Culture

HSC professor on team using stem cells to combat COVID-19 pneumonia

image: Dr. Jin relied on his more than 20 years of knowledge about stem cells to work with an international team driven to save lives.

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HSC Fort Worth

When news of the coronavirus emerged from Wuhan, China, Kunlin Jin, PhD, and a team of international researchers quickly joined forces to fight the mysterious disease.

Dr. Jin relied on his more than 20 years of knowledge about stem cells to work with an international team driven to save lives. He used the messaging app WeChat to bridge the distance between his laboratory at The University of North Texas Health Science Center at Fort Worth, and experts in China.

"A lot of people are trying find the answers," said Dr. Jin, who spends most of his time working alongside graduate students on stem cell therapies to fight strokes at the HSC Institute for Healthy Aging.

Dr. Jin and his colleagues used a 21st century solution to address an unfolding pandemic. Instead of finding the next Tamiflu, they started testing whether stem cells can be used to boost a person's immune system to ward off COVID-19 pneumonia.

Dr. Jin said early findings are promising, and their international effort to test this treatment continues as a long-term study with more patients in China.

"I am proud to be part of the team I work with to fight COVID-19," Dr. Jin said. "Our study showed that intravenous infusion of clinical-grade human mesenchymal stem cells is a safe and efficient approach for treating patients with COVID-19 pneumonia, including in elderly patients displaying severe pneumonia."

Dr. Jin and his colleagues worked in real time. He said they had a sense of urgency because the outbreak "posed great threats to global public health."

As part of the experimental treatment, stem cells were injected intravenously into the bloodstream of seven patients in Beijing who were severely sick. Three patients were injected with a placebo, the study states.

The people tested were patients at YouAn Hospital in Beijing, Dr. Jin said. Testing began on Jan. 30, according to the study.

The seven patients who received stem cells were successfully treated and were discharged from the hospital within 14 days, Dr. Jin said. Of the patients who received the placebo, one died, one became severe and the third had Acute Respiratory Distress Syndrome (ARDS).

Before stem cells can be used in the United States to fight the virus, there would have to be clinical trials in this country and approval from the U.S. Food and Drug Administration.

The team's findings will be included in the upcoming April 2020 issue of Aging and Disease." The article is titled: "Transplantation of ACE2-Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia."

As international headlines about the virus evolved, research and clinical colleagues from several countries, including the United States, United Kingdom, South Korea, China and Russia pooled their expertise.

The team is made up of medical researchers who meet at conferences and often discuss science, aging and health-related issues. They work together as part of the International Society on Aging and Disease, which was founded by Dr. Jin.

When coronavirus strikes, it can result in a virus-induced cytokine storm - the term used when the immune system is so triggered that fluids fill the lungs and tissues are damaged.

"This is thought to be one of the main reasons why the COVID-19 pneumonia actually kills an individual - this storm of activity trying to fight the virus," said David P. Siderovski, PhD, Professor and Chair Pharmacology & Neuroscience in HSC's Graduate School of Biomedical Sciences.

"No specific drugs or vaccines are available to cure the patients with COVID-19 infection," according to the journal article. "Hence, there is a large unmet need for a safe and effective treatment for COVID-19 infected patients, especially the severe cases."

Additionally, finding antivirals for patients with COVID-19 is a difficult task, Dr. Siderovski said.

"When HIV broke in the 1980s, we scrambled to make AZT (azidothymidine)," he said, adding that researchers are trying different ideas to combat the virus. "There is a desperate need for anything - anything experimental, anything that could be tried off the shelf to address COVID-19 pneumonia."

Credit: 
University of North Texas Health Science Center

New Yorkers think feds not doing enough for the city and state

image: Perceived risk of catching COVID-19 and number of people who know someone who tested positive.

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CUNY SPH

A majority (56%) of New York City residents did not think the assistance provided by the federal government for NYC and the state as a whole is sufficient to manage the current coronavirus crisis. Only 22% thought assistance was sufficient, with the remaining 23% unsure. The findings are part of the third week of data from a city and statewide CUNY Graduate School of Public Health & Health Policy (CUNY SPH) tracking survey conducted March 27-29.

As social distancing extends under Governor Cuomo's PAUSE order, the number of New Yorkers who reported feeling "not at all" socially connected in the past week rose to 43%, nearly doubling the percentage (22%) of those who felt similarly isolated the previous week.

The strain of the pandemic is taking its toll on the mental health of New York residents; 44% reported feeling nervous, anxious or on-edge more than half the time (at least 3-4 days a week or more often), while 35% reported similar levels of feeling down, depressed, or hopeless.

Health concerns

As the number of confirmed cases in the city and state surged this week, perceived risk of contracting COVID-19 also increased, with well more than half the respondents (55%) thinking they have a high or very high risk of getting sick with coronavirus, compared to 39% the previous week.

Similarly, consistent with the mounting number of confirmed cases, another major shift in the latest tracking survey saw 28% of respondents reporting they personally knew someone who tested positive for coronavirus, double the result (14%) from the previous week.

In an additional a new finding, one in eight New Yorkers (12%) reported that someone in their household was sick at home with symptoms of COVID-19. This was even higher among respondents in the 18-29 age group, with nearly one in six (15.9%) reporting someone sick at home with a fever or other symptoms.

"We continue to see a generational divide in our tracking survey," said Scott Ratzan MD, distinguished lecturer at CUNY SPH and editor in chief, Journal of Health Communication. "Younger New Yorkers believe they have a significantly higher chance of getting sick than their older counterparts, and this finding has been consistent for the last three weeks."

"As older people are most likely to suffer serious health consequences from COVID-19, we would expect them to be most concerned about their risk," Dr. Ratzan explained. "It may be that our public health communication on risk and consequences of getting COVID-19 are not reaching older people adequately."

The pandemic is impacting the healthcare of New Yorkers in ways unrelated to the COVID-19 illness. More than a third (35%) of respondents reported the cancellation of medical care for other health problems due to the epidemic, and almost one respondent in 10 (9%) reported losing their health insurance as a result of virus-related job loss.

