bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenofovir for prevention of mother to child transmission of hepatitis B in migrant women in a resource-limited setting on the Thailand-Myanmar border: a commentary on challenges of implementation
Authors: Bierhoff M. , Rijken M. J. , Yotyingaphiram W. , Pimanpanarak M. , van Vugt M. , Angkurawaranon C. , Nosten F. , Ehrhardt S. , Thio C. L. , McGready R.
Published: September 2020

Background

The aim of this manuscript is to highlight challenges in the implementation of maternal tenofovir disoproxil fumarate (tenofovir) for prevention of mother to child transmission (PMTCT) of hepatitis B virus (HBV) in resource limited setting. Current preventive strategies in resource-limited settings fail mainly due to prohibitive costs of hepatitis B immunoglobulin (HBIG) and a high proportion of homebirths, meaning both HBIG and hepatitis B birth dose vaccine are not given. A new strategy for PMTCT without the necessity of HBIG, could be daily tenofovir commenced early in gestation. Implementation challenges to early tenofovir for PMTCT can provide insight to elimination strategies of HBV as the burden of disease is high in resource-limited settings.

Methods

Challenges encountered during implementation of a study of tenofovir for PMTCT before 20 weeks gestation in rural and resource-limited areas on the Thailand-Myanmar border were identified informally from trial study logbooks and formally from comments from patients and staff at monthly visits. ClinicalTrials.gov Identifier: NCT02995005.

Main body

During implementation 171 pregnant women were hepatitis B surface antigen (HBsAg) positive by point of-care test over 19 months (May-2018 until Dec-2019). In this resource-limited setting where historically no clinic has provided tenofovir for PMTCT of HBV, information provided by staff resulted in a high uptake of study screening (95.5% (84/88) when offered to pregnant women. False positive point-of-care rapid tests hinder a test and treat policy for HBV and development of improved rapid tests that include HBeAg and/or HBV DNA would increase efficiency. Integrated care of HBV to antenatal care, transport assistance and local agreements to facilitate access, could increase healthcare at this critical stage of the life course. As safe storage of medication in households in resource-limited setting may not be ideal, interactive counseling about this must be a routine part of care.

Conclusion

Despite challenges, results from the study to date suggest tenofovir can be offered to HBV-infected women in resource-limited settings before 20 weeks gestation with a high uptake of screening, high drug accountability and follow-up, with provision of transportation support. This commentary has highlighted practical implementation issues with suggestions for strategies that support the objective of PMTCT and the World Health Organization goal of HBV elimination by 2030.
Socio-economic inequalities in suffering at the end of life among advanced cancer patients: results from the APPROACH study in five Asian countries
Authors: Malhotra Chetna , Krishnan Anirudh , Yong Jing Rong , Teo Irene , Ozdemir Semra , Ning Xiao Hong , Hapuarachchi Thushari , Palat Gayatri , Bhatnagar Sushma , Joad Anjum Khan , Tuong Pham Nguyen , Ssu Wynn Mon , Finkelstein Eric
Published: September 2020

Background

A systematic understanding of socio-economic inequalities in end-of-life (EOL) suffering among advanced cancer patients is required to inform efforts to reduce these inequalities as part of Universal Health Coverage goals.

Aims

To assess inequalities in multiple domains of EOL suffering among advanced cancer patients – physical, functional, psychological, social, and spiritual –, using two socio-economic status (SES) indicators, education and perceived economic status of the household.

Methods

We used cross-sectional data from surveys of stage IV cancer patients (n = 1378) from seven hospitals across five countries (China, Sri Lanka, India, Vietnam and Myanmar). We conducted separate multivariable linear regression models for each EOL suffering domain. We also tested interactions between the two SES indicators and between each SES indicator and patient age.

Results

Patients living in low economic status households /with fewer years of education reported greater suffering in several domains. We also found significant interaction effects between economic status of the household and years of education for all EOL suffering outcomes. Age significantly moderated the association between economic status of the household and social suffering and between years of education and psychological, social, and spiritual suffering (p < 0.05 for all).

Conclusion

Results highlight that SES inequalities in EOL suffering vary depending on the suffering domain, the SES indicator assessed, and by patient age. Greater palliative care resources for patients with low SES may help reduce these inequalities.
Gridded population survey sampling: a systematic scoping review of the field and strategic research agenda
Authors: Thomson Dana R. , Rhoda Dale A. , Tatem Andrew J. , Castro Marcia C.
Published: September 2020

Introduction

In low- and middle-income countries (LMICs), household survey data are a main source of information for planning, evaluation, and decision-making. Standard surveys are based on censuses, however, for many LMICs it has been more than 10 years since their last census and they face high urban growth rates. Over the last decade, survey designers have begun to use modelled gridded population estimates as sample frames. We summarize the state of the emerging field of gridded population survey sampling, focussing on LMICs.

Methods

We performed a systematic scoping review in Scopus of specific gridded population datasets and "population" or "household" "survey" reports, and solicited additional published and unpublished sources from colleagues.

Results

We identified 43 national and sub-national gridded population-based household surveys implemented across 29 LMICs. Gridded population surveys used automated and manual approaches to derive clusters from WorldPop and LandScan gridded population estimates. After sampling, some survey teams interviewed all households in each cluster or segment, and others sampled households from larger clusters. Tools to select gridded population survey clusters include the GridSample R package, Geo-sampling tool, and GridSample.org. In the field, gridded population surveys generally relied on geographically accurate maps based on satellite imagery or OpenStreetMap, and a tablet or GPS technology for navigation.

