New findings pave the way for hearing loss therapies

 As we age, many of us will eventually need hearing aids. In some cases, the reason for this may be a signaling pathway that controls auditory sensory cell function and is downregulated with age. Researchers at the University of Basel are uncovering clues.

Hearing loss eventually affects almost everyone: Loud noises or simple aging gradually cause the auditory sensory cells and their synapses in the inner ear to degenerate and die off. The only treatment option is a hearing aid or, in extreme cases, a cochlear implant.

"In order to develop new therapies, we need to better understand what the auditory sensory cells need for proper function," explains Dr. Maurizio Cortada from the Department of Biomedicine at the University of Basel and University Hospital Basel. In collaboration with Professor Michael N. Hall's research group at the Biozentrum, Cortada investigated which signaling pathways influence the so-called sensory "hair cells" in the inner ear. In the process, the researchers discovered a central regulator, as they report in the journal iScience.

This signaling pathway, known by researchers as the mTORC2-signaling pathway, plays an important role, among other things, for cell growth and the cytoskeleton. The role it plays for the hair cells in the inner ear has not previously been studied.

When the researchers removed a central gene of this signaling pathway in the hair cells of the inner ear of mice, the animals gradually lost their hearing. By the age of twelve weeks, they were completely deaf, the authors report in the study.

Fewer synapses

Closer examination indicated that the sensory hair cells in the inner ear lost their sensors without the mTORC2 signaling pathway: hair cells have protuberances similar to tiny hairs that are important for transducing sound into nerve signals. These "tiny hairs" were shortened, as the researchers determined with the use of electron microscopes. The number of synapses that transmit the signals to the auditory nerve was also reduced.

"From other studies, we know that the production of key proteins in this signaling pathway decreases with age," Cortada explains. There may be a connection to the loss of synapses and the reduced function of the auditory sensory cells in the inner ear that leads to hearing loss with increasing age.

"If this is confirmed, it would be a possible starting point for future therapies," says the researcher. The middle and inner ear, for example, would be readily accessible for locally-administered medications or gene therapies. The results could pave the way for the development of such treatment options.

Journal Reference:

1. Maurizio Cortada, Soledad Levano, Michael N. Hall, Daniel Bodmer. mTORC2 regulates auditory hair cell structure and function. iScience, 2023; 26 (9): 107687 DOI: 10.1016/j.isci.2023.107687

https://www.sciencedaily.com/releases/2023/10/231005110802.htm

Increased deep sleep benefits your heart

 Sleep is a vital aspect of human life, with deep sleep being particularly crucial for overall health. The brain recovers during this sleep stage, and the rest of the body seems to regenerate then as well.

Recently, researchers at ETH Zurich and the University of Zurich have shown that increased deep sleep is of particular benefit to the cardiovascular system: targeted stimulation with brief tones during deep sleep causes the heart -- in particular the left ventricle -- to contract and relax more vigorously. As a result, it pumps blood into the circulatory system and draws it out again more efficiently. The left ventricle supplies most organs, the extremities, and the brain with oxygen-rich arterial blood.

When the heart contracts, the left ventricle is squeezed and wrung out like a wet sponge. The more immediate and more powerful this wringing action, the more blood enters the circulation and the less remains in the heart. This increases blood flow, which has a positive effect on the cardiovascular system.

An interdisciplinary team of heart specialists led by Christian Schmied, Senior Consultant for Cardiology at the University Hospital Zurich, used echocardiography (cardiac ultrasound examinations) to demonstrate that the left ventricle undergoes more intense deformation after nocturnal stimulation. This is the first time anyone has shown that an increase in brain waves during deep sleep (slow waves) improves cardiac function. The corresponding study was recently published in the European Heart Journal.

"We were expecting that stimulation with tones during deep sleep would impact the cardiovascular system. But the fact that this effect was so clearly measurable after just one night of stimulation surprised us," explains project leader and sleep expert Caroline Lustenberger, SNSF Ambizione Fellow at the Neural Control of Movement Lab at ETH Zurich.

Heart specialist Schmied is also delighted: "We clearly saw that both the heart's pumping force and its relaxation were greater after nights with stimulation compared to nights without stimulation." Both factors are an excellent measure of cardiovascular system function.

