Body

SALT LAKE CITY - Researchers at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) discovered in laboratory studies that an experimental drug called selinexor may block a crucial survival pathway exploited by myelofibrosis cells. Their study was published in Clinical Cancer Research, a journal of the American Association of Cancer Research. Based on these findings, they designed a clinical trial now open at HCI to examine this drug's effectiveness in patients with myelofibrosis (National Clinical Trial 03627403)

Myelofibrosis is a rare cancer that prevents the bone marrow from making healthy blood cells. Life expectancy varies, but most patients will not live beyond five years after the diagnosis. HCI treats about 25 newly diagnosed myelofibrosis patients a year.

Srinivas Tantravahi, MBBS, MRCP, a physician-scientist at HCI and assistant professor of medicine at the U of U, takes care of patients with myelofibrosis, and says it is a very debilitating disease. "Essentially, it's a bone marrow failure. The patient will experience severe symptoms including enlargement of the spleen, anemia, pain in the belly, fatigue, and a very poor quality of life," says Tantravahi, who was part of the study team. "A stem cell transplant can potentially cure the disease, but most patients diagnosed with myelofibrosis are older or not healthy enough to undergo the weeks-long procedure."

A drug called ruxolitinib is the current primary treatment for myelofibrosis patients who are not healthy enough to receive a stem cell transplant. This drug can decrease spleen size, improve symptoms and improve quality of life, but it does not typically reduce the percentage of malignant cells. The lack of available therapies for myelofibrosis patients motivated the research team at HCI to look for new avenues for treatment. "Ruxolitinib is a fine drug, but its effects are mostly short-lived. And, until now, there were no other options for patients who aren't healthy enough for a stem cell transplant," said Dongqing Yan, PhD, a research associate in the Deininger/O'Hare Lab at HCI and lead author on the study.

The team discovered myelofibrosis cells are highly sensitive to blockade a cellular process called nuclear-cytoplasmic transport. Anthony Pomicter, MS, manager of the Deininger/O'Hare lab explains, "Our results opened a new window for therapeutic intervention. By wonderful coincidence, selinexor, an inhibitor of this specific mechanism, is in clinical trials for certain blood cancers and now will be tested specifically in myelofibrosis patients."

The researchers worked to establish whether blocking the nuclear cytoplasmic transport process would slow the growth of myelofibrosis cells. To accomplish this, they generated a type of mouse with a specific mutation that leads to symptoms very similar to those experienced by myelofibrosis patients. When these mice were treated with the newly tested drug selinexor they responded just as well as those treated with ruxolitinib, and importantly, selinexor actually appeared to reduce the percentage of malignant cells.

Based on these findings, the researchers designed a new clinical trial to study the effectiveness of selinexor in people with myelofibrosis. The clinical trial of selinexor in the treatment of relapsed/refractory myelofibrosis is now open at HCI. The researchers aim to enroll at least 24 patients who will receive the treatment in a setting that will allow for rigorous examination of any clinical benefit and monitoring of side effects. If this early trial indicates positive outcomes for patients, more extensive studies involving additional sites and more patients will be planned.

"The ability to advance a study like this from bench to bedside - from first discovery in a laboratory setting to first in the world clinical trial - is a credit to the unique environment at HCI," says Michael Deininger, MD, PhD, HCI senior director of transdisciplinary research and professor of medicine at the U of U, and senior author on the study. "Myelofibrosis is a rare cancer, and it makes life miserable for those affected. It is extremely important that HCI and other institutions continue to push the discovery effort in all types of cancer, including rare diseases like myelofibrosis, so can we bring better treatment options to our patients."

NEW YORK, NY (June 19, 2019)--Limiting ovarian cancer surgery to high-volume hospitals could improve survival but may also reduce access for many rural and underserved patients, a new study from researchers at Columbia University Vagelos College of Physicians and Surgeons has found.

Although mortality was higher than average at hospitals that performed 3 or fewer procedures, more than 75% of low-volume hospitals had better-than-expected outcomes at 60-days and 51% had better-than-expected outcomes at 2 years based on their patient population.

Applying a minimum-volume cutoff of 3 procedures would prevent nearly 35% of hospitals, mainly in rural areas, from performing ovarian cancer surgery--affecting nearly 8% of patients. Over 300 patients would need to be moved from a hospital treating 3 or fewer patients to a higher-volume center to prevent 1 death in the year after surgery.

"Our study shows that hospitals considering implementing minimum-volume standards for cancer surgery could unintentionally prevent many patients from getting timely care for a minimal increase in survival," says Jason Wright, MD, an associate professor of gynecologic oncology at Columbia University Vagelos College of Physicians and Surgeons and the study's senior author.

The findings were published in Obstetrics & Gynecology.

Ovarian cancer surgery is a complex procedure with a high risk of complications. Studies have shown that patients undergoing cancer surgery often have better outcomes when treated at hospitals that perform these procedures routinely.

