bluuebunny/crossref_metadata_2025 huggingface dataset:
Structures of human mitofusin 1 provide insight into mitochondrial tethering
Authors: Qi Yuanbo , Yan Liming , Yu Caiting , Guo Xiangyang , Zhou Xin , Hu Xiaoyu , Huang Xiaofang , Rao Zihe , Lou Zhiyong , Hu Junjie
Published: December 2016

Mitochondria undergo fusion and fission. The merging of outer mitochondrial membranes requires mitofusin (MFN), a dynamin-like GTPase. How exactly MFN mediates membrane fusion is poorly understood. Here, we determined crystal structures of a minimal GTPase domain (MGD) of human MFN1, including the predicted GTPase and the distal part of the C-terminal tail (CT). The structures revealed that a helix bundle (HB) formed by three helices extending from the GTPase and one extending from the CT closely attaches to the GTPase domain, resembling the configuration of bacterial dynamin-like protein. We show that the nucleotide-binding pocket is shallow and narrow, rendering weak hydrolysis and less dependence on magnesium ion, and that association of HB affects GTPase activity. MFN1 forms a dimer when GTP or GDP/BeF3−, but not GDP or other analogs, is added. In addition, clustering of vesicles containing membrane-anchored MGD requires continuous GTP hydrolysis. These results suggest that MFN tethers apposing membranes, likely through nucleotide-dependent dimerization.
Mining non-lattice subgraphs for detecting missing hierarchical relations and concepts in SNOMED CT
Authors: Cui Licong , Zhu Wei , Tao Shiqiang , Case James T , Bodenreider Olivier , Zhang Guo-Qiang
Published: December 2016

Objective: Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT.

Material and Methods: All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs. Non-lattice subgraphs exhibiting such lexical patterns are often indicative of missing hierarchical relations or concepts. Each lexical pattern is associated with a potential specific type of error.

Results: Applying the structural-lexical method to SNOMED CT (September 2015 US edition), we found 6801 non-lattice subgraphs that matched these lexical patterns, of which 2046 were amenable to visual inspection. We evaluated a random sample of 100 small subgraphs, of which 59 were reviewed in detail by domain experts. All the subgraphs reviewed contained errors confirmed by the experts. The most frequent type of error was missing is-a relations due to incomplete or inconsistent modeling of the concepts.

Conclusions: Our hybrid structural-lexical method is innovative and proved effective not only in detecting errors in SNOMED CT, but also in suggesting remediation for these errors.
Protein Profile and Molecular Markers Related to the Baking Quality of Brazilian Wheat Cultivars
Authors: Dias Renata de O. , de Souza Moacil A. , Pirozi Mônica R. , Oliveira Ludmilla de C. , Pimentel Adérico J. B.
Published: December 2016

To carry out wheat breeding programs, proteins were identified and quantified (through sodium dodecyl sulfate polyacrylamide gel electrophoresis [SDS‐PAGE] and size‐exclusion high‐performance liquid chromatography [SE‐HPLC]) and six allele‐specific markers were tested on 45 Brazilian cultivars. A microscale baking test was applied to associate analytical and genetic responses with baking quality. The results suggested a prevalence of the subunits 2* and 1 in chromosome 1A; 7+8, 7+9, and 17+18 in 1B; and 5+10 in 1D; absence of 1BL/1RS translocation in 62.2% of the genotypes; and presence of Pinb‐D1b and Glu‐A3d in 8.9% of the genotypes. The average SE‐HPLC values were 37.50 and 45.42% for polymeric protein in total protein (PPP) and unextractable polymeric protein (UPP), respectively, and 1.29 for the gliadin‐to‐glutenin (GLI/GLU) ratio, with significant variation among the genotypes (P ≤ 0.05). The baking test also showed a significant difference (P ≤ 0.05) between the cultivars under the same conditions. The cultivars without the 1BL/1RS translocation with rye also showed better results for UPP, PPP, and GLI/GLU in relation to those possessing translocation. These results corroborate for selection of HMW subunits 5+10, cultivars without translocation with rye, with high UPP values and a balanced GLI/GLU ratio (around 1.0) with the objective of obtaining greater wheat baking quality.
Changes in Stroke Volume Induced by Lung Recruitment Maneuver Predict Fluid Responsiveness in Mechanically Ventilated Patients in the Operating Room
Authors: Biais Matthieu , Lanchon Romain , Sesay Musa , Le Gall Lisa , Pereira Bruno , Futier Emmanuel , Nouette-Gaulain Karine
Published: December 2016

Background

Lung recruitment maneuver induces a decrease in stroke volume, which is more pronounced in hypovolemic patients. The authors hypothesized that the magnitude of stroke volume reduction through lung recruitment maneuver could predict preload responsiveness.

Methods

Twenty-eight mechanically ventilated patients with low tidal volume during general anesthesia were included. Heart rate, mean arterial pressure, stroke volume, and pulse pressure variations were recorded before lung recruitment maneuver (application of continuous positive airway pressure of 30 cm H2O for 30 s), during lung recruitment maneuver when stroke volume reached its minimal value, and before and after volume expansion (250 ml saline, 0.9%, infused during 10 min). Patients were considered as responders to fluid administration if stroke volume increased greater than or equal to 10%.

