bluuebunny/crossref_metadata_2025 huggingface dataset:
A Staged Approach for Facilitating Joint End User, Vendor, and Multi-Disciplinary Subject Matter Expert Input to Health Information Technology Recommendations
Authors: Bass Ellen J. , Pankok Carl , Yang Yushi , Potashnik Sheryl , Bowles Kathryn H. , Sockolow Paulina S.
Published: September 2019

Design of health information technology (HIT) that improves patient outcomes is an ongoing process. We propose a methodology that takes a human factors engineering approach to develop systems-engineering-style requirements and design recommendations for both HIT and aspects beyond the scope of the HIT itself (e.g., policies and procedures). Our approach includes: (1) data collection and analysis; (2) preliminary recommendations generation; (3) recommendation review by methodological and domain subject matter experts; (4) revised recommendation review by end users; (5) revised recommendation review by HIT vendors; and (6) final recommendation generation. We illustrate the methodology by presenting a case study focusing on home health care nurses using HIT during the home care admission process.
The Importance of Testing Sets of Clinical Alarm Sounds and Navigating Tradeoffs to Translate Research Findings into Implementation
Authors: Fitzgerald Morgan , Rayo Michael F. , Reynolds Morgan E. , Abdel-Rasoul Mahmoud , Moffatt-Bruce Susan D.
Published: September 2019

Despite noticeable efforts over the last 30 years to try and resolve the clinical alarm problem, the utilization of opinion-based and nonscientific alarm interventions has resulted in ineffective solutions. The field of human factors offers many insights to permanently solving the burdens of this problem, however often times the field’s direct applications are not salient or tangible enough to organizational stakeholders. This has resulted in a utilization deficit of human factors principles in practice today. In order to progress the level of impact human factors has on the clinical alarm problem for the future, this paper discusses how a human factors team tested science-based clinical alarm solutions within a multidisciplinary medical center, and then navigated tradeoffs in order to implement these solutions into practice.
Augmented Reality Adaptive Training Principles
Authors: Militello Laura , Sushereba Christen , Hernandez Olivia , Patterson Emily S.
Published: September 2019

As augmented reality (AR) technology offers enhanced capabilities for medical simulation training, research is required to understand how to best leverage the strengths of AR. We describe a literature review that will provide the foundation for articulating and testing candidate principles for AR adaptive training design. Our goal is to articulate and test design principles for designing recognition skills training as described in the recognition-primed decision model (Klein, 1997). We identified seminal articles from the the Naturalistic Decision Making literature, and used those to seed a systematic review of the medical education and combat medic training literatures. Findings from the literature review suggest three categories of candidate design principles: 1) fidelity and realism, 2) engagement, and 3) scaffolding. Next steps will include articulating specific design principles and designing a series of studies to test them using the VPIT AR training platform.
Smart Monitoring of Population Health Risk Behaviour
Authors: Sahu Kirti Sundar , Oetomo Arlene , Morita Plinio
Published: September 2019

Monitoring population-level health-risk behaviour is integral to preventing chronic diseases (i.e., diabetes, cardiovascular disease, cancer, etc.). Physical activity and sleep are the key behaviours which influence human health. Smart technologies can be used to improve real-time monitoring of risky behaviours. The objective of this study is to explore population- and individual-level remote monitoring of sleep, indoor physical activity and sedentary behaviours in Canada using data from the Internet of Things (IoT) (ecobee smart thermostat) and fitness trackers. Method: 386 person-hours of data were collected in a pilot study (n =8) to validate the motion sensor data from ecobee smart thermostats. Then, using “Donate your Data” data from ecobee indicators of population-level health were calculated. Results: A positive Spearman correlation coefficient 0.8 (p>0.0001) was found between standard fitness tracker data and ecobee sensors validating its use for population-level analysis. Our results were similar to the Public Health Agency of Canada’s results derived from self-reported surveillance methods. Discussion: This project demonstrates the use of data from non-health sources, like ubiquitous IoT to curate population- and individual-level health indicators. We will deliver novel indicators and insights into health status through the creation of user-centered designed dashboards for individuals, researchers, and policy-makers.
Lessons Learned from Journey Mapping in Health Care
Authors: Maddox Kyle , Baggetta Donna , Herout Jennifer , Ruark Kurt
Published: September 2019

The Department of Veterans Affairs’ Human Factors Engineering team recognizes the value of journey maps as a means for communication among stakeholder groups and develops maps to showcase the experience of users with health services and technology systems. The uniqueness of health care environments caused difficulties in following available trade guidance for creating journey maps. Anticipating that other Human Factors Engineers working in health care settings will encounter similar challenges, this paper showcases our lessons learned while creating two distinct journey maps and offers a process for constructing journey maps in health care environments. We learned to selectively limit the content of journey maps, ensure design quality by utilizing a template and rubric, and apply alternate approaches for data gathering. Our improved process includes steps to partner with stakeholders, produce a journey map framework and confirm it with user research, and visualize findings in the completed journey map.
Comparison of Gait Speed Estimation of Multiple Sensor-Based Technologies
Authors: Morita Plinio P. , Rocha Adson S. , Shaker George , Lee Doojin , Wei Jing , Fong Brandon , Thatte Anjali , Karimi Amir-Hossein , Lin Xu Lin , Ma Avery , Wong Alex , Boger Jennifer
Published: September 2019

