Culture

Madrid, Spain: West Nile virus (WNV), which is transmitted via mosquito bites, reemerged and spread to new territories of Greece in 2017 following a two-year hiatus in reported human cases, according to findings presented at the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) [1].

During this reemergence, in the summer and early autumn of 2017, researchers diagnosed 45 cases from blood samples and cerebral spinal fluid from 180 patients who had symptoms and signs that probably indicated WNV. Prof. Athanassios Tsakris, who is head of the Microbiology Department at the University of Athens Medical School, and his team of researchers analysed the reemergence and presented the findings.

The researchers diagnosed 26 patients, or 57.8% of the new cases, with WNV neuroinvasive disease. They characterized the remaining 19 patients, or 42.2%, with WNV fever. The age of patients diagnosed with the neuroinvasive disease ranged from 15 to 91, with a median age of 63. Elderly patients with underlying diseases were particularly affected. Of the five patients who died (19.2% of those with neuroinvasive disease), all were older than 70.

All new cases emerged from southern Greece and most were reported in regions that had not been affected before. Of the 45 confirmed cases, 40 were in new territories: 37 in Argos and three in Corinthia prefecture. One case was reported in Crete and the remaining four were reported from previously affected prefectures of northwestern Peloponnese. Researchers analysed geographical data of the areas affected by the virus and concluded that Greece's landscape, such as natural and constructed wetlands, seem to influence the transmission and rate of new cases.

Prof. Tsakris says: "The reemergence of WNV after a two-year hiatus of reported human cases and its subsequent geographic expansion in newly affected areas demonstrates that Greece provides the appropriate ecological and climatic conditions for WNV circulation. The virus has been established in Greece and disease transmission may continue in the future."

"Epidemiological surveillance, intensive mosquito management programmes and public education about personal protective measures are crucial to prevent WNV transmission, especially among susceptible population groups," Tsakris said.

"The risk of WNV transmission is complex and multifactorial; it concerns the virus, the vectors, the animal reservoirs, the environmental conditions and human behaviour. Preventing or reducing of WNV transmission depends on successful controlling vector's abundance or interruption of human-vector contact. Also, targeted WNV surveillance within mosquito populations may contribute to the well-timed detection of the virus prior to its emergence in equine species or human populations", Prof. Tsakris emphasizes.

WNV is transmitted to humans via infected mosquito bites. The transmission period is typically between mid-summer and early autumn when mosquitos are most active. Most people infected with WNV have no symptoms, but 20% develop West Nile fever, a flu-like illness that causes fever and body aches. Less than 1% of infections progress to diseases with sever neurological manifestations, such as aseptic meningitis, encephalitis and acute flaccid paralysis.

Prof. Tsakris explains that the dramatic decline in cases in the previous two years may be result of the mosquito management strategy, i.e. the timely and proper use of effective larvicides, which has shrunk the populations of adult mosquitoes, and the preventive measures taken by the community to limit their exposure to WNV. Still, WNV continued to circulate in Greek territories as it was demonstrated by serological testing of birds in 2015, he adds.

"Additionally, the development of immune response against WNV may have reduced human cases by depleting the susceptible human population. It is also possible that WNV caused infections that were asymptomatic, as occurs in approx. 80% of cases, or that remained undetected including neuro-invasive cases", Tsakris says. "Of course, climatic conditions cannot be excluded since virus replication rate within mosquitoes, as well as vector competence and population dynamic, are mainly weather dependent."

The first outbreak of WNV in Greece was recorded in 2010 and was considered to be the largest epidemic in Europe since the 1996 outbreak in Romania. Most outbreaks in western Europe have been caused by WNV Lineage 1. In eastern Europe, however, Lineage 2, which emerged in Hungary in 2004, has been responsible for human and bird mortality, particularly in Greece.

It sounds like a late-night commercial: In just one hour you can reduce your anxiety levels and some heart health risk factors. But a recent study with 14 participants shows preliminary data that even a single session of meditation can have cardiovascular and psychological benefits for adults with mild to moderate anxiety.

John Durocher, assistant professor of biological sciences, is presenting the work of a team of Michigan Technological University researchers about mindfulness meditation and its ability to reduce anxiety at the 2018 Experimental Biology meeting April 21-25 in San Diego, which is attended by approximately 14,000 people.

In "Mindfulness Meditation Reduces Aortic Pulsatile Load and Anxiety in Mild to Moderately Anxious Adults," Durocher, along with fellow researchers Hannah Marti, a recent Michigan Tech graduate, Brigitte Morin, lecturer in biological science, and Travis Wakeham, a graduate student, explains the finding that 60 minutes after meditating the 14 study participants showed lower resting heart rates and reduction in aortic pulsatile load--the amount of change in blood pressure between diastole and systole of each heartbeat multiplied by heart rate. Additionally, shortly after meditating, and even one week later, the group reported anxiety levels were lower than pre-meditation levels.

"Even a single hour of meditation appears to reduce anxiety and some of the markers for cardiovascular risk," Durocher says.

