bluuebunny/crossref_metadata_2025 huggingface dataset:
Transferring critically ill babies and children home to die from intensive care
Authors: Morton Kathryn E. , Richardson Alison , Coombs Maureen A. , Darlington Anne‐Sophie E.
Published: March 2019

Background

A significant proportion of hospital deaths occur in intensive care units (ICU) and often follow a decision to limit or withdraw life‐sustaining treatment. Facilitating the preferred choice in place of death for babies/children is increasingly being advocated, although the literature on a home death is often limited to case reports.

Aims and objectives

To examine (a) health care professionals' (HCPs) views and experience of transferring babies/children home to die from intensive care, (b) patient clinical characteristics that HCPs would consider transferring home and (c) barriers to transferring home.

Design

A cross‐sectional descriptive web‐based survey.

Methods

A total of 900 HCPs from paediatric and neonatal ICU across the United Kingdom were invited to participate.

Results

A total of 191 (22%) respondents completed the survey; 135 (70.7%) reported being involved in transferring home to die. However, most (58.4%) had just transferred one or two patients in the last 3 years. Overall, respondents held positive views towards transfer, although there was some evidence of divided opinion. Patients identified as unsuitable for transfer included unstable patients (57.6%) and those in need of cardiovascular support (56%). There was statistically significant difference in views between those with and without experience, in that those with experience had more positive views. The most significant barrier was the lack of access to care in the community.

Conclusions

HCPs view the concept of transferring critically ill babies/children home to die positively but have infrequent experience. Views held about transfers are influenced by previous experience. The clinical instability of patients and access to community care are central to decision‐making.

Relevance to clinical practice

A home death for critically ill babies/children is occurring in the United Kingdom but infrequently. Experience of a transfer home positively influences views and increases confidence. Improved multi‐organizational collaboration between ICU and community care teams would assist decision‐making and facilitation for a transfer home.
CTSC compound heterozygous mutations in two Chinese patients with Papillon–Lefèvre syndrome
Authors: Wu Yuelin , Zhao Lei , Xu Chunmei , Wu Yafei
Published: March 2019

Objectives

To identify the molecular basis of Papillon–Lefèvre syndrome in two Chinese families.

Methods

Peripheral blood and mouth swab samples were obtained, from which genomic DNA and RNA were isolated. Sanger sequencing was employed to identify the mutations. mRNA expression was tested by real‐time quantitative PCR. Evolutionary conservation, pathogenicity prediction and impact of protein structures of the mutations were conducted with bioinformatics tools and homology modelling. HEK293 cells were transfected with plasmids expressing wild‐type or mutated CTSC. CTSC protein expression level and enzyme activity were explored.

Results

Mutation analysis revealed two novel compound heterozygous mutations, the c.190‐191insA and c.1211‐1212delA in patient 1 and the c.716A>G and c.757+1G>A in patient 2. In both patients, the levels of CTSC mRNA were significantly lower than in their relatives. Homology modelling analysis predicted that the mutations affect the structure and stability of the protein, and in vitro study showed that the CTSC proteins containing the mutations c.190‐191insA and c.1211‐1212delA, which result in truncated versions of protein, display impaired enzyme activity. The protein containing c.716A>G mutation showed quite similar enzyme activity compared to wild‐type CTSC.

Conclusion

Our data support the molecular mechanism of PLS and enlarge the scope of CTSC gene mutations related to PLS.
Long‐term outcomes of cardiac resynchronization therapy in adult congenital heart disease
Authors: Leyva Francisco , Zegard Abbasin , Qiu Tian , de Bono Joseph , Thorne Sara , Clift Paul , Marshall Howard , Hudsmith Lucy
Published: March 2019

Background and Aims

Randomized, controlled trials of cardiac resynchronization therapy (CRT) excluded patients with adult congenital heart disease (ACHD). We sought to explore long‐term clinical outcomes.

Methods and Results

In this single‐center, observational study, events were collected from hospital records on patients with structural ACHD (sACHD) and adults with ischemic (ICM) or nonischemic (NICM) cardiomyopathy undergoing CRT. Patients with sACHD (n = 23, age: 41.6 ± 13.5 years [mean ± standard deviation]) and adults with ICM (n = 533) or NICM (n = 458) were followed‐up for 4.1 years (median; interquartile range: 2.2‐6.1). Total mortality was 5/23 (21.7%; 4.4 per 100 person‐years) in sACHD, 221/533 (41.5%; 11.8 per 100 person‐years) in ICM, and 154/458 (33.6%; 9.7 per 100 person‐years) in NICM. In univariate analyses, total mortality in sACHD was lower than in ICM (hazard ratio [HR]: 0.38; 95% confidence interval [CI] 0.15‐0.91), but similar to NICM (HR: 0.48, 95% CI 0.20‐1.16). Cardiac mortality in sACHD was similar to ICM (HR: 0.78, 95% CI 0.32‐1.92) and NICM (HR: 1.12, 95% CI 0.45‐2.78). Heart failure (HF) hospitalization rates were similar to ICM (HR: 0.44, 95% CI 0.11‐1.77) and NICM (HR: 0.75, 95% CI 0.18‐3.08). In multivariate analyses, no differences emerged in total mortality, cardiac mortality, or HF hospitalization between sACHD and NICM or ICM, after adjustment for age, sex, New York Heart Association class, diabetes, atrial rhythm, QRS duration, QRS morphology, systemic ventricular ejection fraction, and medical therapy.

