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Comparison of clear cell carcinoma and benign endometriosis in episiotomy scar – two cases report and literature review – BMC Blogs Network

§ January 21st, 2020 § Filed under Nano Medicine Comments Off on Comparison of clear cell carcinoma and benign endometriosis in episiotomy scar – two cases report and literature review – BMC Blogs Network

Functioning endometrial tissue located outside of the uterine cavity is defined as endometriosis [9]. Cutaneous endometriosis is rare and mostly occurs in the abdominal wall, usually developing at the site of a caesarian scar. Perineal and vulvar lesions are more rare; the iatrogenic transplantation of endometrial cells via an episiotomy scar appears to be the mechanism involved [10]. Both of our cases support this hypothesis. These lesions appear as a blue-black nodule under the surgical scar, accompanied by cyclic pain and enlargement during menstruation. Three criteria for diagnosing malignant endometriosis were first proposed by Sampson in 1925: menstrual irregularity, a continuously enlarging mass and increased pain [4].

Tumor markers are not very sensitive for extraovarian lesions, even in malignant cases. Previously, Cuisenier reported that the levels of CA125 are normal in almost half of patients with extraovarian lesions but are normal in only 15.38% of cases with ovarian endometriosis [11]. Both of our patients had normal levels of CA 125. Ultrasound and MRI can help us to identify the exact anatomical position, and in our experience, MRI is highly sensitive and offers excellent differentiation of endometriosis from neighboring tissue; this is important for diagnosis and operative management. The differential diagnosis should include anal cancer, abscesses, fistula, atheroma and hidradenitis.

Malignant degeneration of cutaneous endometriosis is extremely rare, representing 0.31% of surgical scars [5]; and its origin is still unclear, although we know that some specific events occur in this process. On the one hand, the mutation of tumor suppressor genes, such as PTEN and P53 may be related to the development of endometriosis associated cancer [12]. The pathological results of our malignant patient were negative for P53, but positive for HNF1 and AMACR. On the other hand, hormones are also known to play a role. It has been confirmed that high levels of estrogen are consistent with the progression of endometrioid cancer and clear cell carcinoma. In addition, inflammatory reactions and cytokines such as IL-1, which can cause angiogenesis, proliferation and the inhibition of apoptosis, can also contribute to the development of this disease [13].

Benign and malignant perineal endometriosis are difficult to distinguish by symptoms or signs [14]. However, we identified a key point in that the malignant diseases are recurrent. The malignant patient in our report, and those in the existing literature, had undergone a perineal mass excision previously. This means that the initial case of this disease is always benign, but the transition of malignancy occurs after several years if the tumor relapses. Because all of the known malignant patients described in the literature, our present patient included, had undergone a resection previously, we suspect that the tumor had not been totally removed during the first surgery. After a long period of stimulation by local inflammation and hormones, these tumors ultimately became malignant. Thus, resection of the whole endometrial mass is crucially important during initial treatment, especially for patients with anal sphincter involvement. The diagnostic accuracy of anal sphincter involvement could be improved by the use of anal endosonography [3, 15]. Previous authors have recommended wide excision of endometrioma with primary sphincteroplasty for these patients [16], and that this is particularly important if the tumor boundary is unclear. Thus, a safe resection margin of more than 0.5cm of surrounding healthy tissue is necessary in order to avoid relapse or malignancy. To achieve wide excision in cases of perineal endometrioma with anal sphincter invasion, partial removal of external anal sphincter is necessary [16, 17].

Some clinicians have suggested the use of oral drugs to manipulate hormone levels [18,19,20]. However, assisted drug therapy has not been proven to be effective in controlling or postponing the recurrence of perineal endometriosis [21]. For our patient, the use of danazol achieved symptomatic relief but did not prevent recurrence or malignant change. Because of the low incidence of perineal endometriosis, the ideal treatment is still unknown. Table1 shows previously reported cases of malignant transformation of episiotomy scar endometriosis. In recent literature, a total of four patients with clear cell carcinoma and one patient with serous papillary cystadenocarcinoma have been reported [5,6,7,8, 22]. All of these patients had a history of benign perineal endometriosis. Methods of treatment include radical excision, radiotherapy and chemotherapy. Most of these patients received combined therapies. For our patient, we performed radical surgery and post-operative radiation. Although the results of long-term follow-up remain unknown, a 1 year period of follow up shows no recrudescence or metastasis.

Perineal endometriosis is rare but should be suspected if there is a history of episiotomy and cyclic pain. Ultrasonography, magnetic resonance imaging and PET/CT can be used for diagnosis. Complete resection of the nidus is key to treating this disease because malignancy only happens in recurrent patients. To achieve this, we should consider two key points: (1) adequate and wide excision is the principle of management to prevent recurrence and future malignancy; and (2) we must be very careful not to rupture tumors during surgery as this can cause remnants to remain and subsequent re-implantation to occur. The effect of assisted drug therapy after surgery is not very clear. Adjunctive chemotherapy and radiotherapy are recommended as the prognosis may be improved in malignant patients. Finally, it is very important to follow-up these patients with care.

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Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form N | IJN – Dove Medical Press

§ January 21st, 2020 § Filed under Nano Medicine Comments Off on Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form N | IJN – Dove Medical Press

Xiaoyi Zhang, 1, 2 Yixin Zhang, 1, 2 Yaonan Wang, 1, 2 Jianhui Wu, 1, 2 Haiyan Chen, 1, 2 Ming Zhao, 13 Shiqi Peng 1, 2

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, Peoples Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, Peoples Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Department of Biomaterials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100026, Peoples Republic of China

Correspondence: Shiqi Peng; Ming ZhaoDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, No. 10, Youanmenwaixitoutiao, Fengtai District, Beijing 100069, Peoples Republic of ChinaTel +86 10 8391 1528; +86 10 8391 1535Fax +86 10 8391 1528; +86 10 8391 1533Email sqpeng@bjmu.edu.cn; maozhao@126.com

Background: 1-(4-isopropylphenyl)--carboline-3-carboxylic acid (ICCA) was modified by Trp-Phe-Phe to form 1-(4-isopropylphenyl)--carboline-3-carbonyl-Trp-Phe-Phe (ICCA-WFF).Purpose: The object of preparing ICCA-WFF was to enhance the in vivo efficacy of ICCA, to explore the possible targeting action, and to visualize the nano-feature.Methods: The advantages of ICCA-WFF over ICCA were demonstrated by a series of in vivo assays, such as anti-tumor assay, anti-arterial thrombosis assay, anti-venous thrombosis assay, P-selectin expression assay, and GPIIb/IIIa expression assay. The nano-features of ICCA-WFF were visualized by TEM, SEM and AFM images. The thrombus targeting and tumor-targeting actions were evidenced by FT-MS spectrum analysis.Results: The minimal effective dose of ICCA-WFF slowing tumor growth and inhibiting thrombosis was 10-fold lower than that of ICCA. ICCA-WFF, but not ICCA, formed nano-particles capable of safe delivery in blood circulation. In vivo ICCA-WFF, but not ICCA, can target thrombus and tumor. In thrombus and tumor, ICCA-WFF released Trp-Phe-Phe and/or ICCA.Conclusion: Modifying ICCA with Trp-Phe-Phe successfully enhanced the anti-tumor activity, improved the anti-thrombotic action, formed nano-particles, targeted tumor tissue and thrombus, and provided an oligopeptide modification strategy for heterocyclic compounds.

Keywords: ICCA, modification, Trp-Phe-Phe, anti-tumor, thrombus targeting, release, toxicity, nano-species

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on | IJN – Dove Medical Press

§ January 21st, 2020 § Filed under Nano Medicine Comments Off on Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on | IJN – Dove Medical Press

Hossein Derakhshankhah, 1, 2,* Samira Jafari, 1, 2,* Sajad Sarvari, 3 Ebrahim Barzegari, 4 Faezeh Moakedi, 5 Milad Ghorbani, 6 Behrang Shiri Varnamkhasti, 1 Mehdi Jaymand, 7 Zhila Izadi, 1, 8 Lobat Tayebi 9

1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Zistmavad Pharmed Co., Tehran, Iran; 3Department of Pharmaceutical and Pharmacological Science, School of Medicine, West Virginia University, Morgantown, WV, USA; 4Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 5Department of Biochemistry and Molecular Biology, School of Medicine, West Virginia University, Morgantown, WV, USA; 6Department of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 7Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 8Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 9Marquette University School of Dentistry, Milwaukee, WI 53201, USA

*These authors contributed equally to this work

Correspondence: Zhila Izadi; Lobat Tayebi Email izadi_zh@razi.tums.ac.ir; lobat.tayebi@marquette.edu

Abstract: The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.

Keywords: zeolite, mesoporous, nanostructure, biosafety, biomedical applications

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating | IJN – Dove Medical Press

§ January 21st, 2020 § Filed under Nano Medicine Comments Off on Nanocarriers for Stroke Therapy: Advances and Obstacles in Translating | IJN – Dove Medical Press

Syed Abdullah Alkaff, 1 Krishna Radhakrishnan, 1 Anu Maashaa Nedumaran, 1 Ping Liao, 2 Bertrand Czarny 1, 3

1School of Materials Science and Engineering, Nanyang Technological University 639798, Singapore; 2Calcium Signalling Laboratory, National Neuroscience Institute 308433, Singapore; 3Lee Kong Chian School of Medicine, Nanyang Technological University 639798, Singapore

Correspondence: Bertrand CzarnySchool of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Ave, Block N4.1, #02-17 639798, SingaporeTel +65 67904613Email bczarny@ntu.edu.sg

Abstract: The technology of drug delivery systems (DDS) has expanded into many applications, such as for treating neurological disorders. Nanoparticle DDS offer a unique strategy for targeted transport and improved outcomes of therapeutics. Stroke is likely to benefit from the emergence of this technology though clinical breakthroughs are yet to manifest. This review explores the recent advances in this field and provides insight on the trends, prospects and challenges of translating this technology to clinical application. Carriers of diverse material compositions are presented, with special focus on the surface properties and emphasis on the similarities and inconsistencies among in vivo experimental paradigms. Research attention is scattered among various nanoparticle DDS and various routes of drug administration, which expresses the lack of consistency among studies. Analysis of current literature reveals lipid- and polymer-based DDS as forerunners of DDS for stroke; however, cell membrane-derived vesicles (CMVs) possess the competitive edge due to their innate biocompatibility and superior efficacy. Conversely, inorganic and carbon-based DDS offer different functionalities as well as varied capacity for loading but suffer mainly from poor safety and general lack of investigation in this area. This review supports the existing literature by systematizing presently available data and accounting for the differences in drugs of choice, carrier types, animal models, intervention strategies and outcome parameters.

Keywords: nanoparticle, drug delivery system, stroke, animal model, nano medicine, therapeutics

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Nanotechnology in Medical Market Outlook, Recent Trends and Growth Forecast 2020 – News by aeresearch

§ January 21st, 2020 § Filed under Nano Medicine Comments Off on Nanotechnology in Medical Market Outlook, Recent Trends and Growth Forecast 2020 – News by aeresearch

The Analysis report titled Nanotechnology in Medical Market 2025 highly demonstrates the current Nanotechnology in Medical market analysis scenario, impending future opportunities, revenue growth, pricing and profitability of the industry.

Growth Analysis Report onNanotechnology in Medical Market size | Industry Segment by Applications (Hospitals, Clinics and Others), by Type (Nano Medicine and Nano Diagnosis), Regional Outlook, Market Demand, Latest Trends, Nanotechnology in Medical Industry Share & Revenue by Manufacturers, Company Profiles, Growth Forecasts 2025.Analyzes current market size and upcoming 5 years growth of this industry.

Nanotechnology in Medical Market report delivers the close outlook of top companies with their strategies, growth factors, Nanotechnology in Medical industry analysis by region and so on. Also, this report is analyzed based on the Key Stakeholders, Downstream Vendors, Distributors, Traders and new entrants in the Nanotechnology in Medical Market.

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Additionally, the report discusses key trends driving the growth of the market, opportunities involved, major challenges and risks that are often confronted by key manufacturers besides presenting an overall idea of the market. The report also analyses in details emerging trends in the marketplace and their impact on current and future development of the Nanotechnology in Medical market.

