Category: Health

{Using a technique that avoids the use of high-dose chemotherapy and radiation in preparation for a stem cell transplant, physicians at the University of Illinois Hospital & Health Sciences System have documented the first cure of an adult patient with congenital dyserythropoietic anemia. CDA is a rare blood disorder in which the body does not produce enough red blood cells, causing progressive organ damage and early death.}

The transplant technique is unique, because it allows a donor’s cells to gradually take over a patient’s bone marrow without using toxic agents to eliminate a patient’s cells prior to the transplant.

Dr. Damiano Rondelli, the Michael Reese Professor of Hematology at the University of Illinois at Chicago, says the protocol can be used even in patients with a long history of disease and some organ damage because of the minimal use of chemotherapy.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant,” said Rondelli, who is also division chief of hematology and oncology and director of the stem cell transplant program at UI Health.

“This procedure gives some adults the option of a stem cell transplant which was not previously available.”

For more than 30 years, Northbrook, Illinois, resident David Levy’s only course of treatment for CDA was regular blood transfusions to ensure his organs and tissues received enough oxygen. Levy was 24 when the pain became so severe he had to withdraw from graduate school.

“I spent the following years doing nothing — no work, no school, no social contact — because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every two to three weeks; had lost his spleen; had an enlarged liver; and was suffering severely from fatigue, heart palpitations and iron poisoning, a side effect of regular blood transfusions.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr. Rondelli.”

Rondelli says that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a stem cell transplant. UI Health’s advances in curing sickle cell patients opened up a new possibility. Rondelli performed Levy’s transplant in 2014.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, now 35. “I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Rondelli says the potential of this approach to stem cell transplantation is very promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias — perhaps the only possible cure,” Rondelli said.

This case report is published in a letter to the editor in the journal Bone Marrow Transplantation.

Source:Science Daily

{Intervention induced several months of remission in up to 40 percent of clinical trial participants}

Type 2 diabetes can be reversed with intensive medical treatment using oral medications, insulin and lifestyle therapies, according to a study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Type 2 diabetes is typically thought of as a chronic condition. As it progresses, individuals with type 2 diabetes often need to use a healthy diet, exercise and an increasingly complex combination of medications to manage the condition.

“By using a combination of oral medications, insulin and lifestyle therapies to treat patients intensively for two to four months, we found that up to 40 percent of participants were able to stay in remission three months after stopping diabetes medications,” said the study’s first author, Natalia McInnes, MD, MSc, FRCPC, of McMaster University and Hamilton Health Sciences, in Hamilton, Ontario, Canada. “The findings support the notion that type 2 diabetes can be reversed, at least in the short term — not only with bariatric surgery, but with medical approaches.”

One in 10 American adults has type 2 diabetes, according to the Society’s Endocrine Facts and Figures report. The condition occurs when an individual doesn’t produce enough insulin — the hormone that allows cells to absorb glucose in the blood — or the pancreas isn’t making insulin as efficiently as it could. As a result, blood sugars build up in the body and the cells do not receive the energy they need.

To study ways to put type 2 diabetes into remission, the researchers randomly divided 83 individuals with the condition into three study groups. Two of the groups received an intensive metabolic intervention where they were provided with a personalized exercise plan and a suggested meal plan that reduced their daily calorie intake by 500 to 750 calories a day. These study participants met regularly with a nurse and dietitian to track their progress and received oral medications and insulin at bedtime to tightly manage their blood glucose levels. One group underwent the intervention for eight weeks, while the other was treated intensively for 16 weeks. After the intervention, individuals in both groups stopped taking diabetes medications and were encouraged to continue with lifestyle changes.

The two intervention groups were compared to a control group of individuals with type 2 diabetes. Participants in this group received standard blood sugar management advice from their usual healthcare provider for the duration of the trial, and they received standard lifestyle advice. Participants in all three groups received usual diabetes care if they experienced a diabetes relapse.

Study participants had their average blood glucose levels from the past two to three months measured using a HbA1C blood test at eight, 20, 28 and 52 weeks to gauge how well their blood sugar was controlled. They also undertook oral glucose tolerance tests.

Three months after the intervention was completed, 11 out of 27 individuals in the 16-week intervention group met HbA1C criteria for complete or partial diabetes remission, compared to four out of 28 individuals in the control group. Three months after finishing the eight-week intervention, six out of 28 individuals in that group met the same criteria for complete or partial diabetes remission.

