Kids outfitted with new hands made on 3-D printers
Hopkins doctor joins big volunteer network using high-tech printers to fill need for little prosthetic hands
Articles and news from the latest research reports.
At the 22nd United European Gastroenterology Week (UEG Week 2014) in Vienna, Austria, Professor Sigrid Elsenbruch from the University of Duisburg-Essen in Germany, will be presenting a new study which suggests that depression, but not anxiety, contributes to the abnormal pain processing observed in IBS in a model that addresses central pain inhibition during placebo analgesia. “Our study has shown that patients with IBS are less able to suppress pain signals in the brain coming from the bowel and that depression plays a role herein,” she says. “This study confirms the complex relationship between the gut and the brain and shows that affective disorders may contribute to the development or maintenance of disturbed pain processing in IBS.”
IBS, anxiety and depression
IBS is the most common functional gastrointestinal disorder with prevalence rates of up to 23% reported. The condition is characterised by recurrent abdominal pain or discomfort, in combination with bloating and altered bowel habits (e.g. diarrhoea and/or constipation). Depression and anxiety frequently co-exist with IBS, with a recent study reporting that 38% of IBS patients had clinically-confirmed depression (compared with 6% of healthy controls) and 32% had anxiety (compared with 13% of healthy controls).
“The fact that so many people with IBS have anxiety and depression has led many to speculate that IBS is primarily a psychological, not a physical, disorder,” says Prof. Elsenbruch. “However, the condition is complex and most likely results from an interplay between psychological and biological factors. In fact, we don’t really know whether anxiety and depression result from having IBS or whether they contribute to the development or maintenance of symptoms. In many patients, both possibilities may be true at the same time.”
The “brain–gut” axis in IBS
There has been significant scientific interest in the role of central nervous system mechanisms along the “brain–gut” axis in IBS. Neuroimaging studies have demonstrated that neural processing of visceral stimuli (i.e. stimuli generated from internal organs such as the intestine) is altered in IBS, with many IBS patients showing lowered pain thresholds. In Prof. Elsenbruch’s latest study, painful rectal distensions were performed using a pressure-controlled barostat system in 17 patients with IBS and 17 sex- and age-matched healthy controls. Neural activation in pain-related brain areas was assessed using functional MRI (fMRI) while subjects received sequential intravenous administrations of saline and what they thought was an anti-spasmolytic drug (but was actually a saline placebo), in order to observe activation patterns during a typical placebo pain response.
The fMRI results in the healthy volunteers demonstrated reduced neural activation in pain-related brain areas during both the saline and sham treatment (placebo), indicating significant central pain inhibition. However, there was no such inhibition in the group of IBS patients, suggesting a deficiency in central pain inhibitory mechanisms in IBS. Interestingly, higher depression (but not anxiety) scores on the Hospital Anxiety and Depression Scale (HADS) were associated with reduced central pain inhibition in this study.
“Our findings suggest that patients with IBS do not process visceral pain signals in the same way as healthy people and are unable to suppress pain signals in the brain and, as a result, experience more pain from the same stimuli,” says Prof. Elsenbruch. “The fact that the presence of depression was associated with altered brain responses suggests that depression may contribute to these abnormal pain processes in IBS patients.”
How curiosity changes the brain to enhance learning
The more curious we are about a topic, the easier it is to learn information about that topic. New research publishing online October 2 in the Cell Press journal Neuron provides insights into what happens in our brains when curiosity is piqued. The findings could help scientists find ways to enhance overall learning and memory in both healthy individuals and those with neurological conditions.
"Our findings potentially have far-reaching implications for the public because they reveal insights into how a form of intrinsic motivation—curiosity—affects memory. These findings suggest ways to enhance learning in the classroom and other settings," says lead author Dr. Matthias Gruber, of University of California at Davis.
For the study, participants rated their curiosity to learn the answers to a series of trivia questions. When they were later presented with a selected trivia question, there was a 14 second delay before the answer was provided, during which time the participants were shown a picture of a neutral, unrelated face. Afterwards, participants performed a surprise recognition memory test for the faces that were presented, followed by a memory test for the answers to the trivia questions. During certain parts of the study, participants had their brains scanned via functional magnetic resonance imaging.
The study revealed three major findings. First, as expected, when people were highly curious to find out the answer to a question, they were better at learning that information. More surprising, however, was that once their curiosity was aroused, they showed better learning of entirely unrelated information (face recognition) that they encountered but were not necessarily curious about. People were also better able to retain the information learned during a curious state across a 24-hour delay. “Curiosity may put the brain in a state that allows it to learn and retain any kind of information, like a vortex that sucks in what you are motivated to learn, and also everything around it,” explains Dr. Gruber.
