bluuebunny/crossref_metadata_2025 huggingface dataset:
Wellbeing as a policy framework for health promotion and sustainable development
Authors: Corbin J Hope , Abdelaziz Faten Ben , Sørensen Kristine , Kökény Mihály , Krech Rüdiger
Published: April 2021

For years Gross Domestic Product (GDP) has served as a key indicator of human progress and “successful” societies. Unfortunately, GDP has failed to robustly capture the human experience or predict resilience through crises; and obscures the presence of inequity -- a key determinant of suffering. It is clear the global community needs a new organizing principle: one that envisions and measures progress by focusing on the conditions that support health, resilience, and overall wellbeing. This paper examines key health promotion concepts and approaches, juxtaposed with philosophical underpinnings of the concept of wellbeing, alternative measurement strategies, and examples of wellbeing policy initiatives. In doing so, the paper highlights the relevance of wellbeing policy frameworks to health promotion, the utility of health promotion strategies for implementing wellbeing policy frameworks, and controversies and pitfalls that require consideration. The paper concludes by outlining how health promotion is uniquely poised to contribute to wellbeing policy frameworks that promote the sources of human and planetary thriving through sustainable development, and that promoting a wellbeing agenda can strengthen efforts to promote health by addressing social determinants and ensuring universal access to resources that support coping with emerging challenges and strengthen resilience.
Assessment of intra-sample variability in HIV-1 DNA drug resistance genotyping
Authors: Millière Laurine , Bocket Laurence , Tinez Claire , Robineau Olivier , Veyer Nathalie , Wojciechowski Fanny , Lambert Valérie , Meybeck Agnès , Huleux Thomas , Ajana Faiza , Hober Didier , Alidjinou Enagnon Kazali
Published: April 2021

Background and objectives

HIV-1 drug resistance testing can be performed in proviral DNA. The non-homogenous distribution of viral variants in cells can impact the performance of this method. We assessed the variability of HIV-1 DNA genotyping results in the same blood sample using a next-generation sequencing (NGS) method.

Methods

For each included patient, a blood sample from a single venipuncture was split into five 1 mL aliquots, which were independently tested in the same run. HIV-1 DNA was quantified in blood samples using real-time PCR, and NGS was performed with the Sentosa platform combined with the Sentosa SQ HIV genotyping Assay.

Results

A total of 60 aliquots from 12 samples (12 patients) were tested. The median age was 45.50 years old, and all patients were treated with antiretrovirals. A significant variability can sometimes be observed in HIV-1 DNA quantification between aliquots from the same sample, with a coefficient of variation ranging from 23% to 89%. The analysis of resistance-associated mutations (RAMs) with a 20% cut-off found some discordances in RAMs profile between aliquots from the same sample for 5, 3 and 3 patients in the reverse transcriptase, protease and integrase genes, respectively. The analysis with a lower cut-off (10%) showed additional mutations, but did not improve the intra-sample concordance.

Conclusions

There is an intra-sample variability in HIV-1 DNA resistance test results, and repetition may sometimes bring additional information, but the extent of its clinical impact still requires further investigation.
Validation of the Eclipse Farm 4G & COMET for Detection of Antibiotics in Raw Bovine Milk: AOAC Performance Tested MethodSM 022101
Authors: Razquin Pedro , Sanz David , Marco Adrián , Carrascón Vanesa , Andaluz Sofía , Soler Lourdes , Antón Alejandra , Mata Luis
Published: April 2021

Background

The Eclipse Farm 4G test coupled to the COMET device allows for automatic and easy screening of a broad range of antimicrobials in raw bovine milk. All results obtained with this system are available in real-time through a smartphone application (App) and in the Test4all cloud platform.

Objective

The objective of this study was to validate Eclipse Farm 4G & COMET for the screening of antimicrobials in raw bovine milk according to AOAC Performance Tested MethodSM procedures.

Method

The test is based on the inhibition of microbial growth of Geobacillus stearothermophilus in the presence of antimicrobials. When sample tubes are incubated in the absence of antibiotics, spores germinate and cells grow, changing the medium color from purple to yellow (negative result). The presence of antimicrobials in the milk sample hinders bacterial growth, preventing the tubes from changing color from purple to yellow (positive result). The COMET device automatically integrates all assay steps (incubation, time control, and results interpretation) and communications between the device, smartphone, and cloud.

Results

LODs and detection capabilities were confirmed to be at or below the European Union (EU) maximum residue limit (MRL) for most of the evaluated molecules representing the main families of antimicrobials (penicillins, cephalosporins, tetracyclines, sulfonamides, macrolides, and aminoglycosides). False-positive rates and the effect of potentially interfering substances showed sufficient selectivity/specificity. The Eclipse Farm 4G & COMET system was shown to be robust, consistent, and stable during shelf life.

Conclusions

The Eclipse Farm 4G & COMET system has been shown to be suitable for screening antibiotics in raw bovine milk.

