bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically predicted higher educational attainment decreases the risk of stroke: a multivariable Mendelian randomization study
Authors: Zhang Weihao , Li Yuanjin , Li Yuming , Zheng Kai , Zou Shenghui , Jia Xing , Yang Hua
Published: June 2022

Background

The causal association between educational attainment (EA) and stroke remains unclear. Hence, a novel multivariable Mendelian randomization (MVMR) approach was applied to solve this issue.

Methods

The single nucleotide polymorphisms (SNPs) from a recent genome-wide association study (GWAS) on years of schooling served as instruments. Univariable mendelian randomization (MR) and MVMR analyses were performed to detect the relationship between genetically predicted EA and the stroke risk. In the MVMR, cigarette consumption, alcohol consumption, body mass index (BMI), intelligence, and hypertension were adjusted. The summary statistics for stroke from the MEGASTROKE consortium included 446,696 participants (40,585 cases of stroke and 34,217 cases of ischemic stroke), most of whom were of European descent.

Results

In the univariable MR, genetically predicated EA could decrease the risks of total stroke (OR = 0.66, 95% CI 0.61–0.72, P = 2.70 × 10–23), ischemic stroke (OR = 0.67, 95% CI 0.61–0.73, P = 2.58 × 10–18), large artery atherosclerosis (OR = 0.51, 95% CI 0.40–0.64, P = 1.80 × 10–8), small vessel stroke (OR = 0.60, 95% CI 0.49–0.73, P = 5.59 × 10–7), and cardioembolic stroke (OR = 0.81, 95% CI 0.68–0.96, P = 1.46 × 10–2) using the inverse-variance weighted (IVW) estimator. Higher EA might be negatively correlated with the odds of total stroke (OR = 0.62, 95% CI 0.50–0.77, P = 1.44 × 10–5), ischemic stroke (OR = 0.63, 95% CI 0.50–0.80, P = 1.41 × 10–4), and cardioembolic stroke (OR = 0.59, 95% CI 0.39–0.90, P = 0.01), but was not significant in large artery atherosclerosis (OR = 0.65, 95% CI 0.37–1.15, P = 0.14) and small vessel stroke (OR = 0.68, 95% CI 0.41–1.13, P = 0.14) after controlling other exposures.

Conclusions

We found that genetically predicated higher EA decreased the risks of total stroke, ischemic stroke, and cardioembolic stroke, independent of smoking, alcohol consumption, BMI, intelligence, and hypertension.
Application of high-frequency ultrasound to assess facial skin thickness in association with gender, age, and BMI in healthy adults
Authors: Meng Ying , Feng Lan , Shan Jiali , Yuan Zixu , Jin Lin
Published: June 2022

Background and objective

High-frequency ultrasound plays an extremely important role in normal skin measurement, skin disease diagnosis, and aesthetic medicine. This study aimed to estimate the epidermal and dermal thicknesses at eight different facial sites in healthy adults using high-frequency ultrasound, and to evaluate the correlation of epidermal and dermal thicknesses with age and body mass index (BMI).

Methods

Facial skin assessment was performed on 118 participants using high-frequency ultrasound. The epidermal and dermal thicknesses of forehead, glabella, temple, eyelid, nasal dorsum, zygoma, submandibular, and neck were measured. The correlation of the epidermal and dermal thicknesses with age and BMI was analyzed by the linear correlation analysis.

Results

The epidermal and dermal thicknesses in men were significantly higher than those in women (P < 0.05), except for the thicknesses of zygomatic epidermis and neck dermis. The dermal thickness on zygoma and submandibular in young women was significantly higher than in middle age and old women (P < 0.05). Overall, with the increase of age, the thickness of facial skin decreased in women, mainly in the forehead, glabella, zygoma, and submandibular. In women, the epidermal and dermal thicknesses of neck were correlated with BMI (r = 0.392, 0.241, P < 0.05, respectively). However, in men, the epidermal and dermal thicknesses were correlated with age only in zygoma dermis (r = − 0.327, P < 0.05), while there was no correlation between the epidermal and dermal thicknesses and BMI.

Conclusion

Gender, age, and BMI had significant effects on the epidermal and dermal thicknesses at different facial sites.
Managing acute presentations of atheromatous renal artery stenosis
Authors: de Bhailis Áine , Al-Chalabi Saif , Hagemann Rodrigo , Ibrahim Sara , Hudson Amy , Lake Edward , Chysochou Constantina , Green Darren , Kalra Philip A.
Published: June 2022

Background

Atherosclerotic renovascular disease (ARVD) often follows an asymptomatic chronic course which may be undetected for many years. However, there are certain critical acute presentations associated with ARVD and these require a high index of suspicion for underlying high-grade RAS (renal artery stenosis) to improve patient outcomes. These acute presentations, which include decompensated heart failure syndromes, accelerated hypertension, rapidly declining renal function, and acute kidney injury (AKI), are usually associated with bilateral high-grade RAS (> 70% stenosis), or high-grade RAS in a solitary functioning kidney in which case the contralateral kidney is supplied by a vessel demonstrating renal artery occlusion (RAO). These presentations are typically underrepresented in large, randomized control trials which to date have been largely negative in terms of the conferred benefit of revascularization.