Conclusion

Total mortality, cardiac mortality, and HF hospitalization after CRT in patients with sACHD was similar to adults with ICM or NICM.
The taste of origin in a lady beetle: do males discriminate between females based on cuticular hydrocarbons?
Authors: Legrand Pauline , Vanderplanck Maryse , Marko Istvan , Gillard Laurent , Lognay Georges , Lorge Stéphanie , Maesen Philippe , Vilcinskas Andreas , Vogel Heiko , Foucaud Julien , Estoup Arnaud , Francis Frédéric , Facon Benoit , Verheggen François J.
Published: March 2019

The Asian lady beetle Harmonia axyridis originates from Asia and has established invasive populations worldwide. Recent population genetic studies trace their invasion routes and demonstrate that bottlenecks in population size have reduced their genetic diversity. Consequently, phenotypical differences are highlighted between native and invasive populations. Among phenotypical traits, cuticular hydrocarbons (CHCs) might reflect the geographical origin of a lady beetle, especially because of their genetic basis. The present study investigates whether (i) the CHC profiles qualitatively and quantitatively differ between females of H. axyridis from native and invasive populations and (ii) males discriminate females from native and invasive populations using CHC profiles. CHCs are solvent‐extracted before being quantified and identified by gas chromatography and mass spectrometry. In total, 17 CHCs are detected from female elytra, including six alkanes, three polyunsaturated and eight monounsaturated alkenes. The total quantity of CHCs differs among the populations, with lady beetles from Tai'an (China) displaying higher CHC concentrations than lady beetles from Gembloux (Belgium) and from Beijing (China) populations. Multivariate analyses detect differences in CHC qualitative profiles, with females from Tai'an being different from the two other populations. Finally, behavioural assays show that females originating from the native Tai'an population are less preferred by males, whereas females from the invasive population are mounted more often. The behavioural assays suggest that CHCs are not involved in discrimination of mating partners based on their origin.
Increasing the germination percentage of a declining native orchid (Himantoglossum adriaticum) by pollen transfer and outbreeding between populations
Authors: Del Vecchio S. , Pierce S. , Fantinato E. , Buffa G.
Published: March 2019

The declining native orchid Himantoglossum adriaticum H. Baumann is a European endemic of priority interest (92/43/ EEC, Annex II). Northern Italian populations of H. adriaticum are small and isolated, with depressed seed set. Given the important implications for plant population conservation, we tested the hypothesis that artificial pollen transfer (hand‐pollination) and outbreeding between populations increases fruit set and seed germination percentage.

The background fruit set and in vitro germination rates were determined for ten reference populations. An artificial cross‐pollination experiment included (a) pollen transfer from one large population to two small and isolated populations; (b) pollen transfer between two small but not isolated populations; (c) within‐population pollen transfer (control). All seeds were sown on a modified Malmgren's medium and cultured in a controlled environment. Germination percentage was compared using a Kruskal‐Wallis anova.

The background fruit set (mean = 18%) and germination (<5%) rates were consistently low across populations. Fruit set after hand‐pollination was consistently 100%. Pollen transfer from the largest population to smaller populations resulted in an increase in total germination ranging from 0.9% to 2.9%. The largest increase in germination occurred between small‐sized and less isolated populations (from 1.7% to 5.1%).

The results of pollen transfer between the small populations are particularly encouraging, as the mean increase in germination was almost four times that of the control. Outbreeding can be considered a valuable tool to increase genetic flow and germination in natural populations, limit the accumulation of detrimental effects on fitness driven by repeated breeding with closely‐related individuals, thereby increasing the possibility of conservation of rare or endangered species.
Relation of depression symptoms to sustained reward and loss sensitivity
Authors: Berry Michael P. , Tanovic Ema , Joormann Jutta , Sanislow Charles A.
Published: March 2019

Depression is characterized by altered sensitivity to rewards, with recent evidence suggesting that the ability to sustain responses to rewards across long experimental tasks is diminished. Most work on sustained reward responsiveness has taken a categorical approach and focused on major depressive disorder. However, impairments in reward sensitivity are also found at lower levels of symptom severity and may be relevant for understanding basic mechanisms linking reward processing abnormalities to depression. The current study took a dimensional approach to examine the relation between depression symptoms and sustained reward responsiveness by examining how early neural responses to rewards and losses change over a short time course (i.e., during the experiment). In a sample of 45 unselected undergraduates, changes in the amplitude of the reward positivity (RewP) and feedback negativity (FN) were examined over the course of a simple gambling task using multilevel modeling. Amplitude of the RewP was sustained and amplitude of the FN increased during the task. Unlike prior work focused on clinical populations, depression symptoms in this unselected sample were associated with enhanced RewP and FN responding over the course of the task. Results echo prior work that underscores the importance of examining changes in response to reward across trials and further suggests that sustained responses to both rewards and losses vary in relation to symptom level.
Exercise and physical activity for people receiving peritoneal dialysis: Why not?
Authors: Isnard‐Rouchon Myriam , West Mike , Bennett Paul N.
Published: March 2019