Highlights

The assay is an automatic and easy system for the detection of a broad range of antibiotics in raw bovine milk consistent with EU MRLs and can provide results any time and anywhere through a smartphone App and a cloud platform.
On the role of resonances in polluting white dwarfs by asteroids
Authors: Smallwood Jeremy L , Martin Rebecca G , Livio Mario , Veras Dimitri
Published: April 2021

Pollution of white dwarf atmospheres may be caused by asteroids that originate from the locations of secular and mean-motion resonances in planetary systems. Asteroids in these locations experience increased eccentricity, leading to tidal disruption by the white dwarf. We examine how the ν6 secular resonance shifts outwards into a previously stable region of the asteroid belt, as the star evolves to a white dwarf. Analytic secular models require a planet to be engulfed in order to shift the resonance. We show with numerical simulations that as a planet gets engulfed by the evolving star, the secular resonance shifts and the rate of tidal disruption events increases with the engulfed planet’s mass and its orbital separation. We also investigate the behaviour of mean-motion resonances. The width of a mean-motion resonance increases as the star loses mass and becomes a white dwarf. The ν6 secular resonance is more efficient at driving tidal disruptions than mean-motion resonances with Jupiter. By examining 230 observed exoplanetary systems whose central star will evolve into a white dwarf, we find that along with an Earth mass planet at $1\, \rm au$, hot Jupiters at a semimajor axis $a\gtrsim 0.05\, \rm au$ and super-Earths of mass $10\, \rm M_\oplus$ at $a\gtrsim 0.3\, \rm au$ represent planet types whose engulfment shifts resonances enough to cause pollution of the white dwarfs to a degree in agreement with observations.
A comprehensive review of m6A/m6Am RNA methyltransferase structures
Authors: Oerum Stephanie , Meynier Vincent , Catala Marjorie , Tisné Carine
Published: April 2021

Gene expression is regulated at many levels including co- or post-transcriptionally, where chemical modifications are added to RNA on riboses and bases. Expression control via RNA modifications has been termed ‘epitranscriptomics’ to keep with the related ‘epigenomics’ for DNA modification. One such RNA modification is the N6-methylation found on adenosine (m6A) and 2′-O-methyladenosine (m6Am) in most types of RNA. The N6-methylation can affect the fold, stability, degradation and cellular interaction(s) of the modified RNA, implicating it in processes such as splicing, translation, export and decay. The multiple roles played by this modification explains why m6A misregulation is connected to multiple human cancers. The m6A/m6Am writer enzymes are RNA methyltransferases (MTases). Structures are available for functionally characterized m6A RNA MTases from human (m6A mRNA, m6A snRNA, m6A rRNA and m6Am mRNA MTases), zebrafish (m6Am mRNA MTase) and bacteria (m6A rRNA MTase). For each of these MTases, we describe their overall domain organization, the active site architecture and the substrate binding. We identify areas that remain to be investigated, propose yet unexplored routes for structural characterization of MTase:substrate complexes, and highlight common structural elements that should be described for future m6A/m6Am RNA MTase structures.
MGMTpromoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review
Authors: Brandner Sebastian , McAleenan Alexandra , Kelly Claire , Spiga Francesca , Cheng Hung-Yuan , Dawson Sarah , Schmidt Lena , Faulkner Claire L , Wragg Christopher , Jefferies Sarah , Higgins Julian P T , Kurian Kathreena M
Published: April 2021

Background

The DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) causes resistance of tumor cells to alkylating agents. It is a predictive biomarker in high-grade gliomas treated with temozolomide, however, there is no consensus on which test method, methylation sites, and cutoff values to use.

Methods

We performed a Cochrane Review to examine studies using different techniques to measure MGMT and predict survival in glioblastoma patients treated with temozolomide. Eligible longitudinal studies included (i) adults with glioblastoma treated with temozolomide with or without radiotherapy, or surgery; (ii) where MGMT status was determined in tumor tissue, and assessed by 1 or more technique; and (iii) where overall survival was an outcome parameter, with sufficient information to estimate hazard ratios (HRs). Two or more methods were compared in 32 independent cohorts with 3474 patients.

Results

Methylation-specific PCR (MSP) and pyrosequencing (PSQ) techniques were more prognostic than immunohistochemistry for MGMT protein, and PSQ is a slightly better predictor than MSP.

Conclusions

We cannot draw strong conclusions about use of frozen tissue vs formalin-fixed paraffin-embedded in MSP and PSQ. Also, our meta-analysis does not provide strong evidence about the best CpG sites or threshold. MSP has been studied mainly for CpG sites 76-80 and 84-87 and PSQ at CpG sites ranging from 72 to 95. A cutoff threshold of 9% for CpG sites 74-78 performed better than higher thresholds of 28% or 29% in 2 of the 3 good-quality studies. About 190 studies were identified presenting HRs from survival analysis in patients in which MGMT methylation was measured by 1 technique only.
Failed supernova remnants
Authors: Tsuna Daichi
Published: April 2021

In a failed supernova, partial ejection of the progenitor’s outer envelope can occur due to weakening of the core’s gravity by neutrino emission in the protoneutron star phase. We consider emission when this ejecta sweeps up the circumstellar material, analogous to supernova remnants (SNRs). We focus on failed explosions of blue supergiants, and find that the emission can be bright in soft X-rays. Due to its soft emission, we find that sources in the Large Magellanic Cloud (LMC) are more promising for detection than those in the Galactic disk. These remnants are characteristic in their small size (≲10 pc) and slow speed (100s of km s−1) compared to typical SNRs. Although the expected number of detectable sources is small (up to a few by the eROSITA four-year all-sky survey), prospects are better for deeper surveys targeting the LMC. Detection of these “failed SNRs” will realize observational studies of mass ejection following black hole formation.
P023 Secondary membranous nephropathy in a patient with a background of rheumatoid arthritis treated with biosimilar etanercept
Authors: Sammut Luke , Leach Tim , Yalakki Leena
Published: April 2021

Background/Aims 

There is a growing number of reports of the development of autoimmune processes related to TNF-targeted therapies. This relationship is much more established with the originator biologics as they have been in clinical use for longer, but data for biosimilar safety is still emerging. Here we describe a case of an 80-year-old gentleman with a background of rheumatoid arthritis who developed membranous nephropathy secondary to Benepali®.