Case presentation

Here we describe 9 individual patients with 3 classical presentations including accelerated phase hypertension, heart failure syndromes, AKI and a fourth category of patients who suffered recurrent presentations. We describe their response to renal revascularization. The predominant presentation was that consistent with ischaemic nephropathy all of whom had a positive outcome with revascularization.

Conclusion

A high index of suspicion is required for the diagnosis of RAS in these instances so that timely revascularization can be undertaken to restore or preserve renal function and reduce the incidence of hospital admissions for heart failure syndromes.
Self-rated health and quality of life among Syrian refugees in Ireland – data from a cross-sectional study
Authors: Collins Claire , Pericin Ivana , Larkin James , Diaz Esperanza
Published: June 2022

Introduction

As a response to the humanitarian crisis in Syria, the Irish government agreed to accept up to 4000 refugees for resettlement in Ireland in 2016. Prior to their arrival in Ireland, health screening was carried out by the International Organisation for Migration. However, no population-level measurement of the health status or needs takes place in Ireland to inform policy or health services requirements.

Methods

Cross-sectional data from a self-completed questionnaire among 194 Syrian Refugees aged 16 years and older resident in reception centres in Ireland in 2017/2018 is reported upon. The questionnaire measured self-reported health including quality of life and all study material were available in English and Arabic. The data was examined applying descriptive statistics and regression analysis.

Results

Syrian Refugees in Ireland consist of a relatively young cohort; in this study the majority of participants were younger than 35 years (69.5%). Two-thirds of the respondents reported their overall health status to be good or very good. The most common health condition was found to be headache and the most common medications used were painkillers. Chronic pain was experienced by one quarter of respondents; 27.5% were considered as suffering from anxiety and 10.0% had symptoms compatible with post-traumatic stress disorder (PTSD). A significant relationship was observed between chronic pain and self-rated health, as well as between chronic pain and anxiety. Quality of life (QoL) scores were lowest for the QoL environment domain.

Conclusions

Chronic pain is relatively widespread among these young and otherwise healthy refugees. Psychological distress and trauma are important factors in respondents’ quality of life scores. Chronic pain is associated with one’s mental health. Our findings and the literature suggests that the diagnosis and treatment of pain and providing care in a culturally sensitive manner should be a priority and included in the preparation and training of the relevant care providers. Additionally, the impact of living conditions on quality of life should not be underestimated.
Laparoscopic repair of perforated peptic ulcer: a multicenter, propensity score matching analysis
Authors: Kim Chang Woo , Kim Jong Wan , Yoon Sang Nam , Oh Bo Young , Kang Byung Mo
Published: June 2022

Background

Perforated peptic ulcer (PPU) is a common emergency condition requiring surgery using laparoscopy or open repair of the perforated site. The aim of this study was to assess the role of laparoscopic surgery (LS) based on the safety and efficacy for PPU.

Methods

Medical records of the consecutive patients who underwent LS or open surgery (OS) for PPU at five hospitals between January 2009 and December 2019 were retrospectively reviewed. After propensity score matching, short-term perioperative outcomes were compared between LS and OS in selected patients.

Results

Among the 598 patients included in the analysis, OS was more frequently performed in patients with worse factors, including older age, a higher American Society of Anesthesiologists score, more alcohol use, longer symptom duration, a higher Boey score, a higher serum C-reactive protein level, a lower serum albumin level, and a larger-diameter perforated site. After propensity score matching, 183 patients were included in each group; variables were well-balanced between-groups. Postoperative complications were not different between groups (24.6% LS group vs. 31.7% OS group, p = 0.131). However, postoperative length of hospital stay (10.03 vs. 12.53 days, respectively, p = 0.003) and postoperative time to liquid intake (3.75 vs. 5.26 days, p < 0.001) were shorter in the LS group.

Conclusions

LS resulted in better functional recovery than OS and can be safely performed for treatment of PPU. When performed by experienced surgeons, LS is an alternative option, even for hemodynamically unstable patients.
Exploring the formal assessment discussions in clinical nursing education: An observational study
Authors: Aase Ingunn , Akerjordet Kristin , Crookes Patrick , Frøiland Christina T. , Laugaland Kristin A.
Published: June 2022

Introduction

According to EU standards, 50% of the bachelor education program in nursing should take place in clinical learning environments. Consequently, this calls for high quality supervision, where appropriate assessment strategies are vital to optimize students’ learning, growth, and professional development. Despite this, little is known about the formal assessment discussions taking place in clinical nursing education.

Objective

The aim of this study was to explore the characteristics of the formal assessment discussions taking place during first-year students’ clinical education in nursing homes.

Method

An exploratory qualitative study was performed. The data consist of passive participant observations of 24 assessment discussions (12 mid-term and 12 final assessments) with first-year nursing students (n=12), their assigned registered nurse mentors (n=12) and nurse educators (n=5). The study was conducted in three public nursing homes in a single Norwegian municipality. Data were subjected to thematic analysis. The findings were reported using the Standards for Reporting of Qualitative Research.

