Biomedical Research Laboratories Research Articles

Biomedical Research and Informatics Living Laboratory for Innovative Advances of New Technologies in Community Mobility Rehabilitation: Protocol for Evaluation and Rehabilitation of Mobility Across Continuums of Care.

BackgroundRapid advances in technologies over the past 10 years have enabled large-scale biomedical and psychosocial rehabilitation research to improve the function and social integration of persons with physical impairments across the lifespan. The Biomedical Research and Informatics Living Laboratory for Innovative Advances of New Technologies (BRILLIANT) in community mobility rehabilitation aims to generate evidence-based research to improve rehabilitation for individuals with acquired brain injury (ABI).ObjectiveThis study aims to (1) identify the factors limiting or enhancing mobility in real-world community environments (public spaces, including the mall, home, and outdoors) and understand their complex interplay in individuals of all ages with ABI and (2) customize community environment mobility training by identifying, on a continuous basis, the specific rehabilitation strategies and interventions that patient subgroups benefit from most. Here, we present the research and technology plan for the BRILLIANT initiative.MethodsA cohort of individuals, adults and children, with ABI (N=1500) will be recruited. Patients will be recruited from the acute care and rehabilitation partner centers within 4 health regions (living labs) and followed throughout the continuum of rehabilitation. Participants will also be recruited from the community. Biomedical, clinician-reported, patient-reported, and brain imaging data will be collected. Theme 1 will implement and evaluate the feasibility of collecting data across BRILLIANT living labs and conduct predictive analyses and artificial intelligence (AI) to identify mobility subgroups. Theme 2 will implement, evaluate, and identify community mobility interventions that optimize outcomes for mobility subgroups of patients with ABI.ResultsThe biomedical infrastructure and equipment have been established across the living labs, and development of the clinician- and patient-reported outcome digital solutions is underway. Recruitment is expected to begin in May 2022.ConclusionsThe program will develop and deploy a comprehensive clinical and community-based mobility-monitoring system to evaluate the factors that result in poor mobility, and develop personalized mobility interventions that are optimized for specific patient subgroups. Technology solutions will be designed to support clinicians and patients to deliver cost-effective care and the right intervention to the right person at the right time to optimize long-term functional potential and meaningful participation in the community.International Registered Report Identifier (IRRID)PRR1-10.2196/12506

The U.S. National Library of Medicine's impact on precision and genomic medicine.

Precision medicine offers the potential to improve health through deeper understandings of the lifestyle, biological, and environmental influences on health. Under Dr. Donald A. B. Lindberg’s leadership, the U.S. National Library of Medicine (NLM) has developed the central reference resources for biomedical research and molecular laboratory medicine that enable precision medicine. The hosting and curation of biomedical knowledge repositories and data by NLM enable quality information reachable for providers and researchers throughout the world. NLM has been supporting the innovation of electronic health record systems to implement computability and secondary use for biomedical research, producing the scale of linked health and molecular datasets necessary for precision medicine discovery.

Role of GILT and MHC class II in melanoma cells on regulating the anti-tumor immune response