People with end‐stage kidney disease (ESKD) receiving peritoneal dialysis (PD) are physically inactive leading to low physical function and poor health outcomes. Guidelines recommend that nephrologists encourage PD patients to increase their activity levels; however, PD patients are often discouraged from participating in exercise programs because of perceived barriers and a lack of precision about the appropriate exercise regimen. This review suggests ways forward to assist nephrology professionals to encourage PD patients to exercise, instead of creating barriers. The paper draws on the literature in addition to the experience of programs in France, the United States, and Australia to demonstrate the possibilities when considering increasing physical activity in this group.
Understanding the use of “twinkie,” “banana,” and “FOB”: Identifying the origin, role, and consequences of internalized racism within Asian America
Authors: Trieu Monica M.
Published: March 2019

Where does internalized racism come from? How is it sustained and perpetuated within the Asian American community? What is the role and consequence of internalized racism within the Asian American community? This article reviews the existing literature to map the origin, role, and consequences of internalized racism among Asian Americans. Research on internalized racism must examine more than individual behaviors, otherwise it falls victim to conceiving of individuals as “racial dupes” (i.e., an individual who has been deceived into supporting existing racial hierarchies and systems of racial inequalities). However, the research should also veer away from an over emphasis on individual agency and resistance because doing so ignores the larger structural systems of inequality that exist, via colonial mentality and racialization, which influence individual behaviors. Future research on internalized racism must engage both perspectives to hold accountable the connection between broader racialization processes and everyday interactions driven by internalized racism.
“Explain or change”: The quality and uses of ethnicity data in universities and healthcare organisation in England
Authors: Afridi Asif , Murji Karim
Published: March 2019

“Explain or change” was a key term that came into currency in the UK from 2016 onwards to put the onus on public institutions to account for disparities in outcomes on the basis of class, gender, and ethnicity in the main. One of the most prominent outcomes of this policy initiative was the government Race Disparity Audit. This article aims to go behind the headline figures to understand what it means to either “explain” or “change” figures and policies around race/ethnicity in particular. It outlines the findings of a survey and some interviews with staff working in the NHS in London and in universities in England. The findings point to difficulties with the quality of data generated by these organisations, as well as the uses of data. Practitioners feel that data is incomplete and do not provide the routes to policy measures that will make a clear difference to outcomes. At the same time, there is a feeling there is a lack of will to use data to either explain or change their organisation's response to race inequality. Thus, this article concludes that the use of ethnicity data remains the main concern for many participants in this study.
The impact of an out‐of‐school STEM education program on students’ attitudes toward STEM and STEM careers
Authors: Baran Evrim , Canbazoglu Bilici Sedef , Mesutoglu Canan , Ocak Ceren
Published: March 2019

There is an increasing awareness of out‐of‐school program value in enhancing student interest and understanding of science, technology, engineering, and mathematics (STEM). This study examined the impact of an out‐of‐school STEM education program on student attitudes toward STEM disciplines and STEM careers. A STEM education program implemented at a public research university was designed to integrate STEM disciplines with hands‐on problem‐based activities. Design features included authentic learning contexts, engineering design processes, and content integration. Data sources included an attitude survey and interviews conducted with forty sixth grade middle school student participants. The analysis revealed significant differences between pre and posttests on student attitudes toward personal and social implications of STEM, science and engineering learning, and their relationship to STEM. Findings showed that the program contributed to students’ developing interest in STEM fields, and helped them make connections between schoolwork and daily lives. Recommendations for future research on out‐of‐school STEM education programs were discussed.
Integrated STEM in practice: Learning from Montessori philosophies and practices
Authors: Livstrom Illana C. , Szostkowski Alaina H. , Roehrig Gillian H.
Published: March 2019

In theory, STEM (interdisciplinary science, technology, engineering and mathematics) is cross‐disciplinary and situated in real‐world problem‐solving contexts. In practice, STEM disciplines are often implemented separately using contrived contexts. This paper examines theoretical and empirical aspects of Montessori middle school science in the United States, and its alignment with the conceptual framework of integrated STEM. We selected Montessori adolescent environments because the Montessori philosophy involves interdisciplinary application contextualized in purposeful work and learning. Our research sought to investigate how Montessori middle schools have designed their science programs, and to situate these findings within the current landscape of STEM education and reform‐based science. Based on the results of our survey of 96 U.S. Montessori middle schools, we argue Montessori offers an integrated educational approach that meaningfully situates academic disciplines to mirror local and global challenges, well supported by theory and literature on STEM and situated learning theories. We assert that integrated STEM happens organically in many Montessori middle schools, and takes place through authentic work in communities of practice. Our research communicates the value of looking outside traditional school settings to examine alternative formal education spaces, like Montessori classrooms where integrated STEM happens organically.
A previously undescribed cutaneous paraneoplastic syndrome in a cat with thymoma
Authors: Fournier Quentin , Bavcar Spela , Philbey Adrian W. , Smith Sionagh , Varjonen Katarina
Published: March 2019

Background

Exfoliative dermatitis is a well‐recognized cutaneous paraneoplastic syndrome (PNS) associated with thymoma in cats, of which the clinical and histopathological presentation has been well‐characterized.

