bluuebunny/crossref_metadata_2025_split huggingface dataset:
UDP-4-Keto-6-Deoxyglucose, a Transient Antifungal Metabolite, Weakens the Fungal Cell Wall Partly by Inhibition of UDP-Galactopyranose Mutase
Authors: Ma Liang , Salas Omar , Bowler Kyle , Bar-Peled Maor , Sharon Amir 
Published: November 2017

ABSTRACT

Can accumulation of a normally transient metabolite affect fungal biology? UDP-4-keto-6-deoxyglucose (UDP-KDG) represents an intermediate stage in conversion of UDP-glucose to UDP-rhamnose. Normally, UDP-KDG is not detected in living cells, because it is quickly converted to UDP-rhamnose by the enzyme UDP-4-keto-6-deoxyglucose-3,5-epimerase/-4-reductase (ER). We previously found that deletion of the
er
gene in
Botrytis cinerea
resulted in accumulation of UDP-KDG to levels that were toxic to the fungus due to destabilization of the cell wall. Here we show that these negative effects are at least partly due to inhibition by UDP-KDG of the enzyme UDP-galactopyranose mutase (UGM), which reversibly converts UDP-galactopyranose (UDP-Gal
p
) to UDP-galactofuranose (UDP-Gal
f
). An enzymatic activity assay showed that UDP-KDG inhibits the
B. cinerea
UGM enzyme with a
K

i

of 221.9 µM. Deletion of the
ugm
gene resulted in strains with weakened cell walls and phenotypes that were similar to those of the
er
deletion strain, which accumulates UDP-KDG. Gal
f
residue levels were completely abolished in the Δ
ugm
strain and reduced in the Δ
er
strain, while overexpression of the
ugm
gene in the background of a Δ
er
strain restored Gal
f
levels and alleviated the phenotypes. Collectively, our results show that the antifungal activity of UDP-KDG is due to inhibition of UGM and possibly other nucleotide sugar-modifying enzymes and that the rhamnose metabolic pathway serves as a shunt that prevents accumulation of UDP-KDG to toxic levels. These findings, together with the fact that there is no Gal
f
in mammals, support the possibility of developing UDP-KDG or its derivatives as antifungal drugs.

IMPORTANCE
Nucleotide sugars are donors for the sugars in fungal wall polymers. We showed that production of the minor sugar rhamnose is used primarily to neutralize the toxic intermediate compound UDP-KDG. This surprising finding highlights a completely new role for minor sugars and other secondary metabolites with undetermined function. Furthermore, the toxic potential of predicted transition metabolites that never accumulate in cells under natural conditions are highlighted. We demonstrate that UDP-KDG inhibits the UDP-galactopyranose mutase enzyme, thereby affecting production of Gal
f
, which is one of the components of cell wall glycans. Given the structural similarity, UDP-KDG likely inhibits additional nucleotide sugar-utilizing enzymes, a hypothesis that is also supported by our findings. Our results suggest that UDP-KDG could serve as a template to develop antifungal drugs.
Doctors’ perception of support and the processes involved in complaints investigations and how these relate to welfare and defensive practice: a cross-sectional survey of the UK physicians
Authors: Bourne Tom , De Cock Bavo , Wynants Laure , Peters Mike , Van Audenhove Chantal , Timmerman Dirk , Van Calster Ben , Jalmbrant Maria 
Published: November 2017