Abstract The MHC class I antigen presentation pathway in melanoma cells has a well-established role in immune-mediated destruction of melanoma. However, the role of the MHC class II pathway in melanoma cells is not fully understood. Gamma-interferon-inducible lysosomal thiol reductase (GILT) is critical for MHC class II-restricted presentation of multiple melanoma antigens by antigen presenting cells. While GILT and MHC class II expression is typically limited to antigen presenting cells, GILT and MHC class II can be expressed constitutively or induced by IFN-γ in melanoma cells. In human melanoma specimens, high GILT expression and an active and intact MHC class II pathway are associated with improved survival. The goal of this project is to investigate a causal role for GILT and MHC class II in melanoma cells, using Yale University Mouse Melanoma (YUMM) lines YUMM2.1, YUMMER1.7, and YUMMERG. These cell lines constitutively expressed GILT, and MHC class II expression was IFN-γ-inducible in a subset of cells under serum-free conditions. We have genetically engineered GILT−/− YUMM2.1 cells and MHC class II (H2Ab1)−/− YUMM2.1 cells via CRISPR/Cas9 and verified the deletion. We have generated lentiviral constructs expressing GILT alone, CIITA alone, and dual expression of H2Ab1 and CIITA, to allow for the generation of melanoma cell lines with and without GILT and MHC class II. Transduction of GILT−/− YUMM2.1 cells with GILT resulted in high transduction efficiency and overexpression. Thus, we have developed models to determine the effect of GILT and MHC class II expression in melanoma cells on regulating in vivo tumor growth and the anti-tumor immune response. This work was supported by a Basic Science Award from the Harry J. Lloyd Charitable Trust and a Merit Review Award I01-BX005336 from the US Department of Veterans Affairs (VA), Biomedical Laboratory Research and Development Service (K.T.H.). The contents do not represent the views of the VA or the US Government.

The U.S. National Library of Medicine's Impact on Precision and Genomic Medicine.

Precision medicine offers the potential to improve health through deeper understandings of the lifestyle, biological, and environmental influences on health. Under Dr. Donald A.B. Lindberg's leadership, the U.S. National Library of Medicine (NLM) has developed the central reference resources for biomedical research and molecular laboratory medicine that enable precision medicine. The hosting and curation of biomedical knowledge repositories and data by NLM enable quality information reachable for providers and researchers throughout the world. NLM has been supporting the innovation of electronic health record systems to implement computability and secondary use for biomedical research, producing the scale of linked health and molecular datasets necessary for precision medicine discovery.

A System to Easily Manage Metadata in Biomedical Research Labs Based on Open-source Software.

In most biomedical labs, researchers gather metadata (i.e., all details about the experimental data) in paper notebooks, spreadsheets, or, sometimes, electronic notebooks. When data analyses occur, the related details usually go into other notebooks or spreadsheets, and more metadata are available. The whole thing rapidly becomes very complex and disjointed, and keeping track of all these things can be daunting. Organizing all the relevant data and related metadata for analysis, publication, sharing, or deposit into archives can be time-consuming, difficult, and prone to errors. By having metadata in a centralized system that contains all details from the start, the process is greatly simplified. While lab management software is available, it can be costly and inflexible. The system described here is based on a popular, freely available, and open-source wiki platform. It provides a simple but powerful way for biomedical research labs to set up a metadata management system linking the whole research process. The system enhances efficiency, transparency, reliability, and rigor, which are key factors to improving reproducibility. The flexibility afforded by the system simplifies implementation of specialized lab requirements and future needs. The protocol presented here describes how to create the system from scratch, how to use it for gathering basic metadata, and provides a fully functional version for perusal by the reader. Graphical abstract: Lab Metadata Management System.

Adhesive-Based Fabrication Technique for Culture of Lung Airway Epithelial Cells with Applications in Cell Patterning and Microfluidics.

This work describes a versatile and cost-effective cell culture method for micropatterning and growing adherent cells on porous membranes using pressure-sensitive double-sided adhesives. This technique also allows cell culture using conventional methods and their easy integration into microfluidic chip devices. Adhesives can be used to form different patterns of cultured cells, which can be used for cell proliferation and wound-healing models. To demonstrate the viability of our system, we evaluate the toxicity effect of five different adhesives on two distinct airway epithelial cell lines and show functional applications for cell patterning and microfluidic cell culture chip fabrication. We developed a sandwiched microfluidic device that enabled us to culture cells in a submerged condition and transformed it into a dynamic platform when required. The viability of cells and their inflammatory responses to IL-1β stimulation were investigated. Our technique is applicable for conventional culturing of cells, widely available in biomedical research labs, while enabling the introduction of perfusion for an advanced dynamic cell culture model when needed.

Demonstrating core molecular biology principles using GST-GFP in a semester-long laboratory course.

