Student psychologists help the depressed

Liisa Luuk and Lisa Backlund are in the last term of their Psychology programme. During the spring they will be doing a graduation project in which they will evaluate the effects of cognitive behavioural therapy on depression, where the treatment is a combination of online treatment and actual face-to-face meetings. Their study is a part of a larger European research project in which the results from eight European countries are brought together.

Liisa Luuk och Lisa Backlund There is good support in research for both traditional face-to-face CBT and for treatment delivered online, Ms Backlund explains. What is new, and has not been researched as much, is that in this study there are four face-to-face meetings with the therapist in addition to the online treatment. Many patients request meeting their therapist, and it can result in more people completing their therapy.

“We will be taking part in the entire project,” Ms Luuk says. “We have received general guidelines from the other EU countries taking part, but we have been able to design the online treatment and the form of the treatment meetings. And we are also part of the recruitment process, conducting interviews with the participants prior to treatment. Then we follow up the results afterward, and we will also take part as therapists.”

Meeting and treating patients is not new for them.

“We see patients for three terms during our course at the university clinic ,” Ms Backlund explains. “During that time we are given basic psychotherapy training. And last term we went out for twelve weeks on professional placement, working with patients.”

In Sweden the studies will be carried out in Linköping and Stockholm. There will be places for 150 people who feel depressed to receive treatment and take part in the study, which is free. The criteria for taking part include being over 18 and having access to a telephone and a smart-phone. The treatment itself will start in February and run over ten weeks. Those interested in taking part may indicate their interest now.

“It’s important for us to have a large number of participants to make the results as reliable as possible and so that they can be compared with the various other EU countries,” Ms Luuk says. “It’s great being part of a real research project that is so big, it’s wonderful. Gaining experience of seeing how the research is done when these big names in the field are the ones doing it.”

“If we were to work as psychologists in primary care in the future, it is very possible that we would be the ones actually putting this treatment into practice,” Ms Luuk says.

Ms Backlund agrees with her.

“Yes, there's a good chance that treatment will go in this direction – more online treatment – so it’s an excellent experience for us.”

The treatment includes four face-to-face meetings with the therapist; in between, the treatment is internet-based. The participants will read some texts that talk about depression and how it is dealt with in CBT. Some of it deals with changing what you do – how to do things differently in order to deal with your depression – and part of it deals with how to manage your thinking. These are two key parts of CBT. Then there are small tasks. They might be answering questions or doing some exercises. Then you apply what you’ve read to your daily life.

Later, the treatment will be evaluated.

“We will compare it with a control group,” Ms Backlund says. “We have various questionnaires that the participants will fill in before and after the study, where they will assess how they feel. We will compare the severity of the depression symptoms before and after the treatment. We will also have a control group, that does not take part, to compare with. They will receive online treatment after the study has been completed. So everyone who takes part in the study will receive treatment.”

Professor Gerhard Andersson of the Department of Behavioural Sciences and Learning at Linköping University is behind the project. Naira Topooco is a PhD student in Clinical Psychology, and a part of Professor Andersson’s research team. She is a project manager in the research study and Ms Luuk’s and Ms Backlund’s immediate supervisor. DAY treatment was developed by researchers and psychologists from Linköping University and is based on Cognitive Behavioural Therapy (CBT).

Source: The DAY-studie (article in Swedish)

HIV virus in disguise tricks immune system, Marie Larsson is Professor of Molecular Virology

Name: Marie LarssonTitle: Professor of Molecular Virology
Department: IKE

CONTACT

Phone: +46 (0)10-103 10 55
E-mail: marie.larsson@liu.se

Address:
Linköping University
Department of Clinical and Experimental Medicine
Virology
SE-581 85 Linköping
Sweden

Marie Larsson is Professor of Molecular Virology. Her research is in the area of immunovirology, specifically HIV research with focus on the immunomodulatory effect this virus has on dendritic cells and T cells. She has also ongoing projects exploring new adjuvants and vaccine constellations for cancer and virus. Furthermore, she is investigating the induction and sustainment of cancer associated inflammation and the deleterious effect this has on host immune defense.

Immunomodulatory effects of HIV-1’s interactions with DCs and T cells from

blood and mucosa
So far over 30 million people have died from HIV-1 infection (figure 1), the majority of them in the developing countries, and this epidemic is still cause for major concern. The existing antiretroviral therapy dampens the infection and the destruction of the immune system, i.e. AIDS, but does not cure the disease. Sadly, this therapy is not available to all HIV infected and is a very expensive lifelong commitment with severe side effects.

A vaccine blocking HIV infection is theDendritic cell sought-after solution but there is no hope that we will have such a vaccine in the near future. Instead we can hope for a therapy that induces a potent long lasting immune response consisting of CD4+ and CD8+ T cells, two types of control cells involved in the immune defense, that have proven to be important to control the infection. There exists a unique cell in all tissues in our bodies, the dendritic cell (DC) (Figure 2) with unique ability to activate T cells so they can perform their job in the body. DCs in the vaginal and rectal tissues are one of the first cells to encounter HIV during intercourse with an infected individual (Figure 3 and 4). Unfortunately, HIV hijacks the DCs, which makes this cell responsible for spreading the virus to interacting T cells in the body which provokes HIV-infection of T cells and cell death when it should be initiating immune responses to fight the infection.DC HIV

My research aspires to elucidate the mechanisms behind the immunomodulatory effects HIV exerts on DCs and on their ability to activate T cells. Focus will be on; Elucidation of the mechanisms involved in HIV’s binding to and uptake by DCs and the subsequent degradation that leads to DC antigen presentation of HIV peptides for activation of HIV specific T cells. Elucidation of the mechanisms responsible for the negative effects HIV exerts on DCs and if presence of HIV virions during DC T cell priming impairs the T cell function. Elucidate the effect opsonized HIV-1 exerts on immune cells such as DCs, NK cells and T cells. Identification of receptors and cells involved in the initial HIV infection of cervical mucosa and colorectal mucosa,  and potential microbiocides that can block the initial infection, and elucidation of why HIV affects the T cells in the gut to a higher extent than the T cells in blood.

