Save the Earth. Win some cash.
I’m a writer. My barely-out-of-college kid brother is a computer programmer. Only one of us has the skills to save the world from asteroids. (Okay, spoiler, it’s not me.)
NASA is calling on coders to develop software that automatically spots asteroids in photos taken by large ground telescopes. The software has to work better than existing software, which depends on comparing telescope photos of the same patch of sky, taken at different times, to determine which objects in the photos move. In a description of the contest, NASA’s Tournament Lab says, “The winning solution must increase the detection sensitivity, minimize the number of false positives, ignore imperfections in the data, and run effectively on all computers.”
The winning solution(s) will also win a total of $35,000 in prizes, according to statement from Planetary Resources. The asteroid-mining company signed an agreement with NASA to manage the contest, which is called Asteroid Data Hunter.
The contest is part of NASA’s Asteroid Grand Challenge, an overall program to develop ways to detect if an asteroid threatens Earth. The agency already has plans to capture an asteroid and send astronauts to study it. The point of the Asteroid Grand Challenge is to partner with organizations outside of NASA, including citizen scientists, for asteroid-impact prevention.
You can find out more about what NASA wants for its asteroid-spotting software on the contest’s website. There are also links there for registering for the contest, which opens March 17.
Target Document and the Electronic Trial Master File (eTMF)
Target Health runs a fully paperless operation. While we are very well known for our robust EDC system (Target e*CRF®) for electronic data capture in clinical trials, now fully integrated with Target e*CTR® (eClinical Trial Record eSource solution), we also have a robust document management system (Target Document®) which is being used world-wide for the electronic trial master file (eTMF). We do not buy binders anymore and neither do the clinical research sites. We also do not do wet signatures but sign electronically. These are just some of the features. For our CRO partners, there is just a small annual fee and a cost/study which is a line item with a return on investment. For companies, there is full document management for all processes and no need to go to a document room to view documents, just click on any Browser with any device.
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ON TARGET is the newsletter of Target Health Inc., a NYC-based contract research organization (CRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.
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.
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Amyotrophic Lateral Sclerosis (ALS)
This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. However, typically MRI imaging is unremarkable in a patient with ALS.
Amyotrophic lateral sclerosis (ALS) – also referred to as motor neurone disease (MND) in most Commonwealth countries, and as Lou 1) ___ disease in the United States – is a debilitating disease with varied etiology characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and difficulty breathing (dyspnea). ALS is the most common of the five motor neuron diseases. Amyotrophic comes from the Greek language: A-means no , myo refers to muscle , and trophic means nourishment ; amyotrophic therefore means no muscle nourishment, which describes the characteristic atrophication of the sufferer’s disused muscle tissue. Lateral identifies the areas in a person’s spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ( sclerosis ) in the region. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Unable to function, the 2) ___weaken and exhibit atrophy. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared until the terminal stages of the disease.
Cognitive function is generally spared for most patients, although some (about 5%) also have fronto-temporal dementia. A higher proportion of patients (30-50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include trouble swallowing, muscle fasciculation (twitching), cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal 3) ___. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disease experience limb onset ALS, i.e., first symptoms in the arms or legs. Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a dropped foot which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.
Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski’s sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the 4) ___ (fasciculations). Around 15-45% of patients experience pseudo bulbar affect, also known as emotional lability , which consists of uncontrollable laughter, crying or smiling. To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk or use their hands and arms. They also lose the ability to speak and swallow their food, whilst most end on a portable 5) ___, called BPAP. Disease progression tends to be slower in patients who are younger than 40 at onset, have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms. Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia. Difficulty in chewing and swallowing makes 6) ___ very difficult and increases the risk of choking or of aspirating food into the lungs. In later stages of the disease, aspiration pneumonia can develop, and maintaining a healthy weight can become a significant problem that may require the insertion of a feeding tube. As the diaphragm and intercostal muscles of the rib cage that support breathing weaken, measures of lung function such as vital capacity and inspiratory pressure diminish. Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory 7) ___, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years. Physicist Stephen Hawking has lived with the disease for more than 50 years, though he is an unusual case.
There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families. A defect on chromosome 21, which codes for superoxide dismutase, is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall. This mutation is believed to be transmitted in an autosomal dominant manner, and has over a hundred different forms of mutation. To date, a number of genetic 8) ___ have been associated with various types of ALS. The precise cause of ALS is still not known, though a first important step toward determining the cause came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase(SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive 9) ___ produced by cells during normal metabolism. Free radicals can accumulate and cause damage to both mitochondrial and nuclear DNA and proteins within cells. Evidence suggests that failure of defenses against oxidative stress up-regulates programmed cell death (apoptosis), among many other possible consequences. Although it is not yet clear how gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of a particular gene.
