Culture

BLOOMINGTON, Ind. -- Researchers from three universities have found that extreme price competition in the generic pharmaceutical market -- designed to make medications more affordable -- may be putting more patients at serious health risk, as evidenced by a higher number of product recalls caused by manufacturing-related problems.

The same research, published online today in the Journal of Operations Management, also raises concerns that generic drug makers may be underreporting discretionary recalls due to competitive pressures.

"Extreme price competition in the generic pharmaceutical market has some unexpected risks that regulators and lawmakers may not have foreseen when pushing for cheaper drugs," said George Ball, assistant professor of operations and decision technologies at the Indiana University Kelley School of Business and the study's lead author.

"There's a downside to cheaper drugs: You can't guarantee that they're going to be of the exact same quality," Ball said. "This research demonstrates that regulators and insurers may want to temper their intense public pressure placed upon pharmaceutical companies to bring prices down. Such pressure may come at a cost: poorly manufactured drugs."

Other authors of the paper are Rachna Shah, associate professor of supply chain and operations at the University of Minnesota's Carlson School of Management, and Kaitlin Wowak, assistant professor in the Department of Information, Analytics and Operations at the University of Notre Dame's Mendoza College of Business.

The researchers assessed the impact of the Drug Price Competition and Patent Term Restoration Act -- commonly called the Hatch-Waxman Act -- which was intended to increase competition in the pharmaceutical industry and lower drug prices by expediting the approval process for generic drugs. The process has led to a considerable increase in the number of generic drugs entering the marketplace since its passage in 1984.

It's generally believed that generic drugs are of equivalent quality to the original pioneer drug because they have the same formulation and because generic manufacturers are audited by FDA regulators to the same manufacturing quality standards. But the authors' study of 939 recalls at 64 firms over a 12-year period found that generic drug companies facing more product competition have more serious Class 1 and 2 manufacturing recalls. These are the recall classes designated by the FDA that may cause death or medically reversible harm to the customer.

While generic drug makers are not allowed to change the design of the product, they have considerable leeway regarding manufacturing decisions.

"This may explain why firms producing a higher proportion of generic products may have higher rates of recalls," Shah said. "These decisions may include reducing labor costs, hiring less experienced employees or lowering maintenance costs by servicing manufacturing equipment less often. Firms may also respond to intense competition by purchasing lower-cost ingredients."

Ball, Shah and Wowak used data from the FDA's annual Orange Book, which contains all approved pharmaceutical products for sale in the U.S. and classifies whether a drug is a new drug application (NDA) or an abbreviated new drug application (or a generic). They compared its information with recall data from 2002 to 2014.

"Our results demonstrate that as product competition increases, manufacturing-related recalls increase," Wowak said. "This is particularly evident when firms are encouraged to compete on product price, are free to set prices, and the design of the product is unalterable."

The professors also found that the relationship between product competition and manufacturing-related recalls is not universal but is contingent upon managerial discretion. This finding may indicate that while price competition via more generic drugs leads to more serious manufacturing problems in the production process, it may also encourage managers not to announce recalls when they have discretion.

They believe that their findings suggest the need for changes in processes used by the Food and Drug Administration. These include requiring more detailed and precise documentation about how the generic drug will be produced and how stringently the manufacturing plants that product generic pharmaceuticals are inspected.

Hazardous chemicals such as bromine, antimony and lead are finding their way into food-contact items and other everyday products because manufacturers are using recycled electrical equipment as a source of black plastic, according to a new study.

The substances are among those applied to devices, such as laptops and music systems, as flame retardants and pigments but remain within the products when they reach the end of their useful lives.

Now scientists at the University of Plymouth have shown that a combination of the growing demand for black plastic and the inefficient sorting of end-of-life electrical equipment is causing contaminated material to be introduced into the recyclate.

This is in part because despite black plastics constituting about 15% of the domestic waste stream, this waste material is not readily recycled owing to the low sensitivity of black pigments to near infrared radiation used in conventional plastic sorting facilities.

The study is published in Environmental International and was conducted by Dr Andrew Turner, a Reader in Environmental Science at the University.

As well as posing a threat to human health, he says the study demonstrates there are potentially harmful effects for the marine and coastal environment either through the spread of the products as litter or as microplastics.

For this research, Dr Turner used XRF spectrometry to assess the levels of a range of elements in more than 600 black plastic products such as food-contact items, storage, clothing, toys, jewellery, office items and new and old electronic and electrical equipment.

Bromine, in the form of brominated compounds, is and has been used in electrical plastic housings as a flame retardant, while lead is often encountered in electronic plastics as a contaminant. However, both elements were found extensively in non-electrical black consumer products tested, where they are not needed or desirable.

In many products, including cocktail stirrers, coathangers, various items of plastic jewellery, garden hosing, Christmas decorations and tool handles, concentrations of bromine potentially exceeded legal limits that are designed for electrical items. In other products, including various toys, storage containers and office equipment, concentrations of lead exceeded its legal limit for electrical items.

Speaking about the current study, Dr Turner said: "There are environmental and health impacts arising from the production and use of plastics in general, but black plastics pose greater risks and hazards. This is due to the technical and economic constraints imposed on the efficient sorting and separation of black waste for recycling, coupled with the presence of harmful additives required for production or applications in the electronic and electrical equipment and food packaging sectors."

