bluuebunny/crossref_metadata_2025 huggingface dataset:
The Neurotoxicity of Organic Solvents Studied Using Synaptosomes and Neural Cell Cultures
Authors: Naskali Leila , Engelke Maria , Tähti Hanna
Published: August 2020

The most common acute neurotoxic effect of organic solvents is their central nervous system (CNS) depressant effect. The molecular mechanism underlying this effect is not known. The purpose of our studies has been to evaluate the adverse effects of organic solvents on the CNS in vitro. Synaptosomal membranes, whole brain reaggregate and astrocyte cultures were studied. Our results suggest that cell membrane integral proteins are targets for solvent impact, but that there are differences among various cell types. In addition to lipophilicity, the structure of solvent molecules seems to be important when considering CNS toxicity. Organic solvents increase the fluidity of the membranes, which may disturb the lipid-protein interaction and the optimal functioning of the enzyme. However, direct effects of solvents on proteins cannot be excluded. In vitro cell models can be used in methods designed to predict acute neurotoxic effects of foreign compounds, and in studies of neurotoxic mechanisms.
In Vitro Toxicology and the Test Guidelines
Authors: Louekari Kimmo
Published: August 2020

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.
In Vitro Cytotoxicity Testing of a Candidate Drug Delivery Material
Authors: Sbarbati-DelGuerra Rosella , Maltinti Simona , Cerrai Piero , Tricoli Mario , Guerra Giulio D.
Published: August 2020

Samples of a newly synthesised class of macromolecular compound, poly(N-allyl acrylamide)s, obtained by thermal condensation at 200°C of a polyelectrolyte complex, polyfallylammonium acrylate), were tested for both cytotoxicity and water absorption. The cytotoxicity tests (Level I), carried out on both an unmodified complex and a fully condensed polyamide, indicate that these materials exert no acute toxicity on 3T3 fibroblast cells. The water absorption tests, carried out on both partially condensed and fully condensed polyamides, at three different pH values, indicate that these materials are suitable to be used for the controlled delivery of drugs containing ionic or polar groups.
Family physicians’ perspective on voluntary stopping of eating and drinking: a cross-sectional study
Authors: Stängle Sabrina , Schnepp Wilfried , Büche Daniel , Häuptle Christian , Fringer André
Published: August 2020

Objective

We aimed to determine how often patients who choose voluntary stopping of eating and drinking (VSED) are accompanied by Swiss family physicians, how physicians classify this process, and physicians’ attitudes and professional stance toward VSED.

Methods

We conducted a cross-sectional study between August 2017 and July 2018 among 751 practicing family physicians in Switzerland (response rate 74%; 70.7% men; average age 58 (±9) years). We used a standardized evidence-based questionnaire for the survey.

Results

VSED is well-known among family physicians (81.9%), and more than one-third (42.8%) had accompanied at least one patient during VSED. In 2017, 1.1% of all deaths that occurred in Swiss nursing homes or in a private home were owing to VSED. This phenomenon was classified as a natural dying process (59.3%), passive euthanasia (32.0%), or suicide (5.3%).

Conclusions

Although about one in three Swiss family physicians have accompanied a person during VSED, family physicians lack sufficient in-depth knowledge to address patients and their relatives in an appropriate manner during the process. Further training and development of practice recommendations are needed to achieve more standardized accompaniment of VSED. International Registered Report Identifier: DERR1-10.2196/10358
MicroRNA-122 as a diagnostic biomarker for hepatocellular carcinoma related to hepatitis C virus: a meta-analysis and systematic review
Authors: Wei Xiao-yu , Ding Jing , Tian Wen-guang , Yu Yi-Chuan
Published: August 2020

Objective

MicroRNA-122 (miR-122) has been identified as a biomarker of liver diseases. However, the miR-122 detection accuracy in patients with hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) is inconclusive.

Methods

We conducted a systematic literature search of Web of Science, Cochrane Library, PubMed, and Embase to identify studies related to the diagnostic value of miR-122 in HCV-related HCC. We analyzed the results and validated them using data from the Cancer Genome Atlas (TCGA).

Results

Six articles were included in this meta-analysis, comprising 354 cases and 420 controls. The pooled specificity, sensitivity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve were 0.87, 0.83, 5.1, 0.16, 32, and 0.92, respectively. Additional sub-group analyses showed that results for plasma were more sensitive than those for serum. In addition, miR-122 was better at distinguishing between HCV-associated HCC and healthy people or those with HCV than between those with HCV-associated HCC and HCV-related cirrhosis. Small samples (≤100) had better diagnostic odds ratios than larger samples (>100). Analysis of data from TCGA confirmed that miRNA-122 had a high diagnostic value.

