Culture

Sailors' yarns about the Kraken, a giant sea-monster lurking in the abyss, may have an element of truth.

In 1857, the Danish naturalist Japetus Steenstrup linked the tell tales of ships being dragged to the ocean floor to the existence of the giant squid: A ten-armed invertebrate, that is credibly believed to grow up to 13 meters and weigh over 900 kg.

Now, more than 160 years later, an international team of scientists have sequenced and annotated the genome of a giant squid.

'These new results may unlock several pending evolutionary questions regarding this mantled species', says the research leader, Associate Professor Rute da Fonseca from the Center for Macroecology, Evolution and Climate (CMEC) at the Globe Institute of the University of Copenhagen.

More data, more questions

Throughout the years only relatively few remains of giant squids - or, Architeuthis dux - have been collected around the world.

Using mitochondrial DNA sequences from such samples, researchers at the University of Copenhagen have previously confirmed that all giant squids belong to a single species.

'However, our initial genetic analysis generated more questions than it answered,' says Professor Tom Gilbert of the GLOBE Institute, who was part of the previous work on the giant creature.

Producing a high-quality genome assembly for the giant squid proved as challenging as spotting one of these animals in their natural environment. This was, however, an important effort as the genome is the ultimate toolkit available to an organism.

Uncooperative samples

The challenges in the lab started with the fact that available samples originate from decomposing animals, usually preserved in formalin or ethanol at museums around the world.

This means that most of them cannot be used to obtain the high-quality DNA necessary for a good genome assembly.

Furthermore, elevated levels of ammonia and polysaccharides in the tissues were likely the behind repeated failures in producing suitable libraries for nearly all available sequencing technologies.

'This project reminds us that there are a lot of species out there that require individually optimized laboratory and bioinformatics procedures. An effort that is sometimes underestimated when designing single-pipeline approaches in large genome-sequencing consortia,' says Rute da Fonseca, who started leading the project when working as an Assistant Professor at the Department of Biology in the University of Copenhagen.

A first step towards getting to know the giant

Despite the many challenges, the research group managed to get hold of a freshly frozen tissue sample of a giant squid collected by a fishing vessel near New Zealand. An incredible stroke of luck, according to the research leader.

Using this sample, the researchers were able to produce the currently best available cephalopod genome.

This 'genomic draft' provides for a unique possibility to address many emerging questions of cephalopod genome evolution, the researchers behind the study explain.

By allowing the comparison of the giant squid with the genomes of better-known types of cephalopods, scientists now hope to discover more about the mysterious giant creatures - without necessarily having to catch or observe them in the depths of up to 1200 meters that they inhabit.

For example, the new genomic data might allow scientists to explore the genetic underpinnings of the giant squid's size, growth rate and age.

The enzyme Gemin3 was identified as the molecular 'bridge' between genes whose mutation or disruption causes amyotrophic lateral sclerosis (ALS), according to a new study in Nature's Scientific Reports from scientists at the University of Malta.

ALS robs patients of their ability to walk, eat or breathe. The late-onset neurodegenerative disease destroys motor neurons, the long nerve cells in the brain and spinal cord that tell the muscles what to do. Signals from these nerves gradually stop reaching the muscles, which weaken and die. There is no cure for ALS, and, eventually, the disease is fatal.

Genetics contributes significantly to the development of ALS. Mutations in any of an ever-increasing list of genes have been identified to cause ALS with TDP-43, FUS and SOD1 featuring at the top considering that together they are responsible for a large percentage of ALS cases with a family history.

"We have been perplexed by the seemingly diverse functions of genes linked to ALS. The lack of commonality complicates the process for developing treatments that are broadly beneficial," said the study's lead researcher Dr Ruben J. Cauchi, PhD, a senior lecturer at the University of Malta's Faculty of Medicine & Surgery and principal investigator at the University of Malta's Centre for Molecular Medicine and Biobanking.

Through investigations on fruit flies, the research team were able to identify a gene whose mild perturbation was enough to trigger worsening of ALS symptoms caused by disruption of TDP-43, FUS or SOD1. The gene, named Gemin3, produces an enzyme offering researchers the possibility of tuning its function to ameliorate ALS symptoms.

"Our findings point to an overlap in disease-causing mechanisms underlying each different ALS-causing gene. This can potentially unveil new targets for therapies that are effective in a wide range of ALS patients," added Dr Cauchi.

Gemin3 has long been known for its alliance with the survival motor neuron (SMN) protein. A deficiency of SMN causes spinal muscular atrophy (SMA), a motor neuron disease that strikes infants. Gemin3's activity is crucial for building the splicing machinery which edits the cell's genetic instructions. Earlier discoveries of the research group linked Gemin3 to several key players in this delicate process.

Right now, the research team is determining whether targeting multiple players in the pathway uncovered by Gemin3 can ameliorate ALS, a result that can potentially pave the way for development of treatments that are effective to a broad swathe of ALS patients.

