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Experts at The Ohio State University Wexner Medical Center and 45 worldwide scientific and medical societies pushed for change to the national guidelines that would allow more patients with the chronic diseases of obesity and diabetes to be eligible for bariatric surgery at the 2019 Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Obesity affects almost 40% of the population - or about 93 million adults - in the United States, according to the Centers for Disease Control and Prevention.

As chronic obesity worsens, it comes not only with complications of diabetes, but may also include heart disease and cancer. And just like with any other chronic disease, the best course of action is early intervention, such as bariatric surgery, said Dr. Stacy Brethauer, a surgeon at Ohio State Wexner Medical Center's Bariatric Surgery Center of Excellence.

Bariatric surgery is a weight-loss technique that changes the anatomy of the gastrointestinal tract including the stomach and digestive system and creates physiological changes in the body that alter energy balance and fat metabolism.

"Surgery is, by far, the most effective tool in managing or reversing Type 2 diabetes. Just as doctors wouldn't wait until a patient has advanced-stage cancer to treat their disease, patients shouldn't have to wait until they are severely obese to undergo surgery," Brethauer said. "Too many see obesity as a problem of willpower, and it's simply not. Patients must participate in their care by making healthy lifestyle changes, but the most effective treatment is often surgery, and that should be an option for patients who would benefit."

Patients with obesity who are interested in having bariatric surgery to lose weight must meet certain criteria to qualify for the surgery that were developed nearly three decades ago, and are arbitrarily based on a patient's body mass index (BMI), Brethauer said.

According to the 1991 National Institutes of Health Consensus Conference Guidelines, patients are considered surgical candidates only if their BMI is 40 or higher, or if their BMI is 35 or higher and they suffer from other life-threatening comorbidities such as type 2 diabetes, hypertension or cardiovascular disease.

"For example, if you have two patients who each have obesity with uncontrolled diabetes, the patient who has a BMI of 35 or higher would qualify for bariatric surgery, while the other patient with a BMI of 34 or lower would often be denied coverage by insurance companies," Brethauer said. He wants this to change.

Multiple clinical studies have proven the benefits of bariatric surgery in patients with lower BMIs. The American Society for Metabolic and Bariatric Surgery has drafted new criteria that would make these patients eligible for surgery with a lower BMI and diabetes, said Brethauer, a senior past president of the society who helped draft the new guidelines during his tenure as president.

"The patient who doesn't get the operation, we know very well that their disease will progress and their lifespan will be shortened," said Brethauer, professor of surgery at Ohio State's College of Medicine. "Continuing to increase their insulin requirements will not change the trajectory of the disease. Surgery does."

Brethauer said it's now up to referring physicians and insurance companies to more widely adopt these new standards so that more patients can receive the treatment they need.

In 2016, global guidelines developed during the 2nd Diabetes Surgery Summit were published in the journal Diabetes Care to inform clinicians and policymakers about benefits and limitations of bariatric surgery for patients with type 2 diabetes. These guidelines have been endorsed by more than 45 scientific and medical societies worldwide that urge health care regulators to introduce appropriate reimbursement policies.

"National data says that two-thirds of the population is either overweight or obese, and up to 8% are severely obese and clearly would qualify for bariatric surgery," Brethauer said. "But right now in the United States, we do more than 250,000 bariatric surgeries a year, so that means we're operating on 1% of the patients who are eligible for surgery based on their BMI."

BUFFALO, N.Y. -- A worldwide coalition of researchers and clinicians has agreed that light therapy is among the most effective interventions for the prevention of oral mucositis, painful ulcers in the mouth resulting from cancer therapy.

The new guidelines from the Multinational Association of Supportive Care in Cancer (MASCC) and International Society of Oral Oncology (ISOO), published on July 8 in the journal Supportive Care in Cancer, present a significant upgrade in care guidelines for adult cancer patients worldwide.

The guidelines recommend photobiomodulation therapy, a form of low-dose light therapy, for the prevention of oral mucositis caused by radiation therapy for head and neck cancer or stem cell transplantation.

Video: https://bit.ly/2YKW1KO

"Many cancer patients can now benefit from this treatment, said Praveen Arany, DDS, PhD, co-corresponding author on the paper and assistant professor of oral biology at the University at Buffalo School of Dental Medicine.

"The staggering breadth of clinical application for photobiomodulation therapy has been both a boon and a bane for the field. Several anecdotal clinical reports have been plagued with inconsistent outcomes and questionable rationales, often relegating this treatment to a pseudoscience."

Arany also said recent advancements are enabling rigorous validation of clinical protocols.

"This is a major milestone for the field and we are confident it will set a clear path for several exciting clinical applications for photobiomodulation therapy from concussions and wound healing to exciting new work with regenerative medicine and stem cells," said Arany, who is president of the World Association for photobiomoduLation Therapy (WALT).

Multiple studies have found that patients report oral mucositis as the worst side effect of their cancer treatment. Pain from the condition can slow or delay cancer treatment, and in severe cases require hospitalization.

