Culture

Many hospital patients get medicine or nutrition delivered straight into their bloodstream through a tiny device called a PICC. In just a decade, it's become the go-to device for intravenous care.

But a new study finds that one in every four times a PICC gets inserted, the patient didn't need it long enough to justify the risks that it can also pose.

In fact, in just the five days or less that they had a PICC implanted in their vein, nearly one in ten of these patients suffered a blocked line, an infection, a blood clot or another complication linked to the device.

One in three short-term PICC patients also had serious kidney problems that could make them potential dialysis candidates, the study also shows. They face special risks from the devices, which can harm blood vessels and jeopardize a patient's ability to receive dialysis later, if their kidneys fail.

The study, published in the February issue of the Journal of Hospital Medicine, is based on data from 52 hospitals around the state of Michigan taking part in a massive quality improvement and patient safety effort. It's a detailed analysis of records from 15,397 PICC placements over a two-year period from 2014 to 2016, just before and after guidelines for safe and appropriate PICC use made their debut.

The study is a large-scale examination of real-world use of PICCs, or peripherally inserted central catheters, and the factors associated with their short-term use.

It highlights the need for efforts to reduce short-term use of PICCs and help medical care teams understand current practice and consider other alternatives for short-term IV access that pose less risk.

"When PICCs first came out, they became an 'easy button' for vascular access, and the safety issues weren't recognized," says David Paje, M.D., M.P.H., the University of Michigan hospitalist who led the research team. "Now the dynamics have changed, and we need to be more thoughtful with their use."

Paje, an assistant professor of internal medicine, also helps lead the Medical Short Stay Unit at Michigan Medicine, U-M's academic medical center.

For the new study, he worked with senior author and Division of Hospital Medicine chief Vineet Chopra, M.D., M.Sc., and co-author Scott Flanders, M.D., who directs the Michigan Hospital Medicine Safety Consortium that provided the data for the study. Colleagues from several Michigan hospitals are co-authors.

Moving to MAGIC

Based on previous studies of PICC-associated risks, the team assembled an expert panel that developed a guideline for choosing IV devices appropriately, called MAGIC. They unveiled it in 2015, and turned into a mobile and web app in 2017.

Hospitals in the Michigan consortium, which is funded by Blue Cross Blue Shield of Michigan, began receiving training in MAGIC during the study period, but were still implementing it.

MAGIC guides clinicians to the appropriate option for the individual patient they're treating. For instance, instead of a PICC, it recommends that patients who will need intravenous access for less than five days should receive a different form of IV device, such as a midline or peripheral IV.

"This study helps illustrate how medical devices such as PICCs can be both helpful and harmful," says Chopra, who led the development of MAGIC and is a member of the U-M Institute for Healthcare Policy and Innovation. "Understanding how best to balance appropriate use - using tools like MAGIC - is the way to safe and better patient care."

Factoring into PICC use

As part of the study, Paje and his colleagues looked at which patients were more likely to receive a PICC for short-term use.

The strongest factor was difficult vascular access - a catch-all phrase that means it had been hard to start an IV in the patient in previous visits or earlier in the hospital stay.

Clinicians may default to choosing a PICC in these patients in order to keep an intravenous access point open, rather than having to find a vein each time, Paje says. Or, some experienced patients may even ask for a PICC to avoid so many "pokes."

Patients whose physicians ordered a multilumen IV device, to avoid contact between different medications or nutrition solutions, were also more common among short-term PICCs. But Paje notes that few of the patients' records actually said that they were receiving multiple IV substances that had to be kept separate. And patients who had a short-term multilumen PICC were much more likely to suffer a complication.

Interestingly, patients treated in teaching hospitals were more likely to receive a short-term PICC than those treated in non-teaching hospitals. This could actually be seen as an opportunity to address the issue of inappropriate short-term PICC, if hospitals make a plan to teach their residents about the risks and benefits of PICCs and other IV devices.

A recent paper by members of the consortium showed that at one hospital that implemented MAGIC, inappropriate PICC use decreased compared with hospitals that didn't implement it, and PICC-related complications also decreased modestly.

Paje notes that the body's own reaction to foreign material, and the mechanical stress put on veins when a PICC is inserted, can combine to damage veins and increase the risk of clots or scarring. The damage can keep a dialysis candidate from being able to successfully establish a vascular fistula, which would have been the preferred way to receive long-term dialysis.

In all, 9.6 percent of the short-term PICC patients experienced a complication, including 2.5 percent who experienced a blood clot forming in their vein that could have broken off and caused more serious consequences, and 0.4 percent developing a CLABSI, or central line associated blood stream infection.

"The use of PICCs exploded because the safety issues were not initially recognized, including those associated with clots and infections," says Paje. "Now we're coming back full circle, and we need to adapt and implement quality improvement processes to be more judicious with their use. We need to recognize that PICCs are not without any consequence, even for short-term use."

He notes that most of the reasons cited for PICC use in the patient records used in the study - such as delivering antibiotics -- do not require the deep access to the central bloodstream that PICC provides.

Even as clinicians get the word about the MAGIC guidelines and implement measures to right-size PICC uses, Paje calls on patients and family members to speak up and ask questions before a PICC gets placed.

"Patients or their representatives should be actively engaged, and informed," he says. "Find out what lines they're putting in, and ask questions."

