Body

LA JOLLA, CA--In Type 1 diabetes the immune system mistakenly attacks and destroys insulin-producing pancreatic cells, leaving patients dependent on lifelong insulin injections. The putative perpetrators of the attack--which are called CD8+ cytotoxic T lymphocytes (CTLs)--recognize specific protein fragments displayed on pancreatic islet cells and then kill them. However, even CTLs that cannot recognize islet-specific antigens (but for example viral antigen) nonetheless invade pancreata as inflammation progresses. These cells have been dubbed bystanders, since researchers didn't know what they did. Many thought they might enhance inflammation.

A new study published in the March 23, 2018, issue of Science Immunology solves this mystery, with a surprising revelation. In it a team led by La Jolla Institute for Allergy and Immunology (LJI) diabetes researcher Matthias von Herrath, M.D., reveals that bystander cell accumulation antagonizes rather than abets cell-killing by specific CTLs, curbing inflammation.

This is noteworthy because that chief anti-inflammatory role has been traditionally ascribed to what are called regulatory T cells, or "Tregs", which dampen autoimmune responses. The new study challenges this notion and suggests alternate mechanisms can also be at work.

"We show that the allegedly 'professional class' of immunosuppressive Tregs is not necessarily the key player in resolving inflammation in this experimental model," says von Herrath, a professor in LJI's Division of Developmental Immunology. "We now find that many cells, among them non-specific CTLs, can do that."

To show this, his team employed mouse models in which one can experimentally induce beta cell destruction. Simultaneously, the researchers transferred various ratios of CTLs into mice--including both the cell-killing variety and the non-specific bystanders. They then used state-of-the-art imaging to count surviving beta cells.

Mice infused with low numbers of bystanders relative to specific CTLs showed beta cell destruction and diabetes symptoms, such a hyperglycemia. By contrast, mice receiving equivalent amounts of each showed little beta cell death, and the specific CTLs recruited to the pancreas became less harmful.

Why bystanders exert an immunosuppressive effect is unclear. One possibility is that their influx limits access to beta cells by the cell-killing CTLs, in effect crowding them out. Another is that bystanders interfere with signals sent to cell-killing CTLs by other cells that assist in ramping up inflammation. Whatever the reason, the result was unexpected.

"Some had thought bystanders passively add to damage done by specific CTLs but we found the opposite," says first author Gustaf Christoffersson, PhD, a former postdoc in the von Herrath lab. "When bystander cells were present in sufficient amounts, they dampened those inflammatory responses."

That idea that Tregs are the dedicated inflammation fighters is so entrenched in the field that the group performed experiments proving that protection conferred by bystanders had nothing to do with expanding Treg populations. "Tregs do have profound anti-inflammatory effects in some disease models," says Christoffersson. "But treatments seeking to expand this cohort of cells have not proven as successful in the clinic as they have been in the lab."

Von Herrath says his colleagues in the field must now recognize that diverse immune cell types, not just Tregs, can potentially rein in the inflammatory response in autoimmune disease. "In the end 'professional Tregs' may matter less than we thought," he says. Von Herrath also relishes how his new paper upends dogma in the field. "Right now people are talking about challenges to science," he says. "But the biggest threat to science comes when we hold onto ideas too closely. Then we might miss the obvious."

In fact, his team is already planning ways to widen the therapeutic focus. "We are currently looking into whether there are ways to safely induce a bystander population of T cells to work in our favor as treatment for type 1 diabetes," says Christoffersson, now a researcher at Uppsala University in Sweden.

When infectious diseases (ID) specialists were involved in the care of patients with certain kinds of drug-resistant infections, the patients' 30-day mortality rates were about 50 percent lower, according to a new study published in Open Forum Infectious Diseases. The findings provide additional evidence for the beneficial impact ID physicians have on patient care and outcomes, particularly when individuals have difficult to treat infections that are resistant to multiple antibiotics.

"These are serious infections that anybody can get and end up in the hospital," said study author Jason P. Burnham, MD, of Washington University School of Medicine in St. Louis. "Understanding how we can help improve outcomes in patients like these is really important."

For the single-center, retrospective study, researchers reviewed records from 2006 to 2015 for approximately 4,200 patients with infections resistant to multiple antibiotics who were treated at Barnes-Jewish Hospital, an academic medical center affiliated with Washington University School of Medicine. Patients with positive cultures for a multi-drug resistant pathogen from one of several different types of bacteria were included in the analysis: Enterobacteriaceae, Staphylococcus aureus, Enterococcus, Pseudomonas, and Acinetobacter.

Among patients with multi-drug resistant Enterobacteriaceae infections, ID consultation was associated with a 59 percent reduction in 30-day mortality. In line with previous research, ID consultation was also associated with a 52 percent reduction in 30-day mortality for patients with resistant S. aureus infections. For individuals suffering from several infections simultaneously, each one resistant to multiple antibiotics, an ID consult was associated with a 49 percent drop in 30-day mortality.

Even one year later, the involvement of an ID physician in treating a patient's initial S. aureus infection was associated with a 27 percent reduction in all-cause mortality. For resistant Enterobacteriaceae infections, researchers found a similar 26 percent reduction in one-year all-cause mortality when a patient's initial care included an ID physician. Among those with resistant Enterobacteriaceae infections, ID consultation was also associated with a 26 percent reduction in hospital readmissions in the 30 days following their initial hospital stay for infection.

For the other types of bacteria (Enterococcus, Pseudomonas, and Acinetobacter), small sample sizes limited the authors' ability to associate ID consults with clinical outcomes. According to Dr. Burnham, larger studies are needed to better understand the role of ID consultants for these infections, though he said he suspects it would be positive. In addition, future research will clarify what specific aspects of care provided by ID specialists help patients the most, such as expertise in appropriate antibiotic use or application of relevant clinical practice guidelines.

As antibiotic resistance continues to increase, the specialized care provided by ID physicians will become even more integral to the daily operations of hospitals and for the promotion of patient and public health, Dr. Burnham said. "I think we're moving in a direction where having ID experts on board for these increasingly hard to treat drug-resistant infections will be necessary to ensure that our patients have the best possible outcomes."

Bottom Line: Bacterial load was significantly higher in pancreatic tumor samples from patients with pancreatic ductal adenocarcinoma compared with pancreatic tissue from normal individuals, and in studies using mice, eliminating certain "bad" bacteria slowed the growth of pancreatic cancer, reversed immune suppression, and upregulated the immune checkpoint protein PD1.

Journal in Which the Study was Published: Cancer Discovery, a journal of the American Association for Cancer Research.