Where no family history of the disease is present – i.e., in around 90% of cases – there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in contact 10)___. More recently, some research has suggested that there may be a link between ALS and food contaminated by blue-green algae. Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid. Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease. Certain studies suggested a link between sporadic ALS, specifically in athletes, and a diet enriched with branched-chain amino acids. BCAAs, a common dietary supplement among athletes, cause cell hyper-excitability resembling that is usually observed in ALS patients. The proposed underlying mechanism is that cell hyper-excitability results in increased calcium absorption by the cell and thus brings about cell death of neuronal cells, which have particularly low calcium buffering capabilities. Another very common cause of ALS is a lesion to the motor system in areas such as the fronto-temporal lobes. Lesions in these areas often show signs of early deficit, which can be used to predict the loss of motor function, and result in the spread of ALS. The mechanisms of ALS are present long before any signs or symtoms become apparent. It is estimated that before any muscular atrophy becomes apparent during ALS, roughly one-third of the motor neurons must be destroyed. Many other potential causes, include chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated but without consistent findings.
The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the 11) ___, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation. No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests, EMG, detects electrical activity in muscles. Another common test measures nerve conduction velocity (NCV). The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a 12) ___ field and radio waves to take detailed images of the brain and spinal cord. Based on the patient’s symptoms and findings from the examination and from these tests, the physician may order other tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests.
Current research focuses on abnormalities of neuronal cell metabolism involving glutamate and the role of potential neurotoxins and neurotrophic factors. Riluzole (Rilutek) is the only treatment that has been found to improve survival but only to a modest extent. It lengthens survival by several months. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage (occurring in ~10% of people taking the drug). It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE). Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible. Physical therapists and occupational therapists play a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence. Occupational therapy and special equipment such as assistive technology can also enhance patients’ independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living (ADL’s), walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression.
Researchers have stated that ALS patients suffer from a severe loss of appetite. Both animal and human research suggest that ALS patients should be encouraged to consume as many calories as possible and not to restrict their calorie intake. As of 2012 there remained a lack of robust evidence for interventions for the management of weight loss.
Fruits and vegetables containing carotenoids.
Research has found that people who ate fruits and vegetables containing carotenoids, an oxidative compound, strengthen immune system response, had reduced chance of developing13) ___. There are three primary carotenoids that act as oxidative compounds called beta-carotene, lycopene, and lutein found in fruits and vegetables each found in different foods like carrots, watermelon, and tomatoes.
ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women. Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. This seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of symptoms similar to ALS, parkinsonism, and dementia. Lytico-Bodig disease has been linked to the consumption and topical use of cycad seeds and in particular, the chemical found in cycad seeds, ?-methylamino-L-alanine (BMAA). Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan, both with topical cycad seed use. Although there have been reports of several clusters including three American football players from the San Francisco 49ers, more than fifty association football players in Italy, three association football-playing friends in the south of England, and reports of conjugal (husband and wife) cases in the south of France, these are statistically plausible chance events. Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.
A number of clinical trials are underway globally for ALS; a comprehensive listing of trials in the US can be found at ClinicalTrials.gov. A phase II trial on tirasemtiv has been completed with a follow-on Phase IIb study in progress under the name BENEFIT-ALS . Results of the first study are available here. The current trial is an international, placebo-controlled, multi-center study on 680 participants. This makes it one of the largest studies to date. A phase II trial on Ozanezumab is in progress. It is a large multi-site international research project sponsored by GSK. A phase II clinical trial is being conducted by BrainStorm Cell Therapeutics at the Hadassah Medical Center in Israel and interim results demonstrated a tendency toward stabilization in some parameters in the ALS Functional Rating Scale. Patients in the trial have bone marrow stem cells removed and differentiated in a clean room into cells that express neurotropic factors. The cells are injected back into the same patient via an intrathecal injection and intramuscular injections. A second phase II trial is expected to open in the United States at several institutions including the Mayo Clinic.