Objectives

To describe a novel clinical skin manifestation associated with thymoma in a cat.

Animal

A 14‐year‐old neutered female domestic short hair cat.

Methods and materials

Physical, abdominal ultrasonographic, thoracic radiographic, ultrasonographic and computed tomographic examinations, histopathological assessment of the skin and mediastinal mass.

Results

The cat was presented with noninflammatory alopecia, with a dorsal multifocal distribution. Examination of the alopecic areas using a dermascope indicated an apparent lack of follicular ostia. Histopathological assessment of alopecic areas confirmed follicular and epidermal atrophy, trichilemmal keratinization and mild orthokeratotic hyperkeratosis. Diagnostic imaging revealed a mediastinal mass, which was surgically removed. Histopathological and immunohistopathological examination of the mass was consistent with a thymoma, associated with multiloculated cyst formation and multifocal cholesterol granulomas. Following surgery, hair re‐growth was noted in the previously alopecic areas. The cat was euthanized 3.5 months later because of recurrent chylothorax suspected to be a postoperative complication. The alopecic lesions had improved markedly.

Conclusions and clinical importance

Thymoma‐associated PNS might not always manifest as an exfoliative dermatitis and should be considered in the differential diagnosis of multifocal noninflammatory alopecia.
The current state of the use of large wood in river restoration and management
Authors: Grabowski Robert C. , Gurnell Angela M. , Burgess‐Gamble Lydia , England Judy , Holland David , Klaar Megan J. , Morrissey Ian , Uttley Chris , Wharton Geraldene
Published: March 2019

Trees fall naturally into rivers generating flow heterogeneity, inducing geomorphological features, and creating habitats for biota. Wood is increasingly used in restoration projects and the potential of wood acting as leaky barriers to deliver natural flood management by ‘slowing the flow’ is recognised. However, wood in rivers can pose a risk to infrastructure and locally increase flood hazards. The aim of this paper is to provide an up‐to‐date summary of the benefits and risks associated with using wood to promote geomorphological processes to restore and manage rivers. This summary was developed through a workshop that brought together academics, river managers, restoration practitioners and consultants in the UK to share science and best practice on wood in rivers. A consensus was developed on four key issues: (i) hydrogeomorphological effects, (ii) current use in restoration and management, (iii) uncertainties and risks and (iv) tools and guidance required to inform process‐based restoration and management.
Exploring the origin of low back pain sub-classification: a scoping review protocol
Authors: Jess Mary-Anne , Hamilton Sharon , Ryan Cormac G. , Wellburn Shaun , Martin Denis
Published: March 2019

Objective:

This scoping review aims to map the different working definitions currently being used for the duration of acute, subacute and chronic low back pain (LBP), and to establish where these definitions originated and the rationale provided for the timeframes used.

Introduction:

Low back pain is a major social and economic problem worldwide. One of the most commonly used approaches to classify and manage patients with LBP is the traditional duration-based classification (acute, subacute and chronic). There are significant differences between studies in the timeframes used for what constitutes acute, subacute and chronic LBP. These discrepancies lead to heterogeneity in study results, making it difficult to compare or summarize findings.

Inclusion criteria:

Studies that include participants with non-specific LBP, regardless of sex, will be considered. Studies that include children or participants with specific causes of LBP will be excluded.

Methods:

The following electronic databases will be searched: MEDLINE, Embase, CINAHL and PsycINFO. All types of studies will be included, provided they give a rationale for the definition of duration that they use. Studies will be limited to those published in English. Two independent reviewers will screen the retrieved articles against the eligibility criteria for the scoping review. A narrative synthesis will describe the definitions used in the study and the rationale given for the timeframes reported. This scoping review will give an insight into the background of the variation of timeframes used for duration-based classification of LBP.
Effectiveness of protection strategies for reducing radiation exposure in proceduralists during cardiac catheterization procedures: a systematic review protocol
Authors: Fernandez Ritin , Ellwood Laura , Barrett David , Weaver James
Published: March 2019

Review question:

What is the effectiveness of radiation protection strategies for reducing the radiation dose received by the proceduralist during cardiac catheterization procedures?
Spiritual aspects of the family caregivers’ experiences when caring for a community-dwelling adult with severe mental illness: a qualitative systematic review protocol
Authors: Casaleiro Tiago , Caldeira Silvia
Published: March 2019

Review question:

What are the spiritual aspects of family caregivers’ experiences when caring for a community-dwelling adult with severe mental illness?
Numerical Study on Fretting Wear of Mating Surface Between Piston Crown and Skirt in Heavy Duty Diesel Engine
Authors: Wang Yi , Wu Limin , Liu Shuo , Li Mei , Meng Xianghui , Cui Yi
Published: March 2019