Results

Three themes were identified regarding the characteristics of the formal assessment discussions: (1) adverse variability in structuring, weighting of theoretical content and pedagogical approach; (2) limited three-part dialogue constrains feedback and reflection; and (3) restricted grounds for assessment leave the nurse educators with a dominant role.

Conclusion

These characteristic signal key areas of attention to improve formal assessment discussions to capitalize on unexploited learning opportunities.
Acute association between heatwaves and stillbirth in six US states
Authors: Richards Megan , Huang Mengjiao , Strickland Matthew J. , Newman Andrew J. , Warren Joshua L. , D’Souza Rohan , Chang Howard H. , Darrow Lyndsey A.
Published: June 2022

Background

Heatwaves are becoming more frequent and may acutely increase the risk of stillbirth, a rare and severe pregnancy outcome.

Objectives

Examine the association between multiple heatwave metrics and stillbirth in six U.S. states.

Methods

Data were collected from fetal death and birth records in California (1996–2017), Florida (1991–2017), Georgia (1994–2017), Kansas (1991–2017), New Jersey (1991–2015), and Oregon (1991–2017). Cases were matched to controls 1:4 based on maternal race/ethnicity, maternal education, and county, and exposure windows were aligned (gestational week prior to stillbirth). County-level temperature data were obtained from Daymet and linked to cases and controls by residential county and the exposure window. Five heatwave metrics (1 categorical, 3 dichotomous, 1 continuous) were created using different combinations of the duration and intensity of hot days (mean daily temperature exceeding the county-specific 97.5th percentile) during the exposure window, as well as a continuous measure of mean temperature during the exposure window modeled using natural splines to allow for nonlinear associations. State-specific odds ratios (ORs) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. State-specific results were pooled using a fixed-effects meta-analysis.

Results

In our data set of 140,428 stillbirths (553,928 live birth controls), three of the five heatwave metrics examined were not associated with stillbirth. However, four consecutive hot days during the previous week was associated with a 3% increase in stillbirth risk (CI: 1.01, 1.06), and a 1 °C average increase over the threshold was associated with a 10% increase in stillbirth risk (CI: 1.04, 1.17). In continuous temperature analyses, there was a slight increased risk of stillbirth associated with extremely hot temperatures (≥ 35 °C).

Discussion

Most heat wave definitions examined were not associated with acute changes in stillbirth risk; however, the most extreme heatwave durations and temperatures were associated with a modest increase in stillbirth risk.
Ultrasound-assisted brain delivery of nanomedicines for brain tumor therapy: advance and prospect
Authors: Zhang Shuo , Zhang Shuai , Luo Siyuan , Tang Peng , Wan Mingxi , Wu Daocheng , Gao Wei
Published: June 2022

Nowadays, brain tumors are challenging problems, and the key of therapy is ensuring therapeutic drugs cross the blood–brain barrier (BBB) effectively. Although the efficiency of drug transport across the BBB can be increased by innovating and modifying nanomedicines, they exert insufficient therapeutic effects on brain tumors due to the complex environment of the brain. It is worth noting that ultrasound combined with the cavitation effect of microbubbles can assist BBB opening and enhance brain delivery of nanomedicines. This ultrasound-assisted brain delivery (UABD) technology with related nanomedicines (UABD nanomedicines) can safely open the BBB, facilitate the entry of drugs into the brain, and enhance the therapeutic effect on brain tumors. UABD nanomedicines, as the main component of UABD technology, have great potential in clinical application and have been an important area of interest in the field of brain tumor therapy. However, research on UABD nanomedicines is still in its early stages despite the fact that they have been associated with many disciplines, including material science, brain science, ultrasound, biology, and medicine. Some aspects of UABD theory and technology remain unclear, especially the mechanisms of BBB opening, relationship between materials of nanomedicines and UABD technology, cavitation and UABD nanomedicines design theories. This review introduces the research status of UABD nanomedicines, investigates their properties and applications of brain tumor therapy, discusses the advantages and drawbacks of UABD nanomedicines for the treatment of brain tumors, and offers their prospects. We hope to encourage researchers from various fields to participate in this area and collaborate on developing UABD nanomedicines into powerful tools for brain tumor therapy.

Graphical Abstract
Multistage nucleic acid amplification induced nano-aggregation for 3D hotspots-improved SERS detection of circulating miRNAs
Authors: Sun Yudie , Fang La , Yi Yang , Feng Aobo , Zhang Kui , Xu Jing-Juan
Published: June 2022

Circulating miRNAs in the blood can regulate disease development and thus indicate disease states via their various expression levels. For these reasons, circulating miRNAs constitute useful biomarkers, and an approach to the accurate detection of circulating miRNAs is attractive in the diagnosis and treatment of diseases. However, methods for clinical detecting of circulating miRNA that take both sensitivity and practicality into account are still needed. Therefore, we aimed herein to solve some inherent problems in the actual detection using a robust surface-enhanced Raman scattering (SERS) platform with integrated nucleic acid amplification and nanoparticle aggregation to construct 3D hotspots for improving performance of analyzing circulating miRNAs. After target recognition and initial signal amplification by DNAzyme, we observed that release triggered an open hairpin DNA on gold nanoparticles (AuNPs), which then promote AuNP aggregation, causing the accumulation of a large number of hotspots in three-dimention. The SERS biosensor achieved a better performance than the sandwich-type separation detection, with a low detection limit (0.37 fM) and a broad linear range (1 fM–10 nM) in liquids. This SERS platform can be used as a powerful tool for the detection of circulating miRNAs, and it can be used to improve the sensitivity and accuracy of various clinical-disease diagnoses.

