bluuebunny/crossref_metadata_2025 huggingface dataset:
Cathepsin C modulates myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis
Authors: Durose Wilaiwan Wisessmith , Shimizu Takahiro , Li JiaYi , Abe Manabu , Sakimura Kenji , Chetsawang Banthit , Tanaka Kenji F. , Suzumura Akio , Tohyama Koujiro , Ikenaka Kazuhiro
Published: August 2018

Multiple sclerosis (MS) is an autoimmune disease characterized by immune‐mediated inflammation, which attacks the myelin sheath. MS pursues a relapsing and remitting course with varying intervals between symptoms. The main clinical pathological features include inflammation, myelin sheath destruction and plaque formation in the central nervous system (CNS). We previously reported that cystatin F (CysF) expression is induced in demyelinating lesions that are accompanied by active remyelination (referred to as shadow plaques) but is down‐regulated in chronic demyelinated lesions (plaques) in the spinal cord of MS patients and in several murine models of demyelinating disease. CysF is a cathepsin protease inhibitor whose major target is cathepsin C (CatC), which is co‐expressed in demyelinating regions in Plp4e/− mice, a model of chronic demyelination. Here, we report the time course of CatC and CysF expression and describe the symptoms in a mouse experimental autoimmune encephalomyelitis (EAE) model using CatC knockdown (KD) and CatC over‐expression (OE) mice. In myelin oligodendrocyte glycoprotein (MOG)‐EAE, CatC positive cells were found to infiltrate the CNS at an early stage prior to any clinical signs, in comparison to WT mice. CysF expression was not observed at this early stage, but appeared later within shadow plaques. CatC expression was found in chronic demyelinated lesions but was not associated with CysF expression, and CatCKD EAE mouse showed delayed demyelination. Whereas, CatCOE in microglia significantly increased severity of demyelination in the MOG‐EAE model. Thus, these results demonstrate that CatC plays a major role in MOG‐EAE.

image
Alterations in brain TREM2 and Amyloid‐β levels are associated with neurocognitive impairment in HIV‐infected persons on antiretroviral therapy
Authors: Fields Jerel Adam , Spencer Brian , Swinton Mary , Qvale Emma Martine , Marquine María J. , Alexeeva Arina , Gough Sarah , Soontornniyomkij Benchawanna , Valera Elvira , Masliah Eliezer , Achim Cristian L. , Desplats Paula
Published: August 2018

Neuroinflammation is a common pathological correlate of HIV‐associated neurocognitive disorders (HAND) in individuals on antiretroviral therapy (ART). Triggering receptor expressed on myeloid cells 2 (TREM2) regulates neuroinflammation, clears extracellular Amyloid (A)‐β, surveys for damaged neurons, and orchestrates microglial differentiation. TREM2 has not been studied in HIV+ brain tissues. In this retrospective study, we investigated TREM2 expression levels and localization to microglia, Aβ protein levels, and tumor necrosis factor (TNF)‐α transcript levels in the frontal cortices of 52 HIV+ decedents. All donors had been on ART; 14 were cognitively normal (CN), 17 had an asymptomatic neurocognitive impairment (ANI), and 21 had a minor neurocognitive disorder (MND). Total TREM2 protein levels were increased in the soluble and decreased in the membrane‐enriched fractions of MND brain tissues compared to CN; however, brains from MND Hispanics showed the most robust alterations in TREM2 as well as significantly increased TNF‐α mRNA and Aβ levels when compared to CN Hispanics. Significant alterations in the expression of total TREM2 protein and transcripts for TNF‐α were not observed in non‐Hispanics, despite higher levels of Aβ in the non‐Hispanic CN group compared to the non‐Hispanic MND groups. These findings show that decreased and increased TREM2 in membrane‐bound fractions and in soluble‐enriched fractions, respectively, is associated with increased Aβ and neuroinflammation in this cohort of HIV+ brains, particularly those identifying as Hispanics. These findings suggest a role for TREM2 in the brain of HIV+ individuals may deserve more investigation as a biomarker for HAND and as a possible therapeutic target.

Open science badges

This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

image
Demographic and genetic approaches to study dispersal in wild animal populations: A methodological review
Authors: Cayuela Hugo , Rougemont Quentin , Prunier Jérôme G. , Moore Jean‐Sébastien , Clobert Jean , Besnard Aurélien , Bernatchez Louis
Published: August 2018

Dispersal is a central process in ecology and evolution. At the individual level, the three stages of the dispersal process (i.e., emigration, transience and immigration) are affected by complex interactions between phenotypes and environmental factors. Condition‐ and context‐dependent dispersal have far‐reaching consequences, both for the demography and the genetic structuring of natural populations and for adaptive processes. From an applied point of view, dispersal also deeply affects the spatial dynamics of populations and their ability to respond to land‐use changes, habitat degradation and climate change. For these reasons, dispersal has received considerable attention from ecologists and evolutionary biologists. Demographic and genetic methods allow quantifying non‐effective (i.e., followed or not by a successful reproduction) and effective (i.e., with a successful reproduction) dispersal and to investigate how individual and environmental factors affect the different stages of the dispersal process. Over the past decade, demographic and genetic methods designed to quantify dispersal have rapidly evolved but interactions between researchers from the two fields are limited. We here review recent developments in both demographic and genetic methods to study dispersal in wild animal populations. We present their strengths and limits, as well as their applicability depending on study objectives and population characteristics. We propose a unified framework allowing researchers to combine methods and select the more suitable tools to address a broad range of important topics about the ecology and evolution of dispersal and its consequences on animal population dynamics and genetics.
Hypoalbuminaemia at time of surgery is associated with an increased risk for overall graft loss after kidney transplantation
Authors: Anderson Benjamin , Khalil Khalid , Evison Felicity , Nath Jay , Sharif Adnan
Published: August 2018

Aim

The aim of this retrospective cohort study was to investigate whether pre‐operative hypoalbuminaemia (<35 g/L) is associated with adverse outcomes post‐kidney transplantation.