"There's a strong rationale for implementing minimum-volume standards at hospitals that perform cancer surgeries--large procedures that require experience and a very specialized skill set," Wright says. "But while some hospital systems are voluntarily implementing minimum-volume standards, we haven't determined the optimal volume for hospitals performing complex cancer procedures, or how applying minimum-volume standards would affect access to care for women with ovarian cancer, especially in rural areas."

The researchers used a national cancer database containing 136,196 women who were diagnosed with invasive ovarian cancer between 2005 and 2015 and the 1,321 hospitals that had treated them.

They then compared the hospitals' actual (observed) mortality rates with expected mortality rates (based the characteristics of each hospital's caseload) and modeled how eliminating low-volume hospitals would affect outcomes.

A large number (nearly 50%) of hospitals performed 5 or less ovarian cancer surgeries per in 2015, treating approximately 13% of all women with newly diagnosed ovarian cancer.

On average, hospitals performing 5 or less of these procedures had higher-than-expected mortality rates at 6 months, 1 year, 2 years, and 5 years after surgery. The biggest differences in mortality occurred in the first 6 months to 2 years after surgery, when the risk of complications is higher.

But individually, a large number of low-volume hospitals had better-than-expected mortality rates. For examples, among hospitals that performed 3 or fewer surgeries in the previous year, 51% had lower than expected 2-year mortality rates.

Implementing a minimum-volume standard of 3 or more surgeries a year would have eliminated 35% of hospitals that treated 7.7% of all patients with ovarian cancer in 2015. Yet this restriction would have only avoided 1 death for every 300 patients treated.

"An arbitrary minimum-volume standard may be unnecessarily punitive for low volume centers with good outcomes," says Wright. "We have previously found that outcomes are better at low-volume centers that rigorously adhere to evidence-based treatment guidelines for ovarian cancer, suggesting that metrics other than volume may be more appropriate."

A new International Journal of Cancer study indicates that rates of invasive cervical cancer (ICC) are particularly high in women living with HIV in South Africa or Latin America.

For the study, researchers compared ICC rates in 45 countries across Europe, South Africa, Latin, and North America among women living with HIV who initiated antiretroviral therapy between 1996 and 2014, through a collaboration between global HIV cohort research networks. Among 64,231 women in the analysis, 356 incident ICC cases were diagnosed (164 in Europe, 156 in South Africa, 19 in North America, and 17 in Latin America). Compared with rates in European women, ICC rates at 5 years after initiating antiretroviral therapy were more than double in Latin America and 11-times higher in South Africa, but similar in North America.

The investigators noted that improving access to early antiretroviral treatment and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

"Cervical cancer is a preventable disease, but many women living with HIV, especially in Latin America and South Africa, are still being diagnosed with this potentially deadly cancer," said corresponding author Dr. Eliane Rohner, of the University of Bern, in Switzerland, representing the International epidemiology Databases to Evaluate AIDS (IeDEA) Southern Africa collaboration. "We need to improve access to effective cervical cancer screening and treatment for women living with HIV globally."

An investigational drug for the treatment of sickle cell disease is showing early promise in clinical trials for impacting biomarkers of the disease in patients, reported UConn School of Medicine researchers at the European Hematology Association Congress in Amsterdam this week.

For the rare, painful red blood cell disease, which impacts blood circulation, pre-clinical laboratory data had already illuminated the potential of the experimental drug IMR-687 for reducing both the sickling of red blood cells and blood vessel blockages. The drug was shown to reduce these two major culprits that lead to sickle cell disease's debilitating pain, organ damage, and early mortality of patients - who have an average life expectancy of 40. That is why the drug has been granted U.S. Orphan Drug Designation, U.S. Rare Pediatric Designation, and Fast Track Designation by the Food and Drug Administration (FDA).

After 13 weeks of testing in its current clinical trial, the orally administered, once-a-day phosphodiesterase 9 (PDE9) inhibitor in adult patients with sickle cell disease is demonstrating tolerability and the ability to impact both red and white blood cell biomarkers of the disease, says Dr. Biree Andemariam, lead investigator for the clinical trial, associate professor of medicine at UConn School of Medicine and director of the New England Sickle Cell Institute at UConn Health.

"These initial Phase 2a data demonstrate the potential of IMR-687 to significantly impact key biomarkers associated with the pathology of this serious disease," she says.

A biomarker is a measurable indicator of a biological condition, often evaluated to examine normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

The clinical trial is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating doses of IMR-687 administered once daily for 16 to 24 weeks in two groups of patients with sickle cell disease.

Patient groups include those receiving the current standard of care dose of hydroxyurea - a drug that helps reduce the frequency of pain episodes in sickle cell patients - and those who are not on hydroxyurea. Their white and red blood cell markers and quality of life are also being analyzed.

At 13 weeks, there has already been a significant increase in the percent of F-cells, the red blood cells containing fetal hemoglobin (HbF) that often precede rises in total HbF. Also, there has been a corresponding decrease in absolute reticulocyte count and the percentage of reticulocytes, the immature red blood cells produced by the body's bone marrow, along with a trend toward improved pain.