"Black plastic may be aesthetically pleasing, but this study confirms that the recycling of plastic from electronic waste is introducing harmful chemicals into consumer products. That is something the public would obviously not expect, or wish, to see and there has previously been very little research exploring this. In order to address this, further scientific research is needed. But there is also a need for increased innovation within the recycling industry to ensure harmful substances are eliminated from recycled waste and to increase the recycling of black plastic consumer products."

This research is the latest work by Dr Turner examining the presence of toxic substances within everyday products. He has previously conducted research which showed that decorated drinking glasses can contain harmful levels of lead and cadmium, that the plastic used in second hand toys often fails to meet international safety directives, and that playground paints should be more closely monitored to reduce potential danger to public health.

A portable device common in optometrists' offices may hold the key to faster diagnosis of schizophrenia, predicting relapse and symptom severity and assessing treatment effectiveness, a Rutgers University study finds.

In the study, published in the May 2018 issue of the Journal of Abnormal Psychology, researchers used RETeval, a hand-held device developed to record electrical activity from the retina, to replicate and extend prior studies showing that people with schizophrenia had abnormal electrical activity in the retina. This was the first time a portable device was used for these tests. The results show the device accurately indicated reduced electrical activity in the retina in multiple cell layers in the participants who had schizophrenia, including in cell types that had not been studied before in this disorder.

"Schizophrenia is a devastating disorder, probably the most disabling disorder long term. Although we know quite a bit about it, it's still not that well understood," said Steven Silverstein, professor of psychiatry at Rutgers Robert Wood Johnson Medical School and director of research at Rutgers University Behavioral Health Care (UBHC), who designed the study. "Our study should help generate further research into developing a test that clinicians - like psychologists, psychiatrists or nurses - can use in their offices to diagnose, treat and monitor the condition of people with schizophrenia."

Looking at biomarkers in the eye as a way to understand psychiatric disorders is a new field of study.

"Since the retina is part of the nervous system, what is happening in the retina is likely reflective of what is occurring in the brain," Silverstein said. "For example, we know that certain changes in the retina, like thinning tissue [due to cell loss] or weakening electrical activity, occur alongside loss of brain tissue and reduced brain activity in patients with neurological disorders like multiple sclerosis and Parkinson's disease. We and other researchers are now investigating whether retinal changes are related to brain structure and function changes in schizophrenia."

In the just-published study, the researchers evaluated 50 participants: 25 with schizophrenia and 25 with no diagnosed psychiatric disorder. In the test, the participants closed one eye and placed the other against the RETeval device, which flashed 10 to 20 white or colored lights of various intensity against a white or colored background. A tiny skin electrode was placed on the skin under the eye to record the retina's electrical activity. The participants were tested in normal light and after sitting in the dark for 10 minutes to assess activity in different types of retinal cells. Most individual tests were completed within two minutes.

"Since many of our participants were experiencing severe psychiatric symptoms, such as hallucinations and delusions, we wanted to use a test that was as noninvasive and quick as possible," Silverstein said.

"While the portable device clearly distinguished people with schizophrenia from those without a psychiatric diagnosis, it's too soon to call this a diagnostic tool," said lead author Docia Demmin, a graduate assistant in UBHC's Division of Schizophrenia Research and a doctoral student in Rutgers Department of Psychology. "However, since every prior study has found that people with schizophrenia exhibit reduced retinal wave forms and slowed retinal responses, our research shows that we closing in on an accurate test that is faster, less invasive, inexpensive and more accessible to patients."

For centuries Inuit children in Greenland, Canada, and Alaska have been observed as small.
But recently they have begun to grow a lot.

»During the last couple of years people have noticed that Greenlandic boys and girls are getting taller compared to older generations. These common observations have now been scientifically proved,&laquo says Marius Kløvgaard, MD and one of the scientists behind a newly published study of growth of Greenlandic children.

Previous studies of growth of the indigenous Inuit people of Greenland, Canada and Alaska has characterized them as shorter but with the same weight as European or continental US citizens. Yet, this specific growth pattern was no longer found in the new study of growth of Greenlandic children conducted by researchers from University of Southern Denmark, which has just been published in the scientific journal Acta Paediatrica.

»We evaluated the growth of 279 healthy Greenlandic boys and girls aged 6-10 years and found that at puberty, Greenlandic children are now as tall as children in Denmark,&laquo says Marius Kløvgaard.

As a part of the study the research group has also conducted specific growth charts for children in Greenland that can be used for monitoring growth and thrive. Growth charts for Greenlandic children have never been published before.

Genes and obese mothers

The fact that the growth of Greenlandic children is no longer stunted has several explanations.

»Many people in Greenland have one or more ancestors of Scandinavian origin so genetic admixture is quite common. That might to some extent explain why children in Greenland have a similar growth pattern to children in Denmark,&laquo says Marius Kløvgaard.

Another important finding is a high number of obese mothers.

»It is well-known that obese mothers get large babies, and it seems like these larges babies keep on being large during their childhood,&laquo says Marius Kløvgaard.

Healthy children

Furthermore, in a recent study, the research group found, that children in Greenland are as healthy as children in Denmark. Actually, children in Greenland have fewer visits to the doctors than Danish children.

»Chronic diseases might hamper growth. But improvements in health and nutrition have reduced these kind of problems,&laquo says Marius Kløvgaard.