Methods

Our retrospective, single‐centre analysis included all patients who received their kidney transplant between 2007 and 2017, with documented admission albumin levels prior to surgery. Survival analyses were undertaken to explore the relationship of pre‐transplant hypoalbuminaemia versus other baseline variables upon post‐transplant outcomes.

Results

We analysed 1131 kidney allograft recipients transplanted at our centre (2007–2017), with median follow‐up 746 days (interquartile range 133–1750 days). Kidney transplant recipients with pre‐operative hypoalbuminaemia were more likely older, female, recipients of deceased‐donor kidneys and to have longer cold ischaemic times. Recipients with pre‐operative hypoalbuminaemia had longer hospital admissions post‐operatively but no difference in delayed graft function rates. There was no difference in 1 year creatinine but recipients with hypoalbuminaemia had reduced risk for cellular rejection. We observed significantly worse patient survival (83.2% vs 90.7%, P < 0.001) and overall graft survival (72.5% vs 82.0%, P < 0.001) for recipients with hypoalbuminaemia vs normal albumin levels, respectively, but no difference in death‐censored graft survival. In a Cox regression model, adjusted for baseline pre‐operative variables, hypoalbuminaemia was independently associated with an increased risk for overall graft loss after kidney transplantation (hazard ratio 1.468, 95% confidence interval 1.087–1.982, P = 0.012).

Conclusion

Pre‐operative hypoalbuminaemia is an independent risk factor for overall graft loss after kidney transplantation. Further work is warranted to investigate the underlying pathophysiology to determine what supportive measures can be undertaken to attenuate adverse post‐transplant outcomes.
TWI1 regulates cell‐to‐cell movement of OSH15 to control leaf cell fate
Authors: Cui Xuean , Zhang Zhiguo , Wang Yanwei , Wu Jinxia , Han Xiao , Gu Xiaofeng , Lu Tiegang
Published: August 2018

Cell pattern formation in plant leaves has attracted much attention from both plant biologists and breeders. However, in rice, the molecular mechanism remains unclear.

Here, we describe the isolation and functional characterization of TWISTED‐LEAF1 (TWI1), a critical gene involved in the development of the mestome sheath, vascular bundle sheath, interveinal mesophyll and sclerenchyma in rice leaves. Mutant twi1 plants have twisted leaves which might be caused by the compromised development and disordered patterning of bundle sheath, sclerenchyma and interveinal mesophyll cells.

Expression of TWI1 can functionally rescue these mutant phenotypes. TWI1 encodes a transcription factor binding protein that interacts with OSH15, a class I KNOTTED1‐like homeobox (KNOX) transcription factor.

The cell‐to‐cell trafficking of OSH15 is restricted through its interaction with TWI1. Knockout or knockdown of OSH15 in twi1 rescues the twisted leaf phenotype. These studies reveal a key factor controlling cell pattern formation in rice leaves.
Cost analysis of combining congenital cardiac catheterization and electrophysiology procedures in an outpatient setting
Authors: Bansal Manish , Molian Vaelan A. , Maldonado Jennifer R. , Aldoss Osamah , Ochoa Luis A. , Law Ian H.
Published: August 2018

Background

Patients with congenital heart disease require multiple procedures over their lifetime. These procedures increase cost and time commitment. Previous studies in the field of medicine have shown that combining procedures is an effective method to reduce cost and time. There has been no such study to evaluate the cost and efficiency of combining pediatric cardiac procedures.

Objective

The objective of this study was to compare the cost and time commitment of combined cardiac catheterization (cath) and electrophysiology (EP) outpatient procedures against separate cath and EP procedure.

Methods

Outpatient combination procedures performed in the pediatric cardiac cath lab from 2013 to 2016 were matched to a control population of two or three similar single outpatient procedures from 2009 to 2016 for patients of similar age and cardiac anatomy. Procedure duration, recovery duration, length of stay, equipment charges, physician charges, all other hospital charges, and total admission charges were analyzed. The two groups were compared using an unpaired t‐test.

Results

A total of 92 subjects, 32 study subjects and 60 control subjects, were included in this study. Study group procedures had a significantly shorter recovery duration (P = 0.04) and length of stay (P = 0.01). Study group procedure duration trended shorter on average but statistically insignificant (P = 0.20). The total median savings for patients undergoing combined procedures in the study group was $13,181 (interquartile range $423.8–$26710).