ANSWERS: 1) GehrIg’s; 2) muscles; 3) speech; 4) skin; 5) ventilator; 6) eating; 7) failure; 8) mutations; 9) molecules; 10) sports; 11) brain; 12) magnetic; 13) ALS
Jean-Martin Charcot MD (1825 – 1893)
In the last analysis, we see only what we are ready to see,what we have been taught to see. We eliminate and ignore everything that is not a part of our prejudices . Jean-Martin Charcot
Jean-Martin Charcot was a French neurologist and professor of anatomical pathology. He is known as the founder of modern neurology and is associated with at least 15 medical eponyms, including Charcot-Marie-Tooth disease andamyotrophic lateral sclerosis (motor neurone disease). Charcot has been referred to as the father of French neurology and one of the world’s pioneers of neurology . His work greatly influenced the developing fields of neurology and psychology; modern psychiatry owes much to the work of Charcot and his direct followers. He was the foremost neurologist of late nineteenth-century France and has been called the Napoleon of the neuroses .
Born in Paris, Charcot worked and taught at the famous Salpetriere Hospital for 33 years. His reputation as an instructor drew students from all over Europe. In 1882, he established a neurology clinic at Salpetriere, which was the first of its kind in Europe. Charcot was a part of the French neurological tradition and studied under, and greatly revered, Duchenne de Boulogne. He married, Madame Durvis, in 1862 and had two children, Jeanne and Jean-Baptiste, the latter becoming both a doctor and a famous polar explorer .
Charcot’s primary focus was neurology. He named and was the first to describe multiple sclerosis. Summarizing previous reports and adding his own clinical and pathological observations, Charcot called the disease sclerose en plaques. The three signs of Multiple sclerosis now known as Charcot’s triad 1 are nystagmus, intention tremor, and telegraphic speech, though these are not unique to MS. Charcot also observed cognition changes, describing his patients as having a marked enfeeblement of the memory and conceptions that formed slowly . He was also the first to describe a disorder known as Charcot joint or Charcot arthropathy, a degeneration of joint surfaces resulting from loss of proprioception. He researched the functions of different parts of the brain and the role of arteries in cerebral hemorrhage. Charcot was among the first to describe Charcot-Marie-Tooth disease (CMT). The announcement was made simultaneously with Pierre Marie of France (his resident) and Howard Henry Tooth of England. The disease is also sometimes called peroneal muscular atrophy.
Charcot’s studies between 1868 and 1881 were a landmark in the understanding of Parkinson’s disease. Among other advances he made the distinction between rigidity, weakness and bradykinesia. He also led the disease formerly named paralysis agitans (shaking palsy) to be renamed after James Parkinson. Charcot received the first European professional chair of clinical diseases for the nervous system in 1882.
Charcot is best known today, outside the community of neurologists, for his work on hypnosis and hysteria. He initially believed that hysteria was a neurological disorder for which patients were pre-disposed by hereditary features of their nervous system, but near the end of his life concluded that hysteria was a psychological disease. Charcot first began studying hysteria after creating a special ward for non-insane females with hystero-epilepsy ; he discovered two distinct forms of hysteria among these women; minor hysteria and major hysteria. His interest in hysteria and hypnotism developed at a time when the general public was fascinated in ?animal magnetism’ and ?mesmerization’ , which was later revealed to be a method of inducing hypnosis. His study of hysteria attracted both scientific and social notoriety . Charcot and his school considered the ability to be hypnotized as a clinical feature of hysteria. For the members of the Salpetriere School, susceptibility to hypnotism was synonymous with disease, i.e. hysteria, although they later recognized that grand hypnotisme(in hysterics) should be differentiated from petit hypnotisme, which corresponded to the hypnosis of ordinary people .
The Salpetriere School’s position on hypnosis was sharply criticized by Hippolyte Bernheim, a leading neurologist of the time. Charcot himself long had concerns about the use of hypnosis in treatment and about its effect on patients. He also was concerned that the sensationalism hypnosis attracted had robbed it of its scientific interest, and that the quarrel with Bernheim, furthered mostly by his pupil Georges Gilles de la Tourette, had damaged hypnotism.
Charcot demonstrates hypnosis on a hysterical Salpetriere patient, Blanche (Blanche Wittmann), who is supported by Dr. Joseph Babinski (rear).
Charcot thought of art as a crucial tool of the clinico-anatomic method. He used photos and drawings, many made by himself or his students, in his classes and conferences. He also drew outside the neurology domain, as a personal hobby. Like Duchenne, he is considered a key figure in the incorporation of photography to the study of neurological cases.
Charcot’s name is associated with many diseases and conditions including:
1. Charcot’s artery (lenticulostriate artery)
2. Charcot’s joint (diabetic arthropathy)
3. Charcot’s disease (amyotrophic lateral sclerosis, the most-common subtype of motor neurone disease – also known as Lou Gehrig’s disease.)