Authors: George Miller, MD, HL Pachter Professor in the Departments of Surgery and Cell Biology at New York University School of Medicine; Deepak Saxena, PhD, associate professor in the Department of Basic Science and Craniofacial Biology at New York University College of Dentistry.

Background: "The gut microbiome has been studied in many different cancers, including liver and colorectal cancer, and is shown to affect cancer progression," said Miller. "Because the pancreas is remote from the gut, it is considered a sterile organ, and there haven't been many studies that looked at the role of the gut microbiome in pancreatic cancer."

How the Study Was Conducted and Results: The researchers also compared fecal samples from 32 patients with pancreatic ductal adenocarcinoma with fecal samples from 31 normal individuals and found that the bacterial composition of cancer patients was distinct from that of normal individuals. "The bacterial composition was more diverse in the fecal samples than from cancer patients," noted Miller.

"The dysbiosis [imbalance] in the gut microbiome can potentially be used as a biomarker to define a high-risk population," noted Saxena. Among the more abundant strains of bacteria found in pancreatic cancer patients were Proteobacteria, Bacteroidetes, and Firmicutes.

In mouse studies, the team demonstrated that bacteria translocate from the gut to the pancreas during pancreatic cancer. With further studies, the researchers showed that eliminating these bacteria using antimicrobial treatment slowed the progression of pancreatic cancer and lowered the tumor burden by about 50 percent. This process also affected T-cell differentiation, leading to increased T-cell infiltration into the tumor and reduction in myeloid-derived suppressor cell (MDSC) population. Antimicrobial treatment also resulted in increased expression of PD1 on CD4+ and CD8+ T cells within the tumors.

Reintroduction of bacteria in antimicrobial treated mice reversed the tumor protection and reduced the immunogenicity of the tumors, suggesting that the microbiome promotes pancreatic ductal adenocarcinoma by inducing immune suppression in the tumor.

The researchers also found that combining antimicrobial treatment with an anti-PD1 immunotherapy resulted in enhanced CD4+ and CD8+ T-cell activation in mice, suggesting that such a combination is a potential treatment option for pancreatic ductal adenocarcinoma.

The team is preparing to launch a clinical trial to test a combination of antibiotics (ciprofloxacin and metronidazole) and an anti-PD1 antibody in patients with pancreatic ductal adenocarcinoma.

Authors' Comments: "We were surprised to see that the human pancreatic tissue samples had an active microbiome," said Saxena. "And we found that not only are there bacteria in the pancreas but the bacterial load is significantly higher in pancreatic cancer tissue compared to normal pancreas tissue."

"Our studies show that the bacteria may serve both as biomarkers of increased risk for pancreatic cancer as well as potential therapeutic targets," said Miller. "We believe that targeting the microbiome in patients with pancreatic cancer can make immunotherapy effective."

Saxena noted, "Pancreatic cancer is a very aggressive disease with a five-year survival rate of a dismal 8.2 percent. Extending the life of these patients by manipulating the microbiome and decelerating tumor progression would be a significant step forward in managing this deadly disease."

Thousands of older people in low and middle-income countries are at risk of abuse and human rights violations when being admitted to care homes, according to new research led by the University of East Anglia (UEA).

The study provides the first systematic analysis of admissions practices for residential long-term care facilities, assessing the extent to which older people are involved in admission decisions and whether current practices respect fundamental human rights.

The research, which focused on care homes in Argentina, reveals that a substantial proportion of those admitted do not have high levels of care dependency, raising questions about the grounds for admitting them.

In some cases, this may be due to homelessness or the genuine unavailability of family members to provide low-level care. However, the authors found indications of coercive admission by family members, sometimes in order to obtain access to older people's homes and other property and finances.

Care homes do not usually require or even seek the informed consent of older people, regardless of their cognitive status. The results also suggest that care home owners and staff sometimes collude with family members in inappropriately admitting residents.

There are a growing number of care homes in Asia, Africa and Latin America, yet there is very little information about the appropriateness of procedures for admitting older people. Previous research has suggested that the industry is weakly regulated.

As well as data from a government-commissioned national survey, this new research used care homes in the city of La Plata, 35 miles south of Buenos Aires, as a case study. A novel aspect was a patient survey led by local pensioners who went 'undercover' to find out about admissions practices.

The study, published in The Gerontologist, involved researchers from UEA's Schools of International Development and Health Sciences, and the SIDOM Foundation in Argentina.

Lead author Peter Lloyd-Sherlock, professor of social policy and international development at UEA, said that in light of their findings, changes to national legal provisions are now being considered by policy-makers.

"Assessing the appropriateness of care home admissions is a complex challenge in all countries," said Prof Lloyd-Sherlock. "Regardless of the quality of care individuals receive once they have been admitted into a residential care home, inappropriate admission in some cases amounts to abuse, criminal behaviour and the infringement of fundamental human rights."

Prof Lloyd-Sherlock and his co-authors, Bridget Penhale of UEA and Nelida Redondo at the SIDOM Foundation, are calling for comparative research to be conducted in other countries, in order to establish both the extent of abuses and raise awareness.

"Our research indicates that this practice, which can entail elements of kidnap and false imprisonment, appears to be widespread in countries like Argentina," said Prof Lloyd-Sherlock. "To date, it has received scant recognition from policy-makers, human rights organizations or academics.

"If the Argentine experience of admissions is representative of this region, hundreds of thousands of older people will be experiencing this form of abuse. There is an urgent need for researchers, policy-makers, and civil society to acknowledge the scale of abuse and develop safeguards."

Commenting on the findings Bethany Brown, a researcher at Human Rights Watch, added: "Argentina is a party to the Inter American Convention on Protecting the Human Rights of Older Persons, which requires that states party to the Convention establish mechanisms to ensure that the initiation of long-term care services are subject to an indication by the older person of their free and express will."

The authors point to a number of other factors that exacerbate older people's vulnerability to coercive care home admission, many of which are evident elsewhere in Latin America and beyond. They include a failure of state agencies to develop appropriate legal frameworks to safeguard rights, and their limited capacity to enforce whatever safeguards do exist.

Increased economic opportunity gaps between older people and younger generations, minimal state support for family carers and an inheritance law that fails to protect the interests of surviving spouses also increase the risk of coercive admission.

The case study in La Plata drew on interviews with hospital staff working in geriatric care, local government officials responsible for care services and representatives of local NGOs, as well as focus group discussions with pensioners in different neighbourhoods.