Conclusions

For gridded population survey sampling to be adopted more widely, several strategic questions need answering regarding cell-level accuracy and uncertainty of gridded population estimates, the methods used to group/split cells into sample frame units, design effects of new sample designs, and feasibility of tools and methods to implement surveys across diverse settings.
Tissue Doppler Imaging and strain rate of the left atrial lateral wall: age related variations and comparison with parameters of diastolic function
Authors: Argento Laura V. , Travetto Carolina M. , Colicigno Maria de las M. , Marambio Gerardo , Gentile Silvia , Salvati Ana , Lax Jorge , Cianciulli Tomás
Published: September 2020

Background

Strain Rate Imaging (SRI) is one of the most used techniques to study left atrial (LA) and diastolic function. Its availability in low-income countries is diminished since it requires additional expensive software, among other limitations. In contrast, Tissue Doppler Imaging (TDI) is widely available and easy to use. We hypothesize TDI could detect changes in LA and diastolic function associated with age similarly to SRI. The aim of this study is to evaluate the effects of age on LA and diastolic function assessed by LA lateral wall TDI online by spectral pulse, and to compare them with age-related variations of LA SRI and other parameters of diastolic function in a population of healthy adults.

Materials and methods

Ninety-one healthy adults were prospectively evaluated. In apical four - chamber view the LA lateral wall was divided in three portions. Peak velocities of basal and mid portions were measured with TDI online by spectral pulse and with SRI by speckle tracking. A first positive wave (S’la and SRS) and two negative waves (E’la and SRE, and A’la and SRA respectively) were obtained. E’la/A’la ratio and SRE/SRA ratio were analyzed. The distribution of the variables by age subgroups was described and analyzed. Correlation analyses were performed.

Results

The median age was 42 years old and 54.9% were female. E’la/A’la showed a negative good correlation with age. E’la/A’la and SRE/SRA ratios changed from > 1 to < 1 in the age group of 41–50 years old, while this occurred in the group of 51–60 years old for the E/A ratio. Lateral and septal mitral annulus E´ showed decrease with age and prolongation of E-wave deceleration time was observed in the age group over 61 years old.

Conclusion

Normal values​​ according to age group of TDI of the LA lateral wall were obtained. Age-related changes in LA and diastolic function could be detected as early with TDI as with SRI. Future studies are required to explore if this method could be used to address in part LA or diastolic function in other populations with established cardiovascular disease or at risk of presenting it, which could be useful in low-income settings, where SRI is not available.
Hydroxychloroquine and dexamethasone in COVID-19: who won and who lost?
Authors: Ortolani Claudio , Pastorello Elide A.
Published: September 2020

Background

On June 30, 2020, the WHO reported over 10 millions of COVID-19 cases worldwide with over half a million deaths. In severe cases the disease progresses into an Acute Respiratory Distress Syndrome (ARDS), which in turn depends on an overproduction of cytokines (IL-6, TNFα, IL-12, IL-8, CCL-2 and IL1) that causes alveolar and vascular lung damage. Clearly, it is essential to find an immunological treatment that controls the “cytokine storm”. In the meantime, however, it is essential to have effective antiviral and anti-inflammatory drugs available immediately.

Pharmacologic therapy for COVID-19

Hydroxychloroquine or chloroquine have been widely adopted worldwide for the treatment of SARS-CoV-2 pneumonia. However, the choice of this treatment was based on low quality of evidence, i.e. retrospective, non-randomized controlled studies. Recently, four large Randomized Controlled Trials (RCTs) have been performed in record time delivering reliable data: (1) the National Institutes of Health (NIH) RCT included 60 hospitals participating all over the world and showed the efficacy of remdesivir in reducing the recovery time in hospitalized adults with COVID-19 pneumonia; (2) three large RCTs already completed, for hydroxychloroquine, dexamethasone and Lopinavir and Ritonavir respectively. These trials were done under the umbrella of the 'Recovery' project, headed by the University of Oxford. The project includes 176 participating hospitals in the UK and was set up to verify the efficacy of some of the treatments used for COVID-19. These three ‘Recovery’ RCTs concluded definitely: (a) that treatment with hydroxychloroquine provides no benefits in patients hospitalized with COVID-19; (b) that treatment with dexamethasone reduced deaths by one-third in COVID-19 patients that were mechanically ventilated, and by one-fifth in patients receiving oxygen only; (c) that the combination of Lopinavir and Ritonavir is not effective in reducing mortality in COVID-19 hospitalized patients.