Conclusions

Combining cath and EP outpatient procedures reduces the time commitment and provides some economic advantage.
DictyonemaHall and its importance for the evolutionary history of the Graptoloidea
Authors: Maletz Jörg
Published: August 2018

Dictyonema retiformehas been regarded as the benthic ancestor to the planktic Graptoloidea, represented by the earliest plankticRhabdinopora flabelliformisand its descendants. The revision of the type material ofDictyonema retiforme, the type species of the genusDictyonema, from the Silurian of New York State shows compound stipes formed by the complexly growing and overlapping tubular thecae of acanthograptid type. The connections between adjacent stipes are formed by thecal tubes or thecal bridges and not by dissepiments. Thus, the species has to be transferred to the Acanthograptidae and cannot be regarded as being related to the early planktic Graptoloidea. The tubarium meshwork ofDictyonemais phylogenetically unrelated to the meshwork of the plankticRhabdinopora, and represents a case of convergent evolution. The origins of the planktic graptoloids lie among members of middle to upper Cambrian Dendrograpidae, as can be seen from the thecal style and the triad budding patterns with regularly developed bithecae in this group.
Incidence and magnitude of post‐transplant cardiovascular disease after pediatric kidney transplantation: Risk factor analysis of 1058 pediatric kidney transplants at the university of Minnesota
Authors: Serrano Oscar K. , Bangdiwala Ananta S. , Vock David M. , Chinnakotla Srinath , Dunn Ty B. , Finger Erik B. , Kandaswamy Raja , Pruett Timothy L. , Najarian John S. , Matas Arthur J. , Chavers Blanche
Published: August 2018

Background

KT recipients have increased the risk of CVD. The incidence of post‐transplant CVEs among pediatric recipients has not been well‐characterized.

Patients and Methods

Between 1963 and 2015, 884 pediatric (age: 0‐17 years old) recipients received 1058 KTs at our institution. The cumulative incidence of CVEs was analyzed. Statistical models were used to estimate risk factors for developing post‐transplant CVEs.

Results

Overall median patient survival was 33 years (IQR: 18.7‐47). A total of 362 CVEs occurred in 161 (18.3%) patients at a median age of 20.5 years. Arrhythmias (18%) were most common. Cumulative risk of post‐transplant CVEs was 9% at 10 years, 17% at 20 years, 25% at 30 years, and 36% at 40 years. Development of post‐transplant CVEs was associated with increased mortality (HR 2.25 [95% CI 1.61‐3.14]); of those who developed a CVE and died, 22/51 (43.1%) died of CVD. Multivariable risk factors for post‐transplant CVEs included a history of pretransplant CVD (aHR 1.92 [1.18‐3.13] and graft failure (4.57 [3.13‐6.67]).

Discussion

A pretransplant history of CVD and a failed graft are significant risk factors for the development of post‐transplant CVE. CVD increases the risk of post‐transplant death or graft loss.
Conceptualizing ecological restoration: a concise and adaptable framework for researchers and practitioners
Authors: Perkins Lora B. , Leffler A. Joshua
Published: August 2018

Restoration ecology is challenged by taking the knowledge gained from individual projects and generalizing to broader hypotheses and theories. A simple conceptual framework that is easily adapted to many diverse situations has the ability to improve communication among restoration researchers and practitioners, to increase our ability to generalize among our often very diverse projects, and encourage a comprehensive view of the many factors that influence the outcome of an ecological restoration. We propose the restoration triangle as three sets of factors all scientists and practitioners should consider: the attributes and characteristics of the desired focal restoration species, the biotic characteristics of the restoration site, and the environmental conditions of the restoration site. This framework will help scientists and practitioners establish a common language and organizing principles to help move our discipline forward.
Afro‐descendants in Peru: Do beauty and race matter in the labor market?
Authors: Galarza Francisco B. , Yamada Gustavo
Published: August 2018

This is a first study about labor discrimination against Afro‐descendants in Peru. We randomly assigned Afro‐Peruvian and white surnames and photographs (subjectively beautiful, homely looking, or not photos) to 3,828 fictitious résumés, sent for unskilled, technical, and professional occupations. We find an unprecedented, sizeable beauty premium in unskilled occupations (232.5 percent), no effect of looks in technical occupations, and a beauty penalty in professional occupations (–71.3 percent). Overall, whites receive 19.37 percent more callbacks than similarly qualified Afro‐Peruvians; this racial discrimination affects only Afro‐Peruvian females, and particularly those employed in technical occupations. These results remain unaltered when we restrict the sample to those markedly “Afro” surnames. Our findings unveil different dynamics of discrimination across job categories, which tend to be overlooked by the existing literature.
The Influence of Context and Practitioner Attitudes on Implementation of Person‐Centered Assessment and Support for Family Carers Within Palliative Care
Authors: Diffin Janet , Ewing Gail , Harvey Gill , Grande Gunn
Published: August 2018

Background

The Carer Support Needs Assessment Tool (CSNAT) intervention is an evidence‐based, person‐centered approach to carer assessment and support within palliative care. As such, it requires a change in practice from a practitioner‐ to a carer‐led assessment and support process. A paucity of research has investigated factors affecting implementation of evidence‐based interventions within palliative care.

Objective

To examine differences between high and low adopters of the CSNAT intervention in terms of practitioner attitudes to the intervention and organizational context.

