Culture

Meaningful movies help people cope with life's difficulties

COLUMBUS, Ohio - Watching meaningful films - those that we find moving and poignant - can make us feel more prepared to deal with life's challenges and want to be a better person, a new study found.

The findings point to one reason why people may choose to see movies that make them sad as well as happy and that may explore difficult subjects that aren't always uplifting.

Researchers found that when people recalled watching meaningful films like The Shawshank Redemption and Up, they reported a variety of positive reactions, such as being better able to accept the human condition and make sense of problems in life.

Those positive experiences were less likely to be reported when people thought about watching Hollywood fare like The Big Lebowski or Catch Me if You Can.

"Meaningful movies actually help people cope with difficulties in their own lives, and help them want to pursue more significant goals," said Jared Ott, lead author of the study and a graduate student in communication at The Ohio State University.

While many studies have looked at how people react to watching meaningful films or clips from films in a lab setting, this research was designed to see how these films affect people in the real world, said co-author Michael Slater, professor of communication at Ohio State.

"We wanted to find out how people experience these movies in their everyday lives," Slater said. "There hasn't been much research on that."

Ott and Slater conducted the study with Naomi Q.P. Tan, a former graduate student at Ohio State. The research was published online recently in the journal Mass Communication and Society.

The researchers created two lists of 20 Hollywood films, one a list of meaningful films and one a list of less meaningful films, all made after 1985 and with high viewer ratings.

Meaningful films, which included Hotel Rwanda, Schindler's List and Slumdog Millionaire, were ones that user-generated lists on the movie site IMDB described using terms like poignant, inspiring and meaningful.

These films were matched with films produced about the same time and with similar MPAA ratings (G, PG, R) that were not described by users with the same terms as meaningful films. Some of these movies included Ratatouille, Fight Club and Pulp Fiction.

The study involved 1,098 adults recruited online.

Participants were randomly selected to receive either the list of meaningful films or the list of less meaningful films and asked to indicate which ones they had seen. One of the films they had seen before was then randomly selected for each participant, who responded to the rest of the survey in relation to that movie.

The survey asked a variety of questions about how each participant reacted to the movie chosen for him or her.

Results showed that people who recalled a meaningful movie were more likely than the others to say the film helped them make sense of difficulties in life. For example, the film helped them "feel like struggles in life are for a reason" and "more easily handle difficult situations with grace and courage."

Meaningful films were also more likely than the other movies to help viewers accept the human condition, results showed. Participants recalling these movies said that the film left them with the feeling that "both happy and sad experiences give meaning to our life" and "gains and losses are part of life," among other similar statements.

Participants recalling the meaningful films were also more likely to say the movie motivated them to be a better person, do good things for other people and seek what really matters in life.

How did meaningful movies have these positive effects? The study found that the key elements of these films were their poignancy, the mixture of happiness and sadness; their emotional range; and their ability to make people feel elevated and inspired by watching them.

Overall, the meaningful films did have more of these positive effects than the other movies. But that doesn't mean people can't find meaning in films that are meant to be more entertaining than meaningful, the research showed.

The researchers asked participants to select up to three values from a list of 16 that they had seen represented in the film they were asked to recall. Some of those values included "achievement and personal success," "love and intimacy" and "courage and bravery." Participants then rated the personal importance of each value.

"We found that people felt better able to make sense of difficulties in their own life when they recalled a movie that focused on values that were important to them," Slater said.

"That happened even when the movie was classified as one of the less meaningful films."

The findings suggest why many people see movies as more than just entertainment, Ott said.

"Some films may help people cope and grow through difficult periods in their life," he said. "And people may recognize this effect years after they have seen a particular movie."

Credit: 
Ohio State University

Blocking lipoxygenase leads to impaired cardiac repair in acute heart failure

image: In search of individualized heart failure therapies, Ganesh Halade, PhD, an associate professor of cardiovascular sciences at the University of South Florida Health (USF Health) Morsani College of Medicine, leads a team studying unresolved inflammation after heart attack.

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USF Health/University of South Florida

TAMPA, Fla. (May 10, 2021) -- Blocking the fat-busting enzyme lipoxygenase with a synthetic inhibitor throws the immune system's innate inflammatory response out of whack, compromising cardiac repair during acute heart failure, USF Health researchers found.

Their new preclinical study was published April 13 in Biomedicine & Pharmacotherapy.

Acute heart failure - triggered by a heart attack, severely irregular heartbeats, or other causes -- occurs suddenly when the heart cannot pump enough blood to meet the body's demands.

Following a heart attack or any cardiac injury, signals to immune cells called leukocytes carefully control physiological inflammation. Normally, there are two distinct but overlapping processes: an acute inflammatory response ("get in" signal), where leukocytes travel from the spleen to the injured heart to start removing dead or diseased cardiac tissue, and a resolving phase ("get out" signal), where inflammation is cleared with the help of macrophages that arrive to further repair the damage and form a stable scar.

A delay in either the initiation of inflammation or its timely clearance (resolution) can lead to impaired cardiac healing and progression to heart failure, said study principal investigator Ganesh Halade, PhD, an associate professor of cardiovascular sciences at the USF Health Morsani College of Medicine and a member of the USF Health Heart Institute.