Conclusions

The results of these four large RCTs have provided sound indications to doctors for the treatment of patients with COVID-19 and prompted the correction of many institutional provisions and guidelines on COVID-19 treatments (i.e. FDA, NIH, UK Health Service, etc.). Even though a definitive treatment for COVID-19 has not yet been found, large RCTs stand as the Gold Standards for COVID-19 therapy and offer a solid scientific base on which to base treatment decisions.
Plasma proteins facilitates placental transfer of polystyrene particles
Authors: Gruber Michael M. , Hirschmugl Birgit , Berger Natascha , Holter Magdalena , Radulović Snježana , Leitinger Gerd , Liesinger Laura , Berghold Andrea , Roblegg Eva , Birner-Gruenberger Ruth , Bjelic-Radisic Vesna , Wadsack Christian
Published: September 2020

Background

Nanoparticles, which are exposed to biological fluids are rapidly interacting with proteins and other biomolecules forming a corona. In addition to dimension, charge and material the distinct protein corona influences the interplay of nanoparticles with tissue barriers. In this study we were focused on the impact of in situ formed human plasma protein corona on the transfer of 80 nm polystyrene nanoparticles (PS-particles) across the human placenta. To study materno-to fetal PS transfer we used the human ex vivo placental perfusion approach, which represents an intact and physiological tissue barrier. To analyze the protein corona of PS particles we performed shotgun proteomics of isolated nanoparticles before and after tissue exposure.

Results

Human plasma incubated with PS-particles of 80 nm and subsequent formed protein corona enhanced the transfer across the human placenta compared to PS-corona formed by bovine serum albumin and dextran which served as a control. Quantitative and qualitative changes of plasma proteins determined the changes in PS transfer across the barrier. Based on the analysis of the PS-proteome two candidate proteins, namely human albumin and immunoglobulin G were tested if these proteins may account for the enhanced PS-transfer across the placenta. Interestingly, the protein corona formed by human albumin significantly induced the transfer of PS-particles across the tissue compared to the formed IgG-corona.

Conclusion

In total we demonstrate the PS corona dynamically and significantly evolves upon crossing the human placenta. Thus, the initial composition of PS particles in the maternal circulation is not predictive for their transfer characteristics and performance once beyond the barrier of the placenta. The precise mechanism of these effects remains to be elucidated but highlights the importance of using well designed biological models when testing nanoparticles for biomedical applications.
Snus cessation patterns - a long-term follow-up of snus users in Sweden
Authors: Sohlberg Tove , Wennberg Peter
Published: September 2020

Background

Several studies have investigated the role of snus as an aid to become smoke-free, but few have focused on who use snus, how they perceive snus use, why and how they quit, and their perception of being non-snus users. The purpose of this paper is to describe snus cessation patterns.

Methods

Respondents are part of a 7-year follow-up of former smokers in Sweden. Initially, 1400 respondents were contacted regarding participation and 705 answered a web-based survey (response rate 50%). Out of them, 118 had used snus. The analyses include percentage distributions, as well as factor analyses of inventories, and configural frequency analysis in order to examine configurations of snus-related patterns.

Results

Over 80% found snus of great importance to succeed with smoking cessation and half of them continued to use snus on a long term. Those who experienced both physical and psychological effects of switching to snus were the ones who continued and vice versa; those who did not experience such effects quit using snus. None made use of professional help but had their own strategies (60%), and most respondents who quit obtained psychological benefits (68%).

Conclusions

The distinction between the concepts smoke-free, tobacco-free, and nicotine-free contributes to nuances in the debate on snus as harm reduction. Continued snus use does not mean that snus is not an effective aid to become smoke-free. Snus cessation is mostly mentioned in relation to advices on how to succeed, but the cessation process has rarely been described; therefore, this study expands the knowledge on this quite neglected topic and contributes to a more nuanced picture of snus cessation.
Evaluation of the content validity index of the Australian/Canadian osteoarthritis hand index, the patient-rated wrist/hand evaluation and the thumb disability exam in people with hand arthritis
Authors: Bobos Pavlos , MacDermid Joy C. , Boutsikari Eleni C. , Lalone Emily A. , Ferreira Louis , Grewal Ruby
Published: September 2020

Background

The Australian/Canadian Osteoarthritis Hand Index (AUSCAN), the Patient-Rated Wrist/Hand Evaluation (PRWHE) and the Thumb Disability Exam (TDX) are patient-reported outcome measures (PROM) designed to assess pain and hand function in patients with hand arthritis, hand pain and disability, or thumb pathology respectively. This study evaluated the content validity of AUSCAN, PRWHE and TDX in people with hand arthritis.

Methods

This study enrolled participants with hand arthritis to rate the items of all 3 PROM in terms of relevance and clarity. The Content Validity Index (CVI) was computed for each item in each scale (I-CVI) as well as for the overall scale (S-CVI). Kappa was used to determine the inter-rater agreement among the raters.

Results

Overall, 64 individuals with hand arthritis (27% with OA, 67% with rheumatoid arthritis and 6% with psoriatic arthritis) participated in the study. The I-CVI for all items and all scales were very high (I-CVI > 0.76) and the modified Kappa agreement among the raters demonstrated excellent agreement (k > 0.76). The S-CVI for all PROMs was very high for relevance (AUSCAN = 0.92, 95% CI 0.90 to 0.94; PRWHE = 0.85, 95% CI 0.82 to 0.88 and TDX = 0.87, 95% CI 0.85 to 0.89) and for clarity (AUSCAN = 0.99, 95% CI 0.98 to 1.00; PRWHE = 0.95, 95% CI 0.93 to 0.97 and TDX = 0.91, 95% CI 0.89 to 0.94), respectively.