It also involved pensioner-researchers calling and visiting care homes to ask staff questions, for example about the services offered, admissions procedures and requirements. They also carried out observational research regarding perceived quality of care. Interviews were conducted in 30 homes, which account for roughly half of those in La Plata.

Barcelona, Spain: Women with small, low grade, well-defined breast tumours and a genetic profile that shows they are at low risk of the cancer metastasising have only a 1.4% risk of the cancer returning to the site of the original tumour or the nearby lymph nodes (known as locoregional recurrence) within five years, according to new results from a large randomised trial of nearly 7000 patients.

This low risk of locoregional recurrence was seen regardless of whether the women had a mastectomy (the whole breast removed) or breast conserving surgery, in which just the tumour and some surrounding tissue are removed, followed by radiotherapy of the whole breast.

Presenting the latest results from the MINDACT trial [1] at the 11th European Breast Cancer Conference, Professor Emiel Rutgers, a surgeon at the Netherlands Cancer Institute in Amsterdam (The Netherlands), said the findings meant that it was possible to identify women who could safely avoid not only chemotherapy after surgery, but possibly also radiotherapy - both toxic treatments that can have debilitating effects on women's physical and mental well-being and quality of life.

"These findings show that, for these selected women, breast conservation is as good as mastectomy, and the risk of relapse is so low that we should look for ways of giving them less aggressive treatment. For instance, even though radiotherapy reduces the risk of locoregional recurrence two- to three-fold, can we do without it in some selected patients, such as these low risk women, and also in some women aged over 50 with small tumours, less than 2cms in diameter, who have a 1.4% risk of relapse within five years as well," said Prof Rutgers.

Among 6693 patients enrolled in the MINDACT trial, 5470 (82%) underwent breast conserving surgery and 1223 (18%) mastectomy. Decisions on how the women were treated were made on the basis of the tumour characteristics (size, grade, hormonal and HER2 status, and whether or not the disease had spread to any lymph nodes). In addition, their genetic make-up was investigated using the 70-gene-signature test (MammaPrint®). This analyses the activity of certain genes in early breast cancer and has been shown to accurately predict the risk of the cancer spreading (metastasising) to other parts of the body within five or ten years. Women who were at low risk of a recurrence, based on these clinical and genomic factors, did not receive chemotherapy after surgery, while those who were at high risk, did. Women with a mixture of high and low risk factors were randomised to receive chemotherapy or not. Almost all women who had breast conserving surgery also had radiotherapy, but not all of the women who had a mastectomy.

In this latest part of the study, Prof Rutgers and his colleagues looked at the rate of locoregional recurrences five years after surgery and analysed them according to the clinical and genetic characteristics. They found that women who had breast conserving surgery had an overall 2.1% risk of recurrence by five years, but if they had a low 70-gene signature score, the risk dropped to 1.4%, while if they had a high score the risk was 3.6%. Among women who had a mastectomy, the overall risk of recurrence was 2.5%, but this dropped to 0.7% in those with a low genetic score and went up to 4.9% in those with a high score. After full statistical analysis, tumour grade and size were the only factors significantly associated with the risk of locoregional recurrences.

Prof Rutgers said: "The importance of this MINDACT analysis is that local and regional control, in which breast cancer does not come back in the preserved breast, or in the skin after mastectomy, or in the surrounding lymph nodes, is extremely good. The odds of the cancer coming back are about 2% in five years after breast conservation and 2.5% after mastectomy. This includes relapses in the surrounding lymph nodes. This very low risk is determined by the biology of the primary cancer, such as grade, size and growth pattern, and to some extent also by age, with women over 50 years also having a lower overall risk. Among these women aged over 50, those with slow-growing 'lazy' breast cancers have a 0.88% risk, and those with more aggressive ones have a 3.5% risk at five years. We should remember that some 10-15 years ago a 10% recurrence rate at 10 years was considered the norm.

"Another important message from these findings is that well-performed breast conserving surgery in women with good indications is as good as mastectomy. Doing a mastectomy when you could very well perform breast conservation will not add a day to the life of a breast cancer survivor.

"This is a wonderful trial that provides wonderful opportunities for further research."

As a result of these findings, Prof Rutgers says that a study should be performed that prospectively investigates whether women at low risk of a recurrence could avoid radiotherapy.

"For instance, could a woman with an early grade, small tumour, perhaps with a low risk 70-gene signature score, only have breast conserving surgery, and no radiotherapy or chemotherapy? I believe she could. I would very much support a study of women between the ages of 50-70 years with 'lazy' small, low grade tumours, in whom the cancer has been completely excised with cancer-free margins. They would receive only hormone therapy and no radiotherapy if the 70-gene signature score shows them as having a low risk. With 1000 patients, such a trial could come to a practice-changing conclusion," he said.

Chair of the conference, Professor Robert Mansel, Emeritus Professor of Surgery in Cardiff University School of Medicine, Cardiff. UK, who was not involved with the study, commented: "These latest results from the MINDACT trial show the benefits to patients of large, international trials that have the power to detect whether or not it is possible to treat some women safely with less aggressive therapies. Professor Rutgers and colleagues have shown that there is a group of breast cancer patients who are low risk of locoregional recurrence and might be able to avoid radiotherapy and chemotherapy and the associated adverse side effects. I support his suggestion of a prospective trial to investigate this further in older, low-risk women."

Barcelona, Spain: The average number of moderate or marked side-effects reported by breast cancer patients is lower if they are treated with radiotherapy to part of the breast or a reduced dose to the whole breast, rather than with standard radiotherapy to the whole breast, according to new findings presented at the 11th European Breast Cancer Conference on Friday.

The IMPORT LOW study of 2016 women in 41 centres in the UK has already shown that partial breast and reduced dose radiotherapy was as effective as whole breast radiotherapy in controlling the cancer at five years, and women in the partial breast and reduced dose groups reported fewer side-effects, including less change in the appearance of the breast.

These latest results, which focus predominantly on side-effects affecting the breast and also body image reported during the five years following radiotherapy, show that over half of patients in the study did not report moderate or marked side-effects at any point and that most side-effects reduced over time. The number of side-effects reported per person were fewer in the partial breast and reduced dose groups compared with the whole breast radiotherapy group.

Dr Indrani Bhattacharya, a clinical research fellow at the Institute of Cancer Research's Clinical Trials and Statistics Unit (London, UK), from where the IMPORT LOW trial was coordinated, told the conference: "The findings from this study are reassuring for women who are offered either whole breast or partial breast radiotherapy using this technique of radiotherapy, which is simple to deliver and already available in centres worldwide.