While it's well-documented that meditation over the course of several weeks reduces anxiety, there have been few comprehensive research studies on the benefits of a single meditation session. Durocher's team wanted to understand the effect of acute mindfulness on cognition and the cardiovascular system to improve how anti-anxiety therapies and interventions are designed.

Studying the physiological effects of mindfulness meditation

Durocher said the study hinged on a research design proposed by recent graduate Hannah Marti '17. Marti, who graduated from Michigan Tech with a bachelor's degree in Biomedical Engineering, will begin medical school in July at the Medical College of Wisconsin.

Marti designed the mindfulness study to include three sessions:

An orientation session during which researchers measured anxiety using the Beck Anxiety Inventory (BAI) and conducted cardiovascular testing by measuring heart rate variability, resting blood pressure and pulse wave analysis;

A meditation session that included repetition of the cardiovascular testing plus the mindfulness meditation--20 minutes introductory meditation, 30 minutes body scan and 10 minutes self-guided meditation--as well as repeating cardiovascular measurements immediately following meditation and 60 minutes after;

A post-meditation anxiety test one week later.

During a body scan, the participant is asked to focus intensely on one part of the body at a time, beginning with the toes. By focusing on individual parts of the body, a person can train his or her mind to pivot from detailed attention to a wider awareness from one moment to the next.

"The point of a body scan is that if you can focus on one single part of your body, just your big toe, it can make it much easier for you to deal with something stressful in your life. You can learn to focus on one part of it rather than stressing about everything else in your life," Marti says.

One participant in the study commented that following the session they were the least stressed they'd been in a decade.

Durocher says Marti was capable of designing such a study because of her experiences with research during her undergraduate studies at Michigan Tech and by securing support through two Pavlis Honors College and Portage Health Foundation internships.

"She had some experience during the first internship so she could propose her own study for the second one," he says. "I helped to make minor adjustments, but Hannah did much of this project on her own."

New avenues of research in the health sciences at Michigan Tech

The single session mindfulness meditation study and the NIH-funded study to come (see sidebar), are excellent examples of the emphasis on student participation in research at Michigan's northern-most public university.

"In Michigan Tech's health science research programs, I want our students to get hands-on experience that they can carry into their futures, gaining experiences to advance their educational careers or their professional careers," Durocher says. "When they go for an interview, they have something real to talk about, there's substance."

Marti says this has been her experience.

"I had so much to talk about in my medical school interviews," she says. "I didn't have to say 'I just helped the professor do this,' because with Dr. Durocher's help, I was able to do most of the research myself."

Case in point, Durocher notes that nearly 20 former students who participated in laboratory research with him have gone on to physical therapy programs, medical school or to pursue a research doctorate.

And just as important, after students move on to the next chapter of their lives, there remains the legacy of their involvement in research: research designs are used in future projects and upcoming students will carry the research forward.

AUGUSTA, Ga. (April 20, 2018) - An experimental compound appears to improve stroke outcome by reducing the destructive inflammation that can continue months after a stroke, scientists report.

Rats consuming compound 21 following a clot-based stroke - the most common type in humans - don't have a smaller stroke size but do have better memory and movement in its aftermath, says Dr. Adviye Ergul, vascular physiologist and Regents' Professor in the Department of Physiology at the Medical College of Georgia at Augusta University.

"We don't see acute neuroprotection, but it definitely affects long-term outcome," says Ergul, a senior author on the study in the Journal of Cerebral Blood Flow and Metabolism. "We think it will help the recovery and, at this moment, we really have no drugs to do that."

"Our evidence to date indicates that compound 21 helps directly address lingering inflammation and its destructive impact," says Dr. Susan Fagan, assistant dean for the University of Georgia College of Pharmacy campus in Augusta, Albert W. Jowdy Professor and Director of the Center for Pharmacy and Experimental Therapeutics at MCG.

In preclinical studies designed more like clinical trials, relatively young and otherwise healthy rats were given a clot in the middle cerebral artery - a common site for big strokes in humans. They received different doses of compound 21 - known to stimulate the angiotensin type 2 receptor, which is thought to reduce inflammation and improve cell survival - for five days, with the first dose given three, six or 24 hours after stroke. Some rats also received the clot buster tPA, still the only medicine approved by the Food and Drug Administration for stroke, at either two or four hours post stroke and compound 21 at three hours.

Neither compound 21 alone or in concert with tPA reduced the size of the stroke, says Fagan, also a senior author of the study. In fact tPA was essentially ineffective in these studies. However rats that got compound 21 had less brain inflammation in the days following a stroke, performed better on cognitive tests and had better nerve and movement function.

The scientists think the compound not only inhibits bad things like inflammation and oxidative stress, but also stimulates good ones like brain derived neurotrophic factor, which is known to help ailing brain cells recover, and production of the blood vessel dilator nitric oxide.

The prevailing thought has been that increasing cognitive decline with time results from additional strokes, Ergul notes. But there is evidence that the first stroke alone can initiate a progressive and lasting inflammatory process that can continue to damage the brain for months or longer.

