bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing Harm in the ICU—Building a Culture of Safety and Engaging Patients and Families
Authors: Thornton Kevin C. , Schwarz Jennifer J. , Gross A. Kendall , Anderson Wendy G. , Liu Kathleen D. , Romig Mark C. , Schell-Chaple Hildy , Pronovost Peter J. , Sapirstein Adam , Gropper Michael A. , Lipshutz Angela K. M. 
Published: June 2017

Objective:
Preventing harm remains a persistent challenge in the ICU despite evidence-based practices known to reduce the prevalence of adverse events. This review seeks to describe the critical role of safety culture and patient and family engagement in successful quality improvement initiatives in the ICU. We review the evidence supporting the impact of safety culture and provide practical guidance for those wishing to implement initiatives aimed at improving safety culture and more effectively integrate patients and families in such efforts.

Data Sources:
Literature review using PubMed including evaluation of key studies assessing large-scale quality improvement efforts in the ICU, impact of safety culture on patient outcomes, methodologies for quality improvement commonly used in healthcare, and patient and family engagement. Print and web-based resources from leading patient safety organizations were also searched.

Study Selection:
Our group completed a review of original studies, review articles, book chapters, and recommendations from leading patient safety organizations.

Data Extraction:
Our group determined by consensus which resources would best inform this review.

Data Synthesis:
A strong safety culture is associated with reduced adverse events, lower mortality rates, and lower costs. Quality improvement efforts have been shown to be more effective and sustainable when paired with a strong safety culture. Different methodologies exist for quality improvement in the ICU; a thoughtful approach to implementation that engages frontline providers and administrative leadership is essential for success. Efforts to substantively include patients and families in the processes of quality improvement work in the ICU should be expanded.

Conclusions:
Efforts to establish a culture of safety and meaningfully engage patients and families should form the foundation for all safety interventions in the ICU. This review describes an approach that integrates components of several proven quality improvement methodologies to enhance safety culture in the ICU and highlights opportunities to include patients and families.
Outcomes of Keratoplasty After Ocular Surface Stem Cell Transplantation
Authors: Sepsakos Lorena , Cheung Albert Y. , Holland Edward J. 
Published: June 2017

Purpose:
To investigate the long-term outcomes of penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) after ocular surface stem cell transplantation (OSST).

Methods:
An observational retrospective review was performed on all patients who underwent OSST followed by either PK or DALK with a minimum of 6-month follow-up.

Results:
One hundred two eyes fulfilled the inclusion criteria. The mean time to keratoplasty after OSST was 19 months, and the mean follow-up was 57 months after keratoplasty. A Kaplan–Meier analysis demonstrated 92% graft survival at year 1, 77% at year 2, 62% at year 3, 55% at year 4, and 54% at year 5. During the study period, a total of 44 grafts failed. The mean time to graft failure was 32 months. Preoperative median best-corrected visual acuity for all eyes was 20/550, which improved to 20/100 (P < 0.001) at 1 year postoperatively, 20/60 (P < 0.001) at 2 years, and 20/100 (P < 0.001) at last follow-up.

Conclusions:
Without addressing the underlying stem cell deficiency, keratoplasty in patients with total limbal stem cell deficiency will ultimately fail in all cases. OSST with either subsequent PK or DALK provides successful visual outcomes with an acceptable complication profile.
Spinal microglia are required for long-term maintenance of neuropathic pain
Authors: Echeverry Stefania , Shi Xiang Qun , Yang Mu , Huang Hao , Wu YiChen , Lorenzo Louis-Etienne , Perez-Sanchez Jimena , Bonin Robert P. , De Koninck Yves , Zhang Ji 
Published: June 2017

Abstract
While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor–TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia–neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.
Pain and learning in primary school: a population-based study
Authors: Kosola Silja , Mundy Lisa K. , Sawyer Susan M. , Canterford Louise , van der Windt Danielle A. , Dunn Kate M. , Patton George C. 
Published: June 2017