Light therapies have existed for decades, but improvements in the technology have made the treatment more affordable for wider use. At a high power, light, often in the form of a laser, is used in medicine to cut or destroy tissue. But at a low power, it has the ability to relieve pain or inflammation and promote healing.

The treatment is rising in use across Europe, Brazil, India, Canada and several other nations. The findings provide an upgrade to previous guidelines published in 2013, which noted the effectiveness of light therapy and recommended, based on relatively limited evidence at that time, the intervention as an optional therapy in specific cancer patient populations and settings.

The review was led by Zadik Yehuda, DMD, senior lecturer at the Hebrew University-Hadassah School of Dental Medicine in Jerusalem, Israel; and Sharon Elad, DMD, chair of the MASCC/ISOO Mucositis Study Group. Along with 14 other global experts, they triaged hundreds of research papers published on photobiomodulation therapy for oral mucositis.

"These updated guidelines will provide health care professionals with better tools to deliver care for cancer patients, said Elad, also professor at Eastman Institute for Oral Health at the University of Rochester Medical Center.

"But even with the best evidence-based interventions, we don't yet have an ultimate guideline for mucositis in all clinical settings. We look forward to future research to help shape a more universal implementation of photobiomodulation therapy as well as identify additional effective and validated protocols."

Among other findings, the investigators identified five new protocols, recommending light therapy for the prevention of oral mucositis in stem cell transplant patients, and head and neck cancer patients receiving radiation therapy with or without chemotherapy. No major short-term side effects of light therapy were reported.

The therapy could potentially serve as an alternative to opioids, often prescribed to alleviate the symptoms of oral mucositis, said Arany.

Light therapy was also the subject of a recent congressional hearing before the House Science, Space and Technology Committee in Washington, D.C. The briefing, held in October 2018, invited a panel of international experts to discuss the potential of photobiomodulation to improve health care and lower dependence on opioids.

Future studies are needed to verify the effectiveness of light therapy in managing oral mucositis in pediatric cancer patients and in adult cancer patients receiving only chemotherapy.

Bottom Line: The new, nonlive shingles vaccine reduced the occurrence of shingles (herpes zoster) compared with placebo among patients who had undergone stem cell transplantation with their own stem cells. Shingles risk is increased after this type of stem cell transplantation and a vaccine that contains a weakened live strain of the shingles virus isn't recommended for these immunocompromised patients. This randomized clinical trial conducted in 28 countries included 1,846 patients who had undergone stem cell transplantation; 922 to receive two doses of the vaccine within a few months after transplantation and 924 to receive placebo. During a follow-up of about 21 months, at least one episode of shingles was confirmed in 49 patients who received the vaccine compared to 135 patients who received placebo (an incidence of 30 cases per 1000 person-years after 2 doses of the vaccine compared with 94 per 1000 person-years after placebo). The difference was statistically significant. A limitation of the study is that long-term protection from the vaccine wasn't assessed.

Authors: Keith M. Sullivan, M.D., Duke University Medical Center, Durham, North Carolina, and coauthors

(doi:10.1001/jama.2019.9053)

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.

Kidney diseases affect 850 million people worldwide, a figure twice as high as that of diabetes. Yet patients with chronic kidney disease (CKD) are still being excluded from clinical trials. This gives rise to severe problems, because many beneficial therapies cannot be authorised by regulatory authorities for this subgroup of patient, this means that the therapies in question cannot be prescribed for CKD patients. It is crucial, however, that CKD patients be eligible for new treatments, especially in the fields of diabetes, cardiovascular disease, cancer, and liver disease.

CKD is bidirectionally linked to cardiovascular disease, in that CKD engenders a high risk of cardiovascular complications, while heart disease may induce or aggravate CKD. CKD is also bidirectionally linked to neoplasia because, regardless of other factors, cancers or treatments targeting cancers may engender CKD, while CKD may predispose to cancer. Furthermore, there is a strong relationship between CKD and diabetes: over a third of all dialysis patients have suffered from diabetes for a long time, and their need for dialysis treatment results from the fact that diabetes has damaged the kidneys (a condition called diabetic nephropathy). As a public health epidemic, CKD patients require innovative therapies. It is highly problematic, therefore, if CKD patients cannot benefit from innovative therapies for diabetes, cancer or cardiovascular diseases.

Since 1964 the ERA EDTA maintains a Registry of Dialysis and Transplantation in Europe. Starting about 10 years ago, this Registry has extended its research to pre-dialysis CKD by establishing a consortium of existing CKD cohorts in Europe and in 2007 provided expert advice to the European commission by contributing to the European Global Health Report by putting in focus the CKD epidemic. In recent years the ERA EDTA has directly funded clinical trials in renal diseases and in dialysis patients.

'The fact of the matter is that many innovative treatments fail to reach our patients', explains Professor Carmine Zoccali, President of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA). 'Let's take SGLT inhibitors, a new group of antidiabetic drugs, as an example. We know from studies that these substances may protect kidney function, but they have not been tested in CKD patients with an eGFR below 30 ml/min. This means that kidney patients are excluded from therapies that might slow down the progression of CKD.'

