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All bay area doctors are invited for a trip to the enchanting beach in Palawan, Philippines. I will be there with you as your free tour guide to thank you for serving the bay area population.
Connie Dello Buono
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In a new study from the National Cancer Institute (NCI), part of the National Institutes of Health, researchers found a higher than expected prevalence of cancer at baseline screening in individuals with Li-Fraumeni syndrome (LFS), a rare inherited disorder that leads to a higher risk of developing certain cancers. The research demonstrates the feasibility of a new, comprehensive cancer screening protocol for this high-risk population.
The study was led by Sharon A. Savage, M.D., of NCI’s Division of Cancer Epidemiology and Genetics (DCEG), and was published with a companion meta-analysis on August 3, 2017, in JAMA Oncology.
LFS is most often caused by germline, or hereditary, mutations in a tumor suppressor gene known as TP53. The disorder results in many kinds of cancers — including bone and soft-tissue cancers (sarcomas), breast cancer, brain tumors, and cancer of the adrenal gland — that frequently occur at young ages. Individuals with LFS have an approximately 50 percent chance of developing cancer by age 40, and up to a 90 percent chance by age 60. Many patients with LFS develop more than one primary cancer over their lifetimes.
Dr. Frederick Pei Li and Dr. Joseph F. Fraumeni, Jr., first described LFS at NCI in 1969. “Researchers at the NCI have evaluated families with LFS extensively to better understand how germline mutations in TP53 influence risk, and how best to prevent cancers or treat them at the earliest possible stage,” said Dr. Fraumeni, Scientist Emeritus and Founding Director of DCEG. “However, because of the broad spectrum of cancers in LFS families, it has been challenging to put in place universally accepted cancer strategies.”
To address this gap in clinical care, researchers modified a cancer surveillance protocol from a previously published study and screened 116 LFS patients with germline TP53 mutations using a variety of tools including whole body, brain, and breast MRI, as well as mammography, colonoscopy, bloodwork, and abdominal ultrasound. The study only used modalities that do not utilize ionizing radiation for imaging, since patients with LFS appear to be radiosensitive.
They found that 40 trial participants (34 percent) had abnormalities on baseline screening examination with whole body, brain, or breast MRI that required further evaluation. Eight of these patients (7 percent) were diagnosed with a new primary cancer. All but one of the cancers found through screening were fully removed with surgery. In contrast, the non-MRI techniques used in the trial did not lead to a diagnosis of cancer at baseline screening.
“For high-risk populations, like families with LFS, personalized prevention approaches like this are critical to the early detection of the many kinds of cancers seen in this group,” Dr. Savage explained. “This protocol, along with other published studies, offers patients with LFS a new road map for early cancer detection going forward.”
The meta-analysis, published in the same issue of the journal, involved 578 participants with LFS in 13 cohorts at multiple research centers around the world. Similarly utilizing rapid whole body MRI, the investigators had an overall detection rate of 7 percent for new primary cancers, confirming the results of the study conducted at NCI.
“The findings from this international team effort further demonstrate the utility of whole body MRI screening for individuals with LFS,” Dr. Savage said. “With long-term follow-up, additional refinement, and through international collaborations, we hope to establish a screening regimen that could extend and improve the lives of this unique population.”
About the National Cancer Institute (NCI): NCI leads the National Cancer Program and the NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s Contact Center (formerly known as the Cancer Information Service) at 1-800-4-CANCER (1-800-422-6237).
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Source: Western Sydney University.
The way you speak to your baby can tell a very specific story.
Through the subconscious mechanism of babytalk, a parent’s voice can offer encouragement, discipline or comfort, and according to new research findings, it can even facilitate early language development in infants.
A research paper published by the MARCS Institute (opens in new window)Opens in a new window at Western Sydney University shows that mothers unconsciously shorten their vocal tract when speaking to their babies, creating a higher pitch that is thought to have evolved from pre-speech, primate ancestors to provide comfort and appear less threatening to offspring.
Research leader Dr Marina Kalashnikova suggests that it was only once human language emerged, that babytalk, formally referred to as Infant Directed Speech (IDS), acquired a second purpose – to facilitate language learning in infants.
“Infant Directed Speech is actually a powerful tool that parents instinctively use to aid language development in their infant’s first months and years of life,” says Dr Kalashnikova.
“Shortening of the vocal tract is not unique to humans – it is an adjustment that several species make to appear smaller and less threatening.
“But specifically for humans, by shortening their vocal tract, mothers produce clearer speech sounds (especially vowel sounds like ee, oo, and ah).
“Mothers’ speech also sounds more similar to an infants’ own vocalization and this has been proposed to drive their preference for IDS; further, infants prefer to listen to speech that is similar to the sounds that they produce.”
In comparison to adult-directed speech, Dr Kalashnikova said IDS had simpler grammar; more varied pitch, longer pauses, greater emotion and inflection, as well as distinguishable speech sounds and exaggerated facial expressions.