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Nanotechnology in Medical Market Outlook, Recent Trends and Growth Forecast 2020 - News by aeresearch

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2020 Injectable Nanomedicines Market Demand Analysis, Statistics, Trends and Investment Opportunities to 2023 – Fusion Science Academy

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on 2020 Injectable Nanomedicines Market Demand Analysis, Statistics, Trends and Investment Opportunities to 2023 – Fusion Science Academy

Intracranial Pressure(ICP) Monitoring Market (2018) Report Provides an in-depth summary of Intracranial Pressure(ICP) Monitoring Market Status as well as Product Specification, Technology Development, and Key Manufacturers. The Report Gives Detail Analysis on Market concern Like Intracranial Pressure(ICP) Monitoring Market share, CAGR Status, Market demand and up to date Market Trends with key Market segments.

The latest report about the Intracranial Pressure(ICP) Monitoring market provides a detailed evaluation of the business vertical in question, alongside a brief overview of the industry segments. An exceptionally workable estimation of the present industry scenario has been delivered in the study, and the Intracranial Pressure(ICP) Monitoring market size with regards to the revenue and volume have also been mentioned. In general, the research report is a compilation of key data with regards to the competitive landscape of this vertical and the multiple regions where the business has successfully established its position.

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Leading manufacturers of Intracranial Pressure(ICP) Monitoring Market:

MedtronicIntegra LifeSciencesSpiegelburgRAUMEDICVittamedGaeltec DevicesHeadSense MedicalNeuroDx DevelopmentSophysaThird Eye DiagnosticsVivonicsDePuy Synthes

Segment by RegionsNorth AmericaEuropeChinaJapanSoutheast AsiaIndia

Segment by TypeInvasive Intracranial Pressure MonitorNon-invasive Intracranial Pressure Monitor

Segment by ApplicationTraumatic Brain InjuryIntracerebral HemorrhageMeningitisSubarachnoid HemorrhageOthers (Cerebral Edema, CNS Infection, etc.)

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This research report for Intracranial Pressure(ICP) Monitoring Market explores different topics such as product scope, product market by end users or application, product market by region, the market size for the specific product Type, sales and revenue by region forecast the Market size for various segments. The Report provides detailed information regarding the Major factors (drivers, restraints, opportunities, and challenges) influencing the growth of the Intracranial Pressure(ICP) Monitoring market. The Intracranial Pressure(ICP) Monitoring Market Report analyzes opportunities in the overall Intracranial Pressure(ICP) Monitoring market for stakeholders by identifying the high-growth segments.

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Table of Content of The Report

Chapter 1- Intracranial Pressure(ICP) Monitoring Industry Overview:

1.1 Definition of Intracranial Pressure(ICP) Monitoring

1.2 Brief Introduction of Major Classifications

1.3 Brief Introduction of Major Applications

1.4 Brief Introduction of Major Regions

Chapter 2- Production Market Analysis:

2.1 Global Production Market Analysis

2.1.1 Global Capacity, Production, Capacity Utilization Rate, Ex-Factory Price, Revenue, Cost, Gross and Gross Margin Analysis

2.1.2 Major Manufacturers Performance and Market Share

2.2 Regional Production Market Analysis

Chapter 3- Sales Market Analysis:

3.1 Global Sales Market Analysis

3.2 Regional Sales Market Analysis

Chapter 4- Consumption Market Analysis:

4.1 Global Consumption Market Analysis

4.2 Regional Consumption Market Analysis

Chapter 5- Production, Sales and Consumption Market Comparison Analysis

Chapter 6- Major Manufacturers Production and Sales Market Comparison Analysis

Chapter 7- Major Classification Analysis

Chapter 8- Major Application Analysis

Chapter 9- Industry Chain Analysis:

9.1 Up Stream Industries Analysis

9.2 Manufacturing Analysis

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2020 Injectable Nanomedicines Market Demand Analysis, Statistics, Trends and Investment Opportunities to 2023 - Fusion Science Academy

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Commentary: AI can’t resolve the ambiguities of early cancer diagnosis – Austin American-Statesman

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on Commentary: AI can’t resolve the ambiguities of early cancer diagnosis – Austin American-Statesman

The new decade opened with some intriguing news: the journal Nature reported that artificial intelligence was better at identifying breast cancers on mammograms than radiologists. Researchers at Google Health teamed up with academic medical centers in the United States and Britain to train an AI system using tens of thousands of mammograms.

But even the best artificial intelligence system cant fix the uncertainties surrounding early cancer diagnosis.

To understand why, it helps to have a sense of how AI systems learn. In this case, the system was trained with images labeled as either cancer or not cancer. From them, it learned to deduce features from the images such as shape, density and edges that are associated with the cancer label.

Thus, the process is wholly dependent on starting with data that are correctly labeled. In the AI mammography study, the initial diagnoses were determined by a pathologist who examined breast biopsy specimens under a microscope after an abnormal mammogram. In other words, the pathologist determined whether the mammogram showed cancer or not.

Unfortunately, this pathologic standard is problematic. Over the last 20 years there has been a growing recognition that screening mammography has led to substantial overdiagnosis the detection of abnormalities that meet the pathological definition of cancer, yet are not destined to ever cause symptoms or death.

Furthermore, pathologists can disagree about who has breast cancer even when presented with the same biopsy specimens under the microscope. The problem is far less for large, obvious cancers far greater for small (even microscopic), early-stage cancers. Thats because there is a gray area between cancer and not cancer. This has important implications for AI technology used for cancer screening.

AI systems will undoubtedly be able to consistently find subtle abnormalities on mammograms, which will lead to more biopsies. This will require pathologists to make judgments on subtler irregularities that may be consistent with cancer under the microscope, but may not represent disease destined to cause symptoms or death. In other words, reliance on pathologists for the ground truth could lead to an increase in cancer overdiagnosis.

The problem is not confined to breast cancer. Overdiagnosis and disagreement over what constitutes cancer are also problems relevant to melanoma, prostate and thyroid cancer. AI systems are already being developed for screening skin moles for melanoma and are likely to be employed in other cancers as well.

In a piece for the New England Journal of Medicine last month, we proposed a better way of deploying AI in cancer detection. Why not make use of the information contained in pathological disagreement? We suggested that each biopsy used in training AI systems be evaluated by a diverse panel of pathologists and labeled with three distinct categories: unanimous agreement of cancer, unanimous agreement of not cancer, and disagreement as to the presence of cancer. This intermediate category of disagreement would not only help researchers understand the natural history of cancer, but could also be used by clinicians and patients to investigate less invasive treatment for cancers in the gray area.

The problem of observer disagreement is not confined to pathologists; it also exists with radiologists reading mammograms. Thats the problem AI is trying to solve. Yet, while the notion of disagreement may be unsettling, disagreement also provides important information: Patients diagnosed with an early-stage cancer should be more optimistic about their prognoses if there were some disagreement about whether cancer was present, rather than all pathologists agreeing it was obviously cancer.

Artificial intelligence cant resolve the ambiguities surrounding early cancer diagnosis, but it can help illuminate them. And illuminating these gray areas is the first step in helping patients and their doctors respond wisely to them. We believe that training AI to recognize an intermediate category would be an important advance in the development of this technology.

Adamson is a dermatologist and assistant professor of internal medicine at Dell Medical School at the University of Texas. Welch is a senior researcher in the Center for Surgery and Public Health at Brigham and Womens Hospital in Boston. Their commentary first appeared in The Los Angeles Times.

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Most engineered nanoparticles enter tumours through cells not between them, U of T researchers find – News@UofT

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on Most engineered nanoparticles enter tumours through cells not between them, U of T researchers find – News@UofT

University of Toronto researchers have discovered that an active rather than passive process dictates which nanoparticles enter solid tumours, upending decades of thinking in the field of cancer nanomedicine and pointing toward more effective nanotherapies.

The prevailing theory in cancer nanomedicine an approach that enables more targeted therapies than standard chemotherapy has been that nanoparticles mainly diffuse passively into tumours through tiny gaps between cells in the endothelium, which lines the inner wall of blood vessels that support tumour growth.

The researchers previously showed thatless than one per centof nanoparticle-based drugs typically reach their tumour targets. In the current study, they found that among nanoparticles that do penetrate tumours, more than 95 per cent pass through endothelial cells not between gaps among those cells.

Our work challenges long-held dogma in the field and suggests a completely new theory, saysAbdullah Syed, a co-lead author on the study and post-doctoral researcher in the lab ofWarren Chan, a professor at theInstitute of Biomaterials and Biomedical Engineeringand theDonnelly Centre for Cellular and Biomolecular Research.

We saw many nanoparticles enter the endothelial cells from blood vessels and exit into the tumour in various conditions. Endothelial cells appear to be crucial gatekeepers in the nanoparticle transport process.

The findings were recently published in thejournalNature Materials.

From left to right: U of T researchers Jessica Ngai, Shrey Sindhwani, Abdullah Syed and Benjamin Kingston (photo by Qin Dai)

Syed compares nanoparticles to people trying to get into popular restaurants on a busy night. Some restaurants dont require a reservation, while others have bouncers who check if patrons made reservations, he says. The bouncers are a lot more common than researchers thought, and most places only accept patrons with a reservation.

The researchers established that passive diffusion was not the mechanism of entry with multiple lines of evidence. They took over 400 images of tissue samples from animal modelsand saw few endothelial gaps relative to nanoparticles. They observed the same trend using 3D fluorescent imaging and live-animal imaging.

Similarly, they found few gaps between endothelial cells in samples from human cancer patients.

The group then devised an animal model that completely stopped the transportation of nanoparticles through endothelial cells. This allowed them to isolate the contribution of passive transport via gaps between endothelial cells, which proved to be miniscule.

The researchers posit several active mechanisms by which endothelial cells might transport nanoparticles into tumours, including binding mechanisms, intra-endothelial channels and as-yet undiscovered processes all of which they are investigating.

Meanwhile, the results have major implications for nanoparticle-based therapeutics.

These findings will change the way we think about delivering drugs to tumours using nanoparticles, saysShrey Sindhwani, also a co-lead author on the paper and an MD/PhD student in the Chan lab. A better understanding of the nanoparticle transport phenomenon will help researchers design more effective therapies.

The research included collaborators from U of Ts department of physics in the Faculty of Arts & Science, Cold Spring Harbor Laboratory In New York and the University of Ottawa. The study was funded by the Canada Research Chairs Program, Canadian Cancer Society, Natural Sciences and Engineering Research Council of Canadaand the Canadian Institutes of Health Research.

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Nanomedical Devices and Therapeutics Market : Information, Figures and Analytical Insights 2012 2018 – Fusion Science Academy

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on Nanomedical Devices and Therapeutics Market : Information, Figures and Analytical Insights 2012 2018 – Fusion Science Academy

The research study presented in this report offers complete and intelligent analysis of the competition, segmentation, dynamics, and geographical advancement of the Global Ultrasonic Dental Devices Market. The research study has been prepared with the use of in-depth qualitative and quantitative analyses of the global Ultrasonic Dental Devices market. We have also provided absolute dollar opportunity and other types of market analysis on the global Ultrasonic Dental Devices market.

It takes into account the CAGR, value, volume, revenue, production, consumption, sales, manufacturing cost, prices, and other key factors related to the global Ultrasonic Dental Devices market. All findings and data on the global Ultrasonic Dental Devices market provided in the report are calculated, gathered, and verified using advanced and reliable primary and secondary research sources. The regional analysis offered in the report will help you to identify key opportunities of the global Ultrasonic Dental Devices market available in different regions and countries.

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The authors of the report have segmented the global Ultrasonic Dental Devices market as per product, application, and region. Segments of the global Ultrasonic Dental Devices market are analyzed on the basis of market share, production, consumption, revenue, CAGR, market size, and more factors. The analysts have profiled leading players of the global Ultrasonic Dental Devices market, keeping in view their recent developments, market share, sales, revenue, areas covered, product portfolios, and other aspects.

Market segments and sub-segments

The regional analysis covers:

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

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Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Ultrasonic Dental Devices Market Size and Forecast

In terms of region, this research report covers almost all the major regions across the globe such as North America, Europe, South America, the Middle East, and Africa and the Asia Pacific. Europe and North America regions are anticipated to show an upward growth in the years to come. While Ultrasonic Dental Devices Market in Asia Pacific regions is likely to show remarkable growth during the forecasted period. Cutting edge technology and innovations are the most important traits of the North America region and thats the reason most of the time the US dominates the global markets. Ultrasonic Dental Devices Market in South, America region is also expected to grow in near future.

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This Ultrasonic Dental Devices Market research report aids as a broad guideline which provides in-depth insights and detailed analysis of several trade verticals.