When it comes to treatment of other illnesses and/or comorbidities, CKD patients should also have the same right to receive the best possible treatment as any other patients. However, the truth is that many new therapies are not tested on this subgroup, which means that CKD patients are unable to benefit from promising therapies. The International Society of Nephrology charged the research community with enrolling 30% of CKD patients by 2030. By encouraging the inclusion of CKD patients in high-quality clinical trials we can ensure they receive equal opportunity to receive evidence-based prevention and treatment of the disease. 'It is a fact that the efficacy and the safety of treatments tested on patients without CKD cannot be assumed in CKD patients, and similarly that withholding treatment due to the presence of CKD may significantly and unfairly disadvantage those affected', explains Professor David Harris, Past-President of the International Society of Nephrology. 'We need studies that include CKD patients.'

The Kidney Health Initiative, the American Society of Nephrology's public-private partnership with the US Food and Drug Administration, addresses this issue through its "Overcoming Barriers to Including Kidney Disease Patients in Cardiovascular Trials". The project aims to understand the barriers to involving patients with kidney diseases into cardiovascular trials, with a focus on patients with advanced chronic kidney disease (stage 4) and end-stage renal diseases and identify strategies to overcome these challenges. The workgroup intends to submit their findings to a peer-reviewed medical journal in Summer 2019.

'It is time for a change in clinical research practice', confirms Professor Mark D. Okusa, Past-President of the American Society of Nephrology (ASN). 'The already large and growing group of kidney patients cannot be ignored any longer in clinical trials.' This is the reason why ASN, ERA-EDTA and ISN have collaboratively launched an information campaign that aims to bring about this paradigm change.

The power and convenience of modern-day word-processing programs, like Microsoft Word, have revolutionized our daily tasks. Need to create a quick resume for a new job opportunity? Procrastinating on that final term paper due tomorrow? Even creating a quick grocery list- Most of us rely on word-processing programs as stewards of our written lives. The functionality is impressive and unlike its archaic predecessor, the type writer, just a few keystrokes can change, delete, or add words as the user desires.

For years researchers have been searching for ways to mimic these capabilities but on the genetic scale, in order to accurately and efficiently alter genetic information. Developing a "Microsoft Word of DNA", would allow scientists the opportunity to better study the functioning of individual genes and the mutations that contribute to genetic disorders. With a single discovery, called CRISPR-Cas9, scientists were forever upgraded from DNA typewriters to a DNA word-processor; editing genes with the same ease, precision and versatility. The technology has gained immense traction and popularity due to its flexibility and customizable nature.

Though powerful, CRISPR is far from a perfect technique and like any other, has its drawbacks and limitations. One of its primary uses, involves precisely targeting and mutating a gene of interest so that it no longer functions within a specific type of cell. When a gene is rendered nonfunctional, any characteristic changes to the cell (known as phenotypes) can be studied in order to get a better picture of what that particular gene does. But the way CRISPR mutates individual genes can pose a challenge to researchers. When placed in a cell, the CRISPR-Cas9 system precisely mutates a targeted gene by cutting the cell's DNA. The cell then repairs its broken DNA predominantly through a process called nonhomologous end-joining (NHEJ). But this repair process is error prone and can cause variability in the repaired DNA; often leading to substitutions, deletions or additions to the genetic code. Adding to the challenge is that the efficiency of CRISPR can vary, acting to render both copies of a targeted gene nonfunctional or sometimes only one. These unknown CRISPR caused DNA changes can make it extremely difficult for scientists to interpret the underlying genetic cause of an observed phenotype; making the tool far less useful.

In a recent publication in Cell Reports, the Taniguchi Lab at the Max Planck Florida Institute for Neuroscience (MPFI) have developed a new methodology that allows the linking of phenotype to genotype. Innovatively combining the cutting-edge technique of laser microdissection with single cell genotyping, the Taniguchi Lab has designed an experimental pipeline capable of studying CRISPR mediated effects in cells while accurately ascertaining the exact DNA changes that caused them. This novel protocol will open up new avenues of study for neurobiology and further upgrade the already powerful abilities of CRISPR.

"Though CRISPR precisely targets a gene of interest, due to NHEJ, its effects can be highly variable," explains Andre Steinecke, Ph.D., Research Fellow and first author of the publication. "CRISPR can leave cells with either fully nonfunctional genes, weakened genes or sometimes even enhance their function. This isn't such a problem when removing one that causes a very noticeable effect in cells because you can easily visualize the change and absence of the protein coded by the gene. But some, especially genes in the brain, don't have strikingly obvious effects or are very difficult to visualize. Our goal was to create a widely applicable strategy, capable of reliably determining the exact genetic cause and correlate it to observed phenotype."

