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Thursday, June 29, 2017

Brain Tumors: Still Devastating, but Treatment Has Come a Long Way

Progress being made on Brain Tumor treatment
 Newswise, June 29, 2017-- – A brain tumor was the furthest thing from Kathy English’s mind that day in 2003 when she walked into a neurologist’s office. She’d had some uncontrolled sinus issues, so her doctors had ordered a variety of tests, including an MRI. When she arrived to get the MRI results, the neurologist said he had not yet had a chance to look at them himself. 

“He said we’d look at them together,” English recalled. “As he looked over the scan, he pointed out a small abnormality, a tumor which he described as a meningioma. Then he saw another one. And another. By this time, I was getting pretty worried. Ultimately, he found 12, and now I was really worried.”

A meningioma is a usually benign, slow-growing tumor. While referred to as a brain tumor, it actually does not grow from brain tissue but rather from the meninges, layers of tissue which cover the brain. Still, 12 meningiomas are not to be taken lightly.

The neurologist immediately referred English to neurosurgeon James Markert, M.D., an internationally renowned brain tumor expert at the University of Alabama at Birmingham.

Markert, who is professor and chair of the Department of Neurosurgery in the UAB School of Medicine, says meningiomas are relatively rare, but certainly not unheard of. He followed English for several years, and when one of the tumors began to grow, he surgically removed it, along with eight others that were easily accessible.

Two more were later eliminated through a gamma knife radiation procedure. Markert continues to monitor the others. Through it all, English never had any symptoms, other than a bucket-full of anxiety. 

“It was like knowing you have bugs on your head … ‘Get them off! Get them off!’” she said. “It’s so reassuring to know that I’m being treated and monitored by some of the top brain tumor people in the nation.”

Her experiences made English something of a brain tumor expert herself, certainly enough to realize something was not right when her husband, John, became dizzy and off-balance after bending over to unplug a computer cord.

He’d had a couple of bad headaches in the previous weeks, and that evening in the fall of 2016, there was something obviously wrong.

“We ruled out stroke pretty quickly, and our physician ordered an MRI,” English said. “The results came back — astrocytoma. A brain tumor. We were stunned.”

Two days later, John English was in Markert’s office, and in less than two weeks, had surgery to remove a Grade 2 tumor. His recovery has been robust, and he knows he is lucky.

“While we never anticipated having a second person in the family with a brain tumor, Kathy’s experiences made us proactive,” John said. “My prognosis is so much better due to the quick recognition of the tumor, and the quick response by UAB.”

The Englishes did not consider themselves prime candidates for brain tumors. Both are pescatarians (individuals who add fish to a vegetarian diet) who stay fit and keep a close eye on their health.  

“The scientific community still has much to learn in order to predict the onset of a brain tumor or who is at risk,” said Markert, who holds the James Garber Galbraith Endowed Chair of Neurosurgery at UAB and is a senior scientist in the Comprehensive Cancer Center.

“Some, called primary tumors, arise in the brain. Others are called metastatic tumors, which arise elsewhere in the body and migrate to the brain.”

The good news, Markert says, is that the landscape for brain tumor therapy is much better now than ever before.

“A diagnosis of a malignant brain tumor is still devastating, but we’ve come a long way,” he said. “The horizon is very bright for the development of even more impactful treatments in the very near future.”

Markert credits improved imaging with some of that optimism. Improvements in neuroimaging can now reveal much more information about the makeup of tumors.

“We used to classify tumors based simply on their microscopic appearance,” Markert said.

“We are now able to look at mutations within tumor cells, and we’ve found that certain sets of mutations are associated with different tumor types and subtypes. This really is precision medicine, as we can now tailor therapy based on our better understanding of the genetic signature of an individual tumor.”

A new oral chemotherapy agent called temozolomide is a good example. It is effective on some tumors, but others are resistant to the drug. Advances in genetic testing can predict which patients will respond best to the drug and which will not.

Another new agent, aminolevulinic acid, or 5-ALA, is used in a fluorescence imaging technique. The drug is absorbed into tumors and causes them to glow when viewed on an MRI. Surgeons can then better visualize the tumor, especially at its boundaries with healthy cells.

Those boundaries are usually indistinct, and the line between tumor and healthy tissue can be blurred. 5-ALA helps guide surgeons as they attempt to remove as much of a tumor as possible while leaving healthy tissue intact. 5-ALA is expected to be approved for use by the FDA in the near future.

New technology will soon be in place at UAB, such as intraoperative MRI scanning, where surgeons will have the ability to do real-time MRI scans in the operating room during surgery.

Another advance, also based on improved MRI use, will employ lasers surgically inserted into the tumor to precisely destroy tumor cells with heat energy.

Markert says proton therapy, an option over traditional radiation technology and coming to UAB in 2019, can be a valuable tool for pediatric tumors or tumors situated close to delicate structures such as the brain stem or optic nerve.

Another promising therapy has been under investigation in Markert’s lab for years. In 2001, Markert and his colleagues published initial results of a first-generation genetically engineered herpes virus as a therapy to destroy brain tumors.

A second generation virus, known as M032, is currently undergoing clinical trials. The virus infects tumor cells and replicates, while leaving healthy cells alone.

The act of viral replication in the tumor kills the infected tumor cells and causes the tumor cell to act as a factory to produce new viruses. As the tumor cell dies, progeny viruses are released from the cell.

These viruses infect other tumor cells in the vicinity and continue the process of tumor killing. The virus also causes the patient’s own immune system to attack the tumor.