Methods

Phase IV study of the implementation of the CSNAT intervention at scale in 36 UK palliative care services over 6 months. Survey at baseline and 6 months of practitioners at implementation sites, informed by the Promoting Action on Research Implementation in Health Services (PARIHS) Framework. Survey tools: (a) questionnaire to assess attitudes to the CSNAT intervention; (b) Alberta Context Tool (ACT) to assess organizational context. Monthly data on intervention use enabled service classification as “high” or “low” adopters.

Results

Surveys returned at baseline were 157/462 and at 6 months were 69/462. Compared with low adoption services, high adopters were more likely to be hospice, at home, and day services; have a higher ratio of internal facilitators to total staff numbers; and higher scores for ACT “informal interactions” denoting more discussions about care between colleagues. Both had similarly positive attitudes to the CSNAT intervention pre‐implementation, but by 6 months low adoption services developed significantly more negative attitudes, while high adoption services attitudes mostly remained the same or improved.

Linking Evidence to Action

Implementation may be more successful for services that offer regular opportunities to use the intervention in practice, have sufficient levels of facilitators, stimulate more staff discussion, and encourage maintenance of positive motivation. Implementation of person‐centered interventions needs to plan for such factors. This has informed an implementation toolkit for the CSNAT intervention.
High circulation of Hepatitis E virus in pigs and professionals exposed to pigs in Laos
Authors: Khounvisith Vilaysone , Tritz Silvia , Khenkha Latdavone , Phoutana Vannaphone , Keosengthong Amphone , Pommasichan Sisavath , Nouanthong Phonethipsavanh , Hübschen Judith M. , Snoeck Chantal J. , Reinharz Daniel , Muller Claude P. , Black Antony P. , Pauly Maude
Published: August 2018

Epidemiological characteristics of hepatitis E Virus (HEV) differ due to the vast spatial heterogeneity in sanitation status, dietary habits and extent of exposure to animals. Although HEV infections are mostly asymptomatic, prognosis is poor for patients with compromised immune systems or pre‐existing liver disease and during pregnancy. In developing countries, low hygienic standards and close human–animal interactions at farms and slaughterhouses likely favour zoonotic transmission of the virus. In this cross‐sectional study from Lao People's Democratic Republic, anti‐HEV IgG was detected by ELISA in 54.0% (136/252) of slaughter pigs, in 41.0% (57/139) of professionals exposed to pigs and in 18.1% of the nonrisk controls (38/210). We show that people occupationally exposed to pigs are at higher risk of infection (p < 0.001). In particular, contact to young piglets as compared to contact to the older slaughter pigs was a major risk factor (p = 0.011). Besides, consumption of bottled water significantly reduced the risk of infection (p = 0.018). In conclusion, we show that in Lao PDR, the high endemicity of HEV, the inadequate implementation of hygiene measures and the limited access to safe water jeopardize the health of professionals exposed to pigs.
Hyper-articulation in Lombard speech: An active communicative strategy to enhance visible speech cues?
Authors: Garnier Maëva , Ménard Lucie , Alexandre Boris
Published: August 2018

This study investigates the hypothesis that speakers make active use of the visual modality in production to improve their speech intelligibility in noisy conditions. Six native speakers of Canadian French produced speech in quiet conditions and in 85 dB of babble noise, in three situations: interacting face-to-face with the experimenter (AV), using the auditory modality only (AO), or reading aloud (NI, no interaction). The audio signal was recorded with the three-dimensional movements of their lips and tongue, using electromagnetic articulography. All the speakers reacted similarly to the presence vs absence of communicative interaction, showing significant speech modifications with noise exposure in both interactive and non-interactive conditions, not only for parameters directly related to voice intensity or for lip movements (very visible) but also for tongue movements (less visible); greater adaptation was observed in interactive conditions, though. However, speakers reacted differently to the availability or unavailability of visual information: only four speakers enhanced their visible articulatory movements more in the AV condition. These results support the idea that the Lombard effect is at least partly a listener-oriented adaptation. However, to clarify their speech in noisy conditions, only some speakers appear to make active use of the visual modality.
Eliminating backwall effects in the phased array imaging of near backwall defects
Authors: Zhang Chao , Huthwaite Peter , Lowe Michael
Published: August 2018

Ultrasonic array imaging is widely used to provide high quality defect detection and characterization. However, the current imaging techniques are poor at detecting and characterizing defects near a surface facing the array, as the signal scattered from the defect and the strong reflection from the planar backwall will overlap in both time and frequency domains, masking the presence of the defect. To address this problem, this paper explores imaging algorithms and relevant methods to eliminate the strong artefacts caused by the backwall reflection. The half-skip total focusing method (HSTFM), the factorization method (FM) and the time domain sampling method (TDSM) are chosen as the imaging algorithms used in this paper. Then, three methods, referred to as full matrix capture (FMC) subtraction, weighting function filtering, and the truncation method, are developed to eliminate or filter the effects caused by the strong backwall reflection. These methods can be applied easily with few tuning parameters or little prior knowledge. The performances of the proposed imaging techniques are validated in both simulation and experiments, and the results show the effectiveness of the developed methods to eliminate the artefacts caused by the backwall reflections when imaging near backwall defects.
Improved fisheries management could offset many negative effects of climate change
Authors: Gaines Steven D. , Costello Christopher , Owashi Brandon , Mangin Tracey , Bone Jennifer , Molinos Jorge García , Burden Merrick , Dennis Heather , Halpern Benjamin S. , Kappel Carrie V. , Kleisner Kristin M. , Ovando Daniel
Published: August 2018