Conclusion

This meta-analysis demonstrates that miR-122 may be a useful diagnostic biomarker for HCV-associated HCC.
Protective effects of irbesartan and benazepril against vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats
Authors: Ma Ruixin , Zhao Yang , Yu Xiaorong , Li Ningyin , Wang Qiongying , Liang Wei , Zhao Xu , Yu Jing
Published: August 2020

Objective

To compare the potential beneficial effects of the angiotensin converting enzyme inhibitor (ACEI) benazepril and the angiotensin II receptor 1 blocker (ARB) irbesartan on vaginal vascular remodeling and fibrosis in female spontaneously hypertensive rats (SHRs).

Methods

Twelve-week-old female SHRs were treated with irbesartan or benazepril for 12 weeks. Vaginal renin angiotensin system (RAS) components were detected by polymerase chain reaction and western blot and vaginal α-smooth muscle actin (α-SMA), endothelial nitric oxide synthase (eNOS), and collagen III (Col III) were analyzed by western blot. Vaginal tissue sections were examined by hematoxylin and eosin staining, Masson trichrome staining, and immunohistochemical analysis of α-SMA and Col III.

Results

Irbesartan and benazepril had different impacts on vaginal RAS components. Both agents decreased vaginal α-SMA and Col III and increased eNOS expression in SHR. The wall/lumen thickness ratio of vaginal arterioles was similarly decreased following irbesartan and benazepril treatment. Both drugs also decreased collagen deposition in SHRs. There was no difference in vaginal vascular remodeling or fibrosis between the two groups.

Conclusions

Irbesartan and benazepril have different effects on vaginal RAS expression but similar positive effects against vaginal vascular remodeling and fibrosis.
Ulnar Collateral Ligament Reconstruction in Adolescents: A Systematic Review
Authors: Hadley Christopher J. , Edelman David , Arevalo Alfonso , Patel Nimit , Ciccotti Michael G. , Dodson Christopher C.
Published: August 2020

Background:

Ulnar collateral ligament (UCL) reconstruction is an established surgical technique to restore UCL deficiency, especially in the overhead throwing athlete. Over the past decade, the number of patients requiring UCL reconstruction has increased significantly, particularly in the adolescent patient population. Return-to-play rates after UCL reconstruction reported in the literature have ranged from 33% to 92%, and a recent systematic review noted a return-to-play rate of 89.40% in all high school athletes.

Purpose:

To evaluate the outcomes, particularly return-to-play rates and subjective outcome scores, of UCL reconstruction of the elbow in adolescent throwing athletes.

Study Design:

Systematic review.

Methods:

A systematic review of the literature was conducted via the electronic databases Embase, PubMed, and Cochrane. Studies that reported on outcomes, particularly return-to-play rates, in adolescent throwing athletes met the inclusion criteria and were included in our analysis. Studies that did not report on adolescent throwing athletes and studies that reported on adolescent throwing athletes but did not specify the return-to-play outcomes for these athletes were excluded from our analysis.

Results:

Nine studies met the inclusion criteria and were included in this review. There were 404 baseball players and 10 javelin throwers included in our analysis. A total of 349 of the 414 patients (84.30%) were successfully able to return to play at the same level of competition or higher. Successful rates of return to prior performance ranged from 66.67% to 91.49% in our analysis. Javelin throwers had a mean 80.00% rate of return to prior performance, while baseball players had a mean return-to-play rate of 84.40%. Complications were evaluated for 8 (88.9%) studies and 283 (68.4%) patients. There were 11 (3.9%) reported complications and 5 (1.8%) reoperations.

Conclusion:

The findings of this systematic review revealed that adolescent patients are generally able to return to their preinjury level of performance or higher with limited complications. Further investigation is necessary to determine long-term outcomes for return to play after UCL reconstruction of the elbow in adolescent throwing athletes.
STEM and Soft Occupational Competencies: Analyzing the Value of Strategic Regional Human Capital
Authors: Stewart Fran , Yeom Minkyu , Stewart Alice
Published: August 2020

This research examines the distribution of STEM—science, technology, engineering, and mathematics—and soft-skill competencies in occupations within regional economies in the United States. This research explores the public policy question: Do occupational competencies offer a better measure of regional human capital than the commonly used metric of educational attainment? Policy makers at all levels of government have increasingly emphasized STEM education as vital to economic well-being. This research finds support for the importance of STEM occupational competencies to regional median wage and productivity, but findings also indicate the important contributions of “soft skills” to regional economic well-being. This suggests new avenues for region-focused training and human capital development aligned to occupational skill demands that reward workers and benefit regions.
Environmental variability off NE Greenland (western Fram Strait) during the past 10,600 years
Authors: Zehnich Marc , Spielhagen Robert F , Bauch Henning A , Forwick Matthias , Hass H Christian , Palme Tina , Stein Ruediger , Syring Nicole
Published: August 2020