Methods 

An 80-year-old Caucasian gentleman with a background of seropositive rheumatoid arthritis, diagnosed at the age of 35 years, was maintained in a clinical remission on oral methotrexate 15 mg weekly, until 2017, when his disease started to flare. At that time, his treatment was switched to sulfasalazine, but due to ongoing high disease activity, this was changed again in December 2018 to methotrexate with Benepali®. His rheumatoid arthritis was controlled with these disease-modifying anti-rheumatic drugs (DMARDs) and his blood test monitoring including full blood count, liver and renal profile (eGFR 80 ml/min/1.73m2) remained normal during the first seven months of treatment. In June 2019, his eGFR deteriorated to 46 and methotrexate was held. Despite this, his eGFR continued to worsen to 28 in July. At that point his Benepali® was discontinued and he was referred to the renal physicians.

Results 

He was normotensive (blood pressure 120/68) and had no dependent oedema. A renal tract ultrasound scan showed normal appearing (with a couple of simple cysts) 10.7/9.4 cm kidneys. Urine dipstick showed 2+ blood and 2+ protein, urine protein:creatinine ratio was 138 mg/mmol (normal ≤ 23) and serum albumin 31 g/L (normal ≥ 34). Serum electrophoresis, HIV and Hepatitis PCRs and serum anti-phospholipase A2 receptor antibody were negative. Renal biopsy confirmed stage I to II membranous nephropathy with mild focal segmental glomerulosclerosis. Reassuringly his renal function and proteinuria continued to improve off Benepali® and both returned to normal a few months after stopping this agent.

Conclusion 

This is the case of an 80-year-old gentleman who developed membranous nephropathy eight months after commencing etanercept biosimilar - Benepali® - for rheumatoid arthritis. Although attribution to a single agent is challenging, we believe that it is likely Benepali® was the main attributing factor for the development of membranous nephropathy. The temporal relationship between the initiation of Benepali® and the subsequent development of biopsy proven membranous nephropathy along with the resolution following withdrawal of Benepali® supports drug-related renal injury. Although TNF inhibitor-induced renal injury is uncommon, this case highlights the need for physicians to maintain a high level of suspicion if a patient on a TNF inhibitor, including biosimilars, develops proteinuria and renal injury.

Disclosure 

L. Sammut: None. T. Leach: None. L. Yalakki: None.
P056 Recurrent ACE-inhibitor induced angioedema in a patient with long COVID-19 syndrome
Authors: Crawshaw Helena , Webber Stuart
Published: April 2021

Background/Aims 

Here we present the case of a 47-year-old female with long COVID-19 syndrome presenting with four episodes of acute onset angioedema in the absence of urticaria or pruritis affecting the mucosal layer of the lips and tongue.

Methods 

She had been taking lisinopril for the last 18 months. She was diagnosed with COVID-19 in March 2020 presenting with fever, cough, shortness of breath and anosmia. She did not require hospital admission initially however has been readmitted twice with profound breathlessness and fever. She has subsequently developed a long COVID-19 syndrome with a daily, fluctuating fever of up to 39 °C for the last six months, profound fatigue, persistent shortness of breath with bilateral ground glass changes seen on high resolution CT chest imaging and mild anaemia. During this time, she subsequently reported four episodes of acute onset of severe angioedema affecting the lips and tongue for which she self-medicated with anti-histamines.

Results 

Following disclosure of these episodes her lisinopril was ceased and there have been no further episodes to date. There are two other case reports in the literature that propose a potential relationship between angiotensin-converting enzyme (ACE) inhibitor induced angioedema and COVID-19. It is known that SAR-CoV-2 binds with high affinity to angiotensin converting enzyme 2 receptors which are found in oral tissues, heart, kidneys and the lung. ACE inhibitors can be associated with angioedema in approximately 0.5% of patients prescribed an ACE inhibitor. It occurs most commonly in the first year following instigation of treatment but can occur years later. The proposed mechanism of action is via the degradation of bradykinin. Bradykinin is converted from Kallikrenin by C1 esterase, and ACE in turn metabolises bradykinin.

Conclusion 

Bradykinin affects vascular permeability and results in vasodilatation, when patients take an ACE inhibitor there is a slower rate of bradykinin degradation and therefore this accumulation results in ACE inhibitor induced angioedema. SARS-CoV-2 binds to the ACE2 receptors. ACE2 is thought to counterbalance ACE in the renin-angiotensin system, it is theorised that the potential downregulation of ACE2 by the presence of bound SARS-CoV-2 may therefore potentiate angioedema in susceptible individuals. At present we cannot confirm this proposed relationship and global current consensus supports the ongoing use of ACE inhibitors during the pandemic but clinicians should continue to be aware of emergent pathologies related to the COVID-19 pandemic.

