Body

Researchers have developed a simple blood test that measures the body's own immune response to improve diagnosis of ovarian cancer.

Ovarian cancer is one of the most common gynaecologic cancers, with the highest mortality rate. About 300,000 new cases are diagnosed globally each year, with an estimated 60% of women dying within five years after diagnosis.

The new study found that testing for a specific immune biomarker allows clinicians to identify whether growths on the ovaries are cancerous or not, without the need for tests like MRI scans or ultrasounds.

The clinical trial was conducted in two hospitals in Melbourne, Australia, with the results published in Scientific Reports.

Senior Author and Chief Investigator, RMIT University's Professor Magdalena Plebanski, said the test could be an important diagnostic tool for assessing suspicious ovarian growths before operations.

"Our new test is as accurate as the combined results of a standard blood test and ultrasound," said Plebanski, a Senior National Health and Medical Research Council Fellow at RMIT.

"This is especially important for women in remote or disadvantaged communities, where under-resourced hospitals may not have access to complex and expensive equipment like ultrasound machines or MRI scanners.

"It also means patients with benign cysts identified through imaging could potentially be spared unnecessary surgeries.

"This study looked at women with advanced ovarian cancer, but we hope further research could explore the potential for adding this biomarker to routine diagnostic tests at earlier stages of the disease."

The study used an immune marker for inflammation (IL-6) together with cancer markers to detect epithelial ovarian cancer in blood. Results were validated across two separate human trial cohorts.

"Ovarian cancer is the deadliest women's cancer, a statistic that has not changed in 30 years," Plebanski said.

"Every day in Australia, four women are diagnosed with ovarian cancer and three will die from the disease.

"Developing tests that are simpler and more practical may help get more women to hospital for treatment more effectively, with the hope that survival rates will improve."

Pregnancy hypertension, or Pre-eclampsia, is a complex disorder of pregnancy. Treatment of elevated blood pressure can manage the condition in the mother, but in severe cases delivery is needed, which can present a major problem to the baby if it is born prematurely.

Now, research from the Department of Pharmacology & Therapeutics at University College Cork (UCC), the INFANT Centre at UCC and the University of Liverpool, as well as The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain) at Technical University of Denmark, have shown in a rat model that a natural diet?derived antioxidant L-ergothioneine can relieve some of the clinical symptoms of Pre-eclampsia. The hope is that the same will be in evidence in humans.

"Our research shows that treating rats with pre-eclampsia with the natural antioxidant L-ergothioneine reduced blood pressure, prevented fetal growth restriction and dampened production of the damaging substances released from the placenta during pre-eclampsia," says Dr. Cathal McCarthy, leader of this research in a press release from the INFANT Centre at UCC.

In order to be able to make enough L-ergothioneine to eventually treat patients, the scientists are looking into ways of producing this compound efficiently in high amounts using yeast cell factories. Ergothioneine can be found in a wide variety of foods, but in particular in mushrooms, where amounts are relatively high compared to other foods.

"Today, ergothioneine is either made chemically or extracted from mushrooms, but at DTU Biosustain we are developing a method to make it biologically. This should lead to its much wider availability at competitive prices," says Douglas Kell, Associated Scientific Director at DTU Biosustain and Research Chair in Systems Biology Department of Biochemistry, University of Liverpool. At DTU Biosustain, Douglas Kell and his team work closely together with the group of Senior Researcher Irina Borodina to produce L-ergothioneine biologically using advanced genomic engineering.

Much evidence exists for L-ergothioneine's benefits in a variety of neurological and vascular disorders as well. Thus, L-ergothioneine appears to be a safe, natural diet?derived antioxidant whose therapeutic potential looks promising but remains to be validated in human clinical trials.

Researchers at Karolinska Institutet in Sweden and the University of Milan in Italy have identified a gene in human neurons that protects against the degeneration of motor neurons in the deadly diseases ALS and SMA. Gene therapy in animal models of these diseases was shown to protect against cell death and increase life expectancy. The study is published in the eminent journal Acta Neuropathologica.

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are deadly diseases characterised by a gradual loss of motor neurons. Since these neurons control all voluntary muscles in the body, this loss leads to muscular atrophy, weakness and paralysis. However, some motor neurons are more sensitive than others, so that those in the spinal cord, for example, are extremely sensitive to degeneration, while the ocular motor neurons in the brain stem, which we use to move our eyes, are highly resistant.

Researchers at Karolinska Institutet and the University of Milan have now identified a gene, Synaptotagmin 13 (SYT13), that is relatively abundant in resistant oculomotor neurons in mice, rats and humans compared with the sensitive motor neurons in the spinal cord. SYT13 codes for (gives rise to) a protein that belongs to a group of membrane proteins.

In experiments with human motor neurons formed from induced pluripotent stem cells (iPS cells) taken from ALS and SMA patients, the researchers were able to show that the introduction of SYT13 protects the cells from degeneration by reducing endoplasmatic reticulum (ER) stress and blocking programmed cell death. The gene had a protective effect regardless of the genetic causes of the diseases.

"This is extremely useful from a therapeutic perspective, since the mechanisms behind neuronal loss are largely unknown in 90 per cent of all ALS patients and can differ from one individual to another," says Eva Hedlund, researcher at the Department of Neuroscience, Karolinska Institutet, and one of the senior authors of the study.