New York, NY (February 23, 2018)--Children from low-income neighborhoods had a higher mortality rate and higher hospital costs after heart surgery compared with those from higher-income neighborhoods, found a national study of more than 86,000 kids with congenital heart disease. The magnitude of the neighborhood effect, which persisted even after accounting for race, type of insurance, and hospital, was similar for children of all disease severities.

The findings were published online today in Pediatrics.

"These results were surprising," said Brett Anderson, MD, MBA, an attending pediatric cardiologist at NewYork-Presbyterian Morgan Stanley Children's Hospital, assistant professor of pediatrics at Columbia University Irving Medical Center, and the study's lead investigator. "The fact that disparities exist in healthcare is nothing new. But the fact that we see such a big effect in this population is shocking. We think of this group of children as being particularly well integrated into the healthcare system, regardless of their background. Most children with congenital heart disease are diagnosed prenatally or as newborns, and the children in this study--mostly infants--all had access to highly specialized cardiac care teams at major tertiary children's hospitals. While we expected to see some differences, we assumed the effect would be minor compared to what is seen in general pediatric populations. In fact, the effect was essentially identical to that observed in general pediatric patients."

How the study was conducted

The researchers used data from the Pediatric Health Information System (the largest U.S. database of pediatric discharges) to evaluate post-surgical mortality, length of stay, and standardized hospital costs in 86,104 children with congenital heart defects at 46 U.S. pediatric hospitals between 2005 and 2015. The results were combined with U.S. Census Bureau data on median household income by zip code.

What the study found

Overall, 2.9 percent of the children who had heart surgery died. Children from the lowest-income neighborhoods, which included more families with public insurance, had an 18 percent increase in risk of death compared with children from the highest-income neighborhoods, after adjusting for differences in race, insurance, and disease severity. Length of hospital stay and costs were both 7 percent higher for children from the lowest-income neighborhoods compared to children from the highest-income neighborhoods.

The researchers also looked at outcomes in 857,833 children who were hospitalized for other conditions between 2013 and 2015. About half of this group had a chronic condition. Similarly, children from the lowest-income neighborhoods had a 22 percent greater chance of dying in the hospital compared with kids from higher-income neighborhoods. Length of stay and in-hospital costs were about 3 percent higher for children from the lowest-income neighborhoods.

What caused the disparities?

"When neighborhood disparities have been described in other studies, they have been largely attributed to differences among hospitals or in environmentally-mediated differences in behavioral health," said Dr. Anderson. "In our study, even when the hospital effect was taken into account, neighborhood remained an important predictor of outcomes."

The study found a higher incidence of severe heart disease in children from low-income neighborhoods, but the neighborhood effect remained after controlling for disease severity.

"Certain environmental factors--such as maternal stress, nutrition, or health expectations--might have contributed to the differences in outcomes that we saw in children from low-income neighborhoods," said Dr. Anderson. "But until we conduct detailed qualitative studies, we can't be sure why these disparities persist. Ideally, such studies would examine the role of both families and providers--such as how long it takes before a family makes or obtains an appointment with a subspecialist, and whether providers knowingly or unknowingly make different care choices based on a family's income level or the socioeconomics of the neighborhood from which the child comes."

Lizards have special superpowers. While birds can regrow feathers and mammals can regrow skin, lizards can regenerate entire structures such as their tails. Despite these differences, all have evolved from the same ancestor as lizards.

Spreading through the Americas, one lizard group, the anoles, evolved like Darwin's finches, adapting to different islands and different habitats on the mainland. Today there are more than 400 species.

Constructing a family tree for three lizard species collected in Panama at the Smithsonian Tropical Research Institute (STRI) and a fourth from the southeastern U.S., scientists at Arizona State University compared lizard genomes--their entire DNA code--to those of other animals.

The researchers discovered that changes in genes involved in the interbrain (the site of the pineal gland and other endocrine glands), for color vision, hormones and the colorful dewlap that males bob to attract females, may contribute to the formation of boundaries between species. Genes regulating limb development also evolved especially quickly.

"While some reptiles such as tortoises changed remarkably little over millions of years, anole lizards evolved quickly, generating a diversity of shapes and behaviors," said Kenro Kusumi, corresponding author and professor at ASU School of Life Sciences. "Now that sequencing entire genomes is cheaper and easier, we discovered molecular genetic evidence for rapid evolution that may account for striking differences between bodies of animals living in different environments."

Kusumi's lab, working with colleagues at the University of Arizona College of Medicine-Phoenix, is especially interested in how reptiles' genomes shape their ability to regenerate and to develop a diversity of body forms.

"This is the first time the complete genetic code--the genome--of any vertebrate species from Panama has been sequenced and analyzed," said Oris Sanjur, co-author and Associate Director for Science Administration at STRI. "Information from these three species is an important contribution to our understanding of biodiversity and the evolution of new species."

Scientists estimate that there are 40 species of anolid lizards living in Panama, compared to only one in the U.S. A team from ASU collected three species with permission from the Ministry of the Environment, MiAmbiente: the Central American giant anole, Anolis frenatus, lives high on tree trunks; the grass anole, A. auratus, perches on bushes or on grassy vegetation and the slender anole, A. apletophallus, found only in Panama, hangs out lower on tree trunks or on the ground.

