Culture

Like humans, bacteria live together in communities, sometimes lending a hand -- or in the case of bacteria, a metabolite or two -- to help their neighbors thrive. Understanding how bacteria interact is critical to solving growing problems such as antibiotic resistance, in which infectious bacteria form defenses to thwart the medicines used to fight them.

Now, researchers at the University of Delaware have discovered that bacteria do more than just work together. Bacterial cells from different species can combine into unique hybrid cells by fusing their cell walls and membranes and sharing cellular contents, including proteins and ribonucleic acid (RNA), the molecules which regulate gene expression and control cell metabolism. In other words, the organisms exchange material and lose part of their own identity in the process.

This unprecedented observation, which was reported on Tuesday, Sept. 1 in mBio, a journal of the American Society for Microbiology, has the potential to shed light on unexplained phenomena affecting human health, energy research, biotechnology and more.

The research team, led by Eleftherios (Terry) Papoutsakis, Unidel Eugene Du Pont Chair of Chemical and Biomolecular Engineering, studied interactions between Clostridium ljungdahlii and C. acetobutylicum. These species of bacteria work together in a syntrophic system, producing metabolites that are mutually beneficial to each other's survival.

The team found that C. ljungdahlii invades C. acetobutylicum. The two organisms combine cell walls and membranes and exchange proteins and RNA to form hybrid cells, some of which continue to divide and in fact differentiate into the characteristic sporulation program.

"They mix their machinery to survive or do metabolism, and that's kind of extraordinary, because we always assumed that each and every organism has its own independent identity and machinery," said Papoutsakis.

Previously, researchers have observed that bacteria could exchange some material through nanotubes. The combination into hybrid cells was unexpected.

"This is the first time we've shown this in this bacteria, and it's also a new mechanism of how material is exchanged," said Kamil Charubin, a doctoral student in chemical and biomolecular Engineering and first author of the paper.

Although this phenomenon of interspecies microbial fusion is now being reported for the first time, it is likely ubiquitous in nature among many bacterial pairs.

So why do bacteria bother to fuse together? The simple answer is likely because this process allows the microbes to share machinery that will increase their odds of survival.

For example, some pathogenic bacteria -- those that can cause disease -- may borrow proteins from other antibiotic-resistant bacteria in order to shore up their own resistance. Some bacteria might borrow machinery from others in order to evade detection by the immune system. This could also help to explain why some bacteria are difficult to culture, or grow for study or medical diagnostic purposes. These difficult-to-culture bacteria might combine with or work with and depend on other microorganisms for their existence instead of growing and multiplying on their own.

The team's findings may influence understanding of the evolution of biology because once bacterial species share machinery, they can evolve together instead of only evolving on their own, said Papoutsakis.

September 2, 2020 - States that have expanded Medicaid eligibility under the Affordable Care Act have seen an "early surge in demand" for hip and knee replacement surgery, reports a study in the September 2, 2020 issue of The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

"Patients with Medicaid expansion plans have a shorter time from enrollment to the surgical procedure, suggesting that there may be an unmet need for total hip arthroplasty [THA] and total knee arthroplasty [TKA] among newly enrolled Medicaid expansion beneficiaries," according to the new research by Christopher J. Dy MD, MPH, and colleagues of Washington University School of Medicine, St. Louis, Mo. "This need should be considered by surgeons, hospitals, and policymakers in ensuring access to care."

Shorter Times to THA and TKA in Medicaid-Expansion Patients

With use of data from a Medicaid managed care program, the researchers analyzed the timing of primary THA and TKA procedures in adults under age 65 between 2008 to 2015. The study included patients in four states that expanded Medicaid eligibility in 2014 (Illinois, Ohio, Oregon, and Washington) and four states without Medicaid expansion (Louisiana, Mississippi, Texas, and Wisconsin).

Times to joint replacement surgery were compared for Medicaid-expansion patients, a relatively healthy group of adults without dependent children; Medicaid patients with Supplemental Security Income (SSI), a group of relatively unhealthy adults with disabilities; and patients receiving Temporary Assistance for Needy Families (TANF), who are parents of children with Medicaid insurance. The analysis included a total of 4,117 patients across groups.

The median time to THA or TKA surgery for Medicaid-expansion patients (7.5 months) was significantly shorter than for SSI patients (16.1 months) and TANF patients (12.2 months).

A further analysis was adjusted for other factors, including patient age and sex, social deprivation, surgeon supply and reimbursement, and state-level Medicaid enrollment. The results of that analysis suggested that the time to THA or TKA was 70 percent shorter for Medicaid-expansion patients than for SSI patients. For TANF patients, the time to THA or TKA was 24 percent shorter than for SSI patients.

Expansion of state Medicaid programs has led to dramatic increases in insurance coverage among Americans. In August, Medicaid expansion was approved by voters in Missouri, making it the 38th state to expand Medicaid coverage.

