October 12, 2017
Lewy body dementia and other illnesses of aging brains cause immeasurable suffering for patients and their families. sabthai/Shutterstock.com Melissa J. Armstrong, University of Florida Lewy body dementia reached the public eye in 2014 after reports that Robin Williams died with diffuse Lewy body disease. But, despite the fact that Lewy body dementia is the second most common dementia, it remains frequently unrecognized. In one study, almost 70 percent of people diagnosed with Lewy body dementia saw three consultants before receiving the diagnosis. For a third of people with the disease, getting the correct diagnosis took more than two years. October is Lewy Body Dementia Awareness Month. As a physician specializing in Lewy body dementia, I often hear patients and families describe delays in getting a diagnosis. It doesn’t have to be this way. Awareness is critical, particularly as new opportunities emerge for diagnosis and treatment. What is Lewy body dementia? The word “dementia” describes a condition affecting a person’s memory and thinking that is a decline from how he or she used to function and that is severe enough to affect day-to-day life. Alzheimer’s disease dementia and Lewy body dementia are the two most common types. Lewy body dementia gets its name from the abnormal protein clumps that are seen on autopsies of the brains of people with Lewy body dementia. The protein alpha-synuclein – a protein found in the brain, not one you eat – clumps into spheres called Lewy bodies which can be seen using a microscope. These are named after F. H. Lewy, the person who first described them. The diagnosis Lewy body dementia is an umbrella term that includes two different conditions: dementia with Lewy bodies and Parkinson’s disease dementia. Robin Williams was diagnosed with diffuse Lewy body disease only after his death in 2014. Kathy Hutchins/Shutterstock.com In dementia with Lewy bodies, a person develops memory and thinking problems before or at the same time as he or she develops movement problems that resemble Parkinson’s disease. In Parkinson’s disease dementia, a person who has experienced Parkinson’s disease movement problems for years then also develops trouble with memory and thinking. These two conditions share many of the same features. In addition to memory and thinking problems and movement problems, people with these conditions can have fluctuations in their alertness and concentration, hallucinations and paranoia, acting out dreams during sleep (something called REM sleep behavior disorder), low blood pressure with standing, daytime sleepiness and depression, among other symptoms. Diagnosis is important Getting the correct diagnosis is critical for patients and families. While no one wants to hear that they have a disease that currently can’t be cured, patients and families often feel relief that they finally have an explanation for what’s happening. The diagnosis of Lewy body dementia is often missed due to lack of awareness by physicians, patients and families. Even for people eventually receiving a diagnosis of Lewy body dementia, research shows their first diagnosis is commonly incorrect. In that study, 26 percent of people later diagnosed with Lewy body dementia were first diagnosed with Alzheimer’s disease and 24 percent were given a psychiatric diagnosis like depression. Knowing the correct diagnosis lets patients and families connect to resources such as the Lewy Body Dementia Association, an organization dedicated to helping people living with this disease. The organization provides education on Lewy body dementia, helps patients and families know what to expect, links patients and families to support and resources and connects them to research opportunities. Once a diagnosis is made, physicians can also suggest potentially helpful treatments. Medications can include carbidopa/levodopa (Sinemet®), a drug that helps with slow movements, and cholinesterase inhibitors, which are drugs developed for Alzheimer’s disease that may also help people with Lewy body dementia. Avenues for research There is a great deal that we still need to learn about the Lewy body dementias. Increasing research is a priority of the National Institutes of Health. Earlier this year, experts published new criteria for the diagnosis of dementia with Lewy bodies, aiming to improve accurate diagnosis. There are also currently multiple research studies trying to find drugs to help people with Lewy body dementias, including studies to investigate drugs hoped to improve thinking, hallucinations and walking. For Parkinson’s disease dementia, a new drug called pimavanserin was approved by the Food and Drug Administration in 2016 to treat hallucinations. Current research studies are testing drugs hoped to improve memory and thinking. Researchers into Lewy body dementia hope that continued studies will lead to improved treatments. toeytoey/Shutterstock.com Scientists also hope to learn more about the alpha-synuclein protein clumps in the Lewy body diseases. Recent vaccine studies suggested that the body might be able to create antibodies against alpha-synuclein. This could be the first step toward a vaccine to help people with Parkinson’s disease and dementia with Lewy bodies. If effective, a vaccine would prompt the immune systems of people with these diseases to create antibodies to attack and clear the protein clumps. With advances in diagnosis and treatment, there is reason for hope. Melissa J. Armstrong, Assistant Professor, Neurology, University of Florida This article was originally published on The Conversation. Read the original article.