In light of our aging population, there is an immediate need for non-obtrusive, continuous, and ubiquitous health monitoring technologies that will enable our population to age with a higher quality of life and independence. Research has demonstrated that gait indicators, such as walking speed, can reflect cognitive and physical functioning. However, gradual changes in such indicators usually go undetected until critical problems arise; being able to detect changes in indicators, such as gait deterioration, of older adults while in their home environments would enable clinicians to tailor more effective and personalized interventions by better understanding user behaviour in real-world settings. Real-world data is essential to enabling our healthcare system to act where patients most need help and to optimize the effect of designed eHealth solutions.
Guidance for Custom Alarm Design: You Don’t Have to “Crank it up to 11”
Authors: Reynolds Morgan E. , Rayo Michael F. , Fitzgerald Morgan , Abdel - Rasoul Mahmoud , Moffatt - Bruce Susan D.
Published: September 2019

Changes in alarm perception and response after prolonged daily exposure is not well studied due to the difficulties in setting up rigorous longitudinal studies in real work domains. A prime example of this is the absence of research studying how conveyed urgency and identifiability of auditory alarms change over time. We conducted a three-year study to understand how alarm performance with respect to these two measures changed over time, ostensibly due to prolonged nurse exposure. Gaining a better understanding of the relationship between these two aspects of a sound’s sensory dimension could be extremely valuable to acoustical alarm designers, as it allows them to anticipate changes in the sounds’ sensory performance over time, and not be overly sensitive to first impressions of the auditory alarm set.
Identifying Medical Equipment Usability Issues from Social Media Reports
Authors: Fuller Helen J. A. , Arnold Timothy
Published: September 2019

Traditional methods of investigating usability include usability tests, heuristic evaluations, surveys, and field methods. User self-reports of equipment problems such as through the FDA MAUDE database are also available, but there may be limited information reported. Often, people turn to social media to share stories and learn from others. In this study, the authors explored using social media as a means of identifying possible usability issues with medical devices and products. As a proof of concept, the authors focused on insulin pumps, continuous glucose monitors, and sleep apnea machines. Reports of medical equipment use issues were grouped into three categories: 1) correct instructions for product use, 2) apparently inadvertent incorrect instructions for use and 3) instructions that encouraged or could promote deliberate misuse. Each of these has different implications for designers, clinical product review committee members, and clinicians.
Upside Down Hospital: Co-Producing Safety With Patients
Authors: Subbe CP , Barach P
Published: September 2019

Safety in healthcare has not significantly improved in the last 20 years with an estimated 5 to 10% of patients admitted to hospital suffering from adverse events. Health care is a service that can encourage optimal health outcomes only through meaningful, collaborative partnerships between patients and clinicians. Co-production of health services can be used as a means to rethink how health care is delivered with patients as co-creators rather than passive recipients of health care assisting healthcare organisations towards safer and more responsive care. Technology can improve patients’ agency over their care when consumers are able to personalize their experience while using an organization’s service and in return undertake specific tasks needed by the organization. Patients can be the pivot point of safer hospital care, not only in the context of face-to-face encounters in which the benefits of working together are obvious, but also in designing systems that can improve patient care, increase satisfaction and enhance the value of care.
The Patient in Patient Safety: Clinicians’ Experiences Engaging Patients as Partners in Safety
Authors: Lerner Papautsky Elizabeth , Holden Richard J. , Valdez Rupa S. , Gruss Valerie , Panzer Jeffrey , Perry Shawna J.
Published: September 2019

Patients and families play a role in the safety of care provided across clinical settings, highlighting the need to understand clinician perspectives and experiences related to their engagement. Through a panel discussion entitled, The Patient in Patient Safety: Clinicians’ Experiences Engaging Patients as Partners in Safety, we elicited clinician perspectives that have implications for human factors relevance in both, research and solution development/evaluation. We provide an overview of the panel including participants, format and content, and the resulting discussion.
Working to Instill the Entrepreneurial Mindset Across the Curriculum
Authors: Blake Hylton J. , Mikesell David , Yoder John-David , LeBlanc Heath
Published: September 2019