Composite pistons are often used in heavy duty diesel engines due to its good reliability and durability. Owing to the alternating loads, fretting wear usually happens on the mating surfaces between piston crown and skirt. In this paper, a fretting wear finite element model is developed to analyze the mating surface wear of composite piston of heavy-duty diesel engine. The fretting wear model predicts the wear depth evolution for each working cycle based on Archard model and mesh updating technique, which is validated by previous pin and disk contact experiments. The wear evolution of the top contact surface of piston skirt is simulated according to engine operating condition, and fretting wear life is estimated by the decreasing process of crown-skirt connecting bolt preload. Effects of the shape of piston skirt top surface are also evaluated. In the end, the rationality of fretting wear model is validated by durability tests of diesel engine.
Re-adaptation from alternative prey to target prey increased predation of predator on target mite
Authors: Su Jie , Zhu An-Di , Han Guo-Dong , Dong Fang , Chen Jing , Zhang Jian-Ping
Published: March 2019

Neoseiulus bicaudus (Wainstein) is a natural enemy of spider mite and thrip and also a potential biocontrol agent for Tetranychus turkestani (Tetranychidae). Tyrophagus putrescentiae (Schrank) is an important alternative prey of N. bicaudus for mass rearing. We aimed to determine whether previous long-term feeding history, rearing on alternative prey versus target prey affected the performance of N. bicaudus. Therefore, the prey preference and functional response of predatory mites were compared between three strains: N. bicaudus fed on T. turkestani (TTS); N. bicaudus fed on T. putrescentiae (TPS); and N. bicaudus re-adapted from T. putrescentiae to T. turkestani (TPRS). When fed with the target prey, the preference rate and consumption of the TPS strain were significantly lower than the TTS strain. In addition, after 3-day-re-adaptation, the predatory mites (TPRS) increased their preference rate and consumption to target prey. The results suggested that re-adaptation before release could improve the ability of N. bicaudus to control its target prey.
First record of the mite genus Denheyernaxoides Smiley (Acari: Bdelloidea: Cunaxidae) for North America and a redescription of D. americanus Rocha et al.
Authors: Nowell Victoria Jean , Schwarzfeld Marla Dahlie
Published: March 2019

Here we present the first records of Denheyernaxoides from North America: D. americanus, collected from coniferous litter, soil, and moss in Nova Scotia, Canada. These new records significantly expand the known distribution of the species. Denheyernaxoides americanus is redescribed to include Canadian specimens and to rectify discrepancies in the species’ description identified during examination of the holotype. The deutonymph of D. americanus is also described. Sequences, representing a 658 bp region of the mitochondrial cytochrome c oxidase subunit I (COI), were obtained from representative specimens collected in Canada. Comparison of these sequences with those from the Barcode of Life database (BOLD) suggests that a second species of Denheyernaxoides may occur in British Columbia, Canada. A revised key to world species of Denheyernaxoides is provided.
Next Generation of Tn
7
-Based Single-Copy Insertion Elements for Use in Multi- and Pan-Drug-Resistant Strains of Acinetobacter baumannii
Authors: Ducas-Mowchun Kaleigh , De Silva P. Malaka , Crisostomo Leandro , Fernando Dinesh M. , Chao Tzu-Chiao , Pelka Peter , Schweizer Herbert P. , Kumar Ayush
Published: March 2019

Acinetobacter baumannii
is a high-priority pathogen for which research on mechanisms of resistance and virulence is a critical need. Commonly used antibiotic selection markers are not suitable for use in MDR and XDR isolates of
A. baumannii
due to the high antibiotic resistance of these isolates, which poses a barrier to the study of this pathogen. This study demonstrates the practical potential of using apramycin and zeocin mini-Tn
7
- and Flp recombinase-encoded constructs to carry out genomic manipulations in clinical isolates of
A. baumannii
displaying MDR and XDR phenotypes.
Role and Recruitment of the TagL Peptidoglycan-Binding Protein during Type VI Secretion System Biogenesis
Authors: Santin Yoann G. , Camy Claire E. , Zoued Abdelrahim , Doan Thierry , Aschtgen Marie-Stéphanie , Cascales Eric
Published: March 2019

Bacteria use weapons to deliver effectors into target cells. One of these weapons, called the type VI secretion system (T6SS), could be compared to a nano-spear gun using a springlike mechanism for effector injection. By targeting bacteria and eukaryotic cells, the T6SS reshapes bacterial communities and hijacks host cell defenses. In enteroaggregative
Escherichia coli
, the T6SS is a multiprotein machine that comprises a cytoplasmic tail and a peptidoglycan-anchored trans-envelope channel. In this work, we show that TagL comprises an N-terminal domain that mediates contact with the channel and a peptidoglycan-binding domain that binds the cell wall. We then determine at which stage of T6SS biogenesis TagL is recruited and how TagL absence impacts the assembly pathway.
Stress-Induced MazF-Mediated Proteins in Escherichia coli
Authors: Nigam Akanksha , Ziv Tamar , Oron-Gottesman Adi , Engelberg-Kulka Hanna
Published: March 2019