Conclusions

This study demonstrated very high content validity indices for the AUSCAN, PRWHE and TDX; with strong consensus across raters. This augments prior studies demonstrating appropriate statistical measurement properties, to provide confidence that all three measures assess important patient concepts of pain and disability.
G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone
Authors: Zhao Xiao-Fan
Published: September 2020

G protein-coupled receptors (GPCRs) are cell membrane receptors for various ligands. Recent studies have suggested that GPCRs transmit animal steroid hormone signals. Certain GPCRs have been shown to bind steroid hormones, for example, G protein-coupled estrogen receptor 1 (GPER1) binds estrogen in humans, and Drosophila dopamine/ecdysteroid receptor (DopEcR) binds the molting hormone 20-hydroxyecdysone (20E) in insects. This review summarizes the research progress on GPCRs as animal steroid hormone cell membrane receptors, including the nuclear and cell membrane receptors of steroid hormones in mammals and insects, the 20E signaling cascade via GPCRs, termination of 20E signaling, and the relationship between genomic action and the nongenomic action of 20E. Studies indicate that 20E induces a signal via GPCRs to regulate rapid cellular responses, including rapid Ca2+ release from the endoplasmic reticulum and influx from the extracellular medium, as well as rapid protein phosphorylation and subcellular translocation. 20E via the GPCR/Ca2+/PKC/signaling axis and the GPCR/cAMP/PKA-signaling axis regulates gene transcription by adjusting transcription complex formation and DNA binding activity. GPCRs can bind 20E in the cell membrane and after being isolated, suggesting GPCRs as cell membrane receptors of 20E. This review deepens our understanding of GPCRs as steroid hormone cell membrane receptors and the GPCR-mediated signaling pathway of 20E (20E-GPCR pathway), which will promote further study of steroid hormone signaling via GPCRs, and presents GPCRs as targets to explore new pharmaceutical materials to treat steroid hormone-related diseases or control pest insects.

Graphical abstract
Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation
Authors: Al Haddad Maria , El-Rif Rayane , Hanna Samer , Jaafar Leila , Dennaoui Rayanne , Abdellatef Sandra , Miskolci Veronika , Cox Dianne , Hodgson Louis , El-Sibai Mirvat
Published: September 2020

Background

Lung cancer is the second most commonly occurring cancer. The ability to metastasize and spread to distant locations renders the tumor more aggressive. Members of the Rho subfamily of small GTP-binding proteins (GTPases) play a central role in the regulation of the actin cytoskeleton and in cancer cell migration and metastasis. In this study we investigated the role of the RhoA/Cdc42 GAP, StarD13, a previously described tumor suppressor, in malignancy, migration and invasion of the lung cancer cells A549.

Methods

We knocked down StarD13 expression in A549 lung cancer cells and tested the effect on cell migration and invadopodia formation using time lapse imaging and invasion assays. We also performed rescue experiments to determine the signaling pathways downstream of StarD13 and transfected the cells with FRET biosensors for RhoGTPases to identify the proteins involved in invadopodia formation.

Results

We observed a decrease in the level of expression of StarD13 in lung tumor tissues compared to normal lung tissues through immunohistochemistry. StarD13 also showed a lower expression in the lung adenocarcinoma cell line A549 compared to normal lung cells, WI38. In addition, the depletion of StarD13 increased cell proliferation and viability in WI38 and A549 cells, suggesting that StarD13 might potentially be a tumor suppressor in lung cancer. The depletion of StarD13, however, inhibited cell motility, conversely demonstrating a positive regulatory role in cell migration. This was potentially due to the constitutive activation of RhoA detected by pull down and FRET assays. Surprisingly, StarD13 suppressed cell invasion by inhibiting Cdc42-mediated invadopodia formation. Indeed, TKS4 staining and invadopodia assay revealed that StarD13 depletion increased Cdc42 activation as well as invadopodia formation and matrix degradation. Normal lung cells depleted of StarD13 also produced invadopodia, otherwise a unique hallmark of invasive cancer cells. Cdc42 knock down mimicked the effects of StarD13, while overexpression of a constitutively active Cdc42 mimicked the effects of its depletion. Finally, immunostaining and FRET analysis revealed the absence of StarD13 in invadopodia as compared to Cdc42, which was activated in invadopodia at the sites of matrix degradation.

Conclusion

In conclusion, StarD13 plays distinct roles in lung cancer cell migration and invasion through its differential regulation of Rho GTPases.
A code within the genetic code: codon usage regulates co-translational protein folding
Authors: Liu Yi
Published: September 2020

