Body

A study into the impact of flavoured e-cigarettes, on allergic airways disease, suggests that some flavours may worsen the severity of diseases such as asthma. For the first time a model of asthma was used to investigate the effect of a range of popular e-cigarette flavours, with and without nicotine.

The use of e-cigarettes has dramatically increased in the past few years especially among younger smokers - an estimated nine percent of 18-24 year olds in the United States are current e-cigarette users.

Despite the suggestion they are a healthier alternative to tobacco cigarettes there is a lack of evidence in both animal studies and human data on the effect of e-cigarettes on lung function.

The results of a study led by researchers from the University of Technology Sydney (UTS), University of Vermont, USA and the Woolcock Institute of Medical Research, Australia, show that some flavoured e-cigarettes, even without nicotine, may change how airways, affected by an allergic disease, function.

Dr David Chapman, UTS researcher and lead author of the study published in Scientific Reports, said this was the first study to investigate the effects of flavoured e-cigarettes with and without nicotine on allergic airways disease.

"This is especially important for those with respiratory disease, whom are vulnerable to the effects of smoking," Dr Chapman said.

"The majority of e-cigarette smokers use flavoured liquids but there is some evidence that flavour additives can be toxic when inhaled," Dr Chapman said.

The researchers found some flavoured e-cigarettes, even in the absence of nicotine, can worsen disease severity.

"The exact effects on features of asthma were dependent upon the specific flavour, suggesting not all flavoured e-cigarettes will have the same consequences on lung health," Dr Chapman said.

In this study the flavour Black Licorice exaggerated airway inflammation whereas Cinnacide had the opposite effect, suppressing airway inflammation. Additionally, Cinnacide increased airway sensitivity and Banana Pudding flavour exaggerated the level of tissue scarring. All e-cigarette liquids containing nicotine suppressed airway inflammation, consistent with the known anti-inflammatory properties of nicotine.

The researchers didn't analyse the liquids directly, to confirm what they contained, however there is evidence from previous research that flavours categorised as "buttery/creamy" and "cinnamon", which likely include Banana Pudding and Cinnacide, respectively, are toxic.

The researchers conclude that caution should be taken in promoting the use of flavoured e-cigarettes to patients with respiratory disease such as asthma and that policy makers should consider restricting the use of flavoured e-cigarettes.

Individuals who make concrete plans to meet their goals may engage in more physical activity, including visits to the gym, compared to those who don't plan quite so far ahead, research shows. These research findings, published in Psychological Science, a journal of the Association for Psychological Science, suggest that self-reported levels of a trait called 'planfulness' may translate into real world differences in behavior.

Some people seem to be able to more consistently meet their goals than others, but it remains unclear if personality traits that have been found to promote goal achievement in the lab similarly encourage individuals to achieve long-term goals in their day-to-day lives, says lead researcher Rita M. Ludwig of the University of Oregon.

Conscientiousness, a measure of individuals' orderliness and dependability on the Big Five Inventory of personality, has long been tied with healthy behaviors, notes Ludwig and colleagues Sanjay Srivastava and Elliot T. Berkman, also of the University of Oregon. Narrowing their focus to a single facet of this trait, planfulness, allows researchers to zero in on the psychological processes--such as mental flexibility, and a person's ability to make short-term sacrifices in pursuit of future success--that contribute directly to achieving long-term goals.

"There indeed appears to be a certain way of thinking about goals that correlates with long-term progress," Ludwig says. "What's new in this study is that we used an objective measure of goal progress that could be recorded as participants naturally went about their lives: their check-ins at a local gym."

Ludwig and colleagues examined this relationship by analyzing the gym attendance of 282 participants over a 20-week period. The researchers tracked the number of times each participant swiped into the campus recreation center after enrolling in the study at the start of the winter 2018 academic semester. They also retroactively collected data on gym attendance throughout the fall 2017 term.

The participants, many of whom were students, provided a written description of their exercise plans and completed measures of self-control and grit, in addition to the Big Five Inventory of personality and Ludwig and colleagues' 30-item Planfulness Scale.

While all participants experienced a similar decline in gym attendance over the course of each semester, individuals who rated themselves high on planfulness items such as "developing a clear plan when I have a goal is important to me" went to the gym more throughout both semesters compared to those who ranked themselves lower on planfulness. The researchers found that a one point increase on the five-point Planfulness Scale corresponded with an additional 5.9 recreation center visits during the fall semester, and an additional 8.5 visits after enrolling in the study for the winter semester.

Planfulness was only significantly associated with the frequency of participants' gym attendance during the winter semester, possibly due to participants completing their physical activity plan later in the year, the researchers noted.

"This work is broadly informative for those who are curious about how people pursue health goals, including their own patterns of thought around goals," Ludwig says. "Clinicians might find it helpful in understanding how their patients tend to think about goals and whether person-to-person differences in such thinking are related to outcomes."

While there was a small, but significant relationship between participant planfulness and the level of detail in their physical activity plans, descriptiveness was unexpectedly found to have no relationship with gym attendance, Ludwig and colleagues noted.

"It seems logical that people who are successful with their goals would be able to write in detail about their planning process," Ludwig says. "We were surprised, then, to find no relationship between people's goal pursuit behavior and how they wrote about their goals."

