bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of putative regulatory isoforms of porcine tumor necrosis factor receptor 2 in endothelial cells
Authors: Uribe‐Herranz Mireia , Kuguel Sebastián G. , Casós Kelly , Costa Cristina
Published: August 2020

Tumor necrosis factor α (TNFα) and its receptors contribute to rejection of transplanted cells and organs. To elucidate how TNFα affects xenograft rejection, we previously cloned the cDNA of pig TNF‐receptor 2 (pTNFR2) and found four isoforms: one comprising the full receptor with four cysteine‐rich domains (CRD), a shorter variant (pTNFR2ΔE7‐10) encoding for a soluble isoform, another lacking exon 4 (pTNFR2ΔE4) displaying only 3 CRD and poor ligand binding, and the smallest one generated by the two alternative splicings. All isoforms contained the pre‐ligand assembly domain (PLAD) responsible for receptor trimerization. We now investigated their roles by structural, expression, and subcellular localization studies. Structural in silico analyses identified four amino acids potentially involved in TNFα binding and lacking in pTNFR2ΔE4. Quantitative RT‐PCR determined regulated expression affecting the two pTNFR2 alternative splicings in cytokine‐stimulated porcine aortic endothelial cells (PAEC). Particularly, human IL‐1α and TNFα produced a strong mRNA upregulation of all isoforms, being the full receptor the predominant one. However, expression of pTNFR2 on PAEC did not correlate with mRNA and decreased after 24‐hour exposure to IL‐1α or TNFα. Notably, confocal microscopy confirmed the presence of pTNFR2 inside and on the plasma membrane, whereas pTNFR2ΔE4 located only intracellularly. Most interestingly, FRET analyses showed that membrane‐bound isoforms pTNFR2 and pTNFR2ΔE4 colocalized intracellularly and associated through the PLAD. Our data show that pTNFR2ΔE4 bind and may retain the full receptor intracellularly. This mechanism has not been described in other species and represents a particularity that may affect the pathophysiology of pig xenografts.
Konec školní nudy: didaktické metody pro 21. století
Authors: Pecina Pavel
Published: August 2020

SIEGLOVÁ, D. 2019. Konec školní nudy: didaktické metody pro 21. století. Praha: Grada Publishing. 336 s. ISBN 978-80-271-2254-7.
Nitric oxide is fundamental to neurovascular coupling in humans
Authors: Hoiland Ryan L. , Caldwell Hannah G. , Howe Connor A. , Nowak‐Flück Daniela , Stacey Benjamin S. , Bailey Damian M. , Paton Julian F. R. , Green Daniel J. , Sekhon Mypinder S. , Macleod David B. , Ainslie Philip N.
Published: August 2020

Key points

Preclinical models have demonstrated that nitric oxide is a key component of neurovascular coupling; this has yet to be translated to humans.

We conducted two separate protocols utilizing intravenous infusion of a nitric oxide synthase inhibitor and isovolumic haemodilution to assess the influence of nitric oxide on neurovascular coupling in humans.

Isovolumic haemodilution did not alter neurovascular coupling.

Intravenous infusion of a nitric oxide synthase inhibitor reduced the neurovascular coupling response by ∼30%, indicating that nitric oxide is integral to neurovascular coupling in humans.

Nitric oxide is a vital neurovascular signalling molecule in preclinical models, yet the mechanisms underlying neurovascular coupling (NVC) in humans have yet to be elucidated. To investigate the contribution of nitric oxide to NVC in humans, we utilized a visual stimulus paradigm to elicit an NVC response in the posterior cerebral circulation. Two distinct mechanistic interventions were conducted on young healthy males: (1) NVC was assessed during intravenous infusion of saline (placebo) and the non‐selective competitive nitric oxide synthase inhibitor NG‐monomethyl‐l‐arginine (l‐NMMA, 5 mg kg−1 bolus & subsequent 50 μg kg−1 min−1 maintenance dose; n = 10). The order of infusion was randomized, counterbalanced and single blinded. A subset of participants in this study (n = 4) underwent a separate intervention with phenylephrine infusion to independently consider the influence of blood pressure changes on NVC (0.1–0.6 μg kg−1 min−1 constant infusion). (2) NVC was assessed prior to and following isovolumic haemodilution, whereby 20% of whole blood was removed and replaced with 5% human serum albumin to reduce haemoglobin concentration (n = 8). For both protocols, arterial and internal jugular venous blood samples were collected at rest and coupled with volumetric measures of cerebral blood flow (duplex ultrasound) to quantify resting cerebral metabolic parameters. l‐NMMA elicited a 30% reduction in the peak (P = 0.01), but not average (P = 0.11), NVC response. Neither phenylephrine nor haemodilution influenced NVC. Nitric oxide signalling is integral to NVC in humans, providing a new direction for research into pharmacological treatment of humans with dementia.
XPS characterization of Mn2O3 nanomaterials functionalized with Ag and SnO2
Authors: Wagner Tobias , Valbusa Daniele , Bigiani Lorenzo , Barreca Davide , Gasparotto Alberto , Maccato Chiara
Published: August 2020

