Buck Institute scientists say impaired interactions between macrophages and stem cells are likely players in human intestinal maladies like IBS, leaky gut and colorectal cancers
May 25, 2015/NOVATO, CA: Having a healthy gut may well depend on maintaining a complex signaling dance between immune cells and the stem cells that line the intestine. Scientists at the Buck Institute are now reporting significant new insight into how these complex interactions control intestinal regeneration after a bacterial infection. It’s a dance that ensures repair after a challenge, but that also goes awry in aging fruit flies — the work thus offers important new clues into the potential causes of age-related human maladies, such as irritable bowel syndrome, leaky gut and colorectal cancer.
“We’ve dissected a very complex signaling interaction,” said senior scientist and Buck faculty Heinrich Jasper, PhD. “By doing so temporally we’ve clearly established a role for the immune system both in initiating the regenerative process and in shutting it down – activities that are essential for maintaining tissue homeostasis.”
Publishing in the May 25, advance online edition of Nature Cell Biology, researchers in the Jasper lab show that the macrophage-like hemocytes (which comprise the cellular immune system in flies) go to the intestines ofDrosophila following damage. The hemocytes secrete the growth factor Dpp (a homologue of BMP, which has many functions, including the control of mobility, differentiation and invasiveness of normal cells), setting off the regenerative process by activating specific receptors in stem cells. In a fascinating twist, stem cells switch their response to Dpp in the middle of the regenerative response by turning on other Dpp-related receptors, which in turn instruct the stem cells to go back to a quiescent or quiet state. Jasper says it’s a balancing act that both allows for healing and prevents excessive cell proliferation, which could lead to pre-cancerous dysplasia. “The temporal sequence of cell interactions during injury-induced regeneration is only beginning to be understood,” said Jasper. “The proper timing of these interactions may be key in maintaining a healthy gut.”
Jasper says aging makes it harder for the stem cells to switch gears between proliferation and quiescence and that flies suffer from age-related intestinal dysfunctions similar to those experienced by humans.
Conventional wisdom has it that the more people stay within their own social groups and avoid others, the less likely it is small disease outbreaks turn into full-blown epidemics. But the conventional wisdom is wrong, according to two SFI researchers, and the consequences could reach far beyond epidemiology.
In a paper published in the July 20 early edition of the Proceedings of the National Academy of Sciences, Laurent Hébert-Dufresne and Benjamin Althouse show that when two separate diseases interact with each other, a population clustered into relatively isolated groups can lead to epidemics that spread like wildfire.
“We thought we understood how clustering works,” Hébert-Dufresne says,”but it behaves exactly opposite to what we thought once interactions are added in. Our intuition was totally wrong.”
At the heart of the new study are two effects that have had a lot of attention in recent years—social clustering and coinfection, in which one disease can change the infection dynamics of another—but haven’t been studied together. That, Hébert-Dufresne and Althouse say, turns out to be a major omission
Ordinarily, the pair say, clustering limits outbreaks. Maybe kids in one preschool get sick, for example, but since those kids don’t see kids from other preschools as often, they’re not likely to spread the disease very far. Coinfection often works the other way. Once someone is sick with, say, pneumococcal pneumonia, they’re more likely than others to come down with the flu, lowering the bar for an epidemic of both diseases.
But put the effects together, Hébert-Dufresne and Althouse discovered, and you get something that is more—and different—than the sum of its parts. While clustering works to prevent single-disease epidemics, interactions between diseases like pneumonia and the flu help keep each other going within a social group long enough that one of them can break out into other clusters, becoming a foothold for the other—or perhaps a spark in a dry forest. Both diseases, Althouse says, “can catch fire.” The end result is a larger, more rapidly developing, epidemic than would otherwise be possible.
That conclusion has immediate consequences for public health officials, whose worst-case scenarios might be different or even tame compared with the outbreaks Hébert-Dufresne and Althouse hypothesize. But there are equally important consequences for network scientists and complex systems researchers, who often think in epidemiological terms. Two ideas, for example, might interact with each other so that both spread more rapidly than they would on their own, just as diseases do.
Now that they’ve realized the importance of such interactions, “we hope to take this work in new and different directions in epidemiology, social science, and the study of dynamic networks,” Althouse says. “There’s great potential.”
More information: “Complex dynamics of synergistic coinfections on realistically clustered networks.”PNAS 2015 ; published ahead of print July 20, 2015, DOI: 10.1073/pnas.1507820112
In a nearly three-year investigation of the state of knowledge about environmentally influenced cancers, the scientists studied low-dose effects of 85 common chemicals not considered to be carcinogenic to humans.
The researchers reviewed the actions of these chemicals against a long list of mechanisms that are important for cancer development. Drawing on hundreds of laboratory studies, large databases of cancer information, and models that predict cancer development, they compared the chemicals’ biological activity patterns to 11 known cancer “hallmarks” – distinctive patterns of cellular and genetic disruption associated with early development of tumors.
n a nearly three-year investigation of the state of knowledge about environmentally influenced cancers, the scientists studied low-dose effects of 85 common chemicals not considered to be carcinogenic to humans.
The researchers reviewed the actions of these chemicals against a long list of mechanisms that are important for cancer development. Drawing on hundreds of laboratory studies, large databases of cancer information, and models that predict cancer development, they compared the chemicals’ biological activity patterns to 11 known cancer “hallmarks” – distinctive patterns of cellular and genetic disruption associated with early development of tumors.
The chemicals included bisphenol A (BPA), used in plastic food and beverage containers; rotenone, a broad-spectrum insecticide; paraquat, an agricultural herbicide; and triclosan, an antibacterial agent used in soaps and cosmetics.
A paper published today in the Proceedings of the National Academy of Sciences argues against the commonly held “accumulation of mutations” model of oncogenesis in favor of a model that depends on evolutionary pressures acting on populations of cells. Basically, the paper states that the ecosystem of a healthy tissue landscape lets healthy cells outcompete ones with cancerous mutations; it is when the tissue ecosystem changes due to aging, smoking, or other stressors, that cells with cancerous mutations can suddenly find themselves the most fit, allowing their population to expand over generations of natural selection.
The answer that DeGregori and CU Cancer Center colleague Andrii Rozhok, PhD propose is that in addition to activating mutation, cancer may require age-associated changes to the tissue landscape in order for evolution to favor the survival and growth of cancer cells over the competition of healthy cells.
Consider the following two evolutionary scenarios: In a grassy lawn, the health of the lawn is the best defense against dandelions; and in the time of the dinosaurs, the environment selected for giant lizards until the meteor hit at which point the new context favored the evolution of new species better adapted to the changed environment, including larger mammals.
Let’s start with the lawn: “Healthy cells are optimized for the ecosystem of the healthy body. But when the tissue ecosystem changes, such as with aging or smoking, cancer-causing mutations are often very good at exploiting the conditions of a damaged tissue landscape,” DeGregori says. In this scenario, DeGregori’s suggestion to explore the development of interventions supporting the fitness of healthy tissues is like applying fertilizer to the lawn rather than herbicide to the weeds.
Your gut’s “village” of bacteria may protect you against C. difficile infection – or not.
Like a collection of ragtag villagers fighting off an invading army, the mix of bacteria that live in our guts may band together to keep dangerous infections from taking hold, new research suggests.
But some “villages” may succeed better than others at holding off the invasion, because of key differences in the kinds of bacteria that make up their feisty population, the team from theUniversity of Michigan Medical School reports.
The researchers even show it may be possible to predict which collections of gut bacteria will resist invasion the best — opening the door to new ways of aiding them in their fight.
…these models could serve as a diagnostic tool, to predict which patients will need the most protection against C-diff before they go to the hospital, or even to custom-design a protective dose of bacteria before or after a C-diff exposure.
In other words, to see which villages need the most reinforcements to prevail in battle.
Schloss, who is a key member of the Medical School’s Host Microbiome Initiative, notes that no one species of bacteria by itself protected against colonization. It was the mix that did it. And no one particular mix of specific bacteria was spectacularly better than others – several of the diverse “villages” resisted invasion.
Resistance was associated with members of the Porphyromonadaceae, Lachnospiraceae, Lactobacillus, Alistipes, and Turicibacter families of bacteria. Susceptibility to C. difficile, on the other hand, was associated with loss of these protective species and a rise in Escherichia or Streptococcus bacteria.
“It’s the community that matters, and antibiotics screw it up,” Schloss explains. Being able to use advance genetic tools to detect the DNA of dozens of different bacteria species, and tell how common or rare each one is in a particular gut, made this research possible.
Clostridium difficile bacteria kill thousands of Americans each year.
Then, this massive amount of information about the villages of bacteria present in each of the mice in the experiment, and the relative success of each village in fighting off C-diff, was fed into the computer model created by the team.
For those who believe that birth order influences traits like personality and intelligence, a study of 377,000 high school students offers some good news: Yes, the study found, first-borns do have higher IQs and consistently different personality traits than those born later in the family chronology. However, researchers say, the differences between first-borns and “later-borns” are so small that they have no practical relevance to people’s lives.