September 28, 2017
Florentina Amaya of Houston looks at mold damage to her home, Sept. 5, 2017. AP Photo/David J. Phillip Katherine Allen, University of Florida One of the biggest issues surrounding flooding after natural disasters is mold, a problem that can stay with a structure long after floodwaters have receded. Considering that over 17 percent of homes already have some physical condition that contributes to leaks and that mold grows in temperatures between 40 degrees Fahrenheit and 100°F, there is no wonder that we see mold and mildew problems after a disaster that brings flooding in homes and buildings. Molds are fungi. Dampness supports mold and can create an unhealthy living space for people. When present in large quantities, all molds are allergenic and potentially harmful. Mold was implicated in the deaths of four Southern University at New Orleans professors after Hurricane Katrina, and mold remained a persistent problem in thousands of homes even after cleanup. I have been an extension agent, or someone who shares the university’s consumer and agricultural research advances directly with the public, working with indoor environmental quality issues for over 20 years. From my work, I know that the health effects from exposure to mold can be short-term or long-term. But there’s a lot people can do to reduce or avoid potential problems. Fast action essential Always consider safety first when going back into a flooded home. Check for structural stability. If damage was severe, you may need to call a specialist to inspect your home to ensure it is safe to enter. For areas that are less than 10 square feet, the National Center for Healthy Housing recommends that homeowners or renters clean it up themselves. For larger areas, consider using a professional. Hire a mold inspection or remediation professional affiliated with or certified by the National Environmental Health Association, the American Industrial Hygiene Association , the Institute of Inspection, Cleaning and Restoration Certification or the American Council for Accredited Certification to inspect, repair and restore the damaged parts of your home. If you do the work yourself, keep children away while work is being done. For bigger jobs or for more protection, use a P100, which blocks 99.9 percent of all particulates, or a P95 respirator. Wear eye protection that does not have open vent holes. Use gloves that are nonlatex, vinyl, nitrile or rubber and coveralls to protect clothing. Change into “work” clothes before entering the work area and remove when leaving. You may need to contain the area to prevent the spread of the spores. (Check out HUD’s Rebuild Healthy Homes publication for more great information, including on how to create a containment area.) Identify the extent of the damage, what you can do to stop it from continuing to get in and how to protect people in the space. A meter for measuring moisture content can be helpful. Andrey_Popov/www.shutterstock.com A moisture meter can be useful in determining how wet a material is, as well as identifying the source. Something that looks dry may have hidden moisture. Wood moisture content should be less than 16 percent. Dry the wet areas – completely – as quickly as you can after the event. The water content is the most critical factor in determining if fungi can germinate and grow on a surface. Mold grows on almost any material that stays wet more than about two days. The longer the mold and wetness remain, the faster it spreads. And it is a survivor. It can grow even in dry spaces with humidity levels between 25 percent and 70 percent. If you have mud and silt, shovel it out before it dries. Open doors, cabinets and drawers and use air-conditioning, heaters, fans and dehumidifiers to remove moisture. But if mold has started to grow, do not use fans, as they can spread the mold spores. To bleach, or not to bleach? Supplies for removing mold include a hard brush and cleaning solution, but not necessarily bleach. Burdun Iliya/www.shutterstock.com Many people want to reach for bleach when they first see mold. While bleach can be effective in killing mold on nonporous surfaces such as tile and porcelain, it does not work on wood and other porous material, such as drywall. On those surfaces, bleach can actually encourage more mold growth. Bleach does not prevent the regrowth of new colonies when materials stay damp. If you do use bleach on bathroom and other nonporous surfaces, the Centers for Disease Control and Prevention