Future psycholinguistic research might investigate alternative explanations for these findings, the researchers conclude.

Monash University researchers, along with industry partner Haemokinesis, have developed the world's first blood incubator using laser technology.

This technology can slash blood incubation time to just 40 seconds, compared to the current industry gold standard of five minutes.

The study shows that laser incubation can improve pre-transfusion testing for millions of patients undergoing blood transfusions across the world, including those having major surgery, women in labour or casualties of mass trauma.

Researchers from BioPRIA, based at Australia's Monash University, together with industry partner Haemokinesis, have developed the world's first blood incubator using laser technology. This could prevent fatal blood transfusions in critically ill patients, and can detect antibodies in pregnant women that can kill a foetus.

According to results published in Nature's Scientific Reports, these findings could bring pre-transfusion testing out of the pathology lab to point-of-care, with blood incubation time slashed to just 40 seconds, compared with the industry gold standard of five minutes.

This breakthrough has the potential improve the pre-transfusion testing of millions of patients undergoing blood transfusions across the world, especially those having major surgery, going into labour, or causalities of mass trauma and individual trauma.

The detection of immunoglobulin G (IgG) antibodies requires incubation at 37°C, often for up to 15 minutes. But current incubation technology relies on slow thermal procedures, such as heating blocks and hot-water baths.

This delay adds to pathology costs and turnaround time, which substantially affects a patient's chance of survival.

To address this problem, BioPRIA's blood diagnostics team developed a laser incubation model where a targeted illumination of a blood-antibody sample in a diagnostic gel card is converted into heat, via photothermal absorption.

The laser-incubator heats the 75 μL blood-antibody sample to 37°C in under 30?seconds. Most importantly, no significant damage is detected to the cells or antibodies for laser incubations of up to 15 minutes.

The study was led by Dr Clare Manderson from the Bioresource Processing Institute of Australia (BioPRIA), located within the Department of Chemical Engineering at Monash University, in conjunction with blood diagnostics manufacturer Haemokinesis.

"Laser incubation can be extremely valuable when time and accuracy is vital, especially in critical and emergency settings - like mass trauma - where pre-transfusion testing needs to be performed quickly in order to save lives," Dr Manderson said.

"We show that red blood cells act as photothermal agents under near-infrared laser incubation, triggering rapid antigen-antibody binding with no significant damage to the cells or antibodies for up to 15 minutes.

"This study demonstrates laser-incubated immunohaematological testing to be both faster and more sensitive than current best practice, with clearly positive results seen from incubations of just 40 seconds."

For this study, researchers explored the roles of incubation time and temperature of the IgG anti-D antibody and the Rh blood group system's D antigen, which indicates the positive or negative attributed to a person's ABO blood type group.

Anti-D is the most common antibody, and is present in a person's plasma. It's the biggest cause of haemolytic disease of the foetus and newborn - a blood disorder that occurs when the blood types of a mother and baby are incompatible. Accurate testing for pregnant women's antibodies is vital to save the life of the foetus.

Blood group type is based on the presence of antigens on the surface of the red blood cell membranes, consisting of proteins, glycoproteins, glycophorins, glycolipids and polysaccharide macromolecules forming roughly 346 known blood groups.

"Giving blood transfusions to people isn't as simple as giving O-negative to anybody. The 'universal donor' of O-negative blood can seriously harm a lot of people, even kill them. The world of pre-transfusion of blood group typing is huge, and it's really important that it's done quickly and accurately to help save lives," Dr Manderson said.

"For the patient, it can mean that if there's a critical blood-loss scenario and they're in desperate need of a transfusion, they need to have their blood group typed and antibody screened as quickly as possible. We're aiming to bring that down to seconds instead of tens of minutes."

Blood transfusion is a critical treatment for a variety of haematological conditions, including cancer chemotherapy, bleeding trauma, childbirth and major surgery. Transfusion reactions are common if the recipient and donor aren't correctly matched.

More than 1.2 million blood components are transfused each year in Australia, and 21 million in the US.

While the technology isn't yet commercially available, Haemokinesis holds a patent for this innovation.

Every year, more than 500,000 children have their tonsils and adenoids surgically removed as a way to treat symptoms related to sleep apnea, making it one of most widely performed pediatric surgical procedures in the United States.

Clinicians believe that the benefits of surgery can be seen in an improvement in the severity of sleep apnea, as measured by a sleep study. The downside of the sleep study is that it is expensive, costing as much as $3,000, and often inaccessible in many parts of the country. Despite these issues, the test is recommended as part of the decision during and after surgery.

Gautam Das, a professor in UTA's Computer Science and Engineering Department, worked with lead researcher Amal Isaiah, M.D., Ph.D., a pediatric ear, nose and throat surgeon, and Kevin Pereira, M.D.--both from the University of Maryland School of Medicine--to understand whether sleep studies predicted the improved outcomes following surgery for sleep apnea in children. For their analysis, they re-analyzed the data collected during the Childhood Adenotonsillectomy Trial (CHAT), a randomized trial published in 2013 that compared adenotonsillectomy with watchful waiting for seven months to treat sleep apnea in children.

