Body

MINNEAPOLIS - A new study finds that up to 10 percent of people with headaches also have facial pain. The study is published in the August 21, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"Facial pain has not been well recognized as a symptom of headache, and some people end up waiting a long time for a proper diagnosis and treatment," said study author Arne May, MD, PhD, of the University of Hamburg in Germany. "This study shows that facial pain is not uncommon, and for many people their pain occurs mainly in the face, not the head."

The study involved 2,912 people with primary headaches, which are headaches not due to another condition and include migraine and cluster headache. Participants were asked to fill out questionnaires about their headaches and any facial pain. People with dental problems that could explain the facial pain were not included in the study.

Of the study participants, 291 people, or 10 percent, had facial pain. Only 2 percent, or 44 of the 1,935 people with migraine had facial pain. Of those, 41 percent experienced pain predominantly in the face. Among people with cluster headache, 15 percent, or 42 of 283 people, had facial pain. Of those, 31 percent had pain mainly in the face.

Among the 20 people with paroxysmal hemicrania, a rare type of headache with severe, often short attacks on one side of the head, 45 percent had facial pain. Facial pain affected 21 percent of the 42 people with hemicrania continua, another rare type of headache with continuous pain that varies in severity.

In another rare type of headache, called short-lasting unilateral neuralgiform headache, 20 percent of the 15 people in the study had facial pain. This type of headache involves very frequent attacks on one side of the head.

The researchers also reported on six people who had constant facial pain on one side of the head only in addition to facial pain attacks lasting 10 to 30 minutes and occurring several times a day. May said this type of pain syndrome has not been described before and proposed calling it constant unilateral facial pain with added attacks.

"For a better understanding of these types of facial pain and ultimately for the development of treatments, it's crucial that we understand more about facial pain and whether it is the same disease as the headache, but showing up in a different place, or whether they are two different syndromes," May said.

A limitation of the study was that participants were asked about their headaches in the past and they may not remember all symptoms. Also, facial pain may not have been mentioned by participants to their doctors nor asked about by the doctors, so the percentage of people with facial pain may have been underestimated, May said.

Washington, DC, August 21, 2019 - Safe reproductive health services, including contraception and abortion, can be lifesaving for some women. However, accessing these services can be a challenge for many women in the United States, particularly low-income women of color. Restrictive state legislation, disparities in access to trained providers, and a lack of evidence-based, standardized guidelines for counseling serve as barriers for women receiving the health services they need.

Among continued efforts to prevent maternal morbidity and mortality, the Society for Maternal-Fetal Medicine (SMFM), hosted a two-day workshop entitled "Reproductive Services for Women at High Risk for Maternal Mortality." The workshop was held in conjunction with SMFM's 39th Annual Pregnancy Meeting in Las Vegas, Nevada in February 2019 and was co-sponsored by the American College of Obstetricians and Gynecologists, Fellowship in Family Planning, and Society of Family Planning.

Workshop participants discussed assessment, counseling, and training for providers who care for women with high-risk pregnancies. A summary of the workshop and its recommendations titled, "Executive Summary: Reproductive Services for Women at High Risk for Maternal Mortality Workshop," has been published in the American Journal of Obstetrics and Gynecology (AJOG).

"Access to the full spectrum of reproductive health services, including pregnancy termination, is critical to women's overall health and saves women's lives," said Sean Blackwell, MD, SMFM's immediate past-president and originator of the workshop. "We hope that this presidential workshop and its summary shine a light on the unique considerations of women who have an increased risk of death during or after pregnancy."

The executive summary emphasizes the need for a wide range of safe, equitable reproductive health services for women at high risk for maternal death and makes recommendations on how to remove barriers and improve patient care. Family planning interventions, particularly access to safe, timely abortion, have been shown to prevent maternal deaths worldwide. Patient-centered, shared decision-making should be highly valued when counseling women, and more research must be conducted with high-risk women to develop evidence-based solutions for the current maternal mortality crisis.

More in-depth publications on this topic with clinical guidance and future research questions will be published by SMFM at a later date. "We hope our summary of the workshop will inspire future research and prompt further collaboration between maternal-fetal medicine subspecialists, family planning subspecialists, and obstetrician-gynecologists," said Blackwell.

ST. LOUIS - Research from Saint Louis University finds treatment for Post-Traumatic Stress Disorder (PTSD) that leads to an improvement in symptoms was associated with a 49 percent lower risk of incident type 2 diabetes.

The study, "Clinically Meaningful PTSD Improvement and Risk for Type 2 Diabetes," by Jeffrey Scherrer, Ph.D., professor in Family and Community Medicine at SLU, was published online Aug. 21 in JAMA Psychiatry.

"Some long-term chronic health conditions associated with PTSD may be less likely to occur among patients who experience clinically meaningful symptom reduction either through treatment or spontaneous improvement," Scherrer said.

PTSD affects up to 12 percent of civilians and nearly 30 percent of the veteran population. Those with PTSD are at risk for other health issues and improvement in PTSD symptoms is associated with parallel improvements in depression, emotional well-being, sleep, blood pressure and general physical health.

PTSD is associated with an increased risk of type 2 diabetes, which may be explained by the high prevalence of obesity, glucose dysregulation, inflammation, metabolic syndrome and depression among those diagnosed with PTSD versus those without PTSD.

This retrospective cohort study reviewed Veterans Health Affairs medical record data from 2008 to 2015. The researchers randomly selected 5,916 cases from among a veteran patient population aged 18 to 70 who had more than two visits to PTSD specialty care between 2008 and 2012. The patients were followed through until 2015.

After applying eligibility criteria, 1,598 patients with PTSD and free of diabetes risk were available for analysis.