The genetic code is degenerate, and most amino acids are encoded by two to six synonymous codons. Codon usage bias, the preference for certain synonymous codons, is a universal feature of all genomes examined. Synonymous codon mutations were previously thought to be silent; however, a growing body evidence now shows that codon usage regulates protein structure and gene expression through effects on co-translational protein folding, translation efficiency and accuracy, mRNA stability, and transcription. Codon usage regulates the speed of translation elongation, resulting in non-uniform ribosome decoding rates on mRNAs during translation that is adapted to co-translational protein folding process. Biochemical and genetic evidence demonstrate that codon usage plays an important role in regulating protein folding and function in both prokaryotic and eukaryotic organisms. Certain protein structural types are more sensitive than others to the effects of codon usage on protein folding, and predicted intrinsically disordered domains are more prone to misfolding caused by codon usage changes than other domain types. Bioinformatic analyses revealed that gene codon usage correlates with different protein structures in diverse organisms, indicating the existence of a codon usage code for co-translational protein folding. This review focuses on recent literature on the role and mechanism of codon usage in regulating translation kinetics and co-translational protein folding.
Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study
Authors: Bauer A. , Haufe E. , Heinrich L. , Seidler A. , Schulze H. J. , Elsner P. , Drexler H. , Letzel S. , John S. M. , Fartasch M. , Brüning T. , Dugas-Breit S. , Gina M. , Weistenhöfer W. , Bachmann K. , Bruhn I. , Lang B. M. , Brans R. , Allam J. P. , Grobe W. , Westerhausen S. , Knuschke P. , Wittlich M. , Diepgen T. L. , Schmitt J. ,   for the FB181 study group, Bieber Thomas , Bonness Sonja , Brecht Beate , Grabbe Stephan , Küster Denise , Ruppert Linda , Stephan Victoria , Thielitz Anja , Zimmermann Elisabeth
Published: September 2020

Background

A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates.

Objectives

To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure.

Methods

Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated.

Results

Participants with high versus no (OR 2.08; 95% CI 1.24–3.50;p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15–3.65;p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses.

Conclusion

The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.
Comparing effects of two higher intensity feedback interventions with simple feedback on improving staff communication in nursing homes—the INFORM cluster-randomized controlled trial
Authors: Hoben Matthias , Ginsburg Liane R. , Easterbrook Adam , Norton Peter G. , Anderson Ruth A. , Andersen Elizabeth A. , Boström Anne-Marie , Cranley Lisa A. , Lanham Holly J. , Weeks Lori E. , Cummings Greta G. , Holroyd-Leduc Jayna M. , Squires Janet E. , Wagg Adrian S. , Estabrooks Carole A.
Published: September 2020

Background

Effective communication among interdisciplinary healthcare teams is essential for quality healthcare, especially in nursing homes (NHs). Care aides provide most direct care in NHs, yet are rarely included in formal communications about resident care (e.g., change of shift reports, family conferences). Audit and feedback is a potentially effective improvement intervention. This study compares the effect of simple and two higher intensity levels of feedback based on goal-setting theory on improving formal staff communication in NHs.

Methods

This pragmatic three-arm parallel cluster-randomized controlled trial included NHs participating in TREC (translating research in elder care) across the Canadian provinces of Alberta and British Columbia. Facilities with at least one care unit with 10 or more care aide responses on the TREC baseline survey were eligible. At baseline, 4641 care aides and 1693 nurses cared for 8766 residents in 67 eligible NHs. NHs were randomly allocated to a simple (control) group (22 homes, 60 care units) or one of two higher intensity feedback intervention groups (based on goal-setting theory): basic assisted feedback (22 homes, 69 care units) and enhanced assisted feedback 2 (23 homes, 72 care units). Our primary outcome was the amount of formal communication about resident care that involved care aides, measured by the Alberta Context Tool and presented as adjusted mean differences [95% confidence interval] between study arms at 12-month follow-up.

Results

Baseline and follow-up data were available for 20 homes (57 care units, 751 care aides, 2428 residents) in the control group, 19 homes (61 care units, 836 care aides, 2387 residents) in the basic group, and 14 homes (45 care units, 615 care aides, 1584 residents) in the enhanced group. Compared to simple feedback, care aide involvement in formal communications at follow-up was 0.17 points higher in both the basic ([0.03; 0.32], p = 0.021) and enhanced groups ([0.01; 0.33], p = 0.035). We found no difference in this outcome between the two higher intensity groups.

Conclusions

Theoretically informed feedback was superior to simple feedback in improving care aides’ involvement in formal communications about resident care. This underlines that prior estimates for efficacy of audit and feedback may be constrained by the type of feedback intervention tested.

Trial registration

ClinicalTrials.gov (NCT02695836), registered on March 1, 2016
Percutaneous vertebroplasty (PVP) to treat specialized type of endplate fractures around the Schmorl’s node: a prospective study of 65 patients
Authors: Zhang Yaoshen , Yin Peng , Yang Jincai , Hai Yong
Published: September 2020

Background

The Schmorl’s nodes (SNs) are defined as the herniation of the intervertebral disc into the vertebral body. Endplate fractures around the Schmorl’s node could result in severe back pain that is similar to vertebral compression fractures. The objective of this study was to prospectively analyze the surgical effectiveness and safety of percutaneous vertebroplasty (PVP) for endplate fractures around the SNs.

Methods

Seventy-one consecutive patients with the fresh endplate fracture around SNs from October 2017 to February 2018 were enrolled in this study. The visual analog scale (VAS) and Oswestry disability index (ODI) scores of low back pain were evaluated in all patients preoperatively, postoperatively, and at 1 month, 6 months, and 1 year after primary single level PVP. Surgery-related data including duration of the operation, injected cement volumes, and surgical complications were recorded.

Results

Sixty-five patients with fresh endplate fractures around the SNs were treated successfully via percutaneous vertebroplasty. Our study showed that the VAS scores and ODI scores of patients were obviously improved after operation. Cement leakage into the disc space occurred in 5 patients (7.7%), and adjacent segment refractures occurred in 2 patients (3.1%). No other surgical complications, including infections or nerve root injuries were encountered.