4. Charcot-Marie-Tooth disease (peroneal muscular atrophy), named with Pierre Marie and Howard Henry Tooth.
5. Charcot-Wilbrand syndrome (visual agnosia and loss of ability to revisualise images), named with Hermann Wilbrand.
6. Charcot’s intermittent hepatic fever (intermittent pain, intermittent fever, intermittent jaundice, and loss of weight)
7. Charcot-Bouchard aneurysms (tiny aneurysms of the penetrating branches of middle cerebral artery in hypertensives), named with Charles-Joseph Bouchard.
8. Charcot’s triad of acute cholangitis (right upper quadrant pain, jaundice, and fever)
9. Charcot’s triad of multiple sclerosis (nystagmus, intention tremor, and dysarthria)
10. Charcot-Leyden crystals due to the lysis ofeosinophils in cases of allergic diseases, named with Ernst Viktor von Leyden.
11. Souques-Charcot geroderma: a variant of Hutchinson-Gilford disease, named with Alexandre-Achille Souques.
12. Charcot-Gombault necrosis: a biliary infarct, named with Albert Gombault.
One of Charcot’s greatest legacies as a clinician is his contribution to the development of systematic neurological examination, correlating a set of clinical signs with specific lesions. This was made possible by his pioneering long-term studies of patients, coupled with microscopic and anatomic analysis derived from eventual autopsies. This led to the first clear delination of various neurological diseases and classic description of them. For example, amyotrophic lateral sclerosis.
Charcot is just as famous for his students: Sigmund Freud, Joseph Babinski, Pierre Janet, William James, Pierre Marie, Albert Londe, Charles-Joseph Bouchard, Georges Gilles de la Tourette, Alfred Binet, Jean Leguirec and Albert Pitres. Charcot bestowed the eponym for Tourette syndrome in honor of his student, Georges Gilles de la Tourette. Although by the 1870s, Charcot was France’s best known physician, according to Edward Shorter, his ideas in psychiatry were refuted, and France did not recover for decades. Shorter wrote in his A History of Psychiatry that Charcot himself understood almost nothing about major psychiatric illness, and that he was quite lacking in common sense and grandiosely sure of his own judgement . This perspective overlooks that Charcot never claimed to be practicing psychiatry or to be a psychiatrist, a field that was separately organized from neurology within France’s educational and public health systems. After his death, Shorter said the illness hysteria that Charcot described was claimed to be nothing more than an artifact of suggestion , however American psychologist Gardner Murphy referred to Charcot’s position in French psychiatry and psychology as prominent .
After Charcot’s death, Freud and Janet wrote articles on his importance. The Charcot-Janet school, which formed from the work of Charcot and his student Janet, contributed greatly to knowledge of double and multiple personality, before being extended by Morton Prince’s Dissociation of a personality (1905). The judgment of Charcot’s work on hysteria is influenced by a significant shift in diagnostic criteria and understanding of hysteria which occurred in the decades following his death. The historical perspective on Charcot’s work on hysteria has also been distorted by viewing him as a precursor of Freud (whose markedly different conception of hysteria was extensively addressed by feminist historians in the last decades of the 20th century). Charcot argued vehemently against the widespread medical and popular prejudice that hysteria was rarely found in men, presenting several cases of traumatic male hysteria. He taught that due to this prejudice these cases often went unrecognized, even by distinguished doctors and could occur in such models of masculinity as railway engineers or soldiers. Charcot’s analysis, in particular his view of hysteria as an organic condition which could be caused by trauma, paved the way for understanding neurological symptoms arising from industrial-accident or war-related traumas.
A 2012 French historical drama film, Augustine, is about a love affair between Charcot and a patient. The New York Times film review describes Charcot as a complicated figure in retrospect, at once a charlatan and a pioneer, a monster and a modernizer . Charcot appears, along with Maria Sklodowska-Curie (Madame Curie) and Charcot’s patient Blanche (Marie Wittman), in Per Olov Enquist’s 2004 novel The Book about Blanche and Marie (English translation, 2006,ISBN 1-58567-668-3). He also appears in the 2005 novel by Sebastian Faulks, Human Traces, and in Axel Munthe’s 1929 autobiographical novel The Story of San Michele. In a letter to the New York Times Book Review of January 18, 1931, however, Charcot’s son wrote that Dr Munthe never was trained by my father. And in his 2008 biography of Munthe (ISBN 978-1-84511-720-7), Bengt Jangfeldt says that ‘Charcot is not mentioned in a single letter of Axel’s out of the hundreds that have been preserved from his Paris years. Distorted views of Charcot as harsh and tyrannical have arisen from some sources that mistakenly identify Munthe as Charcot’s assistant and take Munthe’s autobiographical novel as a factual memoir. In fact, Munthe was just a medical student among hundreds of others. Munthe’s most direct contact with Charcot was when he helped a young female patient escape from a ward of the hospital and took her into his home. Charcot threatened to advise the police and ordered that Munthe not be allowed on the wards of the hospital again.