“The research might shift the paradigm of treating diabetes from simply controlling glucose to an approach where we induce remission and then monitor patients for any signs of relapse,” McInnes said. “The idea of reversing the disease is very appealing to individuals with diabetes. It motivates them to make significant lifestyle changes and to achieve normal glucose levels with the help of medications. This likely gives pancreas a rest and decreases fat stores in the body, which in turn improves insulin production and effectiveness.”

The senior investigator on the trial, Hertzel C. Gerstein, MD, MSc, FRCPC, of McMaster University and Hamilton Health Sciences added, “We chose to use metformin, acarbose and basal insulin glargine in this trial as these medications have all been shown to slow or prevent the development of type 2 diabetes. However, other drug combinations could lead to higher remission rates and need to be systematically studied with regard to this outcome.”

Source:Science Daily

{Treatment with deep brain stimulation can provide lasting relief to patients suffering from previously non-treatable, severe forms of depression several years into the therapy or even eliminate symptoms entirely. This is the finding of the first long-term study on this form of therapy, conducted by scientists at the Medical Center — University of Freiburg. Seven of the eight patients receiving continuous stimulation in the study showed lasting improvements in their symptoms up to the last observation point four years into treatment. The therapy remained equally effective over the entire period. The scientists prevented minor side-effects from appearing by adjusting the stimulation. The study was published in the journal Brain Stimulation on 1 March 2017.}

“Most of the patients respond to the therapy. The remarkable thing is that the effect is also lasting. Other forms of therapy often lose their effectiveness in the course of time. This makes deep brain stimulation a highly promising approach for people with previously non-treatable depression,” says principal investigator Prof. Dr. Thomas Schläpfer, head of the Interventional Biological Psychiatry Unit at the Department of Psychiatry and Psychotherapy of the Medical Center — University of Freiburg. Deep brain stimulation is a method based on mild electric impulses that can be used to influence selected brain regions with great precision.

Stimulation Takes Effect from the First Month On

The eight test subjects had suffered continuously for three to eleven years from a severe depression that responded neither to drugs nor to psychotherapy or treatments like electroconvulsive therapy. The doctors implanted razor-thin electrodes and stimulated a brain region that is involved in the perception of pleasure and is thus also important for motivation and quality of life. The doctors evaluated the effect of the therapy each month with the help of the established Montgomery-Asberg Rating Scale (MARDS). The patients’ average MARDS score fell from 30 points to 12 points already in the first month and even dropped slightly further by the end of the study. Four patients achieved a MARDS score of less then 10 points, the threshold for diagnosis of depression.

Some of the patients suffered briefly from blurred or double vision. “We managed to alleviate the side effects by reducing the intensity of the stimulation, without diminishing the antidepressant effect of the therapy,” says Prof. Dr. Volker A. Coenen, head of the Stereotactic and Functional Neurosurgery Unit at the Department of Neurosurgery of the Medical Center — University of Freiburg. The doctors did not observe personality changes, thought disorders, or other side effects in any of the patients.

{{Larger Follow-Up Study Aims at Registration of Therapy in Europe}}

If a further five-year study with 50 patients currently underway at the Medical Center — University of Freiburg confirms the effectiveness and safety of the therapy, Prof. Coenen sees the possibility of registering the therapy in Europe. This would allow the therapy to be used outside of studies: “In a few years, deep brain stimulation of this kind could be an effective treatment option for patients with severe depressions,” says Prof. Coenen.

Source:Science Daily

{Giving vitamin D supplements to mice during pregnancy prevents autism traits in their offspring, University of Queensland researchers have discovered.}

The discovery provides further evidence of the crucial role vitamin D plays in brain development, said lead researcher Professor Darryl Eyles, from UQ’s Queensland Brain Institute.

“Our study used the most widely accepted developmental model of autism in which affected mice behave abnormally and show deficits in social interaction, basic learning and stereotyped behaviours,” Professor Eyles said.

“We found that pregnant females treated with active vitamin D in the equivalent of the first trimester of pregnancy produced offspring that did not develop these deficits.”

In human studies, QBI researchers recently found a link between pregnant women with low Vitamin D levels and the increased likelihood of having a child with autistic traits.

Autism — or autism spectrum disorder — describes lifelong developmental disabilities including difficulty or inability to communicate with others and interact socially.

Sun exposure is the major source of vitamin D — which skin cells manufacture in response to UV rays — but it is also found in some foods.

Dr Wei Luan, a postdoctoral researcher involved in the study, said vitamin D was crucial for maintaining healthy bones, but the active hormonal form of vitamin D cannot be given to pregnant women because it may affect the skeleton of the developing fetus.