ObjectiveHow adverse outcomes and complaints are managed may significantly impact on physician well-being and practice. We aimed to investigate how depression, anxiety and defensive medical practice are associated with doctors actual and perceived support, behaviour of colleagues and process issues regarding how complaints investigations are carried out.DesignA survey study. Respondents were classified into three groups: no complaint, recent/current complaint (within 6 months) or past complaint. Each group completed specific surveys.SettingBritish Medical Association (BMA) members were invited to complete an online survey.Participants95 636 members of the BMA were asked to participate. 7926 (8.3%) completed the survey, of whom 1780 (22.5%) had no complaint, 3889 (49.1%) had a past complaint and 2257 (28.5%) had a recent/current complaint. We excluded those with no complaints leaving 6144 in the final sample.Primary outcomes measuresWe measured anxiety and depression using the Generalised Anxiety Disorder Scale 7 and Physical Health Questionnaire 9. Defensive practice was assessed using a new measure for avoidance and hedging.ResultsMost felt supported by colleagues (61%), only 31% felt supported by management. Not following process (56%), protracted timescales (78%), vexatious complaints (49%), feeling bullied (39%) or victimised for whistleblowing (20%), and using complaints to undermine (31%) were reported. Perceived support by management (relative risk (RR) depression: 0.77, 95% CI 0.71 to 0.83; RR anxiety: 0.80, 95% CI 0.74 to 0.87), speaking to colleagues (RR depression: 0.64, 95% CI 0.48 to 0.84 and RR anxiety: 0.69, 95% CI 0.51 to 0.94, respectively), fair/accurate documentation (RR depression: 0.80, 95% CI 0.75 to 0.86; RR anxiety: 0.81, 95% CI 0.75 to 0.87), and being informed about rights (RR depression 0.96 (0.89 to 1.03) and anxiety 0.94 (0.87 to 1.02), correlated positively with well-being and reduced defensive practice. Doctors worried most about professional humiliation following a complaint investigation (80%).ConclusionPoor process, prolonged timescales and vexatious use of complaints systems are associated with decreased psychological welfare and increased defensive practice. In contrast, perceived support from colleagues and management is associated with a reduction in these effects.
An easy, prompt and reproducible methodology to manage an unexpected increase of incident reports in surgery theatres
Authors: Moccia Adriana , Quattrin Rosanna , Battistella Claudio , Fabbro Elisa , Brusaferro Silvio 
Published: November 2017

ObjectivesSurgery is a high-risk hospital area for adverse events (AEs) occurrence. This study aims to develop an effectiveness and reactive methodology to manage an unexpected increase of AEs in the operating rooms (ORs) of a large Academic Hospital providing about 30 000 surgeries per year.MethodsThe study included three phases: 1. analysis of the AEs collected through the hospital incident reporting system from 2014 to 2015; 2. development of a programme to improve the surgical patient’s safety and 3. application and evaluation of the programme effectiveness.ResultsIn 2014, all hospital AEs were 825 (10.3% in ORs), while in the first 5 months of 2015, they were 645 (17.7% in ORs) [relative risk (RR) 2015 vs 2014=1.7; 95% CI=1.3 to 2.2;p<0.0001] with two sentinel events. Due to this increase, 177 real-time observations were planned in 12 ORs with external staff (n.25) during 1 week in June, July and November 2015 using a checklist with 14 items related to the patient’s pathway (surgical site, time-out, medical records and sponges count). After the observations, the AEs decreased from 11.4×1000 surgeries (January–June 2015) to 8.6×1000 (July–December 2015) (RR=0.7, 95% CI=0.6 to 0.9,p<0.05). Compliance to the correct procedures applied by ORs staff has improved during the year for all items.ConclusionsThe methodology of this study has been revealed effective to control an unexpected increase in AEs and to improve the healthcare workers’ adherence to correct procedures and it could be translated in other patients’ safety settings.
Transliteration versus Translation of Greek Plant Names in the Syriac Medical Writings of Sergius of Reš ʿAynā: On the Tables of Contents in BL Add. 14,661
Authors: Calà Irene , Hawley Robert 
Published: November 2017

This article explores some of the translational choices made by Sergius of Reš ʿAynā in translating the Greek plant names found in Books VI–VIII of Galen’s treatise On simple drugs into Syriac, and especially as found in the “tables of contents”—or pínakes—which preface these books. These latter took the form of alphabetically ordered lists of Greek phytonyms transliterated into Syriac characters, occasionally followed by a translational gloss in Syriac. After a brief introduction, we discuss the form, function and content of these pínakes, outline a typology, and suggest explanations for selected problematic features.
Extended Versus Short-Course Corticosteroid Taper Regimens in the Management of Chronic Obstructive Pulmonary Disease Exacerbations in Critically Ill Patients
Authors: Poon Teresa , Paris Daryl Glick , Aitken Samuel L. , Patrawalla Paru , Bondarsky Eric , Altshuler Jerry 
Published: November 2017

