November 19, 2015
University of Queensland
A new form of secret light communication used by marine animals has been discovered by scientists. The findings may have applications in satellite remote sensing, biomedical imaging, cancer detection, and computer data storage.
Researchers from the Queensland Brain Institute at The University of Queensland have uncovered a new form of secret light communication used by marine animals.
The findings may have applications in satellite remote sensing, biomedical imaging, cancer detection, and computer data storage.
Dr Yakir Gagnon, Professor Justin Marshall and colleagues previously showed that mantis shrimp (Gonodactylaceus falcatus) can reflect and detect circular polarising light, an ability extremely rare in nature. Until now, no-one has known what they use it for.
The new study shows the shrimp use circular polarisation as a means to covertly advertise their presence to aggressive competitors.
“In birds, colour is what we’re familiar with; in the ocean, reef fish display with colour. This is a form of communication we understand. What we’re now discovering is there’s a completely new language of communication,” said Professor Marshall.
Linear polarised light is seen only in one plane, whereas circular polarised light travels in a spiral — clockwise or anti-clockwise — direction.
The team determined that mantis shrimp display circular polarised patterns on the body, particularly on the legs, head and heavily armoured tail; these are the regions most visible when when they curl up during conflict.
“These shrimp live in holes in the reef,” said Professor Marshall. “They like to hide away; they’re secretive and don’t like to be in the open.”
Researchers dropped a mantis shrimp into a tank with two burrows to hide in: one reflecting unpolarised light and the other, circular polarised light. The shrimp chose the unpolarised burrow 68% of the time — suggesting the circular polarised burrow was perceived as being occupied by another mantis shrimp.
“If you essentially label holes with circular polarising light, by shining circular polarising light out of them, shrimps won’t go near it,” said Professor Marshall. “They know — or they think they know — there’s another shrimp there.
The findings may help doctors to better detect cancer. “Cancerous cells do not reflect polarised light, in particular circular polarising light, in the same way as healthy cells,” said Professor Marshall. So cameras equipped with circular polarising sensors may detect cancel cells long before the human eye can see them.
Another study involving Professor Marshall, published in the same edition ofCurrent Biology, showed that linear polarised light is used as a form of communication by fiddler crabs.
Fiddler crabs (Uca stenodactylus) live on mudflats, a very reflective environment, and they behave differently depending on the amount of polarisation reflected by objects, the researchers found.
“It appears that fiddler crabs have evolved inbuilt sunglasses, in the same way as we use polarising sunglasses to reduce glare,” Professor Marshall said.
The crabs were able to detect and identify ground-base objects base on how much polarised light was reflected. They either moved forward in a mating stance, or retreated back into their holes, at varying speeds.
“These animals are dealing in a currency of polarisation that is completely invisible to humans,” Professor Marshall said. “It’s all part of this new story on the language of polarisation.”
Both studies will be published in the print edition of Current Biology in December 2015.
- Yakir Luc Gagnon, Rachel Marie Templin, Martin John How, N. Justin Marshall. Circularly Polarized Light as a Communication Signal in Mantis Shrimps. Current Biology, 2015; DOI: 10.1016/j.cub.2015.10.047
- Martin J. How, John H. Christy, Shelby E. Temple, Jan M. Hemmi, N. Justin Marshall, Nicholas W. Roberts. Target Detection Is Enhanced by Polarization Vision in a Fiddler Crab. Current Biology, 2015; DOI:10.1016/j.cub.2015.09.073
Source: University of Queensland. “Marine animals use new form of secret light communication.” ScienceDaily. ScienceDaily, 19 November 2015. <www.sciencedaily.com/releases/2015/11/151119113510.htm>.
Gamma interferon given 24 hours before and up to 24 hours after exposure completely protects mice from death from Ebola
November 18, 2015
University of Iowa Health Care
A new study suggests that gamma interferon, which is an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus. The study found that gamma interferon, given up to 24 hours after exposure, can inhibit Ebola infection in mice and completely protect the animals from death.
The recent Ebola outbreak in West Africa has claimed more than 11,300 lives and starkly revealed the lack of effective options for treating or preventing the disease. Progress has been made on developing vaccines, but there is still a need for antiviral therapies to protect health care workers and local populations in the event of future outbreaks.
A new study led by University of Iowa virologist Wendy Maury, PhD, suggests that gamma interferon, which is an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus.