To validate their strategy, the team at MPFI designed CRISPR technology to target a gene in pyramidal neurons encoding a critical structural protein, called Ankyrin-G (AnkG). Normally, the AnkG protein is confined to a specialized region of the neuron known as the axon initial segment (AIS), which is responsible for generating action potentials. When AnkG is removed, the AIS undergoes a noticeable thickening that can be detected using microscopy. With this characteristic feature, neurons that lack AnkG could be readily distinguished and their exact genotype could then be confirmed. They found that predominately, neurons transfected with their CRISPR probe exhibited a loss of AnkG as well as substantially thickened AIS. But a small portion of neurons transfected with CRISPR still exhibited AnkG levels and AIS thickness comparable with wildtype neurons; demonstrating the varying effects of CRISPR on different cells. To probe and confirm the underlying genetic causes, the team then used laser microdissection to isolate and extract individual neurons whose phenotype had already been characterized. Once extracted, the team sequenced each individual cell separately to determine the genotype. They found that their strategy could reliably and reproducibly link observed phenotype to genotype, where neurons lacking AnkG with thickened axons showed loss-of-function mutations in both copies of the gene whereas neurons with normal levels of AnkG either showed mutations in only one copy (neurons transfected with CRISPR) or normal genotypes (control neurons). The team then confirmed their strategy using two additional genes, MeCP2 and Satb2, finding that their process could once again effectively correlate observed feature to underlying genetics.

"CRISPR/Cas9-based gene targeting holds great promise for systematic understanding of the molecular basis underlying the assembly, function, and dysfunction of neural circuits," notes Hiroki Taniguchi, Ph.D. "The perfect matching between genotypes determined by our single cell sequencing and those deduced from phenotype evaluation, suggests that our approach is a powerful new method capable of enhancing the reliability and expanding the applications of CRISPR-based techniques."

Amsterdam, July 9, 2019 - Duchenne muscular dystrophy occurs in boys and is characterized by progressive muscle degeneration and weakness leading to a decline in respiratory function. Strategies to arrest this severe progressive deterioration are needed to extend lives and improve quality of life. Results of three clinical trials using eteplirsen, an exon-skipping antisense oligonucleotide, show promising results, according to a study published in the Journal of Neuromuscular Diseases.

Muscular dystrophy is a group of genetic disorders that results in increasing weakening and breakdown of skeletal muscles. Near absence of dystrophin, a critical protein, results in inflammation, necrosis, and eventual replacement of functional muscle tissue with fibrosis and fat. Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy in boys that has a predictable disease course. Muscle weakness usually begins around the age of four in the thighs and pelvis followed by the arms. Most patients are unable to walk by the age of 12. Natural history data show that respiratory function declines linearly and predictably in the second decade of life. Respiratory decline in glucocorticoid-treated DMD patients is typically 5% annually in patients aged 10 to 18 years. Patients require increasing levels of clinical intervention as the disease progresses.

Investigators led by Navid Z. Khan, PhD, Senior Director, Global Medical Affairs, Sarepta Therapeutics, Inc., Cambridge, MA, USA, evaluated respiratory function in eteplirsen-treated patients from three clinical trials and compared them to patients matched by age range, steroid use, and genotype from the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) global database. These three trials studied eligible ambulatory DMD patients for at least four years (studies 201 and 202), primarily non-ambulatory DMD patients for two years (study 204), and an ongoing open label multicenter study of ambulatory DMD patients aged seven to 16 years (study 301).

The CINRG DNHS, one of the largest prospective natural history studies of DMD conducted to date, comprises more than 400 DMD patients with complete characterization of demographic data, along with assessments of clinical parameters affected by DMD. The three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (20 patients), all glucocorticoid-treated CINRG patients (172 patients), and all glucocorticoid-treated genotyped CINRG DNHS patients (148 patients). Approximately 13% of cases of DMD are amenable to exon 51 skipping therapies.

Patients in the global patient database experienced respiratory decline at rates in line with the well-established natural history of DMD. In contrast, the respiratory decline in patients treated with eteplirsen was significantly lower, and this was true across all stages of the disease evaluated. Specifically, both ambulatory and non-ambulatory patients demonstrated a slower rate of respiratory decline.

As the disease progresses, patients require increasing levels of clinical intervention including cough assist and ventilation support, and patients are at increased risk of death once this respiratory decline reaches a critical threshold. This work demonstrates that eteplirsen may slow the rate of respiratory decline and therefore may delay time to milestones of decline. This may have notable positive implications on quality of life, and because pulmonary decline is linked to mortality, slowing of decline may result in delayed mortality. The investigators acknowledge that longer term follow-up is needed.

Eteplirsen is an antisense oligonucleotide approved by the FDA for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.

LOGAN, UTAH -- The 2019 Tour de France has just begun. As 190 riders speed through the streets of France, spectators will marvel at the tightly-packed formation of cyclists known as the peloton. Fans will argue that a peloton creates an aerodynamic advantage, allowing riders to conserve energy throughout the grueling three-week race.

But what if the patterns in the peloton are formed not because of aerodynamics but rather due to visual limitations? In a recent study published in the Journal of the Royal Society Interface, researchers at Utah State University, the Naval Undersea Warfare Center, Baylor University, VeloCam Services and the Massachusetts Institute of Technology reveal that vision is the main factor in the formation and shape of a peloton.

The study began four years ago when Professor Tadd Truscott of Utah State University and Jesse Belden from the Naval Undersea Warfare Center set out to unravel the fluid-like behavior of the peloton.