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Transparency Market Research (TMR) is a global market intelligence company providing business information reports and services. The companys exclusive blend of quantitative forecasting and trend analysis provides forward-looking insight for thousands of decision makers. TMRs experienced team of analysts, researchers, and consultants use proprietary data sources and various tools and techniques to gather and analyze information.

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Nanomedical Devices and Therapeutics Market : Information, Figures and Analytical Insights 2012 2018 - Fusion Science Academy

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At US$ 300 Mn Reached Injectable Nanomedicines Market With 8.2% CAGR Value In The Year of 2026 – Fusion Science Academy

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on At US$ 300 Mn Reached Injectable Nanomedicines Market With 8.2% CAGR Value In The Year of 2026 – Fusion Science Academy

The research study presented in this report offers complete and intelligent analysis of the competition, segmentation, dynamics, and geographical advancement of the Global Ultrasonic Dental Devices Market. The research study has been prepared with the use of in-depth qualitative and quantitative analyses of the global Ultrasonic Dental Devices market. We have also provided absolute dollar opportunity and other types of market analysis on the global Ultrasonic Dental Devices market.

It takes into account the CAGR, value, volume, revenue, production, consumption, sales, manufacturing cost, prices, and other key factors related to the global Ultrasonic Dental Devices market. All findings and data on the global Ultrasonic Dental Devices market provided in the report are calculated, gathered, and verified using advanced and reliable primary and secondary research sources. The regional analysis offered in the report will help you to identify key opportunities of the global Ultrasonic Dental Devices market available in different regions and countries.

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The authors of the report have segmented the global Ultrasonic Dental Devices market as per product, application, and region. Segments of the global Ultrasonic Dental Devices market are analyzed on the basis of market share, production, consumption, revenue, CAGR, market size, and more factors. The analysts have profiled leading players of the global Ultrasonic Dental Devices market, keeping in view their recent developments, market share, sales, revenue, areas covered, product portfolios, and other aspects.

Market segments and sub-segments

The regional analysis covers:

The report has been compiled through extensive primary research (through interviews, surveys, and observations of seasoned analysts) and secondary research (which entails reputable paid sources, trade journals, and industry body databases). The report also features a complete qualitative and quantitative assessment by analyzing data gathered from industry analysts and market participants across key points in the industrys value chain.

A separate analysis of prevailing trends in the parent market, macro- and micro-economic indicators, and regulations and mandates is included under the purview of the study. By doing so, the report projects the attractiveness of each major segment over the forecast period.

Highlights of the report:

Note:Although care has been taken to maintain the highest levels of accuracy in TMRs reports, recent market/vendor-specific changes may take time to reflect in the analysis.

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Ultrasonic Dental Devices Market Size and Forecast

In terms of region, this research report covers almost all the major regions across the globe such as North America, Europe, South America, the Middle East, and Africa and the Asia Pacific. Europe and North America regions are anticipated to show an upward growth in the years to come. While Ultrasonic Dental Devices Market in Asia Pacific regions is likely to show remarkable growth during the forecasted period. Cutting edge technology and innovations are the most important traits of the North America region and thats the reason most of the time the US dominates the global markets. Ultrasonic Dental Devices Market in South, America region is also expected to grow in near future.

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The Ultrasonic Dental Devices Market report highlights is as follows:

This Ultrasonic Dental Devices market report provides complete market overview which offers the competitive market scenario among major players of the industry, proper understanding of the growth opportunities, and advanced business strategies used by the market in the current and forecast period.

This Ultrasonic Dental Devices Market report will help a business or an individual to take appropriate business decision and sound actions to be taken after understanding the growth restraining factors, market risks, market situation, market estimation of the competitors.

The expected Ultrasonic Dental Devices Market growth and development status can be understood in a better way through this five-year forecast information presented in this report

This Ultrasonic Dental Devices Market research report aids as a broad guideline which provides in-depth insights and detailed analysis of several trade verticals.

About TMR

Transparency Market Research (TMR) is a global market intelligence company providing business information reports and services. The companys exclusive blend of quantitative forecasting and trend analysis provides forward-looking insight for thousands of decision makers. TMRs experienced team of analysts, researchers, and consultants use proprietary data sources and various tools and techniques to gather and analyze information.

Contact

Mr. Rohit BhiseyTransparency Market ResearchState Tower90 State Street,Suite 700,Albany, NY 12207United StatesTel: +1-518-618-1030USA Canada Toll Free: 866-552-3453Email: [emailprotected]Website: http://www.transparencymarketresearch.com

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At US$ 300 Mn Reached Injectable Nanomedicines Market With 8.2% CAGR Value In The Year of 2026 - Fusion Science Academy

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Microscopic Colitis Diet, Treatment, Symptoms & Causes

§ January 19th, 2020 § Filed under Nano Medicine Comments Off on Microscopic Colitis Diet, Treatment, Symptoms & Causes

What is colitis?

Colitis means inflammation of the colon. The colon, also known as the large intestine or large bowel, constitutes the last part of the digestive tract. The colon is a long, muscular tube that receives digested food from the small intestine. It removes water from the undigested food, stores the undigested food, and then eliminates it from the body through bowel movements. The rectum is the last part of the colon adjacent to the anus. The common symptoms of colitis include:

There are many different types of colitis with different causes. Some examples of colitis include:

Infectious, radiation, ischemic, ulcerative, and Crohn's colitis all have visible abnormalities of the inner lining of the colon. These abnormalities include edema (swelling of the lining), redness, bleeding from the lining with gentle rubbing (friability), and ulcers. These abnormalities can be seen duringcolonoscopy (examination of the entire colon using a long flexible viewing tube) or flexible sigmoidoscopy (examination of the rectum and the sigmoid colon - the segment of the colon closest to the rectum).

Edema and inflammation of the colon's lining interferes with the absorption of water from the undigested food, and the unabsorbed water exits the rectum as diarrhea. Pus and fluid also are secreted into the colon and add to the diarrhea. The redness, bleeding from the lining with gentle rubbing (friability), and ulcerations in the lining of the colon contribute to the rectal bleeding.

What diseases are not colitis?

Individuals with irritable bowel syndrome (IBS) do not have colitis, even though this condition is sometimes referred to as having "spastic colitis." These individuals may have symptoms that mimic colitis such as diarrhea, abdominal pain, and mucus in stool. Nevertheless, there is no inflammation of the colon in patients with IBS. The cause of symptoms in IBS is not clearly known; it may be caused by either abnormal motility (abnormal contractions) of the intestinal muscles or abnormally sensitive nerves in the intestines (visceral hypersensitivity).

What is microscopic colitis?

Microscopic colitis refers to inflammation of the colon that is only visible when the colon's lining is examined under a microscope. The appearance of the inner colon lining in microscopic colitis is normal by visual inspection during colonoscopy or flexible sigmoidoscopy. The diagnosis of microscopic colitis is made when a doctor, while performing colonoscopy or flexible sigmoidoscopy, takes biopsies (small samples of tissue) of the normal-appearing lining, and then examines the biopsies under a microscope.

There are two types of microscopic colitis: 1) lymphocytic colitis and 2) collagenous colitis.

Some experts believe that lymphocytic colitis and collagenous colitis represent different stages of the same disease.

The inflammation and the collagen probably interfere with absorption of water from the colon, resulting in the diarrhea.

What are the symptoms of microscopic colitis?

The primary symptom of microscopic colitis is chronic, watery diarrhea. Individuals with microscopic colitis can have diarrhea for months or years before the diagnosis is made. Typically, the symptoms begin very gradually and are intermittent in nature with periods when the person feels well, followed by bouts of chronic diarrhea. This chronic diarrhea of microscopic colitis is different from the acute diarrhea of infectious colitis, which typically lasts only days to weeks. Some individuals with microscopic colitis also may experience mild abdominal cramps and pain. Blood in the stool is unusual.

How common is microscopic colitis and who is at risk?

The prevalence of microscopic colitis in the U.S. is not clearly known.

Microscopic colitis most commonly occurs in the middle aged and elderly patients and is more common among women than men.

When should I seek medical care for microscopic colitis?

A person should seek medical care if the diarrhea lasts for more than 2 weeks or is accompanied with symptoms such as weight loss, fatigue, and abdominal pain.

How is microscopic colitis diagnosed?

The diagnosis of microscopic colitis is made by performing biopsies from different regions of the colon during colonoscopy or sigmoidoscopy.

The abnormalities of the colon's lining in microscopic colitis occur in a patchy distribution (areas of normal lining may coexist adjacent to areas of abnormal lining). For this reason, multiple biopsies should be taken from several different regions of the colon in order to accurately make a diagnosis.

The patchy nature of microscopic colitis also is the reason why flexible sigmoidoscopy often is inadequate in diagnosing the condition because the abnormalities of microscopic colitis may be absent from the sigmoid colon (the colonic segment that is closest to the rectum and is within the reach of a sigmoidoscope) in some of the patients with microscopic colitis.

Thus, biopsies of other regions of the colon accessible only with colonoscopy may be necessary for diagnosing microscopic colitis.

What is the treatment for microscopic colitis?

The treatment of microscopic colitis has not been standardized because there have not been adequate large scale, prospective, placebo controlled treatment trials. The following strategies are safe and may relieve diarrhea in some patients:

Controlled trials showed that budesonide (Entocort, a poorly absorbed steroid) is effective in controlling diarrhea in more than 75% of the patients with collagenous colitis, but the diarrhea tends to recur soon after stopping Entocort.

Though data supporting their use is lacking, some doctors may use medications that potently suppress the immune system such as azathioprine (Imuran, Azasan) and 6-mercaptopurine in patients with severe microscopic colitis that is unresponsive to other treatments.

Can microscopic colitis be prevented?

Since the cause of microscopic colitis is not known, no advice can be provided about preventing this disease.

What is the prognosis of microscopic colitis?

The long term prognosis (course) of microscopic colitis is not clear. In approximately two-thirds of the patients with microscopic colitis, the diarrhea resolves spontaneously after several years. The remaining one-third of the patients with microscopic colitis experience persistent or intermittent diarrhea and/or abdominal pain for many years (possibly indefinitely) as there is no cure for the condition.

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References

REFERENCES:

MedscapeReference.com. Collagenous and Lymphocytic Colitis.

R H Riddell, M Tanaka, and G Mazzoleni. Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study. Gut. 1992 May; 33(5): 683686.

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Someone just built microscopic robots from living cells, and its Westworld-level creepy – SYFY WIRE

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on Someone just built microscopic robots from living cells, and its Westworld-level creepy – SYFY WIRE

  1. Someone just built microscopic robots from living cells, and its Westworld-level creepy  SYFY WIRE
  2. Worlds First Living Robot Invites New Opportunities And Risks  Forbes
  3. A research team builds robots from living cells  The Economist
  4. Tiny 'living robots' made from FROG embryos could be used to destroy cancer cells  Daily Mail
  5. View full coverage on Google News

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Someone just built microscopic robots from living cells, and its Westworld-level creepy - SYFY WIRE

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Adamson, Welch: Using artificial intelligence to diagnose cancer could mean unnecessary treatments – St. Paul Pioneer Press

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on Adamson, Welch: Using artificial intelligence to diagnose cancer could mean unnecessary treatments – St. Paul Pioneer Press

The new decade opened with some intriguing news: The journal Nature reported that artificial intelligence was better at identifying breast cancers on mammograms than radiologists. Researchers at Google Health teamed up with academic medical centers in the United States and Britain to train an AI system using tens of thousands of mammograms.

But even the best artificial intelligence system cant fix the uncertainties of early cancer diagnosis.

To understand why, it helps to have a sense of how AI systems learn. In this case, the system was trained with images labeled as either cancer or not cancer. From them, it learned to deduce features such as shape, density and edges that are associated with the cancer label.

Thus, the process is dependent on starting with data that are correctly labeled. In the AI mammography study, the initial diagnoses were determined by a pathologist who examined biopsy specimens under a microscope after an abnormal mammogram. In other words, the pathologist determined whether the mammogram showed cancer.

Unfortunately, this pathologic standard is problematic. Over the last 20 years there has been a growing recognition that screening mammography has led to substantial overdiagnosis the detection of abnormalities that meet the pathological definition of cancer, yet wont ever cause symptoms or death.

Furthermore, pathologists can disagree about who has breast cancer even when presented with the same biopsy specimens under the microscope. The problem is far less for large, obvious cancers far greater for small (even microscopic), early-stage cancers. Thats because there is a gray area between cancer and not cancer. This has important implications for AI technology used for cancer screening.