Graphical Abstract
Health system learning with Indigenous communities: a study protocol for a two-eyed seeing review and multiple case study
Authors: Milligan Crystal , Mantla Rosa , Blake Grace , Zoe John B. , Steinwand Tyanna , Greenland Sharla , Keats Susan , Nash Sara , Kakfwi-Scott Kyla , Veldhorst Georgina , Mashford-Pringle Angela , Stewart Suzanne , Chatwood Susan , Berta Whitney , Dobrow Mark J.
Published: June 2022

Background

It is well documented that Canadian healthcare does not fully meet the health needs of First Nations, Inuit or Métis peoples. In 1996, the Royal Commission on Aboriginal Peoples concluded that Indigenous peoples’ healthcare needs had to be met by strategies and systems that emerged from Indigenous worldviews and cultures. In 2015, the Truth and Reconciliation Commission also called on health organizations to learn from Indigenous knowledges and integrate Indigenous worldviews alongside biomedicine and other western ways of knowing. These calls have not yet been met. Meanwhile, the dynamic of organizational learning from knowledges and evidence within communities is poorly understood—particularly when learning is from communities whose ways of knowing differ from those of the organization. Through an exploration of organizational and health system learning, this study will explore how organizations learn from the Indigenous communities they serve and contribute to (re-)conceptualizing the learning organization and learning health system in a way that privileges Indigenous knowledges and ways of knowing.

Methods

This study will employ a two-eyed seeing literature review and embedded multiple case study. The review, based on Indigenous and western approaches to reviewing and synthesizing knowledges, will inform understanding of health system learning from different ways of knowing. The multiple case study will examine learning by three distinct government organizations in Northwest Territories, a jurisdiction in northern Canada, that have roles to support community health and wellness: Tłı̨chǫ Government, Gwich’in Tribal Council, and Government of Northwest Territories. Case study data will be collected via interviews, talking circles, and document analysis. A steering group, comprising Tłı̨chǫ and Gwich’in Elders and representatives from each of the three partner organizations, will guide all aspects of the project.

Discussion

Examining systems that create health disparities is an imperative for Canadian healthcare. In response, this study will help to identify and understand ways for organizations to learn from and respectfully apply knowledges and evidence held within Indigenous communities so that their health and wellness are supported. In this way, this study will help to guide health organizations in the listening and learning that is required to contribute to reconciliation in healthcare.
Non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement: a single-centre retrospective study
Authors: Frise Matthew C. , Holdsworth David A. , Sandhu Manraj S. , Mellor Adrian J. , Kasim Adetayo S. , Hancock Helen C. , Maier Rebecca H. , Dorrington Keith L. , Robbins Peter A. , Akowuah Enoch F.
Published: June 2022

Background

Iron deficiency has deleterious effects in patients with cardiopulmonary disease, independent of anemia. Low ferritin has been associated with increased mortality in patients undergoing cardiac surgery, but modern indices of iron deficiency need to be explored in this population.

Methods

We conducted a retrospective single-centre observational study of 250 adults in a UK academic tertiary hospital undergoing median sternotomy for non-emergent isolated aortic valve replacement. We characterised preoperative iron status using measurement of both plasma ferritin and soluble transferrin receptor (sTfR), and examined associations with clinical outcomes.

Results

Measurement of plasma sTfR gave a prevalence of iron deficiency of 22%. Patients with non-anemic iron deficiency had clinically significant prolongation of total hospital stay (mean increase 2.2 days; 95% CI: 0.5–3.9; P = 0.011) and stay within the cardiac intensive care unit (mean increase 1.3 days; 95% CI: 0.1–2.5; P = 0.039). There were no deaths. Defining iron deficiency as a plasma ferritin < 100 µg/L identified 60% of patients as iron deficient and did not predict length of stay. No significant associations with transfusion requirements were evident using either definition of iron deficiency.

Conclusions

These findings indicate that when defined using sTfR rather than ferritin, non-anemic iron deficiency predicts prolonged hospitalisation following surgical aortic valve replacement. Further studies are required to clarify the role of contemporary laboratory indices in the identification of preoperative iron deficiency in patients undergoing cardiac surgery. An interventional study of intravenous iron targeted at preoperative non-anemic iron deficiency is warranted.
Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure
Authors: Segev Amitai , Lavee Jacob , Kassif Yigal , Shemesh Yedida , Kogan Alexander , Freimark Dov , Morgan Avi , Lotan Dor , Itelman Edward , Grupper Avishay
Published: June 2022

Objective

Investigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation.

Methods

Consecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012–2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up.

Results

Final cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64).

