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Πέμπτη 31 Οκτωβρίου 2019

21.
 2019 Oct 28;17(1):137. doi: 10.1186/s12964-019-0446-z.

Targeting PKCι-PAK1 signaling pathways in EGFR and KRAS mutant adenocarcinoma and lung squamous cell carcinoma.

Author information

1
Pangaea Oncology, Laboratory of Molecular Biology, Quiron-Dexeus University Institute, Barcelona, Spain.
2
Laboratory of Cellular and Molecular Biology, Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain.
3
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
4
IDIBELL/CReST/Translational Research Laboratori L'Hospitalet de Llobregat, Barcelona, Spain.
5
Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
6
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
7
Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China. njpcao@126.com.
8
Laboratory of Cellular and Molecular Biology, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China. njpcao@126.com.
9
Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China. njpcao@126.com.
10
Laboratory of Cellular and Molecular Biology, Institute for Health Science Research Germans Trias i Pujol (IGTP), Badalona, Spain. rrosell@iconcologia.net.
11
Institute of Oncology Rosell (IOR), Quiron-Dexeus University Institute, Barcelona, Spain. rrosell@iconcologia.net.
12
Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol Campus Can Ruti (Edifici Muntanya), Ctra. de Can Ruti, Cami de les Escoles s/n, Badalona, 08916, Barcelona, Spain. rrosell@iconcologia.net.

Abstract

INTRODUCTION:

p21-activated kinase 1 (PAK1) stimulates growth and metastasis in non-small cell lung cancer (NSCLC). Protein kinase C iota (PKCι) is an enzyme highly expressed in NSCLC, regulating PAK1 signaling. In the present study we explored whether the PKCι-PAK1 signaling pathway approach can be an efficient target in different types of NSCLC cell and mouse models.

METHODS:

The effect of IPA-3 (PAK1 inhibitor) plus auranofin (PKCι inhibitor) combination was evaluated by cell viability assay, colony formation and western blotting assay, using three types of NSCLC cell lines: EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma with PAK1 amplification. In addition, for clinical availability, screening for new PAK1 inhibitors was carried out and the compound OTSSP167 was evaluated in combination with auranofin in cell and mice models.

RESULTS:

The combination of IPA-3 or OTSSP167 plus auranofin showed high synergism for inhibiting cell viability and colony formation in three cell lines. Mechanistic characterization revealed that this drug combination abrogated expression and activation of membrane receptors and downstream signaling proteins crucial in lung cancer: EGFR, MET, PAK1, PKCι, ERK1/2, AKT, YAP1 and mTOR. A nude mouse xenograft assay demonstrated that this drug combination strongly suppressed tumor volume compared with single drug treatment.

CONCLUSIONS:

Combination of IPA-3 or OTSSP167 and auranofin was highly synergistic in EGFR or KRAS mutant adenocarcinoma and squamous cell carcinoma cell lines and decreased tumor volume in mice models. It is of interest to further test the targeting of PKCι-PAK1 signaling pathways in EGFR mutant, KRAS mutant and squamous NSCLC patients.
PMID:
 
31660987
 
DOI:
 
10.1186/s12964-019-0446-z
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22.
 2019 Oct 28;17(1):111. doi: 10.1186/s12951-019-0542-7.

Nanosensors and particles: a technology frontier with pitfalls.

Author information

1
Laboratory of Applied Mechanobiology, Department of Health Sciences and Technology, ETH Zurich, Vladimir-Prelog Weg 4 (HCI F443 Hönggerberg), 8093, Zurich, Switzerland. viola.vogel@hest.ethz.ch.

Abstract

As we are approaching 20 years after the US National Nanotechnology Initiative has been announced, whereby most of that funding was spend to engineer, characterize and bring nanoparticles and nanosensors to the market, it is timely to assess the progress made. Beyond revolutionizing nonmedical applications, including construction materials and the food industry, as well as in vitro medical diagnostics, the progress in bringing them into the clinic has been far slower than expected. Even though most of the advances in nanosensor and nanoparticle research and development have been paid for by disease-oriented funding agencies, much of the gained knowledge can now be applied to treat or learn more about our environment, including water, soil, microbes and plants. As the amount of engineered nanoparticles that enter our environment is currently exponentially increasing, much tighter attention needs to be paid to assessing their health risk. This is urgent as the asbestos story told us important lessons how financial interests arising from a rapid build up of a flourishing industry has blocked and is still preventing a worldwide ban on asbestos, nearly 100 years after the first health risks were reported.
PMID:
 
31660986
 
DOI:
 
10.1186/s12951-019-0542-7
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23.
 2019 Oct 28;17(1):77. doi: 10.1186/s12960-019-0421-1.

Status of healthcare workers after comprehensive reform of urban public hospitals in Beijing, China: sustainable supply, psychological perception, and work outcomes.

Deng J1,2Sun Y1,2Lei R1,2Guo Y1,2Liu J3Yang T4,5,6.

Author information

1
School of Management and Economics, Beijing Institute of Technology, 5 Zhongguancun South Street, Beijing, 100081, China.
2
Sustainable Development Research Institute for Economy and Society of Beijing, 5 Zhongguancun South Street, Beijing, 100081, China.
3
Beijing City Chaoyang District ShuangQiao Hospital, ShuangQiao East Road, Chaoyang District, Beijing, 100024, China.
4
School of Management and Economics, Beijing Institute of Technology, 5 Zhongguancun South Street, Beijing, 100081, China. tianan.yang@bit.edu.cn.
5
Sustainable Development Research Institute for Economy and Society of Beijing, 5 Zhongguancun South Street, Beijing, 100081, China. tianan.yang@bit.edu.cn.
6
Chair of Sport and Health Management, School of Management, Technical University of Munich, Uptown Munich Campus D, Georg-Brauchle-Ring 60/62, 80992, Munich, Germany. tianan.yang@bit.edu.cn.

Abstract

BACKGROUND:

Healthcare reform in China has attracted worldwide interest and reached a new juncture. In an attempt to improve healthcare quality and patient satisfaction, the government of Beijing introduced comprehensive reform of urban public hospitals in 2016 and implemented new policies on personnel, compensation, management, and diagnosis and treatment. As the agents of healthcare service, and a target of reform measures, healthcare workers were greatly affected by these reforms but have not been carefully studied.

METHODS:

This study used mean value analysis, variance analysis, and qualitative content analysis to investigate the status of healthcare workers after comprehensive reform of urban public hospitals in Beijing.

RESULTS:

We found a gradual but constant increase in the number of healthcare workers in poor health in Beijing public hospitals. After the reforms, this population reported high challenge stress, public service motivation, job satisfaction, job performance and quality of healthcare, moderate presenteeism, and low hindrance stress and turnover intention. The status of healthcare workers differed by subgroup and changed during the reform process.

CONCLUSIONS:

Our study provides data useful for policy recommendations regarding the implementation and extension of future reforms and offers important lessons for developing and developed countries that are reforming public hospitals to improve efficiency and reduce costs.

KEYWORDS:

Government data; Healthcare reform; Healthcare workers; Psychological perception; Quality of healthcare; Sustainable supply
PMID:
 
31660985
 
DOI:
 
10.1186/s12960-019-0421-1
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24.
 2019 Oct 28;18(1):61. doi: 10.1186/s12937-019-0494-7.

Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study.

Chen C1Chen Y1Weng P1Xia F1Li Q1Zhai H1Wang N2Lu Y3.

Author information

1
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.
2
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China. wnj486@126.com.
3
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China. luyingli2008@126.com.

Abstract

BACKGROUND:

Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology.

METHODS:

Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria.

RESULTS:

Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRSsynthesis determined increase of 25(OH) D levels.

CONCLUSIONS:

We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.

