scholarly journals Genomic Prediction of Antimicrobial Resistance: Ready or Not, Here It Comes!

2020 ◽  
Vol 66 (10) ◽  
pp. 1278-1289
Author(s):  
Eric M Ransom ◽  
Robert F Potter ◽  
Gautam Dantas ◽  
Carey-Ann D Burnham
Keyword(s):  
Antimicrobial Resistance ◽  
Diagnostic Testing ◽  
Turnaround Time ◽  
Added Value ◽  
Clinical Settings ◽  
Bioinformatic Pipeline ◽  
Current State ◽  
Resistance Prediction ◽  
Diagnostic Microbiology ◽  
Next Generation Sequencing Ngs

Abstract Background Next-generation sequencing (NGS) technologies are being used to predict antimicrobial resistance. The field is evolving rapidly and transitioning out of the research setting into clinical use. Clinical laboratories are evaluating the accuracy and utility of genomic resistance prediction, including methods for NGS, downstream bioinformatic pipeline components, and the clinical settings in which this type of testing should be offered. Content We describe genomic sequencing as it pertains to predicting antimicrobial resistance in clinical isolates and samples. We elaborate on current methodologies and workflows to perform this testing and summarize the current state of genomic resistance prediction in clinical settings. To highlight this aspect, we include 3 medically relevant microorganism exemplars: Mycobacterium tuberculosis, Staphylococcus aureus, and Neisseria gonorrhoeae. Last, we discuss the future of genomic-based resistance detection in clinical microbiology laboratories. Summary Antimicrobial resistance prediction by genomic approaches is in its infancy for routine patient care. Genomic approaches have already added value to the current diagnostic testing landscape in specific circumstances and will play an increasingly important role in diagnostic microbiology. Future advancements will shorten turnaround time, reduce costs, and improve our analysis and interpretation of clinically actionable results.

Transcranial Electrical Stimulation in Post-Stroke Cognitive Rehabilitation

2016 ◽  
Vol 21 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Silvia Convento ◽  
Cristina Russo ◽  
Luca Zigiotto ◽  
Nadia Bolognini
Keyword(s):  
Electrical Stimulation ◽  
Cognitive Rehabilitation ◽  
Cognitive Disorders ◽  
Spatial Neglect ◽  
Transcranial Electrical Stimulation ◽  
Clinical Settings ◽  
Post Stroke ◽  
Neuropsychological Disorders ◽  
Current State ◽  
Stimulation Technique

Abstract. Cognitive rehabilitation is an important area of neurological rehabilitation, which aims at the treatment of cognitive disorders due to acquired brain damage of different etiology, including stroke. Although the importance of cognitive rehabilitation for stroke survivors is well recognized, available cognitive treatments for neuropsychological disorders, such as spatial neglect, hemianopia, apraxia, and working memory, are overall still unsatisfactory. The growing body of evidence supporting the potential of the transcranial Electrical Stimulation (tES) as tool for interacting with neuroplasticity in the human brain, in turn for enhancing perceptual and cognitive functions, has obvious implications for the translation of this noninvasive brain stimulation technique into clinical settings, in particular for the development of tES as adjuvant tool for cognitive rehabilitation. The present review aims at presenting the current state of art concerning the use of tES for the improvement of post-stroke visual and cognitive deficits (except for aphasia and memory disorders), showing the therapeutic promises of this technique and offering some suggestions for the design of future clinical trials. Although this line of research is still in infancy, as compared to the progresses made in the last years in other neurorehabilitation domains, current findings appear very encouraging, supporting the development of tES for the treatment of post-stroke cognitive impairments.

scholarly journals 458. Molecular SARS-CoV-2 Testing During the COVID-19 Outbreak: Experiences of a Hospital in Southeast Michigan, USA