Charcot Island in Antarctica was discovered by his son, Jean-Baptiste Charcot, who named the Island in honor of his father.
Fatty Acid Supplementation in Children and Sleep
Higher levels of omega-3 DHA (docosahexaenoic acid), the group of long-chain fatty acids are found in algae and seafood. Sleep problems in children have been associated with poor health, behavioral and cognitive problems, as are deficiencies of long-chain omega-3 fatty acids such as (DHA). Theory and some evidence support a role for these fatty acids in sleep regulation, but this topic has received little formal investigation. As a result, a study published in the Journal of Sleep Research (8 MAR 2014), examined associations between blood fatty acid concentrations (from fingerstick blood samples) and subjective sleep (using an age-standardized parent questionnaire) in a large epidemiological sample of healthy children aged 7-9 years (n=395) from mainstream UK schools. The study was a randomized controlled trial, to explore whether a 16-week supplementation (600 mg day) with algal DHA versus placebo might improve sleep in a subset of those children (n = 362) who were underperforming in reading. In a randomly selected subsample (n=43), sleep was also assessed objectively via actigraphy, a non-invasive method of monitoring human rest/activity cycles. To do this, a small actigraph unit, also called an actimetry sensor, is worn by a subject to measure gross motor activity. Motor activity often under test is that of the wrist, measured by an actigraph in a wrist-watch-like package. Results from the study showed that in 40% of the epidemiological sample, Child Sleep Habits Questionnaire scores indicated clinical-level sleep problems. Furthermore, poorer total sleep disturbance scores were associated weakly but significantly with lower blood DHA and a lower DHA : arachidonic acid ratio. While results from the treatment trial showed no significant effects on subjective sleep measures, in the small actigraphy subsample, DHA supplementation led on average to seven fewer wake episodes and 58 minutes more sleep per night compared to those taking the corn or soybean placebo. The authors, with some caution, concluded that higher blood levels of DHA acid may relate to better child sleep, as rated by parents and that exploratory pilot objective evidence from actigraphy suggests that DHA supplementation may improve children’s sleep. Of course, further investigations are needed in larger trials.
Anti-Psychotic Medications May Offer Hope Against Brain Cancer
Glioblastoma remains one of the deadliest of human cancers, with most patients succumbing to the disease within two years of diagnosis. The available data suggest that simultaneous inactivation of critical nodes within the glioblastoma molecular circuitry will be required for meaningful clinical efficacy. As a result, a study published online in Oncotarget (7 March 2014), performed parallel genome-wide shRNA screens to identify such nodes. The discovery that led to the shRNA technology won the Nobel Prize in Physiology/Medicine in 2006. According the authors, ShRNAs are invaluable tools in the study of what genes do in that they function like molecular erasers, and that if these erasers can be designed against every gene in the human genome, the shRNAs can then be packaged into viruses and introduced into cancer cells. If a gene is then required for glioblastoma growth and the shRNA erases the function of that gene, then the cancer cell will either stop growing or die.
Results from the investigation uncovered a number of G-Protein Coupled Receptor (GPCR) neurotransmitter pathways, including the Dopamine Receptor D2 (DRD2) signaling pathway. Dopamine is a small molecule that is released by nerve cells and binds to the dopamine receptor in surrounding nerve cells, enabling cell communication. Abnormal dopamine regulation is associated with Parkinson’s disease, schizophrenia, and Attention Deficit Hyperactivity Disorder. Because of the importance of dopamine in these diseases, drugs have been developed to neutralize the effect of dopamine, called dopamine antagonists.
