USC researchers discover the healing power of “rib-tickling”

Unlike salamanders, mammals can’t regenerate lost limbs, but they can repair large sections of their ribs.

In a new study in the Journal of Bone and Mineral Research, a team directed by USC Stem Cell researcher Francesca Mariani takes a closer look at rib regeneration in both humans and mice.

The first author of the paper, USC medical student Marissa K. Srour, was a USC undergraduate when she started the project, which earned a 2011 USC Discovery Scholar Prize. Each year, 10 graduating seniors win these coveted prizes, which recognize exceptional new scholarship.

Using CT imaging, Srour, Mariani and their colleague Janice Lee from the University of California, San Francisco, monitored the healing of a human rib that had been partially removed by a surgeon. The eight centimeters of missing bone and one centimeter of missing cartilage did partially repair after six months.

To better understand this repair process, they surgically removed sections of rib cartilage — ranging from three to five millimeters — from a related mammal, mice. When they removed both rib cartilage and its surrounding sheath of tissue — called the “perichondrium,” the missing sections failed to repair even after nine months. However, when they removed rib cartilage but left its perichondrium, the missing sections entirely repaired within one to two months.

They also found that a perichondrium retains the ability to produce cartilage even when disconnected from the rib and displaced into nearby muscle tissue — further suggesting that the perichondrium contains progenitor or stem cells.

“We believe that the development of this model in the mouse is important for making progress in the field of skeletal repair, where an acute clinical need is present for ameliorating skeletal injury, chronic osteoarthritis and the severe problems associated with reconstructive surgery,” said Mariani, assistant professor of Cell and Neurobiology and principal investigator in the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “At the early stages in our understanding, the mouse provides us with an exceptional ability to make progress, and we are excited about the potential for using cells derived from the rib perichondrium or using rib perichondrium-like cells for regenerative therapy.”

Additional co-authors include: Jennifer L. Fogel, Kent T. Yamaguchi, Aaron P. Montgomery, Audrey K. Izuhara, Aaron L. Misakian, Stephanie Lam and Daniel L. Lakeland from USC; and Mark M. Urata from Children’s Hospital Los Angeles.

Funding came from an Oral and Maxillofacial Surgery Foundation Research Award; the Baxter Medical Scholar Research Fellowship; USC undergraduate fellowships; the Provost, Dean Joan M. Schaeffer, and Rose Hills fellowships; a California Institute of Regenerative Medicine (CIRM) training fellowship; CIRM BRIDGES fellowships through California State University, Fullerton, and Pasadena City College; and the James H. Zumberge Research and Innovation Fund.

The lab also received support for this study and future work from a new National Institutes of Health (NIH) Exploratory/Developmental Research Grant Award (R21AR064462) — given to high-risk, high-reward studies that break new ground or embark in novel directions. The lab earned this prestigious $450,000 grant from the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

The Mariani Lab will also continue its pioneering research through a second new grant from the Merck Investigator Studies Program as well as through a USC Regenerative Medicine Initiative Award with colleagues Gage Crump and Jay Lieberman.

As Mariani explained, “These grants will allow us to address several key questions: Which cells are involved in mediating the repair? How big of a piece of rib can we take out and still see repair? And can we use cells from the rib to get repair in another part of the skeleton? By answering these questions, we are accelerating the discovery of new regenerative therapies for the patients who need them the most.”

Source:USC Stem cell

Milestone Reached in Work to Build Replacement Kidneys in the Lab

 

(A) The explanted engineered porcine kidney construct from implantation. (B) Fluoroscopic angiogram image to demonstrate vascular patency of the harvested kidney construct. Renal artery (RA) and renal vein (RV). 

Regenerative medicine researchers at Wake Forest Baptist Medical Center have addressed a major challenge in the quest to build replacement kidneys in the lab. Working with human-sized pig kidneys, the scientists developed the most successful method to date to keep blood vessels in the new organs open and flowing with blood. The work is reported in journal TECHNOLOGY.

"Until now, lab-built kidneys have been rodent-sized and have functioned for only one or two hours after transplantation because blood clots developed," said Anthony Atala, M.D., director and professor at the Wake Forest Institute for Regenerative Medicine and a senior author on the study. "In our proof-of-concept study, the vessels in a human-sized pig kidney remained open during a four-hour testing period. We are now conducting a longer-term study to determine how long flow can be maintained."

If proven successful, the new method to more effectively coat the vessels with cells (endothelial) that keep blood flowing smoothly, could potentially be applied to other complex organs that scientists are working to engineer, including the liver and pancreas.

The current research is part of a long-term project to use pig kidneys to make support structures known as "scaffolds" that could potentially be used to build replacement kidneys for human patients with end-stage renal disease. Scientists first remove all animal cells from the organ - leaving only the organ structure or "skeleton." A patient's own cells would then be placed in the scaffold, making an organ that the patient theoretically would not reject.

The cell removal process leaves behind an intact network of blood vessels that can potentially supply the new organ with oxygen. However, scientists working to repopulate kidney scaffolds with cells have had problems coating the vessels and severe clotting has generally occurred within a few hours after transplantation.

The Wake Forest Baptist scientists took a two-pronged approach to address this problem. First, they evaluated four different methods of introducing new cells into the main vessels of the kidney scaffold. They found that a combination of infusing cells with a syringe, followed by a period of pumping cells through the vessels at increasing flow rates, was most effective.