Researchers at ASU's School of Life Sciences lined up the DNA sequences of the lizards with the DNA sequences of 31 other animals: the lobe-finned fish and the four-legged animal groups that evolved from them. They also took a careful look at genes that code for proteins: more than 22,000 genes in the green anole, A. carolinensis, versus approximately 20,000 identified each in A. auratus and A. frenatus and 13,000 in A. apletophallus.

One obvious explanation for a faster rate of evolution is the anole lizards' faster rate of reproduction. Anoles typically mate in their first year of life, while other reptiles take much longer to reach sexual maturity. They also breed with many other individuals so mutations that make it difficult for individuals to survive are eliminated fairly quickly.

The first and only other anole lizard to be sequenced previously was the green anole, A. carolinensis, the only anole species resident in the U.S. In that study from MIT, the A. carolinensis genome held evidence of more recent evolution and the loss of ancient repeated elements in the part of the DNA that does not code for proteins. In this sense, it was important to sequence the three Panamanian species, because the U.S. species may not be the most representative of the diverse anole group.

"For 15 years, an impressive amount of time and money poured into discovering the genomes of mammals, motivated by our drive to understand human evolution and to look for cures for disease. Even though the squamate reptiles include more than 10,000 species--almost double the number of mammal species--a single genome was not enough to understand the variability within this group," said the first author of the report, Marc Tollis, a post-doctoral fellow at ASU.

"By comparing these four anole lizard genomes, we're beginning to understand how one of the most diverse groups of vertebrates regenerate, develop and diversify," he added.

A study of the unusual digestive system of an ancient group of insects has provided new insights into future biofuel production.

Published in Nature Communications, the research reveals that the ability of some insects to efficiently digest cellulose could be exploited for industrial processes, such as the production of sustainable low carbon fuels to cut greenhouse gas emissions associated with fossil fuel use.

The surprising find occurred when the team at the University of York were investigating the digestive system of firebrats, which had been previously shown to thrive on crystalline cellulose, the natural fibre, abundant in straw, paper and cardboard.

Professor Simon McQueen Mason, from the University of York's Department of Biology, said: "Firebrats belong to one of the most primitive groups of insects; they appeared on land during the Devonian Period, some 420 million years ago. Despite this long evolutionary history, however, these insects have been generally overlooked by scientists. "Cellulose forms the fibres that give the cell walls of plants their strength and has a high degree of structural order, making it solid and tough."

Until now it was a mystery how firebrats had found a way to digest cellulose so effectively. In looking at their digestive system, the scientists discovered something they weren't expecting.

Dr Federico Sabbadin, from the University of York's Department of Biology, said: "Inside their gut the firebrats had a group of uncharacterised proteins that make up 20% of their carbohydrate digestive enzymes.

"On further inspection, these proteins proved to be a new class of enzyme, called lytic polysaccharide monooxygenases (LPMOs), which attack crystalline polysaccharides. Our study revealed that these enzymes are used by firebrats to greatly increase the rate of cellulose digestion."

Previously, LPMOs were only known to occur in fungi, bacteria and viruses, but analysis of this new family showed it was widespread among invertebrates. Scientists suggest that it is possible that these enzymes could be adopted in industrial processes to break down cellulose into fermentable sugars for biofuel production.

Professor McQueen Mason said: "These digestive LPMOs appear to have evolved from enzymes that digest a substance called chitin, which protects the respiratory system of insects.

"We found that these ancestral genes are essential for metamorphosis and that interfering with their function is lethal to insects. This could have important implications for the development of new methods to control disease-carrying mosquitoes and agricultural pests such as locusts."

More than half of gun owners do not safely store all their guns, according to a new survey of 1,444 U.S. gun owners conducted by researchers at the Johns Hopkins Bloomberg School of Public Health.

The survey, believed to be the first nationally representative sample in 15 years to examine gun storage practices in U.S. households, found that 54 percent of gun owners reported not storing all their guns safely. The internet-based survey was fielded by the survey research firm GfK Knowledge Networks between March 15 and April 13, 2016.

The survey defined safe storage as all guns stored in a locked gun safe, cabinet or case, locked into a gun rack or stored with a trigger lock or other lock. This definition is based on research showing these practices reduce the risk of unauthorized access or use.

The findings will be published Feb. 22 in the American Journal of Public Health.

"Household gun ownership can increase the risk of homicides, suicides, and unintentional shootings in the home, but practicing safe storage for all guns reduces these risks," says lead study author Cassandra Crifasi, PhD, MPH, an assistant professor with the Johns Hopkins Center for Gun Policy and Research. "The survey findings indicate a real public health emergency. More than half of gun owners in the U.S. are not storing all of their guns safely--in a locked gun safe, cabinet or case, locked into a gun rack, or secured with a trigger lock."

The survey also found that children under the age of 18 were present in approximately one-third, or 34 percent, of the homes. Gun owners were 44 percent more likely to report safely storing all their firearms if they have a child under the age of 18 in the home: Slightly more than half, or 55 percent, of gun owners with children under 18 reported storing all of their guns safely.

Respondents were also asked about factors that influenced their gun storage practices. Concerns about home defense was selected by 43 percent, a gun safety training course by 35 percent, and family discussions by 30 percent.