Medicaid-expansion states have seen increases in certain "elective" but medically indicated surgical procedures, including THA and TKA, which raises questions of whether pent-up demand will strain the capacity of the health-care system or exceed the supply of orthopaedic surgeons willing to accept Medicaid insurance.

The new study finds a significantly shorter time from enrollment to THA and TKA for Medicaid-expansion patients compared with those with other routes of access to Medicaid coverage. "Our findings may represent an unmet need for THA and TKA among newly enrolled beneficiaries with Medicaid expansion plans," Dr. Dy and coauthors write. They suggest that Medicaid expansion is likely to lead to "an early surge in demand rather than a gradual increase."

"This need should be considered by surgeons, hospitals, and policymakers in ensuring access to care," Dr. Dy and coauthors conclude. They believe that healthcare policy and resource planning should also consider the existing disparities in access to orthopedic care already faced by Medicaid patients, as surges in demand may exacerbate these differences.

The human brain has about 100 billion neurons, linked in intricate ways, that the Spanish neuroanatomist Ramón y Cajal compared to "the impenetrable jungles where many investigators have lost themselves."

But to decipher how the brain works and understand how it can go awry in many diseases, it is essential to figure out how many classes of neurons it actually has and how they are connected with each other.

Now, in a paper published recently in Nature Neuroscience, a Columbia-led international group has proposed a unified nomenclature of the neurons of the cerebral cortex, the outermost layer of the brain that plays a key role in attention, perception, awareness, memory, language, and consciousness.

"A broadly agreed-upon classification is essential to archiving the hundreds of neuron types and their properties," said Rafael Yuste, a professor in the Department of Biological Sciences at Columbia University. "If we could decipher how the cortex is built and what it does, one could scientifically understand our minds."

How to classify neurons has been much debated since the inception of modern neuroscience. Many efforts to describe their anatomical, physiological, and molecular features have been unsuccessful due to their cellular diversity, Yuste said.

During the last two decades, however, the Human Genome Project has produced a host of molecular methods that enable identifying and phenotyping cells in great numbers.

"This molecular revolution is generating databases that are complete, accurate, and permanent--a triumvirate considered the golden standard of biology," Yuste said.

In particular, using highly automated techniques that sequence the RNA of individual cells rapidly and cost-effectively, several groups have started to assemble datasets to classify cell types in the cortex. "The approach enables sampling tens of thousands of cells, generating what could be an essentially complete coverage of all the existing cell types in the cortex," Yuste said.

Two years ago, during discussions at an international meeting on cortical neurons in Copenhagen, participants agreed that the time was right to finally tackle the creation of a unified classification.

A group of 74 scientists proposed the use of single-cell RNA sequencing as the skeleton for a unified classification of cortical neurons. Known as the "Copenhagen Classification," the proposal is described in the Nature Neuroscience article.

"This could be a historic event, as it tackles one of the core problems in neuroscience," Yuste said. "A unified framework is important not only for researchers and clinicians interested in understanding how the cortex works but also could inspire similar community classifications of cells."

In fact, he added, "there are major consortia worldwide charted with classifying all the cells in the body something that could be a breakthrough for biology and medicine."

With neuroscience rapidly transitioning to digital data, the researchers propose the classification be updated regularly using a type of algorithm often employed by the software industry for automatic data aggregation.

"It's exciting to think that neuroscientists in the not-too-distant future could finally, through technology, break the impasse that has plagued us for centuries," Yuste said.

CATONSVILLE, MD, September 2, 2020 - If you are a budget-conscious traveler, there is a chance you've used a travel site aggregator like Orbitz to book your air transportation. Or, perhaps you shopped around on multiple aggregators, and made your final booking on an airline website. Did you ever wonder if you were presented with all airline options, or what kind of itineraries you could have received had you explored all airline sites one by one? Between aggregators and airlines, who ultimately has the upper hand?

Those questions were on the minds of two data scientists who conducted a comprehensive study on who has more clout: the airline or the aggregator? What they found was that the aggregator can come out losing the most when its site is not comprehensive.

The research study, to be published in the September issue of the INFORMS journal Marketing Science, titled "Value of Aggregators," is authored by Selin Akca of the University of Zurich and Anita Rao of the University of Chicago.

"Search aggregators, such as Google, Kayak, Expedia, and Orbitz, improve consumers' search experience by providing a quick and comprehensive view of all available options," said Rao. "But those aggregators are facing increased scrutiny by regulatory authorities who fear that many firms are now at the mercy of aggregators and their ranking algorithms. This can pose significant operational, and even survival challenges for firms that are not part of an aggregator."

At the same time, some firms like Southwest Airlines have consistently bypassed aggregators, choosing instead to sell directly to consumers. This has given successful firms more market power.

