Cochlear and Oticon Medical merger could result in higher prices, says CMA

 The UK’s Competition and Markets Authority (CMA) has announced that the merger of two major hearing implant providers, namely Cochlear and Oticon Medical, may lead to higher prices for the National Health Service (NHS).

The deal could also lead to reduced quality as well as impact innovation for UK patients who depend on these devices.

In April, Cochlear agreed to acquire Oticon Medical, the hearing implant division of Demant, for kr850m ($119.8m).

According to the CMA, Cochlear’s proposed acquisition would create a negative impact on patients requiring implants, most of whom purchase their devices through the NHS.

Both Cochlear and Demant are involved in the supply of cochlear implants and bone conduction solutions, which are surgically implanted.

These devices help enhance hearing for people with mild to severe or total hearing loss, meeting the requirements of different patients based on the cause of each individual’s hearing loss.

CMA’s phase one investigation revealed that the proposed deal would result in the merged businesses holding a 90%-100% share of the bone conduction solutions market in the UK.

CMA expressed concern that the closing of the deal would result in the elimination of the strongest competitor in this segment.

This is expected to lead to decreased innovation, higher prices, or fewer choices for hospitals and their patients.

The investigation also focused on the impact of the merger on the supply of cochlear implants, where Cochlear has a significant presence.

It revealed that Oticon Medical has a minor presence in this segment in the UK and was not expected to become a significant rival in the future.

CMA’s findings also found that the merged businesses will have competition from two other providers in the UK.

CMA Mergers senior director Sorcha O’Carroll said: “We’re concerned that this deal could lead to higher costs for the NHS and worse outcomes for patients who rely on life-changing hearing implants.

“The merger will wipe out one of the main suppliers and leave Cochlear with a near monopoly in the supply of bone conduction implants.”

https://www.medicaldevice-network.com/news/cochlear-oticon-medical-prices-cma/

Kim Kardashian, other celebrities beat EMax crypto investors' lawsuit

 

A federal judge in California on Wednesday dismissed a lawsuit against reality TV star Kim Kardashian, boxing legend Floyd Mayweather Jr. and others over their role in promoting a cryptocurrency, saying it was not clear that the investors who sued actually saw the promotions.

The lawsuit filed in January claims EthereumMax executives schemed with celebrity promoters to induce investors to buy the EMax token, driving up its price and allowing them to sell their own tokens at a profit.

U.S. District Judge Michael Fitzgerald in Los Angeles said that the investors may amend and refile their proposed class action.

The decision comes as other celebrity promoters face lawsuits from users of the failed cryptocurrency exchange FTX, whose collapse has deepened an ongoing "crypto winter."

Sean Masson, an attorney who represents the investors in the EthereumMax case, said they plan to revise their claims to add "a host of additional facts demonstrating defendants' wrongdoing and liability."

Michael Rhodes, the lead attorney for Kardashian, said the defense is "pleased with the court's well-reasoned ruling."

Attorneys for Mayweather did not immediately respond to a request for comment. Also named in the lawsuit was former National Basketball Association star Paul Pierce.

Kardashian promoted EthereumMax in a June 2021 post on Instagram, and Mayweather wore the company's logo on his boxing trunks during a widely viewed fight, the investors said.

In Wednesday's ruling, Fitzgerald said that investors had failed to show that the executives and promoters schemed to mislead investors, rather than acting in their own self-interest.

The investors' fraud claims failed because they had not stated whether or when they saw the promotions, the judge wrote.

While the investors may revise those claims, Fitzgerald permanently dismissed their claim under California's consumer protection law, which he said applies to tangible goods and services, not "intangible goods" such as cryptocurrency.

Kardashian agreed in October to pay the SEC $1.26 million to settle claims that she failed to disclose she was paid to promote EthereumMax tokens. She did not admit wrongdoing.

The case is In Re: Ethereummax Investor Litigation, No. 22-00163

https://www.marketscreener.com/quote/stock/PIERCE-GROUP-AB-PUBL-120591128/news/Kim-Kardashian-other-celebrities-beat-EMax-crypto-investors-lawsuit-42500059/

Scientists confirm smallpox vaccine also teaches T cells to fight mpox

 There's even more reason to think a vaccine developed against smallpox can help the body fight against mpox (monkeypox virus disease) as well, according to researchers at La Jolla Institute for Immunology (LJI). Their new study, published in Cell Host & Microbe, is the first to provide evidence that the vaccinia vaccine MVA-BN (brand name JYNNEOS) should also train virus-fighting T cells to recognize mpox sequences.