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S296-S297
Author(s):  
Trini A Mathew ◽  
Jonathan Hopkins ◽  
Diane Kamerer ◽  
Shagufta N Ali ◽  
Daniel Ortiz ◽  
...  
Keyword(s):  
Clinical Features ◽  
Diagnostic Testing ◽  
Beaumont Hospital ◽  
High Capacity ◽  
Turnaround Time ◽  
Molecular Diagnostic ◽  
The Novel ◽  
Repeat Testing ◽  
Asymptomatic Patients ◽  
Novel Coronavirus

Abstract Background The novel Coronavirus SARS CoV-2 (COVID-19) outbreak was complicated by the lack of diagnostic testing kits. In early March 2020, leadership at Beaumont Hospital, Royal Oak Michigan (Beaumont) identified the need to develop high capacity testing modalities with appropriate sensitivity and specificity and rapid turnaround time. We describe the molecular diagnostic testing experience since initial rollout on March 16, 2020 at Beaumont, and results of repeat testing during the peak of the COVID-19 pandemic in MI. Methods Beaumont is an 1100 bed hospital in Southeast MI. In March, testing was initially performed with the EUA Luminex NxTAG CoV Extended Panel until March 28, 2020 when testing was converted to the EUA Cepheid Xpert Xpress SARS-CoV-2 for quicker turnaround times. Each assay was validated with a combination of patient samples and contrived specimens. Results During the initial week of testing there was > 20 % specimen positivity. As the prevalence grew the positivity rate reached 68% by the end of March (Figure 1). Many state and hospital initiatives were implemented during the outbreak, including social distancing and screening of asymptomatic patients to increase case-finding and prevent transmission. We also adopted a process for clinical review of symptomatic patients who initially tested negative for SARS-CoV-2 by a group of infectious disease physicians (Figure 2). This process was expanded to include other trained clinicians who were redeployed from other departments in the hospital. Repeat testing was performed to allow consideration of discontinuation of isolation precautions. During the surge of community cases from March 16 to April 30, 2020, we identified patients with negative PCR tests who subsequently had repeat testing based on clinical evaluation, with 7.1% (39/551) returning positive for SARS- CoV2. Of the patients who expired due to COVID-19 during this period, 4.3% (9/206) initially tested negative before ultimately testing positive. Figure 1 BH RO testing Epicurve Figure 2: Screening tool for repeat COVID19 testing and precautions Conclusion Many state and hospital initiatives helped us flatten the curve for COVID-19. Our hospital testing experience indicate that repeat testing may be warranted for those patients with clinical features suggestive of COVID-19. We will further analyze these cases and clinical features that prompted repeat testing. Disclosures All Authors: No reported disclosures

scholarly journals Characteristics and Clinical Application of Extracellular Vesicle-Derived DNA

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3827
Author(s):  
Jae Young Hur ◽  
Kye Young Lee
Keyword(s):  
Therapeutic Potential ◽  
Extracellular Vesicle ◽  
Clinical Settings ◽  
Biomarker Detection ◽  
Diagnosis And Prognosis ◽  
Double Stranded Dna ◽  
Fundamental Research ◽  
The Stability ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Extracellular vesicles (EVs) carry RNA, proteins, lipids, and diverse biomolecules for intercellular communication. Recent studies have reported that EVs contain double-stranded DNA (dsDNA) and oncogenic mutant DNA. The advantage of EV-derived DNA (EV DNA) over cell-free DNA (cfDNA) is the stability achieved through the encapsulation in the lipid bilayer of EVs, which protects EV DNA from degradation by external factors. The existence of DNA and its stability make EVs a useful source of biomarkers. However, fundamental research on EV DNA remains limited, and many aspects of EV DNA are poorly understood. This review examines the known characteristics of EV DNA, biogenesis of DNA-containing EVs, methylation, and next-generation sequencing (NGS) analysis using EV DNA for biomarker detection. On the basis of this knowledge, this review explores how EV DNA can be incorporated into diagnosis and prognosis in clinical settings, as well as gene transfer of EV DNA and its therapeutic potential.