“This process, especially combined with advances in immunotherapy, presents a very promising approach to treating tumors,” Markert said.

Markert explains that the body’s immune system is designed to patrol for foreign cells in the body, including mutated cancer cells. The immune system’s killer T cells have an off-switch, known as a checkpoint.

The checkpoint is usually turned off, keeping T cells from attacking healthy cells. It turns on — again, usually — in the presence of a foreign cell, prompting T cells to attack. But tumor cells are very good at fooling the checkpoint so it remains in the off position.

Drugs known as checkpoint inhibitors are under development which would turn the checkpoint on, stimulating the T cells to attack the tumor.

“One approach we are considering now is a combination of viral and immunotherapy,” Markert said.

“The viral therapy using our modified herpes virus should produce a vibrant immune response, followed by introduction of the checkpoint inhibitors, which would turn on the checkpoints and activate individual T cells.”

Markert is excited about the future of brain tumor research and treatment. As a leading academic medical center home of one of the nation’s Comprehensive Cancer Centers, and the state’s leader in personalized medicine, UAB is primed to be at the forefront of new discovery.

“We have a remarkable array of talent here, in radiation oncology, hematology/oncology, neurology, neurosurgery, and other fields,” he said. “We have an outstanding research enterprise in both adult and pediatric brain tumors. It’s an exciting time to be in this field.”

Brain cancer is not the most prevalent kind of cancer — breast and lung cancer top the list; but malignant brain tumors can be particularly devastating.

The National Cancer Institute predicts 33,800 new cases in 2017. The NCI also estimates that 16,700 Americans will die of brain cancer this year.

“We are turning a corner, but there are still too many people who die from brain tumors each year,” Markert said. “These patients and their families are very courageous people. We owe it to them to find better treatments.”

The Englishes had two firsthand experiences to convince them to continue to be proactive and involved in their health care.


“Pay attention to your body, and if something unusual happens, don’t blow it off,” John said. “Be aggressive in following up. We are two people who paid attention to our medical issues and, as a result, got the right care to provide us the best possible outcomes.”

Minimizing the Effects of Radiation Injury

New research conducted at the University of Kansas Medical Center could make treatment for gastrointestinal cancers safer—while also helping to mitigate the dangers of nuclear accidents and terrorist attacks

Newswise, June 29, 2017 — New research conducted at the University of Kansas Medical Center could make treatment for gastrointestinal cancers safer—while also helping to mitigate the dangers of nuclear accidents and terrorist attacks.

The research, led by Subhrajit Saha, Ph.D., assistant professor in the Department of Radiation Oncology at KU Medical Center, began more than five years ago when his team embarked on a quest to understand the biology behind radiation-induced gastrointestinal syndrome (RIGS)—a serious risk for people being treated for stomach, pancreatic, colorectal and other cancers in the abdominal area.

RIGS prevents the body from absorbing nutrients and often causes nausea, vomiting and diarrhea. RIGS occurs primarily when radiation treatment for these abdominal cancers destroys healthy tissue in the GI tract, especially the outer layer of the intestines, known as the epithelium. And when the epithelium is lost, bacteria can spill into the body and cause sepsis, which can kill a patient.

Because there is no drug treatment for RIGS, doctors must turn to radiation to treat their patients, which requires them to use extreme caution up to the point of compromising on the necessary treatment.

This is of specific concern to cancer patients as more than half of patients treated with abdominal radiotherapy are affected by RIGS.

"That's why when the colon is involved, doctors don't want to treat with radiation," said Saha. "And often they can't use aggressive doses of radiation even for other organs in the area because of the sensitivity of the epithelium. They have to be very, very careful."

RIGS also occurs when people are subjected to radiation through a nuclear accident or a nuclear attack.

 "This is hugely significant—the government has been investing in research for an effective countermeasure for terrorism involving radiation," says Saha. "The problem is, it's hard to treat someone post-radiation because the damage happens so fast, and the patient typical dies in seven to 10 days."

Macrophages, the Pac-Men for cellular debris, help intestinal stem cells regenerate

While Saha was still at the Albert Einstein College of Medicine in New York, his research team began with the knowledge that one reason RIGS is so hard to treat is that the abdominal area of the body has a high turnover of intestinal stem cells. Cells like these that divide quickly are especially susceptible to damage from radiation because their DNA gets more exposed.

To figure out how to get around that, the researchers needed to know more about the biology of the epithelium, specifically how intestinal stem cells (ISCs) renew and proliferate.

They published their first discovery six years ago, after they injected radiation-injured mice with stromal cells, a mixture of different cell types that make up connective tissue, and found that they stimulated intestinal stem cell regeneration and lessened the damage done by RIGS.

Now they knew that ISCs depend on the stromal niche to reproduce new cells, and of the different types of stromal cells, the macrophages were critical. Macrophages are white blood cells that eat up cellular debris, especially infected cells.

 "We knew that macrophages are the missionaries of the immune system," said Saha. "But we learned they also assist in organ growth, repair, and regeneration."

The question was how?

Solving the mystery of intestinal stem cell renewal

The first question for Saha, who had by then moved to KU Medical Center, was whether macrophages can help intestinal stem cells self-renew and multiply. The researchers had read studies showing that WNT proteins—a family of proteins that regulate the proliferation of cells, and related signaling—were very important for the intestinal stem cell renewal and proliferation. Moreover, they have found that macrophages also release these WNT proteins.

To learn more, the researchers set up a mouse model to halt the release of all 19 varieties of WNTs specifically produced by macrophages.