Abstract
Despite the frequency of pain among children, little is known about its effects on learning and school outcomes. The objective of this study was to quantify the association of pain and academic achievement while taking into account the presence of co-occurring emotional symptoms. A population-based stratified random sample of 1239 students aged 8 to 9 years from primary schools in Melbourne, Australia, was recruited for the Childhood to Adolescence Transition Study. Children indicated sites of pain that had lasted for a day or longer in the past month using a pain manikin. Depressive- and anxiety-related symptoms were assessed using child-reported items. National assessment results for reading and numeracy were used to measure academic achievement. Sixty-five percent of children reported pain in at least 1 body site and 16% reported chronic pain. Increasing number of pain sites was associated with poorer reading scores in a dose–response fashion (β = −3.1; 95% confidence interval −4.9 to −1.3; P < 0.001). The association was only partly attenuated when adjusting for emotional symptoms (β = −2.6; 95% confidence interval −4.5 to −0.8; P < 0.001) and was not moderated by emotional symptoms. Children with chronic pain were a year behind their peers in both reading and numeracy. Among primary school students, pain was associated with lower reading scores even after adjusting for the presence of emotional symptoms. Although population-based longitudinal studies will be required to ascertain consistency and possible causality, grounds exist for considering pain and emotional symptoms in the assessment of children with reading difficulties.
Is Intravenous Thrombolysis Safe and Effective in Central Retinal Artery Occlusion? A Critically Appraised Topic
Authors: Dumitrascu Oana M. , Shen Joanne F. , Kurli Madhavi , Aguilar Maria I. , Marks Lisa A. , Demaerschalk Bart M. , Wingerchuk Dean M. , O’Carroll Cumara B. 
Published: June 2017

Background:
Central retinal artery occlusion (CRAO) is a neurological and ophthalmologic emergency associated with poor visual recovery. There is a dilemma regarding the appropriate treatment, as formal guidelines are lacking. Despite being considered an ocular equivalent of cerebral infarction, the time window of intravenous (IV) thrombolysis administration for maximum efficacy and safety in CRAO remains uncertain.

Objective:
To critically assess the current evidence regarding the safety and effectiveness of IV thrombolysis in the treatment of patients with CRAO.

Methods:
The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, and content experts in the fields of vascular neurology and ophthalmology.

Results:
A recent patient-level meta-analysis was selected for critical appraisal. The study compared the visual recovery rates after IV thrombolysis in CRAO against the natural history of this illness and conservative therapies (ocular massage, anterior chamber paracentesis, and/or hemodilution). Time to thrombolytic therapy administration had a significant impact on visual recovery in CRAO (P<0.001). IV thrombolysis within the first 4.5 hours after symptom onset resulted in recovery of vision in 50.0% of the patients [95% confidence interval (CI), 32.4%-67.6%]. The rate of visual recovery was nearly 3 times higher than in the natural history cohort [odds ratio, 4.7 (95% CI, 2.3-9.6); P<0.001], with a 32.3% absolute risk reduction and a number needed to treat of 4.0 (95% CI, 2.6-6.6). There was no significant difference in the recovery rate after thrombolysis compared with the natural history cohort for those patients treated after 4.5 hours. No major hemorrhages occurred after alteplase administration in this meta-analysis.

Conclusions:
IV thrombolysis in CRAO seems to be safe and effective within the first 4.5 hours of symptom onset. A clinical decision based on this meta-analysis alone cannot be made due to several limitations. A randomized controlled clinical trial of early IV alteplase administration in CRAO is necessary to provide evidence-based therapeutic guidance.
Intravenous Alteplase for Acute Stroke and Pulmonary Embolism in a Patient With Recent Abdominoplasty
Authors: Christiansen Michael E. , Kumar Gyanendra , Mahabir Raman C. , Helmers Richard A. , Bendok Bernard R. , O’Carroll Cumara B. 
Published: June 2017

Introduction:
Major surgery in the past 14 days is a relative contraindication to treatment of acute stroke with intravenous (IV) alteplase. The 2016 American Heart Association/American Stroke Association scientific statement discussing inclusion and exclusion criteria for alteplase in acute stroke allows for provider judgment citing a lack of evidence to support surgery as an absolute contraindication.