scholarly journals Different Methods in HPV Genotyping of Anogenital and Oropharyngeal Lesions: Comparison between VisionArray® Technology, Next Generation Sequencing, and Hybrid Capture Assay

2021 ◽  
Vol 2 (1) ◽  
pp. 29-41
Author(s):  
Giorgia Acquaviva ◽  
Michela Visani ◽  
Viviana Sanza ◽  
Antonio De Leo ◽  
Thais Maloberti ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Turnaround Time ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Next Generation ◽  
Hybrid Capture ◽  
Capture Assay ◽  
Anogenital Area ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

(1) Background: Human papillomaviruses (HPVs) are known to be related to the development of about 5% of all human cancers. The clinical relevance of HPV infection has been deeply investigated in carcinomas of the oropharyngeal area, uterine cervix, and anogenital area. To date, several different methods have been used for detecting HPV infection. The aim of the present study was to compare three different methods for the diagnosis of the presence of the HPV genome. (2) Methods: A total of 50 samples were analyzed. Twenty-five of them were tested using both next generation sequencing (NGS) and VisionArray® technology, the other 25 were tested using Hybrid Capture (HC) II assay and VisionArray® technology. (3) Results: A substantial agreement was obtained using NGS and VisionArray® (κ = 0.802), as well as between HC II and VisionArray® (κ = 0.606). In both analyses, the concordance increased if only high risk HPVs I(HR-HPVs) were considered as “positive”. (4) Conclusions: Our data highlighted the importance of technical choice in HPV characterization, which should be guided by the clinical aims, costs, starting material, and turnaround time for results.

Mycoplasma genitalium: test positivity in syndromic presentations and clinicians’ adherence with treatment guidelines at Sydney Sexual Health Centre

2021 ◽  
pp. 095646242110225
Author(s):  
Calvin Cheung ◽  
Christopher Bourne ◽  
Rick Varma
Keyword(s):  
Decision Making ◽  
Antimicrobial Resistance ◽  
Sexual Health ◽  
Treatment Guidelines ◽  
Health Centre ◽  
Diagnostic Testing ◽  
Mycoplasma Genitalium ◽  
Macrolide Resistance ◽  
Adherence To Treatment ◽  
Real World Data

Mycoplasma genitalium ( M.genitalium) is associated with urethritis, cervicitis, pelvic inflammatory disease, proctitis and epididymitis. Its treatment is complicated by antimicrobial resistance. To assess clinicians’ adherence to M.genitalium diagnostic testing recommendations for syndromic presentations, as well as resistance-guided management of M.genitalium at Sydney Sexual Health Centre, we reviewed patients presenting between August and December 2018. 349/372 (94%) syndromic presentations were tested for M.genitalium with 16% M.genitalium test positivity and 81% macrolide resistance. 16/27 (59%) macrolide-sensitive infections and 65/77 (84%) macrolide-resistant infections received resistance-guided treatment. Tests of cure (TOCs) were unnecessarily ordered for 82% macrolide-sensitive cases, while 88% macrolide-resistant cases were correctly ordered TOCs. Co-existing STIs at the time of macrolide-sensitive ( p = 0.30) or macrolide-resistant M.genitalium ( p = 0.94) diagnosis did not significantly affect adherence to treatment guidelines. This study confirms the expected prevalence of M.genitalium and macrolide resistance in syndromic presentations while our real-world data highlight the decision-making challenges involved with managing M.genitalium, offering insights for further research.

scholarly journals Microfluidic PCR Combined with Pyrosequencing for Identification of Allelic Variants with Phenotypic Associations among Targeted Salmonella Genes

2012 ◽  
Vol 78 (20) ◽  
pp. 7480-7482 ◽  
Author(s):  
Min Yue ◽  
Robert Schmieder ◽  
Robert A. Edwards ◽  
Shelley C. Rankin ◽  
Dieter M. Schifferli
Keyword(s):  
Genetic Variation ◽  
Antimicrobial Resistance ◽  
Host Species ◽  
Massive Parallel Sequencing ◽  
Allelic Variants ◽  
Parallel Sequencing ◽  
Content Type ◽  
Potential Applications ◽  
Fimbrial Adhesins ◽  
Diagnostic Microbiology