X-ray photoelectron spectroscopy was used to characterize the chemical composition and elemental states of bare and composite Mn2O3 (Mn2O3-Ag, Mn2O3-SnO2) nanomaterials. The target systems were prepared by the initial plasma enhanced-chemical vapor deposition of manganese oxides on alumina substrates, followed by annealing in inert atmospheres and functionalization with Ag and SnO2 by radio frequency-sputtering on the Mn2O3 surface. The survey scans of the fabricated samples, along with detailed spectra of the C 1s, O 1s, Mn 2p, Mn 3s, and, eventually, Ag 3d, Ag MVV, and Sn 3d regions, were collected and analyzed in detail. The obtained results revealed the formation of composite systems characterized by the presence of Mn2O3 free from other manganese oxides and pure SnO2, whereas appreciable Ag oxidation was observed. The O 1s photoelectron peaks could be fitted by means of two components related to lattice oxygen and to hydroxyl groups/oxygen species chemisorbed on surface O defects. The occurrence of the latter could exert a beneficial effect on the system functional behavior in gas sensing and electrocatalytic applications.
Low-pressure thermogravimetric analysis for finding sublimation temperatures for organic precursors in atomic/molecular layer deposition
Authors: Multia Jenna , Khayyami Aida , Heiska Juho , Karppinen Maarit
Published: August 2020

Atomic/molecular layer deposition (ALD/MLD) is strongly emerging as the state-of-the-art gas-phase fabrication technique for novel functional inorganic-organic thin-film materials. In the actual ALD/MLD process development, selecting the proper sublimation temperatures for the inorganic and organic precursors is an important task. In particular, the latter ones tend to require higher sublimation temperatures. In this work, we systematically investigate a representative set of most common ALD/MLD organic precursors using low-pressure (4 mbar) thermogravimetric (TG) analysis. The onset temperature (TGonset) where the weight loss starts is found to well foretell us the optimal precursor source temperature (TMLD) for ALD/MLD; typically, the TMLD value used in a practical ALD/MLD experiment is lower by approximately 14% than the TGonset value. Moreover, we discuss the possibility to utilize the melting point of the compound as a starting point if such vacuum TG measurements are not available.
Numerical continuation of a physical model of brass instruments: Application to trumpet comparisons
Authors: Fréour Vincent , Guillot Louis , Masuda Hideyuki , Usa Satoshi , Tominaga Eiji , Tohgi Yutaka , Vergez Christophe , Cochelin Bruno
Published: August 2020

The system formed by a trumpet player and his/her instrument can be seen as a non-linear dynamic system and modeled by physical equations. Numerical tools can then be used to study these models and clarify the influence of the model parameters. The acoustic input impedance, for instance, is strongly dependent on the geometry of the air column and is therefore of primary interest for a musical instrument maker. In this study, a method of continuation of periodic solutions based on the combination of the Harmonic Balance Method (HBM) and the Asymptotic Numerical Method (ANM) is applied to a physical model of brass instruments. It allows the study of the evolution of the system where one parameter of the model (static mouth pressure) varies. This method is used to compare different B♭ trumpets on the basis of two descriptors (hysteresis behavior and dynamic range) computed from the continuation outputs. Results show that this methodology enables the differentiation of instruments in the space of the calculated descriptors. Calculations for different values of the lip parameters are also performed to confirm that the obtained categorization is independent of variations of lip parameters.
Efficacy of an 8-Week Resistance Training Program in Older Adults: A Randomized Controlled Trial
Authors: Baker Breanne S. , Weitzel Kelsey J. , Royse Lisa A. , Miller Kristin , Guess Trent M. , Ball Stephen D. , Duren Dana L.
Published: August 2020

Older adults are challenged with aging-related declines in skeletal muscle mass and function. Although exercise interventions of longer duration typically yield larger changes, shorter-term interventions may kick-start positive effects, allowing participants to begin engaging in more activity. This study aimed to determine whether 8 weeks of a resistance training program (Stay Strong, Stay Healthy [SSSH]) improved dynamic muscle strength, balance, flexibility, and sleep. Inactive adults aged ≥60 years were randomized into SSSH (n = 15), walking (WALK; n = 17), or control (CON; n = 14) groups. The SSSH and WALK groups met 2 times per week for 60 min. The participants completed pre/post general health, activity, and sleep questionnaires; DXA scans; and functional tasks. One-way repeated-measures multivariate analysis of variance was used to determine interactions and decomposed using repeated-measures analysis of variance. SSSH improved sit-to-stand performance, back scratch distance, and sleep quality and reported more auxiliary physical activity than WALK or CON (p < .05). Resistance training interventions in sedentary older adults can improve physical function and encourage additional activity in 8 weeks.
The Association Between the Single Leg Hop Test and Lower-Extremity Injuries in Female Athletes: A Critically Appraised Topic
Authors: Guild Paige , Lininger Monica R. , Warren Meghan
Published: August 2020

Clinical Scenario: Female college student-athletes (SA) often experience time loss from musculoskeletal injuries to the lower extremities. This can lead to lengthy rehabilitation, expensive medical bills, and declines in health-related quality of life. Identifying at-risk athletes prior to the start of an athletic season may allow coaches or athletic trainers to prescribe an injury prevention program. Clinical Question: In female college SA, are preseason single leg hop (SLH) scores associated with identifying those at risk for lower-extremity musculoskeletal injuries? Summary of Key Findings: Five prospective cohort studies in female SA scored athletes on the SLH prior to the start of the athletic sport season. One of 5 studies found an association of SLH with injury risk. An additional 2 studies found that the SLH as part of a battery of functional performance tests was associated with injury risk in some anatomic locations (eg, thigh/knee), but not overall injury risk. Clinical Bottom Line: Methodological limitations of the reviewed studies limits a final conclusion, and there is insufficient evidence to determine if the SLH should be used as a sole functional performance test to identify at-risk female SA; it may be useful as part of a battery of functional performance tests for female college SA. Strength of Recommendation: All studies were prospective cohort studies (level 3).
EED-mediated histone methylation is critical for CNS myelination and remyelination by inhibiting WNT, BMP, and senescence pathways
Authors: Wang Jiajia , Yang Lijun , Dong Chen , Wang Jincheng , Xu Lingli , Qiu Yueping , Weng Qinjie , Zhao Chuntao , Xin Mei , Lu Q. Richard
Published: August 2020

