Credit: Photo by Getty. A liver condition could be a cause of Type 2 diabetes, new published research shows. Analysis Suggests the Liver's Failure to Properly Process Insulin Could Provide Early Warning of Diabetes for At-Risk Individuals Newswise — A liver condition long associated with Type 2 diabetes might actually cause the disease, and testing for it could provide an early warning for at-risk individuals, according to a Cedars-Sinai study. Type 2 diabetes is the most common form of diabetes, a condition that affects more than 30 million Americans. In Type 2 diabetes, chronic high blood sugar levels can lead to serious health problems, such as heart disease, stroke, vision loss and kidney disease. Although it is sometimes called adult-onset diabetes, the disease increasingly strikes children as well, and it disproportionately affects African Americans. The hormone insulin regulates blood sugar and enables cells to use it. Patients with Type 2 diabetes either cannot make use of insulin, or cannot produce enough of it. Despite decades of research, the disease's underlying causes remain unclear. The authors of the recent study, in the journal Diabetes, propose that a primary driver of Type 2 diabetes may be a condition known as reduced hepatic insulin clearance, in which the liver fails to eliminate excess insulin from the body. "Understanding the liver's role has wide potential to improve both diagnosis and treatment of Type 2 diabetes, especially for African Americans," said Richard Bergman, PhD, director of the Sports Spectacular Diabetes and Obesity Wellness and Research Center at Cedars-Sinai. Bergman is the study's corresponding author. Previous research by Bergman's team has shown that African Americans tend to have more trouble with hepatic insulin clearance. The scientific community has long regarded reduced hepatic insulin clearance to be a result of diabetes. But an analysis of recent and historic data from multiple studies suggests that the condition may be a primary driver of Type 2 diabetes, according to Bergman, professor of Biomedical Sciences and Medicine and the Alfred Jay Firestein Chair in Diabetes Research. The liver plays an important role in regulating many systems in the human body. When a liver cannot adequately process and clear out excess insulin, the hormone floods the bloodstream and throws the body's chemistry out of balance. Bergman and his team propose that this chain of events triggers Type 2 diabetes in patients who already have been made vulnerable by multiple genetic and lifestyle factors. The investigators cautioned that their hypothesis has not been proven. "We realize that the data presented are primarily associative and therefore do not prove causality," said Marilyn Ader, PhD, associate director of the diabetes and obesity center and associate professor of Biomedical Sciences at Cedars-Sinai. She was co-investigator for the study. Bergman said he and colleagues plan to pursue further studies to help clarify whether reduced hepatic insulin degradation can lead to Type 2 diabetes, at least in some at-risk groups. "It seems clear that the roles of insulin clearance and the underlying mechanisms and genetics deserve increased attention," he said. Funding: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers DK27619 and DK29867. Duality of interest: Bergman is supported by grants from AstraZeneca and Janssen Research and Development and is an advisory board member of Novo Nordisk. DOI: 10.2337/db19-0098 Read more on the Cedars-Sinai Blog: Prediabetes: A Tool for Change
Credit: Andy Duback Robert Gramling is the Holly and Bob Miller Chair in Palliative Medicine at the University of Vermont Larner College of Medicine. In a new paper, Gramling and his colleagues show how machine learning can be used to better understand conversations about death and dying, which could help healthcare providers improve their end-of-life communication. Newswise — Some of the most important, and difficult, conversations in healthcare are the ones that happen amid serious and life-threatening illnesses. Discussions of the treatment options and prognoses in these settings are a delicate balance for doctors and nurses who are dealing with people at their most vulnerable point and may not fully understand what the future holds. Now researchers at the University of Vermont’s Vermont Conversation Lab have used machine learning and natural language processing to better understand what those conversations look like, which could eventually help healthcare providers improve their end-of-life communication. “We want to understand this complex thing called a conversation,” says Robert Gramling, director of the lab in UVM’s Larner College of Medicine who led the study, published December 9 in the journal Patient Education and Counselling. “Our major goal is to scale up the measurement of conversations so we can re-engineer the healthcare system to communicate better.” Gramling and his colleagues wanted to understand the types of conversations that people have around serious illness, to identify the common features they have and determine if they follow common storylines. To do this they borrowed the techniques used in the study of fiction, in which machine learning algorithms analyze the language of fiction manuscripts to identify different types of stories. Gramling’s team adapted this method to analyze 354 transcripts of palliative care conversations collected by the Palliative Care Communication Research Initiative, involving 231 patients in New York and California. They broke each conversation into 10 parts with an equal number of words in each, and examined how the frequency and distribution of words referring to time, illness terminology, sentiment, and words indicating possibility and desirability changed between each decile. “We picked up some strong signals,” says Gramling. Conversations tended to progress from talking about the past to talking about the future, and from sadder to happier sentiments. “There was quite a range, they went from pretty sad to pretty happy,” says Gramling. The discussions also progressed from talking about symptoms at the beginning of the conversation, to treatment options in the middle and the prognosis at the end. And the use of modal verbs – words like “can”, “might”, and “will” that refer to probability and desirability – also increased as the conversation went on. “At the end there was more evaluation than description,” says Gramling. The consistent results