Next, the research team coated the scaffold's vessels with an antibody designed to make them more "sticky" and to bind endothelial cells. Laboratory and imaging studies -- as well as tests of blood flow in the lab - showed that cell coverage of the vessels was sufficient to support blood flow through the entire kidney scaffold.

The final test of the dual-approach was implanting the scaffolds in pigs weighing 90 to 110 pounds. During a four-hour testing period, the vessels remained open.

"Our cell seeding method, combined with the antibody, improves the attachment of cells to the vessel wall and prevents the cells from being detached when blood flow is initiated," said In Kap Ko, Ph.D., lead author and instructor in regenerative medicine at Wake Forest Baptist.

The scientists said a long-term examination is necessary to sufficiently conclude that blood clotting is prevented when endothelial cells are attached to the vessels. If the new method is proven successful in the long-term, the research brings them an important step closer to the day when replacement kidneys can be built in the lab.

"The results are a promising indicator that it is possible to produce a fully functional vascular system that can deliver nutrients and oxygen to engineered kidneys, as well as other engineered organs," said Ko.

Using pig kidneys as scaffolds for human patients has several advantages, including that the organs are similar in size and that pig heart valves - removed of cells - have safety been used in patients for more than three decades.

This study was supported, in part, by Telemedicine and Advanced Technology Research Center at the U.S. Army Medical Research and Materiel Command. Co-researchers were Mehran Abolbashari, M.D., Jennifer Huling, B.S., Cheil Kim, M.D., Ph.D., Sayed-Hadi Mirmalek-Sani, Ph.D., Mahmoudreza Moradi, M.D., Giuseppe Orlando, M.D., John D. Jackson, Ph.D., Tamer Aboushwareb, M.D., Shay Soker, Ph.D., and Anthony Atala, M.D., all with Wake Forest Baptist.

Decoding 'sweet codes' that determine protein fates

Depicting the dynamic structures of sugar chains by an NMR-validated simulation

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of the Institute for Molecular Science, National Institutes of Natural Sciences developed a methodology for quantitatively describing the dynamic behaviors of complicated sugar chains in solution at atomic resolution by combining a sophisticated NMR spectroscopic approach with an ingenious molecular dynamics simulation technique. This study has just been published in Angewandte Chemie International Edition (published online on September 4, 2014), a scientific journal that is published on behalf of the German Chemical Society.
The sugar chains are flexible accessories decorating the surface of proteins. These variable accessories actually mediate protein-protein communication and even determine the fates of the protein. In other words, the sugar chains serve as transformable "code" that governs the protein's action in our body. For example, it has been revealed that particular sugar chains modifying lipids on cell surfaces offer acceptor sites for viral infections and trigger conformational changes of proteins involved in neurodegenerative disorders including Alzheimer's disease. Hence, decoding the sugar codes is desired not only for better understanding the molecular mechanisms behind a variety of biological processes but also for designing new drugs targeting these processes. However, conformational characterization of the sugar chains has been hampered by their dynamic properties.
Many experimentalists and theorists have taken on the challenge to solve this problem. NMR spectroscopy is one of the most promising experimental approaches for conformational analyses of the sugar chains because of its ability to determine geometrical arrangements of the atoms constituting biomolecules in solution. However, if a biomolecule undergoes rapid motion as in the case of the sugar chains, NMR provides information averaged over all its possible conformational snapshots. By contrast, a molecular dynamics simulation can provide a movie that describes the dynamic behaviors of sugar chains. However, the simulation results should be experimentally validated to guarantee their accuracy.
Kato's research group successfully combined these two complementary approaches and thereby captured distinct conformational snapshots of two very similar sugar chains in dynamic motion. This success was achieved on the basis of several key breakthrough techniques. Firstly, the group employed genetically engineered yeast cells for production of homogeneous oligosaccharides in sufficient quantity with stable isotope labeling, which is necessary for detailed NMR analyses. Secondly, a paramagnetic probe was introduced specifically at one end of the oligosaccharides in order to obtain atomic-distance information. Thirdly, they used the high-field NMR spectrometers and the supercomputer facility operated by the Institute for Molecular Science.
As Professor Kato notes, "This success enables us quantitative and highly sensitive characterization of minor but biologically relevant conformational species of sugar chains and will open the door for observing the dynamic behavior of flexible biomolecules as potential drug targets".
Source:Angewandte Chemie International Edition

 

Estrogen Increases Cannabis Sensitivity: Study

New research from Washington State University suggests that smoking today's concentrated pot might be risky business for women.

The study is the first to demonstrate sex differences in the development of tolerance to THC.

 Psychology professor Rebecca Craft showed that, thanks to their estrogen levels, female rats are at least 30 percent more sensitive than males to the pain-relieving qualities of THC—the key active ingredient in cannabis. Females also develop tolerance to THC more quickly. These sensitivities could increase vulnerability to negative side effects like anxiety, paranoia and addiction. 

The findings were recently published in the journal Drug and Alcohol Dependence. The research was supported by a grant from the National Institute on Drug Abuse. 

Many unknowns
Craft said other researchers, like Margaret Haney at the Columbia University Medical Center, have shown that women are more susceptible to cannabis abuse and dependence than men. Haney has documented a cannabis withdrawal syndrome of irritability, sleep disruption and decreased food intake that Craft said tends to be more severe in women. Women also have a greater tendency to relapse when trying to stop using the drug. 

