A 14-month-old boy in need of life-saving heart surgery is the beneficiary of a collaboration among University of Louisville engineers, physicians and Kosair Children’s Hospital.
Roland Lian Cung Bawi of Owensboro was born with four congenital heart defects and his doctors were looking for greater insights into his condition prior to a Feb. 10 operation.
Philip Dydynski, chief of radiology at Kosair Children’s Hospital, recently had toured the Rapid Prototyping Center at the University of Louisville’s J.B. Speed School of Engineering and became impressed with the 3D printing capabilities available there.
He asked the center’s operations manager, Tim Gornet, if a 3D model of the child’s heart could be constructed using a template created by images from a CT scan to allow doctors to better plan and prepare for his surgery. No problem, Gornet said.
The result of the Rapid Prototyping Center’s work was a model heart 1.5 times the size of the child’s. It was built in three pieces using a flexible filament and required about 20 machine hours – and only about $600 — to make, Gornet said.
Once the model was built, Erle Austin III, cardiothoracic surgeon with University of Louisville Physicians, was able to develop a surgical plan and complete the heart repair with only one operation.
“I found the model to be a game changer in planning to do surgery on a complex congenital heart defect,” he said.
Roland was released from Kosair Children’s Hospital Feb. 14 and returned Feb. 21 for checkups with his doctors. His prognosis is good.
That’s good news for Gornet, whose work at the Rapid Prototyping Center routinely benefits manufacturers and heavy industry. Helping surgeons save a life was new territory for him.
“Knowing we can make somebody’s life better is exciting,” he said.
Animal study highlights potential new target for treating anxiety disorders
Increasing acidity in the brain’s emotional control center reduces anxiety, according to an animal study published February 26 in The Journal of Neuroscience. The findings suggest a new mechanism for the body’s control of fear and anxiety, and point to a new target for the treatment of anxiety disorders.
Anxiety disorders, which are characterized by an inability to control feelings of fear and uncertainty, are the most prevalent group of psychiatric diseases. At the cellular level, these disorders are associated with heightened activity in the basolateral amygdala (BLA), which is known to play a central role in emotional behavior.
Many cells in the BLA possess acid-sensing ion channels called ASIC1a, which respond to pH changes in the environment outside of the cell. Maria Braga, DDS, PhD, and colleagues at the Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, found that activating ASIC1a decreased the activity of nearby cells and reduced anxiety-like behavior in animals. These findings add to previous evidence implicating the role of ASIC1a in anxiety.
“These findings suggest that activating these channels, specifically in fear-related areas such as the amygdala, may be a key to regulating anxiety,” explained Anantha Shekhar, MD, PhD, who studies panic disorders at Indiana University and was not involved in this study. “Developing specific drugs that can stimulate these channels could provide a new way to treat anxiety and fear disorders such a post-traumatic stress and panic disorders.”
To determine the effect ASIC1a activation has on neighboring cells, Braga’s group bathed BLA cells in an acidic solution in the laboratory and measured the signals sent to nearby cells. Lowering the pH of the solution decreased the activity of cells in the BLA.
Activating ASIC1a also affected animal behavior. When the researchers administered a drug that blocks ASIC1a directly into the BLA of rats, the rats displayed more anxiety-like behavior than animals that did not receive the drug. In contrast, when rats received a drug designed to increase the activity of ASIC1a channels in the BLA, the animals displayed less anxiety-like behavior.
“Our study emphasizes the importance of identifying and elucidating mechanisms involved in the regulation of brain function for the development of more efficacious therapies for treating psychiatric and neurological illnesses,” Braga said. While the findings suggest that drugs targeting ASICs may one day lead to novel therapies for anxiety disorders, Braga noted that “more research is needed to understand the roles that ASIC1a channels play in the brain.”
Link to the article:
The WordPress.com stats helper monkeys prepared a 2013 annual report for my blog.
Here’s an excerpt:
A New York City subway train holds 1,200 people. This blog was viewed about 7,600 times in 2013. If it were a NYC subway train, it would take about 6 trips to carry that many people.
