In much the same way that glucometers and pregnancy tests have revolutionized in-home diagnostic testing, researchers from Florida Atlantic University and collaborators have identified a new biosensing platform that could be used to remotely detect and determine treatment options for HIV, E-coli, Staphylococcus aureas and other bacteria. Using a drop of blood from a fingerprick, this novel biosensing platform provides clinically relevant specificity, sensitivity and detection of pathogens from whole blood and plasma.
The thin, lightweight and flexible materials developed by these researchers can be fabricated and operated without the need for expensive infrastructure and skilled personnel, potentially solving real-world healthcare problems for both developed and developing countries. Using this technology, they also have developed a phone app that could detect bacteria and disease in the blood using images from a cellphone that could easily be analyzed from anywhere in the world.
Waseem Asghar, Ph.D., assistant professor of electrical engineering in the College of Engineering and Computer Science at FAU, co-first author on the study, along with Hadi Shafiee, Ph.D., instructor in medicine at the Division of Biomedical Engineering at Brigham and Women’s Hospital, Harvard Medical School; Fatih Inci, Ph.D.; and Utkan Demirci, Ph.D., Stanford School of Medicine, senior authors on the study, have published their findings inNature Scientific Reports in an article titled “Paper and Flexible Substrates as Materials for Biosensing Platforms to Detect Multiple Biotargets.” Other team members on the study include Mehmet Yuksekkaya, Ph.D.; Muntasir Jahangir; Michael H. Zhang; Naside Gozde Durmus, Ph.D.; Umut Atakan Gurkan, Ph.D., and Daniel R. Kuritzkes, M.D.
In the article, the researchers address the limitations of current paper and flexible material-based platforms and explain how they have integrated cellulose paper and flexible polyester films as new diagnostic tools to detect bioagents in whole blood, serum and peritoneal fluid. They employed three different paper and flexible material-based platforms incorporated with electrical and optical sensing modalities. They were able to demonstrate how these new materials can be widely applied to a variety of settings including medical diagnostic and biology laboratories.
Using paper and flexible substrates as materials for biosensors, Asghar and his colleagues have identified a new rapid and cost-effective way to diagnose diseases and monitor treatment in point-of-care settings. They have been able to show how their new platforms are uniquely able to isolate and detect multiple biotargets selectively, sensitively, and repeatedly from diverse biological mediums using antibodies.
“There is a dire need for robust, portable, disposable and inexpensive biosensing platforms for clinical care, especially in developing countries with limited resources,” said Asghar.
Existing paper and flexible material-based platforms use colorimetric, fluorometric and electrochemical approaches that require complex labeling steps to amplify their signal, are very costly to fabricate and also require expensive equipment and infrastructure.
“The future of diagnostics and health monitoring will have potentially cell-phone based or portable readers sipping saliva or blood and continuously monitoring human health taking it way beyond where we are with counting steps today,” said Demirci, who is the corresponding author.
Asghar notes that because their materials are easy to make, easy to use, and can easily and safely be disposed by burning, they provide appealing strategies for developing affordable tools that have broad applications such as drug development, food safety, environmental monitoring, veterinary medicine and diagnosing infectious diseases in developing countries.
“Our paper microchip technologies can potentially have a significant impact on infectious diseases management in low- and middle-income countries where there is limited laboratory infrastructure,” said Shafiee.
Demirci notes that these platforms could potentially be adapted and tailored to detect other pathogens and biotargets with well-known biomarkers.
The above story is based on materials provided by Florida Atlantic University. Note: Materials may be edited for content and length.
A team of Cornell University researchers focusing on a fictional zombie outbreak as an approach to disease modeling suggests heading for the hills, in the Rockies, to save your brains from the undead.
Reading World War Z, an oral history of the first zombie war, and a graduate statistical mechanics class inspired a group of Cornell University researchers to explore how an “actual” zombie outbreak might play out in the U.S.
During the 2015 American Physical Society March Meeting, on Thursday, March 5 in San Antonio, Texas, the group will describe their work modeling the statistical mechanics of zombies–those thankfully fictional “undead” creatures with an appetite for human flesh. (See the abstract: http://meeting.aps.org/Meeting/MAR15/Session/S48.8)
Why model the mechanics of zombies? “Modeling zombies takes you through a lot of the techniques used to model real diseases, albeit in a fun context,” says Alex Alemi, a graduate student at Cornell University.
Alemi and colleagues’ work offers a nice introduction to disease modeling in general, as well as some techniques of statistical physics for measuring second-order phase transitions. “It’s interesting in its own right as a model, as a cousin of traditional SIR [susceptible, infected, and resistant] models–which are used for many diseases–but with an additional nonlinearity,” points out Alemi.
All told, the project was an overview of modern epidemiology modeling, starting with differential equations to model a fully connected population, then moving on to lattice-based models, and ending with a full U.S.-scale simulation of an outbreak across the continental U.S.
It involved a lot of computational results generated from simulations the researchers wrote themselves. “At their heart, the simulations are akin to modeling chemical reactions taking place between different elements and, in this case, we have four states a person can be in–human, infected, zombie, or dead zombie–with approximately 300 million people,” Alemi explains.