The USF Health researchers applied three investigational approaches (in vitro, ex vivo, and in vivo) to assess whether a potent lipoxygenase (12/15 LOX) inhibitor ML351 could selectively alter inflammatory responses in adult mice following cardiac injury similar to a heart attack. Previous studies by Dr. Halade's laboratory reported that lipoxygenase-deficient mice showed improved cardiac repair and heart failure survival after cardiac injury.

"We wondered if blocking a lipoxygenase with an external pharmacological compound (drug) would have the same beneficial effect -- but the answer was no," Dr. Halade said. "Instead, the collective results of our study indicate that ML351 dysregulated control of the normal physiological pathway of inflammation in cardiac repair, causing collateral damage."

In the mice treated mice with ML351, leukocyte recruitment to the site of cardiac injury was delayed, which subsequently amplified inflammation at the site. At the same time, instead of leaving once the repair job was done, the immune cells remained at the site beyond the typical acute (and beneficial) inflammatory response phase. Basically, the late arrival (get-in signal) and delayed clearance (get-out signal) of immune cells impaired cardiac repair, Dr. Halade said.

The latest study helps explain one more piece of the puzzle about the important role of immune-mediated acute inflammation and its clearance - both in promoting cardiac health and stopping the progression of heart failure, Dr. Halade said. Lipoxygenases, fatty-acid modifying enzymes that control metabolic and immune signaling, can promote either resolving (beneficial) or nonresolving (harmful) inflammation, he added.

"The take-home message is do not mess with (block) the lipoxygenase. Preserve it, because it's a key enzyme for our defensive, innate immune response," he said. "Knowing how drugs interact with the body's precisely-balanced immune responses will be critical for understanding mechanisms to prevent, delay or treat the unresolved inflammation influencing heart failure."

Credit: 
University of South Florida (USF Health)

New finding suggests cognitive problems caused by repeat mild head hits could be treated

WASHINGTON - A neurologic pathway by which non-damaging but high frequency brain impact blunts normal brain function and causes long-term problems with learning and memory has been identified. The finding suggests that tailored drug therapy can be designed and developed to reactivate and normalize cognitive function, say neuroscientists at Georgetown University Medical Center.

The investigators, working with collaborators at the National Institutes of Health, had previously found that infrequent mild head impacts did not have an effect on learning and memory, but in their new study, reported May 10 in Nature Communications (DOI: 10.1038/s41467-021-22744-6), the investigators found that when the frequency of these non-damaging head impacts are increased, the brain adapts and changes how it functions. The investigators have found the molecular pathway responsible for this down-tuning of the brain that can prevent this adaptation from occurring.

This study is the first to offer a detailed molecular analysis of what happens in the brain after highly repetitive and very mild blows to the head, using mice as an animal model, says the study's senior investigator, Mark Burns, PhD, an associate professor in Georgetown's Department of Neuroscience and head of the Laboratory for Brain Injury and Dementia.

"Most research in this area has been in mouse models with more severe brain injury, or in human brains with chronic traumatic encephalopathy (CTE)," he says. CTE is a degenerative brain disease found in people with a history of repetitive head impact. "This means that we have been focusing only on how CTE pathology develops. Our goal was to understand how the brain changes in response to the low-level head impacts that many young football players, for example, are regularly experiencing."

Researchers have found that the average high school and college football player receives 21 head impacts per week, while some specialized players, such as defensive ends, experience twice as many. Behavioral issues believed to come from head impact have been reported in athletes with exposure to repeated head impacts. Issues range from mild learning and memory deficits to behavioral changes that include aggression, impulsivity and sleep disorders.

"These findings represent a message of hope to athletes and their families who worry that a change in behavior and memory means that CTE is in their future," says Burns.

In this study with mice, researchers mimicked the mild head impacts experienced by football players. The mice showed slower learning and impaired memory recall at timepoints long after the head impacts had stopped. After the experiment, a detailed analysis of their brains showed that there was no inflammation or tau pathology, as is usually seen in the brains of brain trauma or people with CTE.

To understand the physiology underlying these memory changes, the study's co-first author, Bevan Main, PhD, assistant professor of neuroscience at Georgetown, conducted RNA sequencing of the brain. "There are many things that this type of analysis can point you to, such as issues with energy usage or CTE-like pathways being activated in nerve cells, and so on," Main says. "All of our sequencing studies kept pointing to the same thing - the synapses that provide communication between neurons."

The next step was to figure out how synaptic function was altered. Stephanie Sloley, PhD, a graduate of Georgetown's Interdisciplinary Program for Neuroscience and the study's other first co-author, conducted electrophysiology studies of different neurons charged with releasing varied neurotransmitters - chemicals passed between neurons, via synapses, that carry functional instructions. "The brain is wired via synaptic communication pathways, and while we found that these wires were intact, the way that they communicated using glutamate was blunted, repressed," says Sloley.

Glutamate is the most abundant neurotransmitter in the brain, and is found in more than 60% of brain synapses. It plays a role in synaptic plasticity, which is the way the brain strengthens or weaken signals between neurons over time to shape learning and memory.