HIV will continue to kill people and have a great impact on mankind until we have a drug that can stop this infection. My ambition is that the planed research will answer some basic questions regarding the role of DCs in HIV pathogenesis and induction of potent immune response against this virus. This knowledge will guide how a vaccine/therapy needs to be constructed in order to have high efficacy.

                                                             Mucosal transmission

                                                                Cervix

Cancer research

Elucidation the role of IL-1α and the microenvironment in development of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is a common gastrointestinal malignancy with an exceptional poor prognosis and a mortality rate that nearly matches the rate of incidence. The cross-talk between PDAC and stroma cells, e.g. cancer associated fibroblasts (CAF), and immune cells, may create an environment with chronic inflammation augmenting tumor transformation and maintenance.

In PDAC, more than 70% of the total tumor mass can consist of fibrotic stroma, which makes CAFs the major component in this cancer. PDAC inflammatory environment consists of many mediators, e.g. IL-1, COX-2, IL-6, and CXCL8, and some of these factors correlate to tumor development and poor prognosis. Of note, elevated expression of IL-1 in tumors has been associated with more aggressive disease. Several studies, including ours have reported that dendritic cells (DCs), one of the immune cells found in the tumor microenvironment, show phenotypic and functional abnormalities when isolated from tumor bearing animals and individuals with PDAC. Recent findings provided some evidence that the COX-2 metabolite PGE2 is involved in the upregulation of immunomodulatory factors in DCs impairing their T cell stimulatory ability. The aims are to examine the receptor-ligands and signaling pathways involved in the cross talk between stroma cells, i.e. CAFs, and PDAC cells giving rise to the inflammatory environment and creating an environment sustaining the PDAC. To examine the role IL-1 cytokine family and effects these cytokines cell signaling have on creating the inflammatory environment and in tumor development and survival. To examine whether neutralization of IL1 signaling pathway enhances the survival and quality of life for individuals with pancreatic cancer.

The information gained from the proposed research will help us understand the mechanisms underlying the development of PDAC and the effect this solid tumor exert on the body and may help designing therapies for PDAC.

Source: Linköping University

Scheduling tool a big help in healthcare

The HIV virus avoids the body’s immune cells by disguising itself using proteins that normally take part in the defence against infections. These are the findings of research conducted at the Division of Molecular Virology.

Professor Marie LarssonThese “complement proteins” are soluble molecules that attach themselves to foreign particles and those of the body in different patterns. These patterns help the immune system to identify and attack dangerous intruders such as viruses and bacteria.

Phd student Rada EllegårdInstead, HIV exploits the complement proteins present in all body fluids in order to make its way into the body tissues without being attacked. It was known previously that infections are much more effective if the virus is surrounded by the bodily fluids normally present in blood or sexual contagion than if it is isolated in a laboratory environment. In an article in the Journal of Immunology Marie Larsson, professor of molecular virology (left) and PhD student Rada Ellegård (right) provide an explanation of this phenomenon.

“The ability to use our complement proteins in this way is probably key to the success of HIV in being transmitted. We are currently carrying out further work to investigate these mechanisms in the male genital mucous membrane – the tissue where the virus infection takes place in sexual transmission,” says Ms Larsson.

The first thing HIV particles come into contact with is dendritic cells, immune cells that function as sentry posts. Their job is to identify viruses as dangerous and hostile to the body, and to respond by producing the substances that combat infections and moving to a lymph node to set a specific immune defence in motion.

In the case of HIV, this process does not seem to work very well. The disguise stops the dendritic cells recognising the virus, which instead establishes an infection in the mucous membrane and uses the movement to the lymph nodes as a way to spread around the whole body.

As more and more cells are infected and killed, the virus slowly breaks down our immune system. Without treatment this sequence of events leads to AIDS, a condition where the victim becomes extremely vulnerable to infection and where normally harmless viruses and bacteria become life-threatening.

Related content

Marie Larsson - research presentation >>

                                       HIV-illustration

When a virus is captured by a dendritic cell, it is recognised by a virus sensor that normally sets in motion infection reduction factors which inhibit the production of new virus particles (picture, left). HIV has the ability to clothe itself in complements, a type of protein present in our bodily fluids. In this way it can dampen the signals from the virus sensors and produce many new particles (picture, right).


Source: Linköping University

Feelings of awe and joy can bolster your mental and physical health.

              POSITIVE EMOTIONS CAN STRENGTHEN YOUR IMMUNE SYSTEM
                                         Image Credit: Mens Health

The wonders of the world can be just as good for your health as they are for your enjoyment, suggests a UC Berkley study.