On conducting gene therapy experiments in animal models of ALS and SMA, the team was then able to show that the introduction of SYT13 saves sensitive motor neurons from degeneration in both diseases. The treated mice also lived up to 50 per cent longer in the case of SMA and 14 per cent longer in the case of ALS.

"Our results suggest that SYT13 is a very promising gene therapy candidate for patients with motor neuron disease," says Monica Nizzardo, researcher of the Centro Dino Ferrari, University of Milan, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, and first author of the study.

There are currently no effective treatments for ALS and its causes are known only in the 10 per cent of patients that present with familial inherited disease. SMA, on the other hand, is caused by mutations in a gene called survival motor neuron 1 (SMN1). Two new SMA therapies targeted at SMN1 were recently approved with very promising results, but the benefits vary depending on the time of treatment and the degree of disease severity.

"New complementary treatments for SMA and a form of therapy that helps all patients with ALS, regardless of pathogenesis, are needed," says Stefania Corti, researcher of the Centro Dino Ferrari, University of Milan, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, and the other senior author of the study.

"We'll continue looking for additional factors that are unique to resistant motor neurons, and thus identify more potential therapeutic targets," says Eva Hedlund.

PHILADELPHIA, PA - Results from the NRG Oncology clinical study NRG-CC001 concluded that lowering radiotherapy dose to hippocampal stem cells improves cognitive and patient-reported outcomes for patients with brain metastases. These findings were presented at Plenary Sessions at the 2018 Society for Neuro-Oncology (SNO) and the 2019 American Academy of Neurology (AAN) Annual Meetings and are now published in the Journal of Clinical Oncology.

"NRG-CC001 provides physicians with the information needed to offer patients a safer alternative to standard whole-brain radiotherapy. Hippocampal avoidance whole-brain radiotherapy with memantine should be a standard of care that providers offer for patients with brain metastases who are seeking whole-brain radiotherapy," stated Paul D. Brown, MD, of Mayo Clinic and co-lead author of the NRG-CC001 manuscript.

The NRG-C001 phase III trial enrolled 518 patients, which were randomly assigned to either receive whole-brain radiotherapy plus memantine with hippocampal avoidance or standard whole-brain radiotherapy plus memantine. The primary endpoint of the trial was cognitive function failure and the trial looked at secondary endpoints including overall survival, intracranial progression-free survival, toxicity, and patient-reported neurologic symptoms.

"Hippocampal avoidance during whole-brain radiotherapy in NRG-CC001 leads to a 26% relative reduction in cognitive toxicity risk following treatment. This is the first definitive and most important clinical evidence that the hippocampus is important in determining the negative effects that radiotherapy can have on cognitive function," added Vinai Gondi, MD, the Director of Research at the Northwestern Medicine Chicago Proton Center, Co-Director of the Brain Tumor Center at the Northwestern Medicine Cancer Center Warrenville, and co-lead author of the NRG-CC001 manuscript.

With a median follow up of 7.9 months, the risk of cognitive function failure was lower following hippocampal avoidance whole-brain radiotherapy versus standard whole-brain radiotherapy (adjusted hazard ratio, 0.74, 95% confidence interval: 0.58-0.95, p=0.02). The difference was attributable to less deterioration in executive function at 4 months (23.3% vs. 40.4%, p=0.01) and learning and memory at 6 months (11.5% vs. 24.7%, p=0.049, and 16.4% vs. 33.3%, p=0.02, respectively). At 6 months, patients who received whole-brain radiotherapy with hippocampal avoidance reported less fatigue (p=0.04), less difficulty remembering things (p=0.01), and less difficulty speaking (p=0.0049), in addition to fewer cognitive symptoms (p=0.01) and less interference of neurologic symptoms in daily activities (p=0.008). There was no statistically significant difference between overall survival, intracranial progression-free survival, or toxicity between treatment arms.

University of Kent research has found that moderate intensity exercise such as brisk walking, water aerobics or cycling can have the most benefcial effect on memory performance.

These findings suggest that it is not necessary for people to carry out highly strenuous exercise to achieve observable improvements in long-term memory, as moderate exercise can have a more positive influence.

This study could be significant for supporting new approaches to preserve memory in older age, in particular the treatment of patients with memory defciencies. Furthermore, guidelines for memory enhancement through exercise could provide a boost for students in exam settings or even help people with daily tasks such as remembering the items on a shopping list.

Dr Amir-Homayoun Javadi and his research team at the University of Kent concluded these findings after investigating how varying intensities of exercise, or different types of rest, could directly affect participants' performances on a recognition memory test.

Dr Javadi said: 'Our research indicates that it is not necessary to overexert oneself in order to achieve observable cognitive improvements. If clear guidelines were developed to enhance memory through moderate intensity exercise it could not only help support patients with memory deficiencies, but be useful for initiatives in schools, workplaces and society.'

A new medical approach recommended by University of Cincinnati physician-researchers may reduce organ wait times, save money, boost quality of life and prolong life expectancy for kidney patients.

According to a computer analysis conducted by faculty in the UC College of Medicine, using kidneys from hepatitis C (HCV)-infected donors for transplant in non-HCV-infected dialysis patients and then treating the infection afterward could reduce the average wait for a kidney from four years to 1.56 years. That's a reduction of 61 percent.