In 2016, the most recent year of complete data, there were 1,637 firearm deaths among children under the age of 18; 39 percent of these deaths were the result of suicide. States with child access prevention laws that require gun owners to ensure children do not gain unauthorized access to their firearms report fewer firearm suicides among adolescents. Studies have also shown a decreased risk for self-inflicted injury among adolescents when guns are stored safely.

This new research finds that gun owners who reported a gun safety training course influenced their gun storage practices were twice as likely to practice safe storage for all their guns, and gun owners who cited discussions with family members as influencing their decisions were 39 percent more likely to practice safe storage.

"It's encouraging to see the positive associations between safety training and reporting safe storage practices," said study co-author Daniel Webster, ScD, MPH, director of the Johns Hopkins Center for Gun Policy and Research. "Requiring gun purchasers to take safety training classes, as a handful of states already do, might lead to more gun owners storing their guns safely."

The survey also found that gun owners who reported that their storage decisions were influenced by concerns about home defense were 30 percent less likely to practice safe storage for all their firearms.

"Many bring guns into their homes for self-defense, but unsecured guns can lead to unintentional shootings, suicides, and tragic cases of troubled teens using guns to commit acts of violence," said Crifasi. "Communicating with gun owners about the importance of safe storage is a challenging opportunity. If we are successful at improving storage practices among gun owners, particularly those with children in the home, we could reduce risks for gun violence and injury."

The survey also asked gun owners which groups could best communicate information about safe storage practices: 77 percent of respondents selected law enforcement as good messengers to teach gun owners about safe storage, followed by hunting/outdoor organizations (73 percent), active duty military (73 percent), military veterans (72 percent), and the NRA (71 percent). Physicians and celebrities scored lowest (19 percent and 11 percent, respectively).

Using an innovative crystallization technique for studying three-dimensional structures of gene transcription machinery, an international team of researchers, led by scientists at Penn State, has revealed new insights into the long debated action of the "magic spot"--a molecule that controls gene expression in Eschericahia coli and many other bacteria when the bacteria are stressed. The study contributes to our fundamental understanding of how bacteria adapt and survive under adverse conditions and provides clues about key processes that could be targeted in the search for new antibiotics. A paper describing the research appears on February 22, 2018 in the journal Molecular Cell.

"When bacteria experience stress, such as starvation, they remodel their gene expression," said Katsuhiko Murakami, professor of biochemistry and molecular biology at Penn State and an author of the paper. "In 1969, our coauthor, Michael Cashel, discovered that a new molecule appeared in E. coli when the bacteria were starved of key nutrients. Cashel called this molecule, which showed up as a new spot on a chromatogram, the 'magic spot,' because of its appearance from seemingly nowhere when bacteria were starved."

The magic spot subsequently was shown to be guanosine tetraphosphate, or ppGpp, a chemically modified analog of the G nucleotide in the ATCG alphabet of the genome. Its appearance following starvation and other stresses is associated with changes in the expression of over 500 genes, most prominently genes for the structural RNAs that are components of the ribosome-- the enzyme responsible for protein synthesis.

The ppGpp molecule interacts with E. coli's RNA polymerase--the cellular machine that produces RNA from genomic DNA--but precisely how this interaction controls gene expression remains a mystery. The new X-ray crystal structures, however, provide clues to this process by showing for the first time three-dimensional images of E. coli RNA polymerase in complex with ppGpp and another important factor that works with ppGpp, DksA.

The three-dimensional structure of RNA polymerase is well established, but seeing the structure of RNA polymerase while it is interacting with other molecules has proved to be technically difficult. The interacting molecules often disassociate during the crystallization process necessary to see their structure. The researchers overcame this difficulty by adding molecules of DksA and ppGpp to RNA polymerase that had been crystalized independently.

"We first created crystals of RNA polymerase, then soaked in DksA and ppGpp," said Vadim Molodtsov, assistant research professor in biochemistry and molecular biology at Penn State and another author of the paper. "When we did this, we saw that ppGpp bound to the complex of RNA polymerase and DksA in a way that changed the interaction between RNA polymerase and DksA. We think this change could be key to explain how ppGpp alters transcription so that the bacteria can respond to stress."

RNA polymerase in bacteria controls the expression of all genes, but in response to the presence of ppGpp, the expression levels of some genes are turned down, while many are unaffected and some are turned up. These changes in expression levels allow the bacteria to alter their composition to better survive stress. The researchers speculate that the different responses may be due to individual differences in the promotors--DNA sequences near the beginnings of genes that initiate expression--of individual genes.

"We are full of bacteria," said Sarah Ades, associate professor of biochemistry and molecular biology at Penn State and an author of the paper. "They affect our mood, they affect our weight, they affect our immune systems. The ppGpp system is important in lots of these bacteria, allowing them to sense their environment and adjust to stress. Understanding how ppGpp functions will allow us to better understand these bacteria and how they affect us. The system is also important in bacterial pathogens that cause infectious disease. Understanding how ppGpp works could allow us to find ways to disrupt its functions and develop new antibiotics."

Schizophrenia may be related to neurodevelopment changes, including brain’s inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ). The results broaden the understanding about the causes of this severe and disabling disorder, which affects about 1% of the world's population.