KEYWORDS:

Cardiometabolic risk factors; Mendelian randomization analysis; Metabolic syndrome; Vitamin D
PMID:
 
31660975
 
DOI:
 
10.1186/s12937-019-0494-7
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25.
 2019 Oct 28;26(1):87. doi: 10.1186/s12929-019-0578-x.

Human iPSC banking: barriers and opportunities.

Author information

1
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
2
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. phsieh@ibms.sinica.edu.tw.
3
Graduate Institute of Medical Genomics and Proteomics and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. phsieh@ibms.sinica.edu.tw.
4
Cardiovascular Surgery Division, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. phsieh@ibms.sinica.edu.tw.

Abstract

The introduction of induced pluripotent stem cells (iPSCs) has opened up the potential for personalized cell therapies and ushered in new opportunities for regenerative medicine, disease modeling, iPSC-based drug discovery and toxicity assessment. Over the past 10 years, several initiatives have been established that aim to collect and generate a large amount of human iPSCs for scientific research purposes. In this review, we compare the construction and operation strategy of some iPSC banks as well as their ongoing development. We also introduce the technical challenges and offer future perspectives pertaining to the establishment and management of iPSC banks.

KEYWORDS:

Cell bank; Induced pluripotent stem cell (iPSC); Personalized medicine
PMID:
 
31660969
 
DOI:
 
10.1186/s12929-019-0578-x
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26.
 2019 Oct 28;15(1):377. doi: 10.1186/s12917-019-2115-2.

Bacitracin resistance and enhanced virulence of Streptococcus suis via a novel efflux pump.

Ma J1,2Liu J1Zhang Y1,2Wang D1,2Liu R3Liu G1,2Yao H1,2,4Pan Z5,6,7.

Author information

1
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
2
OIE Reference Laboratory for Swine Streptococcosis, Nanjing, 210095, China.
3
South Dakota State University, Brookings, SD, 57007, USA.
4
MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing, China.
5
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China. panzihao@njau.edu.cn.
6
OIE Reference Laboratory for Swine Streptococcosis, Nanjing, 210095, China. panzihao@njau.edu.cn.
7
MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing, China. panzihao@njau.edu.cn.

Abstract

BACKGROUND:

Streptococcus suis is a prominent pathogen causing septicemia and meningitis in swine and humans. Bacitracin is used widely as a growth promoter in animal feed and to control the spread of necrotic enteritis in most developing countries. This study aimed to characterize a novel membrane transporter module Sst comprising SstE, SstF, and SstG for bacitracin resistance.

RESULTS:

Comparative genomics and protein homology analysis found a potential efflux pump SstFEG encoded upstream of well-known bacitracin-resistance genes bceAB and bceRS. A four-fold decrease in bacitracin susceptibility was observed in sstFEG deletion mutant comparing with S. suis wildtype strain CZ130302. Further studies indicated that the bacitracin tolerance mediated by SstFEG is not only independent of the BceAB transporter, but also regulated by the two-component system BceSR. Given that SstFEG are harbored by almost all virulent strains, but not in the avirulent strains, we managed to explore its potential role in bacterial pathogencity. Indeed, our results showed that SstFEG is involved in S. suis colonization and virulence in animal infection model by its potential competitive survival advantage against host bactericidal effect.

CONCLUSION:

To our knowledge, this is the first study to functionally characterize the bacitracin efflux pump in S. suis to provide evidence regarding the important roles of the novel ABC transporter system SstFEG with respect to drug resistance and virulence.

KEYWORDS:

Bacitracin; Efflux pump; Serotype Chz; SstFEG; Streptococcus suis; Virulence
PMID:
 
31660968
 
DOI:
 
10.1186/s12917-019-2115-2
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27.
 2019 Oct 28;19(1):762. doi: 10.1186/s12913-019-4555-6.

Public engagement in health technology assessment in Brazil: the case of the Trastuzumab public consultation.

Author information

1
University of Brasília, Brasília, Brazil. vivi_unb@hotmail.com.
2
Oswaldo Cruz Foundation, Brasília, Brazil.
3
University of Brasília, Brasília, Brazil.

Abstract

BACKGROUND:

Public engagement in health technology assessment (HTA) is increasing worldwide. There are several forms of public engagement and it is not always possible to determine which stakeholders participate in the HTA process and how they contribute. Our objective was to investigate which types of social representatives contributed to the public consultation on the incorporation of Trastuzumab for early-stage breast cancer treatment within the public health system in Brazil, held in 2012 by the National Committee for Health Technology Incorporation (CONITEC).

METHODS:

A mixed methods approach was used to analyze social representativeness and the composition of the corpus from the public consultation, which consisted of 127 contributions. Three types of analysis were performed using IRaMuTeQ software: classic lexical analysis, descending hierarchical classification and specificities analysis. The contributions were clustered according to the main categories of discourse observed, into four social representation categories: 1) patient representation/advocacy; 2) pharmaceutical industry/advocacy; 3) healthcare professionals; and 4) individual contributions.

RESULTS:

Category 1 contained words related to increased survival due to use of the drug and a low score for words pertaining to studies on Trastuzumab. The word "safety" obtained a positive score only in category 2, which was also the only category that exhibited a negative score for the word "risk". Category 3 displayed the lowest scores for "diagnosis" and "safety". The word "efficacy" had a negative score only in category 4.

CONCLUSIONS:

Each category exhibited different results for words related to health systems and to key concepts linked to HTA. Our analysis enabled the identification of the most prominent contributions for each category. Despite the promising results obtained, further research is needed to validate this software for use in analyzing public contributions.

KEYWORDS:

Analytical methods; Health technology assessment (HTA); Public consultation; Public engagement; Public opinion; Social participation
PMID:
 
31660957
 
DOI:
 
10.1186/s12913-019-4555-6
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28.
 2019 Oct 28;19(1):1391. doi: 10.1186/s12889-019-7749-2.

Changes in drowning mortality rates and quality of reporting from 2004-2005 to 2014-2015: a comparative study of 61 countries.

Author information

1
Institute of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
2
NCKU Research Center for Health Data and Department of Public Health, College of Medicine, National Cheng Kung University, No. 1, Dah Hsueh Road, Tainan, 701, Taiwan. lywang@mail.ncku.edu.tw.
3
NCKU Research Center for Health Data and Department of Public Health, College of Medicine, National Cheng Kung University, No. 1, Dah Hsueh Road, Tainan, 701, Taiwan.

Abstract

BACKGROUND:

This study assessed international variations in changes in drowning mortality rates and the quality of reporting specific information in death certificates over the past decade.

METHODS:

Drowning mortality data of 61 countries were extracted from the World Health Organization Mortality Database. We calculated the percentage change (PC) in age-standardized drowning mortality rates and percentage of drowning deaths reported with unspecified codes between 2004 and 2005 and 2014-2015.

RESULTS:

Of the 61 countries studied, 50 exhibited a reduction in drowning mortality rates from 2004 to 2005 to 2014-2015. Additionally, five countries-Lithuania, Moldova, Kyrgyzstan, Romania, and El Salvador-with a high mortality rate in 2004-2005 (> 40 deaths per 100,000) showed improvement (PC < - 32%). By contrast, four countries-South Africa, Guyana, Morocco, and Guatemala-exhibited a more than twofold increase in mortality rates. Regarding the quality of reporting, 34 countries exhibited a decrease in the percentage of unspecified codes. Additionally, three countries-Paraguay, Serbia, and Croatia-with moderate and high percentages of unspecified codes (> 40%) exhibited a marked reduction (PC < - 60%), whereas three countries-Malaysia, Belgium, and Nicaragua-exhibited a notable increase.

CONCLUSIONS:

Large international variations in the extent of changes in drowning mortality rates and the quality of reporting specific information on the death certificate were observed during the study period.