Hormone therapy (HT) is prescribed to alleviate some of the symptoms of menopause in women. Menopausal women are more likely to be diagnosed with Alzheimer’s disease but not other forms of dementia, and HT has been prescribed to treat cognitive decline in post-menopausal women with variable degrees of effectiveness. New research by Dr. Liisa Galea, at the University of British Columbia, suggests the form of estrogens used in HT and previous motherhood could be critical to explain why HT has variable effects. Research in women, and Dr. Galea’s research in animals, shows that one form of estrogens, called estradiol, which is the predominant form of estrogens in young women, had beneficial effects, while estrone, which is the predominant form of estrogens in older women, did not. Furthermore, the effects of estrone also depended on whether the rats had experienced motherhood: estrone-based HT impaired learning in middle-aged rats that were mothers, while it improved learning in rats that were not. Dr. Galea’s latest results were presented at the 9th Annual Canadian Neuroscience Meeting, on May 25th 2015 in Vancouver British Columbia.
“Our most recent research shows that previous motherhood alters cognition and neuroplasticity in response to hormone therapy, demonstrating that motherhood permanently alters the brain” says Dr. Liisa Galea.
WINSTON-SALEM, N.C. – May 27, 2015 – Picture yourself in a medical office, anxiously awaiting your annual flu shot. The nurse casually states, “This won’t hurt a bit.” But when the needle pierces your skin it hurts, and it hurts a lot. Your expectations have been violated, and not in a good way.
In a study published in the early online edition of the journal PAIN, researchers atWake Forest Baptist Medical Center have identified through imaging the part of the brain that is activated when a person expects one level of pain but experiences another.
“This finding gives us a better understanding of the importance of how our expectations of pain affect the experience of pain,” said Fadel Zeidan, Ph.D., assistant professor of neurobiology and anatomy at Wake Forest Baptist and first author of the study. “This effect shows us how important it is to manage people’s expectations when it comes to pain.”
Previous studies have shown that the expectation of intense pain can make pain feel worse while the expectation of milder pain can make it hurt less. However, the brain mechanisms associated with processing mismatches between expected and experienced pain have been poorly understood.
This Wake Forest Baptist study found that activation of the parietal lobe and insular cortex are involved in processing real-time mismatches between expected and experienced pain.
Jonathan Berg, MD, PhD, is a UNC Lineberger member and an assistant professor in the UNC School of Medicine. James P. Evans, MD, PhD, is a Lineberger member and the UNC School of Medicine Bryson Distinguished Professor of Genetics and Medicine. (Source: UNC)
From the 2 June 2015 news release
CHAPEL HILL – Millions of genetic variants have been discovered in the last 25 years, but interpreting the clinical impact of the differences in a person’s genome remains a major bottleneck in genomic medicine. In a paper published today in The New England Journal of Medicine, a consortium including investigators from the University of North Carolina School of Medicine and UNC Lineberger Comprehensive Cancer Center present ClinGen, a program launched to evaluate the clinical relevance of genetic variants for use in precision medicine and research.
“Sequencing has revealed that there are potentially several million genetic variants per person,” said Jonathan Berg, MD, PhD, a UNC Lineberger member, an assistant professor in the UNC School of Medicine Department of Genetics and this year’s ClinGen steering committee chair. “Right now there is a certain degree to which we can infer what those variants do, but most of them remain really beyond our understanding of how they are affecting human health, if at all. Through ClinGen, we’re working to evaluate the clinical relevance of genes and variants, and to provide a public database so that labs and clinicians will have a resource that they can go to as a way to understand their patients’ genetic testing results.”
Clinicians and researchers hope to use information about genetic variants not only to make predictions about an individual’s risk of disease, but also to develop more accurate clinical trials and better, tailored treatments and care for patients. However, labs and clinicians may interpret the same variant differently.
From the 26 May 2015 Florida State University news release
Foam. We wear it. We sit on it. We sleep on it. We even use it to protect ourselves.
Whether it’s a football helmet, hospital bed, knee pad or body armor, the foam it contains plays a critical role in making that product both comfortable and safe. But can that foam be transformed into something significantly better, safer and more comfortable?
Changchun “Chad” Zeng with Florida State University’s High Performance Materials Institute (HPMI) says yes, and his brand new, high-performing auxetic foam is proving the point as it heads to the marketplace through a license agreement with Auxadyne LLC.
“We know what is not working with current products and technology, and what it is going to take to make it better,” said Zeng. “For example, the socks that amputees currently use to attach prosthetic devices do not adjust to limb shape and volume, creating lots of problems. My invention solves those issues.”
Part of what makes Zeng’s auxetic foam truly unique is its ability to get thicker, rather than thinner, when stretched. In practical terms, this counter-intuitive behavior, totally opposite to that of conventional foam, leads to many enhanced materials properties including a better and more comfortable fit that adjusts on the fly.
A new study led by Shi, chair of the section of oral biology at the UCLA School of Dentistry, describes more precisely the mechanism that makes the mouthwash’s active ingredient so effective.
The research, published in the June issue (PDF) of the Proceedings of the National Academy of Sciences, explains how a specifically targeted antimicrobial peptide, or STAMP, known as C16G2 works to eradicate only the harmful acid-producing Streptococcus mutans bacteria, the main cause of tooth decay, without disturbing the benign and beneficial bacteria in the mouth.
These changes resulted in a microbial community structure that supports better oral health.
The finding is a critical advance because, as scientists have understood for about two decades, the vast majority of bacterial cells in the human mouth are not harmful to our health. Most common broad-spectrum antibiotics and conventional mouthwashes indiscriminately kill both beneficial and harmful pathogenic organisms, and their effects last for only about 12 hours. In addition, overusing broad-spectrum antibiotics can seriously disrupt the body’s ecological balance, which can make people more susceptible to microbial infections. As a result, there is no effective treatment for bacteria-induced tooth decay.
Shi said the STAMP approach would be a unique solution for re-engineering the mouth’s microbiome for long-term health.
C16G2, which is now delivered via a gel tray, is being developed for use in preventing tooth decay and cavities under an investigational new drug application with the U.S. Food and Drug Administration by Los Angeles-based C3 Jian, a company Shi founded around patent rights he developed at UCLA. It is currently in Phase 2 clinical trials.
Women who use feminine care products called douches may increase their exposure to harmful chemicals called phthalates–and black women may be at particularly high risk due to frequent use. Public health officials advise against the use of douching products, which can hide vaginal infections and lead to other serious health problems. Despite that, douching products are still a popular item on the drug store shelf, and are disproportionately used by black women.
“This study suggests, for the first time, that vaginal douches may increase a woman’s exposure to phthalates, chemicals that may alter hormone action and are associated with serious health problems,” says senior author of the study Ami Zota, ScD, MS.
“These findings raise questions about the health and safety of vaginal douches and other fragranced products used in and around the vaginal area.”
This study did not directly tie phthalates in douching products to health problems in women–additional research will have to make that direct connection. Still, the research did find that vaginal douching may increase a woman’s exposure to DEP and that’s a troubling finding that needs to be explored further.
The American College of Obstetricians and Gynecologists and other health experts recommend against douching because this practice has been associated with increased risks of vagina infection, pelvic inflammatory disease, problems during pregnancy and sexually transmitted diseases. Now, this study adds the worry that douching may also expose women to chemicals that can lead to health problems later in life or can harm their developing baby–if women are pregnant while using such products.
From the 29 May 2015 University of Maryland news release
COLLEGE PARK, Md. – The introduction of Craigslist led to an increase in HIV-infection cases of 13.5 percent in Florida over a four-year period, according to a new study conducted at the University of Maryland’s Robert H. Smith of Business. The estimated medical costs for those patients will amount to $710 million over the course of their lives.
Online hookup sites have made it easier for people to have casual sex—and also easier to transmit sexually transmitted diseases. The new study measured the magnitude of the effect of one platform on HIV-infection rates in one state, and offered a detailed look at the varying effects on subpopulations by race, gender and socio-economic status. Looking at the period 2002 to 2006, it found that Craigslist led to an additional 1,149 Floridians contracting HIV.
The study “underscores the need for broader communication and dissemination of the risks posed by the type of online matching platforms studied here,” noted Ritu Agarwal, a professor at the University of Maryland’s Robert H. Smith School of Business and founding director of the Center for Health Information and Decision Systems (CHIDS), and Brad N. Greenwood, a 2013 Smith Ph.D. and assistant professor at Temple University’s Fox School of Business.
The study also found that the new HIV cases came disproportionately from one racial-ethnic group, African Americans, who accounted for some 63 percent of the new cases. “That is a bit of paradox,” says Agarwal, “because research suggests that the African American community is one which uses the Internet the least, even though the gap is narrowing.”
Greenwood described African Americans as suffering the effects of a “double digital divide.” He said, “Not only have studies shown there is lower utilization of the Internet for welfare-enhancing activities, but now there’s evidence of utilization for negative activities as well.”
There was also an increase in new HIV cases among Latinos and Caucasians—although only intermittently statistically significant and not statistically different from each other. The lack of difference between Latinos and Caucasians was notable, as Latinos have a higher baseline rate of HIV infection. One explanation could be that fewer Latinos may have sought treatment. Or Florida’s Latino community, which is especially large and well-off, may not be reflective of national trends.