Clinically meaningful symptom reduction is a decrease of 20 points on the PTSD Checklist score. The research found the results were independent of numerous demographic, psychiatric and physical comorbidities. The sample was 84.3 percent male, 66 percent Caucasian and 22 percent African-American. The mean age of the patients was 42.

The association was also independent of the number of PTSD psychotherapy sessions used.

"In patients with only PTSD, clinically meaningful PCL decrease is associated with lower risk for diabetes and in patients with PTSD and depression, we found improvement in PTSD was coupled with a decrease in depression," Scherrer said. "Thus decreased risk for type 2 diabetes appears to follow large PTSD symptom decrease and in patients with both PTSD and depression, improvement in both conditions may be necessary to reduce risk for type 2 diabetes."

"Surprisingly, clinically meaningful PTSD improvement was not associated with a change in BMI and A1C values."
A prospective study is needed to advance research, Scherrer says, due in part to the limitations of medical record data. Such a study could determine if large decreases in PTSD checklist scores are associated with improved insulin resistance and reduced inflammation.

Take-aways

The observational study examined whether veterans who experienced a greater reduction in symptoms of posttraumatic stress disorder (PTSD) had an associated lower risk of developing type 2 diabetes.

The analysis included medical records from almost 1,600 veterans who received PTSD specialty care and had repeated completion of the PTSD Checklist as part of their treatment at the VA.

Patients with versus patients without clinically meaningful improvement in PTSD symptoms had a 49 percent lower risk for type 2 diabetes over a 3-6-year follow-up period.

In patients with PTSD and depression, improvement in both conditions was associated with lower risk for diabetes.

By integrating translational imaging techniques with improvements to production methods, Tina Binderup and colleagues have scaled up a promising nanoimmunotherapy for atherosclerosis in mice, rabbits and pigs - surmounting a major obstacle in nanomedicine. Their study brings the anti-inflammatory treatment for one of the most common chronic conditions worldwide closer to application in humans and identifies strategies for overcoming challenges in translating nanoimmunotherapies from small animal models to the clinic. Nanomedicine - the use of nanotechnology and nanomaterials to treat disease - has become a major field of interest, and hundreds of new nanoformulations are being developed every year. However, most nanomedicine research is limited to proof-of-concept studies in mice, and challenges in producing enough nanomaterials have hampered larger animal testing and the approval of practical and effective drugs for humans. In a previous study, the researchers created a nanotherapeutic called S-HDL that reduced inflammation in blood vessels in mouse models of atherosclerosis. Here, they tested a new production method for S-HDL based on devices named microfluidizers, which boosted production rates of the therapeutic by up to 80-fold compared to older methods. The authors used PET and MRI imaging to visualize how the new S-HDL formulation performed in rabbits and a pig model of atherosclerosis and found two weeks of the treatment halted the accumulation of plaque and curtailed vessel wall inflammation in the animals without causing toxicity. Binderup et al. say their new workflow and use of noninvasive imaging could allow researchers to gather meaningful results even when restricted to using small groups of larger animals.

COLUMBUS, Ohio - Research led by Dr. Krystof Bankiewicz, who recently joined The Ohio State University College of Medicine, shows that gene replacement therapy for Niemann-Pick type A disease is safe for use in nonhuman primates and has therapeutic effects in mice.

These research findings are published online in the journal Science Translational Medicine.

Prior to joining Ohio State as a professor of neurosurgery, Bankiewicz conducted this translational gene therapy research at the University of California at San Francisco, in conjunction with researchers in New York, Massachusetts and Spain.

Niemann-Pick disease primarily affects children, has no known cure and is often fatal. It's caused by mutations in a gene that causes a deficiency of a specific enzyme, acid sphingomyelinase (ASM). With this disease, the body's ability to metabolize fat within cells is affected, causing these cells to malfunction and, eventually, die. This inherited disease can affect the brain, nerves, liver, spleen, bone marrow and lungs.

Researchers evaluated the safety and effectiveness of adeno-associated viral vector serotype 9 (AAV9)-based gene therapy. Using a newly developed cerebrospinal fluid delivery method into a specific area of the brain allowed widespread gene expression in the brain and spinal cord of nonhuman primates without signs of toxicity.

In addition, the treatment provided a "bystander effect" by preventing motor and memory impairment and increased survival in a mouse model of the disease, said Bankiewicz, who also is a member of Ohio State's Neurological Institute.

"This is the 'proof of concept' of gene therapy in animal models for this disease. It's a big jump in the development process as we work toward one day being able to safely give this therapy to children who otherwise would die by age 3," Bankiewicz said. "Our plan is to translate this exciting data into human clinical trials at The Ohio State University Wexner Medical Center within the next couple of years.

Based on this research, Bankiewicz and his team, including co-author Lluis Samaranch, an assistant professor of neurological surgery at Ohio State, will move forward with additional animal studies in preparation to eventually begin clinical trials in humans.

"Dr. Bankiewicz is a world leader in neuro-restorative medicine - particularly gene therapy. With his recruitment here - along with the expertise of his five-member research team he's bringing with him - The Ohio State University College of Medicine is making a strong commitment to developing a gene therapy program to develop treatments for this and other diseases, such as Parkinson's and Alzheimer's," said Dr. K. Craig Kent, dean of Ohio State College of Medicine.

Throughout his career, Bankiewicz has maintained a strong focus on the development of translational approaches to drug, gene and cell replacement therapies.

His research has focused on new treatments of serious diseases, including brain cancer, Parkinson's disease, Huntington's disease, Alzheimer's diseases, pediatric neurotransmitter deficiency and lysosomal storage disorders. At Ohio State, Bankiewicz will work closely with the department of neurological surgery to conduct other gene replacement therapy clinical trials in humans.