Over the past two decades, significant work has been done to increase the opportunities for engineering students to develop an entrepreneurial mindset (EM). These have included curricular, cocurricular, and extracurricular activities on many campuses. This article describes efforts to build the EM comprehensively into the mechanical engineering curriculum at Ohio Northern University. While several frameworks have been proposed related to the EM, the work here is motivated by the Kern Entrepreneurial Engineering Network framework (KEEN). A core group of college faculty identified the institutional definitions of the KEEN student outcomes and identified courses for deployment of these outcomes to provide comprehensive, curriculum-wide exposure to the EM. This article discusses how the work was completed, incentive and reporting structures for onboarding faculty, the adopted strategies for program assessment of the EM outcomes, and efforts to ensure long-term sustainability of the curricular modifications. Observations, challenges, and unexpected benefits are discussed, as well as anticipated next steps for college-wide implementation.
Genetic characterization of B-cell prolymphocytic leukemia: a prognostic model involving MYC and TP53
Authors: Chapiro Elise , Pramil Elodie , Diop M'boyba , Roos-Weil Damien , Dillard Clémentine , Gabillaud Clémentine , Maloum Karim , Settegrana Catherine , Baseggio Lucile , Lesesve Jean-François , Yon Mélanie , Jondreville Ludovic , Lesty Claude , Davi Frederic B , Le Garff-Tavernier Magali , Droin Nathalie M , DESSEN Philippe , Algrin Caroline , Leblond Veronique , Gabarre Jean , Bouzy Simon , eclache virginie , Gaillard Baptiste , Callet-Bauchu Evelyne , Muller Marc , LEFEBVRE Christine , NADAL Nathalie , Ittel Antoine , Struski Stephanie , Collonge-Rame Marie-Agnès , QUILICHINI BENOIT , Fert-Ferrer Sandra , Auger Nathalie , Radford-Weiss Isabelle , Wagner Lena , Scheinost Sebastian , Zenz Thorsten , Susin Santos A. , Bernard Olivier A , Nguyen-Khac Florence
Published: September 2019

Key Points

B-PLL is tightly linked to MYC aberrations (translocation or gain) and 17p (TP53) deletion. Cases of B-PLL with MYC aberration and 17p (TP53) deletion have the worst prognosis.
Protoporphyrin IX-loaded laminarin nanoparticles for anticancer treatment, their cellular behavior, ROS detection, and animal studies
Authors: Yu Yueming , Wang Bingjie , Guo Chunjing , Zhao Feng , Chen Daquan
Published: September 2019

Laminarin conjugate-based nano-scaled particles were in this study proposed as a delivery system for protoporphyrin IX (Pp IX) in photodynamic therapy (PDT) of human breast cancer cells (MCF-7). Hematin-Laminarin-Dithiodipropionic Acid-MGK, named as HLDM, was an amphiphilic carrier material with dual pH/redox sensitive that could be used to load hydrophobic drug to improve their solubility and enhance biocompatibility. Therefore, we combined photosensitizer (Pp IX) with HLDM to fabricate a novel nano-micelles, herein called Pp IX-loaded HLDM micelles. The Pp IX-loaded HLDM micelles were 149.3 ± 35 nm sized in neutral water. Phototoxicity, in vitro PDT effect, and dual sensibility to pH and redox microenvironment of Pp IX-loaded HLDM micelles were examined at different concentrations by using MCF-7 human breast cancer cells. The experiments on phototoxicity and reactive oxygen species (ROS) production proved that the micelles could produce PDT to kill the cancer cells with a certain wavelength light. The apoptosis experiment indicated that the micelles could cause nuclear damage. In vivo PDT effect of the micelles was studied by constructing the tumor-bearing nude mouse model of MCF-7 cells. In vivo studies showed that the Pp IX-loaded HLDM micelles could induce remarkable anti-tumor effect. A promising laminarin-based nanomedicine platform acts as a new drug delivery system to enhance the uptake, accumulation, and PDT efficacy of Pp IX in vitro and in vivo.
Impact of age on the seasonal prevalence of hypernatremia in the emergency department: a single-center study
Authors: Imai Naohiko , Sumi Hirofumi , Shibagaki Yugo
Published: September 2019

Background

Hypernatremia is one of the most commonly encountered electrolyte disorders in the emergency department (ED). Few studies have reported the seasonal fluctuations of the prevalence of hypernatremia with conflicting results. We investigated the seasonal prevalence of hypernatremia in an emergency department in Japan.

Methods

A total of 12,598 patients presented to the ED between January 2015 and December 2017 were reviewed. The adult group aged between 18 and 64 years old consisted of 5427 patients and the elderly group aged over 65 years consisted of 7171 patients. Information collected included age, sex, serum sodium, and serum creatinine. Hypernatremia was defined as a serum sodium leve1 > 145 mEq/L, and moderate to severe hypernatremia was defined as a serum sodium level ≥ 150 mEq/L.

Results

The prevalence of hypernatremia was significantly higher in the elderly group than in the adult group (2.6% vs. 0.7%; p < 0.001). Similarly, the prevalence of moderate to severe hypernatremia was significantly higher in the elderly group than in the adult group (1.0% vs. 0.1%; p < 0.001). The prevalence of hypernatremia and moderate to severe hypernatremia was significantly higher in the elderly group than in the adult group in all seasons. In the elderly group, the seasonal prevalence of moderate to severe hypernatremia was significantly higher during the winter. Also, there was a correlation between weather temperature and the prevalence of moderate to severe hypernatremia in the elderly group (r = − 0.34, p = 0.04).