KEYWORDS:

Accidents; Death certificate; Drowning; International comparisons; Mortality
PMID:
 
31660919
 
DOI:
 
10.1186/s12889-019-7749-2
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29.
 2019 Oct 28;19(1):1393. doi: 10.1186/s12889-019-7805-y.

Evaluation of a school based comprehensive sexuality education program among very young adolescents in rural Uganda.

Author information

1
Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda. ekemigisha@must.ac.ug.
2
International Centre for Reproductive Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. ekemigisha@must.ac.ug.
3
Mbarara University of Science and Technology, P.O. Box 1410, Mbarara, Uganda.
4
Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich (LMU), 80802, Munich, Germany.
5
International Centre for Reproductive Health, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
6
Centre of Expertise on Gender, Diversity and Intersectionality, Vrije universiteit Brussels, Brussels, Belgium.

Abstract

BACKGROUND:

Limited research has been conducted on the effectiveness of sexuality education for very young adolescents (VYAs) ages 10-14 years in Sub-Saharan Africa. Furthermore, evaluations of sexuality education programs often report outcomes of risky sexual practices, yet positive aspects of sexuality are hardly studied and rarely reported. This study evaluates the effectiveness of a Comprehensive Sexuality Education (CSE) intervention for VYAs in Uganda, analyzing both positive and negative outcome indicators.

METHODS:

We conducted a mixed methods study, incorporating a cluster randomized trial (NCT03669913) among pupils in 33 randomly selected primary schools in Mbarara district. This was followed by a qualitative evaluation of the intervention in 4 schools that included 14 in-depth interviews and 3 focus group discussions distributed among pupils, teachers and parents. Quantitative data were analyzed using ordered logistic regression to compare differences in the change from baseline to endline between the intervention and control arms. We conducted bivariate analysis and multiple regression analysis controlling for key covariates, including age, gender, school location (rural vs urban), truancy, and orphanhood. Qualitative data were analyzed by thematic approach using ATLAS TI.

RESULTS:

Between July 2016 and August 2017, 1096 pupils were recruited. Outcomes were studied among 380 pupils in the intervention arm and 484 pupils in the control arm. The proportion of pupils who ever had sex increased from 9 to 12.1% in intervention compared to 5.2 to 7.4% in the control group between baseline and endline, however the differences between groups were not statistically significant. We found greater improvements in sexual and reproductive health (SRH) knowledge among intervention schools (AOR: 2.18, 95% CI: 1.66-2.86) and no significant differences in self-esteem, body image or gender equitable norms. Qualitative evidence echoes perceived SRH knowledge acquisition, increased their perception of SRH related risks, and intentions to delay sexual intercourse to prevent unwanted pregnancy, HIV and other STIs.

CONCLUSION:

This study demonstrates that CSE can improve SRH knowledge and behavioral intentions among VYAs in Uganda. These results further emphasize the importance of initiating sexuality education before most adolescents have started engaging in sexual activity, enabling them to make informed decisions in the future.

TRIAL REGISTRATION:

NCT03669913 , registered retrospectively on September 13th, 2018.

KEYWORDS:

Comprehensive sexuality education; Evaluation; Sexual and reproductive health; Uganda; Very young adolescents
PMID:
 
31660918
 
DOI:
 
10.1186/s12889-019-7805-y
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30.
 2019 Oct 28;19(1):902. doi: 10.1186/s12879-019-4540-z.

Bayesian modeling of spatiotemporal patterns of TB-HIV co-infection risk in Kenya.

Author information

1
Department of Mathematical Sciences, Pan African University Institute of Basic Sciences Technology and Innovation, Nairobi, Kenya. otiende.verrah@students.jkuat.ac.ke.
2
School of Mathematics, Statistics & Computer Science, University of KwaZulu-Natal, Pietermaritzburg, South Africa.

Abstract

BACKGROUND:

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) diseases are globally acknowledged as a public health challenge that exhibits adverse bidirectional relations due to the co-epidemic overlap. To understand the co-infection burden we used the case notification data to generate spatiotemporal maps that described the distribution and exposure hypotheses for further epidemiologic investigations in areas with unusual case notification levels.

METHODS:

We analyzed the TB and TB-HIV case notification data from the Kenya national TB control program aggregated for forty-seven counties over a seven-year period (2012-2018). Using spatiotemporal poisson regression models within the Integrated Nested Laplace Approach (INLA) paradygm, we modeled the risk of TB-HIV co-infection. Six competing models with varying space-time formulations were compared to determine the best fit model. We then assessed the geographic patterns and temporal trends of coinfection risk by mapping the posterior marginal from the best fit model.

RESULTS:

Of the total 608,312 TB case notifications, 194,129 were HIV co-infected. The proportion of TB-HIV co-infection was higher in females (39.7%) than in males (27.0%). A significant share of the co-infection was among adults aged 35 to 44 years (46.7%) and 45 to 54 years (42.1%). Based on the Bayesian Defiance Information (DIC) and the effective number of parameters (pD) comparisons, the spatiotemporal model allowing space-time interaction was the best in explaining the geographical variations in TB-HIV coinfection. The model results suggested that the risk of TB-HIV coinfection was influenced by infrastructure index (Relative risk (RR) = 5.75, Credible Interval (Cr.I) = (1.65, 19.89)) and gender ratio (RR = 5.81e-04, Cr. I = (1.06e-04, 3.18e-03). The lowest and highest temporal relative risks were in the years 2016 at 0.9 and 2012 at 1.07 respectively. The spatial pattern presented an increased co-infection risk in a number of counties. For the spatiotemporal interaction, only a few counties had a relative risk greater than 1 that varied in different years.

CONCLUSIONS:

We identified elevated risk areas for TB/HIV co-infection and fluctuating temporal trends which could be because of improved TB case detection or surveillance bias caused by spatial heterogeneity in the co-infection dynamics. Focused interventions and continuous TB-HIV surveillance will ensure adequate resource allocation and significant reduction of HIV burden amongst TB patients.

KEYWORDS:

Bayesian modeling; Kenya; TB-HIV co-infection; co-epidemic burden
PMID:
 
31660883
 
DOI:
 
10.1186/s12879-019-4540-z
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31.
 2019 Oct 28;19(1):904. doi: 10.1186/s12879-019-4533-y.

Correction to: Public health impact and cost effectiveness of routine childhood vaccination for hepatitis a in Jordan: a dynamic model approach.

Author information

1
Department of Pediatrics, Faculty of Medicine, Jordan University of Science and Technology, PO Box 3030, Irbid, 22110, Jordan. wailh@just.edu.jo.
2
Merck & Co., Inc., Kenilworth, NJ, USA.
3
Agile-1 for Merck & Co., Inc., Kenilworth, NJ, USA.

Abstract

Following publication of the original article1, the authors noted the following.
PMID:
 
31660877
 
DOI:
 
10.1186/s12879-019-4533-y
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32.
 2019 Oct 28;19(1):898. doi: 10.1186/s12879-019-4522-1.

Chromosomal and plasmid-mediated fluoroquinolone resistance in human Salmonella enterica infection in Ghana.

Author information

1
Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana.
2
Department of Medical Laboratory Technology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
3
Department of Clinical Microbiology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
4
Komfo Anokye Teaching Hospital, Kumasi, Ghana.
5
Agogo Presbyterian Hospital, Agogo, Ghana.
6
Department of Theoretical and Applied Biology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
7
Institute of Plant and Microbial Biology, Academia Sinica, Taipei, Taiwan.
8
Department of Epidemiology, International Vaccine Institute, Seoul, South Korea.
9
Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, 764 Vo Van Kiet, Quant 5, Ho Chi Minh City, Vietnam.
10
Department of Global and International Health, School of Public Health, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. owusudabo@yahoo.com.