Stimulation with pink noise

The study involved 18 healthy men aged 30 to 57, who spent three non-consecutive nights in the sleep laboratory. On two nights, the researchers stimulated the subjects with sounds; on one night, they did not.

While the subjects slept, the scientists continuously measured their brain activity, blood pressure and heart activity. They coupled their measurements to a computer system that analysed the incoming data.

As soon as the readings indicated that the subject had fallen into deep sleep, the computer played a series of very brief tones at certain frequencies, called pink noise, which sound like static. Ten seconds of such tones were followed by 10 seconds of silence, and then the same procedure could be repeated. A feedback mechanism ensured that the noise was played at the right time and -- depending on the brain wave pattern -- stopped again.

This experimental setup allowed the researchers to directly monitor whether the sound simulation enhanced deep sleep and whether it influenced the subjects' heart rate and blood pressure. "During stimulation, we clearly see an increase in slow waves, as well as a response from the cardiovascular system that is reminiscent of cardiovascular pulsation," says lead author Stephanie Huwiler, describing the direct effects during sleep.

The next morning, the heart specialists examined the subjects' cardiac function using echocardiography (ultrasound).

Significant results despite small group

"Despite the relatively small group of subjects, the results are significant. We were also able to reproduce the results on two separate nights, which in statistical terms makes them very strong," Lustenberger says.

A small group size is typical for laboratory sleep studies, she adds, because they require a lot of resources. In addition, the researchers deliberately selected only men. This is because they are more homogeneous as a group of subjects than women in a comparable age bracket, whose menstrual cycle or menopause has a major effect on their sleep. "When all you've got to work with is one night a week for three weeks, the effects of the menstrual cycle will play a role in women. These effects might have masked the stimulation effect in this sort of initial study," Lustenberger explains.

She emphasizes, however, that future studies should definitely include women, as gender differences in sleep and cardiovascular health are becoming increasingly apparent and have profound implications for primary healthcare.

Practical future benefits

This study is of great interest not only to cardiologists but to athletes as well. "Especially in preventive medicine, but also in competitive sport, this kind of deep sleep stimulation system might enable improved cardiac function in the future -- and possibly ensure faster and better recovery after intense workouts," says Huwiler, who presented the initial results of the study at the Zurich Symposium for Sports Cardiology in March 2023. Lustenberger adds: "The treatment of cardiovascular diseases may be enhanced with this or similar stimulation methods. However, it's crucial to first investigate whether patients can benefit from this kind of deep sleep stimulation method as well."

The researchers are now looking for further, more powerful stimulation methods to positively impact the cardiovascular system. To this end, Huwiler is applying to Innosuisse for a Bridge Proof of Concept grant and for an ETH Pioneer Fellowship grant. In addition, she is in the process of setting up a start-up called EARDREAM together with Lustenberger, Simon Baur, and Rafael Polanía to further develop the findings and transfer them into practice.

Journal Reference:

1. Stephanie Huwiler, Manuel Carro-Domínguez, Fabia M Stich, Rossella Sala, Florent Aziri, Anna Trippel, Tabea Ryf, Susanne Markendorf, David Niederseer, Philipp Bohm, Gloria Stoll, Lily Laubscher, Jeivicaa Thevan, Christina M Spengler, Joanna Gawinecka, Elena Osto, Reto Huber, Nicole Wenderoth, Christian Schmied, Caroline Lustenberger. Auditory stimulation of sleep slow waves enhances left ventricular function in humans. European Heart Journal, 2023; DOI: 10.1093/eurheartj/ehad630

https://www.sciencedaily.com/releases/2023/10/231005110805.htm

Gateway helping pneumonia bacteria become resistant to antibiotics

 The new research has identified a genetic scar left in the genomes of bacteria as they become resistant to antibiotic treatment.

This significant breakthrough in understanding how antibiotic resistance occurs will allow scientists to better predict which strains of pneumonia will become highly resistant in the future, giving them time to put control measures in place to help save patients' lives.

Pneumonia is a very serious infection and the third leading cause of death in the UK population. Often these infections are caused by a bacterium called Streptococcus pneumoniae (S.pneumoniae). Antibiotics are given to patients to kill the bacteria, however the bacteria are finding ways to become resistant and this resistance threatens patient treatment in the long-term.