Conclusions

Hypernatremia is prevalent in the elderly and the prevalence is highest during the winter. Special attention should be paid in the elderly patients to prevent hypernatremia especially in the winter.
A genome-wide association study explores the genetic determinism of host resistance to Salmonella pullorum infection in chickens
Authors: Li Xinghua , Nie Changsheng , Liu Yuchen , Chen Yu , Lv Xueze , Wang Liang , Zhang Jianwei , Li Kaiyang , Jia Yaxiong , Ban Liping , Ning Zhonghua , Qu Lujiang
Published: September 2019

Background

Salmonellainfection is a serious concern in poultry farming because of its impact on both economic loss and human health. Chicks aged 20 days or less are extremely vulnerable toSalmonella pullorum(SP), which causes high mortality. Furthermore, an outbreak of SP infection can result in a considerable number of carriers that become potential transmitters, thus, threatening fellow chickens and offspring. In this study, we conducted a genome-wide association study (GWAS) to detect potential genomic loci and candidate genes associated with two disease-related traits: death and carrier state.

Methods

In total, 818 birds were phenotyped for death and carrier state traits through a SP challenge experiment, and genotyped by using a 600 K high-density single nucleotide polymorphism (SNP) array. A GWAS using a single-marker linear mixed model was performed with the GEMMA software. RNA-sequencing on spleen samples was carried out for further identification of candidate genes.

Results

We detected a region that was located between 33.48 and 34.03 Mb on chicken chromosome 4 and was significantly associated with death, with the most significant SNP (rs314483802) accounting for 11.73% of the phenotypic variation. Two candidate genes,FBXW7andLRBA, were identified as the most promising genes involved in resistance to SP. The expression levels ofFBXW7andLRBAwere significantly downregulated after SP infection, which suggests that they may have a role in controlling SP infections. Two other significant loci and related genes (TRAF3andgga-mir-489) were associated with carrier state, which indicates a different polygenic determinism compared with that of death. In addition, genomic inbreeding coefficients showed no correlation with resistance to SP within each breed in our study.

Conclusions

The results of this GWAS with a carefully organizedSalmonellachallenge experiment represent an important milestone in understanding the genetics of infectious disease resistance, offer a theoretical basis for breeding SP-resistant chicken lines using marker-assisted selection, and provide new information for salmonellosis research in humans and other animals.
Use of genomic information to exploit genotype-by-environment interactions for body weight of broiler chicken in bio-secure and production environments
Authors: Chu Thinh T. , Bastiaansen John W. M. , Berg Peer , Romé Hélène , Marois Danye , Henshall John , Jensen Just
Published: September 2019

Background

The increase in accuracy of prediction by using genomic information has been well-documented. However, benefits of the use of genomic information and methodology for genetic evaluations are missing when genotype-by-environment interactions (G × E) exist between bio-secure breeding (B) environments and commercial production (C) environments. In this study, we explored (1) G × E interactions for broiler body weight (BW) at weeks 5 and 6, and (2) the benefits of using genomic information for prediction of BW traits when selection candidates were raised and tested in a B environment and close relatives were tested in a C environment.

Methods

A pedigree-based best linear unbiased prediction (BLUP) multivariate model was used to estimate variance components and predict breeding values (EBV) of BW traits at weeks 5 and 6 measured in B and C environments. A single-step genomic BLUP (ssGBLUP) model that combined pedigree and genomic information was used to predict EBV. Cross-validations were based on correlation, mean difference and regression slope statistics for EBV that were estimated from full and reduced datasets. These statistics are indicators of population accuracy, bias and dispersion of prediction for EBV of traits measured in B and C environments. Validation animals were genotyped and non-genotyped birds in the B environment only.

Results

Several indications of G × E interactions due to environmental differences were found for BW traits including significant re-ranking, heterogeneous variances and different heritabilities for BW measured in environments B and C. The genetic correlations between BW traits measured in environments B and C ranged from 0.48 to 0.54. The use of combined pedigree and genomic information increased population accuracy of EBV, and reduced bias of EBV prediction for genotyped birds compared to the use of pedigree information only. A slight increase in accuracy of EBV was also observed for non-genotyped birds, but the bias of EBV prediction increased for non-genotyped birds.

Conclusions

The G × E interaction was strong for BW traits of broilers measured in environments B and C. The use of combined pedigree and genomic information increased population accuracy of EBV substantially for genotyped birds in the B environment compared to the use of pedigree information only.
Vasospasm and delayed cerebral ischemia after uneventful clipping of an unruptured intracranial aneurysm – a case report
Authors: Campe Christin , Neumann Jens , Sandalcioglu I. Erol , Rashidi Ali , Luchtmann Michael
Published: September 2019

Background

Due to improvements in both the quality and availability of intracranial imaging as well as the evolution of surgical and endovascular techniques during the last decade, the number of treatments of unruptured intracranial aneurysms (UIA) has increased steadily. However, it is not generally known that vasospasm can arise after an uneventful clipping.

Case presentation

We present a case of a 69-year-old woman who suffered from vasospasm and delayed cerebral ischemia that occurred after an uneventful clipping of a UIA.

The aneurysm of the right middle cerebral artery was found incidentally via magnetic resonance imaging ordered after the patient complained of a short period of slight gait disturbances. To avoid a subarachnoid hemorrhage and consecutive complications like vasospasms, the patient elected microsurgical treatment. Clipping was managed by keyhole approach. Temporal clipping of the M1 was not necessary. After clip placement, appropriate flow in all distal segments was confirmed by indocyanine green video-angiography and micro-Doppler. The patient was discharged seven days after surgery without neurological deficits.

