Low levels of vitamin D significantly increase the risk of developing multiple sclerosis (MS), according to a study led by Dr. Brent Richards of the Lady Davis Institute at the Jewish General Hospital. This finding, the result of a sophisticated Mendelian randomization analysis, confirms a long-standing hypothesis that low vitamin D is strongly associated with an increased susceptibility to MS. This connection is independent of other factors associated with low vitamin D levels, such as obesity.

“Our finding is important from a public health perspective because vitamin D insufficiency is common, especially in northern countries like Canada where exposure to sunlight – a common natural source of vitamin D – is decreased through the long winter and where we see disproportionately high rates of MS,” asserts Dr. Richards, who is also an Associate Professor of Medicine and Human Genetics and William Dawson Scholar at McGill University. “We would recommend that individuals, particularly those with a family history of MS, should ensure that they maintain adequate vitamin D levels. This is a common sense precaution, given that vitamin D supplementation is generally safe and inexpensive.”

Adequate intake of vitamin D is defined by the United States’ Institute of Medicine as 600 international units per day for both males and females under the age of 70. Many people, especially in northern climates, may require supplements in order to maintain this level.

“The link between vitamin D insufficiency or deficiency and risk of developing MS has been an important area of investigation in the MS research community,” says Dr. Karen Lee, Vice President of Research at the MS Society of Canada. “This research brings us a step closer to understanding whether low vitamin D is a trigger of MS and not just a result of the disease itself. I’m encouraged by the data and hope that it will prompt further research into whether supplementing with vitamin D could reduce the risk or slow the progression of MS.”

By taking the precaution of maintaining a normal level of vitamin D, a person at risk could decrease their risk of acquiring MS by an important degree. “While low vitamin D is by no means the only risk factor, we have identified one risk that can be removed from the equation, which could have a significant impact towards preventing this terrible disease,” concludes Lauren Mokry, who is the first author on the paper. McGill University

Stress induced cardiomyopathy after cerebral haemorrhage has been shown to increase the risk of further brain damage. These patients can now be identified by a simple blood test, and a possible treatment for stress induced cardiomyopathy has been discovered – a different kind of anaesthesia than that currently being used.

Stress induced cardiomyopathy is a relatively recently discovered disease where part of the heart muscle ceases to function and results in the heart having reduced pumping capacity. Approximately 90 percent of those affected are upper middle-aged women. The onset is similar to a heart attack, with chest pain and difficulty breathing, but stress induced cardiomyopathy follows a different course.

With stress induced heart failure, the heart spontaneously recovers within a few weeks and thus the prognosis has been seen as good; but, new findings show the prognosis to be approximately the same as for acute ischemic heart disease.

In a new thesis from Sahlgrenska Academy, all patients from the region that suffered a specific type of cerebral haemorrhage (subarachnoid haemorrhage) were followed for two years. In conjunction with the haemorrhage, patients experience a strong stress component. Stress induced cardiomyopathy is therefore relatively common (10-20 percent of the patients) following this type of cerebral haemorrhage, which can cause significant brain damage.
“We saw that patients with stress induced cardiomyopathy had an increased risk of further brain damage in the aftermath of a cerebral haemorrhage and had a worse long-term prognosis, even after we made adjustments for other risk factors,” says Jonatan Oras, PhD Student at Sahlgrenska Academy.

In the thesis, two biomarkers were identified that can be used to identify patients who suffer from stress induced heart failure.
“With a blood test, we are now able to quickly identify patients with stress induced heart failure and apply the right measures sooner,” says Jonatan Oras.

In the experimental part of the thesis, an animal model was used with rats to find a possible treatment for stress induced heart failure. It was found that if the animals were anesthetized with a particular anaesthetic (isoflurane), they did not develop heart failure and the heart muscle retained its elasticity and pumping capacity.

“When we used other anaesthetics, including those currently in use in healthcare, we saw no cardioprotective effect. This is the first potential cardioprotective treatment for stress induced cardiomyopathy to be presented,” says Jonatan Oras.

Further studies of this possible treatment for stress induced cardiomyopathy on patients at risk of developing stress induced cardiomyopathy should be conducted,” Jonatan Oras points out. Sahlgrenska Academy

A blood test may be able to sound early warning bells that patients with advanced melanoma skin cancer are relapsing, according to a study.

Scientists from the Cancer Research UK Manchester Institute studied the DNA shed by tumours into the bloodstream – called circulating tumour DNA – in blood samples from seven advanced melanoma patients at The Christie NHS Foundation Trust.

“Being able to track cancers in real time as they evolve following treatment has huge potential for the way we monitor cancers and intervene to stop them growing back.’ – Professor Peter Johnson, Cancer Research UK’s chief clinician
In this early work they found they could see whether a patient was relapsing by tracking levels of circulating tumour DNA. And they found that new mutations in genes like NRAS and PI3K appeared, possibly causing the relapse by allowing the tumour to become resistant to treatment.

Most melanoma patients respond to treatment at first but their cancer can become resistant within a year. It is hoped that these approaches will allow doctors to use circulating tumour DNA to tailor treatment for individual patients to get the best result.