Undergraduate laboratory courses are essential to teaching core principles in STEM. This course, Quantitative Biological Methods, provides a unique approach to teaching molecular biology research techniques to students, in a laboratory that is delivered in a sequence that parallels standard biomedical research laboratory protocols. Students attend a lecture where they are taught the essential principles of biomedical research, and a lab where they learn to use laboratory equipment, perform experiments, and purify and quantify DNA and proteins. The course begins with an introduction to laboratory safety, pipetting, centrifugation, spectrophotometry, and other basic laboratory techniques. Next, the lab focuses on the purification and analysis of glutathione S‐transferase (GST) fused to green fluorescent protein (GFP) from an Escherichia coli lysate. Students study this GST‐GFP fusion protein and perform protein quantification, enzyme assays, chromatography, fluorescent detection, normalization, SDS‐PAGE, and western blotting. Students then learn recombinant DNA technology using the GST‐GFP vector that was the source of the fusion protein in the prior labs, and perform ligation, transformation of E. coli cells, blue/white screening, DNA purification via a miniprep, PCR, DNA quantification, restriction enzyme digestion, and agarose gel electrophoresis. Students write laboratory reports to demonstrate an understanding of the principles of the laboratory methods, and they must present and critically analyze their data. The lab methods described herein aim to emphasize the core molecular biology principles and techniques, prepare students for work in a biomedical research laboratory, and introduce students to both GST and GFP, two versatile laboratory proteins.

Two-color super-resolution localization microscopy via joint encoding of emitter location and color.

Multi-color super-resolution localization microscopy (SRLM) provides great opportunities for studying the structural and functional details of biological samples. However, current multi-color SRLM methods either suffer from medium to high crosstalk, or require a dedicated optical system and a complicated image analysis procedure. To address these problems, here we propose a completely different method to realize multi-color SRLM. This method is built upon a customized RGBW camera with a repeated pattern of filtered (Red, Green, Blue and Near-infrared) and unfiltered (White) pixels. With a new insight that RGBW camera is advantageous for color recognition instead of color reproduction, we developed a joint encoding scheme of emitter location and color. By combing this RGBW camera with the joint encoding scheme and a simple optical set-up, we demonstrated two-color SRLM with ∼20 nm resolution and < 2% crosstalk (which is comparable to the best-reported values). This study significantly reduces the complexity of two-color SRLM (and potentially multi-color SRLM), and thus offers good opportunities for general biomedical research laboratories to use multi-color SRLM, which is currently mastered only by well-trained researchers.

The Graphene Field Effect Transistor Modeling Based on an Optimized Ambipolar Virtual Source Model for DNA Detection

The graphene-based Field Effect Transistors (GFETs), due to their multi-parameter characteristics, are growing rapidly as an important detection component for the apt detection of disease biomarkers, such as DNA, in clinical diagnostics and biomedical research laboratories. In this paper, the non-equilibrium Green function (NEGF) is used to create a compact model of GFET in the ballistic regime as an important building block for DNA detection sensors. In the proposed method, the self-consistent solutions of two-dimensional Poisson’s equation and NEGF, using the nearest neighbor tight-binding approach on honeycomb lattice structure of graphene, are modeled as an efficient numerical method. Then, the eight parameters of the phenomenological ambipolar virtual source (AVS) circuit model are calibrated by a least-square curve-fitting routine optimization algorithm with NEGF transfer function data. At last, some parameters of AVS that are affected by induced charge and potential of DNA biomolecules are optimized by an experimental dataset. The new compact model response, with an acceptable computational complexity, shows a good agreement with experimental data in reaction with DNA and can effectively be used in the plan and investigation of GFET biosensors.

Commentaries on Viewpoint: The academic biomedical research laboratory as a "small business".

Commentaries on Viewpoint: The academic biomedical research laboratory as a "small business".

A novel undergraduate biomedical laboratory course concept in synergy with ongoing faculty research.