Future effects of climate change on ocean fisheries could be more than offset by management reforms for current fisheries.
Toward cities without slums: Topology and the spatial evolution of neighborhoods
Authors: Brelsford Christa , Martin Taylor , Hand Joe , Bettencourt Luís M. A.
Published: August 2018

Describing the mathematical logic of cities shows a way to help slum residents make space for streets where they do not yet exist.
Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability
Authors: King Andrew J. , Siegel Matthew , He Ying , Nie Baoming , Wang Ji , Koo-McCoy Samantha , Minassian Natali A. , Jafri Qumber , Pan Deng , Kohler Jill , Kumaraswamy Padmapriya , Kozuka Kenji , Lewis Jason G. , Dragoli Dean , Rosenbaum David P. , O’Neill Debbie , Plain Allein , Greasley Peter J. , Jönsson-Rylander Ann-Cathrine , Karlsson Daniel , Behrendt Margareta , Strömstedt Maria , Ryden-Bergsten Tina , Knöpfel Thomas , Pastor Arroyo Eva M. , Hernando Nati , Marks Joanne , Donowitz Mark , Wagner Carsten A. , Alexander R. Todd , Caldwell Jeremy S.
Published: August 2018

Tenapanor inhibits sodium/hydrogen exchanger isoform 3 to reduce intestinal phosphate absorption via reduction of passive paracellular phosphate flux.
HDAC inhibition improves autophagic and lysosomal function to prevent loss of subcutaneous fat in a mouse model of Cockayne syndrome
Authors: Majora Marc , Sondenheimer Kevin , Knechten Maren , Uthe Ingo , Esser Charlotte , Schiavi Alfonso , Ventura Natascia , Krutmann Jean
Published: August 2018

The HDAC inhibitor SAHA rescues the skin phenotype in CSB-deficient mice by enhancing protein acetylation and inducing autophagy.
Enantioselective Dechlorination of Polychlorinated Biphenyls in Dehalococcoides mccartyi CG1
Authors: Yu Ling , Lu Qihong , Qiu Lan , Xu Guofang , Zeng Yanhong , Luo Xiaojun , Wang Shanquan , Mai Bixian
Published: August 2018

A variety of agrochemicals and pharmaceuticals are chiral. Due to the enantioselectivity in biological processes, enantiomers of chiral compounds may have different environmental occurrences, fates, and ecotoxicologies. Many chiral organohalides exist in anaerobic or anoxic soils and sediments, and organohalide-respiring bacteria play a major role in the environmental attenuation and global cycling of these chiral organohalides. Therefore, it is important to investigate the dehalogenation enantioselectivity of organohalide-respiring bacteria. This study reports the discovery of enantioselective dechlorination of chiral PCBs by
Dehalococcoides mccartyi
CG1, which provides insights into the dehalogenation enantioselectivity of
Dehalococcoides
and may shed light on future PCB bioremediation efforts to prevent enantioselective biological side effects.
Probiotic Product Enhances Susceptibility of Mice to Cryptosporidiosis
Authors: Oliveira Bruno C. M. , Widmer Giovanni
Published: August 2018

The results of our study show that
C. parvum
responded to changes in the intestinal microenvironment induced by a nutritional supplement. This outcome paves the way for research to identify nutritional interventions aimed at limiting the impact of cryptosporidiosis.
Staphylococcus pseudintermedius Surface Protein L (SpsL) Is Required for Abscess Formation in a Murine Model of Cutaneous Infection
Authors: Richards Amy C. , O'Shea Marie , Beard Philippa M. , Goncheva Mariya I. , Tuffs Stephen W. , Fitzgerald J. Ross , Lengeling Andreas
Published: August 2018

Staphylococcus pseudintermedius
is the leading cause of pyoderma in dogs and is often associated with recurrent skin infections that require prolonged antibiotic therapy. High levels of antibiotic use have led to multidrug resistance, including the emergence of epidemic methicillin-resistant clones.
Positive and Negative Regulation of Glycerol Utilization by the c-di-GMP Binding Protein PlzA in Borrelia burgdorferi
Authors: Zhang Jun-Jie , Chen Tong , Yang Youyun , Du Jimei , Li Hongxia , Troxell Bryan , He Ming , Carrasco Sebastian E. , Gomelsky Mark , Yang X. Frank
Published: August 2018

The Lyme disease pathogen,
Borrelia burgdorferi
, has a simple cyclic dimeric GMP (c-di-GMP) signaling system essential for adaptation of the pathogen to the complicated tick environment. The c-di-GMP effector of
B. burgdorferi
, PlzA, has been shown to regulate multiple cellular processes, including motility, osmolality sensing, and nutrient utilization. The findings of this study demonstrate that PlzA not only controls multiple targets but also has different functional modalities, allowing it to act as both positive and negative regulator of the
glp
operon expression. This work highlights how bacteria with a small genome can compensate for the limited regulatory repertoire by increasing the complexity of targets and modes of action in their regulatory proteins.
Development of Assay Systems for Amber Codon Decoding at the Steps of Initiation and Elongation in Mycobacteria
Authors: Govindan Ashwin , Miryala Sandeep , Mondal Sanjay , Varshney Umesh
Published: August 2018