African swine fever (ASF) is one of the most pathogenic viral diseases in pigs caused by African swine fever virus (ASFV). The fatality rate is almost 100%, which brings huge economic losses to the hog industry in countries with epidemics. China was the first Asian country to have an ASF epidemic, and it spread quickly across the country after the first epidemic was reported in August 2018. After that, Mongolia, Vietnam, Cambodia and North Korea also reported on the ASF epidemic in succession. The African swine fever virus is a member of the Asfarviridae family and is the only known DNA virus that can be transmitted by ticks. The virion is 175-215 nm in diameter and is icosahedral symmetrical with an envelope and the genome enclosed in it is a double-stranded linear DNA with a size of 170-190 kb. In pigs, ASFV can replicate in the cytoplasm of a variety of cells, especially reticuloendothelial cells and mononuclear macrophages. Given that the genome of the African swine fever virus is very complex and whole genome information is currently inadequate, it is important to efficiently obtain virus genome sequence for genomic and epidemiological studies.

"We first use the nanopore platform to directly sequence clinical samples from pigs infected with ASFV, and explore the possibility of TGS acquiring large viral genomes such as ASFV." said Dr. Lijia Jia, the first author for this work. The results of this research indicated that the Nanopore technology can obtain ASFV genome faster than next-generation sequencing."As for working time, the NGS library preparation and on-machine sequencing took significantly longer than the TGS. The Hiseq X10 yields 100 Gb data for 76 h, while the nanopore library preparation time and the time to generate 100 Gb data on the promethION sequencer add up to less than 24 h", said Jia. The advantage of nanopore sequencing is the rapid obtaining of the pathogen genome, and the advantage of NGS is sequencing accuracy. The method of using TGS+NGS is a good choice in terms of time and accuracy."Although the current data suggest that the outbreak of African swine fever in China seemed like a single source, our results show that there are still 6-93 variations in the genome of ASFV isolates in different provinces and cities. As a large double-stranded DNA virus, ASFV has a relatively conservative genome, and its natural variation is very slow, but it can be accelerated by interaction with the host and stimulation of environmental factors. In this context, it is necessary to promote whole genome sequencing of ASFVs in different regions, which can provide us with more meaningful variation information and may play an important role in re-establishing the ASFV transmission route", said Professor Di Liu, the co-corresponding author.

These encouraging results confirm the utility of ONT sequencing as a non-cultured direct sequencing method for ASFV genomes from PCR-positive clinical tissue. Real time sequencing of the entire genome of the outbreak strain provides a baseline for subsequent epidemiological tracking and evolutionary studies.

Infections are a dreaded threat that can have fatal consequences after an operation, in the treatment of wounds, and during tissue engineering. Biomimetic hydrogels with "built-in" antimicrobial properties can significantly decrease this danger. In the journal Angewandte Chemie, scientists have now introduced a gel that is activated by red light to produce reactive oxygen compounds that effectively kill bacteria and fungi.

Hydrogels are molecule networks that hold water within their grid. Antimicrobial hydrogels can be produced by mixing with or attaching antimicrobial components to a polymer gel. Researchers at the Hebei University of Technology, Tianjin (China), Radboud University, Nijmegen (the Netherlands), and the University of Queensland, Brisbane (Australia) chose an alternative route and used photodynamic antimicrobial chemotherapy as their model. In this technique, photosensitizers enter an excited state when irradiated with light. Through a non-radiative transition, the photosensitizer enters a different, long-lived excited state. The transition can transfer energy to oxygen molecules, forming highly reactive oxygen species that kill microbes.

To date, synthetic gels with photodynamic antimicrobial activity have been neither biocompatible nor biodegradable. Products from biological sources, in contrast, harbor the risk of contamination or immune reactions and deliver results that are difficult to reproduce. The team led by Chengfen Xing overcame this challenge by using fully synthetic hydrogels with biomimetic properties, which are properties that mimic biological systems. They selected a polymer with a helical backbone (polyisocyanide with grafted ethylene glycol chains) that forms porous, highly biocompatible hydrogels with a thread-like architecture that resembles the structures and mechanical properties of biogels based on collagen and fibrin.

The researchers combined this type of hydrogel with a photosensitizer based on a polythiophene. In solution it forms disordered clumps and absorbs violet light. Incorporation into the spiral-shaped regions of the hydrogel forces the polythiophenes into a straight, linear configuration. In this form, the absorption is significantly stronger and shifted into the red region of the spectrum. This is preferable because red light can penetrate deeper and causes less bleaching of the pigment.

The researchers thus obtained a gel with outstanding antimicrobial power against bacteria, such as Escherichia coli and Bacillus subtilis, as well as fungi like Candida albicans. This could be a starting point for making wound dressings with "built-in infection stoppers". The advantages of this method of fighting pathogens: it is non-invasive and its effect is controllable both in location and duration. Even antibiotic-resistant bacteria can be killed and the risk of causing new resistances is much lower.

Whether a sick cell dies, divides, or travels through the body is regulated by a sophisticat-ed interplay of signal molecules and receptors on the cell membrane. One of the most im-portant molecular cues in the immune system is Tumour Necrosis Factor α (TNFα). Now, for the first time, researchers from Goethe University have visualised the molecular organ-isation of individual TNFα receptor molecules and the binding of TNFα to the cell mem-brane in cells using optical microscopy.