"Glutamate is usually very tightly regulated in the brain, but we know that head impacts cause a burst of glutamate to be released. We believe that brain is adapting to the repeated bursts of glutamate caused by high frequency head impact, and dampens its normal response to glutamate, perhaps as a way to protect the neurons," explains Sloley. She found that there was a shift in the way that neurons detected and responded to glutamate release, which reduced the neurons ability to learn new information.

With a single head hit or infrequent hits, the synapses do not go through this readjustment, Burns says. But after only a week of frequent mild hits, glutamate detection remained blunted for at least a month after the impacts ended. The affected mice showed deficits in learning and memory, compared to a placebo group of animals.

The authors confirmed that the changes in cognition were due to glutamate by giving a group of mice a drug to block glutamate transmission before they experienced the series of head knocks. This drug is FDA-approved for the treatment of Alzheimer's disease. Despite being exposed to the hits, these mice did not develop adaptations in their synapses or neurotransmission, and did not develop cognitive problems.

"This tells us that the cognitive issues we see in our head impact mice are occurring due to a change in the way the brain is working, and not because we have irreparable brain damage or CTE," Main says. "It would be very unlikely that we would use a drug like this in young players as a neuroprotectant before they play sports, because not all players will develop cognitive disorders," he says. "More much likely is that we can use our findings to develop treatments that target the synapses and reverse this condition. That work is already underway"

Burns believes that CTE and this newly discovered mechanism is different. "I believe that CTE is a real concern for athletes exposed to head impact, but I also believe that our newly discovered communication issue is independent of CTE. While it is concerning that head impacts can change the way the brain works, this study reveals that learning and memory deficits after repeated head impacts do not automatically mean a future with an untreatable neurodegenerative disease."

Credit: 
Georgetown University Medical Center

THz emission spectroscopy reveals optical response of GaInN/GaN multiple quantum wells

image: Acoustic strain waves are optically generated, propagate, and emit THz waves into free space at the surface.

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Osaka University

A team of researchers at the Institute of Laser Engineering, Osaka University, in collaboration with Bielefeld University and Technical University Braunschweig in Germany, came closer to unraveling the complicated optical response of wide-bandgap semiconductor multiple quantum wells and how atomic-scale lattice vibration can generate free space terahertz emission. Their work provides a significant push towards the application of laser terahertz emission microscopes to nano-seismology of wide-bandgap quantum devices.

Terahertz (THz) waves can be generated by ultrafast processes occurring in a material. By looking at THz emission, researchers have been able to study different processes at the quantum level—from simple bulk semiconductors to advanced quantum materials such as multiple quantum wells (Fig.1).

The THz research group led by Prof. Masayoshi Tonouchi at the Institute of Laser Engineering, Osaka University and his PhD student Abdul Mannan, together with international collaborators Prof. Dmitry Turchinovich at Bielefeld University and Prof. Andreas Hangleiter at Technical University of Braunschweig, has measured multifunction response in buried GaInN/GaN multiple quantum wells (MQWs) which includes dynamic screening effect of the built-in field inside the GaInN quantum wells, capacitive charge oscillation between GaN and GaInN quantum wells, and acoustic wave beams launched by the stress release between GaN and GaInN. All these functions can be monitored by observing THz emission into free space. In addition, it was proven that the propagating acoustic waves provide a new technique to evaluate the thickness of buried structure in devices at the resolution of 10 nm on the wafer scale, making nano-seismology a unique LTEM application for wide-bandgap quantum devices.

Probing buried structures in opto-acoustic devices at ultra-high resolution is still an unexplored area of research. In the present work, acoustically driven electromagnetic THz emission into free space is utilized for probing GaInN/GaN MQWs sandwiched in GaN material (Fig.2(a)). Laser-induced polarization dynamics of charge carriers results in a partial release of coherent acoustic phonons (CAPs) in GaInN/GaN MQW. This CAP pulse propagating within a material creates the associated electric polarization wave-packet. Once the propagating CAP pulse encounters the discontinuity of acoustic impedance or piezoelectric constant within the structure, this will lead to the transient change in the associated electric polarization, which serves as the source of the acoustically driven electromagnetic THz emission into free space. The temporal separation between ultrafast polarization dynamics in GaInN/GaN MQW and acoustically driven THz emission gives the thickness of the CAP-propagating medium (nano seismology) (Fig.2(b)).

The specialist team organized for THz emission spectroscopy, opto-THz science, and wide-bandgap/quantum-well semiconductor material science has made a significant step towards 3D dynamic characterization, including buried active layers in various materials and devices. "A 3D active tool to characterize ultrafast carrier dynamics, strain physics, phonon dynamics, and ultrafast dielectric responses locally in a non-contact and non-destructive manner has become an essential area of research for new materials and devices. We hope the present work contributes to such an evolution," says Prof. Masayoshi Tonouchi.

Credit: 
Osaka University

Point-of-care ultrasonography offers enormous advantages in acute diagnostics

Point-of-Care UltraSonography (POCUS) deployed during the emergency treatment of patients with acute dyspnea has enormous advantages over standard diagnostic pathways. This is the finding of a joint review conducted by Danube University Krems and MedUni Vienna and recently published in the prestigious Annals of Internal Medicine. It allows serious conditions to be identified more quickly so that appropriate treatment can be initiated.