The clinical trial study also found patients had no clinical significant changes in white blood cell counts and no evidence of neutropenia, a reduction in the level of white blood cells needed to help fight infection.

"The interim Phase 2a data reflect trends that could be indicative of meaningful clinical translation of these important measures in sickle cell disease," Andemariam adds.

Imara Inc., the maker of the drug and sponsor of the clinical trial, is a clinical-stage biopharmaceutical company developing novel therapies for sickle cell disease and other inherited blood disorders.

"We are encouraged by this interim Phase 2a analysis that reinforces our belief in the potential of IMR-687 as a single oral, once-a-day therapeutic," said Rahul D. Ballal, chief executive officer of Imara. "IMR-687 uniquely targets both red cell and white cell aspects of the disease, and we are working to expeditiously advance this novel therapy through clinical development, with a goal of delivering it to patients with SCD who are in need of innovative treatment options."

More clinical trial data is expected to be shared later in 2019.

Says Andemariam, "We are so proud of the efforts of the clinical and research staff at UConn Health who have been vital to the success of this clinical trial so far, always putting first the high-quality care and future health of sickle cell patients."

(SACRAMENTO) -- A UC Davis study of nine emergency departments and urgent care centers in California and Colorado found educating physicians and patients about safe antibiotic use can cut overuse by one-third.

The study, funded under a contract from the U.S. Centers for Disease Control and Prevention (CDC), appears in June 19 in the journal Academic Emergency Medicine.

It compared two approaches designed to help physicians make better antibiotic-prescribing decisions for viral acute respiratory infections (ARIs) without limiting the choices available. Viral ARIs are common conditions that range from ear ache and laryngitis to influenza and bronchitis.

One approach offered educational materials from the CDC's Be Antibiotics Aware campaign for patients and providers, and an on-site physician champion. The other more intensive approach provided education and behavioral "nudges," which gave each physician feedback on prescribing rates, comparisons with their colleagues and public commitment to reduce unnecessary use.

"We found education with an on-site champion reduced inappropriate antibiotic use by a third across the board," said Larissa May, professor of emergency medicine at UC Davis Health and senior author. "Our study shows that this relatively simple approach can get us to near-zero inappropriate antibiotic use for acute respiratory infections."

Of the 10 million prescriptions for antibiotics that emergency department physicians in the U.S. write each year, half are prescribed for known viral infections such as acute bronchitis and upper respiratory infections, which do not respond to antibiotics.

Inappropriate use exposes patients to opportunistic infections and adverse drug events. It also increases the ability of pathogens to become resistant to antibiotics. According to the CDC, antibiotic resistant bacteria cause two million illnesses and approximately 23,000 deaths in the U.S. each year.

There have been few tested approaches to reducing antibiotic overprescribing in emergency departments and urgent care settings due to the challenges of seeing patients quickly and having limited information. The researchers believe their stewardship program made a difference because it was tailored for each site, incorporated feedback from physician champions, displayed public commitment to avoiding unnecessary antibiotics and had the support of engaged stakeholders throughout the study made a difference.

For the study, the researchers tracked 44,820 viral ARI visits among 292 providers at five adult and pediatric emergency departments and four urgent care centers. They tallied the proportion of inappropriate antibiotic treatment by individual providers. The sites included UC Davis Medical Center, Harbor-UCLA Medical Center, Children's Hospital Colorado and University of Southern California.

"We need strategies that promote the careful prescribing of antibiotics in emergency departments and urgent care centers to slow the spread of antibiotic resistance and reduce unnecessary harm to patients from antibiotics," May said.

May developed the MITIGATE antimicrobial stewardship toolkit for health care providers and administrators interested in designing quality improvement programs in antimicrobial stewardship.

New research indicates that perfectionism is related to breast size dissatisfaction, but only in non-mothers - suggesting that mothers are more comfortable with their bodies.

The study, carried out by Professor Viren Swami of Anglia Ruskin University (ARU) and academics from Sapienza University of Rome, has been published in the journal Body Image.

Of the 484 Italian women surveyed, 69% reported breast size dissatisfaction with 44% wanting larger breasts. These findings are similar to a previous study carried out by Professor Swami focusing on women in the UK.

Perfectionistic self-presentation - the desire to create an image of flawlessness in the eyes of other people - is known to contribute towards negative body image.

The study found that breast size dissatisfaction was associated with higher levels of two of the three factors behind perfectionistic self-presentation (non-display of imperfection and perfectionistic self-promotion).

However, this association was not found among the 54% of women surveyed who were mothers. This was particularly the case among women who had more than one child.

Viren Swami, Professor of Social Psychology at Anglia Ruskin University, said: "Our findings suggest that motherhood may help to decouple the link between perfectionistic self-presentation and breast size dissatisfaction.

"There are a number of potential reasons why the association between perfectionistic self-presentation and breast size dissatisfaction was significant only amongst non-mothers. There is the fact that becoming a mother naturally results in changes to the appearance of the breasts, particularly in terms of their size.