“Recent funding will now allow us to determine how much cholecalciferol — the supplement form that is safe for pregnant women — is needed to achieve the same levels of active hormonal vitamin D in the bloodstream,” said Dr Luan.

“This new information will allow us to further investigate the ideal dose and timing of vitamin D supplementation for pregnant women.

It was previously thought vitamin D had a protective anti-inflammatory effect during brain development, but the study didn’t find this to be the case.

New funding from the National Health and Medical Research Council will allow researchers to continue to study how vitamin D protects against autism.

Source:Science Daily

{MSI-1436 holds potential to restore heart function after a heart attack}

Scientists at the MDI Biological Laboratory and Novo Biosciences have identified a drug candidate to restore heart muscle function following a heart attack. Their research on the role of MSI-1436 in regenerating heart muscle tissue in zebrafish and mice was described in a paper in the peer-reviewed journal, npj Regenerative Medicine.

Cardiovascular disease is the world’s leading killer, taking the lives of 17.5 million people annually, according to the World Health Organization, and disabling millions more. Currently, no drug exists to restore heart muscle function after a heart attack.

“The potential impact of MSI-1436 is enormous,” MDI Biological Laboratory scientist Viravuth P. Yin, Ph.D., one of the paper’s authors, said. “If it shows similar results in humans, it will be a game-changer for patients who suffer a heart attack and/or are living with heart disease.”

The institution is seeking to move the drug into human clinical trials through a spinoff company, Novo Biosciences. The next step is to test the drug in pigs, the animal whose heart most closely resembles that of humans.

The drug has two advantages that are expected to smooth the path to the clinic. First, MSI-1436 stimulates tissue regeneration in zebrafish and mice, which are separated by approximately 450 million years of evolution. This increases the likelihood it will work in humans too. Second, it has already been shown to be well tolerated by patients in Phase 1 and 1b clinical trials for an unrelated indication. The maximum well-tolerated human dose is 5 to 50 times higher than the dose shown to be effective in stimulating heart repair in zebrafish and mice.

“The previous clinical trials of MSI-1436 make a big difference in bringing this drug to market,” said Kevin Strange, Ph.D., president of the MDI Biological Laboratory and one of the paper’s authors. “The path from laboratory bench to patient bedside can be long and difficult. But the fact that MSI-1436 has been shown to be safe for use in humans shaves years off the drug development process.”

Strange is also the CEO and co-founder of Novo Biosciences and the co-inventor of MSI-1436, along with Yin and collaborator Michael A. Zasloff, M.D., Ph.D. Yin is the co-founder and chief scientific officer of Novo Biosciences. The scientists have been issued a patent on the use MSI-1436 for the treatment of heart disease.

The original research on MSI-1436 was conducted by Yin in zebrafish, an organism that can regenerate the form and function of almost any body part. He found that the administration of MSI-1436 increased appendage regeneration by 200 to 300 percent. Follow-up research showed that MSI-1436 also stimulated zebrafish heart regeneration to the same degree.

“That was definitely a ‘Eureka!’ moment,” Yin said of the day in the laboratory when the appendage study was conducted. He was so astonished by the results that he repeated the study several times and under different conditions.

Yin followed the studies in zebrafish with studies in adult mice, which, like humans, have a limited capacity for regeneration. The goal was to see if MSI-1436 could stimulate regeneration in higher organisms. Though mammals such as mice and humans share the genetic pathways for regeneration with zebrafish, they have been largely deactivated for reasons that are still unclear.

The results in mice, which are detailed in the paper, show that the administration of MSI-1436 24 hours after an artificially induced heart attack increased survival; improved heart function two- to three-fold; reduced the size of the infarct or scar tissue by 53 percent; reduced ventricular wall thinning; and stimulated heart muscle cell proliferation in the infarct border zone by six-fold.

When a patient suffers a heart attack, part of the heart muscle dies and the associated scarring interferes with the heart’s ability to effectively pump blood. The authors believe MSI-1436 to be the first drug candidate that has been shown to reduce scarring and induce heart regeneration in an adult mammal.

Strange and Yin view their MSI-1436 results as a validation of the MDI Biological Laboratory’s and Novo Biosciences’ unique approach to regenerative medicine. Regenerative medicine has focused on complex stem cell, gene and tissue-engineering approaches for the last 15 years or more, but thus far these approaches have failed to deliver on their promise, despite the investment of hundreds of millions of dollars.

By contrast, MDI Biological Laboratory and Novo Biosciences scientists are focused on decoding the instruction manual for repair and regeneration that has been conserved by evolution in human DNA for hundreds of millions of years. This approach has been very effective: in only a few years and at modest cost, they have identified three potential regenerative medicine drugs.