Disclosure 

H. Crawshaw: None. S. Webber: None.
P066 Telephone clinics: what are our patients saying?
Authors: Abdullah Muhammad Azhar , Heng Nicholas , Noor Sajjad , Ahmed Urooj , Lavery Clare , Bawa Sandeep
Published: April 2021

Background/Aims 

Telemedicine has not previously been a regular part of routine rheumatology services.Our department adopted telephone clinics during the COVID-19 pandemic. We assessed patient satisfaction by conducting a feedback survey. Our aim was to obtain a patient perspective on remote consultations and on preferred future follow up options including video or face-to-face consultations.

Methods 

The cohort included 160 rheumatology patients who had a telephone consultation between May and mid-June 2020. All patients consented to receive a further phone call by a different member of the team. Patients had to answer a questionnaire about recent consultation and to rate this on a scale of 1-5. Other questions included whether all their queries were answered; clear action plan made; perceived benefits or disadvantages of telephone consultation; and views about future follow up and any additional comments.

Results 

71.9% of 160 patients were females while 28.1 % males. Mean age 58.6 yrs. More than half of the patients (60.6%) had a diagnosis of inflammatory arthritis, followed by connective tissue disease (19.3%), other diagnosis (8.1% ) & vasculitis (5.6%). 94.4 % of the patients in this study were return appointments-the remainder new. Feedback results revealed 92.5% patients were satisfied with their consultation with mean score of 4.3/5 (5=best,1= worst). More than 80% agreed that all their queries were answered and a clear action plan was formed during consultation. However ,71.2% would want a face to face consultation if given choice while 54 % happy to have further follow up over the phone. 65% of patients preferred not to have video consultation. Subgroup analysis showed that majority of patients who would accept video consultation were aged between 30-39. Most common benefits described were noted to be convenience; reduced time of work; travel time and safety during pandemic, whilst difficulty in describing symptoms; hearing problems; and severity of disease were disadvantages raised, but numbers were small in our cohort.

Conclusion 

Telephone clinics were the mainstay during the COVID-19 pandemic.The large majority of the rheumatology patients in our cohort were highly satisfied with this form of consultation. However, interestingly the majority (71% ) would still prefer face-to-face consultation as follow up in the future. Regular follow up in carefully selected patient groups can successfully be performed by telephone clinics with good patient satisfaction. This would help increase capacity within the clinic setting.

Disclosure 

M. Abdullah: None. N. Heng: None. S. Noor: None. U. Ahmed: None. C. Lavery: None. S. Bawa: None.
P099 Risk of obstructive sleep apnoea in patients with rheumatic disease: a prospective cohort study
Authors: Ng Wan Lin , Kamarudin Nurasyikin , Anjum Aqeel , Devlin Joe , O'Brien Aidan , Fraser Alexander
Published: April 2021

Background/Aims 

Sleep plays an important component in our lives and sleep abnormalities have been known to be linked with various rheumatic conditions. Obstructive sleep apnoea (OSA) could potentially affect the severity of rheumatic symptoms such as pain, fatigue and also influence the disease activity. This study aims to evaluate the risk of OSA in patients with rheumatic diseases in an Irish cohort.

Methods 

Patients with a diagnosis of a rheumatic disease were recruited from rheumatology outpatients. These patients were asked to complete the Berlin Sleep Questionnaire (BSQ) to evaluate their level of risk for OSA. The Health Assessment Questionnaire (HAQ), Patient Global Assessment (PtGA) and the Physician Global Assessment (PhGA) were also completed.

Results 

These patients were asked to complete the Berlin Sleep Questionnaire (BSQ) to evaluate their level of risk for OSA. The Health Assessment Questionnaire (HAQ), Patient Global Assessment (PtGA) and the Physician Global Assessment (PhGA) 111 patients were recruited. Mean age was 52 years and 22 (19.8%) were males. The most common diagnosis in our cohort was rheumatoid arthritis 54 (45.4%), followed by spondyloarthritis 12 (10.1%), psoriatic arthritis 11 (9.2%), systemic lupus erythematosus 9 (7.6%), Behçet’s disease 7 (5.9%), scleroderma 6 (5.0%) and others 20 (16.8%); with 8 patients having two diagnoses. Our cohort also completed the HAQ which demonstrated 98 (88.3%) having mild to moderate disability and 13 (11.7%) having moderate to severe disability. 39 out of 111 were noted to have a high risk for OSA based on the BSQ. In the high risk cohort, the mean PtGA score was 46.5 while PhGA score was 30.3, compared to the low risk cohort which was 36.7 for PtGA and 24.9 for PhGA. 33 (84.6%) patients in the high risk cohort had mild to moderate disability and 6 (15.4%) had moderate to severe disability as compared to 64 (88.9%) with mild to moderate disability and 8 (11.1%) with moderate to severe disability in the low risk cohort.were also completed.

Conclusion 

This is the first prospective study in Ireland to evaluate the risk of OSA in patients with rheumatic diseases. 35.1% from our cohort were found to be at high risk for OSA and are due to undergo overnight pulse oximetry and polysomnography to objectively assess the presence or absence of OSA. The disease activity reported by both patient and physician along with the level of disability were greater in the high risk cohort. This suggests that OSA increases the likelihood of exacerbating rheumatic activities.