To determine who benefits the most in the airline-aggregator relationship, the study's authors conducted an in-depth analysis of a 2011 dispute between American Airlines and aggregators Orbitz and Expedia, which centered on distribution fees on flight reservation systems.

"That dispute created a clear shift in the choice set available to consumers visiting Orbitz, with the timing being driven entirely by the contract renegotiation deadline," said Akca. "Expedia then delisted American's flights for a shorter three-month period in 2011. During that time, by bypassing the aggregators, American saved on its distribution costs, and its fares were not being presented on either Orbitz or Expedia."

The researchers revealed that loyalty to airlines is more common than loyalty to aggregators. According to the authors, nearly 52% of aggregator users browse only one airline, while most users use multiple aggregators in their searches. This means that more consumers tend to express loyalty to a specific airline over a specific aggregator, and they will use multiple aggregators to get the best option on the airline to which they are most loyal from a brand perspective. This further underscores the need for aggregators to be more comprehensive.

"When we studied the dispute between American Airlines and the aggregators, we found that the aggregator was negatively impacted in both site visits and purchases," said Rao. "Site visits at both Orbitz and Expedia dropped by nearly 11%, and purchases declined 2%."

Akca added, "Our results suggest that aggregators and search engines do not always have substantial market power. We learned that where consumers can choose between multiple aggregators and fewer airlines, the aggregator does not have as much market power as many might assume."

New Rochelle, NY, September 2, 2020—A meta-analysis of non-human primate (NHP) studies showed that adeno-associated virus (AAV) gene therapy often caused dorsal root ganglion (DRG) pathology. There were no clinical effects. The study is reported in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website through October 2, 2020.

The dorsal root ganglion is a cluster of neurons in the dorsal root of a spinal nerve. DRG pathology was present in 83% of NHP given AAV through the cerebrospinal fluid and 32% of NHP that received an intravenous injection.

 The data suggest that “DRG pathology is almost universal after AAV vectors are delivered into the cerebral spinal fluid of nonhuman primates. However, none of the animals receiving a vector expressing a therapeutic transgene displayed any clinical signs,” stated James M. Wilson, MD, PhD, a professor of Medicine and director of the Gene Therapy Program and the Orphan Disease Center, and coauthors from the Perelman School of Medicine at the University of Pennsylvania. 

“The DRG pathology associated with AAV has triggered an increase in the intensity of preclinical evaluation of AAV vectors prior to initiation of clinical trials of new vectors,” according to Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School. “The insights offered by Dr. Wilson’s paper provide an excellent summary perspective on this phenomenon, which could potentially eliminate the need for a number of redundant preclinical safety studies and thus shorten the path to the clinic for new vectors.”

Individual studies utilized for data extraction were supported by REGENXBIO (all studies previously published), Biogen (some studies previously published), Passage Bio, Amicus Therapeutics, ODC MPS I pilot grant MPS-18-D010-01 and MPS-19-001-0, Janssen, Cure FA, Rett Syndrome Research Trust and Elaaj Bio. These entities funded the original studies whose samples were later run through the comparative meta-analysis covered in the manuscript. The studies, company sponsor, and transgenes representing each data point are not disclosed.

About the Journal
Human Gene Therapy ,the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of human gene therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.

About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 90 journals, books, and newsmagazines is available on the  Mary Ann Liebert, Inc., publishers website.

Journal

Human Gene Therapy

DOI

10.1089/hum.2020.167

BIRMINGHAM, Ala. - Why is the COVID-19 virus more dangerous in people with comorbidities?

Sadis Matalon, Ph.D., of the University of Alabama at Birmingham and colleagues in Texas and San Francisco asked that question in a hypothesis paper published online in Physiological Reviews. This study was made available online in March 2020 ahead of final publication in issue on July 1, 2020. They reviewed, in detail, research literature for comorbidities like hypertension, diabetes, coronary heart disease, cerebrovascular illness, chronic obstructive pulmonary disease and kidney dysfunction, as well as many viral studies, studies of COVID-19 pathology and clinical presentation, and literature on the life-threatening acute respiratory distress syndrome.

Twelve days later, UAB Professor Emeritus Timothy Ness, M.D., Ph.D., posted plans on ClinicalTrials.gov for an exploratory COVID-19 outpatient study to test Matalon's hypothesis and prevent worse clinical outcomes.

In the Physiological Reviews paper, the researchers noted that all those comorbidities feature elevated levels of the extracellular protease plasmin. Plasmin is able to nick proteins at amino acid sequences called furin sites. For many viruses, this nicking at furin sites increases their infectivity. Both SARS and MERS -- the two virulent coronaviruses that are related to the COVID-19 virus -- "have evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population," the researchers wrote.

They noted that the COVID-19 virus, SARS-CoV-2, also has a furin site on its spike protein, the vital, viral protein for viral attachment to a lung cell. The researchers proposed that plasmin may cleave that furin site in the spike protein to increase its infectivity and virulence, and they hypothesized that, "the plasmin system may prove a promising therapeutic target for combating COVID-19."