The study, published in the journal PLOS Pathogens, found that gamma interferon, given up to 24 hours after exposure, can inhibit Ebola infection in mice and completely protect the animals from death.
Ebola infection appears to be a stepwise process. First, the virus targets and infects macrophages or dendritic cells, two types of immune system cells found in the liver, spleen, and lymph nodes. Ebola then replicates in those cells. Following this initial infection, which happens at day 3 or 4 in non-human primates, Ebola virus is released into the blood and infects a plethora of other different cell populations.
“It goes from an early stage with a very targeted infection of only these few cell types, to everything being infected,” explains Maury, who is a professor of microbiology in the UI Carver College of Medicine. “We think what’s happening with gamma interferon is that it’s targeting macrophages and blocking the infection of those initial cell targets so you don’t get the second round of infection.”
The UI does not have a specializing BioSafety Level 4 (BSL4) lab that is required for experiment using Ebola virus, so Maury and her UI colleagues made their initial findings using a surrogate virus, which targets and infects the same cells as Ebola, but does not cause the disease. This Ebola lookalike — a sheep in wolf’s clothing — consists of a less dangerous vesicular stomatitis virus (VSV) that expresses Ebola glycoproteins on its surface.
However, all of the results Maury’s team found using the surrogate virus, were repeated using mouse-adapted Ebola virus in the BSL4 lab of Maury’s long-time collaborator Robert Davey at Texas Biomedical Institute in San Antonio, Texas.
The team showed that gamma interferon inhibits the virus’s ability to infect human and mouse macrophages, in part by blocking virus replication in the cells. The researchers then showed that pretreating mice with interferon gamma 24 hours before exposure protects the animals from infection and death. To their surprise, the researchers found that treatment up to 24 hours after what would have been a lethal exposure also completely protected the animals from death, and the scientists could no longer detect any Ebola virus in the mouse cells. These findings suggest that interferon gamma may be useful both as a prophylaxis and post-exposure treatment against Ebola.
The team still has to determine how late gamma interferon can be given to the mice and still prevent infection. However, the results suggest a window of time after exposure when gamma interferon may be an effective antiviral therapy
“My guess is that if you delay the gamma interferon too much, you miss this window of opportunity to block the infection in macrophage cells and the gamma interferon can no longer provide protection,” Maury says.
Working with Martha Monick, PhD, now a UI professor emeritus in internal medicine, Maury and lead study author Bethany Rhein, PhD, investigated how gamma interferon might be helping the cells fight off Ebola virus. They identified that expression of more than 160 genes in human macrophages are stimulated by gamma interferon. Introduction of some of these genes into cells was sufficient to prevent Ebola infection.
“This mechanistic information might suggest more precise drug targets rather than the broad effects, including adverse side-effects, that are produced by gamma-interferon,” Maury says.
Gamma interferon is approved by the FDA to treat Chronic Granulomatous Disease (an immune disease) and Severe Malignant Osteopetrosis.
In addition to moving the studies into larger animal models, Maury now plans to study the ability of gamma interferon to inhibit Ebola infection in conjunction with other developing antivirals.
“Right now there are no FDA-approved antiviral therapies for Ebola, but there are some being developed that target virus entry,” she says. “We know that gamma interferon blocks replication but not entry into cells. So combining an entry inhibitor with gamma interferon may allow us to reduce amount of gamma interferon needed and target two different steps in the virus’s life cycle, which has been shown in HIV to be critically important for controlling virus.”
In addition to Maury, Monick, Rhein, and Davey, the research team included Linda Powers, Kai Rogers Manu Anantpadma, Brajesh Singh, Yasuteru Sakurai, Thomas Bair, Catherine Miller-Hunt, and Patrick Sinn.
- Bethany A. Rhein, Linda S. Powers, Kai Rogers, Manu Anantpadma, Brajesh K. Singh, Yasuteru Sakurai, Thomas Bair, Catherine Miller-Hunt, Patrick Sinn, Robert A. Davey, Martha M. Monick, Wendy Maury. Interferon-γ Inhibits Ebola Virus Infection. PLOS Pathogens, 2015; 11 (11): e1005263 DOI: 10.1371/journal.ppat.1005263
Source: University of Iowa Health Care. “FDA-approved drug protects mice from Ebola: Gamma interferon given 24 hours before and up to 24 hours after exposure completely protects mice from death from Ebola.” ScienceDaily. ScienceDaily, 18 November 2015. <www.sciencedaily.com/releases/2015/11/151118131734.htm>.