While 17-time Tour de France finisher Jens Voigt says "cycling is not rocket science," Truscott and his colleagues -- who are cyclists themselves -- share a different perspective. The team speculated that the peloton emerges because of certain knowledge within the group, team dynamics and strategy, aerodynamics or perhaps sensory perception.

Researchers watched hours of aerial footage from the 2016 Tour de France and found that motion from the front of the pack appeared to pass through the peloton in a network fashion, with individuals reacting to one another in a relatively short time and space.

"Tour de France riders are often only a few centimeters apart from neighbors on all sides," said Truscott, "Our image analysis revealed that cyclists align in patterns within a plus or minus 30-degree arc corresponding to the human near-peripheral visual field. This helps them safely react to changes or disturbances from neighboring riders."

Researchers also noticed that riders generally don't align in optimal aerodynamic drafting positions. However it has been shown that peloton formations can lower individual rider energy expenditures.

Truscott's team found that group structures change near the end of a race as the peloton shape elongates, suggesting a narrowing of the field of vision as the race speeds up. As riders' heart rates increase, their field of vision narrows due to physiological restrictions of the human body. This decreases the field of perception which leads to a stretching out of the peloton. According to the study, these arousal-dependent neurological effects set the local arrangement of cyclists, the mechanisms of interaction and the implicit communication across the group of cyclists.

"In other words, the visual ability of individual riders governs the underlying shape, response to changes in the road and spacing between individuals," said Truscott.

The researchers say they anticipate that their mechanistic description of the peloton will enable a more detailed understanding of the interaction principles for collective behavior in a variety of animals and help formulate new ways of predicting behavior.

The findings will develop a better understanding of how systems of thousands of individuals can work together to perform group tasks. This work could set the framework for directing a network of individual machines such as robots or autonomous vehicles.

Some people live much longer than average, partly thanks to their DNA. An all-Italian research, published in the European Heart Journal, shows that it could be possible to replicate this "genetic gift" even for those lacking it. The way is now open to an innovative therapy model, capable of preventing and fighting cardiovascular diseases through a real rejuvenation of blood vessels.

The study, conducted by the I.R.C.C.S. Neuromed, the I.R.C.C.S. Multimedica and the Department of Medicine, Surgery, and Dentistry, Salerno Medical School University of Salerno, with the support of the Cariplo Foundation and the Italian Ministry of Health, focuses on the gene that encodes the BPIFB4 protein. In the past, the same research group had identified a variant of this gene, the so-called LAV ("longevity associated variant"), which prevails in people with very long lives: over one hundred years. Now researchers have inserted, through a viral vector, the LAV-BPIFB4 gene in the DNA of animal models particularly susceptible to atherosclerosis and, consequently, to cardiovascular diseases.

"The results - says Annibale Puca, coordinator of a research team at the University of Salerno and at I.R.C.C. MultiMedica - were extremely encouraging. We observed an improvement in the functionality of the endothelium (the inner surface of blood vessels), a reduction of atherosclerotic plaques in the arteries and a decrease in the inflammatory state".

In other words, the inclusion of the "centenarian gene" in animal models has caused a real rejuvenation of the cardiovascular system. The same positive effect was also achieved in the laboratory, this time not by inserting genes but by delivering the LAV-BPIFB4 protein to human blood vessels.

To these experimental data researchers added further studies conducted on groups of patients. First of all, they saw that at a higher level of BPIFB4 protein in the blood was associated with healthier blood vessels. Moreover, carriers of the LAV genetic variant had higher protein levels.

"This study - comments Carmine Vecchione, dean of the Faculty of Medicine of the University of Salerno, director of the Cardiology Unit at Ruggi D'Aragona Hospital and head of Vascular Physiopathology Laboratory at I.R.C.C.S. Neuromed - paves the way to the possibility of therapeutic solutions based on the LAV-BPIFB4 protein. Of course, much research will still be needed, but we think it is possible, by administering the protein to patients, to slow down cardiovascular damage due to age. In other words, even if a person does not possess those particular genetic characteristics, we could be able to offer the same level of protection."

BINGHAMTON, N.Y. - The herb kratom is increasingly being used to manage pain and treat opioid addiction, but it's not safe to use as an herbal supplement, according to new research led by faculty at Binghamton University, State University of New York.

William Eggleston, clinical assistant professor of pharmacy practice at Binghamton University, had been seeing more and more patients presenting with toxicity or withdrawal from kratom use. Kratom is an herbal supplement derived from a plant that grows throughout southeast Asia. It is well-reported that the active chemicals in the plant act on opioid receptors in the body. Patients report using the supplement to treat/prevent withdrawal, treat opioid use disorder, or treat pain.

Eggleston was curious to see what types of toxicities were being reported to Poison Centers nationally in order to better assess whether or not kratom is safe enough to be used as an herbal supplement. His team conducted a retrospective review of kratom exposures reported to the National Poison Data System to determine the toxicities associated with kratom use. They also reviewed records from a County Medical Examiner's Office in New York State to identify kratom?associated fatalities.