I figured it is about time to write something about the blog’s title, bell’s palsy, since I’ve seen there are a lot of people searching for this topic about facial paralysis.
Bell’s palsy is a common condition that presents with an acute onset of lower motor neuron (LMN – could say like peripheral nerves) facial weakness affecting the muscles on one side of the face.
People of all ages may be affected, including children, although it is most common in patients aged 30-50 years. The exact cause in not known, but there are certain conditions known to be responsible.
If we take a look in pathogenesis, how the condition evolves, we see that there is segmental demyelination in a local conduction block proximally. And what this actually means? Every nerve has its sheath around that is made of substance called myelin. This myelin sheath does not cover the whole nerve, but in segments, leaving tiny gaps, called Nodes of Ranvier (take a look at the picture below). And these gaps are like capacitors that stores electrical charge and allows bursts of electric impulses (know as action potentials) to move along the neuron in a saltatory fashion. Think of it as the action potential would jump from one of these gaps to the next one. This actually prevents loosing the charge. Now imagine that you widen this gap. This slows the nerve conduction, spread it even more and you get a block, conduction block. Now you cannot get the full use of that nerve leaving you weakness.
Since this conduction block happens proximally (closer to its origin), it allows a relatively rapid and complete recovery in about 85% of cases. This is because myelin rapidly regenerates. In others, axonal degeneration occurs, which will produce a severe paralysis. Again, think of it as the whole neuron is cut, and that is why it is so severe. Often this is then followed by incomplete recovery associated with aberrant re-innervation, that is, fibers from the periocular muscles my regenerate and supply the mouth, and vice versa. Such faulty re-innervation may lead to “jaw-winking”, and even hemifacial spasm. Where axonal degeneration has occurred, electromyography of the facial muscles will show fibrillation and features of denervation, although these changes may not appear until some 10 days after the onset. In some instances the pathogenesis is a mixture of axonal degeneration and demyelination.
Ok, let’s leave this aside and let’s carry on and look how this condition actually presents clinically. Normally patients may present with pain in or behind the ear preceding or appearing with the development of facial weakness. There is inability to close the eye or move the lower face and mouth on one side of the face.
The lack of blinking leads to tears spilling out of the eye, which waters to cause complaints of blurred vision. The cheek is flaccid and saliva and fluids may escape from the corner of the mouth. The weakness commonly progresses over 24-72 hours to reach a maximum. In many patients there are complaints of numbness in the affected side of the face, although trigeminal sensation is spared and there should be no weakness of jaw movement, since it is supplied by the motor root of the trigeminal nerve. Trigeminal sensation is sensation on the skin of the face, because sensory innervation of it comes from fifth cranial nerve – trigeminal nerve. Hence the name.
About 40-50% of patients are aware of disturbed taste on the ipsilateral anterior part of the tongue (ipsilateral means it is on the same side as the lesion). This points to a lesion in the distal part of the facial nerve below the geniculate ganglion, but above the origin of the chorda tympani (branch of facial nerve that is responsible for taste). Many patients also notice hyperacusis (over-sensitivity to certain frequency ranges of sound and difficulty tolerating everyday sounds, some of which may seem unpleasantly loud) because the stapedius muscle (very small muscle that moves the smallest bone in the human body and makes us hear) is supplied by a branch of the facial nerve, which leaves the nerve in the facial canal proximal to the chorda tympani.
If a zoster infection is responsible, there will be herpetic vesicles on the pinna (the visible part of the ear that resides outside of the head, also called auricle or auricula) or in the external auditory canal on the affected side. Ramsay Hunt described a herpetic infection of the geniculate ganglion with the development of an acute facial palsy – Hunt’s syndrome. In some of these patients the 8th cranial nerve (auditory nerve, responsible for hearing) may also be infected, producing acute vertigo, deafness and tinnitus (ringing of the ears). A few patients may show a bilateral (on both sides) facial palsy of lower motor neuron (LMN) pattern; this may appear as part of a Guillain-Barre syndrome, from Lyme disease, from sarcoidosis or even carcinomatous meningitis.