Before TNFα can bind to a membrane receptor, the TNFR receptor must first be activated. By doing so, the key will only fit the lock under certain circumstances and prevents, among other things, that a healthy cell dies from programmed cell death. "For TNFR1 in the membrane, the binding of TNFα is mediated through several cysteine-rich domains, or CRDs," explains Sjoerd van Wijk form the Institute for Experimental Cancer Research in Paediatrics and the Frankfurt Stiftung für Krebskranke Kinder at Goethe University.

In particular, CRD1 of the TNFR1 makes it possible for TNFα to "attach". Researchers already knew that TNFR1 molecules cluster in a fashion similar to a dance, in which two, three or more partners grasp hands - with the dimers, trimers or oligomers consisting of single TNFR1 mole-cules - in the case of TNFR1. This kind of "structural reorganization" also takes place when there is no TNFα present. "Despite the significance of TNFα for many diseases, including in-flammation and cancer, the physiology and patterns of TNFR1 in the cell membrane still remain largely unknown up to now," says Sjoerd Van Wijk, explaining the starting point for his research.

In order to understand the processes in the cell membrane in detail, van Wijk approached Mike Heilemann from the Institute for Physical and Theoretical Chemistry at Goethe University. Using a combination of quantitative microscopy and single-molecule super-resolution microscopy that he developed, Heilemann can visualise individual protein complexes as well as their molecular organisation in cells. Together with Ivan Dikic (Institute for Biochemistry II) and Simone Fulda (Institute for Experimental Cancer Research in Paediatrics) from Goethe University, Harald Wa-jant from the University Hospital Würzburg and Darius Widera from University Reading/UK, they were able to observe the dance of the TNFα receptors. Financial support was provided by the Deutsche Forschungsgemeinschaft (DFG) through the Collaborative Research Centre 807 "Transport and Communication across Biological Membranes".

As the researchers report in the current issue of Science Signaling, membrane TNFR1 recep-tors exist as monomers and dimers in the absence of TNFα. However, as soon as TNFα binds TNFR1, receptor trimers and oligomers are formed in the membrane. The researchers also found indications for mechanisms that determine cell fate independently of TNFα. These findings could be relevant for cancer or and inflammatory diseases such as rheumatoid arthritis. "It clear-ly opens new paths for developing novel therapeutic approaches," states van Wijk.

Cancer patients responded better to immunotherapy and had a better prognosis if their melanoma tumours contained specific clusters of B cells, according to new research from Lund University in Sweden. The study is published in Nature.

Immunotherapy strengthens the immune system so that it can fight cancer more effectively. One type of immunotherapy is checkpoint therapy, that targets the checkpoints that exist to prevent the immune system from becoming too active. However, releasing these brakes on the immune system is necessary to fight certain types of cancer, something that can be done with antibodies.

But far from all patients are being helped by the treatment, and intensive research is underway to understand who benefits the most from checkpoint therapy, and how it can be made even more effective. A great deal of focus so far has been on the immune cells called T cells.

The new study sheds light on the role of another immune cell in immunotherapy: B cells. Researchers at Lund University, together with several other international research groups, have shown that clusters of B cells in melanoma tumors, so-called tertiary lymphoid structures, are linked to the prognosis.

"By studying tissue samples from 177 melanoma patients, we have been able to see that when these B-cell structures were present in the tumour, the patient had a better prognosis and responded better to immunotherapy", says Göran Jönsson, the professor at Lund University who led the study.

It has previously been known that these structures are sometimes found in tumours, but it is only now that they have been linked to prognosis and treatment response. In the same issue, Nature has published two other research articles that involve the same B-cell structures, albeit in other tumours - soft tissue sarcoma and kidney cancer - where there was also an association with improved response to immunotherapy.

The results of the Lund study confirm that it is not only the T-cells that are important, but that the B-cells also play a role in the immune response against cancer cells.

"Now we want to continue with prospective studies and investigate whether it is possible to stimulate the immune system to form these structures in tumours, and thus improve the effect of immunotherapy", concludes Ana Carneiro, chief physician at Skåne University Hospital and associate professor at Lund University, who also participated in the study.

A team of physicists from McMaster University has developed a process to modify red blood cells so they can be used to distribute drugs throughout the body, which could specifically target infections or treat catastrophic diseases such as cancer or Alzheimer's.

The modified red blood cells are designed to circulate in the body for several weeks at a time, seeking out specific targets including bacteria, tumours or organs.

The technology, described in the online edition of the journal Advanced Biosystems, solves a major problem with current drug delivery methods that use synthetic molecules and cannot reach specific targets or are rejected by the body.

"We call these super-human red blood cells. We think that they could work as the perfect stealth drug carriers which can outsmart our immune system," explains Maikel Rheinstädter, a senior advisor on the study and professor in the Department of Physics & Astronomy at McMaster.