Optimal integration of education and ongoing faculty research in many undergraduate science programs is limited to the capstone project. Here, we aimed to develop a novel course‐based undergraduate research experience (CURE) in synergy with ongoing faculty research. This 10‐week course called Biomedical Research Lab is embedded in the curriculum of the undergraduate program Biomedical Sciences and grounded in the theoretical framework of research‐based learning. Four groups of four students work together in a dedicated laboratory on an actual ongoing research problem of faculty. All groups work on the same research problem, albeit from different (methodological) perspectives, thereby stimulating interdependence between all participants. Students propose new research, execute the experiments, and collectively report in a single research article. According to students, the course enhanced scientific, laboratory, and academic skills. Students appreciated ownership and responsibilities of the research, laboratory teachers as role models, and they were inspired and motivated by doing authentic actual research. The course resulted in a better understanding of what doing research entails. Faculty valued the didactical experience, research output and scouting opportunities. Since topics can change per course edition, we have showcased a widely applicable pedagogy creating synergy between ongoing research and undergraduate education.

An End-to-End Integrated Clinical and CT Based Radiomics Nomogram for Predicting Disease Severity and Need for Ventilator Support in COVID-19 Patients: A Large Multi-Site Retrospective Study

Objective: The disease COVID-19 has caused a widespread global pandemic with ~3.93 million deaths worldwide. In this work, we present three models- Radiomics (MRM), Clinical (MCM), and combined Clinical-Radiomics (MRCM) nomogram to predict COVID-19 positive patients who will end up needing invasive mechanical ventilation from the baseline CT scans. Method: We performed a retrospective multicohort study of individuals with COVID-19 positive findings for a total of 980 patients from 2 different institutions (Renmin hospital of Wuhan University, D1 =787 and University Hospitals, US D2 = 110). The patients from institution-1 were divided into 60% training, D1 T (N=473), and 40% test set D1 V (N=314). The patients from institution-2 were used for an independent validation test set D2 V(N=110). A U-Net-based neural network (CNN) was trained to automatically segment out the COVID consolidation regions on the CT scans. The segmented regions from the CT scans were used for extracting first-order and higher-order Radiomic textural features. The top Radiomic and clinical features were selected using the Least Absolute Shrinkage and Selection Operator (LASSO) with an optimal binomial regression model within D1 T. Results: The 3 out of the top 5 features identified using D1 T were higher-order textural features (GLCM, GLRLM, GLSZM), whereas the last two features included the total infection size on the CT scan and the total intensity of the COVID consolidations. The Radiomics Model (MRM ) was constructed using the Radiomic Score built using the coefficients obtained from the LASSO logistic model used within the linear regression (LR) classifier. The MRM yielded an area under the receiver operating characteristic curve (AUC) of 0.754 [0.709-0.799] on D1 T, 0.836 on D1 V, and 0.748 D2 V. The top prognostic clinical factors identified in the analysis were dehydrogenase (LDH), age, and albumin (ALB). The clinical model had an AUC of 0.784 [0.743-0.825] on D1 T, 0.813 on D1 V, and 0.723 on D2 V. Finally, the combined model, MRCM integrating Radiomic Score, age, LDH and ALB, yielded an AUC of 0.814 [0.774-0.853] on D1 T, 0.847 on D1 V, and 0.772 on D2 V. The MRCM had an overall improvement in the performance of ~3.77% (D1 T: p = 0.0003; D1 V p= 0.0165; D2 V : p = 0.024) over MCM Conclusion: The novel integrated imaging and clinical model (MRCM) outperformed both models (MRM) and (MCM). Our results across multiple sites suggest that the integrated nomogram could help identify COVID-19 patients with more severe disease phenotype and potentially requiring mechanical ventilation. Funding: National Cancer Institute of the US National Institutes of Health, National Center for Research Resources, US Department of Veterans Affairs Biomedical Laboratory Research and Development Service, Department of Defense, National Institute of Diabetes and Digestive and Kidney Diseases, Wallace H Coulter Foundation, Case Western Reserve University, and Dana Foundation. Declaration of Interest: AM reports grants from National Cancer Institute of the National Institutes of Health, grants from National Center for Research Resources, grants from VA Merit Review Award, grants from DOD Cancer Investigator-Initiated Translational Research Award, during the conduct of the study; grants from DOD Prostate Cancer Idea Development Award, grants from DOD Peer Reviewed Cancer Research Program, grants from National Institute of Diabetes and Digestive and Kidney Diseases , grants from the Ohio Third Frontier Technology Validation Fund, grants from the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University, grants from Department of Defense Peer Reviewed Cancer Research Program (PRCRP) Career Development Award, grants from Dana Foundation David Mahoney Neuroimaging Program. Ethical Approval: The study conformed to HIPAA guidelines was approved by University Hospitals, Cleveland (STUDY20200463), and the Ethics committee of the Renmin Hospital of Wuhan University (ethics number: V1.0).