“If we can decode the instruction manual for regeneration in highly regenerative species,” Yin said, “we can use drug therapies to reignite our own dormant regenerative capacity. Our research in these highly regenerative species is showing that regenerating damaged or lost tissues and organs could be as simple as taking a drug.”

MSI-1436 also has potential applications for the regeneration of skeletal muscle tissue in Duchenne muscular dystrophy, which is characterized by progressive muscle degeneration and untimely death due to heart and/or respiratory failure. Other potential applications include stimulation of wound healing and regeneration of multiple other tissues, including nervous tissue.

Source:Science Daily

{Improving your sleep quality is as beneficial to health and happiness as winning the lottery}

Improving your sleep quality is as beneficial to health and happiness as winning the lottery, according to research by the University of Warwick.

Dr Nicole Tang in the Department of Psychology has discovered that working on getting a better night’s sleep can lead to optimal physical and mental wellbeing over time — and that quality of sleep is more important than how many hours you get.

Analysing the sleep patterns of more than 30,500 people in UK households across four years, Dr Tang finds that improving your sleep quality leads to levels of mental and physical health comparable to those of somebody who’s won a jackpot of around £200,000.

The study shows that positive changes in sleep over time — improved quality and quantity, and using less sleep medication — are linked with improved scores on the General Health Questionnaire (GHQ), which is used by mental health professionals to monitor psychological wellbeing in patients.

People surveyed who reported positive improved sleep scored a 2-point change in the GHQ — a result comparable to those recorded from patients completing an eight-week programme of mindfulness-based cognitive therapy designed to improve psychological wellbeing.

Furthermore, the same people showed improved scores on the 12-Item Short Form Survey, which tests levels of physical and emotional health, as well as people’s ability to perform everyday activities.

Conversely, it was found that a lack of sleep, bad quality sleep, and using more sleep medication can lead to worsened medical and emotional states.

Dr Tang’s research proves that improving the quality and quantity of sleep amongst the population — as well as discouraging the use of sleep medication — is an effective, simple and cheap method of raising the health and wellbeing of society as a whole.

Consequently, she argues that working on getting good quality sleep, and the reduction of sleep medication, should be promoted as a public health value — something that everyone can do easily to stay physically and mentally healthy.

{{Dr Tang comments:}}

“We are far from demonstrating a causal relationship, but the current findings suggest that a positive change in sleep is linked to better physical and mental wellbeing further down the line.

“It is refreshing to see the healing potential of sleep outside of clinical trial settings, as this goes to show that the benefits of better sleep are accessible to everyone and not reserved for those with extremely bad sleep requiring intensive treatments.

“An important next step is to look at the differences between those who demonstrate a positive and negative change in sleep over time, and identify what lifestyle factors and day-to-day activities are conducive to promoting sleep. Further research in this area can inform the design of public health initiatives.”

Source:Science Daily

{French researchers have identified a marker that makes it possible to differentiate “dormant” HIV-infected cells from healthy cells. This discovery will make it possible to isolate and analyze reservoir cells which, by silently hosting the virus, are responsible for its persistence even among patients receiving antiviral treatment, whose viral load is undetectable. It offers new therapeutic strategies for targeting infected cells. This research is part of the ANRS strategic program “Réservoirs du VIH.” It is the result of a collaboration between the CNRS, Montpellier University, Inserm, the Institut Pasteur, the Henri-Mondor AP-HP hospital in Créteil, the Gui de Chauliac hospital (CHU de Montpellier) and the VRI (Vaccine Research Institute), and is published in the journal Nature on March 15, 2017. A patent owned by the CNRS has been filed for the diagnostic and therapeutic use of the identified marker.}

Since 1996, there has been consensus among the scientific community that a cure for HIV will involve targeting “reservoir cells” that host the virus in the organisms of patients undergoing triple therapy. HIV can remain hidden in these reservoirs, in latent form, for several decades, eluding the immune system’s response and antiviral treatments, without any viral protein being expressed. But if treatment ceases, the virus massively proliferates and the disease progresses again. Patients must therefore receive treatment for life. To envisage eliminating this dormant virus, a first stage consists in distinguishing the HIV-infected reservoir cells from their healthy counterpart cells, which resemble them to a very large degree. This is what has been achieved by a team of researchers, who have identified a marker of reservoir cells: a protein present only on the surface of infected cells.