Disclosure 

W. Ng: None. N. Kamarudin: None. A. Anjum: None. J. Devlin: None. A. O'Brien: None. A. Fraser: None.
P130 The relationship between antinuclear antibodies and erosive disease in patients with rheumatoid arthritis
Authors: Guruparan Thushyanthan , Hutchinson Matthew , Hayward Rhys , Penn Henry , Kalia Parul
Published: April 2021

Background/Aims 

The effects of antinuclear antibodies (ANA) in rheumatoid arthritis (RA) are not fully characterised. Studies investigating the effect of ANA on disease activity in RA have yielded mixed results. The presence of ANA has been correlated with higher levels of CRP and joint inflammation in RA. Evidence suggests that ANA positivity at baseline may predict poor response to both traditional disease modifying agents and biologic therapy. ANA may also be associated with higher incidences of ocular disease, Felty’s syndrome, vasculitis and subjective pain in RA patients. On the other hand, other studies showed a lack of correlation between ANA status and joint inflammation in RA. Our study investigates the relationship between ANA positivity and joint erosions in rheumatoid patients.

Methods 

This is a cross-sectional study of patients attending the early arthritis clinic at Northwick Park Hospital in London over a five year period (2014-2019). A total of 631 patients were identified of whom 261 had RA. We collected data on the age, gender, ANA positivity, the presence of anti-CCP (anti cyclic-citrullinated peptide) antibodies and rheumatoid factor (RF) at presentation as well as the presence of erosive disease on radiological reports of hand X-rays. Positive ANA was defined as having a titre of 1:80 or greater. Patients with missing ANA result or hand X-ray reports were excluded, leaving 228 patients. Two-tailed Chi-square tests for categorical data and two-tailed student’s t-tests for continuous data were performed to determine the statistical significance of comparisons made between the ANA positive and negative groups.

Results 

Of the 228 patients, 49 (21.5%) were male and 179 (78.5%) were female. The mean age was 58 years. 84 (36.8%) patients were ANA positive (group 1) and 144 (63.2%) were ANA negative (group 2). In group 1, 23/84 (27.4%) patients had erosive disease. In group 2, erosions were found in 25/144 patients (17.4%). This difference was not statistically significant (p = 0.073). The number of patients who were RF positive in groups 1 and 2 were 79.5% and 73.6% respectively (p = 0.317); 75/84 (89.3%) patients in group 1 and 113/143 (79.0%) in group 2 were anti-CCP antibody positive (p = 0.048). The means of the age of patients were 53 and 62 years in group 1 and group 2 respectively (p < 0.0001); the ANA positive group was significantly younger. The male:female ratio was 13:71 in group 1 and 36:108 in group 2 (p = 0.091).

Conclusion 

Our study showed no significant association between ANA status and erosive disease in RA, although a greater proportion of patients had erosions in the ANA positive group. Larger observational studies may better study this relationship.

Disclosure 

T. Guruparan: None. M. Hutchinson: None. R. Hayward: None. H. Penn: None. P. Kalia: None.
Individual Alpha Frequency Determines the Impact of Bottom-Up Drive on Visual Processing
Authors: Nelli Stephanie , Malpani Aayushi , Boonjindasup Max , Serences John T
Published: April 2021

Endogenous alpha oscillations propagate from higher-order to early visual cortical regions, consistent with the observed modulation of these oscillations by top-down factors. However, bottom-up manipulations also influence alpha oscillations, and little is known about how these top-down and bottom-up processes interact to impact behavior. To address this, participants performed a detection task while viewing a stimulus flickering at multiple alpha band frequencies. Bottom-up drive at a participant’s endogenous alpha frequency either impaired or enhanced perception, depending on the frequency, but not amplitude, of their endogenous alpha oscillation. Fast alpha drive impaired perceptual performance in participants with faster endogenous alpha oscillations, while participants with slower oscillations displayed enhanced performance. This interaction was reflected in slower endogenous oscillatory dynamics in participants with fast alpha oscillations and more rapid dynamics in participants with slow endogenous oscillations when receiving high-frequency bottom-up drive. This central tendency may suggest that driving visual circuits at alpha band frequencies that are away from the peak alpha frequency improves perception through dynamical interactions with the endogenous oscillation. As such, studies that causally manipulate neural oscillations via exogenous stimulation should carefully consider interacting effects of bottom-up drive and endogenous oscillations on behavior.
Two distant helicases in one mycovirus: evidence of horizontal gene transfer between mycoviruses, coronaviruses and other nidoviruses
Authors: Abdoulaye Assane Hamidou , Hai Du , Tang Qing , Jiang Daohong , Fu Yanping , Cheng Jiasen , Lin Yang , Li Bo , Kotta-Loizou Ioly , Xie Jiatao
Published: April 2021

Nidovirales, which accommodates viruses with the largest RNA genomes, includes the notorious coronaviruses; however, the evolutionary route for nidoviruses is not well understood. We have characterized a positive-sense (+) single-stranded (ss) RNA mycovirus, Rhizoctonia solani hypovirus 2 (RsHV2), from the phytopathogenic fungus Rhizoctonia solani. RsHV2 has the largest RNA genome size of 22,219 nucleotides, excluding the poly(A) tail, in all known mycoviruses, and contains two open reading frames (ORF1 and ORF2). ORF1 encodes a protein of 2,009 amino acid (aa) that includes a conserved helicase domain belonging to helicase superfamily I (SFI). In contrast, ORF2 encodes a polyprotein of 4459 aa containing the hallmark genes of hypoviruses. The latter includes a helicase belonging to SFII. Following phylogenetic analysis, the ORF1-encoded helicase (Hel1) unexpectedly clustered in an independent evolutionary branch together with nidovirus helicases, including coronaviruses, and bacteria helicases. Thus, Hel1 presence indicates the occurrence of horizontal gene transfer between viruses and bacteria. These findings also suggest that RsHV2 is most likely a recombinant arising between hypoviruses and nidoviruses.
Teaching Strategies and Tools for Ensuring Safe and Quality Care: A Scoping Review
Authors: Marcomini Ilaria , Terzoni Stefano , Destrebecq Anne
Published: April 2021

AIM

The aim of this scoping review was to map teaching strategies incorporating Quality and Safety Education for Nurses (QSEN) competencies and assessment tools based on the QSEN framework.