Today there are no prescribed therapies to tamp down this inflammation and damage, Fagan says of stroke, a leading cause of disability in the United Sates.

"More people are surviving stroke but often with consequences like cognitive deficits and impaired ability to function," Ergul says.

But even the lowest dose of compound 21 given three hours after stroke resulted in significant improvement in these functions although, conversely, no dose reduced the initial size of the stroke, which is typically determined after about three days. However in subsequent studies, the scientists found compound 21 dampened inflammation when given even 24 hours after stroke.

In their follow up studies, they are giving the compound as far as seven days out - as the stroke moves from the acute to the more chronic stage - ideally to help the immune response be more reparative.

The compound works by stimulating the angiotensin type 2 receptor, a cell receptor known to aid blood vessel dilation, minimize cell death, or apoptosis, and reduce inflammation. The type 2 receptor is expressed less in adults than its antithesis, angiotensin type 1 receptor, which typically mediates the more detrimental effects of the renin-angiotensin system, like high blood pressure and inflammation. In fact, drugs that block the angiotensin type 1 receptor on blood vessels, the heart and other tissues, are among the most prescribed drugs, primarily for high blood pressure and heart failure, she says.

Previous work has indicated that stimulating the angiotensin type 2 receptor could aid stroke recovery and that when the receptor is missing, the size of the brain infarct is larger. Additionally, another drug that increases activity of the receptor, but must be directly injected into the brain, has been shown to improve stroke outcome, the investigators write. Ergul, Fagan and their colleagues looked at an antihypertensive that increased the angiotensin type 2 receptor indirectly by blocking the angiotensin type 1 receptor. But in clinical trials, the drug reduced blood pressure too much.

"We thought that a drug that directly stimulated the angiotensin type 2 receptor - and could be taken by mouth - might work better and decided to look at compound 21," Fagan says. Even high doses of compound 21, did not affect blood pressure, she and Ergul note, which is important because there is conflicting evidence on whether driving pressure up or down is bad following stroke.

In keeping with their desire for translatable findings, the scientists are now working to answer questions like will the results hold in female rats; only male rats were used in the published study to eliminate the stroke protection high estrogen provides. They also are looking at the compound in the face of existing diseases, like hypertension and diabetes, two major stroke risks, as well as increasing age.

Many stroke therapies that looked promising in the laboratory failed in humans, Ergul says, which has led groups like the National Institutes of Health to push for more rigor in study design and reproducibility of results in preclinical trials. Basically this means ensuring that laboratory studies mimic the clinical scenario as closely as possible. In the case of stroke, they suggest studies should include blinding results, so scientists don't know which animals got which treatment, randomized enrollment of older animals and looking at the impact of tPA on whatever new therapy is being studies. In the case of the MCG studies, even the stroke cause was more translatable: previous lab studies were in models where the event was caused by clamping or putting a balloon in a big artery in the brain rather than by an actual clot.

Patients with a rare medical condition can receive life-saving treatment at the touch of a button thanks to a new device developed by scientists.

Researchers at Newcastle University, UK, have devised a way for patients and healthcare professionals to access web-based emergency clinical management information for Addison's disease.

The chronic disorder means the body fails to produce the stress hormone, cortisol. It can be life-threatening if a patient suffers adrenal crisis and is not urgently given an injection of hydrocortisone.

If the patient develops an illness, undergoes surgery, or stops taking their medication, they can develop adrenal crisis due to insufficient levels of the stress hormone.

A team of experts have now developed a Quick Response (QR) code which may be carried by patients and scanned to access vital medical support.

Vital patient information

The QR code is printed on bracelets and plastic cards and, when scanned using a smartphone, links to the Addison's Disease Information System (ADIS), which provides comprehensive clinical management advice specific to the patient.

Information displayed by the ADIS includes emergency treatment the patient may require, a letter from a medical consultant and advice about preparation for surgery.

A study, published today in BMJ Innovations, shows that the use of QR codes allows patients in a serious condition to receive better emergency care by giving a healthcare professional immediate access to treatment protocols.

Dr Jolanta Weaver, Senior Lecturer at the Institute of Cellular Medicine, Newcastle University, is lead author of the study that involves experts from the Queen Elizabeth Hospital in Gateshead.

She said: "Rare medical conditions are prone to poor management in non-specialist units as, by definition, their presentation is uncommon.

"Some healthcare professionals do not feel they have the appropriate knowledge or confidence to manage these cases and they may need more support from information systems such as ADIS.

"Our ADIS uses a web app running on a smart device, linked to a QR code. It is accessible at all times and shareable with healthcare professionals, patients, their carers, or when required in an emergency by bystanders.

"The system offers immediate access to clinical guidance, which we hope will prevent unnecessary deaths linked to Addison's disease."

Improving condition's management

Experts became interested in improving the management of Addison's disease and developing the ADIS after hearing about the preventable deaths of a number of patients due to adrenal crisis.

Hydrocortisone maintains health by helping control blood pressure and glucose levels and manage the body's response to stress. The disease is treated by daily tablets of a 'synthetic' cortisol.