Results

Sixteen patients were responders. Lung recruitment maneuver induced a significant decrease in mean arterial pressure and stroke volume in both responders and nonresponders. Changes in stroke volume induced by lung recruitment maneuver were correlated with those induced by volume expansion (r
2 = 0.56; P < 0.0001). A 30% decrease in stroke volume during lung recruitment maneuver predicted fluid responsiveness with a sensitivity of 88% (95% CI, 62 to 98) and a specificity of 92% (95% CI, 62 to 99). Pulse pressure variations more than 6% before lung recruitment maneuver discriminated responders with a sensitivity of 69% (95% CI, 41 to 89) and a specificity of 75% (95% CI, 42 to 95). The area under receiver operating curves generated for changes in stroke volume induced by lung recruitment maneuver (0.96; 95% CI, 0.81 to 0.99) was significantly higher than that for pulse pressure variations (0.72; 95% CI, 0.52 to 0.88; P < 0.05).

Conclusions

The authors’ study suggests that the magnitude of stroke volume decrease during lung recruitment maneuver could predict preload responsiveness in mechanically ventilated patients in the operating room.
Vertebroplasty and Return to Work for Thoracolumbar Fractures Within the Workers’ Compensation Population
Authors: Levin Jay M. , Anderson Joshua T. , Haas Arnold R. , Percy Rick , Woods Stephen T. , Ahn Uri M. , Ahn Nicholas U.
Published: December 2016

Study Design.

Retrospective cohort study.

Objective.

Analyze efficacy of vertebroplasty and its affect on return to work (RTW) in a workers’ compensation (WC) population

Summary of Background Data.

Vertebroplasty remains a controversial treatment modality for vertebral compression fractures (VCFs). No studies have analyzed use of vertebroplasty in the clinically distinct WC population.

Methods.

A total of 371 Ohio WC subjects were identified who sustained VCFs and were treated with either vertebroplasty or conservative medical therapy between 1993 and 2013 using Current Procedural Terminology procedural and International Classification of Diseases, Ninth Revision diagnosis codes. Subjects with a prior smoking history, prior thoracolumbar surgery or comorbidities, or underwent decompression and/or fusion within 3 months after injury were excluded. Forty-six subjects had undergone vertebroplasty within 1 year of injury and were therefore included in the vertebroplasty group. The remaining 325 subjects received spinal orthosis and formed the control group. The primary outcomes were whether subjects returned to work at early and late time points. Early RTW was defined as returning to work within 3 months and remaining at work for more than 6 months of the following year. Late RTW was defined as returning to work within 2 years and remaining at work for more than 6 months of the following year. Secondary outcomes included opioid use, all-cause mortality, and additional VCFs.

Results.

Approximately 37% (17/46) of vertebroplasty group made an early RTW, compared with 35.4% (115/325) of control group (P = 0.835). Regarding late RTW, only 54.3% (25/46) of vertebroplasty group made a sustainable RTW, compared with 70.8% (230/325) of subjects in control group (P = 0.025). In addition, the vertebroplasty group was associated with significantly higher postoperative opioid use.

Conclusion.

Vertebroplasty may not be an effective treatment modality for VCFs in the WC population when RTW is the primary goal.

Level of Evidence: 3
Generalization of serotonin and dopamine ligands to the discriminative stimulus effects of different doses of ±3,4-methylenedioxymethamphetamine
Authors: Webster Jeremy I. , Harper David N. , Schenk Susan
Published: December 2016

Studies that have attributed the discriminative stimulus effects of ±3,4-methylenedioxymethamphetamine (MDMA) to serotonergic mechanisms typically use a relatively low training dose of 1.5 mg/kg. The role of serotonin in the discriminative stimulus effects of higher doses of MDMA is, however, unknown. Separate groups of rats were trained to discriminate MDMA (1.5 or 3.0 mg/kg) from saline using a two-lever, food-reinforced drug-discrimination procedure. Generalization tests were carried out with a range of serotonin and dopamine ligands. Fluoxetine (0.3–3 mg/kg), clomipramine (1–10 mg/kg) and meta-chlorophenylpiperazine (0.3–2 mg/kg) dose-dependently substituted for the 1.5 mg/kg MDMA stimulus, but not the 3.0 mg/kg MDMA stimulus. 8-OH-DPAT (0.03–0.3 mg/kg) and RU-24969 (0.3–3 mg/kg) substituted for both the low-dose and the high-dose MDMA stimulus. The generalization dose–effect curve produced by 2,5-dimethoxy-4-iodoamphetamine (0.3–3 mg/kg) was shifted to the right for the 3.0 mg/kg MDMA-trained group. Amphetamine (0.25 and 0.5 mg/kg) and apomorphine (0.125 and 0.25 mg/kg) substituted for the 3.0 mg/kg, but not the 1.5 mg/kg MDMA stimulus. The results suggest some differences in the role of serotonin and dopamine in the discriminative stimulus effects of a low versus a higher dose of MDMA.
UNREPORTED SIDE EFFECT OF INTRAVITREAL DICLOFENAC IN CHRONIC DIABETIC MACULAR EDEMA
Authors: Chidambara Lavanya , Singhal Rekha , Srinivasan Priya , Yadav Naresh Kumar
Published: December 2016

Purpose:

To evaluate the safety and efficacy of intravitreal diclofenac sodium.