They found that mice without macrophage-derived WNT were much more sensitive to radiation and had more severe intestinal injury from radiation compared to mice who had not been treated.

"This told me that macrophage-derived WNT is important for intestinal resistance to radiation," said Saha.

For Saha, this discovery made for one of his best days in the lab, but it also was just the first finding. Additional studies showed that damage could be repaired in mice treated with macrophages capable of releasing WNT proteins. The intestinal epithelium was repaired, and the intestinal stem cells were also rescued.

Multiple subsequent studies have since reinforced their findings. They have confirmed that WNT release by macrophages is essential to the regeneration of intestinal stem cells and repair of epithelial tissue. Interestingly, in mice not exposed to radiation, WNTs don't seem critical to keeping the intestines healthy. But where there is a need for regeneration, they become critical.

"We were very much surprised," Saha said. "Macrophages are known for immune system surveillance, but now we know that they can get involved in organ repair."

It's all in the packaging

Working in collaboration with Andrew Godwin, Ph.D., deputy director of the University of Kansas Center Center, and his team, Saha's team also observed that macrophages release the WNTs via extracellular vesicles, tiny sacs of membrane released from the surface of cells. "That was not known," said Saha. "Now we know how WNTS are transported in the system."

Armed with this knowledge, researchers can begin to think about developing therapies using macrophage-derived WNT to allow doctors to treat gastrointestinal cancers more aggressively and lessen the damage done in the event of a nuclear mishap. Their study was published last year in Nature Communications.


Saha's team is currently working to develop small molecules that can modulate these macrophages to augment their role in regeneration. "We are confident that we can come up with an answer for the mitigation of acute radiation syndrome very soon," he said.

Good Nutrition, Physical Training and Mental Exercises Can Reverse Physical Frailty in the Elderly: NUS Study

Newswise, June 29, 2017 — Physical frailty is common among the elderly and is strongly associated with cognitive impairment, dementia and adverse health outcomes such as disability, hospitalisation, and mortality. A four-year study conducted by researchers from the National University of Singapore (NUS) showed that a combination of nutritional, physical and cognitive interventions can reverse physical frailty in elderly people.

Associate Professor Ng Tze Pin, who is from the Department of Psychological Medicine at the NUS Yong Loo Lin School of Medicine, and the leader of the research team, said that earlier research findings from the Singapore Longitudinal Ageing Studies (SLAS) by his team showed that physically frail elderly persons compared to their robust counterparts are eight times as likely to be cognitive impaired at the same time, and if they are not cognitively impaired, they are more than five times at risk of becoming cognitively impaired on follow up three years later.

“In addition, physically frail elderly persons are two to 10 times as likely to become functionally disabled on daily living activities, hospitalised and die earlier than their robust counterparts. When physical frailty and cognitive impairment are present together in the same individual, he or she is more than 20 times as likely to become disabled, hospitalised or die earlier. With such compelling evidence, if it is possible to reduce or even reverse physical frailty in the elderly, we could greatly improve their quality of life,” Assoc Prof Ng explained.

Assoc Prof Ng and his team conducted a four-year trial between 2010 and 2013, involving 250 community-living older persons in Singapore who were 65 years old and above and who showed signs of frailty.

“Our study shows that it is feasible to identify pre-frail and frail older persons in the community and primary care settings and provide them with lifestyle interventions to reverse frailty. We found that better nutrition, physical training and mental exercises can reverse frailty, enhance muscle strength and gait speed, reduce depressive symptoms and improve cognitive functioning. As such, these interventions can go a long way to reducing the high prevalence of physical disability, hospitalisation and mortality in an ageing society like Singapore,” Assoc Prof Ng added.

Fighting frailty in elderly people

Participants for the trial were recruited from October 2009 to August 2012 from various senior activity centres in Singapore. They were randomly allocated to receive lifestyle interventions in one of five groups for a period of six months. Three groups of participants were provided with either physical training, nutritional enhancement or cognitive training, while the fourth group received a combination of all three interventions. The last group was a control group which did not receive any intervention. The trial was conducted in collaboration with Khoo Teck Puat Hospital and St Luke’s Hospital.

Assessment of the participants’ frailty and other outcomes were made before the start of intervention. During the six-month trial, the participants’ progress were measured after three months and six months. A follow-up assessment was also conducted six months after the trial (i.e. 12 months after the start of intervention).

The NUS researchers found that the three types of intervention, as well as a combination of all three approaches, were able to reduce frailty and depressive symptoms, and improve cognitive functioning of the elderly.

Assoc Prof Ng noted, “The important message from our studies is that frailty is not an inevitable part of ageing. There is much that older people can do for themselves to avoid becoming frail and disabled, so it is vital that they pay attention to good quality diet and nutrition, engage in physical exercise, and participate in socially and cognitively stimulating activities.”

Intervention programmes to benefit the elderly

Following the encouraging findings from the trial, the research team is working with the Geriatric Education and Research Institute (GERI) and social service organisations to develop and implement pilot frailty screening and multi-domain lifestyle intervention community programmes. They hope that such programmes when successfully scaled up for mass intervention can help improve the physical, psychological and cognitive well-being of large numbers of senior citizens.






I Can Hear You Now: Clinic Provides Free Hearing AIDS for Low-Income Adults


U
University of Michigan Photo

How a new Ann Arbor program helps those with hearing loss — and provides a blueprint other academic medical centers may follow

New Ann Arbor program helps those with hearing loss — and provides a blueprint other academic medical centers may follow.
Newswise, June 29, 2017 — Low-income people dealing with hearing loss just got a little hope.