The team found that the resolution of sleep apnea, as determined by sleep study results, did not correlate with most of the improvements, including behavior, cognitive performance, sleepiness and symptoms of attention deficit hyperactivity disorders.

Their findings were published in the September 2019 issue of the journal Pediatrics. "Causality is very complex. There are a lot of factors that explain why things happen, and analysis has to be thorough to ensure that all variables are considered for modeling," Das said. "We applied causal mediation analysis and discovered additional relationships through the process that showed there were more factors at work in the original CHAT study

That original study randomly allocated 450 children with sleep apnea to two groups based on whether they would have surgery immediately or after a period of waiting.

The trial results concluded that surgery led to greater improvement in most domains, including behavior and quality of life in children. However, an important question remained--how did they get better? Clinicians previously suggested that the underlying mechanism is an improvement in the severity of upper airway obstruction defined by the sleep study.

Das and Isaiah worked together to address this problem using causal mediation analysis, which estimates the potential outcomes of surgery by simulating those related to watchful waiting and keeping the level of the mediator--the change in sleep apnea severity--constant. With this algorithm, the researchers built a network with treatment and outcomes as nodes, and the edges replicated the effects of treatment as explained by the change in sleep apnea severity.

"This new process allowed us to see if the causality paths estimated by the algorithm were different from what was assumed in the original study," Das said.

Das first collaborated with Isaiah while Isaiah was a trainee at UT Southwestern, and their current collaboration shows the potential of multidisciplinary research in data science, computer science and medicine.

The work is an example of how UTA researchers are contributing to knowledge in data-driven discovery and health and the human condition, two themes of the University's Strategic Plan 2020.

"As data science becomes increasingly significant and sophisticated, it is important to understand how it can be applied to existing research and discovery to provide additional context and improve upon our knowledge," said Hong Jiang, chair of UTA's Computer Science and Engineering Department. "Dr. Das' collaboration with Dr. Isaiah has shed new light on an accepted medical practice that will allow physicians to make better-informed decisions for half a million children undergoing tonsillectomy each year."

A drug used to treat chronic myeloid leukemia appears to be more effective at stopping a type of medulloblastoma in mouse models than existing treatments for the deadly pediatric brain tumor, reports a multi-institutional team led by researchers at Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego.

In the study, published September 20, 2019 in PLOS One, the team demonstrated how use of a single drug -- in this case nilotinib -- specifically targets cancer cells that have an abnormal activation of a cell communication system, called the Hedgehog pathway, via two different mechanisms, making it more effective and less toxic than combining drugs.

"We discovered a previously unknown activity of nilotinib that may be leveraged to treat a large fraction of cases of medulloblastoma, a type of childhood brain cancer," said senior author Ruben Abagyan, PhD, professor in the Skaggs School of Pharmacy. "While more research is needed, this pharmaceutical could potentially be used for several cancer types with an overactive cell-signaling pathway."

Several types of basal cell carcinoma, myeloid leukemia, rhabdomyosarcoma, pancreatic adenocarcinoma, glioblastoma and one third of medulloblastoma cases have an impairment in the Hedgehog signaling pathway -- a key cellular system that regulates embryonic development and adult tissue regeneration. As a result of this impairment, the cancer cells overproduce a cell-surface receptor called Smoothened. Malignancies with this abnormality account for a quarter of all cancer deaths, said Abagyan.

"Only a fraction of patients with this subtype of medulloblastoma respond well to current therapies that only target Smoothened," said Abagyan. "Knowing that dysregulation of the Hedgehog pathway is important to the maintenance of cancer stem cells, and that it plays a critical role in several cancers, we wanted to find a single drug that inhibits this pathway in addition to several other essential anti-cancer activities."

In the study, Abagyan and team discovered that mice bearing human medulloblastoma tumors saw tumor growth reduced and no drug resistance occurring. Nilotinib simultaneously inhibits Smoothened and several protein kinases critical for tumor growth.

Nilotinib is already a U.S. Food and Drug Administration approved therapy for chronic myeloid leukemia with a safety profile, making it a good therapeutic candidate alone or in combination with surgery, radiation therapy and chemotherapy, wrote the authors.

WASHINGTON (September 20, 2019) - A new shock classification scheme released by the Society for Cardiovascular Angiography and Interventions (SCAI) and endorsed by the American College of Cardiology (ACC), American Heart Association, the Society of Critical Care Medicine and the Society of Thoracic Surgeons was recently applied in a retrospective study analyzing patients in the cardiac intensive care unit (CICU) at the Mayo Clinic. The study was published today in early view in the Journal of the American College of Cardiology (JACC).

Cardiogenic shock (CS) is a condition in which the heart, often abruptly, cannot pump enough blood to meet the body's needs (Mayo Clinic). Most often accompanying larger heart attacks such as myocardial infarction (MI), outcomes for patients with cardiogenic shock complicating MI have not significantly improved over the last 30 years despite the development of various percutaneous mechanical circulatory support technologies and the national standard of emergent angioplasty and stenting. CS continues to be associated with high rates of morbidity and mortality, posing a therapeutic challenge for clinicians.