PHILADELPHIA (May 29, 2018) - About 70 percent of all variations in health care outcomes are explained by individuals' social conditions including housing, neighborhood conditions, and income, data show. In order to establish community cultures of health where people are empowered to live healthier lives, health care providers and community sector leaders in transportation, government, schools, and businesses must collaborate to address the social conditions that affect population health.

New research points to the types of skills necessary for nurse leaders to encourage such collaborations. The study, Promoting a Culture of Health Through Cross-Sector Collaborations, has been published in the journal Health Promotion Practice.

The study focused on the experiences of members of the American Academy of Nursing's Edge Runner program, which recognizes nurses who have designed and/or are leading care models that have demonstrated positive clinical and financial outcomes. By studying the experiences of these innovative nurses who have developed cross-sector collaborations that promote a culture of health, the researchers discovered four key skills that enable leaders to successfully manage such collaborations.

"Health care providers can be important leaders and 'bridgers' in collaborations, but they must possess the knowledge, attitudes and skills of facilitators, partners, and relationship-builders," says Antonia Villarruel, PhD, RN, FAAN, Professor and the Margaret Bond Simon Dean of Nursing at the University of Pennsylvania School of Nursing (Penn Nursing), one of the authors of the study.

The four key themes discovered to be relevant to cross-sector collaborations that develop a community's culture of heath include:

Being bilingual - Edge Runners found they needed to be able to speak the language of both the community and the institutions of power.

Neighborliness and trust - Successful Edge Runners are able to demonstrate to community leaders their long-term commitment to the communities they serve and a willingness to listen and understand community needs.

Having a business sense - Ensuring continued support often requires Edge Runners to make a business case for their programs, particularly in explaining how to sustain or expand these programs.

Shared vision and language - Being able to communicate shared visions with potential collaboration partners is an essential way Edge Runners gain trust and engagement.

"The study results have a number of important implications for policy and health professional education," explains Villarruel. "It also provides initial insights into how health care providers can collaborate with both health and non-health entities, on the ground at community level and at the funder level, to benefit local communities and populations."

LOS ANGELES (May 29, 2018) -- Physician satisfaction scores on online third-party review sites tend to be skewed and can easily mislead patients, according to a new study by Cedars-Sinai investigators.

This distortion may have significant consequences as consumers rely increasingly on these scores when choosing a physician. Research shows that patients largely trust these ratings as the sole source of information when choosing a physician.

"Patients put so much trust into ratings, and the stakes are much higher than simply choosing a restaurant," said lead author Timothy J. Daskivich, MD, MSHPM, assistant professor and director of Health Services Research in the Department of Surgery at Cedars-Sinai. "It's important to interpret this data correctly because selecting the right physician can have a serious impact on health and wellbeing."

Daskivich and his co-authors pulled reviews from October 2014 to March 2017 on Healthgrades, a consumer ratings website that ranks medical providers from 1-5 stars. The investigators linked this data to providers listed in the U.S. Centers for Medicare & Medicaid Services' Physician Compare tool. They narrowed the field to 212,933 providers, who had at least four reviews evaluating overall patient satisfaction. They grouped the providers by medical, surgical and allied health specialties, and performed a statistical analysis to examine the distribution of the providers' average satisfaction scores.

The study, published in the Journal of Medical Internet Research, found that overall satisfaction ratings consistently skewed positively, fell within narrow ranges and had different distributions across specialties. As a result, scores that appear high might actually be comparatively average or low, effectively misleading patients. For example, if 90 percent of physicians in a particular specialty are rated higher than four stars, patients could be misled into thinking the physician they select is at the top of their field.

Providers' satisfaction ratings also differed significantly by specialty group. Median scores for allied health providers (physical therapists, optometrists) were much higher than those of physicians in medical and surgical specialties.

Some of the differences in rankings between specialties might be related to the nature of the work. That may explain why psychiatrists, who field emotional trauma, get lower ratings than chiropractors, who provide physical relief and lots of one-on-one interaction, Daskivich said. But he and his co-authors think review sites should flag such statistical quirks and caveats.

The study comes at a time when consumers increasingly are turning to third-party websites to post reviews of physicians and comments about a wide variety of healthcare services and experiences. Although there has been a proliferation of these third-party sites (including Healthgrades, Zocdoc and Yelp), they often present information based on a small number of reviews and incomplete or unverified information. As a result, many health systems (such as Stanford, Cleveland Clinic and University of Utah) have begun posting more complete ratings and comments from their own outpatient satisfaction surveys.

These hospital-driven tools measure satisfaction with providers for attributes such as communication, friendliness and time spent with patients. The tools do not measure healthcare quality. Healthcare providers are giving consumers access to this information to offer greater transparency and visibility into feedback from real patients.

The authors of the ratings study suggest that third-party online review sites can do better by posting median star ratings for each medical provider and noting where they rank among peers in their specialty. The investigators also note in the study that they created an online tool, Compare My Doc, which uses a provider's specialty and online rating to show how that provider compares to their colleagues.

"Scores from third-party sites aren't going away," said senior author Brennan Spiegel, MD, director of Cedars-Sinai Health Services Research. "These sites have a responsibility to tell consumers that these reviews can be skewed and to provide more guidance around interpreting them."

The first human corneas have been 3D printed by scientists at Newcastle University, UK.

It means the technique could be used in the future to ensure an unlimited supply of corneas.

As the outermost layer of the human eye, the cornea has an important role in focusing vision.