Wednesday, August 21, 2019, CLEVELAND: A new international study co-led by Cleveland Clinic has identified a new drug target for treating glioblastoma. This target is part of a never-before defined cellular pathway found to contribute to the spread and proliferation of a dangerous subset of cancer cells, called glioma stem cells.

While previous research has shown that a protein called FGF2 (fibroblast growth factor 2), when activated ("turned on"), contributes to glioma stem cell self-renewal and tumor growth, it was not understood how. This study, co-led by Justin Lathia, Ph.D., Cleveland Clinic Lerner Research Institute, identifies FGF2 as an important intermediary in a multi-step, pro-cancer signaling loop and suggests that "turning off" FGF2 may halt the growth and spread of glioblastoma.

Published in the August 21 issue of Cancer Discovery, this study is the first to identify FGF2 as a novel druggable target for glioblastoma, the most common primary malignant brain tumor. With standard treatment, the median survival for adults with glioblastoma is only between 11 and 15 months, and recurrence is very common. New therapies are greatly needed.

Extracellular matrix (ECM) is a network of molecules that--like brick and mortar--help to hold and anchor nearby cells together. The research team found that a protein called ADAMDEC1 (a disintegrin and metalloproteinase domain-like protein decysin 1), which is secreted by glioma stem cells, breaks down ECM. In its absence, cancer cells are able to access key nutrients for their growth that otherwise would not be available.

One of these nutrients is FGF2. The team of researchers showed that ADAMDEC1 activates FGF2, which is found within the tumor microenvironment. Like a lock and key, the "turned on" FGF2 selectively binds to and activates a receptor found on the surface of glioma stem cells, called FGFR1 (FGF receptor 1).

FGFR1, mediated through a few additional signaling cascades, plays two important roles in driving glioblastoma. It helps to mediate the hallmark pro-cancer characteristics of glioma stem cells, including their ability to self-renew and spread. Additionally, FGFR1 signaling ultimately induces the expression of ADAMDEC1, which sends this whole cellular feedback loop into motion again.

"These findings are exciting because they put forth a new paradigm for glioma stem cell regulation," said Dr. Lathia. "This pathway shows that glioma stem cells' ability to access key nutrients in their surrounding microenvironment, by way of ADAMDEC1, is integral for their maintenance and spread. Finding a way to interrupt this feedback loop will be important for treating glioblastoma."

While additional research is necessary, this study suggests that therapeutically targeting FGF2 may be the key to interrupting this cancer-driving loop.

All print, broadcast and online journalists who receive the Obesity embargo alert agree to abide by the embargo and may not publish, post, broadcast or distribute embargoed news releases or details of the embargoed studies before the embargo date and time.

When writing about these studies, journalists are asked to attribute the source as the journal Obesity and to include the online link to the Obesity articles as provided below. Links become active when articles post at 3:00 a.m. (EDT) on Aug. 23, 2019.

About the journal - Obesity is the peer-reviewed, scientific journal of The Obesity Society.

Editors' Choice 1 - Mitigating Cardiometabolic Risks with Brief Interruptions of Sitting, Robyn Larsen, robyn.larsen@baker.edu.au, Hamza Ali, Paddy C. Dempsey, Megan Grace, Francis Dillon, Bronwyn A. Kingwell, Neale Cohen, Neville Owen, Daniel J. Green, and David W. Dunstan
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22554)

Editors' Choice 2 - Community Diffusion Strategies are Key Driver of Pediatric Program, Matt Kasman, Ross A. Hammond, Benjamin Heuberger, bheuberger@brookings.edu, Austen Mack-Crane, Rob Purcell, Christina Economos, Boyd Swinburn, Steven Allender, and Melanie Nichols
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22553)

Editors' Choice 3 - Salivary Amylase Gene Copy Number and BMI: No Association Found, Nzar A. A. Shwan and John A. L. Armour, john.armour@nottingham.ac.uk
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22565)

Editors' Choice 4 - Does Psychiatric Medication Use Reduce Weight Loss Outcomes?, Sean Wharton, Jennifer L. Kuk, Lana Petrova, Peter I. Rye, Valerie H. Taylor, and Rebecca A.G. Christensen, christensen@mail.utoronto.ca
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22567)

Scroll down to find abstracts for each of the above papers. To request the full text of any of these studies and agree to the embargo policy, or to arrange an interview with a study's author or an obesity expert, please contact communications@obesity.org.

Editors' Choice Abstracts

Editors' Choice 1 - Interrupting Sitting Time with Simple Resistance Activities Lowers Postprandial Insulinemia in Adults with Overweight or Obesity

Objective: This study aimed to examine the effects on postprandial glucose and insulin responses of interrupting sitting time with brief bouts of simple resistance activities (SRAs) in adults with overweight or obesity.

Methods: Participants (n = 19) were recruited for a randomized crossover trial involving the following two 6-hour conditions: (1) uninterrupted sitting or (2) sitting with 3-minute bouts of SRAs (half-squats, calf raises, gluteal contractions, and knee raises) every 30 minutes (total duration = 27 minutes). Incremental areas under the curve (iAUC) for glucose, insulin, and insulin:glucose ratio were analyzed as pre-specified secondary outcomes using mixed-effects log-linear regression adjusted for sex, BMI, treatment order, and pre-prandial values. Results are reported as multiplicative change (exponentiated coefficient [EC] with 95% CI) relative to the control condition.

Results: Glucose iAUC during the SRA condition was not significantly different from the prolonged sitting condition (EC = 0.92; 95% CI: 0.73-1.16; P = 0.43). However, SRAs lowered the postprandial insulin response by 26% (EC = 0.74; 95% CI: 0.64-0.85; P

Conclusions: In adults with overweight or obesity, frequent interruptions to sitting time with SRAs lowered postprandial insulin responses and insulin:glucose. These findings may have implications for mitigating cardiometabolic risk in adults with overweight or obesity who engage in prolonged periods of sitting.

