Noise-induced hearing loss restored in mice

searchers from the University of Michigan and Harvard Medical School in Boston, MA, may be well on the way to finding new therapies that restore noise-induced and age-related hearing loss in humans. In a new study, the team describes how they recovered hearing in mice partially deafened by noise.

 

The researchers, led by Gabriel Corfas, PhD, of the University of Michigan, publish their findings online in the journal eLife.

Approximately 50 million Americans have hearing loss in at least one ear, with around 26 million Americans aged 20-69 experiencing high-frequency hearing loss as a result of noise exposure. Hearing loss is also common as we age, affecting around 30% of adults aged 65-74 and 47% of adults aged 75 and over.

In their study, the researchers explain how they were able to increase production of a protein called Neurotrophin-3 (NT3) in mice, which they found plays a key role in communication between the ears and the brain.

NT3 allows sound signals to be sent from the ear to the brain. The protein is crucial in establishing a super-fast connection between the ear’s hair cells and nerve cells – a connection the researchers call the “ribbon synapse.” But this ribbon synapse can become damaged as a result of noise exposure or normal aging, which can lead to hearing loss.

Boosting NT3 production in mice

In their study, the researchers identified supporting cells in the inner ear that produce NT3. They set out to see what would happen if they increased production of NT3 through these supporting cells.

Fast facts about hearing loss

• Hearing loss is more common among men than women
• Around 60% of veterans returning from Iraq or Afghanistan have some form of hearing loss ortinnitus – ringing in the ears
• Approximately 2-3 in every 1,000 children in the US are born with detectable levels of hearing loss in one or both ears.

Learn more about hearing loss

They adopted a method called conditional gene recombination. This allows researchers to activate genes in particular cells by administering a drug that prompts the cells to “read” additional copies of a gene that have been inserted into them.

For this study, the team used the technique to activate additional NT3 genes that had been introduced to the supporting cells of the inner ear in mice that had been partially deafened by loud noise.

The drug tamoxifen was introduced to the supporting cells in the inner ear, which prompted them to produce extra NT3 protein. The researchers then tested the hearing of the mice through a test normally used in humans – the auditory brainstem response (ABR).

The researchers found the mice that had experienced boosted NT3 production regained their hearing over a 2-week period, compared with mice that had not had additional NT3 production.

According to the team, these findings indicate that NT3 production is important for making ribbon synapses, and that boosting production of this protein may restore noise-induced and age-related hearing loss.

The potential to restore hearing loss in humans

Corfas and his team say they now plan to investigate the role of NT3 in human ears and identify drugs that produce the same effect as the protein, offering the potential to restore hearing loss in humans.

The researchers note that the gene therapy technique used in this study has the potential to work in humans, but that a drug-based method would be “simpler” and a drug could be repeatedly administered for as long as it takes for hearing to be restored. Corfas says he already has some drug candidates in mind.

The researchers stress, however, that since the mice in this study were only partially deaf, it is unclear whether increased NT3 production would restore hearing in subjects that are fully deaf.

But the team believes their findings are promising. Corfas says:

“It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it’s due to noise or normal aging. We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people. It’s very exciting.”

Their findings may even reach further than hearing loss. The researchers say they may offer new strategies to treat neurodegenerative diseases, in which nerve cell connections are impaired.

Medical News Today recently reported on a study from the University of Leicester in the UK, in which researchers reveal how loud noises damage hearing in more detail.

Written by Honor Whiteman

http://www.medicalnewstoday.com/articles/284159.php

 

 

Effectiveness of treatment to reduce blood clots in otolaryngology patients admitted for surgery examined

The effectiveness of a treatment to reduce blood clots among otolaryngology patients admitted for surgery appears to differ based on patient risk and the procedure.

Blood clots (venous thromboembolism [VTE], which includes deep vein thrombosis [DVT] and pulmonary embolism[PE]) are common complications in surgical patients. Treatment (primary thromboprophylaxis with anticoagulant medication [chemoprophylaxis]) can help reduce the incidence of VTE in surgical patients. But treatment should be considered in light of the risk of VTE and bleeding complications. The American College of Chest Physician’s guidelines for thromboprophylaxis do not specifically apply to otolaryngology. The authors sought to examine the effectiveness and safety of VTE chemoprophylaxis for otolaryngology patients admitted for surgery.