The stress response, the strategy that bacteria have developed in order to cope up with all kinds of adverse conditions, is so far understood at the level of transcription. Our previous findings of a uniquely modified stress-induced translation machinery (STM) generated in
E. coli
under stress by the endoribonucleolytic activity of the toxin MazF opens a new chapter in understanding microbial physiology under stress at the translational level. Here, we performed a proteomic analysis of all the
E. coli
stress-induced proteins that are mediated by chromosomally borne MazF through STM.
Rapid Replacement of Acinetobacter baumannii Strains Accompanied by Changes in Lipooligosaccharide Loci and Resistance Gene Repertoire
Authors: Adams Mark D. , Wright Meredith S. , Karichu James K. , Venepally Pratap , Fouts Derrick E. , Chan Agnes P. , Richter Sandra S. , Jacobs Michael R. , Bonomo Robert A.
Published: March 2019

Multidrug-resistant (MDR)
A. baumannii
is a difficult-to-treat health care-associated pathogen. Knowing the resistance genes present in isolates causing infection aids in empirical treatment selection. Furthermore, knowledge of the genetic background can assist in tracking patterns of transmission to limit the spread of infections in hospitals. The appearance of a new genetic background in
A. baumannii
strains with a different set of resistance genes and cell surface structures suggests that strong selective pressures exist, even in highly MDR pathogens. Because the new strains have levels of antimicrobial resistance similar to those of the strains that were displaced, we hypothesize that other features, including host colonization and infection, may confer additional selective advantages and contribute to their increased prevalence.
Independent Microevolution Mediated by Mobile Genetic Elements of Individual Clostridium difficile Isolates from Clade 4 Revealed by Whole-Genome Sequencing
Authors: Wu Yuan , Liu Chen , Li Wen-Ge , Xu Jun-Li , Zhang Wen-Zhu , Dai Yi-Fei , Lu Jin-Xing
Published: March 2019

Mobile genetic elements play a key role in the continuing evolution of
Clostridium difficile
, resulting in the emergence of new phenotypes for individual isolates. On the basis of whole-genome sequencing analysis, we comprehensively explored transposons, CRISPR, prophage, and genetic sites for drug resistance within clade 4
C. difficile
isolates with different sequence types. Great diversity in MGEs and a high rate of multidrug resistance were found within this clade, including new transposons, Tn
4453a/b
with
aac(6
′
) aph(2
′′
)
instead of
catD
, and a relatively high rate of prophage-carried CRISPR arrays. These findings provide important new insights into the mechanism of genome remodeling within clade 4 and offer a new method for typing and tracing the origins of closely related isolates.
Core Microbiota in Agricultural Soils and Their Potential Associations with Nutrient Cycling
Authors: Jiao Shuo , Xu Yiqin , Zhang Jie , Hao Xin , Lu Yahai
Published: March 2019

Disentangling the roles of the core microbiota in community maintaining and soil nutrient cycling is an important yet poorly understood topic in microbial ecology. This study presents an exploratory effort to gain predictive understanding of the spatial atlas and ecological roles of the core microbiota. A systematic, continental-scale survey was conducted using agro-soils in adjacent pairs of maize (dryland) and rice (wetland) fields across eastern China. The results indicate that the core microbiota play major ecological roles in maintaining complex connections between bacterial taxa and are associated with belowground multinutrient cycling. A continental atlas was built for mapping the bacterial spatial distributions in agro-soils through identifying their habitat preferences. This study represents a significant advance in forecasting the responses of agricultural ecosystems to anthropogenic disturbance and thus helps manage soil bacterial communities for better provisioning of key ecosystem services—the ultimate goal of microbial ecology.
Does fluoxetine improve recovery after stroke?
Authors: Cook Rob , Thomas Vaughan , Martin Rosie
Published: March 2019

The study

FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial.
Lancet
2019;393:256-74.

The study was funded by the UK Stroke Association and the NIHR Health Technology Assessment Programme project number 13/04/30.

To read the full NIHR Signal, go to:
https://discover.dc.nihr.ac.uk/content/signal-000729/a-commonly-used-antidepressant-doesnt-improve-recovery-after-stroke
Management of acute upper gastrointestinal bleeding
Authors: Stanley Adrian J , Laine Loren
Published: March 2019

Upper gastrointestinal bleeding (UGIB) is a common medical emergency, with a reported mortality of 2-10%. Patients identified as being at very low risk of either needing an intervention or death can be managed as outpatients. For all other patients, intravenous fluids as needed for resuscitation and red cell transfusion at a hemoglobin threshold of 70-80 g/L are recommended. After resuscitation is initiated, proton pump inhibitors (PPIs) and the prokinetic agent erythromycin may be administered, with antibiotics and vasoactive drugs recommended in patients who have cirrhosis. Endoscopy should be undertaken within 24 hours, with earlier endoscopy considered after resuscitation in patients at high risk, such as those with hemodynamic instability. Endoscopic treatment is used for variceal bleeding (for example, ligation for esophageal varices and tissue glue for gastric varices) and for high risk non-variceal bleeding (for example, injection, thermal probes, or clips for lesions with active bleeding or non-bleeding visible vessel). Patients who require endoscopic therapy for ulcer bleeding should receive high dose proton pump inhibitors after endoscopy, whereas those who have variceal bleeding should continue taking antibiotics and vasoactive drugs. Recurrent ulcer bleeding is treated with repeat endoscopic therapy, with subsequent bleeding managed by interventional radiology or surgery. Recurrent variceal bleeding is generally treated with transjugular intrahepatic portosystemic shunt. In patients who require antithrombotic agents, outcomes appear to be better when these drugs are reintroduced early.
Shock index as a predictor of hospital admission and inpatient mortality in a US national database of emergency departments
Authors: Al Jalbout Nour , Balhara Kamna Singh , Hamade Bachar , Hsieh Yu-Hsiang , Kelen Gabor D , Bayram Jamil D
Published: March 2019

