norms and the environment.

Ultrasound-guided Breast Biopsy in the Resource-limited Setting: An Initial Experience in Rural Uganda

Fri, 06/30/2017 - 12:00pm

Purpose: To describe the methodology and initial experience behind creation of an ultrasoundguided percutaneous breast core biopsy program in rural Uganda.

Methods and Materials: Imaging the World Africa (ITWA) is the registered non-governmental organization division of Imaging the World (ITW), a not-for-profit organization whose primary aim is the integration of affordable high-quality ultrasound into rural health centers. In 2013, ITWA began the pilot phase of an IRB-approved breast care protocol at a rural health center in Uganda. As part of the protocol’s diagnostic arm, an ultrasound-guided percutaneous breast core biopsy training curriculum was implemented in tandem with creation of regionally supplied biopsy kits.

Results: A surgeon at a rural regional referral hospital was successfully trained and certified to perform ultrasound-guided percutaneous breast core biopsies. Affordable and safe biopsy kits were created using locally available medical supplies with the cost of each kit totaling $10.62 USD.

Conclusion: Successful implementation of an ultrasound-guided percutaneous breast core biopsy program in the resource-limited setting is possible and can be made sustainable through incorporation of local health care personnel and regionally supplied biopsy materials. Our hope is that ITWA’s initial experience in rural Uganda can serve as a model for similar programs in the future.

mRNA Decay Pathways Use Translation Fidelity and Competing Decapping Complexes for Substrate Selection

Wed, 06/28/2017 - 10:52am

mRNA decay is an important step in gene regulation, environmental responsiveness, and mRNA quality control. One such quality control pathway, Nonsense-mediated mRNA Decay (NMD), targets transcripts whose translation terminates prematurely. However, the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we re-evaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency, lower average codon optimality scores, and higher ratios of out-of-frame translation.

General mRNA decay is predominantly mediated by decapping by the Dcp1-Dcp2 complex and 5' to 3' decay by Xrn1, but the exact mechanism of decapping regulation has remained largely unknown. Several in vitro and in vivo studies have revealed the importance of the C-terminal extension of Dcp2 and the identities of many decapping regulators that interact with the decapping complex. To better understand how decapping regulation is achieved by the C-terminal extension of Dcp2 we generated RNA-Seq libraries from a Dcp2 allele that lacks this portion of Dcp2 along with libraries from strains that contain single deletions of several decapping activators. Our transcriptome-wide results indicate that the C-terminal extension of Dcp2 is crucial for efficient regulation of decapping, and different decapping activators are responsible for targeting different sets of mRNAs. Considering the limited pool of Dcp1-Dcp2 in the cell decapping activators might be in competition for decapping complex binding.

Collectively, our results yield valuable insights into the mechanism of substrate selection for mRNA quality control and decay in yeast.

Phase 1 – Community Forums Deaf ACCESS: Adapting Consent Through Community Engagement and State-Of-The-Art Simulation

Wed, 06/28/2017 - 8:25am

In 2016, the University of Massachusetts Medical School (UMMS), in partnership with Brown University, was awarded a 2-year grant from the National Institute on Deafness and Other Communication Disorders (NIDCD) to improve Deaf people’s trust and involvement in biomedical research. The Deaf ACCESS: Adapting Consent through Community Engagement and State-of-the-art Simulation research team is led by Melissa Anderson from UMMS and Co-Investigator Timothy Riker from Brown University. The study team also includes four Deaf Community Advisors. Because the research team includes five Deaf members, American Sign Language is the primary language used while working together.

The first research brief for the Deaf ACCESS project at UMass Medical School related to Phase 1: Community Forums is available in ASL.

Comparison of characteristics among Korean American male smokers between survey and cessation studies

Tue, 06/27/2017 - 3:18pm

This study compared characteristics of Korean American men in two studies: a telephone survey with a random sample of Korean American men who reported daily smoking versus a smoking cessation clinical trial with a convenience sample of Korean American men who reported smoking at least 10 cigarettes a day. Guided by the Theory of Planned Behavior (TPB), both studies attempted to explain how much its theoretical variables (attitudes, perceived social norms, and self-efficacy) would explain quit intentions in Korean American men. Participants in the cessation study were less likely to have health insurance coverage (χ2 [2, 271] = 138.31, p = 0.001) than those in the survey study. The cessation group was more likely to smoke in indoor offices (χ2 [1, 231] = 18.09, p = 0.003) and had higher nicotine dependence than the survey group (t269 = 3.32, p = 0.001) but these differences became insignificant when only those who smoked 10 or more cigarettes were compared. Participants in the cessation study had more positive attitudes towards quitting (t267 = 4.99, p < 0.001), stronger perceived social norms favoring quitting (t269 = 5.63, p < 0.001) and greater quit intentions (t268 = 9.86, p < 0.001) at baseline than those in the survey study. Korean American men are more likely to have a quit intention and make a quit attempt when they have more positive and fewer negative attitudes towards quitting and perceive stronger social norms favoring quitting. To motivate Korean American men to quit smoking, clinicians should underscore the immediate health benefits of quitting, promote quitting with cessation aids to reduce perceived risks of quitting in anticipation of withdrawal symptoms, and encourage family members to relate firm anti-smoking messages.