Despite the known differences in how marijuana affects the sexes, Craft said most THC tolerance studies have been done on males. 

With recent legalization of recreational marijuana in Washington and Colorado—and many more states allowing medicinal use—Craft said there is greater burden on researchers to understand the effects of cannabis and ferret out differences between males and females. 

She said the "munchie effect" appears to be the only THC reaction where males show more sensitivity than females. Studies in California found that THC stimulated the appetites of male animals more than those of females. 

Cannabis complex The marijuana plant contains more than 60 compounds known as cannabinoids. THC, or tetrahydrocannabinol, is the psychoactive ingredient behind the characteristic mental high. Cannabidiol and cannabinol occur in smaller amounts but may be useful for medical purposes. 

All three compounds are present in the most common species of marijuana, Cannabis sativa and C. indica, but in varying proportions. 

Craft said most medical marijuana patients prefer a balance between the cannabinoids. But when it comes to recreational pot, selective breeding has resulted in THC concentrations double or triple those seen in the 1960s and 70s. 

"Marijuana is very different than it was 40 years ago," she said. "It's much higher in THC and lower in cannabidiol, so a little bit goes a very long way. 

"We're more likely to see negative side effects today like anxiety, confusion, panic attacks, hallucinations or extreme paranoia," she said. "And women are at higher risk." 

One of the few female studies 
Most clinical drug trials have been conducted on men due to their more stable hormonal profile. Despite the recommendation of the National Institutes of Health in 1993 to include more women in studies or give good reasons not to, many researchers still avoid dealing with the hormone swings inherent in a woman's biology. 

But Craft has been studying drug sensitivities in females for years. 

Working with rats in her laboratory, Craft said she and her team "routinely manipulate hormones and follow females across their cycles to see if their drug sensitivities change along with their hormones. And they do...very frequently." Estrogen is the culprit. 

"What we're finding with THC is that you get a very clear spike in drug sensitivity right when the females are ovulating - right when their estrogen levels have peaked and are coming down," she said. 

Surprise finding In the current study, Craft and her team examined the pain relieving effects of THC in male and female rats. After 10 days of treatment, tolerance to THC was shown to be significantly greater in females than males. 

Tolerance occurs when the rat "adapts" to THC so that larger doses are required to produce the same pain-relieving effects initially seen with the first dose. 

Because Craft already knew that females were more sensitive to THC, she adjusted their doses to be 30 percent lower than doses for males. The females still developed more tolerance. 

"This is the lowest dose anyone has ever used to induce tolerance," she said. 

The team also found that a low dose of THC did not disrupt the reproductive cycle in female rats, something that has been under debate and, Craft said, needs more study. 

Medical marijuana 
Hoping to gain greater insights into marijuana's medical potential, Craft and her team are also studying the effects of cannabidiol, which can counter some of THC's negative side effects. 

The THC and cannabidiol studies will be extended to include chronic types of pain typically seen in people who request medical marijuana—such as those with debilitating back or joint pain, cancer, Crohn's disease, multiple sclerosis, severe muscle spasms and more. 

"These people have pain that lasts for months or years," Craft said. "Tolerance develops differently and sometimes you get a lot less tolerance to a drug when people are in chronic pain." 

Craft uses a standard research formulation of delta-9-THC for her studies and is approved by the U.S. Drug Enforcement Administration to work with Schedule I drugs such as cannabis. 

 

Centre to bring all paramedical studies in the country under a single regulatory body

In order to streamline and standardise the allied medical education in the country, the Union health ministry will soon take initiatives under which all paramedical studies in the country will be brought under a single regulatory body.  In this direction, the ministry will form a National Board of Allied Health Services by the year-end as a facilitator. 

This was announced recently by Vishwas Mehta, joint secretary in the Union Ministry of Health and Family Welfare, while addressing a two-day conference on Allied Health Professionals and their importance in the role of healthcare services at the Amrita Institute of Medical Sciences (AIMS), Kochi. 

Mehta said that a national task force set up by the health ministry with experts from all over the country would decide the curriculum for various courses that would be brought under the bracket of allied health services. 

He said that there are about 130 courses that follow different course schedules and different curriculum in about thousand institutions and the task force would first focus on ten courses that would soon get a proper guideline and curriculum. Allied courses related to ophthalmology, rehabilitation, medical lab technology, audiology, dental assistance, surgery and anaesthesia are among the subjects that will get immediate attention. 

Kavitha Narayan, Project Director of National Initiative for Allied Health Sciences (NIAHS) said the recommendation of the task force would be to conduct these courses in medical colleges or institutes affiliated to tertiary-level medical care. She said the course would be offered in five different levels certificate course, diploma, degree, post-graduation and doctoral levels. However, she said that without clinical exposure, the courses would not meet international quality norms. 

Earlier in its report submitted to the union health ministry, the NIAHS had pointed out that a considerable regulatory gap in the allied health space is attributed to the lack of a comprehensive regulatory framework and absence of centres for excellence or apex bodies for professional development and training of AHPs.  A number of councils such as the Medical Council of India (MCI), Dental Council of India (DCI) to name a few, have already been established by government of India for regulating the standards of education and training, as well as the registration of practitioners in respective fields.  The aim is to prevent unqualified people from practicing and also for maintain the standards of these professions. 