Another counterintuitive result was that more cases came from non-Medicaid patients, the wealthier patients, than from the population covered by the government program. That was the case even though the base rate of HIV infection is higher among lower-income citizens. “It could be the case that higher-income people face a higher social penalty for engaging in casual, quasi-anonymous sex, and that the freedom of internet anonymity changes their behavior more than it does for the less wealthy,” Agarwal suggested. “Or it could be a byproduct of substantially better internet access.” (Together with the finding for African Americans, that would suggest that degree of internet access affects different sub-populations in different ways).
HIV-prevention efforts tend to focus on the highest-risk populations, such as the economically disadvantaged, but public-health officials should be aware than online platforms may be “changing the game,” says Agarwal.
Perhaps most surprising of all, given the relatively high rates of infection among bi- and homosexual men, there was not a statistically significant difference in HIV-infection-rate increases across men and women.
It could be the case that homosexual men with HIV who used Craigslist were more likely to practice safe sex than infected heterosexuals, the authors speculated. Or matching platforms may lead to more homosexual activity by men who do not identify publically as homosexuals, who then spread the virus to their female partners. The question demands more research, the authors said.
Agarwal and Greenwood were careful to note that they weren’t making a statement about the overall value of Craigslist. Nevertheless, the study offers a reminder of the downside of connectivity. “While there is a general belief that connectivity is good on average, unfortunately ‘on average’ means that some people are going to benefit more and others are going to lose more,” Agarwal says. “We need to better understand both the beneficial as well as the punitive effects of the Internet on individual and public health.”
A study, co-authored by Professor Bruce McCandliss, provides some of the first evidence that a specific teaching strategy for reading has direct neural impact.
From the 28 May 2015 Stanford news release
Stanford Professor Bruce McCandliss found that beginning readers who focus on letter-sound relationships, or phonics, increase activity in the area of their brains best wired for reading.
Words learned through the letter-sound instruction elicited neural activity biased toward the left side of the brain, which encompasses visual and language regions. In contrast, words learned via whole-word association showed activity biased toward right hemisphere processing.
McCandliss noted that this strong left hemisphere engagement during early word recognition is a hallmark of skilled readers, and is characteristically lacking in children and adults who are struggling with reading.
In addition, the study’s participants were subsequently able to read new words they had never seen before, as long as they followed the same letter-sound patterns they were taught to focus on. Within a split second, the process of deciphering a new word triggered the left hemisphere processes.
“Ideally, that is the brain circuitry we are hoping to activate in beginner readers,” McCandliss said.
By comparison, when the same participants memorized whole-word associations, the study found that they learned sufficiently to recognize those particular words on the reading test, but the underlying brain circuitry differed, eliciting electrophysiological responses that were biased toward right hemisphere processes.
May 29, 2015 / B3C newswire / — In the German Center for Infection Research (DZIF), scientists from the universities of Tübingen, Münster and Munich join forces and prepare together with the company Hyglos clinical studies on an active substance against the dreaded hospital pathogen Staphylococcus aureus: A highly effective protein from bacteria-specific viruses, so-called bacteriophages, shall rapidly kill the bacteria, which frequently occur in the nose. Due to the specific action, the natural microflora is maintained. Such prophylactic treatment of nasal colonization could counteract the spread of especially methicillin-resistant staphylococcus aureus (MRSA) in hospitals and thereby prevent infections in patients.
From the 26 May 2015 Max-Planck Institute news release
Different languages can have subtly different effects on the way we think and perceive, a phenomenon known as linguistic relativity. In a new paper in the journal Cognition, researcher Monique Flecken from the Max Planck Institute for Psycholinguistics, together with colleagues, shows that even when we are not speaking, the grammar of our native language may influence the way we perceive motion events.
In the study, Flecken, with colleagues Panos Athanasopoulos (Lancaster University), Jan Rouke Kuipers (University of Stirling) and Guillaume Thierry (Bangor University), measured the extent to which German and English participants allocated attention totrajectory and endpoint of motion events in a task in which they did not have to speak. Participants were presented with short animations of a dot travelling along a trajectory towards a geometrical shape (endpoint), followed by a picture symbolising the event.
…German participants allocated more attention to endpoints than English speakers, in accordance with the grammatical patterns of their language. Prior work has suggested that linguistic relativity effects may only occur when people are (silently) speaking or planning to speak. In a second experiment, Flecken and colleagues were able to show that this was unlikely.
…linguistic relativity extends to the domain of non-verbal motion perception.” So, even in a non-verbal context, the grammatical properties of a language, including the ways in which events are normally encoded in sentences, influence the way people perceive and attend to motion events.
Since President Barack Obama’s State of the Union Address in January 2015, the nation has been talking about a revolution in patient care, known by many as precision medicine.
Of course, the country is used to hearing the president talk about health care, especially the Affordable Care Act. But when the White House starts launching $215 million initiatives to accelerate research—in this case, the Precision Medicine Initiative, according to a White House Press release—you can be sure it’s not just a passing fad.
First, what is precision medicine?
Precision medicine is about tailoring treatments to the patient’s genome and body function. The promise is that this detailed personal health data can determine what’s most effective for each individual, which can lead to better outcomes.
Most of precision medicine’s application currently focuses on cancer. Launched in 2013, Penn Medicine’s Center for Personalized Diagnostics (CPD) helps oncologists determine the best treatment for their cancer patients by looking at the cancer’s genome. Here’s how precision medicine is being practiced at Penn:
A patient is diagnosed with cancer.
If the cancer involves a solid tumor—like breast, lung, or colon cancer—the tumor is surgically removed during a biopsy, and a chunk of the tissue is sent to Penn Medicine’s CPD. If the cancer involves blood or bone marrow—like leukemia—a sample of the blood or bone marrow is sent.
The CPD sequences a panel of genes that are known to be involved in cancer. This test examines DNA within the tumor, blood or bone marrow sample. The goal is to find DNA mutations that are driving the cancer.
A report on the mutations found is sent to the patient’s oncologist.
The oncologist determines if there are therapies or treatments available that work better than others—or not at all—on the patient’s particular type of cancer.
“We’re using precision medicine to give patients the right drugs, guided by the DNA sequence information from their cancer, so we’re not exposing them to potentially toxic effects,” explains David Roth, MD, PhD, director of the CPD. “This individualized therapy is better than treatment based on the ‘average patient.’”
Precision Medicine is being researched, translated and applied across Penn Medicine. Here,
experts from the Center for Personalized Diagnostics share four predictions on how precision medicine will change how cancer is treated in future generations.
1. Cancer will be diagnosed earlier.
Jennifer Morrissette, PhD, clinical director of the CPD:
“There are different stages of tumors. The earlier you catch the tumor, the more likely you are to survive it. My theory is that this century will be the century of diagnostics. We will be diagnosing people’s cancers earlier and earlier.
“That way, we are not dealing with advanced metastatic tumors that have acquired so many different changes that they’re hard to treat. We’ll be capturing tumors very early, in stage one; have a definitive surgery; follow the patient for a certain number of years to make sure that the cancer hasn’t spread; and then they’ll be cured.
“Some people put off seeing a physician because they don’t want chemo, but the longer they put it off, the more likely they are going to have metastatic disease.”
2. Cancer treatment will be based on each person’s health profile.
“[In the past,] doctors had been treating [the average patient] based upon results from a large study.
“The revolution in precision medicine is that now we have better tools to understand what’s going on with you as an individual. Instead of saying, ‘Okay, you have this particular cancer, and you have a 30 percent chance. So, go ahead and get this toxic therapy,’ we can be much more specific.
“If we were able to tell you that you have a five percent chance of responding to a chemotherapy based on the makeup of your tumor, would you still do it?”
3. Gene paneling will be used for diagnosis, not just treatment.
David Lieberman, MS, CGC (certified genetic counselor):
“We tend to see certain genes mutated in certain cancers. For example, there is a certain set of
genes [that are] typically mutated in lung cancer or another set in lymphoma.
“It is not always clear using historical methods what type of cancer a patient has. This makes treatment decisions challenging. Sequencing the tumor’s DNA on a panel of known cancer-related genes may help clarify the cancer’s origin and, in this way, assist the clinician in determining treatment or prognosis.”
$215 million: The amount the White House will invest in the Precision Medicine Initiative in 2016
4. More cancer patients will have a treatment team, rather than just an oncologist.
Jennifer Morrissette PhD, clinical director of the CPD:
“It’s not going to be one physician making all the decisions. Cancer treatment has gotten much more complex. Because of the availability of multi-gene testing, you need a group of people with different types of expertise to make the best decision for a patient.
“In addition to the team directing care for the appropriate approach—whether it’s surgery, radiation, chemotherapy, pain management—now there is also the genetic component.
“[The team’s] able to sit in a room with people from the lab who can talk about what the result means, have the oncologist tell them about the patient and then get the clinical geneticist’s notion that there may be an inherited predisposition. Then, they walk out with a consolidated treatment plan for that patient.”