The researchers have developed a method to open up the red blood cell, modify its outer cell wall, and replace its contents with a drug molecule, which would then be injected back into the body.

The hybrid appears and behaves as a normal red blood cell, but has a sticky surface which can attach itself to bacteria, for example, open up and release antibiotics exactly where they are needed.

"We have combined synthetic material with biological material and created a new structure, which has never been done before in this way," says Sebastian Himbert, lead author and a graduate student in the Department of Physics & Astronomy at McMaster.

"The entire process is very efficient and can be completed in one day in the lab," he says.

Researchers believe this targeted delivery method could help to minimize dosages and therefore, potential side effects. This is particularly important for very potent drugs used in cancer and Alzheimer's disease, and the treatment of infections of potentially resistant bacteria.

Amsterdam, NL, January 16, 2020 - The International Parkinson Disease Genomics Consortium (IPDGC) has now been in existence for ten years. In an article published in the Journal of Parkinson's Disease the consortium reviews the progress made over the past decade in the genomics of Parkinson's disease (PD) and related disorders including Lewy body diseases, progressive supranuclear palsy, and multiple system atrophy and looks ahead at its future direction and research priorities.

Since PD was first defined, it has been suspected that there was a genetic component. In June 2009, a small group of investigators met to discuss a potential research alliance focused on the genetics of PD. The outcome was the creation of the IPDGC, a group focused on collaborative genetics research, enabled by trust, sharing, "and as little paperwork as possible." This article summarizes the efforts of the IPDGC to date and places these in the context of a decade of progress in PD genomics. It also discusses the future direction of IPDGC and its stated research priorities for the next decade.

"The IPDGC was born out of a realization that no single investigator could deliver on the promise of modern human genetics in isolation," explained lead author Andrew Singleton, PhD, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. "We realized that to truly leverage the incredible gains in genetic technologies in the PD space, at scale, would require a highly collaborative approach. This notion brought a small group of PD geneticists together with the common goal of building an effective, transparent, and functional collaboration."

Since its inception, the IPDGC has grown considerably, now including more than 100 scientists from around the world with meetings at least once a year. The focus has also expanded to include clinical and functional investigation of PD at scale. Most recently, the IPDGC initiated major research efforts in East Asia and Africa and has prioritized collaborations with ongoing major efforts in India and South America.

"The coordinated analysis of genome-wide association (GWA) data was perhaps the first success for IPDGC and has continued to be a mainstay of our work," noted Dr. Singleton. This work has centered on available genome-wide SNP genotyping of IPDGC members' case and control cohorts from the USA, Canada, England, Wales, The Netherlands, France, Germany, Italy, Spain, Austria, Finland, Norway, Estonia, and Australia. These studies have involved collaboration within IPDGC and with groups from industry, including Genentech and 23andMe. The source diversity and size of these sample series have grown considerably, from the first efforts that centered on around 1,500 cases and a similar number of controls, to the most recent effort that included dense genotyping in more than 50,000 cases and proxy-cases, and around 1.4 million controls. As in other disorders, as sample size has grown, so has power and the number of loci detected. Currently, there are about 90 known risk variants for PD.

Collaboration among IPDGC members has furthered knowledge, including:

Discovery that brain tissue generally, and nigral neurons specifically, are critical in the disease process, contrasting quite strikingly to what has been observed in Alzheimer's disease, in which immune cells are a key effector of genetic risk.

Application of heritability estimation methods such as Genome-wide Complex Trait Analysis (GCTA) and Linkage Disequilibrium Score Regression (LDSC), suggesting that 16-36% of the liability of disease is driven by common genetic variability.

Using the large IPDGC genetic datasets (currently including over 20,000 cases and 20,000 controls) as a basis, multiple advanced analyses can be performed to predict disease, assign more "function" or biology to GWAS loci and identify potential disease-relevant pathways.

Identification of new genes or pathways associated with PD such as VPS13C mutations as a cause of young-onset PD.

Creation of resources including the development genotyping array and browsable result pages.

Providing the research community with easy access result summaries that are usable and understandable to basic researchers. Currently under development are the IPDGC sequencing browser and the IPDGC GWAS browser.

Future challenges the consortium has identified include expanding the known genetic architecture; genetics in diverse ancestries; advanced cohort building; and creating PD resources for the research community.

The importance of the dissection of genetic risk in non-European ancestry populations has led the consortium to invest more in establishing research in underrepresented groups. With the support of the Michael J. Fox Foundation for Parkinson's Research, the IPDGC has initiated largescale efforts in South East Asia and China and across Africa. It is also working closely with collections centered in India, LUX-GIANT, and LARGE-PD.

"The field of PD genetics is one that has changed dramatically over the last ten years," commented Dr. Singleton. "There has been an exponential growth in our appreciation of the genetic architecture of the disease and a greater understanding of how to proceed with genetic prosecution of PD.

"Our future path promises to expand this work and leverage its clinical, mechanistic, and biological potential. Thus, while we believe the work of the IPDGC has had a significant and lasting impact on our field over the last ten years, we are even more excited by the course we have charted for the next decade."