Abstract

BACKGROUND:

Salmonella infection poses significant public health threat globally, especially in resource-limited countries. Emergence and spread of antibiotic resistant strains to fluoroquinolones have led to treatment failures and increased mortality in Salmonella infection. However, there is dearth of information regarding mechanisms of resistance to fluoroquinolones in Ghana. This study therefore sought to identify chromosomal mutations and plasmid-mediated resistance as possible mechanisms of fluoroquinolone resistance from clinical isolates in Ghana.

METHODS:

This was a retrospective study of archived isolates biobanked at Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. Isolates were obtained from blood, stool and oropharynx samples at two hospitals, between May, 2016 and January, 2018. Salmonella identification was done using standard microbiological protocols and antibiotic susceptibility testing performed by Kirby-Bauer disc diffusion method. Isolates with intermediate susceptibility and/or resistance to nalidixic acid and/or ciprofloxacin were selected and examined for chromosomal mutations by Sanger sequencing and plasmid-mediated resistance by PCR.

RESULTS:

Of 133 biobanked isolates cultured, 68 (51.1%) and 16 (12%) were identified as Salmonella Typhi and non-typhoidal Salmonella (NTS), respectively. Sequence analysis of gyrA gene revealed the presence of 5 different nonsynonymous mutations, with the most frequent mutation (Ile203Ser) occurring in 12 out of 13 isolates tested. Gyrase B (gyrB) gene had 1 nonsynonymous mutation in 3 out of 13 isolates, substituting phenylalanine with leucine at codon 601 (Phe601Leu). No mutation was observed in parC and parE genes. Two NTS isolates were found to harbour qnrS plasmid-mediated resistant gene of molecular size 550 bp with high ciprofloxacin MIC of 0.5 μg/ml.

CONCLUSION:

This study reports for the first time in Ghana plasmid-mediated fluoroquinolone resistant gene qnrS in Salmonella clinical isolates. Nonsynonymous mutations of gyrA and gyrB genes likely to confer Salmonella reduced susceptibility to ciprofloxacin were also reported.

KEYWORDS:

Fluoroquinolone resistance; Mutations; Plasmids; Salmonella enterica
PMID:
 
31660876
 
DOI:
 
10.1186/s12879-019-4522-1
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33.
 2019 Oct 28;19(1):236. doi: 10.1186/s12866-019-1616-2.

Aging progression of human gut microbiota.

Xu C1,2Zhu H1Qiu P3.

Author information

1
Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.
2
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, 30332, USA.
3
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, 30332, USA. peng.qiu@bme.gatech.edu.

Abstract

BACKGROUND:

Human gut microbiota are important for human health and have been regarded as a "forgotten organ", whose variation is closely linked with various factors, such as host genetics, diet, pathological conditions and external environment. The diversity of human gut microbiota has been correlated with aging, which was characterized by different abundance of bacteria in various age groups. In the literature, most of the previous studies of age-related gut microbiota changes focused on individual species in the gut community with supervised methods. Here, we aimed to examine the underlying aging progression of the human gut microbial community from an unsupervised perspective.

RESULTS:

We obtained raw 16S rRNA sequencing data of subjects ranging from newborns to centenarians from a previous study, and summarized the data into a relative abundance matrix of genera in all the samples. Without using the age information of samples, we applied an unsupervised algorithm to recapitulate the underlying aging progression of microbial community from hosts in different age groups and identify genera associated to this progression. Literature review of these identified genera indicated that for individuals with advanced ages, some beneficial genera are lost while some genera related with inflammation and cancer increase.

CONCLUSIONS:

The multivariate unsupervised analysis here revealed the existence of a continuous aging progression of human gut microbiota along with the host aging process. The identified genera associated to this aging process are meaningful for designing probiotics to maintain the gut microbiota to resemble a young age, which hopefully will lead to positive impact on human health, especially for individuals in advanced age groups.

KEYWORDS:

16S rRNA sequencing; Aging; Human gut microbiota; Sample progression discovery
PMID:
 
31660868
 
DOI:
 
10.1186/s12866-019-1616-2
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34.
 2019 Oct 10. doi: 10.2174/1389203720666191011105624. [Epub ahead of print]

Biomedical and Pharmaceutical-Related Applications of Laccase.

Author information

1
Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2
Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
3
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran 1417614411, Iran.

Abstract

Oxidation of a vast range of phenolic and non-phenolic substrates has been catalyzed by laccases. Given wide range of substrates, laccases can be applied in different biotechnological applications. The present review was conducted to provide a broad context in pharmaceutical- and biomedical-related applications of laccases for academic and industrial researchers. First, an overview on biological roles of laccases was presented. Furthermore, laccase-mediated strategies for imparting antimicrobial and antioxidant properties to different surfaces were discussed. In this review, laccase-mediated mechanisms for endowing antimicrobial properties were divided into laccase-mediated biografting of phenolic compounds on lignocellulosic fiber, chitosan and catheters, and laccase-catalyzed iodination. Accordingly, a special emphasis was placed on laccase-mediated functionalization for creating antimicrobials, particularly chitosan-based wound dressings. Additionally, oxidative biografting and oxidative polymerization were described as two main laccase-catalyzed reactions for imparting antioxidant properties. Recent laccase-related studies were also summarized regarding synthesis of antibacterial and antiproliferative agents and degradation of pharmaceuticals and personal care products.

KEYWORDS:

HIV-1; Laccases; antimicrobial effect; antiproliferative effect; biografting ; degradation
35.
 2019 Oct 29:191422. doi: 10.1148/radiol.2019191422. [Epub ahead of print]

State of the Art in Abdominal CT: The Limits of Iterative Reconstruction Algorithms.

Author information

1
From the Department of Radiology, University of Washington School of Medicine, Seattle, Wash (A.M.); Joint Department of Medical Imaging, Sinai Health System, University of Toronto, Toronto, Ontario, Canada (L.S.G.); and Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (C.H.M., J.G.F., L.Y.).

Abstract

The development and widespread adoption of iterative reconstruction (IR) algorithms for CT have greatly facilitated the contemporary practice of radiation dose reduction during abdominal CT examinations. IR mitigates the increased image noise typically associated with reduced radiation dose levels, thereby maintaining subjective image quality and diagnostic confidence for a variety of clinical tasks. Mounting evidence, however, points to important limitations of this method involving radiologists' ability to perform low-contrast diagnostic tasks, such as the detection of liver metastases or pancreatic masses. Radiologists need to be aware that use of IR can result in a decline of spatial resolution for low-contrast structures and degradation of low-contrast detectability when radiation dose reductions exceed approximately 25%. This article will review the principles of IR algorithm technology, describe the various commercial implementations of IR in CT, and review published studies that have evaluated the ability of IR to preserve diagnostic performance for low-contrast diagnostic tasks. In addition, future developments in CT noise reduction techniques and methods to rigorously evaluate their diagnostic performance will be discussed.
PMID:
 
31660806
 
DOI:
 
10.1148/radiol.2019191422
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36.
 2019 Oct 29:1545968319886485. doi: 10.1177/1545968319886485. [Epub ahead of print]

Moving Stroke Rehabilitation Research Evidence into Clinical Practice: Consensus-Based Core Recommendations From the Stroke Recovery and Rehabilitation Roundtable.

Author information

1
Department of Physical Therapy, University of British Columbia, Vancouver, Canada.
2
School of Health Sciences, University of Tasmania, Launceston, Australia.
3
School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.
4
Centre for Research in Evidence-Based Practice, Bond University, Gold Coast, Australia.
5
Ottawa, Ontario, Canada.
6
Department of Medical Rehabilitation, Obafemi Awolowo University, Ile-Ife, Nigeria.
7
Department of Physiotherapy, School of Allied Health Sciences, Manipal Academy of Higher Education, Manipal, India.
8
Parkwood Institute Research, Lawson Health Research Institute and Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.
9
University of Central Lancashire, Preston, UK and Australian Catholic University, Sydney, Australia.
10
School of Medicine, University of Nottingham, Nottingham, UK.