"But perhaps the most relevant is that becoming a mother - and particularly the experience of breastfeeding - may focus women's attention on breast functionality as opposed to focusing on the aesthetics of breasts and the body."

CAMBRIDGE, MA and YORK, ENGLAND - June 19, 2019 - Shimmer Research, a global leader in wearable technology for research applications, and ClearSky Medical Diagnostics, a leader in analyzing wearable data for medical applications, today announced they are partnering to bring a new level of analytic capabilities to the use of wearable sensors in clinical research. This partnership will employ Shimmer's Verisense™ wearable sensors platform, which has been designed specifically for use in clinical research, with ClearSky algorithms and machine learning to transform wearables data into actionable insights for central nervous system (CNS) diseases.

Verisense is a comprehensive and flexible solution for reliably capturing accurate and complete biometric data. Worn on the wrist, the Verisense Inertial Measurement Unit (IMU) sensor can monitor activity and sleep seamlessly. But Verisense can be used for any IMU application with up to seven sensors worn on different parts of a participant's body, making it invaluable for studying complex musculoskeletal or neurological conditions, such as dystonia or epilepsy.

ClearSky Medical Diagnostics specializes in developing technologies for the diagnosis and monitoring of Parkinson's disease, Alzheimer's disease and other neurodegenerative conditions. Its clinically-validated medical devices have been used in medical centers worldwide and in clinical trials to demonstrate the efficacy of new drugs. For example, ClearSky's LID-Monitor can distinguish Levodopa-induced dyskinesia from Parkinson's tremors, allowing doctors to optimize Levodopa dosage. This approach significantly improves patients' quality of life and also saves time and money due to the reduction in consultations required. ClearSky's technical team has more than 15 years' experience analyzing clinical trial data and has developed a range of machine learning technologies to meet current and future clinical needs.

"The Verisense platform is truly a breakthrough for conducting clinical research," said Dr. Stephen Smith, co-founder of ClearSky Medical Diagnostics. "It can provide the continuous raw data from wearables needed for sophisticated algorithms, yet places almost no burden on the participant or the clinical site. It has multiple layers of redundancy and quality checking to ensure that high-quality data are collected without interruption."

"ClearSky's algorithms can be used with Verisense data right away," said Geoff Gill, president of Shimmer Americas, "but what we are really excited about is the potential for our clinical research customers to leverage ClearSky's experience and datasets to develop endpoints for a wide variety of CNS disorders based on Verisense data. ClearSky has taken raw motion data and transformed it with machine learning into actionable insights for physicians in a wide range of applications. This experience is ideally suited to develop endpoints for diseases like Parkinson's, multiple sclerosis, Huntington's, and many others using real-world data."

"Literally thousands of researchers have been using Shimmer sensors for more than 10 years to develop algorithms to understand the data from wearable sensors," said Gill. "By capturing continuous raw data, the Verisense platform allows us to leverage tens of thousands of person-years of research. We anticipate collaborating with many leading researchers and are excited that ClearSky shares our vision."

Interested parties can see the Verisense platform in action in booth #533 at the DIA Annual Meeting, which will be held from June 24-26 at the San Diego Convention Center, San Diego, CA.

Women's awareness of alcohol's role in boosting breast cancer risk is poor, indicates research published in the online journal BMJ Open.

Only one in five women attending breast clinics and screening appointments and only half of the staff questioned at one NHS UK centre knew that alcohol is a risk factor for breast cancer, the findings show.

This low level of awareness may not be the same everywhere, caution the researchers. But they nevertheless suggest that understanding of modifiable risk factors for the disease needs to be increased: breast clinic and screening appointments may offer the opportunity to do that.

Breast cancer is the most common cancer in the UK, with more than 54,000 new cases diagnosed and 11,000 deaths every year. Lifestyle factors account for nearly a quarter of all cases, with alcohol consumption and obesity topping the list.

Alcohol consumption is estimated to be responsible for between 5% and 11% of cases, with the risk increasing in tandem with the amount consumed, say the researchers.

They wanted to find out if women and staff using breast care services would find the provision of brief information on the health risks associated with alcohol acceptable.

They particularly wanted to know about prevailing levels of awareness of alcohol's role in breast cancer risk; and whether women were able to correctly identify alcohol units in drinks.

They drew on questionnaire and verbal feedback from 102 women attending for breast screening, 103 attending breast clinics because of symptoms, and 33 clinical staff at one UK NHS breast care centre.

Knowledge of modifiable risk factors was more or less the same in both patient groups. Around a third of participants (30%) in each group recognised obesity as a risk factor and one in two correctly identified smoking as another.

But only around one in six (16%) in the screening group, and around one in four (23%) in the breast clinic group knew that alcohol is a risk factor.

Between 60% and 73% of the women said they drank alcohol. Awareness of its role in upping breast cancer risk was significantly more likely among the breast clinic women (35%) than it was among those coming for screening (4%).