Hypothesizing that HIV might leave a mark on the surface of its host cell, researchers from the Institut de génétique humaine (CNRS/Montpellier University) first worked in vitro on an infection model developed in their laboratory. After comparing infected cells and healthy cells, they noticed one particular protein, coded by a gene among the hundred of those expressed in a specific way by infected cells. Present only on the surface of the infected cells, the CD32a protein thus met, in vitro, the criteria of a reservoir cell marker. This was then confirmed by experiments on clinical samples. By studying blood samples from 12 patients living with HIV and receiving treatment, the researchers isolated the cells expressing the marker and observed that almost all were HIV carriers. In vitro, the activation of these cells induced a production of viruses capable of reinfecting healthy cells whereas their elimination entailed a significant delay in viral production.

In the fight against HIV, this discovery paves the way to a better fundamental understanding of viral reservoirs, which it will now be possible to isolate more easily and analyze directly. In the longer term, it should lead to therapeutic strategies aiming to eliminate the latent virus from the organism and make remission — at least temporary — possible in the absence of antiviral treatments.

Source:Science Daily

{Scientists have uncovered a method for improving short-term working memory, by stimulating the brain with electricity to synchronise brain waves.}

Researchers at Imperial College London found that applying a low voltage current can bring different areas of the brain in sync with one another, enabling people to perform better on tasks involving working memory.

The hope is that the approach could one day be used to bypass damaged areas of the brain and relay signals in people with traumatic brain injury, stroke or epilepsy.

The brain is in constant state of chatter, with this activity seen as brainwaves oscillating at different frequencies and different regions keeping a steady ‘beat’.

In a small study, published today in the journal eLife, the Imperial team found that applying a weak electrical current through the scalp helped to align different parts of the brain, synchronising their brain waves and enabling them to keep the same beat.

“What we observed is that people performed better when the two waves had the same rhythm and at the same time,” said Dr Ines Ribeiro Violante, a neuroscientist in the Department of Medicine at Imperial, who led the research.

In the trial, carried out in collaboration with University College London, the team used a technique called transcranial alternating current stimulation (TACS) to manipulate the brain’s regular rhythm.

They found that buzzing the brain with electricity could give a performance boost to the same memory processes used when people try to remember names at a party, telephone numbers, or even a short grocery list.

Dr Violante and team used TCAS to target two brain regions — the middle frontal gyrus and the inferior parietal lobule — which are known to be involved in working memory.

Ten volunteers were asked to carry out a set of memory tasks of increasing difficulty while receiving theta frequency stimulation to the two brain regions at slightly different times (unsynchronised), at the same time (synchronous), or only a quick burst (sham) to give the impression of receiving full treatment.

In the working memory experiments, participants looked at a screen on which numbers flashed up and had to remember if a number was the same as the previous, or in the case of the harder trial, if it the current number matched that of two-numbers previous.

Results showed that when the brain regions were stimulated in sync, reaction times on the memory tasks improved, especially on the harder of the tasks requiring volunteers to hold two strings of numbers in their minds.

“The classic behaviour is to do slower on the harder cognitive task, but people performed faster with synchronised stimulation and as fast as on the simpler task,” said Dr Violante.

Previous studies have shown that brain stimulation with electromagnetic waves or electrical current can have an effect on brain activity, the field has remained controversial due to a lack of reproducibility.

But using functional MRI to image the brain enabled the team to show changes in activity occurring during stimulation, with the electrical current potentially modulating the flow of information.

“We can use TACS to manipulate the activity of key brain networks and we can see what’s happening with fMRI,” explained Dr Violante.

“The results show that when the stimulation was in sync, there was an increase in activity in those regions involved in the task. When it was out of sync the opposite effect was seen.”

However, one of the major hurdles for making such a treatment widely available is the individual nature of people’s brains. Not only do the electrodes have to get the right frequency, but target it to the right part of the brain and get the beat in time.

Dr Violante added: “We use a very cheap technique, and that’s one of the advantages we hope it will bring if it’s translatable to the clinic.

“The next step is to see if the brain stimulation works in patients with brain injury, in combination with brain imaging, where patients have lesions which impair long range communication in their brains.

“The hope is that it could eventually be used for these patients, or even those who have suffered a stroke or who have epilepsy.”

Professor David Sharp, a neurologist in Imperial’s Department of Medicine and senior author on the paper, added: “We are very excited about the potential of brain stimulation to treat patients. I work with patients who often have major problems with working memory after their head injuries, so it would be great to have a way to enhance our current treatments, which may not always work for them.

“Our next step is to try the approach out in our patients and we will see whether combining it with cognitive training can restore lost skills.”

Source:Science Daily