Supporting the importance of DRD2 in glioblastoma, DRD2 mRNA and protein expression were elevated in clinical glioblastoma specimens relative to matched non-neoplastic cerebrum. Interestingly, treatment with independent si-/shRNAs against DRD2 or with DRD2 antagonists suppressed the growth of patient-derived glioblastoma lines both in vitro and in vivo. Most importantly, glioblastoma lines derived from independent genetically engineered mouse models (GEMMs) were more sensitive to haloperidol, an FDA approved DRD2 antagonist, than the premalignant astrocyte lines by approximately an order of magnitude. Results also showed that the pro-proliferative effect of DRD2 was, in part, mediated through a GNAI2/Rap1/Ras/ERK signaling axis, and that combined inhibition of DRD2 and Epidermal Growth Factor Receptor (EGFR) led to synergistic tumoricidal activity as well as ERK suppression in independent in vivo and in vitro glioblastoma models. The authors concluded that combined EGFR and DRD2 inhibition may be a promising strategy for glioblastoma treatment.
3-D Changes in DNA May Lead to a Genetic Form of Lou Gehrig’s Disease
According to an article published online in Nature (5 March 2014), new findings reveal how a mutation, a change in the genetic code that causes neurodegeneration, alters the shape of DNA, making cells more vulnerable to stress and more likely to die. The particular mutation, in the C9orf72 gene, is the most common cause for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease), and frontotemporal degeneration (FTD), the second most common type of dementia in people under 65.
In ALS, the muscle-activating neurons in the spinal cord die, eventually causing paralysis. In FTD neurons in particular brain areas die leading to progressive loss of cognitive abilities. The mutation may also be associated with Alzheimer’s and Huntington’s diseases.
DNA contains a person’s genetic code, which is made up of a unique string of bases, chemicals represented by letters. Portions of this code are divided into genes that provide instructions for making molecules (proteins) that control how cells function. The normal C9orf72 gene contains a section of repeating letters; in most people, this sequence is repeated two to 25 times. In contrast, the mutation associated with ALS and FTD can result in up to tens of thousands of repeats of this section.
Using sophisticated molecular techniques, the authors showed that the mutation causes changes in the three-dimensional shape of DNA. DNA is normally shaped like a twisted ladder. However, the repeating sequences can fold into G-quadruplexes, stacks of square-shaped molecules known as G-quartets. According to the authors, the structure has been described as a square building with each floor representing one G-quartet, normally two to four stories high. The results also showed that C9orf72 mutated DNA has profound effects on how the genetic message is processed in the cell. RNA, short for ribonucleic acid, acts as an important intermediary – a middleman – in the process that converts genetic information from DNA into functional proteins. This happens in two stages: conversion of the DNA code into RNA is called transcription. RNA then forms proteins during a process known as translation.
The authors discovered that the mutated DNA forms DNA-RNA hybrid structures called R loops. Then they showed that G-quadruplexes and R-loops interfered with the transcription process. Cells taken from patients (containing the C9orf72 mutation) produced shorter transcription products (or transcripts) compared with control cells (without the mutation) taken from healthy volunteers. These short transcripts result in abnormal functioning of the cell and can lead to cell death. According to the authors, unfortunately, these alternative DNA arrangements impede normal processing, much like a car encountering a series of speed bumps or the occasional roadblock while traveling to its destination. Additional findings from the study also suggest that the C9orf72 mutation has an effect in the nucleolus, a cellular structure located within the nucleus (which contains the cell’s DNA) and the site where initial steps in protein assembly occur. The nucleolus also plays a key role in directing the cell’s response to stress.
The key protein inside the nucleolus is nucleolin and the authors decided to study the effects of the C9orf72 mutation on nucleolin. Results showed that binding of the short transcription products formed by the C9orf72 mutation to nucleolin has toxic effects on cells, and that in healthy cells without the mutation, nucleolin is present only in a certain area of the nucleus. However, in cells obtained from ALS patients, nucleolin is scattered throughout the nucleus. The authors postulated that abnormal distribution of nucleolin causes cells to become stressed and more likely to die, which can result in the pathology associated with ALS and FTD.
For those experiments, the authors used induced pluripotent stem cells (iPSC) containing the C9orf72 mutation that were derived from the skin of ALS patients. The iPSCs can be turned into different types of cells, in this case into motor neurons, which are the cells that die in patients with ALS. The iPSC technology lets scientists study in a dish the direct effects of disease-causing human mutations on brain or spinal cord cells.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area.
Proposed Changes to the Nutrition Facts Label
FDA issued two proposed rules on the nutrition facts label. The rules are published in the Federal Register so that members of the public can review them and send their comments to FDA.