Conclusions

Based on the results of this prospective study, PVP was an effective and safe procedure for endplate fractures around the SNs.

Trial registration

ChiCTR, ChiCTR1800016453. Registered 2 June 2018—retrospectively registered,

http://www.chictr.org.cn/com/25/historyversionpuben.aspx?regno=ChiCTR1800017602
A novel three-dimensional printed vacuum bell for pectus excavatum treatment: a preliminary study
Authors: Deng Xicheng , Huang Peng , Luo Jinwen , Wang Jinghua , Yi Liwen , Yang Guangxian , He Siping , Li Xun , Xiang Shiting
Published: September 2020

Objective

Conservative treatment with a vacuum bell (VB) for pectus excavatum (PE) has now been gradually popularized as an alternative to surgery. We describe our initial experience with a novel three dimensional (3D) printed VB device.

Methods

Prospectively collected data of all patients who started using a 3D printed VB in 2018 at our institution were analyzed. Linear and logistic regressions were used to identify factors associated with effectiveness of device usage.

Results

In total, forty-two patients with a median age of 3.6 years were treated with the device. The median follow-up duration was 11.1 months and the mean initial Depth Ratio (DR) was 0.129. There were no permanent sequelae from side effects. Thirty patients with at least one follow-up body scan data showed varying improvement (z = − 4.569, p = 0.0000). Linear regression suggested that longer usage improved outcomes (R2 = 0.235, p = 0.014). By logistic regression there was a trend of younger ages and less initial DR for better improvement though neither was statistically significant (p = 0.086, 0.078, respectively).

Conclusion

Our initial experience has shown the 3D printed VB may be as effective as other conventional VBs and could be used as an alternative to surgical treatment for selected patients with PE. More experience and studies with this type of VB are needed to demonstrate its superiority with regard to the 3D printing design and optimal timing and indication for use.
Evaluation of right ventricle pulmonary artery coupling on right ventricular function in post operative tetralogy of Fallot patients underwent for pulmonary valve replacement
Authors: Sandeep Bhushan , Huang Xin , Li Yuan , Wang Xiaowei , Mao Long , Kan Yue , Xiong Dan , Gao Ke , Zongwei Xiao
Published: September 2020

Background

To evaluate RV-PA coupling in post operative TOF patients with ventricular dilatation underwent for PVR and investigate the correlation between ventricular functions measuring Ea/Emax ratio using cardio magnetic resonance and the effect of surgical type at primary repair of TOF on coupling.

Method

RV-PA coupling was measured noninvasively by Ea/Emax ratio from CMRI and ECHO. From CMRI results the patients were divided in two groups, RV-PA coupling and RV-PA uncoupling. Ea/Emax ≤1 was considered for coupling patients and Ea/Emax > 1 for uncoupling patients.

Results

Ninety patients were uncoupled (Ea/Emax: 1.55 ± 0.46) and 45 were coupled (Ea/Emax: 0.81 ± 0.15). Out of 75 TAP repaired patients 60 were uncoupled RV-PV. In addition, higher pro-BNP is an important factor for uncoupled RV-PV (P = 0.001). CMR evaluation for right ventricular function between uncoupling and coupling were RVEDVi (196.65 ± 63.57 vs. 154.28 ± 50.07, P = 0.001), RVESVi (121.19 ± 51.47 vs. 83.94 ± 20.43, P = 0.001), RVSVi (67.19 ± 19.87 vs. 106.31 ± 33.44, P = 0.001), and RVEF (40.90 ± 8.73 vs. 54.63 ± 4.76, P = 0.001). The increased RVEDVi, RVESVi and RVSVi and decreased RVEF have significant correlation with Ea/Emax. Ea/Emax was also found positively correlated with RVEDVi (P = < 0.05, r = 0.35), RVESVi (P = < 0.001, r = 0.41) and negatively correlated with RVSVi (P = < 0.05, r = 0.22) and RVEF (P = < 0.05, r = 0.78).

Conclusions

Unfavorable RV-PA coupling is present in post operative TOF patients and it is affected by several factors. Our results explain a new concept of RV-PA interactions as a contributing mechanism for the observed decline in RV function.
Safety and efficacy of transaxillary transcatheter aortic valve replacement using a current-generation balloon-expandable valve
Authors: Zhan Yong , Toomey Nicholas , Ortoleva Jamel , Kawabori Masashi , Weintraub Andrew , Chen Frederick Y.
Published: September 2020

Background

Transaxillary access (TAx) has shown promise as an excellent alternative TAVR option, but data on the Edwards SAPIEN 3 in TAx-TAVR is limited. We sought to study the safety and efficacy of TAx-TAVR using this current-generation balloon-expandable valve.

Methods

A retrospective study of our first 24 TAx and 20 transthoracic (TT) TAVR patients treated with the SAPIEN 3 valve was performed, and the patients’ preoperative characteristics, procedural outcomes, and clinical outcomes were compared to our first 100 transfemoral (TF) patients using the SAPIEN 3 device.