However, there is no central regulatory mechanism for AHPs. As these councils are established by an Act, it is recommended to set up a National Board for Allied Health Sciences as an interim measure to undertake the work of capacity augmentation and re-organization for this group of the healthcare workforce, the NIAHS in its report to the ministry had recommended.
Source:Pharmabiz

New Evidence Points to Outcomes and Cost Benefits of Telemedicine in Managing Chronic Diseases

Congestive heart failure, stroke, and chronic obstructive pulmonary disease (COPD) are three of the leading causes of death in the U.S. The use of telemedicine to help manage chronic diseases such as these can yield clear benefits including fewer and shorter hospital stays, fewer emergency room visits, less severe illness, and even fewer deaths, as reported in a study published inTelemedicine and e-Health, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Telemedicine and e-Healthwebsite until October 10, 2014. 

Rashid Bashshur, PhD, Gary Shannon, PhD, and Brian Smith, MS, led a team of clinicians and researchers from the U.S. and Canada that included Telemedicine and e-Health Co-Editors-in-Chief Charles R. Doarn, MBA, and Ronald C. Merrell, MD, in the study entitled "The Empirical Foundations of Telemedicine Interventions for Chronic Disease Management." The advantages enabled by telemedicine derive from its ability to help patients become more involved in their own care, facilitate continuous monitoring and early detection of new and recurring symptoms, and allow for prompt responses to worsening illness.

"The integration of telemedicine into healthcare adds great value in managing chronic disease both for patient and provider," says Co-Editor-in-Chief Charles R. Doarn, MBA, Research Professor of Family and Community Medicine, University of Cincinnati, Ohio. "Dr. Bashshur has presented this work to both the U.S. Congress and the Congressional Budget Office, and with concomitant efforts by the American Telemedicine Association and others, the Congress may finally move telemedicine forward as an important element in healthcare for all Americans."  
Source: Telemedicine and e-Health

  

Even small stressors may be harmful to men’s health, new OSU research shows

Older men who lead high-stress lives, either from chronic everyday hassles or because of a series of significant life events, are likely to die earlier than the average for their peers, new research from Oregon State University shows.

“We’re looking at long-term patterns of stress – if your stress level is chronically high, it could impact your mortality, or if you have a series of stressful life events, that could affect your mortality,” saidCarolyn Aldwin, director of the Center for Healthy Aging Research in the College of Public Health and Human Sciences at OSU.

Her study looked at two types of stress: the everyday hassles of such things as commuting, job stress or arguments with family and friends; and significant life events, such as job loss or the death of a spouse.

Both types appear to be harmful to men’s health, but each type of stress appears to have an independent effect on mortality. Someone experiencing several stressful life events does not necessarily have high levels of stress from everyday hassles, Aldwin said. That is determined more by how a person reacts to the stress.

“It’s not the number of hassles that does you in, it’s the perception of them being a big deal that causes problems,” Aldwin said. “Taking things in stride may protect you.”

Aldwin’s latest research on long-term patterns of stress in men was published recently in the journal “Experimental Gerontology.” Co-authors of the study were Yu-Jin Jeong of Chonbuk National University in Korea; Heidi Igarashi and Soyoung Choun of OSU; and Avron Spiro III of Boston University. The research was funded by the National Institutes of Health and the Department of Veterans Affairs.

The researchers used data from the Veterans Affairs Normative Aging Study. They studied stressful life events and everyday hassles for 1,293 men between 1989 and 2005 then followed the men until 2010. About 43 percent of the men had died by the end of the study period.

About a third of the men who reported having few stressful life events had died, while closer to half of the men reporting moderate or high numbers of stressful events had died by the end of the study.

Men who reported few everyday hassles had the lowest mortality rate, at 28.7 percent. Just under half of the men reporting a mid-range number of hassles had died by the end of the study, while 64.3 percent of the men reporting a high number of hassles had died.

Stressful life events are hard to avoid, but men may live longer if they’re able to control their attitudes about everyday hassles, such as long lines at the store or traffic jams on the drive home, Aldwin said.

“Don’t make mountains out of molehills,” she said. “Coping skills are very important.”

The study gives a snapshot of the effects of stress on men’s lives and the findings are not a long-term predictor of health, she said. Stress and other health issues can develop over a long period of time.

Aldwin said future research will look more closely at the different stressors’ effects on health to see if the two types of stress have similar or different impacts on the body’s physiology. Understanding how stress affects health.

Source:Experimental Gerontology

Study examines vitiligo, alopecia areata and chronic graft vs. host disease

Vitiligo (depigmentation of the skin) and alopecia areata (AA, patchy or complete hair loss) in patients with chronic graft-vs-host disease (GvHD) following a stem cell transplant appear to be associated with having a female donor and the sex mismatch of a female donor and male recipient.
GvHD is a frequent complication of donor stem cell transplants because donor cells can attack the recipient's body and cause death and other illnesses. The skin is the most commonly affected organ. The underlying biology of chronic GvHD has not been fully explained. The authors looked for laboratory markers, transplant-related and other factors associated with vitiligo and/or AA in patients with chronic GvHD.
The study conducted by the NIH included 282 adult and pediatric patients with chronic GvHD seen under an NIH protocol between 2004 and 2013.
A total of 15 patients (5.3 percent) from among 282 participants with vitiligo and/or AA were identified. The most common reasons for transplantation were types of leukemia. In the study group, a donor who is female, in particular a female donor and a male recipient sex mismatch, as well as the presence of certain antibodies were associated with the risk of vitiligo and/or AA.