Around 40 to 50 per cent of melanoma patients have a faulty BRAF gene and they can be treated with the targeted drugs vemurafenib or dabrafenib. But for many of these patients the treatments don’t work, or their tumours develop resistance after a relatively short time. When this happens these patients can be offered immunotherapy drugs including pembrolizumab, nivolumab and ipilimumab. Detecting this situation early could be key to improving their care and chances of survival. Cancer Research UK Manchester Institute

A group of researchers, led by Prof. Matozaki Takashi and Associate Prof. Murata Yoji at the Kobe University Graduate School of Medicine Division of Molecular and Cellular Signalling, were the first to demonstrate the role of stomach cancer–associated protein tyrosine phosphatase (SAP)-1 in the pathogenesis and prevention of Crohn’s disease, ulcerative colitis, and other inflammatory bowel disorders. Their findings are expected to accelerate the development of targeted therapies for inflammatory gastrointestinal diseases.

Inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, are disorders of unknown etiology that are often characterized by abdominal pain, diarrhoea, bloody stool, fever, and weight loss. These symptoms frequently interfere with activities of daily living and place patients at an elevated risk of mortality. Patients are also associated with a high risk of developing colorectal cancer. In Japan, there are an estimated 200,000 patients with Crohn’s disease and ulcerative colitis, who qualify for the special Government-led medical assistance system for intractable diseases. Currently, the administration of anti-inflammatory agents only provides palliative results, and the medical community is awaiting new definitive therapies.

Although recent studies have demonstrated that intestinal epithelial cells play a critical role in regulating bowel inflammation, the underlying mechanism remains largely unknown. Previously, Prof. Matozaki, Assistant Prof. Murata, and their colleagues found that SAP-1 localizes to the microvilli of the brush border in gastrointestinal epithelial cells. The transmembrane-type tyrosine phosphatase SAP-1 has an extracellular domain that protrudes into the intestinal lumen and a cytoplasmic domain that mediates tyrosine dephosphorylation of proteins. Here, they showed that SAP-1 ablation in a mouse model of inflammatory bowel disease resulted in a marked increase in the incidence and severity of bowel inflammation, suggesting that SAP-1 plays a protective role against colitis.

In addition, carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific membrane protein, was identified as the target of SAP-1 tyrosine dephosphorylation. Suppression of CEACAM20 functions via dephosphorylation was suggested to contribute to preventing colitis. By shedding light on the anti-inflammatory mechanism of the intestinal epithelial cells, Prof. Matozaki and colleagues believe that their findings will drive the development of drugs that target SAP-1 and CEACAM20 to overcome intractable inflammatory bowel diseases. Kobe University

The Beatson Institute of Cancer Research, Bearsden, Glasgow, hosted ‘Circulating Biomarkers 2015’, a Biotexcel conference and workshop. The role of circulating biomarkers in early diagnosis and treatment monitoring is gaining momentum with kits for analysing DNA and RNA from circulating tissue already on the market, and liquid biopsy products in development. The analysis of circulating biomarkers allows less expensive and less invasive screening of patients, and so would enable the early diagnosis of disease and hence timely treatment, for example in pancreatic cancer where presentation typically occurs too late for a cure to be achieved. Also, monitoring of treatment in, for example, breast cancer patients by screening of circulating tumour cells will allow clinicians to make better and quicker decisions about the best therapy for the patient.
In the now familiar format, the meeting included a mix of lectures, a networking workshop, a panel debate, and technology presentations.  The lectures included, among others, presentations on the analysis of circulating tumour DNA (Prof. Charles Coombes, Imperial College London, UK; Dr Gerhardt Attard, Institute of Cancer Research and the Royal Marsden, Surrey, UK), RNA (Prof. Sue Burchill, Leeds Institute of Cancer and Pathology, UK), circulating tumour cells (CTCs) (Dr Vera Cappelletti, National Cancer Institute, Milan, Italy; Dr François-Clément Bidard, Institut Curie, Paris, France) and micro RNA (Dr Alberto Rocci, Manchester Royal Infirmary, Manchester, UK). Other talks discussed the potential of metabolomic biomarkers in cancer (Dr Oliver Maddocks, Beatson Institute for Cancer Research, Glasgow, UK) and how to use a variety of biomarkers and other parameters for the evaluation of the complex  situation of ageing and lifespan (Prof. Paul Shiels, University of Glasgow, Glasgow, UK).
The technology presentations included talks on technology for the enrichment of circulating cell-free DNA (Dr Vipulkumar Patel, Analytik Jena), coupling the CellSearch system (CellSearch) and DEPArray platform (Silicon Biosystems) to isolate single CTCs (by Dr Francesca Fontana (Silicon Biosystems) and targeted biomarker detection by MassARRAY (Dr Malcolm Plant, Agena Bioscience).
The panel debate was centred around the question, ‘CTCs vs. cfDNA vs. miRNA vs. mRNA: which is better and why?’ but perhaps the more interesting discussion that evolved was on the ethics of biomarker analysis (Is it ethical to screen for a condition where there is no treatment ?) and the practicalities of screening (How do we screen for conditions that need to be caught before the presentation of symptoms?). Additionally, the meeting provided many networking opportunities and the benefit of such discussion will, no doubt, be borne out by the development and continuation of new and existing collaborations. A very profitable meeting for all involved.