For the study, 54 healthcare professionals - doctors, nurses, paramedics and dentists - were asked for their experience in managing adrenal crisis and their professional views of the ADIS.

Findings revealed that 37% of healthcare professionals have never seen and 59% have never managed an adrenal crisis.

The survey showed that there is a clinical need to improve the acute management of adrenal crisis. Healthcare professionals expressed a preference for QR code-linked information and as many as 96% of those who took part in the study thought that the ADIS would be helpful in an acute setting.

Dr Kilimangalan Narayanan, Consultant Physician and Head of Service Medicine, at the Queen Elizabeth Hospital in Gateshead, welcomed the use of the ADIS.

He said: "Dr Weaver's work has highlighted an important area of patient safety relevant to patients who have cortisol deficiency.

"Her team's work has formed the basis for subsequent further improvements in care by introducing a system of 'alerts' within the patient record on our hospital patient management system."

Quick Response codes

QR codes are free and can easily be generated and printed using free web-based software. Although they have been used for labeling medicines, and patients, to prevent wrong site surgery, their use to access clinical management information is a new development.

Dr Andrew Colman, a computer scientist, physician and research associate at Newcastle University, developed and implemented the ADIS.

He said: "I was motivated to develop this computer system to improve the care of patients with Addison's disease when I heard Dr Weaver give a lecture to medical staff about the condition.

"Dr Weaver explained that recently in the country two patients with Addison's disease had died unnecessarily due to poor clinical management and I wanted to find a way to help prevent this happening again.

"Many healthcare professionals lack the experience and knowledge of treating such rare conditions and the ADIS enables them to access life-saving information in a critical situation."

Patient's story

Pauline Copeland is the first to receive a QR-code bracelet linking to her Addison's Disease Information System.

The grandmother-of-eight was diagnosed with the condition almost 40 years ago and has suffered critical situations where medics have not known what to do when she has had an adrenal crisis.

The 67-year-old, of Pity Me, County Durham, said: "Addison's disease can be a life or death situation. If I become acutely ill I need to be treated straight away - not in a few hours or tomorrow, but immediately.

"As my illness is rare, medical staff do not always know how best to treat me and this can be a worry as they need to understand the importance of my condition and how to treat an adrenal crisis.

"The QR-code will give me confidence to know that professional healthcare staff, or anybody else using the ADIS, will be given access to medical information on adrenal crisis immediately so that I am given appropriate care."

What makes a person cool? Is it clothes? Attitude? Social standing? One University of Arizona researcher says the difference in being seen as cool or not can be found in something as simple as a smile.

Caleb Warren, assistant professor of marketing in the UA's Eller College of Management, has spent his career trying to answer the question: What makes things and people cool? When he started his research, it was generally assumed that the way to become cool was by being different or rebellious (think actor James Dean in "Rebel Without A Cause"). And to a certain extent, Warren's early research proved that theory true.

The second most common answer was that people become cool by being indifferent and not showing their emotions.

"Is it actually cool to be inexpressive rather than showing emotion?" Warren asked. "The most common emotional expression, at least in advertisements and magazines, is to smile. So the narrow question we tested is: Is it more cool to smile or to be inexpressive?"

Rapper Kanye West once told the press he doesn't smile for photos because "it just wouldn't look as cool," and academics have written that the reason Dean became cool was because he didn't smile. But was it true?

To test the theory, Warren and his co-authors -- Todd Pezzuti from the University of Chile and Shruti Koley from Texas A&M University -- created several advertisements. The same endorser was depicted twice, once with a smile and once without, and people were asked to rate how cool or uncool they thought the endorser was.

"We found that the endorser seemed less cool when they were inexpressive compared to when they smiled," Warren said of the ads that included amateur and professional models, athlete Michael Jordan and Dean. "My favorite one was that even James Dean, who people have said became cool by being inexpressive, became less cool when he was inexpressive than when he smiled."

The researchers also asked people how they felt about the brand being represented, and in each case people liked the brand less when they thought the endorser was less cool.

The only time being inexpressive was deemed more cool, according to the research, was in a hypercompetitive situation. When presented with an announcement of a news conference between two mixed martial arts competitors, respondents said the inexpressive fighter was more cool than his smiling counterpart.

"In less competitive situations, the reason not smiling doesn't seem cool is because the person seems cold rather than cool, so you don't like that person. The way I interpret it is it's not so much that smiling makes someone cool as much as not smiling tends to make people less cool," Warren said. "In a highly competitive situation, the more important question is not 'Do I like this person?' but 'Is this person going to succeed in this competition?' In highly competitive situations, being inexpressive is interpreted as a sign of dominance, which is cool."

Across the board, the study showed that the person who smiled seemed more genuine and likable than the person who was inexpressive. The results have important implications for companies marketing a brand, as well as for anyone who wants to be seen as cool.

"If you're being photographed, whether it's on the cover of a magazine or for a Facebook post, you should probably be smiling rather than being inexpressive," Warren advised. "Because most people don't think that being inexpressive is cool."