Case Report:
A 59-year-old woman presented with acute left hemiparesis, dysarthria, and acute respiratory failure. National Institutes of Health Stroke Scale was 17. Two days prior she underwent abdominoplasty and liposuction. Computed tomography angiogram of the head demonstrated acute occlusion of right M2, and computed tomography angiogram of the chest was positive for bilateral pulmonary emboli. After urgent consultation with the plastic surgery and neurosurgery teams, the patient was treated with IV alteplase followed by cerebral mechanical thrombectomy. This was complicated by surgical-site hemorrhage in the abdomen requiring operative intervention. Abdominal hemorrhage was controlled and the patient showed remarkable neurological recovery, later being discharged with no residual neurological deficits.

Conclusions:
Interdisciplinary collaboration can successfully inform the decision to treat acute ischemic stroke with IV alteplase in the setting of recent major surgery.
Host-related Risk Factors for Adherent Perinephric Fat in Healthy Individuals Undergoing Laparoscopic Living-donor Nephrectomy
Authors: Narita Shintaro , Kumazawa Teruaki , Tsuchiya Norihiko , Mingguo Huang , Saito Mitsuru , Inoue Takamitsu , Tsuruta Hiroshi , Numakura Kazuyuki , Maeno Atsushi , Nanjo Hiroshi , Satoh Shigeru , Habuchi Tomonori 
Published: June 2017

Purpose:
The purpose of this study is to assess the risk factors and characteristics of adherent perinephric fat (APF) in healthy individuals.

Patients and Methods:
Men who underwent laparoscopic donor nephrectomy were included. Video review was used to divide patients on the basis of APF severity. Relationship between APF scores and clinical and radiographic features was evaluated.

Results:
Of the 92 patients, 43 (46.7%) and 8 (8.7%) were categorized as APF and severe APF, respectively. The median total operative time was significantly associated with APF severity. Sex, body mass index, and perinephric fat area, stranding, and thickness were significantly associated with severe APF. In the multivariate analysis, perinephric fat areas and stranding were independent risk factors for severe APF (HR, 1.189 and 14.450, respectively). In the 44 analyzed cytokines, levels of sIL-6R in the perinephric adipose tissue-conditioned medium were significantly higher for APF group than that for non-APF group (P=0.049).

Conclusions:
Host-related risk factors for APF could predict surgical difficulty in patients undergoing partial nephrectomy.
A high-throughput assay to identify robust inhibitors of dynamin GTPase activity
Authors: Mohanakrishnan Aparna , Tran Triet Vincent M. , Kumar Meera , Chen Hong , Posner Bruce A. , Schmid Sandra L. 
Published: June 2017

AbstractClathrin-mediated endocytosis is the major pathway by which cells internalize materials from the external environment. Dynamin, a large multidomain GTPase, is a key regulator of clathrin-mediated endocytosis. It assembles at the necks of invaginated clathrin-coated pits and, through GTP hydrolysis, catalyzes scission and release of clathrin-coated vesicles from the plasma membrane. Several small molecule inhibitors of dynamin’s GTPase activity, such as Dynasore and Dyngo-4a, are currently available, although their specificity has been brought into question. Previous screens for these inhibitors measured dynamin’s stimulated GTPase activity due to lack of sufficient sensitivity, hence the mechanisms by which they inhibit dynamin are uncertain. We report a highly sensitive fluorescence-based assay capable of detecting dynamin’s basal GTPase activity under conditions compatible with high throughput screening. Utilizing this optimized assay, we conducted a pilot screen of 8000 compounds and identified several “hits” that inhibit the basal GTPase activity of dynamin-1. Subsequent dose-response curves were used to validate the activity of these compounds. Interestingly, we found neither Dynasore nor Dyngo-4a inhibited dynamin’s basal GTPase activity, although both inhibit assembly-stimulated GTPase activity. This assay provides the basis for a more extensive search for robust dynamin inhibitors.
Viral apoptosis evasion via the MAPK pathway by use of a host long noncoding RNA
Authors: Barichievy Samantha , Naidoo Jerolen , Boullé Mikaël , Scholefield Janine , Parihar Suraj P. , Coussens Anna K. , Brombacher Frank , Sigal Alex , Mhlanga Musa M. 
Published: June 2017