Background: Previous literature has suggested that a short course of corticosteroids is similarly effective as an extended course for managing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, there are limited data regarding the optimal corticosteroid regimen in critically ill patients and the dosing strategies remain highly variable in this population. Methods: This retrospective cohort study evaluated patients with AECOPD admitted to the intensive care unit within a 2-year period. Patients were divided into short-course (≤5 days) or extended-course (>5 days) corticosteroid taper groups. The primary end point was treatment failure, defined as the need for intubation, reintubation, or noninvasive mechanical ventilation. Secondary end points included the duration of mechanical ventilation, hospital and intensive care unit length of stay, and adverse events. Results: Of the 151 patients who met the inclusion criteria, 94 received an extended taper and 57 received a short taper. Treatment failure occurred in 3 patients, who were all in the extended taper group ( P = .17). In a propensity score-matched cohort, the hospital length of stay was 7 days in the short taper group compared to 11 days in the extended taper group ( P < .0001). No differences in adverse events were observed. Conclusion: A short-course corticosteroid taper in critically ill patients with AECOPD is associated with reduced hospital length of stay and decreased corticosteroid exposure without increased risk of treatment failure. A prospective randomized trial is warranted.
Breastfeeding Among Women With Physical Disabilities in the United States
Authors: Powell Robyn M. , Mitra Monika , Smeltzer Suzanne C. , Long-Bellil Linda M. , Smith Lauren D. , Rosenthal Eliana , Iezzoni Lisa I. 
Published: November 2017

Background: The benefits of breastfeeding are well established, and breastfeeding is now widely practiced in the United States. Although increasing numbers of women with physical disabilities are having children, little information is available about breastfeeding practices among these women. Nonetheless, the children of women with physical disabilities should benefit from breastfeeding just as children of nondisabled mothers do. Research aim: This study aimed to explore the facilitators and barriers to breastfeeding among women with physical disabilities. Methods: This study involved semistructured telephone interviews with a convenience sample of women ( N = 25) with diverse physical disabilities from across the United States. All participants had given birth within the past 10 years. Interviews were audio-recorded, professionally transcribed, and analyzed using content analysis. Results: Analyses found four broad themes indicating facilitators to breastfeeding: (a) adaptations and equipment, (b) use of breast pump, (c) physical assistance from others, and (d) peer support. We also found five broad themes suggesting barriers to breastfeeding: (a) lack of supports, (b) disability-related health considerations, (c) limited information, (d) difficulties with milk production, and (e) difficulties latching. Conclusion: The need for greater supports for women with physical disabilities who desire to breastfeed as well as information for women and their clinicians about facilitating breastfeeding.
Confronting the Challenge of Beta-Lactam Allergies: A Quasi-Experimental Study Assessing Impact of Pharmacy-Led Interventions
Authors: Krey Steven C. , Waise Jeff , Skrupky Lee P. 
Published: November 2017