Editors' Choice 2 - Activating a Community: An Agent-Based Model of Romp & Chomp, a Whole-of-Community Childhood Obesity Intervention

Objective: Successful whole-of-community childhood obesity prevention interventions tend to involve community stakeholders in spreading knowledge about and engagement with obesity prevention efforts through the community. This process is referred to by the authors as stakeholder-driven community diffusion (SDCD). This study uses an agent-based model in conjunction with intervention data to increase understanding of how SDCD operates.

Methods: This agent-based model retrospectively simulated SDCD during Romp & Chomp, a 4-year whole-of-community childhood obesity prevention intervention in Victoria, Australia. Stakeholder survey data, intervention records, and expert estimates were used to parameterize the model. Model output was evaluated against criteria derived from empirical data and experts' estimates of the magnitude and timing of community knowledge and engagement change.

Results: The model was able to produce outputs that met the evaluation criteria: increases in simulated community knowledge and engagement driven by SDCD closely matched expert estimates of magnitude and timing.

Conclusions: Strong suggestive evidence was found in support of a hypothesis that SDCD was a key driver of the success of the Romp & Chomp intervention. Model exploration also provided additional insights about these processes (including where additional data collection might prove most beneficial), as well as implications for the design and implementation of future interventions.

Editors' Choice 3 - No Evidence for Association of BMI with Salivary Amylase Gene Copy Number in the UK 1958 Birth Cohort

Objective: In a 2014 publication, evidence was presented supporting the association of BMI with the copy number of the salivary amylase 1 (AMY1) gene, with an unprecedented effect size of -0.15 kg/m2 (SE 0.02) per copy of AMY1. Most well-powered attempts to reproduce these findings have not been successful. However, because of different study designs, a significant association may still apply under restricted conditions such as in particular age groups. This study specifically tested the BMI-AMY1 association at different age points in the same individuals using longitudinal BMI information from participants in the UK 1958 Birth Cohort study.

Methods: This study measured the AMY1 copy number by paralogue ratio tests in genomic DNA and by using array comparative genomic hybridization data. BMI data from 1958 Birth Cohort participants were available from eight different age points between 7 and 50 years.

Results: No evidence, even at nominal significance, was found for association of the AMY1 copy number with BMI at any age point in approximately 1,400 members of the 1958 Birth Cohort or in 2,835 people from two disease cohorts from the Wellcome Trust Case Control Consortium.

Conclusions: The results do not support an association between BMI and AMY1 copy number at any age point.

Editors' Choice 4 - Effectiveness of a Community-Based Weight Management Program for Patients Taking Antidepressants and/or Antipsychotics

Objective: This study aimed to compare weight loss (WL) outcomes for patients taking antidepressants and/or antipsychotics with those not taking psychiatric medication.

Methods: A total of 17,519 adults enrolled in a lifestyle WL intervention at the Wharton Medical Clinics in Ontario, Canada, were analyzed. Sex-stratified multivariable linear regression analysis was used to examine the association of taking anti-depressants, anti-psychotics, both, or neither with WL when adjusting for age, initial weight, and treatment time.

Results: Twenty-three percent of patients were taking at least one psychiatric medication. Patients lost a significant amount of weight (P 0.05). Conversely, men taking antidepressants lost only slightly less weight than men taking both classes or neither class of psychiatric medication (3.2 ± 0.3 kg vs. 5.6 ± 0.9 kg and 4.3 ± 0.1 kg; P 0.05).

Conclusions: Results of this study suggest that those who participate in a weight management program can lose significant amounts of weight regardless of psychiatric medication use.

In an extensive "data mining" analysis of British medical records, researchers at the Johns Hopkins Kimmel Cancer Center conclude that taking even a single course of antibiotics might boost--albeit slightly--the risk of developing colon cancer--but not rectal cancer--a decade later. The findings, reported in the August 20 issue of the journal Gut , highlight the need for judicious use of this broad category of drugs, which are frequently improperly or overprescribed, the report authors say.

"The primary message of this study is the importance of antibiotic stewardship: not treating common viral infections with antibiotics, using them for the shortest time period possible, and using targeted antibiotics rather than broad spectrum ones," says study leader Cynthia L. Sears, M.D., Bloomberg~Kimmel Professor of Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center. "This research adds to our understanding that these drugs can have significant off-target effects, including the induction of chronic illnesses."

Sears cautions that medical records studies like hers are not designed to demonstrate cause and effect, but to identify possible associations between risk factors and disease. But she notes that because the database held so much specific information over a long period of time that the study authors concluded that the most likely explanation for the bump in colon cancer risk is the radical change that antibiotics wreak on the microbiome--the collection of bacteria that live in the intestines.

Antibiotics are widely prescribed throughout the world to treat bacterial infections, and there is growing evidence, including several epidemiological database studies, that link use of these drugs to the risk of colorectal cancer, explains Sears and Jiajia Zhang, M.D., M.P.H., a Bloomberg~Kimmel Institute for Cancer Immunotherapy researcher. However, the investigators say, these past studies have had a variety of drawbacks, including failure to control for other colorectal cancer risk factors (family history, history of obesity, smoking, alcohol use, and diabetes) recall bias in patients' recollections about antibiotic use, failure to separate data about colon and rectal cancers, and too few study participants to produce meaningful conclusions.

To learn more about the association between antibiotics and colorectal cancers, Sears, Zhang, and their colleagues mined data from the Clinical Practice Research Datalink (CPRD), one of the world's largest electronic medical record databases of "anonymized" clinical records, information that does not identify individual patients. CPRD holds information on more than 11 million patients in the U.K., including data on drug prescribing and diagnoses, making this study the first population-based study to examine the association of antibiotic exposure and risk of colorectal cancer.