How the Study Was Conducted:

The study included 3,498 patients treated by surgeons at an academic medical center between September 2003 and June 2010. The authors analyzed the incidence of VTE and bleeding complications within 30 days after surgery.

Results:

Of the 1,482 patients who received VTE chemoprophylaxis, 18 (1.2 percent) developed a VTE compared with 27 of 2,016 patients (1.3 percent) who did not receive treatment. Patients with higher scores on a risk assessment were less likely to have a VTE with perioperative chemoprophylaxis (5.3 percent vs. 10.4 percent). Of the patients who underwent treatment, 3.5 percent developed a bleeding complication compared with 1.2 percent of patients without treatment. Among patients who underwent free tissue transfer, treatment decreased the incidence of VTE (2.1 percent vs. 7.7 percent) and increased bleeding complications (11.9 percent vs. 4.5 percent). In all other patients, treatment did not significantly influence the likelihood of VTE (1 percent vs. 0.6 percent) or bleeding (1.5 percent vs. 0.9 percent).

Discussion:

“Results from this study provide the basis for future research. … An examination of additional benefits and harms of VTE prophylaxis is warranted, including its impact on mortality due to PE. Free tissue transfer patients merit special analysis when developing recommendations for VTE prophylaxis because of the high risk of both VTE and bleeding. … Finally, further tests of the incidence of VTE by risk level and of the effectiveness and safety of chemoprophylaxis should be conducted for other otolaryngology patients, in populations large enough to produce sufficiently powered analyses.”

http://www.medicalnewstoday.com/releases/283314.php

 

Viral infection causes bacteria to colonize privileged sites like the middle ear

Influenza infection can enhance the ability of the bacterium Streptococcus pneumonia to cause ear and throat infections, according to research published ahead of print in the journal Infection and Immunity.

In the study, the investigators infected mice with either influenza alone, pneumococci alone, or both at once, and then monitored the populations of bacteria and virus over time. They also monitored the mice for development of middle ear infection.

Influenza infection enhanced the bacterium’s ability to colonize the nasopharynx, and to infect the normally sterile middle ear.

“We learned that once influenza virus is introduced, all of the “rules” regarding phase variants are out the window,” says corresponding author W. Edward Swords of Wake Forest University, Winston-Salem, NC. Phase variation refers to the fact that the colonizing bacteria have transparent cell surfaces, while those that spread within the host have opaque surfaces.

“However, in the presence of influenza, opaque variants can readily colonize the nasopharynx, and transparent variants can persist in the ear,” says Swords. “This indicates that the host environs are more permissive for infection by the entire bacterial population.”

Furthermore, recent research had shown that influenza interferes with innate immunity in a way that enables pneumococci to flourish. In this research, Swords shows that that interference manifests as increased inflammatory responses at the mucosal surface in the influenza-infected mice, such as within the middle ear, and in the nasopharynx.

“As with most pneumococcal infections, it should be appreciated that localized nonlethal infections are much more common than the rapidly lethal presentations,” says Swords. “For example, influenza is a contributing factor in otitis media (middle ear infections) in children.”

“If we can understand why and how viral infection causes bacteria to colonize privileged sites like the middle ear, we will better know what aspects of disease to focus on with preventive or therapeutic treatments,” says Swords.

http://www.medicalnewstoday.com/releases/282910.php

Picture courtesy to www.chori.org

 

 

Tinnitus less common in women who drink more coffee

A new study finds that women who consume more caffeine are less likely to have tinnitus – a condition where a person perceives noise in one or both ears, or in the head, even though there is no external sound.

 

The researchers, from Brigham and Women’s Hospital (BWH) in Boston, MA, write about their findings in The American Journal of Medicine.

According to the American Tinnitus Association, around 50 million people in the US experience some degree of tinnitus, which is often described as “ringing in the ears” although some people also hear hissing, buzzing, roaring, clicking or chirping. Of these, about 1 million are so badly affected they cannot function normally day to day.