Researchers have linked positive emotions—awe, contentment, spirituality—with lower levels of pro-inflammatory cytokines, proteins that signal your immune system to work harder and bolster good health.

In two separate experiments, more than 200 young adults were asked to log the extent to which they experienced amusement, awe, compassion, joy, love, and pride on a given day. Samples of gum and cheek tissue taken that same day showed that those who experienced more of these positive emotions had the lowest levels of the cytokine Interleukin 6, a marker of inflammation that can cause autoimmune disease and depression.

“That awe, wonder and beauty promote healthier levels of cytokines suggests that the things we do to experience these emotions—a walk in nature, losing oneself in music, beholding art—has a direct influence upon health and life expectancy,” says UC Berkeley psychologist Dacher Keltner, a co-author of the study.

An added emphasis on spirituality and mindfulness may just be enough to get you through this winter happy and healthy. 

Source: Mensfitness

Climate change accelerates maturing of grape in wine production

                             Johann Martínez-Lüscher , Nafarroako Unibertsitatea

The increase in temperatures and of CO2 levels – the consequences of climate change – accelerates the maturing of grapes in wine production, affecting colour and possibly aromas”. This was the conclusion of the PhD thesis defended by Johann Martínez-Lüscher, undertaken jointly by the University of Navarra and the University of Bordeaux.

The biologist explained that if the forecasts by the Intergovernmental Panel on Climate Change of a level of 700ppm of carbon dioxide and a temperature increase of 4ºC are proved correct, “the accumulation of sugars could be so rapid that the rest of these processes that depend on this will not be capable of keeping up. This will mean that, on comparing grapes with the same concentration of sugars or degree of alcohol, the crops under climate change conditions will have poorer colouration and this will be noticed in the wine”.

In fact, “it is increasingly more frequent to find wines with a higher alcoholic degree due to the over maturing of the grape”. Nonetheless, in the framework of climate change, the consequences can vary. “For example, the changes in levels of ultraviolet radiation or the decrease in rainfall may have antagonistic effects to those caused by an increase in temperature or CO2 levels. Thus, there are many unknowns about what the future holds”, he added.

Wine in a new scenario

In this way wine production will have to find solutions in order to confront environmental challenges. “The use of slower maturing ‘clones’ (sub-varieties) could be one of the possible strategies. It would also be very tempting to substitute the varieties planted in each location by others better adapted to warmer climates, but this would to a great extent mean giving up the typical characteristics of each variety of our wines – something unthinkable to date”.

Nevertheless, as this expert pointed out, climate change can provide new opportunities: for example, the production of a type of wine in cooler climes where it was not possible before. “This is the case of the incipient wine industry in the United Kingdom where I intend to continue working”, stated the researcher.

Mr. Martínez-Lüscher’s research has been financed by the University of Navarra, the Navarre-Aquitane Cross-Border Cooperation Programme, the Spanish Ministry of Science and Innovation, and the 7th European Union Framework Programme.

Source: Elhuyar Fundazioa

February 2015 Supermarket Orchid, Mass marketing has hit the orchid world!

The phalaenopsis, or moth orchid, is a favorite gift orchid and is readily available in supermarkets and garden centers. It comes in a variety of colors and exotic patterns, and with care the long-lived blooms can be enjoyed for weeks. Photo by P. McDaniels, courtesy UTIA

Did someone bless you with a beautiful orchid? Mass marketing has hit the orchid world!
Among the most popular orchids for gifting are cattleyas (pronounced “KAT-lee-uh”). Another favorite gift orchid is the genus phalaenopsis (pronounced “fail-en-NOP-sis”).  This orchid is nicknamed the moth orchid because of the shape of its blooms. Both come in a variety of sizes and colors, are readily available in grocery stores and garden centers, and can look just as good in your home as the store.

In spite of the fact that my friends think I can grow anything with little regard for plant rules, I will confess that I managed to kill the first two orchids I was given years ago by simply not consulting the experts. Orchids are epiphytes or air plants that have developed specialized water-storage organs. They like to attach to moist tree bark in a tropical atmosphere. Thus, they have their own set of recommended growing practices. The American Orchid Society (aos.org) gives great advice on keeping your new friend healthy and blooming. 

Both cattleyas and phalaenopsis appreciate a lot of air movement and a long day of filtered, bright light. They don’t appreciate direct sunlight but do thrive in temperatures between 60 and 85 degrees Fahrenheit. Living in an east-facing window usually makes them happiest.

Both orchids should be kept in free-draining growing media. The AOS recommends even moisture, although allowing the media to dry slightly can be beneficial. I recommend you water your orchid once a week, at most. Be sure the water can drain and does not stand in the pot. The pot it came in probably has no drainage, so your job is to not overwater. You can also create drainage holes.

Orchids should be watered in the morning. Because the water should run through the pot, place the plants in the sink. Tepid water is recommended. Also, do not use salt-softened or distilled water. Let the water run through the plant for a minute or so. Be sure to let the plant drain completely. If any water gets trapped in the leaves, use a paper towel to blot. This will help avoid crown rot. If you’ve read that you should just lay some ice cubes around the roots, I have found that generally works, also.