Only just over half of those who said they drank alcohol (88 out of 152; 58%) thought they knew how to estimate the alcohol content of drinks, although less than three quarters correctly estimated the alcohol content of a standard glass of wine, and just over half the amount in a pint of beer.

Asked how they felt about a 5-minute cancer prevention information session at either screening or breast clinic appointments, nearly a third (30.5%) of all the women said it would make them more likely to attend while more than two thirds (69.5%) said it would make no difference.

The preferred option, stated by 40%, was for a trained nurse to give them this information. But they voiced some concerns about feeling stigmatised and 'blamed' for drinking.

Clinical staff had better levels of awareness of breast cancer risk factors than patients, but they also had gaps in their knowledge.

Obesity was correctly identified as a risk factor by 58% (19 out of 33) of those asked, but only around half (52%) knew that alcohol also posed a risk. And less than half (45%) said they knew how much alcohol was in a drink.

But they cited various drawbacks to providing preventive information, including extra time and resource; the potential to make people anxious and contribute to the 'worried well' culture; as well as fears that it could come across as blaming and/or patronising.

The researchers acknowledge that the study involved only one breast care centre, and so may not be applicable elsewhere. And they recognise that substantial cultural and systemic changes might be needed to introduce such an approach.

But they write: "Over 20% of women aged 45 to 64 reportedly drink more than 14 units per week, so any intervention to reduce population level consumption could have a significant influence on breast cancer rates, as well as help to manage the side effects of treatment and improve the overall health of survivors."

Good heart and lung (cardiorespiratory) fitness in middle age is associated with a lower long term risk of chronic lung disease (COPD), suggests Danish research published online in the journal Thorax.

Physical activity that boosts fitness should be encouraged "to delay development, progression and death from COPD," conclude the researchers.

COPD, short for chronic obstructive pulmonary disease, is an umbrella term for respiratory conditions that narrow the airways, such as bronchitis and emphysema. Smoking is the main risk factor for COPD, which the World Health Organization ranks as the fourth most frequent cause of death worldwide.

Studies have suggested that a high level of physical activity and/or leisure time exercise is associated with a reduced risk of COPD, and that physical inactivity may speed up its progression.

To explore this further, the researchers tracked the respiratory health of 4,730 healthy middle-aged men from the Copenhagen Male Study, who were recruited from 14 large workplaces in Copenhagen between 1970 and 1971. Their average age was 49.

Those with a previous diagnosis of COPD, asthma, or with symptoms of chronic bronchitis were excluded. Participants were monitored for up to 46 years to January 2016.

All participants provided information on smoking, alcohol intake, physical activity levels, educational attainment, occupation, and medical history.

Height, weight, and resting blood pressure were measured, and cardiorespiratory fitness (CRF) was calculated as low, normal, or high, using a VO2 max test--a measure of the body's ability to use oxygen during exercise. National registers were used to identify cases of COPD and death from COPD.

Compared with low CRF, the estimated risk of COPD diagnosis was 21% lower in men with normal CRF and 31% lower in men with high CRF.

Similarly, compared with low CRF, the estimated risk of death from COPD was 35% lower in men with normal CRF and 62% lower in men with high CRF.

High CRF in middle age was also associated with a delay to both diagnosis of, and death from, COPD by 1.5 to 2 years.

The results were largely unchanged after excluding those who were diagnosed with COPD or who died during the first 10 years of monitoring, suggesting that the findings withstand scrutiny, say the researchers.

This is an observational study, and as such, can't establish cause. And it's possible that participants with high levels of CRF were more resilient to underlying COPD, delaying time to diagnosis, say the researchers.

But their results are in line with those of previous studies and provide further insight into the association between cardiorespiratory fitness and the long-term risk of COPD over an exceptionally long monitoring period.

And while the processes that link CRF with the development and progression of COPD aren't clear, the researchers nevertheless speculate that inflammation, linked to physical inactivity, may have a key role.

Research supported by the Accelerating Medicines Partnership (AMP) on Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) provides new insights into tissue damage for these autoimmune conditions. Findings include the identification of novel molecular signatures related to immune system signaling in kidney cells that may reflect their active role in disease process; molecular targets, including specific white blood cells, for potential treatment in lupus nephritis; and specific types of fibroblasts and white blood cells that are involved in rheumatoid arthritis. These discoveries set the stage for uncovering potential drug target candidates that could advance to experimental treatments. Results of the studies were published today (June 18, 2019) in three papers in Nature Immunology.

"AMP is laying the foundation for precision medicine in rheumatoid arthritis and lupus," said NIH Director Dr. Francis S. Collins, M.D., Ph.D. "The public and private sector working together has sparked new hope for those living with these and other autoimmune diseases, and we anticipate that these early results are only the beginning of what is serving as a new model to transform medical care."

A primary goal of the AMP RA/SLE program, which is led by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), is to study tissues where the disease is active in patients, whereas most previous work studied mouse models or only blood samples from humans. AMP researchers looked at all the cell types in either biopsy samples from kidneys of people with SLE or the synovial tissues of joints from people with RA. The program seeks to quickly find the most promising treatment targets so less time is lost chasing unsuccessful leads.