A prognostic and predictive computational pathology image signature for added benefit of adjuvant chemotherapy in early stage non-small-cell lung cancer.

We developed and validated a prognostic and predictive computational pathology risk score (CoRiS) using H&E stained tissue images from patients with early-stage non-small cell lung cancer (ES-NSCLC). 1330 patients with ES-NSCLC were acquired from 3 independent sources and divided into four cohorts D1-4. D1 comprised 100 surgery treated patients and was used to identify prognostic features via an elastic-net Cox model to predict overall and disease-free survival. CoRiS was constructed using the Cox model coefficients for the top features. The prognostic performance of CoRiS was evaluated on D2 (N=331), D3 (N=657) and D4 (N=242). Patients from D2 and D3 which comprised surgery+chemotherapy were used to validate CoRiS as predictive of added benefit to adjuvant chemotherapy (ACT) by comparing survival between different CoRiS defined risk groups. CoRiS was found to be prognostic on univariable analysis, D2 (hazard ratio (HR)=1.41, adjusted (adj.) P=.01) and D3 (HR=1.35, adj. P < .001). Multivariable analysis showed CoRiS was independently prognostic, D2 (HR=1.41, adj. P < .001) and D3 (HR=1.35, adj. P < .001), after adjusting for clinico-pathologic factors. CoRiS was also able to identify high-risk patients who derived survival benefit from ACT D2 (HR=0.42, adj. P=.006) and D3 (HR=0.46, adj. P=.08). CoRiS is a tissue non-destructive, quantitative and low-cost tool that could potentially help guide management of ES-NSCLC patients. Data collection, anlaysis, and computation resources of the research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers: 1U24CA199374-01, R01CA202752-01A1, R01CA208236-01A1, R01 CA216579-01A1, R01 CA220581-01A1, 1U01 CA239055-01. National Center for Research Resources under award number 1 C06 RR12463-01. VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.

Fresh and cryopreserved ovarian tissue from deceased young donors yields viable follicles

Ovarian tissue cryopreservation is one of the crucial options for fertility preservation. Transplantation of cryopreserved ovarian tissue was proven to restore ovarian endocrine function in patients with premature ovarian insufficiency. Ovaries from deceased donors potentially serve as an excellent and readily available tissue for the translational and basic research. In this study, we used ovaries obtained from 5 deceased donors aged 18-26 years, to evaluate the number and quality of ovarian follicles isolated before and after cryopreservation. Preclinical. Academic biomedical research laboratory. De-identified deceased human donors. Slow-freeze cryopreservation and thawing. Follicle count, follicle density, follicle viability using immunohistochemical staining (TUNEL). The follicle density negatively correlated with age in both cryopreserved/thawed and fresh group. A total of 2803 follicles from fresh and 1608 follicles from cryopreserved tissues were classified and analyzed using Hematoxylin and eosin staining. There was no significant difference in the percent of morphologically normal follicles between two groups. TUNEL assay indicated no higher DNA damage in the follicles and the stroma cells after cryopreservation. Morphologically normal preantral follicles were enzymatically isolated from both fresh and cryopreserved tissue with 88.51 ± 5.93% (mean ± SD) of the isolated follicles confirmed viable using LIVE/DEAD evaluation. Our results indicate the ovarian tissue from deceased donors maintain high quality after long time extracorporeal circulation and transportation from the hospital to the laboratory. High survival rate of follicles at different developmental stages suggested tolerance to the cryopreservation process. Human ovarian tissues obtained from deceased donors is an ample source tissue and can be applied to promoting research and future clinical applications.