A total of 2312 kratom exposures were reported, with 935 cases involving kratom as the only substance. Kratom most commonly caused agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), and confusion (8.1%). Serious effects of seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%) were also reported. Kratom was listed as a cause or contributing factor in the death of four decedents identified by the County Medical Examiner's Office.

The findings suggest kratom is not reasonably safe and poses a public health threat due to its availability as an herbal supplement.

"Although it is not as strong as some other prescription opioids, kratom does still act as an opioid in the body," said Eggleston. "In larger doses, it can cause slowed breathing and sedation, meaning that patients can develop the same toxicity they would if using another opioid product. It is also reported to cause seizures and liver toxicity. Kratom may have a role in treating pain and opioid use disorder, but more research is needed on its safety and efficacy. Our results suggest it should not be available as an herbal supplement."

Eggleston and his team are working with colleagues at SUNY Upstate Medical University to better assess how many patients are actually using kratom and if the risk for toxicity changes depending on the dose of kratom taken.

DALLAS, July 9, 2019 -- Significantly more patients suffer cardiac arrests in U.S. hospitals each year than previously estimated, according to new research in Circulation: Cardiovascular Quality and Outcomes, an American Heart Association journal.

Cardiac arrest, which occurs when the heart malfunctions and stops beating, is not the same as a heart attack, which occurs when blood flow to the heart is blocked.

Researchers developed a model for estimating cardiac arrest incidence using data on facilities from the American Hospital Association annual survey, which included hospitals linked to the American Heart Association's Get With The Guidelines®-Resuscitation (GWTG-R) registry. In 2011 when cardiac arrest data from the two registries was last analyzed, annual incidence was estimated to be 211,000 for adults and 6,000 in children.

The new study estimates that there are about 292,000 adult in-hospital cardiac arrests and 15,200 pediatric in-hospital events (of which 7,100 cases were pulseless cardiac arrests and 8,100 cases in which there was a pulse but still requiring CPR) in the United States each year. Compared to previous reports, the public health burden of adult and pediatric pulseless in-hospital cardiac arrest is approximately 38% and 18% greater than previously estimated.

"Our findings illustrate a concerning trend in U.S. hospitals, and show that cardiac arrest is a major public health problem," said Lars W. Andersen, M.D., M.P.H., Ph.D., D.M.Sc., study co-author and associate professor at Aarhus University in Denmark, who oversaw the study as a visiting researcher at Beth Israel Deaconess Medical Center's Department of Emergency Medicine in Boston. "Previous incidence estimates may no longer reflect the current public health burden of cardiac arrest in hospitalized patients across the U.S. Unfortunately, the data does not provide an explanation for the increase in adult in-hospital cardiac arrest, but it is likely due to many factors and may reflect an increase in actual events or in the reporting of cases over time."

Andersen said the findings may suggest that basic life support and advanced cardiac life support training programs - which traditionally have focused on out-of-hospital resuscitation - may need to be expanded to include potential in-hospital responders.

Researchers found no indication that the number of pediatric events has increased over time. Instead, the current estimates are based on a larger database and provide the most robust estimate of pediatric in-hospital cardiac arrest cases in the United States to date.

In 2015, prevention of in-hospital cardiac arrest was added to the Chain of Survival in the American Heart Association's Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Although preventing cardiac arrest is complex, possible steps to reduce in-hospital cases include educating more medical personnel, identifying deteriorating patients through early warning signs and early intervention by rapid response and emergency response teams.

"It is also important to note that end-of-life discussions and decisions are crucial in order to avoid attempts at resuscitation in patients where it is likely futile or against a patient's wishes," Andersen said.

He also noted that the findings should be interpreted with caution as data was limited to data from GWTG-R hospitals.

New findings out of the University of Tübingen show that, on top of its benefits for metabolism, mood, and general health, exercise also improves brain function. In recent studies, researchers learned that obese and overweight individuals are prone to insulin resistance in the brain, where it provides information about current nutritional status, as well as the rest of the body. So researchers wanted to know whether exercise can improve insulin sensitivity in the brain and improve cognition in overweight individuals.

In the current study, led by Dr. Stephanie Kullmann, 22 sedentary adults with overweight or obesity (an average BMI of 31) underwent two brain scans before and after an 8-week exercise intervention, including cycling and walking. Brain function was measured before and after using an insulin nasal spray to investigate insulin sensitivity of the brain. Participants were also assessed for cognition, mood, and peripheral metabolism.

Even though the exercise intervention only resulted in a marginal weight loss, brain functions important for metabolism "normalized" only after 8-weeks. Exercise increased regional blood flow in areas of the brain important for motor control and reward processes, both of which depend on the neurotransmitter dopamine. Dopamine is an important neurotransmitter for learning new motor skills and in reward-related learning and this research shows that exercise significantly improves dopamine-related brain function. One area in particular, the striatum, had enhanced sensitivity to insulin after the 8-weeks of exercise such that the brain response of a person with obesity after exercise training resembled the response of a person with normal-weight. Interestingly, the greater the improvement in brain function, the more belly fat a person lost during the course of the exercise intervention. Behaviorally, participants reported an improvement in mood and task switching, which is an indicator for improved executive function.