Economic concerns

Job loss is an escalating problem, with 36% in the city reporting that someone in their household had lost their job as a result of the virus, almost a 25% increase over the job loss of 29% reported in the previous week. Job losses continued to affect the Hispanic community disproportionately, with 46% reporting a household job loss. Women (42%) were more affected by job loss than men (29%), a significantly different finding from last week's survey results. Lower income (less than $50,000) workers were almost twice as likely to report household job loss at 41%, than the highest earners (more than $100,000), 24% of whom reported job loss.

"It is clear that the economic burden of coronavirus is falling disproportionately on the people in our city who are least able to afford it," said Dr. Ayman El-Mohandes, dean of CUNY SPH. "It remains to be seen how well we can address these disparities."

More than two in five New Yorkers (44%) say they are concerned about their housing situation; 27% said they would not be able to pay next month's rent and 17% said they could not meet next month's mortgage payment. A substantial majority (59%) of those unable to pay rent fear they will be evicted.

About a third of residents (33%) are considering moving out of the city, with 12% saying they would move within New York state and 21% considering moving out of state, a troubling finding considering the current importance of people staying at home as much as possible. Two-thirds (67%) said they were not considering moving out of the city.

Other key findings

Despite respondents reporting an increased perception of the likelihood of contracting the virus, only 22% of respondents sought healthcare or advice from a health professional about coronavirus this past week, down by one-third from the two previous weeks, when 34% reported seeking medical care or advice.

There was an increase in those who said they were tested, with 5% reporting they had a nasal or throat swab performed by a medical professional; about one-fourth of those tested reporting testing positive for the virus.

A majority (62%) of New York City residents said they would take a vaccine for coronavirus right now if it were available; 19% would not and an additional 19% were unsure.

A majority (56%) think that asking New Yorkers who leave the state to self-quarantine for two weeks is helpful in containing the spread, 23% are unsure and 21% think it is not helpful.

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CUNY Graduate School of Public Health and Health Policy

How stress remodels the brain

image: The branches of astrocytes retract from synapses 3 hours after stress and remain retracted for 24 hours.

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Bender et al. JNeurosci 2020

Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Stress harms the brain and body in profound ways. One way is by altering astrocytes, the brain's housekeepers tasked with mopping up neurotransmitters after they've been released into the synapse. On the cellular level, stress causes the branches of astrocytes to retract from the synapses they wrap around.

Bender et al. investigated what controlled astrocyte changes after mice experienced exposure to the urine of a fox, their natural predator. This single stressful event caused quick but long-lasting retraction of the astrocyte's branches. Stress induces this change by halting the production of GluA1, an essential subunit of glutamate receptors. During a stressful event, the stress hormone norepinephrine suppresses a molecular pathway that normally culminates in the protein synthesis of GluA1. Without functional GluA1 or glutamate receptors, neurons and astrocytes lose their ability to communicate with each other.

Credit: 
Society for Neuroscience

How we perceive close relationships with others determines our willingness to share food

LAWRENCE -- In the midst of a global pandemic, a lot of people rightly will be reluctant to offer food from their plate to another person, or accept such an offer due to the fear of contamination.

But for people with "attachment avoidance," a psychological term for reluctance to form close personal relationships, this was true long before anybody had heard the term "COVID-19."

"When we share food, it shows trust -- it shows we're willing to give up some of our resources, and it shows we want to get close with someone," said Omri Gillath, professor of psychology at the University of Kansas. "Think about the psychological aspect of comfort food. When people are feeling down, when they're upset, when they're stressed, food is a source of comfort. We think in part this is because of the connection between food and love. If you think about breastfeeding, babies are getting both the food and the nutrition they need, and the warmth and love from their mom, this creates a strong connection between food and love."

Gillath is a co-author of a new paper, led by KU doctoral student Sabrina Gregersen, that examines the links between food-sharing and styles of attachment. It was just published in the peer-reviewed journal Appetite.

"'Attachment' is a theory that explains how people bond to each other and how they regulate their emotions," Gillath said. "People have an attachment style based on early interactions with their primary caregivers -- parents usually. The three main styles are secure, anxious and avoidant. If you have parents that were supportive and sensitive and find a good balance between helping you on the one hand and providing autonomy on the other, you're more likely to be secure. If you had parents that were insensitive and intrusive and weren't consistent about the help they provided, you're more likely to be anxious. And then if you had parents that were cold and rejecting, you are more likely to develop an avoidant attachment style. These differences that people develop pretty early predict a lot of relational behaviors and outcomes."

To see how these attachment styles affected people's food-sharing behaviors, the KU researchers conducted several studies. In one study, participants answered a battery of questions, many of which touched on how food preferences might be tied to romantic or dating behavior for people with various attachment styles. In a different study, participants were placed in a situation where they interacted with another person while one of them had a pack of fruit snacks.

"We brought people to the lab and had them fill out a few questionnaires, then we exposed them to either attachment-security-related cues or control cues," Gillath said. "For example, we asked them to think about a secure relationship, which activated their security-related models. Then we asked them to wait outside in a waiting area. In both studies they happened to meet another 'participant' in that area. In one study, we gave the participant a bag of treats and wanted to see if they would share it, and in the other study, we gave our confederate, who was supposedly another participant, a bag of treats and they offered to share. We wanted to see whether participants would accept the food offering. Many participants were reluctant to take food or give it. However, some people -- those who were exposed to security-related cues -- were more likely to share their treat with a stranger."

From the first study, the researchers found people high on attachment avoidance were less likely to share food or date a potential partner who had dissimilar food preferences. In the second study, they found enhancing attachment security increased the tendency to offer one's food to a fellow participant. In the final study, the team found the tendency to accept food from a fellow participant was positively associated with attachment anxiety, but security priming did not affect this tendency.

Gillath said a better understanding of the links between attachment and food could potentially help inform efforts to extend help to people during the current coronavirus pandemic -- particularly among people with high attachment avoidance, who, the authors wrote, "were less likely to engage in food sharing behaviors with current romantic partners and less likely to cook and eat meals with their partners."

