bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Course on Complex Humanitarian Emergencies: Preparation for the Impact of Climate Change
Authors: Williams Holly , Downes Elizabeth
Published: September 2017

Purpose

The effects of climate change are far‐reaching and multifactorial, with potential impacts on food security and conflict. Large population movements, whether from the aftermath of natural disasters or resulting from conflict, can precipitate the need for humanitarian response in what can become complex humanitarian emergencies (CHEs). Nurses need to be prepared to respond to affected communities in need, whether the emergency is domestic or global. The purpose of the article is to describe a novel course for nursing students interested in practice within the confines of CHEs and natural disasters.

Methods and Framework

The authors used the Sphere Humanitarian Charter and Minimum Standards as a practical framework to inform the course development. They completed a review of the literature on the interaction on climate change, conflict and health, and competencies related to working CHEs. Resettled refugees, as well as experts in the area of humanitarian response, recovery, and mitigation from the Centers for Disease Control and Prevention and nongovernmental organizations further informed the development of the course.

Clinical Relevance

This course prepares the nursing workforce to respond appropriately to large population movements that may arise from the aftermath of natural disasters or conflict, both of which can comprise a complex humanitarian disaster. Using The Sphere Project e‐learning course, students learn about the Sphere Project, which works to ensure accountability and quality in humanitarian response and offers core minimal standards for technical assistance. These guidelines are seen globally as the gold standard for humanitarian response and address many of the competencies for disaster nursing (http://www.sphereproject.org/learning/e-learning-course/).
Hepatitis C in a new therapeutic era: Recontextualising the lived experience
Authors: Whiteley David , Whittaker Anne , Elliott Lawrie , Cunningham‐Burley Sarah
Published: September 2017

Aims and objectives

To explore the experience of adults living with hepatitis C in a new era of interferon‐free treatment.

Background

Hepatitis C is a leading cause of morbidity and mortality worldwide, posing a significant challenge to global public health. Historically, the treatment of hepatitis C was poorly efficacious and highly demanding; however, more effective and tolerable therapies have become available in high‐income nations in recent years. This is the first study to explore how these significant developments in the treatment of hepatitis C may have influenced the experience of those living with the virus, and their understanding of the disease.

Design

A qualitative study underpinned by social phenomenological theory.

Methods

Data were generated through semi‐structured interviews with a purposive sample of 20 hepatitis C positive adults living in a large city in Scotland.

Results

Thematic analysis identified three overriding themes. “Positioning hepatitis C” illustrated how the disease was understood within wider sociocultural, medical and politico‐economic contexts. “Beyond a physical burden” emphasised the emotional aspect of infection, and “a new uncertainty” revealed participants’ cautious response to the advances in hepatitis C therapy.

Conclusions

Interthematic discourse portrayed the new era of hepatitis C treatment as holding little sway over constructions of the illness, as narratives resonated with previous studies. Such unmoving “lay” understandings of hepatitis C may pose potential barriers to the new therapeutic era from reaching its full potential.

Relevance to clinical practice

How people living with the virus perceive and understand hepatitis C can have an adverse impact on their engagement with care and treatment. Whilst global medical discourse eulogises the arrival of a new era of therapy, there remain significant challenges for nurses engaging those with hepatitis C in therapeutic pathways.
Prevalence of pressure ulcer and associated risk factors in middle‐ and older‐aged medical inpatients in Norway
Authors: Børsting Tove E , Tvedt Christine R , Skogestad Ingrid J , Granheim Tove I , Gay Caryl L , Lerdal Anners
Published: September 2017

Aims and objectives

To describe the prevalence of pressure ulcers among middle‐ and older‐aged patients in a general medical hospital in Norway and to describe the associations between pressure ulcers and potential risk factors additional to the Braden risk score.

Background

Degrees of mobility, activity, perfusion and skin status are risk factors for development of pressure ulcer. Nurses’ clinical judgements combined with risk assessment tools are effective to detect pressure ulcer risk.

Design

Cross‐sectional study.

Methods

The study was performed as part of a research project conducted between September 2012–May 2014 in a general hospital in the capital of Norway. Registered nurses and nursing students collected data from all eligible patients on 10 days during the students’ clinical practice studies. The Braden scale was used to measure pressure ulcer risk, and skin examinations were performed to classify the skin area as normal or as indicative of pressure ulcer according to the definitions by the National Pressure Ulcer Advisory Panel. Comorbidities were collected by patient's self‐report. This analysis focused on the 255 inpatients at the medical wards ≥52 years of age, most of whom had more than one comorbidity.

Results

The prevalence of pressure ulcers was 14.9% in this sample. Higher age, underweight, diabetes and worse Braden scores were factors associated with pressure ulcer, and pressure ulcer was most frequently sited at the sacrum or heel.

Conclusion

Adding age, weight and diabetes status to pressure ulcer risk assessment scales may improve identification of patients at risk for pressure ulcers.

Relevance to clinical practice

Knowledge about strengths and limitations of risk assessment tools is important for clinical practice. Age, weight and diabetes status should be considered for inclusion in risk assessment tools for pressure ulcers in medical wards.
Factors associated with demoralisation syndrome in patients before and after cardiac surgery
Authors: Liao Hsiu‐Yun , Chiu Chaw‐Chi , Ko Ying‐Ying , Chen Hsing‐Mei
Published: September 2017

Aims and objectives

To investigate the incidence of and contributors to demoralisation syndrome among patients before and after cardiac surgery.