Polycomb repressive EED protein orchestrates WNT, BMP, and senescence pathways to ensure proper CNS myelination and repair.
Cellular diversity of the regenerating caudal fin
Authors: Hou Yiran , Lee Hyung Joo , Chen Yujie , Ge Jiaxin , Osman Fujr Osman Ibrahim , McAdow Anthony R. , Mokalled Mayssa H. , Johnson Stephen L. , Zhao Guoyan , Wang Ting
Published: August 2020

A single-cell atlas defines cell type composition and cell state transitions in zebrafish caudal fin regeneration.
Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency
Authors: Stoszko Mateusz , Al-Hatmi Abdullah M. S. , Skriba Anton , Roling Michael , Ne Enrico , Crespo Raquel , Mueller Yvonne M. , Najafzadeh Mohammad Javad , Kang Joyce , Ptackova Renata , LeMasters Elizabeth , Biswas Pritha , Bertoldi Alessia , Kan Tsung Wai , de Crignis Elisa , Sulc Miroslav , Lebbink Joyce H.G. , Rokx Casper , Verbon Annelies , van Ijcken Wilfred , Katsikis Peter D. , Palstra Robert-Jan , Havlicek Vladimir , de Hoog Sybren , Mahmoudi Tokameh
Published: August 2020

Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency.
Dissociation of broadband high-frequency activity and neuronal firing in the neocortex
Authors: Leszczyński Marcin , Barczak Annamaria , Kajikawa Yoshinao , Ulbert Istvan , Falchier Arnaud Y. , Tal Idan , Haegens Saskia , Melloni Lucia , Knight Robert T. , Schroeder Charles E.
Published: August 2020

BHA (aka high gamma) correlates with neuronal firing, but is generated mainly by dendritic processes separable from firing.
Molecular insights into the human CLC-7/Ostm1 transporter
Authors: Zhang Sensen , Liu Yang , Zhang Bing , Zhou Jun , Li Tianyu , Liu Zhiqiang , Li Yang , Yang Maojun
Published: August 2020

Structural and functional studies of the human CLC-7/Ostm1 transporter help understand the slow gating of CLC proteins.
Reelin depletion protects against autoimmune encephalomyelitis by decreasing vascular adhesion of leukocytes
Authors: Calvier Laurent , Demuth Guillaume , Manouchehri Navid , Wong Connie , Sacharidou Anastasia , Mineo Chieko , Shaul Philip W. , Monson Nancy L. , Kounnas Maria Z. , Stüve Olaf , Herz Joachim
Published: August 2020

Anti-Reelin is a therapeutic approach that selectively targets endothelial adhesion of leukocytes, blocking neuroinflammation and demyelination.
Engineered PLGA microparticles for long-term, pulsatile release of STING agonist for cancer immunotherapy
Authors: Lu Xueguang , Miao Lei , Gao Wenting , Chen Ziqi , McHugh Kevin J. , Sun Yehui , Tochka Zachary , Tomasic Stephanie , Sadtler Kaitlyn , Hyacinthe Alain , Huang Yuxuan , Graf Tyler , Hu Quanyin , Sarmadi Morteza , Langer Robert , Anderson Daniel G. , Jaklenec Ana
Published: August 2020

Microfabricated particles mimic multiple intratumoral injections of STING agonist over weeks to improve ease of use and decrease metastasis.
Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates
Authors: Wu Yongqin , Grossman Nina , Totten Marissa , Memon Warda , Fitzgerald Anna , Ying Chunmei , Zhang Sean X.
Published: August 2020

Lomentospora prolificans
is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the
in vitro
susceptibility of 8 drugs against 42 clinical
L. prolificans
isolates. All isolates showed high MICs to voriconazole (MIC
90
>16 μg/ml), itraconazole (MIC
90
>16 μg/ml), posaconazole (MIC
90
>16 μg/ml), isavuconazole (MIC
90
>16 μg/ml), amphotericin B (MIC
90
>16 μg/ml), and terbinafine (MIC
90
>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC
90
>8 μg/ml), with the exception of miltefosine showing an MIC
90
value of 4 μg/ml.
Pharmacokinetics, Safety, and Tolerability of Oxfendazole in Healthy Adults in an Open-Label Phase 1 Multiple Ascending Dose and Food Effect Study
Authors: Bach Thanh , Galbiati Shirley , Kennedy Jessie K. , Deye Gregory , Nomicos Effie Y. H. , Codd Ellen E. , Garcia Hector H. , Horton John , Gilman Robert H. , Gonzalez Armando E. , Winokur Patricia , An Guohua
Published: August 2020

Neurocysticercosis and trichuriasis are difficult-to-treat parasitic infections that affect more than 1.5 billion people worldwide. Oxfendazole, a potent broad-spectrum benzimidazole anthelmintic approved for use in veterinary medicine, has shown substantial antiparasitic activity against neurocysticercosis and intestinal helminths in preclinical studies. As part of a program to transition oxfendazole from veterinary medicine to human use, phase I multiple ascending dose and food effect studies were conducted.
Longitudinal Surveillance and Combination Antimicrobial Susceptibility Testing of Multidrug-Resistant
Achromobacter
Species from Cystic Fibrosis Patients
Authors: Okoliegbe Ijeoma N. , Hijazi Karolin , Cooper Kim , Ironside Corinne , Gould Ian M.
Published: August 2020