AI systems will undoubtedly be able to consistently find subtle abnormalities on mammograms, which will lead to more biopsies. This will require pathologists to make judgments on subtler irregularities that may be consistent with cancer under the microscope, but may not represent disease destined to cause symptoms or death. In other words, reliance on pathologists for the ground truth could lead to an increase in cancer overdiagnosis.

The problem is not confined to breast cancer. Overdiagnosis and disagreement over what constitutes cancer are also problems relevant to melanoma, prostate and thyroid cancer. AI systems are already being developed for screening skin moles for melanoma and are likely to be employed in other cancers as well.

In a piece for the New England Journal of Medicine last month, we proposed a better way of deploying AI in cancer detection. Why not make use of the information contained in pathological disagreement? We suggested that each biopsy used in training AI systems be evaluated by a diverse panel of pathologists and labeled with three distinct categories: unanimous agreement of cancer, unanimous agreement of not cancer, and disagreement as to the presence of cancer. This intermediate category of disagreement would not only help researchers understand the natural history of cancer, but could also be used by clinicians and patients to investigate less invasive treatment for cancers in the gray area.

The problem of observer disagreement is not confined to pathologists; it also exists with radiologists reading mammograms. Thats the problem AI is trying to solve. Yet, while the notion of disagreement may be unsettling, disagreement also provides important information: Patients diagnosed with an early-stage cancer should be more optimistic about their prognoses if there were some disagreement about whether cancer was present, rather than all pathologists agreeing it was obviously cancer.

Artificial intelligence cant resolve the ambiguities surrounding early cancer diagnosis, but it can help illuminate them. And illuminating these gray areas is the first step in helping patients and their doctors respond wisely to them. We believe that training AI to recognize an intermediate category would be an important advance in the development of this technology.

Adewole S. Adamson is a dermatologist and assistant professor of medicine at Dell Medical School at the University of Texas at Austin. H. Gilbert Welch is a senior researcher in the Center for Surgery and Public Health at Brigham and Womens Hospital in Boston and author of Should I Be Tested for Cancer? Maybe Not and Heres Why. They wrote this piece for the Los Angeles Times.

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Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries – Science Advances

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries – Science Advances

Abstract

Microcirculatory obstruction is a hallmark of severe malaria, but mechanisms of parasite sequestration are only partially understood. Here, we developed a robust three-dimensional microvessel model that mimics the arteriole-capillary-venule (ACV) transition consisting of a narrow 5- to 10-m-diameter capillary region flanked by arteriole- or venule-sized vessels. Using this platform, we investigated red blood cell (RBC) transit at the single cell and at physiological hematocrits. We showed normal RBCs deformed via in vivolike stretching and tumbling with negligible interactions with the vessel wall. By comparison, Plasmodium falciparuminfected RBCs exhibited virtually no deformation and rapidly accumulated in the capillary-sized region. Comparison of wild-type parasites to those lacking either cytoadhesion ligands or membrane-stiffening knobs showed highly distinctive spatial and temporal kinetics of accumulation, linked to velocity transition in ACVs. Our findings shed light on mechanisms of microcirculatory obstruction in malaria and establish a new platform to study hematologic and microvascular diseases.

Microcirculatory disorders are associated with both infectious and noninfectious diseases, including Plasmodium falciparum malaria (1), sickle cell disease (2), and type 2 diabetes (3). Sequestration of P. falciparuminfected red blood cells (IRBCs) in the microcirculation has been recognized as a critical event in severe malaria pathogenesis and associated life-threatening complications, leading to approximately 500,000 deaths per year (4, 5). During the blood stage of infection, P. falciparum parasites extensively modify the host erythrocyte cytoskeleton and membrane, resulting in altered red blood cell (RBC) deformability and new adhesive properties. In particular, IRBCs display knob-like surface protrusions that stiffen the erythrocyte membrane (6, 7) and present the P. falciparum erythrocyte membrane protein 1 (PfEMP1) ligands that mediate cytoadhesion to the vascular endothelium (8, 9). Both knobs and PfEMP1 are thought to contribute to IRBC sequestration, giving rise to enhanced disease severity through small vessel occlusion, tissue ischemia, and eventual organ failure (1, 8, 1013). In addition, sequestered IRBCs may localize host or parasite-derived products that contribute to endothelial dysfunction and organ damage (14). Worldwide deaths attributed to malaria remain high, even after the introduction of more effective, faster-acting, antimalaria drugs (15). Investigating disease mechanisms and new therapeutic approaches to combine with antimalaria drugs has proven challenging as P. falciparum is a human tropic pathogen with complications focused at the capillary and postcapillary venule (16, 17). As no proper in vitro human capillary model exists, inferences must instead be drawn from postmortem analysis or studies in non-natural hosts [primate infections (18) or ex vivo rat microcirculatory models (12)], in which host receptors are not the natural binding partners for P. falciparum ligands.

Within the microcirculation, RBCs (diameter dAVG = 7.5 m) deform as they traverse capillaries (dAVG = 3 to 10 m) that are often narrower than their resting-state diameters. To understand how the altered deformability of P. falciparumIRBCs contributes to microcirculatory obstruction, the mechanics of RBC flow have been modeled in vitro using narrow glass tubes or wedge-shaped, rigid PDMS (polydimethylsiloxane)based microfluidic devices (1924). While these approaches have demonstrated geometric thresholds for mechanical trapping of IRBCs (20, 25), they do not account for either the lubricating properties of the endothelial glycocalyx or the adhesive contributions of endothelial cells (26, 27). Conversely, flow-based, endothelial monolayer models have investigated the role of different host receptors in parasite cytoadhesion (2830), yet they are unable to capture the geometric constraints that govern IRBC flow through narrow capillary constrictions or the flow rate transitions encountered as cells traverse different-size microvessels. The altered adhesive and mechanical properties of IRBCs and the alterations in flow dynamics experienced by IRBCs within microvessels likely all contribute to sequestration in a mutually dependent manner. Without an adequate human capillary model, the contributions of these biophysical and biochemical factors of IRBC sequestration cannot be explored.

We addressed these challenges by developing a three-dimensional (3D) arteriole-capillary-venule (ACV) microvessel unit, in which endothelial cells are grown in a native extracellular matrix. After optimizing the design parameters of 3D capillary fabrication and endothelialization, we used the ACV unit to identify the distinct spatiotemporal dynamics of RBC capillary transit and dissect the individual contributions of cytoadhesion and mechanical stiffening to IRBC sequestration. Our study sheds light on the mechanisms underlying IRBC sequestration during severe malaria infection and provides a unique platform to study the cellular, microfluidic, and geometric factors that give rise to microvascular obstruction in hematologic diseases.

To create an efficient capillary model, we first fabricated an acellular 3D ACV microvessel unit via a two-step process. First, large arteriole or venule-sized microchannels (lumen diameter d = 200 m, spaced 450 m apart) were lithographically fabricated in collagen hydrogels (7.5 mg/ml, ~200 to 500 Pa), as previously described (31). Then, an array of capillary-sized microchannels or features of arbitrary user-defined geometries (32) were generated between the two main channels using multiphoton microscopyguided femtosecond laser photoablation (fig. S1A). Ablated regions were confirmed using second harmonic imaging of collagen fibers (fig. S1B). Arrays of channels ranging from 5 to 20 m in diameter were rapidly produced (~75 channels/hour) with high density and robust perfusability by 0.22-m fluorescent beads (fig. S1, C and D). The density generated (~11,600 channels/mm2 for 5-m arrays; fig. S1D) can reach a similar or higher level than that observed in the human heart [1100 capillaries/mm2 in vivo; (33)].

Endothelialization of this ACV model posed substantial challenges as conventional methods of cell seeding after microvessel fabrication (31) led to sparse endothelial coverage within the microchannel arrays and nonperfusable vessels even after 7 days of culture. Successful endothelialization was achieved by leveraging the precise yet destructive nature of photoablation to simultaneously incur local endothelial cell injury while generating capillary-sized void spaces between two preformed main microvessels (Fig. 1A). This methodology encouraged endothelial cell migration and ingrowth into the ablated channels (Fig. 1B). Stable endothelial coverage was observed in the capillary-sized channels as early as 18 hours following photoablation (Fig. 1C and movie S1), and complete endothelialization of 20-m channels was observed after 4 days of culture under gravity-driven flow across the microvessels (Fig. 1B).

(A) Diagram of device assembly and capillary fabrication. Main channels were generated by soft lithography in acrylic jigs followed by capillary generation by photoablation and endothelial ingrowth. (B) Array (2 2) of 20-m-diameter vessels demonstrates stable vessel lumens. Green: F-actin; blue: nuclei. (C) Endothelial ingrowth over 18 hours demonstrates complete vessel formation. (D and E) Cryosectioned capillaries were stained with (D) hematoxylin and eosin as well as (E) type IV collagen, demonstrating lumen formation by single endothelial cells and robust basement membrane deposition. (F) Constriction vessel design allows for the generation of sub10-m-diameter capillaries shown in both projected and cross-sectional views. Red: VE-cadherin; blue: nuclei. (G to I) Ultrastructural analysis of capillary vessel regions by transmission electron microscopy (TEM) shows vessels at varying diameters (from 40 to 10 m) in cross-sectional (G and I) and longitudinal (H) views and varying wall thicknesses and junctions at cell-cell contact in zoomed views (I). Cross-sectional views of vessel regions near the connection. Col: collagen substrate; *: lumen; C: cells. (J) Stitched confocal image demonstrates complete vessel network consisting of 33 capillaries. Green: von Willebrand factor; blue: nuclei; red: VE-cadherin; purple: F-actin.

In vivo, capillary lengths range from 150 to 500 m (34). To determine the vessel patency at high vessel density, 2 2 arrays of straight channels, consisting of either 10- or 20-m lumen diameters spaced 5, 10, or 20 m apart, were photoablated between two preformed main microvessels of 200-m diameter (fig. S2). Microchannels that were initially separated by only 5 or 10 m demonstrated partial or complete fusion after endothelial cell ingrowth from the two main microvessels, leading to a larger vessel diameter (fig. S2, B and C). By comparison, microchannels of 20-m diameter separated by a 20-m distance maintained high vessel diameter fidelity (Fig. 1B and fig. S2C), Whereas 10-m diameter channels exhibited incomplete endothelialization and patchy endothelial coverage (fig. S2B), vascularization was more efficient in 20-m channels. The average length of continuous endothelium in 10-m diameter channels was approximately 126.7 60.2 m, corresponding to an aspect ratio [AR = length (l): lumen diameter (d) of 12.7 6.0] (fig. S2D). In contrast, 20-m-diameter vessels demonstrated near-complete endothelialization (365 105.4 m) (AR = 18.3 5.3). Moreover, 20-m-diameter vessels exhibited clear lumens upon histological staining and deposited abundant type IV collagen, suggesting the generation of a robust basement membrane (Fig. 1, D and E). Together, these data suggest geometric constraints for small vessel size formation (a minimum distance of 20 m between two parallel small channels and maximum AR of approximately 12 to 18) to maintain vessel patency, which has consistent range with human in vivo measurements for the length-to-diameter ratio (33).

In vivo, RBCs experience changes in velocity as they traverse different-sized microvessels within the ACV unit (35). To build a robust capillary model at smaller diameters (5 to 10 m) that more accurately mimics the in vivo vascular tree, we designed a constriction-shaped ACV geometry with a gradual change of diameter and a reduced AR for the capillary regions. This design consisted of five distinct regions that combine to form a symmetric hourglass shape: a precapillary arteriole and a postcapillary venule mimicking vessels with constant width (w = 40 m, l = 80 m, thereby AR = 2), which were connected to a capillary-sized region (w = 5 m, l = 80 m, AR = 16) by two flanking narrowing/expanding transition regions (w = 40 to 5 m, l = 105 m). This vessel design decreased the length of the capillary-sized region and increased the width or diameter of the sections that connected with the two main larger-sized microvessels, therefore promoting endothelial cell ingrowth and capillary patency (Fig. 1, F to J).