The academic biomedical research laboratory as a "small business".

The academic biomedical research laboratory as a "small business".

3D printed alginate bead generator for high-throughput cell culture.

Alginate hydrogel beads are a common platform for generating 3D cell cultures in biomedical research. Simple methods for bead generation using a manual pipettor or syringe are low-throughput and produce beads showing high variability in size and shape. To address these challenges, we designed a 3D printed bead generator that uses an airflow to cleave beads from a stream of hydrogel solution. The performance of the proposed alginate bead generator was evaluated by changing the volume flow rates of alginate (QAlg) and air (QA), the diameter of device nozzle (d) and the concentration of alginate gel solution (C). We identified that the diameter of beads (D = 0.9 -2.8mm) can be precisely controlled by changing QA and d. Also the bead generation frequency (f) can be tuned by changing QAlg. Finally, we demonstrated that viability and biological function (pericellular matrix deposition) of chondrocytes were not adversely affected by high f using this bead generator. Because 3D printing is becoming a more accessible technique, our unique design will allow greater access to average biomedical research laboratories, STEM education and industries in cost- and time-effective manner.

Resonance Energy Transfer-Based Biosensors for Point-of-Need Diagnosis-Progress and Perspectives.

The demand for point-of-need (PON) diagnostics for clinical and other applications is continuing to grow. Much of this demand is currently serviced by biosensors, which combine a bioanalytical sensing element with a transducing device that reports results to the user. Ideally, such devices are easy to use and do not require special skills of the end user. Application-dependent, PON devices may need to be capable of measuring low levels of analytes very rapidly, and it is often helpful if they are also portable. To date, only two transduction modalities, colorimetric lateral flow immunoassays (LFIs) and electrochemical assays, fully meet these requirements and have been widely adopted at the point-of-need. These modalities are either non-quantitative (LFIs) or highly analyte-specific (electrochemical glucose meters), therefore requiring considerable modification if they are to be co-opted for measuring other biomarkers. Förster Resonance Energy Transfer (RET)-based biosensors incorporate a quantitative and highly versatile transduction modality that has been extensively used in biomedical research laboratories. RET-biosensors have not yet been applied at the point-of-need despite its advantages over other established techniques. In this review, we explore and discuss recent developments in the translation of RET-biosensors for PON diagnoses, including their potential benefits and drawbacks.

Application of Polymer Microspheres for Assessing the Role of Mechanical Factors in the Formation of Neutrophilic Extracellular Traps

Abstract—At present, quite a large number of inducers forming neutrophilic extracellular traps (NET) have been described. Mechanical factors (MF) are of particular importance, since they are constantly acting as neutrophils pass through the microcirculatory system. An adequate choice of therapy for various diseases accompanied by excessive NET formation requires assessment of the ability of a patient’s neutrophils to form NET in response to various inducers. Studying the role of MF in neutrophil activation in patients presents certain difficulties associated with introducing expensive and complex recording systems into laboratory practice. A possible alternative to the existing approaches can be joint incubation of whole blood with hemocompatible polymer microspheres (PMS). To develop this approach, polystyrene microspheres containing quaternary ammonium groups were obtained, on the surface of which hemocompatible aggregates consisting of thiooctadecyl poly-N-vinyl-2-pyrrolidone (PMSnano) were attached. The data obtained indicate that with incubation of blood samples with PMSnano under gentle stirring, the amount of formed NET is statistically significantly higher than in a stationary incubation mode. This confirms the idea that MF are capable of activating neutrophils and triggering the NET formation process. The proposed approach to assessing the effect of MF on neutrophil activation processes owing to its ease of implementation may find wide application both in biomedical research and clinical laboratories.