Working on behalf of the American College of Physicians, a joint study group from MedUni Vienna and Danube University Krems conducted a review of the value of Point-of-Care UltraSonography (POCUS) in patients with acute dyspnea (shortness of breath), with a view to drawing up a practical clinical treatment guideline.

Point-of-care ultrasonography involves the use of a mobile ultrasound device by the treating clinician to carry out an ultrasound scan at bedside. This allows several organs (scanning of lung and usually also heart, inferior vena cava and leg veins) to be scanned very quickly.

"In this systematic review, we were able to show that, when added to a standard diagnostic pathway, multi-organ point-of-care ultrasonography can significantly improve the correctness of diagnosis compared to the standard diagnostic pathway alone," explains principal investigator Gerald Gartlehner from Cochrane Austria at Danube University Krems.

"It allows conditions such as heart failure, pneumonia, pulmonary embolism, pleural effusion or pneumothorax to be diagnosed more quickly, so that appropriate treatment can be initiated," adds Alexander Spiel, MedUni Vienna emergency doctor (on leave, head of the emergency department of the Clinic Ottakring, Vienna HealthCare Group), "the results of the review demonstrate the relevance of point-of-care ultrasonography as part of the acute diagnostic work-up."

Credit: 
Medical University of Vienna

Smartphone breath alcohol testing devices vary widely in accuracy

PHILADELPHIA-- Alcohol-impaired driving kills 29 people a day and costs $121 billion a year in the U.S. After years of progress in reducing alcohol-impaired driving fatalities, efforts began to stall in 2009, and fatalities started increasing again in 2015. With several studies demonstrating that drinkers cannot accurately estimate their own blood alcohol concentration (BAC), handheld alcohol breath testing devices, also known as breathalyzers, allow people to measure their own breath alcohol concentration (BrAC) to determine if they are below the legal limit of .08% before attempting to drive.

The latest generation of personal alcohol breath testing devices pair with smartphones. While some of these devices were found to be relatively accurate, others may mislead users into thinking that they are fit to drive, according to a new study from the Perelman School of Medicine at the University of Pennsylvania.

The findings, published today in Alcoholism: Clinical & Experimental Research, compares the accuracy of six such devices with that of two validated alcohol-consumption tests - BAC taken from venipuncture, and a police-grade handheld breath testing device.

"All alcohol-impaired driving crashes are preventable tragedies," says lead investigator M. Kit Delgado, MD, MS, an assistant professor of Emergency Medicine and Epidemiology at Penn. "It is common knowledge that you should not drive if intoxicated, but people often don't have or plan alternative travel arrangements and have difficulty judging their fitness to drive after drinking. Some may use smartphone breathalyzers to see if they are over the legal driving limit. If these devices lead people to incorrectly believe their blood alcohol content is low enough to drive safely, they endanger not only themselves, but everyone else on the road or in the car."

To assess these devices, researchers engaged 20 moderate drinkers between the ages of 21 and 39. The participants were given three doses of vodka over 70 minutes with the goal of reaching a peak BAC over the legal driving limit of around 0.10%. After each dose, participants' BrAC was measured using smartphone-paired devices and a police-grade handheld device. After the third dose, their blood was drawn and tested for BAC, the most accurate way of measuring alcohol consumption. Researchers also explored the devices' ability to detect breath alcohol concentration above common legal driving limits (0.05% and 0.08%). They used statistical analysis to explore differences between the measurements.

All seven devices underestimated BAC by more than 0.01%, though the some were consistently more accurate than others. Two devices failed to detect BrAC levels of 0.08% as measured by a police-grade device more than half the time. Since the completion of the study, one of the devices was discontinued and is no longer sold, and other models have been replaced by newer technologies. However, two of the other devices had similar accuracy as a police-grade device. These devices have been used to remotely collect accurate measurements of alcohol consumption for research . They could also be used to scale up contingency management addiction treatment programs that have been shown to help promote abstinence among patients with alcohol use disorders. These programs, which have proven to be highly effective, have traditionally provided prizes for negative in person breathalyzer measurements. Smartphone breathalyzer apps allow these programs to be administered remotely as breath alcohol readings can be verified with automatically captured pictures of the person's face providing the reading and prize redemption could be automated.

"While it's always best to plan not to drive after drinking, if the public or addiction treatment providers are going to use these devices, some are more accurate than others. Given how beneficial these breathalyzer devices could be to public health, our findings suggest that oversight or regulation would be valuable," Delgado concludes. "Currently, the Food and Drug Administration doesn't require approval for these devices - which would involve clearance based on review of data accuracy - but it should reconsider this position in light of our findings."

Credit: 
University of Pennsylvania School of Medicine

How proteins control information processing in the brain

A complicated interaction between different proteins is needed for information to pass from one nerve cell to the next. Researchers at the Martin Luther University Halle-Wittenberg (MLU) have now managed to study this process in the synaptic vesicles, which play an important role in this process. The study appeared in the journal Nature Communications.