Yet there is a significant shortage of corneas available to transplant, with 10 million people worldwide requiring surgery to prevent corneal blindness as a result of diseases such as trachoma, an infectious eye disorder.

In addition, almost 5 million people suffer total blindness due to corneal scarring caused by burns, lacerations, abrasion or disease.

The proof-of-concept research, published today in Experimental Eye Research, reports how stem cells (human corneal stromal cells) from a healthy donor cornea were mixed together with alginate and collagen to create a solution that could be printed, a 'bio-ink'.

Using a simple low-cost 3D bio-printer, the bio-ink was successfully extruded in concentric circles to form the shape of a human cornea. It took less than 10 minutes to print.

The stem cells were then shown to culture - or grow.

Che Connon, Professor of Tissue Engineering at Newcastle University, who led the work, said: "Many teams across the world have been chasing the ideal bio-ink to make this process feasible.

"Our unique gel - a combination of alginate and collagen - keeps the stem cells alive whilst producing a material which is stiff enough to hold its shape but soft enough to be squeezed out the nozzle of a 3D printer.

"This builds upon our previous work in which we kept cells alive for weeks at room temperature within a similar hydrogel. Now we have a ready to use bio-ink containing stem cells allowing users to start printing tissues without having to worry about growing the cells separately."

The scientists, including first author and guest researcher Ms Abigail Isaacson from the Institute of Genetic Medicine, Newcastle University, also demonstrated that they could build a cornea to match a patient's unique specifications.

The dimensions of the printed tissue were originally taken from an actual cornea. By scanning a patient's eye, they could use the data to rapidly print a cornea which matched the size and shape.

Professor Connon added: "Our 3D printed corneas will now have to undergo further testing and it will be several years before we could be in the position where we are using them for transplants.

"However, what we have shown is that it is feasible to print corneas using coordinates taken from a patient eye and that this approach has potential to combat the world-wide shortage."

Just because you stopped smoking years ago doesn't mean you're out of the woods when it comes to developing lung cancer. That's the "bad" news. The good news is your risk of lung cancer drops substantially within five years of quitting.

These are the main findings of a new analysis of the landmark Framingham Heart Study by researchers at Vanderbilt University Medical Center published May 16 by the Journal of the National Cancer Institute.

"If you smoke, now is a great time to quit," said first author Hilary Tindle, MD, MPH, the William Anderson Spickard Jr., MD Professor of Medicine at the Vanderbilt University School of Medicine and director of the Vanderbilt Center for Tobacco, Addiction and Lifestyle.

"The fact that lung cancer risk drops relatively quickly after quitting smoking, compared to continuing smoking, gives new motivation," she said.

Tindle and her colleagues examined the health records of residents of Framingham, Massachusetts, who have been followed for decades by the Framingham Heart Study.

The study, which is supported by the National Heart, Lung, and Blood Institute, helped establish high blood pressure and high cholesterol as key risk factors for cardiovascular disease. But it also tracked cancer outcomes.

The current study looked at 8,907 participants who had been followed for 25 to 34 years. During this period, 284 lung cancers were diagnosed, nearly 93 percent of which occurred among heavy smokers, those who had smoked at least a pack of cigarettes a day for 21 years or more.

Five years after quitting, the risk of developing lung cancer in former heavy smokers dropped by 39 percent compared to current smokers, and continued to fall as time went on. Yet even 25 years after quitting, their lung-cancer risk remained over threefold higher compared to people who had never smoked.

The Framingham study is unique because it asked people about their smoking every two to four years, and could account for increases or decreases in smoking over time.

Current federal guidelines, which mandate insurance coverage of lung cancer screening for current and former smokers, exclude those who haven't smoked for 15 years or more. Yet four of 10 cancers in heavy smokers in the current study occurred more than 15 years after they quit.

Further study is warranted to determine whether extending the cut-off point for mandated screening would be cost-effective and save lives, the researchers concluded.

"While the importance of smoking cessation cannot be overstated, former heavy smokers need to realize that the risk of lung cancer remains elevated for decades after they smoke their last cigarette, underscoring the importance of lung cancer screening," said senior author Matthew Freiberg, MD, MSc, professor of Medicine.

Alzheimer's disease patients lose up to 60% of a component called plasmalogen from the membranes of the cells in their brains, but it's still not known how or why. In a paper to be published in the June 1 issue of the Journal of Biological Chemistry, researchers at Washington University in St. Louis provide the first report of an enzyme that breaks down plasmalogens, a breakthrough in understanding the molecular processes that occur during Alzheimer's and other diseases.

Plasmalogens are particularly abundant in the heart and brain, where they are involved in structuring cell membranes and mediating signals. Plasmalogens are phospholipids defined by a particular chemical bond, called a vinyl-ether linkage. Because of the technical difficulties of studying plasmalogens, however, many aspects of their biology are unknown, including how the vinyl-ether bond is broken to break down plasmalogens in cells.

"These molecules, plasmalogens, have been swept under the rug because nobody likes to think about them," said Richard Gross, the professor at Washington University who oversaw the new study. "(They're) hard to work with. They're susceptible to light, they're stable in only certain solvents, they have a limited lifespan after they're synthesized unless extreme precautions are taken, and they're expensive to make and synthesize."

In the new study, Gross' team performed painstaking experiments to find the elusive mechanism by which plasmalogens are enzymatically degraded. Cytochrome c is typically found in mitochondria where it facilitates electron transport, but it is released into the cell under stressful conditions. Gross' team showed that cytochrome c released from the mitochondria can catalyze the breakdown of plasmalogens in the cell. Further, the products of this reaction are two different lipid signaling molecules which were not previously known to originate from plasmalogen breakdown.