Achromobacter
spp. are recognized as emerging pathogens in patients with cystic fibrosis (CF). Though recent works have established species-level identification using
nrdA
sequencing, there is a dearth in knowledge relating to species-level antimicrobial susceptibility patterns and antimicrobial combinations, which hampers the use of optimal antimicrobial combinations for the treatment of chronic infections. The aims of this study were to (i) identify at species-level referred
Achromobacter
isolates, (ii) describe species-level antimicrobial susceptibility profiles, and (iii) determine the most promising antimicrobial combination for chronic
Achromobacter
infections.
Three-Dimensional
In Vitro
Staphylococcus aureus Abscess Communities Display Antibiotic Tolerance and Protection from Neutrophil Clearance
Authors: Hofstee Marloes I. , Riool Martijn , Terjajevs Igors , Thompson Keith , Stoddart Martin J. , Richards R. Geoff , Zaat Sebastian A. J. , Moriarty T. Fintan
Published: August 2020

Staphylococcus aureus
is a prominent human pathogen in bone and soft-tissue infections. Pathophysiology involves abscess formation, which consists of central staphylococcal abscess communities (SACs), surrounded by a fibrin pseudocapsule and infiltrating immune cells. Protection against the ingress of immune cells such as neutrophils, or tolerance to antibiotics, remains largely unknown for SACs and is limited by the lack of availability of
in vitro
models. We describe a three-dimensional
in vitro
model of SACs grown in a human plasma-supplemented collagen gel.
Type IV-Like Pili Facilitate Transformation in Naturally Competent Archaea
Authors: Fonseca Dallas R. , Halim Mohd Farid Abdul , Holten Matthew P. , Costa Kyle C.
Published: August 2020

Microbial organisms adapt and evolve by acquiring new genetic material through horizontal gene transfer. One way that this occurs is natural transformation, the direct uptake and genomic incorporation of environmental DNA by competent organisms. Archaea represent up to a third of the biodiversity on Earth, yet little is known about transformation in these organisms. Here, we provide the first characterization of a component of the archaeal DNA uptake machinery. We show that the type IV-like pilus is essential for natural transformation in two archaeal species. This suggests that pili are important for transformation across the tree of life and further expands our understanding of gene flow in archaea.
Testing of
In Vitro
Susceptibility of Neisseria gonorrhoeae to Azithromycin: Comparison of Disk Diffusion and Reference Agar Dilution Methods
Authors: Gianecini Ricardo , Irazu Lucia , Rodríguez Marcelo , Cristaldo Paula , Oviedo Claudia , Turco Marisa , Rodrigo Veronica , Canigia Liliana Fernández , Schneider Ana , Guelfand Liliana , Scocozza Laura ,   GASSP-AR Working Group, Galarza Patricia
Published: August 2020

Azithromycin in combination with ceftriaxone is recommended as the first-line treatment for uncomplicated gonorrhea in many countries. Therefore, monitoring of azithromycin susceptibility of
Neisseria gonorrhoeae
isolates is essential. In 2019, the Clinical and Laboratory Standards Institute (CLSI) listed the MIC breakpoint for a susceptible-only category to azithromycin, but breakpoints for disk diffusion are not yet available. In this study, we evaluated the usefulness of disk diffusion for testing the susceptibility of
N. gonorrhoeae
isolates to azithromycin.
Mosquito Defensins Enhance Japanese Encephalitis Virus Infection by Facilitating Virus Adsorption and Entry within the Mosquito
Authors: Liu Ke , Xiao Changguang , Xi Shumin , Hameed Muddassar , Wahaab Abdul , Shao Donghua , Li Zongjie , Li Beibei , Wei Jianchao , Qiu Yafeng , Miao Denian , Zhu Huaimin , Ma Zhiyong
Published: August 2020

In this study, we observed the complex roles of mosquito defensin in JEV infection; mosquito defensin exhibited a weak antiviral effect but strongly enhanced binding. In the latter, defensin directly binds the ED III domain of the viral E protein and promotes the adsorption of JEV to target cells by interacting with lipoprotein receptor-related protein 2 (LRP2), thus accelerating virus entry. Together, our results indicate that mosquito defensin plays an important role in facilitating JEV infection and potential transmission.
Porcine Reproductive and Respiratory Syndrome Virus Promotes SLA-DR-Mediated Antigen Presentation of Nonstructural Proteins To Evoke a Nonneutralizing Antibody Response
In Vivo
Authors: Wu Chunyan , Shi Bingjun , Yang Di , Zhang Kun , Li Jie , Wang Jie , Liu Hongliang , Zhao Qin , Zhou En-Min , Nan Yuchen
Published: August 2020

PRRSV has haunted the swine industry for over 30 years since its emergence. Besides the limited efficacy of PRRSV modified live vaccines (MLVs) against heterogeneous PRRSV isolates, rapid induction of nonneutralizing antibodies (non-NAbs) against PRRSV NSPs after MLV immunization or wild-strain infection is one of the reasons why development of an effective vaccine has been hampered. By using
in vitro
-generated BMDCs as models to understand the antigen presentation process of PRRSV, we obtained data indicating that PRRSV infection of BMDCs promotes functional SLA-DR upregulation to present PRRSV NSP-derived immunopeptides for evoking a non-NAb response
in vivo
. Our work not only uncovered a novel mechanism for interference in host antigen presentation by PRRSV but also revealed a novel insight for understanding the rapid production of nonneutralizing antibodies against PRRSV NSPs, which may have benefit for developing an effective vaccine against PRRSV in the future.
Consensus statement: loneliness in older adults, the 21st century social determinant of health?
Authors: Prohaska Thomas , Burholt Vanessa , Burns Annette , Golden Jeannette , Hawkley Louise , Lawlor Brian , Leavey Gerard , Lubben Jim , O"Sullivan Roger , Perissinotto Carla , van Tilburg Theo , Tully Mark , Victor Christina , Fried Linda
Published: August 2020

Objective

The purpose of this consensus statement is to determine the state of the field of loneliness among older people, highlighting key issues for researchers, policymakers and those designing services and interventions.