Several billion nerve cells communicate with each other in the body so that humans and other living beings can perceive and react to their environment. A host of complex chemical and electrical processes occur within a few milliseconds. "Special messenger substances - known as neurotransmitters - are released at the synapses of the nerve cells. They transmit information between the individual nerve cells," explains Dr Carla Schmidt, an assistant professor at the Centre for Innovation Competence HALOmem at MLU. The messenger substances are packed into small vesicles called synaptic vesicles, which fuse with the cell membrane in response to an electrical impulse and release the messenger substances. The messenger substances are then recognised by special receptor proteins in the next nerve cell. For this to succeed, numerous proteins have to work together, meshing like cogs in a clockwork mechanism. However, too little is currently known about how this process precisely works, says Schmidt.

The researchers have used a special form of mass spectrometry to investigate the process. Cross-linking mass spectrometry helps identify the interaction sites of the proteins. These are mixed with a substance that binds together nearby proteins. This substance reacts at different places depending on how the proteins interact with one another. The mass spectrometer analyses the binding patterns, which can be used to draw conclusions about the arrangement of the proteins. This enables researchers to examine different stages of the vesicles and to detect which protein networks have formed.

The study from Halle enables a more thorough understanding of the process of signal transmission in nerve cells. Knowledge about normal processes helps scientists recognize and understand malfunctions that could trigger diseases such as Alzheimer's.

Credit: 
Martin-Luther-Universität Halle-Wittenberg

Body mass index during childhood linked with risk of anorexia nervosa and bulimia nervosa in later life

New research being presented at the European Congress on Obesity (ECO) held online this year, suggests that among girls a low body mass index (BMI) during childhood indicates a higher risk of developing anorexia nervosa as young adults, whereas a high BMI or overweight in childhood indicates a higher risk of bulimia nervosa.

"By examining the records of thousands of girls over their lifetime in national health registers, we have discovered early warning profiles that could signal girls at risk for anorexia nervosa and bulimia nervosa", says lead author Dr Britt Wang Jensen from Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. "The difference in childhood BMI of girls who later developed eating disorders started to emerge at an early age. These results highlight the importance of regularly monitoring weight and height during childhood to identify these patterns as early as possible."

In the UK, the annual number of new cases of anorexia nervosa among 8 to 12-year-olds doubled from 1.5/100,000 in 2006 to 2019 to 3.2/100,000 [1]. Whether premorbid (pre-illness) BMI is associated with anorexia nervosa and bulimia nervosa is unclear. So far, studies have reported conflicting findings, with some suggesting that a high BMI precedes both diseases, whereas others suggest that a low BMI precedes anorexia nervosa and a high BMI precedes bulimia nervosa.

To explore this further in a population-based cohort, Danish researchers analysed data for 66,576 girls from the Copenhagen School Health Records Register born between 1960 and 1996 who had information on height and weight measured at annual school health examinations from ages 7 to 13 years. Cases of anorexia nervosa and bulimia nervosa were identified by linking with the Danish National Patient Register and the Danish Psychiatric Central Research Register. The girls were followed from ages 10 to 50 years.

During the study, 514 women were diagnosed with anorexia nervosa at an average age of 20 years, and 315 women were diagnosed with bulimia nervosa at an average age of 23 years.

The analyses suggest significant "inverse associations" between childhood BMI and the risk of anorexia nervosa in later life, which means that the risk of anorexia nervosa fell as BMI increased. For example, when comparing two 7-year-old girls with an average height and one z-score difference in BMI (equivalent to 2.4 kg), the girl with the higher BMI had a 14% lower risk of developing anorexia nervosa than the girl with the lower BMI; at age 13 years the risk was 28% lower.

In contrast, significant and positive associations were observed between childhood BMI and the risk of bulimia nervosa. For example, when comparing two 7-year-old girls with an average height and one z-score difference in BMI (equivalent to 2.4 kg), the heaviest girl had a 50% higher risk of bulimia nervosa than the leaner child in later life; at age 13 years the risk was 33% higher.

In addition, compared to girls with normal weight at age 7 years, girls with overweight had twice the risk of developing bulimia nervosa in later life; at age 13 years the risk remained but was lower. The associations did not vary by age at diagnosis.

The authors say that further studies are needed to uncover the mechanisms underlying these associations. They acknowledge that the findings are associations only, and point to several limitations, including that diagnoses in this study may be more severe cases as they are based on hospital admissions and contacts, which may limit the generalisability of these findings to less severe forms of these eating disorders. Moreover, the analyses were restricted to girls as there were too few cases to analyse among boys.

Credit: 
European Association for the Study of Obesity

Most comprehensive studies to date find 'insufficient evidence' to support herbal and dietary supplements for weight loss

The first global review of complementary medicines (herbal and dietary supplements) for weight loss in 16 years--combining 121 randomised placebo-controlled trials including nearly 10,000 adults--suggests that their use cannot be justified based on the current evidence.

The findings of two studies, being presented at The European Congress on Obesity (ECO) held online this year, suggest that although some herbal and dietary supplements show statistically greater weight loss than placebo, it is not enough to benefit health, and the authors call for more research into their long-term safety.