After 12 days, the patient developed at home a sudden drooping on the left side of the face. Upon admission to the emergency room, the patient was alert but slightly confused. Neurological examination revealed a left-sided hemiparesis and motor speech disorder. In contrast to the preoperative transfemoral catheter angiography, the subsequent right internal carotid angiogram showed clear signs of vasospasm along the M1 and M2 segments of the right middle cerebral artery.

Antithrombotic treatment with acetylsalicylic acid was begun. In accordance with guidelines for the treatment of subarachnoid hemorrhage and vasospasm, nimodipine was added. After 11 days the patient was discharged with no symptoms.

Conclusion

Cerebral vasospasm as a cause of ischemic stroke after uneventful surgery for a UIA seems to be a rare but possibly underestimated etiology that demands particular attention with respect to providing appropriate treatment. In future, it may be prudent to perform follow-up transcranial ultrasonography testing after the clipping of a UIA, especially considering the availability of potentially neuroprotective medications like nimodipine.
Prevalence and laboratory analysis of malaria and dengue co-infection: a systematic review and meta-analysis
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar
Published: September 2019

Background

A clear understanding of the epidemiology of malaria and dengue co-infection is essential for informed decisions on appropriate control strategies for dengue and malaria. This systematic review synthesized evidence on the relationship of malaria and dengue co-infection and related it to alterations in platelet, hemoglobin, hematocrit, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels when compared to malaria mono-infection.

Methods

A systematic review in accordance with PRISMA guidelines was conducted. All published articles available in PubMed and Web of Science (ISI) databases before October 21, 2017 were recruited. All epidemiological studies except case reports on the prevalence or incidence of malaria and dengue co-infection among patients visiting hospitals with febrile illness were included. Studies that involved conference abstracts, protocols, systematic reviews, only mono-dengue or mono-malaria infections, and only animal or in vitro studies were excluded after screening the titles, abstracts, and body texts. Studies were additionally excluded after full text review when they lacked epidemiologic data on malaria and dengue co-infection. Two reviewers independently screened, reviewed, and assessed all the studies. Cochrane Q (Chi-square) and Moran’s I2were used to assess heterogeneity, and the funnel plot was used to examine publication bias. The summary odds ratio (OR) and 95% confidence intervals (CI) were estimated using a fixed-effects model. Thirteen cross-sectional and two retrospective studies were eligible to be included in the systematic review and meta-analysis.

Results

Out of the 2269 citations screened, 15 articles were eligible to be included in the systematic review and meta-analysis. The 15 studies involved 13,798 (10,373 cases with malaria and 3425 with dengue) patients in 9 countries. Thirteen studies compared the incidence and odds ofPlasmodiumsp. infection, five studies compared the odds of mean platelet, three studies comparedPlasmodiumparasite density, and four studies compared the odds of hemoglobin, hematocrit, AST, and ALT levels among co-infected groups and single-malaria-infected groups.

Conclusions

This study showed that dengue and malaria co-infection was associated with decreased odds of malaria infection, malaria parasitemia, AST, and ALT levels when compared to malaria mono-infection. However, malaria and dengue co-infection was associated with increased odds of platelet and hemoglobin levels when compared to malaria mono-infection.
Metformin therapy in patients with diabetes mellitus is associated with a reduced risk of vasculopathy and cardiovascular mortality after heart transplantation
Authors: Ram Eilon , Lavee Jacob , Tenenbaum Alexander , Klempfner Robert , Fisman Enrique Z. , Maor Elad , Ovdat Tal , Amunts Sergei , Sternik Leonid , Peled Yael
Published: September 2019

Background

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Reduced cardiovascular mortality and morbidity have been reported in non-HT patients treated with metformin. Given the high prevalence of type 2 diabetes mellitus (T2DM) in HT patients, we investigated the association between metformin therapy and cardiovascular outcomes after HT.

Methods

The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. We excluded from the study patients with type 1 diabetes mellitus. Fifty-five HT patients (53%) in the cohort were treated with metformin. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV, survival, and the combined end-point of CAV or cardiovascular mortality.

Results

Kaplan–Meier survival analysis showed that the CAV rate at 20 years of follow-up was lower in DM patients treated with metformin than in those who were not (30 vs. 65%; log-rank p = 0.044). Similarly, the combined risk of CAV or cardiovascular mortality was lower in the metformin-treated patients than in those not receiving metformin (32 vs. 68%; log rank p = 0.01). Consistently, multivariate analysis adjusted for age and comorbidities showed that metformin therapy was independently associated with a significant 90% reduction (95% confidence interval 0.02–0.46, p = 0.003) in the risk for the development of CAV, and a 91% reduction (95% confidence interval 0.02–0.42; p = 0.003) in the risk for CAV or cardiovascular mortality.