January 16, 2020 - A virtual system for in-home physical therapy (PT) provides good outcomes for patients undergoing rehabilitation following total knee arthroplasty (TKA) - with lower costs than traditional in-person PT, reports a study in the January 15, 2020 issue of The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

"Relative to traditional home or clinic PT, virtual PT with telerehabilitation for skilled clinical oversight significantly lowered three-month health-care costs after TKA while providing similar effectiveness," according to the clinical trial report by Janet Prvu Bettger, ScD, of Duke University, Durham, N.C., and colleagues.

Virtual PT After TKA Is Safe and Effective, Randomized Trial Reports

The study included 306 patients with an average age of 65 years undergoing a knee replacement procedure. Patients were randomly assigned to undergo traditional PT, either at home or at clinic visits, or virtual PT with use of a virtual telehealth system.

The FDA-cleared Virtual Exercise Rehabilitation Assistant (VERA) was designed to provide remote rehabilitation services. The cloud-based system features a digitally simulated coach to demonstrate and guide activity, including visual and audio instructions. The system also uses 3D tracking technology to assess the patient's pose and movement, enabling immediate feedback on exercise quality.

The VERA system provides a virtual video connection for weekly live telehealth visits with a remote physical therapist, who monitors the patient's progress and reports back to the surgeon before follow-up clinic visits. Patients were able to receive in-person PT, if deemed necessary.

The study compared the costs and effectiveness of rehabilitation following TKA for the virtual and traditional PT groups. In the 12 weeks after TKA, median total costs were $1,050 for patients assigned to the virtual PT system, compared with $2,805 with traditional PT. Mean costs were $2,745 lower in the virtual PT group.

Patients using the VERA system participated in PT an average of 5.9 days per week, compared with 3.3 days in the traditional PT group. Eighty-eight percent of patients in the virtual PT group said they completed all assigned exercises, compared with 65 percent with traditional PT.

After 12 weeks of rehabilitation, knee function, walking speed, and other functional outcomes were similar with virtual and traditional PT. Patients in the virtual PT group reported less difficulty with knee function during sports and recreational activities.

There was no difference in physician, urgent care, and emergency room visits, but patients in the virtual PT group had fewer hospital readmissions. Safety outcomes were also similar between groups. The risk of falls was somewhat higher for patients assigned to virtual PT.

Postoperative PT is important for helping patients to regain physical function following TKA. But PT care can be challenging to access, with barriers including cost and a shortage of physical therapists. Virtual or telerehabilitation programs such as VERA might help to increase home-based access to PT for patients undergoing TKA.

The new study finds substantially lower costs in the three months after TKA for patients assigned to virtual PT, compared with traditional PT. Effectiveness and safety are similar between groups. Some outcomes might be even better with virtual PT (ie, knee function during sports/activities and rehospitalization risk), although the risk of falls may be higher.

"These findings have important implications for patients, health systems, and payers and suggest that virtual PT with a telehealth therapist for remote clinical monitoring and guidance should be considered for patients after TKA," Dr. Bettger and colleagues conclude. Although further study to guide implementation and uptake is needed, the authors believe that virtual PT systems have the potential to improve access while lowering costs of PT for patients undergoing TKA.

LEXINGTON, Ky. (Jan. 16, 2020) -- Current policies that include restrictions on the sale of menthol flavored tobacco and nicotine products are less likely to reach those that would benefit from them the most, according to new research from the University of Kentucky's College of Medicine published in Health Promotion Practice Jan. 7.

The research led by Shyanika Rose, assistant professor in the Department of Behavioral Science, examined local policies across the nation that restricted flavored tobacco products to see how they reached at-risk populations including youth, people of color, LGBTQ and low-income groups. The study revealed that while bans on flavored tobacco products are reaching populations most at-risk for using them, policies that include restrictions on menthol flavors were less likely to reach them, particularly African Americans.

According to Rose, menthol cigarettes have a long history of being disproportionately marketed toward African Americans, to the point that nearly 90% of the African Americans who smoke use them. Menthol flavoring eases the harshness of cigarette smoking and has been associated with more difficulty quitting and progression to regular use.

The study is particularly timely with the recent federal restrictions on flavored vaping products, which exempts menthol and tobacco flavors. Rose says that while these policies are important to protect youth from tobacco use, their adoption and implementation may overlook the need to protect others at higher risk for using flavored tobacco products, including racial and ethnic minorities.

"Flavored tobacco restrictions that do not include menthol cigarettes unfairly affect people who are harmed by them the most and it negatively impacts public health," Rose said.

Rose says next steps are to examine the impacts of "strong" policies that include a ban on menthols to see how they affected the smoking behavior of youth, racial/ethnic minority and low-income populations. Additional bans on menthols are gaining momentum at the local, state and federal level and Rose's ongoing research could help lawmakers create policies that are more equitable.

"As more localities are considering flavored tobacco restrictions, they really need to think about having the strongest restrictions including bans on menthol cigarettes to adequately protect public health and reduce these disparities," Rose said.