Genetic analysis of the translational apparatus in Gram-positive bacteria has remained largely unexplored because of the unavailability of appropriate
in vivo
assay systems. We developed chloramphenicol acetyltransferase (CAT)-based reporters which utilize specific decoding of amber codons by mutant tRNAs at the steps of initiation and/or elongation to allow structure-function analysis of the translational machinery. We show that formylation of the initiator tRNA (i-tRNA) is crucial even for slow-growing bacteria and that i-tRNA mutants with a CUA anticodon are aminoacylated by nondiscriminating GluRS. The discriminator base position, and/or a weak Watson-Crick base pair at the top of the acceptor stem, provides important determinants for transamidation of the i-tRNA-attached Glu to Gln by the mycobacterial GatCAB.
Kaposi's Sarcoma-Associated Herpesvirus Deregulates Host Cellular Replication during Lytic Reactivation by Disrupting the MCM Complex through ORF59
Authors: Strahan Roxanne , Dabral Prerna , Dingman Kammi , Stadler Christian , Hiura Kayla , Verma Subhash C.
Published: August 2018

KSHV is the causative agent of various lethal malignancies affecting immunocompromised individuals. Both lytic and latent phases of the viral life cycle contribute to the progression of these cancers. A better understanding of how viral proteins disrupt functions of a normal healthy cell to cause oncogenesis is warranted. One crucial lytic protein produced early during lytic reactivation is the multifunctional ORF59. In this report, we elucidated an important role of ORF59 in manipulating the cellular environment conducive for viral DNA replication by deregulating the normal functions of the host MCM proteins. ORF59 binds to specific MCMs and sequesters them away from replication origins in order to sabotage cellular DNA replication. Blocking cellular DNA replication ensures that cellular resources are utilized for transcription and replication of viral DNA.
Draft Genome Sequence of “Candidatus Izimaplasma sp.” Strain ZiA1, Obtained from a Toluene-Degrading and Iron-Reducing Enrichment Culture
Authors: Kim So-Jeong , Park Soo-Je , Kim Jong-Geol , Jung Man-Young , Gwak Joo-Han , Rhee Sung-Keun
Published: August 2018

Here, we report the draft genome sequence of “
Candidatus
Izimaplasma sp.” strain ZiA1 (1.88 Mb and 29.6% G+C content).
Complete Genome Sequence of Avian Coronavirus Strain D274
Authors: Brandão Paulo E. , Hora Aline S. , Silva Sheila O. S. , Berg Mikael , Taniwaki Sueli A.
Published: August 2018

Avian coronavirus
, the causative agent of avian infectious bronchitis, occurs as multiple genotypes and lineages, and full genomes are not available for the majority of them. This paper reports the (previously unknown) complete genome sequence of strain D274 of this virus (27,599 nucleotides), isolated from chickens in The Netherlands in 1979.
Draft Genome Sequences of Two Carbapenemase-Producing Klebsiella pneumoniae Strains Isolated from Blood Cultures
Authors: Le Guern Rémi , Grandjean Teddy , Faure Karine , Bauduin Marvin , Kipnis Eric , Dessein Rodrigue
Published: August 2018

Carbapenemase-producing
Klebsiella pneumoniae
represents an emerging public health issue. Here, we present the draft whole-genome sequences of
K. pneumoniae
clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase).
Differential Innervation of Tissues Located at Traditional Acupuncture Points in the Rat Forehead and Face
Authors: Wang Jia , Cui Jingjing , She Chen , Xu Dongsheng , Zhang Zhiyun , Wang Hui , Bai Wanzhu
Published: August 2018

Objectives

To compare the neural pathways associated with the tissues located at different traditional acupuncture points in the rat forehead and face using the cholera toxin B subunit (CTB) neural tracing technique.

Methods

After injection of CTB into the tissues at GB14, ST2 and ST6 in the rat, the neural labelling associated with each acupuncture point was revealed by fluorescent immunohistochemistry of the nervous system, including the trigeminal ganglion (TRG), cervical dorsal root ganglia (DRG), spinal cord and brain.

Results

The CTB labelling included sensory neurons and their transganglionic axonal terminals, as well as motor neurons. The labelled sensory neurons associated with GB14, ST2 and ST6 were distributed in both the TRG and cervical DRG, and their centrally projected axons terminated in an orderly fashion at their corresponding targets in the spinal trigeminal nucleus and cervical spinal dorsal horn. In addition, labelled motor neurons were observed in the facial motor nucleus, trigeminal motor nucleus and cervical spinal ventral horn, in which facial motor neurons projected to the tissues located at all three acupuncture points. Trigeminal motor neurons innervated both ST2 and ST6, while spinal motor neurons only correlated with ST6.