Methods:

A 61-year-old male with persistent diabetic macular edema was treated with 450 μg of intravitreal diclofenac sodium (systemic preparation).

Results:

Postinjection Day 1, the spectral domain optical coherence tomography showed irregular vitreoretinal interface with wrinkling and separation of the internal limiting membrane from the nerve fiber layer with homogeneity of the inner layers. At 1 month, the compactness of the retinal layers was restored. Complete resolution of the cystoid macular edema was seen. At 1 year, there was mild flattening of the foveal depression with epiretinal membrane.

Conclusion:

Various studies have shown the safety and efficacy of intravitreal diclofenac without any reported side effect. We report the inner retinal toxicity in the form of cystic spaces and splitting of internal limiting membrane from nerve fiber layer on the first follow-up day, postinjection, which resolved over a period of 1 month. Further studies are needed to assess the safety of intravitreal diclofenac sodium.
A Simple and Effective Technique for Anatomical Approximation of the Upper Pericardium Using Hemostatic Clips
Authors: Husain Mubassher , Acharya Metesh Nalin , Cummings Ian , Raja Shahzad Gull
Published: December 2016

Closure of the pericardium is important to protect bypass grafts, the great vessels, and the heart from injury due to sternal dehiscence. Furthermore, it is reported to reduce the formation of pericardial adhesions and thus facilitate entry into the chest at resternotomy. We here describe a simple, reproducible, and effective technique for tension-free approximation of the upper pericardium by applying small hemostatic clips to the preserved thymic fascia overlying the pericardium.
Embracing a Nurse-Driven Alcohol Withdrawal Protocol Through Quality Improvement
Authors: Barrett John , Jansen Maria , Cooper April , Felbinger Matthew , Waters Faith
Published: December 2016

Background

Alcohol withdrawal can lead to severe complications including seizures, delirium tremens, and death if not treated appropriately. Nurses are critical to the safety and outcomes of these patients.

Objective

The objective of this retrospective study was to determine if nursing education on a community hospital’s alcohol withdrawal protocol led to improved nursing compliance.

Methods

This is a quality improvement project involving a two-part retrospective review—an initial needs assessment followed by nursing education and a subsequent posteducation retrospective review. The initial needs assessment included 65 patients. The subsequent posteducation group included 50 patients.

Results

Nursing compliance of 1-hour assessments increased after the educational intervention; however, there was no statistically significant difference in 6-hour assessment or medication administration protocol compliance between preeducation and posteducation groups.

Conclusion

Nursing education is a good place to start in improving compliance with an alcohol withdrawal protocol, but physicians need to be included to increase standardization within the institution. Future study should look at the effectiveness of different assessment frequency intervals and its impact on patient-centered outcomes.
Blanching Spots on the Trunk
Authors: Jacob Sharon E.
Published: December 2016

Teledermatology is a term to describe the provision of dermatologic medical services through telecommunication technology. In this modality, there is transfer of patient medical information electronically (including history and visual data) obtained in one location to a provider who is in another location (Roman & Jacob, 2015). The construct of the TeleDermViewPoint column is such that cases are presented in a standardized teledermatology reader format reflective of an actual teledermatology report. This is a case of blanching spots on the trunk.
Vismodegib
Authors: Siddiqui Fariha , Zito Patrick M.
Published: December 2016

By definition, a drug is a medicine or substance that exerts a physiologic effect on an organism. In dermatology, medications and substances are utilized on a daily basis from topical treatments to anesthetics in surgery. The purpose of this section is to focus on some of the more common substances, specifically how they work, how they are utilized, and their routine alternatives (if available). The mechanism of action, usage, and alternatives of the medication vismodegib are discussed.
The post-transplant course of patients undergoing liver transplantation for nonalcoholic steatohepatitis versus cryptogenic cirrhosis: a retrospective case–control study
Authors: Unger Lukas W. , Herac Merima , Staufer Katharina , Salat Andreas , Silberhumer Gerd , Hofmann Michael , Trauner Michael , Rasoul-Rockenschaub Susanne , Soliman Thomas , Reiberger Thomas , Berlakovich Gabriela A.
Published: December 2016

Background

Nonalcoholic fatty liver disease (NAFLD) can be considered the hepatic manifestation of the metabolic syndrome with nonalcoholic steatohepatitis (NASH) as its progressive form. With increasing prevalence of the metabolic syndrome, NASH cirrhosis is becoming a leading cause for liver transplantation. Some cases of orthotopic liver transplantation (OLT) due to cryptogenic cirrhosis (CC) might show typical features of NASH cirrhosis. Therefore, our aim was to assess recurrence of liver fibrosis in patients transplanted for NASH versus CC after OLT.

Patients and methods

Patients transplanted for CC or NASH between 1 January 2004 and 30 September 2015 were included. The histological NAFLD activity score and the NAFLD fibrosis score (NFS) were assessed.

Results

In total, 15 and 12 patients underwent OLT because of NASH and CC, respectively. The case load for OLT because of NASH was constantly increasing (n=2 in 2004–2007 vs. n=9 in 2012–2015) whereas decreasing for CC (n=6 in 2004–2007 vs. n=2 in 2012–2015). Patient characteristics at OLT were similar, except for an older age and a higher BMI in NASH patients (59.1±2.2 vs. 51.8±2.9 years, P=0.05; 27.7±1.2 vs. 24.3±0.8 kg/m2, P=0.035). Although post-OLT plasma lipid levels and incidence of de-novo hypertension, diabetes, and hyperlipidemia were similar between groups, the post-transplant NFS re-increased in the NASH group (but not in the CC: −0.1317 vs. −1.3645 at 12 months post-OLT, P=0.0400). Post-transplant survival was similar in NASH and CC patients.