advises that you use no more than one cup of household bleach to one gallon of water. Make sure you open windows and ventilate your work space. Also, do not use bleach on air conditioning systems, as bleach is corrosive. Do not use on fine wood furnishings, as it can raise the grain. And never mix bleach with ammonia; that can cause toxic fumes. Sometimes, letting go can be best Discard items that cannot be washed and disinfected. Remove carpeting, padding, draperies, upholstered furniture, pillows, stuffed animals and mattresses, as they absorb water quickly and dry slowly. Ceiling tiles that are wet lose their insulative properties and need to be replaced. If you are removing building materials, like flooring or popcorn ceilings, trim or siding, be aware that in older homes they may have lead paint and asbestos. Cleaning mold means we must remove it, not just kill it. Dead spores can still cause health problems. Wipe or vacuum the area. If using a vacuum, consider using one that has a High Efficiency Particulate Arrestance filter. Professionals use commercial certified HEPA filter vacuums. Then, use a nonphosphate cleaning solution and hot water. Use cloths, stiff brushes and, if needed, mist-spray bottles. Do not use high-pressure sprayers, as this could dislodge and spread mold spores. And finally, keep an eye out for new growth or continued dampness. Remember, mold can form in as little as two to three days. Check the outside grade to make sure you have good drainage of rainwater away from your house. Make sure you are using indoor humidity controls like bathroom and kitchen exhaust fans vented to the outside to help prevent added moisture. If you see new mold, repeat cleaning and drying procedures. In some cases, it may mean that extended removal of building materials may be needed. Keep in mind that damage to your home may cause you to have an emotional reaction. This is normal. Refocus your attention on positive things and what you can do. You can safely repair and rebuild your home after water damage. Katherine Allen, County Extension Director and Family and Consumer Sciences Agent IV, University of Florida This article was originally published on The Conversation. Read the original article.
September 27, 2017
Singers from the New York City Gay Men’s Choir sing Dec. 1, 2015 at the Apollo Theater in New York for World AIDS Day. A new health foe has emerged among gay and bisexual men. AP Photo/Seth Wenig Ashish A. Deshmukh, University of Florida; Elizabeth Chiao, Baylor College of Medicine ; Jagpreet Chhatwal, Harvard Medical School , and Scott B. Cantor, The University of Texas MD Anderson Cancer Center Almost 620,000 gay and bisexual men in the United States were living with HIV in 2014, and 100,000 of these men were not even aware of their infection. These men are 100 times more likely to have anal cancer than HIV-negative men who exclusively have sex with women. Yet, no national screening guidelines exist for anal cancer prevention in any population. Anal cancer is predominantly caused by chronic or persistent human papillomavirus (HPV) infection. HPV infection can lead to the development of anal precancer which, if remains undetected or not adequately treated, may lead to anal cancer. Likewise, HPV infection is also responsible for causing cervical, vaginal, vulvar, oropharyngeal, penile and rectal cancers. The objective of screening is to identify and treat these precancers to prevent occurrence of anal cancer. However, one of the reasons for the lack of screening guidelines is that anal precancer treatment has not yet been shown to prevent invasive cancer. Our study, published today in the journal Cancer, attempts to find a possible solution to prevent anal cancer in HIV-positive gay and bisexual men, using the best available data. We found that age-specific anal precancer management, including post-treatment HPV vaccination, can potentially lead to an 80 percent decrease in lifetime risk of anal cancer and anal cancer mortality among gay and bisexual men. Anal cancer: the next big crisis Some in the medical community have identified anal cancer as the next big crisis among HIV-infected gay and bisexual men. Initiation of anti-retroviral therapy in the 1990s greatly reduced the AIDS-related death rate and improved survival. However, this improvement in survival led to an increase in the lifetime risk of developing anal cancer, especially among HIV-positive gay and bisexual men. Anal cancer is typically preceded by persistent