As for fertilizer, there are a number of mixtures and brands, but the AOS recommends that any fertilizer you use should not contain urea. Their website discusses recommended methods. If you want to try a home fertilizer brew, you might try your morning brew. I dump the dregs of my coffee pot into my orchids once a week, all year around.  For an average pot with a 5-inch top measurement, about 1/4 cup of these leavings works best. Doing this will negate the job of occasional fertilizing, as the dregs give your new friend all the encouragement it needs to do its best. I use “high test” (caffeine) coffee leavings, but a friend is using decaf on hers. It will be interesting to see which formula produces the best results. 

When orchids have completed their flowering cycle, it’s time to cut the flower stem to encourage a new bloom on a healthy plant. Again, the AOS has a number of tips about getting your orchid to re-bloom. For phalaenopsis, they recommend cutting the flower stem ½-inch above the first or second node. Be sure your pruners have been disinfected. The plant will most often grow another flower stem and re-bloom.

Repotting may be necessary every one to three years if the plant becomes root-bound or the media needs replenished.  Don’t be tempted to substitute the loose medium that came with your orchid with your favorite soil mix. Orchids like orchid mixes that drain well, otherwise they may decline to the point of no return.

Source: UTIA

Drug combo supresses growth of late-stage prostate cancer turmors

By Natalie van Hoose

Low doses of metformin, a widely used diabetes medication, and a gene inhibitor known as BI2536 can successfully halt the growth of late-stage prostate cancer tumors, a Purdue University study finds.

Prostate cancer causes the second-highest number of cancer-related deaths in men in the U.S., and methods of treating advanced prostate cancer are limited.

Xiaoqi Liu (pronounced zhow-CHEE' LEE'-oo), associate professor of biochemistry and cancer research, and fellow researchers found that the drugs metformin and BI2536 can work together to suppress the spread of prostate cancer that resists all other available treatments, potentially prolonging patients' lives.

"We've found a promising way to treat late-stage prostate cancer," Liu said. "By combining low levels of two well-tolerated drugs, the progression of this disease could be significantly delayed. Completely curing the cancer at the advanced stage is pretty much impossible, but this treatment might manage it for a while - that's exciting."

A number of treatments exist for the earlier stages of prostate cancer, which grows slowly compared with many other cancers. Because prostate cancer cells need the male sex hormone androgen to develop, one way to treat the disease is to suppress androgen - a process known as castration. If the cancer continues to spread, the patient often undergoes chemotherapy. As a last resort, drugs that block the synthesis of androgen by prostate cancer cells can be used, but these medications only extend a patient's lifespan for several months.

New approaches to treating the most persistent forms of prostate cancer are "urgently needed," Liu said.

Adding to the challenge is the fact that castration treatment can inadvertently encourage the cancer to get tougher. It can heighten oxidative stress on the prostate gland, which increases the expression of Plk1, a gene that has been linked to many cancers. Over-expression of Plk1 can also trigger the synthesis of androgen.

"The goal of castration is to block androgen synthesis," Liu said. "But cancer cells eventually become 'smart' enough to make androgen anyhow, which is why the cancer continues to grow."

Additionally, castration can disrupt the body's metabolism and lead to insulin resistance, which also can stimulate the production of androgen. The cancer will spread until both of these side effects are stopped, Liu said.

Previous studies showed that metformin - an inexpensive, antidiabetic drug that has been commonly used for more than 40 years - is particularly potent to prostate cancer tumors.

Working with fellow researchers from Purdue, the University of Wisconsin-Madison and the Indiana University School of Medicine, Liu found that a combination of low levels of metformin and BI2536, a drug that stifles the activity of Plk1, could work in tandem to slow the growth of prostate tumors too advanced for current treatments by promoting the self-destruction of cancer cells and preventing androgen synthesis.

The drugs did not impact healthy prostate cells, a "key finding," Liu said. "Ideally, cancer therapy will have minimal effects on normal cells."

Because metformin helps regulate metabolism, it may reverse some of the metabolic damage caused by castration, he said.

The researchers tested the drugs in a classical cell culture assay of prostate cancer cells and in advanced prostate tumors in mice. Low concentrations of the drugs significantly slowed the development of cancer in both trials. The mice tumors were grown from the tumor cells of a late-stage prostate cancer patient, suggesting that the treatment would prove effective in humans.

"Those results were amazing," Liu said. "These are the first data we've generated from a real patient, so I was almost jumping in the air when I saw that it worked."

Liu said that the next step in the research is to test the combination of drugs in clinical trials. Further research is also needed to understand the underlying mechanism of metformin and why it is effective at suppressing prostate cancer

Source: Purdue Univesity

Small change in blood acidity could prove detrimental to kidney disease patients

A University of Manchester scientist has discovered that very small changes in the level of acidity in blood may have a detrimental impact on the health of patients with kidney disease.

Chronic Kidney Disease (CKD) is common in the UK.  It is estimated that about one in five men and one in four women between the ages of 65 and 74 has some degree of CKD. The leading single cause of CKD is diabetes which is increasing so it’s expected that more patients will be diagnosed with CKD in the future.

Dr Donald Ward from the Faculty of Life Sciences has been studying the impact of kidney disease on the body. He has found that very small changes in the pH (acidity) level in the blood prevents the body from being able to accurately monitor calcium levels. This leads to too much of the hormone PTH being released which is likely to lead to a greater risk of calcium and phosphate from the bone damaging the arteries. This often proves fatal to patients with CKD. His research has been published in the Journal of the American Society of Nephrology. 