Methods

In December 2018, an international meeting on loneliness was held in Belfast with leaders from across the USA and Europe. A summary of the conclusions reached at this event is presented following a consensus-building exercise conducted both during this event after each presentation as well as after the event through the drafting, reviewing and agreement of this statement by all authors for over 6 months.

Results

This meeting resulted in an agreement to produce a consensus statement on key issues including definitions of loneliness, measurement, antecedents, consequences and interventions.

Discussion

There has been an exponential growth in research on loneliness among older adults. However, differing measurements and definitions of loneliness mean the incidence and prevalence, associated risk factors and health consequences are often conflicting or confusing especially for those developing policy and services.
Management in the paediatric wards facing novel coronavirus infection: a rapid review of guidelines and consensuses
Authors: Luo Wen-Yi , Sun Ji-Wen , Zhang Wen-Lan , Li Qian , Ni Ping , Zhao Lie-Bin , Tian Jin-Hui , Zhang Ya-Qing , Lu Hong
Published: August 2020

Objectives

Relevant guidelines and consensuses for COVID-19 contain recommendations aimed at optimising the management in paediatric wards. The goal of this study was to determine the quality of those recommendations and provide suggestions to hospital managers for the adjustment of existing hospital prevention and control strategies, and also to offer recommendations for further research.

Design

A rapid review of the guidelines and consensuses for the management in paediatric wards facing COVID-19.

Methods

PubMed, EMBASE, the Cochrane Library, UpToDate, China National Knowledge Infrastructure, the Wanfang database and relevant websites such as medlive.cn, dxy.cn, the National Health and Health Commission and the China Center for Disease Control and Prevention were systematically searched through late May 2020. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool was then used to assess the quality of the selected articles and summarise the relevant evidence concerning management in paediatric wards.

Results

A total of 35 articles were included, composed of 3 consensus guidelines, 25 expert consensuses and 7 expert opinions. Of the 35 papers, 24 were from China, 2 from the USA, 1 from Spain, 1 from Brazil, 1 from Saudi Arabia and 6 from multinational cooperative studies. Scores for the six domains of the AGREE II tool (scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence) were 98.57%, 53.57%, 17.92%, 69.62%, 26.96% and 50.35%, respectively. Recommendations for nosocomial infection and control, human resource management as well as management of paediatric patients and their families were summarised.

Conclusions

Due to the outbreak of COVID-19, the quality of rapid guidelines and consensuses for the management in paediatric wards affected by COVID-19 is unsatisfactory. In the future, it will be necessary to develop more high-quality guidelines or consensuses for the management in paediatric wards to deal with nosocomial outbreaks in order to fully prepare for emergency medical and health problems.
Therapeutic radiographers’ delivery of health behaviour change advice to those living with and beyond cancer: a qualitative study
Authors: Pallin Nickola D , Beeken Rebecca J , Pritchard-Jones Kathy , Charlesworth Laura , Woznitza Nick , Fisher Abigail
Published: August 2020

Objectives

Therapeutic radiographers (TRs) are well placed to deliver health behaviour change advice to those living with and beyond cancer (LWBC). However, there is limited research on the opinions of TRs around delivering such advice to those LWBC. This study aimed to explore TRs’ practices and facilitators in delivering advice on physical activity, healthy eating, alcohol intake, smoking and weight management.

Setting and participants

Fifteen UK-based TRs took part in a telephone interview using a semi‐structured interview guide. Data was analysed using the framework analysis method.

Results

Emergent themes highlighted that TRs are mainly aware of the benefits of healthy behaviours in managing radiotherapy treatment related side effects, with advice provision lowest for healthy eating and physical activity. Participants identified themselves as well placed to deliver advice on improving behaviours to those LWBC, however reported a lack of knowledge as a limiting factor to doing so. The TRs reported training and knowledge as key facilitators to the delivery of advice, with a preference for online training.

Conclusions

There is a need for education resources, clear referral pathways and in particular training for TRs on delivering physical activity and healthy eating advice to those LWBC.
Evidence that informs feeding practices in very low birthweight and very preterm infants in sub-Saharan Africa: an overview of systematic reviews
Authors: Akindolire Abimbola , Talbert Alison , Sinha Ian , Embleton Nicholas , Allen Stephen
Published: August 2020

Background

Optimal feeding of very low birthweight (VLBW <1500 g)/very preterm (gestation <32 weeks) infants in resource-limited settings in sub-Saharan Africa (sSA) is critical to reducing high mortality and poor outcomes.

Objective

To review evidence on feeding of VLBW/very preterm infants relevant to sSA.

Methods

We searched the Cochrane Database of Systematic Reviews, Embase, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to July 2019 to identify reviews of randomised and quasi-randomised controlled trials of feeding VLBW/very preterm infants. We focused on interventions that are readily available in sSA. Primary outcomes were weight gain during hospital stay and time to achieve full enteral feeds (120 mL/kg/day). Secondary outcomes were growth, common morbidities, mortality, duration of hospital stay and cognitive development. Quality of evidence (QOE) was assessed using the Measurement Tool to Assess Systematic Reviews (AMSTAR2).