Focusing on a 23-year period from January 1, 1989, to December 31, 2012, the researchers found 28,890 cases of colorectal cancer. They matched each of these patient records with up to five healthy "controls" who never developed this disease, but who had similar characteristics, including age, gender, and where their general practitioner practiced, for a total of 137,077 "control" cases for comparison.

They then used the medical records to identify and evaluate each case history for colorectal cancer risk factors, such as a history of obesity, smoking, alcohol use, and diabetes, as well as antibiotic use.

As expected, the researchers found that those patients who developed colorectal cancer were more likely to have one or more of the known risk factors. However, when they accounted for these factors in their statistical evaluation, they found that those who developed colon cancer were slightly more likely to have been exposed to antibiotics (71.3% compared to 69.1%). Those with rectal cancers did not show that association and had about the same antibiotic exposure compared to healthy subjects.

Further investigation showed that antibiotic exposure was only associated with increased risk of approximately 15% for cancer in the proximal colon (the first and middle parts of the colon) but not the distal colon (last part of the colon), and this risk happened particularly after exposure to classes of antibiotics that kill anaerobic bacteria, such as those in the penicillin family.

Among the compelling findings, the researchers say, was the rapid onset of increased colon cancer risk, beginning with only 15-30 days of total antibiotic exposure (approximately 8% increased risk with 15-30 days of total antibiotic exposure and approximately 15% increased risk with 30 or more days of total antibiotic exposure). However, the association was reversed for rectal cancer: the more total antibiotic exposure, specifically total exposures of 60 days or more, the less likely they were to have cancer in this location. Cancers that developed in the colon were linked with antibiotic exposure at least 10 years earlier. There was no increased risk with exposures less than 10 years prior.

Although antibiotics are most often highly effective at eradicating bacterial infections, Sears explains, they also can change the balance of the gut biome by killing beneficial bacteria and allowing pathogenic ones to thrive. Some of these surviving bacteria could be carcinogenic, encouraging polyps to grow and develop into malignant tumors.

In recent years, she notes, probiotic-rich foods and supplements have become popular, in part to address gut biome imbalances. But the data on probiotics is mixed, she adds, with some studies showing positive effects and others showing no effects or negative effects of using these supplements. Rather than trying to add beneficial bacteria back to the intestines, Sears says, a better way to avoid potentially increased colon cancer risk from antibiotic use is through more cautious prescribing of antibiotics.

Simple, fast and flexible: It could become significantly easier to vaccinate plants against viruses in future. Scientists at Martin Luther University Halle-Wittenberg (MLU), the Leibniz Institute of Plant Biochemistry (IPB) and the National Research Council in Italy (CNR) have developed a new method for this purpose. It enables the rapid identification and production of precisely tailored substances that combat different pathogens. The researchers discuss their work in the next edition of the journal "Nucleic Acids Research".

The new method is based on a molecular defence program of plants that is triggered, for example, by viral infections. During a virus attack, the plant's cells serve as a host to multiply the virus, which results in the creation of viral ribonucleic acid molecules (RNAs). Plants can detect and cut up these molecules using special enzyme scissors. This process produces "small interfering RNAs" (siRNAs) which spread throughout the plant and may initiate a second stage of defence for the plant. Here, the siRNA molecules attach themselves to so-called Argonaute protein complexes and lead these to the virus RNAs, which then, in the best-case scenario can be dismantled and broken down into harmless compounds. "By implementing this two-stage process, the plant is trying to protect itself from the virus both at the site of the infection and throughout its structure", says Professor Sven-Erik Behrens from MLU's Institute of Biochemistry and Biotechnology.

The process is not particularly efficient, however, as the biochemist explains: "When a viral infection occurs, lots of different siRNA molecules are produced, but very few of them have a protective effect. The majority simply saturate the Argonaute complexes, rendering them inactive." Behrens' team has discovered a novel way to identify the few effective antiviral siRNA molecules for different viruses and harness them as plant vaccines. The scientists have developed a screening process based on plant cell extracts, which is being used instead of lengthy, complex breeding efforts. To qualify as potential vaccines, the siRNA molecules must have two key properties: On the one hand, they have to bind strongly to the Argonaute complexes. On the other hand, they have to lead these proteins to sites of the viral RNAs that are accessible for Argonaute-mediated degradation.

The team of scientists have already been able to prove the effectiveness of their new method in the laboratory. To achieve this, two groups of the tobacco plant N. benthamiana were infected with a model virus that attacks tomatoes and tobacco. Before being infected, one group was vaccinated with highly efficient siRNA molecules that the researchers had identified using the new method. The other group didn't receive any treatment. The effects were striking: After six weeks, 90 per cent of the vaccinated plants did not show any signs of infection, but all the untreated plants had been killed by the virus.

The MLU research team's method follows the modular principle. "If the pathogen changes or the plant needs to be protected against another virus, the established screening process enables suitable RNA molecules to fight the respective pathogen to be identified very quickly. This means we can be very flexible when it comes to combatting new pests", Behrens concludes. A patent application has been filed for the method.

The researchers hope to continue exploring and improving their method in future. It is, for example, still unclear how long a vaccination will last in different species and whether drug depots can be created on plants. Further studies will clarify how vaccines can be produced in larger quantities and how they can be applied to or absorbed by plants. According to Behrens, a spray that can be applied in greenhouses is conceivable: "Tomato growers have to contend with whiteflies, for example, and these can transfer viruses from one plant to another very quickly." Until now, pesticides have been used to kill off the insects. The new MLU development could prove to be an alternative that's much gentler both to the insects and to the environment.