"In the CICU we see a wide spectrum of shock severity including undifferentiated and mixed shock states, so we wanted to see whether a simplified, functional definition of the SCAI shock stages classification could be applied in an unselected CICU population using data from early after CICU admission," said Jacob C. Jentzer, MD, director for CICU Research at the Mayo Clinic in Rochester, MN. "We found a dramatic incremental increase in mortality with each successive SCAI shock stage, with an additive mortality hazard among patients who suffered a cardiac arrest highlighting the importance of shock and cardiac arrest as major drivers of mortality in CICU patients. This confirms the validity of the SCAI CS stages construct and emphasizes its potential utility for clinical practice and future research," he continued.

The study analyzed 10,004 patients admitted to the CICU between 2007 and 2015. The patients were classified as SCAI CS stages A through E, based on the presence of hypotension/tachycardia, hypoperfusion, deterioration and refractory shock.

Among the patients, 43 percent had acute coronary syndrome, 46 percent had heart failure and 12 percent had cardiac arrest. Study investigators found a stepwise increase in unadjusted CICU and hospital mortality with each increase in the SCAI shock stage. These results preliminarily validate the feasibility and prognostic value of the SCAI classification system.

"When we initially set out to create a new lexicon for cardiogenic shock, the goal was always to prove first and foremost that the increasing severity of shock predicted by the new classification would correspond to actual increasing hazard. This study is the first to validate the SCAI shock stages and add a relative risk to each successive stage, indicating in essence at what stage clinicians really have to worry about excessive mortality," said Srihari S. Naidu, MD, FSCAI, chair of the SCAI Shock expert consensus document writing group.

"The tremendous value of the SCAI CS staging system lies in its simplicity. It can easily be used across the spectrum of care from pre-hospital to intensive care unit and will allow clinicians to estimate mortality risk over time. When the SCAI Shock stage increases, it will be a signal to decide if transfer is warranted and potentially improve outcomes for patients. In addition, the SCAI CS classification highlights the potent risk of cardiac arrest and its effect on outcomes", said David Baran, MD, system director for Advanced Heart Failure, Transplant and MCS at Sentara Heart Hospital in Norfolk, Virginia.

Investigators believe the next step is prospective validation and implementation in clinical and research settings to ensure consistent outcomes reporting and to assess whether the effects of the tested intervention vary by CS stage.

Alexandria, VA, USA - 2019 marks the Centennial of the Journal of Dental Research (JDR). Over the last century the JDR has been dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry and to the oral cavity and associated structures in health and disease.

To celebrate, the JDR is featuring a yearlong, monthly commemorative article and podcast series that highlights topics that have transformed dental, oral and craniofacial research over the past 100 years.

Over the past 100 years, tremendous progress has been made in the fields of dental tissue engineering and regenerative dental medicine, collectively known as translational dentistry. The October 2019 JDR Centennial article, "Tooth Bioengineering and Regenerative Dentistry" by Pamela Yelick, Tufts University, Boston, Mass., USA and Paul Sharpe, King's College London, England, discuss key successes that have contributed most to current knowledge and understanding of regenerative dentistry and hypothesize what to expect over the next century.

"This is an exciting era in Regenerative Dentistry, and in particular for whole tooth tissue engineering," said Yelick. "We anticipate that continued advances in the fields of dental tissue engineering and regenerative dental medicine will facilitate the development of improved dental repair therapies, including whole tooth tissue engineering."

"At the present time, the overall concept of tooth bioengineering has been proven in principle. Combinations of adult and embryonic cells from mice and humans have been shown to form tooth primordia in vitro," said Sharpe. "Surgical transplantation of these constructs into the mouth was shown to provide a suitable environment for their development into fully functional, erupted teeth."

A key requirement for future facilities that aim to capture and control on Earth the fusion energy that drives the sun and stars is accurate predictions of the pressure of the plasma -- the hot, charged gas that fuels fusion reactions inside doughnut-shaped tokamaks that house the reactions. Central to these predictions is forecasting the pressure that the scrape-off layer, the thin strip of gas at the edge of the plasma, exerts on the divertor -- the device that exhausts waste heat from fusion reactions.

Researchers at the U.S. Department of Energy's (DOE) Princeton Plasma Physics Laboratory (PPPL) have developed new insights into the physics governing the balance of pressure in the scrape-off layer. This balance must ensure that the pressure of the plasma throughout the tokamak is high enough to produce a largely self-heating fusion reaction. The balance must also limit the potentially damaging impact of heat and plasma particles that strike the divertor and other plasma-facing components of the tokamak.

"Previous simple assumptions about the balance of pressure in the scrape-off layer are incomplete," said PPPL physicist Michael Churchill, lead author of a Nuclear Fusion paper that describes the new findings. "The codes that simulate the scrape-off layer have often thrown away important aspects of the physics, and the field is starting to recognize this."

Fusion, the power that drives the sun and stars, is the fusing of light elements in the form of plasma -- the hot, charged state of matter composed of free electrons and atomic nuclei -- that generates massive amounts of energy. Scientists are seeking to replicate fusion on Earth for a virtually inexhaustible supply of power to generate electricity.