Dr Donald Ward

He says: “It was not realised before that the blood pH changes we see in patients with kidney disease can have an impact on their ability to monitor blood calcium levels. My research has demonstrated that the effect of those changes may be more significant than previously thought and thus might need to be looked at more carefully by clinicians.”

Dr Ward’s research focussed on the high level of parathyroid hormone (PTH) in patients suffering from CKD. This causes the body to release calcium and phosphate from the bones which can then damage their blood vessels. 

Dr Ward explains why this is so harmful: “The diseased kidneys prevent the body getting rid of both excess phosphate and excess acidity. So if that acidity also causes the body to release more PTH then this could compound the problem by releasing further phosphate from the bone. This vicious circle might accelerate the potentially fatal calcification of the arteries.” 

He continues: “What is so important about this research is that we have demonstrated that changes in PTH release can be prompted by very small changes in blood pH level. Before, it was assumed that only a larger change in acidity would cause problems for patients.”

The research was funded by Kidney Research UK. Elaine Davies, Director of Research Operations, from the charity says: “Donald’s work has used novel pharmacological and molecular tools in generating these new findings which increase our knowledge about the complex balance that clinicians need to consider when treating patients with CKD.”

Dr Ward is hoping to take his research to the next step, testing for therapeutic targets that could lead to better treatments for CKD.

Source: Manchester University

Stanford bioengineers develop tool for reprogramming genetic code

Stanford bioengineers have developed a new tool that allows them to preferentially activate or deactivate genes in living cells. VITSTUDIO/SHUTTERSTOCK

Biology relies upon the precise activation of specific genes to work properly. If that sequence gets out of whack, or one gene turns on only partially, the outcome can often lead to a disease.

Now, bioengineers at Stanford and other universities have developed a sort of programmable genetic code that allows them to preferentially activate or deactivate genes in living cells. The work is published in the current issue of Cell, and could help usher in a new generation of gene therapies.

The technique is an adaptation of CRISPR, itself a relatively new genetic tool that makes use of a natural defense mechanism that bacteria evolved over millions of years to slice up infectious virus DNA.

Standard CRISPR consists of two components: a short RNA that matches a particular spot in the genome, and a protein called Cas9 that snips the DNA in that location. For the purposes of gene editing, scientists can control where the protein snips the genome, insert a new gene into the cut and patch it back together.

Inserting new genetic code, however, is just one way to influence how the genome is expressed. Another involves telling the cell how much or how little to activate a particular gene, thus controlling how much protein a cell produces from that gene and altering its behavior.

It's this action that Lei Stanley Qi, an assistant professor of bioengineering and of chemical and systems biology at Stanford, and his colleagues aim to manipulate.

Influencing the genome
In the new work, the researchers describe how they have designed the CRISPR molecule to include a second piece of information on the RNA, instructing the molecule to either increase (upregulate) or decrease (downregulate) a target gene's activity, or turn it on/off entirely.

Additionally, they designed it so that it could affect two different genes at once. In a cell, the order or degree in which multiple genes are activated can produce different metabolic products.

"It's like driving a car. You control the wheel to control direction, and the engine to control the speed, and how you balance the two determines how the car moves," Qi said. "We can do the same thing in the cell by up- or downregulating genes, and produce different outcomes."

As a proof of principle, the scientists used the technique to take control of a yeast metabolic pathway, turning genes on and off in various orders to produce four different end products. They then tested it on two mammalian genes that are important in cell mobility, and were able to control the cell's direction and how fast it moved.

Future therapies
The ability to control genes is an attractive approach in designing genetic therapies for complex diseases that involve multiple genes, Qi said, and the new system may overcome several of the challenges of existing experimental therapies.

"Our technique allows us to directly control multiple specific genes and pathways in the genome without expressing new transgenes or uncontrolled behaviors, such as producing too much of a protein, or doing so in the wrong cells," Qi said. "We could eventually synthesize tens of thousands of RNA molecules to control the genome over a whole organism."

Next, Qi plans to test the technique in mice and refine the delivery method. Currently the scientists use a virus to insert the molecule into a cell, but he would eventually like to simply inject the molecules into an organism's blood.

"That is what is so exciting about working at Stanford, because the School of Medicine's immunology group is just around the corner, and working with them will help us address how to do this without triggering an immune response," said Qi, who is a member of the interdisciplinary Stanford ChEM-H institute. "I'm optimistic because everything about this system comes naturally from cells, and should be compatible with any organism."

Source: Stanford university

Ebola: Reports from the front lines

Dr. Noah Rosenberg “Ebola was never the only killer here, and our ability to appropriately diagnose and treat these patients is woefully limited.”

Alpert Medical School professors Michael Smit and Noah Rosenberg are in Sierra Leone and Liberia respectively, treating Ebola patients. There are some signs of a slowdown in the epidemic, but the doctors emphasize that the virus must be fought “until the last case.”

PROVIDENCE, R.I. [Brown University] — In a limited sense, two Brown University medical professors who have been fighting Ebola in West Africa this winter have good news to report. They have seen some signs of slowing disease transmission. But the broader reality of what Ebola has done in Sierra Leone and Liberia is grim, according to Drs. Michael Smit and Noah Rosenberg.

Ebola shouldn’t just be contained, they note: It must be treated until all cases are resolved.