Ness already knew there is an inexpensive, commonly used drug -- tranexamic acid, or TXA -- that targets plasmin by inhibiting its conversion from the inactive precursor, plasminogen, to the active protease, plasmin.

TXA is approved by the U.S. Food and Drug Administration for treatment of heavy menstrual bleeding because having lower plasmin levels allows better clotting. TXA has a long track record of safety and is commonly given off-label. At UAB Hospital, TXA is used perioperatively as a standard-of-care for orthopedic and cardiac bypass surgeries; it is commonly used for hemorrhaging trauma patients and also has been used for spinal surgery, neurosurgery and corrective jaw surgeries. It is currently being studied for perioperative use in Cesarean section surgeries.

For the clinical trial, Ness and colleagues have started a double-blind study, giving either TXA or a placebo pill to COVID-19 outpatients who were recently diagnosed with COVID-19. Patients also receive an anticoagulant. The overall goal of the exploratory study is to assess both safety and efficacy of five days of TXA versus placebo in the COVID-19 population. Enrollment is ongoing.

Ness and colleagues hypothesize that the TXA treatment will reduce the infectivity and virulence of the virus, as measured by reduced need for hospitalization within a week if a patient's condition deteriorates. Adults 19 years old and older are eligible, and all patients -- whether in the control group or the TXA group -- receive standard care as directed by their primary caretakers.

BOSTON - Researchers from Boston Medical Center's Maxwell Finland Laboratory for Infectious Diseases have identified properties in placenta tissue that may play an important role in preventing the transmission of COVID-19 from a mother with the virus to her fetus. The study results demonstrate that the COVID-19 virus universally invades the placenta in cases with and without evidence of fetal infection, highlighting the protection that the placenta may offer against COVID-19 infection as current data indicates a less than five percent COVID-19 transmission rate in newborns from their mothers. Published in Placenta, these results underscore the importance of using placenta tissue in COVID-19 research studies aimed at developing novel ways to diagnose, treat and prevent COVID-19 virus transmission.

For this study, the researchers examined placental tissue, which shares many developmental and physiological similarities with the lung and the immune response of the small and large intestine, making it a key source of human tissue that can be used for ongoing COVID-19 research. It also contains a unique expression pattern of COVID-19 receptors that are different from other organs, which could be helpful in the development of COVID-19 treatments.

"The results of this study provide evidence for ongoing research of COVID-19 infection at the maternal-fetal interface as means to better understand virus transmission and infection in other human tissues," said Elisha Wachman, MD, a neonatologist at Boston Medical Center, associate professor of pediatrics at Boston University School of Medicine, and principal investigator of this study. "Previous research has shown that the placenta protects the fetus from various types of infection, and exploring the particular ways in which it protects the fetus from COVID-19 transmission may help identify new targets of COVID-19 prevention and treatment."

Throughout April and May 2020, samples from 15 COVID-19 positive maternal-fetal dyads were collected for this study; five cases had evidence of fetal transmission. The placental tissue of the positive cases was analyzed and compared with ten COVID-19 negative controls. The researchers found that the COVID-19 virus was present in the placental tissues in cases with and without evidence of fetal infection. They also found that the placenta contains a unique pattern of cell surface proteins (TMPRSS2 and ACE2) that are important for COVID-19 viral entry, which is different from other cell types. The demographics of mother-baby dyads were also studied and no differences were found to be significant, showing the fetal transmission does not discriminate.

"Determining how the placenta could be preventing COVID-19 infections during pregnancy can help provide clues on how to prevent infection in other organs, such as the lungs and gut," said Elizabeth Taglauer, MD, PhD, a neonatologist and placental biologist based at Boston Children's Hospital. "As a readily available tissue for research, the placenta can be a valuable source of scientific study for a variety of human diseases in pregnancy and beyond."

HOUSTON - (Sept. 2, 2020) - Microscopic crystals in tantalum disulfide have a starring role in what could become a hit for 3D displays, virtual reality and even self-driving vehicles.

A two-dimensional array of the material has unique optical characteristics that can be controlled in ambient conditions and under general illumination, according to engineer Gururaj Naik and graduate student Weijian Li of Rice's Brown School of Engineering.

When they pull a two-dimensional sliver off a bulk sample (with that tried-and-true tool, adhesive tape) and shine light on it, the layered material rearranges the charge density waves of electrons that flow through, altering its refractive index.

Light emitted along the affected axis changes its color depending on the strength of the light that goes in.

The discovery is detailed in the American Chemical Society journal Nano Letters.

"We need an optical material that can change the refractive index for applications like virtual reality, 3D displays, optical computers and lidar, which is necessary for autonomous vehicles," said Naik, an assistant professor of electrical and computer engineering. "At the same time, it has to be fast. Only then can we enable these new technologies."