HPV infection that often leads to precancer. HPV is common among U.S. men; about one out of two men in the general population has HPV infection. HPV typically clears naturally; however, under certain circumstances, it might persist longer and might progress to anal precancer. If it remains undetected, untreated or inadequately treated, this precancer can progress to anal cancer. The American Cancer Society estimates there will be 8,200 new anal cancer cases in 2017. In the absence of national screening recommendations, more than 50 percent of these individuals will be diagnosed at stage III or IV, when five-year survival is less than 40 percent. This creates a major public health concern. We do not yet know how best to manage anal precancer (also known as high-grade squamous intraepithelial lesions) so that anal cancer could be prevented. A national randomized clinical trial study – Anal Cancer HSIL Outcomes Research (ANCHOR) – is currently determining optimal anal precancer management by comparing treatment and active monitoring. The question then arises: How do we start managing our patients using the best available evidence? Likewise, it is imperative that these individuals have as much information as possible about anal cancer prevention. How our study brings insight Using a mathematical model, we simulated the life course of 100,000 hypothetical HIV-positive men who have sex with men (MSM) who were 27 years or older and were diagnosed with high-grade squamous intraepithelial lesions. In our model, we compared four different management strategies: (1) individuals were not provided any form of treatment, which is the current practice; (2) individuals were actively monitored (followed biannually) and those who developed early cancer were treated; (3) individuals were immediately treated using surgery (current most popular strategy among clinicians who treat precancer); and (4) individuals in addition to surgical treatment received HPV vaccination (potential strategy). We followed these hypothetical patients over their lifetime in our computer model to estimate harms and benefits of the management strategies. We tracked the number of individuals who developed anal cancer and then estimated their risk of death from anal cancer. We then estimated above outcomes by patient age. For each strategy, we estimated age-specific lifetime outcomes considering cost, quality of life and life expectancy. We found that HIV-infected gay and bisexual men who are 38 years or older should be treated using surgical treatment of ablation (either infrared coagulation or electrocautery), and that HPV vaccination should be administered at the time of surgery. This strategy is cost-effective and has the potential to decrease the lifetime risk of anal cancer by up to 80 percent in those men. The model also found that because younger men are more likely to be cured of their precancer without intervention, patients younger than 29 should not be treated and those between 29 and 38 years old should be actively monitored (watch-and-wait approach) in order to prevent treatment-related inconvenience and morbidity that might affect their quality of life. How the HPV vaccine could help Currently, HPV vaccination is not recommended for administration among individuals 27 years or older. However, multiple observational studies have shown, and our findings have confirmed, that a practice of vaccinating individuals who have already been diagnosed with precancer may decrease the risk of the precancer coming back after treatment. Given that the HPV vaccine has minimal side effects, we believe that clinicians can consider adopting this practice. Such practice may have many advantages, such as decreasing the number of treatments a patient needs for precancer recurrence thus decreasing the adverse outcomes of surgical treatment (possibility of scarring, anal stenosis and incontinence). In the long run, post-treatment HPV vaccination also has the potential to decrease the lifetime risk of anal cancer, save health care costs for treating patients for recurrence and cancer, and improve their life expectancy and quality of life. Ashish A. Deshmukh, Assistant Professor, University of Florida; Elizabeth Chiao, Associate professor, Baylor College of Medicine ; Jagpreet Chhatwal, Assistant Professor, Harvard Medical School , and Scott B. Cantor, Professor, The University of Texas MD Anderson Cancer Center This article was originally published on The Conversation. Read the original article.