Doctors from Michigan Medicine’s Department of Otolaryngology — Head and Neck Surgery partnered with the Hope Clinic to create Hope for Hearing, a program that provides free hearing aids to uninsured adults.

The partnership between the free independent clinic and University of Michigan started in 2010 to provide Hope Clinic patients with access to specialty care.

“We saw there was a need for hearing aids,” says Aileen P. Wertz, M.D., a fifth-year resident in otolaryngology who also sees patients at the Hope Clinic. “Over half of the patients referred to us with ear complaints had hearing loss and could simply benefit from a hearing aid.”

After recognizing the need, Wertz and her colleagues looked to design a self-sufficient subspecialty program within the clinic that could act as a model for similar projects.

They began by soliciting hearing aid donations and a hearing aid verification system and securing a $5,000 grant for a computer enabled with audiological software and other equipment.

Primary care providers then referred adults with hearing complaints to the program.

Patients went through an initial assessment that included a formal audiogram and screening evaluation. If the audiometric test suggested a significant hearing loss and the otolaryngologist determined that a patient was medically cleared for hearing aids, the patient was referred to audiologists for hearing aid counseling and fitting.

In a study published in JAMA Otolaryngology—Head & Neck Surgery, Wertz and her colleagues examined the feasibility and outcomes of the program.

“During the study period — September 2013 through March 2016 — we garnered 84 hearing aids, and most of them were donated,” says Wertz. “Thirty-four patients were determined to be eligible for the free program and were offered hearing aid services. Of them, 20 patients (59 percent) have been fitted or are being fitted with free hearing aids.”

The cost of hearing aids

Most people who need hearing aids are surprised that neither Medicare nor most commercial insurance plans cover the cost. As a result, there is no price negotiation or consumer benefit.

Wertz says the average Hope for Hearing patient would pay about $2,260 to obtain equivalent equipment themselves or pay $1,210 for the most basic hearing aid available at U-M.

The only costs for Hope for Hearing patients are batteries for the hearing aid and transportation to and from their clinic visits.

What’s ahead

Deemed a success with room to grow, Wertz says the Hope for Hearing program is looking for ongoing funding to cover the costs of ear mold and hearing aid supplements.

Wertz attributes some of the success to date to the strong relationship between the Hope Clinic and U-M.

“This hearing aid program began with an established, successful academic center-community program partnership,” she says. “That was an important factor because enthusiastic audiologists and otolaryngologists were already invested and volunteering regularly at clinics.”

Wertz suggests that other institutions considering similar programs think about the target population’s cultural needs.


“Many patients in this program have required an interpreter to get through the audiologic evaluation and hearing aid fitting,” says Wertz. “Our program has been fortunate that a family member or friend with bilingual abilities has been able to serve as an interpreter for appointments.”

Tuesday, June 6, 2017

Stem Cell Treatment May Restore Vision to Patients with Damaged Corneas

Newswise, June 6, 2017 — Researchers working as part of the University of Georgia’s Regenerative Bioscience Center have developed a new way to identify and sort stem cells that may one day allow clinicians to restore vision to people with damaged corneas using the patient’s own eye tissue. They published their findings in Biophysical Journa

The cornea is a transparent layer of tissue covering the front of the eye, and its health is maintained by a group of cells called limbal stem cells. But when these cells are damaged by trauma or disease, the cornea loses its ability to self-repair.

“Damage to the limbus, which is where the clear part of the eye meets the white part of the eye, can cause the cornea to break down very rapidly,” said James Lauderdale, an associate professor of cellular biology in UGA’s Franklin College of Arts and Sciences and paper co-author.

“The only way to repair the cornea right now is do a limbal cell transplant from donated tissue.”

In their study, researchers used a new type of highly sensitive atomic force microscopy, or AFM, to analyze eye cell cultures. Created by Todd Sulchek, an associate professor of mechanical engineering at Georgia Tech, the technique allowed researchers to probe and exert force on individual cells to learn more about the cell’s overall health and its ability to turn into different types of mature cells.

They found that limbal stem cells were softer and more pliable than other cells, meaning they could use this simple measure as a rapid and cost-effective way to identify cells from a patient’s own tissue that are suitable for transplantation.

“Todd’s technology is unique in the tiniest and most sensitive detection to change,” said Lauderdale. “Just think about trying to gently dimple or prod the top of an individual cell without killing it; with conventional AFM it’s close to impossible.”

Building on their findings related to cell softness, the research team also developed a microfluidic cell sorting device capable of filtering out specific cells from a tissue sample.

With this device, the team can collect the patient’s own tissue, sort and culture the cells and then place them back into the patient all in one day, said Lauderdale. It can take weeks to perform this task using conventional methods.

The researchers are quick to caution that more tests must be done before this technique is used in human patients, but it may one day serve as a viable treatment for the more than 1 million Americans that lose their vision to damaged corneas every year.

The group first started this research with the hope of helping children with aniridia, an inherited malformation of the eye that leads to breakdown of the cornea at an early age.

Because aniridia affects only one in 60,000 children, few organizations are willing to commit the resources necessary to combat the disease, Lauderdale said.

“Our first goal in working with such a rare disease was to help this small population of children, because we feel a close connection to all of them,” says Lauderdale, who has worked with aniridia patients for many years.

“However, at the end of the day this technology could help hundreds of thousands of people, like the military who are also interested in corneal damage, common in desert conditions.”