Key factors

Churchill and PPPL colleagues determined the key factors behind the pressure balance by running the state-of-the-art XGCa computer code on the Cori and Edison supercomputers at the National Energy Research Scientific Computing Center (NERSC), a DOE Office of Science User Facility. The code treats plasma at a detailed kinetic -- or particle motion-- level rather than as a fluid.

Among key features found was the impact of the bulk drift of ions, an impact that previous codes have largely ignored. Such drifts "can play an integral role" the authors wrote, and "are very important to take into account."

Also seen to be important in the momentum or pressure balance were the kinetic particle effects due to ions having different temperatures depending on their direction. Since the temperature of ions is hard to measure in the scrape-off layer, the paper says, "increased diagnostic efforts should be made to accurately measure the ion temperature and flows and thus enable a better understanding of the role of ions in the SOL."

The new findings could improve understanding of the scrape-off layer pressure at the divertor, Churchill said, and could lead to accurate forecasts for the international ITER experiment under construction in France and other next-generation tokamaks.

CHAPEL HILL, NC - A new study published today in Nature Communications shows a promising alternative for those who have to take a daily pill regimen. Targeting HIV treatment and prevention, researchers across multiple departments at the University of North Carolina at Chapel Hill collaborated on a seven-year study in animals to make a better injectable drug implant that can combine multiple drugs and is ultra-long-acting, while also addressing many of the challenges faced with current HIV treatment and prevention methods.

"There is no FDA-approved or marketed technology for long-acting prevention of HIV, and we are the first to use this delivery method with multiple antiretroviral drugs," said Rahima Benhabbour, PhD, MSc, first author of the study and assistant professor in the UNC_NCSU Joint Department of Biomedical Engineering. "To have an HIV prevention treatment that consists of an injection once or twice a year would make an incredible impact for patients." She added, "This technology is not only promising for HIV, but for any kind of condition that requires a daily intake of medication. We're talking about a safe, removable, long-lasting injection that takes away the burden of adhering to a daily medication regimen."

Antiretroviral drugs are used in both prevention and treatment of HIV, and multiple types are used in combination to counteract resistance to any one antiretroviral drug. These drugs need to be taken consistently every day. There are many obstacles that stand in the way of adherence to these medication regimens. Benhabbour says this especially applies to otherwise healthy people trying to prevent infection.

"In sub-Saharan Africa where prevalence of HIV is highest, accessibility to these medications can be difficult, and there is much stigma associated with the virus," Benhabbour said. "It is a very big deal for someone who doesn't have HIV to go out of their way to not only access the drugs, but then associate themselves with HIV by taking a pill every day."

There's also the factor of human error. Anyone who strives to take a daily multivitamin can understand that some days the pill gets skipped, or gets taken at a different time of day. But such small deviations can make antiretroviral drugs less effective.

"Because one of the biggest difficulties associated with HIV prevention is lack of adherence to drug treatment, we wanted to create a drug delivery system that essentially solved this problem," said senior author J. Victor Garcia, PhD, professor of medicine at UNC School of Medicine, director of the International Center for the Advancement of Translational Science and member of the UNC Center for AIDS Research.

The injectable implant is comprised of three elements - an organic solvent, a polymer, and the drug or drugs that need to be delivered. The formulation results in a honey-like liquid that turns into a solid when injected under the skin. This phase inversion happens when the solvent diffuses into the body leaving behind the polymer and medication(s) - the combination of which determines over what time period the medication(s) will be released into the blood system.

In this study six antiretroviral drugs were tested, and all kept their physical and chemical properties within the formulation and upon release. All six were also released from the implant at effective levels for a sustained amount of time ranging from one month to a year.

The injectable drug implant created by UNC's research team is the first to address several drawbacks to the current method of long-acting drug delivery for HIV - namely the ability to remove it and quickly eliminate the presence of residual drug(s) in the system.

"If a patient needs to withdraw from the treatment because they've had a bad reaction to the drug(s), or maybe a woman has become pregnant, our implant can be easily surgically removed," said Martina Kovarova, PhD, contributing author to the study and associate professor of medicine at UNC SOM.

This is the first ever injectable implant for HIV that can be removed as early as one week, or as late as months after the injection, and have drug levels virtually eliminated from the system within one week. If the implant does not need to be removed, it biodegrades into lactic and glycolic acids, which are already found in the body and are easily absorbed.

Researchers plan to continue developing and improving this multi-drug delivery system, observing its effects in relevant in vivo models and eventually humans.

New research led by the University of South Australia shows just how effective bowel cancer screening is in helping to reduce the number of bowel cancer deaths by up to 45 per cent.

Bowel (or colorectal) cancer kills almost 6000 people in Australia each year and 700,000 worldwide but this number would be much higher without pre-diagnostic colonoscopies, a study has found.

Data from 12,906 bowel cancer patients indicate that faecal occult blood testing (FOBT) with a follow-up colonoscopy plays a key role in catching the disease early, before symptoms appear.

Researchers from UniSA's Cancer Epidemiology and Population Health found that having one pre-diagnostic colonoscopy was associated with a 17 per cent reduction in cancer deaths; a 27 per cent reduction with two pre-diagnostic colonoscopy procedures and 45 per cent for three or more.