Abstract

Moving research evidence to practice can take years, if not decades, which denies stroke patients and families from receiving the best care. We present the results of an international consensus process prioritizing what research evidence to implement into stroke rehabilitation practice to have maximal impact. An international 10-member Knowledge Translation Working Group collaborated over a six-month period via videoconferences and a two-day face-to-face meeting. The process was informed from surveys received from 112 consumers/family members and 502 health care providers in over 28 countries, as well as from an international advisory of 20 representatives from 13 countries. From this consensus process, five of the nine identified priorities relate to service delivery (interdisciplinary care, screening and assessment, clinical practice guidelines, intensity, family support) and are generally feasible to implement or improve upon today. Readily available website resources are identified to help health care providers harness the necessary means to implement existing knowledge and solutions to improve service delivery. The remaining four priorities relate to system issues (access to services, transitions in care) and resources (equipment/technology, staffing) and are acknowledged to be more difficult to implement. We recommend that health care providers, managers, and organizations determine whether the priorities we identified are gaps in their local practice, and if so, consider implementation solutions to address them to improve the quality of lives of people living with stroke.

KEYWORDS:

consensus; implementation; knowledge translation; recovery; rehabilitation; stroke
PMID:
 
31660783
 
DOI:
 
10.1177/1545968319886485
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37.
 2019 Oct 29:1545968319886477. doi: 10.1177/1545968319886477. [Epub ahead of print]

Standardized Measurement of Quality of Upper Limb Movement After Stroke: Consensus-Based Core Recommendations From the Second Stroke Recovery and Rehabilitation Roundtable.

Author information

1
Amsterdam UMC, VU Medical Centre, Department of Rehabilitation Medicine, Amsterdam Movement Sciences, Amsterdam Neuroscience, Amsterdam, The Netherlands.
2
Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Rehabilitation Medicine, Amsterdam Movement Sciences, Amsterdam Neuroscience, Amsterdam, The Netherlands.
3
School of Health Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK.
4
Division of Biokinesiology and Physical Therapy, University of Southern California, Los Angeles, CA, USA.
5
I2FH, Institue d'imagerie Fonctionelle Humaine, Montpellier University Hospital Guide, Chauliac, France.
6
Department of Clinical Neuroscience, Rehabilitation Medicine, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
7
School of Physical and Occupational Therapy, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
8
Departments of Neurology, Neuroscience, Physical Medicine & Rehabilitation, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

The second Stroke Recovery and Rehabilitation Roundtable "metrics" task force developed consensus around the recognized need to add kinematic and kinetic movement quantification to its core recommendations for standardized measurements of sensorimotor recovery in stroke trials. Specifically, we focused on measurement of the quality of upper limb movement. We agreed that the recommended protocols for measurement should be conceptually rigorous, reliable, valid and responsive to change. The recommended measurement protocols include four performance assays (i.e. 2D planar reaching, finger individuation, grip strength, and precision grip at body function level) and one functional task (3D drinking task at activity level) that address body function and activity respectively. This document describes the criteria for assessment and makes recommendations about the type of technology that should be used for reliable and valid movement capture. Standardization of kinematic measurement protocols will allow pooling of participant data across sites, thereby increasing sample size aiding meta-analyses of published trials, more detailed exploration of recovery profiles, the generation of new research questions with testable hypotheses, and development of new treatment approaches focused on impairment. We urge the clinical and research community to consider adopting these recommendations.

KEYWORDS:

Stroke; biomechanics; consensus; measurement; recovery; rehabilitation; upper extremity
PMID:
 
31660781
 
DOI:
 
10.1177/1545968319886477
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38.
 2019 Oct 29. doi: 10.1002/humu.23938. [Epub ahead of print]

Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy.

Bryen SJ1,2Ewans L3,4Pinner J3MacLennan SC5,6Donkervoort S7Castro D8Töpf A9O'Grady G1,2Cummings B10,11,12Chao KR10,11,12Weisburd B10,11,12Francioli L10,11,12Faiz F13Bournazos AM1,2Hu Y7Malicki DM14Doyle H15Witting N16Vissing J16Claeys KG17,18Urankar K19Beleza-Meireles A19Baptista J20,21Ellard S20,21Majumdar A19Straub V9Bonnemann C7MacArthur DG10,11,12Davis MR13Cooper ST1,2,22.

Author information

1
Kids Neuroscience Centre, Kids Research, Children's Hospital at Westmead, Westmead, NSW, Australia.
2
Discipline of Child and Adolescent Health, The University of Sydney Children's Hospital Westmead Clinical School, Westmead, NSW, Australia.
3
Department of Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
4
Central Clinical School, University of Sydney, Sydney, NSW, Australia.
5
Neurology Department, Women's and Children's Hospital, North Adelaide, SA, Australia.
6
School of Paediatrics and Reproductive Health, University of Adelaide, Women's and Children's Hospital, North Adelaide, SA, Australia.
7
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
8
University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
9
John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.
10
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
11
Center for Mendelian Genomics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
12
Program in Medical and Population Genetics, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
13
Department of Diagnostic Genomics, PathWest Laboratory Medicine, Nedlands, WA, Australia.
14
Department of Pathology, Rady Children's Hospital University of California San Diego, San Diego, CA, USA.
15
Department of Histopathology, The Children's Hospital at Westmead, Sydney Children's Hospital Network, Westmead, NSW, Australia.
16
Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
17
Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
18
KU Leuven-University of Leuven, Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, Experimental Neurology, Leuven, Belgium.
19
University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom.
20
Molecular Genetics Department, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom.
21
Institute of Biomedical and Clinical Science, University of Exeter Medical School University of Exeter, Exeter, United Kingdom.
22
The Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW, Australia.

Abstract

We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans with a second pathogenic TTN variant. Muscle-derived RNA studies of three individuals confirmed mis-splicing induced by the c.39974-11T>G variant; in-frame exon 214 skipping or use of a cryptic 3' splice-site effecting a frameshift. Confounding interpretation of pathogenicity is the absence of exons 213-217 within the described skeletal muscle TTN N2A isoform. However, RNA-sequencing from 365 adult human gastrocnemius samples revealed 56% specimens predominantly include exons 213-217 in TTN transcripts (inclusion rate ≥ 66%). Further, RNA-sequencing of five fetal muscle samples confirms 4/5 specimens predominantly include exons 213-217 (fifth sample inclusion rate 57%). Importantly, contractures improved significantly with age for four individuals, which may be linked to decreased expression of pathogenic fetal transcripts. Our study extends emerging evidence supporting a vital developmental role for TTN isoforms containing metatranscript-only exons. This article is protected by copyright. All rights reserved.

KEYWORDS:

TTN metatranscript-only; alternative splicing; arthrogryposis; congenital titinopathies; intronic splice variant
PMID:
 
31660661
 
DOI:
 
10.1002/humu.23938
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39.
 2019 Oct 29:18180. doi: 10.14670/HH-18-180. [Epub ahead of print]

Moderate-to-strong expression of FGFR3 and TP53 alterations in a subpopulation of choroid plexus tumors.

Author information

1
BioMediTech Institute and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. kirsi.granberg@gmail.com.
2
Science Center, Tampere University Hospital, Tampere, Finland.
3
Fimlab Laboratories Ltd., Tampere University Hospital, Tampere, Finland.
4
Department of Pathology, Tampere University, Tampere, Finland.
5
BioMediTech Institute and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
6
Department of Pediatrics, Tampere University Hospital, Tampere Center for Child Health Research, Tampere University, Tampere, Finland.
7
Department of Cancer Biology, Wake Forest Baptist Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC USA.