This research, conducted by Dr Marina Kalashnikova, Dr Chris Carignan and Professor Denis Burnham from the MARCS BabyLab, is the first study of its kind to not only measure the sound qualities of the speech that mothers produce when speaking to their infants, but also measured the movements that they make when producing speech (the movements of their lips and tongue).
Source: LMU.
An LMU study reveals that sound-evoked activity of neurons in the auditory system of the mouse increases the thickness of their myelin sheaths – and enhances the speed of signal transmission – both during development and in the adult brain.
As a rule, transmission speeds are positively correlated with the diameter and the thickness of the sheath. In mammals, the functional demands made on the auditory system require extremely precise and rapid neural processing of acoustic information, and it contains a strikingly high proportion of myelinated axons.
Using the mouse as an experimental model, LMU neurobiologist PD Dr. Conny Kopp-Scheinpflug and her research group have now demonstrated that the activity of nerve cells in the auditory system has a direct effect on myelinization – higher levels of activity correlate with the formation of thicker myelin sheaths. Their findings appear in the Journal of Neuroscience.
Specialized sensory neurons in the inner ear, called hair cells, are responsible for the detection of sounds, and this information is transmitted to the auditory cortex via several intermediate structures.
“The mouse is a particularly suitable model in which to study the development of the auditory system, because newborn mice are deaf and only begin to perceive acoustic signals at 12 days after birth. At this point, the level of activity of auditory neurons begins to increase,” Kopp-Scheinpflug explains.
She and her colleagues focused on the neuronal activity in the trapezoid body, a structure located in the brainstem that forms part of the pathway that eventually leads to the auditory cortex.
They were able to demonstrate that both the speed and frequency of signal transmission in the trapezoid body doubles as soon as the young mice begin to perceive sounds. Moreover, both the diameter of the axons and the thickness of their myelin sheaths progressively increased until they reached the values observed in the auditory system of the adult animal.
“To do so, we simply inserted earplugs in the ears of 10-day-old mice and left them in position for 10 more days. This intervention leads to a reversible hearing loss, i.e. rise in the hearing threshold of about 50 decibels“, says Kopp-Scheinpflug.
In these animals, the normal increase in axon diameter is mostly absent, and the myelin sheaths are also thinner. When the same experiment was carried out on adult mice, a decrease in the thickness of the myelin sheaths was also seen, although the diameter of the axons was not affected. Based on these results, the researchers conclude that neuronal activity itself plays an important role in the synthesis and maintenance of the myelin sheath, and that myelinated nerve cells therefore require a minimal level of sound-evoked stimulation.
“In order to understand the effects of reduced stimulation, we also developed a computer model based on our results. The model predicts that not only axonal conductivity, but also the capacity to transmit high-frequency action potentials should decline,” says Kopp-Scheinpflug.
Source: Luise Dirscherl – LMU
Image Source: NeuroscienceNews.com image is credited to J. Sinclair & C. Kopp-Scheinpflug, LMU.
Original Research: Abstract for “Sound-evoked activity influences myelination of brainstem axons in the trapezoid body” by James L. Sinclair, Matthew J. Fischl, Olga Alexandrova, Martin Heß, Benedikt Grothe, Christian Leibold and Conny Kopp-Scheinpflug in Journal of Neuroscience. Published online July 31 2017 doi:10.1523/JNEUROSCI.3728-16.2017
Abstract
Sound-evoked activity influences myelination of brainstem axons in the trapezoid body
Plasticity of myelination represents a mechanism to tune the flow of information by balancing functional requirements with metabolic and spatial constraints. The auditory system is heavily myelinated and operates at the upper limits of action potential generation frequency and speed observed in the mammalian CNS.
This study aimed to characterize the development of myelin within the trapezoid body, a central auditory fiber tract, and determine the influence sensory experience has on this process in mice of both sexes.
We find that in vitro conduction speed doubles following hearing onset and the ability to support high frequency firing increases concurrently. Also in this time, the diameter of trapezoid body axons and the thickness of myelin double, reaching mature-like thickness between 25-35 days of age. Earplugs were used to induce approximately 50dB elevation in auditory thresholds.
If introduced at hearing onset, trapezoid body fibers developed thinner axons and myelin than age-matched controls.
If plugged during adulthood, the thickest trapezoid body fibers also showed a decrease in myelin.
These data demonstrate the need for sensory activity in both development and maintenance of myelin and have important implications in the study of myelin plasticity and how this could relate to sensorineural hearing loss following peripheral impairment.
SIGNIFICANCE STATEMENT
The auditory system has many mechanisms to maximize the dynamic range of its afferent fibers, which operate at the physiological limit of action potential generation, precision and speed.
The current study suggests that changes in CNS myelination occur as a downstream mechanism following peripheral deficit.
Given the required submillisecond temporal precision for binaural auditory processing, reduced myelination might augment sensorineural hearing impairment.
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