DALLAS, August 21, 2019 -- Type 2 diabetes affects the structure of the heart in heart failure patients and increases their risk for repeat hospitalizations and/or death, according to new research published in the Journal of the American Heart Association, the Open Access Journal of the American Heart Association/American Stroke Association.

Type 2 diabetes frequently coexists with heart failure, and the prevalence of diabetes has increased worldwide. While diabetes and heart failure together have been extensively studied among Western populations, there is less known about their collective impact among Asian populations. An international team of researchers analyzed data from more than nearly 6,200 heart failure patients participating in the ASIAN-HF Study.

The study found that having Type 2 diabetes and heart failure was associated with:

structural abnormalities in the heart;

poorer quality of life; and

increased risk of heart failure-related re-hospitalizations and/or death within one year.

Researchers also noted that the overall prevalence of Type 2 diabetes was high among these heart failure patients, with more than 40% having diabetes. The prevalence was highest in Singapore and Hong Kong.

"Primary prevention strategies and tailored treatment options are needed to tackle this twin scourge of diseases," said study co-author Jonathan Yap, M.B.B.S., M.P.H., consultant from the department of cardiology of the National Heart Centre Singapore. "Our findings emphasize the need for preventative public health measures at the community and primary care level. For heart failure patients who have diabetes, physicians should closely monitor and optimize their management."

A new DNA test to detect chlamydia infection in koalas which can be run in the field and gives on-the-spot results within 30 minutes has been developed in a research collaboration between researchers from Queensland University of Technology (QUT) and University of Queensland (UQ) in Brisbane, Australia.

Disease caused by chlamydia impacts as many as 90 per cent of koalas in areas of Australia, causing blindness, serious urinary tract infections and infertility, and if not treated can be fatal.

Current standard laboratory testing for koala chlamydia takes several days, whereas the new quick-turnaround diagnostic test means no delay in starting infected koalas on treatment.

The new test has been trialled successfully at Currumbin Wildlife Hospital on Queensland's Gold Coast.

The test uses the innovative LAMP (loop mediated isothermal amplification) technology and targets a specific sequence of DNA in the chlamydia bacteria.

Research into the development and validation of the LAMP test was conducted by UQ PhD student Lyndal Hulse, with supervisors QUT Immunology Professor Ken Beagley, who first proposed using LAMP technology to develop a koala chlamydia test, and UQ Zoologist Associate Professor Stephen Johnston. Their report on development and evaluation of the test has been published in the journal MicrobiologyOpen.

The test detects the most common chlamydia strain that affects koalas, Chlamydia pecorum. Swabs of the urogenital tract and eyes are collected and the test is run on the OptiGene Genie platform. The equipment is distributed in Australia by GeneWorks, which assisted with the research project.

Ms Hulse said DNA testing for chlamydia in koalas is usually performed in a diagnostic laboratory using a molecular test known as PCR (polymerase chain reaction), which is the standard due to its reliability, sensitivity and specificity.

"However, this is time-consuming and wildlife veterinarians and koala ecologists have to wait days or longer after they have sent in their samples to get the results," she said.

"We wanted to design a test that was equally reliable and as accurate as PCR, but one that was more cost-effective, with simplistic swab preparation, that could be done at the point-of-care and provide on-the-spot results.

"The LAMP method provided that opportunity."

Professor Beagley said the LAMP koala chlamydia test was extremely sensitive, successfully detecting even small quantities of the bacteria present.

"When 43 clinical swabs were tested, the LAMP test results matched those obtained through the PCR method," he said.

"Lyndal has also developed a range of LAMP assays for other koala pathogens, such as Chlamydia pneumoniae and Bordetella bronchiseptica which cause respiratory disease and pneumonia in koalas, so these could in the future be incorporated with the Chlamydia pecorum assay into a single panel test."

Associate Professor Johnston said the test was fulfilling a need in the fight against the spread of chlamydia among koala populations.

"Koalas can often show no obvious clinical signs of chlamydia, yet they can be highly infectious carrying a heavy bacterial load," he said.

"This test has such a rapid turnaround time that it means decisions about treatment can be made quickly. And the Genie testing equipment is compact, portable and battery-powered so you can run the test anywhere - for ecologists out in the field it would be simple to set up the required equipment."

Currumbin Wildlife Hospital general manager and senior vet Michael Pyne said 500 injured, orphaned and sick koalas were brought to the hospital last year, and 80 per cent of them tested positive for chlamydia.

"Chlamydia is so common it is crucial that we test all the koalas, and this test is not only quick, it gives us a semi-quantitative measure to indicate how badly infected the koala is so we can make the appropriate treatment decisions," he said.

"It's a minimum of four weeks of antibiotics for chlamydia, so the sooner we can start treatment the better. And with this test we can monitor the koalas and easily test them again to make sure they are clear of infection before they are released back in the wild."

Doctors tell parents too late that their child is near death, suggest the results of a small survey, published online in the journal BMJ Supportive & Palliative Care.

National guidance is needed for doctors on how and when to give parents bad news, so that they can be properly prepared, say the researchers.

Open, accurate, and timely information about terminal illness and associated life expectancy are key tenets of high quality palliative care. But previous research suggests that doctors often find it difficult and distressing to discuss end of life issues.

The researchers scrutinised a national Danish register of child deaths between 2012 and 2014 to find those who had died of a terminal illness: 402 out of 951.

A modified version of a validated questionnaire about the loss of a child was sent to the bereaved parents together with an explanatory leaflet about the nature of the study.

The questionnaire contained 122 questions designed to probe parents' perceptions of the type and quality of communication with healthcare professionals throughout their child's illness and imminent death.