Conclusions

Levosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.
Increasing African genomic data generation and sharing to resolve rare and undiagnosed diseases in Africa: a call-to-action by the H3Africa rare diseases working group
Authors: Lumaka Aimé , Carstens Nadia , Devriendt Koenraad , Krause Amanda , Kulohoma Benard , Kumuthini Judit , Mubungu Gerrye , Mukisa John , Nel Melissa , Olanrewaju Timothy O. , Lombard Zané , Landouré Guida ,   as members of the Rare Disease Working Group of the H3Africa Consortium
Published: June 2022

The rich and diverse genomics of African populations is significantly underrepresented in reference and in disease-associated databases. This renders interpreting the Next Generation Sequencing (NGS) data and reaching a diagnostic more difficult in Africa and for the African diaspora. It increases chances for false positives with variants being misclassified as pathogenic due to their novelty or rarity. We can increase African genomic data by (1) making consent for sharing aggregate frequency data an essential component of research toolkit; (2) encouraging investigators with African data to share available data through public resources such as gnomAD, AVGD, ClinVar, DECIPHER and to use MatchMaker Exchange; (3) educating African research participants on the meaning and value of sharing aggregate frequency data; and (4) increasing funding to scale-up the production of African genomic data that will be more representative of the geographical and ethno-linguistic variation on the continent. The RDWG of H3Africa is hereby calling to action because this underrepresentation accentuates the health disparities. Applying the NGS to shorten the diagnostic odyssey or to guide therapeutic options for rare diseases will fully work for Africans only when public repositories include sufficient data from African subjects.
Lived experiences of children and adolescents with obsessive–compulsive disorder: interpretative phenomenological analysis
Authors: Sravanti Lakshmi , Kommu John Vijay Sagar , Girimaji Satish Chandra , Seshadri Shekhar
Published: June 2022

Background

Childhood obsessive–compulsive disorder (OCD) is distinct from OCD in adults. It can be severely disabling and there is little qualitative research on OCD in children. The present study aims to explore the subjective experiences of diagnosis, treatment processes and meaning of recovery in children and adolescents suffering from OCD and provide a conceptual model of the illness.

Methods

It is a qualitative study of ten children and adolescents selected by purposive sampling. MINI KID 6.0, Children’s Yale-Brown Obsessive–Compulsive Scale and Clinical Global Impression-Severity Scale were administered at the time of recruitment of subjects into the study. Interviews were conducted using an in-depth semi-structured interview guide and audio-recorded. The transcribed interviews were analyzed using Interpretative Phenomenological Analysis (IPA). The study sought to explore participants’ sense-making of their world, their thoughts, feelings and perceptions through interpretative enquiry. The findings were confirmed by a process called investigator triangulation, member check and peer validation.

Results

IPA yielded five major themes—‘illness perception changes over time’, ‘disclosure on a spectrum’, ‘cascading effects of OCD’, ‘treatment infuses hope and helps’, and ‘navigating through OCD’. A summary of these themes and their subthemes is presented as a conceptual model. The essence of this model is to show the inter-relationship between themes and provide a comprehensive understanding of the phenomenon of OCD.

Conclusions

To the best of our knowledge, this is the first study to explore lived experiences of children and adolescents with OCD using interpretative phenomenological analysis (IPA). It was noted that perception of illness and treatment processes evolves over time, and recovery is viewed as a process. Future qualitative research can be carried out with a focus on ‘therapist-related barriers’ or ‘student–teacher dyads’ that can inform clinical practice and school policies respectively.

Trial registration NIMH/DO/IEC (BEH. Sc. DIV)/2018, l1 April 2018.
The regulation of insulin receptor/insulin-like growth factor 1 receptor ratio, an important factor for breast cancer prognosis, by TRIP-Br1
Authors: Nguyen Thi Ngoc Quynh , Jung Samil , Nguyen Hai Anh , Lee BeomSuk , Vu Son Hai , Myagmarjav Davaajargal , Eum Hye Hyeon , Lee Hae-Ock , Jo Taeyeon , Choi Yeongseon , Lee Myeong-Sok
Published: June 2022

Much higher risk of cancer has been found in diabetes patients. Insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) have been extensively studied in both breast cancer and diabetes therapies. Interestingly, a recent study proposed that IR/IGF1R ratio is an important factor for breast cancer prognosis. Women with higher IR/IGF1R ratio showed poor breast cancer prognosis as well as hyperinsulinemia. Here, we propose a novel mechanism that oncogenic protein TRIP-Br1 renders breast cancer cells and insulin deficient mice to have higher IR/IGF1R ratio by positively and negatively regulating IR and IGF1R expression at the protein level, respectively. TRIP-Br1 repressed IR degradation by suppressing its ubiquitination. Meanwhile, TRIP-Br1 directly interacts with both IGF1R and NEDD4-1 E3 ubiquitin ligase, in which TRIP-Br1/NEDD4-1 degrades IGF1R via ubiquitin/proteasome system. TRIP-Br1-mediated higher IR/IGF1R ratio enhanced the proliferation and survival of breast cancer cells. In conclusion, current study may provide an important information in the regulatory mechanism of how breast cancer cells have acquired higher IR/IGF1R ratio.
Treatment fidelity monitoring, reporting and findings in a complex aphasia intervention trial: a substudy of the Very Early Rehabilitation in SpEech (VERSE) trial
Authors: Godecke Erin , Brogan Emily , Ciccone Natalie , Rose Miranda L. , Armstrong Elizabeth , Whitworth Anne , Ellery Fiona , Holland Audrey , Middleton Sandy , Rai Tapan , Hankey Graeme J. , Cadilhac Dominique , Bernhardt Julie
Published: June 2022