"That was one thing that surprised us," Gross said of the signaling products. "The second thing that surprised us was the ease (with which the bond is broken)...The implication is that there is probably a lot of plasmalogen (breakdown) that's going on in conditions of oxidative stress."
The results tie in with another observation about the brain cells of Alzheimer's disease patients, which is that they often have dysfunctional mitochondria and a resultant release of cytochrome c. Gross is now interested in delving deeper into how and why plasmalogen loss occurs in Alzheimer's patients, particularly those who develop the disease in old age, not due to familial mutations.
Gross speculates that as people age, the accumulation of reactive oxygen species leads to cytochrome c release, activation of its peroxidase activity and plasmalogen breakdown in many membranes.

The results also have implications for understanding disorders in the heart and other plasmalogen-rich tissues, integrating studies of mitochondria, cell membranes and cell signaling under stressful conditions.

"This is like a quantum jump into the future," Gross said.

Scientists at the Virginia Tech Carilion Research Institute have added a new dimension to the understanding of how cells alter their communication with one another during development, wound healing, and the spread of cancer.

The researchers published their results in Molecular Biology of the Cell, a journal published by the American Society for Cell Biology.

"We have gained a new insight into how an individual cell can dynamically modulate its synthesis of proteins from existing genetic instructions," said James Smyth, an assistant professor in the VTCRI Center for Heart and Regenerative Medicine Research at the VTCRI and lead author on the study. "This understanding of fine-tuning is new to the field."

When tissue grows or heals, its outer layer of epithelial cells takes on characteristics that allow cells to migrate, change their size and behavior, and act as other cell types, specifically multipotent mesenchymal cells that are useful for making repairs. The process is known as the epithelial mesenchymal transition, or EMT.

"The problem is that EMT is also activated in various disease processes, such as fibrosis and cancer metastasis," said Smyth, who is also an assistant professor of biological sciences in Virginia Tech's College of Science. "Fortunately, these cells are very amenable to manipulation. We've developed a powerful new tool to study this process to help us get to the heart of cancer metastasis. We can observe cancer cells change their communication with each other to become more invasive, to separate, and to disperse throughout the body."

Smyth said researchers will also be able to use their techniques to better understand cellular responses to injury and disease in other pathologies, such as cardiac disease, as well.

Smyth normally studies communication between cardiac cells, with a specific focus on the role of a type of protein called connexin 43. Connexins are found in every tissue of the body. When six connexin 43 proteins come together, they form channels called gap junctions through which cells communicate.

Historically, people thought that the more connexin proteins in the cell, the more gap junctions the cell would make, thus enriching cellular communication.

Like all proteins, Connexin 43 is synthesized from the message encoded in RNA that has read out the DNA code. The RNA can also encode for smaller pieces or fragments of connexins 20k, that ensure gap junction formation.

"It was thought that the amount of RNA correlated with the amount of connexin protein, but we now know that it's much more complicated than that," Smyth said. "The point of protein synthesis for translation is tightly regulated by the cell, and it is dynamic, changing with development and with disease."

In this study, Smyth found that RNA and protein synthesis of connexin increased during EMT, but the amount of gap junctions on the surface of the cell did not increase as expected.

In an effort to understand why, Smyth collaborated with Samy Lamouille, a research assistant professor at the VTCRI. Lamouille is an expert in EMT and the cellular signaling involved in protein translation, which he has studied since he was a postdoctoral associate at the University of California San Francisco.

Lamouille, who is also a research assistant professor of biological sciences in Virginia Tech's College of Science, focuses on understanding the mechanisms that regulate cell-to-cell interaction in cancer and how deregulated intercellular communication can lead to cancer progression through EMT.

"In this study, we found the formation of gap junction structures that allow cells to communicate was disrupted during EMT despite an abundance of connexin 43," Lamouille said.

Normally, the cell makes the 20k connexin fragments to direct the full-length connexin 43 to the surface of the cell -- a process that becomes altered to the detriment of gap junction formation.

Smyth and Lamouille hypothesized that the connexin (20k) fragments were being suppressed during the internal translation process of protein synthesis.

"We had this increase in proteins, but they weren't going to the cell membrane surface," Smyth said. "Could it be that the connexins were getting stuck somewhere?"

The researchers used the VTCRI's super resolution microscope to examine individual molecules and to analyze the connexins within the cells. They found that the full-length connexins were arrested in the cell's Golgi apparatus, which acts as a packaging plant for proteins heading to the surface of the cell.

To counteract the suppressed expression of 20K connexin fragments, Smyth used a lentivirus vector to cause the cells' RNA to make 20k connexin, thereby rescuing the full-length connexin 43, the formation of gap junctions, and normal cellular communications.

Smyth is now applying the information he learned in this research to cardiovascular disease, where he's seen the same cellular communication issues.

Infectious disease preparedness work focuses predominantly on an historical list of pathogens derived from biological warfare agents, political considerations, and recent outbreaks. That fails to account for the most serious agents not currently known or without historical precedent, write scholars from the Johns Hopkins Center for Health Security in a new report on the traits of microorganisms with high pandemic potential.