Background

Demoralisation syndrome is a common but neglected phenomenon in nursing practice. Patients who require cardiac surgery experience demoralisation syndrome more often than they experience depression.

Design

A prospective correlational design was applied.

Methods

A convenience sample of 76 participants undergoing cardiac surgery was recruited from the cardiovascular wards of two medical centres in Taiwan. The instruments applied included the Demoralization Scale (DS), the Patient Outcome Questionnaire‐9 (PHQ‐9) and the Perception of Intensive Care Unit (ICU) Stay Questionnaire.

Results

High demoralisation was present in 44.7% of the participants before surgery but significantly decreased to 36.8% after surgery (p < .05); conversely, depression was present in 15.8% of participants before surgery and did not significantly decrease after surgery (rate after surgery, 9.2%; p > .05). A multiple regression analysis using the backward‐selection method showed that depression (p < .001) and retirement (p < .05) were important predictors of pre‐operative demoralisation syndrome (R2 = 0.250), whereas depression (p < .001) and perceptions of ICU stay (p > .05) remained in the regression model after surgery (R2 = 0.291).

Conclusions

The study findings suggest that demoralisation syndrome is highly prevalent in patients undergoing cardiac surgery but is significantly reduced after cardiac surgery. Before surgery, depression and retirement were significant predictors of demoralisation. After surgery, depression was the only predictor. Although the perception of ICU stay was not an important predictor, it was significantly correlated with demoralisation.

Relevance to clinical practice

Before cardiac surgery, nurses should emphasise the importance of demoralisation development among patients who suffer from depressive symptoms and are retired. After cardiac surgery, continued follow‐up is needed for the early detection and minimisation of the effect of depression and the development of demoralisation.
High prevalence of developmental concern amongst infants at 12 months following hospitalised parechovirus infection
Authors: Britton Philip N , Khandaker Gulam , Khatami Ameneh , Teutsch Suzy , Francis Stephanie , McMullan Brendan J , Jones Cheryl A
Published: September 2017

Aim

The human parechovirus (HPeV) is an increasingly recognised cause of sepsis and central nervous system infection in young infants for which there are limited long‐term outcome data. We aimed to assess neurodevelopmental outcome and quality of life in infants following hospitalised HPeV infection.

Methods

This cohort study was a 12‐month follow‐up of infants who were hospitalised with confirmed HPeV infection at the Sydney Children's Hospitals Network during an outbreak in Sydney in 2013. Telephone interviews were conducted with parents/guardians. We administered standardised questionnaires, including: Ages and Stages Questionnaire (ASQ), Liverpool Outcome Score‐follow‐up, Pediatric Quality of Life Inventory(PedsQL) Infant scales and Short‐Form health survey (SF‐12).

Results

We followed up 46 of 79 infants (58%) aged between 12 and 16 months who had been hospitalised with HPeV infection; 19% showed significant concern in developmental attainment (ASQ3 score <2 standard deviation below population mean), and 50% showed some concern (<1 standard deviation below mean). ASQ3 developmental outcome was associated with the presence of neurodevelopmental sequelae (lower total Liverpool Outcome Score) and poorer health‐related quality of life (HRQOL) in physical functioning (PedsQL physical component score), but not overall HRQOL (total PedsQL score) or parental HRQOL (SF‐12 scores). No significant associations were identified between clinical or laboratory features during acute hospitalisation and adverse outcome on ASQ3.

Conclusions

A high proportion of infants show developmental concern at 12‐month follow‐up post‐hospitalisation with HPeV infection. Clinical features during hospitalisation were not associated with adverse outcomes at 12 months. These results suggest that careful follow‐up of young infants hospitalised with HPeV disease may be warranted.
JAK1/2 Inhibitors AZD1480 and CYT387 Inhibit Canine B‐Cell Lymphoma Growth by Increasing Apoptosis and Disrupting Cell Proliferation
Authors: Lu Z. , Hong C.C. , Jark P.C. , Assumpção A.L.F.V. , Bollig N. , Kong G. , Pan X.
Published: September 2017

Background

Canine diffuse large B‐cell lymphoma (DLBCL) is a common and aggressive hematologic malignancy. The lack of conventional therapies with sustainable efficacy warrants further investigation of novel therapeutics. The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathways play important roles in the pathogenesis of hematologic malignancies in humans including DLBCLs. AZD1480 and CYT387 are novel JAK1/2 inhibitors that have been used in clinical trials for treating various hematologic cancers in humans. No studies have characterized the antitumor effects of JAK inhibitors on DLBCL in dogs.

Hypothesis/Objectives

We hypothesize that JAK1/2 inhibitors AZD1480 and CYT387 can effectively inhibit growth of canine DLBCL in vitro. We aim to assess the antitumor activity of AZD1480 and CYT387 in canine DLBCL and to determine the underlying mechanisms of action.

Methods

In vitro study of canine lymphoma cell growth, proliferation, and apoptosis by viability, proliferation and apoptosis assays.