The future of medicine
For more than 250 years, advancements like “precision medicine” have been the hallmark of Penn Medicine. As the first school of medicine in the United States, it has been and continues to be a place where the future of medicine and the future leaders in medicine are being developed.
The age that children hit puberty has been found to be a significant predictor of their health in later life, researchers say.
The University of Cambridge study confirms previous findings of a link between early puberty in women and heart disease and type 2 diabetes, and has shown for the first time that early puberty in men is also associated with these conditions.
Those who went through puberty relatively early had around 50% higher relative risks for type 2 diabetes and heart disease. However, women and men who went through puberty relatively late had a higher relative risk of developing asthma.
Researchers from the Medical Research Council (MRC) epidemiology unit at theUniversity of Cambridge found that the age at which both men and women begin puberty is associated with a total of 48 different health conditions including irritable bowel syndrome, arthritis, glaucoma, psoriasis and depression – along with early menopause in women.
Low-energy activities that involve sitting down are associated with an increased risk of anxiety, according to research published in the open-access journal BMC Public Health
Low energy activities that involve sitting down are associated with an increased risk of anxiety, according to research published in the open access journal BMC Public Health. These activities, which include watching TV, working at a computer or playing electronic games, are called sedentary behavior. Further understanding of these behaviors and how they may be linked to anxiety could help in developing strategies to deal with this mental health problem.
Many studies have shown that sedentary behavior is associated with physical health problems like obesity, heart disease, type 2 diabetes and osteoporosis. However, there has been little research into the link between sedentary behavior and mental health. This is the first systematic review to examine the relationship between anxiety and sedentary behavior.
Anxiety is a mental health illness that affects more than 27 million people worldwide. It is a debilitating illness that can result in people worrying excessively and can prevent people carrying out their daily life. It can also result in physical symptoms, which amongst others includes pounding heartbeat, difficulty breathing, tense muscles, and headaches.
Megan Teychenne, lead researcher and lecturer at Deakin University’s Centre for Physical Activity and Nutrition Research (C-PAN) in Australia, said: “Anecdotally – we are seeing an increase in anxiety symptoms in our modern society, which seems to parallel the increase in sedentary behavior. Thus, we were interested to see whether these two factors were in fact linked. Also, since research has shown positive associations between sedentary behavior and depressive symptoms, this was another foundation for further investigating the link between sedentary behavior and anxiety symptoms.”
The C-PAN team suggests the link between sedentary behavior and anxiety could be due to disturbances in sleep patterns, social withdrawal theory and poor metabolic health. Social withdrawal theory proposes that prolonged sedentary behavior, such as television viewing, can lead to withdrawal from social relationships, which has been linked to increased anxiety. As most of the studies included in this systematic-review were cross-sectional the researchers say more follow-up work studies are required to confirm whether or not anxiety is caused by sedentary behavior.
Megan Teychenne said: “It is important that we understand the behavioral factors that may be linked to anxiety – in order to be able to develop evidence-based strategies in preventing/managing this illness. Our research showed that evidence is available to suggest a positive association between sitting time and anxiety symptoms – however, the direction of this relationship still needs to be determined through longitudinal and interventional studies.”
Everything from your risk of a heart attack to the sex of your unborn child may depend on the forecaster’s predictions
From the 17 July 2015 BBC post
In 2013, neuroscientists reported one of the strangest case reports in the history of medicine: a man who claimed to be able to smell the weather. An approaching storm, he said, produced an almost unbearable odour of skunk excrement, mixed with onions. The scientists were at a loss to explain what could be causing these strange symptoms.
Most of us are thankfully lacking this rather unwelcome talent, but even subtle shifts in the atmosphere seem to correlate with changes in our bodies. While scientists have yet to confirm many of these proposed links, the evidence so far is intriguing. If true, it would mean everything from your risk of a heart attack to the sex of your unborn child may, to a greater or lesser extent, depend on the forecaster’s predictions.
Read on to discover the myths and the genuine mysteries.
1) Rain gives you rheumatism… maybe
MIT neuroscientists have shown that they can cure the symptoms of depression in mice by artificially reactivating happy memories that were formed before the onset of depression.
The findings, described in the June 18 issue of Nature, offer a possible explanation for the success of psychotherapies in which depression patients are encouraged to recall pleasant experiences. They also suggest new ways to treat depression by manipulating the brain cells where memories are stored. The researchers believe this kind of targeted approach could have fewer side effects than most existing antidepressant drugs, which bathe the entire brain.
“Once you identify specific sites in the memory circuit which are not functioning well, or whose boosting will bring a beneficial consequence, there is a possibility of inventing new medical technology where the improvement will be targeted to the specific part of the circuit, rather than administering a drug and letting that drug function everywhere in the brain,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, director of the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory, and senior author of the paper.
In their new study, the researchers sought to discover if their ability to reactivate existing memories could be exploited to treat depression.
To do this, the researchers first exposed mice to a pleasurable experience. In this case, all of the mice were male and the pleasurable experience consisted of spending time with female mice. During this time, cells in the hippocampus that encode the memory engram were labeled with a light-sensitive protein that activates the neuron in response to blue light.
After the positive memory was formed, the researchers induced depression-like symptoms in the mice by exposing them to chronic stress. These mice show symptoms that mimic those of human sufferers of depression, such as giving up easily when faced with a difficult situation and failing to take pleasure in activities that are normally enjoyable.
However, when the mice were placed in situations designed to test for those symptoms, the researchers found that they could dramatically improve the symptoms by reactivating the neurons that stored the memory of a past enjoyable experience. Those mice began to behave just like mice that had never been depressed — but only for as long as the pleasant memory stayed activated.
Objective -To determine whether trial publications of glucose lowering drugs are dominated by a small group of highly prolific authors (“supertrialists”) and to identify some of their characteristics.
ConclusionThe past two decades have seen an explosive increase in the number of published clinical trials regarding glucose lowering treatment. Some authors have made a disproportionate contribution to the therapeutic evidence base; one third of the RCT evidence base on glucose lowering drug treatment for diabetes was generated by<1% of authors. Of these, 44% were company employees and 56% were academics who work closely with the pharmaceutical companies.
What is already known on this topic
Honorary authors (authors with little or no contribution to the work described) and ghost authors (professional writers whose contribution is not acknowledged) threaten the integrity of the evidence base in medicine
Honorary authorship is known to be more frequent in research articles than in reviews
Anecdotally, a few highly prolific authors with multiple conflicts of interest have appeared to dominate clinical trial publications, but this has not previously been quantified
What this study adds
This analysis shows that 110 highly prolific authors contributed to one third of the evidence base for glucose lowering treatment; of these, 44% were company employees and 56% were academics who work closely with the pharmaceutical companies
Eleven authors, including nine academics—here designated supertrialists—contributed 10% of the entire evidence base
This concentration of influence adds to concerns about the independence and integrity of the evidence base for treatment for diabetes.
A team comprised of scientists at VIB, KU Leuven and UZ Leuven has made significant progress in uncovering the connection between psychological factors and the immune system. Their findings are based on an investigation of a massive drinking water contamination incident in Belgium in 2010, and are now published in the leading international medical journal Gut.
In December 2010, the Belgian communities of Schelle and Hemiksem in the province of Antwerp faced an outbreak of gastroenteritis, with more than 18,000 people exposed to contaminated drinking water. During the outbreak, VIB and KU Leuven set up a scientific task force to study the incident’s long-term effects, led by Guy Boeckxstaens (UZ Leuven / KU Leuven) and Adrian Liston (VIB / KU Leuven).
Seizing an unexpected opportunity
Adrian Liston (VIB/KU Leuven): “The water contamination in Schelle and Hemiksem was an ‘accidental experiment’ on a scale rarely possible in medical research. By following the patients from the initial contamination to a year after the outbreak we were able to find out what factors altered the risk of long-term complications.”
Anxiety and depression affect immune system
The scientists found that individual with higher levels of anxiety or depression prior to the water contamination developed gastrointestinal infections of increased severity. The same individuals also had an increased risk of developing the long-term complication of irritable bowel syndrome, with intermittent abdominal cramps, diarrhea or constipation a year after the initial contamination.
Guy Boeckxstaens (UZ Leuven / KU Leuven): “Irritable Bowel Syndrome is a condition of chronic abdominal pain and altered bowel movements. This is a common condition with large socio-economic costs, yet there is so much that still remains to be discovered about the causes. Our investigation found that that anxiety or depression alters the immune response towards a gastrointestinal infection, which can result in more severe symptoms and the development of chronic irritable bowel syndrome.”
Psychological factors key in preventing long-term complications
The study’s results provide valuable new insight into the cause of irritable bowel syndrome, and underscoring the connection between psychological factors and the immune system.
Adrian Liston (VIB/KU Leuven): “These results once again emphasize the importance of mental health care and social support services. We need to understand that health, society and economics are not independent, and ignoring depression and anxiety results in higher long-term medical costs.”
Scientists have at their disposal a way to explore the possible prevention of genetic diseases before birth. But should they? Currently, the most promising path forward involves editing the genes of human embryos, a procedure rife with controversy. An article in Chemical & Engineering News (C&EN), the weekly newsmagazine of the American Chemical Society, parses the explosive issue.