The report, "The Characteristics of Pandemic Pathogens," establishes a framework for identifying naturally occurring microorganisms that pose a global catastrophic biological risk (GCBR) and makes broad recommendations for improving GCBR preparedness efforts. GCBRs are events in which biological agents could lead to a sudden, extraordinary, widespread disaster beyond the collective capability of national and international governments and the private sector to control. No exhaustive catalogue of GCBR culprits exists, leaving the health security community to rely on historical examples (e.g., 1918 Spanish Flu) to guide their preparedness priorities.

"Health security preparedness needs to be adaptable to new threats and not exclusively wedded to historical notions," said Amesh Adalja, MD, project lead and senior scholar at the Center. "A more active-minded approach to this problem will, in the end, help guard against a GCBR event occurring."

Adalja's project team included senior scholar Eric Toner, MD, and senior analyst Matthew Watson. To formulate the findings and recommendations in their report, they reviewed published literature and reports on emerging infectious disease characteristics, the pathogenic potential of microbes, and other related topics; interviewed more than 120 technical experts from academia, industry, and government; and convened a meeting of a subset of those experts to discuss preliminary analysis of the information the team had gathered.

The first and primary finding presented in the report outlines common characteristics of a potential GCBR-level pandemic pathogen. Its mode of transmission, the team concluded, will most likely be respiratory. It will be contagious during the incubation period, prior to symptom development, or when infected individuals show only mild symptoms. Finally, it will need specific host population factors (e.g., immunologically naïve persons) and additional intrinsic microbial pathogenicity characteristics (e.g., a low but significant case fatality rate) that together substantially increase disease spread and infection.

The report continues its findings with an explanation of the pandemic potential of certain categories of microbes, noting that RNA viruses are the biggest threat. The project team's preparedness-related findings are reflected in 8 key recommendations:

Preparedness against GCBR-level threats should have a focused approach with some flexibility.

Historical pathogen list-based approaches should not stand as permanent fixed ideas that stultify thinking on pandemic pathogens.

Improving surveillance of human infections from respiratory-borne RNA viruses should become a higher priority.

An increased emphasis on developing a specific pipeline of various antiviral agents for RNA respiratory viruses--both broad spectrum and virus-specific--would add resiliency against potential GCBR agents.

Vaccines against RNA respiratory viruses--including a universal influenza vaccine--should be pursued with increased priority.

A clinical research agenda for optimizing the treatment of respiratory-spread RNA viruses should be funded by pharmaceutical companies and medical device companies and pursued by clinical centers.

Special review is warranted for respiratory-borne RNA virus research that could increase pandemic risks.

Pursuing microbiologically specific diagnoses of infectious disease syndromes in all locations globally should become more routine.

"We hope policymakers and practitioners consider our recommendations in their work to strengthen health sector resilience and fortify pandemic preparedness," said Adalja.

The benefits of antibiotics to both human and animal health are undisputed. However, as microbes have become increasingly resistant to antimicrobials and other drugs, scientists have become interested in new solutions to the growing superbug crisis, including the use of defensive microbes and faecal transplants. In new research, Oxford University scientists have developed a lab-based approach, creating positive co-dependent relationships between hosts and bacteria, termed 'mutualisms', quickly. These lab-developed bacterial relationships demonstrate how microbes can work with their hosts to prevent infection.

Defensive host-microbe relationships are prevalent in nature across plants and animals, including humans. The mutual benefit comes from the host benefiting from the protection of the bacteria, and the bacteria then benefiting from the host being a healthy living environment - allowing it to accumulate further over time.

In a study published in Evolution Letters, scientists from Oxford's Department of Zoology worked with the University of Bath to test whether these defensive host-microbe 'mutualisms' could evolve from scratch to protect against attack from harmful and infectious parasites.

The team tracked the evolution of a nematode worm host and a gut bacterium (Enterococcus faecalis) with the potential to protect against more pathogenic bacterial infection. After just a few short weeks of evolution, changes in both the worm and gut bacteria resulted in the species working together and ultimately forging a mutually beneficial alliance, protecting them both from attacks from parasites. The effect was only seen when host and gut bacterium coevolved in the presence of the parasite.

Dr Charlotte Rafaluk-Mohr, lead author on the paper and a post-doctoral researcher in the Department of Zoology, explains: 'Our study shows that protection by gut microbes is a benefit that is strengthened and reciprocated when both microbe and host evolve together. The bacteria evolved to become more protective, and in turn, hosts evolved to allow more E.faecalis colonisation. Evolving to allow protective bacteria to colonise and help could be a common means of defence against infectious diseases.'

Of the difference between this research and other bacterial symbiosis studies, Dr Rafaluk-Mohr, said: 'In itself, hosts and bacteria forming co-dependent relationships is not a new concept. However, our study is the first to develop this relationship from scratch. Some 'mutualisms' take years of evolutionary history before they reap any defensive benefit, but in our case, the relationship was developed and formed in a matter of weeks in a laboratory - before that the host worm and bacteria were completely foreign entities.

To understand when defensive mutualisms are most likely to evolve in nature, the team worked with Dr Ben Ashby from the University of Bath to study mathematical models of coevolving hosts and bacteria. The models predict that if protection is too low, then there is little benefit to the host of harbouring the bacteria, but if protection is too high then other microbes may be wiped out, removing the need for protection. It is therefore when microbes provide a moderate level of protection that 'mutualisms' are most likely to evolve.