To reconstruct the climatic and paleoceanographic variability offshore Northeast Greenland during the last ~10 ka with multidecadal resolution, sediment core PS93/025 from the outermost North-East Greenland continental shelf (80.5°N) was studied by a variety of micropaleontological, sedimentological and isotopic methods. High foraminiferal fluxes, together with high proportions of ice-rafted debris and high Ca/Fe ratios, indicate a maximum in bioproductivity until ~8 ka related to a low sea-ice coverage. Sortable silt values, planktic foraminifer associations, and stable isotope data of planktic and benthic foraminifers suggest a strong westward advection of relatively warm Atlantic Water by the Return Atlantic Current during this time, with a noticeable bottom current activity. This advection may have been facilitated by a greater water depth at our site, resulting from postglacial isostatic depression. For the following mid-Holocene interval (ca. 8–5 ka), isotope data, lower foraminiferal fluxes and a shift in grain size maxima point to a lasting but successively decreasing Atlantic Water inflow, a weakening productivity, and a growing sea-ice coverage which is also revealed by the PIIIIP25 index. A final stage in the environmental development was reached at ~5 ka with the establishment of pre-industrial conditions. Low Ca/Fe ratios, low foraminiferal fluxes, low sortable silt values and the sea-ice indicating PIIIIP25 index point to a limited productivity and a weak Atlantic Water inflow by the Return Atlantic Current to our research area, as well as a higher and/or seasonally more extended sea-ice coverage during the Late Holocene. Two intervals with somewhat enhanced Atlantic Water advection around 2.0 and 1.0 ka are indicated by slightly increased foraminiferal fluxes and the reoccurrence of subpolar foraminifers. These intervals may correlate with the Roman Warm Period and the Medieval Climate Anomaly, as defined in the North Atlantic region.
Histoprotective effect of rutin against cisplatin-induced toxicities in tumor-bearing mice: Rutin lessens cisplatin-induced toxicities
Authors: Prasad R , Prasad SB
Published: August 2020

Cisplatin is an effective anticancer drug used against a variety of cancers. The full therapeutic potential of cisplatin is often hampered due to concurrent development of various side effects in the hosts. Rutin, a naturally occurring bioflavonoid shows several pharmacological activities. It has been earlier reported by us that rutin and cisplatin in combination show better antitumor activity against murine ascites Dalton’s lymphoma. As cisplatin is given to cancer-bearing hosts only, the present study was undertaken to explore the histoprotective effect of rutin against some toxicities induced by cisplatin in tumor-bearing mice. Cisplatin treatment caused severe damages in tissue architecture such as degenerated hepatocytes with nuclear condensation and sinusoidal dilatation in the liver, glomerular deterioration, infiltration of cells, and tubular congestion in the kidney, and vacuolization of Sertoli cells or dense granules in the cytoplasm and damaged seminiferous tubules in the testes. In the rutin plus cisplatin combination-treated mice, all the abnormal tissue architectural features were decreased. Further, as compared to cisplatin treatment, combination treatment did not show any significant elevation in the liver functional biomarkers (serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) and renal functional biomarkers (serum urea and creatinine levels). The combination treatment reduced the sperm abnormalities also as compared to the cisplatin alone treatment. The in vitro hemolysis assay of red blood cells and scanning electron microscopy revealed that combination treatment lessened the cisplatin-induced hemolysis and abnormalities in RBCs. Thus, the present findings demonstrate that rutin has histoprotective ability against cisplatin-induced toxicities in tumor-bearing mice.
On the evolution of library and information science doctoral dissertation topics in China
Authors: Song Yanhui , Zhu Li , Shu Fei
Published: August 2020

Previous studies have presented a radical change in library and information science research topics in North America. This article investigates library and information science doctoral dissertations in China in terms of their topics and interdisciplinarity in the past 20 years. The results do not find a significant change in library and information science dissertation topics in China but reveal that the increase of library and information science doctoral research in the area of information science is attributed to an increase in admissions to Information Science majors compared to other majors (Library Science and Archive Studies). This study also shows that the academic background of library and information science doctoral advisors does not affect the interdisciplinarity of their students’ doctoral dissertations in China.
Learning to Like or Dislike: Revealing Similarities and Differences Between Evaluative Learning Effects
Authors: De Houwer Jan , Hughes Sean
Published: August 2020

Researchers study phenomena such as the mere-exposure effect, evaluative conditioning, and persuasion to learn more about the ways in which likes and dislikes can be formed and changed. Often, these phenomena are studied in isolation. Here, we review and integrate conceptual analyses that highlight ways to relate these different phenomena and that reveal new avenues for research on evaluative learning. At the core of these analyses lies the idea that evaluative learning can be defined as changes in liking that are due to regularities in the environment. We discuss how this definition allows one to distinguish different types of evaluative learning on the basis of the nature of regularities (e.g., in the presence of one stimulus vs. in the presence of two stimuli) and the function of regularities (i.e., symbolic vs. nonsymbolic).
Public Awareness Toward Coronavirus Disease-2019
Authors: Bdair Izzeddin A. , Alshloul Mohammad N. , Maribbay Gladys L.
Published: August 2020

Background

The emergence of the coronavirus disease 2019 (COVID-19) infection has become a global issue of concern. Since its occurrence, about 18 million cases have been reported globally and about 280 000 in the Kingdom of Saudi Arabia.