"This matters because patients on dialysis have a much higher risk of dying each year," said Mark Eckman, professor and director of the UC Division of General Internal Medicine. "Patients receiving hemodialysis face an excess mortality rate as high as 15% per year, while the mortality rate for patients receiving kidney transplants is 2% annually. If we can shorten the amount of time that patients need to live on hemodialysis, survival can improve."

The findings are available online in the American Journal of Kidney Diseases and Eckman, also a UC Health physician, is the study's lead author.

The computerized decision analytic model uses data from United Network for Organ Sharing and the Scientific Registry of Transplant Recipients to establish an average wait time for dialysis patients of four years for a non-infected kidney, said Eckman.

In the United States, roughly 103,000 patients are waitlisted for kidney transplantation. In 2018, only 14,725 or 4% received kidney transplants, said Eckman.

The computer model shows results for both effectiveness, measured in quality-adjusted life years, as well as cost. Patients receiving transplants with an HCV-infected kidney gained nearly 10 months in quality-adjusted life expectancy compared with those who waited longer for transplantation with a kidney not infected with HCV. Quality-adjusted life years take into account duration of survival and the quality of those years.

Eckman says the quality of life during the time following kidney transplantation is higher than that for the years a patient remains on dialysis.

There is also a cost savings of $37,918 over the life of the patient when someone accepts an HCV-infected kidney and is then treated for hepatitis C compared to waiting for a non-infected kidney and continuing dialysis in the process, according to computer analysis. Eckman said patients receiving hemodialysis have medical costs exceeding $95,000 annually, while costs after transplantation surgery are roughly $36,000 per year. Physicians can now cure hepatitis C thanks to a new 12-week treatment regimen.

The latest findings showing possible benefits for transplanting HCV-infected kidneys into patients not infected with hepatitis C mirror a 2018 study authored by Eckman that also found a benefit in transplanting HCV-infected kidneys into patients already infected with hepatitis C.

The decision analytic model simulates events occurring over time looking at two different strategies. One strategy uses kidneys from a non-HCV-infected donor while the other uses kidneys from an HCV-infected donor. Many factors affect waiting time for a donated kidney such as blood type and location of a patient's transplant center. The increased availability of HCV-infected kidneys is largely the result of a surge in the number of deaths from opioid-related drug overdoses, said Eckman.

Hemodialysis is tough on the body and is an important factor in patients seeking a kidney replacement, said Eckman.

"Patients on dialysis have large shifts of fluid volume and rebalancing of electrolytes during each dialysis session that typically occur three times a week," said Eckman. "That creates physiological stresses. A large part of the mortality associated with dialysis is due to cardiovascular events, some of which may be related to the volume shifts, changes in blood pressure and changes in electrolytes that accompany dialysis."

A patient's quality of life is also impacted; dialysis patients spend three-hour sessions three times a week hooked up to a dialysis machine, said Eckman. "It's hard to travel anywhere since you are tethered to the dialysis center. Thus the quality of life while receiving chronic dialysis is not as good as that of a patient following a kidney transplant. Anything that can shorten the number of years the patient is on dialysis waiting for a transplant is an improvement. That's the benefit of accepting an HCV-infected kidney."

WEST LAFAYETTE, Ind. -- Pancreatic cancer has one of the worst survival rates among cancers. Patients can expect as low as a 9% chance to live for at least five years after being diagnosed.

Going back in time to observe how cells with key gene mutations interact and become invasive would help researchers better understand how the cancer starts and identify it sooner.

A pancreatic cancer "time machine" engineered by Purdue University researchers has revealed that the disease is even more unpredictable than previously thought: Cancer cells promote each other's invasiveness when they grow together.

The study, published in the journal Small, is just the beginning of a new discovery about how pancreatic cancer evolves. Since the paper's publication, the researchers also have found drug resistance in cancer cell types originating from two drug-sensitive ones.

The time machine is a hollow tube of collagen that realistically mimics the microanatomy of a pancreatic duct. By injecting cancer cell lines into microfluidic channels within the artificial duct, the researchers can use the system as a model for observing how pancreatic cancer behaves over time.

Typically, it takes 10-20 years for pancreatic cancer to develop in a patient. Even in an animal model, the process is several months long. This pancreatic tumor model condenses cancer development to just two weeks.

"We can observe what happens over a long period of time. This helps us to see trends that we wouldn't normally see," said Bumsoo Han, a Purdue professor of mechanical engineering who builds models for studying how cancer cells move in biological systems.

The tumor model speeds up time because researchers can load in cell lines from an animal model or patient without waiting for gene mutation to happen first. The life-like structure of the tumor model allows the researchers to reconstruct the mutation as it would happen in the body.

To go back in time, the researchers just rewind footage taken by imaging equipment from the side of the artificial duct.

For this study, a group led by Stephen Konieczny, a professor of biological sciences at Purdue, developed the pancreatic cell line in a mouse model. Han's team then loaded the cell line through the microfluidic channels of the artificial pancreatic duct. Once inside, the cell lines fill the duct and start growing.

What makes the tumor model so realistic is its shape.

"The curvature of the pancreatic duct affects the behavior of cells. We could culture these cancer cells on a petri dish, but because the dish is flat, we wouldn't see the same behavior," said Han, who is the program leader of the Purdue University Center for Cancer Research and has a courtesy appointment in biomedical engineering.

The researchers saw that after two different cancer cell types merged into the pancreatic tumor model device, these cells became more invasive and sprouted from the duct to form tumors.