Results

Eight systematic reviews were included. Higher feed volume of day 1 (80 mL/kg) reduced late-onset sepsis and time to full enteral feeds, and higher feed volume (up to 300 mL/kg/day) improved weight gain without adverse events (QOE: low–moderate). Rapid advancement of feeds (30–40 mL/kg/day) was not associated with harm. Breast milk fortification with energy and protein increased growth and with prebiotics increased growth and reduced duration of admission (QOE: low–very low) and did not result in harm. Evidence regarding feeding tube placement and continuous versus bolus feeds was insufficient to draw conclusions. We found no reviews meeting our selection criteria regarding when to start feeds, use of preterm formula, cup-and-spoon feeding or gravity versus push feeds and none of the reviews included trials from low-income countries of sSA.

Conclusions

The evidence base informing feeding of VLBW/very preterm babies in resource-limited settings in sSA is extremely limited. Pragmatic studies are needed to generate evidence to guide management and improve outcomes for these highly vulnerable infants.

PROSPERO registration number

CRD42019140204.
Pet dog bites in children: management and prevention
Authors: Jakeman Molly , Oxley James A , Owczarczak-Garstecka Sara C , Westgarth Carri
Published: August 2020

Dog bite injuries are a significant public health problem and many are sustained by children. These injuries can be complex, both physically and psychologically, and in rare cases fatal. This paper will review current evidence-based approaches to treatment, explore identified patterns in biting incidents and discuss the effectiveness of prevention strategies. Safe management of these patients requires a comprehensive approach. Physical injuries need to be accurately assessed with a high index of suspicion for underlying injuries, particularly in younger children less able to communicate. Treatment depends on severity and location, but all bites must be irrigated to reduce the risk of infection but may not always require prophylactic antibiotic use. Careful exploration of the circumstances in which the bite occurred is essential to make safeguarding decisions and prevent future bites. Reducing the incidence of paediatric dog bites requires education of both children and parents that any dog can bite, regardless of breed, and all child–dog interactions must be highly supervised. However, education alone is unlikely to prevent dog bites. Policies that support environmental changes need to be developed such as provision of pet dogs less likely to bite (or bite as severely), through breeding for temperament and appropriate socialisation. Additionally, investment in psychological support for bite victims and their families is required to reduce the long-term impacts of being bitten.
Early neurodevelopmental outcomes of congenital gastrointestinal surgical conditions: a single-centre retrospective study
Authors: Batta Vamsi , Rao Shripada , Wagh Deepika , Tan Jason Khay Ghim , Gollow Ian , Simmer Karen , Bulsara Max K , Patole Sanjay
Published: August 2020

Background

Evidence is emerging that surgery in the neonatal period is associated with increased risk of suboptimal neurodevelopmental outcomes (SNDO). The aim of this study was to describe neurodevelopmental outcomes (at 1 year) of neonatal surgery for congenital gastrointestinal surgical conditions (CGSC) and to explore risk factors.

Methods

Retrospective study (2005–2014) of infants born ≥34 weeks gestation with CGSC and admitted to the surgical neonatal intensive care unit of Perth Children’s Hospital, Western Australia. Clinical details and 1-year developmental outcomes based on Griffiths Mental Developmental Assessment Scales were collated from the database and by reviewing the medical records of study infants. SNDO was defined as one or more of the following: a general quotient less than 88 (ie, >1 SD below mean), cerebral palsy, blindness or sensorineural deafness. Univariable and multivariable logistic regression analyses were carried out to explore risk factors for SNDO. A total of 413 infants were included, of which 13 died. Median gestation was 37.6 weeks (IQR: 36.4–39.1). Information on developmental outcomes was available from 262 out of 400 survivors. A total of 43/262 (16.4%) had SNDO. On univariable analysis, lower z scores for birth weight, prolonged duration of antibiotics, increased episodes of general anaesthesia and prolonged duration of hospital stay were associated with SNDO. On multivariable analysis, lower z scores for birth weight and prolonged hospital stay were associated with increased risk of SNDO.

Conclusions

Late preterm and term infants undergoing neonatal surgery for CGSC may be at risk for SNDO. Studies with longer duration of follow-up are needed to further evaluate the role of potentially modifiable risk factors on their neurodevelopmental outcomes.
Characterisation of antithrombin-dependent anticoagulants through clot waveform analysis to potentially distinguish them from antithrombin-independent inhibitors targeting activated coagulation factors
Authors: Wakui Masatoshi , Fujimori Yuta , Nakamura Shoko , Oka Shusaku , Ozaki Yuko , Kondo Yoshino , Nakagawa Terumichi , Katagiri Hisako , Murata Mitsuru
Published: August 2020

Aims

While antithrombin (AT)-independent inhibitors targeting thrombin or activated factor X have been assessed through clot waveform (CWA), there are no reports on assessment with respect to AT-dependent anticoagulants. The present study aims to characterise AT-dependent anticoagulants through CWA to distinguish them from AT-independent inhibitors.

Methods

CWA was applied to the activated partial thromboplastin time (APTT) assay of plasma samples spiked with each of AT-dependent drugs (unfractionated heparin, enoxaparin and fondaparinux) and AT-independent drugs (rivaroxaban, apixaban, edoxaban, dabigatran, argatroban, hirudin and bivalirudin), which was performed using the CS-5100 or CN-6000 (Sysmex). The APTT-CWA data were automatically gained by the analyser program. The positive mode of clotting reaction curves was defined as the direction towards fibrin generation.