Conclusions

In diabetic HT patients, metformin therapy is independently associated with a significant reduction in the long-term risk for CAV and the combined end-point of CAV or cardiovascular mortality after HT.
Functional roles of circular RNAs during epithelial-to-mesenchymal transition
Authors: Shang Bing-Qing , Li Min-Le , Quan Hao-yu , Hou Ping-Fu , Li Zhong-Wei , Chu Su-Fang , Zheng Jun-Nian , Bai Jin
Published: September 2019

Cancer has become a major health issue worldwide, contributing to a high mortality rate. Tumor metastasis is attributed to the death of most patients. Epithelial-to-mesenchymal transition (EMT) plays a vital role in inducing metastasis. During EMT, epithelial cells lose their characteristics, such as cell-to-cell adhesion and cell polarity, and cells gain motility, migratory potential, and invasive properties to become mesenchymal stem cells. Circular RNAs (circRNAs) are closely associated with tumor metastasis and patient prognosis, as revealed by increasing lines of evidence. CircRNA is a type of single-stranded RNA that forms a covalently closed continuous loop. CircRNAs are insensitive to ribonucleases and are widespread in body fluids. This work is the first review on EMT-related circRNAs. In this review, we briefly discuss the characteristics and functions of circRNAs. The correlation of circRNAs with EMT has been reported, and we discuss the ways circRNAs can regulate EMT progression through EMT transcription factors, EMT-related signaling pathways, and other mechanisms. This work summarizes current studies on EMT-related circRNAs in various cancers and provides a theoretical basis for the use of EMT-related circRNAs in targeted management and therapy.
A near infrared light-triggerable modular formulation for the delivery of small biomolecules
Authors: Francisco Vitor , Lino Miguel , Ferreira Lino
Published: September 2019

Background

Externally triggered drug delivery systems hold considerable promise for improving the treatment of many diseases, in particular, diseases where the spatial–temporal release of the drug is critical to maximize their biological effect whilst minimizing undesirable, off-target, side effects.

Results

Herein, we developed a light-triggerable formulation that takes advantage of host–guest chemistry to complex drugs functionalized with a guest molecule and release it after exposure to near infrared (NIR) light due to the disruption of the non-covalent host–guest interactions. The system is composed by a gold nanorod (AuNR), which generates plasmonic heat after exposure to NIR, a thin layer of hyaluronic acid immobilized to the AuNR upon functionalization with a macrocycle, cucurbit[6]uril (CB[6]), and a drug functionalized with a guest molecule that interacts with the macrocycle. For proof of concept, we have used this formulation for the intracellular release of a derivative of retinoic acid (RA), a molecule known to play a key role in tissue development and homeostasis as well as during cancer treatment. We showed that the formulation was able to conjugate approximately 65 μg of RA derivative per mg of CB[6] @AuNR and released it within a few minutes after exposure to a NIR laser. Importantly, the bioactivity of RA released from the formulation was demonstrated in a reporter cell line expressing luciferase under the control of the RA receptor.

Conclusions

This NIR light-triggered supramolecular-based modular platform holds great promise for theranostic applications.
An ethical comparison of living kidney donation and surrogacy: understanding the relational dimension
Authors: Beier Katharina , Wöhlke Sabine
Published: September 2019

Background

The bioethical debates concerning living donation and surrogacy revolve around similar ethical questions and moral concepts. Nevertheless, the ethical discourses in both fields grew largely isolated from each other.

Methods

Based on a review of ethical, sociological and anthropological research this paper aims to link the ethical discourses on living kidney donation and surrogacy by providing a comparative analysis of the two practices’ relational dimension with regard to three aspects, i.e. the normative role of relational dynamics, social norms and gender roles, and reciprocity. Based on this analysis, we derive conclusions for the framing of living organ donation and surrogacy in ethical theory and practice.

Results

First, our analysis emphasizes the relevance of acknowledging the complex relational implications of living kidney donation and surrogacy. Underestimating this relational dimension may not only lead to individual crises but endanger existing as well as newly emerging familial relationships. Second, we point out differences in the normative assessment of social norms and gender roles in the ethical debates about living kidney donation and surrogacy. In particular, we show how different evaluations of altruism affect the understanding of autonomy in both contexts. In addition, we sensitize for biased perceptions of gender roles. Finally, we argue that challenges resulting from unresolved reciprocity are an issue in living kidney donation and surrogacy independent of whether the exchange of body parts or bodily services is framed as a gift or commercial exchange. By pointing out the limits of financial compensation, we stress the relevance of non-material, relational rewards as potential remedy.
Seizures of illicit substances for personal use in two Italian provinces: analysis of trends by type and purity from 2008 to 2017
Authors: Verri Patrizia , Rustichelli Cecilia , Ferrari Anna , Marchesi Filippo , Baraldi Carlo , Licata Manuela , Vandelli Daniele , Palazzoli Federica , Potì Francesco , Silingardi Enrico
Published: September 2019

Background

The use of illicit substances represents one of the most difficult problems to confront in the health system. Drug use is a global problem but is not uniform throughout the world, within the same country and changes over time. Therefore, knowing the illicit substances that are used in a territory is essential to better organize health services in that specific geographical area. To this aim, we analysed 4200 samples confiscated from individuals who held them for personal use by police forces in the Italian provinces of Modena and Reggio Emilia from 2008 to 2017.