Of the 12,906 records analysed, 37 per cent of the patients had pre-diagnostic colonoscopies and were more likely to live longer than those who were diagnosed after experiencing cancer symptoms.

Dr Ming Li, one of the study leaders, says that in South Australia, where the study was undertaken, those patients who had pre-diagnostic colonoscopies showed a "significant increase" in survival.

The risk of colorectal cancer death reduces step-wise with increasing numbers of colonoscopy examinations before symptoms appear, cutting the mortality rate from 17 per cent to 45 per cent," she says.

"Our findings show the value of the National Bowel Screening Program which is now being rolled out to everyone in Australia over the age of 50 on a two-yearly basis. It involves doing a simple, non-invasive faecal occult blood test (FOBT) which, if positive, is followed up with a colonoscopy."

Bowel cancer causes the second highest number of cancer deaths in Australia after lung cancer, and is the third most common cancer worldwide, but 90 per cent can be cured if detected early, according to the Cancer Council.

Currently, just 39 per cent of the eligible population in Australia undertake a FOBT if invited, which is predicted to prevent 92,000 cancer cases in the next 20 years. If the participation rate were to increase to 60 per cent, an additional 24,300 bowel cancer deaths would be prevented, the Cancer Council estimates.

What The Study Did: This randomized clinical trial compared the outcomes of heart attack, stroke or death from cardiovascular causes among 6,000 patients with type 2 diabetes who were treated with the glucose-lowering medications linagliptin or glimepiride.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Nikolaus Marx, M.D., of Aachen University in Aachen, Germany, is the corresponding author.

(doi:10.1001/jama.2019.13772)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

New research presented at this year's Annual Meeting of the European Association for the Study of Diabetes (EASD) in Barcelona, Spain (16-20 September) shows that in patients with type 1 diabetes, hospitalization for either ketoacidosis or a hyperglycaemic (high blood sugar) coma are both linked to a subsequent increase in the risk of attempting suicide. The study is by Dr Jean Michel Petit, CHU (University Hospital) Dijon, France, and colleagues.

Patients with T1D and hospitalised for ketoacidosis are at an increased risk of subsequent hospitalisation for suicide attempt (2.2 times increased risk), while for hyperglycaemic coma the risk of subsequent hospitalisation for suicide attempt is tripled.

Diabetic ketoacidosis develops when the body is unable to produce enough insulin. Without enough insulin (or if not enough is injected by the patient with diabetes), the body begins to break down fat as fuel. This process produces a buildup of acids in the bloodstream called ketones, eventually leading to diabetic ketoacidosis if untreated. The symptoms include nausea and vomiting, abdominal pain, weakness or fatigue, shortness of breath and fruity-scented breath. Shortage of insulin also allows blood sugar to rise, which if left untreated can lead to a hyperglycaemic coma.

Several studies suggest that type 1 diabetes can significantly increase the risk of suicide. In this new research, the authors evaluated whether history of ketoacidosis or hyperglycemic coma hospitalisation could be associated with an increased risk of re-hospitalization for suicide attempt among people with type 1 diabetes.

This population-based retrospective cohort study examined hospital data including all patients hospitalised in France for T1D, from 2008. People with T1D were identified from hospital records. To reduce the risk of including people with type 2 diabetes, only individuals aged 35 years and under were included (such younger patients with diabetes are far more likely to have T1D than T2D)

The patients who died during the index hospitalization were excluded. Then, people with an hospitalization for ketoacidosis between the index hospitalization and 31 December 2010 (as their main, related or associated diagnoses) were included in the group "ketoacidosis" and the others were included in the group "no ketoacidosis".

People with an hospitalization for hyperglycaemic coma (meaning ketoacidosis with accompanying loss of consciousness) between the index hospitalisation and 31 December 2010 (as their main, related or associated diagnoses) were included in the group "hyperglycaemic coma".

An epidemiologic follow-up focused on hospitalisation for suicide attempts from medicine and psychiatric hospital data was conducted from 2008 to 2017. Statistical modelling was then used to establish any association.

From 2008 to 2010, 16 431 patients aged 18 to 35 years old, were hospitalised for type 1 diabetes in France. Among them, 1 539 (9.4%) had at least one hospitalisation for ketoacidosis and 279 (1.7%) had at least one hospitalisation for hyperglycemic coma. From 2008 to 2017, 107 individuals (7.0%) with ketoacidosis and 29 (10.4%) with hyperglycemic coma between 2008 and 2010 were subsequently hospitalised for suicide attempt. Among patients without ketoacidosis 365 (2.5%) were hospitalised for suicide attempt.

After adjustment for age, gender and psychiatric disorders (acute or chronic depressive disorders, or psychosis), survival analyses showed that ketoacidosis (by 2.2 times) and hyperglycemic coma (by 3.1 times) among people with type 1 diabetes were strongly associated with increased risks of subsequent re-hospitalisation for suicide attempt from 2008 to 2017. Among the 36 paitents with at least 2 hospitalisations for hyperglycemic coma during the nine years after the index hospitalisation, 8 (22%) were hospitalized for suicide: a nine-times increased risk compared to patients hospitalised with type 1 diabetes but without ketoacidosis.