ABSTRACTA novel targeted massive parallel sequencing approach identified genetic variation in eight known or predicted fimbrial adhesins for 46Salmonellastrains. The results highlight associations between specific adhesin alleles, host species, and antimicrobial resistance. The differentiation of allelic variants has potential applications for diagnostic microbiology and epidemiological investigations.

scholarly journals Proteomic Research on Medicinal Mushrooms Antitumor Properties

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6708
Author(s):  
Boris Jakopovic ◽  
Nada Oršolić ◽  
Ivan Jakopovich
Keyword(s):  
Therapeutic Modality ◽  
Whole Body ◽  
Clinical Settings ◽  
Medicinal Mushroom ◽  
Mushroom Species ◽  
Medicinal Mushrooms ◽  
Current State ◽  
Antitumor Properties ◽  
Proteomic Research ◽  
Complementary Oncology

Medicinal mushrooms are increasingly being recognized as an important therapeutic modality in complementary oncology. Until now, more than 800 mushroom species have been known to possess significant pharmacological properties, of which antitumor and immunomodulatory properties have been the most researched. Besides a number of medicinal mushroom preparations being used as dietary supplements and nutraceuticals, several isolates from mushrooms have been used as official antitumor drugs in clinical settings for several decades. Various proteomic approaches allow for the identification of a large number of differentially regulated proteins serendipitously, thereby providing an important platform for a discovery of new potential therapeutic targets and approaches as well as biomarkers of malignant disease. This review is focused on the current state of proteomic research into antitumor mechanisms of some of the most researched medicinal mushroom species, including Phellinus linteus, Ganoderma lucidum, Auricularia auricula, Agrocybe aegerita, Grifola frondosa, and Lentinus edodes, as whole body extracts or various isolates, as well as of complex extract mixtures.

scholarly journals Mathematical Modelling to Study the Horizontal Transfer of Antimicrobial Resistance Genes in Bacteria: Current State of the Field and Recommendations

2019 ◽  
Author(s):  
Quentin J. Leclerc ◽  
Jodi A. Lindsay ◽  
Gwenan M. Knight
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Mathematical Modelling ◽  
Resistance Genes ◽  
Horizontal Transfer ◽  
Evolutionary Dynamics ◽  
Research Field ◽  
Contact Transformation ◽  
Current State ◽  
Antimicrobial Resistance Genes

Antimicrobial resistance (AMR) is one of the greatest public health challenges we are currently facing. To develop effective interventions against this, it is essential to understand the processes behind the spread of AMR. These are partly dependent on the dynamics of horizontal transfer of resistance genes between bacteria, which can occur by conjugation (direct contact), transformation (uptake from the environment) or transduction (mediated by bacteriophages). Mathematical modelling is a powerful tool to investigate the dynamics of AMR, however its application to study the horizontal transfer of AMR genes is currently unclear. In this systematic review, we searched for mathematical modelling studies which focused on horizontal transfer of AMR genes. We compared their aims and methods using a list of predetermined criteria, and utilized our results to assess the current state of this research field. Of the 43 studies we identified, most focused on the transfer of single genes by conjugation in Escherichia coli in culture, and its impact on the bacterial evolutionary dynamics. Our findings highlight the existence of an important research gap on the dynamics of transformation and transduction, and the overall public health implications of horizontal transfer of AMR genes. To further develop this field and improve our ability to control AMR, it is essential that we clarify the structural complexity required to study the dynamics of horizontal gene transfer, which will require cooperation between microbiologists and modellers.