Two cell seeding approaches were tested for endothelialization efficiency and perfusability: (i) direct cell seeding of fully acellular channels followed by 7 days of culture and (ii) photoablation-guided capillary ingrowth for 4 days from two large preformed main vessels after 3 days of culture (7 days total). The hourglass-shaped ACV unit design supported robust endothelial cell ingrowth throughout the capillary-sized channels using both seeding approaches (fig. S3, A to D). While successful endothelialization could be achieved using either of the seeding methods (65 1% versus 77 7%, mean SEM), the percentage of perfusable capillaries was significantly higher when endothelial cells grew into the photoablated channels from preformed microvessels (57 12% versus 17 7%, mean SEM, **P < 0.002) (fig. S3E). Implementation of photoablation-guided capillary ingrowth resulted in robust, consistent, and perfusable capillary-sized microvessels of 5- to 10-m diameter, measured via confocal microscopy (Fig 1, F to J, and fig. S3, A and B). Similar to the two main vessels, the endothelium within the ACV regions was positive for vascular endothelial (VE)cadherin (a marker of intercellular junctions) and von Willebrand factor (a marker of Weibel-Palade bodies) (Fig. 1, F to J). We further measured the diameter at the narrowest region of the capillary constriction zones, which ranged from 7.5 to 13.6 m (10.9 1.8 m, mean SD, n = 25 capillaries) in confocal microscopy and 5.6 to 13.2 m (8.6 2.1 m, mean SD, n = 15 capillaries) in two-photon microscopy.

Electron microscopic analysis confirmed the gradual changes of vessel diameter along the longitudinal direction (Fig. 1, G to I, and fig. S4). Ultrastructure of vessel regions with cross-sectional diameters larger than 20 m was often formed from two or more endothelial cells, connected with focal contacts and junctions between surrounding cells (Fig. 1, G1 and G2). By comparison, at regions of 10 m or smaller in diameter, lumens appeared to be enclosed by a single endothelial cell, which formed extensive focal contacts and complex junctions with overlapping cell peripherals from one or two neighboring cells (Fig. 1, G3). The lumenal wall displayed heterogeneous thickness, ranging from approximately 100 nm to several micrometers at the regions of cell bodies or overlapping cell regions. This also led to varying vessel diameters in both longitudinal and circumferential directions across the ACV unit, although vessels remained intact and continuous across almost all planes examined (Fig. 1, G and H, and fig. S4). Together, our data suggest an efficient approach to fabricate a continuous, endothelialized, perfusable ACV unit with high fidelity and patency.

(A) Superimposed time lapse image series of RBC motion through an endothelialized vessel. Time lapse interval: 0.1 s. Scale bar, 25 m. (B) Schematic showing RBC perfusion through constriction-shaped vessel. wc = 10 m; wm = 40 m. (C) Representative examples of parachute-, slipper-, and discocyte-like RBC deformations in capillary constrictions. Scale bar, 10 m. (D) Representative traces of RBC major axis length and orientation for (i) stretching and (ii) tumbling RBCs, where x = 0, y = 0 is the center of the capillary; gray boxes: capillary extents. (E) Normalized extent of deformation, defined as the ratio of major axis length at a given position to the average major axis length in the precapillary region for (i) normal RBCs and (ii) knobless malaria-IRBCs (n = 3; each biological replicate is represented by one symbol, , , , or ).

When normal RBCs were perfused through the completely endothelialized ACV devices at full hematocrit, the presence of endothelium appeared to facilitate the smooth perfusion of RBCs through the capillary constriction region (movie S2). By comparison, in acellular collagen microchannels with the same hourglass geometry, RBCs accumulated upstream before entering the narrowest region, leading to local increases of hematocrit, as well as intermittent jetting of RBCs into the capillary constriction zones and much lower hematocrit further downstream (movie S3). This comparison of acellular and endothelialized microvessels reinforces the importance of the endothelium in understanding the interaction of RBCs and capillaries.

We next exploited this endothelialized capillary model to study the biomechanical and functional differences between normal and infected RBCs under flow. To allow visualization of individual cells as they traverse the ACV units, RBCs were perfused at a low hematocrit. When normal RBCs were perfused through ACVs at low hematocrit and velocities similar to in vivo capillary flow rates (250 to 1500 m/s) (34, 36), they displayed in vivolike stretching in the capillary region and tumbling behavior in the pre- and postcapillary regions (Fig. 2, A and B, and movies S4 and S5). Normal RBCs readily traversed the capillary regions down to 5 m in diameter and assumed a variety of deformations, including parachute-like, slipper-like, and discocyte shapes (Fig. 2C), in agreement with previous in vivo observations (19), computational simulations (37, 38), and microfluidic studies in narrow glass tubes (38). Using edge detectionbased image analysis (see the Supplementary Materials and Methods and fig. S5), we tracked the position, velocity, shape, and orientation of individual RBCs throughout the capillaries (Fig. 2D). Normal RBCs showed two major modes of motion in the capillary regions: elongation, characterized by stretching along the major axis by up to twofold (Fig. 2D (i) and movie S4), and tumbling, characterized by oscillations in major axis orientation (Fig. 2D (ii) and movie S5). Compared with normal RBCs, P. falciparumIRBCs present increased rigidity due to knob-like modifications to the erythrocyte cytoskeleton (6, 7) and modest changes in RBC volume and its biconcave shape due to the growing intracellular parasite (39), which might change the IRBC mechanics through capillary-sized vessels. To understand how the intracellular parasite body contributes to the biomechanics of IRBC traversal through the microcirculation, independently of knob rigidification and cytoadhesion, we perfused a clonally derived parasite variant called 2G2 (fig. S6), which has been selected for lack of knobs by gelatin (40). Although not statistically different compared with normal RBCs, 2G2-IRBCs presented minimal elongation and mostly tumbled through the capillary region despite being perfused at similar velocities to normal RBCs (Fig. 2E and movie S6). Because rolling and tumbling along the microvascular endothelium enhance cytoadhesion and increase the probability of ligand-receptor interaction at high shear stress (41), we expect that these differences in tumbling motion may enhance the ability of malaria-infected RBCs to both be mechanically trapped and cytoadhere in capillaries.

In the microcirculation, hydrodynamic forces encourage separation and margination of IRBCs from their uninfected RBC counterparts toward the vessel wall, enhancing cytoadhesive interactions with endothelial cells (42, 43). To investigate whether IRBCs sequester at physiological hematocrit concentrations (Fig. 3A), fluorescently labeled IRBCs (0.4 to 4% parasitemia) or normal RBCs were perfused at 40% hematocrit using gravity-driven flow, leading to an average flow rate at approximately 0.002 l/min in each capillary during the first 30 min of perfusion. The cell accumulation was assessed at 1, 4, 7, and 20 min by fluorescence imaging and was compared with flow modeling to relate predicted flow dynamic changes across the microvessels to retention and occlusion events (Fig. 3, B and C). Normal RBCs traversed the entire constriction zone with minimal sequestration in any vessel region (Fig. 3, C to I, and movie S7). Both labeled and unlabeled normal RBCs deformed as necessary to pass through the narrowest regions, suggesting that the membrane-labeling procedure did not significantly increase sequestration potential. By comparison, IT4VAR19, a knob-positive (K+) and cytoadherent parasite variant (PfEMP1+) (fig. S6) (44) displayed steady accumulation (Fig. 3C (ii) and movie S8). Kinetic video analysis demonstrated sequestration throughout the capillary constriction zone with highest accumulation in the first half. Complete occlusion of the capillary region could be observed within minutes after initiation of flow, followed by accumulation of fluorescent IRBCs upstream of the blockage. At end point, K+PfEMP1+ IRBCs demonstrated high fluorescent signals centered in the capillary region and extending into the post- and precapillary regions. Ultrastructural analysis showed that the capillary regions contained a mixture of both infected and normal RBCs (fig. S7, A and B), suggesting that occluded vessels may trap normal RBCs. By transmission electron microscopy (TEM), IRBCs were found in close apposition to lumenal walls, even following perfusion washing (fig. S7). Moreover, some IRBCs were trapped or encircled by the endothelial cell membranes (fig. S7) or appeared to have been fully engulfed by an endothelial cell (fig. S7B), as observed previously in monolayer assays with immortalized endothelial cells (45).

(A) Bright-field image of RBCs flowing through a constriction vessel. Dotted lines demonstrate capillary outline trace. (B) Flow velocity model of a single capillary based on fabrication dimensions. (C) Left: Schematic illustrations of the different types of perfused RBCs and IRBCs. Middle: Representative image of binding kinetics within the capillary constriction zones. IRBCs are shown in red. Right: Spatial distribution of accumulation after 20 min of perfusion represented by a combined heat map of average fluorescence from multiple experiments. Normal RBC (n = 24), IT4VAR19 (n = 26), trypsinized IT4VAR19 (n = 19), and 2G2 (n = 19). (D and E) Quantification of average intensity as a measure of x position (D) and comparison among precapillary, capillary, and postcapillary regions (E). n = 24, 26, 17, and 19 ACV units quantified from N = 4 independent experiments for each condition of perfusion: normal RBC, IT4VAR19, trypsinized IT4VAR19, and 2G2, respectively. Analysis of variance (ANOVA) F = 11.61, P < 0.00001 for precapillary region, ANOVA F = 47.83, P < 0.00001 for capillary region, and ANOVA F = 6.41, P < 0.001 for postcapillary region.

To elucidate the relative contributions of altered adhesive and mechanical properties in IRBC microvessel obstruction, we trypsinized IT4VAR19 IRBCs to remove the surface presentation of PfEMP1s while leaving the knobs intact (K+PfEMP1) (fig. S8). Previous work by atomic force microscopy has established that P. falciparum knobs are unaffected by trypsin treatment (46). Following trypsinization, there was a marked loss of antibody recognition with two polyclonal antibody reagents against the first and fourth DBL domains in the IT4VAR19 PfEMP1 variant (fig. S8). Perfusion of K+PfEMP1 IRBCs demonstrated minimal sequestration throughout the constriction zone, with binding levels similar to normal RBCs in all vessel regions (Fig. 3, C to E, and movie S9). These findings suggest that while mechanical stiffening may contribute to IRBC margination toward the vessel wall in the postcapillary regions (43), surface-active PfEMP1 is necessary to cause IRBC sequestration. Furthermore, despite the geometric confinement in capillaries, mechanical stiffening on its own is insufficient to induce the same trapping in the 5- to 10-m capillary-sized constrictions observed with the K+PfEMP1+ IRBCs.

We next perfused 2G2 (K) to better understand the contribution of knobs to cytoadhesion (40), as they are thought to enhance PfEMP1-mediated adhesion (9, 12, 47) and increase the mechanical stiffening of IRBCs (48). Notably, both IT4VAR19 and 2G2 express endothelial protein C receptor (EPCR)binding var transcripts (49), but 2G2 exhibits much weaker cytoadhesive capabilities under flow conditions (50). Although the weakly adherent 2G2 parasites (K) exhibited higher sequestration rates than the trypsinized IT4VAR19 (K+PfEMP1), cell accumulation was concentrated to the second half of the capillary constriction zone, where cells would experience deacceleration and less flow shear as they transition into the larger-diameter region (Fig. 3, C and D, and movie S10). Together, this analysis identifies distinct and independent contributions of the microcirculatory hemodynamics and parasite-induced modifications to RBCs in microvascular obstruction.

Cytoadhesion of P. falciparumIRBCs is a major virulence determinant, but knowledge gaps exist in how parasites cause microvascular obstruction, and the ability to study important human microcirculatory disorders in vitro has been limited to nondeformable glass or microfluidic chamber platforms. Here, we describe an efficient fabrication approach for engineering robust and patent capillary arrays in an ACV unit. Our studies exploited this model to investigate normal and malaria-infected RBCs under perfusion and to identify sequential events of biomolecular and biophysical interactions between RBCs and capillary walls that led to parasite sequestration and microvascular occlusion.