Results

A significant decrease in viable canine lymphoma cells was observed after AZD1480 and CYT387 treatments. In addition, AZD1480 and CYT387 treatment resulted in decreased lymphoma cell proliferation and increased early apoptosis.

Conclusion and Clinical Importance

AZD1480 and CYT387 inhibit canine lymphoma cell growth in a dose‐dependent manner. Our findings justify further phase I/II clinical investigations of the safety and efficacy of JAK1/2 inhibitors in canine DLBCL and suggest new opportunities for novel anticancer therapies.
Chronic Gingivostomatitis with Esophagitis in Cats
Authors: Kouki M.I. , Papadimitriou S.A. , Psalla D. , Kolokotronis A. , Rallis T.S.
Published: September 2017

Background

Chronic gingivostomatitis in cats (FCG) is a debilitating disease with potentially deleterious effects on overall health.

Hypothesis/Objectives

Little is known about the pathophysiology and overall impact of FCG. The aims of our study were to investigate whether gingivostomatitis occurs concurrently with esophagitis, if FCG treatment contributes to esophagitis and if esophagitis exacerbates signs of FCG.

Animals

Fifty‐eight cats with clinical signs of FCG and 12 healthy control cats exhibiting no signs of oral disease, all client‐owned.

Methods

Prospective study. Physical, oral and endoscopic examinations were performed on all cats. Measurements of salivary and esophageal lumen pH were obtained from both groups. Biopsies were acquired from sites of esophageal inflammation in cats with FCG and from normal‐appearing esophageal mucosa in control cats.

Results

The majority of cats with clinical signs of FCG exhibited some degree of esophagitis especially in the proximal (44/58) and distal (53/58) parts (P < 0.001) with or without columnar metaplasia, compared to controls. All cats lacked signs related to gastrointestinal disease. Salivary and esophageal lumen pH were not statistically different compared to controls.

Conclusions and Clinical Importance

Feline chronic gingivostomatitis seems to occur concurrently with esophagitis. Esophagitis also should be managed in cats with chronic gingivostomatitis because it may aggravate the existing condition.
Monopoly v. Openness: Two sides of IP coin in the pharmaceutical industry
Authors: Gurgula Olga
Published: September 2017

The pharmaceutical industry extensively relies on the patent system. It actively lobbies for the strengthening of patent protection of its medical products and the results of its efforts may be found in the majority of bilateral and multilateral agreements, including the TRIPS and the most recent TPPA, augmented by private patent strategies pursued by pharmaceutical companies. However, some recent developments show the emerging tendency of implementing different business models by pharmaceutical companies that may mark the beginning of transformation of this industry. Among these developments is an “Open innovation” model, which has increasingly been followed by some research institutions and pharmaceutical companies aiming at facilitating the creation of new and affordable medicines, as well as providing transparency in order to enhance safety and efficacy of drugs. This article will discuss these two current developments in the pharmaceutical industry, that is, strong IP protection against open innovation.
Coordinated EDX and micro‐Raman analysis of presolar silicon carbide: A novel, nondestructive method to identify rare subgroup SiC
Authors: Liu Nan , Steele Andrew , Nittler Larry R. , Stroud Rhonda M. , De Gregorio Bradley T. , Alexander Conel M. O'D. , Wang Jianhua
Published: September 2017

We report the development of a novel method to nondestructively identify presolar silicon carbide (SiC) grains with high initial 26Al/27Al ratios (>0.01) and extreme 13C‐enrichments (12C/13C ≤ 10) by backscattered electron‐energy dispersive X‐ray (EDX) and micro‐Raman analyses. Our survey of a large number of presolar SiC demonstrates that (1) ~80% of core‐collapse supernova and putative nova SiC can be identified by quantitative EDX and Raman analyses with >70% confidence; (2) ~90% of presolar SiC are predominantly 3C‐SiC, as indicated by their Raman transverse optical (TO) peak position and width; (3) presolar 3C‐SiC with 12C/13C ≤ 10 show lower Raman TO phonon frequencies compared to mainstream 3C‐SiC. The downward shifted phonon frequencies of the 13C‐enriched SiC with concomitant peak broadening are a natural consequence of isotope substitution. 13C‐enriched SiC can therefore be identified by micro‐Raman analysis; (4) larger shifts in the Raman TO peak position and width indicate deviations from the ideal 3C structure, including rare polytypes. Coordinated transmission electron microscopy analysis of one X and one mainstream SiC grain found them to be of 6H and 15R polytypes, respectively; (5) our correlated Raman and NanoSIMS study of mainstream SiC shows that high nitrogen content is a dominant factor in causing mainstream SiC Raman peak broadening without significant peak shifts; and (6) we found that the SiC condensation conditions in different stellar sites are astonishingly similar, except for X grains, which often condensed more rapidly and at higher atmospheric densities and temperatures, resulting in a higher fraction of grains with much downward shifted and broadened Raman TO peaks.
The TPR domain of BepA is required for productive interaction with substrate proteins and the β‐barrel assembly machinery complex
Authors: Daimon Yasushi , Iwama‐Masui Chigusa , Tanaka Yoshiki , Shiota Takuya , Suzuki Takehiro , Miyazaki Ryoji , Sakurada Hiroto , Lithgow Trevor , Dohmae Naoshi , Mori Hiroyuki , Tsukazaki Tomoya , Narita Shin‐ichiro , Akiyama Yoshinori
Published: September 2017