"This new information will help doctors discuss the risks and benefits of this type of radiotherapy with patients and may improve shared decision-making, as well as enabling them to tailor treatment for individual patients."

The IMPORT LOW study randomised women to receive standard radiotherapy at a dose of 40 Gy to the whole breast (the control group), or 36 Gy to the whole breast and 40 Gy to the part of the breast that contained the original tumour (reduced dose group), or 40 Gy only to the site of the original tumour (partial breast group). The radiotherapy was given using hypofractionated intensity modulated radiotherapy (IMRT) - a technique that can deliver an even dose of radiation, minimising the chances of hotspots of unwanted high doses and reducing the cosmetic problems that can occur after breast radiotherapy.

More than half of the women (1265) took part in the sub-study that looked at patient-reported outcomes (PROMs). At the start of the study, after six months and one, two and five years after radiotherapy the women were asked about adverse side-effects, such as a hardening of tissue, pain, over-sensitivity of the treated area and build-up of fluid. Most of the side- effects reported by the women related to changes affecting the breast, and the commonest reported side-effect was "overall change in breast appearance".

The researchers found that women were more likely to report adverse side-effects if they were younger, had larger breasts, had a larger volume of breast tissue removed at surgery, if the cancer had spread to any of their lymph nodes, and if, at the start of the study, they were feeling anxious or depressed.

"Now that we can identify these patients who are at higher risk of reporting side-effects, this knowledge can be discussed with patients, may modify treatment and enable doctors to put in place more personalised and frequent monitoring if necessary. For example, patients with higher levels of anxiety and depression could be offered psychosocial support at the start of treatment, although we do not know from this study whether this would reduce the reporting of side effects," said Dr Bhattacharya.

"We have previously reported that partial breast radiotherapy is as effective as whole breast radiotherapy with similar or fewer side-effects over five years and can be safely delivered in a selected group of patients with low-risk breast cancers. This new analysis shows that patients requiring whole breast radiotherapy can be reassured about the low risk of side-effects affecting the breast and body image. The technique of radiotherapy used in IMPORT LOW is easy to implement and deliver as the equipment and expertise is available in all centres worldwide."

The IMPORT LOW trial is the largest randomised trial to study the use of IMRT to deliver partial or low dose breast radiotherapy compared to whole breast radiotherapy, and has provided the largest complete set of PROMs data for several points in time over five years.

"PROMs are very important for both women and clinicians as they describe side-effects from the patients' perspective and allow us to see the long-term effects of treatment as recorded by the patient. We know from this study and other studies that patients report more side-effects compared to doctors. This means that if we did not assess side-effects using PROMs, then the impact of the treatment-related side-effects on the patient may be underestimated," said Dr Bhattacharya.

Co-chair of the European Breast Cancer Conference, Professor Isabel Rubio, director of the Breast Surgical Unit at Clinica Universidad de Navarra (Spain), who was not involved with the research, commented: "Patient-reported outcomes are among the most important factors that we have added to assessments of outcomes in breast cancer in recent years. PROMs can improve relationships between physicians and patients, and enhance shared decision-making; this strategy will impact on the final outcomes in the management of breast cancer patients. These latest results from the IMPORT LOW trial provide important and reassuring information for clinicians and patients about side effects after partial or reduced dose radiotherapy, and will help them to make the best choices in each individual case."

More than 135,500 cases of cancer a year in the UK could be prevented through lifestyle changes, according to new figures from a Cancer Research UK landmark study published today.

This equates to 37.7% of all cancers diagnosed each year in the UK - rising to 41.5% in Scotland.

The latest figures, calculated from 2015 cancer data, found that smoking remains the biggest preventable cause of cancer despite the continued decline in smoking rates.

Tobacco smoke caused around 32,200 cases of cancer in men (17.7% of all male cancer cases) and around 22,000 (12.4%) in women in 2015, according to the research published in the British Journal of Cancer.

Excess weight is the second biggest preventable cause of cancer. Around 22,800 (6.3%) cases of cancer a year are down to being overweight or obese. This amounts to around 13,200 (7.5%) cases of cancer in women and around 9,600 (5.2%) in men.

Obesity causes 13 types of cancer, including bowel, breast, womb and kidney. And the results suggest that more than 1 in 20 cancer cases could be prevented by maintaining a healthy weight.

The third biggest preventable cause of cancer is overexposure to UV radiation from the sun and sunbeds, which causes around 13,600 cases of melanoma skin cancer a year (3.8% of all cancer cases).

Other preventable causes of cancer include drinking alcohol, eating too little fibre (causing around 11,900 and around 11,700 cases respectively, which is 3.3% each) and outdoor air pollution. While air pollution is to blame for around 3,600 lung cancer cases a year (1% of all cancer cases), it still causes far fewer cases of lung cancer than tobacco.

Sir Harpal Kumar, Cancer Research UK's chief executive, said: "Leading a healthy life doesn't guarantee that a person won't get cancer, but it can stack the odds in your favour. These figures show that we each can take positive steps to help reduce our individual risk of the disease. "This research clearly demonstrates the impact of smoking and obesity on cancer risk. Prevention is the most cost-effective way of beating cancer and the UK Government could do much more to help people by making a healthy choice the easy choice."

Professor Linda Bauld, Cancer Research UK's prevention expert, said: "These new figures show that the battle to conquer smoking-related cancer is far from over. But the declining numbers of smokers show that prevention strategies are working.

"Obesity is a huge health threat right now, and it will only get worse if nothing is done. The UK Government must build on the successes of smoking prevention to reduce the number of weight-related cancers. Banning junk food TV adverts before the 9pm watershed is an important part of the comprehensive approach needed."

Janet Boak, 55, a grandmother of three from Carlisle, was diagnosed with womb cancer at 51 after she noticed spots of blood four years after her menopause. During surgery to remove two fibroids from her womb, cancer was found. Janet then had a full hysterectomy to remove her womb and cervix. Because the cancer was caught in the earliest stages and hadn't spread, she avoided any further treatment.

Volunteering to take part in some womb cancer research after her treatment, Janet was shocked to find out that the possible contributing factors for womb cancer included being obese and being inactive.

Janet said: "That was me. At almost 20st and wearing up to a size 30, I was huge and most of my weight was around my stomach. I couldn't remember the last time I did any exercise.

"Of course I'd known I needed to lose weight but I hadn't realised just how much I was putting my life at risk." Janet joined a local slimming group in 2015, changed her diet and started taking exercise.