Tantalum disulfide, a semiconducting, layered compound with a prismatic metal center, appears to fit the bill. The material is already known for harboring charge density waves at room temperature that allow adjustments to its electrical conductivity, but the strength of light input also changes its refractive index, which quantifies the speed at which light travels through. That makes it tunable, Naik said.

When exposed to light, the tantalum layer reorganizes into a lattice of 12-atom stars, like the Star of David or sheriff's badges, that facilitate charge density waves. How these stars are stacked determines whether the compound is insulating or metallic along its c-axis.

It turns out that also determines its refractive index. Light triggers the stars to realign, changing the charge density waves enough to affect the material's optical constants.

"This belongs to a class of what we call strongly correlated materials, which means the electrons strongly interact with each other," Li said. "In this case, we can predict the properties that show a strong response to some external stimulus."

That the stimulus is as mild as ambient white light is a plus, Naik added. "This is the first material we've seen where the interaction of light happens not just with single particles, but with a collection of particles together, at room temperature," he said. The phenomenon appears to work in tantalum disulfide as thin as 10 nanometers and as thick as a millimeter, he said.

"We think this is an important discovery for those who study strongly correlated materials for applications," Naik said. "We show light is a very powerful knob to change how correlation extends in this material."

COLUMBUS, Ohio - A bioengineering technique to boost production of specific proteins could be the basis of an effective vaccine against the novel coronavirus that causes COVID-19, new research suggests.

Scientists manipulated a natural cellular process to ramp up levels of two proteins used by the virus to infect other cells, packaged the protein-boosting instructions in nanoparticles and injected them into mice. Within a month, the mice had developed antibodies against the SARS-CoV-2 virus.

The technique involves altering specific sequences of messenger RNA, molecules that translate genetic information into functional proteins. While these sequences are not translated to proteins, the researchers changed their structures to promote higher-than-usual levels of proteins. The sequences are known as untranslated regions, or UTRs.

"We've been engineering messenger RNA for four years, and earlier this year we made some progress identifying a role for UTRs - and then COVID-19 happened," said Yizhou Dong, senior author of the study and associate professor of pharmaceutics and pharmacology at The Ohio State University.

Though Phase 3 clinical trials of fast-tracked COVID-19 vaccine candidates are in progress, Dong said his lab's platform offers a potential alternative.

"If the current vaccines work well, that's wonderful. In case the field needs this, then it's an option. It worked as a vaccine is expected to, and we can scale this up very fast," he said. "For now, it's a proof of concept - we've demonstrated we can optimize a sequence of messenger RNA to improve protein production, produce antigens and induce antibodies against those specific antigens."

The study is published today in the journal Advanced Materials.

The crux of the method is typical to vaccine development: using snippets of a pathogen's structure to produce an antigen - the foreign substance that triggers an appropriate immune response - and finding a safe way to introduce it to the body.

But the engineering technique takes antigen design to a new level by making use of messenger RNA UTRs, Dong said.

His lab worked with the two UTRs that bookend the start and finish of protein assembly, functioning as regulators of that process and influencing how the resulting protein interacts with others. UTRs themselves are strings of nucleotides, the molecules that compose RNA and DNA.

"For our application we tried to optimize the UTRs to improve the protein production process. We wanted as much protein produced as possible - so we can give a small dose of messenger RNA that produces enough antigen to induce antibodies against the virus," Dong said.

The team experimented with two potential antigens that the novel coronavirus is known to use to cause infection: a spike protein on its surface and a receptor binding domain, a component of the spike protein, that the virus uses to make its way into host cells - a necessary step to make copies of itself. Both are used in other SARS-CoV-2 vaccine candidates.

After manipulating the messenger RNA for these two proteins, the team encased them in lipid nanoparticles developed previously in Dong's lab. They injected mice with the experimental vaccine and gave them a booster two weeks later. A month after the first injection, immune cells in the mice had taken up the antigens of the two proteins and developed antibodies against them.

"It takes some time for the immune system to process the antigens and have cells produce antibodies," Dong said. "In this study, we detected antibodies after 30 days."

And even if this vaccine candidate is not needed for COVID-19, he is continuing to refine this latest method of engineering messenger RNA.

"UTR is a platform that we can apply to any type of messenger RNA. We are exploring other therapeutics," Dong said.

A new study uses magnetic resonance elastography to compare the stiffness of the hippocampus in patients who have epilepsy with healthy individuals. The technique can improve the detection and characterization of the disease.

The study "Hippocampal stiffness in mesial temporal lobe epilepsy measured with MR elastography: Preliminary comparison with healthy participants" was published in NeuroImage: Clinical. The work was done through a collaboration with the Carle Neuroscience Institute and the Beckman Institute for Advanced Science and Technology at the University of Illinois Urbana-Champaign.