November 17, 2015
Florida State University
A high-performance computing researcher has predicted a physical effect that would help physicists and astronomers provide fresh evidence of the correctness of Einstein’s general theory of relativity.
A Florida State University high-performance computing researcher has predicted a physical effect that would help physicists and astronomers provide fresh evidence of the correctness of Einstein’s general theory of relativity.
Bin Chen, who works at the university’s Research Computing Center, describes the yet-to-be-observed effect in the paper “Probing the Gravitational Faraday Rotation Using Quasar X-ray Microlensing,” published today in the journal Scientific Reports.
“To be able to test general relativity is of crucial importance to physicists and astronomers,” Chen said.
This testing is especially so in regions close to a black hole, according to Chen, because the current evidence for Einstein’s general relativity — light bending by the sun, for example — mainly comes from regions where the gravitational field is very weak, or regions far away from a black hole.
Electromagnetism demonstrates that light is composed of oscillating electric and magnetic fields. Linearly polarized light is an electromagnetic wave whose electric and magnetic fields oscillate along fixed directions when the light travels through space.
The gravitational Faraday effect, first predicted in the 1950s, theorizes that when linearly polarized light travels close to a spinning black hole, the orientation of its polarization rotates according to Einstein’s theory of general relativity. Currently, there is no practical way to detect gravitational Faraday rotation.
In the paper, Chen predicts a new effect that can be used to detect the gravitational Faraday effect. His proposed observation requires monitoring the X-ray emissions from gravitationally lensed quasars.
“This means that light from a cosmologically distant quasar will be deflected, or gravitationally lensed, by the intervening galaxy along the line of sight before arriving at an observer on the Earth,” said Chen of the phenomenon of gravitational lensing, which was predicted by Einstein in 1936. More than 100 gravitational lenses have been discovered so far.
“Astronomers have recently found strong evidence showing that quasar X-ray emissions originate from regions very close to supermassive black holes, which are believed to reside at the center of many galaxies,” Chen said. “Gravitational Faraday rotation should leave its fingerprints on such compact regions close to a black hole.
“Specifically, the observed X-ray polarization of a gravitationally microlensed quasar should vary rapidly with time if the gravitational Faraday effect indeed exists,” he said. “Therefore, monitoring the X-ray polarization of a gravitationally lensed quasar over time could verify the time dependence and the existence of the gravitational Faraday effect.”
If detected, Chen’s effect — a derivative of the gravitational Faraday effect — would provide strong evidence of the correctness of Einstein’s general relativity theory in the “strong-field regime,” or an environment in close proximity to a black hole.
Chen generated a simulation for the paper on the FSU Research Computing Center’s High-Performance Computing cluster — the second-largest computer cluster in Florida.
- Bin Chen. Probing the gravitational Faraday rotation using quasar X-ray microlensing. Scientific Reports, 2015; 5: 16860 DOI:10.1038/srep16860
Source: Florida State University. “More proof of Einstein’s general theory of relativity.” ScienceDaily. ScienceDaily, 17 November 2015. <www.sciencedaily.com/releases/2015/11/151117145055.htm>.
November 16, 2015
University of Liverpool
Seismologists studying the 2011 Chile earthquake have discovered a previously undetected earthquake that took place seconds after the initial rupture. This newly discovered phenomena, which they called a `closely-spaced doublet,’ presents a challenge to earthquake and tsunami early warning systems as it increases the risk of larger-than-expected tsunamis in the aftermath of a typical subduction earthquake.
Seismologists at the University of Liverpool studying the 2011 Chile earthquake have discovered a previously undetected earthquake which took place seconds after the initial rupture.
This newly discovered phenomena which they called a `closely-spaced doublet’ presents a challenge to earthquake and tsunami early warning systems as it increases the risk of larger-than-expected tsunamis in the aftermath of a typical subduction earthquake.
In a study published in Nature Geoscience, University researchers analysed in detail the seismic wave recordings from 2 January 2011 when an earthquake of magnitude 7 occurred in Chile along the plate boundary separating the subducting Nazca plate from the South American continent.