The authors say: "Our results showed that people with a past history of hospitalisation for ketoacidosis or hyperglycemic coma have an increased risk of re-hospitalisation for suicide attempt within 9 years from that first hospitalisation. The risk is strongly increased in patients with 2 or more hospitalisations for hyperglycemic coma."

They add: "Identification of the risk factors of suicide is very important for the development of effective prevention strategies for suicide. Health-care professionals need to be aware of the higher suicidal risk in patients with ketoacidosis or hyperglycemic coma. The primary implication of our study is that all people with type 1 diabetes hospitalised for diabetic ketoacidosis and/or hyperglycaemic coma should have a screening of depressive symptoms and suicide ideation to reduce the risk of future suicides."

Fluoride varnish has become a popular anti-cavity treatment for children, and it isn't hard to see why. It's relatively easy to apply, and not just for dentists or dental hygienists. Pediatricians can do it as well, with minimal instruction. The sticky varnish goes on with a brush and then dries in a few hours. There's little risk of children swallowing the fluoride, as they might with other topical treatments such as gels.

Nor is it very expensive, with treatment costs generally ranging from about $25 to $55. That doesn't seem to be a prohibitive price to pay to guard a child against tooth decay.

Yet a new study by two University of Washington researchers and their colleagues questions the cost-effectiveness of fluoride varnish for preschoolers and calls its anti-cavity effects "modest and uncertain" in this age group.

Dr. Joana Cunha-Cruz and Dr. Philippe Hujoel of the UW School of Dentistry and four research colleagues came up with their conclusion after reviewing 20 clinical trials of fluoride varnish in 13 countries. They examined trials in which fluoride varnish was used by itself or in an oral health program, and also checked the results of using fluoride varnish compared with placebo, usual care, or no treatment.

"As much as we want fluoride varnish to be effective, the current evidence doesn't support a huge benefit for its use in young children," Dr. Cunha-Cruz said.

In their new study, which was recently published in the journal Caries Research, she and her colleagues noted that fluoride varnish applications are aimed especially at children with a high risk of caries, or tooth decay. It's not considered a primary form of treatment, but rather a complement to other fluoride treatments such as toothpaste or fluoridated water.

Nonetheless, the researchers reported that more recent clinical trials in both low-risk and high-risk groups "failed to show a protective effect of fluoride varnish applications."

"Cost-effectiveness analyses are needed to assess whether fluoride varnish should be adopted or abandoned by dental services," they said in their study.

The researchers don't assert that fluoride varnish doesn't work. Their analysis showed that the risk of developing new cavities declined by 12 percent among the children who received fluoride varnish, compared with those who did not. And they added that fluoride varnish could still be a cost-effective alternative in some cases. However, they also stated, "This was a rather modest benefit, as a large number of the children developed new dentine caries lesions, regardless of fluoride varnish use."

Concentrations of fluoride can also vary among different varnishes, Dr. Cunha-Cruz said.

That's not to say that there aren't highly effective topical treatment alternatives. Sealants do a good job of protecting the teeth, especially those hard-to-reach ones in the rear of the mouth, Dr. Cunha-Cruz said. Even better are sealants with glass ionomer, which releases fluoride, as opposed to resin-based sealants, which don't have it.

Sealants are more difficult to apply than varnish, but Dr. Cunha-Cruz said that they remain effective for two to three years. Silver diamine fluoride has also been growing in popularity and is very effective in stopping decay, she said, but more research is needed on its preventive effect. It can also discolor teeth, but that isn't as much of a concern for preschoolers who still haven't lost their primary teeth.

"The evidence still supports the use of fluoride toothpaste, which is easy and low-cost," Dr. Cunha-Cruz said. "The value of toothpaste lies in how it creates a daily presence of fluoride in the mouth." Fluoride rinse is also effective in this way, she said.

For now, she and her research colleagues are calling for more studies of fluoride varnish's cost-effectiveness among different populations and application settings. She suggests caregivers discuss the pros, cons and alternatives to fluoride varnish to prevent cavities with a child's dentist.

Meanwhile, aside from using fluoride toothpaste and rinses each day, Dr. Cunha-Cruz suggests another approach: "Reducing sugar intake is an even more cost-effective strategy."

"Good morning. Bill. Please. Step onto the scale. Touch the metal pads." The device records an electrocardiogram from Bill's fingers and - more importantly - circulation pulsing that makes his body subtly bob up and down. Machine learning tools compute that Bill's heart failure symptoms have worsened.

This is how researchers at the Georgia Institute of Technology envision their experimental device reaching patients someday, and in a new study, they reported proof-of-concept success in recording and processing data from 43 patients with heart failure. A future marketable version of the medical monitoring scale would ideally notify a doctor, who would call Bill to adjust his medication at home, hopefully sparing him a long hospital stay and needless suffering.

The pulsing and bobbing signal is called a ballistocardiogram (BCG), a measurement researchers took more commonly about 100 years ago but gave up on as imaging technology far surpassed it. The researchers are making it useful again with modern computation.