Mesial temporal lobe epilepsy is the most common form of epilepsy that is resistant to medication. Unfortunately, current detection methods, which include magnetic resonance imaging, can only visualize the epilepsy-induced changes in the brain after significant damage has occurred.

"The structural changes in the brain, in response to seizures, causes the death of neurons and the formation of scar tissue," said Graham Huesmann, a neurologist at Carle and a research assistant professor of molecular and integrative physiology, who is a part-time faculty member at the Beckman Institute. "By the time we see any changes on the MRI, the disease is pretty advanced. We wanted to detect these changes earlier using MRE."

MRE uses the MRI scanner to look at the stiffness of brain tissues. "MRE is a non-invasive technique. Essentially a person lies on a little vibrating pillow, sending the vibrations into the tissues which change as the composition and the organization of the tissue changes," said Hillary Schwarb, a Beckman Institute research scientist who also is affiliated with the Interdisciplinary Health Sciences Institute. "It's like hitting the surface of a pond and watching the ripples that are formed. If there is a big rock underneath the surface, those ripples are going to move and change."

MRE is already used clinically for the staging of various liver diseases and has replaced invasive liver biopsies. "For epilepsy in the brain, MRE may prove similarly useful for staging progressive epilepsies, like mesial temporal lobe epilepsy, toward earlier detection" said Aaron Anderson, a Carle Foundation Hospital-Beckman Institute Postdoctoral Fellow.

The researchers used MRE to see if there were any changes in the hippocampus. "The hippocampus is the part of the brain that is involved in memory," said Brad Sutton, a professor of bioengineering and the technical director of Beckman's Biomedical Imaging Center. "In the early stages of epilepsy, there is a little bit of damage to the structure, which we can detect with MRE."

Early detection of these changes is critical for the disease, especially because it causes very mild symptoms in the beginning stages. "It starts with a feeling of déjà vu, which becomes more common as the disease progresses. Eventually it develops into a form that is medication resistant," Huesmann said. "MRE allows us to detect these changes earlier affording us the opportunity to change the course of treatment."

"MRE can also inform doctors about when to intervene with surgery," said Tracey Wszalek, the director of the Biomedical Imaging Center. If the surgery is done too early, it may affect a part of the brain that is still in use. However, if it is done too late, the patients lose their ability to make new memories.

The researchers are now focusing on how to optimize the technique and also look at other types of epilepsy. "All of our imaging techniques currently depend on looking at brain chemistry and the static images of the brain," Huesmann said. "Using MRE to see how the brain jiggles is an exciting way to approach this problem. It is also an inexpensive technique and can therefore be used by anyone."

Below please find a summary and link(s) of new coronavirus-related content published today in Annals of Internal Medicine. The summary below is not intended to substitute for the full article as a source of information. A collection of coronavirus-related content is free to the public at http://go.annals.org/coronavirus.

COVID-19 death risk varies significantly by age, race, ethnicity and sex

Infection fatality rate 2.5 times greater than flu for patients over 60

Regardless of age, IFR 3 times higher in non-whites

COVID-19 infection fatality ratios (IFR) vary significantly and in order of magnitude by age, race, ethnicity and sex. Risk for death is significantly higher among patients who are older or those who are non-White. A brief research report is published in Annals of Internal Medicine.

Current mortality rates for COVID-19 are calculated from confirmed cases, which overestimates IFR. To calculate the true IFR among the community-dwelling population, researchers from Indiana University Richard M Fairbanks School of Public Health and the School of Medicine combined prevalence estimates from a statewide random sample with Indiana vital statistics data of confirmed COVID-19 deaths for all state residents aged 12 and older. They excluded deceased individuals, incarcerated persons, and nursing home residents from the random sample. Participants were tested April 25 to April 29 2020 for active viral infection and SARS-CoV-2 antibodies, which would indicate prior infection, and demographic information was collected.

The researchers found that the overall noninstitutionalized IFR was 0.26 percent. Persons younger than 40 years had an IFR of 0.01 percent, and those aged 60 or older had an IFR of 1.71 percent. Indiana's IFR for noninstitutionalized persons older than 60 years was found to be just below 2 percent. In comparison, the ratio is approximately 2.5 times greater than the estimated IFR for seasonal influenza, 0.8 percent, among those aged 65 years and older. With regard to race, Whites had an IFR of 0.18 percent, and non-Whites had an IFR of 0.59 percent. The researchers note that the IFR for non-Whites is more than 3 times that for Whites, despite COVID-19 decedents in that group being 5.6 years younger on average. Read the full text: https://www.acpjournals.org/doi/10.7326/M20-5352.

Media contacts: A PDF for this article is not yet available. Please click the link to read full text. To reach the lead author, Justin Blackburn, PhD, please contact Amanda Briggs at amanbrig@iu.edu.