SUMMARYAn emerging realisation of infectious disease is the high incidence of genetic instability resulting from pathogen-induced DNA lesions, often leading to classical hallmarks of cancer such as evasion of apoptosis. The Human Immunodeficiency Virus type 1 (HIV-1) induces apoptosis in CD4+ T cells but is largely non-cytopathic in macrophages, thereby leading to long-term dissemination of the pathogen specifically by these host cells. Apoptosis is triggered by double-strand breaks (DSBs), such as those induced by integrating retroviruses, and is coordinated by the p53-regulated long noncoding RNA lincRNA-p21, in a complex with its protein binding partners HuR and hnRNP-K. Here, we monitor the cellular response to infection to determine how HIV-1 induces DSBs in macrophages yet evades apoptosis in these cells. We show that the virus does so by securing the pro-survival MAP2K1/ERK2 cascade early upon entry, in a gp120-dependent manner, to orchestrate a complex dysregulation of lincRNA-p21. By sequestering HuR in the nucleus, HIV-1 enables lincRNA-p21 degradation. Simultaneously, the virus permits transcription of pro-survival genes by sequestering hnRNP-K in the cytoplasm via the MAP2K1/ERK2 pathway. Notably, this pro-survival cascade is unavailable for similar viral manipulation in CD4+ T cells. The introduction of MAP2K1, ERK2 or HDM2 inhibitors in HIV-infected macrophages results in apoptosis providing strong evidence that the viral-mediated apoptotic block can be released, specifically by restoring the nuclear interaction of lincRNA-p21 and hnRNP-K. These results reveal pathogenic control of apoptosis and DNA damage via a host long noncoding RNA, and present MAP2K1/ERK2 inhibitors as a novel therapeutic intervention strategy for HIV-1 infection in macrophages.
WDR5 stabilizes actin architecture to promote multiciliated cell formation
Authors: Kulkarni Saurabh S. , Griffin John N. , Liem Karel F. , Khokha Mustafa K. ,   on behalf of the PCGC Investigators
Published: June 2017

HIGHLIGHTSWDR5 has an H3K4 independent role in the formation of multiciliated cells.WDR5 controls apical cell expansion, basal body patterning, and ciliogenesis in multiciliated cells.WDR5 localizes near the ciliary base where it connects basal bodies to F-actin.WDR5 stabilizes the apical actin network in multiciliated cells.SUMMARYThe actin cytoskeleton is critical to shape cells and pattern intracellular organelles to drive tissue morphogenesis. In multiciliated cells (MCCs), apical actin forms a lattice that drives expansion of the cell surface necessary to host hundreds of cilia. The actin lattice also uniformly distributes basal bodies across this surface. This apical actin network is dynamically remodeled, but the molecules that regulate its architecture remain poorly understood. We identify the chromatin modifier, WDR5, as a regulator of apical F-actin in multiciliated cells. Unexpectedly, WDR5 functions independently of chromatin modification in MCCs. Instead, we discover a scaffolding role for WDR5 between the basal body and F-actin. Specifically, WDR5 binds to basal bodies and migrates apically, where F-actin organizes around WDR5. Using a monomer trap for G-actin, we show that WDR5 stabilizes F-actin to maintain apical lattice architecture. In summary, we identify a novel, non-chromatin role for WDR5 in stabilizing F-actin in multiciliated cells.IN BRIEFKulkarni et al discover a chromatin independent function for WDR5 in multiciliated cell formation. WDR5 localizes to the base of cilia and functions as a scaffold between the basal bodies and the apical actin lattice. There, WDR5 stabilizes the actin lattice that allows multiciliated cells to expand their apical surface, pattern basal bodies, and generate hundreds of cilia.
Varying water deficit stress (WDS) tolerance in grain amaranths involves multifactorial shifts in WDS-related responses
Authors: González-Rodríguez América Tzitziki , Hernández Ismael Cisneros , Martínez-Gallardo Norma A. , Mellado-Mojica Erika , López-Pérez Mercedes , Ramírez-Chavez Enrique , Molina-Torres Jorge , Délano-Frier John P. 
Published: June 2017