Abstract

INTRODUCTION:

Deregulation of fibroblast growth factor receptor (FGFR) signaling is tightly associated with numerous human malignancies, including cancer. Indeed, FGFR inhibitors are being tested as anti-tumor drugs in clinical trials. Among gliomas, FGFR3 fusions occur in IDH wild-type diffuse gliomas leading to high FGFR3 protein expression and both, FGFR3 and FGFR1, show elevated expression in aggressive ependymomas. The aim of this study was to uncover the expression of FGFR1 and FGFR3 proteins in choroid plexus tumors and to further characterize FGFR-related as well as other genetic alterations in FGFR3 expressing tumors.

METHODS:

Expression levels of FGFR1 and FGFR3 were detected in 15 choroid plexus tumor tissues using immunohistochemistry of tissue microarrays and 6 samples were subjected to whole mount FGFR3 staining. Targeted sequencing was used for deeper molecular analysis of two FGFR3 positive cases.

RESULTS:

Moderate expression of FGFR1 or FGFR3 was evidenced in one third of the studied choroid plexus tumors. Targeted sequencing of a choroid plexus carcinoma and an atypical choroid plexus papilloma, both with moderate-to-strong FGFR3 expression, revealed lack of protein-altering mutations or fusions in FGFR1 or FGFR3, but TP53 was altered in both tumors.

CONCLUSIONS:

FGFR3 and FGFR1 proteins are expressed in a subpopulation of choroid plexus tumors. Further studies using larger cohorts of patients will allow identification of the clinicopathological implications of FGFR1 and FGFR3 expression in choroid plexus tumors.
PMID:
 
31660579
 
DOI:
 
10.14670/HH-18-180
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40.
 2019 Oct 1. doi: 10.1115/1.4045343. [Epub ahead of print]

Efficacy of Clinical Simulation Based Training in Biomedical Engineering Education.

Author information

1
Biomedical Engineering, School of Engineering, Widener University, Chester PA.
2
School of Nursing, Widener University, Chester PA.
3
Drexel University, School of Biomedical Engineering, Sciences and Health Systems, Philadelphia, PA.

Abstract

The need for biomedical engineering (BME) students to be trained in real-world health care settings, where most medical device industry emerges, is imperative. Clinical immersion helps accomplish this training goal. However, the growing student population in the field of BME and a shortage of clinical collaborators offer serious limitations to the clinical immersion experience. This paper describes the use of a clinical simulation-based training (SBT) tool in BME education as an alternative resource to the real-world clinical immersion experience. Through the inclusion of simulation labs in BME courses, we assessed their efficacy in need-finding and enhancing students' understanding of the current challenges of existing medical technology. We also explored the possibility of offering cross-disciplinary learning environments in these simulation labs, including engineers and students from other healthcare disciplines such as nursing. Simulation labs served as a helpful tool in the need-finding phase of the design process, and the immersed students reported higher adaptive and life-long learning outcomes. Students also reported the simulation lab immersion to be valuable to their future goals as engineers. Furthermore, the SBT labs offered repetitive training in a controlled learning environment, inclusion of an interdisciplinary setting, and feedback through student reflections. The inclusion of simulation lab immersion and SBT labs in the two BME courses served as an useful and alternative educational tool that helped train students to better understand the needs of the health care industry while working in interdisciplinary settings.
PMID:
 
31660578
 
DOI:
 
10.1115/1.4045343
41.
 2019 Oct 29. doi: 10.1039/c9tb01730e. [Epub ahead of print]

Progress in electrospun composite nanofibers: composition, performance and applications for tissue engineering.

Gao X1Han S1Zhang R1Liu G1Wu J2.

Author information

1
Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 510006, P. R. China. wujun29@mail.sysu.edu.cn liugt3@mail.sysu.edu.cn.
2
Key Laboratory of Sensing Technology and Biomedical Instrument of Guangdong Province, School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, 510006, P. R. China. wujun29@mail.sysu.edu.cn liugt3@mail.sysu.edu.cn and Research Institute of Sun Yat-Sen University in Shenzhen, Shenzhen, 518057, P. R. China.

Abstract

The discovery of novel methods to fabricate optimal scaffolds that mimic both mechanical and functional properties of the extracellular matrix (ECM) has always been the "holy grail" in tissue engineering. In recent years, electrospinning has emerged as an attractive material fabrication method and has been widely applied in tissue engineering due to its capability of producing non-woven and nanoscale fibers. However, from the perspective of biomimicry, it is difficult for single-component electrospun fiber membranes to achieve the biomimetic purposes of the multi-component extracellular matrix. Based on electrospinning, various functional components can be efficiently and expediently introduced into the membranes, and through the complementation and correlation of the properties of each component, composite materials with comprehensive and superior properties are obtained while maintaining the primitive merits of each component. In this review, we will provide an overview of the attempts made to fabricate electrospinning-based composite tissue engineering materials in the past few decades, which have been divided into organic additives, inorganic additives and organic-inorganic additives.
PMID:
 
31660575
 
DOI:
 
10.1039/c9tb01730e
42.
 2019 Oct 29. doi: 10.1039/c9fo01304k. [Epub ahead of print]

Effects of dietary apple polyphenol supplementation on carcass traits, meat quality, muscle amino acid and fatty acid composition in finishing pigs.

Xu X1Chen X1Chen D1Yu B1Yin J2Huang Z1.

Author information

1
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China. zqhuang@sicau.edu.cn.
2
State Key Lab of Animal Nutrition, College of Animal Science & Technology, China Agricultural University, Beijing 100193, P. R. China.

Abstract

As health awareness is increasing, consumers have changed their focus with a desire to purchase safer, healthier, and higher quality and nutritional value meat. The aim of this study was to investigate whether dietary apple polyphenol (APP) supplementation in finishing pigs could provide pork with high quality and nutritional value. In the present study, 36 castrated Duroc × Landrace × Yorkshire pigs with an average body weight of 71.25 ± 2.40 kg were randomly divided into three treatments and fed with a basal diet supplemented with 0, 400, or 800 mg kg-1 APPs for 7 weeks. The results showed that dietary 800 mg kg-1 APP supplementation not only decreased backfat thickness and abdominal adipose tissue index but also decreased L* (lightness) and b* (yellowness) in the longissimus dorsi (LD) muscle. The LD muscle crude protein content, the proportions of essential amino acids, flavor amino acids, and total amino acids, as well as the amino acid transporter (SLC7A1, SLC7A2, SLC7A7, SLC1A2) mRNA levels were increased by 800 mg kg-1 APPs. The proportions of docosahexaenoic acid and n-3 polyunsaturated fatty acid (PUFA) and the ratio of PUFA to saturated fatty acid in LD muscle were increased by 400 mg kg-1 APPs. Meanwhile, dietary 400 mg kg-1 and 800 mg kg-1 APP supplementation decreased the contents of blood urea nitrogen and total cholesterol, as well as increased the content of inosinic acid in LD muscle. In conclusion, these results suggested that dietary 800 mg kg-1 APP supplementation improved the carcass traits, meat color, and meat flavor in finishing pigs. These results also suggested that dietary 400 mg kg-1 and 800 mg kg-1 APP supplementation improved the meat nutritional value in finishing pigs. The present study provides effective evidence for the application of APP supplementation for healthy high-quality and nutritional value pork production.
PMID:
 
31660546
 
DOI:
 
10.1039/c9fo01304k
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43.
 2019 Oct 21;3:41. doi: 10.1186/s41927-019-0088-1. eCollection 2019.

A review of accelerometer-derived physical activity in the idiopathic inflammatory myopathies.