Second, the investigators found that when curiosity is stimulated, there is increased activity in the brain circuit related to reward. “We showed that intrinsic motivation actually recruits the very same brain areas that are heavily involved in tangible, extrinsic motivation,” says Dr. Gruber. This reward circuit relies on dopamine, a chemical messenger that relays messages between neurons.
Third, the team discovered that when curiosity motivated learning, there was increased activity in the hippocampus, a brain region that is important for forming new memories, as well as increased interactions between the hippocampus and the reward circuit. “So curiosity recruits the reward system, and interactions between the reward system and the hippocampus seem to put the brain in a state in which you are more likely to learn and retain information, even if that information is not of particular interest or importance,” explains principal investigator Dr. Charan Ranganath, also of UC Davis.
The findings could have implications for medicine and beyond. For example, the brain circuits that rely on dopamine tend to decline in function as people get older, or sooner in people with neurological conditions. Understanding the relationship between motivation and memory could therefore stimulate new efforts to improve memory in the healthy elderly and to develop new approaches for treating patients with disorders that affect memory. And in the classroom or workplace, learning what might be considered boring material could be enhanced if teachers or managers are able to harness the power of students’ and workers’ curiosity about something they are naturally motivated to learn.
Altered Activity in the Central Medial Thalamus Precedes Changes in the Neocortex during Transitions into Both Sleep and Propofol Anesthesia
How general anesthetics cause loss of consciousness is unknown. Some evidence points toward effects on the neocortex causing “top-down” inhibition, whereas other findings suggest that these drugs act via subcortical mechanisms, possibly selectively stimulating networks promoting natural sleep. To determine whether some neuronal circuits are affected before others, we used Morlet wavelet analysis to obtain high temporal resolution in the time-varying power spectra of local field potentials recorded simultaneously in discrete brain regions at natural sleep onset and during anesthetic-induced loss of righting reflex in rats. Although we observed changes in the local field potentials that were anesthetic-specific, there were some common changes in high-frequency (20–40 Hz) oscillations (reductions in frequency and increases in power) that could be detected at, or before, sleep onset and anesthetic-induced loss of righting reflex. For propofol and natural sleep, these changes occur first in the thalamus before changes could be detected in the neocortex. With dexmedetomidine, the changes occurred simultaneously in the thalamus and neocortex. In addition, the phase relationships between the low-frequency (1–4 Hz) oscillations in thalamic nuclei and neocortical areas are essentially the same for natural sleep and following dexmedetomidine administration, but a sudden change in phase, attributable to an effect in the central medial thalamus, occurs at the point of dexmedetomidine loss of righting reflex. Our data are consistent with the central medial thalamus acting as a key hub through which general anesthesia and natural sleep are initiated.
Researchers Find Promise in New Treatments for GBM
Glioblastoma multiforme (GBM) is one of the most lethal primary brain tumors, with median survival for these patients only slightly over one year. Researchers at Boston University School of Medicine (BUSM), in collaboration with researchers from the City of Hope, are looking toward novel therapeutic strategies for the treatment of GBM in the form of targeted therapies against a unique receptor, the interleukin-13 receptor α chain variant 2 (IL13Rα2).
In a review paper published in the October issue of Neuro-Oncology, the researchers discuss various targeted therapies against IL13Rα2 and early successes of clinical trials with these therapies in the treatment of GBM. The paper also highlights the need for future trials to improve efficacy and toxicity profiles of targeted therapies in this field.
Targeted therapies, which are drugs that interfere with specific molecules involved in cancer growth, have been successfully used in the treatment of many cancers, including breast and blood cancers. Successful targets for therapies are specific to tumor cells and not found on normal cells. Selectively expressed on GBM and absent on surrounding brain tissue, the interleukin-13 receptor α chain variant 2 (IL13Rα2) was identified as a potential target for therapy for GBM two decades ago. IL13Rα2 also plays an important role in the growth of tumors. In normal physiologic conditions, IL-13 binds to the receptor IL13Rα1 and helps regulate immune responses. In cancer cells, IL-13 binds to the receptor IL13Rα2 and, through a series of steps, prevents cancer cells from undergoing normal cell death. Increased expression of IL13Rα2 promotes the progression of GBM.
Since its discovery, IL13Rα2 has provided a target for therapies in GBM. These therapies have ranged from fusion proteins of IL-13 and bacterial toxins, oncolytic viruses, and immunotherapies. A phase I clinical trial and a phase III clinical trial have been completed for a T-cell based immunotherapy and IL-13/ bacterial toxin fusion protein respectively, both with promising outcomes.