The Sheffield team discovered mutations called pde1 act as an evolutionary gateway through which the S.pneumoniae cells start to become resistant to antibiotics.

Lead author, Dr Andrew Fenton from the School of Biosciences at the University of Sheffield, said: "Pneumonia is a dangerous and deadly infection and effective treatment with antibiotics is essential for patient care. However, the effectiveness of antibiotics is increasingly under threat as the bacteria which cause pneumonia become resistant to antibiotic treatment over time.

"This research has identified a genetic scar left in the genomes of bacteria as they become resistant to antibiotic treatment. This is a major step forward in understanding how resistance occurs and how we might be able to predict it.

"If we understand the emergence of antibiotic resistance then we can predict what groups of bacterial strains are becoming more dangerous. Giving us time to put control measures in place to stop their spread, saving patients' lives."

Over the last 10 years there have been many large-scale genome association and genetic studies focused on S.pneumoniae antibiotic resistance but these have, so far, not led to effective mitigations.

This study, published in the journal PNAS, is a significant step forward in the molecular understanding of resistance and adds pde1 to the select few mutations known to promote antibiotic resistance in S. pneumoniae.

Journal Reference:

1. Carolin M. Kobras, William Monteith, Sophie Somerville, James M. Delaney, Imran Khan, Camilla Brimble, Rebecca M. Corrigan, Samuel K. Sheppard, Andrew K. Fenton. Loss of Pde1 function acts as an evolutionary gateway to penicillin resistance in Streptococcus pneumoniae. Proceedings of the National Academy of Sciences, 2023; 120 (41) DOI: 10.1073/pnas.2308029120

https://www.sciencedaily.com/releases/2023/10/231002170831.htm

Dengue 'set to 'take off' in Southern US'

 Dengue fever, an infection caused by mosquito bites, may become increasingly common across the Southern U.S. within the next decade.

The disease has been on the rise in several regions worldwide including Africa, the Middle East, Asia and the Pacific Islands, as well as in tourist regions like the Caribbean, Puerto Rico, both Central and South America and Southeast Asia, according to the CDC.

"In the United States, local cases and limited spread of dengue does occur periodically in some states with hot, humid climates and Aedes mosquitoes," the agency's website states. 

Infectious disease expert for the World Health Organization, Jeremy Farrar, said clinicians in the Southern U.S. should be prepared to care for increased cases of Dengue as climate change increases regional temperatures, making the environment more hospitable for the infection-causing mosquitoes, according to an Oct. 6 report from Reuters. 

Dengue, Dr. Farrar told Reuters, is likely to become endemic in the U.S. According to the CDC, to date most outbreaks in the nation have been small-scale. The states that have experienced local spread of the infection in recent years include Texas, Florida, Hawaii and Arizona.

https://www.beckershospitalreview.com/public-health/the-disease-set-to-take-off-in-southern-us-reuters.html

Healthcare discounts absent from Amazon's next Prime day

 Amazon Prime customers looking to get a deal on healthcare will have to wait.

Unlike July's Prime Day, the upcoming Prime Big Deal Days will not have any healthcare-related discounts.

For Prime Day, in a first for the online retailer, Amazon offered discounts for One Medical, the membership-based primary care company it acquired in February for $3.9 billion. The annual memberships for One Medical, which typically cost $199, were discounted to $144.

But there will be no healthcare sales this time around, Amazon confirmed to Becker's. Prime Big Deal Days runs Oct. 10-11.

https://www.beckershospitalreview.com/disruptors/healthcare-discounts-absent-from-amazons-next-prime-day.html

AHA asks CMS to stop telehealth rule

 The American Hospital Association is asking CMS to stop a pending requirement that healthcare providers list their addresses if they're providing telehealth from their homes.

During the pandemic's public health emergency, CMS removed a rule that clinicians delivering telemedicine from their homes list their addresses on enrollment and claims forms. But that flexibility is scheduled to end Dec. 31.

"Requiring providers to list their personal home addresses on enrollment and claims forms, to which patients or others in the public have access, poses privacy and safety risks. This is a particular concern to us given the increased incidence in violence against healthcare workers," wrote Ashley Thompson, senior vice president of public policy analysis and development for the AHA, in an Oct. 4 letter to CMS. "At a minimum, CMS must implement a mechanism to automatically mask the home address from any public sites and directories."