Understanding the origin and maintenance of defensive relationships between hosts and their "good bacteria" are pressing questions for evolutionary biologists. The team found that the speed of the relationship's evolution could have a significant role to play in its overall success, and also in its potential use as treatment for human health. As Dr Rafaluk-Mohr, explains: 'We have an increasing problem with antibiotics not being able to treat disease, and our research shows that both using and engineering 'mutualisms' has the potential to benefit people by preventing infection by disease causing parasites.' The study also indicates that the interaction of host and microbe genetic background may play a role in the establishment of these host-bacteria defensive relationships, and thus the potential success of bacteriotherapy and faecal transplants, for example.

Dr Kayla King, senior author and Associate Professor in Parasite Biology at Oxford, added: 'Entire human and animal bodies are covered in microbes inside and out. Many of these bacteria can help by defending us (their hosts) against attack from harmful parasites. Essentially, a slightly parasitic relationship develops to become mutually beneficial.

'With funding for further research we intend to investigate how hosts allow these protective bacteria to colonise inside them, and what they do to support this interaction. Is the host's immune system not targeting the good bacteria or are hosts actively selecting good bacteria amongst others in the microbiota?'

May 29, 2018 - Computer-designed, 3D-printed models are emerging as a useful new tool for planning and carrying out cosmetic plastic surgery of the nose, reports a paper in the June issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS).

Customized, life-sized, 3D-printed, models can provide a useful visual reference in the operating room for plastic surgeons performing rhinoplasty, according to a special "Ideas and Innovations" article by ASPS Member Surgeon Bardia Amirlak, MD, FACS, of University of Texas Southwestern Medical Center in Dallas, and colleagues. They write, "Patient-specific 3D-printed models reflecting the actual 3D anatomy provides additional visual and tactile information to the surgeon, which may contribute to achieving the desired clinical result."

Printed 3D Models Provide Visual Guide for Rhinoplasty

In recent years, digital imaging technology has become widely used in planning many types of plastic and reconstructive surgery procedures. When discussing cosmetic surgery, the ability to create 3D "before and after" images - showing the patient's current appearance and the planned results of surgery - has been a valuable aid to the preoperative consultation between patient and surgeon.

For Dr. Amirlak and colleagues, the growing availability of 3D printing technology provides a logical next step: using 3D digital images to crate printed models of the proposed appearance of the new nose. Once the patient and surgeon agree on the "idealized outcome" of rhinoplasty, the digital images of the patient's current appearance and simulated outcome are converted into 3D-printed models. Full-color models are printed using gypsum powder - providing a more detailed and lifelike appearance than with 3D printing using polymer resin.

In the operating room, the surgeon can refer to the 3D-printed models as a "side-by-side reference," helping to see and appreciate subtle changes occurring during the rhinoplasty procedure. The models help to ensure that the outcomes of cosmetic rhinoplasty are as close as possible to the planned appearance of the patient's nose.

Three-dimensional printed models can also help to improve communication with the patient before surgery, Dr. Amirlak and colleagues have found. They write, "The tactile feedback and ease of visualization from different angles and profiles have complemented the 2D and 3D photographs, making the surgical possibilities and limitations of the procedure easier to understand for the patient." The models take about a week to create, with an average cost of $300.

While 3D printing technology isn't new, it is increasingly available and affordable for a wide range of applications. Three-dimensional printed models have been used for craniofacial and other types of reconstructive surgery, but have received relatively little attention in cosmetic surgery.

Rhinoplasty - sometimes called a "nose job" or nose reshaping - is a common yet challenging procedure for plastic surgeons. It is one of the most frequently performed types of cosmetic surgery. About 219,000 rhinoplasty procedures were performed in the United States in 2017, according to ASPS statistics.

"Given the complexity of rhinoplasty, 3D printing may be a natural fit as part of the surgical care of these patients," Dr. Amirlak and coauthors write. In addition to improving the preoperative consultation process and providing a guide to the surgeon during the procedure, they believe that 3D printing technology "has numerous prospective clinical and research uses in aesthetic surgery."

Plastic and Reconstructive Surgery® is published in the Lippincott portfolio by Wolters Kluwer.

Oxytocin's effects on human social behavior aren't clear. Some studies reveal significant positive changes, yet others show none at all. In many animals, from rodents to non-human primates, it's a different story: Oxytocin has been proven to increase positive social behaviors and attention paid to others, and reduce negative social behaviors like threats and vigilance.

Such findings typically derive from work that includes specific tasks performed by the subjects, either people or animals. But Penn neuroscientist Michael Platt and postdoctoral researcher Yaoguang Jiang wanted to understand what happens during spontaneous, naturally occurring interactions following inhalation and injection of both oxytocin and a similar neuropeptide, vasopressin.

In a study published in Scientific Reports, they found that in male rhesus macaques, the hormones flatten group hierarchy, resulting in dominant monkeys becoming more relaxed and subordinate monkeys becoming more confident. This holds even when just one of a pair receives oxytocin or vasopressin, indicating some sort of non-verbal communication between the animals.

"This society, which is often described as despotic, hierarchical, and regulated by aggression and submission, becomes more egalitarian. Everyone is a little nicer to everyone else," says Platt, a Penn Integrates Knowledge professor with appointments in the Perelman School of Medicine, the School of Arts and Sciences, and Wharton. "They synchronize their facial expressions and their behavior more tightly in time. In other words, they're paying more attention to each other and when you do this, you get information more quickly and you respond more quickly."