A brief manifestation of anti-bacterial nanofiller reinforced coatings against the microbial growth based novel engineering problems

An anti-bacterial material coating can help to break the spread of bacteria and viruses via metallic surfaces of biomedical devices, communication devices, food packages, research laboratories and public infrastructures like shopping malls, transports, toilets, etc. In addition, anti-bacterial material coatings owing to adequate tribomechanical and anti-corrosion properties can also help to resolve a major engineering problem of biofouling on marine installations and watercrafts’ surfaces. In recent times, the use of anti-bacterial nanocomposites coatings is emerging rapidly for various engineering applications. Here, metal matrix nanocomposites (MMNCs) are acquiring a significant role in the upcoming field of anti-bacterial material applications owing to high tribo-mechanical and anti-corrosion properties. The bio-responsive mechanism of MMNC coatings to perform anti-bacterial activities can protect the surfaces in biological environments. The nanofillers in the metal matrix plays a key role during anti-bacterial activities to kill the microbials. The composition of nanofillers can be inorganic, organic and hybrid, including advance nano tropes (i.e., allotropes of carbon and BNNT), which can be reinforced in metal matrix. This review study is addressing a problem of bacterial colonization on the surfaces that causing microbial growth based novel engineering problems and suggesting a facile and low-cost solution through an anti-bacterial MMNC coating.

Azithromycin susceptibility of Neisseria gonorrhoeae in the USA in 2017: a genomic analysis of surveillance data

The number of cases of gonorrhoea in the USA and worldwide caused by Neisseria gonorrhoeae is increasing (555 608 reported US cases in 2017, and 87 million cases worldwide in 2016). Many countries report declining in vitro susceptibility of azithromycin, which is a concern because azithromycin and ceftriaxone are the recommended dual treatment in many countries. We aimed to identify strain types associated with decreased susceptibility to azithromycin. We did a genomic analysis of N gonorrhoeae isolates obtained by the US Gonococcal Isolate Surveillance Project. Isolates were whole-genome sequenced based on decreased susceptibility to azithromycin (minimal inhibitory concentration [MIC] ≥2 μg/mL, using agar dilution antibiotic susceptibility testing) and geographical representation. Bioinformatic analyses established genomic diversity, strain population dynamics, and antimicrobial resistance profiles. 410 isolates were sorted into more than 20 unique phylogenetic clades. One predominant persistent clade (consisting of 97 isolates) included the most isolates with azithromycin MICs of 2 μg/mL or higher (61 of 97 [63%] vs 59 of 311 [19%]; p<0·0001) and carried a mosaic mtr (multiple transferable resistance) locus (68 of 97 [70%] vs two of 313 [1%]; p<0·0001). Of the remaining 313 isolates, 57 (18%) had decreased susceptibility to azithromycin (MIC ≥4 μg/mL), which was attributed to 23S rRNA variants (56 of 57 [98%]) and formed phylogenetically diverse clades, showing various levels of clonal expansion. Reduced azithromycin susceptibility was associated with expanding and persistent clades harbouring two well described resistance mechanisms, mosaic mtr locus and 23S rRNA variants. Understanding the role of recombination, particularly within the mtr locus, on the fitness and expansion of strains with decreased susceptibility has important implications for the public health response to minimise gonorrhoea transmission. US Centers for Disease Control and Prevention (CDC), CDC Combating Antibiotic Resistant Bacteria initiative, Oak Ridge Institute for Science Education, US Department of Energy/CDC/Emory University, National Institutes of Health, and Biomedical Laboratory Research and Development Service of the US Department of Veterans Affairs.