"This study gives us confidence that T cell response induced by the JYNNEOS vaccine should be able to also recognize mpox virus," says LJI Professor Alessandro Sette, Dr.Biol.Sci., who co-led the new study with LJI Instructor Alba Grifoni, Ph.D.

The study comes as more than 100 countries reported unprecedented mpox outbreaks. In the United States, there have been more than 28,000 reported cases and 11 deaths attributed to mpox since May 2022.

Why we need mpox vaccine data

Although the JYNNEOS vaccine, based on a non-live attenuated orthopox virus called modified vaccine ankara (MVA), is approved to prevent mpox infection and severe disease, researchers don't yet have clinical efficacy data from human trials. Still, researchers know that mpox virus is similar enough to other orthopoxviruses that immunization against an orthopoxvirus called vaccinia (VACV) can also train the immune system to fight mpox.

Mpox (termed "monkeypox" until recently) is a member of the orthopox family of viruses. The deadliest, of course, was variola virus,causing the disease known as smallpox. Smallpox was eradicated worldwide in 1980 thanks to a massive and successful vaccination campaign to administer the Dryvax vaccine, based on VACV.

VACV and variola virus have a lot of immune system targets (called antigens), in common. This means training the body to recognize VACV also taught immune cells to recognize variola virus. But there was a downside—Dryvax (and a newer version called Acambis 2000) had harmful side effects, especially in immunocompromised people.

JYNNEOS was designed to have a better safety profile. While the vaccine performed well in pre-clinical tests, the eradication of smallpox meant scientists couldn't see how JYNNEOS performed in human patients in real-world infection scenarios, such as a smallpox outbreak or possible case of smallpox-based biological warfare (a concern in the early days of the Iraq War).

How a smallpox vaccine protects against mpox

For the new study, the LJI team set out to study if the viral proteins known to be targeted by T cells induced by VACV vaccination, would also be conserved in JYNNEOS and in mpox. As Grifoni explains, while antibodies are key for vaccine efficacy and preventing reinfections, T cells are essential for both preventing severe infections and "remembering" past infections.

"By recognizing infected cells, T cells are able to limit how much viruses can spread inside the body modulate disease severity, and ultimately terminate the infection" says Grifoni. "T cell responses also tend to be long lasting, and resilient to viral mutations to escape immune recognition. What we have seen in the context of SARS-CoV-2 is that even if the virus mutates somewhat, T cells reactivity is still largely preserved."

The researchers demonstrated that the known targets of T cell responses seen in the VACV proven -efficacy vaccine, are also found in JYNNEOS and mpox, suggesting that the JYNNEOS vaccine can indeed trigger an effective T cell response against mpox infection. The initial test of their hypothesis was based on developing viral peptide "megapools," or reagents designed to detect T cell reactivity to mpox antigens. The experiments further showed that these megapools can be used to accurately detect specific T cells.

"Vaccines such as JYNNEOS should be able to induce T cells that also recognize mpox and can provide protection from severe disease," says Grifoni.

Could the vaccine work in immunocompromised patients?

"The majority of mpox cases have been in men who have sex with men," Sette explains. "In that community, a significant fraction of the people that have been infected with mpox also happened to be HIV-positive. So it is important to learn how people who are HIV-positive respond to infection and vaccination compared to HIV-negative individuals. The present study enables future study to establish this key point"

Sette emphasizes that most HIV-positive individuals are not necessarily at greater risk of mpox infection or severe disease. "We do not expect that HIV-positive individuals will respond differently to infection and vaccination, because in most cases, people who live with HIV live with a controlled HIV because of the available therapies," he says. "Nevertheless, it's important to provide these data to the community affected by this outbreak and to the general scientific community."

Whether the JYNNEOS vaccine sparks a similar immune response in people with and without HIV—and the role of T cells—will have to be determined in future studies. "We also expect to see no difference in the duration of protection between HIV positive and HIV negative individuals, but that still all needs to be proven and evaluated experimentally. We are actively engaging the community most affected by the outbreak and the scientific community at large " says Sette.

Next steps for the LJI team

The researchers are now working to characterize the T cell response to mpox in more detail. They are especially interested in how T cell responses differ after vaccination versus natural infection. Sette and Grifoni would also like to compare T cell responses following JYNNEOS vaccination with the older Dryvax vaccination.