Oldroyd A1,2,3,4Little MA5,6Dixon W1,2,3,4Chinoy H1,2,3.

Author information

1
1Centre for Epidemiology Versus Arthritis, The University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT UK.
2
2NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
3
3Centre for Musculoskeletal Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
4
4Department of Rheumatology, Salford Royal NHS Foundation Trust, Salford, UK.
5
5School of Computer Science, University of Birmingham, Birmingham, UK.
6
6MIT Media Lab, Massachusetts Institute of Technology, Cambridge, MA USA.

Abstract

BACKGROUND:

The idiopathic inflammatory myopathies (IIMs) are a group of rare conditions characterised by muscle inflammation (myositis). Accurate disease activity assessment is vital in both clinical and research settings, however, current available methods lack ability to quantify associated variation of physical activity, an important consequence of myositis.This study aims to review studies that have collected accelerometer-derived physical activity data in IIM populations, and to investigate if these studies identified associations between physical and myositis disease activity.

METHODS:

A narrative review was conducted to identify original articles that have collected accelerometer-derived physical activity data in IIM populations. The following databases were searched from February 2000 until February 2019: Medline via PubMed, Embase via OVID and Scopus.

RESULTS:

Of the 297 publications screened, eight studies describing accelerometer use in 181 IIM cases were identified. Seven out of the eight studies investigated juvenile dermatomyositis (JDM) populations and only one reported on an adult-onset population. Population sizes, disease duration, accelerometer devices used, body placement sites, and study duration varied between each study.Accelerometer-derived physical activity levels were reduced in IIM cohorts, compared to healthy controls, and studies reported improvement of physical activity levels following exercise programme interventions, thus demonstrating efficacy.Higher levels of accelerometer-derived physical activity measurements were associated with shorter JDM disease duration, current glucocorticoid use and lower serum creatine kinase. However, no clear association between muscle strength and accelerometer-derived physical activity measures was identified.

CONCLUSIONS:

The use of accelerometer-derived physical activity in IIM research is in its infancy. Whilst knowledge is currently limited to small studies, the opportunities are promising and future research in this area has the potential to improve disease activity assessment for clinical and research applications.

KEYWORDS:

Accelerometry; Human activities; Muscle; Myositis; Outcome measures; Review
PMID:
 
31660533
 
PMCID:
 
PMC6805320
 
DOI:
 
10.1186/s41927-019-0088-1
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44.
 2019 Oct 23;5(10):1648-1662. doi: 10.1021/acscentsci.9b00551. Epub 2019 Oct 10.

A Localized Chimeric Hydrogel Therapy Combats Tumor Progression through Alteration of Sphingolipid Metabolism.

Author information

1
Laboratory of Nanotechnology and Chemical Biology, Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, Haryana, India.
2
Kalinga Institute of Industrial Technology, Bhubaneswar 751024, Odisha, India.
3
Manipal Academy of Higher Education, Manipal 576104, Karnataka, India.
4
Department of Chemistry, Indian Institute of Science Education and Research, Bhopal 462066, Madhya Pradesh, India.
5
Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad 121001, Haryana, India.
6
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurgaon 122413, Haryana, India.
7
SCIEX, 121 Udyog Vihar, Phase IV, Gurgaon 122015, Haryana, India.
8
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
9
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.

Abstract

Rapid proliferation of cancer cells assisted by endothelial cell-mediated angiogenesis and acquired inflammation at the tumor microenvironment (TME) lowers the success rate of chemotherapeutic regimens. Therefore, targeting these processes using localized delivery of a minimally toxic drug combination may be a promising strategy. Here, we present engineering of a biocompatible self-assembled lithocholic acid-dipeptide derived hydrogel (TRI-Gel) that can maintain sustained delivery of antiproliferating doxorubicin, antiangiogenic combretastatin-A4 and anti-inflammatory dexamethasone. Application of TRI-Gel therapy to a murine tumor model promotes enhanced apoptosis with a concurrent reduction in angiogenesis and inflammation, leading to effective abrogation of tumor proliferation and increased median survival with reduced drug resistance. In-depth RNA-sequencing analysis showed that TRI-Gel therapy induced transcriptome-wide alternative splicing of many genes responsible for oncogenic transformation including sphingolipid genes. We demonstrate that TRI-Gel therapy targets the reversal of a unique intron retention event in β-glucocerebrosidase 1 (Gba1), thereby increasing the availability of functional Gba1 protein. An enhanced Gba1 activity elevates ceramide levels responsible for apoptosis and decreases glucosylceramides to overcome drug resistance. Therefore, TRI-Gel therapy provides a unique system that affects the TME via post-transcriptional modulations of sphingolipid metabolic genes, thereby opening a new and rational approach to cancer therapy.
PMID:
 
31660434
 
PMCID:
 
PMC6813554
 
DOI:
 
10.1021/acscentsci.9b00551
45.
 2019 Jun 27;6(9):ofz302. doi: 10.1093/ofid/ofz302. eCollection 2019 Sep.

Blurred Molecular Epidemiological Lines Between the Two Dominant Methicillin-Resistant Staphylococcus aureus Clones.

Author information

1
Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York City, New York Department of Medicine.
2
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York.
3
Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York City, New York.
4
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York City, New York.

Abstract

BACKGROUND:

Methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening infections in both community and hospital settings and is a leading cause of health care-associated infections (HAIs). We sought to describe the molecular epidemiological landscape of patients with MRSA bloodstream infections (BSIs) at an urban medical center by evaluating the clinical characteristics associated with the two dominant endemic clones.

METHODS:

Comprehensive clinical data from the electronic health records of 227 hospitalized patients ≥18 years old with MRSA BSI over a 33-month period in New York City were collected. The descriptive epidemiology and mortality associated with the two dominant clones were compared using logistic regression.

RESULTS:

Molecular analysis revealed that 91% of all single-patient MRSA BSIs were due to two equally represented genotypes, clonal complex (CC) 5 (n = 117) and CC8 (n = 110). MRSA BSIs were associated with a 90-day mortality rate of 27%. CC8 caused disease more frequently in younger age groups (56 ± 17 vs 67 ± 17 years old; P < .001) and in those of nonwhite race (odds ratio [OR], 3.45; 95% confidence interval [CI], 1.51-7.87; P = .003), with few other major distinguishing features. Morbidity and mortality also did not differ significantly between the two clones. CC8 caused BSIs more frequently in the setting of peripheral intravenous catheters (OR, 5.96; 95% CI, 1.51-23.50; P = .01).

CONCLUSIONS:

The clinical features distinguishing dominant MRSA clones continue to converge. The association of CC8 with peripheral intravenous catheter infections underscores the importance of classical community clones causing hospital-onset infections. Ongoing monitoring and analysis of the dynamic epidemiology of this endemic pathogen are crucial to inform management and prevent disease.

KEYWORDS:

bloodstream infections; methicillin-resistant Staphylococcus aureus; molecular epidemiology; peripheral intravenous catheters
PMID:
 
31660395
 
PMCID:
 
PMC6735859
 
DOI:
 
10.1093/ofid/ofz302
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46.
 2019 Sep 29;6(10):ofz419. doi: 10.1093/ofid/ofz419. eCollection 2019 Oct.

The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015-2017.

Author information

1
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
2
Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, UK.
3
University of Minnesota, Minneapolis, Minnesota, USA.
4
Clinical Research Department, London School of Hygiene and Tropical Medicine, London, UK.
5
Mbarara University of Science and Technology, Mbarara, Uganda.

Abstract

BACKGROUND:

Central nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%-25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving.

METHODS:

We prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures.

RESULTS:

We screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person.

CONCLUSIONS:

Despite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics.