"We could also use the findings to better understand people's tendencies when it comes to prosocial behavior," he said. "Right now, with the coronavirus crisis, trust -- or the lack of -- is a major obstacle. On the one hand, some people don't have food, they don't have a job, they don't have the means to support themselves. On the other hand, there are people who want to help others by giving them food or other resources but are afraid of the consequences. Fear and confusion -- of contamination or starvation -- may lead people to hoard, preventing them from sharing resources -- not giving to those who need them, or buying too much and not leaving to people who also might need -- see the rush to buy toilet paper. How can we fix that? If people aren't taking food because of trust issues, we should ask, 'Are you guys willing to starve (or not getting the right treatment because of your fears)?' I'm not saying we want to make people trust anyone and everyone; however, we do want to reduce anxiety, increase security and facilitate food -- and resource sharing -- in a safe way."

According to Gillath, in a crisis situation sharing and accepting food and other resources could have psychological benefits beyond just making sure people have enough to eat.

"Not having food and feeling insecure about the whole situation is definitely going to increase mental health issues -- whereas having food and having people looking out for you can not only keep people from starving but also potentially help with their mental health and anxieties," he said. "It is in times like these when we need to find a way to come together, reduce anxiety and help each other out. Making people feel secure can help with that."

Credit: 
University of Kansas

TAVR found non-inferior to surgery in broad patient population

Patients who underwent transcatheter aortic valve replacement (TAVR) did not have a higher rate of death at one year compared with those who had their heart valve replaced via open-heart surgery, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

The trial compared approaches to replacing the aortic valve in patients with severe aortic stenosis, a condition in which the valve becomes narrowed, impeding the proper flow of blood. Untreated, aortic stenosis causes breathlessness, fatigue and other symptoms and increases the risk of other heart problems. Traditionally, surgeons have replaced the valve via open-heart surgery, but the less invasive TAVR approach, in which clinicians thread the new valve through a small tube inserted into an artery in the groin, underarm or chest into the aorta and up to the heart, has rapidly become more common in recent years.

Previous clinical trials have found TAVR to be non-inferior or superior to open-heart surgery for various patient groups, but most trials have been limited to medical centers that perform a high volume of procedures or focus on the use of specific types of replacement valves. The new trial involved a broad group of patients who were treated at every medical center that performs TAVR across the United Kingdom.

"The importance of this trial is that it confirms the effectiveness of the TAVR strategy in a real-world setting," said William D. Toff, MD, professor of cardiology at the University of Leicester and the study's lead author. "It wasn't only conducted at the best centers, and it wasn't limited to a particular valve under ideal conditions. This was TAVR as it is in the real world compared with surgery as it is in the real world."

The trial enrolled 913 patients referred for treatment of severe aortic stenosis at 34 U.K. sites from 2014-2018. Half were randomly assigned to receive TAVR and half underwent open-heart surgery. Enrollment was limited to participants age 70 years or older (with additional risk factors) or age 80 years or older (with or without additional risk factors).

Overall, participants were at intermediate to low risk from surgery, with a median Society of Thoracic Surgeons risk score of 2.6% (a score below 3% is considered low risk). However, researchers did not specify a particular risk score cut-off for enrollment. This allowed the trial to evolve along with changes in guidelines and practice regarding TAVR over the course of the study and to reflect physicians' nuanced, real-world approach to considering risk in decision-making rather than taking a formulaic approach, Toff said.

At one year, the rate of death from any cause was 4.6% among patients undergoing TAVR and 6.6% among those undergoing open-heart surgery, a difference that met the trial's pre-specified threshold for non-inferiority of TAVR. Rates of death from cardiovascular disease, stroke and a composite of those two outcomes were similar between the two groups.

Patients who received TAVR had a significantly higher rate of vascular complications, which occurred in 4.8% of TAVR patients and 1.3% of those receiving surgery. TAVR patients were also more likely to have a pacemaker implanted, which was necessary in 12.2% of TAVR patients and 6.6% of those receiving surgery. In addition, patients who underwent TAVR had a higher rate of aortic regurgitation (blood leaking through the valve), a finding that might, in some cases, adversely affect long-term outcomes. Mild aortic regurgitation occurred at one year in 38.3% of patients undergoing TAVR and 11.7% of patients undergoing surgery, while moderate regurgitation occurred in 2.3% of TAVR patients and 0.6% of surgery patients.

On the other hand, patients undergoing TAVR had a significantly lower rate of major bleeding complications, which occurred in 6.3% of TAVR patients and 17.1% of those undergoing surgery. TAVR was also associated with a shorter hospital stay, fewer days in intensive care, and better functional capacity and quality of life measures at six weeks after the procedure. Functional capacity and quality of life were similar between the two groups at one year, however.

Toff said that the results reflect only a relatively short follow-up period, and that longer-term outcomes could reveal important differences. The researchers plan to continue to track outcomes for a minimum of five years.

"I think it's important that we take a measured approach and individualize the decision-making for these patients, factoring in the patient's preference and attitude to risk," Toff said. "The results from our trial and others are encouraging, but patients need to be fully informed and know that the long-term durability of the TAVR valves and the long-term implications of the increased risk of aortic regurgitation are still uncertain."

Credit: 
American College of Cardiology

The desire for information: Blissful ignorance or painful truth?

We live in a time of unprecedented access to information. And in this era of sheltering-in-place around the nation and the globe, the desire for news may be higher than ever - at least for some people. But do we really want all this information, all the time? Some may indeed prefer to think happier thoughts and maintain an (overly) optimistic outlook about the health threat we face. On the other hand, others may prefer not to know what the swings in the market are doing to their retirement savings.

Recent work has found that people at times prefer less information, even when this means they might not be able to make fully informed decisions. However, little is known about the prevalence of such avoidance. Who are the people who choose blissful ignorance over facing reality?

While previous work has looked at isolated decisions, researchers from Carnegie Mellon University, Northwestern and Harvard Universities set out to measure the desire for information across different areas of life. Are some people generally averse to learning information that could be painful, or do most people have some areas of their lives in which they would like to face the truth and others in which they would rather remain uninformed? To address questions such as these, and measure individual preferences for obtaining or avoiding information, they crafted 11 scenarios involving three domains - personal health, finances and other people's perceptions of oneself - in which there was information that could help the respondent to make better decisions but might be painful to learn. For each scenario, over 2,000 respondents indicated whether they would want to receive information or to remain ignorant.