across multiple conversations show just how much people make meaning out of stories in healthcare, says Gramling. “What we found supports the importance of narrative in medicine,” he says. More practical applications of the work are still some way off, says Gramling. For now, his team is focused on using it as a tool to identify the different types of conversations that can occur in healthcare. “I think this is going to be a potentially important research tool for us to begin fostering an understanding of a taxonomy of conversations that we have so that we can begin to learn how to improve upon each one of those types,” he says. That knowledge could eventually help healthcare practitioners understand what makes a “good” conversation about palliative care, and how different kinds of conversations might require different responses. That could help create interventions that are matched to what the conversation indicates the patient needs the most. “One type of conversation may lead to an ongoing need for information, while another may have an ongoing need for functional support,” says Gramling. “So one of the ways those types can help us is to identify what are the resources we are going to need for individual patients and families so that we’re not just applying the same stuff to everybody.” A deeper understanding of these conversations, which are often freighted with emotion and uncertainty, will also help reveal what aspects or behaviors associated with these conversations are more valuable for patients and families. That will allow educators to target their training of healthcare professionals to provide the skills needed in palliative care. Gramling says perhaps the most useful application of the work would be at a systemic level that could monitor how hospitals respond to patients in aggregate – and reward those that allow patients to express and deal with their fears in a better way with more funding. “We already measure other processes of clinical care, we just don’t do it routinely for actual communication,” he says.
Credit: University of Michigan The expansion of Medicaid in Michigan included special emphasis on health risk reduction and prevention, including financial incentives. Two new studies look at the impacts. Newswise — When the state of Michigan expanded its Medicaid program to provide health coverage to more low-income residents, its leaders built special features into the plan, different from most states. They wanted to encourage enrollees to understand their individual health risks, and incentivize them to prevent future health problems, or find them early. According to two new studies, that effort has paid off. The percentage of enrollees in the Healthy Michigan Plan who saw a primary care doctor in a given year doubled, and many of those visits included a discussion of healthy behaviors that could improve their long-term health, the studies show. Half of the enrollees said they completed the Healthy Michigan Plan “health risk assessment” questionnaire and went over it with a physician. A majority of enrollees got preventive care, such as cancer screenings or dental visits. It appears that the special financial incentives that the state built into the program played only a partial role in completion of the health risk assessment. In fact, many of the enrollees didn’t even know they could get a cost-sharing discount by filling it out and discussing it with their doctor. The new findings appear in two papers published in the Journal of General Internal Medicine by several members of the Healthy Michigan Plan evaluation team from the University of Michigan Institute for Healthcare Policy and Innovation. A focus on primary care and prevention The studies are based on results from a survey of more than 4,000 Michiganders, out of the more than 1 million who have gotten coverage from the Healthy Michigan Plan since its launch in 2014. The program currently covers more than 642,000 state residents who make less than about $16,000 a year for an individual, or $33,000 for a family of four. Among those surveyed, over two-thirds are working, going to school, retired or unable to work. “Customizing Medicaid expansion to emphasize primary care and prevention took extra effort, but appears successful, at least according to the snapshot of enrollees that these data represent,” says Susan Dorr Goold, M.D., MHSA, M.A., the lead author of one of the two papers and a professor of internal medicine at U-M. Former IHPI National Clinician Scholar Taylor Kelley, M.D., M.P.H., M.Sc., now at the University of Utah, notes, “While too early to tell whether the program will lead to sustained behavior change, it is clear more conversations are happening between doctors and patients about lifestyle change, and patients have been surprisingly eager to commit to healthy behaviors.” Kelley is lead author of the other of the two papers. “The role of primary care providers, and their teams, in helping low-income and working-poor people understand what health risks they face, and encouraging them to modify the risk factors they can change, is crucial,” says Renuka Tipirneni, M.D., M.Sc., senior author of the paper led by Kelley and an assistant professor of internal medicine. Goold, Kelley, Tipirneni and many of their co-authors have been part of the IHPI team that is carrying out the official evaluation of the Healthy Michigan Plan for the Michigan Department of Health and Human Services. The team surveyed 4,090 HMP participants between the ages of 19 and 64 years who had been enrolled in the program for more than a year, using their preferred language of English, Spanish, or Arabic. The survey was carried out in 2016, and claims data were also used to examine enrollees’ use of health care services. Some of their key findings: Insurance status: Nearly 58% of those surveyed had not had health insurance in the year before they enrolled in HMP, and half of the rest said they had previously had insurance through Medicaid or another state program. One-third said they hadn’t gotten care they needed in the 12 months before enrolling, mostly because of cost or a lack of insurance coverage. Nearly two-thirds of this subgroup said they’d gone without dental care they needed. Nearly 90% said that having HMP coverage had reduced their stress and worry; those who had been uninsured before they obtained HMP coverage were even more likely to say so. Where they received care: One in five enrollees said they hadn’t had a primary care visit in the five years before their HMP coverage began, and only two-fifths had seen a primary care provider in the year before they enrolled in HMP coverage. Nearly 90% of enrollees had seen a primary care provider since enrolling, and nearly 95% of those enrollees said they had discussed wellness and prevention as part of a primary care visit. Ninety-two percent said that they now had a regular source of medical care, compared to under 73% before they were covered by HMP. The percentage who said that their regular source of care was an emergency room or urgent care center dropped from 25.3% before enrollment, to 7% after they enrolled in HMP. Getting covered didn’t automatically mean access to care: 15% said that despite their HMP coverage, they had still gone without needed care in the past 12 months, for varied reasons including costs and their health plan’s coverage provisions. 