METHOD

The search was conducted through MEDLINE, Embase, Scopus, and Web of Science databases and carried out through the framework developed by Arksey and O'Malley and revised by Levac et al.

RESULTS

Thirty-one studies were included. Among QSEN competences, patient-centered care, safety, and teamwork and collaboration were most frequently incorporated into teaching strategies. Most assessment tools aimed at capturing the achievement of QSEN competencies after a classroom learning experience.

CONCLUSION

The scoping review made it possible to identify various teaching strategies and assessment tools developed on the QSEN framework. Further studies are needed to test teaching strategies to facilitate students’ acquisition of QSEN competencies in clinical environments.
A Proactive Curriculum With Remediation Intervention Tool for Nursing Education Success
Authors: Wallace Laura J.
Published: April 2021

Mastering the Content is a proactive curriculum whose At-Risk Student Identification Criteria-Based Remediation Interventions Tool leads to nursing student success. The curriculum integrates active learning strategies and problem-solving activities throughout the nursing program to develop clinical judgment. Remediation includes guided metacognitive learning tool construction, individualized student support, and study plans to increase learning and decrease attrition. The curriculum and interventions tool were developed based on evidence gathered from a meta-analysis of research on best practices in basic RN prelicensure program remediation success and one nursing program’s successful implementation of best practices.
Escape Into a Nursing Career: An Active Recruitment Strategy for Prospective Students
Authors: Goodman Joely T. , Landgren Amy
Published: April 2021

A purpose of this activity was to determine if an escape room activity could familiarize prospective students with information about a program, nurture an interest in a nursing career, and expose individuals to active teaching strategies. Ten prospective nursing students participated in an escape room recruitment activity that introduced them to aspects of nursing care. The activity decreased participants’ nervousness about beginning the nursing program. Escape rooms are an active and engaging strategy that can be used to introduce prospective students to nursing and facilitate team building for groups.
Anesthesiology: Resetting Our Sights on Long-term Outcomes: The 2020 John W. Severinghaus Lecture on Translational Science
Authors: Orser Beverley A.
Published: April 2021

Anesthesiologists have worked relentlessly to improve intraoperative anesthesia care. They are now well positioned to expand their horizons and address many of the longer-term adverse consequences of anesthesia and surgery. Perioperative neurocognitive disorders, chronic postoperative pain, and opioid misuse are not inevitable adverse outcomes; rather, they are preventable and treatable conditions that deserve attention. The author’s research team has investigated why patients experience new cognitive deficits after anesthesia and surgery. Their animal studies have shown that anesthetic drugs trigger overactivity of “memory-blocking receptors” that persists after the drugs are eliminated, and they have discovered new strategies to preserve brain function by repurposing available drugs and developing novel therapeutics that inhibit these receptors. Clinical trials are in progress to examine the cognitive outcomes of such strategies. This work is just one example of how anesthesiologists are advancing science with the goal of improving the lives of patients.
Efficacy of Sclerotherapy With Polidocanol (Ethoxysclerol) in Primary Aneurysmal Bone Cysts in Children and Adolescents
Authors: Jasper Jorrit , van der Heijden Lizz , van Rijswijk Carla S.P. , van de Sande Michiel A.J.
Published: April 2021

Background:

Aneurysmal bone cysts (ABC) are rare benign osseous lesions that can be locally aggressive. Traditionally, curettage with or without bone grafting is the treatment of choice. Recent data suggest that percutaneous sclerotherapy is a safe alternative to surgery. We present our experience with percutaneous sclerotherapy. Primary study aims were success rate, risk factors for treatment failure, and complications.

Methods:

In this single-center retrospective study (January 2003 to June 2019), 70 patients were treated with percutaneous sclerotherapy for primary ABC at various skeletal sites. Median age was 11 years (range: 3 to 17 y). Median follow-up was 40 months (range 18 to 144 mo). Clinical and radiologic assessments were performed until cyst healing.

Results:

Successful healing was seen in 58 of 70 patients (83%) after 1 or more injections with polidocanol. In 12 patients (17%), definitive curettage was performed after previous sclerotherapy, which was considered failure of primary sclerotherapy treatment. Trends toward increased risk for >3 treatments or treatment failure included age younger than 5, epiphyseal plate involvement, and lower leg lesions. The only complication was anaphylaxis in 1 patient shortly after injection of polidocanol/contrast agent and ropivacaine, with full recovery after short resuscitation.

Conclusions:

Our results show that percutaneous sclerotherapy with polidocanol has high efficacy in the treatment of primary ABC, with a low complication rate. Our only complication may have been an immediate allergic reaction to polidocanol/contrast agent or ropivacaine. Trends toward increased risk for treatment failure were age younger than 5, epiphyseal plate involvement, and lower leg lesions.