To see the scenarios for yourself and how you compare to others who have responded to the questionnaire, go to this link:

Test Your Own Information Preferences

"Economists have long thought 'the more, the better', when it comes to information," said George Loewenstein, the Herbert A. Simon University Professor of Economics and Psychology at Carnegie Mellon. "This thinking doesn't fully reflect people's complex relationship with information. We wanted to create a way to measure an individual's tendency to pursue or shy away from information."

In one scenario, for example, participants had the option to learn as part of a routine medical exam the extent to which their body had suffered lasting damage from stress: a third of respondents preferred not to learn this information. And if they had gifted their favorite book to a close friend, 1 in 4 participants would rather not learn whether their friend had read and enjoyed the book.

"This work is a first step to understanding the pervasiveness and features of information avoidance in many real-life contexts," said Emily Ho, the lead author of the paper and an incoming assistant research professor at Northwestern University School of Medicine's Department of Medical Social Sciences.

The study showed that the desire to avoid information is widespread, and that most people had at least some domains, be it their health, finances or perception by others, in which they preferred to remain uninformed. The study also showed that the desire for information was consistent over time; those who expressed a preference for avoiding information at one point in time expressed similar preferences when asked again weeks later. Furthermore, how people responded to the hypothetical scenarios predicted real consequential decisions they were presented with to receive or avoid obtaining information.

Although information may feel painful in the moment, such knowledge often leads to better decisions in the future. The researchers found that people who are more impatient are also more likely to avoid learning information, preferring to avoid the prospect of immediate pain rather than make better long-term decisions. Information is also uncertain in that it can be either good news or bad news, and survey respondents who were more willing to take risks with monetary stakes were also more likely to want to learn information, risking bad news for the possibility of good news.

Were certain demographics more information-avoidant than others? "It is tempting to think that people on the opposite end of the political spectrum from you are the ones engaging in information avoidance," said David Hagmann, a fellow at the Harvard Kennedy School and a Carnegie Mellon graduate. "But we find no differences in information avoidance by political ideology, income, gender or - perhaps surprisingly - education. Trading off the potential pain from receiving bad news against the uncertain and delayed benefits from making more informed decisions is something we all seem to do."

Being able to measure people's preferences for obtaining and avoiding information has wide-ranging implications in many areas of public life, from financial decision-making to health interventions. "If there are some individuals who just won't respond to informational campaigns, and you can assess who they are, you might design a different intervention just for them," said Ho. "This can be for reducing an unwanted behavior, such as smoking, or to encourage a positive behavior, such as obtaining a vaccine or exercising regularly. Just as personalized medicine has the promise to revolutionize treatment, so can informational interventions be tailored to take into account an individual's desire for information."

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Carnegie Mellon University

Editorial calls for a precision medicine approach to follow-up of diverticulitis

INDIANAPOLIS -- An editorial challenges physicians and the U.S. healthcare system to reconsider the current "one size fits all" care for diverticulitis and to employ a precision medicine approach to determine which patients should be referred for colonoscopy.

The editorial, by Regenstrief Institute research scientist Thomas F. Imperiale, M.D., the Lawrence Lumeng Professor of Gastroenterology and Hepatology and Eddie Krajicek, M.D., a fellow in gastroenterology, both at Indiana University School of Medicine, highlights what they term "sign posts" to support individualized decision-making and strongly recommends their use.

"While national guidelines equivocate, conventional care is to refer all individuals with diverticulitis for a colonoscopy," said Dr. Imperiale, who is a practicing gastroenterologist. "But employing the tools of health information technology, we can and should consider sign posts - such as the specific nature of the diverticulitis episode, preceding changes in bowel habit or other symptoms, personal and family medical histories, the dates and findings of previous colonoscopies - before making a decision to refer the patient for colonoscopy.

"While an episode of diverticulitis may be a sentinel event that brings someone who may have been avoiding routine screening into the doctor's office and subsequently gets them into the colonoscopy suite, many patients who are automatically referred for a colonoscopy may not need one, which wastes colonoscopy resources. Taking a personalized, precision medicine approach uses healthcare resources wisely and provides better patient care," he said.

If a patient's primary care physician orders a colonoscopy without first asking sign post questions, Dr. Imperiale encourages patients to start a discussion to determine if colonoscopy is necessary.

The editorial, "Colonoscopy After Acute Diverticulitis: From Clinical Epidemiology to Clinical Management. Are We There Yet?" is published in the peer-reviewed journal Gastrointestinal Endoscopy.

What is diverticulitis?

Diverticulitis may follow diverticulosis, one of the most common medical conditions in the United States and other developed countries. Diverticulosis is a condition in which small pouches form and push outward through weak spots in the wall of the colon, the final portion of the intestinal tract. According to the National Institutes of Health, diverticulosis exists in about a third of U.S. adults age 50 or younger and more than half of people older than age 60. When one or more of these pouches becomes inflamed, the condition is called diverticulitis, which causes abdominal pain, usually with fever. A computed tomography (CT) scan of the abdomen is used to diagnose diverticulitis. There is no clear cause and effect relationship between diverticulitis and colon cancer.

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Regenstrief Institute

New research sheds light on potentially negative effects of cannabis

image: Coughing fits, anxiety and paranoia are three of the most common adverse reactions to cannabis, according to a recent study by Washington State University researchers.

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WSU

Coughing fits, anxiety and paranoia are three of the most common adverse reactions to cannabis, according to a recent study by Washington State University researchers.

The researchers surveyed more than 1,500 college students on the type and frequency of adverse reactions they had experienced while using cannabis for their study in the Journal of Cannabis Research. They also collected information on the students' demographics, personality traits, cannabis use patterns and motives for using the drug.

"There's been surprisingly little research on the prevalence or frequency of various adverse reactions to cannabis and almost no research trying to predict who is more likely to experience these types of adverse reactions," said Carrie Cuttler, assistant professor of psychology and an author on the paper. "With the legalization of cannabis in Washington and 10 other states, we thought it would be important to document some of this information so that more novice users would have a better sense of what types of adverse reactions they may experience if they use cannabis."