A new Pain Practice study indicates that biofeedback-assisted relaxation may help manage pain and anxiety in children undergoing medical procedures.

BrightHearts is a biofeedback mediation relaxation app designed for mobile phones and tablet computers that responds to changes in heart rate and can be used to teach children biofeedback assisted relaxation.

In the study of 30 children aged 7 to 18 years undergoing a medical procedure (peripheral blood collection, botulinum toxin injections, or intravenous cannula insertion), BrightHearts was acceptable to patients, their parents, and their healthcare providers. The pilot study also demonstrated that the use of BrightHearts did not impede the administration of medical procedures and in some cases was perceived to facilitate the procedure. The majority of patients, parents and healthcare providers indicated that they would use BrightHearts again during a procedure.

"BrightHearts taps into children's interest in devices like smart phones and tablets," said co-author Dr. Angela Morrow, of The Children's Hospital at Westmead and the University of Sydney, in Australia. "Biofeedback is a modality that we hope will empower children and help them to manage their pain and anxiety without the need for medications."

A new Journal of Neuroimaging study provides insights into the biochemical mechanisms by which Tai Chi-- a mind-body exercise--may provide both physical and psychological benefits.

Using magnetic resonance spectroscopy, a non-invasive method of measuring brain and muscle chemistry using MRI machines, tests conducted in 6 older adults enrolled in a 12-week Tai Chi program revealed significant increases in a marker of neuronal health in the brain and significantly improved recovery rates of a metabolite involved in energy production in leg muscles.

"The benefits of Tai Chi have been well known anecdotally; however recent research such as our study can quantify these improvements using objective measures," said senior author Dr. Alexander Lin, of Brigham and Women's Hospital and Harvard Medical School.

Pediatrician Hans Asperger, after whom the condition of Asperger Syndrome was named, actively cooperated with the Nazi regime, according to a study published in the open access journal Molecular Autism.

Herwig Czech, a historian of medicine at the Medical University of Vienna and author of the study, analyzed Asperger's Nazi-era publications along with previously unexplored documents from Austrian archives, including the doctor's personnel files and case records from his patients. He concludes that the narrative of Asperger as an active opponent of the Nazi regime and its policies cannot be upheld in the light of the examined evidence; his role was much more problematic than that.

The study points to instances where Asperger referred profoundly disabled children to the Am Spiegelgrund clinic, which participated in the Third Reich's child euthanasia program. The program served the Nazi goal of eugenically engineering a genetically 'pure' society through 'racial hygiene' and the elimination of lives deemed a 'burden' and 'not worthy of life'.

In the Am Spiegelgrund clinic, hundreds of children, many of them with severe mental disabilities, were killed, mostly through lethal drugs. Their deaths were mostly recorded as due to pneumonia.

Herwig Czech said: "These findings about Hans Asperger are the result of many years of careful research in the archives. What emerges is that Asperger successfully sought to accommodate himself to the Nazi regime and was rewarded with career opportunities in return. This is part of a broader effort by historians to expose what doctors were doing during the Third Reich."

The article is accompanied by an editorial by the two Editors-in-Chief of the journal, Simon Baron-Cohen (Cambridge University) and Joseph Buxbaum (Mount Sinai Medical School), and two of the reviewers, Steve Silberman (author of the book Neurotribes, and winner of the Samuel Johnson Prize) and Ami Klin (Emory University). In the editorial, the editors and reviewers explain their reasons for publishing the article.

Simon Baron-Cohen said: "We are aware that the article and its publication will be controversial. We believe that it deserves to be published in order to expose the truth about how a medical doctor who, for a long time, was seen as only having made valuable contributions to the field of pediatrics and child psychiatry, was guilty of actively assisting the Nazis in their abhorrent eugenics and euthanasia policies. This historical evidence must now be made available."

Joseph Buxbaum said: "We are persuaded by Herwig Czech's article that Asperger was not just doing his best to survive in intolerable conditions, but was complicit with his Nazi superiors in targeting society's most vulnerable people".

Ami Klin commented: "The degree of Asperger's involvement in the targeting of Vienna's most vulnerable children has remained a vexing question in autism research for a long time. Some will say that many of Asperger's colleagues were more vociferous supporters of Nazi racial ideology than he was. Some may also say he sacrificed some children to save others. We believe that the value of Czech's scholarship is that it establishes the necessary evidentiary framework for future discussion."

Steve Silberman said: "Herwig Czech has performed a valuable service to history by diving deep into the archives and making his findings available to fellow scholars. The case of Hans Asperger provides a troubling example of the horror that can be unleashed when medical professionals allow themselves to become complicit with a brutal ideology."

The editorial also discusses a new book by Edith Sheffer entitled "Asperger's Children: The origins of autism in Nazi Vienna" which covers similar evidence.

Maternal depressive symptoms during pregnancy, in the first year postpartum, and in early childhood were linked with poorer child neurodevelopment in a recent Depression & Anxiety study.