BepA (formerly YfgC) is an Escherichia coli periplasmic protein consisting of an N‐terminal protease domain and a C‐terminal tetratricopeptide repeat (TPR) domain. We have previously shown that BepA is a dual functional protein with chaperone‐like and proteolytic activities involved in membrane assembly and proteolytic quality control of LptD, a major component of the outer membrane lipopolysaccharide translocon. Intriguingly, BepA can associate with the BAM complex: the β‐barrel assembly machinery (BAM) driving integration of β‐barrel proteins into the outer membrane. However, the molecular mechanism of BepA function and its association with the BAM complex remains unclear. Here, we determined the crystal structure of the BepA TPR domain, which revealed the presence of two subdomains formed by four TPR motifs. Systematic site‐directed in vivo photo‐cross‐linking was used to map the protein–protein interactions mediated by the BepA TPR domain, showing that this domain interacts both with a substrate and with the BAM complex. Mutational analysis indicated that these interactions are important for the BepA functions. These results suggest that the TPR domain plays critical roles in BepA functions through interactions both with substrates and with the BAM complex. Our findings provide insights into the mechanism of biogenesis and quality control of the outer membrane.
Behavioural and experimental public administration: Emerging contributions and new directions
Authors: James Oliver , Jilke Sebastian R. , Van Ryzin Gregg G.
Published: September 2017

This article introduces the symposium on the emerging subfield of behavioural public administration. The nine articles of the symposium each combine a focus on behavioural theory with the use of experiments as the method for testing theoretical expectations. The contribution of this work to public administration theory is revealed in the expanding set of insights into core topic areas, and there are associated contributions to public administration as a design science informing policy and practice. We analyse the variety of experimental methods employed by investigators in the subfield and the current relative popularity of survey experiments. We note maturation of the subfield embodied in emerging programmes of multiple experiments on particular topic areas. In conclusion, we propose directions for future research in which behavioural public administration develops as complementary to more established approaches to theory and method.
Recovery of mammal diversity in tropical forests: a functional approach to measuring restoration
Authors: Derhé Mia A. , Murphy Helen T. , Preece Noel D. , Lawes Michael J. , Menéndez Rosa
Published: September 2017

Ecological restoration is increasingly applied in tropical forests to mitigate biodiversity loss and recover ecosystem functions. In restoration ecology, functional richness, rather than species richness, often determines community assembly, and measures of functional diversity provide a mechanistic link between diversity and ecological functioning of restored habitat. Vertebrate animals are important for ecosystem functioning. Here, we examine the functional diversity of small‐to‐medium sized mammals to evaluate the diversity and functional recovery of tropical rainforest. We assess how mammal species diversity and composition and functional diversity and composition, vary along a restoration chronosequence from degraded pasture to “old‐growth” tropical rainforest in the Wet Tropics of Australia. Species richness, diversity, evenness, and abundance did not vary, but total mammal biomass and mean species body mass increased with restoration age. Species composition in restoration forests converged on the composition of old‐growth rainforest and diverged from pasture with increasing restoration age. Functional metrics provided a clearer pattern of recovery than traditional species metrics, with most functional metrics significantly increasing with restoration age when taxonomic‐based metrics did not. Functional evenness and dispersion increased significantly with restoration age, suggesting that niche complementarity enhances species' abundances in restored sites. The change in community composition represented a functional shift from invasive, herbivorous, terrestrial habitat generalists and open environment specialists in pasture and young restoration sites, to predominantly endemic, folivorous, arboreal, and fossorial forest species in older restoration sites. This shift has positive implications for conservation and demonstrates the potential of tropical forest restoration to recover rainforest‐like, diverse faunal communities.
Clinoform development and topset evolution in a mud‐rich delta – the Middle Triassic Kobbe Formation, Norwegian Barents Sea
Authors: Klausen Tore Grane , Torland Jonas Aas , Eide Christian Haug , Alaei Behzad , Olaussen Snorre , Chiarella Domenico
Published: September 2017

Clinoform surfaces are routinely used to mark transitions from shallow waters to deep basins. This concept represents a valuable tool for screening potential reservoir intervals in frontier basins where limited data are available. Variations in the character of clinoform geometries and shoreline and shelf‐edge trajectories are indicators of a range of different factors, such as palaeobathymetry, changes in relative sea‐level and sediment supply. Applications of conceptual and generalized models might, however, lead to erroneous assumptions about the supply of coarse‐grained material to the delta front and basin when superficial similarities between clinoform geometries are not treated holistically. The present study examines the mudstone‐dominated Middle Triassic Kobbe Formation – a potential hydrocarbon reservoir interval in the Barents Sea, where prodeltaic to deltaic deposits can be examined in cores, well logs and two‐dimensional and three‐dimensional seismic data. Despite pronounced acoustic impedance contrast to the surrounding shale, channel belt networks are not observed close to the platform edge in seismic datasets, even at maximum regressive stages. However, sub‐seismic prodeltaic deposits observed on the shallow platform indicate that prodeltaic deposits were sourced directly from the delta plain. Clinoform surfaces with different geometries and scale are observed basinward of the palaeoplatform edge of underlying progradational sequences, correlative to mudstone‐dominated prodeltaic core sections. Results indicate that platform‐edge deltas developed at discrete sites in the basin due to normal regression, but the positions of these deltas are not directly relatable to variations in clinoform geometries. Transitions from third‐order to fourth‐order clinoform geometries record discrete transgressive–regressive cycles but are not necessarily good indicators of sandstone deposition. Because of prolonged periods with high accommodation, channel avulsions were frequent and only very fine‐grained sandstone was deposited in heterolithic units at the delta front. Sandstones with good reservoir properties are predominantly found along basin margins.
Sedimentary architecture and depositional controls of a Holocene wave‐dominated barrier‐island system
Authors: Fruergaard Mikkel , Johannessen Peter N. , Nielsen Lars H. , Nielsen Lars , Møller Ingelise , Andersen Thorbjørn J. , Piasecki Stefan , Pejrup Morten
Published: September 2017