About 85% of patients show signs of improvement within some 3 weeks of the onset. About 70% of patients recover normal function in the face but some 16% are left with asymmetry, signs of aberrant re-innervation and some weakness. An incomplete palsy at the onset or signs of recovery starting within 3-4 weeks usually are good prognostic features for recovery. This is mirrored in the electrophysiological findings. In the more severely affected, where axonal degeneration has taken place, recovery is slower and often incomplete. Recurrent facial palsies require more intensive investigation to exclude any compressive lesion on the middle ear or skull base, and to look for any systemic upset such as sarcoidosis, hypertension, diabetes.
Normally when there is suspicion of Bell’s palsy several investigations are made. Such as blood tests. Full blood count, erythrocyte sedimentation rate (ESR), fasting glucose levels, tests for Borrelia. Of course there is imaging; in selected patients MRI and/or CT scanning, chest X-ray. Electromyography (EMG) studies as these may assess the severity of damage and help in prognosis; they may also indicate a more widespread neuropathy. ENT examination…
Once all the tests are conclusive and the Bell’s palsy diagnosis is made, patients can undergo treatment. There appears to be little difference in outcome between patients treated with steroids and those who are not. Many doctors believe that a short intensive course of steroids given within 5-7 days of the onset of palsy may reduce the swelling of the facial nerve and so prevent axonal degeneration. Prednisolon 40 mg daily for 5 days and then tapered off over the next week is a typical regimen. It has been suggested that such a course should be given to all patients seen acutely with a complete palsy at the time of consultation or with impaired taste.
Because of the possible infective causation by herpes virus, acyclovir has also been used in treatment of an cute facial palsy. This certainly should be given if a zoster infection (Hunt’s syndrome) is suspected. The combination of acyclovir with steroids in those patients with complete facial palsies has also been used. Surgical decompression of the facial nerve has had its supporters over the years, although there has been no rigorous controlled trial to indicate benefit and as over 70% of patients will make a full recovery with no treatment it is hard to justify the surgical risks.
Care of the eye is always important if there is incomplete lid closure but as the cornea is not anesthetic, the patient will be aware of any intruding foreign body. Occasionally it may be necessary to suture the lids partially together, a tarsorrhaphy, to protect the eye.
In those patients left with marked residual weakness or asymmetry, a number of surgical measures may be used to try to improve their appearance. These include plastic surgery with implants of soft tissues to restore the contours. Such measures will improve the symmetry of the face at rest but are by no means a ‘cure’.
Scientists at the Gladstone Institutes have deciphered how a protein called Arc regulates the activity of neurons – providing much-needed clues into the brain’s ability to form long-lasting memories.
These findings, reported in Nature Neuroscience, also offer newfound understanding as to what goes on at the molecular level when this process becomes disrupted.
Led by Gladstone senior investigator Steve Finkbeiner, MD, PhD, this research delved deep into the inner workings of synapses. Synapses are the highly specialized junctions that process and transmit information between neurons. Most of the synapses our brain will ever have are formed during early brain development, but throughout our lifetimes these synapses can be made, broken and strengthened. Synapses that are more active become stronger, a process that is essential for forming new memories.
However, this process is also dangerous, as it can overstimulate the neurons and lead to epileptic seizures. It must therefore be kept in check.
Neuroscientists recently discovered one important mechanism that the brain uses to maintain this important balance: a process called “homeostatic scaling.” Homeostatic scaling allows individual neurons to strengthen the new synaptic connections they’ve made to form memories, while at the same time protecting the neurons from becoming overly excited. Exactly how the neurons pull this off has eluded researchers, but they suspected that the Arc protein played a key role.
“Scientists knew that Arc was involved in long-term memory, because mice lacking the Arc protein could learn new tasks, but failed to remember them the next day,” said Finkbeiner, who is also a professor of neurology and physiology at UC San Francisco, with which Gladstone is affiliated. “Because initial observations showed Arc accumulating at the synapses during learning, researchers thought that Arc’s presence at these synapses was driving the formation of long-lasting memories.”
But Finkbeiner and his team thought there was something else in play.