Shyanika Rose is a member of the University of Kentucky's Center for Health Equity Transformation (CHET), which fosters innovative, transdisciplinary and impactful research and training to improve the health of the most vulnerable residents of Kentucky and beyond. Learn more about CHET and Rose's research here: https://uknow.uky.edu/research/center-health-equity-transformation-seeks-improve-health-all-kentuckians

A study of more than 4 million Medicaid claims records during a recent seven-year period concludes that less than a third of the nearly 3,800 U.S. adolescents and young adults who experienced a nonfatal opioid overdose got timely (within 30 days) follow-up addiction treatment to curb or prevent future misuse and reduce the risk of a second overdose.

The analysis, led by researchers at Johns Hopkins Medicine, also found that only 1 in 54 -- less than 2% -- received standard-of-care counseling and medications recommended by the American Academy of Pediatrics (AAP) for treating opioid use disorder.

"If 1 in 54 young people with asthma or diabetes failed to receive standard therapies for emergency situations with their diseases, we wouldn't accept it," says Rachel Alinsky, M.D., M.P.H., a pediatrician and adolescent medicine fellow at the Johns Hopkins Children's Center and lead researcher of the study described recently in JAMA Pediatrics. "Yet, this is where we are now with the treatment our system is able to provide to youths who have survived an opioid overdose -- and we need to do better for them."

The U.S. Centers for Disease Control and Prevention (CDC) reports that in 2017, about 68% of the more than 70,200 drug overdose deaths in the United States involved one of the three types of opioids: illegal drugs such as heroin; prescription medications such as oxycodone (OxyContin), hydrocodone (Vicodin), morphine and methadone; and synthetic opioids such as Fentanyl. Of those deaths, just over 4,000 were among those ages 15 to 24. Additionally, the CDC says that the opioid mortality rate for people under age 20 has tripled since the year 2000.

Rates of nonfatal opioid overdoses for teens and young adults also have escalated, accounting for more than 7,000 hospitalizations and an estimated 28,000 emergency department visits just in 2015, the most recent year for which data are available.

Alinsky says the risk of a recurrent overdose for this group is extremely high. For example, she says, over 8% of the youths in the new study who survived a heroin overdose experienced another one within three months.

What makes these numbers so alarming is that a proven addiction intervention is available. According to the AAP, a combination of behavioral health counseling and pharmacotherapy -- using prescribed buprenorphine, methadone or naltrexone -- has been shown effective at reducing opioid use and keeping patients in care following an overdose.

"It's been estimated that teens and young adults are only a tenth as likely as those over age 25 to get the recommended evidence-based treatment for opioid use disorder," Alinsky says. "In our study, we wanted to look more specifically at what happens to young patients after a nonfatal opioid overdose and compare that data to those for adults."

Using an established national database of Medicaid claims from 2009 to 2015, the researchers reviewed the records of just over 4 million people, ages 13 to 22, from 16 states and representing all U.S. census regions.

For the 3,606 youths who experienced a nonfatal opioid overdose and were enrolled in Medicaid for 30 days after the incident, the researchers learned the following about the post-overdose treatment received during that time period:

2,483 (68.9%) did not receive any addiction treatment, behavioral or pharmacological

1,056 (29.3%) received behavioral health services alone

Only 67 (1.9%) received one of the three approved medications for opioid use disorder

Alinsky says these results show that more than two-thirds of the youths who had overdoses failed to receive any intervention within 30 days and 98% did not get the medication therapy during that span to help them reduce the risk of a second, and potentially fatal overdose.

There are likely many reasons for this treatment gap, she says.

"For example, opioid use disorder often is not considered a 'pediatric' disease, so pediatricians may not be aware of the problem or know how to effectively deal with a patient who's had an overdose," Alinsky explains. "Additionally, there is a widespread stigma attached to using medications to treat opioid use disorder, with some considering it 'just replacing one drug with another' or 'only to be used as a last resort.'"

Other barriers to care exist as well, she says. These include the limited number of addiction treatment facilities available for youths and the fact that very few pediatric providers have been certified to prescribe the recommended medications.

Based on their findings, Alinsky and her colleagues urge health care providers, especially emergency department physicians and pediatricians, to link adolescent and young adult patients with nonfatal opioid overdoses into addiction treatment programs as soon as possible following treatment of the initial incident. Additionally, she says, clinicians should prioritize improving patient access to pharmacotherapy.

"If patients with overdoses don't get linked right there in the emergency department to the appropriate follow-up care that could help them avoid a recurrence, they or their families should ask for assistance in making it happen," Alinsky says. "We have treatment programs that work effectively and save lives, but that doesn't matter if patients don't get into them."

A highly sensitive, wearable gas sensor for environmental and human health monitoring may soon become commercially available, according to researchers at Penn State and Northeastern University.

The sensor device is an improvement on existing wearable sensors because it uses a self-heating mechanism that enhances sensitivity. It allows for quick recovery and reuse of the device. Other devises of this type require an external heater. In addition, other wearable sensors require an expensive and time-consuming lithography process under cleanroom conditions.