Level of Evidence:

Level IV—therapeutic study.
Diagnostic delay in moderately/poorly differentiated breast cancer types
Authors: Elfgen Constanze , Baumgartner Sabrina , Varga Zsuzsanna , Reeve Kelly , Tausch Christoph J. , Bjelic-Radisic Vesna , Fleisch Markus , Güth Uwe
Published: April 2021

Background

Diagnostic delay of breast cancer related to the false-negative assessment of the healthcare provider leads to tumor progression and might worsen the outcome. Previous studies found some factors associated with provider-related diagnostic delay; however, tumor biology has tended not to be considered. The aim of our study was to find differences in diagnostic delay of poorly differentiated breast cancer types.

Methods

Data of 970 patients with newly diagnosed moderately/poorly differentiated (G2/3) breast cancer at the age ≥40 years was retrospectively analyzed regarding breast cancer type, diagnostic delay and its consequence, clinical factors and physician’s assessment. Multivariate analysis was used to evaluate associated factors with diagnostic delay.

Results

We observed a diagnostic delay in 3.8% (n = 37) of all patients. Mean delay time was 128 days, and clinically relevant tumor growth was observed in 43.2% of these cases. Delay was significantly higher in the group of triple-negative breast cancer (9.9% versus 2.7, 5.3 and 1.8% in hormonal receptor (HR)+/human epidermal growth factor receptor 2 (HER2)−, HR−/Her2+ and HR+/Her2+, respectively; P value <0.001). Age, breast density and reason for presentation were not correlated to diagnostic delay.

Conclusion

Patients with triple-negative breast cancer are at higher risk of receiving a false-negative assessment and experiencing a diagnostic delay. Our results emphasize the importance of a detailed consideration of clinical risk factors and provider training and suggest a broad indication for a core needle biopsy.
Comparison of the Prevalence and Clinical Characteristics of Epiretinal Membrane in Pseudoexfoliation and Primary Open-angle Glaucoma
Authors: Lee Jin Yeong , Sung Kyung Rim , Kim Yoon Jeon
Published: April 2021

Purpose:

The purpose of this study was to investigate and compare the prevalence and clinical characteristics of epiretinal membrane (ERM) in patients with pseudoexfoliation glaucoma (PXG) and primary open-angle glaucoma (POAG).

Methods:

In this retrospective observational study, 211 PXG eyes, 210 age-matched normal eyes, and 220 POAG eyes were included. The presence and staging of ERM (stage 1, 2, and 3 or greater) were independently assessed by 2 observers. Univariate and multivariate linear regression analyses were performed to assess the factors associated with visual field (VF) mean deviation (MD) in PXG eyes.

Results:

Among 211 PXG eyes, 40 (19.0%) had an ERM, while 4.1% of POAG and 2.4% of normal eyes had an ERM (P<0.001). Retinal nerve fiber layer thickness (69.4 vs. 70.4 μm, P=0.477) and VF MD (−7.7 vs. −10.4 dB, P=0.098) were not different between POAG and PXG eyes but macular thickness was greater (259.5 vs. 271.5 μm, P=0.006) in PXG eyes than in POAG. Both lower retinal nerve fiber layer thickness (β=0.337, P<0.001) and the presence of an ERM (β=−4.246, P=0.002) were independently associated with worse VF MD in PXG eyes.

Conclusions:

The prevalence of ERM was significantly greater in PXG eyes than in age-matched normal or POAG eyes. The presence of ERM affected VF in PXG eyes.
The Reality of Hearing Preservation in Cochlear Implantation: Who Is Utilizing EAS?
Authors: Perkins Elizabeth , Lee Jaclyn , Manzoor Nauman , O’Malley Matthew , Bennett Marc , Labadie Robert , Rivas Alejandro , Haynes David , Gifford René
Published: April 2021

Objective:

To report the proportion of subjects successfully fit with combined electroacoustic stimulation (EAS) compared with those with preserved hearing (HP) after cochlear implantation (CI). In addition, to 1) report the trends in HP and EAS fit rates over time and 2) identify and characterize those patients who preferred the electric only condition.

Study Design:

Retrospective chart review.

Setting:

Tertiary referral center.

Patients:

Two hundred five postlingually deafened adults with bilateral SNHL and a preoperative low-frequency pure-tone average 80 dB HL or better in the ear to be implanted.

Interventions:

Subjects underwent CI from 2013 to 2018 with routine pre- and postoperative audiometric testing performed at 6- and 12-months.

Main Outcome Measures:

Percentage of patients fit with EAS, low-frequency pure-tone average, and threshold shift.

Results:

Overall, 141 patients (78.6%) had HP at activation and 42.6% were fit with EAS. Rates of EAS fitting improved from 36.4% in 2013 to 69.0% in 2018. 93.5% of patients had hearing preserved in 2018 compared with 57.9% in 2013. Six patients rejected EAS after a trial period either because of discomfort or poor sound quality. Eight patients had EAS removed because of loss of aidable hearing over time (between activation to 12 mo).

Conclusions:

Despite the high percentages of HP in the literature, EAS may be under-utilized in the adult CI population. Moving toward a universal definition of HP across institutions may better represent the potential for EAS fitting and a clinical measure capable of identifying patients best suited to benefit from EAS.
Age-related Patterns of Vestibular Dysfunction in Dizziness and Imbalance: A Review of Vestibular Testing Results Among 1,116 Patients
Authors: Nimmo Zachary M. , Hwa Tiffany P. , Naples James G. , Shah Ravi , Brant Jason A. , Eliades Steven J. , Bigelow Douglas C. , Ruckenstein Michael J.
Published: April 2021

Objective:

To characterize differences in vestibular testing results among patients presenting with balance-related complaints; to stratify patterns of testing abnormalities by age.