59% said their HMP coverage had helped them get access to prescription drugs, and 46% said it had helped them get access to dental care. Health risk assessments Half of enrollees said they had completed a health risk assessment, or HRA. Nearly four-fifths of those who completed an HRA chose to work on a healthy behavior, and the percentage was even higher among those with chronic illnesses. More than half of them chose to work on eating healthier and/or exercising more. Nearly a fifth of those who chose a healthy behavior to work on said they would try to stop smoking, that percentage was even higher among those with a mental health condition or substance use disorder. Only 31.5% of enrollees said that completing the HRA hadn’t been helpful because they already knew what they needed to do to improve their health. Nearly half of those who completed an HRA said they did it because their primary care provider had encouraged it. Only 2.5% said that the promise of a monetary reward spurred them to complete an HRA, and only 28% said they had known that they could get a reduction in the amount they would have to pay. Preventive health care More than 70% of the women over 50 had received breast cancer screening in the past 12 months under HMP, and more than half of adults over 50 had received colon cancer screening. Cancer screenings, and other proven preventive screenings and vaccinations, are covered by the Healthy Michigan Plan with no co-pay. Sixty percent of enrollees had seen a dentist in the past year through their HMP coverage. More than 10% of enrollees who reported using tobacco had gotten a prescription for an FDA-approved product to help them break their nicotine habit. Those who knew that preventive health services were available at no cost to them were more likely to receive them. But knowledge that completing an HRA could reduce their fees didn’t increase use. For more about these and other results from the IHPI evaluation of the Healthy Michigan Plan, visit http://michmed.org/YljdZ For more about the Healthy Michigan Plan, visit https://www.michigan.gov/healthymichiganplan In addition to Goold and Tipirneni, the authors of the papers include Jeffrey Kullgren, M.D., M.S., M.P.H., the senior author of the paper led by Goold and an assistant professor of internal medicine. Other authors of one or both papers include IHPI director John Z. Ayanian, M.D., M.P.P., and U-M faculty and staff Tammy Chang, M.D., M.P.H., M.S., Minal Patel, Ph.D., M.P.H, Matthias A. Kirch, M.S., Corey Bryant, M.S., Erin Beathard, M.P.H., M.S.W., Erica Solway, Ph.D., M.P.H., M.S.W., Sunghee Lee, Ph.D., M.S., Sarah J. Clark, M.P.H., , as well as former U-M Preventive Medicine resident Eunice Zhang, M.D., M.P.H., former HMP evaluation team member Jennifer Skillicorn, Dr.P.H., M.P.H. and community consultant Zachary Rowe, BBA, the executive director of Friends of Parkside, a non-profit community-based organization in Detroit. References: Journal of General Internal Medicine: Kelley et al: https://rdcu.be/bYEwb , DOI: 10.1007/s11606-019-05562-x; Goold et al: https://rdcu.be/bYbFu, DOI:10.1007/s11606-019-05370-3
Wesley LaBarge Credit: UAB Newswise — BIRMINGHAM, Ala. – The dream of tissue engineering is a computer-controlled manufacturing of complex and functional human tissue for potential organ regeneration or replacement. University of Alabama at Birmingham biomedical researchers have found a way to speed that tissue creation using a novel bioprinter built for $2,000, they report in the journal Micromachines. Building blocks for the tissue are pre-grown spheroids of human induced-pluripotent stem cells that contain 200,000 cells per spheroid. The first commercial bioprinter from Japan builds tissue one spheroid at a time, placing the spheroids on metal pins that can be removed after the growing cells expand and fuse into tissue. The UAB approach could increase the efficiency of that scaffold-free bioprinting by as much as a hundred-fold. The key? The UAB proof-of-concept bioprinter picks up multiple spheroids at the same time and places them simultaneously on a matrix of pins. The UAB prototype used a 4-by-4 matrix of 16 pins, so 16 spheroids could be placed at once, with a cycle speed of 45 seconds. A video, which does not include the reservoir of spheroids, shows how one cycle works. The machine, about the size of a toaster, fits easily in a biosafety hood and its parts can be sterilized by autoclave or ethylene oxide. The machine has three main components. First is a spheroid bath stage that holds a watch glass with a concave bottom. Pre-grown spheroids sit in that reservoir, and the shape settles them into the center of the vessel. For loading, the stage swings into place underneath second main part, the print head. The print head has 16 holes arranged in the shape of a needle matrix at the bottom of the bioprinter. The head dips into the reservoir, and a vacuum pump pulls spheroids onto each of the holes. The head, carrying the spheroids, then lifts, the stage swings away and the head descends to that third main part, the needle-array bath. At the tips of the 16 needles, the print head slowly pushes the spheroids onto the needles. The vacuum is released, freeing the spheroids from the print head, which then rises for another cycle. In development of the prototype, glass beads were used first to measure the spheroid pick-up efficiency for the vacuum pump-print head. Then, alginate beads were used to test the bioprinter’s ability to correctly print onto the needle array. Finally, as proof-of-concept, pre-grown spheroids of human induced-pluripotent stem