In the study that included 2231 mothers, higher average maternal depressive symptoms during and after pregnancy predicted lower total developmental milestones, fine and gross motor skills, communication, problem solving, and personal/social skills when they were assessed in children aged 1.9 to 5.7 years.

"Our findings further suggest that antenatal and post-pregnancy depression have both independent and additive effects on neurodevelopment. Children of mothers with the most chronic and severe depressive symptoms during and after pregnancy had the most neurodevelopmental disadvantages," said co-lead author Dr. Marius Lahti-Pulkkinen, of the University of Helsinki, in Finland.

In a powerful example of bench-to-bedside science showing how observations made in the lab can spark life-altering therapies in clinic, an international team of clinician-investigators has announced that gene therapy for patients with a severe form of the blood disorder beta-thalassemia can be safe and effective.

Led by study director Philippe Leboulch, MD, a sponsored collaborator in Brigham and Women's Hospital's Division of Genetics and lecturer in medicine at Harvard Medical School, the research team reports that a one-time treatment with the gene therapy known as LentiGlobin BB305 vector reduced or eliminated the need for blood transfusions in 22 patients with severe beta-thalassemia. The team's results are published in the April 19 issue of The New England Journal of Medicine.

"It was always our hope to bring our research findings to patients," said co-corresponding author Leboulch, whose primary appointment has transitioned to the University of Paris as a Professor of medicine and Institute Director. "We have taken our work from the lab, through preclinical models, and past the proof-of-principle stage, and are now able to gauge its effectiveness in patients with this disease. It is immensely gratifying."

Beta-thalassemia is a genetic disorder that impairs the body's ability to produce a key component of hemoglobin, a critical protein in red blood cells that carries oxygen to organs and tissue. Beta-thalassemia and sickle-cell disease are related disorders - both hamper hemoglobin production and can have lifelong repercussions. From toddlerhood on, people with the most severe forms of beta-thalassemia require monthly blood transfusions to replenish their red blood cell supplies along with iron chelation to remove extra iron from the body.

As a postdoctoral fellow at MIT, Leboulch began researching a therapeutic approach to compensate for the genetic mutations that lead to both sickle-cell disease and beta-thalassemia. Leboulch joined the Brigham's Division of Genetics in 1996, where he continued his work as an HMS associate professor in medicine to develop a viral carrier, or vector, that could insert genetic instructions into a patient's own blood stem cells and restore hemoglobin production. Leboulch and colleagues hoped that re-introducing the altered cells back into people would allow them to make enough hemoglobin, eliminating the need for blood transfusions. At the Brigham and HMS, Leboulch and colleagues studied the vector, known as "LentiGlobin," in pre-clinical models, publishing results from mouse studies in Science. In 2010, Leboulch and his collaborator, Marina Cavazzana of University Paris-Descartes, published a paper in Nature detailing the success of using Leboulch's LentiGlobin to genetically correct cells and transplant them back into a single beta-thalassemia patient. Last year, they published in the NEJM on a successful gene therapy of the first sickle-cell anemia patient using the same vector.

In the newly published NEJM study, Leboulch, Cavazzana and their colleagues teamed up with a second group of U.S. and international clinical investigators in Australia and Thailand to share data and results from their respective phase II clinical trials. In total, the two teams treated 22 patients at six different sites around the world. Among nine patients with the most severe form of beta-thalassemia, the one-time treatment reduced the need for red-blood cell transfusions by 73 percent. Three of the nine subsequently discontinued transfusions altogether. Twelve of the 13 patients with a slightly less severe form of the disease no longer needed any blood transfusions after treatment. The team reports no safety concerns - treatment-related adverse effects were typical of those seen in patients who receive cell transplants of their own stem cells.

"When you have an anecdote of a single patient, you never know if it will be confirmed. Here, with a multi-center trial in a larger number of patients, we see a convergence of results, and we can measure the magnitude of the therapeutic effect," said Leboulch. "There is room for improvement, as we'd like to see the elimination of dependency on transfusion even for patients with the most severe form of the disease; but there is also hope with protocol modifications we have introduced in our phase III trials."

Based on these results, two pre-drug marketing phase III clinical trials have begun.

Montreal, April 18, 2017— Quebecers do not have equal access to anti-retroviral treatment (ART) for HIV and AIDS, a long-term study undertaken by a team from the Research Institute of the McGill University Health Centre (RI-MUHC) in collaboration with clinics and university health centres in Montreal, has revealed. Researchers observed that HIV-infected persons who count on social assistance and other income security programs in Quebec do not have early access to ART due to their presumed lower socio-economic status.

According to the paper published in the Journal of the International AIDS Society, social welfare recipients and others who do not have paid employment struggle for early access to necessary ART despite access to universal health care. Early ART is a key factor in reducing AIDS and non-AIDS events, including cardiovascular, renal, hepatic and neurocognitive disorders, and cancer among persons living with HIV. In addition, early treatment also significantly decreases the risk of HIV transmission.