Results

Regarding dose–response curves in AT-dependent anticoagulants, the maximum positive values of the first and secondary derivatives (Max1 and Maxp2, respectively) and the maximum negative values of the secondary derivative (Maxn2) seemed to drop to zero without making an asymptotic line, consistent with the irreversibility. Such a feature was observed also in hirudin, as reported previously. Notably, the symmetric property of Max1 peaks in the waveforms was distorted dose dependently in AT independent but not AT-dependent drugs. A plot of Maxp2 logarithm versus Maxn2 logarithm was linear. The slope was about 1 in AT-dependent drugs while that was more than 1 in AT-independent drugs. These features made it possible to distinguish AT-dependent and AT-independent drugs.

Conclusions

The results aid in further understanding of the pharmacological aspects of anticoagulation and in screening of candidates for novel anticoagulants.
IL-6 regulates CCR5 expression and immunosuppressive capacity of MDSC in murine melanoma
Authors: Weber Rebekka , Riester Zeno , Hüser Laura , Sticht Carsten , Siebenmorgen Alina , Groth Christopher , Hu Xiaoying , Altevogt Peter , Utikal Jochen S , Umansky Viktor
Published: August 2020

Background

Myeloid-derived suppressor cells (MDSC) play a major role in the immunosuppressive melanoma microenvironment. They are generated under chronic inflammatory conditions characterized by the constant production of inflammatory cytokines, chemokines and growth factors, including IL-6. Recruitment of MDSC to the tumor is mediated by the interaction between chemokines and chemokine receptors, in particular C–C chemokine receptor (CCR)5. Here, we studied the mechanisms of CCR5 upregulation and increased immunosuppressive function of CCR5+ MDSC.

Methods

The immortalized myeloid suppressor cell line MSC-2, primary immature myeloid cells and in vitro differentiated MDSC were used to determine factors and molecular mechanisms regulating CCR5 expression and immunosuppressive markers at the mRNA and protein levels. The relevance of the identified pathways was validated on the RET transgenic mouse melanoma model, which was also used to target the identified pathways in vivo.

Results

IL-6 upregulated the expression of CCR5 and arginase 1 in MDSC by a STAT3-dependent mechanism. MDSC differentiated in the presence of IL-6 strongly inhibited CD8+ T cell functions compared with MDSC differentiated without IL-6. A correlation between IL-6 levels, phosphorylated STAT3 and CCR5 expression in tumor-infiltrating MDSC was demonstrated in the RET transgenic melanoma mouse model. Surprisingly, IL-6 overexpressing tumors grew significantly slower in mice accompanied by CD8+ T cell activation. Moreover, transgenic melanoma-bearing mice treated with IL-6 blocking antibodies showed significantly accelerated tumor development.

Conclusion

Our in vitro and ex vivo findings demonstrated that IL-6 induced CCR5 expression and a strong immunosuppressive activity of MDSC, highlighting this cytokine as a promising target for melanoma immunotherapy. However, IL-6 blocking therapy did not prove to be effective in RET transgenic melanoma-bearing mice but rather aggravated tumor progression. Further studies are needed to identify particular combination therapies, cancer entities or patient subsets to benefit from the anti-IL-6 treatment.
Is this person with dementia (currently) competent to request euthanasia? A complicated and underexplored question
Authors: Kim Scott YH , Mangino Dominic , Nicolini Marie
Published: August 2020

In euthanasia and/or assisted suicide (EAS) of persons with dementia, the controversy has mostly focused on decisionally incapable persons with very advanced dementia for whom the procedure must be based on a written advance euthanasia directive. This focus on advance euthanasia directive-based EAS has been accompanied by scant attention to the issue of decision-making capacity assessment of persons with dementia who are being evaluated for concurrent request EAS. We build on a previous analysis of concurrent request EAS cases from the Netherlands, which showed that many such cases involve persons with significant cognitive impairment. We use illustrative cases to describe the difficulty of determining decisional capacity in persons whose stage of dementia falls between severely impaired and mildly impaired. We show that the Dutch practice of capacity assessment in such dementia cases is difficult to reconcile with the widely accepted functional model of capacity—a model explicitly endorsed by the Dutch euthanasia review committees. We discuss why such deviations from the standard functional model might be occurring, as well as their ethical implications for dementia EAS policy and practice.
Predicting the degree of difficulty of the trans-radial approach in cerebral angiography
Authors: Khan Nickalus R , Peterson Jeremy , Dornbos III David , Nguyen Vincent , Goyal Nitin , Torabi Radmehr , Hoit Daniel , Elijovich Lucas , Inoa-Acosta Violiza , Morris David , Nickele Christopher , Jabbour Pascal , Peterson Eric C , Arthur Adam S
Published: August 2020

Background

To evaluate anatomical and clinical factors that make trans-radial cerebral angiography more difficult.

Methods

A total of 52 trans-radial diagnostic angiograms were evaluated in a tertiary care stroke center from December 2019 until March 2020. We analyzed a number of anatomical variables to evaluate for correlation to outcome measures of angiography difficulty.

Results

The presence of a proximal radial loop had a higher conversion to femoral access (p<0.03). The presence of a large diameter aortic arch (p<0.01), double subclavian innominate curve (p<0.01), left proximal common carotid artery (CCA) loop (p<0.001), acute subclavian vertebral angle (p<0.01), and absence of bovine aortic arch anatomy (p=0.03) were associated with more difficult trans-radial cerebral angiography and increased fluoroscopy time-per-vessel.