Britt E. Erickson, a senior editor at C&EN, reports that at least one team of scientists has already published a study on altering disease-related genes of human embryos. The experiment was largely unsuccessful, but it stoked fears that such research on embryos could lead to potentially dangerous or unethical applications. Would parents start demanding designer babies engineered to be smarter or more attractive? What would be the long-term consequences of changing people’s genes before they’re born?
Without answers yet to these critical questions and others, many European countries have banned gene editing of human reproductive cells. In the U.S. — where federal dollars cannot go toward this type of work — and in China, scientists are allowed to pursue this type of research. But the landscape is likely going to change as scientists, ethicists and lawmakers hash out a path forward.
From the 6 July 2015 University of San Francisco news release
Deleterious Effects of ‘Pro-Aging Factor’ Can Be Reversed in Mice
A blood-borne molecule that increases in abundance as we age blocks regeneration of brain cells and promotes cognitive decline, suggests a new study by researchers at UC San Francisco and Stanford School of Medicine.
The molecule in question, known as beta-2 microglobulin, or B2M, is a component of a larger molecule called MHC I (major histocompatibility complex class I), which plays a major role in the adaptive immune system. A growing body of research indicates that the B2M-MHC I complex, which is present in all cells in the body except red blood cells and plasma cells, can act in the brain in ways not obviously related to immunity—guiding brain development, shaping nerve cell communication, and even affecting behavior.
“We are in the process of elucidating the exact mechanism by which B2M works,” said Saul A. Villeda, PhD, a UCSF Faculty Fellow and co-senior author of the new study. “Since B2M increases with age, both in the blood and in the brain, we want to know what is the ‘traditional’ immune contribution to effects on cognition, and what is the non-traditional neural contribution.”
In 2014, highly publicized work in the laboratories of Villeda and Tony Wyss-Coray, PhD, professor of neurology at Stanford, showed that connecting the circulatory system of a young mouse to that of an old mouse could reverse the declines in learning ability that typically emerge as mice age.
Over the course of their long-term research on so-called young blood, however, the researchers had noted an opposite effect: blood from older animals appears to contain “pro-aging factors” that suppress neurogenesis—the sprouting of new brain cells in regions important for memory—which in turn can contribute to cognitive decline.
In the new research, published online on July 6, 2015 in Nature Medicine, Villeda and co-senior author Wyss-Coray again joined forces to follow up on these findings, as well as a range of studies correlating high B2M blood levels with cognitive dysfunction in Alzheimer’s disease, HIV-associated dementia, and as a consequence of chronic dialysis for kidney disease.
Members of the Villeda and Wyss-Coray labs first showed that B2M levels steadily rise with age in mice, and are also higher in young mice in which the circulatory system is joined to that of an older mouse. These findings were confirmed in humans, in whom B2M levels rose with age in both blood and in the cerebrospinal fluid (CSF) that bathes the brain.
When B2M was administered to young mice, either via the circulatory system or directly into the brain, the mice performed poorly on tests of learning and memory compared to untreated mice, and neurogenesis was also suppressed in these mice.
These experiments were complemented by genetic manipulations in which some mice were engineered to lack a gene known as Tap1, which is crucial for the MHC I complex to make its way to the cell surface. In these mice, administration of B2M in young mice had no significant effect, either in tests of learning or in assessments of neurogenesis.
The group also bred mice missing the gene for B2M itself. These mice performed better than their normal counterparts on learning tests well into old age, and their brains did not exhibit the decline in neurogenesis typically seen in aged mice.
Villeda emphasized that the effects on learning observed in the B2M-administration experiments were reversible: 30 days after the B2M injections, the treated mice performed as well on tests as untreated mice, indicating that B2M-induced cognitive decline in humans could potentially be treated with targeted drugs.
“From a translational perspective, we are interested in developing antibodies or small molecules to target this protein late in life,” said Villeda. “Since B2M goes up with age in blood, CSF, and also in the brain itself, this allows us multiple avenues in which to target this protein therapeutically.”
From the 6 July 2015 American Chemical news release
Carrying around a spare tire is a good thing — you never know when you’ll get a flat. Turns out we’re all carrying around “spare tires” in our genomes, too. Today, in ACS Central Science, researchers report that an extra set of guanines (or “G”s) in our DNA may function just like a “spare” to help prevent many cancers from developing.
Various kinds of damage can happen to DNA, making it unstable, which is a hallmark of cancer. One common way that our genetic material can be harmed is from a phenomenon called oxidative stress. When our bodies process certain chemicals or even by simply breathing, one of the products is a form of oxygen that can acutely damage DNA bases, predominantly the Gs. In order to stay cancer-free, our bodies must repair this DNA. Interestingly, where it counts — in a regulatory DNA structure called a G-quadruplex — the damaged G is not repaired via the typical repair mechanisms. However, people somehow do not develop cancers at the high rate that these insults occur. Cynthia Burrows, Susan Wallace and colleagues sought to unravel this conundrum.
The researchers scanned the sequences of known human oncogenes associated with cancer, and found that many contain the four G-stretches necessary for quadruplex formation and a fifth G-stretch one or more bases downstream. The team showed that these extra Gs could act like a “spare tire,” getting swapped in as needed to allow damage removal by the typical repair machinery. When they exposed these quadruplex-forming sequences to oxidative stress in vitro, a series of different tests indicated that the extra Gs allowed the damages to fold out from the quadruplex structure, and become accessible to the repair enzymes. They further point out that G-quadruplexes are highly conserved in many genomes, indicating that this could be a factory-installed safety feature across many forms of life.
Due to a premature posting of this paper online, the embargo is now lifted as of July 6.
A newborn’s first stool can signal the child may struggle with persistent cognitive problems, according to Case Western Reserve University Project Newborn researchers.
In particular, high levels of fatty acid ethyl esters (FAEE) found in the meconium (a newborn’s first stool) from a mother’s alcohol use during pregnancy can alert doctors that a child is at risk for problems with intelligence and reasoning.
Left untreated, such problems persist into the teen years, the research team from the Jack, Joseph and Morton Mandel School of Applied Social Sciences found.
“We wanted to see if there was a connection between FAEE level and their cognitive development during childhood and adolescence—and there was,” said Meeyoung O. Min, PhD, research assistant professor at the Mandel School and the study’s lead researcher. “FAEE can serve as a marker for fetal alcohol exposure and developmental issues ahead.”
Detecting prenatal exposure to alcohol at birth could lead to early interventions that help reduce the effects later, Min said.
WEST LAFAYETTE, Ind. — A new “smart capsule” under development could deliver medications directly to the large intestines to target certain medical conditions.
“Usually, when you take medication it is absorbed in the stomach and small intestine before making it to the large intestine,” said Babak Ziaie, a professor of electrical and computer engineering at Purdue University. “However, there are many medications that you would like to deliver specifically to the large intestine, and a smart capsule is an ideal targeted-delivery vehicle for this.”
Such an innovation might be used to treat of irritable bowel syndrome, Crohn’s disease and a potentially life-threatening bacterial infection called Clostridium difficile in which the body loses natural microorganisms needed to fight infection.
Findings are detailed in a research paper that appeared online and will be published in a future print issue of the Institute of Electrical and Electronics Engineers (IEEE) Transactions on Biomedical Engineering. The paper was authored by graduate students Wuyang Yu, Rahim Rahimi and Manuel Ochoa; Rodolfo Pinal, an associate professor of industrial and physical pharmacy; and Ziaie.
I remember studying the parasympathetic system in high school back in the 70’s. Basically we were taught that it exists and it balances the sympathetic system. Also recall we were taught that the nervous system and immune systems were separate, one did not “talk” to the other.
Kevin Tracey, a neurosurgeon based in New York, is a man haunted by personal events – a man with a mission. “My mother died from a brain tumor when I was five years old. It was very sudden and unexpected,” he says. “And I learned from that experience that the brain – nerves – are responsible for health.”
This background made him a neurosurgeon who thinks a lot about inflammation. He believes it was this perspective that enabled him to interpret the results of an accidental experiment in a new way.
In the late 1990s, Tracey was experimenting with a rat’s brain. “We’d injected an anti-inflammatory drug into the brain because we were studying the beneficial effect of blocking inflammation during a stroke,” he recalls. “We were surprised to find that when the drug was present in the brain, it also blocked inflammation in the spleen and in other organs in the rest of the body. Yet the amount of drug we’d injected was far too small to have got into the bloodstream and traveled to the rest of the body.”
After months puzzling over this, he finally hit upon the idea that the brain might be using the nervous system – specifically the vagus nerve – to tell the spleen to switch off inflammation everywhere.
It was an extraordinary idea – if Tracey was right, inflammation in body tissues was being directly regulated by the brain. Communication between the immune system’s specialist cells in our organs and bloodstream and the electrical connections of the nervous system had been considered impossible. Now Tracey was apparently discovering that the two systems were intricately linked.
A new study is the first to directly implicate the cerebellum in the creative process. As for the brain’s higher-level executive-control centers? Not so much.