"Our work is the first time that BCGs have been used to classify the status of heart failure patients," said Omer Inan, the study's principal investigator and an associate professor in Georgia Tech's School of Electrical and Computer Engineering.

Healthcare crisis

Heart failure affects 6.5 million Americans and is a slow-progressing disease, in which the heart works less and less effectively. Many people know it as congestive heart failure because a major symptom is fluid buildup, which can overwhelm the lungs, impeding breathing and possibly causing death.

Patients endure repeat hospitalizations to adjust medications when their condition dips, or "decompensates," making heart failure a major driver of hospital admissions and healthcare costs. Home monitoring reduces hospitalizations but currently requires an invasive procedure.

Georgia Tech research was behind the launch of such an implantable heart failure home monitoring device in 2011. But this new solution would potentially dispense with the procedure, cost much less, and be much simpler to use - lowering patients' resistance to home monitoring.

Given its early stage, the study's BCG-EKG scale performed well in hospital tests but also in in-home tests, which was promising, since the solution principally targets eventual home use.

The research team, which included collaborators from the University of California, San Francisco, and Northwestern University, published their results in the journal IEEE Transactions on Biomedical Engineering. The research was funded by the National Heart, Lung and Blood Institute at the National Institutes of Health.

Ballisto scribble

The EKG part of the experimental scale is not new nor its great diagnostic information, but it alone does not say enough about heart failure. The BCG part is mostly new, and it appears valuable to heart failure monitoring but also challenging to record and interpret.

"The ECG (EKG) has characteristic waves that clinicians have understood for 100 years, and now, computers read it a lot of the time," Inan said. "Elements of the BCG signal aren't really known well yet, and they haven't been measured in patients with heart failure very much at all."

The EKG is electrical; the body conducts its signals well, and the recordings are clear.

The BCG is a mechanical signal; body fat dampens it, and it faces a lot of interference in the body like tissue variations and muscle movement. BCGs are also noisier in people with cardiovascular disease.

Patients with heart failure tend to be feebler, and initially, the researchers worried they would wobble on scales during home tests, adding even more noise to the BCGs. But the recordings were very productive.

Though a BCG read-out is scribble compared to an EKG's near-uniform etchings, BCGs have some patterns that parallel an EKG's. For example, the big upward spike in an EKG is followed by the BCG's big "J-wave."

Inconsistent throbbing

The researchers processed BCGs with three machine learning algorithms, revealing patterns that differ when a patient's heart failure is compensated, that is, healthier, from when it is decompensated.

"In someone with decompensated heart failure, the cardiovascular system can no longer compensate for the reduced heart function, and then the flow of blood through the arteries is more disorderly, and we see it in the mechanical signal of the BCG," Inan said. "That difference does not show up in the ECG because it's an electrical signal."

"The most important characteristic was the degree to which the BCG is variable, which would mean inconsistent blood flow. If you chop up the recording into 20-second intervals and the individual segments differ from each other a lot, that's a good marker of decompensation," Inan said.

PHILADELPHIA -- (Sept. 18, 2019) -- Researchers at The Wistar Institute have described the role of mitochondrial fission factor (MFF) in controlling survival of cancer cells, suggesting the protein could represent a promising therapeutic target. They also found that expression of MFF is regulated by Myc, a ubiquitous mediator of cell proliferation that contributes to development of many cancer types. These results were published online in the journal EBioMedicine.

Mitochondria, the organelles that supply energy to our cells, also control multiple cell death mechanisms and play an intricate role in cancer, which is a field of intense research. In particular, mitochondrial dynamics, a process that orchestrates the size, shape and position of mitochondria within the cell, has been implicated in tumor progression, but, until now, the mechanisms have only been partially elucidated.

"We know that reprogramming of mitochondrial functions is important for cancer development and metastasis," said senior author on the study Dario C. Altieri, M.D., Wistar president and CEO and director of the Institute's Cancer Center and the Robert & Penny Fox Distinguished Professor. "Our findings uncover new players and pathways in this process, opening concrete therapeutic opportunities to selectively eliminate tumor cells in patients."

Altieri's lab and an international team of collaborators showed that the MFF gene is amplified in prostate cancer patients, correlating with disease relapse and reduced survival. They also observed elevated expression of the MFF protein in a mouse model of prostate cancer and in tissue samples from patients with other cancer types, including lung cancer and multiple myeloma, compared to normal tissues.

Importantly, researchers implicated the Myc oncoprotein, which is commonly amplified in various cancer types and controls mitochondrial reprogramming during tumor progression, as a key driver of MFF expression.

Altieri and colleagues showed that, in cancer, MFF interacts with VDAC1, a mitochondrial regulator of cell death, shutting down its function to keep tumor cells alive. The researchers found that disruption of the MFF-VDAC1 complex activated multiple mechanisms of mitochondrial cell death, inhibiting tumor cell proliferation and reducing tumor growth in a preclinical model.

"In our setting, MFF targeting delivered preclinical anticancer activity," said Ekta Agarwal, Ph.D., a postdoctoral fellow in the Altieri laboratory and co-first author on the study. "Our data indicate that disruption of the MFF-VDAC1 complex may represent a novel therapeutic strategy that could potentially be effective in a broad array of cancers."