Whereas normal RBCs readily traversed the narrow capillary constriction zones, P. falciparumIRBCs rapidly accumulated in these regions. Our study identified distinct contributions of parasite-induced knobs and cytoadhesion ligands in cell accumulation by perfusing IRBCs with different knob structures and trypsinized IRBCs to preserve the knob structure while eliminating the cytoadhesion effects (46). Although trypsinized IRBCs with cleaved parasite cytoadhesion ligands exhibited limited accumulation in the capillary constriction regions, parasites lacking knobs accumulated at the capillary-venule transition where flow rates were deaccelerating. The efficient traversal of trypsinized IRBCs through narrow constrictions is consistent with previous microfluidic studies, which demonstrate mechanical trapping of IRBCs only in nondeformable channels below 4 m in diameter (20). Knob membrane stiffening more likely contributes to splenic elimination, where interendothelial slits are as narrow as 3 m (51, 52). The knob-like protrusions anchor both the PfEMP1 cytoplasmic tail and erythrocyte cytoskeleton components, and previous work has established that they contribute to both parasite cytoadhesion strength (9) and the altered mechanical properties of P. falciparumIRBCs (48) and thereby provide mechanical stability to the interactions between PfEMP1 and endothelial cells. In addition, by positioning the PfEMP1 cytoadhesion ligands above the cell body (53), knobs may also facilitate adhesion. With the distinct spatiotemporal binding of knobless parasites, our findings suggest that PfEMP1 physiological display in knobs facilitates IRBC capture from circulation, particularly in regions of higher flow shear in the capillary constriction area. This is consistent with previous work in ex vivo rat microcirculatory models and primate studies (12, 47). Moreover, our findings reinforce the importance of cell deceleration and lower shear stress as cells exit from the capillaries, in mediating IRBC capture from flow. Postmortem autopsy studies have revealed higher IRBC accumulation rates at the postcapillary region (~3-fold increase as compared with precapillary regions) (17). Thus, our capillary model provides the means to dissect the interdependent interactions of microcirculatory hemodynamics and parasite modifications to malaria obstruction mechanisms.

The differences in pre- and postcapillary sequestration have been thought to arise from arterial-venous differences in flow rates or host receptor expression (54); nonetheless, this question has been difficult to study. In an ex vivo rat mesoappendix model, IRBC sequestration initiated in venules and sometimes extended upward by retrograde aggregation into the capillaries and arterioles (12). Although the rat mesoappendix model has been valuable to explore parameters influencing IRBC sequestration, recent work has also shown that severe malaria is linked to EPCR (49, 55, 56), which is highly divergent between humans and rats. Notably, both parasite lines used in this study (IT4VAR19 and 2G2) express EPCR-binding PfEMP1; thus, our human capillary constriction model has advantages in investigating the cytoadherence of severe malaria isolates in an in vitro human model.

A limitation of this model is the use of human umbilical cord endothelial cells (HUVECs), a cell type from large-vessel origin. However, HUVECs are commonly used to develop new 3D vascular platforms, and future studies can build on our design principles to incorporate different endothelial cells to develop organ-specific ACV units. In addition, the study of single-cell dynamics is challenging because of the lack of precise flow control in individual capillaries, owing to the parallel nature of many capillaries between the two main vessels in our system and the varying diameters in each capillary, similar to vessels found in vivo. Nevertheless, our ACV unit mimics physiological flow transitions within the microcirculation and could distinguish spatial and temporal binding differences between normal RBCs and IRBCs, as well as between wild-type parasites and parasites lacking PfEMP1 or the knob-like protrusions. Notably, parasite knob densities differ widely between fresh ex vivo parasites (57) and may also be modified in severe malaria infections (58), but it is unknown whether these variations modify IRBC cytoadhesion efficiency or influence disease severity. Our ACV model provides a fundamentally new approach to investigate microvascular obstruction in an in vitro human model. The success sheds light for future therapeutic development in treating blood-stage malaria and provides a potential platform for the studies of other microvascular disorders, such as sickle cell anemia, or in the context of transfusion medicine of blood products.

First, two parallel microchannels were fabricated via lithography and injection moldingbased techniques in collagen gel, as described previously (31), to mimic arteriole- and venule-sized vessels. Next, multiphoton photoablation was performed in collagen gel between these two parallel microchannels using a Mai Tai DeepSee Ti:S laser (maximum power, 2.57 W) coupled with an Olympus FV1000MPE BX61 microscope fitted with a water immersion objective lens (25, numerical aperture = 1.05). Microchannels and surrounding collagen regions were first identified by imaging of second-harmonic generation signals produced by collagen microfibers at excitation wavelength ex = 860 nm and detection wavelength detector = 420 to 460 nm. Individual capillary-sized channels were designed within the collagen matrix by designating 3D regions of interest using the Olympus Fluoview software and then ablated by laser rastering ( = 800 nm, I = 100%, pixel dwell time = 2 s, 10 to 15 line repeat scans). Laser scanning in the X, Y, and Z dimensions were performed at ~1-m step sizes. After the ablation, 0.22-m-diameter fluorescent microbeads were perfused from one side of the main channels across the newly created capillary-sized channels to the other side at a pressure drop of 1 cmH2O for 10 min, followed by imaging for evaluation of perfusability (fig. S1).

Endothelializing ACV unit. Two different procedures were investigated to form the endothelialized ACV units: (i) direct cell seeding of acellular channels and (ii) endothelial cell ingrowth after photoablation (figs. S2 and S3). In the first approach, the acellular ACV unit is first fabricated by photoablation, followed by seeding cells into the fully acellular device through the inlets of the two main parallel channels with 10-l perfusions of HUVECs (Lonza, passages 3 to 7, with EBM basal medium supplemented with EGM endothelial cell growth medium) at a density of 8 106 cells/ml. Once the cells were attached, the devices were cultured under gravity-driven flow across the capillaries between the two main channels for 7 days. To create a gravity-driven flow, 200 and 180 l of culture media was placed in the two main channel inlets to set the initial pressure drop at approximately 1 cmH2O, leading to a peak velocity of approximately 1 mm/s across the ACV unit between the two main channels. The pressure drop was reset every 12 hours to maintain flow in the capillary regions.

In the second approach, the two main microchannels were first seeded with 10-l perfusions of HUVECs at a density of 8 106 cells/ml and cultured for 3 days to form robust endothelialized lumens. Multiphoton photoablation was then performed to create microchannel void spaces that tapered down to 5 m in diameter within the collagen scaffold between the lumenal wall of the two main vessels and ablate endothelial cells at the two end connections. Cellular and collagen ablation was confirmed by imaging identical areas after ablation using transmitted light and by second-harmonic generation imaging. The ablated vessels were then cultured for an additional 4 days to allow for endothelial cell ingrowth. The culture was maintained at the same pressure drop as the first approach and replenished twice a day with fresh culture media.

P. falciparum parasite lines were cultured using anonymized human O+ type RBCs (Valley Biomedical) in RPMI 1640 (Gibco) supplemented with 10% human type A+ serum in a gas mixture of 90% N2, 5% CO2, and 5% O2. The knobless parasite line 2G2 was previously derived by lack of gelatin floatation followed by limited dilution cloning (40), while the IT4VAR19 line was generated after repeatedly panning on transformed human brain microvascular endothelial cells followed by limited clonal dilution (59, 60). Mature-stage IRBCs were enriched to 60 to 90% parasitemia by magnetic separation (MACS Cell Separator, LD Columns, Miltenyi Biotec) before perfusion for single-cell and population dynamics experiments. Both parasite lines predominantly express a single var gene and were derived from the IT4/FCR3 parasite genotype.

Magnetic enriched mature-stage P. falciparumIRBCs or packed RBCs were resuspended in 10% fetal bovine serum (FBS)containing EGM at 5 106 cells/ml, allowing the visualization of individual cells as they traverse the ACV devices. The dilute cell suspension was placed in the inlet and outlet of one microchannel at a maximum initial pressure drop of approximately 1 cmH2O, creating a hydraulic gradient between the two microchannels and establishing gravity-driven flow across the capillaries. The peak velocity of the RBCs across the center capillary zone was approximately 1 mm/s. In single-cell dynamics studies, the pressure drop and resulting velocity rate were maintained and slightly adjusted over the course of the assay by removing or adding a small volume (~5 l) of cell suspension from the inlet to maintain the RBC velocity in this range and allow for video capture of single-cell dynamics. The motion of individual RBCs within one of the capillary constriction channels was visualized with a Nikon TiE inverted widefield microscope, and videos were acquired at 20 and 250 to 500 frames/s using an Orca-Flash4.0V2 Digital CMOS camera (Hamamatsu). After acquisition, videos were analyzed using custom MATLAB scripts. For experiments with 2G2, videos were previously inspected, and only IRBCs with hemozoin were used in the downstream analysis. Briefly, individual frames containing RBCs were smoothed using a Wiener filter, inverted, then background subtracted using a mean filter. RBCs were detected by applying a Canny edge detection operator. Small gaps in RBC outlines were closed automatically using an edge-linking algorithm or manually (fig. S5). Individual RBC outlines were linked into trajectories based on displacement between outlines in different frames. Out-of-focus and overlapping RBCs were excluded from the analysis. Biological replicates were taken in at least two different days.

Magnetic enriched mature-stage P. falciparumIRBCs or packed RBCs were fluorescently labeled according to the PKH26 Red Fluorescent Cell Linker Kit (Sigma-Aldrich). To simulate blood with physiological parasitemia, labeled cells (normal RBCs or IRBCs) were added to unlabeled normal RBCs at a final parasitemia of 0.4 to 4% (iRBC/total RBC) and then diluted to 40% hematocrit in EGM (containing 5% FBS). RBCs were encouraged to flow across the device driven by a pressure drop of approximately 1 cmH2O for 20 min, leading to a peak velocity of approximately 1 mm/s, mimicking measured physiological velocities within the capillaries (34). The perfusion of RBCs was monitored and imaged at different fields of view (three capillary channels in each field of view) and continuous time frames. At the beginning of the perfusion, devices were quickly scanned to identify perfusable channels. Videos were taken for 10 s for each perfusable channel in the same order at each time point to determine the location and extent of binding after 1, 4, 7, and 20 min of perfusion. Each condition was repeated in independent days.

Population dynamics analysis. Quantification of population dynamics was performed on fluorescent images taken after 20 min of perfusion. Images were normalized between average background values and peak fluorescent intensity values, and a two-pixel radius median filter was used to remove speckle noise using MATLAB. Masks were manually drawn to outline individual capillary constriction channels using ImageJ. Average fluorescent intensity was calculated at each x position as the sum of intensity values across the y dimension divided by the diameter of the vessel at this position. The central point of each capillary region was determined, and the average intensity maps were lined up across all images at this central point.

IT4VAR19 trophozoite-stage enriched IRBCs were treated with a trypsin (66.67 g/ml; Sigma-Aldrich) solution in 1 phosphate-buffered saline for 30 min at 37C, followed by an inhibition with an equal volume of FBS before perfusion of capillary devices. To determine PfEMP1 surface expression after trypsinization, an IT4VAR19 culture was incubated for 30 min at 37C with a trypsin solution (10 g/ml). Surface PfEMP1 was recognized with rat polyclonal antibodies against IT4VAR19 DBL2 and DBL6 (1:10) for 30 min at 4C, followed by an incubation with goat anti-rat immunoglobulin GAlexa Fluor 488 (1:400, Molecular Probes) for 30 min. Infected erythrocytes (parasite nuclei) were detected with ethidium bromide (2 g/ml; Invitrogen). Stained cells were washed in phosphate-buffered saline and analyzed on an LSRII fluorescence-activated cell sorter machine (BD Biosciences). Analysis was performed using FlowJo 10 (Tree Star Inc., Ashland, OR).

All results are presented as means SE and assumed to be distributed approximately normally. The sample number represents the number of microvessel devices (ACV units) fabricated and analyzed unless otherwise noted. Single variable analysis with two-tailed t test assuming unequal variance was used to determine statistical significance between two samples for analysis of perfusability and endothelialization efficiencies. Two-way analysis of variance (ANOVA) was used to determine significance in population dynamics data, followed by Dunnetts multiple comparisons test.

Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/3/eaay7243/DC1

Supplementary Materials and Methods

Fig. S1. Photoablation-guided fabrication of acellular capillary-sized microchannels.

Fig. S2. Cellular limitations of capillary fabrication.

Fig. S3. Endothelialization strategies for capillary network.

Fig. S4. Ultrastructural analysis of vessels at capillary regions across the ACV units imaged via TEM.

Fig. S5. Edge detection workflow for studying traversal of single RBCs through a capillary-sized constriction.

Fig. S6. Transcriptional profiling of var gene expression in the two parasite lines.

Fig. S7. Ultrastructural analysis of capillary region after perfusion of RBCs imaged via TEM.

Fig. S8. Trypsin cleaves the surface-expressed IT4VAR19 PfEMP1 variant.

Movie S1. Endothelial ingrowth into 20-m capillaries between two large vessels after photoablation.

Movie S2. Representative video of normal RBCs perfused through endothelialized capillaries at physiological hematocrit.

Movie S3. Representative video of normal RBCs perfused through acellular collagen capillary-shaped channels at physiological hematocrit accumulating a significant amount before entering the capillary region and jetting and leading to significantly lower hematocrit into the downstream.