Steven Stice, a Georgia Research Alliance Eminent Scholar, who plays an important role in fostering cross-interdisciplinary collaboration as director of the RBC, initially brought the researchers together and encouraged a seed grant application through the center for Regenerative Engineering and Medicine, or REM, a joint collaboration between Emory University, Georgia Tech and UGA. “A culture is developing around seed funding that is all about interdisciplinary collaboration, sharing of resources, and coming together to make things happen,” said Stice.

“Government funding agencies place a high premium on combining skills and disciplines. We can no longer afford to work in an isolated laboratory using a singular approach.”

The REM seed funding program is intended to stimulate new, unconventional collaborative research and requires equal partnership of faculty from two of the participating institutions.

“We tend to get siloed experimentally,” says Lauderdale. “To a biologist like me, all cells are very different and all atomic force microscopes are the same. To an engineer like Todd it’s just the opposite.”

The study, “Cellular Stiffness as a Novel Stemness Marker in the Corneal Limbus,” is available at http://www.cell.com/biophysj/fulltext/S0006-3495(16)30771-8.

Funding was provided by an NIH NIGMS Biotechnology Training Grant on Cell and Tissue Engineering, the Knights Templar Eye Foundation, the Center for Regenerative Engineering and Medicine, the Sharon Stewart Aniridia Research Trust and the NSF CMMI division.



Assessing the Impact of Stress in Age-Related Macular Degeneration

Newswise, June 6, 2017– Age-related macular degeneration (AMD), the leading cause of vision loss among older adults in the United States, is often associated with psychological stress. 

A simple stress rating scale (the Perceived Stress Scale) is a valid and useful way to evaluate the connection between stress and progressive vision loss from AMD, according to a study in the March issue of Optometry and Vision Science, the official journal of the American Academy of Optometry. The journal is published by Wolters Kluwer.

"Because AMD is an inflammatory disease, we are studying the link between inflammation, stress, and AMD treatment outcomes," reported Bradley E. Dougherty, OD, PhD, of The Ohio State University College of Optometry. "In the end, we hope to better understand how general well-being influences disease outcomes."

Measuring Stress May Aid in Assessing the Life Impact and Progression of AMD--Patients with vision loss in AMD experience high rates of stress, anxiety, and other problems, including depression. Less is known about the relationship between the stress that AMD patients experience and the severity of their disease—for example, whether stress can cause AMD to worsen or not.

The Perceived Stress Scale (PSS) is a well-established stress rating scale that can predict objective biological markers of stress, as well as the risk of stress-related diseases. In previous studies, the PSS has been shown to be predictive of general markers of inflammation, including C-reactive proteins. In the new study, Dr. Dougherty and colleagues extend the use of this survey to determine how well it measures perceived stress in patients with vision loss due to AMD.

One hundred thirty-seven patients with AMD, average age 82 years, completed the ten-question PSS. Using a technique called Rasch analysis, Dr. Dougherty and colleagues evaluated the PSS's performance as a stress measure in AMD. About half of the patients filled out the stress questionnaire on a day when they received injections of anti-VEGF antibodies—a relatively new treatment that can slow the progression of the "wet" form of AMD.

Nine of the ten questions normally used with the PSS performed well with the patient group studied. These nine items were also able to separate between patients with higher versus lower levels of perceived stress. For some PSS items, responses differed according to patient age and visual acuity level.

However, the overall PSS score was not significantly related to the patients' visual acuity level. Average visual acuity in the better eye for this group of AMD patients was 20/50, with a range from near normal to very low vision.

"A psychometrically sound, easy-to-administer questionnaire such as the PSS is important for use with patients with AMD, given the evidence for increased rates of psychological symptoms in the population," Dr. Dougherty and coauthors write.

They note that stress-reduction approaches—for example, "mindfulness" interventions—have led to improved outcomes in patients with various health conditions.

Dr. Dougherty and colleagues also note that stress may be associated with increased inflammation and that AMD is an inflammatory disease—raising the possibility that stress may contribute to disease progression.

Future studies using repeated assessments with the PSS and measurement of inflammatory markers might provide evidence on how perceived stress levels affect the risk of AMD progression and worsening vision loss.


Slow the Signs of Aging With Sun Protection


Dermatologist offers advice for spring breakers, staycationers and everyone in between

June 6, 2017— As the winter temperatures begin to thaw, many may be dreaming of a sun-drenched spring and summer, and some may be hoping to show off a tan. While these individuals may believe tanning makes them more beautiful, this habit can actually damage their skin in the long run.

“Ultraviolet radiation from the sun and indoor tanning beds not only can increase your risk of skin cancer but also can contribute to skin aging,” says board-certified dermatologist Arianne Shadi Kourosh, MD, MPH, FAAD, director of community health and co-director of the multiethnic skin clinic in the department of dermatology at Massachusetts General Hospital in Boston.

 “Moreover, other forms of radiation, such as heat and visible light, can negatively impact the skin, as can pollution, so protecting your skin from the environment can benefit both your health and appearance.”

According to Dr. Kourosh, environmental factors can damage the skin in multiple ways, from UVB rays causing sunburns and uneven pigmentation to UVA and infrared radiation penetrating more deeply into the skin to damage existing collagen and reduce collagen production, resulting in wrinkles and sagging skin.

Habitual UV exposure can cause blood vessels to become more prominent, causing skin redness, she says, while visible light and pollution can cause uneven skin tone, especially in darker skin types.

“Although there have been some impressive strides in anti-aging treatments, no one product or procedure can completely reverse the long-term effects of poor skin care decisions, and protective measures are the cornerstone of good skin care,” Dr. Kourosh says.