September 21, 2017
Multiple sclerosis can be inhibited or reversed using a novel gene therapy technique that stops the disease’s immune response in mouse models, University of Florida Health researchers have found. By combining a brain-protein gene and an existing medication, the researchers were able to prevent the mouse version of multiple sclerosis. Likewise, the treatments produced near-complete remission in the animal models. The findings, which researchers said have significant potential for treating multiple sclerosis and other autoimmune disorders, are published today (Sept. 21) in the journal Molecular Therapy. Multiple sclerosis affects about 2.3 million people worldwide and is the most common neurological disease in young adults. The incurable disorder starts when the immune system attacks the myelin sheath surrounding nerve fibers, making them misfire and leading to problems with muscle weakness, vision, speech and muscle coordination. The researchers used a harmless virus, known as an adeno-associated virus, to deliver a gene responsible for a brain protein into the livers of the mouse models. The virus sparked production of so-called regulatory T cells, which suppress the immune system attack that defines multiple sclerosis. The gene was targeted to the liver because it has the ability to induce immune tolerance. “Using a clinically tested gene therapy platform, we are able to induce very specific regulatory cells that target the self-reactive cells that are responsible for causing multiple sclerosis,” said Brad E. Hoffman, Ph.D., an assistant professor in the departments of pediatrics and neuroscience at the University of Florida College of Medicine. The protein, myelin oligodendrocyte glycoprotein, was found to be effective in preventing and reversing muscular dystrophy on its own. A group of five mouse models that received the gene therapy did not develop experimental autoimmune encephalomyelitis, which is the mouse equivalent of multiple sclerosis in humans. In another experiment, all but one mouse model showed a significant reversal of the disease eight days after a single gene therapy treatment. Hoffman said he was also encouraged by the treatment’s longevity. After seven months, the mouse models that were treated with gene therapy showed no signs of disease, compared with a group of untreated mouse models that had neurological problems after 14 days. When the protein was combined with rapamycin — a drug used to coat heart stents and prevent organ transplant rejection — its effectiveness was further improved, the researchers found. The drug was chosen because it allows helpful regulatory T-cells to proliferate while blocking undesirable effector T-cells, Hoffman said. Among the mouse models that were given rapamycin and the gene therapy, 71 percent and 80 percent went into near-complete remission after having hind-limb paralysis. That, Hoffman said, shows the combination can be especially effective at stopping rapidly progressing paralysis. While researchers have established how gene therapy stimulates regulatory T cells in the liver, Hoffman said little else is known about the detailed mechanics of how that process works. Before the therapy can be tested in humans during a clinical trial, further research involving other preclinical models will be needed, Hoffman said. Researchers also need to target the full suite of proteins that are implicated in multiple sclerosis, he added. Still, Hoffman said he is extremely optimistic that the gene therapy can be effective in humans. “If we can provide long-term remission for people and a long-term quality of life, that is a very promising outcome,” he said. The research was funded by grants from the National Multiple Sclerosis Society, the National Institutes of Health and the Children’s Miracle Network.
September 15, 2017
Plants make proteins based on whatever genetic material you give them. Carl Davies, CSIRO, CC BY Kevin M. Folta, University of Florida I was cutting my grass when the battery in my iPod died. Instead of enjoying the distraction of music, my brain switched to its usual nerd mode of thinking about molecules. Within a few passes of cut grass, I was pondering the biggest “Why not?” of my scientific career: Could we discover new drugs and useful agricultural compounds by challenging organisms with clusters of random chemistry? My background is in molecular biology – the study of DNA, genes and how an organism’s blueprints are decoded and assembled into life. The discipline requires an understanding of how molecular codes are deciphered and turned into functional biology. Anyone in this field is plagued with dreams of dancing molecules, interacting and performing the roles that turn DNA information into our food, the plants in our environment and our families. Every day in the lab we move genes around. It’s easy. Not meant to generate new products for consumers, moving DNA is used as a research tool that lets us understand how specific genes work. A classic example is the NPR1 gene from the model plant Arabidopsis; it’s a defense gene that confers enhanced tolerance to disease when you drop it into almost any plant’s genome. Manipulating genetic information – in plants, microbes and some animals – is commonplace. On that half-cut lawn it occurred to me – instead of inserting DNA information we understand, what if we introduced a scrambled mess of random DNA code into a plant or bacterium? Could we identify random bits of genetic information that could give rise to small proteins (called peptides) that change