AbstractIn this study, water deficit stress (WDS)-tolerance in several cultivars of grain amaranth species (Amaranthus hypochondriacus[Ahypo],A. cruentus[Acru] and A.caudatus[Acau]), in addition toA. hybridus(Ahyb), an ancestral amaranth, was examined. Ahypo was the most WDS-tolerant species, whereas Acau and Ahyb were WDS-sensitive. Data revealed that the differential WDS tolerance observed was multifactorial. It involved increased proline and raffinose (Raf) in leaves and/ or roots. Higher foliar Raf coincided with inducedGalactinol synthase 1(AhGolS1) andRaffinose synthase(AhRafS) expression. Unknown compounds, possibly larger RFOs, also accumulated in leaves of WDS-tolerant amaranths, which had high Raf/ Verbascose ratios. Distinct nonstructural carbohydrate (NSC) accumulation patterns were observed in tolerant species under WDS and recovery, such as: i) high Hex/ Suc ratios in roots coupled to increased cell wall and vacuolar invertase and sucrose synthase activities; ii) a severer depletion of starch reserves; iii) lower NSC content in leaves, and iv) higher basal hexose levels in roots which further increased under WDS. WDS-marker gene expression patterns proposed a link between amaranth’s WDS tolerance and abscisic acid-dependent signaling. Results obtained also suggest thatAhTRE,AhTPS9,AhTPS11,AhGolS1 and AhRafSare reliable gene markers of WDS tolerance in amaranth.HighlightDifferential water deficit stress tolerance in grain amaranths and their ancestor,Amaranthus hybridus, is a multifactorial process involving various biochemical changes and modified expression patterns of key stress-related genes.
Children as change agents for family health
Authors: Burrows Lisette 
Published: June 2017

Purpose
The purpose of this paper is to explore ways in which children and young people are being positioned as change agents for families through school health promotion initiatives in New Zealand.

Design/methodology/approach
The paper maps and describes the kinds of policies and initiatives that directly or indirectly regard children as conduits of healthy eating and exercise messages/practices for families. Drawing on post-structural theoretical frameworks, it explores what these resources suggest in terms of how healthy families should live.

Findings
Families are positioned as central to school health promotion initiatives in New Zealand, especially in relation to obesity prevention policies and strategies. Children are further positioned as agents of change for families in many of the resources/policies/initiatives reviewed. They are represented as key transmitters and translators of school-based health knowledge and as capable of, and responsible for, helping their families eat well and exercise more.

Social implications
While recognising children’s agency and capacity to translate health messages is a powerful and welcome message at one level, the author need to consider the implications of requiring children to convey health information, to judge their family practices and, at times, to be expected to change these. This may create anxiety, family division and expect too much of children.

Originality/value
The paper takes a novel post-structural perspective on a familiar health promotion issue. Given the proliferation of family-focussed health initiatives in New Zealand and elsewhere, this perspective may help us to explore, critique and understand more fully how children are expected to be engaged in these initiatives, and the potentially harmful implications of these expectations.