Conclusions

These results indicate that the tissues located at each of these three traditional acupuncture points in the rat forehead and face has its own sensory and motor connection with the nervous system in a region-specific pattern through distinct neural pathways. Understanding the neuroanatomical characteristics of acupuncture points from the peripheral nervous system to the central nervous system should help inform acupuncture point selection according to the demands of the clinical situation.
2% chlorhexidine–70% isopropyl alcohol versus 10% povidone–iodine for insertion site cleaning before central line insertion in preterm infants: a randomised trial
Authors: Kieran Emily A , O’Sullivan Anne , Miletin Jan , Twomey Anne R , Knowles Susan J , O’Donnell Colm Patrick Finbarr
Published: August 2018

Objective

To determine whether 2% chlorhexidine gluconate–70% isopropyl alcohol (CHX–IA) is superior to 10% aqueous povidone–iodine (PI) in preventing catheter-related blood stream infection (CR-BSI) when used to clean insertion sites before placing central venous catheters (CVCs) in preterm infants.

Design

Randomised controlled trial.

Setting

Two neonatal intensive care units (NICUs).

Patients

Infants <31 weeks’ gestation who had a CVC inserted.

Interventions

Insertion site was cleaned with CHX–IA or PI. Caregivers were not masked to group assignment.

Main outcome measures

Primary outcome was CR-BSI determined by one microbiologist who was masked to group assignment. Secondary outcomes included skin reactions to study solution and thyroid dysfunction.

Results

We enrolled 304 infants (CHX–IA 148 vs PI 156) in whom 815 CVCs (CHX–IA 384 vs PI 431) were inserted and remained in situ for 3078 (CHX–IA 1465 vs PI 1613) days. We found no differences between the groups in the proportion of infants with CR-BSI (CHX–IA 7% vs PI 5%, p=0.631), the proportion of CVCs complicated by CR-BSI or the rate of CR-BSI per 1000 catheter days. Skin reaction rates were low (<1% CVC insertion episodes) and not different between the groups. More infants in the PI group had raised thyroid-stimulating hormone levels and were treated with thyroxine (CHX–IA 0% vs PI 5%, p=0.003).

Conclusions

We did not find a difference in the rate of CR-BSI between preterm infants treated with CHX–IA and PI, and more infants treated with PI had thyroid dysfunction. However, our study was not adequately powered to detect a difference in our primary outcome and a larger trial is required to confirm our findings.

Trial registration

This study was registered with the EU clinical trials register before the first patient was enrolled (Eudract 2011-002962-19). (https://www.clinicaltrialsregister.eu)
Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review
Authors: Battersby Cheryl , Santhalingam Tharsika , Costeloe Kate , Modi Neena
Published: August 2018

Objective

To conduct a systematic review of neonatal necrotising enterocolitis (NEC) rates in high-income countries published in peer-reviewed journals.

Methods

We searched MEDLINE, Embase and PubMed databases for observational studies published in peer-reviewed journals. We selected studies reporting national, regional or multicentre rates of NEC in 34 Organisation for Economic Co-operation and Development countries. Two investigators independently screened studies against predetermined criteria. For included studies, we extracted country, year of publication in peer-reviewed journal, study time period, study population inclusion and exclusion criteria, case definition, gestation or birth weight-specific NEC and mortality rates.

Results

Of the 1888 references identified, 120 full manuscripts were reviewed, 33 studies met inclusion criteria, 14 studies with the most recent data from 12 countries were included in the final analysis. We identified an almost fourfold difference, from 2% to 7%, in the rate of NEC among babies born <32 weeks’ gestation and an almost fivefold difference, from 5% to 22%, among those with a birth weight <1000 g but few studies covered the entire at-risk population. The most commonly applied definition was Bell’s stage ≥2, which was used in seven studies. Other definitions included Bell’s stage 1–3, definitions from the Centers for Disease Control and Prevention, International Classification for Diseases and combinations of clinical and radiological signs as specified by study authors.

Conclusion

The reasons for international variation in NEC incidence are an important area for future research. Reliable inferences require clarity in defining population coverage and consistency in the case definition applied.

PROSPERO International prospective register of systematic reviews registration number

CRD42015030046.
Effectiveness of foot orthoses for the prevention of lower limb overuse injuries in naval recruits: a randomised controlled trial
Authors: Bonanno Daniel R , Murley George S , Munteanu Shannon E , Landorf Karl B , Menz Hylton B
Published: August 2018

Objectives

To evaluate the effectiveness of prefabricated foot orthoses for the prevention of lower limb overuse injuries in naval recruits.

Methods

This study was a participant-blinded and assessor-blinded, parallel-group randomised controlled trial. Three-hundred and six participants aged 17–50 years who undertook 11 weeks of initial defence training at the Royal Australian Navy Recruit School (Cerberus, Australia) were randomised to a control group (flat insoles, n=153) or an intervention group (contoured, prefabricated foot orthoses, n=153). The combined incidence of medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy and plantar fasciitis/plantar heel pain during the 11-week training period were compared using incidence rate ratios (IRR). Data were analysed using the intention-to-treat principle.

Results

Sixty-seven injuries (21.9%) were recorded. The control and intervention group sustained 40 (26.1%) and 27 (17.6%) injuries, respectively (IRR 0.66, 95% CI 0.39 to 1.11, p=0.098). This corresponds to a 34% reduction in risk of developing medial tibial stress syndrome, patellofemoral pain, Achilles tendinopathy or plantar fasciitis/plantar heel for the intervention group compared with the control group. Participants in the prefabricated orthoses group were more likely to report at least one adverse event (20.3% vs 12.4%; relative risk (RR) 1.63, 95% CI 0.96 to 2.76; p=0.068; number needed to harm 13, 95% CI 6 to 253). The most common adverse events were foot blisters (n=20, 6.6%), arch pain (n=10, 3.3%) and shin pain (n=8, 2.6%).