The following links will take you to key documents:
2. Serving Sizes of Foods that can Reasonably be Consumed at One-Eating Occasion; Dual-Column Labeling; Updating, Modifying, and Establishing Certain Reference Amounts Customarily Consumed; Serving Size for Breath Mints; and Technical Amendments
Proposed Nutrition Facts Label At-A-Glance
The FDA is proposing to update the Nutrition Facts label found on most food packages in the United States. The Nutrition Facts label, introduced 20 years ago, helps consumers make informed food choices and maintain healthy dietary practices. If adopted, the proposed changes would include the following.
1. Greater Understanding of Nutrition Science
- Require information about added sugars. Many experts recommend consuming fewer calories from added sugar because they can decrease the intake of nutrient-rich foods while increasing calorie intake.
- Update daily values for nutrients like sodium, dietary fiber and Vitamin D. Daily values are used to calculate the Percent Daily Value listed on the label, which help consumers understand the nutrition information in the context of a total daily diet.
- Require manufacturers to declare the amount of potassium and Vitamin D on the label, because they are new nutrients of public health significance. Calcium and iron would continue to be required, and Vitamins A and C could be included on a voluntary basis.
- While continuing to require Total Fat, Saturated Fat, and Trans Fat on the label, Calories from Fat would be removed because research shows the type of fat is more important than the amount.
2. Updated Serving Size Requirements and New Labeling Requirements for Certain Package Sizes
- Change the serving size requirements to reflect how people eat and drink today, which has changed since serving sizes were first established 20 years ago. By law, the label information on serving sizes must be based on what people actually eat, not on what they should be eating.
- Require that packaged foods, including drinks, that are typically eaten in one sitting be labeled as a single serving and that calorie and nutrient information be declared for the entire package. For example, a 20-ounce bottle of soda, typically consumed in a single sitting, would be labeled as one serving rather than as more than one serving.
- For certain packages that are larger and could be consumed in one sitting or multiple sittings, manufacturers would have to provide dual column labels to indicate both per serving and per package calories and nutrient information. Examples would be a 24-ounce bottle of soda or a pint of ice cream. This way, people would be able to easily understand how many calories and nutrients they are getting if they eat or drink the entire package at one time.
3. Refreshed Design
- Make calories and serving sizes more prominent to emphasize parts of the label that are important in addressing current public health concerns such as obesity, diabetes, and cardiovascular disease.
- Shift the Percent Daily Value to the left of the label, so it would come first. This is important because the Percent Daily Value tells you how much of certain nutrients you are getting from a particular food in the context of a total daily diet.
- Change the footnote to more clearly explain the meaning of the Percent Daily Value.
Proposed Serving Size Changes
What’s considered a single serving has changed in the decades since the original nutrition label was created. So now serving sizes will be more realistic to reflect how much people typically eat at one time.
Veggies with Chicken & Brown Rice Mixed with Golden Raisins, Pine Nuts and Peanut Sauce
Just Out of the Oven ©Joyce Hays, Target Health Inc.
Peanut sauce is a favorite thing to eat, with green vegetables, like broccoli, spinach and edamame, and it’s this particular peanut sauce that really makes this recipe different and delicious. Adding left-over chicken or turkey to this casserole, makes for a delicious one dish meal. However, if you want a strictly vegan recipe, a few substitutions can easily make it vegan. I’ve tried baking cubes of firm tofu brushed with olive oil, and using them instead of poultry, with good results. You can substitute chicken stock with vegetable broth.
Get all of your ingredients lined up on the counter. This kind of organization makes cooking much easier.
Lining up the ingredients ©Joyce Hays, Target Health Inc.
Ingredients for Peanut Sauce
1/4 cup natural peanut butter (creamy variety)
2 Tbsp tamari soy sauce (use low-sodium variety)
3 garlic cloves, minced
1/8 tsp grated ginger root (optional)
1/3 cup warm chicken stock or broth
Ingredients for the Rest of the Dish
TOFU or POULTRY - One block of the firmest tofu, cut in cubes, stirred in baking dish with extra virgin olive oil and 2 garlic cloves, juiced — bake in 350 degree oven for 20 minutes or stir fry until golden brown. Set aside
BROWN RICE - Make the (organic) brown rice and set aside. To enhance the flavor of the rice, boil it in chicken stock instead of water. You can use saffron rice instead if you prefer.
BROCCOLI - Clean. Steam or stir fry in olive oil and 1-2 juiced garlic cloves, for 2-3 minutes. Break apart the florets to the size you want. Cut stems into small pieces and use. If you would rather serve the broccoli separately, and not in this casserole, go ahead.
