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A compound related to Vitamin B3 may prevent hearing loss

26th Feb 2015 Hearing, Medical News, Starkey Hearing Foundation

A recent study published in Cell Metabolism by researchers from Weill Cornell Medical College and the Gladstone Institutes have identified a simple compound that may help prevent hearing loss. The compound nicotinamide riboside (NR) is a precursor to vitamin B3.

Noise induced hearing loss is a problem that can affect anyone at any age. The National Institutes on Deafness and Other Communication Disorders (NIDCD) estimates that more than 26 million Americans between the ages of 20 and 69 suffer from noise induced hearing loss. Hearing loss can result from a one-time exposure to an intense sound or from continuous exposure to loud sounds. Continuous or prolonged exposure to sounds over 85 decibels can cause hearing loss.

The process of hearing is based on a series of events that convert sound waves into electrical signals. Vibrations travel to the inner ear causing wave like ripples within the fluid inside the cochlea. There are tiny hair cells sitting along the top of inner membrane. These hair cells move up and down pushing against the sterocilia which transmits a signal to the auditory system within the brain. It is believed that exposure to loud noise can cause to damage to the junction where the nerves and hair cells meet, resulting in hearing loss.

Previous studies had identified that a chemical compound known as nicotinamide adenine dinucleotide (NAD+), which is chemically related to NR in this study, did protect nerve cells from injury however, it is an unstable compound. Using this information, researchers tested NR in lab mice and found that regardless whether the compound was given before or after exposure, NR did prevent hearing loss. It is believed that NR increases the activity of a protein known as SIRT3 (sirtuin 3) which is located within the mitochondria of the cells and is involved in regulating function.

The results of this study appearing to be promising. The researchers believe that the compound NR may also be useful for treating other disorders that are also mediated by the activity of protein sirtuin 3 such as hypertension, diabetes, and other metabolic syndromes.

References:

National Institutes on Deafness and Other Communication Disorders (NIDCD)

Brown KD, Maqsood S, Huang JY, Pan Y, Harkcom W, Li W, Sauve A, Verdin E, Jaffrey SR. Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell Metabolism. 2014 Dec 2; 20(6): 1059-1068.

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The Lone Star Tick in Florida

24th Feb 2015 Medical News, Viruses

Amblyomma Americanum, also known as the Lone Star tick, has been identified throughout the southeastern U.S. including central Florida.   In fact, this is the most common human biting tick in Florida (Clark KL, Leydet B, Hartman S.  International Journal of Medical Sciences 2013). The ticks are commonly found in wooded and animal resting areas.

The Heartland Virus, also known as Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV), was first discovered in the U.S., in northwestern Missouri, in June 2009.  The virus results from a tick-borne illness from the Phlebovirus genus.   The U.S. Center for Disease Control and Prevention (CDC) has traced the virus to the Lone Star Tick. Current investigations are looking at whether the virus can be transmitted by other vectors including mosquitos and flies.

Most of the cases of the Heartland virus identified so far occurred between 2012 and 2014 and have included two deaths.  All patients who became ill had been bitten by a ticks within the previous 14 days between May and September. Reported symptoms included fever in excess of 100.4 F, headaches, lethargy, and diarrhea, loss of appetite, nausea, and joint pains.  Additionally, low white blood cell counts and low platelets (thrombocytopenia) also were seen in these cases. The diagnosis was made after exclusion of other causes of infectious disease and also through antibody titers.

At present, there is no specific treatment for the Heartland virus. Antibiotics are not effect against the virus. Supportive care to include IV fluids and analgesics are recommended.   Recommendations for prevention includes the use of appropriate clothing such as long sleeve shirts and pants. The use of insect repellents including ones that contain DEET are recommended, however, this is not always effective.