Aim

The aim of this study was to investigate the knowledge, attitudes, and practices of the general population toward COVID-19.

Method

A cross-sectional study was conducted. A questionnaire was built by the researchers that was composed of demographics, knowledge, attitudes, and practices sections.

Results

The sample was composed of 575 participants. The mean scores of knowledge, attitudes, and practices were 16.48 ± 2.90, 10.01 ± 2.18, and 8.91 ± 1.91, respectively. The Ministry of Health constitutes the main source of participants’ information.

Conclusion

The findings showed that participants have good knowledge, positive attitudes, and satisfactory practices toward COVID-19. Yet, areas of low knowledge and negative attitudes were noticed. However, further studies are recommended to design an effective measure to control the disease.
Impact of Interdisciplinary Team Care for Children With 22q11.2 Deletion Syndrome
Authors: Hickey Scott E. , Kellogg Brian , O’Brien Meghan , Hall Courtney , Kirschner Richard E. , Santoro Stephanie L. , Leonard Hayley , Baylis Adriane L.
Published: August 2020

Objective:

To evaluate disease-specific guideline adherence among children with 22q11.2 deletion syndrome receiving multidisciplinary team care through a 22q specialty clinic compared to children not receiving team care.

Design:

Retrospective chart review; quality improvement project.

Setting:

Tertiary care pediatric hospital.

Patients:

One hundred eighty-nine patients with 22q11.2 deletion syndrome were categorized into those receiving team care and those not receiving team care. Guideline adherence was compared between the 2 groups.

Main Outcome Measure(s):

Percent adherence across 8 disease-specific guidelines.

Results:

A Welch t test revealed mean adherence among patients receiving team care was significantly higher (83% vs 42%, P < .001) compared those not receiving team care. Among team patients with a single 22q Center visit, a paired samples t test showed that mean adherence increased from 63% before the clinic encounter to 86% six months after the encounter ( P < .001). Some guidelines were more likely to be associated with provider nonadherence, whereas others were more likely to be associated with patient nonadherence.

Conclusions:

Multidisciplinary team care is associated with significantly higher guideline adherence in children with 22q11DS. Additional research is needed to investigate the effect of team care on long-term health outcomes in children with 22q11DS.
Pharmacists’ Patient Care Process: State “Scope of Practice” Priorities for Action
Authors: Adams Alex J. , Weaver Krystalyn K.
Published: August 2020

To fully engage in the Pharmacists’ Patient Care Process, pharmacists must be able to (1) participate in a Collaborative Practice Agreement, (2) order and interpret laboratory tests, (3) prescribe certain medications, (4) adapt medications, (5) administer medications, and (6) effectively delegate tasks to support staff. Each of these activities is dependent on state scope of practice laws, but these laws are not binary. Various state-level restrictions allow us to view these activities on a continuum from more restrictive to less restrictive. This continuum will allow pharmacy and public health stakeholders to identify priorities for action in their states.
Designing Quality Programs that Promote Hope, Purpose and Future Readiness Among High Need, High Risk Youth: Recommendations for Shifting Perspective and Practice
Authors: Solberg V. Scott H. , Park Chong Myung , Marsay Gloria
Published: August 2020

This paper uses a social justice perspective to recommend a number of program design strategies for improving high need, high opportunity youth access to quality education, career and workforce development. Globally, high need, high opportunity youth refer to the estimated 500 million youth who live on less than $2 per day, the estimated 600 million youth who are not in school, not employed, and not in training (i.e., NEET or Opportunity Youth). The recommendations are framed using a number of U.N. Sustainable Development Goals with the central aim being to increase access to decent work.
Anterior approach to hip replacement and associated complications: an independent review
Authors: Vasantharao Praveen , Fenbury David , Khan Riaz , Fick Daniel , Dalgleish Stephen , Finsterwald Michael , Castle Hannah , Haebich Samantha
Published: August 2020

Background:

Direct anterior approach (DAA) to hip replacement is increasingly popular. Despite the well-published benefits of early recovery, the approach can be associated with a number of complications that may be underreported. We aim to report the incidence of some of these complications in a large retrospective case series.

Methods:

270 consecutive DAA hip replacements are studied which are performed by a single high-volume hip surgeon from 2013 to 2015, not including the surgeon’s learning curve. Operation and consultation records were screened, and focused questioning via telephone was employed to capture specific complications including dislocations, wound infections, lateral femoral cutaneous nerve (LFCN) injury and revision surgery.

Results:

240 of 270 patients or family were contactable. The mean age and body mass index of the cohort was 66 (range 30–89) years and 27 (range 18–40) kg/m2 respectively. The mean follow-up was 3.7 years. Wound issues were encountered in 24 patients (8.8%). There were 9 dislocations (3%). 27 (10%) patients needed revision surgery in the follow-up period. Reasons for revision included leg-length discrepancies, dislocations, ongoing pain and aseptic loosening. 9 (3.4%) patients had to return to operating theatre for reasons other than revision surgery. Symptoms of lateral femoral cutaneous nerve injury was reported by 54 patients (21%).