The AHA also said the rule could also hurt workforce retention, as providers could shy away from wanting to provide telehealth from home, and places an undue administrative burden on hospitals and health systems, which would have to track and update home addresses on enrollment forms and update their billing software and EHRs to add providers' homes as sites of care.

https://www.beckershospitalreview.com/telehealth/aha-asks-cms-to-stop-telehealth-rule.html

"This Is Unacceptable": Blue States Blast Biden Over Border Blunders As Backlash Intensifies

Blue states buckling under the strain of hundreds of thousands of migrants bussed into their Democratic strongholds are blaming President Joe Biden for not doing enough to curb the influx of illegals.

The latest politician to blast Biden is Illinois Gov. J.B. Pritzker, who told Biden in a Monday letter that his state is in an "untenable situation," and that the feds need to take "swift action."

In August, New York Gov. Kathy Hochul (D) joined with business leaders to implore the administration to do something about the "humanitarian crisis" that's overwhelmed New York City with more than 100,000 migrants.

The next month, NYC Mayor Eric Adams predicted that the migrant crisis "will destroy New York City."

Massachusetts Gov. Maura Healey (D), meanwhile, issued a state of emergency in August in response to the illegal migrant crisis, telling DHS Secretary Alejandro Mayorkas in a letter that her state has taken action "to address what sadly has been a federal crisis of inaction."

 White House officials are scrambling to respond - and have already fumbled the ball on the border wall. Earlier last week, reports emerged that Department of Homeland Security Secretary Alejandro Mayorkas said, in an official document, that there is "an acute and immediate need to construct physical barriers" along the US border- while the Biden administration waived 26 federal laws to build more border wall.

Two days later, he backpedaled furiously, claiming "There is no new administration policy with respect to the border wall," adding "From day one, this Administration has made clear that a border wall is not the answer. That remains our position and our position has never wavered. The language in the Federal Register notice is being taken out of context and it does not signify any change in policy whatsoever," the statement continues.

White House press secretary Karine Jean-Pierre tried to downplay the move, arguing that the government is following Trump-era laws but still does not believe in the wall's effectiveness.

"We believe that we need border technology that is modernized and land ports of entry. And that’s what we want to see," she told reporters on Thursday, adding that Biden "does not believe it is effective. He has been very clear about that."

Jean-Pierre added that the wall funds were from a Trump-era border appropriations bill.

"We asked Congress to reappropriate the funds," she said, "But they’ve refused, and so now we’re moving forward."

More via The Epoch Times;

Biden Trying to Appease Democratic Leaders: Border Experts

The White House is acting in accordance with the Impoundment Control Act of 1974, which forbids the President or other government officials from bypassing Congress in making funding decisions. This is not, however, the primary reason why the administration is restarting the construction of the wall, according to Andrew Arthur, resident fellow in law and policy for the Center for Immigration Studies, a Washington-based think tank.

The decision is clearly “driven by a need to respond to concerns voiced by Democratic-elected officials in northern U.S. cities,” Mr. Arthur told The Epoch Times.

“Barriers will help agents in the apprehension and processing of illegal entrants, but they will do nothing to discourage those migrants improper entries absent a concomitant policy shift—but at least the administration can claim that it is ‘doing something.’”

'We're Here Abandoned'

Last month, Mayor Rolando Salinas of Eagle Pass, Texas, a Democrat, criticized President Biden for the border crisis. In an interview with CNN, he complained that the White House had not communicated with him while thousands of illegal immigrants poured into his small city.

"We're here abandoned. We're on the border, we're asking for help. This is unacceptable," he said.

In a recent letter to the White House, Gov. Pritzker also raised a similar concern, urging that "there be one person in the federal government" who works directly for the president and is in charge of overseeing efforts at the border.

When asked about this request, Ms. Jean-Pierre said, “There are multiple folks” at the White House who have been in contact with governors across the country.

“Look, let’s not forget, we provided a billion dollars to those counties, states, cities who are dealing with this issue,” she said. “It is an issue that’s incredibly important to this president."

https://www.zerohedge.com/political/unacceptable-blue-states-blast-biden-over-border-blunders-backlash-intensifies