Interestingly, it has been reported that a bite from a Lone Star tick can trigger an immune system response leading to a meat allergy. Dr. Scott Commins and Dr. Thomas Platts-Mills from the University of Virginia, identified the Lone Star tick as the culprit to causing this unusual allergy in 2011 (Current Allergy and Asthma Reports  Feb 2013 13(1): 72-77).  The number of cases have continued to be seen with increasing frequency.  As many of the reactions are often delayed, making the correct diagnosis has been challenging. It is unknown why only some develop the meat allergy.

Some have experienced long term symptoms associated with the Heartland virus from Lone Star tick bites.  It is unknown if the development of a meat allergy from this same tick species is a permanent one.

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Does Coffee Drinking Lower the Risk of Melanoma?

19th Feb 2015 Diseases, Medical News

A study published recently by researchers from the Yale School of Public Health and the Division of Cancer Epidemiology and Genetics at the National Institute of Health (NIH), reported the consumption of coffee was associated with a reduced risk of melanoma.

It is estimated that approximately one in five Americans will develop skin cancer.  Melanoma is currently the leading cause of skin cancer death in the U.S. with an increasing incidence.   Nearly 5000 Floridians are diagnosed with Melanoma annually.

Estimates of coffee consumption reveal that that Americans drink an average of 3.1 cups of coffee daily (NCA Drinking Trends Survey).  Furthermore, 83% of U.S. adults drink coffee.

The recent study looked at 447,357 non-Hispanic whites who were cancer free during at baseline.  They were followed for an average of 10.5 years. During the study period, 2904 developed melanoma.  Using statistical methods to determine risk, those who were in the group with the highest coffee consumption had the lowest risks of developing melanoma. Even after controlling for confounding variables including sex, age, BMI, alcohol intake, smoking status, and ultraviolet radiation exposure, the results held true.

Prior studies looking at the association between coffee consumption and melanoma have had mixed results. In a 2012, published data derived from the Nurses’ Health Study and Health Professionals Follow-up Study found that those women who consumed the most caffeine had an 18% lower risk of basal cell cancer (Song F, Qureshi AA, and Han J.  Cancer Research 2012 Jul 1; 72(13) 3282-3289).  However, caffeine intake was not associated with a lower risk of melanoma. Contrary to this, a prior case control study based out of Italy did show a protective effect of daily coffee consumption on the development of melanoma.

Studies have shown that the components of coffee may protect against oxidative stress and damage to DNA. There is belief that coffee may suppress Ultraviolet (UVB) induced skin cancers. Animal models have shown that caffeine helps to eliminate damaged skill cells before they have a chance to develop into tumors.

Caution should be exercised in considering these results as conclusive.   More research is needed to look at this association.   Differences in populations, possible measurement errors, and other confounding variables must be considered. Furthermore, while the lowest risk of developing melanoma in this study was associated with those who consumed the most coffee, there are known side effects of excessive coffee consumption.

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The Marriage of 3D Printing and Medicine

17th Feb 2015 Hearing, Medical News

The first 3D printer was developed over 2 decades years ago as a means of taking a concept and developing a  prototype that could easily be modified without mass production.  It was believed that 3D printing would revolutionize manufacturing in many different fields.  Now, with continued advancements in 3D printing technology, regenerative medicine, and biological sciences, this unique combination of disciplines coming together is transforming medicine.

Hundreds of thousands prototypes of medical devices and organ tissues are being printed daily.  Based on current medical news and case reports, here are some areas that 3D printing is being used:

Orthopedics– Knee replacements using 3D printing technology are already being used by orthopedists.  Using a CT scan of a knee, hip or other joint, a specific model of the patient’s anatomy is developed. This information is then combined with 3D printing technology to produce a tailored joint replacement and individualized instrumentation.  The true benefit is that patient’s receive an implant that matches with their specific anatomy and not a “mass produced” implant.  It is estimated that there are nearly 30,000 patients who have already received a 3D orthopedic implant.

A 3D printed cast has also been developed to allow for faster bone healing. The device is made of a lightweight, ventilated material (unlike traditional fiberglass casts) and is more conformable to the patient’s specific anatomy.  The manufacturer claims that it can reduce healing time by nearly 40% and improve overall healing rates.