Highlights from the papers:

Profiling kidney and skin cells in lupus nephritis. Lupus nephritis is a potentially fatal kidney disease that occurs in about 50% of people with lupus. There can be a wide variety of changes in the kidneys, making the disease hard to diagnose and treat. AMP investigators led by co-senior investigator Jill Buyon, M.D., at New York University analyzed a large number of individual cells from kidney and skin samples from people with lupus in order to understand more about the complex mechanisms involved in tissue damage. Researchers discovered molecular signatures, related to immune system signaling and scar-forming gene activity, in kidney cells that may reflect their active role in disease process. This finding was unexpected since inflammatory cells were thought to be the primary cause of tissue damage. Single cell analysis of skin revealed similar changes, suggesting that in the future it may be possible to monitor a person's disease progress and treatment responses from skin samples instead of more invasive kidney biopsies.

Understanding the role of immune cells in lupus nephritis. AMP investigators led by Betty Diamond, M.D., at The Feinstein Institute for Medical Research, Manhasset, New York, analyzed kidney, blood and urine samples from people with and without lupus nephritis to learn more about how immune cells cause progressive damage in the kidneys. The scientists uncovered subsets of white blood cells that are active in the disease process and identified molecules that may be potential therapeutic targets. Single cell analysis of immune cells in urine yielded similar results. These findings suggest it may be possible to track immune cell status in the kidneys easily through urine analysis.

Defining inflammatory cell states in rheumatoid arthritis joint tissue. The autoimmune disease rheumatoid arthritis is characterized by chronic inflammation of the synovium - a thin tissue that lines joints. AMP investigators led by Soumya Raychaudhuri, M.D., Ph.D., at Brigham and Women's Hospital, Boston, used single cell profiling technologies to analyze synovial biopsies. They identified subsets of cells - including fibroblasts, which are involved in producing cellular scaffolding, specific white blood cells and others - that appear more often in people with rheumatoid arthritis. Researchers will need to determine whether the identified cell subsets are involved in tissue inflammation, and whether targeting these cells could potentially provide a therapeutic benefit. The white blood cells identified may also play a role in other immune diseases.

"These AMP rheumatoid arthritis and lupus findings offer insights into intriguing immune system targets that are worthy of more investigation," said Robert Carter, M.D., acting director of NIAMS. "We look forward to bringing the most promising of these findings forward to clinical trials, potentially leading to much-needed new treatment options for those living with rheumatoid arthritis, lupus and other immune system disorders."

To date, the program has made major advances in creating standardized ways to collect kidney and synovial tissue for research in the United States. This standardization has allowed scientists to use state-of-the-art technologies to analyze individual immune cells and other cells from affected tissues. By studying genes, proteins and biological pathways at such high resolution, scientists hoped to uncover novel insights into the mechanisms behind RA and lupus nephritis, a serious complication of lupus.

Launched in 2014, AMP is a public-private collaboration between the National Institutes of Health, the U.S. Food and Drug Administration and multiple biopharmaceutical and life science companies and not-for-profit organizations. The current AMP funding commitments for all projects are over $350 million, including in-kind contributions. The Foundation for the NIH (FNIH) manages contributions from AMP private-sector partners, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and the National Institute of Allergy and Infectious Diseases collaborated to oversee AMP RA/SLE, which was recently extended for an additional year.

CLEVELAND, Ohio (June 18, 2019)--Thanks to advanced medical treatments, women diagnosed with breast cancer today will likely survive the disease. However, some treatment options put these women at greater risk for a number of other health problems. A new study out of Brazil shows that postmenopausal women with breast cancer are at greater risk for developing heart disease. Results are published online in Menopause, the journal of The North American Menopause Society (NAMS).

Cardiovascular disease remains the main cause of death in postmenopausal women, and women treated for breast cancer are at greater risk of developing heart disease than those not diagnosed with breast cancer. These cardiovascular effects may occur more than 5 years after radiation exposure, with the risk persisting for up to 30 years.

The goal of the new study was to compare and evaluate risk factors for cardiovascular disease in postmenopausal women who are survivors of breast cancer and women without breast cancer. The researchers found that postmenopausal women who are survivors of breast cancer showed a markedly stronger association with metabolic syndrome, diabetes, atherosclerosis, hypertriglyceridemia, and abdominal obesity, which are major risk factors for cardiovascular disease. The risk of cardiovascular mortality similarly increased to match death rates from the cancer itself.

Findings were published in the article "High risk for cardiovascular disease in postmenopausal breast cancer survivors."

"Heart disease appears more commonly in women treated for breast cancer because of the toxicities of chemotherapy, radiation therapy, and use of aromatase inhibitors, which lower estrogen. Heart-healthy lifestyle modifications will decrease both the risk of recurrent breast cancer and the risk of developing heart disease," says Dr. JoAnn Pinkerton, NAMS executive director. "Women should schedule a cardiology consultation when breast cancer is diagnosed and continue with ongoing follow-up after cancer treatments are completed."