The project’s large-scale simulations are stochastic in nature, meaning that they have an element of randomness. “Each possible interaction–zombie bites human, human kills zombie, zombie moves, etc.–is treated like a radioactive decay, with a half-life that depends on some parameters, and we tried to simulate the times it would take for all of these different interactions to fire, where complications arise because when one thing happens it can affect the rates at which all of the other things happen,” he says.
In most films or books, “if there is a zombie outbreak, it is usually assumed to affect all areas at the same time, and some months after the outbreak you’re left with small pockets of survivors,” explains Alemi. “But in our attempt to model zombies somewhat realistically, it doesn’t seem like this is how it would actually go down.”
Cities would fall quickly, but it would take weeks for zombies to penetrate into less densely populated areas, and months to reach the northern mountain-time zone.
“Given the dynamics of the disease, once the zombies invade more sparsely populated areas, the whole outbreak slows down–there are fewer humans to bite, so you start creating zombies at a slower rate,” he elaborates. “I’d love to see a fictional account where most of New York City falls in a day, but upstate New York has a month or so to prepare.”
If you somehow happen to find yourself in the midst of a fictional zombie outbreak and want to survive as long as possible, Alemi recommends making a run for the northern Rockies. While not an entirely practical implication, it’s “fun to know,” he says, and points out the benefits of applying hard science to fun topics–especially to help make learning more entertaining and enjoyable.
“A lot of modern research can be off-putting for people because the techniques are complicated and the systems or models studied lack a strong connection to everyday experiences,” Alemi adds. “Not that zombies are an everyday occurrence, but most people can wrap their braains around them.”
What’s next for Alemi and colleagues? “Given the time, we could attempt to add more complicated social dynamics to the simulation, such as allowing people to make a run for it, include plane flights, or have an awareness of the zombie outbreak, etc.,” he notes.
The above story is based on materials provided by American Physical Society. Note: Materials may be edited for content and length.
A study published recently in the IBD Journal found significant differences in hospital readmissions, medication usage, and both medical and surgical complications of children with Crohn’s disease related to race. In the study, black children had a 1.5 times higher frequency of hospital readmissions because of Crohn’s disease compared to white children.
“We found racial inequalities exist among children and adolescents with Crohn’s disease, likely due to a combination of genetic and environmental differences,” said Jennifer Dotson, MD, MPH, gastroenterologist at Nationwide Children’s Hospital and principal investigator in the Center for Innovation and Pediatric Practice. “This is one of the first studies to investigate the rate of various health disparities in the Crohn’s disease population in pediatrics, despite the fact that 25 percent of the time, Crohn’s disease is diagnosed in childhood.”
Using data from the Pediatric Health Information System database, a large, regionally diverse system, the researchers examined racial disparities in the treatment and outcomes of hospitalized white and black pediatric patients with moderate to severe Crohn’s disease. The study evaluated more than 4,000 patients up to age 21 who were admitted to a hospital due to their disease between 2004 and 2012. Black children had a shorter time to first readmission.
“A physician or other clinical staff may not readily identify these racial differences at a single-practice level, but these gaps may be important on a larger scale,” explained Dr. Dotson. “Further studies need to help identify the causes of these racial differences so we can design interventions for hospitals and physician offices that can reduce population level disparities. Clinicians at Nationwide Children’s involved in the study are keeping this in mind and continuing to collect data.” They are now examining some of the outpatient factors that may result in disparities, such as frequency of follow-up, and further investigating racial and socioeconomic disparities in treatment and outcomes of children with Crohn’s disease.
The researchers also found black children were more likely to have anemia, vitamin D deficiency, endoscopic procedures, blood product transfusions and treatment with steroids and biologic agents compared to white children with Crohn’s disease. However, race did not influence the risk of bowel surgery, a common procedure for children with Crohn’s disease.
“Some of the differences in our study are likely attributable to intrinsic differences in disease between blacks and whites,” said Dr. Dotson, who is also a faculty member at The Ohio State University Wexner Medical Center. “For example, more procedures are likely a result of the increased rate of perianal disease in blacks. Other differences may reflect disparities in care, although biologic differences can’t be excluded.”
According to Dr. Dotson, the increased usage of corticosteroids and biologic medications among black children in the study could suggest a more severe disease course that may be attributable to worse intrinsic disease in black children. But it is equally possible that black patients were more ill at the time of hospital admissions due to delays in seeking care or impaired access to care, and thus required more intensive therapy, she said. The researchers also found black children had a lower median income and were more likely to have Medicaid.
“Black children were slightly older at the first admission than white children, which could represent a subtle marker of diminished access to medical care or a delay in disease recognition,” said Dr. Dotson, who explained other studies have shown that the role of biology in health disparities in chronic diseases is often modest, and there are many other factors, such as access to care and health literacy, that contribute to disparities in care. Significant racial, ethnic, and socioeconomic disparities in access to healthcare and quality of care have been found throughout the United States in other conditions including the treatment of ovarian cancer, asthma, and ADHD, with little improvement in disparities being reported in the past decade. Disparities have been shown to contribute to suboptimal healthcare outcomes for minorities and low income groups, as well as inefficiencies in healthcare delivery systems. “Financial barriers to outpatient care and self-management, such as transportation, medication and nutrition needs, may have impacted the outcome for these children.”