She said: "The weight gradually fell off and now, over two years on, I've lost more than 6st and wear a size 16. I could barely keep up with my three young grandchildren before but now I'm always running around after them. I even ran Race for Life for Cancer Research UK last year - something I never imagined I would do.

"Getting cancer was terrifying but it was the wake-up call I needed. I don't know what the future holds but at least I know I'm doing all I can to stay healthy and happy."

A multi-institutional study supports the value of a biomarker to accurately diagnose or rule out acute heart failure in patients seen for shortness of breath at hospital emergency departments. The report published in the Journal of the American College of Cardiology also validates the use of age-adjusted thresholds of the protein NT-proBNP to diagnose heart failure in a wide range of such patients.

"Since we did the first U.S.-based studies of NT-proBNP for the identification or exclusion of heart failure, as well as for establishing the risk of bad outcomes, its use has been incorporated into diagnostic guidelines internationally," says James Januzzi Jr., MD, of the Massachusetts General Hospital Division of Cardiology, who led the study. "But over the past 15 years, the characteristics of patients with heart failure have changed - they tend to be older, are more likely to be women and to have additional complications - making a contemporary re-assessment of the assay's performance necessary.

NT-proBNP (N-terminal pro-brain natriuretic peptide) and a related protein called BNP (B-type natriuretic peptide) are both produced when the cardiac muscle is under stress. One of the earliest studies of the value of NT-proBNP testing, conducted in the MGH Emergency Department, suggested age-based diagnostic cutoffs for diagnosis of acute heart failure - 450 pg/ml for patients under 50, 900 pg/ml for those 50 to 75, and 1,800 pg/ml for those over 75. An NT-proBNP level of 300 or below appeared to rule out acute heart failure no matter the patient's age.

Use of those cutoffs was supported by a larger, multi-institutional trial, but while they have been largely adopted at hospitals worldwide, the only NT-proBNP diagnostic cutoffs approved by the U.S. Food and Drug Administration (FDA) are 125 pg/ml for patients under 75 and 450 pg/ml for those 75 and older - levels designed for use in conjunction with outpatient treatment. The current study, conducted by the Baim Institute for Clinical Research, and led by Januzzi, was designed both to validate the emergency-care-based cutoffs and to determine whether they remain useful for assessment of the current population of patients with heart failure.

Conducted in 2015 and 2016 at 19 sites in the U.S. and Canada, the study enrolled 1,461 adult patients who had come to hospital emergency departments with shortness of breath or other breathing difficulties. Blood samples to be measured for NT-proBNP levels were taken upon study enrollment, and determination of the presence of acute heart failure - separate from the clinical diagnosis that guided participants' care - was made by clinicians blinded to individual participants' NT-proBNP levels. Overall, 277 patients - 19 percent of total study enrollment - were determined to have acute heart failure.

Comparison of participants' NT-proBNP levels with their eventual diagnoses supported the usefulness of the age-based cutoff levels and that a level below 300 strongly excluded a heart failure diagnosis. These results were consistent across all groups of participants, no matter their age, gender, racial or ethnic background or the presence of conditions like obesity or kidney disease.

"We found no specific population in which the test did not perform well, and what was most striking to me - as someone who has been working with NT-proBNP since the early 2000s - was how consistent these results were with those of prior studies," says Januzzi, who is the Hutter Family Professor of Medicine in the Field of Cardiology at Harvard Medical School. "Given the changes in the types of patients with heart failure we see today, it's quite remarkable how reliable this test is."

Januzzi and his colleague expect their results will extend the use of age-based NT-proBNP cutoffs even further, which by allowing faster and more accurate diagnosis or exclusion of heart failure should lead to better patient outcomes. They also anticipate FDA approval of the age-based cutoffs for emergency department diagnosis.

The Queen's University N. Ireland Cancer Registry (NICR) today released the number of new cancer cases diagnosed (incidence) in Northern Ireland in 2016. Legislation designating the Northern Ireland Cancer Registry (NICR) as an official producer of statistics came into place 1 April 2012. Website available at: http://www.qub.ac.uk/nicr.

The yearly average of incidence for patients diagnosed 2012-2016 is presented as a stable estimate of incidence in Northern Ireland (NI), and in various geographic groups. The release also updates cancer incidence trends and survival statistics 1993-2016.

Key facts and figures are presented below.

Cancer incidence 2012-2016

In the period 2012-2016 in addition to 3,718 cases per year of non-melanoma skin cancer (NMSC) there were 4,607 male and 4,632 female patients diagnosed with cancer each year during 2012-2016.

The most common cancers diagnosed among males between 2012 and 2016 were prostate (24% of all cancer in males), colorectal (14%) and lung (14%) while the most common cancers among women were breast (30% of all cancer in females), lung (13%) and colorectal (11%).

Cancer risk is strongly related to age with over 60% of cases occurring in people over the age of 65 and incidence rates greatest for those aged 85-89 years.

Excluding NMSC the odds of developing a cancer by the age of 75 was 1 in 3.5 for men and 1 in 3.7 for women.

Cancer incidence trends

Over the last ten years the number of cancer cases (excluding NMSC) has increased from 4,044 among men and 3,885 among women in 2007 to 4,629 among men and 4,817 among women in 2016. These increases are largely due to our ageing population.

After adjusting for age, following a steady increase in cancer incidence rates in males since 1999, rates decreased during 2011 to 2016 by an average of 1.5% per year. In contrast, since 2001 female incidence rates have shown a continuous increase by an average of 1.0% per year. These changes reflect increasing rates of lung cancer linked to historic smoking trends among women and increasing breast cancer incidence.

In 2016, for the first time, there were more cases of lung cancer diagnosed in women than men with 698 cases compared to 653, respectively. Lung cancer incidence rates (adjusted for age) are declining in men however continue to significantly increase in women at almost 6% per year since 2010.

Incidence rates of colorectal cancer have been decreasing in both men and women since 2012 and 2013, respectively, by 5% per year.

The number of in situ-cervix cases and age-adjusted incidence rates are markedly lower in 2016 compared to the previous 10 years. There were 920 cases diagnosed in 2016 compared to 1,162 cases in 2015.

Incidence rates by socio-economic deprivation

Cancer incidence is 10% higher in the most deprived areas compared to the Northern Ireland average and 4% lower in the least deprived areas. This varies significantly by cancer site with incidence of lung, head & neck, oesophagus, stomach, male-colorectal and cervix higher in the most deprived areas and incidence of melanoma and breast cancer higher in the least deprived areas.

Survival statistics updated

Over 55% of all cancer patients survived five years after diagnosis, 20% of patients died within 6 month of diagnosis, while over 70% of patients were alive one year after diagnosis.