The Role of Arc in Homeostatic Scaling
In laboratory experiments, first in animal models and then in greater detail in the petri dish, the researchers tracked Arc’s movements. And what they found was surprising.
“When individual neurons are stimulated during learning, Arc begins to accumulate at the synapses – but what we discovered was that soon after, the majority of Arc gets shuttled into the nucleus,” said Erica Korb, PhD, the paper’s lead author who completed her graduate work at Gladstone and UCSF.
“A closer look revealed three regions within the Arc protein itself that direct its movements: one exports Arc from the nucleus, a second transports it into the nucleus, and a third keeps it there,” she said. “The presence of this complex and tightly regulated system is strong evidence that this process is biologically important.”
In fact, the team’s experiments revealed that Arc acted as a master regulator of the entire homeostatic scaling process. During memory formation, certain genes must be switched on and off at very specific times in order to generate proteins that help neurons lay down new memories. From inside the nucleus, the authors found that it was Arc that directed this process required for homeostatic scaling to occur. This strengthened the synaptic connections without overstimulating them – thus translating learning into long-term memories.
Implications for a Variety of Neurological Diseases
“This discovery is important not only because it solves a long-standing mystery on the role of Arc in long-term memory formation, but also gives new insight into the homeostatic scaling process itself – disruptions in which have already been implicated in a whole host of neurological diseases,” said Finkbeiner. “For example, scientists recently discovered that Arc is depleted in the hippocampus, the brain’s memory center, in Alzheimer’s disease patients. It’s possible that disruptions to the homeostatic scaling process may contribute to the learning and memory deficits seen in Alzheimer’s.”
Dysfunctions in Arc production and transport may also be a vital player in autism. For example, the genetic disorder Fragile X syndrome – a common cause of both mental retardation and autism, directly affects the production of Arc in neurons.
“In the future,” added Dr. Korb, “we hope further research into Arc’s role in human health and disease can provide even deeper insight into these and other disorders, and also lay the groundwork for new therapeutic strategies to fight them.”
Journal reference: Abstract for “Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity” by Erica Korb, Carol L Wilkinson, Ryan N Delgado, Kathryn L Lovero and Steven Finkbeiner in Nature Neuroscience. Published online June 9 2013 doi:10.1038/nn.3429
How does short-term memory work in relation to long-term memory? Are short-term daily memories somehow transferred to long-term storage while we sleep?
Alison Preston, an assistant professor at the University of Texas at Austin’s Center for Learning and Memory, recalls and offers an answer for this question.
A short-term memory’s conversion to long-term memory requires the passage of time, which allows it to become resistant to interference from competing stimuli or disrupting factors such as injury or disease. This time-dependent process of stabilization, whereby our experiences achieve a permanent record in our memory, is referred to as “consolidation.”
Memory consolidation can occur at many organizational levels in the brain. Cellular and molecular changes typically take place within the first minutes or hours of learning and result in structural and functional changes to neurons (nerve cells) or sets of neurons. Systems-level consolidation, involving the reorganization of brain networks that handle the processing of individual memories, may then happen, but on a much slower time frame that can take several days or years.
Memory does not refer to a single aspect of our experience but rather encompasses a myriad of learned information, such as knowing the identity of the 16th president of the United States, what we had for dinner last Tuesday or how to drive a car. The processes and brain regions involved in consolidation may vary depending on the particular characteristics of the memory to be formed.
Let’s consider the consolidation process that affects the category of declarative memory—that of general facts and specific events. This type of memory relies on the function of a brain region called the hippocampus and other surrounding medial temporal lobe structures. At the cellular level, memory is expressed as changes to the structure and function of neurons. For example, new synapses—the connections between cells through which they exchange information—can form to allow for communication between new networks of cells. Alternately, existing synapses can be strengthened to allow for increased sensitivity in the communication between two neurons.
Consolidating such synaptic changes requires the synthesis of new RNA and proteins in the hippocampus, which transform temporary alterations in synaptic transmission into persistent modifications of synaptic architecture. For example, blocking protein synthesis in the brains of mice does not affect the short-term memory or recall of newly learned spatial environments in hippocampal neurons. Inhibiting protein synthesis, however, does abolish the formation of new long-term representations of space in hippocampal neurons, thus impairing the consolidation of spatial memories.