Just as they've done throughout the COVID-19 pandemic, Sette and his colleagues hope to share their reagents freely to and spur more life-saving studies around the globe. "We want to make these reagents widely available to whoever asks," says Sette.

Additional authors of the study, ""Defining antigen targets to dissect vaccinia virus (VACV) and Monkeypox virus (MPXV)-specific T cell responses in humans"," include Yun Zhang, Alison Tarke, John Sidney, Paul Rubiro, Maria Reina-Campos, Gilberto Filaci, Jennifer Dan, and Richard H. Scheuermann.

More information: Alba Grifoni et al, Defining antigen targets to dissect vaccinia virus and monkeypox virus-specific T cell responses in humans, Cell Host & Microbe (2022). DOI: 10.1016/j.chom.2022.11.003

https://medicalxpress.com/news/2022-12-scientists-smallpox-vaccine-cells-mpox.html

New oral compound may help prevent and treat osteoporosis

 Parathyroid hormone can stimulate bone formation, and analogs of the hormone are often prescribed to patients with osteoporosis; however, these medications are only effective when administered by daily injection.

A team led by investigators at Massachusetts General Hospital (MGH) recently identified a promising compound that influences components of the parathyroid hormone signaling pathway and that, when given orally to mice, increases bone mass. The group's discovery, which is published in PNAS, might lead to a new, more convenient drug for preventing and treating osteoporosis.

"Currently there are no orally available medications for osteoporosis that stimulate bone formation. We sought to develop such medications based upon our detailed understanding of the pathways that normally govern bone production," says senior author Marc Wein, MD, Ph.D., an endocrinologist at MGH and an Assistant Professor of Medicine at Harvard Medical School.

The pathway that involves parathyroid hormone inhibits salt-inducible kinase isoforms 2 and 3 (SIK2 and SIK3), which are enzymes with roles in the regulation of bone growth and remodeling. 


Wein and his colleagues generated a novel structural model of these enzymes and then used advanced methods including structure-based drug design and iterative medicinal chemistry to identify a compound that potently inhibits SIK2 and SIK3. This compound, termed SK-124, had parathyroid hormone–like effects when given to cells and, most importantly, when fed to mice. In mice, oral treatment once a day for three weeks increased blood levels of calcium and vitamin D and also boosted bone formation and bone mass without evidence of short-term toxicity.

"Based on these findings, we propose that small molecules like SK-124 might represent 'next generation' oral bone building therapies for osteoporosis," says Wein. "We are currently collaborating with a pharmaceutical company—Radius Health, Inc.—to further optimize and develop this compound into a treatment for patients."

Additional MGH co-authors include Tadatoshi Sato, Christian D. Castro Andrade, Sung-Hee Yoon, Yingshe Zhao, Daniel J. Brooks, Marie B. Demay, and Mary L. Bouxsein.

More information: Tadatoshi Sato et al, Structure-based design of selective, orally available salt-inducible kinase inhibitors that stimulate bone formation in mice, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2214396119

https://medicalxpress.com/news/2022-12-oral-compound-osteoporosis.html

Substantial rise in type 2 diabetes among young people over the past 30 years

 Rates of type 2 diabetes in adolescents and young adults globally rose substantially from 1990 to 2019, finds an analysis of the latest data from over 200 countries and regions in The BMJ today.

The findings show that countries with a low-middle and middle sociodemographic index (a measure of social and economic development) and women aged under 30 were particularly affected, and high body mass index was the main attributable risk factor in all countries.

The researchers argue that weight control is essential in reducing the burden of early onset type 2 diabetes, but countries should establish specific policies to deal with this problem more effectively.

Type 2 diabetes traditionally develops in middle-aged and older people, and carries increased risks of serious complications, including heart disease, vision loss, and death.

Data suggest that early onset of type 2 diabetes (diagnosis before the age of 40) is becoming increasingly common. But no study has specifically described the global burden of early onset type 2 diabetes, or the variations between the sexes and in countries with different levels of socioeconomic development.

Risk factors for early onset type 2 diabetes in different countries are also unclear.

To fill these knowledge gaps, researchers used data from the Global Burden of Disease Study 2019 to estimate new cases (incidence), deaths and disability adjusted life years (DALYs)—a combined measure of quantity and quality of life—due to type 2 diabetes in adolescents and young adults (aged 15-39 years) from 204 countries and territories between 1990 and 2019.

They also examined the proportional DALY attributable to different risk factors, and data were assessed by age, sex and sociodemographic index.