Barrier‐island system evolution is controlled by internal and external forcing mechanisms, and temporal changes in these mechanisms may be recorded in the sedimentary architecture. However, the precise role of individual forcing mechanisms is rarely well understood due to limited chronological control. This study investigates the relative role of forcing conditions, such as antecedent topography, sea‐level rise, sediment supply, storms and climate changes, on the evolution of a Holocene wave‐dominated barrier‐island system. This article presents temporal reconstruction of the depositional history of the barrier‐island system of Rømø in the Wadden Sea in unprecedented detail, based on ground‐penetrating radar profiles, sediment cores, high‐resolution dating and palynological investigations, and shows that ca 8000 years ago the barrier island formed on a Pleistocene topographic high. During the initial phase of barrier evolution, the long‐term sea‐level rise was relatively rapid (ca 9 mm year−1) and the barrier was narrow and frequently overwashed. Sediment supply kept pace with sea‐level rise, and the barrier‐island system mainly aggraded through the deposition of a ca 7 m thick stack of overwash fans. Aggradation continued for ca 1700 years until sea‐level rise had decreased to <2 mm year−1. In the last ca 6000 years, the barrier prograded 4 to 5 km through deposition of a 10 to 15 m thick beach and shoreface unit, despite a long‐term sea‐level rise of 1 to 2 mm year−1. The long‐term progradation was, however, interrupted by a transgression between 4000 years and 1700 years ago. These results demonstrate that the large‐scale morphology of the Danish Wadden Sea shoreline influences the longshore sediment transport flux and the millennial‐scale dispersal of sediment along the shoreline. On decadal to centennial timescales, major storms induced intense beach and shoreface erosion followed by rapid recovery and progradation which resulted in a highly punctuated beach and shoreface record. Major storms contributed towards a positive sediment budget, and the sustained surplus of sediment was, and still is, instrumental in maintaining the aggradational–progradational state of the barrier island.
Feline vaccine‐associated sarcomagenesis: Is there an inflammation‐independent role for aluminium?
Authors: AbdelMageed M. A. , Foltopoulou P. , McNiel E. A.
Published: September 2017

Aluminium has been found in feline vaccine‐associated sarcomas. In this study, we investigated the potential for aluminium to contribute directly to tumourigenesis. Our results indicated that an aluminium hydroxide adjuvant preparation was cytotoxic and mutagenic in human‐Chinese hamster ovary (CHO) hybrid cellsin vitro. Moreover,CHOcells deficient inDNAdouble strand break (DSB), but not single‐strand break (SSB), repair, were particularly sensitive to aluminium exposure compared with repair proficient cells, suggesting that aluminium is associated withDSBs. In contrast toCHOcells, primary feline skin fibroblasts were resistant to the cytotoxic effects of aluminium compounds and exposure to an aluminium chloride salt promoted cell growth and cell cycle progression at concentrations much less than those measured in particular feline rabies vaccines. These findings suggest that aluminium exposure may contribute, theoretically, to both initiation and promotion of tumours in the absence of an inflammatory response.
On-chip photonic synapse
Authors: Cheng Zengguang , Ríos Carlos , Pernice Wolfram H. P. , Wright C. David , Bhaskaran Harish
Published: September 2017

An on-chip photonic device mimics the function of synaptic connections between neurons.
Elovanoids are a novel class of homeostatic lipid mediators that protect neural cell integrity upon injury
Authors: Bhattacharjee Surjyadipta , Jun Bokkyoo , Belayev Ludmila , Heap Jessica , Kautzmann Marie-Audrey , Obenaus Andre , Menghani Hemant , Marcell Shawn J. , Khoutorova Larissa , Yang Rong , Petasis Nicos A. , Bazan Nicolas G.
Published: September 2017

We report the discovery of a novel family of prohomeostatic and neuroprotective lipid mediators called elovanoids.
Scale-dependent erosional patterns in steady-state and transient-state landscapes
Authors: Tejedor Alejandro , Singh Arvind , Zaliapin Ilya , Densmore Alexander L. , Foufoula-Georgiou Efi
Published: September 2017