Conclusions:

While the short-term benefits of DAA have been widely reported, our review shows a relatively high rate of revision surgery. We feel that the enthusiasm for DAA should be tempered until further evidence is available.
Changes in Addressing Patients’ Smoking: Cross-Sectional Data from 2002 and 2014 among Physicians in Estonia
Authors: Põld Mariliis , Pärna Kersti
Published: August 2020

Background:

For health professionals, personal and contextual factors influence addressing patients’ smoking habits. The objective of the study was to describe frequency of addressing patients’ smoking in 2002 and 2014 and to analyse factors related to addressing patients’ smoking habits.

Methods:

Data of physicians from 2 postal cross-sectional surveys were used (n = 4140 in 2002, n = 5666 in 2014). The number of respondents was 2747 in 2002 and 2903 in 2014. The corrected response rate was 67.8% and 53.1%, respectively. Age-standardized frequency of addressing patients’ smoking during the last 7 days was determined. Distribution of other variables along with confidence intervals (CI) was calculated. Logistic regression was used to analyse association of addressing patients’ smoking with attitudes and perceived barriers regarding addressing patients’ smoking and with background factors. Fully adjusted odds ratios (OR) with 95% CIs were calculated.

Results:

The age-standardized prevalence of addressing patients’ smoking habits among men was 84.4% (95% CI 80.3–88.5) in 2002 and 88.3% (95% CI (84.5–92.2) in 2014, among women 82.1% (95% CI 80.2–83.9) and 89.0% (95% CI 87.2–90.8), respectively. According to logistic regression analysis, in 2014, significantly more physicians agreed that it is doctors’ responsibility to convince people to stop smoking (among men, OR 2.32; 95% CI 1.19–4.54, among women OR 1.41; 95% CI 1.06–1.88), that smoking prevention should form part of health professionals’ training, that physicians should have smoking related hand-out materials, and that lack of time was a barrier to addressing patients’ smoking. Addressing patients’ smoking was significantly associated with attitudes and perceived barriers regarding addressing patients’ smoking, age, and other background factors (among women only).

Conclusions:

Addressing patients’ smoking habits was more common in 2014 than in 2002, but the change was significant among women only. Compared to 2002, in 2014 physicians’ attitudes regarding addressing patients’ smoking were more approving. Results of this study are useful for policymakers and institutions involved in organization and development of smoking prevention training and cessation services.
An overview of neuroblastoma cell lineage phenotypes andin vitromodels
Authors: Campos Cogo Sheron , Gradowski Farias da Costa do Nascimento Thatyanne , de Almeida Brehm Pinhatti Fernanda , de França Junior Nilton , Santos Rodrigues Bruna , Cavalli Luciane Regina , Elifio-Esposito Selene
Published: August 2020

This review was conducted to present the main neuroblastoma (NB) clinical characteristics and the most common genetic alterations present in these pediatric tumors, highlighting their impact in tumor cell aggressiveness behavior, including metastatic development and treatment resistance, and patients’ prognosis. The distinct three NB cell lineage phenotypes, S-type, N-type, and I-type, which are characterized by unique cell surface markers and gene expression patterns, are also reviewed. Finally, an overview of the most used NB cell lines currently available for in vitro studies and their unique cellular and molecular characteristics, which should be taken into account for the selection of the most appropriate model for NB pre-clinical studies, is presented. These valuable models can be complemented by the generation of NB reprogrammed tumor cells or organoids, derived directly from patients’ tumor specimens, in the direction toward personalized medicine.
Understanding teacher leaders’ behaviours: Development and validation of the Teacher Leadership Inventory
Authors: Chen Junjun
Published: August 2020

The current paper aims at developing and validating a Teacher Leadership Inventory (TLI). Adopting the theoretical-empirical strategy of instrument development, the procedure consisted of taking a sample of panel experts and undertaking six sequential empirical studies with sufficient samples of teacher leaders from China. After verifying content validity, structural validity, criterion validity, and cross-validity, a 25-item multi-dimensional model on teacher leadership behaviours with five factors was identified. The resulting TLI could provide a validated instrument for future research investigating the nature of teacher leadership behaviours as an independent construct and their relations with other relevant constructs. It is expected that the TLI could serve as a more robust means for promoting the research and practice of teacher leadership.
Hyperthyroidism as a Precipitant Factor for Cerebral Venous Thrombosis: A Case Report
Authors: Elhassan Ahmed Elkhalifa Elawad , Ali Mohammed Omer Khalil , Bougaila Amina , Abdelhady Mohammed , Abuzaid Hassan
Published: August 2020