Since cancer is technically a group of diseases, and pancreatic cancer involves four major driver mutations, Han's team plans to further explore how each of these mutations interacts with each other. The tumor model also can be used as a prescreening tool to discover new drug targets for better drugs, Han said.

A patent has been issued for the pancreatic tumor model via the Purdue Research Foundation Office of Technology Commercialization.

CORVALLIS, Ore. - A report released earlier this month dives deep into the ongoing inequities surrounding childbirth in the U.S., with Oregon emerging as a leading example of how to do better.

Oregon State University associate professor Missy Cheyney, a medical anthropologist who focuses on midwifery, was one of 15 authors on the "Birth Settings in America" report from the National Academies of Sciences, Engineering and Medicine, which was commissioned by Congress. She helped present the findings to lawmakers in Washington, D.C. on Feb. 6.

Despite the U.S. spending more on maternity care than any other country - an estimated $110 billion each year - it has the worst outcomes among peer countries for mothers and babies.

"People giving birth today are more likely to die in childbirth than they were in our parents' generation," Cheyney said. "And that risk is unevenly distributed: It disproportionately affects black and Native American women, who are dying at a rate of 3 to 4 times more than white women."

For the report, authors examined hundreds of articles documenting birth outcomes in three settings: hospitals, birthing centers and home births, and compared them with the medical literature from other countries whose birth outcomes are better than in the U.S.

Based on the report's findings, Cheyney says it is imperative that the U.S. make midwives and home and birth center births more accessible to families who want them, which will help to:

Lower health care costs;

Reduce complications from unnecessary interventions, including some cesarean sections;

Improve patient experience; and

Provide more respectful care that aligns with cultural and personal values, as well as clinical needs

Currently, 98.4% of all U.S. births occur in hospitals, with about 0.6% in birthing centers and 1% at home. Overall, 89% of U.S. births here are attended by physicians, and only 11% by midwives. Very few families are able to access midwifery care in home and birth center settings due to high out-of-pocket costs, limited insurance coverage and a shortage of midwives.

That's the opposite of our peer nations, Cheyney said, where a majority of pregnancies start with a midwife and only receive a higher level of care if complications arise. And in many of those countries, the health care system better supports cooperation across provider types and birth settings.

"In our peer countries, you triage up to a higher level of care when it's indicated," she said, and there is greater exposure to, and acceptance of, a full range of birth settings. "Here, we start everyone at the highest level of care under the assumption that everyone will need a surgeon. In other high-resource nations, they assume that as long as you're healthy, most people can start with a midwife."

Other countries' systems more effectively integrate midwives than in the U.S., where midwives are covered by a state-by-state patchwork of regulations that often serves to further limit access to care and can impact safety.

In those countries, midwives are enabled to perform immediate interventions for complications that can arise in childbirth, such as excessive bleeding by the mother or difficulty breathing by the infant.

With portable oxygen tanks and injectable medications, those are not hard to safely manage in a home or birth center, Cheyney said. But midwives need consistent access to necessary training, licensure and integration into the health care system, including seamless transfers to a hospital when indicated.

Another major issue is the high rate of cesarean births in the U.S.: Today, nearly 1 in 3 mothers give birth via cesarean, and efforts to reverse that trend have been largely unsuccessful.

Cesarean births are associated with a number of complications, including greater blood loss, risk of infection stemming from the incision and risk of complication in future pregnancies. While cesarean births can be life-saving, the World Health Organization finds that rates higher than 10% are not associated with lower maternal and newborn mortality rates.

In comparison, Cheyney said, when low-risk women start their childbirth process at home or in a birth center, only about 5 to 7% result in a cesarean birth.

In hospitals, women of color report higher incidence of being ignored and threatened by providers, having care withheld, and receiving care they did not consent to, compared with other birth settings. Culturally matched midwifery can improve maternal outcomes by connecting families with providers who understand the challenges people of color face when navigating the U.S. health care system.

"We should not separate the outcomes of care from the experience of care," Cheyney said. "How we treat mothers matters as much as the clinical outcome, and we have lost track of that in some places."

On a positive note, Oregon is leading the way when it comes to integrated care and access to midwives and doulas.

In Corvallis specifically, the Community Doula Program, headed by Cheyney, works to match traditionally underserved populations with culturally matched doulas, and the services are free for Medicaid patients.

The integrated care system in Corvallis also means that families can freely choose to give birth at home, in a birthing center or at a hospital, and when someone needs to transfer to the hospital, it is a midwife-to-midwife transfer.

This allows some obstetricians in Corvallis to focus their care at the top of their license, Cheyney said: They can be called in to work on the medically complex births they're actually needed for, rather than on every birth.

Oregon still has its challenges, especially with low insurance reimbursement to birthing centers, but it's "definitely ahead of the curve," Cheyney said.

The next step is to learn how the programs that have been successful here can be scaled up and used nationwide.

LOS ANGELES (Feb. 17, 2020) -- New research from the Center for Cardiac Arrest Prevention at the Smidt Heart Institute at Cedars-Sinai shows that rates of sudden cardiac arrest are rising following decades of a downward trend. While this disturbing uptick was observed in both sexes, in women the increase was mostly among those whose sudden cardiac arrest was the first manifestation of heart disease. In men, the increase was mostly among those with known heart disease.

The study was published in the Go Red for Women issue of the peer-reviewed journal Circulation.