Five-year net survival rates, which take account of background mortality, for patients diagnosed between 2006 to 2010 were as follows: female breast (81.7%), colorectal (57.6%), prostate (88.7%), lung (10.4%). These survival rates have all shown improvement compared to patients diagnosed in the period 1993 to 1999, although gains in lung cancer survival were slight.

Comparisons of five-year survival for patients diagnosed 2006-2010 to those diagnosed 1993-2000 show survival improvements for all cancers except bladder cancer which has decreased in both females and males. This is likely linked with coding changes so not comparing the same types of bladder cancer over time. Comparing these two time periods, significant improvements in leukaemia and oesophageal cancer five-year survival have been observed, likely a reflection of improvements in treatments.

With regard to cancer prevalence, at the end of 2016 there were 61,038 people living in NI who had been diagnosed with cancer since 1993. Of these, 43.7% were male, 47.4% were aged 70 and over and 10.9% had been diagnosed in the previous year.

Scientists have found that drugs are now so prevalent that 13 per cent of those taking part in a test were found to have traces of class A drugs on their fingerprints - despite never using them.

But there is no easy escape for users as researchers from the University of Surrey, who have previously developed a quick fingerprint test to identify users, have created a definitive way to prove the difference between those using cocaine and heroin, and those exposed to the drugs due to environmental factors.

In a study published by Clinical Chemistry, researchers from the University tested the fingerprints of 50 drug free volunteers and 15 drug users who testified to taking either cocaine or heroin in the previous 24 hours.

Researchers tested fingerprints from the unwashed hands of the drug-free volunteers and, despite having no history of drug use, still found traces of class A drugs. Around 13 per cent of fingerprints were found to contain cocaine and one per cent contained a metabolite of heroin. By setting a "cut-off" level, researchers were able to distinguish between fingerprints that had environmental contaminants from those produced after genuine drug use - even after people washed their hands.

To test the possibility of transferring drugs through a handshake, drug free volunteers were asked to shake hands with a drug user. Fingerprints were then collected from the drug free volunteers after contact. Although cocaine and heroin can be transferred by shaking hands with a drug user, the cut-off level established allowed researchers to distinguish between drug use and secondary transfer.

Dr Melanie Bailey, Lecturer in Forensic Analysis at the University of Surrey, said: "Believe it or not, cocaine is a very common environmental contaminant - it is well known that it is present on many bank notes. Even so, we were surprised that it was detected in so many of our fingerprint samples. By establishing a threshold for significance on a fingerprint test, we can give those tested the piece-of-mind of knowing that whatever the result of the test may be, it was not affected by their everyday activities or shaking hands with someone that had taken drugs."

Mahado Ismail, lead-author of the paper from the University of Surrey, said: "It's clear that fingerprint testing is the future of drug-testing. There are many factors that set fingerprint testing apart - it's non-invasive, easy to collect and you have the ability to identify the donor by using the sample. Our study will help to add another robust layer to fingerprint drug testing."

The study was co-funded by Intelligent Fingerprinting, developers of the world's first commercially-available portable drug test that works by analysing the sweat from a fingerprint sample. According to Intelligent Fingerprinting's CEO, Dr Jerry Walker: "this important study confirms the University of Surrey's position as one of the world's foremost academic research groups when it comes to fingerprint diagnostics using mass spectrometry. Critically, it also helps to establish a quantifiable high threshold for environmental drug traces - further establishing the validity of our commercial fingerprint-based drug test for cocaine, opiates, cannabis and amphetamines."

The ancient martial art of tai chi has similar or greater benefits than aerobic exercise for people with the chronic pain condition fibromyalgia, finds a trial published by The BMJ today.

The findings suggest it may be time to rethink what type of exercise is most effective for patients with chronic pain conditions.

Fibromyalgia is a long-term condition that causes widespread body pain. It may also lead to extreme tiredness, muscle stiffness, difficulty sleeping and depression. It affects around 2-4% of the adult population worldwide.

Aerobic exercise is currently recommended as a standard treatment, but many patients find it difficult to exercise due to fluctuations in symptoms.

Some trials have suggested that tai chi alleviates pain and improves physical and mental health in patients with fibromyalgia but concluded that larger and more rigorous trials are needed to confirm the results.

So to investigate further, a team of US researchers set out to compare the effectiveness of tai chi with aerobic exercise and to test whether this depends on its frequency or duration.

They identified 226 adults with fibromyalgia who had not participated in tai chi or other similar types of complementary and alternative medicine within the past six months. The average age of participants was 52 years, 92% were women, 61% were white, and average duration of body pain was nine years.

At the start of the trial, participants completed the fibromyalgia impact questionnaire (FIQR), which scores physical and psychological symptoms such as pain intensity, physical function, fatigue, depression, anxiety, and overall wellbeing.

Participants were then randomly assigned to either supervised aerobic exercise twice weekly for 24 weeks or to one of four tai chi interventions: 12 or 24 weeks of supervised tai chi completed once or twice weekly.

Changes in symptom scores were assessed at 12, 24 and 52 weeks and participants were able to continue routine drugs and usual visits to their physicians throughout the trial.

FIQR scores improved in all five treatment groups at each assessment, but the combined tai chi groups improved significantly more than the aerobic exercise group at 24 weeks. Tai chi also showed greater benefit when compared with aerobic exercise of the same intensity and duration (twice weekly for 24 weeks).

Those who received tai chi for 24 weeks showed greater improvements than those who received it for 12 weeks, but there was no significant increase in benefit for those who received tai chi twice weekly compared with once weekly.

The effects of tai chi were consistent across all instructors and no serious adverse events related to the interventions were reported. The findings also remained largely unchanged after further analyses to test the strength of the results.

The researchers point to several study limitations. For example, participants were aware of their treatment group assignment, and attendance differed between the two treatment groups, both of which could have influenced the results. However, key strengths include the large and diverse sample and longer follow-up than previous studies.

"Tai chi mind-body treatment results in similar or greater improvement in symptoms than aerobic exercise, the current most commonly prescribed non-drug treatment, for a variety of outcomes for patients with fibromyalgia," write the authors. "This mind-body approach may be considered a therapeutic option in the multidisciplinary management of fibromyalgia," they conclude.

In a linked opinion article, lead researcher Dr Chenchen Wang, says the public health problem of chronic pain calls for an "all hands on deck" approach to give patients feasible therapeutic options for the management of fibromyalgia. "It is time, therefore, for physicians to explore new approaches and rethink their strategies in order to provide the best care for patients with chronic pain conditions."