Background

Treatment fidelity is inconsistently reported in aphasia research, contributing to uncertainty about the effectiveness of types of aphasia therapy following stroke. We outline the processes and outcomes of treatment fidelity monitoring in a pre-specified secondary analysis of the VERSE trial.

Methods

VERSE was a 3-arm, single-blinded RCT with a 12-week primary endpoint comparing Usual Care (UC) to two higher intensity treatments: Usual Care-Plus (UC-Plus) and VERSE, a prescribed intervention. Primary outcome results were previously reported. This secondary analysis focused on treatment fidelity. Video-recorded treatment sessions in the higher intensity study arms were evaluated for treatment adherence and treatment differentiation. Treatment components were evaluated using a pre-determined fidelity checklist. Primary outcome: prescribed amount of therapy time (minutes); secondary outcomes: (i) adherence to therapy protocol (%) and (ii) treatment differentiation between control and high intensity groups.

Results

Two hundred forty-six participants were randomised to Usual Care (n=81), Usual Care-Plus (n=82), and VERSE (n=83). One hundred thirty-five (82%) participants in higher intensity intervention arms received the minimum prescribed therapy minutes. From 10,805 (UC 7787; UC-Plus 1450; VERSE 1568) service events, 431 treatment protocol deviations were noted in 114 participants. Four hundred thirty-seven videos were evaluated. The VERSE therapists achieved over 84% adherence to key protocol elements. Higher stroke and aphasia severity, older age, and being in the UC-Plus group predicted more treatment deviations.

Conclusions

We found high levels of treatment adherence and differentiation between the intervention arms, providing greater confidence interpreting our results. The comprehensive systems for intervention fidelity monitoring and reporting in this trial make an important contribution to aphasia research and, we argue, should set a new standard for future aphasia studies.

Trial registration

ACTRN 12613000776707
Internet-based vestibular rehabilitation versus standard care after acute onset vertigo: a study protocol for a randomized controlled trial
Authors: Surano Solmaz , Grip Helena , Öhberg Fredrik , Karlsson Marcus , Faergemann Erik , Bjurman Maria , Davidsson Hugo , Ledin Torbjörn , Lindell Ellen , Mathé Jan , Tjernström Fredrik , Tomanovic Tatjana , Granåsen Gabriel , Salzer Jonatan
Published: June 2022

Background

Dizziness and vertigo affect around 15% of adults annually and represent common reasons for contacting health services, accounting for around 3% of all emergency department visits worldwide. Vertigo is also associated with excessive use of diagnostic imaging and emergency care and decreased productivity, primarily because of work absenteeism. Vestibular rehabilitation is an evidence-based treatment for chronic dizziness and supervised group exercise therapy has recently been shown to be effective after vestibular neuritis, a common cause of acute onset vertigo. However, such interventions are not readily available and there is a need for more easily accessible tools. The purpose of this study is to investigate the effects on vestibular symptoms of a 6-week online vestibular rehabilitation tool after acute onset vertigo, with the aim of aiding vestibular rehabilitation by presenting a more accessible tool that can help to reduce recovery time.

Methods

Three hundred twenty individuals diagnosed with acute vestibular syndrome (AVS) will be recruited from multiple hospitals in Sweden and the effects of an online vestibular rehabilitation tool, YrselTräning, on vestibular symptoms after acute onset vertigo will be compared to standard care (written instructions leaflet) in a two-armed, evaluator-blinded, multicenter randomized controlled trial. The primary outcome will be the Vertigo Symptom Scale Short Form (VSS-SF) score at 6 weeks after symptom onset. Secondary outcomes include effects of the intervention on activities of daily living, mood and anxiety, vestibular function recovery, mobility measures, health economic effects, and the reliability of the Swedish VSS-SF translation.

Discussion

Participants using the online vestibular rehabilitation tool are expected to recover earlier and to a greater extent from their symptoms as compared to standard care. Since up to 50% of people with AVS without treatment develop persistent symptoms, effective treatment of AVS will likely lead to a higher quality of life and help reduce the societal costs associated with dizziness and vertigo.

Trial registration

Clinicaltrials.gov NCT05056324. Registered on September 24, 2021.
Molecular detection of Leishmania infantum in rats and sand flies in the urban sewers of Barcelona, Spain
Authors: Galán-Puchades María Teresa , Solano Jennifer , González Gloria , Osuna Antonio , Pascual Jordi , Bueno-Marí Rubén , Franco Sandra , Peracho Víctor , Montalvo Tomás , Fuentes Màrius V.
Published: June 2022

Background

Classically, dogs have been considered to be the only reservoir of leishmaniasis in urban areas. However, in a previous study, we found a 33.3% prevalence of Leishmania infantum in the spleens of Norway rats (Rattus norvegicus) sampled in the underground sewer system of the city of Barcelona (Spain). The aim of the present study was to verify, using molecular methods, the potential reservoir role of these rats in the same sewer system.