Conclusion

The presence of a proximal radial loop, large diameter aortic arch, double subclavian innominate curve, proximal left CCA loop, acute subclavian vertebral angle, and absence of bovine aortic arch anatomy were associated with more difficult trans-radial cerebral angiography. We also introduce a novel grading scale for diagnostic trans-radial angiography.
Predictors of subsequent injury at work: findings from a prospective cohort of injured workers in New Zealand
Authors: Harcombe Helen , Samaranayaka Ari , Wyeth Emma H , Davie Gabrielle , Cameron Ian D , Lilley Rebbecca , Derrett Sarah
Published: August 2020

Objectives

People who have experienced a work-related injury can experience further work injuries over time. This study examines predictors of subsequent work-related injuries over 24 months among a cohort of injured workers.

Methods

Participants were those recruited to the earlier Prospective Outcomes of Injury Study (POIS) who had a work-related injury (the ‘sentinel’ injury). Data from POIS participant interviews were combined with administrative data from the Accident Compensation Corporation (New Zealand’s no-fault universal injury insurer) and hospital discharge data. Modified Poisson regression modelling was used to examine whether presentinel injury sociodemographic and health, sentinel injury or presentinel injury work-related factors predicted subsequent work-related injuries.

Results

Over a third of participants (37%) had at least one subsequent work-related injury in 24 months. Factors associated with an increased risk of work-related subsequent injury included being in a job involving carrying or moving heavy loads more than half the time compared with those in jobs that never involved such tasks (RR 1.42, 95% CI 1.01 to 2.01), having an inadequate household income compared with those with an adequate household income (RR 1.33, 95% CI 1.02 1.74) and being aged 50–64 years compared with those aged 30–49 years (RR 1.25, 95% 1.00 to 1.57).

Conclusion

Subsequent work-related injuries occur frequently, and presenting with a work-related injury indicates a potentially important intervention point for subsequent injury prevention. While the strength of associations were not strong, factors identified in this study that showed an increased risk of subsequent work-related injuries may provide a useful focus for injury prevention or rehabilitation attention.
Increased risk of suicide after occupational injury in Korea
Authors: Lee Hye-Eun , Kim Inah , Kim Myoung-Hee , Kawachi Ichiro
Published: August 2020

Objectives

This study sought to investigate the association between occupational injury and subsequent risk of suicide in Korea.

Methods

We linked compensation data for 775 537 workers injured at work during 2003–2014 with National Death Registry through 2015. Suicide among injured workers was compared with the economically active population in Korea separately for men and women by calculating SMRs, with 95% CIs.

Results

Injured workers showed higher mortality from suicide for both men (SMR=2.22, 95% CI 2.14 to 2.31) and women (SMR=2.11, 95% CI 1.81 to 2.45) compared with the economically active population in Korea.

Conclusions

Occupational injuries are associated with substantially elevated suicide risk in Korea. The results suggest the importance of social policies to protect and support injured workers as well as intensifying efforts to prevent workplace injuries.
Discrete choice experiment on educating value-based healthcare
Authors: Noben Cindy Y G , Stammen Lorette A , Vaassen Sanne , Haeren Roel , Stassen Laurents , van Mook Walther , Essers Brigitte
Published: August 2020

Introduction

Identifying costs and values in healthcare interventions as well as the ability to measure and consider costs relative to value for patients are pivotal in clinical decision-making and medical education. This study explores residents’ preferences in educating value-based healthcare (VBHC) during postgraduate medical education. Exploring residents’ preferences in VBHC education, in order to understand what shapes their choices, might contribute to improved medical residency education and healthcare as a whole.

Methods

A discrete choice experiment (DCE) examined which conditions for educating VBHC are preferred by residents. DCE gives more insight into the trade-off’s residents make when choosing alternatives, and which conditions for educating VBHC have the most influence on residents’ preference.

Results

This DCE shows that residents prefer knowledge on both medical practice as well as the process of care—to be educated by an expert on VBHC together with a clinician. They prefer limited protected time to conduct VBHC initiatives (thus while at work) and desire the inclusion of VBHC in formal educational plans.

Conclusion

When optimising graduate and postgraduate medical education curricula, these preferences should be considered to create necessary conditions for the facilitation and participation of residents in VBHC education and the set-up of VBHC initiatives.
Clinical Audit Platform for Students (CAPS): a pilot study
Authors: Kumar Prakrit Raj , Hashmi Yousuf , Morad Raimand , Dewan Varun
Published: August 2020

Background

A clinical audit measures specific clinical outcomes or processes against a predefined standard. However, many clinicians are unable to carry out audits given their time constraints. Alternatively, medical students may often wish to complete audits early in their career to strengthen their portfolios. As such, the student clinical audit platform was designed to connect willing supervisors and these medical students.

Methods

Project supervisors were members of a regional trainee-led network. Interested students were familiarised with the various aspects of an audit and allocated to supervisors with similar interests. There was regular communication to track progress and anonymised feedback forms were distributed to all students and supervisors after a year.

Results

A total of 17 responses were received from the 19 students who were involved in a project. Based on a 5-point Likert scale, students displayed a mean improvement in their understanding of a clinical audit (1.18±1.07, p<0.001), the confidence to approach a supervisor (1.29±1.21, p<0.001) and the ability to conduct an audit by themselves in the future (1.77±1.15, p<0.001). Of the seven affiliated supervisors, five provided feedback with 80% indicating they had projects which remained inactive and all happy with the quality of work produced by their students.

Conclusion

Despite limitations to this programme, the platform produced projects which were disseminated both locally and nationally, demonstrating positive collaboration between medical students and clinicians. We present our findings and evaluations to encourage similar audit platforms to be adopted at other locations.