"The study validates the need for the discovery of novel risk factors and diagnostics to reduce the risk of sudden cardiac arrest among women," said Kyndaron Reinier, PhD, MPH, research scientist and associate director of Epidemiology at the Center for Cardiac Arrest Prevention, and first author on the study. "And, because more than 40% of both men and women had known heart disease before their sudden cardiac arrest, prevention and treatment of heart disease remain critically important."

The findings are part of the Oregon Sudden Unexpected Death Study, a comprehensive, 16-hospital, multiyear assessment of cardiac deaths in the Portland, Oregon, metropolitan area led by Sumeet Chugh, MD, director of the Center for Cardiac Arrest Prevention and associate director of the Smidt Heart Institute.

Unlike heart attacks (myocardial infarctions), which are typically caused by clogged coronary arteries reducing blood flow to the heart muscle, sudden cardiac arrest is the result of defective electrical activity of the heart. Patients may have little or no warning, and the disorder usually causes death within minutes if no resuscitation is performed. Sudden cardiac arrest accounts for approximately 300,000 deaths each year in the U.S.

Between 2004-2011, the Oregon Sudden Unexpected Death Study showed a decline in sudden cardiac death for both men and women, probably explained by better prevention and treatments for patients with cardiovascular risk factors. However, between 2012-2016, incidence of sudden cardiac death rose for both men and women.

"This appears to be a recent trend, and to our knowledge there is little data regarding reasons for this rise," said Chugh, who also serves as the Pauline and Harold Price Professor of Cardiac Electrophysiology Research. "It's possible that regional, racial and socioeconomic differences could contribute, but more research is needed."

As a next step, the research team hopes to gather additional biodata from the Oregon Sudden Unexpected Death Study to identify targets for prevention in women.

"This study highlights the important implications of understanding the differences in risk stratification, screening and diagnosis of heart disease between men and women," said Emily Tinsley, MS, program officer in the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). "The information we learn from studies like this is essential for promoting effective and unique preventive strategies for heart disease in women."

The Oregon study, which recently completed its 18th year, has been funded by the NHLBI since 2007. Here are some of the findings from the study published in prior years:

The importance of surveillance to accurately identify sudden cardiac arrests in the community

The majority of sudden cardiac arrest patients do not have severely reduced pumping function of the heart

The development of a simple electrical risk score to predict sudden cardiac arrest from the standard ECG

The importance of warning symptoms in predicting risk of sudden cardiac arrest

Five years ago, Chugh's team began a sister study-also funded by the NHLBI-based in Southern California's Ventura County.

Crotoxin, extracted from the venom of the South American rattlesnake Crotalus durissus terrificus, has been studied for almost a century for its analgesic, anti-inflammatory and antitumor activities and as an even more powerful muscle paralyzer than botulinum toxin. However, the toxicity of crotoxin limits its medicinal use.

A new study, published by Brazilian researchers in the journal Toxins, shows that crotoxin's therapeutic effects can be enhanced and its toxicity reduced when it is encapsulated in nanostructured SBA-15 silica, a material originally developed for use in vaccine formulations.

The study was conducted under the aegis of Brazil's National Science and Technology Institute (INCT) on Toxins, one of the INCTs supported by FAPESP (São Paulo Research Foundation) in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government. The INCT's principal investigator is Osvaldo Augusto Sant'Anna.

The study was part of the doctoral research of Morena Brazil Sant'Anna, whose thesis advisor is Gisele Picolo. Picolo herself was the principal investigator for a project on the same topic. Researchers Flavia Souza Ribeiro Lopes and Louise Faggionato Kimura participated in the study, which was performed at Butantan Institute in São Paulo.

Osvaldo Sant'Anna is the principal investigator for a Thematic Project at Butantan Institute to study mesoporous silica as a vaccine adjuvant in collaboration with Márcia Fantini, a professor at the University of São Paulo's Physics Institute (IF-USP). An adjuvant is an agent used in conjunction with a vaccine antigen to augment the host's antigen-specific immune response.

"People who respond badly to vaccines usually have macrophages that catabolize the antigen very quickly, so there isn't time for their lymphocytes to induce a complete response in terms of producing antibodies," Osvaldo Sant'Anna told Agência FAPESP. "Research has shown that nanostructured silica slows the macrophages down."

Osvaldo Sant'Anna's studies show that mice produce more antibodies against an antigen when it is administered with silica, which is made up of microstructures and can be molded to encapsulate molecules of varying shapes and sizes.

When silica was tested with other toxins, a novel protective effect was discovered. "In tests conducted in horses to produce anti-diphtheria serum and with tetanus toxin, we found that silica makes antigens less potent and reduces the adverse effect of diphtheria toxin," Osvaldo Sant'Anna said.

These findings were welcomed by Picolo and Morena Brazil Sant'Anna, colleagues of Osvaldo Sant'Anna at Butantan Institute. "I've been studying crotoxin since 2011. The results are positive in terms of its analgesic effect, but its toxicity has always been a constraint. Using silica was a great idea. This is the first time the two molecules have been combined," Picolo said.

Neuropathic pain

The article published in Toxins reports on a study designed to investigate the effects of crotoxin combined with SBA-15 silica when used to treat neuropathic pain, a chronic condition caused by injuries to sensitized nerves. Treating chronic pain is a challenge for physicians because ordinary painkillers such as anti-inflammatory drugs and opioids do not have the desired effect.