Results

There were no statistical differences observed for outcomes between the TAx and TF groups, despite the TAx patients having more comorbidities (STS-PROM 11.3 ± 7.6 versus 7.3 ± 5.2, p = 0.042). In addition, no significant difference was found in the fluoroscopy time and contrast amount between the two groups. The patients’ baseline characteristics were similar between the TAx and TT groups. Their procedural and clinical outcomes were comparable, but there was a trend towards lower incidence of acute kidney injury (13.0% versus 23.5%), new-onset atrial fibrillation (5.6% versus 33.3%), shorter median length of stay postoperatively (4 versus 6 days), fewer discharges to rehabilitation (16.7% versus 35.0%), and a lower rate of readmission within 30-days (8.3% versus 35.0%), all favoring TAx access.

Conclusions

TAx-TAVR with the SAPIEN 3 valve is a safe alternative to TF access. It offers advantages of improved recovery over TT access, and appears to be a superior alternative-access option for TAVR. TAx access could be preferred when TF access is not feasible.
Further evidence for POMK as candidate gene for WWS with meningoencephalocele
Authors: Paul Luisa , Rupprich Katrin , Della Marina Adela , Stein Anja , Elgizouli Magdeldin , Kaiser Frank J. , Schweiger Bernd , Köninger Angela , Iannaccone Antonella , Hehr Ute , Kölbel Heike , Roos Andreas , Schara-Schmidt Ulrike , Kuechler Alma
Published: September 2020

Background

Walker-Warburg syndrome (WWS) is a rare form of alpha-dystroglycanopathy characterized by muscular dystrophy and severe malformations of the CNS and eyes. Bi-allelic pathogenic variants in POMK are the cause of a broad spectrum of alpha-dystroglycanopathies. POMK encodes protein-O-mannose kinase, which is required for proper glycosylation and function of the dystroglycan complex and is crucial for extracellular matrix composition.

Results

Here, we report on male monozygotic twins with severe CNS malformations (hydrocephalus, cortical malformation, hypoplastic cerebellum, and most prominently occipital meningocele), eye malformations and highly elevated creatine kinase, indicating the clinical diagnosis of a congenital muscular dystrophy (alpha-dystroglycanopathy). Both twins were found to harbor a homozygous nonsense mutation c.640C>T, p.214* in POMK, confirming the clinical diagnosis and supporting the concept that POMK mutations can be causative of WWS.

Conclusion

Our combined data suggest a more important role for POMK in the pathogenesis of meningoencephalocele. Only eight different pathogenic POMK variants have been published so far, detected in eight families; only five showed the severe WWS phenotype, suggesting that POMK-associated WWS is an extremely rare disease. We expand the phenotypic and mutational spectrum of POMK-associated WWS and provide evidence of the broad phenotypic variability of POMK-associated disease.
Cloning, expression and enzyme activity delineation of two novel CANT1 mutations: the disappearance of dimerization may indicate the change of protein conformation and even function
Authors: Wang Hong-Dan , Guo Liang-Jie , Feng Zhan-Qi , Zhang Da-Wei , Zhang Meng-Ting , Gao Yue , Chen Chuan-Liang , Zhu Bo-Feng
Published: September 2020

Background

Desbuquois dysplasia (DBQD) was a rare autosomal recessive skeletal dysplasia. Calcium activated nucleotidase 1 (CANT1) mutation was identified as a common pathogenic change for DBQD type 1 and Kim variant but not for DBQD type 2. To our knowledge, all patients with DBQD type 1 currently found could be explained by mutations in the CANT1 gene, but mutations in the CANT1 gene might not be directly diagnosed as DBQD type 1.

Results

We have identified two novel CANT1 mutations (mut1: c.594G > A [p.Trp198*], mut2: c.734C > T [p.Pro245Leu]) in three children from a family of Chinese origin for the first time. Two of the three children could be diagnosed as typical DBQD type 1 and one child could not be diagnosed as DBQD type 1 based on the clinical data we had. To further clarify the effect of the two mutations of the CANT1 gene, we studied the CANT1 gene expression and detected the protein secretion and nucleotide enzyme activity through cDNA cloning and expression vectors construction for wild and mutant types. The mut1 was a nonsense mutation which could lead to premature termination and produced the truncated bodies; The CANT1 dimer of mut2 was significantly reduced and even undetectable. The extracellular secretion of mut1 was extremely high while mut2 was significantly reduced compared with the wild type. And mut1 and mut2 also could result in a significant reduction in the activity of CANT1 nucleotidease. From the results we could deduce that the two mutations of the CANT1 gene were the causes of the two cases in this study.

Conclusions

Regarding the particularity of the cases reported in this study, the pathogenesis of CANT1 might be more complicated. The genetic and phenotype of three children with the same genetic background need to be further studied. Larger cohort of patients was needed to establish genotype–phenotype correlations in DBQD.
The first RT-qPCR confirmed case of tick-borne encephalitis in a dog in Scandinavia
Authors: Andersson Elina , Kendall Anna , Url Angelika , Auer Angelika , Leschnik Michael
Published: September 2020

Background

Tick-borne encephalitis (TBE) is a zoonotic neurological disease caused by tick-borne encephalitis virus (TBEV), a flavivirus endemic in parts of Europe and Asia. Seroconversion without signs of clinical disease is common in dogs and most of the cases previously described have been tentatively diagnosed by combining neurologic signs with serum antibody titres. Here, the first Scandinavian RT-qPCR-confirmed clinical case of TBE in a dog is reported.