KEYWORDS:

HIV/AIDS; bacterial meningitis; cryptococcal meningitis; tuberculous meningitis; viral meningitis
PMID:
 
31660375
 
PMCID:
 
PMC6810358
 
DOI:
 
10.1093/ofid/ofz419
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47.
 2019 Sep 30;6(10):ofz370. doi: 10.1093/ofid/ofz370. eCollection 2019 Oct.

Molecular Evidence of Influenza A Virus Circulation in African Dromedary Camels Imported to Saudi Arabia, 2017-2018.

Author information

1
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
2
Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
3
Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
4
Directorate of Agriculture, Ministry of Environment, Water, and Agriculture, Makkah Region, Saudi Arabia.
5
Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Little is known about influenza A viruses in dromedaries. Here, we detected influenza A viral RNA in 11 specimens (1.7 %) out of 665 nasal swabs collected from dromedaries between 2017 and 2018 in Saudi Arabia. Positive samples were detected only in imported camels from Sudan and Djibouti but not local ones. Partial genome sequencing indicates a close relationship to 2009-2019 human/swine influenza A H1N1 isolates from different countries, suggesting possible interspecies transmission. Taken together, dromedaries could represent a potentially unrecognized permissive host for these viruses, highlighting the need for enhanced surveillance in animals to aid implementation of one-health strategies.

KEYWORDS:

Africa; Saudi Arabia; camels; dromedaries; influenza A viruses; surveillance
PMID:
 
31660338
 
PMCID:
 
PMC6767964
 
DOI:
 
10.1093/ofid/ofz370
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48.
 2019 Sep 30;6(10):ofz298. doi: 10.1093/ofid/ofz298. eCollection 2019 Oct.

Recommended First-Line Antiretroviral Therapy Regimens and Risk of Diabetes Mellitus in HIV-Infected Adults in Resource-Limited Settings.

Author information

1
Clinical Epidemiology Program, Faculty of Medicine, Chiang Mai University, Thailand.
2
National Health Security Office, Bangkok, Thailand.
3
Institut de Recherche pour le Developpement (IRD), France.
4
Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
5
Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
6
Department of Surgery, Faculty of Medicine, Chiang Mai University, Thailand.
7
INSERM UMR 1135, Equipe ECSTRA, Centre de Recherche Epidémiologie et Biostatistique Sorbonne Paris Cité, Université Paris Diderot, France.
8
Department of Molecular and Clinical Pharmacology, University of Liverpool, United Kingdom.
9
Department of Medicine, Faculty of Medicine, Chiang Mai University, Thailand.
10
Department of Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
11
School of Medicine, University of Phayao, Thailand.

Abstract

OBJECTIVE:

The use of some antiretroviral drugs has been associated with a higher risk of diabetes mellitus (DM) in HIV-infected patients, but the risk associated with antiretroviral drug combinations remains unclear. We investigated the association between first-line antiretroviral therapy (ART) regimens, recommended by the World Health Organization (WHO) in 2016, and the risk of DM in adults.

METHOD:

We selected all HIV-infected adults within the Thai National AIDS Program who started a first-line ART regimen consisting the following between October 2006 and September 2013: zidovudine+lamivudine+nevirapine; tenofovir disoproxil fumarate (TDF)+lamivudine+nevirapine; zidovudine+lamivudine+efavirenz; TDF+lamivudine/emtricitabine+efavirenz; zidovudine+lamivudine+ritonavir-boosted lopinavir (LPV/r); or TDF+lamivudine+LPV/r. Diagnosis of DM was defined as having at least 2 of the following characteristics: fasting plasma glucose ≥126 mg/dl, 2010 WHO ICD-10 codes E11-E14, or prescription of antidiabetic drugs. To identify ART regimens associated with DM, we used competing risks regression models that considered mortality without DM as a competing event and adjusted for sex, age, pancreas disease, and stratified by groups defined by a score summarizing the propensity to receive a specific first-line ART regimen.

RESULTS:

Data from 35 710 adults (49.1% male; median age, 35.0 years; median follow-up, 2.0 years) were included. In the multivariable analysis with zidovudine+lamivudine+nevirapine as the reference group, a higher risk of DM was observed with TDF+lamivudine/emtricitabine+efavirenz (adjusted sub-distribution hazard ratio [aSHR], 1.6; 95% confidence interval [CI], 1.3-1.9), zidovudine+lamivudine+efavirenz (aSHR, 2.0; 95% CI, 1.7-2.3), and TDF+lamivudine+LPV/r (aSHR, 2.7; 95% CI, 1.9-3.9).

CONCLUSIONS:

Several of the WHO recommended ART regimens, particularly tenofovir + lamivudine +LPV/r and regimens containing efavirenz, may be associated with an increased risk of DM.

KEYWORDS:

HIV; antiretroviral treatment regimen; diabetes mellitus; efavirenz; ritonavir-boosted lopinavir
PMID:
 
31660327
 
PMCID:
 
PMC6778321
 
DOI:
 
10.1093/ofid/ofz298
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49.
 2019 Sep;7(17):423. doi: 10.21037/atm.2019.07.88.

Cardiac technology.

Author information

1
Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
PMID:
 
31660322
 
PMCID:
 
PMC6787381
 
DOI:
 
10.21037/atm.2019.07.88
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50.
 2019 Sep;7(17):417. doi: 10.21037/atm.2019.06.79.

Apple Watch, Wearables, and Heart Rhythm: where do we stand?

Author information

1
Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
2
Department of Medicine, The George Washington University School of Medicine & Health Sciences, Washington, DC, USA.
3
Department of Medicine, Cairo University, Cairo, Egypt.
4
Department of Pharmacy, Methodist University Hospital, Memphis, TN, USA.
5
Department of Internal Medicine, Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis, TN, USA.

Abstract

Atrial fibrillation (AF) poses a major health concern in the United States by affecting over 5 million people accounting for at least 15% to 25% of strokes. It can be asymptomatic or subclinical with its first presentation being stroke in 18%, and AF being only detected at the time of stroke. With evidence of subclinical AF associated with increased risk of ischemic stroke, recent developments indeed point towards wearables, especially smart watches, being quite effective and representing a novel method for screening for silent AF in the general population, and thereby reducing mortality and morbidity associated with it. This manuscript aims to review whether the photoplethysmography (PPG) technology, employed in the wearables to monitor heart rate, is accurate enough to aid in the diagnosis of AF that may remain asymptomatic or paroxysmal. It also explores the option of actually employing this method in the general population, the feasibility of this mode of diagnosis, sensitivity and specificity of this method compared to the conventional electrocardiogram (EKG), and the actual follow up with a practitioner and subsequent treatment of AF, if diagnosed. We conducted a Medline search using various combinations of "smart watch" "atrial fibrillation" "wearables", and "Kardia" to identify pivotal randomized trials published before June 1, 2019, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine the effectiveness of smart watch technology in detecting AF in the general population. Trials reviewed evaluated apple watch, Kardia, Samsung wearables in diagnosis of AF. The fact that there is an increase in consumer use of wearables, smart devices, which can serve as health monitoring devices that can be used as a non-invasive, ambulatory assessment of heart rate and rhythm, is definitely novel. Intermittent short EKG recordings repeated over a longer-term period produced significantly better sensitivity for AF detection, with 4 times as many cases diagnosed compared with a single time-point measurement. Since there are limitations and further research into this new field is required, the wearable technology may not serve as the ultimate tool for diagnosis of AF, rather a nidus for the general population to seek medical advice for confirmation on being notified of having an irregular rhythm leading to prevention of morbidity and mortality associated with it.

KEYWORDS:

Apple watch; arrhythmia; atrial fibrillation (AF); single lead electrocardiogram (single lead EKG); wearables
PMID:
 
31660316
 
PMCID:
 
PMC6787392
 
DOI:
 
10.21037/atm.2019.06.79
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