In a second opinion article, Amy Price, a trauma survivor with chronic pain, describes how tai chi has helped improve her balance, reduce anxiety, and manage pain.

She acknowledges that tai chi does not work for everyone with fibromyalgia, but says the advantage is that "it is low risk and minimally invasive, unlike surgery, and it will not harm your organs, like long term drug use." And there is also the chance that it might complement other interventions to help your body work better, she concludes.

People who have had flu or pneumonia may be six times more likely to suffer from a heart attack or stroke in the days after infection, according to new research published in the European Respiratory Journal [1].

The research, funded by the Academy of Medical Sciences, is the largest study to look at the risk of heart attacks and strokes due to specific respiratory infections. It found that several different organisms that cause respiratory infections also increase heart attack and stroke risk, including S. pneumoniae bacteria and influenza.

The researchers say that the findings suggest that getting vaccinated against these two infections could also have a role in preventing heart attack and stroke, along with preventing infection in the first place.

In general, respiratory infections are thought to increase the risk of heart attack and stroke by causing inflammation, which can lead to the development of blood clots. The influenza virus and S.pneumoniae, the most common pneumonia causing bacteria, can also have harmful effects on the heart muscle.

The new research found that having flu or pneumonia increases the risk of having a heart attack for up to a week after infection, and the risk of having a stroke is increased for one month.

Lead researcher Dr Charlotte Warren-Gash, Associate Professor of Epidemiology at the London School of Hygiene & Tropical Medicine, UK, explained the importance of the study: "Heart disease, strokes and lower respiratory infections have been the three leading causes of death globally for over 15 years, and are important public health problems that affect large numbers of people worldwide.

"As people age, having more than one medical condition becomes more common, so it is even more important to understand the links between different diseases. If we can understand who is at risk of these cardiovascular complications after respiratory infections, we can potentially intervene to prevent them, with methods such as vaccines."

Using national infection surveillance data from the Scottish Morbidity Record, the researchers identified 1,227 adults with a first heart attack and 762 with a first stroke who also had a respiratory virus or bacteria infection at any time between 2004 and 2014.

The research team then investigated the rate of heart attacks and strokes in the periods of time immediately after a respiratory infection, and then compared this to the rate of cardiovascular events in other periods of time in the same people.

The data showed that having a confirmed respiratory infection made people six times more likely to have a heart attack or stroke for three days after infection. Dr Warren-Gash explains: "In Scotland, among those aged 75 years and above, around two in 10,000 people have a heart attack each week. Our analysis found this figure rose to 10 in 10,000 in the week after having a respiratory infection."

The S.pneumoniae bacteria and the influenza virus were found to have the biggest impact on increasing the risk of having heart attacks and strokes.

The effect of infections on heart attack and stroke risk was greater in people aged less than 65 years compared to those aged 65 and above. The researchers note that vaccine uptake is higher among those aged 65 and over, and say that being vaccinated could help to protect against heart attacks and strokes after respiratory infection.

However, Dr Warren-Gash said: "For most young, healthy people, the risk of heart attacks and strokes occurring after a respiratory infection is low. This research is particularly relevant for those over the age of 65, as well as people with pre-existing heart diseases, as these groups are at higher risk of heart attacks and strokes.

"These groups are already recommended to have vaccinations against influenza and S.pneumoniae - the two bugs we found to be linked to the highest cardiovascular risk - but we know that vaccine uptake is not high among younger people with heart problems. Understanding that there is a link between these bugs and heart attacks and strokes is an added incentive to get those vaccinations."

The researchers acknowledge that the study was not able to look at individual effects of less common respiratory viruses, or to examine how respiratory infections affect cardiovascular risk in different age groups in detail.

Dr Warren-Gash added: "Our research highlights the importance of ongoing work into which doses of vaccine are best to protect people from heart attacks and strokes. Although flu and pneumonia seem to have the biggest impact, this research also shows that a group of other respiratory viruses had some triggering effects. We don't currently have vaccines for these viruses so further research is needed."

Professor Mina Gaga, President of the European Respiratory Society, and Medical Director and Head of the Respiratory Department of Athens Chest Hospital, said: "We already know that having a respiratory infection is associated with a temporary increase in the risk of heart attacks in the weeks that follow infection, and there is some evidence that pneumococcal and influenza vaccinations have a protective effect.

"This large study reinforces the importance of making sure patients who are at-risk of heart attacks and strokes, such as people with chronic diseases and those aged over 65, are vaccinated against influenza and pneumonia to help better protect against adverse cardiovascular complications as well as respiratory infection."

ITHACA, N.Y. - Online gift-giving is spreading in social networks and causing people to give more gifts - online and in person - according to a new study led by René Kizilcec, Cornell University assistant professor of information science. About half of these gifts were unlikely to have occurred offline or via another online channel.

"Gift-giving is a fundamental part of human relationships, and technology is changing how it occurs: Social networking sites create greater awareness for gift-worthy occasions like birthdays, and gifts can be given last minute and over long distances. Digital traces of online gift exchanges are lifting the veil off these acts of generosity and inspire people to give more," Kizilcec said.

The paper, "Social Influence and Reciprocity in Online Gift Giving," co-authored with Dean Eckles of the Massachusetts Institute of Technology, and Eytan Bakshy and Moira Burke of Facebook, will be published in the Proceedings of the SIGCHI Conference on Human Factors in Computing Systems.

In the study, Kizilcec and his colleagues analyzed online gift-giving behavior on Facebook among U.S. adults during 2013. During that time, Facebook reminded users of their friends' birthdays and provided the option of sending an online gift - like a $15 Starbucks gift card - through the platform. The researchers complemented this data with surveys to get additional context.

The study found that when a person received a gift on Facebook for their birthday, they were then 56 percent more likely to also give an online gift through Facebook. This meant that approximately a third of all gifts given on Facebook after people's birthdays were inspired by receiving a gift in the first place.

"We found substantial evidence of social influence driving gift-giving behavior," said Kizilcec. "This boost in online gifts was not just the result of substitution away from offline gifts; but rather, it appears that receiving online gifts inspires people to give more gifts overall."

Most of the online gifts were reciprocal, being given to people who previously had given them gifts, online or offline. Three-fourths of gift-givers on Facebook reported having received a gift in the past from the person to whom they gave the gift, but only 11 percent of recipients directly reciprocated gifts on Facebook.