"Over-the-counter herbal and dietary supplements promoted for weight loss are increasingly popular, but unlike pharmaceutical drugs, clinical evidence for their safety and effectiveness is not required before they hit the market", says lead author Erica Bessell from the University of Sydney in Australia. "Our rigorous assessment of the best available evidence finds that there is insufficient evidence to recommend these supplements for weight loss. Even though most supplements appear safe for short term consumption, they are not going to provide weight loss that is clinically meaningful."

The authors report on herbal supplements, containing a whole plant or combinations of plants as the active ingredient, and dietary supplements containing naturally occurring isolated compounds from plants and animal products, such as fibres, fats, proteins, and antioxidants. They can be purchased as pills, powders, and liquids.

Between 1996 and 2006, 1,000 dietary supplements for weight loss included on the Australian Register of Therapeutic Goods weren't evaluated for efficacy. Supplements can be sold and marketed to the public with sponsors (who import, export or manufacture goods) required to have, but not necessarily provide, evidence backing their claims. Just 20% of new listings are audited annually to make sure they meet the requirement. In some countries, the only requirement is that supplements contain acceptable levels of non-medicinal products.

Estimates suggest that 15% of Americans trying to lose weight have tried a weight loss supplement, a USD$41 billion global industry in 2020 [1]. Despite their increasing popularity, it has been 16 years since the last review of the scientific literature on all available herbal and dietary supplements.

Herbal medicines not effective for weight loss

To provide more evidence, Australian researchers did a systematic review of all randomised trials comparing the effect of herbal supplements to placebo on weight loss, up to August 2018 [2]. Data were analysed for 54 studies involving 4,331 healthy overweight or obese adults aged 16 years or older. Weight loss of at least 2.5kg (5.5lbs) was considered clinically meaningful. They also evaluated study design, reporting, and clinical value.

Herbal supplements included in the analysis were: green tea; Garcinia cambogia and mangosteen (tropical fruits); white kidney bean; ephedra (a stimulant that increases metabolism); African mango; yerba mate (herbal tea made from the leaves and twigs of the Ilex paraguariensis plant); veld grape (commonly used in Indian traditional medicine); licorice root; and East Indian Globe Thistle (used in Ayurvedic medicine).

The analysis found that only one single agent, white kidney bean, resulted in a statistically, but not clinically, greater weight loss than placebo (-1.61kg; 3.5Ibs).

In addition, some combination preparations containing African Mango, veld grape, East Indian Globe Thistle and mangosteen showed promising results, but were investigated in three or fewer trials, often with poor research methodology or reporting, and the findings should be interpretated with caution, researchers say.

Dietary supplements don't work for weight loss

A new systematic review up to December 2019, also identified 67 randomised trials comparing the effect of dietary supplements containing naturally occurring isolated compounds to placebo for weight loss in 5,194 healthy overweight or obese adults (aged 16 years or older) [3].

Dietary supplements included in the analysis were: chitosan (a complex sugar from the hard outer layers of lobsters, crabs, and shrimp that claims to block absorption of fat or carbohydrates); glucomannan (a soluble fibre found in the roots of the elephant yam, or konjac, that promotes a feeling of fullness); fructans (a carbohydrate composed of chains of fructose) and conjugated linoleic acid (that claims to change the body composition by decreasing fat).

The analysis found that chitosan (-1.84 kg), glucomannan (-1.27 kg), and conjugated linoleic acid (-1.08 kg) resulted in statistically, but not clinically, significant weight loss compared to placebo.

Some dietary supplements, including modified cellulose (plant fibre that expands in the stomach to induce a feeling of fullness) and blood orange juice extract, showed promising results but were only investigated in one trial and need more evidence before recommending them for weight loss, researchers say.

"Herbal and dietary supplements might seem like a quick-fix solution to weight problems, but people need to be aware of how little we actually know about them", says Bessell. "Very few high-quality studies have been done on some supplements with little data on long-term effectiveness. What's more, many trials are small and poorly designed, and some don't report on the composition of the supplements being investigated. The tremendous growth in the industry and popularity of these products underscores the urgency for conducting larger more rigorous studies to have reasonable assurance of their safety and effectiveness for weight loss."

Credit: 
European Association for the Study of Obesity

Vegetarians have healthier levels of disease markers than meat-eaters

Vegetarians appear to have a healthier biomarker profile than meat-eaters, and this applies to adults of any age and weight, and is also unaffected by smoking and alcohol consumption, according to a new study in over 166,000 UK adults, being presented at this week's European Congress on Obesity (ECO), held online this year.

Biomarkers can have bad and good health effects, promoting or preventing cancer, cardiovascular and age-related diseases, and other chronic conditions, and have been widely used to assess the effect of diets on health. However, evidence of the metabolic benefits associated with being vegetarian is unclear.

To understand whether dietary choice can make a difference to the levels of disease markers in blood and urine, researchers from the University of Glasgow did a cross-sectional study analysing data from 177,723 healthy participants (aged 37-73 years) in the UK Biobank study, who reported no major changes in diet over the last five years.