Methods

The suspected samples were screened by gas-chromatography-mass spectrometry (GC-MS) and by liquid chromatography-tandem mass spectrometry (LC-MS/MS); all samples were subsequently analysed by gas chromatography-flame ionization detector (GC-FID) for quantitative analyses.

Results

Cannabis was the most seized illicit substance (70.7%). Over the study period, the number of seizures of herb with a high content of Δ9-THC increased. The number of cocaine seizures remained stable (total 16.1%), but the median purity of seized cocaine increased to 75% in 2017. Heroin seizures decreased over time, but the median purity of seized heroin reached 16.8% in 2017. In almost all the years, heroin samples with a purity exceeding the 97.5 percentile were found. Especially from 2014, the range of seized substances increased and started to include synthetic cathinones, phenylethylamines, UR-144, LSD, psilocybe, prescription opioid and hypnotics. In two cases, tramadol together with tropicamide was seized. Most of the seizures involved male subjects and 82% of the seizures were from individuals younger than 35 years of age.

Conclusions

The persistence of old illicit drugs and the rapid emergence of new psychoactive substances represented a serious challenge for public health in the studied Italian area. Some useful interventions might be: informing mainly young people about the possible complications of cannabis use; implementing standardized procedures to diagnose and treat cocaine-related emergencies in hospitals; increasing the distribution of naloxone to antagonize possible heroin overdoses; equipping laboratories to be able to identify the new psychoactive substances.
Efficacy of wIRA in the treatment of sacroiliitis in male patients with ankylosing spondylitis and its effect on serum VEGF levels
Authors: Xu Jian , Deng Yao , Yu Chun-Yan , Gao Zhao-Meng , Yang Xi-Rui , Zhang Qi , Zhang Lei
Published: September 2019

Background

This study aimed to assess the efficacy of water-filtered infrared A (wIRA) in sacroiliitis in male patients with ankylosing spondylitis (AS) and the effect of wIRA therapy on serum vascular endothelial growth factor (VEGF).

Methods

One hundred twenty male AS patients with active sacroiliitis were randomly divided into wIRA group and control group. wIRA treatment was performed twice daily for 5 consecutive days with 24-h interval before switching the treatment (crossover design). Bath ankylosing spondylitis disease activity index (BASDAI) scores, pain visual analogue scale (VAS), and morning stiffness VAS were recorded prior to and after each treatment period. Additionally, C-reactive protein (CRP), serum VEGF, and resistance index (RI) of sacroiliac joints detected by ultrasonography were recorded at baseline and after the first and second treatment period, respectively. The efficacy was examined by using repeated measures analysis of variance (ANOVA).

Results

BASDAI, pain VAS, and morning stiffness VAS scores decreased significantly (P < 0.001) after wIRA treatment and no-wIRA treatment (control group), and the difference between the two groups was significant (P < 0.001). CRP declined and RI increased during the wIRA treatment as compared with the no-wIRA treatment (P < 0.001). The increase in RI was associated with improvement of pain VAS scores (P = 0.018), while serum VEGF was unaffected by the treatment.

Conclusions

wIRA treatment achieved symptom and pain relief for AS patients with active sacroiliitis. wIRA treatment also improved RI revealed by ultrasonography, and this effect was associated with improved pain VAS scores.
Left ventricular dysfunction postsurgical patent ductus arteriosus ligation in children: predictor factors analysis
Authors: Abdel-Bary Mohamed , Abdel-Baseer Khaled Abdalla , Abdel-Latif Ahmed Fathy , Abdel-Naser Mohamed Abdella , Nafie Mahmoud , Eisa Karam Mosallam
Published: September 2019

Objective

To identify the predictor factors of left ventricular (LV) dysfunction following patent ductus arteriosus (PDA) surgical ligation.

Background

PDA is viewed as a noticeable amongst the most widely recognized congenital heart defects in children and its closure is responsible for many hemodynamic changes that require intervention and care.

Methods

A retrospective study included fifty children with isolated PDA treated by surgical ligation from June 2015 to June 2018. The LV dimensions and systolic function were assessed by two-dimensional echocardiography pre and post PDA ligation. All cases were followed-up on the first-day, 1 month and 6 months post ligation.

Results

The mean age of cases was 15.78 ± 7.58 months and 72% were females. The mean duct size was 4.08 ± 1.25 mm. There was a marked decrease in LVEDd, LA/Ao, EF and FS in the first-day post ligation contrasted with pre ligation values. Moreover, an amazing decline in LVEDd and LA/Ao ratio was observed 1 month post ligation contrasted with the early post ligation status with asynchronous improvement of FS and EF at one and 6 months postoperatively.

Conclusion

PDA ligation is associated with a noteworthy LV systolic dysfunction within the first day post ligation; that in a significant number of patients may require anti-failure measures, prolong the hospital stay and necessitate a regular follow up and monitoring of LV function. PDA size, age, preoperative LVEDd and FS can be considered as predictor factors for suspicion of acute decrease in the LV systolic function early post PDA ligation.