In all, 136 mothers and 57 fathers completed the questionnaire, representing the parents of 152 children who had died of a terminal illness between 2012 and 2014 (response rate of 38%). Over half the children (56%) had died within the first year of life.

More than half the parents (59%) were told their child's illness was terminal by a doctor. For around a third (30%) this was imparted immediately after the child's birth.

But one in seven (15%) said they received this information in the last 24 hours of the child's life. And around one in 10 (12%) said they weren't told at all.

A similar proportion (11%) said they didn't realise their child was going to die until the event itself. Around one in five (19%) only realised their child's death was imminent a few hours beforehand.

Three out of four of the parents were satisfied with the information they were given by clinicians about their child's illness. Most felt the same (80%) about their child's treatment.

But the information given about how the child's illness and treatment would affect their physical and mental health was judged inadequate by one in three (33%) and nearly half (48%), respectively.

A third (34%) of the parents weren't told how to access end of life care, while four out of 10 (40%) didn't know what to do in the event of an emergency.

Nearly all (98%) of them said that doctors should let parents know as soon as it was clear that all curative treatment options for their sick child had been exhausted.

Most parents (79%) felt the information about the terminal nature of their child's illness had been provided in a timely manner. But more than four out of 10 (42%) said they were told too late that their child was about to die.

Nearly a third (31%) said they were unable to say goodbye to their child as they would have liked. And more than four out of 10 (43%) said that their child's death had come as "a shock."

This is a small observational study, and the distress of caring for a dying child might have affected parental recall, the researchers point out.

"Healthcare professionals are exposed to great challenges in communicating with parents about their children's life limiting illness and imminent death, and even though [they] strive to communicate effectively with the children and their parents, several barriers on the sides of both parents and professionals, may hinder even the best of intentions," they write.

"However, the present study clearly demonstrated that the parents' need for information and support were not sufficiently met, and the study results may raise awareness of the importance of providing improved education and training for healthcare professionals working with children with life limiting diagnoses and their parents," they conclude.

In one of the largest studies of its kind, the research team, led by the London School of Hygiene & Tropical Medicine, analysed the medical records of more than 630,000 people in the UK, including over 100,000 survivors of a range of cancers.

They found raised risks of blood clots forming in the veins among survivors of most cancers, ranging from approximately a two- to ten-fold increase in risk for different cancer sites. Risks decreased over time but were still elevated for more than five years after the cancer diagnosis. Survivors of half of the 20 cancers studied also faced increased risks of heart muscle damage, known as cardiomyopathy, and heart failure.

For example, survivors of blood, oesophagus, lung, kidney and ovarian cancers were more than one and a half times more likely to experience cardiomyopathy or heart failure than people with no prior cancer.

An increased risk of coronary artery disease and stroke was found in some cancer survivors, including those with prior blood cancers.

The researchers stress that for many people the overall risks will still be low, particularly for younger cancer survivors, but say the findings highlight the need for new strategies to prevent and manage heart and circulation problems in cancer survivors, including a need to raise awareness among GPs of the raised risks.

While the researchers could not definitively identify the causes of the increased risks, the team's analysis suggests that exposure to cancer treatments such as chemotherapy is likely to play a key role.

Lead author Helen Strongman from the London School of Hygiene & Tropical Medicine said: "Over recent decades cancer treatment and management have improved substantially, resulting in a large and growing population of long-term cancer survivors. Around half of those diagnosed with cancer in developed countries are now expected to survive for more than 10 years. However, there are concerns that there may be increased long-term risks of cardiovascular disease following cancer diagnosis, driven by treatment side-effect effects and the potential impact of the cancer itself."

While previous studies have demonstrated the short- to medium-term increased risk of cardiovascular disease from some specific cancer treatments, there have been limited data on the overall and long-term differences in cardiovascular risk between cancer survivors and those who have never had cancer.

To address this, the team brought together anonymised data from primary care, hospitals, cancer registries, and death certificates, to quantify the absolute and relative risks of a comprehensive range of cardiovascular diseases in survivors of the 20 most common adult cancers compared with cancer-free general population controls. The research also accounted for other risk factors for cardiovascular disease, such as older age, smoking and body mass index.

The team found large increases in risk of venous thromboembolism (blood clots in the veins) among survivors of 18 of the 20 cancers studied compared to cancer-free controls. Survivors of breast cancer had double the risk of venous blood clots one year after diagnosis compared with similar women with no prior cancer, though the overall level of risk remained low, especially for younger survivors.

For female breast cancer survivors aged under 60 years, six extra blood clot cases per year were observed per 1,000 women, while among older women (80+ years) 12 extra cases per year were observed per 1,000 women. These risks decreased over time but remained elevated for at least five years after diagnosis with most cancers.

The team also observed long-term increased risks of heart failure and heart muscle damage among survivors of 10 of the 20 site-specific cancers studied. Among people who had non-Hodgkin lymphoma five years previously, there were four extra cases of heart failure per year for every 1,000 people aged under 60, rising to 21 extra cases per year for every 1000 people aged over 80 years.

The senior author of the study Professor Krishnan Bhaskaran from the London School of Hygiene & Tropical Medicine said: "With treatment for cancer becoming more effective, we must start thinking about living beyond cancer and improving the health of survivors. Our work revealed raised risks of various cardiovascular diseases in cancer survivors. These findings are important because those affected might benefit from preventative measures and earlier interventions to reduce the impact.

"If patients, primary care doctors, and specialists are more aware of the potential for increased cardiovascular risks in this patient group, we might detect problems earlier and improve outcomes. There is limited guidance at present to help doctors manage cardiovascular risk in cancer survivorship, and further evidence is needed on whether routine monitoring or additional preventative measures would benefit those with the highest risks."