Study objectives

The shock index (SI), defined as the ratio of the heart rate (HR) to the systolic blood pressure (BP), is used as a prognostic tool in trauma and in specific disease states. However, there is scarcity of data about the utility of the SI in the general emergency department (ED)population. Our goal was to use a large national database of EDs in the United States (US) to determine whether the likelihood of inpatient mortality and hospital admission was associated with initial SI at presentation.

Methods

Data from the National Hospital Ambulatory Medical Care Survey were retrospectively reviewed to obtain a weighted sample of all US ED visits between 2005 and 2010. All adults >18 years old who survived the ED visit were included, regardless of their chief complaint. Likelihood ratios (LR) were calculated for a range of SI values, in order to determine SI thresholds most predictive of hospital admission and inpatient mortality. +LRs >5 were considered to be clinically significant.

Results

A total of 526 455 251 adult patient encounters were included in the analysis. 56.9% were women, 73.9% were white and 53.2% were between the ages of 18 and 44 years. 88 326 638 (15.7%) unique ED visits resulted in hospital admission and 1 927 235 (2.6%) visits resulted in inpatient mortality. SI>1.3 was associated with a clinically significant increase in both the likelihood of hospital admission (+LR=6.64) and inpatient mortality (+LR=5.67). SI>0.7 and >0.9, the traditional cited cut-offs, were only associated with marginal increases (+LR= 1.13; 1.54 for SI>0.7 and +LR=1.95; 2.59 for SI>0.9 for hospital admission and inpatient mortality, respectively).

Conclusions

In this largest retrospective study to date on SI in the general ED population, we demonstrated that initial SI at presentation to the ED could potentially be useful in predicting the likelihood of hospital admission and inpatient mortality, which could help guide rapid and accurate acuity designation, resource allocation and disposition.
Effect of scheduled endoscopic dilatation of dominant strictures on outcome in patients with primary sclerosing cholangitis
Authors: Rupp Christian , Hippchen Theresa , Bruckner Thomas , Klöters-Plachky Petra , Schaible Anja , Koschny Ronald , Stiehl Adolf , Gotthardt Daniel Nils , Sauer Peter
Published: March 2019

Objective

Scheduled endoscopic dilatation of dominant strictures (DS) in primary sclerosing cholangitis (PSC) might improve outcome relative to endoscopic treatment on demand, but evidence is limited. Since randomisation is difficult in clinical practice, we present a large retrospective study comparing scheduled versus on-demand endoscopic retrograde cholangiopancreatography (ERCP) based on patient preferences.

Design

Between 1987 and 2017, all new patients with PSC had been offered scheduled ERCP with dilatation of a DS if diagnosed; the latter was repeated at defined intervals until morphological resolution, independent of clinical symptoms (treatment group). Patients who refused participation were clinically evaluated annually and received endoscopic treatment only on demand (control group). The primary clinical endpoint was transplantation-free survival. Secondary outcomes were overall survival, bacterial cholangitis episodes, hepatic decompensation of liver cirrhosis and endoscopy-related adverse events.

Results

The final study included 286 patients, 133 (46.5%) receiving scheduled ERCP and 153 (53.5%) receiving on-demand ERCP. After a mean follow-up of 9.9 years, the rate of transplantation-free survival was higher in patients receiving scheduled ERCP (51% vs 29.3%; p<0.001), as was transplantation-free survival time (median: 17.9 vs 15.2 years; log-rank: p=0.008). However, the benefit of scheduled ERCP was significant only in patients with the initial (17.1%) or later (45.5%) diagnosis of a DS (17.8 vs 11.1 years; log-rank: p<0.001). IBD (p=0.03), DS (p=0.006), higher Mayo Risk Score (p=0.02) and non-adherence to scheduled endoscopy (p=0.005) were independently associated with transplantation-free survival.

Conclusion

In our large retrospective study, regular ERCP with endoscopic balloon dilatation significantly benefits patients with PSC with DS, diagnosed both at initial presentation and during surveillance, even if asymptomatic. Further studies have to find out how to best identify stricture patients non-invasively.
Survey of UK histopathology consultants’ attitudes towards academic and molecular pathology
Authors: Brockmoeller Scarlet , Young Caroline , Lee Jessica , Arends Mark J , Wilkins Bridget S , Thomas Gareth J , Oien Karin A , Jones Louise , Hunter Keith D
Published: March 2019

Objective

Academic pathology is facing a crisis; an ongoing decline in academic pathology posts, a paucity of academic pathologist’s in-training and unfilled posts at a time when cellular pathology departments are challenged to deliver increasing numbers of molecular tests. The National Cancer Research Institute initiative in Cellular & Molecular Pathology commissioned a survey to assess attitudes of cellular pathology consultants towards research in order to understand barriers and identify possible solutions to improve this situation. As cellular pathology is encompassing an increasing number of diagnostic molecular tests, we also surveyed the current approach to and extent of training in molecular pathology.