Kizilcec explained: "It initially appeared as if online gifting was spreading on Facebook by paying forward acts of kindness. Upon closer inspection, it became clear that there is a broader network of gift exchanges, and these acts of reciprocity seamlessly transcend the online and offline worlds."

He noted that Facebook gifts were replacements for offline gifts about half the time. "We found that 58 percent of givers said they would still have given that person a gift without Facebook, but 42 percent reported that it would have been more difficult. This indicates that some Facebook gifts were substitutes for gifts given through other channels, while other Facebook gifts were incremental, this is, they would not have occurred otherwise," he said.

Age was another factor in online gift-giving on Facebook. "While millennials gave fewer gifts on Facebook than non-millennials in absolute terms, millennials were easily influenced to give online gifts after receiving one. On average, millennials were twice as likely to give gifts on Facebook after receiving one," Kizilcec said. "Nevertheless, people between the ages of 45 and 64 still had the highest levels of Facebook giving, partly because they gave gifts to both their peers and younger generations."

Although technology may be changing how gifts are given, "the societal norms and practices transcend the gap between digital and in-person giving," Kizilcec said. "This study reveals that people rapidly internalize social norms about online gift-giving. Those who saw their friends exchange gifts were more likely to consider online giving 'normal' than those who learned about online gifts through other means.

"At a time when the spread of misinformation is in the foreground," he said, "it is especially gratifying to see strong evidence for the spread of kind and cooperative behaviors like gift-giving."

MAYWOOD, IL - Alcohol use early in the pregnancy by the mother may be a risk factor for a condition in which an infant's intestines develop outside the abdomen, according to a study published in the Journal of Maternal-Fetal & Neonatal Medicine.

Loyola Medicine maternal-fetal medicine physician Jean Ricci Goodman, MD, medical director of obstetrical services, was first author of the study.

The national study was conducted with patients who were referred to a university-based tertiary level obstetric clinic for a routine mid-pregnancy ultrasound. The aim was to evaluate the impact of poor maternal nutrition, environmental exposure and vasoactive stimulants (drugs that can either raise or lower blood pressure) as potential risk factors for gastroschisis, a condition in which a baby's intestines form outside the abdomen through a hole next to the belly button.

The study was conducted from September 2010 to June 2012, during which 38 cases of gastroschisis were diagnosed. Thirty cases were included in the analyses, with 76 control cases.

Among cases observed, there were no links found in either group between the use of illicit, prescription or over-the-counter drug use and gastroschisis. Diet and environmental exposures also did not seem to be risk factors.

However, the use of alcohol in mothers of gastroschisis cases one month prior and/or early in the pregnancy showed a significant increase in odds of the condition (36.7 percent in cases of gastroschisis versus 18.4 percent in the control group).

Babies born with gastroschisis are at risk for other anomalies in the gastrointestinal and other organ systems. Previous studies have indicated an increased rate in women from socially disadvantaged environments with nutritional deficits. While there has been an increase across all age groups and races, the largest increase (200 percent in the last decade) was among non-Hispanic African American women younger than 20 years.

"Cases of gastroschisis have been on the rise worldwide for 30 years," Dr. Ricci Goodman said. "It's important to understand why this trend is happening and develop measures to prevent it."

Dr. Goodman is part of a multidisciplinary team at Loyola Medicine offering comprehensive, integrated maternal-fetal medicine care for women who have or may develop pregnancy complications.

Bottom Line: Young mice that received molecularly targeted therapies used to treat brain cancer in human patients sustained cognitive and behavioral deficits, but the deficits were largely reversible through environmental stimulation and physical exercise. The study suggests that pediatric brain cancer patients may experience similar side effects of molecularly targeted therapies, and may benefit from efforts to remediate any cognitive deficits.

Journal in Which the Study was Published: Cancer Research, a journal of the American Association for Cancer Research.

Author: Joseph Scafidi, DO, MS, a neonatal neurologist at Children's National Health System, in Washington, D.C.

Background: "We've made significant progress against many childhood cancers, largely because of new, highly effective drugs," Scafidi said. "Targeted therapies currently used to treat brain cancers work because they target specific pathways in the cancer. However, these pathways are critical to the development of the brain, and so we set out to evaluate the cellular and behavioral effects of these drugs on a normal, developing brain.

"Primary central nervous system tumors continue to be the leading type of solid tumors in the pediatric oncology population," Scafidi continued. He said targeted therapies such as gefitinib (Iressa), sunitinib malate (Sutent), and rapamycin (Sirolimus) are now used to treat brain tumors, and interest in prescribing this class of drugs is growing. However, most clinical trials and pre-clinical studies on the drugs have been conducted in adults, therefore, the effects on pediatric patients are not fully known.

How the Study Was Conducted and Results: In this study, Scafidi and colleagues injected mice with either gefitinib, sunitinib malate, rapamycin, or a vehicle substance. One group of mice received the vehicle or drug when they were between 12 and 17 days old (analogous to early childhood); another group received the vehicle or drug when they were 17 to 22 days old (analogous to adolescence); and in a separate set of experiments, mice received the vehicle or drug when they were between 12 and 14 weeks old (analogous to adulthood).

Researchers assessed the drugs' effects on oligodendrocytes, a type of cell, in the white matter of the brain. They found that the mice that received the drugs at the youngest ages had the most significant decrease in oligodendrocytes; the mice that received the drugs as adults did not have significant changes. The researchers also analyzed myelin protein expression and again found the most significant changes in the mice that received the drugs at the youngest ages.

The researchers also measured other types of cells and found no significant changes, suggesting that the moleculary targeted therapeutics specifically target oligodendrocytes, Scafidi said.

To examine whether the drugs had behavioral effects, the researchers put the mice through a series of tasks: inclined beam-walking, novel object recognition, and maze running. The mice treated at a younger age with any of these three drugs showed the highest degree of behavioral deficits. Mice treated in adulthood showed no difference in cognitive performance.

Finally, the researchers randomized the mice to either typical housing or an "enriched environment," which included a running wheel and assorted toys. Researchers found that after about two weeks of living in the enriched environment, mice performed significantly better on the beam-walking task and the object recognition task.

Author Comment: Scafidi said the mice's improved performance supports the idea that the brain is plastic, and that cognitive deficits that result from childhood brain cancer treatments may be reversible. He said many cancer centers, including his own, provide different forms of cognitive and physical therapy to patients, and if this research is confirmed in further studies, it may provide a basis for making such therapy a widespread clinical practice.

"The fact is, these drugs do have an effect on the developing brain. The good news is that these effects can be attenuated by exposure to a stimulating cognitive and physical environment," Scafidi said.