More than 50% of the study participants reported having experienced coughing fits, anxiety and/or paranoia while using cannabis. On the other end of the spectrum, the three least-common reported reactions were fainting/passing out, non-auditory/visual hallucinations and cold sweats.

The researchers found the most frequently occurring adverse reactions were coughing fits, chest/lung discomfort and body humming, which a subset of the study group reported occurring approximately 30-40% of the time they were using cannabis.

Panic attacks, fainting and vomiting were considered the most distressing of the 26 possible adverse reactions.

"It is worth noting even the most distressing reactions to cannabis were only rated between moderately' and quite distressing," Cuttler said. "This suggests cannabis users do not, in general, find acute adverse reactions to cannabis to be severely distressing."

The least distressing reactions were reported to be body humming, numbness and feeling off balance/unsteady, the researchers found.

The study showed less frequent users are more likely to report negative effects. Additionally, individuals who reported using cannabis to try to fit in with friends, displayed cannabis use disorder symptoms or had anxiety sensitivity--a tendency to imagine the worse possible outcome--were more likely to report adverse reactions as well as experiencing a greater amount of distress.

"Interestingly, we didn't find that quantity of use during a single session predicted very much in terms of whether or not a person was going to have a bad reaction," Cuttler said. "It was the people who smoke on a less frequent basis who tend to have these bad experiences more often."

Moving forward, Cuttler hopes the results of the study will be put to use by doctors, medical cannabis distributors and even bud tenders to give people a better idea of what could go wrong when they get high.

"When you get any other kind of medication, there will be a leaflet or a warning printed on the bottle about the drug's potential side effects," Cuttler said. "There really isn't very much out there on this for cannabis, and we think that it is important for people to have access to this kind of information."

Credit: 
Washington State University

Benefit seen for ticagrelor alone, without aspirin, in patients with ACS

Patients with acute coronary syndrome (ACS) who stopped taking aspirin three months after the insertion of a coronary stent and then took the anti-platelet medication ticagrelor alone for nine months had fewer episodes of bleeding and no increase in heart attacks, stroke or other adverse events caused by blockages in the arteries, compared with patients who took both aspirin and ticagrelor for a year. The research was presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology (ACC.20/WCC).

"This is the first randomized trial to compare ticagrelor monotherapy with dual antiplatelet therapy--the standard of care--exclusively in a population with acute coronary syndrome," said Yangsoo Jang, MD, PhD, professor of cardiology at Yonsei University College of Medicine in Seoul, South Korea, and senior author of the study. "Our findings suggest that for patients with ACS who are treated with stents, ticagrelor monotherapy could be an optimal strategy for reducing bleeding risk without increasing the risk for adverse events caused by arterial blockages."

Most heart attacks and strokes are caused by a blood clot in an artery that's been narrowed by a buildup of fatty deposits, or plaque. ACS is an umbrella term used to describe problems that occur when there isn't enough blood flow to the heart. Examples are heart attack and unstable angina, a condition in which blood clots form, dissolve and form again in an artery carrying blood to the heart.

Blood cells known as platelets help the blood to clot. Both ticagrelor and aspirin stop platelets from forming a clot that can block blood flow. Use of the two drugs together is known as dual antiplatelet therapy, or DAPT. Aspirin, however, also heightens the risk of bleeding, particularly in the gastrointestinal tract.

Stenting, also known as coronary angioplasty or percutaneous coronary intervention, is a minimally invasive procedure in which a flexible tube (catheter) is threaded through an artery under local anesthesia. At the site of the blockage, a tiny balloon at the tip of the catheter is inflated to unblock the artery and a stent, a tiny mesh tube, is inserted to prop it open.

This trial, known as TICO, enrolled 3,056 patients with ACS whose average age was 61 years; 79% were men, 39% were aged over 65 and 27% had diabetes. Everyone received ticagrelor plus aspirin for three months, then the patients were randomly assigned to one of two groups. For nine months, one group continued treatment with ticagrelor and aspirin, while the second group received ticagrelor alone. The study was conducted at 38 centers in South Korea. The primary study endpoint was the combined occurrence of death, heart attack, stroke, a blood clot inside a stent, the need for a second procedure to unblock the same artery or major bleeding (defined as fatal bleeding, bleeding inside the skull or symptomatic internal bleeding) 12 months after stenting.

After a median follow-up of 12 months, 59 patients (3.9%) who had been randomly assigned to ticagrelor alone had a primary-endpoint event, compared with 89 patients (5.9%) who had continued treatment with both ticagrelor and aspirin, a statistically significant difference. This difference was driven by a reduced risk of major bleeding in the group treated with ticagrelor alone (1.7%), compared with the group treated with ticagrelor and aspirin (3%). Rates of other adverse events were similar in the two groups.

A limitation of the study is that patients with an elevated risk for bleeding (defined as aged 80 years or older, having had a stroke within the past year, or having had brain surgery or a traumatic brain injury within the past six months) were excluded, Jang said, adding that such patients account for about 40% of patients undergoing stenting outside of clinical trials.

"Our results cannot be extrapolated to this group of patients," he said.

Credit: 
American College of Cardiology

Psychiatric disorders after first birth reduce likelihood of subsequent children

image: Estimates of the probability of conception leading to subsequent live birth within five years by postpartum psychiatric disorders after first live birth

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Human Reproduction

Women who suffer from psychiatric disorders such as depression, anxiety, mania and schizophrenia following the live birth of their first child are less likely to go on to have more children, according to the first study to investigate this in a large nationwide population.

The study, which is published today (Monday) in Human Reproduction [1], one of the world's leading reproductive medicine journals, found that 69% of women who experienced postpartum psychiatric disorders within the first six months after the birth of their first baby went on to have further children; this contrasts with 82% of mothers who did not experience psychiatric problems.

However, Dr Xiaoqin Liu, a post-doctoral researcher at the National Centre for Register-based Research at Aarhus University (Denmark), who led the study, said: "An important message to women who have a history of severe postpartum psychiatric disorders is that it is possible to prevent relapse. We recommend that they seek help from their family doctors or psychiatrists if they want to have another child, so that plans for treatment that are specific for their individual needs can be made to reduce the risk of relapse, and so that their health, well-being and symptoms can be closely monitored and treated."