The authors acknowledge limitations of their study including that there was only limited information available about the anti-cancer treatments that patients had received. Although the research team had some information on whether patients had received chemotherapy, radiotherapy, and surgery, there was no detailed information on specific chemotherapy drugs, radiotherapy doses, or surgery procedures.

Some cases of the flu are so severe they cause lasting injury to the lungs. New research from the University of Pennsylvania now points to a strategy that may one day offer protection against this damage.

The scientists found that transplanting a certain type of lung cell from healthy mice to those that had been injured by an infection with influenza could improve healing. The transplant--achieved by taking specialized lung cells called alveolar type-two (AT2) cells from the healthy animals and then allowing the sick animals to simply breathe in the cells--led to improved blood-oxygen levels.

"We took this really simple approach," says Andrew Vaughan, senior author on the paper and an assistant professor in Penn's School of Veterinary Medicine, "and asked if we could supplement back these AT2 cells into injured mice, can we make them better, can we improve lung regeneration?"

"Imagine if this were in humans," adds Aaron Weiner, lead author on the study and a graduate student in Vaughan's lab. "If there were a bad flu season coming up, it could be routine to say, can you take some of my AT2 cells, grow them up for me, and if I get sick you can just put them back in to help me recover. That biobank idea is what we're imagining."

The study appears in the journal Regenerative Medicine.

Earlier work by Vaughan and colleagues had focused on the negative outcomes that can arise following injury to the lung, such as a serious infection. In the current investigation, they attempted to recreate a healthy recovery in mice that had been infected with the flu. The healing process involves AT2 cells, which normally produce surfactant, a substance that lowers surface tension in the lung's alveoli to ensure proper function. But AT2 cells can also take on a stem cell-like activity, able to both self-renew and to give rise to alveolar type 1 (AT1) cells, which are responsible for gas exchange in the lungs.

Weiner, Vaughan, and colleagues decided to try to take advantage of this ability of AT2 cells to see if they could aid healing.

They first developed a method to grow AT2 cells taken from healthy mice in culture, and then transplant those cells into mice 11 days after being infected with influenza. Nearly two weeks after the transplant, the researchers found that the cells had grown in the recipient's lungs but either remained as AT2 cells or developed markers associated with unhealthy regeneration.

Trying a different tack, the team took roughly a million AT2 cells isolated from healthy mice and directly transplanted them to sick ones. This approach had more success.

"Only a few thousand of the cells stick around in the lungs," says Weiner. "But the important thing we show is that two weeks after we transplant these cells, we see these huge engraftments where the AT2 cells have proliferated a ton and differentiated into the oxygen-exchanging AT1 cells."

"If you weren't looking for the fluorescent tag that we put on the transplanted cells, you wouldn't even be able to distinguish them from the normal tissue," Vaughan says.

The transplant also had a physiological benefit, the researchers demonstrated. Mice that got the transplant of primary AT2 cells had significantly higher blood-oxygen saturation than mice that got a "mock" transplant of saline solution, a sign of a stronger recovery.

"These engraftments are very long-lived," Weiner notes. "One hundred days after the transplant, we find engraftments that are really robust and maintain the cell lineage and have presumably helped in some way for the mice to get better."

As a final test of their methods, the team transplanted AT2 cells into mice that had experience other types of lung injury, including acid inhalation, chemotherapy exposure, and bacterial pneumonia.

"To our surprise it worked really well in two of the three injury models we tested," Vaughan says. They saw robust engraftment after both acid inhalation and chemotherapy, though not for bacterial pneumonia.

The implementation of a novel quality improvement toolkit has shown to enhance early detection and treatment of iron deficiency in pregnancy, according to a study led by St. Michael's Hospital.

IRON Deficiency in Pregnancy with Maternal IrOn OptiMization (IRON MOM) is a paper-based toolkit that includes clinical pathways and educational resources to guide clinicians and expectant mothers through diagnosis and management of iron deficiency.

The research, published today in PLOS Medicine, compares rates of ferritin testing in the obstetric clinics at Toronto's St. Michael's Hospital before and after the implementation of the IRON MOM toolkit. Ferritin is a blood cell protein that contains iron and ferritin tests can help obstetricians understand how much iron is being stored in the body.

If not treated, iron deficiency can cause serious health consequences, including anemia, early labour, low birth weight and long-term developmental issues in the child.

"Screening for iron deficiency in pregnancy is recommended by health agencies but with low awareness of its implications and competing priorities in busy obstetric clinics, it doesn't happen as often as it should," said Dr. Michelle Sholzberg, co-lead author, a hematologist at St. Michael's and a scientist at the hospital's Li Ka Shing Knowledge Institute.

"That was the impetus for the development of IRON MOM, which provides guidance and supports for women to feel empowered to speak to their care providers to ensure they're receiving enough iron."

One year after implementation of the IRON MOM toolkit, the team found an almost 10 times increase in the average monthly rate of ferritin testing in the obstetric clinics at St. Michael's.

They also found a significant decrease in the risk of anemia - a condition in which the body lacks sufficient healthy red blood cells to carry oxygen to the tissues - and those who required blood transfusions before and after pregnancy to improve their red blood cell count.

"IRON MOM demonstrated that priority setting and simple process changes in patient management can have a large impact on key clinical outcomes," said Dr. Jameel Abdulrehman, co-lead author from the University Health Network.

The researchers said these results provide support for expanding IRON MOM into other clinics and institutions. Currently, the team is working on an IRON MOM smartphone application that would make the toolkit available to women and clinicians across the country.

"It's widely accepted that many women will develop anemia in pregnancy as the result of iron deficiency," said Dr. Sholzberg. "But this doesn't have to be the case. Treating iron deficiency requires a culture change and IRON MOM addresses that need."