For more information about menopause and healthy aging, visit http://www.menopause.org.

Philadelphia, June 18, 2019 -- Autistic adolescents need the support of their parents or guardians to prioritize independence so that they are prepared for learning to drive, according to a study of specialized driving instructors who have worked specifically with young autistic drivers. These findings were compiled by researchers at Children's Hospital of Philadelphia (CHOP) and recently published in the journal Autism in Adulthood.

Driving instructors also emphasized the need to develop and refine best practices to guide assessment and delivery of highly individualized instruction for autistic adolescents.

The study was conducted by a multidisciplinary team of researchers from CHOP's Center for Injury Research and Prevention, Center for Autism Research, and Division of Emergency Medicine, as well as the University of Pennsylvania School of Nursing and the Virginia Tech Transportation Institute (VTTI), as part of a five-year study aimed at understanding mobility issues for autistic adolescents funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the National Institutes of Health (NIH). This is the first paper published as part of the study.

"Through our interviews with specialized driving instructors, we learned they believe parents are a critical partner in preparing for and undertaking independent driving," said Rachel K. Myers, PhD, lead author of the study and scientist at the Center for Injury Research and Prevention at Children's Hospital of Philadelphia (CHOP). "Instructors recommend that parents help their children develop independent life skills, including the use of alternative forms of transportation such as bicycling or mass transit, and to practice pre-driving skills, such as navigation, before undertaking on-road driving lessons."

Driving instructors are an important resource for families, especially for those with autistic adolescents learning to drive. However, because not much is known about the specific experience of teaching autistic adolescents how to drive, this limits the ability to provide adolescents and families with proper guidance preparing for the learning-to-drive process. To help bridge this gap, researchers conducted in-depth interviews with specialized driving instructors who had experience working with autistic adolescents and young adults. This is the first study to examine the process and experience of driving instructors who provide behind-the-wheel training specifically for this population.

The study revealed a set of common themes that underscored the importance of parents of autistic adolescents in preparation for the learning-to-drive process, with driving instructors viewing parents as essential partners in supporting their efforts in teaching driving skills and promoting independence. Participating instructors said parents can support and prioritize independence by encouraging their autistic adolescents to develop life skills, such as mowing the lawn, cooking, and taking public transportation, before learning to drive.

Although the driving instructors identified a need to develop and refine best practices for assessment and instruction, they recognized that specific approaches must be tailored to meet the unique needs of each autistic adolescent driver, reflecting the spectrum that affects each adolescent differently. Other suggestions from the instructors involved in this study included using of state-level vocational rehabilitation services to provide financial support for instruction, identifying and promoting prerequisite life skills prior to undertaking driving, parent-supervised driving instruction in partnership with professional driving instruction, and tailoring instruction to address the particular needs of learner drivers.

"What these specialized driving instructors told us about the disconnect between driving and other life skills was surprising," said Benjamin E. Yerys, PhD, study author and psychologist at the Center for Autism Research at Children's Hospital of Philadelphia. "Some parents may not let their autistic adolescents use a stovetop oven, but are asking if their teens are ready to drive. Whether or not their children decide to drive, parents should encourage greater independence by encouraging them to get around on their own. Traveling independently by driving or other modes of transportation is key to continuing their education, working, and staying connected with friends and family."

Obtaining a driver's license is a major milestone in the transition to adulthood. This milestone increases the independence and mobility of adolescents, which can potentially lead to improved access to educational, occupational training, social, and community engagement opportunities. According to previous CHOP research, nearly one-third of autistic adolescents obtain a driver's license by the time they are 21 years old, which may improve their ability to transition into independent adulthood.

Food neophobia, or fear of new foods, may lead to poorer dietary quality, increase the risk factors associated with chronic diseases, and thus increase the risk of developing lifestyle diseases, including cardiovascular diseases and type 2 diabetes.

These are some of the findings of a study conducted by the Finnish National Institute for Health and Welfare, the University of Helsinki, and the University of Tartu in Estonia.

Food neophobia is an eating behaviour trait in which a person refuses to taste and eat food items or foods they are not familiar with. The study examined the independent impact of eating behaviour, and especially food neophobia, on dietary quality as well as lifestyle diseases and their risk factors. So far, little research has been carried out on this area.

The study monitored individuals aged between 25 and 74 years in the Finnish FINRISK and DILGOM cohorts and an Estonian biobank cohort during a seven-year follow-up.

Food neophobia is hereditary

Food neophobia has been observed to be a strongly hereditary trait: twin studies have found that up to 78% of it may be hereditary. The trait can be easily measured using the FNS questionnaire (Food Neophobia Scale), which contains ten questions charting the respondent's eating behaviour. The FNS questionnaire was also used to measure and quantify the fear of new foods in this study.

Food neophobia is common in children and older persons, in particular. Few studies have so far been carried out on food neophobia in the adult population.