Movie S4. Representative video of normal RBCs stretching through capillaries (diameter, ~10 m) when perfused at the single-cell scale.

Movie S5. Representative video of normal RBCs tumbling through capillaries (diameter, ~10 m) when perfused at the single-cell scale.

Movie S6. Representative video of 2G2 IRBCs tumbling through capillaries (diameter, ~10 m) when perfused at the single-cell scale.

Movie S7. Representative video of normal RBCs perfused through the capillaries at physiological hematocrit with no cell accumulation in the lumen.

Movie S8. Representative video of IT4VAR19 IRBCs perfused through the capillaries at physiological hematocrit accumulating a significant amount and blocking the capillary flow.

Movie S9. Representative video of trypsinized IT4VAR19 perfused through the capillaries showing a significant decrease in cell accumulation and not blocking the capillary flow.

Movie S10. Representative video of 2G2 IRBCs perfused through the capillaries at physiological hematocrit accumulating at postcapillary regions but not blocking the capillary flow.

References (61, 62)

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

Acknowledgments: We acknowledge the Lynn and Mike Garvey Imaging Laboratory in the Institute of Stem Cell and Regenerative Medicine, the Nanotech User Facility, and the Flow Cytometry Facility, all at the University of Washington, and the Electron Microscope Facility in the Fred Hutchinson Cancer Research Institute. We thank R. Nagao for the helpful discussion and N. Sniadecki for sharing his microscope. We acknowledge the imaging and flow cytometry facility at the Seattle Childrens Research Institute. Funding: This work is supported by the NIH R01 HL130488 (to J.D.S. and Y.Z.), R01HL141570, UG3TR002158, and UH2/UH3 DK107343 (to Y.Z.), and 2T32EB001650 and F30HL134298 (to C.A.); the NSF 1652141 and 1807398 (to C.A.D.); and the AHA postdoctoral fellowship (to M.B.). Author contributions: Y.Z. conceived the project. Y.Z., J.D.S., and C.A.D. supervised the project. C.A., C.G., C.H., M.B., J.D.S., and Y.Z. designed the experiments. C.A., C.G., C.H., and M.B. performed the experiments and data analysis with the assistance of K.P. and E.Y. All authors interpreted the data. C.A., C.G., J.D.S., and Y.Z. wrote the manuscript. All authors edited and approved the manuscript. Competing interests: The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in this paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the corresponding author (yingzy{at}uw.edu).

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Biophysical and biomolecular interactions of malaria-infected erythrocytes in engineered human capillaries - Science Advances

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Complete Overview of Cancer Nanomedicine Market to Witness High Rate of Growth in Forthcoming Years – Fusion Science Academy

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on Complete Overview of Cancer Nanomedicine Market to Witness High Rate of Growth in Forthcoming Years – Fusion Science Academy

In 2018, the market size of Cable Cars & Ropeways Market is million US$ and it will reach million US$ in 2025, growing at a CAGR of from 2018; while in China, the market size is valued at xx million US$ and will increase to xx million US$ in 2025, with a CAGR of xx% during forecast period.

In this report, 2018 has been considered as the base year and 2018 to 2025 as the forecast period to estimate the market size for Cable Cars & Ropeways .

This report studies the global market size of Cable Cars & Ropeways , especially focuses on the key regions like United States, European Union, China, and other regions (Japan, Korea, India and Southeast Asia).

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This study presents the Cable Cars & Ropeways Market production, revenue, market share and growth rate for each key company, and also covers the breakdown data (production, consumption, revenue and market share) by regions, type and applications. Cable Cars & Ropeways history breakdown data from 2014 to 2018, and forecast to 2025.

For top companies in United States, European Union and China, this report investigates and analyzes the production, value, price, market share and growth rate for the top manufacturers, key data from 2014 to 2018.

In global Cable Cars & Ropeways market, the following companies are covered:

market taxonomy and product definitions for the global cable cars & ropeways market assessment. In the next section, the report describes the market development background and covers macro-economic factors, industry factors, forecast factors, regional weighted average pricing analysis, value chain overview covering approximate margins, an indicative list of stakeholders involved in each stage and an assessment of the cable cars & ropeways market for the base year considered for the study.

The next section of the report discusses market dynamics, such as drivers, restraints and trends, impacting the market growth at a global level. Market opportunities for manufacturers have been presented in the subsequent section of the same chapter. This section also includes the impact assessment of market dynamics on the global cable cars & ropeways market at a qualitative level, based on analysis facts and insights.

Subsequent sections of the report provide value (US$ Mn) and volume (Unit Systems) projections for the cable cars & ropeways market on the basis of the aforementioned segments at a global level. The global market values represented in these sections have been agglomerated by collecting data and information at a regional level. The market information, along with key facts and insights, covers unique analysis frameworks, such as absolute $ opportunity analysis, year-on-year growth trend comparison, market share and attractiveness analysis, for each of the sub-types covered in each segment.

The next section of the report presents a summarised view of the global cable cars & ropeways market, based on six prominent regions considered in the study. The section includes the regional market position, growth potential, trends, market attractiveness analysis and key insights pertaining to each of these regions.

The market analysis sections cover Y-o-Y growth trends, market share analysis, market attractiveness and incremental $ opportunity assessment for each of the aforementioned segments. These sections analyse the degree to which the global drivers are influencing this market in each region.

All the above sections evaluate the present market scenario and growth prospects in the global cable cars & ropeways market while the forecast presented in the sections assess the market size in terms of volume and value.

In order to offer an accurate forecast, we started by sizing the current market, which forms the basis of how the global cable cars & ropeways market is expected to develop in the future. Given the characteristics of the market, we triangulated the outcome of three different types of analysis, based on primary research, secondary research and our own analysis. However, forecasting the market in terms of various cable cars & ropeways segments and regions is more a matter of quantifying expectations and identifying opportunities rather than rationalising them after the completion of the forecast exercise.

In addition, it is imperative to note that in an ever-fluctuating global economy, we not only conduct forecast in terms of CAGR, but also analyse the market on the basis of key parameters, such as Year-on-Year (Y-o-Y) growth, to understand the predictability of the cable cars & ropeways market and identify the right opportunities available.

As previously highlighted, the cable cars & ropeways market is split into a number of sub-segments. All the cable cars & ropeways sub-segments, in terms of product type, end use and region, have been analysed on the basis of Basis Point Share (BPS) to understand each individual segments relative contribution to the market growth. This detailed level of information is important for the identification of various key trends being witnessed in the cable cars & ropeways market.

Another key feature of this report is the analysis of all the key segments in the cable cars & ropeways market, sub-segments and the regional adoption and revenue forecast in terms of absolute dollar opportunity. This is traditionally overlooked while forecasting the market; however, the absolute dollar opportunity is critical in assessing the level of opportunity that a provider can look to achieve as well as to identify potential resources from a sales and delivery perspective in the cable cars & ropeways market.

In order to understand the key market segments in terms of the growth and consumption of cable cars & ropeways across concerned regions, PMR has developed the attractiveness index, which will help providers to identify real market opportunities.

In the final section of the report, a competitive landscape of the cable cars & ropeways market has been included to provide report audiences with a dashboard view, categorised on the basis of providers present in the value chain, their presence in the cable cars & ropeways market and key differentiating factors and strategies. The primary category of providers covered in the report is cable cars & ropeways manufacturers. This section is primarily designed to provide clients with an objective and detailed comparative assessment of the key providers specific to a market segment in the value chain of the cable cars & ropeways market. Report audiences can gain segment-specific vendor insights to identify and evaluate key competitors on the basis of in-depth assessment of their capabilities and success in the cable cars & ropeways marketplace. Detailed profiles of providers have also been included under the scope of the report to evaluate their long- and short-term strategies, key offerings and recent developments pertaining to the cable cars & ropeways market. Examples of some of the key competitors covered in this report include Doppelmayr/Garaventa Group, Leitner Group, Leitner-Poma of America, Inc, MND Group, Bartholet Maschinenbau AG (BMF), Nippon Cable Co., Ltd., CONVEYOR & ROPEWAY SERVICES PVT. LTD., Damodar Ropeways & Infra Ltd., STM TELEFERIK and CCM FINOTELLO SRL, among others.

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The content of the study subjects, includes a total of 15 chapters:

Chapter 1, to describe Cable Cars & Ropeways product scope, market overview, market opportunities, market driving force and market risks.

Chapter 2, to profile the top manufacturers of Cable Cars & Ropeways , with price, sales, revenue and global market share of Cable Cars & Ropeways in 2017 and 2018.

Chapter 3, the Cable Cars & Ropeways competitive situation, sales, revenue and global market share of top manufacturers are analyzed emphatically by landscape contrast.

Chapter 4, the Cable Cars & Ropeways breakdown data are shown at the regional level, to show the sales, revenue and growth by regions, from 2014 to 2018.

Chapter 5, 6, 7, 8 and 9, to break the sales data at the country level, with sales, revenue and market share for key countries in the world, from 2014 to 2018.

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Chapter 10 and 11, to segment the sales by type and application, with sales market share and growth rate by type, application, from 2014 to 2018.

Chapter 12, Cable Cars & Ropeways market forecast, by regions, type and application, with sales and revenue, from 2018 to 2024.

Chapter 13, 14 and 15, to describe Cable Cars & Ropeways sales channel, distributors, customers, research findings and conclusion, appendix and data source.

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Complete Overview of Cancer Nanomedicine Market to Witness High Rate of Growth in Forthcoming Years - Fusion Science Academy

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Is Spago Nanomedical (NGM:SPAG) In A Good Position To Invest In Growth? – Simply Wall St

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on Is Spago Nanomedical (NGM:SPAG) In A Good Position To Invest In Growth? – Simply Wall St

We can readily understand why investors are attracted to unprofitable companies. For example, biotech and mining exploration companies often lose money for years before finding success with a new treatment or mineral discovery. But the harsh reality is that very many loss making companies burn through all their cash and go bankrupt.

Given this risk, we thought wed take a look at whether Spago Nanomedical (NGM:SPAG) shareholders should be worried about its cash burn. In this report, we will consider the companys annual negative free cash flow, henceforth referring to it as the cash burn. Well start by comparing its cash burn with its cash reserves in order to calculate its cash runway.

Check out our latest analysis for Spago Nanomedical

You can calculate a companys cash runway by dividing the amount of cash it has by the rate at which it is spending that cash. In September 2019, Spago Nanomedical had kr23m in cash, and was debt-free. In the last year, its cash burn was kr45m. That means it had a cash runway of around 6 months as of September 2019. To be frank, this kind of short runway puts us on edge, as it indicates the company must reduce its cash burn significantly, or else raise cash imminently. Importantly, if we extrapolate recent cash burn trends, the cash runway would be noticeably longer. The image below shows how its cash balance has been changing over the last few years.

Notably, Spago Nanomedical actually ramped up its cash burn very hard and fast in the last year, by 135%, signifying heavy investment in the business. As if thats not bad enough, the operating revenue also dropped by 16%, making us very wary indeed. Considering these two factors together makes us nervous about the direction the company seems to be heading. While the past is always worth studying, it is the future that matters most of all. For that reason, it makes a lot of sense to take a look at our analyst forecasts for the company.

Since Spago Nanomedicals revenue is down, and its cash burn is up, shareholders would quite reasonably be considering whether it can raise more money easily, if need be. Generally speaking, a listed business can raise new cash through issuing shares or taking on debt. Commonly, a business will sell new shares in itself to raise cash to drive growth. By looking at a companys cash burn relative to its market capitalisation, we gain insight on how much shareholders would be diluted if the company needed to raise enough cash to cover another years cash burn.

Spago Nanomedicals cash burn of kr45m is about 13% of its kr336m market capitalisation. As a result, wed venture that the company could raise more cash for growth without much trouble, albeit at the cost of some dilution.

Even though its increasing cash burn makes us a little nervous, we are compelled to mention that we thought Spago Nanomedicals cash burn relative to its market cap was relatively promising. After looking at that range of measures, we think shareholders should be extremely attentive to how the company is using its cash, as the cash burn makes us uncomfortable. For us, its always important to consider risks around cash burn rates. But investors should look at a whole range of factors when researching a new stock. For example, it could be interesting to see how much the Spago Nanomedical CEO receives in total remuneration.

If you would prefer to check out another company with better fundamentals, then do not miss this free list of interesting companies, that have HIGH return on equity and low debt or this list of stocks which are all forecast to grow.