We reveal distinct nonuniform erosion-upstream drainage area signatures of dynamic steady-state and transient-state landscapes.
Identification and prioritization of novel anti-
Wolbachia
chemotypes from screening a 10,000-compound diversity library
Authors: Johnston Kelly L. , Cook Darren A. N. , Berry Neil G. , David Hong W. , Clare Rachel H. , Goddard Megan , Ford Louise , Nixon Gemma L. , O’Neill Paul M. , Ward Stephen A. , Taylor Mark J.
Published: September 2017

Screening of 10,000 compounds reveals anti-
Wolbachia
chemotypes with potential to be developed into new drugs for two NTDs.
A Modified Carbapenem Inactivation Method, CIMTris, for Carbapenemase Production in Acinetobacter and Pseudomonas Species
Authors: Uechi Kohei , Tada Tatsuya , Shimada Kayo , Kuwahara-Arai Kyoko , Arakaki Momoko , Tome Takaaki , Nakasone Isamu , Maeda Shiro , Kirikae Teruo , Fujita Jiro
Published: September 2017

The carbapenem inactivation method (CIM) and modified CIM (mCIM) are simple and economical phenotypic screening methods for detecting carbapenemase production in Gram-negative bacteria. Although the mCIM has been recommended by the Clinical and Laboratory Standards Institute, both the CIM and mCIM have limitations. This study describes another modified CIM, called CIMTris, in which carbapenemase was extracted from bacteria with 0.5 M Tris-HCl (pH 7.6) buffer. The ability of the CIMTris to detect carbapenemase production was examined in
Acinetobacter
and
Pseudomonas
species. The CIMTris had an overall sensitivity of 97.6% and an overall specificity of 92.6%, whereas the mCIM had a sensitivity of 45.1% and a specificity of 100% for the isolates tested. These findings indicate that the CIMTris is useful for detecting carbapenemase production in
Acinetobacter
and
Pseudomonas
species.
Implementation of a Clinical Decision Support Tool for Stool Cultures and Parasitological Studies in Hospitalized Patients
Authors: Nikolic D. , Richter S. S. , Asamoto K. , Wyllie R. , Tuttle R. , Procop G. W.
Published: September 2017

There is substantial evidence that stool culture and parasitological examinations are of minimal to no value after 3 days of hospitalization. We implemented and studied the impact of a clinical decision support tool (CDST) to decrease the number of unnecessary stool cultures (STCUL), ova/parasite (O&P) examinations, and
Giardia
/
Cryptosporidium
enzyme immunoassay screens (GC-EIA) performed for patients hospitalized >3 days. We studied the frequency of stool studies ordered before or on day 3 and after day 3 of hospitalization (i.e., categorical orders/total number of orders) before and after this intervention and denoted the numbers and types of microorganisms detected within those time frames. This intervention, which corresponded to a custom-programmed hard-stop alert tool in the Epic hospital information system, allowed providers to override the intervention by calling the laboratory, if testing was deemed medically necessary. Comparative statistics were employed to determine significance, and cost savings were estimated based on our internal costs. Before the intervention, 129/670 (19.25%) O&P examinations, 47/204 (23.04%) GC-EIA, and 249/1,229 (20.26%) STCUL were ordered after 3 days of hospitalization. After the intervention, 46/521 (8.83%) O&P examinations, 27/157 (17.20%) GC-EIA, and 106/1,028 (10.31%) STCUL were ordered after 3 days of hospitalization. The proportions of reductions in the number of tests performed after 3 days and the associated
P
values were 54.1% for O&P examinations (
P
< 0.0001), 22.58% for GC-EIA (
P
= 0.2807), and 49.1% for STCUL (
P
< 0.0001). This was estimated to have resulted in $8,108.84 of cost savings. The electronic CDST resulted in a substantial reduction in the number of evaluations of stool cultures and the number of parasitological examinations for patients hospitalized for more than 3 days and in a cost savings while retaining the ability of the clinician to obtain these tests if clinically indicated.
Transcriptome Analysis of the Spodoptera frugiperda AscovirusIn VivoProvides Insights into How Its Apoptosis Inhibitors and Caspase Promote Increased Synthesis of Viral Vesicles and Virion Progeny
Authors: Zaghloul Heba A. H. , Hice Robert , Arensburger Peter , Federici Brian A.
Published: September 2017

Ascoviruses are double-stranded DNA (dsDNA) viruses that attack caterpillars and differ from all other viruses by inducing nuclear lysis followed by cleavage of host cells into numerous anucleate vesicles in which virus replication continues as these grow in the blood. Ascoviruses are also unusual in that most encode a caspase or caspase-like proteins. A robust cell line to study the novel molecular biology of ascovirus replicationin vitrois lacking. Therefore, we used strand-specific transcriptome sequencing (RNA-Seq) to study transcriptionin vivoin third instars ofSpodoptera frugiperdainfected with the type species,Spodoptera frugiperda ascovirus1a(SfAV-1a), sampling transcripts at different time points after infection. We targeted transcription of two types of SfAV-1a genes; first, 44 core genes that occur in several ascovirus species, and second, 26 genes predictedin silicoto have metabolic functions likely involved in synthesizing viral vesicle membranes. Gene cluster analysis showed differences in temporal expression of SfAV-1a genes, enabling their assignment to three temporal classes: early, late, and very late. Inhibitors of apoptosis (IAP-like proteins; ORF016, ORF025, and ORF074) were expressed early, whereas its caspase (ORF073) was expressed very late, which correlated with apoptotic events leading to viral vesicle formation. Expression analysis revealed that a Diedel gene homolog (ORF121), the only known “virokine,” was highly expressed, implying that this ascovirus protein helps evade innate host immunity. Lastly, single-nucleotide resolution of RNA-Seq data revealed 15 bicistronic and tricistronic messages along the genome, an unusual occurrence for large dsDNA viruses.