East Hanover, NJ. September 2, 2020. Researchers conducting a large international study of progressive multiple sclerosis (MS) examined the impact of the global outbreak of coronavirus disease 2019 (COVID-19) on their study participants. Compared with pre-COVID baseline assessments, findings from a COVID Impact Survey administered during lockdown showed minimal changes in depression, anxiety, and quality of life, and in the impact of MS symptomatology on activities of daily living.

The article, "The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis" (doi: 10.1007/s00415-020-10160-7) was published online August 19, 2020 in Journal of Neurology. The article is included in SpringerLink's COVID collection: https://link.springer.com/article/10.1007/s00415-020-10160-7

The authors are members of the CogEx Research Team, comprised of site investigators from Canada, the United States, Italy, the UK, Denmark, and Belgium. The COVID Impact Survey was administered during the suspension of a randomized clinical trial (RCT) involving 131 participants at 11 sites in the above six countries. The trial's principal investigator is Anthony Feinstein, MD, PhD, of the University of Toronto.

The COVID pandemic has had substantial impact on the general population, raising concern for populations at increased risk for infection, as well as for detrimental psychological and social effects of quarantine and social distancing requirements. The pause in the RCT provided an opportunity for investigators to assess the impact of the pandemic on the population with progressive MS in real time.

Participants from all sites responded to the COVID Impact Survey while under social restrictions from May 2020 to July 2020. COVID infection was reported by 4% of participants, according to lead author Nancy Chiaravalloti, PhD, director of the Centers for Neuropsychology, Neuroscience and Traumatic Brain Injury at Kessler Foundation. Comparing baseline with COVID assessments revealed minimal changes in depression, anxiety, and quality of life. Impact of MS symptomatology on daily life functions was also minimal, except in the small subset with COVID-19 infection, where the impact was significant.

"Minimal effects were not what we expected to see," said Dr. Chiaravalloti, noting that the findings were consistent across different continents. "People with progressive MS appeared to have adapted more effectively to the lockdown conditions. Knowing their increased risk, they may have been early adopters of safety precautions, which may have provided a sense of control that countered negative emotional reactions," she speculated. "They are also accustomed to living with medical uncertainly and social isolation, two major factors that fueled high levels of psychological discomfort in the general population."

The COVID Impact Survey showed that the majority of participants actively engaged in mental and physical activities during lockdown. ""This is not surprising given that the aim of the RTC was to measure the outcomes of such activities," Dr. Chiaravalloti reported. "Focusing on elements of a healthy lifestyle may have mediated the negative effects on wellbeing in this group with progressive MS."

More than half of all African American women in the United States report having at least one family member who is incarcerated, causing higher levels of depressive symptoms and psychological distress than previously understood.

The findings come from a new paper in the Journal of Marriage and Family, whose lead author, Evelyn J. Patterson, associate professor of sociology and a Vanderbilt Chancellor's Faculty Fellow, said the study sheds new light on the challenges facing African American women.

"Most studies that look at the impact of incarceration are examining people who are parents or the children of someone who is incarcerated. That means, if you're not a parent or a child of an incarcerated person, you're excluded," she said. Given that having a sibling incarcerated is the most common form of familial incarceration, prior work misses a large piece of the familial incarceration story. Further, African American women as a whole are rarely the central focus when people examine the toll of familial incarceration, especially those without children.

The study sought to measure the mental health impact on African American women of having a family member incarcerated. Further, the research examined whether social roles such as employment, marriage or parenthood added to, or eased, the psychological burden of having an immediate family member in jail or prison.

"In all models, familial incarceration was associated with worse psychological adjustment," the authors wrote. "Our findings showed that familial incarceration was associated with elevated psychological distress and depressive symptomology, extending a long line of studies documenting the consequences of familial incarceration." Examining role combinations, women who were employed but had no other social roles showed lower levels of psychological distress and depressive symptoms than women who occupied other roles such as marriage/partnership or motherhood.

In addition to Patterson, the co-authors included Ryan D. Talbert from the University of Connecticut and Tony N. Brown from Rice University. The study drew from a nationally representative survey of 1,961 never-incarcerated African American women.

Patterson said the study fits into a broader research context examining how marginalized populations, particularly African American families, face worse outcomes on measures of health and psychological well-being because of the societal burdens they face.

"From slavery, to lynching, to incarceration, generations of African American families have endured having their family members taken away. African Americans have had to learn how to compartmentalize this trauma and have survived, in part, due to their resilience," Patterson said. "But this resilience is a double-edged sword as these experiences worsen health outcomes."

With an increase in HIV and HCV infections as a consequence of the ongoing opioid epidemic, Boston Medical Center researchers found that only a small number of those who test positive for those infections at a drug detoxification center followed up for a clinical visit after their test. The study results showed that only 6 percent of those tested for HIV and HCV followed up with testing care, despite accessing healthcare multiple times. These data demonstrate the need for more coordinated approaches to help patients access testing and treatment, especially as these rates are likely to worsen due to the COVID-19 pandemic.