Conclusion

According to the NFS, some NASH patients show recurrence of fibrosis as early as 6–12 months after OLT.
Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine: Part 1: Fit-for-Purpose Approach to Classification of Clinical Immunohistochemistry Biomarkers
Authors: Cheung Carol C. , D’Arrigo Corrado , Dietel Manfred , Francis Glenn D. , Gilks C. Blake , Hall Jacqueline A. , Hornick Jason L. , Ibrahim Merdol , Marchetti Antonio , Miller Keith , van Krieken J. Han , Nielsen Soren , Swanson Paul E. , Taylor Clive R. , Vyberg Mogens , Zhou Xiaoge , Torlakovic Emina E.
Published: December 2016

Technical progress in immunohistochemistry (IHC) as well as the increased utility of IHC for biomarker testing in precision medicine avails us of the opportunity to reassess clinical IHC as a laboratory test and its proper characterization as a special type of immunoassay. IHC, as used in current clinical applications, is a descriptive, qualitative, cell-based, usually nonlinear, in situ protein immunoassay, for which the readout of the results is principally performed by pathologists rather than by the instruments on which the immunoassay is performed. This modus operandi is in contrast to other assays where the instrument also performs the readout of the test result (eg, nephelometry readers, mass spectrometry readers, etc.). The readouts (results) of IHC tests are used either by pathologists for diagnostic purposes or by treating physicians (eg, oncologists) for patient management decisions, the need for further testing, or follow-up. This paper highlights the distinction between the original purpose for which an IHC test is developed and its subsequent clinical uses, as well as the role of pathologists in the analytical and postanalytical phases of IHC testing. This paper is the first of a 4-part series, under the general title of “Evolution of Quality Assurance for Clinical Immunohistochemistry in the Era of Precision Medicine.”
The Placebo Analgesic Effect in Healthy Individuals and Patients: A Meta-Analysis
Authors: Forsberg June Thorvaldsen , Martinussen Monica , Flaten Magne Arve
Published: December 2016

Objective

The present meta-analysis investigates whether the magnitude of placebo analgesia is different in patients compared with healthy individuals and whether placebo analgesia is different in experimentally induced pain compared with clinical pain in patients.

Methods

A literature search in Web of Science (ISI) on the terms “placebo analgesia” and “placebo analgesic” was conducted. The search resulted in 71 studies, including 4239 participants. Fifty-five studies included healthy individuals and 16 studies included patients. Of the 16 studies with patients, five studies investigated clinical pain and 11 studies investigated experimentally induced pain.

Results

The average effect size was 1.24 for healthy individuals and 1.49 for patients. In the studies with patients, the average effect sizes of placebo treatment were 1.73 for experimentally induced pain and 1.05 for clinical pain. A χ2 test revealed that there were relatively more studies with patients compared with healthy volunteers in which there was a clinically significant reduction in pain (p = .040).

Conclusions

The findings suggest that patients benefited from placebo treatment to a greater degree than healthy individuals did and that studies on healthy individuals may underestimate the magnitude of the placebo analgesic effect in patients. Patients' clinical pain and experimentally induced pain respond to placebo to the same degree.
Validity of the European Society of Cardiology's Psychosocial Screening Interview in Patients With Coronary Artery Disease—The THORESCI Study
Authors: van Montfort Eveline , Denollet Johan , Widdershoven Jos , Kupper Nina
Published: December 2016

Objective

The aim of the study was to examine the validity of the European Society of Cardiology (ESC) psychosocial screening instrument.

Methods

A total of 508 acute (67%) or elective (33%) percutaneous coronary intervention patients (mean [standard deviation]age = 63 [10] years, 81% male) completed the ESC screening interview and established questionnaires for psychosocial risk markers, that is, depression (Patient Health Questionnaire 9), anxiety (Generalized Anxiety Disorder Questionnaire 7), type D personality (Type D Scale 14), hostility (Cook-Medley Hostility Scale 7), and marital/work stress (Maudsley Marital Quality Questionnaire 6, Effort-Reward Imbalance Scale) during or close after hospital admission. At 1-year follow-up, angina and cardiopulmonary symptoms were assessed.

Results

Prevalence estimates of psychosocial factors based on the ESC screener were as follows: depression (18%), anxiety (33%), negative affectivity (11%), social inhibition (41%), work stress (17%), marital stress (2%), and hostility (38%). Analysis of correspondence with validated questionnaires revealed fair to moderate agreement (depression [κ = .39], anxiety [κ = .23], type D personality [κ = .21]), regardless of percutaneous coronary intervention indication. For work and marital stress, there was poor to fair performance (κ range = .04–.24); agreement for hostility was poor (κ = −.27). A positive ESC screen for depression, anxious tension, and type D personality was associated with more angina and cardiopulmonary symptoms at follow-up (odds ratios ranging between 1.85 (95% confidence interval = 0.84–4.08) and 8.01 (95% confidence interval = 2.35–27.35).