Previous research has shown that, overall, around three percent of women develop psychiatric disorders in the first three months after childbirth. These disorders encompass a wide range of mental health problems and usually involve a combination of abnormal thoughts, behaviours and relationships with other people. To date, there has been little research into whether or not this affects women's subsequent reproduction.

Dr Liu said: "We wanted to explore whether women with postpartum psychiatric disorders had a reduced possibility of having a second child. Furthermore, we considered whether a reduction in the live birth rate was due to personal choices or decreased fertility, as these are important issues to consider."

Dr Liu and her colleagues analysed data from Danish registries for 414,571 women who had their first live birth between 1997 and 2015 in Denmark. They followed the women for a maximum of 19.5 years until the next live birth, emigration, death, their 45th birthday or June 2016, whichever occurred first.

They identified women with postpartum psychiatric disorders by seeing if they were given prescriptions for psychotropic medications or had hospital contact for psychiatric disorders during the first six months after the live birth of their first child.

A total of 4,327 (1%) of women experienced psychiatric disorders following the birth of their first child. These women were a third less likely to have a second live birth compared to women who did not experience psychiatric disorders. If the first child died, the difference in subsequent live birth rates disappeared. However, if the psychiatric problem required hospitalisation, the likelihood of a woman having a second child nearly halved and this remained the case irrespective of whether the first child survived or not.

Dr Liu said: "Although fewer women with postpartum psychiatric disorders had subsequent children, it is noteworthy that about 69% of these women still chose to have a second child. For the remaining 31% of women, we need to differentiate the reasons why they did not have another child. If they avoided another pregnancy due to fear of relapse, an important clinical message to them is that prevention of relapse is possible.

"Women whose first child died were nearly four times as likely to have a subsequent live birth as women whose first child survived. These findings suggest that the overall reduced rate of subsequent live births among women who experienced psychiatric disorders after the birth of their first child is, at least in part, voluntary."

The researchers say that other possible explanations for the reduction in the subsequent live birth rate may be that women with postpartum psychiatric disorders are less able to conceive or have more problematic relationships with partners.

"The reason why women with postpartum psychiatric disorders choose to have fewer children needs to be explored further," said Dr Liu.

A limitation of the study is that, although the researchers had an almost complete follow-up of the women through the Danish registries, they did not have accurate information on stillbirths or miscarriages; only pregnancies that led to a live birth were included in the study. Another limitation is that not all women with psychiatric disorders might have received medications or hospital treatment. In addition, it might not be possible to generalise the findings of the study to populations in other countries.

"Denmark offers free and easily available healthcare to all individuals, so we believe our results can inform other, similar populations, although we cannot rule out local differences," concluded Dr Liu.

Credit: 
European Society of Human Reproduction and Embryology

The pros and cons of radiotherapy: Will it work for you?

image: Women are more likely to be cured of cancer with radiotherapy but the side effects are worse.

Image: 
Image by Mark Kostich

Women undergoing radiotherapy for many cancers are more likely than men to be cured, but the side effects are more brutal, according to one of Australia's most experienced radiation oncology medical physicists.

University of South Australia (UniSA) Professor of Medical Radiation, Eva Bezak, says women are generally more sensitive to radiation than men, but this is not considered in international guidelines for radiation dosages.

Current guidelines are generally based on a person's height, weight or BMI, and radiobiological responses of the general population.

In a paper published in Critical Reviews in Oncology/Hematology, Professor Bezak and her colleagues Louis de Courcy from University College Dublin and Professor Loredana Marcu from the University of Oradea in Romania highlight the need for gender to be taken into account when administering radiation.

"It is clear that gender plays a role in the occurrence and response to therapy of many diseases," Professor Bezak says.

"For example, it is already well established that men are more susceptible to head, neck and blood cancers and women are more prone to auto immune diseases as well as developing osteoporosis."

Scientists also know that individual responses to radiotherapy are up to 80 per cent determined by genetics.

So, where do we start with gendered medicine?

"The next step is to ensure that we use both male and female mice even in our pre-clinical testing so we can get a better understanding of how gender influences treatment outcomes.

"It is also important to collect data retrospectively so we can compare the radiotherapy outcomes for men and women who were prescribed radiotherapy for the same cancer."

It is a double-edged coin for men, too. Because they are more radio-resistant than women, their healthy tissues are better protected when receiving radiotherapy with fewer side effects, but their long-term survival rates are shorter.

The differences in radiation responses are highlighted by two major events in history: the Chernobyl nuclear reaction disaster in 1986 and the atomic bombings of Hiroshima and Nagasaki in 1945.

Professor Bezak says following Hiroshima and Nagasaki, the incidence of cancer in Japan was much higher in women (58 per cent) compared to men (35 per cent).

Likewise, after the Chernobyl nuclear accident, millions fewer girls were born to irradiated men and women were at greater risk of endocrine imbalance, thyroid cancer and brain tumours.

The one area that does appear to give women some protection against radiation is the female hormone oestrogen, which has a neuroprotective effect during head irradiation.

"As healthcare becomes progressively more tailored to the individual, gender is a factor that can no longer be disregarded. It needs to be taken into account as an independent prognostic factor," Prof Bezak says.

A video explaining the differences in radiation outcomes between men and women can be viewed at https://youtu.be/BtDniRA7DMs

Credit: 
University of South Australia

Do ER caregivers' on-the-job emotions affect patient care?

image: Linda Isbell is a professor of psychology in the College of Natural Sciences.

Image: 
UMass Amherst

Doctors and nurses in emergency departments at four academic centers and four community hospitals in the Northeast reported a wide range of emotions triggered by patients, hospital resources and societal factors, according to a qualitative study led by a University of Massachusetts Amherst social psychologist.

While they expressed awareness of the possible impact on patient safety, most ER health care providers described strategies they used to regulate their emotions in an effort to keep their feelings from compromising quality of care. The issue of emotion in the ER intensifies as medical workers face additional stresses associated with the Covid-19 pandemic.