“This paper shows we need to take socio-economic factors into consideration when it comes to better controlling the HIV epidemic in Canada. People who are vulnerable economically may be put at greater risk because access to ART is delayed,” says study lead author Dr. Jean-Pierre Routy, a senior scientist from the Infectious Diseases and Immunity in Global Health (IDIGH) Program at the RI-MUHC and a hematologist at the Chronic Viral Illness Service of the MUHC.

From 1996 to 2015, Dr. Routy’s Montreal-based research team looked at a cohort of 549 participants, early in their HIV infection determining those who count on income security such as social assistance and employment insurance benefits were not accessing ART early. Indeed, working persons earning a salary were two-and-a-half times more likely to initiate early ART compared to this group.

This delayed access represents a potential setback in fighting HIV in Quebec. Despite the availability of universal health care and medication insurance, care appears to be inequitable.

“People who are unemployed and depend on income support are faced with tough daily decisions on how they use limited resources. Competing needs may lead to less capacity to engage in care and related expenses. This population needs aid,” explains Dr. Routy, who is also a professor in the Department of Medicine, Division of Hematology at the Faculty of Medicine of McGill University.

“This study is very important because it demonstrates that people delay or end their treatment due to financial reasons, putting their own health at risk,” says study co-author, Dr. Réjean Thomas, founder and president of L'Actuel Medical Clinic in Montreal. “We’re talking about a very worrying public health matter since we’ve known for years that an HIV-infected person with an undetectable viral load undergoing antiretroviral treatment cannot transmit the disease.”

“In a specialized clinic like l’Actuel, over 90 per cent of diagnosed patients begin treatment very early after their diagnosis compared to 30 per cent just 10 years ago,” adds Dr. Thomas.

“The effect of type of care centres on early treatment initiation was an interesting finding that we did not expect,” adds first study author Dr. Vikram Mehraj, postdoctoral fellow in the IDIGH Program at the RI-MUHC. “We believe this finding can be explained in part by the fact that sicker patients may preferentially use university-medical centres.”

Unlike in British Columbia or France, ART for persons living with HIV in Quebec is still not entirely free. Dr. Thomas points to the obstacle of annual charges for treatment ranging from $28,000 to $36,000.

“If we want to eradicate HIV by 2030 – in line with the UNAIDS objectives signed by the city of Montreal on December 1, 2017 – we will have to seriously examine this obstacle moving forward,” says Dr. Thomas.

In 1907, a statistician named Francis Galton recorded the entries from a weight-judging competition as people guessed the weight of an ox. Galton analyzed hundreds of estimates and found that while individual guesses varied wildly, the median of the entries was surprisingly accurate and within one percent of the ox's real weight. When Galton published his results, he ushered the theory of collective intelligence, or the "wisdom of crowds," into the public conscience.

Collective wisdom has its limits, though. In a new study published in the Journal of the Royal Society Interface, researchers Albert Kao (Harvard University), Andrew Berdahl (Santa Fe Institute), and their colleagues examined just how accurate our collective intelligence is and how individual bias and information sharing skew aggregate estimates. Using their findings, they developed a mathematical correction that takes into account bias and social information to generate an improved crowd estimate. In the study, their corrected measures were more accurate than the mean, median, and other traditional statistics.

"There is growing evidence that the wisdom of crowds can be really powerful," Kao says. "A lot of studies show that you can calculate the average of estimates and that average can be surprisingly good."

"However," adds Berdahl, "there is a great deal of evidence that people have strong biases in estimation and decision tasks."

The researchers recruited over 800 volunteers to participate in the study and asked each participant to guess the number of gumballs in a jar, which ranged over several orders of magnitude from 54 to more than 27,000. Additionally, they quantified how individuals incorporate social information into their own opinion. To do so, the researchers offered participants fake details about other people's guesses and allowed them to change their estimate in light of that information.

Kao's team found that while estimates varied considerably, they were highly predictable. People tended to guess numbers smaller than the actual value and guessed a wider range of numbers for larger jars. Social information also plays a role in collective wisdom. For example, the simulated social information revealed that peer advice more strongly influenced an individual if the knowledge suggested the actual number of items was higher than the guesser's initial estimate. Smaller guesses, even if more accurate, appear to be more frequently discounted.

The findings define a clear set of rules for collective estimation, which in turn provide insight into why we observe the wisdom of crowds. This understanding can improve group wisdom in a variety of settings. Whether guessing the weight of a fat ox or predicting the outcome of future elections, Kao and his colleagues have helped the crowd grow smarter.

Mental health diagnosis should be a collaborative and useful process, not a meaningless label - according to new research from Norfolk and Suffolk NHS Foundation Trust (NSFT) and the University of East Anglia.

Doctors should work alongside service users to approach diagnosis in a way that is sensitive to individual needs and preferences, so that they explain difficulties, give hope, empower and guide recovery.

A study, published today in The Lancet Psychiatry, offers practical guidance for doctors and could lead to service users having a better experience of diagnosis.