“The field of targeted therapies in gliomas holds a lot of promise, and IL13Rα2 is in an optimal position to materialize these promises,” explained corresponding author Sadhak Sengupta, PhD, assistant professor of neurosurgery at BUSM and principal investigator of the Brain Tumor Lab at Roger Williams. “While early trials are encouraging, we need further research to achieve better targeting of the receptor and improved safety profiles of the treatments.”
Scientists aim to give botox a safer facelift
New insights into botulinum neurotoxins and their interactions with cells are moving scientists ever closer to safer forms of Botox and a better understanding of the dangerous disease known as botulism. By comparing all known structures of botulinum neurotoxins, researchers writing in the Cell Press journal Trends in Biochemical Sciences on October 1st suggest new ways to improve the safety and efficacy of Botox injections.
"If we know from high-resolution structures how botulinum neurotoxins interact with their receptors, we can design inhibitors or specific antibodies directed at the binding interface to prevent the interaction," said Richard Kammerer of the Paul Scherrer Insititute in Switzerland. "Furthermore, it may be possible to engineer safer toxins for medical and cosmetic applications."
In addition to its popular cosmetic use, the neurotoxin is used for the treatment of muscle conditions related to cerebral palsy, multiple sclerosis, stroke, Parkinson’s disease, and more.
The bacterium known as Clostridium botulinum, classically found as a contaminant in home-canned food, produces the neurotoxins, which pass the intestine and enter the bloodstream when ingested, Kammerer explained. When the neurotoxins reach neurons, they bind to receptors at the cell surface. Through a series of events, a portion of the toxin is released inside the cell. Once inside, that light-chain portion acts as a protease to specifically cleave a protein important for the release of acetylcholine, a neurotransmitter important for signaling from nerve to muscle. The result is paralysis, which can be fatal if the muscles required for breathing are affected.
Kammerer and his colleagues offer a comprehensive review of high-resolution structures of botulinum neurotoxins and their complexes with cell-surface receptors, many of which have become available only recently. While many questions remain, the new picture of BoNT/A and its interactions offers considerable hope for less-risky clinical use of Botox in the future.
"The wide range of BoNT/A dosage used in medical or cosmetic applications bears the substantial risk of accidental BoNT/A overdosage," the researchers write. "The BoNT/A-SV2C complex crystal structure provides a strong platform for the rational design of BoNT/A variants with attenuated SV2C binding properties. Such variants are promising candidate proteins for safer applications of the toxin."
(Source: eurekalert.org)
Medical discovery first step on path to new painkillers
A major medical discovery by scientists at The University of Nottingham could lead to the development of an entirely new type of painkiller.
A drug resulting from the research, published in the journal Neurobiology of Disease, would offer new hope to sufferers of chronic pain conditions such as traumatic nerve injury, for which few effective painkillers are currently available.
The work, led by Dr Lucy Donaldson in the University’s School of Life Sciences, in collaboration with David Bates, Professor of Oncology in the University’sCancer Biology Unit, focuses on a signal protein called vascular endothelial growth factor (VEGF).
VEGF controls the re-growth of blood vessels in tissues which have been damaged by injury. It is a widely targeted compound for cancer, eye disease and other illnesses in which abnormal blood vessel growth occurs.
Drugs are used to inhibit the VEGF in cancer, which can otherwise lead to the formation of new blood vessels that provide oxygen and nutrients to tumours.
Professor Bates and colleagues had previously discovered in 2002 that VEGF comes in two forms and acts like a switch — one which turns on the growth of blood vessels and another that blocks growth.
Pain prevention
However, this latest research has shown for the first time that these two forms of VEGF not only act on blood vessels but also differently affect the sensory nerves that control pain.
The academics discovered that the VEGF that promotes blood vessel growth causes pain, while the other, which inhibits blood vessel growth, prevents pain.
The study has centred on understanding how these two types of VEGF work and why the body makes one form rather than the other.
The academics have been able to switch from the pain stimulating form to the pain inhibiting VEGF in animal models in the laboratory and are now investigating compounds to replicate this in humans. It is thought these compounds could form the basis for new drugs to be tested in humans in clinical trials.
Decreased ability to identify odors can predict death
For older adults, being unable to identify scents is a strong predictor of death within five years, according to a study published October 1, 2014, in the journal PLOS ONE. Thirty-nine percent of study subjects who failed a simple smelling test died during that period, compared to 19 percent of those with moderate smell loss and just 10 percent of those with a healthy sense of smell.