Study Design:

Retrospective chart review.

Setting:

Academic Balance Center at a Tertiary Referral Center.

Patient Population:

All patients who underwent vestibular testing in a 1-year period from 2017 to 2018.

Main outcome measure:

Balance function test results.

Results:

We reviewed 1,116 patients with age ranging from 11 to 94 years, including 521 patients ≥60 years. Most patients had at least 1 abnormal result, with only 21% of patients ≥60 years and 43% of patients <60 years yielding no test abnormalities (p < 0.001). Among 754 individuals with abnormal testing results, caloric testing did not show any significant difference between age groups. Patients ≥60 years of age were more likely to demonstrate abnormalities on saccadic and horizontal tracking eye movements (p < 0.01; sacc 20.8% vs 6.3%; HT 9.2% vs 4.7%), as well as positional and Dix-Hallpike testing with videonystagmography (p < 0.001; pos 52.3% vs 37.5%, DH 14.4% vs 6.8%). On computerized dynamic posturography, there were significantly more abnormal composite scores in the older group for both sensory organization and motor control testing (p < 0.001; SOT 31.8% vs 8.8%, MCT 7.6% vs 1.8%).

Conclusion:

Among patients presenting balance-related complaints, a majority demonstrate at least one abnormality on vestibular testing. While caloric abnormalities occur across the life span, patients ≥60 years of age are more likely to have abnormal results in random saccades, positional, Dix-Hallpike testing, and posturography, with greater effect sizes in tests of central function. While the causes of imbalance and vertigo remain multifactorial, vestibular dysfunction can be considered a major contributor to balance dysfunction in the elderly population and should be thoroughly evaluated.
Quality Improvement in Otologic Surgery Postoperative Instructions
Authors: Sluder Camille E. , Liu Yuan F. , Meyer Ted A. , Rizk Habib G. , Lambert Paul R. , McRackan Theodore R.
Published: April 2021

Objective:

To examine and improve patient satisfaction with otologic surgery postoperative instructions.

Study Design:

Patients undergoing outpatient otologic surgery were compared over two different time periods, before (phase 1) and after (phase 2) modifying postoperative instructions. Key-informant interviews were conducted by phone on postoperative day 7. All patient-initiated communications after surgery were documented.

Setting:

Tertiary, academic hospital.

Patients:

Patients undergoing outpatient otologic surgery.

Interventions:

Otologic surgery.

Main Outcome Measures:

Satisfaction ratings of different postoperative instruction categories (1–10, completely useless to perfectly helpful), including wound care, pain medication, non-pain medication, showering and bathing, activity restrictions, diet restrictions, follow-up appointment, and contact for questions; comments/critiques from patients; and patient-initiated communications.

Results:

Seventy eight patients were included in phase 1 and 52 in phase 2. Patient characteristics and distribution of surgeries were similar between phases. Rating for instructions were high in both phases (phase 1: 8.98[1.50], phase 2: 9.27[1.04], d = 0.216 [−0.271, 0.698]). More patients in phase 2 thought the instructions were adequate and clear (80.0% versus 55.6% in phase 1, d = 0.641 [0.011, 1.271]), and there were fewer critiques per patient (0.09 versus 0.15, d = −0.537 [−1.034, −0.040]) compared with phase 1. There was a shift in phase 2 communications away from wound care questions (17.5% versus 38.9%, d = −0.606 [−1.112, −0.099]) toward questions regarding medications (27.5% versus 6.7%, d = 0.921 [0.325, 1.516]).

Conclusion:

An evidence-based postoperative instructions template led to more patients believing that the instructions were clear, fewer critiques being given, and a shift toward more actionable questions rather than those with answers already addressed in written instructions.
Benefit of Bilateral Cochlear Implantation on Phonological Processing Skills in Deaf Children
Authors: Lee Youngmee
Published: April 2021

Hypothesis:

Children with bilateral cochlear implants (CIs) would have better phonological processing skills than children with unilateral CIs because those with bilateral CIs have better speech perception abilities in noisy environments and higher levels of central auditory system development than those with unilateral CIs.

Background:

Previous studies have focused on the performance of children with bilateral CIs on standardized clinical assessments. However, these tests are not sufficiently sensitive to explain better speech and language outcomes in children with bilateral CIs than children with unilateral CIs. Thus, this study focused on phonological processing skills at more central levels of analysis that reflect the operation of cognitive processes.

Method:

Twenty children with bilateral CIs and 20 children with unilateral CIs, aged 4 to 6 years, participated in this study. The children completed the experience-dependent tasks and phonological processing tasks. The experience-dependent tasks involved the monosyllabic word, articulation, and receptive vocabulary tests. The phonological processing tasks involved the phonological awareness, phonological memory, and rapid automatic naming tasks. Task performance was compared between the unilateral and bilateral CI groups.

Results:

Children with unilateral CIs performed similarly to children with bilateral CIs on all three experience-dependent tasks. However, children with bilateral CIs significantly outperformed children with unilateral CIs on all three phonological processing tasks. Among the phonological processing tasks, the rapid automatic naming task scores differentiated children with unilateral CIs from children with bilateral CIs.

Conclusions:

Bilateral cochlear implantation may positively impact the phonological processing skills of deaf children.