"A partnership between Brazilian and Chilean groups allowed us to create this singular study, combining expertise on neurodevelopment and formation of blood vessels to investigate schizophrenia," says neuroscientist Stevens Rehen, a researcher at D’Or Institute and UFRJ and one of the study’s coordinators. Veronica Palma, from University of Chile, led the study with Rehen and highlights the combined approaches allowed the creation of an environment that mimics the one during embryonic brain development. The study was published on February 22nd in the journal Translational Psychiatry (Nature Publishing Group).

Characterized by episodes of hallucinations, confused thoughts and delusions, schizophrenia has no cure and the available treatment is only partially effective. Investigating causes of the disease can bring new therapeutic solutions and early diagnosis tools.

Previous studies on post-mortem brains and blood samples from patients with schizophrenia indicated that their brains show differences in terms of vascularization. It is also known that the interaction between blood vessels and neurons is essential for the correct development of the brain, as it allows the correct supply of oxygen and nutrients to neural cells and remove potentially harmful molecules.

The group investigated the ability of human neural cells to aid the formation of blood vessels during brain development. They used human induced pluripotent stem (iPS) cells created at D’Or Institute from the skin cells of three patients with schizophrenia and three people without the disorder. These cells were transformed into neural stem cells, which give rise to nerve cells. In addition, the scientists also used neurospheres - three-dimensional clusters of neural stem cells that begin to transform into neurons.

The cells were cultured in a suitable medium and the researchers checked the molecules they produced, in particular the pro-angiogenic ones, that is, molecules that nurture the production of new blood vessels. The experiment showed that neural cells originating from schizophrenic patients produced a smaller amount of these substances. Neurospheres from these patients also showed impairment of the ability to create new vessels, with low concentration of VEGFA, one of the most important angiogenesis regulatory molecules, and increased concentration of TIMP-1, an antiangiogenic protein.

“This is the first demonstration of the profile of angiogenic molecules expression using neural stem cells derived from patients with schizophrenia, which shows they have a less angiogenic profile when compared to controls”, says Palma. “Indeed, this model of cell culture may reproduce what happens under physiological conditions”.

To test the hypothesis that angiogenesis was compromised in the cells of patients with schizophrenia, a second experiment was performed. It consisted in exposing human umbilical cord endothelial cells to the substances produced by the nerve cells of the previous experiment. The same was done with chicken eggs, which served as in vivo model.

The umbilical cord endothelial cells have great capacity to form blood vessels. Chicken eggs have an extra-embryonic membrane that makes strong angiogenesis during development to nourish the embryo – a perfect in vivo assay to test for angiogenesis., as well as the membrane just beneath the eggshell. Therefore, those were chosen to test whether the molecules produced by the neural stem cells of patients alter the angiogenic capacity of the cells. The results confirmed the results – substances produced by schizophrenia patients’ nerve cells can hold back the angiogenic capacity of the endothelial cells.

"Advances on this subject bring new perspectives for the treatment and diagnosis of schizophrenia," Rehen says. Soon, he and his team plan to evaluate new biomarkers - that is, biological indicators, such as molecules that suggest the presence of the disease - that can identify the disorder regardless of symptoms. "This is a completely new approach on neuro-vascular mechanisms in mental disorders”, he concludes.

Researchers at New York University College of Dentistry (NYU Dentistry), in collaboration with Rheonix, Inc. (Ithaca, NY), are developing a novel test for Zika virus that uses saliva to identify diagnostic markers of the virus in a fraction of the time of current commercial tests.

The test, which was adapted from an existing model developed by NYU and Rheonix for rapid HIV testing, is described in two new publications appearing in PLOS ONE and the Journal of Visualized Experiments (JoVE).

How Zika is Tested

Outbreaks of infectious diseases are occurring with growing frequency thanks to factors such as population concentration and global air travel. A 2015 outbreak of Zika virus in Brazil spread to other countries in Central and South America, the Caribbean, and the Southern United States, leading the World Health Organization to declare Zika and its link to birth defects a public health emergency.

"The recent Zika virus outbreak confirms that we need an effective surveillance and diagnostic program to reduce the impact of future emerging infectious diseases," said Maite Sabalza, PhD, a postdoctoral associate at the Department of Basic Science and Craniofacial Biology at NYU Dentistry and the lead author of the studies in PLOS ONE and JoVE.

Identifying pathogens early is critical for combatting the spread of infectious diseases. Testing often involves two separate steps: one to detect a pathogen's nucleic acids (RNA or DNA) and another to test for antibodies, the proteins the body produces in response to pathogens.

Blood samples are most often used to test for Zika virus and are typically processed using a common diagnostic technique called real-time polymerase chain reaction (RT-PCR). But blood may not be the best fluid: While the virus disappears in the blood a week or two after a person is infected, it can persist longer in saliva, semen, and urine. In addition, antibodies can remain for months or years in those bodily fluids, which is why it is essential for diagnosis to also detect antibodies after infection.

Backed by funding from the National Institutes of Health, NYU Dentistry researchers are developing a rapid Zika test that combines both nucleic acid and antibody assays using saliva, given that Zika virus and antibodies persist in saliva. A saliva test is also noninvasive, cost effective, and easier to collect than blood or urine.

Faster Results

The new test also has the potential to produce results in a matter of minutes instead of hours or days. Current RT-PCR tests take around three hours and specific antibody tests can take several weeks. NYU researchers are using a different method called isothermal amplification, which can detect a virus' nucleic acids in as little as 20 minutes, and antibody tests that can take less than an hour using Zika-specific antigens.