Investigators at Stanford University have found a surprising link between creative problem-solving and heightened activity in the cerebellum, a structure located in the back of the brain and more typically thought of as the body’s movement-coordination center.
In designing the study, the researchers drew inspiration from the game Pictionary.
The cerebellum, traditionally viewed as the brain’s practice-makes-perfect, movement-control center, hasn’t been previously recognized as critical to creativity. The new study, a collaboration between the School of Medicine and Stanford’s Hasso Plattner Institute of Design, commonly known as the d.school, is the first to find direct evidence that this brain region is involved in the creative process.
Neuroscientists identify a brain circuit that controls decisions that induce high anxiety.
Some decisions arouse far more anxiety than others. Among the most anxiety-provoking are those that involve options with both positive and negative elements, such choosing to take a higher-paying job in a city far from family and friends, versus choosing to stay put with less pay.
MIT researchers have now identified a neural circuit that appears to underlie decision-making in this type of situation, which is known as approach-avoidance conflict. The findings could help researchers to discover new ways to treat psychiatric disorders that feature impaired decision-making, such as depression, schizophrenia, and borderline personality disorder.
The new study grew out of an effort to figure out the role of striosomes — clusters of cells distributed through the the striatum, a large brain region involved in coordinating movement and emotion and implicated in some human disorders. Graybiel discovered striosomes many years ago, but their function had remained mysterious, in part because they are so small and deep within the brain that it is difficult to image them with functional magnetic resonance imaging (fMRI).
From the 20 May 2015 University of Alabama news release
CreakyJoints, an online, nonprofit, patient support community with more than 80,000 members, has launched Arthritis Power, the first patient-led, patient-generated, patient-centered research registry for arthritis, bone, and inflammatory skin conditions. Focusing on rheumatoid arthritis, psoriasis, psoriatic arthritis as well as numerous other musculoskeletal conditions, the goal of Arthritis Power is to securely collect health data from tens of thousands of arthritis patients to support future research.
Arthritis Power includes a steering committee of patients called the Patient Governor Group that identifies research needs for study development and prioritizes research requests from the CreakyJoints patient community around the world. The new initiative is launched in partnership with the University of Alabama at Birmingham. Arthritis Power is supported in part by the Patient Centered Outcomes Research Institute (PCORI), a nonprofit, nongovernmental organization created by Congress as part of the Patient Protection and Affordable Care Act of 2010. Its overall goal is to enhance informed health-care decision-making and to improve health-care delivery.
Usually patients with rheumatoid, psoriatic arthritis or other chronic conditions learn about opportunities to participate in research from their health-care providers. Arthritis Power will offer a variety of clinical trial and other research opportunities, allowing patients to proactively decide when and how to participate. Securely donated data will be used by patients, universities, research facilities, and physicians to better understand how to fight these diseases and perhaps, contribute to finding elusive cures. Arthritis Power data will be collected using a smart phone, laptop, desktop or tablet where there is an Internet connection.
“Patient-centered research means that we can more effectively use big data to answer questions that are important to those living with these illnesses. This opportunity will produce results that help patients weigh the value of health-care options according to their personal circumstances, conditions, and preferences,” says Jeffrey Curtis, M.D., M.S., MPH, William J. Koopman Endowed Professor in Rheumatology and Immunology in the UAB Division of Clinical Immunology and Rheumatology.
Biometric technologies are on the rise. By electronically recording data about individual’s physical attributes such as fingerprints or iris patterns, security and law enforcement services can quickly identify people with a high degree of accuracy.
The latest development in this field is the scanning of irises from a distance of up to 40 feet (12 metres) away. Researchers from Carnegie Mellon University in the US demonstrated they were able to use their iris recognition technology to identify drivers from an image of their eye captured from their vehicle’s side mirror.
The developers of this technology envisage that, as well as improving security, it will be more convenient for the individuals being identified. By using measurements of physiological characteristics, people no longer need security tokens or cumbersome passwords to identify themselves.
Oral care products containing a natural chemical that stops bacteria harming teeth could help fight decay, research shows.
The plant natural product acts against harmful mouth bacteria and could improve oral health by helping to prevent the build-up of plaque.
The compound – known as trans-chalcone – is related to chemicals found in liquorice root.
This exciting discovery highlights the potential of this class of natural products in food and healthcare technologies.
The University study shows that it blocks the action of a key enzyme that allows the bacteria to thrive in oral cavities.
The bacteria – Streptococcus mutans – metabolise sugars from food and drink, which produces a mild acid and leads to the formation of plaque.
Without good dental hygiene, the combination of plaque and mouth acid can lead to tooth decay.
Researchers found that blocking the activity of the enzyme prevents bacteria forming a protective biological layer – known as a biofilm – around themselves.
Plaque is formed when bacteria attach themselves to teeth and construct biofilms.
Preventing the assembly of these protective layers would help stop bacteria forming plaque.
Oral care products that contain similar natural compounds could help people improve their dental hygiene.
Blocking enzyme function
The study is the first to show how trans-chalcone prevents bacteria forming biofilms.
The team worked out the 3D structure of the enzyme – called Sortase A – which allows the bacteria to make biofilms.
By doing this, researchers were able to identify how trans-chalcone prevents the enzyme from functioning.
The study, published in the journal Chemical Communications, was supported by Wm. Wrigley Jr. Company.
We were delighted to observe that trans-chalcone inhibited Sortase A in a test tube and stopped Streptococcus mutans biofilm formation. We are expanding our study to include similar natural products and investigate if they can be incorporated into consumer products.
But when children’s temper tantrums or mood swings are beyond the norm, or they are overwhelmed by homework organization, do parents speak up?
Today’s University of Michigan C.S. Mott Children’s Hospital National Poll on Children’s Health finds that many parents of children age 5-17 wouldn’t discuss behavioral or emotional issues that could be signs of potential health problems with their doctors. While more than 60 percent of parents definitely would talk to the doctor if their child was extremely sad for more than a month, only half would discuss temper tantrums that seemed worse than peers or if their child seemed more worried or anxious than normal. Just 37 percent would tell the doctor if their child had trouble organizing homework.
The most common reason for not sharing these details with their children’s doctors? Nearly half of parents believed that these simply were not medical problems. Another 40 percent of parents say they would rather handle it themselves and about 30 percent would rather speak to someone other than a doctor.
“Behavioral health and emotional health are closely tied to a child’s physical health, well-being and development, but our findings suggest that we are often missing the boat in catching issues early,” says Sarah J. Clark, M.P.H., associate director of the National Poll on Children’s Health and associate research scientist in the University of Michigan Department of Pediatrics.
New research finds that misdiagnoses lead to increased risk of incorrect antibiotic use, threatening patient outcomes and antimicrobial efficacy, while increasing healthcare costs. The study was published online today in Infection Control & Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.
“Antibiotic therapies are used for approximately 56 percent of inpatients in U.S. hospitals, but are found to be inappropriate in nearly half of these cases, and many of these failures are connected with inaccurate diagnoses,” said Greg Filice, MD, lead author of the study. “The findings suggest that antimicrobial stewardship programs could be more impactful if they were designed to help providers make accurate initial diagnoses and to know when antibiotics can be safely withheld.”
Additionally, researchers found that overall, only 58 percent of patients received a correct diagnosis, indicating that diagnostic errors were more prevalent in this study than in previous studies unrelated to antimicrobial use. The most common incorrect diagnoses identified by researchers were pneumonia, cystitis, urinary tract infections, kidney infections and urosepsis.
Contributing factors which the researchers said may lead to inaccurate diagnosis and inappropriate antibiotic use include:
Healthcare workers (HCWs) relying on intuitive processes, instead of analytical processes which are more reliable, safe and effective.
HCWs experiencing fatigue, sleep deprivation and/or cognitive overload more prevalent in inpatient settings.
HCWs receiving patients with a previous diagnosis from another provider.
Lack of clinical experience and minimal personal experience with adverse drug effects.
People have tried to print graphene before,” Shah said. “But it’s been a mostly polymer composite with graphene making up less than 20 percent of the volume.”
With a volume so meager, those inks are unable to maintain many of graphene’s celebrated properties. But adding higher volumes of graphene flakes to the mix in these ink systems typically results in printed structures too brittle and fragile to manipulate. Shah’s ink is the best of both worlds. At 60-70 percent graphene, it preserves the material’s unique properties, including its electrical conductivity. And it’s flexible and robust enough to print robust macroscopic structures. The ink’s secret lies in its formulation: the graphene flakes are mixed with a biocompatible elastomer and quickly evaporating solvents.
“It’s a liquid ink,” Shah explained. “After the ink is extruded, one of the solvents in the system evaporates right away, causing the structure to solidify nearly instantly. The presence of the other solvents and the interaction with the specific polymer binder chosen also has a significant contribution to its resulting flexibility and properties. Because it holds its shape, we are able to build larger, well-defined objects.”
Supported by a Google Gift and a McCormick Research Catalyst Award, the research is described in the paper “Three-dimensional printing of high-content graphene scaffolds for electronic and biomedical applications,” published in the April 2015 issue of ACS Nano. Jakus is the paper’s first author. Mark Hersam, the Bette and Neison Harris Chair in Teaching Excellence, professor of materials science and engineering at McCormick, served as coauthor.