Advancing Data Management Education and Services

Tue, 06/27/2017 - 1:59pm

This issue’s editorial focuses on the response of librarians and information professionals to the United States government’s open access mandates. Librarians and information professionals realize that developing strong data science education curriculum and data literacy skills, dialoging with each other about shared staffing goals, and discovering which data services an institution needs, are vital in helping institutions be able to meet these mandates.

The Utility of the Systemic Inflammatory Respsonse [Response] Syndrome Score on Admission in Children With Acute Pancreatitis

Tue, 06/27/2017 - 12:47pm

OBJECTIVES: Pediatric patients with acute pancreatitis (AP) may meet criteria at admission for the systemic inflammatory response syndrome (SIRS). Early SIRS in adults with AP is associated with severe disease. Our aim was to evaluate the importance of SIRS in children presenting with AP on various outcomes.

METHODS: This is a retrospective cohort study of children hospitalized with AP at Boston Children's Hospital in 2010. Increased length of stay (LOS) and/or admission to the intensive care unit (ICU) served as the primary outcomes. Statistical analyses of measures studied included the presence of SIRS, demographic, and clinical information present on admission.

RESULTS: Fifty encounters, in which AP was the primary admitting diagnosis, were documented. Patients had a median LOS of 4.5 (interquartile range, 2-9) days. Systemic inflammatory response syndrome was present in 22 (44%) of 50 patients at admission. Systemic inflammatory response syndrome at admission was an independent predictor of increased LOS (odds ratio, 7.99; P = 0.045) as well as admission to the ICU (odds ratio, 12.06; P = 0.027).

CONCLUSIONS: The presence of SIRS criteria on admission serves as a useful and easy-to-calculate predictor of increased LOS and admission to ICU in children with AP.

The Science Policy Implications of a Trump Presidency

Tue, 06/27/2017 - 12:47pm

The U.S. presidential election of 2016 produced a dramatic and unexpected result, putting into office a candidate with no experience in public office and no track record on which to base expectations regarding future science policy and research funding in the United States. During the campaign, there was little discussion as to what a Trump presidency would mean for policy issues such as the funding of the National Institutes of Health (NIH) and the National Science Foundation and the regulatory climate for gene and cell therapy. This has left many scientists in the field of gene therapy anxious and uncertain as to their future.

It is indeed perilous to offer conjecture as to the future in situations such as this one. Nonetheless, it may be worthwhile to consider those areas of policy in which Mr. Trump has expressed opinions. With the Republican Party holding majorities in both houses of the U.S. Congress, it seems likely that the Trump administration's overall policy agenda will be implemented in some form in the relatively near future and that such changes will have implications for the future of gene and cell therapy in the United States.

The role of endoscopy in the management of suspected small-bowel bleeding

Tue, 06/27/2017 - 12:47pm

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text.

Adverse events associated with ERCP

Tue, 06/27/2017 - 12:47pm

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text.

Guidelines for privileging, credentialing, and proctoring to perform GI endoscopy

Tue, 06/27/2017 - 12:47pm

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text.

New Assessments and Treatments in ASD

Tue, 06/27/2017 - 12:47pm

OPINION STATEMENT: The assessment of autism spectrum disorder (ASD) is complex and remains clinical, despite advances in basic research. In this chapter, we review new and updated clinical tools, such as screening and diagnostic tests, and discuss the DSM-5 criteria introduced in 2013. We provide an algorithm to guide clinical evaluation and referrals. We also review non-behavioral treatments and summarize recent research. Current conventional treatment of ASD in children includes intensive behavioral interventions (known as applied behavioral analysis or ABA), rehabilitative services such as speech therapy, occupational therapy, physical therapy, social skills training, and counseling. We present new validated information and provide clinical guidance for the evaluation and treatment of young children and youth with ASD.

Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for alpha-1-antitrypsin deficiency

Tue, 06/27/2017 - 12:47pm

Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder alpha-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector administration. In this report we describe the appearance of transgene-specific T-cell responses in two subjects that were part of the phase II trial. The patient with the more robust T-cell response, which was associated with a reduction in transgene expression, was characterized more thoroughly in this study. We learned that the AAT-specific T cells in this patient were cytolytic in phenotype, mapped to a peptide in the endogenous mutant AAT protein that contained a common polymorphism not incorporated into the transgene, and were restricted by a rare HLA class I C alleles present only in this patient. These human studies illustrate the genetic influence of the endogenous gene and HLA haplotype on the outcome of gene therapy.

NASPGHAN Capsule Endoscopy Clinical Report

Tue, 06/27/2017 - 12:47pm

Wireless capsule endoscopy (CE) was introduced in 2000 as a less invasive method to visualize the distal small bowel in adults. Because this technology has advanced it has been adapted for use in pediatric gastroenterology. Several studies have described its clinical use, utility, and various training methods but pediatric literature regarding CE is limited. This clinical report developed by the Endoscopic and Procedures Committee of the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition outlines the current literature, and describes the recommended current role, use, training, and future areas of research for CE in pediatrics.

The Negative Effects of Immigration Restrictions on the Gene Therapy Community

Tue, 06/27/2017 - 12:47pm

The first several weeks since U.S. President Donald J. Trump was inaugurated have been punctuated by a number of Executive Orders (EO) affecting a broad range of individuals. None has had greater potential impact than the January 27, 2017, EO regarding immigration from seven Muslim majority nations. Unfortunately, these actions have had a direct negative impact on some scientists and physicians engaged in the noble pursuit of improving the lives of patients by harnessing the potential of gene therapy.

Three-dimensional Folding of Eukaryotic Genomes

Tue, 06/27/2017 - 9:42am

Chromatin packages eukaryotic genomes via a hierarchical series of folding steps, encrypting multiple layers of epigenetic information, which are capable of regulating nuclear transactions in response to complex signals in environment. Besides the 1-dimensinal chromatin landscape such as nucleosome positioning and histone modifications, little is known about the secondary chromatin structures and their functional consequences related to transcriptional regulation and DNA replication. The family of chromosomal conformation capture (3C) assays has revolutionized our understanding of large-scale chromosome folding with the ability to measure relative interaction probability between genomic loci in vivo. However, the suboptimal resolution of the typical 3C techniques leaves the levels of nucleosome interactions or 30 nm structures inaccessible, and also restricts their applicability to study gene level of chromatin folding in small genome organisms such as yeasts, worm, and plants. To uncover the “blind spot” of chromatin organization, I developed an innovative method called Micro-C and an improved protocol, Micro-C XL, which enable to map chromatin structures at all range of scale from single nucleosome to the entire genome. Several fine-scale aspects of chromatin folding in budding and fission yeasts have been identified by Micro-C, including histone tail-mediated tri-/tetra-nucleosome stackings, gene crumples/globules, and chromosomally-interacting domains (CIDs). CIDs are spatially demarcated by the boundaries, which are colocalized with the promoters of actively transcribed genes and histone marks for active transcription or turnover. The levels of chromatin compaction are regulated via transcription-dependent or transcription-independent manner – either the perturbations of transcription or the mutations of chromatin regulators strongly affect the global chromatin folding. Taken together, Micro-C further reveals chromatin folding behaviors below the sub-kilobase scale and opens an avenue to study chromatin organization in many biological systems.

Farewell from Founding Editor, Elaine Martin

Tue, 06/27/2017 - 9:22am

Farewell from Journal of eScience Librarianship’s Founding Editor, Elaine R. Martin, who is stepping down as Editor-in-Chief with this issue.

Graphic Medicine in the Library: An Educational Outreach Program

Mon, 06/26/2017 - 5:03pm

Objectives: Graphic medicine refers to the discourse of healthcare by way of the medium of comics and is a growing field with far-reaching impact. The objective of this outreach program was to provide educational opportunity to librarians on building graphic medicine collections and the creation of related programming.

Methods: The outreach program proceeded on several fronts over the course of a six-month period, beginning with a two-part webinar series targeted to librarians both in-and-out of the region. These webinars sought to provide background information on graphic medicine, materials to aid with collection development, including key title lists, and serve as brainstorming opportunities for programming, including potential partners. At the same time, outreach was conducted with libraries in the local region, seeking to build community ties and support for the creation of new collections and programming. The program, in this iteration, concluded by creating a series of book club kits, that target specific medical conditions and include graphic novels, suggested questions, further readings, and more. These kits are available to regional groups for borrowing, including libraries who may find them valuable as a trial before building a new collection.