Hearing Aids– There are estimates that there are more than 10 million 3D hearing aids already in use throughout the world.  Patients are reporting increased comfort with in-the-ear type hearing aids that are 3D produced.

Dental Implants– Crowns, caps, bridges, and veneers are being printed using 3D technology.  Current estimates of more than 750,000 3D dental implants worldwide have been used. Digital scans of the patient’s mouth are more accurate than physical molds that have been traditionally used allowing for betting fitting implants.

Prosthetics – Customized prosthetic limbs that match the symmetry and function of the natural limb are being developed.  3D printing has already made a huge impact within the prosthetics and orthotics field. In 2012, a 12 year Haitian boy received the first 3D printed robotic hand.

Spinal Surgery – Surgeons in China successfully replaced the  C2 verterbral body in a 12 year old with bone cancer body using a 3D printed artificial vertebra replacement.  The implant matched the exact shape and form of his natural anatomy which is believed to provide stronger fixation than a traditional titanium implant.

Other spinal manufacturers have developed customized interbody cages and pedicle screw placement guides using 3D printing.

Organ development – This is still in its infancy. The concept of “bioprinting” to develop living tissue structures is advancing.  Researcher’s are seeking to develop transplant-ready organs.  Using a 3D printed organ combined with the patient’s own cells, this has the potential to eliminate transplant lists and treat organs that are failing.

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Craiglist and HIV: Back to Basics

12th Feb 2015 Diseases, Medical News, Viruses

With the recent study released by the University of Minnesota linking Craigslist personals with an increase in reported HIV cases, it may be a good time to review this disease that has, in a way, fallen under the radar for many individuals. What is HIV? Where does it come from? How can you protect yourself? These are all questions that everyone should know how to answer.

What is HIV?

HIV is the initialism for human immunodeficiency virus. This virus is a type of retrovirus that causes AIDS, or acquired immunodeficiency syndrome. This disease causes progressive loss of immune system function, which can result in infections and cancers.

How does HIV damage the immune system?

HIV attacks certain immune system cells and directly or indirectly causes their death. When the number of these cells gets too low the individual loses cell-mediated immunity, which is a part of the immune response that does not use antibodies.  Without cell-mediated immunity opportunistic infections can take hold.

What are the symptoms of HIV?

Many people with HIV aren’t even aware they have the virus. Symptoms generally appear about a month or two after infection, but they can be so mild that they go unnoticed. These symptoms include: fever, fatigue, diarrhea, coughing, weight loss, shortness of breath, and swollen lymph nodes. The swollen lymph nodes are often the first signs of HIV infection. Some people describe it as “the worst flu ever.”

Without treatment HIV will progress and symptoms may include shaking chills, fever, night sweats, lesions of the tongue and mouth, blurred vision, and skin rashes. Over time cancers and opportunistic infections will develop and will be the cause of death if untreated.

How does someone contract HIV?

HIV can be spread through unprotected sexual intercourse (oral, anal, or vaginal), through blood transfusions (US hospitals screen for HIV to prevent this), sharing contaminated needles, and through pregnancy or breast-feeding. The virus is present in blood, semen, vaginal fluid, pre-ejaculate, and breast milk.

When does HIV become classified as AIDS?

The current standard for diagnosing AIDS is: a positive HIV test along with a CD4 cell count below 200, AND the presence of an AIDS-defining complication. This complication can be a disease like pneumocystosis, tuberculosis, toxoplasmosis, or many others.

How is HIV treated?

There is no cure for HIV or AIDS, but many drugs can be used to manage symptoms. Physicians usually prescribe multiple different types of medication to avoid developing HIV strains that are immune to single drugs. Treatment involves taking multiple pills at certain times every day for the rest of the patient’s life. These drugs can in turn cause their own side effects and if other health issues are present they may interfere with the individual’s ability to tolerate treatment.

Treatment can help a person life a normal life span, but without treatment life-expectancy is only 3 years.