 “Fortunately, there are many sunscreen options available to help you protect yourself, including cosmetic products with SPF. The best sunscreen for each person will depend on many factors, including genetic makeup, environment and lifestyle considerations. A board-certified dermatologist can evaluate the unique needs of your skin and help you develop an appropriate sun protection plan.”

Since both types of UV rays can damage the skin, Dr. Kourosh says, it’s important to use a broad-spectrum sunscreen that provides both UVA and UVB protection, with an SPF of 30 or higher.

She recommends sunscreens containing the active ingredients zinc oxide or titanium dioxide as a good source of broad-spectrum protection suitable for sensitive skin. She also says formulations containing antioxidants may provide some protection against uneven skin tone and aging caused by free radical damage from infrared light, visible light and pollution.

Dr. Kourosh recommends utilizing protective clothing like hats and sunglasses, and she reminds those who will be spending an extended amount of time in the sun to reapply sunscreen every two hours, or after swimming or sweating.

While it’s especially important to be vigilant near sand, water and snow, which can reflect the sun’s rays, sun protection is necessary regardless of weather or location, as 80 percent of the sun’s UV rays can penetrate the skin even on cloudy days.

In addition to practicing sun protection, it’s important to avoid indoor tanning, which exposes users to harmful UV rays that can increase skin cancer risk and accelerate skin aging. Those who wish to look tan may want to consider a self-tanning product but should continue using sunscreen with it.

“Whether you’re on a beach vacation or your daily commute, it’s crucial to protect yourself from exposure to harmful UV rays on a regular basis,” Dr. Kourosh says.

 “If you want healthy, younger-looking skin, it’s better to prevent now than try to correct later. If you have questions about sun protection, talk to a board-certified dermatologist.”



Attitude, Lifestyle May Contribute to Skin Cancer Risk Among Latinos


Dermatologist advises Hispanic patients to be aware of their risk and take steps toward prevention, detection

Newswise, June 6, 2017 As the Hispanic population in the United States continues to grow, the incidence of skin cancer among this population is growing too. Moreover, Hispanic patients are more likely to be diagnosed with the disease in its more advanced stages, when it’s more difficult to treat.1

Many Latinos, however, don’t believe they’re at risk, according to board-certified dermatologist Maritza I. Perez, MD, FAAD, a clinical professor of dermatology at the Icahn School of Medicine at Mount Sinai in New York.

“The belief that Hispanic people don’t have to worry about skin cancer has existed among Latinos for generations,” she says. “They hear it from their parents and grandparents, and then they pass this belief on to their children.”

Exposure to ultraviolet radiation from the sun and indoor tanning beds is the most preventable skin cancer risk factor. Many Hispanic people, however, believe they’re protected from the sun because they have darker skin tones, Dr. Perez says, and those who get sunburned don’t realize that the damage to their skin is increasing their skin cancer risk.

As a result, Dr. Perez says, many Latinos don’t take steps to protect themselves from the sun’s harmful UV rays. Furthermore, she says, some Hispanic people go indoor tanning before spending time in the sun, under the false belief that a “base tan” will protect them.

She advises all her patients, regardless of skin color, to stay out of indoor tanning beds and protect themselves from the sun.

Because skin cancer is most treatable when detected early and Latinos are more likely to be diagnosed with the disease in its advanced stages, Dr. Perez says, it’s also important for this population to perform regular self-exams to look for new, changing or suspicious spots on their skin.

People with skin of color are prone to skin cancer in unusual areas — like on the palms of the hands and the soles of the feet, under the nails, and inside the mouth — so she recommends that Hispanic patients be especially vigilant in performing skin self-exams.

When melanoma, the deadliest form of skin cancer, is detected and treated before it reaches the lymph nodes, the five-year survival rate is 98 percent.2 “Early detection is vital for skin cancer survival,” Dr. Perez says. “And if you don’t look for changes on your skin, you won’t find them.”

While the Hispanic population’s attitude toward skin cancer plays a large role in the disease’s incidence among that population, this group’s access to dermatologic care is also an important factor, according to Dr. Perez.

Many Latino families are uninsured or underinsured, she says, so they may be less likely to see a dermatologist for a skin cancer evaluation.

Further, when Hispanic patients do visit the doctor, she says, skin cancer may not be top of mind during the visit, since the belief that these patients are not at risk for the disease is so pervasive.

To help combat these issues, the American Academy of Dermatology works to raise skin cancer awareness among the underserved Latino population through its Latino Outreach Program.

In addition to providing free skin cancer screenings, this program aims to educate low-income Latino outdoor workers about skin cancer prevention and detection.

The AAD recommends that everyone stay out of indoor tanning beds and protect themselves from the sun’s harmful UV rays by seeking shade, wearing protective clothing, and using a broad-spectrum, water-resistant sunscreen with an SPF of 30 or higher.

The AAD also encourages everyone to perform regular self-exams to check themselves for signs of skin cancer and ask a partner to help them examine hard-to-see areas. Those who notice anything changing, itching or bleeding on their skin should visit a board-certified dermatologist.

While these recommendations apply to all patients, Dr. Perez says, it’s especially important for Latino patients to understand their skin cancer risk, take steps to protect themselves and conduct regular skin self-exams.
“Everyone — no matter their skin color — is at risk for skin cancer,” she says, “so everyone should learn how to protect themselves from the sun and how to check their skin for suspicious spots.”


To learn more about skin cancer prevention and detection, or to find a free SPOTme® skin cancer screening in your area, visit SPOTSkinCancer.org.