Smit, assistant professor of pediatrics and a physician at Hasbro Children’s Hospital, arrived in Sierra Leone Dec. 3, 2014, and will remain there through Jan. 18. Rosenberg, clinical assistant professor of emergency medicine and a Lifespan doctor, arrived in Liberia in mid-December and will stay until Jan. 27. They answered questions for medical science writer David Orenstein about what they are doing and seeing, and what people back in the States need to know.

Please describe a typical day.

NR: I arrive at 7 a.m. and meet with the overnight doctor and nurses to discuss our patients. My team pulls on full personal protective equipment and enters the high-risk area. We examine each patient, inquire about their current symptoms, give routine supportive medications and IV fluids if needed. We take blood to test for Ebola. We remove our equipment while being intermittently sprayed with chlorine. Rounds repeat in the afternoon and we often make an additional trip for a new admission. In the evening we meet with the night team and then rest to return in the morning.

Dr. Michael Smit “The effect of the epidemic goes far beyond those infected with Ebola virus. ... The economic impact on the country is devastating.

MS: I am the medical team leader of one of four medical teams at the Mateneh Ebola Treatment Center (ETC). Our days differ depending on which shift we are working. When working the early shift, we eat breakfast around 7 a.m. and drive to the ETC. We change into our work uniforms of scrubs and rubber boots at the ETC. At 7:30 we receive signout on the patients from the overnight team. We then assign personnel to conduct the nursing rounds, physician rounds, admissions, and discharges. During the heat of the day, we try to limit time in the high-risk area in personal protective equipment (PPE) to one hour. We deliver meals, administer medications, place intravenous catheters, and draw blood for laboratory tests. We triage admissions as they come through the ambulance bay. We also process discharges. These include survivors discharged home and deaths transferred to the morgue. At the end of the shift, we sign out the patients to the oncoming team, change back into our civilian clothes, and go back to the compound to eat. The late and overnight shifts are the same as the early shift for the most part.

What do you observe and hear about the status of the epidemic where you are?

NR: The exponential growth of the epidemic is clearly over in Liberia, but sporadic outbreaks are likely to continue until every case has been eliminated from West Africa, which may take months. Most of our new admissions now test negative for Ebola; they frequently die nonetheless. This may seem counterintuitive, but Ebola was never the only killer here, and our ability to appropriately diagnose and treat these patients is woefully limited.

MS: It is difficult to assess the status of the epidemic from here. We have limited access to the Internet, so our updates of what is happening are intermittent. As for what we observe, after a slow start from our opening in mid-December, we saw a steady increase in cases in our district in Bombali. Over the last week, admissions have decreased. The reason for this is not clear. We hope that it reflects a reduction in transmission, but we cannot assume this given the complexities of case identification and transport here.

What do people in the United States most need to know, based on what you are experiencing?

NR: Before the epidemic Liberia suffered from a large disease burden and severely limited health care system. Decades of civil war, sparked by inequality and tension between descendants of indigenous West Africans and freed slaves, wrecked the infrastructure and economy. Not only was the U.S.A. responsible for the founding of Liberia, but many of the struggles here today have their origins in the slave trade. Ebola will soon fade from the news but the epidemic has only worsened an already grave condition. We have a special responsibility to Liberia and it deserves our sustained attention.

MS: People in the United States need to know that the epidemic here is far from over. Even in a situation with diminished transmission, the United States needs to send personnel and resources here to combat Ebola until the last case. The effect of the epidemic goes far beyond those infected with Ebola virus. The schools here in Sierra Leone have been closed for months. Teen pregnancy is increasing as a result. The economic impact on the country is devastating, with some estimates setting the economy back 10 years. Also, people in the United States need to know about the dedication and resilience of the local and international healthcare workers who are fighting the epidemic, often under challenging physical and emotional conditions.

Source: Brown University

HIV testing yields diagnoses in Kenya but few seek care

A sweeping effort in a rural region of Kenya to test all adults for HIV discovered 1,300 new infections, but few of the newly diagnosed people pursued treatment, a study in the journal Lancet HIV reports.
PROVIDENCE, R.I. [Brown University] — Between December 2009 and February 2011, health workers with the AMPATH Consortium sought to test and counsel every adult resident in the Bunyala subcounty of Kenya for HIV. A study in the journal Lancet HIV reports that the campaign yielded more than 1,300 new positive diagnoses, but few of those new patients sought health care.

“Home-based counseling and testing (HBCT) provided a diagnosis to nearly 40 percent of people living with HIV in this subcounty who otherwise most likely would not have gone for HIV testing,” said study lead author Becky Genberg, assistant professor (research) of health services, policy and practice in the Brown University School of Public Health. “They therefore would not have known about their HIV infection and not had the opportunity to change their behavior to protect others.”

AMPATH’s HBCT program is part of a strategy to identify all individuals living with HIV in the catchment area, start them on antiretroviral medication as soon as possible, and help them stay on their medications. Antiretroviral medication not only suppresses HIV infections for most patients but also reduces their ability to transmit the virus.

Genberg with co-author Edwin Sang “We are working on a variety of studies, all designed to understand the barriers facing the newly diagnosed, and to implement and evaluate strategies to increase their engagement and retention in HIV care over time.”

In Bunyala, home to about 66,000 people, the HBCT program tested about 32,000 adults. Among them, 3,482 had HIV. Of those, 2,122 already knew they were infected, but 1,360 did not know it yet.