Trial registration

ClinTrial.Gov NCT04018079.
Thoracic aortic aneurysms exerting high extrinsic pressure on the airway
Authors: Jung Hanna , Do Young Woo , Lee Sang Yub , Lee Youngok , Oh Tak Hyuk , Kim Gun Jik
Published: September 2019

Background

Thoracic aortic aneurysms, although mostly asymptomatic, are life threatening owing to the risk of rupture. Moreover, the extrinsic pressure of a ruptured aneurysm may encroach the mediastinum.

Case presentation

A 74-year-old woman diagnosed with ruptured descending thoracic aortic aneurysm compressing the lower trachea and both main bronchi underwent thoracic endovascular aortic repair; however, the extrinsic pressure on the airway persisted. Following failing of endobronchial silicon stents insertion, extracorporeal membrane oxygenation support was required, and endobronchial metallic stents were inserted. The patients’ hypoventilation resolved, and the patient was withdrawn from the ventilator.

Conclusions

Technological improvement in endovascular or endobronchial procedures has provided more options for managing complex cases. However, we must be aware of how high the extrinsic pressure might be before management and take steps to minimize complications.
The novel use of oral antibiotic monotherapy in prosthetic valve endocarditis caused by Finegoldia magna: a case study
Authors: Chien Siobhan , Gorman David , Koutsogiannidis Charilaos-Panagiotis , Ravishankar Ramanish , Kamath Ganesh , Zamvar Vipin
Published: September 2019

Background

Finegoldia magna, a Gram-positive anaerobic coccus, is part of the human normal microbiota as a commensal of mucocutaneous surfaces. However, it remains an uncommon pathogen in infective endocarditis, with only eight clinical cases previously reported in the literature.

Currently, infective endocarditis is routinely treated with prolonged intravenous antibiotic therapy. However, recent research has found that switching patients to oral antibiotics is non-inferior to prolonged parenteral antibiotic treatment, challenging the current guidelines for the treatment of infective endocarditis.

Case presentation

This case report focuses on a 52-year-old gentleman, who presented with initially culture-negative infective endocarditis following bioprosthetic aortic valve replacement. Blood cultures later grew Finegoldia magna. Following initial intravenous antibiotic therapy and re-do surgical replacement of the prosthetic aortic valve, the patient was successfully switched to oral antibiotic monotherapy, an unusual strategy in the treatment of infective endocarditis inspired by the recent publication of the POET trial. He made excellent progress on an eight-week course of oral antibiotics and was successfully discharged from surgical follow-up.

Conclusions

This case is the 9th reported case of Finegoldia magna infective endocarditis in the literature. Our case also raises the possibility of a more patient-friendly and cost-effective means of providing long-term antibiotic therapy in suitable patients with prosthetic valve endocarditis and suggests that the principles highlighted in the POET trial can also be applicable to post-operative patients after cardiac surgery.
Documentation of human rights abuses among Rohingya refugees from Myanmar
Authors: Haar Rohini J. , Wang Karen , Venters Homer , Salonen Satu , Patel Rupa , Nelson Tamaryn , Mishori Ranit , Parmar Parveen K.
Published: September 2019

Background

Decades of persecution culminated in a statewide campaign of organized, systematic, and violent eviction of the Rohingya people by the Myanmar government beginning in August 2017. These attacks included the burning of homes and farms, beatings, shootings, sexual violence, summary executions, burying the dead in mass graves, and other atrocities. The Myanmar government has denied any responsibility. To document evidence of reported atrocities and identify patterns, we interviewed survivors, documented physical injuries, and assessed for consistency in their reports.

Methods

We use purposive and snowball sampling to identify survivors residing in refugee camps in Bangladesh. Interviews and examinations were conducted by trained investigators with the assistance of interpreters based on the Istanbul Protocol – the international standard to investigate and document instances of torture and other cruel, inhuman, and degrading treatment. The goal was to assess whether the clinical findings corroborate survivors’ narratives and to identify emblematic patterns.

Results

During four separate field visits between December 2017 and July 2018, we interviewed and where relevant, conducted physical examinations on a total of 114 refugees. The participants came from 36 villages in Northern Rakhine state; 36 (32%) were female, 26 (23%) were children. Testimonies described several patterns in the violence prior to their flight, including the organization of the attacks, the involvement of non-Rohingya civilians, the targeted and purposeful destruction of homes and eviction of Rohingya residents, and the denial of medical care. Physical findings included injuries from gunshots, blunt trauma, penetrating trauma such as slashings and mutilations, burns, and explosives and from sexual and gender-based violence.

Conclusions

While each survivor’s experience was unique, similarities in the types and organization of attacks support allegations of a systematic, widespread, and premeditated campaign of forced displacement and violence. Physical findings were consistent with survivors’ narratives of violence and brutality. These findings warrant accountability for the Myanmar military per the Rome Statute of the International Criminal Court (ICC), which has jurisdiction to try individuals for serious international crimes, including crimes against humanity and genocide. Legal accountability for these crimes should be pursued along with medical and psychological care and rehabilitation to address the ongoing effects of violence, discrimination, and displacement.