Colon Cancer: Early Detection Can Save Your Life

Newswise, June 6, 2017 — Colorectal cancer is the second leading cause of cancer death for men and women in the United States according to the American Cancer Society (ACS).

 In fact, the ACS estimates that 134,490 people in the United States were diagnosed with colorectal cancer in 2016, including 70,820 men and 63,670 women. In addition, the ACS estimates that 49,190 people, 26,020 men and 23,170 women, died from colorectal cancer in 2016.

According to Mitchell Rubinoff, M.D., Chair, Gastroenterology, Valley Medical Group, “In order to reduce the mortality rate of this disease, it is crucial for individuals to be aware of the signs of colon cancer—and not hesitate to have any cause for concern checked out as soon as possible. Early detection saves lives!”

What is Colon Cancer?
Often referred to together as colorectal cancer, colon cancer is cancer of the large intestine (colon), and rectal cancer is cancer of the last few inches of the colon. It most often begins as precancerous polyps on the inside lining of the colon. Colon polyps, as defined by the National Institutes of Health, are growths on the lining of your colon or rectum.

Who is At Risk?
Both men and women are at risk for developing colorectal cancer, even if they do not have any of the identifiable risk factors such as:• A family history of colorectal cancer• Being over age 50• Colorectal polyps• Genetic changes

Early Detection Through Screening Tests
“It is best to catch colorectal cancer before you become symptomatic. Doctors can actually prevent cancers from ever developing by removing polyps and they can cure more patients by diagnosing cancer at an early stage,” explains Dr. Rubinoff.

Possible screening tests for colorectal cancer include stool tests, colonoscopy, or virtual colonoscopy. A colonoscopy is an outpatient procedure that is used to try to detect colon polyps and remove them before they can become cancerous. Your doctor will work with you to decide which test is appropriate for your individual history and symptoms.

It is also important for individuals who are not showing any symptoms of colorectal cancer to go for routine screenings. The CDC states that “The U.S. Preventive Services Task Force recommends that adults age 50 to 75 be screened for colorectal cancer.

“The decision to be screened after age 75 should be made on an individual basis. If you are older than 75, ask your doctor if you should be screened. People at higher risk of developing colorectal cancer should begin screening at a younger age, and may need to be tested more frequently.”

Signs and Symptoms
There are many potential symptoms of colon cancer and it is important to note that there is a great deal of overlap between colon cancer’s symptoms and symptoms of other illnesses. And, while it is possible that your symptoms may be caused by something else, you should still be aware of what to look out for and make sure to see your doctor right away if you experience any of the following symptoms:
• A change in bowel habits, such as diarrhea, constipation, or narrowing of the stool, that lasts for more than a few days• A feeling that you need to have a bowel movement that is not relieved by doing so• Rectal bleeding• Dark stools, or blood in the stool (often, though, the stool will look normal)• Cramping or abdominal (belly) pain• Weakness and fatigue• Unintended weight loss

Recognizing these symptoms, which are outlined by the American Cancer Society, is the first step to early detection. Once you alert your doctor to these symptoms, you may be sent for screening tests to confirm a diagnosis.

Prevention

You can help to prevent cancer by exercising, eating fresh fruits and vegetables, and maintaining a healthy weight. Be proactive and take charge of your health!

Saturday, June 3, 2017

Old Cells That Refuse to Die May Lead to Treatments for Age-Related Diseases

Newswise, June 3, 2017 — One of the things that happens to our bodies as we age is that certain cells start to accumulate.

So-called senescent cells – cells that “retire” and stop dividing but refuse to die – are always present, and they even serve some important functions, such as in wound repair. But in aging organs, these cells don’t get cleared away as they should, and they can clutter up the place. Dr. Valery Krizhanovsky of the Weizmann Institute of Science’s Department of Molecular Cell Biology is revealing just how these cells are tied to disorders of aging and why they refuse to go away.

His work is not only opening new windows onto the aging process, but is pointing to new directions in treatments for many of these disorders and diseases.

Research into cellular senescence has taken off in recent years, due to findings that show that clearing these cells from various parts of the body can reverse certain aspects of aging and disease processes.

Pharmaceutical industries have taken note, as well, of research that could lead to the development of drugs that might target senescent cells in specific organs or tissues.  

In basic research conducted on human cell cultures and on mice, Dr. Krizhanovsky and his team asked, “what, exactly, ties senescent cells to aging?” Are they, for example, a primary cause of age-related disease, or a side effect? And why don’t these cells die, despite being damaged, making the “clean-up crews” of the immune system clear them away?

The researchers hypothesized that the answer to the second question might lie in a family of cellular proteins that regulate a type of cell suicide known as apoptosis.

They identified two proteins in this family that prevent apoptosis and which were overproduced in the senescent cells. When they injected mice that had an extra supply of senescent cells with molecules that inhibit these two proteins, the cells underwent apoptosis and were then eliminated, and there were signs of improvement in the tissue.


“In small amounts, these cells can prevent tumors from growing, help wounds clot, and start the healing process,” says Dr. Krizhanovsky. “But as they amass, they trigger inflammation and even cancer.”

Certain common age-related diseases have been shown to be associated with this buildup of senescent cells – for example, chronic obstructive pulmonary disease (COPD) – and Dr. Krizhanovsky is hoping to apply these findings to research into treatments for such diseases.


The trick, he says, will be to target the offensive cells without causing undue side effects. He has been developing mouse models of COPD and asking whether clearing senescent cells from just the lungs can prevent or ease the disease. Yeda Research and Development, Co., Ltd., the Weizmann Institute’s technology transfer arm, is working with Dr. Krizhanovsky to patent and license his discoveries. 