How can I protect myself from HIV?

There is no vaccine available for HIV, but there are other methods you can use to protect yourself. The biggest way you can protect yourself is to use a new condom every time you have sexual intercourse (either vaginal or anal) and use a dental dam during oral sex. There is a drug called Truvada that MAY reduce the risk of sexually transmitted HIV if you are a high-risk individual (have unprotected sex, use IV drugs, are an uncircumcised male, or have another sexually transmitted disease.)

You should also use a new, clean needle every time if you are injecting drugs. There are needle-exchange programs available in many communities that you can use. Even better – seek help for your drug use.

If you are HIV-positive be sure to inform your sexual partners. If you become pregnant you need to speak to your doctor immediately about treatment to reduce the chance of passing the disease on to your baby.

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Novel Antibiotic Design to Prevent Hearing Loss

10th Feb 2015 Hearing, Medical News

One of ongoing challenges that modern medicine faces is the treatment of bacterial infections. One of the most widely used class of antibiotics to treat serious infections of the upper respiratory tract, urinary tract, and septicemia are the aminoglycosides.  They are also been used in cases where other antibiotics have failed. Aminoglycosides are used primarily in infections involving aerobic, gram negative bacteria.  While this class of antibiotics offers potent antimicrobial properties, the major side effect is loss of hearing. It is estimated that 20 – 50% of those treated with aminoglycosides develop either partial or complete loss of hearing.  In simplest form, aminoglycosides cause hearing loss by inducing sensory hair cell degeneration in the cochlea (Huth ME, Ricci AJ, Chen AG.  International Journal of Otolaryngology 2011).  This can also result in damage to the vestibular system resulting in ataxia and dizziness.

In a recent study published at the beginning of January, researchers from the Stanford University School of Medicine have developed a modified version of an aminoglycoside that has just as effective antimicrobial properties,  but does not carry the major side effect of deafness. Dr. Alan Cheng and Dr. Anthony Ricci spent over 4 years of research to develop and produce a small amount of an antibiotic, now known as N1MS. This newly patented drug was derived from another aminoglycoside, sisomicin.  N1MS was used to treat a urinary tract infection in mice.  The drug successfully eliminated the infection but did not cause deafness, as other drugs in this class have.  Comparatively, treatment with sisomicin caused 75 – 85% hair cell loss and profound hearing loss in treated mice.  The mechanism of action of N1MS was designed so that it avoids entering into the inner ear cell’s ion channels where deafness is known to occur. The other benefit of this newly designed drug is that it is non-toxic to the kidneys, which is also a known major side effect of aminoglycosides.

The continual development of bacterial resistance to antibiotics and toxicities that are known among the most effective drugs, have created a platform for the development of novel therapeutic agents like N1MS.  The aminoglycosides are subject of further research in the treatment of specific human genetic diseases.

Journal Reference:

Huth ME, Han KH, Sotoudeh K, Hsieh YJ, Effertz T, Vu AA, Verhoeven S, Hsieh M, Greenhouse R, Cheng AG, and Ricci AJ. Designer aminoglycosides prevent cochlear hair cell loss and hearing loss.  Journal of Clinical Investigation. 2015 Jan 2

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MOXle Study: Evaluating the drug RTA 408 in the treatment of Friedreich’s Ataxia.

05th Feb 2015 Diseases, Friedreich's Ataxia, Medical News

A clinical trial for a novel medication to treat Friedreich’s Ataxia was announced this past week. Reata Pharmaceuticals, a privately held biopharmaceutical company based out of Texas, announced the beginning of enrollments for a phase 2 and 3 clinical study titled “MOXle – RTA 408 Capsules in Patients with Friedreich’s Ataxia.” The study aims to further evaluate the safety, efficacy and pharmacodynamics of the treatment medication. A randomized, double blind, study to evaluate the maximum tolerated dose will be part one of the study. Part two will consist of splinting participants into two groups and giving two different dose levels of RTA 408. The second part will also be a randomized, placebo-controlled, double blinded study. This will be a multi-center study in which 52 patients are being sought.