If you spot an error that warrants correction, please contact the editor at editorial-team@simplywallst.com. This article by Simply Wall St is general in nature. It does not constitute a recommendation to buy or sell any stock, and does not take account of your objectives, or your financial situation. Simply Wall St has no position in the stocks mentioned.

We aim to bring you long-term focused research analysis driven by fundamental data. Note that our analysis may not factor in the latest price-sensitive company announcements or qualitative material. Thank you for reading.

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Is Spago Nanomedical (NGM:SPAG) In A Good Position To Invest In Growth? - Simply Wall St

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How the Internet of Medical Things Is Impacting Healthcare – HealthTech Magazine

§ January 17th, 2020 § Filed under Nano Medicine Comments Off on How the Internet of Medical Things Is Impacting Healthcare – HealthTech Magazine

What Is IoMT?

The IoMT is a connected infrastructure of medical devices, software applications, and health systems and services.

And while a growing pool and general adoption of IoT technologies are benefiting many industries, its a wave of sensor-based tools including wearables and stand-alone devices for remote patient monitoring and the marriage of internet-connected medical devices with patient information that ultimately set the IoMT ecosystem apart.

The rise of IoMT is driven by an increase in the number of connected medical devices that are able to generate, collect, analyze or transmit health data or images and connect to healthcare provider networks, transmitting data to either a cloud repository or internal servers, the Deloitte report notes.

Ultimately, this connectivity between medical devices and sensors is streamlining clinical workflow management and leading to an overall improvement in patient care, both inside care facility walls and in remote locations.

The capabilities of IoMT are more accurate diagnoses, fewer mistakes and lower costs of care. Paired with smartphone applications, the technology allows patients to send their health information to doctors in order to better surveil diseases and track and prevent chronic illnesses.

In fact, a study conducted by researchers from Cedars-Sinai Medical Center and UCLA demonstrates the ability of Fitbit activity trackers to more accurately evaluate patients with ischemic heart disease by recording their heart rate and accelerometer data simultaneously. That helps explain why mHealthIntelligence reports that 88 percent of care providers are investing in remote patient monitoring solutions.

This type of technology is not only helping to improve the patient experience by eliminating the need for in-person medical visits, but its also helping to reduce costs. Goldman Sachs estimates that IoMT will save the healthcare industry $300 billion annually in expenditures primarily through remote patient monitoring and improved medication adherence.

That said, another positive effect of IoMT is on drug management via the introduction of smart pills that contain microscopic sensors, which, once swallowed, can transmit data to connected devices.

Some digital medicine companies, such as Proteus Discover, have focused their smart pill capabilities on measuring medication treatment effectiveness to improve clinical outcomes. Others, such as HQs CorTemp, are using the pills to monitor patients internal health, wirelessly transmitting data such core temperature measurements that can be critical in life or death situations.

READ MORE: Discover how IoMT will evolve to better fit healthcare needs in 2020.

The global IoMT market was valued at $44.5 billion in 2018 and is expected to grow to $254.2 billion in 2026, according to AllTheResearch. The smart wearable device segment of IoMT, inclusive of smartwatches and sensor-laden smart shirts, made up for the largest share of the global market in 2018, at roughly 27 percent, the report finds.

This area of IoMT is poised for even further growth as artificial intelligence is integrated into connected devices and can prove capable of the real-time, remote measurement and analysis of patient data.

The IoMT ecosystem expansion is paving the way for other new technologies too, such as kiosks that provide connectivity to care providers. These kiosks will further enable clinicians to monitor and treat patients remotely an ever-growing need for patients in rural communities as they struggle to recruit and retain medical specialists.

Regardless of a patients location or condition, an evolution of the IoMT ecosystem will become increasingly impactful. And even the most remote locations will benefit from better access to care as connected medical devices continue to find their way into the hands of both patients and clinicians.

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Flu outbreak worse in Texas than nationally – Runnels County Register

§ January 16th, 2020 § Filed under Nano Medicine Comments Off on Flu outbreak worse in Texas than nationally – Runnels County Register

The flu is bad in 2019 and 2020. Influenza (flu) is a highly contagious seasonal viral illness that is of two types, A and B, with hundreds of different sub-types. It is spread by microscopic droplets that are formed with each cough or sneeze. Droplets can enter the body directly through the mouth or nose, or indirectly when they dry and fall to a surface where hands then carry infectious material into the mouth, eyes or nose. The illness causes fever as well as headache, body aches and sometimes eye, throat or GI symptoms. It can lead to bacterial infections of the ears and also to pneumonia. It is this last complication that is responsible for most of the deaths due to flu, and these are most common in the very young or very old, or those with underlying diseases such as asthma, COPD, cancer or diabetes.

The CDC estimates that flu has resulted in between 9 million 45 million illnesses, resulting in 140,000 810,000 hospitalizations and between 12,000 61,000 deaths annually since 2010. This year is worse than last year at this time and its worse in Texas than it is nationally. Of course, the best thing is to avoid getting it, and vaccination is the best way to do that. The vaccine has proven to have a relatively good match this year, especially for Type B which is the Type on the rise and likely to account for most of the cases going forward. If you have not had the vaccine it is recommended that you get it. Next most valuable is to stay away from people who are infectious. After exposure there is a 1 to 4 day interval before the onset of symptoms (average is 2 days). The infected individuals begin viral shedding (transmitting the infection) in 12 to 48 hours after exposure, and that is 12 to 48 hours prior to the time they begin to feel sick. They continue to be infectious for 4 to 10 days, and sometimes longer (especially in older individuals). It is also known that some people have a partial response to vaccination, resulting in them having infections in which they may transmit the disease, but have few or no symptoms. This means that staying away from people who are sick is helpful, but by itself it is an insufficient strategy. There are prescription medications that can be used prophylactically to reduce the chance of infection, and these should be considered for people at high risk who have known opportunity for exposure.

If you suspect that you have the flu, and you are at high risk for complications, you should be seen by a healthcare provider as soon as you have symptoms. There are medications to treat the flu, and they all work better if they are started earlier. Usually they are not considered worthwhile if not started within 48 hours after symptoms are first noted. Not everyone who has the flu needs to be seen by a healthcare provider, and not all those who are seen need medication. The costs and side effects of these medications are sometimes quite significant, and you should weigh these against expected benefits. (Typically symptoms last about a day less with treatment.) If you or your child are otherwise healthy and between the ages of 2 and 65 years old, symptomatic treatment is usually sufficient if there is no trouble breathing and fever can be controlled with acetaminophen in recommended doses. Symptomatic treatment consists of controlling the fever, rest and plenty of fluids (about 2 -3 quarts/d for adults with fever). Normally symptoms resolve over about a week, and the individual can return to work or school after 24 hours without fever AND without medication that would prevent fever, such as acetaminophen.

This article is intended to provide general information only, and is not to be taken as medical advice. For advice about a particular case or situation, consult your own physician or other trusted health professional.

Bradly Bundrant, MD, MPH

Medicine, Science and Culture is a service of The Health and Wellness Coalition of Runnels County. Our next meeting will be January 16, 2020 at 7:30 pm at the North Runnel Clinic in Winters.

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Immunotherapy Leads to Potentially Durable Response in Patients with Multiple Myeloma – Pharmacy Times

§ January 16th, 2020 § Filed under Nano Medicine Comments Off on Immunotherapy Leads to Potentially Durable Response in Patients with Multiple Myeloma – Pharmacy Times

Immunotherapy Leads to Potentially Durable Response in Patients with Multiple Myeloma

The multi-center, international DREAMM-2 trial evaluated belantamab mafodotin and found that almost one-third of patients whose disease had returned after other therapies achieved a partial response or better when treated with this therapy.

Multiple myeloma is a cancer of the plasma cells, which build up in bone marrow and crowd out healthy blood cells. Patients enrolled in the trial were required to have the disease that had relapsed or was refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody.

The phase 2 trial involved 58 centers in 8 countries. Between June 2018 and January 2019, 196 patients were treated with either a low dose or high dose of the drug. In the low dose treatment group, 31% of patients achieved an overall response. Of that group, 60% had a very good partial response or better.

In the high dose group, 34% achieved an overall response, with 59% of those patients achieving a very good partial response or better. Responses were achieved quickly, after a median of 1.4 months of treatment. The median progression-free survival was 2.9 months and 4.9 months, respectively, although it was not reached in patients who responded.

These data build off the phase 1 trial that showed patient responses improved over time and contributed to prolonged progression free survival. Since this study did not reach the median duration of response, we anticipate that further follow-up on these patients will confirm these responses can be durable, said Adam D. Cohen, MD, senior author and assistant professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania in a press release.

The most common adverse events (AEs) included nausea, fatigue, blurred vision, and dry eye. The majority of AEs were mild to moderate in severity. Microscopic changes to the lining of the cornea were noted through eye examination in 71% of low dose and 75% of high dose patients. Other AEs included thrombocytopenia, which was reported in 35% of low dose patients and 59% of high dose patients.

BCMA is a receptor on the surface of multiple myeloma cells that helps the cells grow and survive. Belantamab mafodotin is an experimental antibody-drug conjugate that consists of an antibody to target BCMA that is linked to a potent chemotherapy drug called MMAF.

After binding to BCMA, belantamab mafadotin is internalized into the melanoma cell and then releases the MMAF, leading to highly targeted killing of the myeloma within the bone marrow while limiting systemic chemotherapy adverse events. Belantamab mafadotin can also attract surrounding immune cells to attack the myeloma cells through a mechanism called antibody-dependent cellular cytotoxicity.

Data from the DREAMM-2 study have been submitted to the FDA for consideration for approval.

ReferenceBCMA-Targeted Immunotherapy Can Lead to Durable Responses in Multiple Myeloma [press release] Penn Medicine News website. Published December 17, 2019. https://www.pennmedicine.org/news/news-releases/2019/december/bcma-targeted-immunotherapy-can-lead-to-durable-responses-in-multiple-myeloma. Accessed January 13, 2020.

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School of Medicines Begins Study on New Phage Therapy – Times Tech Pharma

§ January 16th, 2020 § Filed under Nano Medicine Comments Off on School of Medicines Begins Study on New Phage Therapy – Times Tech Pharma

In an ongoing UC San Diego School of Medicine study, successful mice trials for another treatment show promising outcomes on the utilization of phage treatment to target alcoholic liver malady. These trials are being conducted since Spring 2017.

Bacteriophages, or phages, are normally present infections that contaminate and eat microscopic organisms. In contrast to anti-toxins, which additionally crush microscopic organisms in a murder them-all way, phages focus on a specific sort of microorganisms strain with negligible reactions. Since phages live on microscopic organisms, the phage corrupts when the host microbes kicks the bucket. Because of the high explicitness of the objective microorganisms, phage treatment is as yet a constrained application practically speaking, which makes it a field of monstrous investigation for analysts.

At present, the most ordinarily utilized medications for alcoholic liver malady incorporate liver transplantation and corticosteroids, a hormone used to lessen liver aggravation. In any case, liver transplantation is definitely not a promptly accessible choice as the national shortlist for a sound liver is around 14,000 individuals in length, and medical procedures are offered at a chosen few medicinal focuses. Moreover, corticosteroid treatment isnt an ensured arrangement as the impacts of the treatment change among various people.

Liver harm collects over long stretches of liquor addiction. When extreme indications start to appear, up to 90 percent of patients bite the dust inside 90 days of an analysis of serious alcoholic liver illness, known as alcoholic hepatitis.

With an attention on the connection between liver infection and intestinal microorganisms, the Dr. Bernd Schnabl Lab at UCSD has distinguished and corresponded bacterial contamination with liver infection in their past investigation.

Yi Duan, a postdoctoral understudy in Schnabls lab gathering and the main creator of the examination paper, addressed the UCSD Guardian about the connection betweens liver harm and phage treatment.

In both the human contextual analyses and the mice tries, the gathering found that the translocation of the gut microscopic organisms, Enterococcus Faecalis, can cause bacterial contamination in the liver. Also, proton-siphon inhibitors or PPIs, an ordinarily utilized medication to diminish gastric corrosive emission and indigestion for patients with constant liver sickness because of liquor abuse, make a positive criticism circle in patients which declines the condition.

Consultant respiratory physician at DescriptionThe Perelman School of Medicine, commonly known as Penn Med, is the medical school of the University of Pennsylvania, Philadelphia, PA 19104, United States.

Mail Me : Chrissokol@timestechpharma.com

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