"Although vitiligo and AA are not life threatening, the psychological consequences in patients with chronic GvHD can further impair quality of life. Future studies are needed to clarify whether the risk factors identified in this study could lead to better understanding of other autoimmune manifestations in the setting of chronic GvHD."

Source:JAMA Dermatology

Penn Study Finds Genetic Mutations Linked With Ethnic Disparities in Cancer

One of the goals of genome sequencing is to identify genetic mutations associated with increased susceptibility to disease. Yet by and large these discoveries have been made in people of European or Asian ancestry, resulting in an incomplete picture of global genetic variation in disease vulnerability.

In a new study published in the journal BMC Medical Genomics, researchers at the University of Pennsylvania have addressed this omission. Their investigation identified more than 30 previously undescribed mutations in important regulatory molecules called microRNAs. Many of these mutations influence whether a person develops cancer or the severity of the disease.

One variant has been associated with breast cancer mortality, and the team’s discovery could help explain why, once diagnosed with breast cancer, women with African ancestry are more likely to die from the disease than other women. Knowing about these differences could inform efforts to develop diagnostic tests or even treatments for diseases like cancer.

Renata A. Rawlings-Goss, a postdoctoral fellow in the Department of Genetics in Penn’s Perelman School of Medicine, led the work, collaborating with the department’s Michael C. Campbell. Sarah Tishkoff, a Penn Integrates Knowledge professor with appointments in Penn Medicine’s Department of Genetics and the School of Arts & Sciences’ Department of Biology, was the study’s senior author.

MicroRNAs, or miRNAs, are small molecules that are not translated into proteins but rather serve to regulate gene expression, usually by blocking protein production. A single miRNA can govern the expression of as many as 6,000 different genes, so a change in the way they function can have significant biological effects.

Because miRNAs have the potential to affect a host of genes, scientists have become interested in their role in disease. Several miRNAs have been implicated as biomarkers for diseases including diabetes, asthma and various cancers.

To better understand miRNA diversity across the world, the Penn team searched for miRNA variants in the genome sequences of 69 individuals from 14 populations from Europe, Asia, the Americas and Africa. The samples included genetic material collected by Tishkoff and members of her lab from diverse African populations, including three hunter-gatherer populations.

“We wanted to try to see if there was variability in miRNA that hadn’t been identified before,” Rawlings-Goss said.

Overall, the researchers found that miRNA sequences were similar across the populations they sampled, likely because of how critical they are for regulating genes involved in key physiological functions. Nevertheless, they did identify 33 novel variants that appeared in more than one individual and found many that were closely associated with particular populations. Taken as a whole, African groups had more diversity of miRNA expression than the other populations they examined.

The researchers searched available databases to see which genes these miRNAs were known to inhibit. Their query turned up a large proportion of genes involved in glucose and insulin metabolism, indicating a possible connection between diabetes risk and possessing one of these variants. The search also pointed to effects on genes involved in cell division, a process that is disrupted in cancers.

“Several of the new miRNA variants we identified have been studied in correlation with cancer onset, progression and severity,” Rawlings-Goss said.

Looking specifically at miRNA variants that were more frequently associated with particular ethnic populations, the Penn team found seven that have previously been connected to a variety of types of cancer.

“I was really interested to see that among the diseases that turned up were breast, ovarian and prostate cancer,” Rawlings-Goss said. “All three of those cancers show a pretty systematic and well documented difference between people of African background and European or Asian background.”

One mutation, miRNA 202, was of particular interest.

“There have been some studies done that show that genetic variation at this site changes the amount of miRNAs that are produced,” Rawlings-Goss said. “This variant is protective against breast cancer mortality, and it appears at significantly lower frequency in African samples.”

This finding could help explain the long-observed disparity in breast cancer survival rates between women of African ancestry and women of European ancestry.

“It’s becoming more and more apparent that miRNAs can have a broad-reaching and global effect on our health and adaptation to disease,” said Rawlings-Goss. “Learning more about differences across populations could be helpful to doing early diagnostics and treating disease across diverse populations.”

The study was supported by a National Institutes of Health Pioneer Award to Tishkoff and a National Institute of Health postdoctoral fellowship to Rawlings-Goss.

Source: University of Pennsylvania

An evolutionary approach to epidemics

An evolutionary analysis of public health data during a major disease outbreak, such as bird flu, E. coli contamination of food or the current Ebola outbreak could help the emergency services plan their response and contain the disease more effectively. Details are reported in the International Journal of Innovative Computing and Applications.
Dehai Liu of the Dongbei University of Finance and Economics, in Dalian, Liaoning, China, and colleagues have used evolutionary game theory to examine the data associated with a major public health event - the emergence of a new pandemic virus. The team explains that the characteristics of disease outbreaks in the modern world have shifted since the advent of high-speed air travel. Moreover, increased population density and changes in economics have meant that the progress of an epidemic will not necessarily follow the course nor move at the speed of historical "plagues" even up to the global influenza outbreaks of the twentieth century.
Evolutionary game theory is a mathematical tool that allows researchers to simulate various scenarios and predict outcomes. It essentially applies Darwinian selection to the contests, strategies, and analytics that various "actors" in the scenario might be involved. The Chinese team has now applied this approach to understanding the spread of disease and demonstrated that there are four main outcomes one might see with a pandemic in today's world all affected by the government response to the outbreak, the provision of healthcare, the isolation of patients and availability of treatments of the given disease.
Their approach tested on actual data from the 2009 outbreak of influenza A (H1N1) accords with a scenario involving active prevention and control, which led to limited casualties of the epidemic. The ongoing analysis of data associated with the current outbreak of Ebola might be exploited to ensure quarantine and control measures are put in place effectively to prevent widespread deaths from this lethal disease and likewise with future emergent pathogens.
Source:International Journal of Innovative Computing and Applications