The results show that the age standardized incidence rate for type 2 diabetes in adolescents and young adults globally increased from 117 per 100,000 population in 1990 to 183 in 2019, and the age standardized DALY rate increased from 106 per 100,000 in 1990 to 150 per 100,000 in 2019.

The age standardized mortality rate increased modestly from 0.74 per 100,000 in 1990 to 0.77 per 100,000 in 2019.

When grouped by countries with different sociodemographic indexes, countries with a low-middle and middle sociodemographic index had the highest age standardized incidence rate and age standardized DALY rate in 2019, whereas countries with a low sociodemographic index had the lowest age standardized incidence rate but the highest age standardized mortality rate.

Women generally had higher mortality and DALY rates than men at ages under 30 years, but differences between the sexes were reversed in those aged over 30 years, except in countries with a low sociodemographic index.

The main attributable risk factor for DALY for early onset type 2 diabetes was high body mass index in all regions by sociodemographic index.

The contribution of other risk factors varied across regions, however, with higher proportions of ambient particulate air pollution (12% vs. 7%) and smoking (13% vs. 4%) in countries with a high sociodemographic index and higher proportions of household air pollution from solid fuels (17% vs. 0.07%) and diet low in fruit (9% vs. 6%) in countries with a low sociodemographic index.

The researchers point to some study limitations, such as differences in the definition of type 2 diabetes and a high probability of underdiagnosis in many countries. And while several techniques were used to reduce bias and inaccuracy in the data, bias cannot be fully ruled out.

Nevertheless, they point out that they comprehensively evaluated the global, regional, and national temporal trends for early onset type 2 diabetes and the corresponding contributions of risk factors based on the Global Burden of Disease Study 2019.

"Our study showed a clear upward trend of the burden of early onset type 2 diabetes from 1990 to 2019," they write. "These findings provide a basis for understanding the epidemic nature of early onset type 2 diabetes and call for urgent actions to deal with the issue from a global perspective."

More information: Global burden of type 2 diabetes in adolescents and young adults, 1990-2019: systematic analysis of the Global Burden of Disease Study 2019, The BMJ (2022). DOI: 10.1136/bmj-2022-072385

https://medicalxpress.com/news/2022-12-substantial-diabetes-young-people-years.html

CRISPR insight: How to fine-tune the Cas protein's grip on DNA

 At the heart of every CRISPR reaction, whether naturally occurring in bacteria or harnessed by CRIPSR-Cas gene editing technology, is a strong molecular bond of a Cas protein via a guide RNA to its target site on DNA. It's like a nanoscale ski binding.

"There's a balance between stably bound and coming off at the right time," said Michelle Wang, the James Gilbert White Distinguished Professor of the Physical Sciences and Howard Hughes Medical Institute Investigator in the College of Arts and Sciences. "What we really want is the ability to modulate the affinity. That gives us the possibility of fine-tuning the gene editing potential."

A Cas protein binding can't be too transient, according to Porter Hall, a biophysics doctoral candidate in the Wang Lab and the lead author of the publication. If it can't stably bind the target region of the DNA, precise gene editing may not be efficient, potentially leading to off-target effects. "But if the protein stays there forever, then the gene editing process cannot be completed," Hall said.

Examining the precise, molecular-level mechanisms involved in Cas binding to DNA, Wang and colleagues give the first mechanistic explanation of how a motor protein (RNA polymerase) removes a bound dCas, a version of Cas engineered to recognize a DNA sequence without performing a cut.

This insight reveals how to tune Cas removal, contributing to future CRISPR applications.

"Polarity of the CRISPR Roadblock to Transcription" published Dec. 5 in Nature Structural & Molecular Biology. Other contributors are lab members James Inman, Robert Fulbright and Tung Le, along with collaborators Guillaume Lambert, assistant professor in applied and engineering physics, Cornell Engineering, and Joshua Brewer and Seth Darst from the Rockefeller University.

"To fully realize the potential of CRISPR technology, it is crucial to obtain an in-depth mechanistic understanding of Cas binding stability," the researchers wrote. "This work highlights the importance of the R-loop in dCas binding stability and provides valuable mechanistic insights for broad applications of CRISPR technology."

The Wang Lab investigates how motor proteins move as they travel along DNA strands, carrying out vital biological processes.

The motor protein RNA polymerase exerts force on "roadblocks" as it carries out its function of gene expression, copying DNA to RNA, Wang said. In this study, the roadblock was endonuclease-deficient Cas (dCas).