"The bottom line is that exercise improves brain function", said Kullmann. "And increasing insulin sensitivity in dopamine-related brain regions through exercise may help decrease the risk of a person to develop type 2 diabetes, along with the benefits for mood and cognition".

A team of neuroscience researchers at the University of Southern California have identified a surprising new role for the "hunger hormone" ghrelin. Ghrelin has previously been recognized for its unique role in sending hunger signals from the gut to the brain, but, as presented this week at the annual meeting of the Society for the Study of Ingestive Behavior, these new findings suggest that it may also be important for memory control.

Ghrelin is produced in the stomach and secreted in anticipation of eating, and is known for its role to increase hunger. "For example, ghrelin levels would be high if you were at a restaurant, looking forward to a delicious dinner that was going to be served shortly," said Dr. Elizabeth Davis, lead author on the study. Once it is secreted, ghrelin binds to specialized receptors on the vagus nerve - a nerve that communicates a variety of signals from the gut to the brain. "We recently discovered that in addition to influencing the amount of food consumed during a meal, the vagus nerve also influences memory function," said Dr. Scott Kanoski, senior author of the study. The team hypothesized that ghrelin is a key molecule that helps the vagus nerve promote memory.

Using an approach called RNA interference to reduce the amount of ghrelin receptor, the researchers blocked ghrelin signaling in the vagus nerve of laboratory rats. When given a series of memory tasks, animals with reduced vagal ghrelin signaling were impaired in a test of episodic memory, a type of memory that involves remembering what, when, and where something occurred, such as recalling your first day of school. For the rats, this required remembering a specific object in a specific location.

The team also investigated whether vagal ghrelin signaling influences feeding behavior. They found that when the vagus nerve could not receive the ghrelin signal, the animals ate more frequently, yet consumed smaller amounts at each meal. Dr. Davis thinks these results may be related to the episodic memory problems. "Deciding to eat or not to eat is influenced by the memory of the previous meal," says Davis. "Ghrelin signaling to the vagus nerve may be a shared molecular link between remembering a past meal and the hunger signals that are generated in anticipation of the next meal."

These novel findings add to our understanding of how episodic memories are generated, as well as the relationship between memory and eating behavior. In the future, researchers may be able to develop strategies for improving memory capacity in humans by manipulating ghrelin signaling from the gut to the brain.

Kuwait has some of the highest rates of obesity and diabetes in the world, and scientists don't know why. This question was addressed by Dr. Max Goodson, Emeritus Professor at the Forsyth Institute.

Goodson is the principal investigator of a large-scale study that analyzed diet, salivary bacteria, salivary protein biomarkers, and salivary metabolites of 10-year-old Kuwaiti children. Researchers collected saliva samples from 94 children once in 2012 and again in 2014.

All of the children were healthy at the start of the study, but approximately half of them developed obesity and metabolic syndrome two years later. When analyzing differences in metabolites found in saliva samples, Goodson and his colleagues discovered elevated levels of a biomarker for uranium toxicity were present in the saliva of children who became obese. The results were published recently in Frontiers in Endocrinology.

The biomarker, a compound called N1-Methyl-2-pyridone-5-carboxamide (2PY), is a metabolite of the vitamin niacin. It is present at low levels in almost everyone's saliva. However, 2PY was found at higher than normal concentrations only in the saliva samples of the obese children in Kuwait. In a comparable group of obese children from Maine and Massachusetts, elevated levels of 2PY in obese children were not found.

"The implication," Goodson said, "is that these children may be suffering from uranium toxicity, which may be contributing to the high rates of obesity and diabetes in Kuwait."

The idea that uranium toxicity would be a health concern in Kuwait makes sense. In 1990-1991, the United States dropped almost 300 tons of uranium-containing munitions in the central region of the country, Goodson said. As part of the recent study, researchers found that the highest rates of obesity and salivary 2PY were concentrated in that central region and reduced in peripheral areas of Kuwait.

Goodson is careful to point out that the study measured a biomarker for uranium, not uranium itself. More research is needed to determine whether toxicity from exposure to the heavy metal is truly the culprit for high rates of obesity and diabetes seen in Kuwait.

New findings show how a genetically aberrant, fused protein promotes a rare form of liver cancer in adolescents and young adults. The researchers also saw that a certain mix of drugs could target the fused protein and the enzymes that it recruits. In the lab, this drug combination slowed down the uncontrolled growth of cells carrying the liver cancer mutation.

While the potential treatment approach needs further testing in animal models and in cancerous human liver cells, the early results are encouraging. This preliminary research project was published in eLife.

"There is a great need to improve treatment for patients with this form of liver cancer, called fibrolamellar carcinoma or FLC," said John D. Scott, professor and chair of pharmacology at the University of Washington, who was the senior author on the paper.