For the study, the researchers analyzed data on over 65,000 women with and without tinnitus from the Nurses’ Health Study II.

The women were aged between 30 and 44 at the start of the study in 1991, when researchers collected a wealth of information on medical history, lifestyle and diet. At this point, the average caffeine intake was 242.3 mg per day – the equivalent of nearly two and a half 8-ounce cups of coffee. Most of the caffeine consumed came from coffee drinking.

In 2009, 18 years after they joined the study, the women were asked questions about tinnitus, including date of onset, where applicable. When a woman reported experiencing symptoms either daily or on a few days per week, the researchers counted it as a case. They identified a total of 5,289 cases of reported incident tinnitus.

Women who consumed more caffeine less likely to be among tinnitus cases

When they analyzed the results, the team found the more caffeine women consumed, the less likely they were to be among the tinnitus cases.

Senior author Gary Curhan, a physician-researcher in BWH’s Channing Division of Network Medicine and professor of Medicine at Harvard Medical School, says:

“We observed a significant inverse association between caffeine intake and the incidence of tinnitus among these women.”

He and his and colleagues found that regardless of age, rates of tinnitus were 15% lower among women who consumed 450-599 mg a day of caffeine, compared with women who drank less than 150 mg a day (about one and a half 8-ounce cups of coffee).

Prof. Curham notes that while the reason behind the finding is unclear, we know that “caffeine stimulates the central nervous system, and previous research has demonstrated that caffeine has a direct effect on the inner ear in both bench science and animal studies.”

The researchers say more evidence is required before we can say whether increased caffeine intake might improve tinnitus symptoms.

Funds from the National Institutes of Health helped finance the study.

Medical News Today recently reported on another study where researchers found tinnitus affects processing of emotions. Writing in the journal Brain Research, they describe how, compared with people not affected by the condition, those with tinnitus process emotions differently in the brain.

Written by Catharine Paddock PhD

http://www.medicalnewstoday.com/articles/280775.php

 

 

 

 

Biomarker for head and neck cancers identified

Although mutations in a gene dubbed “the guardian of the genome” are widely recognized as being associated with more aggressive forms of cancer, researchers at the University of California, San Diego School of Medicine have found evidence suggesting that the deleterious health effects of the mutated gene may in large part be due to other genetic abnormalities, at least in squamous cell head and neck cancers.

The study, published online in the journal Nature Genetics, shows that high mortality rates among head and neck cancer patients tend to occur only when mutations in the tumor suppressor gene coincide with missing segments of genetic material on the cancer genome’s third chromosome.

The link between the two had not been observed before because the mutations co-occur in about 70 percent of head and neck tumors and because full genetic fingerprints of large numbers of cancer tumors have become available only recently.

“These two genetic malfunctions are not two separate stab wounds to the body,” said co-senior author Trey Ideker, PhD, chief of the Division of Genetics. “One exposes the Achilles tendon and the other is a direct blow to it.”

To patients with these cancers, the study’s results mean that there may be therapeutic value in testing tumors for the two genetic identifiers, known as a TP53 mutation (short for tumor protein 53) and a 3p deletion (short for deletions of genetic information on the short arm “p” of the third chromosome).

TP53 plays a key role in regulating cell growth, detecting and fixing DNA, and directing cell apoptosis (death) if the DNA damage is irreparable. Because of this, the TP53 protein is sometimes called the “guardian of the genome.”

The study’s findings suggest that if both markers are present, treatment should be intensified. If only one mutation is present, treatment might be de-intensified because the TP53 mutation alone is less deadly than previously thought. The latter would have immediate benefits in reducing deaths caused by complications related to medical care.

“We are in the early stages of being able to personalize head and neck cancer treatments based on the tumor’s actual biology, the same as what’s done with breast cancers,” said co-senior author Quyen Nguyen, MD, PhD, associate professor of Otolaryngology-Head and Neck Surgery. “In the past, treatments have been based largely on the size and location of the tumor. Now, we know that some large tumors may respond to less aggressive treatment while some small tumors may need intensified treatment. This will have a huge impact for patients.”