The above story is based on materials provided by Nationwide Children’s Hospital.Note: Materials may be edited for content and length.
Existing therapies for type 2 diabetes, and the closely associated conditions of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), have had limited success at treating the root causes of these diseases. Building on earlier research, the Yale team — led by Dr. Gerald I. Shulman, the George R. Cowgill Professor of Physiological Chemistry, and professor of medicine and cellular & molecular physiology at Yale School of Medicine — decided to investigate whether an agent that had originally been used for weight loss more than 70 years ago could be reformulated to safely treat NAFLD/NASH and type 2 diabetes in rodent models of these diseases.
Based on their earlier studies, the researchers determined that toxicity associated with the agent — mitochondrial protonophore 2,4-dinitrophenol (DNP) — was related to its peak plasma concentrations. They discovered that DNP’s efficacy in reducing liver fat and liver inflammation could be achieved with plasma concentrations that were more than a 100-fold less than the toxic levels.
“Besides reversing fatty liver disease in a rodent model of NALFD, a low-dose intragastric infusion of DNP that was 100-fold lower than toxic levels also significantly reduced blood glucose, triglyceride, and insulin concentrations in a rodent model of NAFLD and type 2 diabetes”, said Shulman, who is also an investigator with the Howard Hughes Medical Institute.
In the next phase of the study, Shulman and his team developed a new oral, controlled-release form of DNP, known as CRMP, which maintained the drug at concentrations that were more than a 100-fold lower than the toxic threshold. Administered once daily, CRMP delivered similar positive results, reversing fatty liver, insulin resistance, and hyperglycemia in rat models of NAFLD and type 2 diabetes, as well as liver inflammation and liver fibrosis in a rodent model of NASH, with no adverse effects.
“Given these promising results in animal models of NAFLD/NASH and type 2 diabetes we are pursuing additional preclinical safety studies to take this mitochondrial protonophore approach to the clinic” said Shulman.
The above story is based on materials provided by Yale University. The original article was written by Ziba Kashef. Note: Materials may be edited for content and length.
The study finds that laboratory-grown cells experience altered cell states within three days as they adapt to their new environment. Studies of human disease, including cancer, rely on the use of cell cultures that have often been grown for decades. The findings could therefore affect the interpretation of past studies and provide important clues for improving cell cultures in the future.
Scientists typically use models to study the basics of human biology. The most common model system is cultured cells, which are taken from the body and coaxed into growing on a plastic dish in the laboratory. Though a linchpin of modern research, it has long been known that the cells in the laboratory can behave differently from those in the body, affecting the understanding of diseases and the development of drugs.
Researchers from the MRC Human Genetics Unit at the University of Edinburgh, UK, and Linköping University, Sweden, have revealed just how quickly cells change their identity when grown in the laboratory. They found that cells adapt to cell culture systems within one week of growth in a laboratory dish. The analysis provides new insight into how faithfully these cells mimic real tissue, and how models of human disease can still be improved.
Study author Richard Meehan from the MRC Human Genetics Unit at the University of Edinburgh, UK, said: “We were astonished by the speed and spread of the changes. Many cultured cells used in research have been grown for decades and as a result are likely to have very different properties from the cells they are supposed to model. Our findings suggest that we have to be circumspect about the interpretation of some previous experiments, and our data reinforces a growing realisation that cell line models of human diseases, particularly cancer, can be poor surrogates for many aspects of in-vivo biology.”
The researchers compared the DNA of mouse cells, taken from male and female embryos, with cells that were cultured in plastic dishes. They found a number of indicators that the cultured cells underwent an altered cell state as they became adapted to the cell culture environment, including a decrease in gender differences between male and female cultured cells.
The mouse cells in culture experienced a rapid reprogramming of their ‘epigenomes’ – a layer of chemical modifications that mark the genome to control how genes are expressed. This was indicated by a near-complete loss of one epigenetic mark, 5-hydroxymethylcytosine (5hmC), within three days over the whole genome.
They also found similar results in an unrelated tissue. Using mouse CD4+ T-cells, which have a role in the immune system, they found an almost five-fold reduction in 5hmC levels after three days in culture.
In addition, the researchers saw that there were widespread changes in gene expression for cells in culture, affecting over 7,200 genes. Some of these genes were linked to cell adhesion, possibly reflecting adaptation to growth on a two-dimensional plastic surface, and others were involved in a variety of epigenetic processes.
The researchers went on to show that some of these changes could be prevented by adding Vitamin C to the culture medium. This suggests that by improving culturing techniques, researchers may be able to more accurately match cells grown on a dish to cells that are taken directly from tissues. These improvements should allow researchers to have more confidence that what they observe in the laboratory accurately reflects what is happening in the body.
The above story is based on materials provided by BioMed Central. Note: Materials may be edited for content and length.