To evaluate crotoxin's therapeutic potential in this setting, the researchers conducted experiments with mice, inducing a condition similar to neuropathic pain by injuring the sciatic nerve.

The first positive finding resulted from a test to determine the maximum dose of crotoxin with and without silica. "We observed that a larger amount of the toxin combined with silica could be administered without adverse side effects and that the dose could therefore be increased," Morena Brazil Sant'Anna said. It was possible to administer a 35% larger dose of crotoxin when it was combined with silica.

The next step was to test the formulation in animals. They were given the crotoxin/silica complex (CTX:SBA-15) while experiencing acute pain (immediately after a sciatic nerve injury procedure) or chronic pain (a fortnight later). In both cases, the complex was administered in a single dose or in five doses (one daily dose for five consecutive days).

In the acute stage as well as the chronic stage, the analgesic effect lasted longer when crotoxin was combined with silica. In one of the tests, a single dose was sufficient to reverse hypernociception (heightened sensitivity to painful stimuli) until 48 hours after it was administered.

Action mechanisms

Crotoxin is a powerful painkiller because it acts on different pain pathways. To determine whether its action mechanisms would be the same in the new formulation, the researchers administered antagonists of the receptors involved in pain shortly before the crotoxin/silica complex. If the complex was effective even with the receptors blocked, this would mean its action mechanism could be different from that of the conventional molecule.

"We found that muscarinic and adrenergic receptors, which act on the nervous system, and formyl receptors, which are targets for natural anti-inflammatory compounds, were involved in the action of the crotoxin/silica complex. In other words, there was no change in the action mechanism," Morena Brazil Sant'Anna said.

The team observed changes in the levels of pro- and anti-inflammatory cytokines. "Expression of interleukin 6 [IL-6], which is associated with inflammation, decreased, while the level of IL-10, which controls the inflammatory process, increased. We also observed a reduction in activation of astrocytes and microglia, central nervous system cells involved in inflammatory responses," Picolo said.

Because silica influences the immune response, the researchers decided to see whether the defense against toxicity it triggers would end up hindering crotoxin's beneficial action. This possibility was tested and ruled out in the study. The mice produced high levels of antibodies, but this did not affect the outcome, according to Picolo.

"Probably because the crotoxin was encapsulated and the antibodies produced were unable to reach it," she said.

The complex gains another advantage from this protection: it could be administered orally to mice, for the first time, with positive results. This was possible because the structure of SBA-15 is similar to that of a honeycomb, protecting the active ingredient against breakdown in the stomach.

"It also guarantees controlled release of the crotoxin in the organism, which may explain the lasting analgesic effect," Picolo said.

Next steps

The researchers are now investigating whether the combination of crotoxin with SBA-15 can be used to treat multiple sclerosis. The results of this research have also been positive so far, and an article will soon be published.

However, more studies will be necessary before the combination can become medication. "Crotoxin is a large molecule with a complex structure that's hard to replicate in the laboratory, so scaled-up use is a long away off," Picolo said.

Some form of synthesis would be the ideal solution. Trials are currently ongoing with purified venom extracted directly from the rattlesnake.

Accountable Care Organizations -- or ACOs -- formed for the first time in 2011, designed to combat rising medical costs and provide more coordinated care to Medicare patients. But the savings have been inconsistent nationwide.

A new Portland State University study looked at what's driving those inconsistencies and what ACOs might do to resolve the issue. The study was published in the February issue of Health Affairs by OHSU-PSU School of Public Health Assistant Professor Sunny Lin.

"Primary care has the potential to unlock the key to reducing healthcare costs," Lin said.

Decreasing the percent of primary care delivered out-of-network across all Medicare ACOs by just one-tenth of a percentage point could save the Medicare system $45 million a year, the study found.

ACOs are self-organized providers working together to better control healthcare costs. The organizations have federal approval and receive Medicare funding, but in lieu of the traditional fee-for-service model, ACOs are incentivized to spend less per patient.

If they succeed in saving money through coordinated care, they share the remaining government funding. However, ACOs have no control over who their patients see, including whether their patients seek care outside of the ACO network.

"What the study found is that it actually didn't matter how much specialty care was received by non-ACO providers," said Lin, who co-authored the study with John Hollingsworth of the University of Michigan Medical School. "What mattered more was how well their primary care providers were aligned in the ACO."

Those findings go against common wisdom that dictated when it comes to spending, specialty care costs more to the system.

The study found that "leakage" -- the percent of care patients receive outside their network -- impacted healthcare spending more for primary care providers than specialty care providers.

In marginalized communities or ACOs with a higher proportion of patients of color, leakage was even higher. Lin said this was likely because those populations have a harder time maintaining continuity of care and experience more barriers to seeing the same primary care provider repeatedly.

"ACOs need to be cognizant of these barriers and try to find ways to reduce them in order to save money -- and more importantly better serve their patients," she said.

Looking at Medicare data from 1.6 million patients between 2012 and 2015, researchers found that higher specialty care leakage didn't mean higher overall costs for ACOs.

Higher costs were however associated with ACOs that had a higher percentage of patients with primary care services that weren't received in-network. These higher costs were driven largely by outpatient care, emergency room visits and skilled nursing facilities. For each additional percentage-point increase in ACO's out-of-network primary care visits, the ACO paid about $43 a year more per patient.