scholarly journals Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer

2021 ◽  
Vol 22 (18) ◽  
pp. 9953
Author(s):  
Mai Tanaka ◽  
Dietmar W. Siemann
Keyword(s):  
Signaling Pathway ◽  
Receptor Tyrosine Kinase ◽  
Therapeutic Agents ◽  
Therapeutic Interventions ◽  
Therapeutic Resistance ◽  
Clinical Settings ◽  
Affinity Ligand ◽  
Current State ◽  
Cancer Types ◽  
High Affinity Ligand

Many signaling pathways are dysregulated in cancer cells and the host tumor microenvironment. Aberrant receptor tyrosine kinase (RTK) pathways promote cancer development, progression, and metastasis. Hence, numerous therapeutic interventions targeting RTKs have been actively pursued. Axl is an RTK that belongs to the Tyro3, Axl, MerTK (TAM) subfamily. Axl binds to a high affinity ligand growth arrest specific 6 (Gas6) that belongs to the vitamin K-dependent family of proteins. The Gas6/Axl signaling pathway has been implicated to promote progression, metastasis, immune evasion, and therapeutic resistance in many cancer types. Therapeutic agents targeting Gas6 and Axl have been developed, and promising results have been observed in both preclinical and clinical settings when such agents are used alone or in combination therapy. This review examines the current state of therapeutics targeting the Gas6/Axl pathway in cancer and discusses Gas6- and Axl-targeting agents that have been evaluated preclinically and clinically.

Point-Of-Care Clinical Evaluation of the Clungene® SARS-CoV-2 Virus IgG/IgM 15-minute rapid test cassette with the Cobas® Roche RT-PCR platform in patients with or without Covid-19

2021 ◽  
Author(s):  
Fadi Haddad ◽  
Christopher C Lamb ◽  
Ravina Kullar ◽  
George Sakoulas
Keyword(s):  
Symptom Onset ◽  
Serological Test ◽  
Point Of Care ◽  
Diagnostic Testing ◽  
Rapid Test ◽  
Lateral Flow ◽  
Added Value ◽  
Lateral Flow Immunoassay ◽  
Rt Pcr ◽  
Past Infection

Background: Covid-19 remains a pandemic with multiple challenges to confirm patient infectivity: lack of sufficient tests, accurate results, validated quality, and timeliness of results. We hypothesize that a rapid 15-minute Point-Of-Care serological test to evaluate past infection complements diagnostic testing for Covid-19 and significantly enhances testing availability. Method: A three arm observational study at Sharp Healthcare, San Diego, California was conducted using the Clungene® lateral flow immunoassay (LFI) and compared with the Cobas® Roche RT PCR results. Arm 1: Thirty-five (35) subjects with confirmed Covid-19 using RT-PCR were tested twice: prior to 14 days following symptom onset and once between 12 and 70 days. Arm 2: Thirty (30) subjects with confirmed Covid-19 using RT-PCR were tested 12-70 days post symptom onset. Arm 3: Thirty (30) subjects with a negative RT-PCR for Covid-19 were tested 1-10 days following the RT-PCR test date. Results: Specificity of confirmed negative Covid-19 by RT-PCR was 100% (95% CI, 88.4%-100.0%); meaning there was 100% negative positive agreement between the RT-PCR and the Clungene® serological test results. Covid-19 subjects tested prior to day 7 symptom onset were antibody negative. In subjects 7-12 days following symptom onset with a confirmed positive Covid-19 by RT-PCR, the combined sensitivity of IgM and IgG was 58.6% (95% CI, 38.9%-76.5%). In subjects 13-70 days following symptom onset with a confirmed positive Covid-19 by RT-PCR the combined sensitivity of IgM and IgG was 90.5% (95% CI, 80.4%-96.4%). Conclusion: The Clungene® lateral flow immunoassay (LFI) is a useful tool to confirm individuals with an adaptive immune response to SARS-CoV-2 indicating past infection. Providing Point-Of-Care results within 15 minutes without any laboratory instrumentation or specialized software has an added value of increasing test availability to patients who have been symptomatic for more than one week to confirm past infection. Performance characteristics are optimal after 13 days with a sensitivity and specificity of 90% and 100%, respectively.

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