Cerebral venous sinus thrombosis (CVT) is an uncommon yet serious condition. While CVT has many known precipitants and etiologies, hyperthyroidism as a precipitant of CVT is not well understood. This study reported a case of a 41-year-old male with a 4-year history of hyperthyroidism presented with seizure. Consequently, a diagnosis of superior sagittal sinus thrombosis was confirmed by computed tomography and magnetic resonance (MR) venograms. Extensive investigations yielded no apparent underlying cause, but laboratory findings were consistent with uncontrolled hyperthyroidism. The patient improved rapidly following anticoagulation. Follow-up MR and MRV scans 2 months after treatment revealed full recanalization of the superior sagittal sinus. This case report highlighted hyperthyroidism, as a procoagulant condition, resulting specifically in superior sagittal sinus thrombosis.
A new approach to assessing reparability for seismic risk assessment of buildings
Authors: Safiey Amir , Pang Weichiang
Published: August 2020

Advanced performance-based earthquake engineering (PBEE), as documented by FEMA P-58 provisions, can well serve as the bedrock for a building-specific risk assessment framework. The methodology embraces three main sequential steps: collapse assessment, irreparability assessment, and component-wise loss estimation. The consequence of collapse or irreparability is typically assumed to be the total replacement value of the building. The irreparability model adopted by FEMA P-58 uses the residual drift of the building as the sole predictor. This article proposes a new irreparability prediction model tailored for the PBEE that is distinct because of two main features: (1) the monetary loss as a performance metric is chosen to inform the irreparability, enabling incorporation with the influence of different contributing factors, and (2) irreparability assessment is decoupled from the main body of the loss assessment and included as the post-loss analysis decision-making. Eventually, the proposed irreparability model called “post-loss analysis irreparability model (PLAIM)” is demonstrated through an illustrative example of a four-story wood light-frame building.
Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis
Authors: Harrison Tim , Canonica Giorgio Walter , Chupp Geoffrey , Lee Jason , Schleich Florence , Welte Tobias , Valero Antonio , Gemzoe Kim , Maxwell Aoife , Joksaite Sandra , Yang Shibing , Howarth Peter , Van Dyke Melissa K.
Published: August 2020

Introduction

Efficacy of mepolizumab, an anti-interleukin-5 monoclonal antibody, was demonstrated in randomised controlled trials; data on its real-world impact in routine clinical practice are starting to emerge. We assessed the effectiveness and safety of mepolizumab prescribed for patients in the real world.

Methods

REALITI-A is a global, prospective, observational cohort study, collecting data from routine healthcare visits from patients with asthma. Patients newly prescribed mepolizumab for severe asthma with 12 months of relevant medical history pre-mepolizumab (collected retrospectively) were enrolled. An initial analysis of data from early initiators who had completed 1 year of follow-up (as of February 28, 2019) was conducted. The primary objective was to compare the rate of clinically significant exacerbations (requiring oral corticosteroids (OCS) and/or hospitalisation and/or emergency department visit) before and after mepolizumab; exacerbations requiring hospitalisation and/or emergency department visit and change in maintenance OCS use were secondary objectives. Treatment-related adverse events were reported.

Results

Overall, 368 mepolizumab-treated patients were included. Rates of clinically significant exacerbations were reduced by 69% from 4.63 per person per year pre-treatment to 1.43 per person per year during follow-up (p<0.001), as were those requiring hospitalisation and/or emergency department visit (from 1.14 to 0.27 per person per year; 77% reduction). In 159 patients with maintenance OCS dose data available during the pre-treatment period, median daily dose decreased from 10.0 (pre-treatment) to 5.0 mg·day−1by week 21–24 of follow-up, sustained until week 53–56. No new safety signals were reported.

Conclusion

These data demonstrate that the effectiveness of mepolizumab is consistent with clinical trial results under real-world settings, with significant reductions in exacerbations and daily maintenance OCS dose.
Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation
Authors: Lin Jianli , Huang Nana , Li Jing , Liu Xiaoyu , Xiong Qing , Hu Chengshen , Chen Desheng , Guan Lvxin , Chang Kexin , Li Dan , Tsui Stephen Kwok-Wing , Zhong Nanshan , Liu Zhigang , Yang Ping-Chang
Published: August 2020

Background and aims

Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway.

Methods

Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model.

Results

High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues.

Conclusions

HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.
Knockdown of lincRNA PADNA promotes bupivacaine-induced neurotoxicity by miR-194/FBXW7 axis
Authors: Yuning Fan , Liang Chen , Tenghuan Wang , Zhenhua Nan , Shengkai Gong
Published: August 2020

Background

The aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity.

Methods

Mouse DRG neurons were cultured in vitro and treated with bupivacaine to establish a neurotoxicity model. Caspase3 activity, cell viability, and TUNEL assays were analyzed to assess the role of lincRNA PADNA. A dual-luciferase reporter assay was used to determine the binding target of lincRNA PANDA.