Methods

The survey was distributed to all UK-based consultant pathologists via the Pathological Society of Great Britain & Ireland and Royal College of Pathologist networks. Heads of Department were contacted separately to obtain figures for number of academic training and consultant posts.

Results

302 cellular pathologists completed the survey which represents approximately 21% of the total cellular histopathology workforce. Most respondents (89%) had been involved in research at some point; currently, 22% were undertaking research formally, and 41% on an informal basis. Of those previously involved in research, 57% stopped early in their consultant career. The majority of substantive academic posts were Professors of which 60% had been in post for >20 years. Most respondents (84%) used molecular pathology in diagnostic work, independent of where they worked or the length of time in post. Notably, 53% of consultants had not received molecular pathology training, particularly more senior consultants and consultants in district general hospitals.

Conclusions

The survey reveals that the academic workforce is skewed towards senior individuals, many of whom are approaching retirement, with a missing cohort of ‘junior consultant’ academic pathologists to replace them. Most pathologists stop formal research activity at the beginning of a consultant career. While molecular pathology is an increasing part of a pathologist’s workload, the majority of consultant cellular pathologists have not received any formal molecular training.
Pathogenic variants in the AFG3L2 proteolytic domain cause SCA28 through haploinsufficiency and proteostatic stress-driven OMA1 activation
Authors: Tulli Susanna , Del Bondio Andrea , Baderna Valentina , Mazza Davide , Codazzi Franca , Pierson Tyler Mark , Ambrosi Alessandro , Nolte Dagmar , Goizet Cyril , Toro Camilo , Baets Jonathan , Deconinck Tine , DeJonghe Peter , Mandich Paola , Casari Giorgio , Maltecca Francesca
Published: March 2019

Background

Spinocerebellar ataxia type 28 (SCA28) is a dominantly inherited neurodegenerative disease caused by pathogenic variants in AFG3L2. The AFG3L2 protein is a subunit of mitochondrial m-AAA complexes involved in protein quality control. Objective of this study was to determine the molecular mechanisms of SCA28, which has eluded characterisation to date.

Methods

We derived SCA28 patient fibroblasts carrying different pathogenic variants in the AFG3L2 proteolytic domain (missense: the newly identified p.F664S and p.M666T, p.G671R, p.Y689H and a truncating frameshift p.L556fs) and analysed multiple aspects of mitochondrial physiology. As reference of residual m-AAA activity, we included SPAX5 patient fibroblasts with homozygous p.Y616C pathogenic variant, AFG3L2+/− HEK293 T cells by CRISPR/Cas9-genome editing and Afg3l2−/− murine fibroblasts.

Results

We found that SCA28 cells carrying missense changes have normal levels of assembled m-AAA complexes, while the cells with a truncating pathogenic variant had only half of this amount. We disclosed inefficient mitochondrial fusion in SCA28 cells caused by increased OPA1 processing operated by hyperactivated OMA1. Notably, we found altered mitochondrial proteostasis to be the trigger of OMA1 activation in SCA28 cells, with pharmacological attenuation of mitochondrial protein synthesis resulting in stabilised levels of OMA1 and OPA1 long forms, which rescued mitochondrial fusion efficiency. Secondary to altered mitochondrial morphology, mitochondrial calcium uptake resulted decreased in SCA28 cells.

Conclusion

Our data identify the earliest events in SCA28 pathogenesis and open new perspectives for therapy. By identifying similar mitochondrial phenotypes between SCA28 cells and AFG3L2+/− cells, our results support haploinsufficiency as the mechanism for the studied pathogenic variants.
Allele frequency analysis of variants reported to cause autosomal dominant inherited retinal diseases question the involvement of 19% of genes and 10% of reported pathogenic variants
Authors: Hanany Mor , Sharon Dror
Published: March 2019

Background

Next generation sequencing (NGS) generates a large amount of genetic data that can be used to better characterise disease-causing variants. Our aim was to examine allele frequencies of sequence variants reported to cause autosomal dominant inherited retinal diseases (AD-IRDs).

Methods

Genetic information was collected from various databases, including PubMed, the Human Genome Mutation Database, RETNET and gnomAD.

Results

We generated a database of 1223 variants reported in 58 genes, including their allele frequency in gnomAD that contains NGS data of over 138 000 individuals. While the majority of variants are not represented in gnomAD, 138 had an allele count of >1 and were examined carefully for various aspects including cosegregation and functional analyses. The analysis revealed 122 variants that were reported pathogenic but unlikely to cause AD-IRDs. Interestingly, in some cases, these unlikely pathogenic variants were the only ones reported to cause disease in AD inheritance pattern for a particular gene, therefore raising doubt regarding the involvement of 11 (19%) of the genes in AD-IRDs.

Conclusion

We predict that these data are not limited to a specific disease or inheritance pattern since non-pathogenic variants were mistakenly reported as pathogenic in various diseases. Our results should serve as a warning sign for geneticists, variant database curators and sequencing panels’ developers not to automatically accept reported variants as pathogenic but cross-reference the information with large databases.