"ER providers are on the front line of this pandemic, and stress, anxiety and anger are increasing," says Linda Isbell, professor of psychology in the College of Natural Sciences. "As we all face anxiety about the fallout of this pandemic, anger about a healthcare system that was already stretched thin and under-resourced is likely to grow. It is important to be mindful that these emotions might impact patient care."

Isbell interviewed 86 experienced ER health care providers - 45 physicians and 41 nurses - in what is believed to be the first comprehensive, data-driven study of the triggers and consequences of ER providers' emotions. She collaborated with colleagues at UMass Amherst and the University of Massachusetts Medical School in Worcester for the study published in the journal BMJ Quality and Safety.

The researchers, who carried out the face-to-face interviews between February and August in 2018, say the study highlights the need for emotional intelligence training in healthcare education and a shift in the culture of the medical field to promote meaningful discussion about emotions. "A comprehensive research agenda to understand the role of emotions in patient safety is long overdue," the study concludes.

While patients sparked both positive and negative emotions, hospital and societal/system issues - such as understaffing, overcrowding and limited resources for homeless and mentally ill patients - elicited overwhelmingly negative emotions among the doctors and nurses, according to the study.

"These physicians care deeply about their patients. They're working in a health care system that makes it really hard for them to practice the way they envisioned," Isbell says. "They are asked to handle and solve problems that are incredibly trivial or incredibly serious, and some aren't even medical problems. There is awareness that emotions could influence what they do with the patients," even when the caregivers aren't consciously in touch with their feelings.

Said one ER specialist, "Emotions subconsciously play a role in every single patient and how you work them up, and how you diagnose them, and what you do for them."

In interviews with Isbell, doctors and nurses said encounters with angry, difficult or unreasonable patients may lead caregivers to spend less time at the bedside or to order the types of tests that could resolve the medical issue quickly.

"...I do think it is likely that when you have significantly contentious relationships with patients that ... you don't gain as much data [and to an] extent that could lead to diagnostic error," one doctor stated.

Doctors and nurses said their coping strategies include suppressing or ignoring their emotions when working in the ER, which Isbell says may allow them to perform effectively at the time. "But we know from the emotion literature that's not a good strategy," Isbell says. "It tends to rebound. You may take it out later on your kids or your spouse or dog. It's bad for your body physically and for your mental health."

It may also be bad for the patients. The study calls for further research to help determine whether ED providers' strategies to regulate their emotions are effective at reducing the risk to patient safety.

"Obviously, we need system-wide health care reform, more staffing and more community services for vulnerable populations," Isbell says. "There's a lot of work to be done."

Credit: 
University of Massachusetts Amherst

The value of diagnostic testing for SARS-CoV-2: When, whom, what and how often to test?

Washington, DC - March 27, 2020 - As we enter the second quarter of the COVID-19 pandemic, with testing for SARS-CoV-2 increasingly available (though still limited and slow in some areas), clinicians and public health officials are faced with new questions and challenges regarding testing for this novel virus. Since SARS-CoV-2 is a new virus, there is little evidence to fall back on for test utilization and diagnostic stewardship. New research published in mBio, an open-access journal of the American Society for Microbiology, addresses the potential uses of two main types of tests.

ASM convened a summit of coronavirus experts on Monday, March 23rd, who summarized the value and potential uses of two types of tests for SARS-CoV-2, nucleic acid amplification tests for viral RNA and antibody detection tests. The authors, including ASM CEO Stefano Bertuzzi and ASM President Robin Patel, also spoke at a press conference the following day and offered recommendations and limitations for both types of tests.

Credit: 
American Society for Microbiology

German scientists identify microbe that could help degrade polyurethane-based plastics

There may be a small answer to one of the biggest problems on the planet.

German researchers report in the journal Frontiers in Microbiology that they have identified and characterized a strain of bacteria capable of degrading some of the chemical building blocks of polyurethane.

"The bacteria can use these compounds as a sole source of carbon, nitrogen and energy," said Dr. Hermann J. Heipieper, a senior scientist at the Helmholtz Centre for Environmental Research-UFZ in Leipzig, Germany and co-author of the new paper. "This finding represents an important step in being able to reuse hard-to-recycle PU products."

In 2015, polyurethane products alone accounted for 3.5 million tons of the plastics produced in Europe. Polyurethane is used in everything from refrigerators and buildings to footwear and furniture to numerous other applications that can leverage its lightweight, insulating and flexible properties.

Unfortunately, polyurethane is difficult and energy-intensive to recycle or destroy as most of these kinds of plastics are thermosetting polymers that do not melt when heated. The waste mostly ends up in landfills where it releases a number of toxic chemicals, some of which are carcinogenic.

The use of microorganisms like bacteria and fungi to break down oil-based plastics is an ongoing area of research. However, few studies have addressed biodegradation of polyurethanes like the current paper.

The team out of Germany managed to isolate a bacterium, Pseudomonas sp. TDA1, from a site rich in brittle plastic waste that shows promise in attacking some of the chemical bonds that make up polyurethane plastics.

The researchers performed a genomic analysis to identify the degradation pathways at work. They made preliminary discoveries about the factors that help the microbe metabolize certain chemical compounds in plastic for energy. They also conducted other analyses and experiments to understand the bacterium's capabilities.

This particular strain is part of a group of bacteria that are well-known for their tolerance of toxic organic compounds and other forms of stress, according to Dr. Christian Eberlein with the Helmholtz Centre for Environmental Research-UFZ. He is a co-author on the paper who coordinated and supervised the work.

"That trait is also named solvent-tolerance and is one form of extremophilic microorganisms," he said.

The research is part of a European Union scientific program dubbed P4SB (From Plastic waste to Plastic value using Pseudomonas putida Synthetic Biology), which is attempting to find useful microorganisms that can bioconvert oil-based plastics into fully biodegradable ones. As the name implies, the project has focused on a bacterium known as Pseudomonas putida.

In addition to polyurethane, the P4SB consortium, which includes the Helmholtz Centre for Environmental Research-UFZ, is also testing the efficacy of microbes to degrade plastics made of polyethylene terephthalate (PET), which is widely used in plastic water bottles.

Heipieper said that the first step of any future research on Pseudomonas sp. TDA1 will be to identify the genes that code for the extracellular enzymes that are capable of breaking down certain chemical compounds in polyester-based polyurethanes. Extracellular enzymes, also called exoenzymes, are proteins secreted outside of a cell that cause a biochemical reaction.