Previously, using nanophotonic tweezers, the researchers mechanically separated the two DNA strands to map out where the bound dCas protein is on the DNA. They call this the DNA unzipping mapper.

Previous research established that removal of dCas by a motor protein is possible only from one side (a polarity). Using the unzipping mapper for the current study, the Cornell researchers discovered why: because RNA polymerase can collapse the loop formed between the guide RNA and the target DNA (called the "R-loop") of a bound dCas only from one side, the side distal (or distant) from the PAM (protospacer adjacent motif), a short DNA sequence 2-6 base pairs long, that follows the DNA region targeted for cleavage.

Once the researchers describe how the mechanism works, they also show how to tune the dCas R-loop stability by modifying the guide RNA.

"We hope that fundamental knowledge of how Cas proteins work can ultimately lead to more efficient gene editing and broader applications of the CRISPR technology," Wang said.

Story Source:

Materials provided by Cornell University. Original written by Kate Blackwood, courtesy of the Cornell Chronicle. Note: Content may be edited for style and length.

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Journal Reference:

1. Porter M. Hall, James T. Inman, Robert M. Fulbright, Tung T. Le, Joshua J. Brewer, Guillaume Lambert, Seth A. Darst, Michelle D. Wang. Polarity of the CRISPR roadblock to transcription. Nature Structural & Molecular Biology, 2022; DOI: 10.1038/s41594-022-00864-x

https://www.sciencedaily.com/releases/2022/12/221206115719.htm

Potential link between oral bacteria and brain abscesses

 Bacteria known to cause oral infections may also be a contributory factor in patients developing potentially life-threatening abscesses on the brain, new research has shown.

The study, published in the Journal of Dentistry, investigated brain abscesses and their association with bacteria that occur in the oral cavity. While this type of abscess is relatively uncommon, it can result in significant mortality and morbidity.

Researchers examined the records of 87 patients admitted to hospital with brain abscesses, and used microbiological data obtained from abscess sampling and peripheral cultures.

This allowed them to investigate the presence of oral bacteria in patients' brain abscesses where a cause of the abscess had either been found, as was the case in just 35 patients, or not found.

Their results showed that the 52 patients where no cause had been found were about three times as likely to have oral bacteria present in their samples.

Those patients also carried significantly higher counts of Streptococcus anginosus, a bacteria that can lead to pharyngitis, bacteremia, and infections in internal organs such as the brain, lung, and liver. This bacteria is often found in dental abscesses.

Writing in the study, researchers say the findings suggest that the oral cavity could be considered a source of infection in cases of brain abscess where no clear cause has been identified.

The research was led by the University of Plymouth and University Hospitals Plymouth NHS Trust.

Dr Holly Roy, an NIHR Clinical Lecturer in Neurosurgery based at the University of Plymouth and University Hospitals Plymouth NHS Trust, is the study's lead author.

She said: "While many potential causes of brain abscesses are recognised, the origin of infection often remains clinically unidentified. However, it was still surprising to frequently find orally occurring bacteria in brain abscesses of unexplained origin. It highlights the importance of using more sensitive techniques to assess the oral cavity as a potential bacterial source in brain abscess patients. It also highlights the importance of improving dental care and oral hygiene more generally."

The study forms part of ongoing research taking place within the University's Oral Microbiome Research Group, led by Dr Raul Bescos and Dr Zoe Brookes, to explore the links between the oral microbiome and a range of cardiovascular and neurological conditions.

Other clinical trials are underway investigating the links between gum health and Alzheimer's disease and identifying patients under high cardiovascular risk in primary care dental clinics, as an altered balance of oral bacteria (microbiome) during gum disease can lead to high blood pressure and strokes.

These clinical studies are being carried out in primary care dental facilities run by Peninsula Dental Social Enterprise, where the focus of the research is very much on improving clinical outcomes for patients.

Story Source:

Materials provided by University of Plymouth. Note: Content may be edited for style and length.

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Journal Reference:

1. Holly Roy, Raul Bescos, Ewen McColl, Umar Rehman, Elizabeth Cray, Louise A. Belfield, King-David Nweze, Kevin Tsang, William Singleton, Peter Whitfield, Zoe Brookes. Oral microbes and the formation of cerebral abscesses: A single-centre retrospective study. Journal of Dentistry, 2023; 128: 104366 DOI: 10.1016/j.jdent.2022.104366

https://www.sciencedaily.com/releases/2022/12/221207100403.htm