IMPORTANCEUnlike all other DNA viruses, ascoviruses code for an executioner caspase, apparently involved in a novel cytopathology in which viral replication induces nuclear lysis followed by cell cleavage, yielding numerous large anucleate viral vesicles that continue to produce virions. Our transcriptome analysis of genome expressionin vivoby the Spodoptera frugiperda ascovirus shows that inhibitors of apoptosis are expressed first, enabling viral replication to proceed, after which the SfAV-1a caspase is synthesized, leading to viral vesicle synthesis and subsequent extensive production of progeny virions. Moreover, we detected numerous bicistronic and tricistronic mRNA messages in the ascovirus transcriptome, implying that ascoviruses use other noncanonical translational mechanisms, such as internal ribosome entry sites (IRESs). These results provide the first insights into the molecular biology of a unique coordinated gene expression pattern in which cell architecture is markedly modified, more than in any other known eukaryotic virus, to promote viral reproduction and transmission.
Novel Role for Interleukin-17 in Enhancing Type 1 Helper T Cell Immunity in the Female Genital Tract following Mucosal Herpes Simplex Virus 2 Vaccination
Authors: Bagri Puja , Anipindi Varun C. , Nguyen Philip V. , Vitali Danielle , Stämpfli Martin R. , Kaushic Charu
Published: September 2017

It is well established that interferon gamma (IFN-γ) production by CD4+T cells is critical for antiviral immunity against herpes simplex virus 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4+T cells in HSV-2 antiviral immunity is yet to be elucidated. Here we demonstrate that IL-17A plays an important role in enhancing antiviral T helper type 1 (Th1) responses in the female genital tract (FGT) and is essential for effective protection conferred by HSV-2 vaccination. While IL-17A did not play a critical role during primary genital HSV-2 infection, seen by lack of differences in susceptibility between IL-17A-deficient (IL-17A−/−) and wild-type (WT) C57BL/6 mice, it was critical for mediating antiviral responses after challenge/reexposure. Compared to WT mice,IL-17A−/−mice (i) infected intravaginally and reexposed or (ii) vaccinated intranasally and challenged intravaginally demonstrated poor outcomes. Following intravaginal HSV-2 reexposure or challenge, vaccinatedIL-17A−/−mice had significantly higher mortality, greater disease severity, higher viral shedding, and higher levels of proinflammatory cytokines and chemokines in vaginal secretions. Furthermore,IL-17A−/−mice had impaired Th1 cell responses after challenge/reexposure, with significantly lower proportions of vaginal IFN-γ+CD4+T cells. The impaired Th1 cell responses inIL-17A−/−mice coincided with smaller populations of IFN-γ+CD4+tissue resident memory T (TRM) cells in the genital tract postimmunization. Taken together, these findings describe a novel role for IL-17A in regulating antiviral IFN-γ+Th1 cell immunity in the vaginal tract. This strategy could be exploited to enhance antiviral immunity following HSV-2 vaccination.

IMPORTANCET helper type 1 (Th1) immunity, specifically interferon gamma (IFN-γ) production by CD4+T cells, is critical for protection against genital herpesvirus (HSV-2) infection, and enhancing this response can potentially help improve disease outcomes. Our study demonstrated that interleukin-17A (IL-17A) plays an essential role in enhancing antiviral Th1 responses in the female genital tract (FGT). We found that in the absence of IL-17A, preexposed and vaccinated mice showed poor disease outcomes and were unable to overcome HSV-2 reexposure/challenge. IL-17A-deficient mice (IL-17A−/−) had smaller populations of IFN-γ+CD4+tissue resident memory T (TRM) cells in the genital tract postimmunization than did wild-type (WT) mice, which coincided with attenuated Th1 responses postchallenge. This has important implications for developing effective vaccines against HSV-2, as we propose that strategies inducing IL-17A in the genital tract may promote more effective Th1 cell immunity and better overall protection.
NLRX1 Mediates MAVS Degradation To Attenuate the Hepatitis C Virus-Induced Innate Immune Response through PCBP2
Authors: Qin Yuwen , Xue Binbin , Liu Chunyan , Wang Xiaohong , Tian Renyun , Xie Qinya , Guo Mengmeng , Li Guangdi , Yang Darong , Zhu Haizhen
Published: September 2017