Results

The expression of lincRNA PADNA was significantly increased with increasing concentrations of bupivacaine. Functional analysis revealed that knockdown of lincRNA PADNA increased caspase3 activity and inhibited cell viability. Western blot analysis showed that knockdown of lincRNA PADNA promoted cleaved caspase3 levels. We also revealed that lincRNA PADNA may bind with miR-194. Knockdown of miR-194 rescued the function of lincRNA PADNA, suggesting that lincRNA PADNA may sponge miR-194. In addition, we provided new evidence that the lincRNA PADNA/miR-194/FBXW7 axis plays an important role in the neurotoxicity process.

Conclusion

We performed comprehensive experiments to verify the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Our study provides new evidence and clues for the prevention of neurotoxicity.
Healthy China 2030: how to control the rising trend of unintentional suffocation death in children under five years old
Authors: Kong Fanjuan , Xiong Lili , Wang Aihua , Xie Donghua , He Jian , Su Jinping , Wu Kui , Liu Zhiyu , Wang Hua
Published: August 2020

Background

To investigate the occurrence frequency, changing trends, and epidemiological distribution of unintentional suffocation in children under 5 years old.

Methods

The data were collected from the Maternal and Child Health Surveillance system from 2009 to 2018. The cause of death was classified by ICD-10. Data on unintentional suffocation death were calculated according to the characteristics of the population, time, space, cause of death and medical treatment, and constituent ratio were calculated.

Results

The mortality rate of children under 5 years old showed a downward trend, but the mortality of unintentional suffocation initially decreased and then increased. The death rate of unintentional suffocation in children less than 1-year-old was much higher than that in children aged 1 to 4 years old. The death rate of unintentional suffocation was higher in boys than in girls, and the rate was higher for rural children than for urban children. The number of low-weight and pre-term infants in the group under 1-year-old was significantly higher than that in the group of 1–4 years old. Children under 1-year-old are more likely to die at home than children aged 1 to 4 years old, and a higher proportion of younger children did not receive treatment. More than 80% of children under the age of 5 go untreated because it was too late to go to the hospital.

Conclusion

For areas and populations with a high incidence of unintentional suffocation, we suggest that priorities should include prevention, the development of a safe environment, strengthened prevention, the development of safety habits, and the popularization of first aid knowledge.
Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis
Authors: Marakhonov Andrey V. , Voskresenskaya Anna A. , Ballesta Maria Jose , Konovalov Fedor A. , Vasilyeva Tatyana A. , Blanco-Kelly Fiona , Pozdeyeva Nadezhda A. , Kadyshev Vitaly V. , López-González Vanesa , Guillen Encarna , Ayuso Carmen , Zinchenko Rena A. , Corton Marta
Published: August 2020

Background

Mutations in CRYAA, which encodes the α-crystallin protein, are associated with a spectrum of congenital cataract–microcornea syndromes.

Results

In this study, we performed clinical examination and subsequent genetic analysis in two unrelated sporadic cases of different geographical origins presenting with a complex phenotype of ocular malformation. Both cases manifested bilateral microphthalmia and severe anterior segment dysgenesis, primarily characterized by congenital aphakia, microcornea, and iris hypoplasia/aniridia. NGS-based analysis revealed two novel single nucleotide variants occurring de novo and affecting the translation termination codon of the CRYAA gene, c.520T > C and c.521A > C. Both variants are predicted to elongate the C-terminal protein domain by one-third of the original length.

Conclusions

Our report not only expands the mutational spectrum of CRYAA but also identifies the genetic cause of the unusual ocular phenotype described in this report.
Comparison of ultrasonographic versus infrared pupillary assessment
Authors: Yic Christian D. , Prada Gabriel , Paz Sergio I. , Moraes Leandro , Pontet Julio C. , Lasso Marcos E. , Biestro Alberto
Published: August 2020

Objectives

To evaluate the correlation between ultrasonographic and infrared pupillary assessments in critically ill patients, including neurocritically ill patients.

Design

Prospective, observational study.

Setting

Tertiary teaching hospital intensive care unit (ICU) in Montevideo, Uruguay.

Patients

Twenty-six adults patients with age 18 or older admitted to the intensive care unit with and without neurologic pathology. A total of 212 pupillary measures were made between ultrasonographic pupillary assessment (UPA) and infrared pupillary assessment (IPA).

Interventions

This was a study that utilized non-invasive (minimal risk) ultrasonographic and infrared pupillary assessment in patients admitted to the ICU. Time between UPA and IPA in a single patient was consistently less than 3 min.

Measurements and main results

There was a strong positive association between UPA and IPA (right eye [OD]: r = de 0.926, p-value < 0.001; left eye [OS], r = 0.965, p-value < 0.001), also observed in the group of neurocritically ill patients (OD: r = 0.935, p-value < 0.001; OS: r = de 0.965, p-value < 0.001). Taking IPA as reference measure, the percent error for all subjects was 2.77% and 2.15% for OD and OS, respectively, and for neurocritically ill patients it was 3.21% and 2.44% for OD and OS, respectively.