Two clinical interests of the study will be peak workload during exercise as well as the modified Friedreich’s ataxia rating scale (FARS). The latter is a measurement tool which monitors proficiency of patients during activities. Additional biochemical endpoints will also be evaluated. Treatment with the study medication or placebo will be given to patient’s once daily for twelve weeks.

Nrf2 or Nuclear Factor 2, is a protein that regulates the expression of antioxidant proteins that protect against oxidative damage. Friedreich’s Ataxia is caused by defects in the gene for frataxin which is involved in the regulation of iron levels in the mitochondria. In pre-clinical studies, lower expressions of Nrf2 were correlated with frataxin deficiency and lower mitochondrial function. It is believed that RTA 408 can activate the Nrf2 pathways and improve mitochondrial function. Taken from animal models, RTA 408 showed the ability to improve overall cellular metabolism.

The study is expected to achieve final outcome measures by the spring of 2015 and study completion closer to June 2016.

http://www.marketwatch.com/story/reata-enrolls-first-patient-in-the-moxie-study-a-phase-23-study-examining-rta-408-in-friedreichs-ataxia-patients-2015-01-29

http://clinicaltrials.pharmaceutical-business-review.com/news/reata-enrolls-first-patient-in-phase-iiiii-moxie-study-of-rta-408-in-friedreichs-ataxia-patients-300115-4500885

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Hospital-acquired Infections

03rd Feb 2015 Diseases, News and Events, Viruses

Hospital-acquired infections have once again found a place in the news. Thirty-two individuals are reported to have been infected by a number of different drug-resistant strains of bacteria through contaminated endoscopes.  Eleven of these patients have died, but due to their prior severe illnesses it is unclear whether or not the new infections played any role. The endoscopes in question are called duodenoscopes and are used to treat liver and pancreas illnesses. They are professionally sterilized to high standards between patients, which has unfortunately turned out to no longer be adequate.

The disinfection procedures that the manufacturers recommended were approved by the U.S. Food and Drug Administration (FDA), but after the hospital was able to identify the sterilized scopes as the source of infection they had to switch to a method that exceeded the national standards. The FDA is working with the endoscope suppliers and medical centers to develop new solutions, but this is not the first time scopes have been identified as a source of nosocomial infections. Pittsburgh in 2012 and Chicago in 2014 both saw hospital-acquired infections due to contaminated endoscopes, but luckily there were no fatalities.

The most well-known hospital-acquired infection is Methicillin-resistant Staphylococcus aureus, or MRSA. MRSA originated in the hospital setting, but has expanded to locker rooms, livestock, prisons, military barracks, and homeless shelters. Since many of the individuals infected have weakened immune systems they are already at a greater risk of nosocomial infections. In addition, MRSA’s resistance to certain antibiotics (like penicillins and cephalosporins) make it very difficult to treat.

One of the drug resistant strains of bacteria responsible for the infections in Seattle include Carbapenem-resistant enterobacteriaceae (CRE). Two examples of CRE include Klebsiella species and Escherichia coli (E. coli). While these are normal human gut bacteria, they can cause infection in those undergoing invasive treatments due to illness (like the endoscopes) or those that are taking long courses of antibiotics. Many strains of CRE have become resistant to most of the available antibiotics, making them especially deadly.

How can you protect yourself from hospital-acquired infections, like MRSA and CRE? Most of the prevention is done by the hospital – sterilizing equipment, using appropriate isolation procedures, washing hands, wearing gloves, sanitizing surfaces, wearing aprons while treating patients, and even using antimicrobial surfaces like copper bedrails. For patients that want to protect themselves there is a list of questions you can ask your healthcare provider that is provided by the Centers for Disease Control and Prevention: http://www.patientcarelink.org/uploadDocs/1/Massachusetts-Consumer-HAI-Basics.pdf

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