Methods

A sensitive real-time PCR (qPCR) assay, DNA sequencing and phylogenetic analysis were carried out to identify and quantify the presence of L. infantum DNA in sand fly individuals captured in the same underground sewer system of Barcelona as in our previous study and in the spleens and ears of rats captured in the same sewer system.

Results

Leishmania infantum DNA was found in 14 of the 27 (51.9%) sand flies identified as Phlebotomus perniciosus, and 10 of the 24 (41.7%) rats studied were infected. Leishmania infantum was found in the spleens (70%) and in the ears (40%) of the infected rats. Quantitative results revealed the presence of high loads of L. infantum in the rats studied (> 3 × 106 parasites/g ear tissue) and among the sand flies (> 34 × 106 parasites in 1 individual).

Conclusions

The molecular methods used in this study demonstrated a high prevalence of L. infantum in the underground
sewer populations of both R. norvegicus and P. perniciosus. These results suggest that sewer rats, in addition to dogs, are likely to act as reservoirs of leishmaniasis in cities, where sewer systems seem to offer the ideal scenario for the transmission of leishmaniasis. Therefore, to achieve the WHO 2030 target on the elimination of leishmaniasis as a public health problem successfully, an efficient control strategy against leishmaniasis in rats and sand flies should be implemented, particularly in the sewer systems of urban areas of endemic countries.

Graphical Abstract
Therapeutic effects of Lucilia sericata larval excretion/secretion products on Leishmania major under in vitro and in vivo conditions
Authors: Sherafati Jila , Dayer Mohammad Saaid , Ghaffarifar Fatemeh
Published: June 2022

Background

Leishmaniasis is a neglected infectious disease caused by protozoa of the genus Leishmania. The disease generally manifests as characteristic skin lesions which require lengthy treatment with antimonial drugs that are often associated with adverse side effects. Therefore, a number of studies have focused on natural compounds as promising drugs for its treatment. This study aimed to evaluate the effects of larval excretion/secretion products (ES) of Lucilia sericata in crude and fractionated forms on Leishmania major, by using in vitro and in vivo models.

Methods

The in vitro experiments involved evaluation of ES on both promastigotes and macrophage-engulfed amastigotes, whereas the in vivo experiments included comparative treatments of skin lesions in L. major-infected mice with Eucerin-formulated ES and Glucantime.

Results

The half maximal inhibitory concentrations of the crude ES, > 10-kDa ES fraction, < 10-kDa ES fraction, and Glucantime were 38.7 μg/ml, 47.6 μg/ml, 63.3 μg/ml, and 29.1 μg/ml, respectively. Significant differences were observed between percentage viabilities of promastigotes treated with the crude ES and its fractions compared with the negative control (P < 0.0001). The crude ES was more effective on amastigotes than the two ES fractions at 300 μg/ml. The macroscopic measurements revealed that the reduction of lesion size in mice treated with the crude ES followed quicker cascades of healing than that of mice treated with Glucantime and the ES fractions.

Conclusions

The present study showed that the larval ES of L. sericata in both crude and fractionated forms are effective for both intracellular and extracellular forms of L. major. Also, the ES exert both topical and systemic effects on mice experimentally infected with L. major.

Graphical abstract
Susceptibility of Aedes albopictus and Culex quinquefasciatus to Japanese encephalitis virus
Authors: Hernández-Triana Luis M. , Folly Arran J. , Sewgobind Sanam , Lean Fabian Z. X. , Ackroyd Stuart , Nuñez Alejandro , Delacour Sarah , Drago Andrea , Visentin Patrizia , Mansfield Karen L. , Johnson Nicholas
Published: June 2022

Background

Japanese encephalitis virus (JEV) is the principal cause of mosquito-borne encephalitis in human populations within Asia. If introduced into new geographic areas, it could have further implications for public and animal health. However, potential mosquito vectors for virus transmission have not been fully investigated. The Asian tiger mosquito, Aedes albopictus, has emerged in Europe and is now expanding its geographical range into more northerly latitudes. Culex quinquefasciatus, although absent from Europe, has been detected in Turkey, a country with territory in Europe, and could act as a vector for JEV in other regions. To assess the risk of these invasive species acting as vectors for JEV and therefore potentially contributing to its geographical expansion, we have investigated the vector competence of Ae. albopictus and Cx. quinquefasciatus.

Methods

Two colonised lines of Ae. albopictus (Italy and Spain) and a line of Cx. quinquefasciatus (Tanzania) were compared for susceptibility to infection by oral feeding with JEV strain SA-14, genotype III at 106 PFU/ml and maintained at 25 °C. Specimens were processed at 7 and 14 days post-inoculation (dpi). Rates of infection, dissemination and transmission were assessed through detection of viral RNA by real-time polymerase chain reaction (RT-PCR) in mosquito body, legs and saliva, respectively, at each time point. Where possible, infection and dissemination were confirmed by immunohistochemical (IHC) detection of the JEV envelope protein.