The hazards of smell loss were “strikingly robust,” the researchers note, above and beyond most chronic diseases. Olfactory dysfunction was better at predicting mortality than a diagnosis of heart failure, cancer or lung disease. Only severe liver damage was a more powerful predictor of death. For those already at high risk, lacking a sense of smell more than doubled the probability of death.
"We think loss of the sense of smell is like the canary in the coal mine," said the study’s lead author Jayant M. Pinto, MD, an associate professor of surgery at the University of Chicago who specializes in the genetics and treatment of olfactory and sinus disease. "It doesn’t directly cause death, but it’s a harbinger, an early warning that something has gone badly wrong, that damage has been done. Our findings could provide a useful clinical test, a quick and inexpensive way to identify patients most at risk."
The study was part of the National Social Life, Health and Aging Project (NSHAP), the first in-home study of social relationships and health in a large, nationally representative sample of men and women ages 57 to 85.
In the first wave of NSHAP, conducted in 2005-06, professional survey teams from the independent research organization NORC at the University of Chicago used a well-validated test — adapted by Martha K. McClintock, PhD, the study’s senior author — for this field survey of 3,005 participants. It measured their ability to identify five distinct common odors.
The modified smell tests used “Sniffin’Sticks,” odor-dispensing devices that resemble a felt-tip pen but are loaded with aromas rather than ink. Subjects were asked to identify each smell, one at a time, from a set of four choices. The five odors, in order of increasing difficulty, were peppermint, fish, orange, rose and leather.
Measuring smell with this test, they learned that:
- Almost 78 percent of those tested were classified as “normosmic,” having normal smelling; 45.5 percent correctly identified five out of five odors and 29 percent identified four out of five.
- Almost 20 percent were considered “hyposmic.” They got two or three out of five correct.
- The remaining 3.5 percent were labelled “anosmic.” They could identify just one of the five scents (2.4%), or none (1.1%).
The interviewers also assessed participants’ age, physical and mental health, social and financial resources, education, and alcohol or substance abuse through structured interviews, testing and questionnaires. As expected, performance on the scent test declined steadily with age; 64 percent of 57-year-olds correctly identified all five smells. That fell to 25 percent of 85-year-olds.
In the second wave, during 2010-11, the survey team carefully confirmed which participants were still alive. During that five-year gap, 430 (12.5%) of the original 3005 study subjects had died; 2,565 were still alive.
When the researchers adjusted for demographic variables such as age, gender, socioeconomic status (as measured by education or assets), overall health, and race, those with greater smell loss when first tested were substantially more likely to have died five years later. Even mild smell loss was associated with greater risk.
"This evolutionarily ancient special sense may signal a key mechanism that affects human longevity," noted McClintock, the David Lee Shillinglaw Distinguished Service Professor of Psychology, who has studied olfactory and pheromonal communication throughout her career.
Age-related smell loss can have a substantial impact on lifestyle and wellbeing, according to Pinto, a member of the university’s otolaryngology-head and neck surgery team. “Smells impact how foods taste. Many people with smell deficits lose the joy of eating. They make poor food choices, get less nutrition. They can’t tell when foods have spoiled or detect odors that signal danger, like a gas leak or smoke. They may not notice lapses in personal hygiene.”
"Of all human senses," Pinto said, "smell is the most undervalued and underappreciated — until it’s gone."
Precisely how smell loss contributes to mortality is unclear. “Obviously, people don’t die just because their olfactory system is damaged,” McClintock said.
The research team, which includes biopsychologists, physicians, sociologists and statisticians, is considering several hypotheses. The olfactory nerve, the only cranial nerve directly exposed to the environment, may serve as a conduit, they suggest, exposing the central nervous system to pollution, airborne toxins, pathogens or particulate matter.
McClintock noted that the olfactory system also has stem cells which self-regenerate, so “a decrease in the ability to smell may signal a decrease in the body’s ability to rebuild key components that are declining with age and lead to all-cause mortality.”
(Source: uchospitals.edu)
Lift weights, improve your memory
The Georgia Tech research isn’t the first to find that exercise can improve memory. But the study, which was just published in the journal Acta Psychologica, took a few new approaches. While many existing studies have demonstrated that months of aerobic exercises such as running can improve memory, the current study had participants lift weights just once two days before testing them. The Georgia Tech researchers also had participants study events just before the exercise rather than after workout. They did this because of extensive animal research suggesting that the period after learning (or consolidation) is when the arousal or stress caused by exercise is most likely to benefit memory.