The lead researchers were Rigney E. Turnham, who recently received her Ph.D. in pharmacology from the UW, and F. Donelson Smith, research assistant professor of pharmacology at the UW School of Medicine. The study involved several other scientists, and included a collaboration with Raymond S.W. Yeung, professor of surgery and founder of the Liver Tumor Clinic at UW Medical Center, and Kimberly J. Riehle, associate professor of surgery, Division of Pediatric Surgery and a Seattle Children's Hospital surgeon.

At present, fibrolamellar carcinoma is difficult to eradicate in patients because the cancer does not respond consistently to treatment, the researchers explained. FLC tumors are often resistant to standard radiation therapy and chemotherapy. As yet, directed agents have not worked well either. During early stages, the tumors can usually be surgically removed. However, the cancer tends to return and spread to other locations.

By examining tumor genomes from the cancer, other scientists in earlier studies detected a mutation on chromosome 19. Liver cells with this mutation produce a chimeric enzyme with two fused components. Studies by Turnham's and Smith's research team revealed that this fused enzyme also has the unusual ability to recruit a heat shock protein that is commonly overproduced in stressed-out cells.

Obtaining sufficient tumor cell lines to study this rare disorder is difficult. Instead, the research team genetically edited mouse liver cells to mimic the human mutation and produce the chimeric protein. Biochemical analysis of these engineered cells showed that the fused protein rallied a set of enzymes associated with unchecked, accelerated cell proliferation. The researchers confirmed that the same enzymes are activated in human tumor cells from FLC patients.

The fused proteins insert themselves into anchored signaling complexes, which hold them in place inside the cell. Acting as a secondary scaffold, the fused proteins and their associated assemblies mobilize certain cell signals. Its organizational skills may be key to the chimeric protein's cancer-inducing nature. This scenario may be a case, the researchers think, of normal biochemical functions becoming inappropriately incorporated into molecular pathways that promote disease progression. These misdirected mechanisms appear to be likely targets for a precision pharmacology approach.

The researchers additionally conducted a drug sensitivity screening of anti-cancer compounds that were already FDA-approved. They tested several combinations of drugs for the ability to act simultaneously on the fusion protein/heat shock protein pair. The researchers found drug combinations that could blunt the proliferation of cells containing the genetically engineered liver cancer mutation. Normal liver cells were unaffected by the treatment.

The researchers believe that the drug combinations that were effective in this lab bench study warrant further investigation as potential therapeutic strategies against FLC.

The researchers also hope their latest findings overall will be valuable in exploring new treatments of this debilitating disease of adolescents and young adults. The team's studies reflect a strong translational medicine collaboration between basic scientists and clinicians.

Opioids work against severe pain but the risks of side effects and addiction are high. In the USA alone, 26 people die every day from overdoses. Now researchers in an international collaboration have investigated how common opioid prescriptions are for osteoarthritis patients in Sweden. It emerged that every fourth patient was prescribed opioids at some point between November 2014 and October 2015.

"The results show an alarmingly high rate of opioid prescriptions for osteoarthritis patients", says Martin Englund, professor at Lund University and physician at Skåne University Hospital who led the study in collaboration with researchers from Denmark and the United Kingdom.

The researchers based their research on the population registry in southern Sweden of people who were at least 35 years old (a total of 751 579 people) and who had received a diagnosis of knee or hip osteoarthritis at some point during 1998-2015 (a total of 82 379 people). With the help of data from the Swedish Prescribed Drug Register the researchers were able to see how many of these people were prescribed opioid preparations between 1 November 2014 and 31 October 2015. This was reported to be every fourth osteoarthritis patient (24 per cent).

The study also estimated that at least 12 per cent of all new opioid prescriptions are given to patients with osteoarthritis. The most frequently prescribed drugs were codeine, tramadol, oxycodone and morphine preparations.

"The result is remarkable. Opioids are highly addictive preparations and are not on the list of recommended treatments for osteoarthritis in Sweden, except for in extreme cases or in conjunction with surgical treatment. However, even when we removed all prescription in conjunction with surgery, the result was very similar", says Martin Englund.

In Sweden there is a tradition of collecting personal data in a register that is connected to the individual's own personal identification number. Such data is not typically available in most countries.

"In general, a high use, or an increase in the use of opioids among osteoarthritis patients have been reported in the US, Catalonia in Spain and in Australia. But to estimate reliable figures of opioid prescriptions preferably requires careful documentation in registers covering the entire population, and from all levels of health care", says Martin Englund.

He says that the results indicate a significant challenge within the field of osteoarthritis: there is good basic treatment for patients - osteoarthritis education and exercise programs - however, many osteoarthritis patients do not utilise this. Subsequently, or if there is insufficient improvement after basic treatment, there is a significant lack of good pharmaceutical non-surgical treatment alternatives to offer the patient, other than some relief of symptoms.

"If the patient has developed severe osteoarthritis, and other treatments do not offer sufficient relief of symptoms, it is possible to offer prosthetic surgery. However, it is substantial and expensive surgical treatment, and should only be offered to patients that really need the operation. Unfortunately the healthcare system is lacking in pharmaceutical treatment options that can relieve pain and modify the development of the disease itself, i.e. have an impact on the actual biological process. We need more research on this", says Martin Englund.