The work, the first of its kind, involved giving one macaque oxytocin, vasopressin, or saline via inhalation or injection, then pairing him seven times, six with different monkeys and once with an empty chair, in a random order. For their protection, the animals could not physically touch. However, they could interact and could see, hear, and smell each other. The researchers recorded a five-minute exchange, then two separate observers scored the behavior, frame by frame. Seven macaques participated in the inhalation work, and seven participated in the injection work.

"Social dominance in monkeys is a really big deal. They live and breathe for it. But here, the curve got flattened," says Jiang, who has worked in the Platt Labs for more than two years. "If you were in the middle, you stayed in the middle. But if you were lower-ranking and you used to be timid, you got a little more assertive, and if you were super dominant, you still knew you were the boss but you were a little more chill about it. You weren't always trying to pick a fight."

What's more, the alignment of actions--what's known as behavioral synchrony--when only one half of a duo got the hormone indicates non-verbal cues underlying the activity, Jiang explains. "Somehow they were conveying this information to each other," she says. "Communication was obviously not verbal, but little gestures." This is consistent with previous work from Platt showing that oxytocin increases how long one monkey looks at and pays attention to another monkey.

Vasopressin lead to the same outcome as oxytocin, which actually complicates the picture of how such hormones work. Receptors for the two are located in different parts of the brain, and can bind to both hormones. By injecting small amounts of the hormones into a brain area that only contains vasopressin receptors, Platt and Jiang found that oxytocin appeared to be binding to vasopressin receptors to change behavior.

"Our understanding of how all of this is going to work is much more complicated than originally thought," Platt says. "We have to consider this whole other system, the vasopressin system."

In theory, digging deep into these hormones and their underlying mechanisms could potentially lead to breakthroughs in therapeutic treatments for social disorders such as autism and schizophrenia and bipolar disorder. It may also help children who have had pituitary tumors removed, a procedure that can damage the hypothalamus and lead to ravenous overeating for reasons still unknown. Because oxytocin regulates feeding and social behavior, there's treatment potential there, something Platt and colleagues are testing via a clinical trial at the Children's Hospital of Philadelphia.

"We anticipate that for these kids, there is a whole set of underlying social problems that people aren't dialed into because they're focused on the fact that the kids can't stop eating," Platt explains. "We're trying to determine whether when we treat them for overeating, that also improves social functions."

This overall work builds on research Platt has conducted on non-human primates for more than two decades. In particular, rhesus macaques offer a valuable comparison to humans because the animals model many of the same social behaviors, live in large groups, and form long-term social bonds.

Their reaction to oxytocin and vasopressin also seems to mirror that of people. Yet despite such incremental advancements in knowledge, there's still much to understand, Platt says. "We have a lot more to learn about how, when, and in what manner we use these peptide hormones to treat various problems."

A new study by Maanak Gupta, doctoral candidate at The University of Texas at San Antonio, and Ravi Sandhu, Lutcher Brown Endowed Professor of computer science and founding executive director of the UTSA Institute for Cyber Security (ICS), examines the cybersecurity risks for new generations of smart which includes both autonomous and internet connected cars.

"Driverless and connected cars are increasingly becoming a part of our world, where cybersecurity threats are already a reality," Sandhu said. "It's imperative that we support research that addresses these concerns and presents a strong, innovative solution."

Cars with internet connectivity, also known as "connected cars," offer potential for many conveniences and innovations. They could allow for real-time and location-sensitive communication between drivers or even pedestrians, which could help make the roads safer for both. The connectivity could also allow the cars to capture safety and environmental conditions around the vehicle, including road obstructions, accidents, which also enables real-time vehicle-to-vehicle interaction on road.

"Connected cars have almost infinite possibilities for creative technological applications," Gupta said. "Companies could even take advantage of the connectivity to implement location-based marketing tactics, providing drivers with nearby sales and offers."

However, the researchers caution that as soon as cars are exposed to internet supported functionality, they are also open to the same cybersecurity threats that loom over other electronic devices, such as computers and cell phones. For this reason, Gupta and Sandhu created an authorization framework for connected cars which provides a conceptual overview of various access control decision and enforcement points needed for dynamic and short-lived interaction in smart cars ecosystem.

"There are vulnerabilities in every machine," said Gupta. "We're working to make sure someone doesn't take advantage of those vulnerabilities and turn them into threats. The questions of 'who do I trust?' and 'how do I trust?' are still to be answered in smart cars."

Gupta and Sandhu framework discussed an access control oriented architecture for connected cars and proposed authorization framework, which is a key to determine what and where vulnerabilities can be exploited. They further discuss several approaches to mitigate cyber threats in this ecosystem.

Using this framework, the team at ICS is trying to create and use security authorization policies in different access control decision points to prevent cyber attacks and unauthorized access to sensors and data in smart cars.

"There are infinite opportunities in this new IoT domain but at the same time cyber threats will have serious implications in smart cars. Can you imagine if someone controls your car steering remotely, or shuts down the engine in the middle of the road?" Gupta said. "There should not be absolutely any open end to orchestrate attacks on these cars."

According to Gupta, the authorization framework can also be applied to driverless cars, noting that these vehicles may be even more vulnerable to cyber threats.

"If we're going to open the world to cars driven by machines, we must be absolutely certain that they aren't able to be compromised by a malicious attack," he said. "That it what this framework is for."