Some sickle cell patients miss out on treatment

Study looks at reasons why patients do not adhere to available treatment

Experiencing discrimination because of their race or health condition can influence just how much trust people put into the health profession. In fact, having these experiences was associated with a 53-percent increase in the chances that someone suffering from sickle cell disease will not follow their doctors’ orders, says Carlton Haywood Jr. of the Berman Institute of Bioethics and the Johns Hopkins School of Medicine in the US. Haywood led a study1 appearing in the Journal of General Internal Medicine², published by Springer, into the experiences of how patients who suffer from this debilitating genetic disorder experience the healthcare system.

Sickle cell disease is a serious debilitating disorder that affects both a person’s body and psyche. People who suffer from this hereditary condition experience acute and chronic pain, and are more susceptible to infections, strokes and neurological problems. As patients grow older, they also experience more organ- and tissue-related problems. Approximately 100,000 Americans have this condition, which can be detected by genetically screening newborn babies.

To ensure patients enjoy a better quality of life, those suffering from the disease should be able and willing to adhere to the small handful of medication and treatment options available to them. However, many reports show that such patients often do not do so. To scrutinize the reasons behind such non-adherence, Haywood’s team monitored the experiences of 291 patients with sickle cell disease who were treated at two academic medical centers in the Baltimore/Washington D.C. metropolitan area. The results comprise part of the Improving Patient Outcomes with Respect and Trust (IMPORT) study.

In total, more than a third of the patients monitored said that they did not always follow doctors’ orders. Haywood’s team analyzed the results further, and found that 58 percent of the non-adherent group, compared to 43 percent of the adherent group, had at least one experience of being discriminated against based on their race or health status. The researchers also found that people who had previously experienced discrimination were 53 percent more likely to not always stick to their physician’s recommendations.

The findings are consistent with previous studies among other chronically ill patient groups. These also show how discrimination affects a patient’s trust in the healthcare system, and the person’s subsequent willingness to follow prescribed treatment regimens.

Haywood believes the perceptions and experiences of being discriminated against may increase the chances of sickle cell patients not fully benefiting from the health care that is available to them.

“A good relationship between the patient and provider can facilitate adherence, while a problematic relationship can negatively impact patient adherence,” says Haywood. “Improving relationships between healthcare providers and such patients may improve their trust in medical professionals, which in turn may improve other outcomes among this underserved patient population.”

Reference: 
1. Haywood, C. et al (2014). Perceived Discrimination, Patient Trust, and Adherence to Medical Recommendations Among Persons with Sickle Cell Disease, Journal of General Internal Medicine. DOI 10.1007/s11606-014-2986-7.
2. The Journal of General Internal Medicine is the official journal of the Society of General Internal Medicine. 

Another Groundbreaking Study Emerges Linking Agricultural Pesticides To Autism – And That’s Not All

Numerous studies have clearly outlined the health and environmental dangers that are associated with pesticides, more specifically, agricultural pesticides. They’ve been linked to cancer, birth defects, Alzheimer’s disease, Parkinson’s disease, kidney failure and many more.

It’s remarkable how we continue to spray these all over our food. In the past decade alone, scientists from all over the world have conducted studies that now link them with autism. Keep in mind, autism is a very large spectrum, some of it may be evolution, and in many other cases, neurodevelopment is largely hampered  due to the factors mentioned in this article (and more). Here is one of the (out of what could be many) reasons why:

Pesticides Increase Risk By 2/3

A study coming out of the University of California, Davis, determined that pregnant women who live in close proximity to land and farms where chemical pesticides are/were applied experience a two-thirds increased risk of having a child with autism spectrum disorder or some other developmental disorder.

The study examined associations between pesticides, including organophosphates (a main ingredient in Monsanto’s Roundup herbicide)  that were applied during the participants’ pregnancies and a later diagnosis of autism or developmental delay in their children.

The study was published this summer, online in the journal Environmental Health Perspectives.(1) It concluded that proximity to organophosphates alone at some point during gestation was associated with a 60% increased risk for ASD.

“This study validates the results of earlier research that had reported associations between having a child with autism and prenatal exposure to agricultural chemicals in California. While we still must investigate whether certain sub-groups are more vulnerable to exposures to these compounds than others, the message is very clear: Women who are pregnant should take special care to avoid contact with agricultural chemicals whenever possible.”  – Janie F. Shelton, a UC Davis graduate student who now consults with the United Nations, lead author of the study. 