"The sooner you can identify a pathogen, the sooner steps can be taken to treat and isolate people. During an epidemic, you could test people before they get on a plane. The future of going through security at the airport may not be taking off your shoes, but instead spitting into a tube," said study author Daniel Malamud, PhD, professor of basic science at NYU Dentistry.

From HIV to Zika

The research team is building on its earlier collaborative work with Rheonix developing a rapid saliva test for HIV that can detect both viral RNA and antibodies.

"When we developed the HIV test, we knew we could use the same model for any infectious disease. All we need to know is the nucleic acid sequence and an antigen to identify specific antibodies," Malamud said.

In PLOS ONE, the researchers describe how they altered this model to use markers that detect Zika nucleic acid sequences instead of those for HIV. They then used a portable isothermal amplification device - which could be used for point-of-care testing - to identify Zika RNA.

After showing that the test could confirm the presence of the virus using both purified Zika RNA and Zika-infected saliva, they adapted the test to the Rheonix CARD® cartridge and workstation, enabling them to estimate the viral load in saliva samples. Knowing the amount of virus present is useful for understanding disease severity and immune responses, particularly among pregnant women and fetuses.

The researchers also identified Zika-specific antigens - which can be used to detect the Zika specific antibodies needed for testing - using a high density peptide microarray they describe in JoVE. Because Zika can be easily confused with other viruses such as Dengue and Chikungunya, identifying Zika-specific antigens paves the way for more precise diagnostic testing.

With evidence showing that both the nucleic acid and antibody tests work, the researchers can combine them in the Rheonix CARD® cartridge to process both diagnostic assays automatically and simultaneously. Researchers at NYU and around the world are continuing to validate their findings in further experiments using Zika-infected saliva.

"In working towards the goal of quickly making effective diagnostics available, we have developed a generic protocol that can not only be used to test for Zika virus but can be adapted for the next emerging or re-emerging infectious disease," said Sabalza. Study author Richard Montagna, PhD, FACB, Rheonix's Senior Vice President for Scientific & Clinical Affairs, added, "In addition to being able to react very quickly to any newly emerging or re-emerging infectious disease, our fully automated testing platform requires virtually no hands-on efforts and is well suited for use by individuals with minimal training."

MINNEAPOLIS - Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to 27, 2018.

"We believe our research is the first to show that tears may be a reliable, inexpensive and noninvasive biological marker of Parkinson's disease," said study author Mark Lew, MD, of the Keck School of Medicine of the University of Southern California in Los Angeles and a Fellow of the American Academy of Neurology.

Lew says the research team investigated tears because they contain various proteins produced by the secretory cells of the tear gland, which is stimulated by nerves to secrete these proteins into tears. Because Parkinson's can affect nerve function outside of the brain, the research team hypothesized that any change in nerve function may be seen in the protein levels in tears.

For the study, tear samples from 55 people with Parkinson's were compared to tear samples from 27 people who did not have Parkinson's but who were the same age and gender. Tears were analyzed for the levels of four proteins.

Researchers found differences in the levels of a particular protein, alpha-synuclein, in the tears of people with Parkinson's compared to controls. Additionally, levels of another form of alpha-synuclein, oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson's, were also significantly different compared to controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears.

Total levels of alpha-synuclein were decreased in people with Parkinson's, with an average of 423 picograms of that protein per milligram (pg/mg) compared to 704 pg/mg in people without Parkinson's. But levels of oligomeric alpha-synuclein were increased in people with Parkinson's, with an average of 1.45 nanograms per milligram of tear protein (ng/mg) compared to 0.27 ng/mg in people without the disease. A picogram is 1,000 times smaller than a nanogram.

"Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson's disease and those who don't in a noninvasive manner is exciting," said Lew. "And because the Parkinson's disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier."

More research now needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest stages of the disease, before symptoms start.

DURHAM, N.C. -- The fungus that causes athlete's foot and other skin and toenail infections may have lost its ability to sexually reproduce as it adapted to grow on its human hosts.

Scientists analyzed samples of this tenacious organism, called Trichophyton rubrum, and found that nearly all belonged to a single mating type. What's more, when they tried to set the fungi up with members of another mating type, they refused to do the deed, even after the scientists enlisted a variety of seduction schemes -- lowering the lights, cloaking the Petri dishes in plastic, flipping them upside down.

If this fungus can't sexually reproduce, it can't diversify, and if it can't diversify, that may mean its days on this planet are numbered, said Joseph Heitman, MD, PhD, senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine.

But don't expect toenail fungus to appear on the endangered species list anytime soon. "It is commonly thought that if an organism becomes asexual, it is doomed to extinction," Heitman said. "While that may be true, the time frame we are talking about here is probably hundreds of thousands to millions of years."

Though that timeline won't be much help to the nearly 2 billion people who currently suffer from fungal infections of the skin and nails, the discovery that this species may be asexual -- and therefore nearly identical at the genetic level -- does highlight potential vulnerabilities that researchers could exploit in designing more effective antifungal medications. The findings appear online in the journal Genetics.