Conclusions

The ESC screener contributes to the search for a multidimensional and easy-to-use psychosocial screening instrument for cardiac patients. Although the screener, in its current form, may not be sufficiently valid to reliably detect all predefined psychosocial factors, screening scores for depression and anxiety might be useful in clinical practice. Our findings can be used for further refinement and validation of the screener.
Sex Differences in the Relationship Between Depressive Symptoms and Actigraphic Assessments of Sleep and Rest-Activity Rhythms in a Population-Based Sample
Authors: White Kaitlin Hanley , Rumble Meredith E. , Benca Ruth M.
Published: December 2016

Objective

Depression is often associated with disruptions in sleep and circadian rhythms. We aimed to confirm these relationships via actigraphic assessment in a large, population-based sample and test whether sex moderates these relationships.

Methods

A total of 418 participants (age = 35–85 years, mean [standard deviation] = 57.04 [11.47]) completed questionnaires and 1 week of actigraphy, used to calculate sleep and rest-activity statistics including mesor (mean activity level), amplitude (height of rhythm), and acrophase (time of day that rhythm peaks).

Results

Depressive symptoms, assessed via Center for Epidemiologic Studies Depression Scale, were associated with disrupted sleep and rest-activity rhythms. Furthermore, men demonstrated longer sleep onset latency (SOL, B = −13.28, p < .001), longer wake time after sleep onset (B = −6.26, p < .01), lower sleep efficiency (B = 5.91, p < .001), and lower total sleep time (TST, B = 33.16, p < .001) than women. Sex moderated the relationship between depression and SOL, TST, mesor, and amplitude; sex-stratified models revealed that higher depression scores were associated with greater SOL (B = 1.05, p < .001) and less TST (B = −0.87, p < .10) for women with higher depressive symptoms, but lower mesor (B = −1.75, p < .01) and amplitude (B = −1.94, p < .01) for men with higher depressive symptoms.

Conclusions

Depressive symptoms were related to disrupted sleep continuity and rest-activity rhythms in this population-based sample; however, these relationships differed by sex. Women with greater depressive symptoms exhibited difficulty with sleep continuity, whereas men with greater depressive symptoms demonstrated disruption throughout the 24-hour rhythm.
Future prospects for new vaccines against sexually transmitted infections
Authors: Gottlieb Sami L. , Johnston Christine
Published: December 2016

Purpose of review

This review provides an update on the need, development status, and important next steps for advancing development of vaccines against sexually transmitted infections (STIs), including herpes simplex virus (HSV), Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), and Treponema pallidum (syphilis).

Recent findings

Global estimates suggest that more than a million STIs are acquired every day, and many new and emerging challenges to STI control highlight the critical need for development of new STI vaccines. Several therapeutic HSV-2 vaccine candidates are in Phase I/II clinical trials, and one subunit vaccine has shown sustained reductions in genital lesions and viral shedding, providing hope that an effective HSV vaccine is on the horizon. The first vaccine candidate for genital chlamydia infection has entered Phase I trials, and several more are in the pipeline. Use of novel technological approaches will likely see viable vaccine candidates for gonorrhea and syphilis in the future. The global STI vaccine roadmap outlines key activities to further advance STI vaccine development.

Major progress is being made in addressing the large global unmet need for STI vaccines. With continued collaboration and support, these critically important vaccines for global sexual and reproductive health can become a reality.
The Application of a Moldable Skin Barrier in the Self-Care of Elderly Ostomy Patients
Authors: Liu Gaoming , Chen Yongyi , Luo Jiayou , Liu Aizhong , Tang Xinghui
Published: December 2016

The quality of ostomy directly affects the stoma patient's quality of life. This study investigated the application of a moldable skin barrier in the self-care of elderly stoma patients after colostomy for colorectal cancer. A total of 104 elderly stoma patients (65–79 years) who underwent colostomy because of colorectal cancer were randomly divided into an experimental group (56 cases) receiving a moldable skin barrier and a control group (48 cases) receiving a conventional skin barrier. The information on peristomal irritant dermatitis occurrence, the satisfaction of self-care, and related care costs were collected 1 month after patients were discharged from the hospital. The overall incidence of irritant dermatitis was significantly lower (p = .01), the self-care satisfaction score was significantly higher (p = .02), and the cost for leakage-proof cream (p < .001) was significantly lower in the experimental group than in the control group. In contrast, no significant differences in the cost of ostomy equipment and the barrier replacement interval were observed. In conclusion, a moldable skin barrier can reduce the incidence of irritant dermatitis in elderly stoma patients, improve their self-care satisfaction, and reduce the cost of leakage-proof cream use compared with the conventional stoma skin barrier.
Laxative Use and Self-Reported Constipation in a Community-Dwelling Elderly Population
Authors: Werth Barry L. , Williams Kylie A. , Pont Lisa G.
Published: December 2016