The study examined commercial pesticide use in California, and used data from the California Pesticide Use report alongside data from the residential addresses of approximately 1000 participants in the Northern California area that participated in the Childhood Risk of Autism from Genetics and the Environment study (CHARGE)

“CHARGE (Childhood Autism Risks from Genetics and the Environment) was launched in 2003 as the first comprehensive study of environmental causes and risk factors for autism and developmental delay. The CHARGE study recognizes that no single factor accounts for all autism cases, nor is there one event or exposure that can be responsible for the rapid increase in diagnoses over the last few decades. Instead, each child’s path to altered brain development may be different.” 

I think the above explanation for autism is great. I do agree that there is not one single event that is responsible, I think it includes a number of factors that allow toxins to enter into the body from fetal development and early childhood, and there is a lot of evidence which suggests this.

“Organophosphates applied over the course of pregnancy were associated with an elevated risk of autism spectrum disorder, particularly for chlorpyrifos applications in the second trimester. Pyrethroids were moderately associated with autism spectrum disorder immediately prior to conception and in the third trimester. Carbamates applied during pregnancy were associated with developmental delay. Exposures to insecticides for those living near agricultural areas may be problematic, especially during gestation, because the developing fetal brain may be more vulnerable than it is in adults. Because these pesticides are neurotoxic, in utero exposures during early development may distort the complex processes of structural development and neuronal signaling producing alterations to the excitation and inhibition mechanisms that govern mood, learning, social interactions and behaviour.”(1)

More Studies Regarding Autism and Toxins

A new study published in the journal PLOS Computational Biology, from researchers at the University of Chicago revealed that autism and intellectual disability (ID) rates are linked with exposure to harmful environmental factors during congenital development. (2)

The team analyzed data that covered more than one third of the U.S. population. Data from individual states and more than 2,100 counties were used. Fetuses, particularly males, are sensitive to multiple toxins such as environmental lead, medications and a wide variety of other synthetic molecules, like pesticides, mercury and more. Exposure to these toxins during critical stages of development is thought to explain a large portion of congenital reproductive malformations.

Our environment is full of neurodevelopmental toxins, which means they alter how the brain grows. Mercury, polychlorinated diphenyl, lead, brominated flame retardants and pesticides are a few of many examples. Don’t forget about insecticides and herbicides.

Another recent study published in the New England Journal of Medicine compared brain autopsies of autistic children who had died from unrelated causes to those of normal ones. The autistic brains demonstrated abnormal patches of disorganized neurons that disrupted the usual distinct layers in the brain’s cortex. The study suggests that abnormalities occurred in utero during key developmental stages between 19 to 30 weeks gestation. It’s not just the toxin, it’s the timing of the exposure. (3)

Another study outlines how glyphosate toxicity leads to the suppression of critical enzymes, and as a result links the Western diet to heart disease, Alzheimer’s, Parkinson’s, autism and more. (4)

In another case, a group of scientists put together a comprehensive review of existing data that shows how European regulators have known that Monsanto’s glyphosate causes a number of birth malformations since at least 2002. Regulators misled the public about glyphosate’s safety, and in Germany the Federal Office for Consumer Protection and Food Safety told the European Commission that there was no evidence to suggest that glyphosate causes birth defects (5)

A new study published in the journal Biomedical Research International  shows that Roundup herbicide is 125 times more toxic than its active ingredient glyphosate studied in isolation.(16)

There is more research confirming that mothers who are exposed to commonly used, “safe” pesticides give birth to children with lower intelligence, structural brain abnormalities, behavioral disorders, compromised motor skills, higher rates of brain cancer and small head size. (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)

Sources:

http://www.ucdmc.ucdavis.edu/publish/news/newsroom/8978

(1) http://ehp.niehs.nih.gov/1307044/

(2) http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1003518

(3) http://www.nejm.org/doi/full/10.1056/NEJMoa1307491

(4) http://www.mdpi.com/1099-4300/15/4/1416

(5) http://earthopensource.org/files/pdfs/Roundup-and-birth-defects/RoundupandBirthDefectsv5.pdf

(16) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955666/

6.Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, et al. 2011. Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Common Agricultural Pesticide. Environ Health Perspect 119:1196-1201. 

7. Bouchard M, Chevrier J, Harley K, Kogut K, Vedar M, Calderon N, Trujillo C, Johnson C, Bradman A, Barr D, Eskenazi B. Prenatal Exposure to Organophosphate Pesticides and IQ in 7-Year Old Children. Environmental Health Perspectives, 2011; DOI: 10.1289/ehp.1003185

8. Engel S, et al. Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood. Environmental Health Perspectives, 2011; DOI: 10.1289/ehp.1003183

9. Horton M, et al. Impact of Prenatal Exposure to Piperonyl Butoxide and Permethrin on 36-Month Neurodevelopment. Pediatrics 2011; 127:3 e699-e706; doi:10.1542/peds.2010-0133

10.  Horton M, Kahn L, Perera F, Barr D, Rauh V. Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory? Neurotoxicology and Teratology, 2012; DOI: 10.1016/j.ntt.2012.07.004

11. Rauh V, et al. Brain anomalies in children exposed prenatally to a common organophosphate pesticide. PNAS 2012 109 (20) 7871-7876; published ahead of print April 30, 2012, doi:10.1073/pnas.1203396109

12.Oulhote Y, Bouchard M, Urinary Metabolites of Organophosphate and Pyrethroid Pesticides and Behavioral Problems in Canadian Children Environ Health Perspect; DOI:10.1289/ehp.1306667

13.. Ostrea EM, et al. 2011. Fetal exposure to propoxur and abnormal child neurodevelopment at two years of age. Neurotoxicology.