They discovered that just 12 seconds later and 30 km further offshore, a second rupture of a similar size, which was un-detected by national and global earthquake monitoring centres, occurred along an extensional (pull-apart) fault in the middle of the South American plate beneath the Pacific Ocean.
Liverpool seismologist, Professor Andreas Rietbrock, said: “Real-time global seismic monitoring and early warning events have come a long way and it is possible for a magnitude 5 or greater earthquake to be detected within a matter of minutes. Therefore, it is striking that an earthquake with magnitude close to 7 was effectively hidden from our standard monitoring systems.”
“Previous doublet events have been documented in subduction zones before, but such instantaneous triggering of large ruptures at close distances has no known precedent. Such triggered events dramatically complicate potential earthquake impact assessments and tsunami early warning systems as the risk of a larger than expected tsunami is higher following a typical subduction earthquake.”
Dr Stephen Hicks, who was part of the research team, said: “We believe that seismic waves travelling outward from the first rupture immediately shook up and weakened the shallower second fault, causing the hidden rupture. Scientists believe that the overlying plate at collisional plate boundaries is broken up on a large scale and contains networks of faults. It is plausible that similar closely-spaced doublets may occur elsewhere around the Pacific Ring of Fire. ”
Professor Rietbrock added: “This work challenges the commonly-held notion that slip during large earthquakes may only occur along a single fault. The result was surprising as there was no indication of such a complicated rupture from global earthquake monitoring systems. ”
“Our findings present a concern for tsunami early warning systems. Without real-time monitoring of seismometers located close to the fault, it is possible that tsunami and shaking hazard from future subduction earthquakes may be underestimated.”
As part of the University’s Liverpool Earth Observatory, seismologists are installing a seismic network in Southern Peru in close collaboration with the Geophysical Institute of Peru.
This area along the South American continental margin has the potential for a large magnitude 8+ earthquake and it is important to understand the associated seismic and tsunami hazard.
- Stephen P. Hicks, Andreas Rietbrock. Seismic slip on an upper-plate normal fault during a large subduction megathrust rupture. Nature Geoscience, 2015; DOI: 10.1038/ngeo2585
Source: University of Liverpool. “Discovery of hidden earthquake presents challenge to earthquake early-warning systems.” ScienceDaily. ScienceDaily, 16 November 2015. <www.sciencedaily.com/releases/2015/11/151116120806.htm>.
RBM: The Heart of Data Quality – Applied Clinical Trials Quotes Target Health
Recently, Target Health attended and presented at CBI’s meeting entitled Risk-Based Trial Management, Is It Only About Monitoring? Lisa Henderson was there from Applied Clinical Trials and filed a report which can be found in its entirety in ACT. The following was abstracted:
Discussion this year at the RBM conference has the ACT editorial staff wondering how the industry should be defining RBM. They asked Is it Risk-Based Monitoring or Risk-Based Management? This year’s conference showed that the discussion has migrated now to assessing the clinical trial as an entity. For example, remote monitoring to some sponsors has meant having the clinical site fax in every piece of documentation for remote SDV. That was never the goal or intention of RBM, said Jules Mitchel, President of Target Health.
At the end of the ACT article Lisa Henderson added that Mitchel too is a believer in eSource and of the simple protocol. He said that regulators want to know that informed consent is properly obtained, the protocol is followed and monitored, the primary endpoint is measured and documented properly, that all significant safety events are captured and reported and drug/device supply is properly managed. Mitchel also recommends that both FDA and EMA be involved early and often in an RBM-designed trial.
Autumn at the Linn Cove Viaduct, James Farley Master Photographer
James told us that this photo was shot just after the sun came over the horizon. What a way to greet the morning.
©James Farley Photography 2015
For those curious about the specs on the shot, it was done with my Canon 5D Mark III, 17mm Tilt-Shift lens with the 2x Extender, effectively at 34mm focal length and with an aperture of f16. Three bracketed exposures were captured and merged into this High Dynamic Range shot in post-production. Lee Filters Landscape Circular Polarizer used, with a 0.9 Grad ND.
ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212 – 681 – 2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Lewy Body Dementia
National Library of Medicine – NIH
Lewy body dementia, the 1) ___ most common type of progressive dementia after Alzheimer’s disease, causes a progressive decline in mental abilities. It may also cause visual hallucinations, which generally take the form of objects, people or animals that aren’t there. This can lead to unusual behavior such as having conversations with deceased loved ones. Another indicator of Lewy body dementia may be significant fluctuations in alertness and attention, which may include daytime drowsiness or periods of staring into space. And, like 2) ___ disease, Lewy body dementia can result in rigid muscles, slowed movement and tremors.