Published in The Journal of Infectious Diseases, the research findings show that rapid testing for HIV and HCV at a drug detoxification center has a distinct advantage over laboratory-based testing (96 percent compared to 42 percent) in venues serving hard-to-reach populations, demonstrating the opportunities for using drug detoxification centers more frequently for these tests.

One-half of US state health departments and territories are prioritizing identification of acute HIV cases, and moving away from rapid testing in community-based settings. In locations such as drug detoxification center, laboratory-based testing may result in fewer diagnoses due to loss to follow-up before result delivery. When performed in community-based setting, laboratory-based testing results take approximately three days to be delivered. In contrast, results for point-of-care rapid testing are available within 30 minutes.

"We currently have a cure for HCV and effective treatment for HIV," says Sabrina Assoumou, MD, MPH, an infectious diseases physician at Boston Medical Center. "Successfully identifying and linking patients to care at drug detoxification centers during the opioid epidemic could help decrease transmission and improve outcomes for these two infections."

A single-site randomized trial was conducted to compare test results delivery between laboratory-based and rapid testing for HIV and HCV at a short-term inpatient drug and alcohol detoxification center located in Boston. The study included 200 participants with a history of self-reported drug use and who accessed detoxification services at the center between November 2016 and July 2017. Among participants, 48 percent tested positive for HCV and 0.5 percent newly tested positive for HIV. During follow-up, reviews showed that only 6 percent with positive tests were successfully linked to care, attending an HIV or HCV-related visit within four months of testing.

By focusing on linkage to care within four months of testing, research suggests that certain individuals with a history of substance use disorder could greatly benefit from rapid testing to improve their access and continued involvement in care for these infections. Forty-one individuals who did not have a record of HCV-related follow-up utilized other healthcare services, with an average of three visits within four months, of which 61 percent were in an emergency department. Successfully implementing HIV and HCV testing at drug detoxification centers could help identify and link to care persons at-risk during the opioid epidemic, but doing so would require that results obtained in drug detoxification centers be available to nearby healthcare facilities.

"We hope that these findings will encourage changes in local and national HIV and HCV testing practices and policy at non-hospital-based settings caring for populations at-risk during the opioid epidemic," says Assoumou, also an assistant professor of medicine at Boston University School of Medicine.

DURHAM, N.C. - In just a few months, the COVID-19 pandemic swiftly and substantially worsened mental health among U.S. hourly service workers and their children - especially those experiencing multiple hardships, according to new research from the Center for Child and Family Policy at Duke University and Barnard College.

The study leverages real-time, daily survey data collected from Feb. 20, before the pandemic hit the U.S., to April 27, when it was well underway, to examine how the crisis affected parents' and children's mental well-being. The 645 survey respondents were parents of young children working in hourly service-industry positions in retail, food service or hotel industries in a large U.S. city.

Nearly half (49.5%) of the participants were Black Americans, 23% were Hispanic Americans, and 83% were women.

The findings appear today in Pediatrics.

The surveys showed strong, immediate impacts of the pandemic on vulnerable families. Parents saw quick deterioration in their own mental well-being, reporting more frequent "negative moods" since March 14, the day after the first major restrictions in response to COVID-19 were announced. The majority of respondents experienced multiple hardships, including household job loss (60%), income decline (69%), caregiving burden (45%) and illness (12%).

"The COVID pandemic has created substantial hardship for working families," said Anna Gassman-Pines, co-author of the study and associate professor of public policy at Duke's Sanford School of Public Policy. "What's worse is that the more hardship families experienced, the worse parents' and children's mental health."

Not surprisingly, those who experienced two and three hardships reported more negative moods, worse sleep quality and more uncooperative child behavior than those who did not. For both parents and children, mental health was worst among those who suffered all four hardships.

"These results should raise concern, given the strong links between parental psychological well-being and the well-being of children," the authors write.

Gassman-Pines and co-author Elizabeth Ananat of Barnard College suggest pediatricians should screen for mental health problems among children in their practices, with particular attention to children whose families are especially vulnerable to both the economic and health aspects of the crisis.

During the stressful pandemic, pediatricians should also help parents understand and watch for potential signs of mental distress, the authors write. Those may include uncooperative behavior and acting out.

The authors also urge the government to provide more support for families, through restarting expanded unemployment insurance benefits and increasing the generosity of the Supplemental Nutrition Assistance Program.

"What we really see here is that, as hardships pile up, the combined weight causes severe distress for families. Resilience only takes you so far, and the multiple dimensions of hardship caused by this pandemic -- lost jobs, lost child care and education, sickness -- are stretching families to the breaking point," said Ananat. "Families need support, from their pediatricians and, hopefully, from the government."