The 3-D printed graphene scaffold appeared on the cover of ACS Nano.
An expert in biomaterials, Shah said 3-D printed graphene scaffolds could play a role in tissue engineering and regenerative medicine as well as in electronic devices. Her team populated one of the scaffolds with stem cells to surprising results. Not only did the cells survive, they divided, proliferated, and morphed into neuron-like cells.
“That’s without any additional growth factors or signaling that people usually have to use to induce differentiation into neuron-like cells,” Shah said. “If we could just use a material without needing to incorporate other more expensive or complex agents, that would be ideal.”
The printed graphene structure is also flexible and strong enough to be easily sutured to existing tissues, so it could be used for biodegradable sensors and medical implants. Shah said the biocompatible elastomer and graphene’s electrical conductivity most likely contributed to the scaffold’s biological success.
“Cells conduct electricity inherently — especially neurons,” Shah said. “So if they’re on a substrate that can help conduct that signal, they’re able to communicate over wider distances.”
The use of personalized music playlists with tempo-pace synchronization increases adherence to cardiac rehab by almost 70 per cent—according to a study published in Sports Medicine –Open.
“Cardiac rehab has been proven to improve long-term survival for someone who’s had a heart event by 20 per cent,” said Dr. David Alter, Senior Scientist, Toronto Rehab, University Health Network, and Institute for Clinical Evaluative Sciences. “Our challenge is there is a high drop-out rate for these programs and suboptimal adherence to the self-management of physical activity.”
In Dr. Alter’s study, each research subject’s personalized playlist was the music genre they enjoyed with tempos that matched their pre-determined walking or running pace.
“The music tempo-pace synchronization helps cue the person to take their next step or stride and helps regulate, maintain and reinforce their prescribed exercise pace,” explained Dr. Alter, who is also Research Chair in Cardiovascular Prevention and Metabolic Rehabilitation at Toronto Rehab, UHN.
BLOOMINGTON, Ind. — Over nearly 15 years spent studying ticks, Indiana University’s Keith Clay has found southern Indiana to be an oasis free from Lyme disease, the condition most associated with these arachnids that are the second most common parasitic disease vector on Earth.
He has also seen signs that this low-risk environment is changing, both in Indiana and in other regions of the U.S.
A Distinguished Professor in the IU Bloomington College of Arts and Sciences’ Department of Biology, Clay has received support for his research on ticks from over $2.7 million in grants from the National Science Foundation-National Institutes of Health’s Ecology and Evolution of Infectious Diseases Program and others.
Clay’s lab has found relatively few pathogens in southern Indiana ticks that cause common tick-borne diseases compared to the Northeast and states like Wisconsin and Minnesota.
But Lyme disease has been detected just a few hours north of the region around Tippecanoe River State Park and Lake Michigan’s Indiana Dunes, and Clay said the signs are there that new tick species, and possibly the pathogens they carry, are entering the area.
“Just in the past 10 years, we’re seeing things shift considerably,” Clay said. “You used to never see lone star ticks in Indiana; now they’re very common. In 10 years, we’re likely to see the Gulf Coast tick here, too. There are several theories for why this is happening, but the big one is climate change.”
A vector for disease
The conclusions are drawn from years of work spent mapping tick boundaries and disease risks, but the exact cause of the shifting borders is not clear. In addition to changing temperatures, Clay references changes in animal populations, including deer, which provide large, mobile hosts for the parasites.
Exploring a new frontier of cyber-physical systems: The human body
[Series of videos follows, unfortunately unable to insert videos]
Simulation of electrical impulse propagation through the heart during ventricular fibrillation. Colour represents the transmembrane potential–i.e. the voltage across the cell membrane–on the surface of the heart. Yellow indicates largest potential values while dark red represents resting level. This simulation was performed by Pras Pathmanathan and Richard A. Gray at the US Food and Drug Administration (FDA), using the software package Chaste, together with a high-resolution anatomically-detailed computational mesh of the rabbit ventricles, and was run on FDA’s high performance computing resources in the Center for Devices and Radiological Health (CDRH).
Credit: Pras Pathmanathan and Richard A. Gray, US Food and Drug Administration (FDA)
Ok, the emphasis is on “may”. “…[L]earning to swim early in life may give kids a head start in developing balance, body awareness and maybe even language and math skills.”
Am blessed to be able to swim at work during lunch. The campus has a gym, with swim privileges at the hotel pool on campus. Maybe the swim is keeping some math skills intact!
From the 20 May 2015 Science News article
Loosely based on something our mother told us, it’s that learning to swim early in life may give kids a head start in developing balance, body awareness and maybe even language and math skills.
Mom may have been right. A multi-year study released in 2012 suggests that kids who take swim lessons early in life appear to hit certain developmental milestones well before their nonswimming peers. In the study, Australian researchers surveyed about 7,000 parents about their children’s development and gave 177 kids aged 3 to 5 years standard motor, language, memory and attention tests. Compared with kids who didn’t spend much time in the water, kids who had taken swim lessons seemed to be more advanced at tasks like running and climbing stairs and standing on their tiptoes or on one leg, along with drawing, handling scissors and building towers out of blocks.
Hitting milestones related to motor skills isn’t so surprising, the authors note, since swimming is a very physical activity. A bit more unexpected, they say, are the swimming kids’ advanced skills in language and math — tasks like counting, naming objects and recognizing words and letters. Kids who swam also seemed to be better at following directions. And, in some areas, kids had proportionally better scores on the development tests relative to how long they had been taking lessons.
The authors admit that they can’t conclusively claim that swimming alone is responsible for the developmental advances because the analysis was based on survey data and limited testing with young children. “Simply, we can say that children who participate in swimming achieve a wide range of milestones … and skill, knowledge and dispositions … earlier than the normal population,” the researchers write.
Traits passed between generations are not decided only by DNA, but can be brought about by other materials in cells.
Edinburgh scientists studied proteins found in cells, known as histones, which are not part of the genetic code, but act as spools around which DNA is wound.
Histones are known to control whether or not genes are switched on.
Researchers found that naturally occurring changes to these proteins, which affect how they control genes, can be sustained from one generation to the next and so influence which characteristics are passed on.
The finding demonstrates for the first time that DNA is not solely responsible for how characteristics are inherited.
It paves the way for research into how and when this method of inheritance occurs in nature, and if it is linked to particular traits or health conditions.
It may also inform research into whether changes to the histone proteins that are caused by environmental conditions – such as stress or diet – can influence the function of genes passed on to offspring.
The research confirms a long-held expectation among scientists that genes could be controlled across generations by such changes.
However, it remains to be seen how common the process is, researchers say.
Scientists tested the theory by carrying out experiments in a yeast with similar gene control mechanisms to human cells.
They introduced changes to a histone protein, mimicking those that occur naturally, causing it to switch off nearby genes.
The effect was inherited by subsequent generations of yeast cells.
The study, published in Science, was supported by the Wellcome Trust and the EC EpiGeneSys Network.
We’ve shown without doubt that changes in the histone spools that make up chromosomes can be copied and passed through generations. Our finding settles the idea that inherited traits can be epigenetic, meaning that they are not solely down to changes in a gene’s DNA.
“Frontiers in Psychology is an open access journal that aims at publishing the best research across the entire field of psychology. Today, psychological science is becoming increasingly important at all levels of society, from the treatment of clinical disorders to our basic understanding of how the mind works. It is highly interdisciplinary, borrowing questions from philosophy, methods from neuroscience and insights from clinical practice – all in the goal of furthering our grasp of human nature and society, as well as our ability to develop new intervention methods. The journal thus welcomes outstanding contributions in any domain of psychological science, from clinical research to cognitive science, from perception to consciousness, from imaging studies to human factors, from animal cognition to social psychology.”
It’s time to ask uncomfortable questions about the brain mechanisms that allow ‘ordinary’ people to turn violent, says Itzhak Fried.
What happens in the brains of people who go from being peaceable neighbours to slaughtering each other on a mass scale? Back in 1997, neurosurgeon Itzhak Fried at the University of California, Los Angeles, conscious of the recent massacres in Bosnia and Rwanda, described this switch in behaviour in terms of a medical syndrome, which he called ‘Syndrome E’ 2. Nearly 20 years later, Fried brought sociologists, historians, psychologists and neuroscientists together at the Institute of Advanced Studies in Paris to discuss the question anew. At the conference, called ‘The brains that pull the triggers‘, he talked to Nature about the need to consider this type of mass murder in scientific as well as sociological terms, and about the challenge of establishing interdisciplinary dialogue in this sensitive area.
What are the main features of the syndrome?
There was a myth that the primitive brain is held in check by our more-recently evolved prefrontal cortex, which is involved in complex analysis, and that the primitive, subcortical part takes over when we carry out brutal crimes such as repetitive murder. But I saw it the other way around. The signs and symptoms that I gathered in my research indicated that the prefrontal cortex, not the primitive brain, was responsible, because it was no longer heeding the normal controls from subcortical areas. I called it ‘cognitive fracture’ — the normal gut aversions to harming others, the emotional abhorrence of such acts, were disconnected from a hyper-aroused prefrontal cortex. I also proposed a neural circuitry in the brain that could perhaps account for this. In brief, specific parts of the prefrontal cortex become hyperactive and dampen the activity of the amygdala, which regulates emotion.