In Lewy body dementia, protein deposits, called Lewy bodies, develop in nerve cells in regions of your brain involved in thinking, memory and movement (motor control). Lewy body dementia signs and symptoms may include:
Visual hallucinations. You may see visual hallucinations, such as colors, shapes, animals or people that aren’t there. 3) ___ may be one of the first symptoms of Lewy body dementia. Some people also may experience sound (auditory), smell (olfactory) or touch (tactile) hallucinations.
Movement disorders. You may experience symptoms similar to those of Parkinson’s disease (parkinsonian symptoms), such as slowed movement, rigid muscles, tremors or a shuffling walk.
Poor regulations of body function. Blood pressure, pulse, sweating and digestive process are regulated by a part of the nervous system that is often affected by Lewy body dementia. This can result in dizziness, falls and bowel issues.
Cognitive problems. You may experience thinking (cognitive) problems similar to problems experienced in 4) ___ disease, such as confusion, reduced attention span and eventually memory loss.
Sleep difficulties. You may have a sleep disorder called rapid eye movement (REM) sleep behavior disorder that can cause you to physically act out your dreams while you’re asleep.
Fluctuating attention. You may have frequent episodes of drowsiness, long periods of staring into space, long naps during the day or disorganized speech.
Depression. You may experience depression sometime during the course of your illness.
The cause of Lewy body dementia isn’t known, but the disorder may be related to Alzheimer’s or Parkinson’s disease.
Lewy bodies contain a 5) ___ associated with Parkinson’s disease.
Lewy bodies often are present in the brains of people with Parkinson’s disease, Alzheimer’s disease and other dementias.
People who have Lewy bodies in their brains also have the plaques and tangles associated with Alzheimer’s disease.
Although the cause of Lewy body dementia isn’t clear, several factors appear to increase the risk of developing the disease. They include:
Being older than 6) ___
Having a family member with Lewy body dementia
Lewy body dementia is progressive. Signs and symptoms worsen, causing:
Death, on average about eight years after onset of the condition
The set of symptoms typical of LBD, is confusing, explained Dr. Joe Quinn of the Parkinson’s Disease and Movement Disorders program at Oregon Health and Science University. It’s why doctors and even some brain experts struggle to initially diagnose the disease. Because there’s no blood analysis or brain scan to test for the condition, physical confirmation comes only in 7) ___death, when doctors performing an autopsy analyze slivers of brain under a microscope. In this way, LBD is very similar to Alzheimer’s disease, which is confirmed in autopsy by finding plaques and tangles in the brain, and to Parkinson’s disease, which is confirmed in autopsy by Lewy bodies in the areas of the brain that affect movement. While a patient lives, however, clinicians are left to sort through a mess of 8) ___ that might seem like Parkinson’s (muscle rigidity, which Quinn called Parkinson-ism) or Alzheimer’s disease (dementia).
If your patient has the combination of Parkinson-ism and visual hallucinations, and the person is having trouble thinking clearly, that’s an instance where you make a diagnosis of Lewy body dementia with greater confidence, according to Dr. Quinn. Quinn sometimes explains LBD symptoms to others as a blend of both diseases: Patients will struggle to move, and may also suffer mentally. He himself has initially diagnosed patients with Alzheimer’s, only to revise that diagnosis to Lewy body dementia a year later when more symptoms come to light. One major revealer, for LBD, is visual hallucinations that aren’t caused by medication or pre-existing mental illness. For those whose visual hallucinations don’t come until much later in life, it can take a long time to give a diagnosis of Lewy body dementia.
Sometimes, caregivers have to educate doctors about LBD. For instance, medications may have to be monitored, because many doctors don’t realize that common antipsychotics prescribed for the hallucinations are actually very dangerous for people with LBD. It’s a very complex disease to treat, and there are medical people who aren’t aware of this. That can cause stress for caregivers. When the disease progresses, and a patient starts to lose the ability to9) ___, parts of the brain that control singing can escape the brain damage. A caregiver can have some success drawing words out, by singing a well-known song, like Happy Birthday. Brain scans could one day provide a more accurate diagnosis. Scientists have made progress with PET scans to identify plaques in the brain of a living patient who has Alzheimer’s disease, and Dr. Quinn hopes that parallel efforts to create brain 10) ___ for Lewy bodies can one day help neurologists diagnose LBD early and with certainty.