Hand and arm showing sensor applied to inner write with moble phone sized read beside it.

"People like to use nanomaterials for sensing because their large surface-to-volume ratio makes them highly sensitive," said Huanyu Cheng, assistant professor of engineering science and mechanics and materials science and engineering, Penn State. "The problem is the nanomaterial is not something we can easily hook up to with wires to receive the signal, necessitating the need for something called interdigitated electrodes, which are like the digits on your hand."

Cheng and his team use a laser to pattern a highly porous single line of nanomaterial similar to graphene for sensors that detect gas, biomolecules, and in the future, chemicals. In the non-sensing portion of the device platform, the team creates a series of serpentine lines that they coat with silver. When they apply an electrical current to the silver, the gas sensing region will locally heat up due to significantly larger electrical resistance, eliminating the need for a separate heater. The serpentine lines allow the device to stretch, like springs, to adjust to the flexing of the body for wearable sensors.

The nanomaterials used in this work are reduced graphene oxide and molybdenum disulfide, or a combination of the two; or a metal oxide composite consisting of a core of zinc oxide and a shell of copper oxide, representing the two classes of widely used gas sensor materials -- low-dimensional and metal oxide nanomaterials.

"Using a CO2 laser, often found in machine shops, we can easily make multiple sensors on our platform," Cheng said. "We plan to have tens to a hundred sensors, each selective to a different molecule, like an electronic nose, to decode multiple components in a complex mixture."

The U.S. Defense Threat Reduction Agency is interested in this wearable sensor to detect chemical and biological agents that could damage the nerves or lungs, according to the researchers. A medical device company is also working with the team to scale up production for patient health monitoring, including gaseous biomarker detection from the human body and environmental detection of pollutants that can affect the lungs.

Ning Yi, a doctoral student in Chen's lab and co-lead author of the paper posted online in the Journal of Materials Chemistry A, said, "In this paper, we showed that we could detect nitrogen dioxide, which is produced by vehicle emissions. We can also detect sulfur dioxide, which, together with nitrogen dioxide, causes acid rain. All these gases can be an issue in industrial safety."

The researchers said their next step is to create high-density arrays and try some ideas to improve the signal and make the sensors more selective. This may involve using machine learning to identify the distinct signals of individual molecules on the platform.

BALTIMORE, MD - Obstructive sleep apnea (OSA) is a common and costly medical condition leading to a wide range of health risks such as cardiovascular disease, stroke, depression, diabetes and even premature death. Researchers at the University of Maryland School of Medicine (UMSOM) found that the medical costs are substantially higher among older adults who go untreated for the disorder.

The research, which was published in the Journal of Clinical Sleep Medicine, involved a review of a national sample of Medicare claims data. The researchers measured the health care costs over a year among Medicare beneficiaries who were 65 years and older and were ultimately diagnosed with OSA. They found that patients who went undiagnosed with OSA over a 12-month period had more doctor's appointments, emergency room visits, and hospital stays prior to being treated for the disorder. These patients on average had nearly $20,000 more in costs a year than those who were diagnosed and treated for OSA, the research found.

"Sleep disorders represent a massive economic burden on the U.S. health care system," said Emerson Wickwire, PhD, Associate Professor of Psychiatry and Medicine at UMSOM and Director of the Insomnia Program at the University of Maryland Medical Center, Midtown Campus. Dr. Wickwire, who was the Principal Investigator for this research, explained that economic aspects of diseases are increasingly recognized as important drivers of health decisions by patients, those paying for services, policymakers and ultimately the taxpayers.

Medical costs among those untreated for OSA will continue to rise, Dr. Wickwire cautioned, highlighting the importance of early detection and treatment among older adults..

"We conducted the largest economic analysis of sleep apnea among older adults to date," said Dr. Wickwire. "Medicare beneficiaries with obstructive sleep apnea cost taxpayers an additional $19,566 per year and utilized more outpatient, emergency, inpatient, prescription, and overall health care services. It's important to realize that costs associated with untreated sleep disorders are likely to continue to accrue year after year, which is why our group focuses on early recognition and treatment."

Researchers also observed that Medicare patients with OSA were more likely to suffer from other ailments more so than those individuals without the sleep disorder. For example, OSA is linked to an increased risk for high blood pressure, diabetes, heart disease, stroke and depression. The study authors suggest that insurers, legislators, and health systems leaders consider routine screening for OSA in older patients, especially those with medical and psychiatric comorbidities, to better contain treatment costs.

"The good news is that highly effective diagnostic and treatment strategies are available. Our team is currently using big data approaches as well as highly personalized sleep disorders treatments to improve outcomes and reduce costs associated with sleep disorders, "said Dr. Wickwire.

The research is critical as OSA affects up to 70% of elderly nursing home residents, and these individuals are at higher risk of death.

A 2016 report by the American Academy of Sleep Medicine estimated that undiagnosed OSA among U.S. adults costs $149.6 billion annually. While the report projected it would cost the health care system nearly $50 billion to diagnosis and treat every American adult with OSA, treatment would produce savings of $100 billion. The current study in JCSM is the largest analysis to date of the economic burden of untreated OSA among older adult Medicare beneficiaries. Dr. Wickwire's research was funded by RedMed as an investigator-initiated grant.