Objective: To improve allergy history documentation and increase the use of beta-lactams when appropriate in patients with a reported beta-lactam allergy. Methods: This pre–post study was conducted at a 167-bed tertiary care community hospital and evaluated multidisciplinary interventions on allergy documentation and antibiotic selection. Interventions included education, creation of local practice guidelines, and modified practices for pharmacists and pharmacy technicians. Inpatients with a reported beta-lactam allergy receiving at least 1 antibiotic for >24 hours were included; first admissions were assessed. Primary outcomes were documentation of reaction type and percentage of patients receiving non-beta-lactam therapy. Secondary outcomes included documentation of previously tolerated beta-lactams, modification of non-beta-lactam therapy, discharge antibiotics, and adverse reactions. Results: A total of 179 patients were included, 91 preintervention and 88 postintervention. No significant differences were observed between the before versus after groups in the percentage of patients with documentation of reaction type (90.1% vs 89.8%, P = .940) or the overall percentage of patients receiving non-beta-lactams (86.8% vs 84.1%, P = .605). However, significantly more patients in the after phase had documentation of previously tolerated beta-lactams (8.8% vs 28.4%, P = .001), and among patients receiving a non-beta-lactam, a greater percentage was subsequently switched to a beta-lactam (11.4% vs 25.7%, P = .022). One allergic reaction was documented during the study, which occurred in the before phase. Conclusion: Multidisciplinary education and local guideline implementation led by pharmacists may improve allergy documentation and antibiotic selection in patients with reported beta-lactam allergies.
Plugging the Implementation Gap
Authors: Sharma Seema , Bose Arnab , Shekhar Himanshu , Pathania Rohit 
Published: November 2017

This article while discussing global and national climate regimes brings out the need for designing and implementing climate projects locally. It brings to the forefront, the local realities in an Indian urban context. The article particularly highlights disconnects between high level thinking and local implementation realities. It goes on further to suggest a novel idea which is being tested to overcome these disconnects. Global climate regime will primarily constitute the UNFCCC processes, and national climate regime will primarily constitute the National Action Plan on Climate Change (NAPCC) processes for the purposes of this article. The narrative of local realities brought out in the article is based on the work done at a locality in East Delhi through a prototype resilience centre. The centre conducted numerous community engagement activities, utilising an internally devised multi-stakeholder, participatory and inclusive framework. This prototype has managed to create an impact on the entire community through several interventions piloted with the involvement of strategic actors starting from January 2015 till date. The idea has been incubated within University of Delhi, and this article will present the concept of context integrity, which includes ‘nested’ relationships with larger institutions. That is, how an institution like University of Delhi can nest a small institution like the prototype resilience centre committed to larger goals of plugging the implementation gap which will bridge the disconnects between global climate regime and creation of local impact. JEL: R-23
Job Satisfaction and Work Engagement: A Study Using Private Sector Bank Managers
Authors: Garg Kanika , Dar Ishaq Ahmad , Mishra Mridula 
Published: November 2017

The Problem In today’s dynamic environment, organizations face difficulties in retaining their talented employees. Although there are several studies that link job satisfaction with work engagement, a closer examination is needed to understand whether it is intrinsic or extrinsic job satisfaction that enhances work engagement. This shows that the job satisfaction is the key driver of work engagement. So, the purpose of this article is to study the level of job satisfaction among the managers at various hierarchical levels of private sector banks in India and also to study the relationship between job satisfaction and work engagement among managers at various hierarchical levels. The Solution This study follows the descriptive research design, and data were collected by standardized questionnaire developed by Minnesota and by Schaufeli’s Satisfaction Questionnaire, and data were collected from the 148 managers at various hierarchical levels working in private sector banks in India. To attain the objectives, the descriptive statistics and regression analysis have been used. The results show that the managers who are working in private sector banks are more satisfied with intrinsic job satisfaction rather than extrinsic job satisfaction and also found that there is positive relationship between job satisfaction and work engagement among managers at various hierarchical levels of private sector banks in India. The limitation of this study is data were collected at a single point of time. The Stakeholders Stakeholders of this study include private sector bank managers at various hierarchical levels and human resource managers of organizations having hierarchical management system where management is focused toward employee satisfaction and retention in the organization. Consultation agencies dealing in human resource practices, research agencies, and research scholars are other stakeholders as it will be literature for further studies.
Is Hippocampal Avoidance During Whole-Brain Radiotherapy Risky for Patients With Small-Cell Lung Cancer? Hippocampal Metastasis Rate and Associated Risk Factors
Authors: Korkmaz Kirakli Esra , Oztekin Ozgur 
Published: November 2017