Case presentation

A 4-year old castrated male Pointer Labrador cross was presented with acute-onset ataxia. During hospitalisation, the dog developed seizures. Despite aggressive treatment with steroids, antimicrobials and sedation/anaesthesia, there was continued deterioration during the following 24 h after admission and the dog was euthanised and submitted for necropsy. Histopathological changes in the brain were consistent with lymphoplasmacytic and histiocytic meningoencephalomyelitis. RT-qPCR examination of the brain was positive for TBEV, confirming infection.

Conclusions

Meningoencephalomyelitis caused by TBEV should be a diagnostic consideration in dogs presenting with clinical signs of central nervous system disease such as acute-onset ataxia and seizures in areas where TBEV-positive ticks are endemic. Clinical TBE may be underdiagnosed in dogs due to lack of specific testing.
Ocular ultrasonography of sea turtles
Authors: Muramoto Caterina , Cardoso-Brito Vinícius , Raposo Ana Cláudia , Pires Thais Torres , Oriá Arianne Pontes
Published: September 2020

Background

Environmental changes contribute to the development of ophthalmic diseases in sea turtles, but information on their eye biometrics is scarce. The aim of this study was to describe ophthalmic ultrasonographic features of four different sea turtle species; Caretta caretta (Loggerhead turtle; n = 10), Chelonia mydas (Green turtle; n = 8), Eretmochelys imbricata (Hawksbill turtle; n = 8) and Lepidochelys olivacea (Olive ridley; n = 6) under human care. Corneal thickness, scleral ossicle width and thickness, anterior chamber depth, axial length of the lens, vitreous chamber depth and axial globe length were measured by B-mode sonography with a linear transducer. Carapace size and animal weight were recorded. A sonographic description of the eye structures was established.

Results

The four species presented an ovate eyeball, a relatively thin cornea, and a small-sized lens positioned rostrally in the eye bulb, near the cornea, resulting in a shallow anterior chamber. The scleral ossicles did not prevent the evaluation of intraocular structures, even with a rotated eye or closed eyelids; image formation beyond the ossicles and measurements of all proposed structures were possible. B-mode sonography was easily performed in all animals studied. The sonographic characteristics of the eye were similar among the four species. Since there was a correlation between the size of the eye structures and the size of the individual, especially its carapace size, the differences found between E. imbricata and Caretta caretta are believed to be due to their overall difference in size.

Conclusions

Sonography is a valuable tool in ophthalmic evaluation of these species. Only minor differences were found between the species in this study, reinforcing their phylogenetic proximity and their similar functions and habitats.
Addressing COVID-19 in humanitarian settings: a call to action
Authors: Alawa Jude , Alawa Nawara , Coutts Adam , Sullivan Richard , Khoshnood Kaveh , Fouad Fouad M.
Published: September 2020

Refugees and internally displaced persons in humanitarian settings are particularly susceptible to the spread of infectious illnesses such as COVID-19 due to overcrowding and inadequate access to clean water, sanitation, and hygiene facilities. Countries facing conflict or humanitarian emergencies often have damaged or fragmented health systems and little to no capacity to test, isolate, and treat COVID-19 cases. Without a plan to address COVID-19 in humanitarian settings, host governments, aid agencies, and international organizations risk prolonging the spread of the virus across borders, threatening global health security, and devastating vulnerable populations. Stakeholders must coordinate a multifaceted response to address COVID-19 in humanitarian settings that incorporates appropriate communication of risks, sets forth resource-stratified guidelines for the use of limited testing, provides resources to treat affected patients, and engages displaced populations.
Evolution and current state of global research on paediatric resuscitation: a systematic scientometric analysis
Authors: Scholz Sean S. , Borgstedt Rainer , Menzel Leoni C. , Rehberg Sebastian , Jansen Gerrit
Published: September 2020

Background

Paediatric resuscitation is rare but potentially associated with maximal lifetime reduction. Notably, several nations experience high infant mortality rates even today. To improve clinical outcomes and promote research, detailed analyses on evolution and current state of research on paediatric resuscitation are necessary.

Methods

Research on paediatric resuscitation published in-between 1900 and 2019 were searched using Web of Science. Metadata were extracted and analyzed based on the science performance evaluation (SciPE) protocol. Research performance was evaluated regarding quality and quantity over time, including comparisons to adult resuscitation. National research performance was related to population, financial capacities, infant mortality rate, collaborations, and authors’ gender.

Results

Similar to adult resuscitation, research performance on paediatric resuscitation grew exponentially with most original articles being published during the last decade (1106/1896). The absolute number, however, is only 14% compared to adults. The United States dominate global research by contributing the highest number of articles (777), Hirsch-Index (70), and citations (18,863). The most productive collaboration was between the United States and Canada (52). When considering nation’s population and gross domestic product (GDP) rate, Norway is leading regarding population per article (62,467), per Hirsch-Index (223,841), per citation (2226), and per GDP (2.3E-04). Regarding publications per infant mortality rate, efforts of India and Brazil are remarkable. Out of the 100 most frequently publishing researchers, 25% were female.

Conclusion

Research efforts on paediatric resuscitation have increased but remain underrepresented. Specifically, nations with high infant mortality rates should be integrated by collaborations. Additional efforts are required to overcome gender disparities.