A major finding of the study is that three years later only 15 percent of the newly diagnosed people had engaged in care for their infection. A likely reason why, Genberg said, is that newly diagnosed people typically don’t yet feel sick.

“That so few linked to care following HBCT is a call for innovative and creative strategies to work alongside HBCT to support the mostly healthy, asymptomatic newly diagnosed to engage with care in a way that is meaningful for them,” Genberg said.

In an editorial in the journal, Rashida Ferrand of the London School of Hygiene and Tropical Medicine said the study sounds a warning that home-based testing must be paired with effective ways to convince newly diagnosed patients to seek help.

“Unless paired with interventions targeted at hard-to-reach populations, the diagnosing of undiagnosed individuals in many settings will not be cost-effective and will have little effect on individual and population viral suppression,” she and colleagues wrote.

Genberg, who has been in Kenya this winter, said she is working with Kenyan collaborators on developing the needed interventions: “Right now we are working on a variety of studies, all designed to understand the barriers facing the newly diagnosed, and to implement and evaluate strategies to increase their engagement and retention in HIV care over time.”

In addition to Genberg the study’s authors are Joseph Hogan and Corey Duefield of Brown; Violet Naanyu, Juddy Wachira, and Samson Ndege of Moi University in Kenya; Edwin Sang, Monicah Nyambura, and Michael Odawa of AMPATH; and corresponding author Paula Braitstein of the University of Toronto.

The President’s Emergency Plan for AIDS Relief funded the study though USAID (grant AID-623-A-12-0001). Additional support came from the National Institutes of Health (K01MH099966) and the Bill and Melinda Gates Foundation.

Source: Brown University

Reducing Myc gene activity extends healthy lifespan in mice

No bones about it Young mice have good bone density whether they have two copies (top row; +/+) or one copy (bottom row; +/-) of the Myc gene. As they age, researchers found, mice with just one copy maintain better bone density and stay healthy longer. Sedivy lab/Brown University

Mice with one rather than the normal two copies of the gene Myc (also found in humans) lived 15 percent longer and had considerably healthier lives than normal mice, according to a new Brown University-led study in Cell.

PROVIDENCE, R.I. [Brown University] — A team of scientists based at Brown University has found that reducing expression of a fundamentally important gene called Myc significantly increased the healthy lifespan of laboratory mice, the first such finding regarding this gene in a mammalian species.

Myc is found in the genomes of all animals, ranging from ancestral single-celled organisms to humans. It is a major topic of biomedical research and has been shown to be a central regulator of cell proliferation, growth, and death. It is of such widespread and fundamental importance that animals cannot live without it. But in humans and mice, too much expression of the protein that Myc encodes has been closely linked to cancer, making it a well-known but elusive target of drug developers.

In a new study in the journal Cell, the scientists report that when they bred laboratory mice to have only one copy of the gene, instead of the normal two, thus reducing the expression of the encoded protein, those mice lived 15 percent longer on average — 20 percent longer for females and 10 percent longer among males — than normal mice. Moreover, the experimental mice showed many signs of better health into old age.

The experimental — “heterozygous” — mice grew to be about 15 percent smaller than the normal mice (a probable disadvantage in the wild) but that was the only discernable downside found to date for lacking a second copy of the gene, said senior author John Sedivy, the Hermon C. Bumpus Professor of Biology and professor of medical science at Brown.

“The animals are definitely aging slower,” he said. “They are maintaining the function of their organs and tissues for longer periods of time.”

Physiological differences

That assessment is based on detailed studies of the physiology — down to the molecular level — of the heterozygous and normal mice. The researchers conducted these experiments to try to understand the longevity difference between the two groups.

John Sedivy “The animals are definitely aging slower [and[ they are maintaining the function of their organs and tissues for longer periods of time.”

Co-lead author Jeffrey Hoffman, a medical and doctoral student, led the studies of the health of the mice, including various bodily systems. In many cases they were just like their normal counterparts. They reproduced just as well, for example.

“These mice are incredibly normal, yet they are really long-lived,” Sedivy said. “The reason why we were struck by that is because in many other longevity models like caloric restriction or treatment with rapamycin, the animals live longer but they also have some health issues.”

Instead the Myc heterozygous mice simply experienced fewer problems of aging. They did not develop osteoporosis, they maintained a healthier balance of immune system T cells, had less cardiac fibrosis, were more active, experienced less age-related slowing of their metabolic rate, produced less cholesterol, and exhibited better coordination.

Graduate student and co-lead author Xiaoai Zhao, meanwhile, led the molecular analysis of several pathways known to be involved in regulating longevity to find out how they might be different. Sure enough, heterozygous mice exhibited changes in IGF-1 signaling and nutrient and energy-sensing pathways, but how Myc engages those mechanisms is still not clear. Of particular interest, heterozygous mice showed less protein synthesis in several tissues. Regulation of this process is known to be under direct Myc control, and its reduction by a variety of means is known to extend lifespan in diverse species from yeast to mammals.

Genome-wide patterns of gene expression showed that Myc heterozygotes had significant differences in pathways related to metabolism and the immune system. Those patterns, however, only overlapped somewhat with patterns seen in other lifespan extending interventions.

Zhao and Hoffman’s studies also argue against a role for Myc in an oft-cited paradigm of greater longevity: upregulation of a variety of stress defense mechanisms. Their experimental mice seemed to suffer from as much stress and consequences of stress as normal mice.