cells were used to confirm the ability of the bioprinter to place an array of cellular spheroids onto the array. The UAB bioprinter effectively aspirated and transferred a single layer of cellular spheroids onto the needles. “This novel, layer-by-layer scaffold-free bioprinter is efficient and precise in operation, and it can easily be scaled to print large tissues,” said Jianyi “Jay” Zhang, M.D., Ph.D., who led the research and is corresponding author. “Having the ability to build larger, more clinically relevant tissues in a shorter length of time using this method would be very beneficial for various fields of medicine and clinical research.” At UAB, Zhang is chair and professor of the UAB Department of Biomedical Engineering and holder of the T. Michael and Gillian Goodrich Endowed Chair of Engineering Leadership. First author of the paper, “Scaffold-free bioprinter utilizing layer-by-layer printing of cellular spheroids,” is Wesley LaBarge, a UAB Ph.D. candidate in biomedical engineering. Co-authors with LaBarge and Zhang are Andrés Morales, UAB School of Engineering, Department of Mechanical Engineering; and Daniëlle Pretorius, Asher M. Kahn-Krell and Ramaswamy Kannappan, UAB Department of Biomedical Engineering. Biomedical Engineering at UAB is a joint department of the School of Engineering and the UAB School of Medicine. Support came from National Heart, Lung, and Blood Institute grants HL114120, HL131017 and HL134764; and from American Heart Association predoctoral fellowship grant 19PRE34380484 and scientist development grant 17SDG33670677.
Researchers in the pediatrice ICU at Children's Mercy Hospital found that holding infants intubeded for acute respiratory failure was well tolerated and save, with no unplanned extubations and no changes in vital signs. New research published in Critical Care Nure finds holding intubated infants in the PICU was well tolerated, without an increase in adverse events. Newswise — Critically ill infants who are old enough to move on their own but too young to cooperate with care instructions have been among the last to benefit from patient mobility initiatives. Results from a holding intervention in the pediatric intensive care unit (PICU) at Children’s Mercy Hospital, Kansas City, Missouri, may help change that. Concerns for patient safety and medical device removal, lack of resources and disagreement about when patients are sufficiently stable are among the barriers to mobility interventions in the PICU, especially for infants. The researchers addressed many of these barriers as part of a study of a holding intervention of infants intubated for acute respiratory failure. They found that holding intubated infants was well tolerated and safe, with no unplanned extubations and no changes in vital signs in 158 holding episodes. The study, “Early Mobilization of Infants Intubated for Acute Respiratory Failure,” is published in the December issue of Critical Care Nurse (CCN). Co-author Laura Ortmann, MD, conducted the study during her residency at Children’s Mercy. She is now an assistant professor of pediatrics at Children’s Hospital and Medical Center Omaha in Nebraska. “By the time we completed the 16-month study, the practice of holding infants in the PICU was no longer a rare occurrence and had expanded to a wide variety of other critically ill infants, including newborns recovering from surgical procedures for complex congenital heart disease,” she said. Although the effects on parents were not directly examined in this study, nurses reported that the biggest impact appeared to be on the parents’ moods, which led nurses to encourage holding by parents beyond the study protocol. Early mobility has been increasingly integrated into the care of critically ill patients from neonatal preterm infants to adults, but it’s been slower to gain acceptance for the youngest PICU patients. Infants intubated in the PICU do not have access to their normal calming mechanisms and frequently require sedation to treat agitation and prevent extubation. In the study, patients were screened daily to identify infants intubated for acute respiratory failure secondary to either viral or bacterial lower respiratory tract disease with an expected duration of mechanical ventilation of greater than 48 hours. Parents/guardians of eligible infants were approached for consent. The enrolled patients were then assessed daily to ensure they met 10 different criteria related to their individual health, including defined levels of inspired oxygen, inspiratory pressure and sedative dosage. On days each patient met intervention criteria, the goal was for the infant to be held a minimum of two times for at least one hour each, but there was no limit to the number of times per day or length of time the infant could be held. The holder could be any family member designated by the parents, or a nursing or research staff member if a family member was not available. Infants were frequently held more often and for longer than the minimums stated in the protocol, with half of the sessions lasting over 90 minutes. Vital signs were not different when the infants were being held, showing that the stimulation of being moved and held was physiologically well tolerated. During the study period, 23 infants were held a total of 158 times. Enrolled infants were eligible for holding on 54% of ventilator days, and the goal of holding infants a minimum of two times on eligible days was accomplished 64% of the time. The results were compared with the medical records from a historical control group matched by age and other measures. There were no differences between the control and intervention groups in duration of intubation, length of stay in the PICU or overall length of hospital stay. Sedative use was significantly different between the two groups, but this likely has more to do with changes in sedation practices than with the holding intervention. The study was limited by a small sample size of infants intubated for primary respiratory failure. The researchers call for further studies that focus on both infant and parental outcomes and that assess higher-acuity patient populations. As the American Association of Critical-Care Nurses’ bimonthly clinical practice journal for high-acuity and critical care nurses, CCN is a trusted source of information related to the bedside care of critically and acutely ill patients. Access the article abstract and full-text PDF by visiting the CCN website at http://ccn.aacnjournals.org.