ANSWERS: 1) second; 2) Parkinson’s; 3) Hallucinations; 4) Alzheimer’s; 5) protein; 6) sixty; 7) death; 8) symptoms; 9) speak; 10) scans
Friedrich Heinrich Lewy MD (1885-1950); Lewy Body Dementia
Lewy body dementia affects about 1 million individuals in the United States alone.
Frederic Henry Lewey (born Friedrich Heinrich Lewy, January 28, 1885 – October 5, 1950) was a prominent Jewish German-born American neurologist. He is best known for the discovery of Lewy bodies, which are a characteristic indicator of Parkinson’s disease and dementia with Lewy bodies.
Lewy was born in Berlin, Germany on January 28, 1885. He trained in Berlin and Z?rich and graduated from Berlin in 1910. He died in Haverford, Pennsylvania on October 5, 1950, at age 65. Lewy worked in Alois Alzheimer’s Munich laboratory and was contemporary with Hans Gerhard Creutzfeldt (1885-1964), Alfons Maria Jakob (1884-1931) and Ugo Cerletti (1877-1963). He later fled Nazi Germany and moved to the United States.
Kenji Kosaka MD, born in 1939, is a Japanese psychiatrist, known for his pioneer research on Dementia with Lewy bodies (DLB). Kosaka was born in Ise, Mie, and completed his M.D. in 1965 from Kanazawa University. He was appointed as a professor of psychiatry at Yokohama City University School of Medicine in 1991, before becoming a director of Yokohama City University Medical Center in 1995. He has been a director of Medical Care Court Clinic in Yokohama since 2011. He received the 2013 Asahi Prize for discovering Dementia with Lewy bodies. In 1976, Kosaka described the concept of Dementia with Lewy bodies for the first time. Two years later, he reported three autopsied cases of Dementia with Lewy bodies.
The term Dementia with Lewy bodies (DLB) was proposed at the first international workshop held in 1995, and is now in common use. DLB is also known under a variety of other names including Lewy body dementia (LBD), diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of dementia closely associated with Parkinson’s disease. It is characterized anatomically by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons, detectable in post mortem brain histology. LBD only started to be diagnosed in the mid-1990s after the discovery of alpha-synuclein staining first highlighted Lewy bodies in the cortex of post mortem brains of a subset of dementia patients. Because it was only recently discovered, LBD is not a recognized diagnosis in DSM-IV, which was published in 1994. It is, however, briefly mentioned in the DSM-IV-TR (published in 2000) under “Dementia Due to Other General Medical Conditions”. In 1996, a consortium of scientists initially proposed and later revised diagnostic guidelines. Currently, an estimated 60 to 75% of diagnosed dementias are of the Alzheimer’s and mixed (Alzheimer’s and vascular dementia) type, 10 to 15% are Lewy body type, with the remaining types being of an entire spectrum of dementias, including frontotemporal lobar degeneration (Picks Disease), alcoholic dementia, pure vascular dementia, etc. LBD is slightly more prevalent in men than women.
The major cause of LBD is not yet well understood, but a genetic link with the PARK11 gene has been described. As with Alzheimer’s disease and Parkinson’s disease, most cases of LBD appear sporadically and LBD is not thought to have a strong hereditary link. As with Alzheimer’s disease, the LBD risk is heightened with inheritance of the e4 allele of the apolipoprotein E (APOE). Pathologically, LBD is characterized by the development of abnormal proteinaceous (alpha-synuclein) cytoplasmic inclusions, called Lewy bodies, throughout the brain. These inclusions have similar structural features to “classical” Lewy bodies seen subcortically in Parkinson’s disease. Additionally, a loss of dopamine-producing neurons (in the substantia nigra) occurs, similar to that seen in Parkinson’s disease, and a loss of acetylcholine-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer’s disease. Cerebral atrophy (or shrinkage) also occurs as the cerebral cortex degenerates. Autopsy series have revealed the pathology of LBD is often concomitant with the pathology of Alzheimer’s disease. That is, when Lewy body inclusions are found in the cortex, they often co-occur with Alzheimer’s disease pathology found primarily in the hippocampus, including senile plaques (deposited beta-amyloid protein), and granulovacuolar degeneration (grainy deposits within and a clear zone around hippocampal neurons). Neurofibrillary tangles (abnormally phosphorylated tau protein) are less common in LBD, although they are known to occur, and astrocyte abnormalities are also known to occur. It is presently not clear whether LBD is an Alzheimer’s variant or a separate disease entity. Unlike Alzheimer’s disease, the brain may appear grossly normal with no visible signs of atrophy.