If mass murder happens because of activity in the brain, what does this say about personal responsibility?
Perpetrators of repeated killings have the capacity to reason and to solve problems — such as how best practically to kill lots of people rapidly. Proposing the existence of a syndrome does not absolve them of responsibility.
“..today we must assume that if our generation is suffering hardship, violence or the like, not only will we struggle to forget these difficult periods ourselves but our genes too will remember them, carrying traces to be passed on to the next generation or even several generations.”
From the 8 May 2015 post at Scilogs
The science behind a rapid paradigm shift
When the first human genome was decoded, popular thinking went: “If we know the genes, we know the person.” Today, barely 15 years later, science is in the middle of an exciting new area of research, which is entertaining interested members of the public with exciting, if not always serious, headlines. The field alleges that traumatic experiences can be passed down through the generations and even significantly affect the lives of grandchildren. As it turns out, the reality is that genes not only control, but are also controlled. And that is what epigenetics is all about – how are genes controlled and what factors can influence them?
Epigenetics refers to the meta-level of genetic regulation. Under the influence of external factors, epigenetic mechanisms regulate which genes are turned on and off. This helps our fixed genetic material to be more flexible. At the biochemical micro level, epigenetic regulators are responsible for how closely packed individual genomic regions are and therefore how accessible or not they are. This works by small adhered or detached chemical groups. The resulting marking of the genome is read by specialised enzymes that then cause the switching on or off of the genes.
As reasonable as this appears, one consequence is that we will have to say goodbye to a long-established dogma: the idea that genes are immutable in the creation of a living being. And, looking back through the history of science: was Lamarck right, after all? The 19th-century French biologist had claimed that organisms acquired traits to pass on to future generations . It is precisely this mechanism that epigeneticists are on the trail of today. Laboratory experiments with mice have demonstrated that a particular, targeted encoding of individual genes results in the changes being passed on to the offspring. Epigenetic changes, however, are so-called soft changes, as they can be undone. And that is medicine’s great hope – to be able to intervene in the control mechanism from the outside in order to be able to work against, for example, senile dementia.
At this point, the level of possible tension around this new field of research becomes clear. On the one hand, the idea that our human condition can be so strongly “manipulated” by environmental influences can be very disturbing. And rightly so. Previously, we may have had the upbeat expectation that although we are experiencing suffering, the next generation will have it better. However, today we must assume that if our generation is suffering hardship, violence or the like, not only will we struggle to forget these difficult periods ourselves but our genes too will remember them, carrying traces to be passed on to the next generation or even several generations.
A study often mentioned in this context is based on the analysis of data collected in the Netherlands over the years of hunger in 1944-45, during which the population there suffered particularly difficult conditions. The children born at this time were not only smaller, but, as adults, had an increased risk of obesity, cardiovascular problems and neuropsychiatric disorders. In turn, their offspring were again smaller than average – despite food being in ready supply and living conditions having greatly improved.
Use of Force against Inmates with Mental Disabilities in US Jails and Prisons
MAY 12, 2015
This 127-page report details incidents in which correctional staff have deluged prisoners with painful chemical sprays, shocked them with powerful electric stun weapons, and strapped them for days in restraining chairs or beds. Staff have broken prisoners’ jaws, noses, ribs; left them with lacerations requiring stitches, second-degree burns, deep bruises, and damaged internal organs. In some cases, the force used has led to their death.
EVANSTON, Ill. — Treatments used by traditional healers in Nigeria have inspired scientists at Northwestern University to synthesize four new chemical compounds that could one day lead to better therapies for people with psychiatric disorders.
In a paper published online in the journal Angewandte Chemie International Edition, the scientists detail how they created these natural compounds by completing the first total syntheses of two indole alkaloids — alstonine and serpentine. These alkaloids, found in various plant species used by healers in Nigeria to treat people with conditions such as schizophrenia and bipolar disorder, have antipsychotic properties that have potential to improve mental disorder treatments.
The current drugs used for schizophrenia effectively treat delusions and hallucinations but are only partially effective for cognitive impairment. Early experimental research of these new compounds in animal models shows promise in improving cognitive impairment, the Northwestern scientists said.
Traditional healers boil these special plants and produce an extract that they administer to people with symptoms of mental illness. However, this extract isn’t pure, and it contains other compounds and materials that may not be beneficial to people with mental disorders.
“Nature did not intend this plant to produce an antipsychotic drug on its own,” Meltzer said.
The collaborative work to create the compounds took place in the Center for Molecular Innovation and Drug Discovery (CMIDD) at Northwestern, using high-level purification resources and state-of-the-art research instrumentation and equipment. Scheidt is the director of CMIDD.
Through an efficient and stereo-selective synthesis, Scheidt and his team created four separate but related natural products. Now a template exists to continue making these compounds as needed for future studies and ultimately for use in clinical drug trials.
“We can make multi-gram quantities of any of the compounds we want,” Scheidt said. “We built the assembly line and are now uniquely positioned to explore their potential.”
Meltzer is already using these compounds in animal studies in his lab to better understand how they affect brain biology and chemistry in the schizophrenia disease model. Early results from his lab show that the compounds may increase the ability of other antipsychotic drugs to improve cognitive impairment.
Other study authors are Dr. Ashkaan Younai and Bi-Shun Zeng of Northwestern University. This study was supported the Chemistry of Life Processes Institute at Northwestern in the form of an Innovators Grant and the Weisman Family Foundation.
May 11, 2015 – What are the most influential studies on surgery of the lower (lumbar) spine? The “top 100″ research papers in lumbar spine are counted down in a special review in the May 15 issue of Spine, published by Wolters Kluwer.
Dr. Samuel K. Cho and colleagues of Icahn School of Medicine at Mount Sinai, New York City, performed a literature review to analyze and quantify the most important research papers on lumbar spine surgery. Their results raise some interesting “questions, trends and observations”–including the finding that the two most-cited studies focus on situations when spinal surgery should not be performed.
And the Top 100 Lumbar Spine Papers Are…
The goal of the analysis was to identify the 100 most frequently cited papers relevant to lumbar spine surgery and published in spine-related journals. Citation by subsequent papers is a key measure of the relevance and importance of medical studies.
Out of more than 16,500 papers matching the search criteria, 322 were cited at least 100 times. The top-ranked paper–cited more than 1,000 times–was a classic 1990 study showing that many people have common spinal abnormalities on magnetic resonance imaging (MRI) scans–despite having no back pain or other symptoms. A 1994 study on a similar topic was the second most-cited paper, highlighting the need for a “clear correlation” of patients’ symptoms and imaging findings
The third most-cited paper was a 2000 review of an important survey tool (the Oswestry Disability Index) for assessing the impact of low back pain on patients’ lives. Overall, low back pain was the most common topic, addressed by 23 of the top 100 papers. Other frequent topics included spinal biomechanics and degenerative disc disease.
About half of the papers were published during the 1990s, and most originated in the United States. Overall, 63 of the top 100 lumbar spine papers were published in Spine.
Reflecting the current emphasis on evidence-based practice, the most frequently cited author isn’t even a spinal surgeon. That researcher, Dr. Richard Deyo of Oregon Health and Science University, Portland, is a leading authority on patient outcomes research.
The other two most frequently cited authors were Scott D. Boden of Emory University, Atlanta, and Dr. James Weinstein of the Dartmouth Institute, Lebanon, N.H. All three of these “most prolific” authors contributed to the SPORT study–a pivotal clinical trial comparing the benefits of surgery versus nonsurgical treatment for sciatica from herniated lumbar discs. Dr. Weinstein is Editor-in-Chief of Spine, and Dr. Boden and Dr. Deyo are Deputy Editors.
Over the years, rates of spinal surgery have risen, but with wide regional variations. Meanwhile, there are persistent questions about which patients truly benefit from surgery for the common and costly problem of low back pain. Many of the top-cited studies reflect the current emphasis on evidence-based practice–seeking to define groups of patients and characteristics associated with beneficial effects of spinal surgery.
Within the limitations of the review methods used, Dr. Cho and colleagues believe their study provides unique insights into the development and trends of the “challenging subspecialty” of lumbar spine surgery. The researchers add, “This paper identifies those individuals whose contributions to the ever-growing body of knowledge have provided guidance and suggestions for further investigation.”
This blog presents a sampling of health and medical news and resources for all. Selected articles and resources will hopefully be of general interest but will also encourage further reading through posted references and other links. Currently I am focusing on public health, basic and applied research and very broadly on disease and healthy lifestyle topics.
Several times a month I will post items on international and global health issues. My Peace Corps Liberia experience (1980-81) has formed me as a global citizen in many ways and has challenged me to think of health and other topics in a more holistic manner. (For those wishing to see pictures of a 2009 Friends of Liberia service trip to this West African country, please visit www.fol.org. My photo album is included).
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