Researchers encourage states legalizing marijuana to implement poison prevention strategies Newswise — (COLUMBUS, Ohio) – Natural substances with psychoactive effects have been used by people for religious, medicinal and recreational purposes for millennia. Lack of regulation has led to an increase in their availability, especially online. Some psychoactive substances may be appealing to recreational users because of the perception they are safer because they’re “natural.” However, these substances can produce psychedelic, stimulant, sedative, euphoric and anticholinergic symptoms, which are cause for concern. A new study conducted by the Center for Injury Research and Policy and the Central Ohio Poison Center at Nationwide Children’s Hospital found there were more than 67,300 calls to U.S. Poison Control Centers regarding exposures to natural psychoactive substances. The study looked at calls from January 2000 through December 2017, which totaled an average of 3,743 exposures each year, or approximately 10 calls every day. “These substances have been associated with a variety of serious medical outcomes including seizures and coma in adults and children,” said Henry Spiller, MS, D.ABAT, co-author of this study and director of the Central Ohio Poison Center at Nationwide Children’s. The increasing rate of exposures to marijuana accounted for almost half of all natural psychoactive substance exposures and can be attributed, in part, to the increasing number of states that have legalized marijuana for medical or recreational use. “As more states continue to legalize marijuana in various forms, parents and health care providers should treat it like any other medication: locked up, away, and out of sight of children,” said Spiller. “With edibles and infused products especially, curious children are mistaking them for kid-friendly candy or food, and that poses a very real risk for harm.” The study, published online today in the journal Clinical Toxicology, found that most exposures occurred among individuals older than 19 years of age (41%) and 13-19-year-olds (35%). The majority (64%) of cases occurred among males, and 91% occurred at a residence. The substances most commonly involved were marijuana (47%), anticholinergic plants such as jimson weed (21%), and hallucinogenic mushrooms (16%). Kratom, khat, anticholinergic plants, and hallucinogenic mushrooms were the substances with the highest percentages of hospital admission and serious medical outcomes. Despite an increase in the overall rate of exposure to natural psychoactive substances, most substances showed a significant decrease in exposure rate from 2000-2017, except for marijuana (150% increase), nutmeg (64% increase), and kratom. Kratom demonstrated a nearly 5,000% increase from 2011-2017 and accounted for eight of the 42 deaths identified in this study. These findings support the need for increased efforts to prevent kratom-associated morbidity and mortality. Of the 42 deaths identified in this study, seven were among children. Five of the deaths were to 13-19-year-olds and involved anticholinergic plants, hallucinogenic mushrooms, kava kava and marijuana. Both deaths among children 12 years and younger involved marijuana. Similar to previous studies, almost all cases among children younger than 6 years old were primarily exposures associated with exploratory behaviors. Children in this age group are mobile, curious and generally unaware of the potential danger of poisoning. Children younger than 6 years accounted for one-fifth of natural psychoactive substance cases, of which, the majority involved anticholinergic plants and marijuana. Data for this study were obtained from the National Poison Data System, which is maintained by the American Association of Poison Control Centers (AAPCC). The AAPCC receives data about calls to poison control centers that serve the U.S. and its territories. Poison control centers receive phone calls through the Poison Help Line and document information about the product, route of exposure, individual exposed, exposure scenario, and other data. The Central Ohio Poison Center provides state-of-the-art poison prevention, assessment and treatment to residents in 64 of Ohio’s 88 counties. The center services are available to the public, medical professionals, industry, and human service agencies. The Poison Center handles more than 42,000 poison exposure calls annually, and confidential, free emergency poisoning treatment advice is available 24/7. To learn more about the Poison Center, visit www.bepoisonsmart.org. The Center for Injury Research and Policy (CIRP) of The Abigail Wexner Research Institute at Nationwide Children’s Hospital works globally to reduce injury-related pediatric death and disabilities. With innovative research at its core, CIRP works to continually improve the scientific understanding of the epidemiology, biomechanics, prevention, acute treatment, and rehabilitation of injuries. CIRP serves as a pioneer by translating cutting edge injury research into education, policy, and advances in clinical care. For related injury prevention materials or to learn more about CIRP, visit www.injurycenter.org.