There is no cure for LBD. Treatment may offer symptomatic benefit, but remains palliative in nature. Current treatment modalities can be divided into pharmaceutical and caregiving. Pharmaceutical management, as with Parkinson’s disease, involves striking a balance between treating the motor and emotive/cognitive symptoms. Motor symptoms appear to respond somewhat to the drugs used to treat Parkinson’s disease (e.g. levodopa) while cognitive issues may improve with drugs for Alzheimer’s disease such as donepezil. Drugs used in the treatment of Attention deficit/hyperactivity disorder (e.g. methylphenidate) might improve cognition or daytime sleepiness, however drugs for both Parkinson’s disease and ADHD increase levels of the chemical dopamine in the brain and so increase the risk of hallucinations with those classes of pharmaceuticals. Treatment of the movement and cognitive portions of the disease can worsen hallucinations and psychosis, while treatment of hallucinations and psychosis with anti-psychotics can worsen parkinsonian or ADHD symptoms in LBD such as tremor or rigidity and lack of concentration or impulse control. Doctors may find the use of cholinesterase inhibitors represents the treatment of choice for cognitive problems and donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) may be recommended as a means to help with these problems and to slow or prevent the decline of cognitive function. Reports indicate Lewy body dementia may be more responsive to donepezil than Alzheimer’s disease.
Because LBD gradually renders people incapable of tending to their own needs, caregiving is very important and must be carefully managed over the course of the disease. Caring for people with LBD involves adapting the home environment, schedule, activities, and communications to accommodate declining cognitive skills and Parkinsonian symptoms. People with LBD may swing dramatically between good days?high alertness and few cognitive or movement problems?and bad days, and the level of care they require thus may vary widely and unpredictably. Sharp changes in behavior may be due to the day-to-day variability of LBD, but they may also be triggered by changes in the schedule or home environment, or by physical problems, such as constipation, dehydration, bladder infection, injuries from falls, and other problems a person with LBD may not be able to convey to caregivers. Potential physical problems should always be checked out when an individual with LBD becomes agitated. As hallucinations and delusions are not dangerous or troubling to the person with LBD, it may be best for caregivers not to disabuse patients of them. Often the best approach is benign neglect – acknowledging, but not encouraging or agreeing.
Sadly, American actor and comedian Robin Williams committed suicide on August 11, 2014. Upon autopsy it was discovered that he had diffuse Lewy Body dementia. Williams had been incorrectly diagnosed with Parkinson’s disease prior to his death; he had also been suffering from depression, anxiety, and increasing paranoia (all symptoms of DLB).
Lower Blood Pressure Target Can Reduce Cardiovascular Disease, Deaths
NIH-supported researchers are reporting more details on a landmark study that announced preliminary findings in September showing a lower blood pressure target can save lives and reduce the risk of cardiovascular disease in a group of non-diabetic adults 50 years and older with high blood pressure. Results of the Systolic Blood Pressure Intervention Trial (SPRINT) appear online in the New England Journal of Medicine (9 November 2015). The study confirms that, in adults 50 years and older with high blood pressure, targeting a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) reduced rates of cardiovascular events, such as heart attack and heart failure, as well as stroke, by 25%. Additionally, this target reduced the risk of death by 27% — as compared to a target systolic pressure of 140 mm Hg.
The SPRINT study, which began in the fall of 2009, included more than 9,300 participants age 50 and older, recruited from about 100 medical centers and clinical practices throughout the United States and Puerto Rico. About 36% of participants were women, 58% were white, 30% were African-American, and 11% were Hispanic. The SPRINT study did not include patients with diabetes, prior stroke, or polycystic kidney disease, as other NIH trials were studying those particular populations. Approximately 28% were 75 or older and 28% had chronic kidney disease. The study tested a strategy of using blood pressure medications to achieve the targeted goals of less than 120 mm Hg (intensive treatment group) versus 140 mm Hg (standard treatment group). The NIH stopped the blood pressure intervention in August — a year earlier than planned — after it became apparent that this more intensive intervention was beneficial. The original report provided detailed data showing that both cardiovascular deaths and overall deaths were lower in the intensive treatment group.