Activation of innate immunity is essential for host cells to restrict the spread of invading viruses and other pathogens. However, attenuation or termination of signaling is also necessary for preventing immune-mediated tissue damage and spontaneous autoimmunity. Here, we identify nucleotide binding oligomerization domain (NOD)-like receptor X1 (NLRX1) as a negative regulator of the mitochondrial antiviral signaling protein (MAVS)-mediated signaling pathway during hepatitis C virus (HCV) infection. The depletion of NLRX1 enhances the HCV-triggered activation of interferon (IFN) signaling and causes the suppression of HCV propagation in hepatocytes. NLRX1, a HCV-inducible protein, interacts with MAVS and mediates the K48-linked polyubiquitination and subsequent degradation of MAVS via the proteasomal pathway. Moreover, poly(rC) binding protein 2 (PCBP2) interacts with NLRX1 to participate in the NLRX1-induced degradation of MAVS and the inhibition of antiviral responses during HCV infection. Mutagenic analyses further revealed that the NOD of NLRX1 is essential for NLRX1 to interact with PCBP2 and subsequently induce MAVS degradation. Our study unlocks a key mechanism of the fine-tuning of innate immunity by which NLRX1 restrains the retinoic acid-inducible gene I-like receptor (RLR)-MAVS signaling cascade by recruiting PCBP2 to MAVS for inducing MAVS degradation through the proteasomal pathway. NLRX1, a negative regulator of innate immunity, is a pivotal host factor for HCV to establish persistent infection.

IMPORTANCE
Innate immunity needs to be tightly regulated to maximize the antiviral response and minimize immune-mediated pathology, but the underlying mechanisms are poorly understood. In this study, we report that NLRX1 is a proviral host factor for HCV infection and functions as a negative regulator of the HCV-triggered innate immune response. NLRX1 recruits PCBP2 to MAVS and induces the K48-linked polyubiquitination and degradation of MAVS, leading to the negative regulation of the IFN signaling pathway and promoting HCV infection. Overall, this study provides intriguing insights into how innate immunity is regulated during viral infection.
The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparum Intraerythrocytic Life Cycle
Authors: Cobb David W. , Florentin Anat , Fierro Manuel A. , Krakowiak Michelle , Moore Julie M. , Muralidharan Vasant
Published: September 2017

Half of the world’s population lives at risk for malaria. The intraerythrocytic life cycle of
Plasmodium
spp. is responsible for clinical manifestations of malaria; therefore, knowledge of the parasite’s ability to survive within the erythrocyte is needed to combat the deadliest agent of malaria,
P. falciparum
. An outstanding question in the field is how
P. falciparum
undertakes the essential process of trafficking its proteins within the host cell. In most organisms, chaperones such as Hsp70 are employed in protein trafficking. Of the
Plasmodium
species causing human disease, the chaperone PfHsp70x is unique to
P. falciparum
, and it is the only parasite protein of its kind exported to the host (S. Külzer et al., Cell Microbiol 14:1784–1795, 2012). This has placed PfHsp70x as an ideal target to inhibit protein trafficking and kill the parasite. However, we show that PfHsp70x is not required for export of parasite effectors and it is not essential for parasite survival inside the RBC.
Phelan-McDermid syndrome due toSHANK3mutation in an intellectually disabled adult male: successful treatment with lithium
Authors: Egger Jos I M , Verhoeven Willem M A , Groenendijk-Reijenga Renske , Kant Sarina G
Published: September 2017

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in theSHANK3gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective. In addition to two elsewhere published adolescent patients, we here describe in detail the history of an adult male patient with PMS caused by aSHANK3mutation in whom successive treatment regimens with antipsychotics and mood-stabilising anticonvulsants were all ineffective. Ultimately, addition of lithium to existing olanzapine therapy led to enduring stabilisation of mood and behaviour.
PP12 New indicators for measuring patient survival following ambulance service care
Authors: Coster Joanne , Jacques Richard , Turner Janette , Crum Annabel , Nicholl Jon , Niroshan Siriwardena A
Published: September 2017

Background

Developing better measures of quality and performance are key priorities for ambulance services. Using multi-stage, multi-stakeholder consensus studies, we developed eight new indicators of ambulance service quality and performance. We present here a new indicator to measure rates of survival to 7 days post incident in people with a serious emergency condition.

Methods

We linked six months patient level Computer-Aided Dispatch (CAD) and electronic Patient Report Form (ePRF) data from one ambulance service with Hospital Episode Statistics (HES A and E/admitted patient data), and national mortality (ONS) information We identified a cohort of people with one of 16 serious emergency conditions, defined as conditions ‘where death could potentially be prevented by a good emergency system’. We created age and condition adjusted models to calculate two survival measures. 1) Survival to hospital admission, within 7 days of the ambulance call; 2) For patients admitted to hospital, survival to 7 days from admission.

Results

11 264 patients met the inclusion criteria. 1) 10 647 survived to admission and 617 (5.5%) died pre-admission. Most pre-admission deaths were in older people (42%>80 years) and occurred within 1 day of the ambulance call (87.8%). People with ruptured aortic aneurysm and asphyxiation were more likely to die pre-admission than those with other conditions. 2) Of the 10 647 patients admitted to hospital, 94% survived. Survival rates decreased with age: 100% of children under 11 years compared whereas 84% of those aged over 90 years survived to 7 days. People with cardiac arrest, septic shock and ruptured aortic aneurysm were also more likely to die in hospital.

Conclusions

These two indicators relate to people with a serious emergency condition who survive. Further work is being done to develop predictive models that can be used to assess trends over time. For example, survival may improve through taking the right patients to the right specialist care.