Credit: Christina M. Caragine and Alexandra Zidovska, New York University. Human cell nuclei with fluorescently labeled chromatin (green) and nucleoli (red). Newswise — The health of cells is maintained, in part, by two types of movement of their nucleoli, a team of scientists has found. This dual motion within surrounding fluid, it reports, adds to our understanding of what contributes to healthy cellular function and points to how its disruption could affect human health. “Nucleolar malfunction can lead to disease, including cancer,” explains Alexandra Zidovska, an assistant professor in New York University’s Department of Physics and the senior author of the study, which appears in the journal eLife. “Thus, understanding the processes responsible for the maintenance of nucleolar shape and motion might help in the creation of new diagnostics and therapies for certain human afflictions.” Recent discoveries have shown that some cellular compartments don’t have membranes, which were previously seen as necessary to hold a cell together. Researchers have since sought to understand the forces that maintain the integrity of these building blocks of life absent these membranes. What has been observed is the nature of this behavior. Specifically, these compartments act as liquid droplets made of a material that does not mix with the fluid around them—similar to oil and water. This process, known as liquid-liquid phase separation, has now been established as one of the key cellular organizing principles. In their study, the researchers focused on the best known example of such cellular liquid droplet: the nucleolus, which resides inside the cell nucleus and is vital to cell’s protein synthesis. “While the liquid-like nature of the nucleolus has been studied before, its relationship with the surrounding liquid is not known,” explains Zidovska, who co-authored the study with Christina Caragine, an NYU doctoral student, and Shannon Haley, an undergraduate in NYU’s College of Arts and Science at the time of the work and now a doctoral student at the University of California at Berkeley. “This relationship is particularly intriguing considering the surrounding liquid—the nucleoplasm—contains the entire human genome.” Yet, unclear is how the two fluids interact with each other. To better understand this dynamic, the scientists examined the motion and fusion of human nucleoli in live human cells, while monitoring their shape, size, and smoothness of their surface. The method for studying the fusion of the nucleolar droplets was created by the team in 2018 and reported in the journal Physical Review Letters. Their latest study showed two types of nucleolar pair movements or “dances”: an unexpected correlated motion prior to their fusion and separate independent motion. Moreover, they found that the smoothness of the nucleolar interface is susceptible to both changes in gene expression and the packing state of the genome, which surrounds the nucleoli. “Nucleolus, the biggest droplet found inside the cell nucleus, serves a very important role in human aging, stress response, and general protein synthesis while existing in this special state,” observes Zidovska. “Because nucleoli are surrounded by fluid that contains our genome, their movement stirs genes around them. Consequently, because the genome in the surrounding fluid and nucleoli exist in a sensitive balance, a change in one can influence the other. Disrupting this state can potentially lead to disease.” This research was supported by grants from the National Institutes of Health (R00-GM104152) and the National Science Foundation (CAREER PHY-1554880, CMMI-1762506).
Can nutraceuticals help combat diabetes? Newswise — Every five minutes, someone in Australia is diagnosed with diabetes. It’s Australia’s fastest growing chronic condition, but as its prevalence grows more people are adding dietary supplements to their diets in the hope of reducing their risk of the disease. But how effective are dietary supplements? In a new study from the University of South Australia, researchers have examined the efficacy of some of the most commonly used supplements (‘nutraceuticals’) to manage diabetes and its risk factors. The review found that the nutraceuticals resveratrol (a compound from grapes), curcumin (from turmeric) and cinnamon were all effective in combatting various elements of diabetes, including regulating glucose, improving insulin resistance and reducing cholesterol. Diabetes is a chronic condition marked by high levels of glucose in the blood. While Type 1 diabetes cannot be prevented, Type 2 diabetes is most common and preventable in up to nearly 60 per cent of cases by maintaining a healthy weight, being physically active and following a healthy eating plan. The World Health Organization estimates that 422 million people (or one in 11) have diabetes, costing $986 billion in global health expenditure each year. In Australia, approximately 1.7 million people have diabetes, costing the economy an estimated $14.6 billion a year. With complications causing blindness, heart disease and amputations, it’s the biggest challenge confronting Australia’s health system. UniSA researcher, Dr Evangeline Mantzioris says it’s important to recognise the role nutraceuticals have in modern society, especially given their popularity among consumers. “More than 40 per cent of Australian adults regularly use dietary supplements to enhance and improve their diets,” Dr Mantzioris says. “They’re easily available, accessible and affordable, and unlike pharmaceuticals, they don’t need a prescription, making them extraordinarily popular. “The challenge is, however, knowing which nutraceuticals will deliver on their promises. “Our research sought to establish the effectiveness of the most popular types of nutraceuticals, and for diabetes, nutraceuticals that used the active ingredients cinnamon, curcumin or resveratrol were all effective, but in different ways. “We found cinnamon can reduce fasting blood glucose levels in type 2 diabetes; curcumin can improve insulin resistance in pre-diabetic and Type 2 diabetes, and resveratrol can reduce glucose levels and improve insulin resistance. “We also tested the efficacy of nutraceuticals on obesity, a key risk factor for diabetes, and, despite all the hype, none had any significant impact for weight loss.” Dr Mantzioris says while nutraceuticals have their place, a healthy diet and lifestyle is the most important factor influencing health. “People should invest in a diet filled with whole foods – vegetables and fruits, cereals, lean meats, fish, eggs, nuts and seeds, as well as dairy foods – as recommended by the Australian Guide to Healthy Eating. This should provide them with enough of the nutrients essential for good health. “However, if you are considering nutraceuticals to manage or prevent diabetes, we always recommend speaking with your doctor. “Nutraceuticals may have a place in healthcare, but there is still a lot we need to learn about them.”