Certain types of serious consequences were more common in the intensive group, including low blood pressure, fainting, electrolyte abnormalities, and acute kidney damage. However, other serious adverse events associated with lower blood pressure, such as slow heart rate and falls with injuries, did not increase in the intensive group. In patients with chronic kidney disease, there was no difference in the rate of serious decline in kidney function between the two blood pressure goal groups. In addition to its primary cardiovascular outcome, the study continues to examine kidney disease, cognitive function, and dementia among the SPRINT participants; however, these results are not yet available as additional information will be collected and analyzed over the next year.
According to the NIH, although the study provides strong evidence that a lower blood pressure target saves lives, patients and their health care providers may want to wait to see how guideline groups incorporate this study and other scientific reports into any future hypertension guidelines. In the meantime, patients should talk to their health care providers to determine whether this lower goal is best for their individual care. The NIH added that it is also important to remember that healthy lifestyle changes can make a difference in controlling high blood pressure, and that following a healthy diet, being physically active, maintaining a healthy weight, as well as learning to check your blood pressure, also contribute.
Neuromodulation Targeted to the Prefrontal Cortex Induces Changes in Energy Intake and Weight Loss in Obesity
Obesity is associated with decreased activity in the prefrontal cortex. Since transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating, a study published in Obesity (4 November 2015), was performed to evaluate the effects of non-invasive brain stimulation on weight loss.
The authors studied a total of nine obese men and women who resided in the metabolic ward on two separate visits, each for eight days. On each visit, the participants ate a weight-maintaining diet for five days. Then for three days, they unknowingly received either active or sham (fake) transcranial direct current stimulation, or tDCS. Participants then ate and drank as much as they wanted from computerized vending machines. Applied to the scalp, the active tDCS targeted the brain region controlling behavior and reward.
Results showed that the four people who got the sham stimulation during both visits consumed the same number of calories from the vending machines on each visit and did not lose weight. But the five people who got inactive stimulation on the first visit, and active tDCS at the brain target on the second visit, consumed an average of 700 fewer calories and lost an average of 0.8 pounds on the second visit.
According to the authors, the results indicated a role for the LDLPFC in obesity and food intake and that this proof of concept study suggested, for the first time, the potential application of anodal tDCS to facilitate weight loss
Next, authors will compare a group getting only active tDCS with a separate group getting only sham stimulation as more study is needed to confirm the safety and effectiveness of tDCS for weight loss.
Hemophilia A is an inherited, gender-linked, blood-clotting disorder that primarily affects males, which is caused by defects found in the Factor VIII gene. According to the Centers for Disease Control and Prevention, Hemophilia A affects one in every 5,000 male births in the United States. Patients with hemophilia A may experience repeated episodes of serious bleeding, primarily into the joints, which can be severely damaged as a result.
The FDA has approved Adynovate, Antihemophilic Factor (Recombinant), PEGylated for use in adults and adolescents, aged 12 years and older, who have Hemophilia A. Adynovate consists of the full-length Coagulation Factor VIII molecule (historically known as Antihemophilic Factor) linked to other molecules, known as polyethylene glycol (PEGylated). This link makes the product last longer in the patient’s blood. Thus, Adynovate is modified to last longer in the blood and potentially require less frequent injections than unmodified Antihemophilic Factor when used to reduce the frequency of bleeding. Adynovate is approved for on-demand (as needed) treatment and control of bleeding episodes and to reduce the frequency of bleeding episodes (prophylaxis) in patients with Hemophilia A.
The safety and efficacy of Adynovate were evaluated in a clinical trial of 137 adults and adolescents aged 12 years and older, which compared the recommended routine prophylactic (preventative) treatment regimen to on-demand therapy. The trial demonstrated that Adynovate was effective in reducing the number of bleeding episodes during routine care. Additionally, Adynovate was effective in treating and controlling bleeding episodes. No safety concerns were identified during the trial.
Adynovate is manufactured by Baxalta US Inc., based in Westlake Village, California.