Lin said this cost increase may be because primary care providers act as gatekeepers. As providers, they manage referrals to potentially high-cost services and when in-network, are more likely to provide more cost-effective care.

Policymakers could help reduce leakage by supporting primary care providers, Lin added, and putting more focus on their vital role in the healthcare system.

The combination of green tea extract and exercise reduced the severity of obesity-related fatty liver disease by 75% in mice fed a high-fat diet, according to Penn State researchers, whose recent study may point to a potential health strategy for people.

The outcome is important, explained Joshua Lambert, associate professor of food science, because nonalcoholic fatty liver disease is a significant global health problem that is expected to worsen. Because of the high prevalence of risk factors such as obesity and type 2 diabetes, fatty liver disease is forecast to afflict more than 100 million people by 2030. And there are currently no validated therapies for the disease.

In the study, mice fed a high-fat diet for 16 weeks that consumed green tea extract and exercised regularly by running on a wheel were found to have just a quarter of the lipid deposits in their livers compared to those seen in the livers of a control group of mice. Mice that were treated with green tea extract alone or exercise alone had roughly half as much fat in their livers as the control group.

In addition to analyzing the liver tissues of mice in the study, which was published recently in the Journal of Nutritional Biochemistry, researchers also measured the protein and fat content in their feces. They found that the mice that consumed green tea extract and exercised had higher fecal lipid and protein levels.

"By examining the livers of these mice after the study concluded and by screening their feces during the research, we saw that the mice that consumed green tea extract and exercised actually were processing nutrients differently -- their bodies were handling food differently," Lambert said.

"We think the polyphenols in green tea interact with digestive enzymes secreted in the small intestine and partially inhibit the breakdown of carbohydrates, fat and protein in food," he added. "So, if a mouse doesn't digest the fat in its diet, that fat and the calories associated with it pass through the mouse's digestive system, and a certain amount of it ends up coming out in its feces."

It may be significant, Lambert explained, that mice treated with both green tea extract and exercise had higher expression of genes related to the formation of new mitochondria. That gene expression is important, he said, because it provides markers that will help researchers understand the mechanism by which green tea polyphenols and exercise might work together to mitigate fatty liver deposits.

"We measured the expression of genes that we know are related to energy metabolism and play an important role in energy utilization," Lambert said. "In the mice that had the combination treatment, we saw an increase in the expression of genes that wasn't there before they consumed green tea extract and exercised."

More research is needed to see if there is a synergy created by green tea extract and exercise working together to reduce fat deposited in the liver, or if the effects are simply additive, Lambert pointed out. His research group in the College of Agricultural Sciences for 12 years has studied the health benefits of polyphenols -- often called antioxidants -- from green tea, cocoa, avocados and other sources.

In previous related research, Lambert and colleagues demonstrated that green tea extract and exercise together sharply reduced body mass and improved cardiovascular health of high-fat-fed mice. But because no human trials assessing the health benefits and risks of green tea combined with exercise have been conducted, he urges caution for people who decide to experiment with the health strategy on their own.

"I believe people should engage in more physical activity, and replacing high-calorie beverages with decaffeinated, diet green tea -- which has no calories -- is a smart move," he said. "Combining the two might have health benefits for people, but we don't have the clinical data yet."

Most everyone experiences the pain of social rejection at some point in their lives. It can be triggered by the end of a romantic relationship, losing a job or being excluded by friends.

The emotional distress that often accompanies these experiences is called social pain, and it may cause sadness, depression and loneliness, as well as actual physical pain, research has shown.

A study, published recently in the Annals of Behavioral Medicine may have found an antidote - forgiveness combined with acetaminophen, the active ingredient in Tylenol.

For the study, researchers followed a group of healthy adults for three weeks and randomly assigned them to receive daily doses of either 1,000 mg of acetaminophen, 400 mg of a placebo potassium pill, or no pill. They also measured their levels of forgiveness on a daily basis using a questionnaire. For example, participants were asked to rate how strongly they agree or disagree with statements, such as, "I hope this person gets what's coming to them for what he/she did to me."

George Slavich, PhD, director of the UCLA Laboratory for Stress Assessment and Research, a senior author on the study discussed the results.

What is the key takeaway from this study?

When combined with a tendency to forgive, taking acetaminophen substantially reduced how much social pain people felt over time. More specifically, participants taking acetaminophen who were high in forgiveness exhibited an 18.5% reduction in social pain over the 20-day study period.

What made researchers think that acetaminophen and forgiveness might ease the pain of rejection?

Research has shown that physical pain and social pain are influenced by some of the same biological processes in the brain and body. Based on this research, we thought that acetaminophen, which is commonly used to treat physical pain, might also be able to reduce social pain.

Based on the study's findings, what is it about acetaminophen and forgiveness that help alleviate social pain? Do they act synergistically?

We think they help reduce experiences of social pain in different ways. For example, acetaminophen likely reduces social pain by influencing pain signaling in the brain through its effects on specific brain pathways. On the other hand, forgiveness has been found to lessen peoples' feelings of stress and anger following experiences of social rejection and exclusion. Based on the findings from our study, it appears as though acetaminophen acts synergistically with peoples' ability to forgive to alleviate the feelings of social pain that are commonly associated with rejection and exclusion.

How does social pain affect people emotionally?