Newswise — November 19, 2019 – Three models of off-site integrated care can help to meet the growing need for mental health services in children and adolescents, according to a report in the November/December issue of Harvard Review of Psychiatry. The journal is published in the Lippincott portfolio by Wolters Kluwer. Led by Andrea E. Spencer, MD, of Boston University School of Medicine and Rheanna E. Platt, MD, MPH, of Johns Hopkins University School of Medicine, the researchers analyzed available evidence on direct and remote approaches to integrating mental health care services with primary care for children. "Off-site interventions are feasible, acceptable, and often adopted widely with adequate planning, administrative support, and interprofessional communication," the researchers write. Off-Site Approaches to Pediatric Mental Health Care – What's the Evidence? Up to 20 percent of children have a psychiatric disorder, highlighting a "large and growing gap" between the need for and availability of pediatric mental health care. Integrating mental health services with primary care is a promising strategy for increasing access to pediatric mental health care. But for several reasons, it's difficult to "co-locate" qualified metal health providers (MHPs) at primary care practices or clinics. Off-site integration – referring to various types of partnerships between primary care practices and specialty MHPs – may offer advantages over on-site integration. The new report provides an overview of available evidence on emerging approaches to off-site integration of mental health care services for children and adolescents. In a scoping review of the evidence, Drs. Spencer and Platt and colleagues identified 39 papers reporting on 24 off-site integrated pediatric mental health and behavioral care programs. The researchers analyzed three categories of programs: Direct in-person models – In-person evaluations performed at specialty agencies, coordinated through primary care. Most of these programs involved partnerships between primary care sites and existing mental health agencies. Direct remote models – Remote evaluations of children with mental health or behavioral issues using technology: telepsychiatry approaches using videoconferencing or telephone calls. Indirect remote models – Real-time telephone consultations between primary care practitioners and MHPs – usually child and adolescent psychiatrists. On analysis of implementation outcomes, all three models were well used and well accepted by providers and families. Programs with strong communication, timely and reliable specialty services, additional support after the initial evaluation, standardized care approaches, and ongoing support were better accepted by primary care practitioners. Programs with adequate planning and ongoing administrative support had better feasibility, adoption, and penetration. Off-site integrated care seemed more appropriate for some groups of patients, such as those with less-complicated attention-deficit/hyperactivity disorder, depression, or anxiety; but less so for others, including preschool-aged children and those with conduct disorders. "Funding and adequate reimbursement were barriers to sustainability in all models." the researchers add. "[O]ff-site pediatric integrated behavioral health programs...have the potential to expand integrated care without substantial infrastructure changes and to reach a broader population of patients than on-site programs," Drs. Spencer and Platt and coauthors conclude. They emphasize that further studies testing guidelines, protocols, and application of integrated care models in specific groups of patients will be needed for successful future expansion of these programs. Click here to read "Implementation of Off-Site Integrated Care for Children" DOI: 10.1097/HRP.0000000000000239 ### About the Harvard Review of Psychiatry The Harvard Review of Psychiatry is the authoritative source for scholarly reviews and perspectives on a diverse range of important topics in psychiatry. Founded by the Harvard Medical School Department of Psychiatry, the journal is peer reviewed and not industry sponsored. It is the property of Harvard University and is affiliated with all of the Departments of Psychiatry at the Harvard teaching hospitals. Articles encompass major issues in contemporary psychiatry, including neuroscience, epidemiology, psychopharmacology, psychotherapy, history of psychiatry, and ethics. About Wolters Kluwer Wolters Kluwer (WKL) is a global leader in professional information, software solutions, and services for the clinicians, nurses, accountants, lawyers, and tax, finance, audit, risk, compliance, and regulatory sectors. We help our customers make critical decisions every day by providing expert solutions that combine deep domain knowledge with advanced technology and services. Wolters Kluwer reported 2018 annual revenues of €4.3 billion. The group serves customers in over 180 countries, maintains operations in over 40 countries, and employs approximately 18,600 people worldwide. The company is headquartered in Alphen aan den Rijn, the Netherlands. Wolters Kluwer provides trusted clinical technology and evidence-based solutions that engage clinicians, patients, researchers and students with advanced clinical decision support, learning and research and clinical intelligence. For more information about our solutions, visit http://healthclarity.wolterskluwer.com and follow us on LinkedIn and Twitter @WKHealth. For more information, visit www.wolterskluwer.com, follow us on Twitter, Facebook, LinkedIn, and YouTube.