The objectives of this study were to (1) determine the prevalence of laxative use and self-reported constipation and (2) identify risk factors associated with constipation in a community-dwelling elderly population. A retrospective cross-sectional survey using data from the Australian Longitudinal Study of Ageing was used to explore laxative use and constipation in a cohort of community-dwelling older persons. The prevalence of laxative use was 15% and the prevalence of self-reported constipation was 21%. Females were more likely to report constipation and use laxatives. Of those using laxatives, men were more likely to have their laxatives prescribed by a doctor whereas women were more likely to self-medicate. Poor self-rated health and a higher need for assistance with activities of daily living were identified as risk factors for constipation. Constipation is a common condition affecting the community-dwelling elderly. There is a need to optimize the management of constipation and use of laxatives in such populations.
Mode of Information Delivery Does Not Effect Anesthesia Trainee Performance During Simulated Perioperative Pediatric Critical Events
Authors: Watkins Scott C. , Anders Shilo , Clebone Anna , Hughes Elisabeth , Patel Vikram , Zeigler Laura , Shi Yaping , Shotwell Matthew S. , McEvoy Matthew D. , Weinger Matthew B.
Published: December 2016

Introduction

Cognitive aids (CAs), including emergency manuals and checklists, have been recommended as a means to address the failure of healthcare providers to adhere to evidence-based standards of treatment during crisis situations. Unfortunately, users of CAs still commit errors, omit critical steps, fail to achieve perfect adherence to guidelines, and frequently choose to not use CA during both simulated and real crisis events. We sought to evaluate whether the mode in which a CA presents information (ie, paper vs. electronic) affects clinician performance during simulated critical events.

Methods

In a prospective, randomized, controlled trial, anesthesia trainees managed simulated events under 1 of the following 3 conditions: (1) from memory alone (control), (2) with a paper CA, or (3) with an electronic version of the same CA. Management of the events was assessed using scenario-specific checklists. Mixed-effect regression models were used for analysis of overall checklist score and for elapsed time.

Results

One hundred thirty-nine simulated events were observed and rated. Approximately, 1 of 3 trainees assigned to use a CA (electronic 29%, paper 36%) chose not to use it during the scenario. Compared with the control group (52%), the overall score was 6% higher in the paper CA group and 8% higher (95% confidence interval, 0.914.5; P = 0.03) in the electronic CA group. The difference between paper and electronic CA was not significant. There was a wide range in time to first use of the CA, but the time to task completion was not affected by CA use, nor did the time to CA use impact CA effectiveness as measured by performance.

Conclusions

The format (paper or electronic) of the CA did not affect the impact of the CA on clinician performance in this study. Clinician compliance with the use of the CA was unaffected by format, suggesting that other factors may determine whether clinicians choose to use a CA or not. Time to use of the CA did not affect clinical performance, suggesting that it may not be when CAs are used but how they are used that determines their impact. The current study highlights the importance of not just familiarizing clinicians with the content of CA but also training clinicians in when and how to use an emergency CA.
Electroconvulsive Therapy Practice in New Zealand
Authors: Fisher Mark Wilkinson , Morrison John , Jones Paul Anthony
Published: December 2016

Objectives

The aim of this study was to describe the contemporary practice of electroconvulsive therapy (ECT) in New Zealand.

Methods

A 53-item questionnaire was sent to all services providing ECT as of December 2015.

Results

Electroconvulsive therapy was provided by 16 services covering 15 district health boards funded by the New Zealand government. No private facilities provided ECT. All services providing ECT responded to an online survey questionnaire. Rates of ECT utilization were low relative to similar countries. Survey results indicated ECT was practiced to an overall good standard. Several resource and logistical issues potentially contributing to low ECT utilization were identified.

Conclusions

Electroconvulsive therapy in New Zealand is provided using modern equipment and practices. However, overall rates of utilization remain low, perhaps as a result of controversy surrounding ECT and some resourcing issues.
Impact of climatic changes in the Late Pleistocene on migrations and extinctions of mammals in Europe: four case studies
Authors: Baca Mateusz , Nadachowski Adam , Lipecki Grzegorz , Mackiewicz Paweł , Marciszak Adrian , Popović Danijela , Socha Paweł , Stefaniak Krzysztof , Wojtal Piotr
Published: December 2016

Climate changes that occurred during the Late Pleistocene have profound effects on the distribution of many plant and animal species and influenced the formation of contemporary faunas and floras of Europe. The course and mechanisms of responses of species to the past climate changes are now being intensively studied by the use of direct radiocarbon dating and genetic analyses of fossil remains. Here, we review the advances in understanding these processes by the example of four mammal species: woolly mammoth (Mammuthus primigenius), cave bear (Ursus spelaeus s. l.), saiga antelope (Saiga tatarica) and collared lemmings (Dicrostonyx ssp.). The cases discussed here as well as others show that the migrations, range shifts and local extinctions were the main responses to climate changes and that the dynamics of these climate driven processes were much more profound than it was previously thought. Each species reacted by its individual manner, which depended on its biology and adaptation abilities to the changing environment and climate conditions. The most severe changes in European ecosystems that affected the largest number of species took place around 33–31 ka BP, during the Last Glacial Maximum 22–19 ka BP and the Late Glacial warming 15–13 ka BP.
The Tell-Tale Genome
Authors: Bortolini Eugenio , Pagani Luca , Crema Enrico R. , Sarno Stefania , Barbieri Chiara , Boattini Alessio , Sazzini Marco , Graça da Silva Sara , Martini Gessica , Metspalu Mait , Pettener Davide , Luiselli Donata , Tehrani Jamshid J.
Published: December 2016