Participants were categorised as either vegetarian (do not eat red meat, poultry or fish; 4,111 participants) or meat-eaters (166,516 participants) according to their self-reported diet. The researchers examined the association with 19 blood and urine biomarkers related to diabetes, cardiovascular diseases, cancer, liver, bone and joint health, and kidney function.

Even after accounting for potentially influential factors including age, sex, education, ethnicity, obesity, smoking, and alcohol intake, the analysis found that compared to meat-eaters, vegetarians had significantly lower levels of 13 biomarkers, including: total cholesterol; low-density lipoprotein (LDL) cholesterol--the so-called 'bad cholesterol; apolipoprotein A (linked to cardiovascular disease), apolipoprotein B (linked to cardiovascular disease); gamma-glutamyl transferase (GGT) and alanine aminotransferase (AST)--liver function markers indicating inflammation or damage to cells; insulin-like growth factor (IGF-1; a hormone that encourages the growth and proliferation of cancer cells); urate; total protein; and creatinine (marker of worsening kidney function).

However, vegetarians also had lower levels of beneficial biomarkers including high-density lipoprotein 'good' (HDL) cholesterol, and vitamin D and calcium (linked to bone and joint health). In addition, they had significantly higher level of fats (triglycerides) in the blood and cystatin-C (suggesting a poorer kidney condition).

No link was found for blood sugar levels (HbA1c), systolic blood pressure, aspartate aminotransferase (AST; a marker of damage to liver cells) or C-reactive protein (CRP; inflammatory marker).

"Our findings offer real food for thought", says Dr Carlos Celis-Morales from the University of Glasgow, UK, who led the research. "As well as not eating red and processed meat which have been linked to heart diseases and some cancers, people who follow a vegetarian diet tend to consume more vegetables, fruits, and nuts which contain more nutrients, fibre, and other potentially beneficial compounds. These nutritional differences may help explain why vegetarians appear to have lower levels of disease biomarkers that can lead to cell damage and chronic disease."

The authors point out that although their study was large, it was observational, so no conclusions can be drawn about direct cause and effect. They also note several limitations including that they only tested biomarker samples once for each participant, and it is possible that biomarkers might fluctuate depending on factors unrelated to diet, such as existing diseases and unmeasured lifestyle factors. They also note that were reliant on participants to report their dietary intake using food frequency questionnaires, which is not always reliable.

Credit: 
European Association for the Study of Obesity

Mild COVID-19 infection is very unlikely to cause lasting heart damage

Mild Covid-19 infection is very unlikely to cause lasting damage to the structure or function of the heart, according to a study led by UCL (University College London) researchers and funded by the British Heart Foundation (BHF) and Barts Charity.

The researchers say the results, published in JACC Cardiovascular Imaging, should reassure the public, as they relate to the vast majority of people who had Covid-19 infections with mild or no symptoms.

This study of 149 healthcare workers recruited from Barts Health and Royal Free London NHS Trusts is the largest and most detailed study to date into mild Covid-19 infection and its longer-term impact on the heart. It follows concerns that because severe hospitalised Covid-19 infections are associated with blood clots, inflammation of the heart and heart damage, mild infections may cause similar complications. However, up until now, there has been little information specifically looking at this group of people and the effects on the heart further down the line after infection.

Researchers identified participants with mild Covid-19 from the COVIDsortium, a study in three London hospitals where healthcare workers had undergone weekly samples of blood, saliva and nasal swabs for 16 weeks. Six months after mild infection, they looked at the heart structure and function by analysing heart MRI scans of 74 healthcare workers with prior mild Covid-19 and compared them to the scans of 75 healthy age, sex and ethnicity matched controls who had not previously been infected.

They found no difference in the size or amount of muscle of the left ventricle - the main chamber of the heart responsible for pumping blood around the body - or its ability to pump blood out of the heart. The amount of inflammation and scarring in the heart, and the elasticity of the aorta - which is important for blood to easily flow out of the heart - remained the same between the two groups.

When the researchers analysed blood samples, they found no differences in the two markers of heart muscle damage - troponin and NT-proBNP - six months after mild Covid-19 infection.

Now, the team of researchers and cardiologists suggest that there is little benefit from screening the hearts of people who've had mild infection, and research should focus on those who've suffered severe Covid-19, high risk groups or those with ongoing symptoms.

Dr Thomas Treibel (UCL Institute of Cardiovascular Science and Barts Health NHS Trust), said: "Disentangling the impact Covid-19 has on the heart has been a challenge. But we're now at the stage of the pandemic where we can really start to get a grip on the longer-term implications Covid-19 has on the health of our heart and blood vessels.

"We've been able to capitalise on our incredible frontline staff who've been exposed to the virus this past year and we're pleased to show that the majority of people who've had Covid-19 seem to not be at increased risk of developing future heart complications. We now need to focus our attention on the long term impact the virus has in those who've been hit hardest by the disease."

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist, said: "These findings one year on from the start of the pandemic are welcome reassurance to the hundreds of thousands of people who have experienced Covid-19 with mild or no symptoms.