Fungal infections affect approximately 25 percent of the world's population, and Trichophyton rubrum is usually the species to blame. People can pick up this infection by walking barefoot around swimming pools, showers or locker rooms, or by sharing personal items such as towels or nail clippers. Though there are plenty of over-the-counter powders and ointments along with prescription anti-fungal drugs on the market, most keep the infection at bay but don't clear it. The infection is notoriously difficult to cure, and recent evidence suggests it may often be drug-resistant.

In this study, an international team of researchers decided to take a close look at the genetic makeup and sexual predilections of this fungus. They collected 135 different Trichophyton rubrum samples from around the world and determined their mating type by searching the fungal genome for either the alpha or the HMG domain, which is essentially the molecular equivalent of looking between a dog's legs. The researchers were amazed to find that all but one of the samples were from a single mating type.

Though the findings suggested the fungi had become asexual, the scientists wondered if they would mate if given the opportunity. They placed the isolates in petri dishes along with a variety of potentially compatible mating types, under a variety of different conditions, and then waited to see if any magic would happen. After five months, the researchers looked at the petri dishes under a light microscope, scanning for the growth of coiled appendages that might contain spores. They didn't see any.

Curious, the researchers sequenced the genome of the organism. They found that the organism is very clonal, meaning that different isolates (populations) are nearly perfect clones of each other, with little variation from one genome to the next. Any two genomes of Trichophyton rubrum are 99.97 percent identical, which translates to three differences out of every 10,000 genetic letters. Other fungi such as Cryptococcus are only 99.36 percent identical, differing in 64 out of 10,000 letters, making them 21 times more diverse than the toenail fungus.

"Such incredibly high clonality across isolates from around the world is remarkable, and suggests that this organism is very well adapted to humans," said Christina Cuomo, PhD, senior study author and a group leader for the Fungal Genomics Group at the Broad Institute of MIT and Harvard.

But there is a silver lining. Because the fungus is so clonal and could also be asexual, its ability to adapt further may be more limited than some other fungi. Thus, any new strategies that researchers could develop against this species may have a higher chance of success than those targeting sexual species, which are more capable of mutating or amplifying drug-resistance genes.

Researchers who analyzed gene expression in synovial tissue samples from rheumatoid arthritis patients' joints identified different patterns that may be clinically meaningful. The findings, which are published in Arthritis & Rheumatology, indicate that the mechanisms of pain differ in patients with different synovial subtypes of rheumatoid arthritis, and they may help guide clinicians as they develop optimal treatment strategies for patients.

"We were surprised to find that some patients had high pain, tenderness, and even swollen joint counts while exhibiting minimal inflammation in their tissue or blood. This suggests that some patients can have high disease activity scores with little inflammation," said lead author Dr. Dana Orange, of The Rockefeller University. "It stands to reason that patients with minimal tissue inflammation may not respond to our usual immune-targeting drugs."

Prior studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs) may be linked with higher cardiovascular risks, but few have assessed potential different cardiovascular risk between NSAID classes or across individual NSAIDs.

A British Journal of Clinical Pharmacology study including 55,629 patients with hypertension in a Taiwanese database did not observe different cardiovascular risks in patients who received cyclooxygenase-2 enzyme selective NSAIDs or nonselective NSAIDs during 4 weeks of follow-up.

The study also found no apparent difference in cardiovascular risk when comparing celecoxib with diclofenac, ibuprofen, or naproxen, although a significantly increased risk was observed when comparing celeocxib with mefenamic acid.

"Our results provide important information about the comparative safety of alternative NSAID use in patients with hypertension in real-world settings. Under low-to-moderate daily dose and a short-term treatment period, most commonly used NSAIDs have similar cardiovascular safety profiles," said co-author Dr. Chia-Hsuin Chang, of the National Taiwan University Hospital.

AUGUSTA, Ga. (Feb. 22, 2018) - A portable ultrasound can help nephrologists better detect fluid in the lungs of patients with end-stage kidney disease, according to a study by physicians at the Medical College of Georgia at Augusta University.

Patients with the disease, characterized by the kidneys' inability to work well enough to meet your body's basic needs, can accumulate fluid all over their bodies, and commonly in the lungs says second-year nephrology fellow Dr. Omar Saleem.

The trick is knowing where the fluid is and how much needs to be removed, Saleem says, and accumulation in the lungs can lead to complications like heart failure and high blood pressure.

Saleem, and other faculty and students from MCG, will present their research at the Southern Regional Meetings of the American Federation for Medical Research this week in New Orleans.

When it comes to diagnosing "wet lungs," the standard has been listening for chest crackling sounds with a stethoscope and measuring blood pressure - more fluid on the lungs prevents oxygen from being absorbed into the bloodstream. "But that's quite subjective," he says. "For instance, sometimes you can't hear the crackling. That's why the ultrasound adds to the physical exam."

He examined 24 ESKD patients at Augusta University Health. As part of the normal physical exam, he placed the ultrasound probe on the patients' chests to get a good view of the lungs. If there was fluid, he would see B-lines, which are actually reflections of the water in the lungs that appear as long, vertical white lines on an ultrasound. The higher the number of B-lines and the more intense, or bright, they were, the more fluid was present.

"This is an objective marker of lung water, the accumulation of which can lead to serious complications for already fragile patients. We're right at the edge here and we're trying to keep people from tipping over into heart failure," says Dr. Stanley Nahman, MCG nephrologist and director of the Department of Medicine's Translational Research Program. "This will change the way we manage these people with dialysis."