14. Greenop K, Peters S, Bailey H, et al. Exposure to pesticides and the risk of childhood brain tumors. Cancer Causes & Control. April 2013

15. Kimura-Kuroda J, Komuta Y, Kuroda Y, Hayashi M, Kawano H (2012) Nicotine-Like Effects of the Neonicotinoid Insecticides Acetamiprid and Imidacloprid on Cerebellar Neurons from Neonatal Rats. PLoS ONE 7(2): e32432. doi:10.1371/journal.pone.003243

New Study Uses MDMA To Treat Social Anxiety In Autistic People – Can Psychedelics Find A Place In Modern Medicine?

For decades, the empathogenic drug known as MDMA, or 3,4-Methylenedioxy-N-methamphetamine, has been a subject often associated with the early 2000′s rave culture, far extended from association with therapy and other medicinal applications. Unfortunately, being that MDMA is a heavily controlled drug in many countries, proper research for therapeutic applications has been extremely limited, until recently.

MAPS (The Multidisciplinary Association for Psychedelic Studies) broke news this year of the preliminary steps of a ground-breaking new study which is looking at treating autistic patients who suffer from social anxiety with MDMA.

Autistic Therapeutic Interventions

Conventional medication and therapy interventions fail to help treat Autistic patients with social anxiety, could MDMA-assisted therapy be a possible solution?

Although the complex set of distinctions between autistic and non-autistic neurology is not fully understood, we do know that the subjective experience of autistic people tends to bemore intense and chaotic than that of non-autistic individuals, as the impact of information processing tends to be both stronger and less predictable on both the sensorimotor and cognitive levels.

According to MAPS, “the early lives of autistic individuals often involve repeated traumatic experiences of social rejection and abuse (by family, professionals, peers, and others). As a result, many autistic individuals suffer from diagnosed conditions such as anxiety (particularly social anxiety), post-traumatic stress disorder (PTSD), and depression, as well as difficulties with interpersonal connection and social adaptability.”

For the most part, conventional medications are ineffective in treating stress related issues among autistic people, and because autistic people have difficulties building rapport with therapists, traditional psychotherapy also fails to treat the issue. Therefore, new treatment options are being explored in order to provide autistic individuals with an improved quality of life.

Why MDMA?

MDMA has a unique set of psychoactive properties which makes it a viable adjunct to conventional psychotherapy.

First synthesized in 1912, MDMA has been a popular topic of discussion due to its unique psychoactive properties. It is considered an entheogen, a substance which produces spiritual, transcendent experiences for its users.“Its unique pharmacological properties make it a viable adjunct as a therapy for social anxiety in autistic patients”, states the MAPS official study website. Some of these properties include:

• Decreased feelings of fear
• Increased feelings of well-being
• Increased sociability
• Increased interpersonal trust
• Alert state of consciousness
• Increased awareness of some domains of empathy

MDMA-assisted therapy combines the techniques of traditional psychotherapy along with the controlled administration of MDMA in order to enhance the therapy’s effectiveness.

The therapeutic method will be adapted from therapy techniques that have shown clinical effectiveness in adults with an Autism Spectrum diagnosis. Best practices from clinical research on MDMA-assisted psychotherapy for PTSD also will be applied.

MAPS states that the method will focus on developing a therapeutic relationship with the subjects that will provide a permissive setting in which to learn and practice social skills.

A Determined Team of Researchers

Alicia Danforth, Ph.D., co-investigator of the study. Alicia has been studying psychedelic assisted therapy since 2006.

Charles S. Grobs, M.D., will be heading the study looking at MDMA assisted therapy in treating social anxiety among autistic patients.

The study is headed by Charles S. Grob, M.D.,  Director of the Division of Child and Adolescent Psychiatry at Harbor-UCLA Medical Center, as well as Professor of Psychiatry and Pediatrics at the University of California, Los Angeles School of Medicine. Grob’s co-investigator is Alicia Danforth Ph.D, research associate at the Los Angeles Biomedical Research Institute at the Harbor-UCLA Medical Center. 

“The question is: ‘Can we re-engage this area in a responsible, objective way to explore methods of a treatment?’ ” Grob said to the Daily News. “But to do so in a responsible way, unlike what happened in the ’60s.”

Each study participant (who are all adults) who receives the active drug will be given a small dose of 75 to 125 milligrams, and a male and female researcher will sit with them throughout the six to eight hour process, during which they will be closely monitored.

“We try to optimize ‘set and setting’ in order to ensure strong, safe parameters,” Grob said. “I suppose that is ultimately derived from the shamanic model.”

Grobs is one of the growing number of scientists and researchers who believe that psychedelics such as psilocybin, ayahuasca, and MDMA hold the answers for treatment of various mental illnesses and addictions.  His resume definitely isn’t shy of psychedelic research- since the 1990′s Grobs has been involved with rare studies examining the benefits of ayahusaca, and psilocybin.  In both of his studies, Grobs found that psychedelics are helpful in ways that conventional medicine is not.

“We’re looking for something to facilitate positive, ongoing change,” Grob said. “You can’t take an autistic person and make them un-autistic, but you can treat the overwhelming social anxiety.”