The different benefits of Myc reduction compared to other laboratory longevity extenders shows that just as there are many ways the body can break down with aging, Sedivy said, there may be many ways to forestall that.

“There is more than one way to become long-lived,” Sedivy said.

Help for humans?

In the long term, Sedivy said he is optimistic that the findings about Myc could prove to matter to human health.

Finding the right target for a drug in one of Myc’s key metabolic or immune system pathways may or may not extend human lifespan, he said, but it might help people stay healthier as they age — for example, if it can reduce osteoporosis in people the way it does in mice. In particular, Sedivy said, it emphasizes the importance of the process of protein synthesis as a target of interventions that are likely to have widespread benefits on many organ systems.

And the study also offers encouragement to companies seeking to develop cancer drugs that block Myc overexpression. As important as normal Myc expression is to physiology, it appears that at least in mice there were many substantial benefits in reducing it by, say, half. Thus, Sedivy said, any drug that can target Myc directly is likely to find many applications beyond cancer.

In addition to Sedivy, Hoffman, and Zhao, the paper’s other authors are Marco De Cecco, Abigail Peterson, Luca Paglilaroli, Jayameenakshi Manivannan Bin Feng, Thomas Serre, Kevin Bath, Haiyan Xu, and Nicola Neretti of Brown; Gene Hubbard, Wenbo Qi, and Holly Van Remmen of the University of Texas; Yongqing Zhang and Rafael de Cabo of the National Institute on Aging; and Richard Miller of the University of Michigan.

The National Institutes of Health (grants R37AG016694, F30AG035592), the Ellison Medical Foundation, and the Glenn Award for Research on the Biological Mechanism of Aging supported the research. Some experiments were conducted in the Brown University molecular pathology and genomics cores.

Not just a longer life, but a healthier, stronger body “Do you think she might be a Myc hypomorph?” Drawing: Emma Sedivy

Source: Brown University

Smart device delivers results for kids with asthma

Smart device

A new smart asthma inhaler with an audio-visual function has dramatically improved child and adolescent use of preventative asthma medication.

The users also experienced significant improvements to their symptoms, well-being and quality of life and needed their reliever medication less frequently.

The University of Auckland study, funded by Cure Kids and the Health Research Council, showed a significant improvement in night time awakening, coughing and wheezing.

Clinical pharmacist, Amy Chan, a doctoral student with the University of Auckland, is the lead author on the paper.  

“We know one of the key reasons for children not taking their medication is parent and patient forgetfulness.  The Smartinhaler reminder system is now clinically proven to be a real solution to the problem,” she says.

“What we’ve been able to establish for the first time with this study is that the ringtone Smartinhaler significantly improves adherence to preventative medication, which results in improved quality of life for children with asthma. It’s hugely exciting,” says Ms Chan.

Children in the study were also given a Smartinhaler tracker for their rescue or ‘blue’ inhaler to measure the amount of rescue medication they used. The device was able to objectively count date and time of rescue medication use. This provided a good indication of asthma being out of control.

When symptoms worsened participants used their rescue reliever inhaler (blue inhaler), which is also known as a rescue medication because it provides immediate relief.  Recent studies have shown that overuse of the blue inhaler is a predictor of worsening asthma and general morbidity.

The study found that use of the rescue medication was significantly reduced in the group using the Nexus6 Smartinhaler reminder device.

Cure Kids Chair of Child Health Research and Ms Chan's supervisor on the study, Professor Ed Mitchell, says he is “absolutely staggered by the size of the effect. To see the improvement in the lives of these children is astounding.”

The participants also reported taking part in more sports and family activities. Parents reported feeling less frightened by their child’s asthma.

New Zealand has the second highest rates of asthma in the world and one in four Kiwi children experiences asthma symptoms. Despite this, regular adherence to asthma medication is poor.

New Zealand digital health company Nexus6 Ltd created the new Smartinhaler device called the SmartTrack, which was used in the study. The device has 14 different ringtones, which are cycled so users don’t get reminder fatigue. The SmartTrack reminder is only triggered when a dose is missed.

The results were published this month in The Lancet Respiratory Medical Journal.  To the researchers’ knowledge, this is the largest study in the world to investigate the effects of an inhaler device with audio-visual reminder function on asthma adherence and outcomes in children and adolescents.

It is also the first to show significant benefits in asthma outcomes and quality of life. The results are expected to gain international interest.

The controlled trial recruited 220 children between the ages of six and 15 who presented to emergency departments with asthma symptoms.

The study was randomised with half of the participants receiving a SmartTrack device for use with their preventative or ‘orange’ inhaler that had the audiovisual elements turned on, and the other half receiving the same device with the audiovisual elements turned off.

Participants were followed up every two months for six months and general asthma control was checked.

Key findings from the study were:

Medication adherence rate for the patient group given the audiovisual enabled SmartTrack inhaler were 84 percent compared to 30 percent for the control group. This equals a 180% increase in medication adherence.
The use of emergency medication or the ‘blue’ inhaler was significantly reduced. The median percentage days on which a reliever was used in the intervention group was 9.5 percent compared to 17.4 percent in the control group. This equals a 45percentreduction in rescue medication use.
Symptoms, well-being and quality of life for the children was significantly improved.

Source: Auckland University