The study began with everyone looking at a series of 90 photos on a computer screen. The images were evenly split between positive (i.e. kids on a waterslide), negative (mutilated bodies) and neutral (clocks) pictures. Participants weren’t asked to try and remember the photos. Everyone then sat at a leg extension resistance exercise machine. Half of them extended and contracted each leg at their personal maximum effort 50 times. The control group simply sat in the chair and allowed the machine and the experimenter to move their legs. Throughout the process, each participant’s blood pressure and heart rate were monitored. Every person also contributed saliva samples so the team could detect levels of neurotransmitter markers linked to stress.
The participants returned to the lab 48 hours later and saw a series of 180 pictures – the 90 originals were mixed in with 90 new photos. The control group recalled about 50 percent of the photos from the first session. Those who exercised remembered about 60 percent.
“Our study indicates that people don’t have to dedicate large amounts of time to give their brain a boost,” said Lisa Weinberg, the Georgia Tech graduate student who led the project.
Although the study used weight exercises, Weinberg notes that resistance activities such as squats or knee bends would likely produce the same results. In other words, exercises that don’t require the person to be in good enough to shape to bike, run or participate in prolonged aerobic exercises.
While all participants remembered the positive and negative images better than the neutral images, this pattern was greatest in the exercise participants, who showed the highest physiological responses. The team expected that result, as existing research on memory indicates that people are more likely to remember emotional experiences especially after acute (short-term) stress.
But why does it work? Existing, non-Georgia Tech human research has linked memory enhancements to acute stress responses, usually from psychological stressors such as public speaking. Other studies have also tied specific hormonal and norepinephrine releases in rodent brains to better memory. Interestingly, the current study found that exercise participants had increased saliva measures of alpha amylase, a marker of central norepinephrine.
“Even without doing expensive fMRI scans, our results give us an idea of what areas of the brain might be supporting these exercise-induced memory benefits,” said Audrey Duarte, an associate professor in the School of Psychology. “The findings are encouraging because they are consistent with rodent literature that pinpoints exactly the parts of the brain that play a role in stress-induced memory benefits caused by exercise.”
The collaborative team of psychology and applied physiology faculty and students plans to expand the study in the future, now that the researchers know resistance exercise can enhance episodic memory in healthy young adults.
“We can now try to determine its applicability to other types of memories and the optimal type and amount of resistance exercise in various populations,” said Minoru Shinohara, an associate professor in the School of Applied Physiology. “This includes older adults and individuals with memory impairment.”
Judgment and decision-making: brain activity indicates there is more than meets the eye
Published today in PLOS ONE, the study is the first in the world to show that it is possible to predict abstract judgments from brain waves, even though people were not conscious of making such judgments. The study also increases our understanding of impulsive behaviours and how to regulate it.
It found that researchers could predict from participants’ brain activity how exciting they found a particular image to be, and whether a particular image made them think more about the future or the present. This is true even though the brain activity was recorded before participants knew they were going to be asked to make these judgments.
Lead authors Dr Stefan Bode from the Melbourne School of Psychological Sciences and Dr Carsten Murawski from the University of Melbourne Department of Finance said these findings illustrated there was more information encoded in brain activity than previously assumed.
“We have found that brain activity when looking at images can encode judgments such as time reference, even when the viewer is not aware of making such judgments. Moreover, our results suggest that certain images can prompt a person to think about the present or the future,” they said.
The authors said the results contributed to our understanding of impulsive behaviours, especially where those behaviours were caused by ‘prompts’ in the world around us.
“For instance, consider someone trying to quit gambling who sees a gambling advertisement on TV. Our results suggest that even if this person is trying to ignore the ad, their brain may be unconsciously processing it and making it more likely that they will relapse,” he said.
The researchers used electroencephalography technology (EEG) to measure the electrical activity of people’s brains while they looked at different pictures. The pictures displayed images of food, social scenes or status symbols like cars and money.
After the EEG, researchers showed participants the same pictures again and asked questions about each image, such as how exciting they thought the image was or how strongly the image made them think of either the present or the future.
A statistical ‘decoding’ technique was then used to predict the judgments participants made about each of the pictures from the EEG brain activity that was recorded.
Co-author Daniel Bennett said just as certain prompts might cause impulsive behaviour, images could be used to prompt people to be more patient by regulating impulse control.
“Our results suggest that prompting people with images related to the future might cause processing outside awareness that could make it easier to think about the future. In theory, this could make people less impulsive and more likely to make healthy long-term decisions. These are hypotheses we will try to test in the future,” he said. The research was done in collaboration with the University of Cologne, Germany.