The study analyzed the complete genomic signatures of 250 cases of squamous cell head and neck cancer extracted from The Cancer Genome Atlas, a repository of sequenced cancer genomes for more than 20 different types of human cancers maintained by the National Institutes of Cancer. All of the tumors were from patients younger than 85 years of age.

Of these, 179 had both mutations; 50 had one of the two mutations; and 22 had neither mutation. Comparisons with patient outcome data showed that half of patients with both mutations would likely die of cancer within 2 years, while 66 percent of patients with one or neither mutation would be expected to live five years or more. These survival statistics were independent of the patients’ clinical cancer stage.

Besides causing cervical cancer, the human papilloma virus (HPV) is implicated in the growing epidemic of head and neck cancers in otherwise healthy adults. It is believed that the virus can co-opt the activity of TP53, affecting cells in much the same way as a TP53 mutation but without causing a mutation. For this reason, the analysis examined HPV-positive and HPV-negative tumors separately.

One of the study’s more compelling discoveries is that among HPV-positive tumors, the most aggressive cancer cases were also highly linked to the presence of 3p deletions.

“Our findings raise fundamental questions about the role of TP53 in cancer and suggest that some of the deleterious health effects of TP53 mutations might actually be due to something else going on in the third chromosome,” said lead author Andrew Gross, a graduate student in the Bioinformatics and Systems Biology Program.

 

http://www.medicalnewstoday.com/releases/280558.php

 

 

 

Next-generation hearing aids emulate fly’s ability to pinpoint sound

ere is a fly that can locate a cricket from the sound it makes, despite other noises in the background. Yet the hearing mechanism that helps the fly do this spans only 1.5 mm, which is 50 times smaller than the wavelength of the cricket’s chirp. Now, engineers have found a way to mimic the fly’s super-hearing in a tiny device that does not require a bulky battery.

A paper describing the work is published in the journal Applied Physics Letters.

The engineers, from the Cockrell School of Engineering at the University of Texas at Austin, say the new device could be used in a new generation of hypersensitive hearing aids that use intelligent microphones to select only those sounds or conversations that the wearer wants to hear.

Fly’s sophisticated hearing can locate a cricket with remarkable accuracy

Neal Hall, an assistant professor in the Cockrell School’s Department of Electrical and Computer Engineering, and his team of graduate students, drew their inspiration from pioneering work by Ronald Miles at Binghamton University, NY, and Ronald Hoy at Cornell University, Ithaca, NY.

 

They were the first to describe the technological potential of emulating the super-hearing mechanism of the yellow-colored parasitoid flyOrmia ochracea, which stalks and locates male field crickets from their chirps and lays live larvae on and around them.

The fly can locate the cricket with remarkable accuracy because it has a sophisticated sound processing mechanism that determines the direction of the sound within an angle of 2 degrees.

Using the fly’s super-evolved hearing structure as a model, Prof. Hall and colleagues made a tiny pressure-sensing device out of silicon. With a span of only 2 mm, the device is nearly the same size as the fly’s hearing organ.

Unlike many insects, the reason humans and other mammals can pinpoint the source of a sound is because we have a much larger distance between our ears. The sound processing mechanism in our brains uses the time difference in the arrival of the sound at the two ears to locate the source.

But insects’ bodies are generally too small to do this – the sound waves effectively hit both sides almost at the same time.

That is, except for insects like O. ochracea – it can locate the direction of a cricket’s chirp even though its ears are less than 2 mm apart. Its highly evolved hearing mechanism can sense the 4 millisecond gap between the sound entering one ear and the other. It also amplifies this time difference using a “teeter-totter” or “see-saw” mechanism that allows it to locate the cricket with remarkable accuracy.

Engineers emulated fly’s hearing mechanism using a flexible beam

To replicate the fly’s hearing mechanism, the team made a flexible beam incorporating piezoelectric materials that allowed them to use the flexing and rotation of the beam as a way to measure sound pressure and pressure gradient at the same time.

While other teams have already tried to build hearing devices that emulate the fly’s super-hearing, Prof. Neal and colleagues are the first to use piezoelectric materials, which convert mechanical pressure into electrical signals and allow the device to work with very little power.