Conclusions

Ultrasonographic pupillary assessment is strongly correlated with infrared pupillary assessment in critically ill patients, including neurocritically ill patients. Ultrasonographic pupillary assessment is a quick, feasible, non-invasive method that allows accurate pupillary assessment, particularly neurologic function, in patients in whom a more precise measurement of the pupil is required or eye opening is not possible (e.g., periorbital edema due to traumatic brain injury).
Surgical or non-surgical treatment of traumatic skeletal fractures in adults: systematic review and meta-analysis of benefits and harms
Authors: Skou Søren T. , Juhl Carsten B. , Hare Kristoffer B. , Lohmander L. Stefan , Roos Ewa M.
Published: August 2020

Background

A comprehensive overview of treatments of common fractures is missing, although it would be important for shared decision-making in clinical practice. The aim was to determine benefits and harms of surgical compared to non-surgical treatments for traumatic skeletal fractures.

Methods

We searched Medline, Embase, CINAHL, Web of Science, and CENTRAL until November 2018, for randomized trials of surgical treatment in comparison with or in addition to non-surgical treatment of fractures in adults. For harms, only trials with patient enrollment in 2000 or later were included, while no time restriction was applied to benefits. Two reviewers independently assessed studies for inclusion, extracted data from full-text trials, and performed risk of bias assessment. Outcomes were self-reported pain, function, and quality of life, and serious adverse events (SAEs). Random effects model (Hedges’ g) was used.

Results

Out of 28375 records screened, we included 61 trials and performed meta-analysis on 12 fracture types in 11 sites: calcaneus, clavicula, femur, humerus, malleolus, metacarpus, metatarsus, radius, rib, scaphoideum, and thoraco-lumbar spine. Seven other fracture types only had one trial available. For distal radius fractures, the standardized mean difference (SMD) was 0.31 (95% CI 0.10 to 0.53,n= 378 participants) for function, favoring surgery, however, with greater risk of SAEs (RR = 3.10 (1.42 to 6.77),n= 436). For displaced intra-articular calcaneus fractures, SMD was 0.64 (0.13 to 1.16) for function (n= 244) and 0.19 (0.01 to 0.36) for quality of life (n= 506) favoring surgery. Surgery was associated with a smaller risk of SAE than non-surgical treatment for displaced midshaft clavicular fractures (RR = 0.62 (0.42 to 0.92),n= 1394). None of the other comparisons showed statistical significance differences and insufficient data existed for most of the common fracture types.

Conclusions

Of 12 fracture types with more than one trial, only two demonstrated a difference in favor of surgery (distal radius fractures and displaced intra-articular calcaneus fractures), one of which demonstrated a greater risk of harms in the surgical group (distal radius fractures). Our results highlight the current paucity of high-quality randomized trials for common fracture types and a considerable heterogeneity and risk of bias in several of the available trials.

Systematic review registration

PROSPEROCRD42015020805
Signals of adverse drug reactions communicated by pharmacovigilance stakeholders: protocol for a scoping review of the global literature
Authors: Sartori Daniele , Aronson Jeffrey K. , Onakpoya Igho J.
Published: August 2020

Background

Signals of adverse drug reactions (ADRs) form the basis of some regulatory risk-minimization actions in pharmacovigilance. Reviews of limited scope have highlighted that such signals are mostly supported by reports of ADRs or multiple types of evidence. The time that elapses between a report of a suspected ADR and the communication of a signal has not been systematically characterized. Neither has the features of reports of suspected ADRs that authors used to support putative causal relationships, although difficulties with establishing causal relationships between medicinal products and adverse events have been highlighted. The objectives of this study will be to describe the evidence underpinning signals in pharmacovigilance, the features of reports of ADRs supporting signals, and the time that it takes to communicate a signal.

Methods

We shall retrieve records from PubMed, EMBASE, Web of Science, and PsycINFO (from inception onwards), without language/design restrictions, and apply backward citation screening. We shall hand-search the websites of 35 regulatory agencies/authorities, restricted publications from the Uppsala Monitoring Centre, and drug bulletins. Signals will be requested from the competent stakeholder, if absent from websites. We shall use VigiBase, the World Health Organization’s Global Individual Case Safety Report database, to determine the dates on which ADRs were reported. We shall manage records using EndNote (v. 8.2); one reviewer will screen titles/abstracts and full texts, a second will cross-validate the findings, and a third will arbitrate disagreements. Data will be charted via the Systematic Reviews Data Repository, following the same procedures as for data retrieval. Evidence will be categorized according to the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Features of reports of ADRs will be coded. Tables will display frequencies of types of evidence and features of reports of ADRs. We shall use plots or pictograms (if appropriate) to represent the time from the first report of a suspected ADR to a signal.

Discussion

We expect the findings from this review will allow a better understanding of global patterns of similarities or differences in terms of supporting evidence and timing of communications and identify relevant research questions for future systematic reviews.

Systematic review registration

osf.io/a4xns