"Early detection and treatment for disorders such as obstructive sleep apnea is critical, particularly among older adults who face the risk of the most serious illnesses such as cardiovascular disease, hypertension, stroke, and diabetes," said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor, University of Maryland School of Medicine.

CHICAGO, January 16, 2020 - A sleep medication already approved to treat insomnia in the general population may also be beneficial for individuals with Alzheimer's, according to a new study published online today by Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

The drug, suvorexant, was found to improve total sleep time for individuals with probable Alzheimer's disease dementia and insomnia as compared to a placebo. Sleep disturbances are common among individuals with Alzheimer's and other dementias. The researchers note that there is a potential for making cognitive declines worse when treating sleep problems in individuals with Alzheimer's who may also be taking other medications for symptoms or behavioral problems related to their dementia. Surovexant did not worsen the underlying cognitive impairment in the study participants.

W. Joseph Herring, M.D., Ph.D., from Merck & Co., Inc. and colleagues conducted a four-week, randomized phase 3 clinical trial with 277 participants. The researchers found that total sleep time improved from baseline by 73 minutes for the suvorexant group and 45 minutes for the placebo group. The study authors note that the suvorexant-mediated sleep effects are maintained over the course of the night, unlike other currently available sleep drugs.

Link: "Polysomnographic assessment of suvorexant in patients with probable Alzheimer's disease dementia and insomnia: A randomized trial"

The December print issue of Alzheimer's & Dementia includes articles that add to the growing body of research suggesting risk and progression of Alzheimer's varies by race. There are also differences found within the broader terms of Hispanic or Latino depending on a person's family background. These studies illustrate the need for more diversity in research studies to better understand the racial and ethnic disparities in the risk and prevalence of Alzheimer's. By understanding how race may alter Alzheimer's risk and genetics, researchers may be able to create better diagnostic tools and treatment strategies that are effective in all communities. Key findings include:

Researchers found nearly 10% of middle-age and older Latinos have mild cognitive impairment (MCI), a decline in memory and thinking skills. Prevalence ranges from 12.9% for individuals with Puerto Rican backgrounds to 8.0% among individuals with Cuban backgrounds.

Older age, high cardiovascular disease risk and depression symptoms were significantly associated with MCI diagnosis.

The studies include:

Link: "Sex/gender differences in cognitive trajectories vary as a function of race/ethnicity"

Link: "Local ancestry at APOE modifies Alzheimer's disease risk in Caribbean Hispanics"

Link: "Prevalence and correlates of mild cognitive impairments among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results"

Artificial intelligence may be useful to identify individuals at high risk for developing dementia by sorting through hospital discharge summaries, according to a study available online by Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

Thomas H. McCoy, Jr., M.D., Massachusetts General Hospital, Boston created computer software to analyze the cognitive and behavioral symptoms documented in discharge notes in electronic health records of more than 500,000 individuals from two academic medical centers. McCoy and colleagues found that their machine learning system may help predict the risk of a healthy person developing dementia up to eight years in advance of a diagnosis.

According to the Alzheimer's Association, early detection may identify individuals at high risk so they can get further clinical evaluation. An earlier and more accurate diagnosis enables access to approved drug treatments, and allows individuals to participate in planning for their future.

Link: "Stratifying risk for dementia onset using large-scale electronic health record data: a retrospective cohort study"

These articles and the rest of the January and December issues of Alzheimer's & Dementia: The Journal of the Alzheimer's Association are available online.

Bottom Line: Researchers for this observational study examined the association between the expansion of Medicaid coverage in some states after the Patient Protection and Affordable Care Act (ACA) was passed and the diagnosis and treatment of patients with head and neck squamous cell carcinoma (HNSCC). The analysis included nearly 91,000 adults with newly diagnosed HNSCC who were identified from the National Cancer Database. Researchers report that between the pre-ACA (2010-2013) and post-ACA (2014-1026) periods, the percentage of uninsured patients with HNSCC decreased but those decreases didn't differ significantly between expansion and nonexpansion states. The percentage of patients diagnosed with localized (stage I or II) HNSCC decreased from the pre-ACA to post-ACA periods in both expansion and nonexpansion states but the decreases were smaller in Medicaid expansion states so that resulted in a small relative increase in patients diagnosed with localized disease in Medicaid expansion states. The average time to beginning treatment didn't differ overall between expansion and nonexpansion states but was improved for patients with nonoropharyngeal HNSCC ?in expansion states relative to nonexpansion states. Limitations of the study include possible misclassification of insurance coverage.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Evan M. Graboyes, M.D., Medical University of South Carolina, Charleston, and coauthors.

(doi:10.1001/jamaoto.2019.4310)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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Media advisory: To contact corresponding author Evan M. Graboyes, M.D., email Montez Seabrook at seabromo@musc.edu">seabromo@musc.edu. The full study is linked to this news release.

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