Results

Aedes albopictus from Italy showed no susceptibility to infection with JEV strain SA-14. Conversely, Ae. albopictus colonised in Spain was susceptible and 100% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Culex quinquefasciatus was highly susceptible to infection as early as 7 dpi and 50% of infected mosquitoes that were subjected to saliva screening expressed viral RNA at 14 dpi. Infection and dissemination were confirmed in Cx. quinquefasciatus by IHC detection of JEV envelope protein in both the mid-gut and salivary glands.

Conclusions

Aedes albopictus from two different locations in Europe range from being susceptible to JEV and capable of transmission through to being resistant. Culex quinquefasciatus also appears highly susceptible; therefore, both species could potentially act as vectors for JEV and facilitate the emergence of JEV into new regions.

Graphical Abstract
Influence of initial glucocorticoid co-medication on mortality and hospitalization in early inflammatory arthritis: an investigation by record linkage of clinical and administrative databases
Authors: Sakellariou Garifallia , Scirè Carlo Alberto , Rumi Federica , Carrara Greta , Zanetti Anna , Cerra Carlo , Migliazza Simona , Bugatti Serena , Montecucco Carlomaurizio
Published: June 2022

Background

While low-dose oral glucocorticoids (GCs) are recommended in the management of early arthritis, their impact on mortality is unclear. The aim of this study is to evaluate the effect of GCs on mortality in patients with early arthritis, by linking clinical and administrative databases.

Methods

The study included patients with new-onset rheumatoid arthritis (RA) or undifferentiated arthritis (2005–2010), who received DMARDs (MTX in RA or UA with poor prognosis, hydroxychloroquine in UA) and were alive at the second year of follow-up. Low-dose GCs could be prescribed. Clinical and administrative data were linked from Administrative Health Databases (AHD) of the corresponding province, which provided us with information on drug delivery, comorbidities, hospitalization, and mortality. The effect of GCs in the first year was defined using a dichotomous variable or a 3-level categorization (not delivered, ≤7.5 mg/day, or >7.5 mg/day of prednisone) on all-cause mortality, assessed with Cox regression, either crude or adjusted for age, gender, Charlson Comorbidity Index (CCI) or single comorbidities, ACPA, HAQ, and MTX in the first year. A secondary analysis of the effect of GCs on related hospitalizations (for cardiovascular events, diabetes, serious infections, osteoporotic fractures) was also carried.

Results

Four hundred forty-nine patients were enrolled (mean age 58.59, RA 65.03%) of which 51 (11.36%) died during the study. The median (IQR) follow-up was equal to 103.91 (88.03–126.71) months. Treatments with GCs were formally prescribed to 198 patients (44.10%) at ≤7.5 mg/day, although by the end of the study such treatments were received by 257 patients (57.24%); 88 patients (19.6%) were treated with GCs at >7.5 mg/day. In adjusted analyses, the GC delivery (HR, 95% CI 1.35 (0.74, 2.47)) did not significantly predict mortality — both at a low (HR, 95% CI 1.41 (0.73, 2.71)) and at a high (HR, 95% CI 1.23 (0.52, 2.92)) dosage. When “all-cause hospitalization” was used as an outcome, the analysis did not show a difference between patients receiving GC and patients not receiving GC.

Conclusion

In patients with early inflammatory arthritis, the initial GC dose was higher than that prescribed by rheumatologists; however, on background treatment with DMARDs, GC treatments did not seem to increase mortality and hospitalizations.
Isolated bursal-side infraspinatus tear diagnosed by computed tomography bursography: a case series
Authors: Onada Yoshihiro , Sasanuma Hideyuki , Umemoto Takahisa , Kajino Tomomichi , Shimizu Tadashi
Published: June 2022

Background

Partial-thickness rotator cuff tears are commonly found in the articular-side tendon of the supraspinatus; however, isolated lesions, except those occurring in the supraspinatus tendons, are rare. We report three cases of isolated bursal-side infraspinatus tears that were difficult to detect by magnetic resonance imaging but could be visualized by computed tomography bursography.

Case presentation

Three Asian patients (59–71 years old) with shoulder pain ranging from 1 month to 3 years in duration were each diagnosed with shoulder impingement syndrome. Magnetic resonance imaging studies failed to show a tear of the rotator cuff tendon complex. However, computed tomography bursography showed a longitudinal infraspinatus partial-thickness tear on the bursal side in each case. Arthroscopic decompression of the subacromial space and debridement of the infraspinatus tendon tear successfully alleviated the shoulder pain in two of the three patients; the third patient did not undergo surgery and remained symptomatic at follow-up.

Conclusions

In patients with chronic shoulder pain but normal magnetic resonance imaging findings, computed tomography bursography should be considered, as bursal-side infraspinatus tears may be found in these patients. Furthermore, our findings provide a basis for larger studies to further establish the accuracy of computed tomography bursography for these lesions.