an organism’s physiology or development? In all living things, the ‘words’ in the genetic material code for particular amino acids, so the organism can build the proteins it needs. Boumphreyfr, CC BY-SA Normally DNA encodes instructions that coordinate the order of the amino acid building blocks in a protein. Each amino acid has specific chemical characteristics. Strung together in a peptide chain, they fold into a protein that provides cellular structure or function, based on the complementary chemistries of its amino acid components. My hypothesis was that a short, scrambled DNA message could give rise to a novel string of amino acids. This would be a small cluster of discrete chemistry that likely never existed before on the planet. The vast majority of the time it would be meaningless and just become cellular rubbish. But maybe on rare occasion it could do something new and desirable. To test the hypothesis, our research team used randomized templates to synthesize trillions of random DNA fragments using simple DNA amplification techniques. Each was flanked by the genetic instructions to start and stop production of a peptide inside the plant. Then we used standard genetic engineering techniques to insert a novel DNA sequence into thousands of individual Arabidopsis thaliana plants – and sat back to watch what would happen when the plants turned the random genetic information into little random peptides. We were hoping for cases where specific protein structures might find a connection with biological chemistry and we’d see the result in the plants themselves. As the plants grew, we were blown away by what we observed. In some cases, adding a random ‘gene’ had a big effect on how plants grew… or not. Kevin Folta, CC BY-ND Some plants were flowering early. Others were small and stunted. Others grew larger leaves. Some were loaded with healthy purple pigments. Still others grew up to a point…then died. We then retrieved the particular random DNA sequence we’d added to each, a simple feat for a molecular biologist, and inserted the same sequence into new plants. Most of the time the random information affected the new generation of plants in exactly the same way, demonstrating that something was indeed happening related to the added, garbled information. We recently published our results in the journal Plant Physiology. What is this random information doing inside the cell? The small random molecules generated from the inserted DNA instructions could affect a specific process, just by chance. They could bind a needed nutrient. They might inhibit a key enzyme. They could turn on flowering or protect a plant from freezing. Nobody really knows exactly how until the plants are examined in detail one by one. These new proteins may also be good models to design new useful molecules with similar chemical properties, but that are more durable in the cell. Our goal is to produce a compound that may be applied to crops to change the way plants grow and behave, or perhaps stop the growth of invasive or weedy plants. The process is like throwing monkey wrenches into a complicated machine. Most of the time they clank around and affect nothing; but once in a long while a wrench catches in some critical gears and brings the machine to a halt. Other times the wrench might short-circuit a wasteful process, allowing the machine to run more efficiently. These peptides are molecular monkey wrenches. Small proteins created through this process might be the future of safe, sustainable and specific weed control. KegRiver, CC BY-NC-ND Some of these peptides must interfere with an important biological process because they kill the plant. These findings bring to light new vulnerabilities in plants that researchers could exploit to develop environmentally friendly and nontoxic herbicides. Agriculture currently relies on a few relatively old chemistries, cultivation (using fossil fuels) or human labor to control the weeds that compete with food plants for resources. Good weed control means that valuable fertilizers, water and sunlight go only to the desired plants, rather than weeds. So new herbicide chemistries would be extremely valuable as farmers work to produce food for growing populations. But why stop at plants? We are using the same approach to discover the next generation of antibiotics. The goal is to identify random information that affects a single species of problematic bacterium. For instance, we could potentially target S. aureus, the antibiotic-resistant bacteria that causes MRSA. We are hunting for new molecules that could destroy MRSA-related bacteria while leaving the rest of the microbiome unaffected. These experiments are underway in our lab. Randomness may pinpoint undiscovered vulnerabilities or opportunities in plants, bacteria and other organisms. There even may be applications in solving human disease. The future is exciting as we mine the vast collections of new molecules and study how they integrate with biology to produce important desired outcomes. Several of the molecules we’ve already identified slow plant growth. Future products from this technology might even be applied to make lawns grow more slowly. While others may find this advance helpful, I’ll have to skip using it. Cutting the grass gets my good ideas flowing. Kevin M. Folta, Professor and Chair, Horticultural Sciences Department, Graduate Program in Plant Molecular and Cellular Biology, University of Florida This article was originally published on The Conversation. Read the original article.
WEEKLY NEWS: July 27, 2017