Observable patterns of cultural variation are consistently intertwined with demic movements, cultural diffusion, and adaptation to different ecological contexts (Cavalli-Sforza and Feldman 1981; Boyd and Richerson 1985). The quantitative study of gene-culture co-evolution has focused in particular on the mechanisms responsible for change in frequency and attributes of cultural traits, on the spread of cultural information through demic and cultural diffusion, and on detecting relationships between genetic and cultural lineages. Here, for the first time, we make use of worldwide whole-genome sequences (Pagani et al. 2016) to assess the impact of demic diffusion on cultural diversity, focusing on the variability observed in folktale traditions (N=596) (Uther 2004) in Eurasia and Africa. We show that at small geographic scales (<=5000 km) there is a strong correlation between folktale and genomic distance when the effect of geography is corrected, while geographic distance has no independent effect on the distribution of folkloric narratives at the same spatial scale. This points to demic processes (i.e. population movement and replacement) as the main driver of folktale transmission at limited geographic ranges. The role of population movements becomes more apparent when regions characterized by episodes of directional expansions, such as the Neolithization of West Eurasia, are examined. Furthermore, we identify 89 individual tales which are likely to be predominantly transmitted through demic diffusion, and locate putative focal areas for a subset of them.
Gene expression models based on a reference laboratory strain are bad predictors ofMycobacterium tuberculosiscomplex transcriptional diversity
Authors: Chiner-Oms Alvaro , González-Candelas Fernando , Comas Iñaki
Published: December 2016

Species of theMycobacterium tuberculosiscomplex (MTBC) kill more people every year than any other infectious disease. As a consequence of its global distribution and parallel evolution with the human host the bacteria is not genetically homogeneous. The observed genetic heterogeneity has relevance at different phenotypic levels, from gene expression to epidemiological dynamics. However current systems biology datasets have focused in the laboratory reference strain H37Rv. By using large expression datasets testing the role of almost two hundred transcription factors, we have constructed computational models to grab the expression dynamics ofMycobacterium tuberculosisH37Rv genes. However, we have found that many of those transcription factors are deleted or likely dysfunctional across strains of the MTBC. In accordance, we failed to predict expression changes in strains with a different genetic background when compared with experimental data. The results highlight the importance of designing systems biology approaches that take into account the tubercle bacilli, or any other pathogen, genetic diversity if we want to identify universal targets for vaccines, diagnostics and treatments.
Identification of regulatory targets for the bacterial Nus factor complex
Authors: Baniulyte Gabriele , Singh Navjot , Benoit Courtney , Johnson Richard , Ferguson Robert , Paramo Mauricio , Stringer Anne M. , Scott Ashley , Lapierre Pascal , Wade Joseph T.
Published: December 2016

Nus factors are broadly conserved across bacterial species, and are often essential for viability. A complex of five Nus factors (NusB, NusE, NusA, NusG and SuhB) is considered to be a dedicated regulator of ribosomal RNA folding, and has been shown to prevent Rho-dependent transcription termination. We have established the first cellular function for the Nus factor complex beyond regulation of ribosomal assembly: repression of the Nus factor-encoding gene,suhB. This repression occurs by translation inhibition followed by Rho-dependent transcription termination. Thus, the Nus factor complex can prevent or promote Rho activity depending on the gene context. Extensive conservation of NusB/E binding sites upstream ofnusfactor genes suggests that Nus factor autoregulation occurs in many species. Putative NusB/E binding sites are also found upstream of many other genes in diverse species, and we demonstrate Nus factor regulation of one such gene inCitrobacter koseri. We conclude that Nus factors have an evolutionarily widespread regulatory function beyond ribosomal RNA, and that they are often autoregulatory.
Genome-wide survey ofPseudomonas aeruginosaPA14 reveals a role for the glyoxylate pathway and extracellular proteases in the limited utilization of mucin
Authors: Flynn Jeffrey M. , Phan Chi , Hunter Ryan C.
Published: December 2016

Chronic airway infections by the opportunistic pathogenPseudomonas aeruginosaare major cause of mortality in cystic fibrosis (CF) patients. While this bacterium has been extensively studied for its virulence mechanisms, biofilm growth and immune evasion within the CF airways, comparatively little is known about the nutrient sources that sustain its growthin vivo. Respiratory mucins represent a potentially abundant bioavailable nutrient source, though we have recently shown that canonical pathogens inefficiently use these host glycoproteins as a growth substrate. Yet, given thatP. aeruginosa, particularly in its biofilm mode of growth is thought to grow slowlyin vivo, the inefficient use of mucin glycoproteins may have relevance to its persistence within the CF airways. To this end, here we use whole genome fitness analysis combining transposon mutagenesis with high throughput sequencing (TnSeq) to identify genetic determinants required forP. aeruginosagrowth using intact purified mucins as a sole carbon source. Our analysis reveals a biphasic growth phenotype, during which the glyoxylate pathway and amino acid biosynthetic machinery are required for mucin utilization. Secondary analyses confirmed the simultaneous liberation and consumption of acetate during mucin degradation and revealed a central role for the extracellular proteases LasB and AprA. Together, these studies identified theP. aeruginosagenes required for mucin-based nutrient acquisition and reveal a host-pathogen dynamic that may contribute to its persistence within the CF airways.
Precise Quantification of Translation Inhibition by mRNA Structures that Overlap with the Ribosomal Footprint in N-terminal Coding Sequences
Authors: Espah Borujeni Amin , Cetnar Daniel , Farasat Iman , Smith Ashlee , Lundgren Natasha , Salis Howard M
Published: December 2016