14 oz frozen bag (thawed) of organic sodium-free edamame.
1 bunch fresh broccoli
1 cup golden raisins
1 cup pine nuts, toasted ahead of time. You could substitute cashews or peanuts.
2 Tablespoons extra virgin olive oil
2/3 cup cilantro, chopped
1 onion, chopped
3 garlic cloves, chopped
Pinch black pepper (grind to your taste)
Pinch cayenne powder (optional and to your taste)
1 teaspoon turmeric
1 teaspoon cardamom
1/4 teaspoon fresh ginger root, grated (or to your taste)
1. Make the Peanut sauce and set aside
2. Bake or stir-fry the tofu or chicken and set aside
3. Make organic brown rice and set aside. You could also use saffron rice.
Here, I’m sauteing ©Joyce Hays, Target Health Inc.
In fry pan, saut? the onion and garlic in the olive oil, when onion is transparent, add the cilantro, Pinch black pepper, Pinch cayenne, turmeric, cardamom and grated ginger root, stir well and cook for a few more minutes. Add the thawed out edamame and stir well again. If you need more liquid, gradually add more chicken stock or vegetable broth, and stir.
In a large baking dish add the chicken or tofu, brown rice, onion/edamame mixture and stir well. Add all of the broccoli and stir again. Now, add the golden raisins and toasted pine nuts. Finally, pour all of the peanut sauce over all and stir it in well. Use a spatula to get every last bit of this delicious sauce.
Bake in 350 oven for 15 to 20 minutes. I raised the heat for the last 5 minutes for a more crispy top. Serve adding some of the cilantro on top for garnish
Mixing the Ingredients ©Joyce Hays, Target Health Inc.
About to sit down with a nice Cabernet. The veggie casserole with peanut sauce was a great success. We both loved it and came back for more. The edamame is a particularly good addition in this recipe. There was enough left over to be able to enjoy this meal again during the week. ©Joyce Hays, Target Health Inc.
Second helping, it was so good ©Joyce Hays, Target Health Inc.
The case of the voluntary out-of-body experience.
After a class on out-of-body experiences, a psychology graduate student at the University of Ottawa came forward to researchers to say that she could have these voluntarily, usually before sleep. “She appeared surprised that not everyone could experience this,” wrote the scientists in a study describing the case, published in February in Frontiers in Human Neuroscience.
Pretty crazy, right? One would think that if you could leave your own body and float above it, you’d be a little more… vocal about it. But since it was a common experience for her–one she “began performing as a child when bored with ‘sleep time’ at preschool… moving above her body” instead of napping–it may have appeared unremarkable. This is way more interesting than what I did, which was indeed napping.
The most exciting thing about this case, to me, is ”the possibility that this phenomenon may have a significant incidence but [is] unreported because people do not think this is exceptional,” as the authors wrote. “Alternatively,” they continued, ”the ability might be present in infancy but is lost without regular practice. This would be reminiscent of the discovery and eventual study ofsynesthesia that some researchers now hypothesized is more prevalent in young people or can be developed.”
“She was able to see herself rotating in the air above her body”
Those are fascinating suggestions–both that these out-of-body experiences may be more common than previously thought, or could be learned during a critical window early in life.
But back to the case study. The 24-year-old “continued to perform this experience as she grew up assuming, as mentioned, that ‘everyone could do it.’” This is how she described her out-of-body experiences: “She was able to see herself rotating in the air above her body, lying flat, and rolling along with the horizontal plane. She reported sometimes watching herself move from above but remained aware of her unmoving “real” body. The participant reported no particular emotions linked to the experience.”
An unusual find, wrote the scientists, University of Ottawa researchers Andra M. Smith and Claude Messier–this is the first person to be studied able to have this type of experience on demand, and without any brain abnormalities. Instead of an “out-of-body” experience, however, the researchers termed it a “extra-corporeal experience” (ECE), in part because it lacks the strong emotions that often go hand-in-hand (such as shock & awe, for example).
To better understand what was going on, the researchers conducted a functional magnetic resonance imaging (fMRI) study of her brain. They found that it surprisingly involved a “strong deactivation of the visual cortex.” Instead, the experience ”activated the left side of several areas associated with kinesthetic imagery,” such as mental representations of bodily movement.
Her experience, the scientists wrote, “really was a novel one.” But just maybe, not as novel as previously thought. If you are capable of floating out of your body, don’t keep it to yourself!