Physicians can then better target dialysis treatments. "I can set the fluid removal goal at a higher point during dialysis," Saleem says. "Where I might normally take off two liters of fluid, I might take three or four in someone who has water in their lungs"

"Our kidneys take all the fluid that comes from normal intake through diet and drinking and they filter the waste products, which we excrete in urine," says "But these patients rarely urinate. They count on dialysis to keep their fluid in balance." The kidneys also help the body reabsorb essential nutrients into the bloodstream.

Hemodialysis uses a special filter called a dialyzer - or an artificial kidney - to filter waste, balance electrolytes and remove extra fluid. End-stage kidney disease (ESKD) patients are typically receiving dialysis three times each week.

Also presenting is Dr. Elizabeth Chu, a second-year internal medicine resident and 2016 MCG graduate, who proposes a new way to manage the way former inmates with ESKD re-enter society.

The Georgia Department of Corrections is one of the largest state correctional systems in the country, supervising nearly 52,000 inmates - many of them have ESKD and are on three-times weekly dialysis at Augusta State Medical Prison. But there is currently no plan to help them figure out how to navigate treatment when they get out of prison, Chu says.

"We were finding that nephrologists were frequently called to the emergency room to provide dialysis to former inmates with ESKD and nowhere else to go," she says. "When we consulted Augusta State Medical Prison regarding discharge of these patients, we found that most did not have active Medicare, which pays for dialysis. When they were released, inmates were given copies of their dialysis run sheets, documenting their treatments, the address of the nearest Social Security Office with instructions to 'go sign up for Medicare' and instructions to go to the ER for their dialysis until they got Medicare."

With an average 12-week waiting period for Medicare, these former inmates were not eligible to enroll at private dialysis treatment centers, instead heading to their local emergency rooms for up to 36 treatments before they received insurance through Medicare.

"Not only was the funding gap resulting in erratic and inadequate care, but it also generated unnecessary costs borne by society," Chu says.

A year of dialysis (150 treatments) in an outpatient facility costs about $89,000; one dialysis treatment in the Augusta University Medical Center Emergency Department is around $25,000. For a patient, receiving three treatments a week over 12 weeks costs could add up to around $900,000. The lack of regular medical care can also result in complications and unnecessary hospitalizations, which are also costly.

To define the scope of the problem, Chu reviewed the records of all ESKD patients at Augusta State Medical Prison from 2014-16, looking for demographic information and anticipated re-entry years. She also made comparisons to a national cohort.

Over the three-year study period, the prison had 180 dialysis patients. From this group, 73, or 41 percent, were discharged from the prison, which is an average of 24 patients per year - comparable to numbers for prison systems outside of Georgia.

"Assuming 24 re-entry patients per year at an ER dialysis cost of $900,000 per patient, the state could save around $21 million annually," Chu said.

She proposes a Comprehensive Disease Management Program instead. Chu says hiring a re-entry navigator with a background in corrections social work and case management who initiates applications for Medicare four to six months before inmates are released would be a huge help. This navigator would also contact dialysis centers, hospitals and parole officers in the area where the inmate intended to live, and could have post-release visits at least monthly for two years, to make sure patients were following through with treatment plans.

It is difficult to distinguish males from females among King Penguins, but a new Ibis study reveals that King Penguins can be sexed with an accuracy of 100% based on the sex-specific syllable pattern of their vocalisations. Using the beak length, King Penguin individuals can be sexed with an accuracy of 79%.

The new findings may help investigators understand how King Penguins choose mates, and they offer a cost- effective, non-invasive technique for researchers to sex King Penguins in the field.

"The sex-specific syllable pattern in King Penguin calls is a very interesting finding, both from an evolutionary perspective as it is rare in non-passerine species, but also because it allows researchers with very little training to reliably identify the gender of King Penguins without handling the individuals," said lead author Hannah Kriesell, of the Centre Scientifique de Monaco and the University of Strasbourg.

For previously healthy children, brain infections are rare. But about one out of every 10,000 people who are exposed to common viruses like herpes simplex or influenza will develop a potentially deadly disease, encephalitis.

Rockefeller's Jean-Laurent Casanova has identified mutations in a single gene that may explain what goes wrong in cases of encephalitis of the brain stem, the part of the brain that controls many basic functions including heart rate and breathing. Shen-Ying Zhang, assistant professor of clinical investigation in the Casanova lab, evaluated seven children from unrelated families who had been exposed to a common virus (herpes simplex virus 1, influenza virus, or norovirus) and developed a life-threatening or lethal infection of the brain stem. The scientists discovered mutations in a gene called DBR1, which is responsible for producing a protein that helps process the loops formed in RNA during a step called mRNA splicing. Without it, immunity to viruses is selectively impaired in the brain stem. Casanova's experiments, published in Cell, point to an almost complete loss of DBR1 as the culprit, enabling brain stem virus invasion in all seven patients. The findings also reveal an unexpected connection between an RNA processing mechanism and protective immunity in a specific region of the brain.

The study is a new example of the Casanova lab's ongoing work to identify mutations that underlie infectious diseases in otherwise healthy individuals. Previous work has found genetic factors that cause increased vulnerability to staph infections, the flu, and fungal infections, among others.