“Because hearing aids rely on batteries, minimizing power consumption is a critical consideration in moving hearing-aid device technology forward,” says Prof. Hall.

He sees this technology being attractive to people with hearing problems in the future. While as many as 1 in 10 Americans could benefit from a hearing aid, currently only a fifth of this number use one, he adds.

He says many believe the main reason for the gap is hearing aid wearers’ dissatisfaction with the devices:

“Turning up the volume to hear someone across from you also amplifies all of the surrounding background noise – resembling the sound of a cocktail party.”

As well as taking hearing aid technology to a new level, the device could also be useful in military and defense applications. For example, in dark environments where visual cues are absent.

Funds from the Defense Advanced Research Projects Agency (DARPA) helped finance the study.

In February 2014, Medical News Today reported how researchers have developed a new low-powered chip that offers the prospect of cochlear implants without external hardware.

Written by Catharine Paddock PhD

http://www.medicalnewstoday.com/articles/280000.php

 

 

 

Tinnitus affects processing of emotions

Patients with persistent ringing in the ears – a condition known as tinnitus – process emotions differently in the brain from those with normal hearing, researchers report in the journal Brain Research.

Tinnitus afflicts 50 million people in the United States, according to the American Tinnitus Association, and causes those with the condition to hear noises that aren’t really there. These phantom sounds are not speech, but rather whooshing noises, train whistles, cricket noises or whines. Their severity often varies day to day.

University of Illinois speech and hearing science professor Fatima Husain, who led the study, said previous studies showed that tinnitus is associated with increased stress, anxiety, irritability and depression, all of which are affiliated with the brain’s emotional processing systems.

“Obviously, when you hear annoying noises constantly that you can’t control, it may affect your emotional processing systems,” Husain said. “But when I looked at experimental work done on tinnitus and emotional processing, especially brain imaging work, there hadn’t been much research published.”

She decided to use functional magnetic resonance imaging (fMRI) brain scans to better understand how tinnitus affects the brain’s ability to process emotions. These scans show the areas of the brain that are active in response to stimulation, based upon blood flow to those areas.

Three groups of participants were used in the study: people with mild-to-moderate hearing loss and mild tinnitus; people with mild-to-moderate hearing loss without tinnitus; and a control group of age-matched people without hearing loss or tinnitus. Each person was put in an fMRI machine and listened to a standardized set of 30 pleasant, 30 unpleasant and 30 emotionally neutral sounds (for example, a baby laughing, a woman screaming and a water bottle opening). The participants pressed a button to categorize each sound as pleasant, unpleasant or neutral.

The tinnitus and normal-hearing groups responded more quickly to emotion-inducing sounds than to neutral sounds, while patients with hearing loss had a similar response time to each category of sound. Over all, the tinnitus group’s reaction times were slower than the reaction times of those with normal hearing.

Activity in the amygdala, a brain region associated with emotional processing, was lower in the tinnitus and hearing-loss patients than in people with normal hearing. Tinnitus patients also showed more activity than normal-hearing people in two other brain regions associated with emotion, the parahippocampus and the insula. The findings surprised Husain.

“We thought that because people with tinnitus constantly hear a bothersome, unpleasant stimulus, they would have an even higher amount of activity in the amygdala when hearing these sounds, but it was lesser,” she said. “Because they’ve had to adjust to the sound, some plasticity in the brain has occurred. They have had to reduce this amygdala activity and reroute it to other parts of the brain because the amygdala cannot be active all the time due to this annoying sound.”

Because of the sheer number of people who suffer from tinnitus in the United States, a group that includes many combat veterans, Husain hopes her group’s future research will be able to increase tinnitus patients’ quality of life.

“It’s a communication issue and a quality-of-life issue,” she said. “We want to know how we can get better in the clinical realm. Audiologists and clinicians are aware that tinnitus affects emotional aspects, too, and we want to make them aware that these effects are occurring so they can better help their patients.”

http://www.medicalnewstoday.com/releases/278846.php

Picture courtesy of tinnitusart.com