Another Reason to Exercise: Burning Bone Fat – a Key to Better Bone Health UNC School of Medicine researchers use new imaging methods

Newswise, June 3, 2017 – It’s a fat-burning secret anyone interested in bone health should know. For the first time, UNC School of Medicine researchers show that exercising burns the fat found within bone marrow and offers evidence that this process improves bone quality and the amount of bone in a matter of weeks. 

The study, published in the Journal of Bone and Mineral Research, also suggests obese individuals – who often have worse bone quality – may derive even greater bone health benefits from exercising than their lean counterparts.

“One of the main clinical implications of this research is that exercise is not just good, but amazing for bone health,” said lead author Maya Styner, MD, a physician and assistant professor of endocrinology and metabolism at the University of North Carolina at Chapel Hill.

“In just a very short period of time, we saw that running was building bone significantly in mice.”

Although research in mice is not directly translatable to the human condition, the kinds of stem cells that produce bone and fat in mice are the same kind that produce bone and fat in humans.
In addition to its implications for obesity and bone health, Styner said the research also could help illuminate some of the factors behind bone degradation associated with conditions like diabetes, arthritis, anorexia, and the use of steroid medications.

In her patients, Styner is all too familiar with the chronic toll of osteoporosis and fractures. This new evidence shows it’s possible to use exercise to reverse some of the effects on bones.

“I see a lot of patients with poor bone health, and I always talk to them about what a dramatic effect exercise can have on bones, regardless of what the cause of their bone condition is,” said Styner.

“With obesity, it seems that you get even more bone formation from exercise. Our studies of bone biomechanics show that the quality and the strength of the bone is significantly increased with exercise and even more so in the obese exercisers” 

Getting to the marrow of the matter
Bone and marrow are more dynamic than you might think. Marrow, in particular, is a hub of activity, coordinating the formation of bone and cartilage while simultaneously churning out blood cells, immune cells, and cancerous cells.

Marrow also produces fat, which has a lot to do with its vaunted status in cuisines around the world. But the physiological role of bone marrow fat in the body – and even whether it is beneficial or harmful for one’s health – has remained somewhat mysterious.

Generally, marrow fat has been thought to comprise a special fat reserve that is not used to fuel energy during exercise in the same way other fat stores are used throughout the body during exercise. The new study offers evidence to the contrary.

Styner’s work also offers fundamental insights on how marrow fat forms and the impact it has on bone health. Previous studies have suggested that a higher amount of marrow fat increases the risk of fractures and other problems.

“There’s been intense interest in marrow fat because it’s highly associated with states of low bone density, but scientists still haven’t understood its physiologic purpose,” said Styner.

“We know that exercise has a profound effect on fat elsewhere in the body, and we wanted to use exercise as a tool to understand the fat in the marrow.”

Vanishing fat cells
The researchers performed their experiments in two groups of mice. One group was fed a normal diet (lean mice) and the other received a high-fat diet (obese mice) starting a month after birth. When they were four months old, half the mice in each group were given a running wheel to use whenever they liked for the next six weeks. Because mice like to run, the group with access to a wheel tended to spend a lot of time exercising.

The researchers analyzed the animals’ body composition, marrow fat and bone quantity at various points. Predictably, the obese mice started with more fat cells and larger fat cells in their marrow.

 After exercising for six weeks, both obese and lean mice showed a significant reduction in the overall size of fat cells and the overall amount fat in the marrow. In these respects, the marrow fat of exercising obese mice looked virtually identical to the marrow fat of lean mice, even those that exercised.

Perhaps more surprising was the dramatic difference in the number of fat cells present in the marrow, which showed no change in lean mice but dropped by more than half in obese mice that exercised compared to obese mice that were sedentary. The tests also revealed that exercise improved the thickness of bone, and that this effect was particularly pronounced in obese mice.

According to Styner, all of this points to the conclusion that marrow fat can be burned off through exercise and that this process is good for bones.

“Obesity appears to increase a fat depot in the bone, and this depot behaves very much like abdominal and other fat depots,” said Styner. “Exercise is able to reduce the size of this fat depot and burn it for fuel and at the same time build stronger, larger bones.”

Setting the stage
The research leaves a few lingering mysteries. A big one is figuring out the exact relationship between burning marrow fat and building better bone. It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone.

Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates these stem cells to churn out more bone cells and less fat cells.

More research will be needed to parse this out. “What we can say is there’s a lot of evidence suggesting that marrow fat is being used as fuel to make more bone, rather than there being an increase in the diversion of stem cells into bone,” said Styner.

But marrow fat, being encased in bone, isn’t easy to study. The team’s new research represents a leap forward not only in understanding bone marrow fat but also in the tools to study it.

The group’s previous work relied on micro CT imaging, which requires the use of a toxic tracer to measure marrow fat. In the new study, they took advantage of UNC’s 9.4 TMRI, a sophisticated MRI machine of which there are only a few around the country.

Using MRI to assess marrow fat eliminates the need for the toxic tracer and allows highly detailed imaging of living organisms. 

“If we want to take this technique to the human level, we could study marrow fat in humans in a much more reliable fashion now,” said Styner. “And our work shows this is possible.”

The team also developed techniques to perform a much more detailed assessment of the number and size of fat cells within the marrow, and even examined some of the key proteins involved in the formation and reduction of bone marrow fat.

Styner is now working with collaborators to adapt these methods for studying the bone marrow dynamics that might be at work in other conditions, including anorexia and post-menopausal osteoporosis.