Credit: Vanderbilt University Medical Center Myrick “Ricky” Shinall Jr., MD, PhD, an assistant professor and general surgeon at Vanderbilt University Medical Center Newswise — Even a minor surgery such as a laparoscopic gallbladder removal can prove to be a high-risk and even fatal procedure for frail patients, according to new research published in JAMA Surgery. A team of researchers from leading U.S. academic medical centers and VA medical centers examined the records of 432,828 patients who underwent a non-cardiac surgical procedure. They found that patients who were classified as frail or very frail had substantially higher mortality rates after surgeries with low and moderate operative stress, with up to 43% dying after moderate stress procedures such as laparoscopic cholecystectomy (minimally invasive gallbladder removal). “It’s been established that frailty is a strong predictor of complications and death related to surgery, but what we learned in this study is that frail patients have alarmingly high rates of postoperative death, no matter how minor the surgical procedure,” said lead author Myrick “Ricky” Shinall Jr., MD, PhD, an assistant professor and general surgeon at Vanderbilt University Medical Center (VUMC). “A laparoscopic cholecystectomy is one of the most common operations I do as a general surgeon, and this has really given me pause to think that for frail to very frail patients — about 10% of our sample — this is a big deal. Our data indicate that there are no ‘low-risk’ procedures among frail patients.” In layman’s terms, frailty is a vulnerability to becoming sick from even minor stress when the body has lost the ability to recover, said Shinall. It is typically measured before surgery by a clinical tool known as the Risk Analysis Index (RAI). With the RAI, several symptoms are assessed such as unintentional weight loss, shortness of breath, weakness, and difficulties with daily activities like walking, eating or bathing. The study’s investigators pulled patient medical records for a four-year period from the VA Surgical Quality Improvement Program (VASQIP) database, a representative sample of all surgeries conducted across the country in the Veterans Health Administration. Data included patient information for a minimum of one year following surgery, and the patients’ postoperative mortality was noted at 30, 90 and 180 days. Past research related to frail patients and surgery has largely focused on small groups undergoing high-risk procedures, but the current study had a large sample size and included a range of procedures grouped according to how much operative stress they cause. Because no tool to consistently measure operative stress existed, an Operative Stress Score (OSS) was created by the study investigators. Surgeries from the patients’ cases were then sorted into five categories of physiologic stress, ranging from the lowest (OSS1) to the highest (OSS5). Of the study’s patient sample, 8.5% were classified as frail, and 2.1% were very frail. The 30-day mortality rates for frail patients undergoing the lowest stress operations and moderate stress operations were 1.55% and 5.13%, both exceeding the 1% mortality rate often used to define high-risk surgery. For very frail patients, 30-day mortality rates after the lowest and moderate-stress procedures was even higher at 10.34% and 18.74%. For frail and very frail patients, mortality continued to rise at 90 days and 180 days after surgery, reaching as high as 43% for very frail patients 180 days after moderate-stress operations. “This leads us to recommend that pre-surgical frailty screenings should be done universally, even for procedures known to cause low to moderate physiological stress, and frail patients and their families should be counseled about the greater risk of undergoing even minor surgery,” said corresponding author Daniel Hall, MD, associate professor at the University of Pittsburgh, staff surgeon at the Veterans Affairs Pittsburgh Healthcare System, and core investigator at the VA Center for Health Equity Research and Promotion. “The greatest volume of surgeries performed at hospitals are those that cause moderate operative stress, and it is expected that all procedures at ambulatory surgical centers are considered to be those with a low mortality risk, but clinicians spend little time considering whether or not their patients can actually endure the stress of surgery,” said Shinall. “It is worth pausing to assess every patient to determine whether they are frail, and if they are, taking steps to mitigate the factors contributing to their frailty before a procedure is ever scheduled or re-evaluating whether they should even undergo a procedure at all.” The study was supported by the US Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development (I21 HX-002345 and XVA 72-909 [Hall] and CIN 13-413 [Massarweh]. Additional support was provided by NIH/NIA 5R03AG050930 [Arya], NIH/NCI K12CA090625 [Shinall] and U01 TR002393 [Hall and Shireman].