Traits similar to food neophobia, including picky and fussy eating, also occur in different age groups in the population. These eating behaviours may also have a significant impact on dietary quality and subsequently health. As different traits associated with eating behaviours have overlapping characteristics making a clear-cut distinction between them is challenging.

Food neophobia has independent health impacts

The study found that food neophobia is linked to poorer dietary quality: for example, the intake of fibre, protein and monounsaturated fatty acids may be lower and the intake of saturated fat and salt greater in food neophobic individuals.

Additionally, a significant association was found between food neophobia and adverse fatty acid profile and increased level of inflammatory markers in blood. Subsequently, food neophobia also increases the risk of developing cardiovascular diseases or type 2 diabetes.

It is often thought that the impacts of eating behaviour and diet on health are mainly mediated through weight changes alone. In this study, however, the impacts of food neophobia emerged independently regardless of weight, age, socioeconomic status, gender or living area.

Your parents were right: you should always try all foods!

"The findings reinforce the idea that a versatile and healthy diet plays a key role, and even has an independent role in health. If we can intervene in deviant eating behaviours, such as food neophobia, already in childhood or youth. This will help to prevent potential future health problems early on", says Research Professor Markus Perola from the National Institute for Health and Welfare.

"Hereditary factors and our genotype only determine our predisposition to food neophobia. Early childhood education and care and lifestyle guidance in adulthood can provide support in the development of a diverse diet."

New Haven, Conn. -- In a new study, Yale researchers offer insight into leptin, a hormone that plays a key role in appetite, overeating, and obesity. Their findings advance knowledge about leptin and weight gain, and also suggest a potential strategy for developing future weight-loss treatments, they said.

The study, led by investigators at Yale and Harvard, was published the week of June 17, 2019, in the journal PNAS.

Leptin, which is secreted by fat cells, informs the brain when fuel stored in body fat and in the liver is becoming depleted. It has not been well understood how low leptin concentrations in plasma -- the largest component of blood -- increase appetite. The researchers studied the biology of leptin in rodents. They also investigated the influence of nerve cells in the brain known as AgRP neurons, which regulate eating behavior.

The researchers discovered that the mechanisms by which reductions in plasma leptin concentrations stimulate food intake are not limited to the brain, as previously thought. In rodents, fasting first activates leptin receptors in the brain, followed by an intermediary step that involves the endocrine system. This system includes the pituitary and adrenal glands, which secrete another hormone, corticosterone, that regulates energy, stress responses, and food intake.

The research team learned that this chain of events is required for leptin to stimulate hunger when food is restricted, or when diabetes is poorly controlled and plasma leptin concentrations drop below a critical threshold, said Gerald Shulman, M.D., the George R. Cowgill Professor of Medicine at Yale School of Medicine, and co-corresponding author of the study.

In further experiments, the researchers also showed that plasma corticosterone activates AgRP neurons, which increases hunger when either leptin or blood-sugar levels are low, Shulman noted. In humans, leptin and blood sugar drop when people diet.

These findings add to scientists' knowledge of leptin, which has been the focus of research on obesity and weight loss since its discovery in the 1990s. The study reveals "the basic biology of leptin, and how the endocrine system is mediating its effect to regulate food intake under conditions of starvation and poorly controlled diabetes," said Shulman.

The research also lends support to a different strategy for developing drugs that treat obesity. "It suggests that AgRP neurons may be an attractive therapeutic target," he said.

When studying biological cells using optical tweezers, one main issue is the damage caused to the cell by the tool. Giovanni Volpe, University of Gothenburg, has discovered a new type of force that will greatly reduce the amount of light used by optical tweezers - and improve the study of all kinds of cells and particles.

"We call it 'intra-cavity feedback force'. The basic idea is that, depending on where the particle or cell you want to study is, the amount of laser light used to trap it changes automatically. Whenever the particle is in focus, the laser switches off. When the particle tries to escape, the laser switches on again", says Giovanny Volpe, senior lecturer at the Department of Physics, University of Gothenburg.

An optical tweezer is a focused laser beam that can trap particles. Previously, two different types of forces that emerge from this type of tool have been identified: gradient force (which means the particle goes against the intensity of the laser) and scattering force (where the particle is pushed towards the laser). Giovanni Volpe and his team have discovered a third type of force in this realm, and a new way of constructing optical tweezers. These break-throughs are poised to greatly improve the study of single biological cells.

"With this method, as much as 100 times less light is needed, in some cases, compared to using a traditional optical tweezer," Giovanni Volpe explains. "With less light, you cause less photo damage to the cell you are studying."

This could be useful for studying any cell that is usually suspended in a solution - a blood cell or a yeast cell, for example - that a researcher would want to study over a long period of time.

"One of the main issues when using optical tweezers is that the light raises the temperature of the cell, which is damaging. A rise of 10 degrees might not be tolerable, but the rise of 0,1 degrees might be fine. So using less light, and therefore limiting the rise in temperature, could make a huge difference. Experiments could be done in a more realistic manner in relation to the cell's natural life cycle," says Giovanni Volpe.