Experiencing a socially painful life event, like a relationship break-up, is one of the strongest predictors of developing depression in adolescence and adulthood. Social pain is also associated with decreased cognitive functioning and increased aggression and engagement in self-defeating behaviors, like excessive risk taking and procrastination.

Why does social rejection also cause physical pain?

We can only speculate about why social rejection causes physical pain, but one possibility is that physical pain alerts the person to the fact that an important social relationship has been threatened or lost. This may motivate the person to try to rekindle the relationship or form other relationships to help ensure continued safety and survival.

Are there further studies planned?

Looking forward, we hope to better understand the mechanisms underlying how acetaminophen and forgiveness alleviate social pain and, most importantly, how we can use this knowledge to enhance human health and wellbeing.

Swansea University research into the threat posed by antifungal drug resistance has been highlighted in two prestigious international journals.

Fungal disease now kills more people than malaria or TB and the Centre for Disease Control in the USA recognises emergence of multi-drug resistance in fungi as a high level threat.

Dr Josie Parker and Prof Steve Kelly, from Swansea University Medical School's Centre for Cytochrome P450 Diversity have been involved in the studies which investigated different aspects of resistance

The first publication in the American Microbiology Society journal mBio saw them working with fellow academics from the University of Lausanne led by Professor Dominque Sanglard to compare whole genomes to identify key mutations involved in resistance to the drugs available that include azoles, amphotericin B and echinocandins.

A second publication in Nature Communications involved an international collaboration led by Manchester University's Professor Paul Bowyer and Dr Mike Bromley.

It examined drug resistance in the filamentous fungal pathogen Aspergillus fumigatus. Breathing in the airborne spores of this fungus can cause the devastating disease invasive aspergillosis which causes more than 200,000 life-threatening infections every year.

Professor Kelly, who has been researching the field of antifungal resistance for more than 30 years, said: "We are very pleased to be involved in both these research projects and that they have been published in such well-regarded journals.

"Improving our understanding of antifungal drug resistance will help in the development of effective and potentially life-saving therapies for the future."

Radiation doses to the heart that occur during radiation therapy treatments for lung cancer, breast cancer and lymphoma can increase fatigue, cause difficulty breathing and lower capacity for physical activity in patients with cancer, according to research presented at the American College of Cardiology's Advancing the Cardiovascular Care of the Oncology Patient course. The course examines new science and best practices in assessing, diagnosing and treating the unique cardiovascular concerns of patients with cancer and/or those requiring survivorship care.

Cardiovascular disease is the second leading cause of death in cancer survivors, and it is estimated that 14.5 million cancer patients and survivors have significant cardiovascular risk factors. As more cancer patients are surviving and living longer, more long-term care issues are coming to light. Thoracic radiation therapy is a type of cancer treatment directed at the chest, heart and torso region and is highly effective in treating certain types of cancers in conjunction with chemotherapy. Thoracic radiation therapy can also cause side effects that can impact quality of life.

Researchers in this study sought to examine thoracic radiation therapy as it impacted quality of life in breast cancer, lung cancer and lymphoma patients. The study, conducted from 2015 to 2018, examined 130 patients with either breast cancer, lung cancer or mediastinal lymphoma who were treated with radiation to the chest. The median age of participants was 54 years and 78.5% were women.

Researchers collected data before radiation therapy was administered, immediately after the patient had received therapy, then five to nine months after the completion of radiation therapy. At each of these three time points, patients were asked to self-report physical activity, which was assessed using the Godin-Shephard Leisure-Time Physical Activity Questionnaire (GSLTPAQ). Fatigue and shortness of breath were assessed using the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue and Dyspnea Scales.

Different types of cancer showed different results:

Lung cancer and lymphoma participants reported an increase in fatigue and dyspnea immediately post-radiation therapy, which later improved. Each 1 Gy of increase in mean heart dose of radiation was associated with decreased GSLTPAQ scores. Additionally, every 10% increase in the volume of heart receiving a radiation dose of 5 Gy was associated with a significant reduction in GSLTPAQ scores.

Breast cancer participants reported significant increases in physical activity and decrease in fatigue over time. In this group, there was a non-significant trend toward increased fatigue with increasing radiation dose. However, when accounting for differences in radiation and chemotherapy treatment in these patients, high baseline moderate to vigorous GSLPTAQ scores were associated with improvements in fatigue over time.

"This study suggests that when a patient is treated with thoracic radiation therapy, it can have a negative impact on their quality of life early on. However, engaging in higher levels of physical activity before treatment may help to improve some of these symptoms over time," said lead author Sheela Krishnan, MD, fellow in the cardiovascular division of the Hospital of the University of Pennsylvania. "This study also confirms that increasing levels of physical activity during treatment are associated with concurrent improvements in quality of life. Though we cannot establish a clear causal relationship from these findings, it does emphasize that physical activity and quality of life are closely linked."

Differences were observed between breast cancer and lung cancer and lymphoma patients, potentially due to differences in the delivered radiation doses. However, for all participants, accounting for the differences in chemotherapy and radiation dose they received, increases in physical activity over time were significantly associated with concurrent improvements in fatigue and shortness of breath.

"While our study is a small study, it suggests that high levels of physical activity prior to initiation of radiation therapy for cancer are associated with better physical functioning and quality of life with cancer treatment," Krishnan said. "Additional work is still needed to understand the types and timing of exercises that can bring about the greatest benefit."