Over time, the brain systems that support individual, declarative memories also change as a result of systems-level consolidation processes. Initially, the hippocampus works in concert with sensory processing regions distributed in the neocortex (the outermost layer of the brain) to form the new memories. Within the neocortex, representations of the elements that constitute an event in our life are distributed across multiple brain regions according to their content. For example, visual information is processed by primary visual cortex in the occipital lobe at the rear of the brain, while auditory information is processed by primary auditory cortex located in the temporal lobes, which lie on the side of the brain.
When a memory is initially formed, the hippocampus rapidly associates this distributed information into a single memory, thus acting as an index to representations in the sensory processing regions. As time passes, cellular and molecular changes allow for the strengthening of direct connections between neocortical regions, enabling the memory of an event to be accessed independently of the hippocampus. Damage to the hippocampus by injury or neurodegenerative disorder (Alzheimer’s disease, for instance) produces anterograde amnesia—the inability to form new declarative memories—because the hippocampus is no longer able to connect mnemonic information distributed in the neocortex before the data has been consolidated. Interestingly, such a disruption does not impair memory for facts and events that have already been consolidated. Thus, an amnesiac with hippocampal damage would not be able to learn the names of current presidential candidates but would be able to recall the identity 16th US president (Abraham Lincoln, of course!).
The role of sleep in memory consolidation is an ancient question dating back to the Roman rhetorician Quintilian in the first century A.D. Much research in the past decade has been dedicated to better understanding the interaction between sleep and memory. Yet little is understood.
At the molecular level, gene expression responsible for protein synthesis is increased during sleep in rats exposed to enriched environments, suggesting memory consolidation processes are enhanced, or may essentially rely, on sleep. Further, patterns of activity observed in rats during spatial learning are replayed in hippocampal neurons during subsequent sleep, further suggesting that learning may continue in sleep.
In humans, recent studies have demonstrated the benefits of sleep on declarative memory performance, thus giving a neurological basis to the old adage, “sleep on it.” A night of sleep reportedly enhances memory for associations between word pairs. Similar overnight improvements on virtual navigation tasks have been observed, which correlate with hippocampal activation during sleep. Sleep deprivation, on the other hand, is known to produce deficits in hippocampal activation during declarative memory formation, resulting in poor subsequent retention. Thus, the absence of prior sleep compromises our capacity for committing new experiences to memory. These initial findings suggest an important, if not essential, role for sleep in the consolidation of newly formed memories.
Why is it that we seem to think better when we walk or exercise?
Justin Rhodes, an associate professor of psychology at the University of Illinois at Urbana-Champaign, responds:
After being cooped up inside all day, your afternoon stroll may leave you feeling clearheaded. This sensation is not just in your mind. A growing body of evidence suggests we think and learn better when we walk or do another form of exercise. The reason for this phenomenon, however, is not completely understood.
Part of the reason exercise enhances cognition has to do with blood flow. Research shows that when we exercise, blood pressure and blood flow increase everywhere in the body, including the brain. More blood means more energy and oxygen, which makes our brain perform better.
Another explanation for why working up a sweat enhances our mental capacity is that the hippocampus, a part of the brain critical for learning and memory, is highly active during exercise. When the neurons in this structure rev up, research shows that our cognitive function improves. For instance, studies in mice have revealed that running enhances spatial learning. Other recent work indicates that aerobic exercise can actually reverse hippocampal shrinkage, which occurs naturally with age, and consequently boost memory in older adults. Yet another study found that students who exercise perform better on tests than their less athletic peers.
The big question of why we evolved to get a mental boost from a trip to the gym, however, remains unanswered. When our ancestors worked up a sweat, they were probably fleeing a predator or chasing their next meal. During such emergencies, extra blood flow to the brain could have helped them react quickly and cleverly to an impending threat or kill prey that was critical to their survival.
So if you are having a mental block, go for a jog or hike. The exercise might help pull you out of your funk.