Objectives: Hippocampal avoidance during whole-brain radiotherapy is performed to prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless, the estimated risk of metastases in hippocampal avoidance area in small-cell lung cancer is unknown. The current study aimed to characterize the metastatic distribution within the brain relative to the hippocampus, estimate the incidence of hippocampal metastasis in patients with small-cell lung cancer, and identify clinical and radiographic variables that may be associated with the risk of hippocampal avoidance area metastasis. Materials and Methods: Patients with small-cell lung cancer treated with therapeutic whole-brain radiotherapy between January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial magnetic resonance images obtained just before therapeutic cranial irradiation were retrieved and reviewed for each patient. The hippocampal avoidance area was defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account for necessary dose falloff between the hippocampus and the whole-brain planning target volume. Metastatic lesions within hippocampal avoidance area were defined as hippocampal metastasis. Hippocampal metastasis rate and characteristics of patients with hippocampal metastasis were analyzed and compared to patients without hippocampal metastasis. Results: Fifty-four patients evaluated with cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was 32% (17 patients). A total of 4.4% of all metastases involved the hippocampal avoidance area. The most common location was frontal lobe. Being younger than 65 years of age was found to be an independent risk factor for HM (odds ratio: 4.8, 95% confidence interval: 1-23.2, P = .049). The number of brain metastases was significantly higher in patients with hippocampal metastasis ( P = .027), and hippocampal metastasis rate was also higher in patients having larger hippocampus ( P = .026) and larger brain volumes ( P = .02). Conclusion: Hippocampal metastasis might be more common in small-cell lung cancer. Reducing the dose to the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small-cell lung cancer may be risky for the development of HM compared with other malignant solid tumors.
Lessons learned from volar plate fixation of scaphoid fracture nonunions
Authors: Dodds Seth D. , Williams John B. , Seiter Max , Chen Clark 
Published: November 2017

Treating scaphoid nonunions presents difficulties particularly when there is bone loss, significant humpback deformity or avascular necrosis. We describe a new type of fixation with a volar scaphoid plate that adds to the methods of internal fixation that are available for the treatment of recalcitrant scaphoid nonunions. We will also discuss ‘lessons learned’ from a cases series. The case series includes 20 consecutive patients treated with volar buttress plating and a pedicled vascularized bone graft from the ipsilateral volar distal radius. There was clinical and radiographic evidence of union in 18 of 20 patients, 13 of which were verified by computed tomographic scan. The range of motion was improved in all patients post-operatively. Four patients with radiographic union experienced intermittent clicking with maximal wrist flexion, believed to be due to the impingement of the plate on the volar aspect of the radioscaphoid articulation and underwent removal at approximately 1 year after the index procedure. Volar scaphoid plating is a useful alternative to headless scaphoid screw fixation in the treatment of unstable scaphoid waist fractures and nonunions. Level of evidence: IV
Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma
Authors: Liu W. Robert , Shipp Margaret A. 
Published: November 2017

Abstract
Classical Hodgkin lymphoma (cHL) is an unusual B-cell–derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number–dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor–positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade.
Blockade of CD7 expression in T cells for effective chimeric antigen receptor targeting of T-cell malignancies
Authors: Png Yi Tian , Vinanica Natasha , Kamiya Takahiro , Shimasaki Noriko , Coustan-Smith Elaine , Campana Dario 
Published: November 2017

Key PointsBlockade of CD7 expression with a novel method, combined with a second-generation CAR, results in highly potent anti-CD7 CAR T cells. This practical strategy provides a new treatment option for patients with high-risk T-cell malignancies, including ETP-ALL.
Correction to: The impact of EU and non-EU immigration on British wages
Authors: Nickell Stephen , Saleheen Jumana 
Published: November 2017

Correction to: IZA journal of development and migration (2017) 7:15 DOI: 10.1186/s40176-017-0096-0
In the original version of this article (Nickell & Saleheen, 2017), published on 11 October 2017, there is an error in the “Country of Birth” section in Appendix 1. In this Correction the incorrect and correct version of the affected sentence is shown. The error and corrected error are in bold.