A mRNA’s translation rate is controlled by several sequence determinants, including the presence of RNA structures within the N-terminal regions of its coding sequences. However, the physical rules that govern when such mRNA structures will inhibit translation remain unclear. Here, we introduced systematically designed RNA hairpins into the N-terminal coding region of a reporter protein with steadily increasing distances from the start codon, followed by characterization of their mRNA and expression levels inE. coli. We found that the mRNAs’; translation rates were repressed, by up to 1410-fold, when mRNA structures overlapped with the ribosome’s footprint. In contrast, when the mRNA structure was located outside the ribosome’s footprint, translation was repressed by less than 2-fold. By combining our measurements with biophysical modeling, we determined that the ribosomal footprint extends 13 nucleotides into the N-terminal coding region and, when a mRNA structure overlaps or partially overlaps with the ribosomal footprint, the free energy to unfold only the overlapping structure controlled the extent of translation repression. Overall, our results provide precise quantification of the rules governing translation initiation at N-terminal coding regions, improving the predictive design of post-transcriptional regulatory elements that regulate translation rate.
Nutrient dynamics and stream order influence microbial community patterns along a 2914 km transect of the Mississippi River
Authors: Henson Michael W. , Hanssen Jordan , Spooner Greg , Fleming Patrick , Pukonen Markus , Stahr Frederick , Cameron Thrash J.
Published: December 2016

Draining 31 states and roughly 3 million km2, the Mississippi River (MSR) and its tributaries constitute an essential resource to millions of people for clean drinking water, transportation, agriculture, and industry. Since the turn of the 20thcentury, MSR water quality has continually rated poorly due to human activity. Acting as first responders, microorganisms can mitigate, exacerbate, and/or serve as predictors for water quality, yet we know little about their community structure or ecology at the whole river scale for large rivers. We collected both biological (16S and 18S rRNA gene amplicons) and physicochemical data from 38 MSR sites over nearly 3000 km from Minnesota to the Gulf of Mexico. Our results revealed a microbial community composed of similar taxa to other rivers but with unique trends in the relative abundance patterns among phyla, OTUs, and the core microbiome. Furthermore, we observed a separation in microbial communities that mirrored the transition from an 8thto 10thStrahler order river at the Missouri River confluence, marking a different start to the lower MSR than the historical distinction at the Ohio River confluence in Cairo, IL. Within MSR microbial assemblages we identified subgroups of OTUs from the phyla Acidobacteria, Bacteroidetes, Oomycetes, and Heterokonts that were associated with, and predictive of, the important eutrophication nutrients nitrate and phosphate. This study offers the most comprehensive view of MSR microbiota to date, provides important groundwork for higher resolution microbial studies of river perturbation, and identifies potential microbial indicators of river health related to eutrophication.
BLISS: quantitative and versatile genome-wide profiling of DNA breaks in situ
Authors: Yan Winston X. , Mirzazadeh Reza , Garnerone Silvano , Scott David , Schneider Martin W. , Kallas Tomasz , Custodio Joaquin , Wernersson Erik , Gao Linyi , Li Yinqing , Federova Yana , Zetsche Bernd , Zhang Feng , Bienko Magda , Crosetto Nicola
Published: December 2016

We present a method for genome-wide DNA double-strand Breaks (DSBs) Labeling In Situ and Sequencing (BLISS) which, compared to existing methods, introduces several key features: 1) high efficiency and low input requirement by in situ DSB labeling in cells or tissue sections directly on a solid surface; 2) easy scalability by performing in situ reactions in multi-well plates; 3) high sensitivity by linearly amplifying tagged DSBs using in vitro transcription; and 4) accurate DSB quantification and control of PCR biases by using unique molecular identifiers. We demonstrate the ability to use BLISS to quantify natural and drug-induced DSBs in low-input samples of cancer cells, primary mouse embryonic stem cells, and mouse liver tissue sections. Finally, we applied BLISS to compare the specificity of CRISPR-associated RNA-guided endonucleases Cas9 and Cpf1, and found that Cpf1 has higher specificity than Cas9. These results establish BLISS as a versatile, sensitive, and efficient method for genome-wide DSB mapping in many applications.
Clonal conversion of B lymphoid leukemia reveals cross-lineage transfer of malignant states
Authors: Somasundaram Rajesh , Åhsberg Josefine , Okuyama Kazuki , Ungerbäck Jonas , Lilljebjörn Henrik , Fioretos Thoas , Strid Tobias , Sigvardsson Mikael
Published: December 2016

Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells. Even though the conversion process involved global changes in gene expression and lineage-restricted epigenetic reconfiguration, the malignant phenotype of the cells was preserved, enabling them to expand as T lineage leukemia cells in vivo. Furthermore, while the transformed pro-B cells displayed plasticity toward myeloid lineages, the converted cells failed to cause myeloid leukemia after transplantation. These data provide evidence that a malignant phenotype can be transferred between hematopoietic lineages. This has important implications for modern cancer medicine because lineage targeted treatment of leukemia patients can be predicted to provoke the emergence of phenotypically altered subclones, causing clinical relapse.