Conclusion

Prefabricated foot orthoses may be beneficial for reducing the incidence of lower limb injury in naval recruits undertaking defence training.

Trial registration number

Australian New Zealand Clinical Trials Registry: ACTRN12615000024549.
Artificial intelligence (AI) and global health: how can AI contribute to health in resource-poor settings?
Authors: Wahl Brian , Cossy-Gantner Aline , Germann Stefan , Schwalbe Nina R
Published: August 2018

The field of artificial intelligence (AI) has evolved considerably in the last 60 years. While there are now many AI applications that have been deployed in high-income country contexts, use in resource-poor settings remains relatively nascent. With a few notable exceptions, there are limited examples of AI being used in such settings. However, there are signs that this is changing. Several high-profile meetings have been convened in recent years to discuss the development and deployment of AI applications to reduce poverty and deliver a broad range of critical public services. We provide a general overview of AI and how it can be used to improve health outcomes in resource-poor settings. We also describe some of the current ethical debates around patient safety and privacy. Despite current challenges, AI holds tremendous promise for transforming the provision of healthcare services in resource-poor settings. Many health system hurdles in such settings could be overcome with the use of AI and other complementary emerging technologies. Further research and investments in the development of AI tools tailored to resource-poor settings will accelerate realising of the full potential of AI for improving global health.
Uptake of medical devices approved by NICE
Authors: Leng Gillian , Williams Sarah , Hung Isaac , Partridge Gemma , Sanghvi Sonali
Published: August 2018

Background

The UK is sometimes considered to be slow in adopting new technologies. The recent Accelerated Access Review examined adoption challenges and identified opportunities for improvements. This study aims to determine the rate of uptake of selected new medical devices approved by the National Institute for Health and Care Excellence over a 10-year period, and to consider what factors may have influenced their uptake.

Methods

The selected devices were approved at least 10 years ago to ensure there was sufficient data to review uptake trends. The devices that met the selection criteria were drug-eluting coronary artery stents, the brush used in liquid-based cytology, and fluid-filled thermal balloon and microwave endometrial ablation. Data on uptake were collected from the National Audit of Percutaneous Coronary Interventions (drug-eluting stents), the national cervical screening programme (liquid-based cytology) and Hospital Episode Statistics (endometrial ablation).

Results

The technologies illustrated different uptake scenarios. Liquid-based cytology showed rapid and complete uptake, probably because it was a nationally driven programme. Neither drug-eluting stents nor endometrial ablation technologies were part of a national programme, and their uptake was slower. The uptake of stents has gradually increased to 88.5% of percutaneous coronary intervention procedures in the most recent data. For both fluid-filled thermal balloon and microwave ablation, there was an increase and then decline in uptake as other technologies were developed.

Conclusions

The data show excellent uptake when promoted through a nationally managed programme. Uptake was slower when left to local systems. Obtaining good, reliable data about the use of medical devices in the National Health Service (NHS) is challenging—collecting real-world data linked to electronic patient records would allow us to better track the impact of new technologies in the future. More robust implementation plans may also increase the uptake rate of cost-effective and potentially life-saving technologies into the NHS.
Electronic, mobile and telehealth tools for vulnerable patients with chronic disease: a systematic review and realist synthesis
Authors: Parker Sharon , Prince Amy , Thomas Louise , Song Hyun , Milosevic Diana , Harris Mark Fort
Published: August 2018

Objectives

The objective of this review was to assess the benefit of using electronic, mobile and telehealth tools for vulnerable patients with chronic disease and explore the mechanisms by which these impact patient self-efficacy and self-management.

Design

We searched MEDLINE, all evidence-based medicine, CINAHL, Embase and PsychINFO covering the period 2009 to 2018 for electronic, mobile or telehealth interventions. Quality was assessed according to rigour and relevance. Those studies providing a richer description (‘thick’) were synthesised using a realist matrix.

Setting and participants

Studies of any design conducted in community-based primary care involving adults with one or more diagnosed chronic health condition and vulnerability due to demographic, geographic, economic and/or cultural characteristics.

Results

Eighteen trials were identified targeting a range of chronic conditions and vulnerabilities. The data provided limited insight into the mechanisms underpinning these interventions, most of which sought to persuade vulnerable patients into believing they could self-manage their conditions through improved symptom monitoring, education and support and goal setting. Patients were relatively passive in the interaction, and the level of patient response attributed to their intrinsic level of motivation. Health literacy, which may be confounded with motivation, was only measured in one study, and eHealth literacy was not assessed.

Conclusions

Research incorporating these tools with vulnerable groups is not comprehensive. Apart from intrinsic motivation, health literacy may also influence the reaction of vulnerable groups to technology. Social persuasion was the main way interventions sought to achieve better self-management. Efforts to engage patients by healthcare providers were lower than expected. Use of social networks or other eHealth mechanisms to link patients and provide opportunities for vicarious experience could be further explored in relation to vulnerable groups. Future research could also assess health and eHealth literacy and differentiate the specific needs for vulnerable groups when implementing health technologies.