The research was undertaken by a team that included a clinician and a service-user from the Department of Research and Development at Norfolk and Suffolk NHS Foundation Trust (NSFT) and researchers at the Norwich Medical School at the University of East Anglia (UEA).

The major review synthesises for the first time the perspectives of service-users, carers and doctors in an attempt to understand and improve the diagnostic journey. It contains data from 13 countries and includes more than 2,220 participants.

One of the authors, Dr Corinna Hackmann, a research clinical psychologist based at Hellesdon Hospital, Norwich, said that diagnosis can be validating and helpful but can also be detrimental and lead to stigma.

"For me, an interesting finding of this study is the discrepancy between the views of service users and clinicians," she said.

"Many doctors feel that service users have a right to know their diagnosis but at the same time rightly fear the potential harm this might cause, which can be associated with withholding or delaying sharing the diagnosis.

"However, the results suggested that if a diagnosis is made, service-users would prefer that it is shared and discussed with them rather than withheld."

Dr Caitlin Notley, from UEA's Norwich Medical School, said: "This research supports a sensitive, individualised, collaborative, and holistic approach to mental health diagnosis, which is informative, can empower service users, provide hope and guide treatment."

A major diagnostic manual, the International Classification of Disease - 11th revision (ICD-11) is set for release by the World Health Organisation (WHO) this summer. This study forms part of an important and timely programme of International research aimed at improving the diagnostic process in collaboration with service-users.

"We have developed research in dialogue with the WHO that feeds service-user views into the process of revision for the ICD-11," said Dr Hackmann.

The paper reports that diagnosis can be experienced as labelling and this can cause stigma.

The authors found evidence of feelings of isolation, confusion, insignificance or distress when a diagnosis is not discussed with service-users, is discovered via health records, in a letter or inadvertently mentioned in a care meeting.

The study suggests that service-users prefer their diagnosis to be given face-to-face, with helpful information, and clearly leading to reciprocal discussions about care-needs and treatment.

Dr Hackmann co-authored the study with Amorette Perkins and Joseph Ridler (former Research Assistant Psychologists) and Daniel Browes (expert by experience and former Peer Support Worker) and colleagues from Norwich Medical School and the School of Health Sciences at UEA - Dr Caitlin Notley, Senior Lecturer in Mental Health; and Dr Guy Peryer, Lecturer in Health Sciences.

As the growing season progresses, you might not notice much about what's happening to plants under the soil. Most of us pay attention to new shoots, stems, leaves, and eventually the flowers and crop we intend to grow. We might think of roots as necessary, but uninteresting, parts of the crop production process.

Paul Hallett and his team disagree. They focus on what's going on in the soil with the plant's roots.

The zone of soil that surrounds a plant's roots is called the rhizosphere. It's the combination of the Latin words for "root" and "area." And it's a busy location for important-but hidden-crop production processes.

In the rhizosphere, plants make a variety of chemical compounds called exudates. Hallett and fellow researchers at the University of Aberdeen look at the effects that exudates have on the plant and surrounding soil community. Their unique work takes small-scale measurements near the surface of the roots. The properties here can be very different from the rest of the soil.

"Roots continuously secrete chemicals into the soil as a way to liberate nutrients that are attached to soil particles," says Hallett. In human digestion, the stomach secretes gastric juices to help break up food; exudates are the plant equivalent of gastric juices.

Hallett describes exudates' chemical composition as "a veritable cocktail or 'buffet' of resources for anything in the rhizosphere." In addition to helping plants procure nutrients, exudates are food sources for the microbes that are an important part of the soil microbiome.

Exudates also have an important role in holding soil together. Roots and fungi that live in the soil hold together larger clumps of soil, but exudates work on the micro level. Like glue, they hold together soil particles in important mechanical networks. Soil scientists call these soil networks aggregates.

Whereas the binding effects of roots and fungal networks are usually long-term, exudates' influence on the soil can be fleeting. "Root exudates won't last in their original form for long in the soil, as they get consumed and transformed by microbes," says Hallett. This process can completely destroy the exudate or create even better compounds for binding soil particles.

"Plant root exudates have a massive impact on aggregate formation," says Hallett. "They do this through a number of ways, including acting like glues or changing how quickly the rhizosphere wets up and dries with rainfall and evaporation."

Hallett's team researched the effects of exudates on different types of soil. They researched environments with a sandy loam soil texture versus a clay loam texture. This is important because chemical reactions between the exudates and soil particles vary with soil type.

They also researched various plant exudates from barley and corn. They found that barley's exudates increased how well soil particles are bound together, but not as much as corn. They also found that while barley exudates didn't impact soil water repellency, corn exudates did.

Research such as Hallett's shows that during the growing season-and beyond-there are delicate interactions between each plant and the surrounding soil. All of these interactions affect the amount of water that is captured by soil and absorbed by plants. Production of exudates also affects how well the plants can pull vital nutrients out of the soil, and even affects the soil in the rhizosphere.

Future research for Hallett's team will include looking at exudate production along plants' roots. They'll also look at the age of roots, and whether younger roots produce exudates with different soil-holding and water-absorbing qualities.