However, there is no immediate plan to engineer these or other enzymes using synthetic biology techniques for bioplastic production. That could involve, for instance, genetically converting the bacteria into mini-factories capable of transforming oil-based chemical compounds into biodegradable ones for planet-friendly plastics.

Heipieper said more "fundamental knowledge" like the one gathered in the current study is needed before scientists can make that technological and commercial leap.

One small step at a time.

Credit: 
Frontiers

A new way to study HIV's impact on the brain

Though many negative repercussions of human immunodeficiency virus infection can be mitigated with the use of antiretroviral therapy (ART), one area where medical advances haven't made as much progress is in the reduction of cognitive impacts. Half of HIV patients have HIV-associated neurocognitive disorders (HAND), which can manifest in a variety of ways, from forgetfulness and confusion to behavior changes and motor deficiencies.

To better understand the mechanisms underlying HAND, researchers from Penn's School of Dental Medicine and Perelman School of Medicine and from the Children's Hospital of Philadelphia (CHOP) brought together their complementary expertise to create a laboratory model system using three of the types of brain cells thought to be involved. Led by doctoral student Sean Ryan, who was co-mentored by Kelly Jordan-Sciutto of Penn Dental Medicine and Stewart Anderson of CHOP and Penn Medicine, the model recapitulates important features of how HIV infection and ART affect the brain.

"Frankly the models we generally use in the HIV field have a lot of weaknesses," says Jordan-Sciutto, co-corresponding author on the paper, which appears in the journal Stem Cell Reports. "The power of this system is it allows us to look at the interaction between different cell types of human origin in a way that is more relevant to patients than other models."

In addition to studying HIV, members of the team plan to use the same model to shed light on the neurological mechanisms that underlie other conditions, such as schizophrenia, Alzheimer's, and even normal aging.

"We're collaborating with a variety of colleagues to use this system to study Alzheimer's disease as well as schizophrenia," says Anderson, co-corresponding author on the paper. "We have the components in a dish that we know are interacting in these diseases, and this gives us a new mix-and-match way to understand how certain cells are contributing to neuronal damage."

Indeed, the impetus to create the model grew not out of HIV research but work that Ryan was pursuing in Anderson's lab on schizophrenia.

"We had been looking at the role of microglia, the resident immune cells of the central nervous system," says Ryan, first author on the work. "We wanted to see if we could see the mechanistic changes that occur with microglia in schizophrenia."

To do so, Ryan and Anderson were interested in using human-induced pluripotent stem cells--adult cells that are reprogrammed to resemble embryonic stem cells--which can be coaxed into differentiating into a variety of different cell types.

But schizophrenia is a complicated disease with a variety of contributing genetic and environmental factors and a broad spectrum of presentations. Rather than looking at something complex, they sought to apply their new system to a disease that likewise causes neurological damage but does so in a more dramatic way and in which microglia are also implicated: HIV/AIDS infection.

They reached out to Jordan-Sciutto, who has deep experience investigating the mechanisms of HAND and was eager for the opportunity to develop a model superior to those currently available. Together, the scientists identified the three cell types they were most interested in studying: neurons, astrocytes, and microglia.

Neurons aren't directly infected by HIV but are known to be damaged during infection. Meanwhile astrocytes are believed to interact with neurons, causing damage by sending pro-inflammatory factors into the spaces between cells, called synapses. And microglia, which are responsible for maintaining a healthy environment in the absence of disease, are seen to expand and contribute to inflammation during HIV infection.

After nailing the technical challenge of creating this tractable model in which each cell type is generated independently and then mixed together, the team used it to probe how HIV infection and ART impact the cells, both alone and in combination.

"A lot of people are taking PreEP [pre-exposure prophylaxis] if they're in a situation where their risk of contracting HIV is heightened," says Ryan. "Just as we want to understand the cognitive impacts of HIV, we also want to see whether these drugs alone are impacting the brain health of otherwise healthy people."

The researchers looked at RNA expression in their cultures to get a sense of what proteins and signaling pathways were becoming activated in each scenario. During infection, they saw inflammatory pathways that had previously been implicated in HIV in earlier research. When they introduced the antiretroviral drug EFZ, which is not in common use in the United States but remains a frontline therapy in many other areas of the world, with an infection, the activity of most of these pathways was reduced.

"But this scenario involved its own unique response," says Ryan. Certain pathways associated with inflammation and damage remained despite the introduction of EFZ.

"EFZ treatment of the tri-cultures that included HIV-infected microglia reduces inflammation by around 70%," Ryan says. Interestingly, EFZ by itself also triggered inflammation, though to a lesser extent than infection.

"It seems a combination of infection and ART is creating its own unique response that is different from the sum of its parts," Ryan says. "Knowing what pathways are still active due to ART could help us appropriately target additional therapies so patients don't develop HAND."

Many features of infection seen in the three-cell culture mirror what is known from HIV infection and ART treatment in people, giving the researchers confidence in the reliability of their model.

"Just looking at the microglia," says Anderson, "we see in our system that they are taking on both of their normal roles in keeping key signaling systems balanced during their normal state and activating and causing damage when they're fighting infection. We're able to model normality and abnormality in a way we haven't been able to before."

For Jordan-Sciutto, the new system "is really going to change the way my lab operates going into the future." She's hopeful many other HIV scientists will take it up to further their studies as she also explores more aspects of HIV's impact on the brain, such as how it navigates through the blood-brain barrier that normally protects the central nervous system from inflammation and infection.

The study authors give credit to the collaborative environment at Penn for this cross-disciplinary project. "Tentacles of this project extend from CHOP to the dental school to the vet school to the medical school," says Anderson. "Penn is a very special place where people seem to be more likely to share their technologies around and let other people work with and develop them. This project is a great example of that."

Kelly L. Jordan-Sciutto is vice chair and professor in the Department of Basic and Translational Sciences in Penn's School of Dental Medicine, associate dean of graduate education, and director of biomedical graduate studies at the Perelman School of Medicine.

Credit: 
University of Pennsylvania