"Throughout the pandemic, BHF researchers have made progress investigating the short and long-term effects of Covid-19 on the heart and circulatory system. There's still a lot more work to be done, but for now it seems the good news is that mild Covid-19 illness does not appear to be linked to lasting heart damage."

There were small abnormalities identified by MRI but these were not found more often in people who had mild Covid-19 than those that have never had it. The changes could have been caused by something other than coronavirus and they may not make any noticeable difference to the health of that person.

Credit: 
University College London

The Lancet Rheumatology: Largest study to date confirms non-steroidal anti-inflammatory medications do not result in worse COVID-19 outcomes

The use of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, does not lead to higher rates of death or severe disease in patients who are hospitalised with COVID-19, according to a new observational study of more than 72,000 people in the UK published in The Lancet Rheumatology journal.

NSAIDs are common treatments for acute pain and rheumatological diseases such as rheumatoid arthritis and osteoarthrosis. Early in the pandemic, there was debate on whether the use of such drugs increased the severity of COVID-19, which led to urgent calls for investigations between NSAIDs and COVID-19.

The ISARIC CCP-UK (International Severe Acute Respiratory and emerging Infection Consortium Clinical Characterisation Protocol United Kingdom) study, which is the largest of its kind, provides clear evidence that the continued use of NSAIDs in patients with COVID-19 is safe.

In the study, around a third of patients (30.4%. 1,279 out of 4,211) who had taken NSAIDs prior to hospital admission for COVID-19 died, a rate which was similar (31.3%. 21,256 out of 67,968) in patients who had not taken NSAIDs. In patients with rheumatological disease, the use of NSAIDs did not increase mortality.

Prof Ewen Harrison, of the University of Edinburgh and lead author of the study, said: "NSAIDs are commonly used to treat people all over the world for a range of conditions, from minor aches and pains to chronic conditions such as arthritis and cardiovascular disease. Many people rely on them to be able to carry out their day-to-day activities. When the pandemic began over a year ago, we needed to be sure that these common medications would not lead to worse outcomes in people with COVID-19. We now have clear evidence that NSAIDs are safe to use in patients with COVID-19, which should provide reassurance to both clinicians and patients that they can continue to be used in the same way as before the pandemic began." [1]

The study collected data on the medication patients had been prescribed, were currently taking, or had taken within 14 days prior to being admitted to hospital, as well as demographic information, and medical history. The study cohort included patients with confirmed or highly suspected COVID-19 infection admitted to 255 healthcare facilities in England, Scotland, and Wales, between January and August 2020. Of the 72,179 patients eligible for the study, 5.8% (4,211) had taken NSAIDs prior to admission

Modelling analyses were used to estimate the effects of NSAIDs taken prior to hospitalisation on mortality rates in hospital, disease severity, admission to critical care, requirement for invasive or non-invasive ventilation, use of supplemental oxygen, or development of acute kidney injury, which were then compared to patients who had not taken NSAIDs. Those who took NSAIDs were no more likely to be admitted to critical care, need invasive or non-invasive ventilation, or require oxygen.

The authors noted some limitations to the study. Despite being the largest ongoing prospective study of patients admitted to hospital, it only represents 60% of hospitalised patients in the UK over the time of the study and it did not include patients with severe COVID-19 who were not hospitalised. However, it would be expected that most patients who had severe COVID-19 would have been admitted to hospital and therefore included in the study, the authors said. The study did not determine whether patients continued to be given NSAIDs while they were in hospital, so the authors cannot make any recommendations on this.

Additionally, the study could not capture how long patients were taking NSAIDs prior to hospital admission and whether they were being taken for long-term conditions or short-term symptom relief. In the UK, ibuprofen is the most commonly used NSAID, so it is unclear whether the results of this study are generalisable to other countries where other NSAIDs are more frequently used. Further analyses performed suggested other non-ibuprofen NSAIDs had a similar safety profile to ibuprofen. Further research and clinical trials may help definitively establish whether NSAIDs are safe in different populations and whether their anti-inflammatory effects have any impact on patients with COVID-19.

Credit: 
The Lancet

New research sets stage for development of salmonella vaccine

With the COVID-19 vaccines on many people's minds, some may be surprised to learn that we do not yet have vaccines for many common infectious diseases.

Take salmonella, for example, which can infect people through contaminated food, water and animals. According to the World Health Organization, non-typhoidal salmonella infection affects more than 95 million people globally each year, leading to an estimated 2 million deaths annually. There is no approved vaccine for salmonella in humans, and some strains are antibiotic-resistant.

But just as scientists spent decades doing the basic research that made the eventual development of the COVID-19 vaccines possible, University of Florida researchers led by Mariola Edelmann in the department of microbiology and cell science, UF/IFAS College of Agricultural and Life Sciences, are laying the groundwork for an effective vaccine for salmonella and other hard-to-treat bacterial infections. In their study supported by the National Institutes of Health and published in PLOS Pathogens, the UF/IFAS scientists demonstrate a novel approach to triggering immunity against salmonella.

This approach takes advantage of how cells communicate with each other, said Winnie Hui, first author of the study, which was conducted while she was a doctoral candidate in microbiology and cell science.

"Cells communicate with each other through particles called extracellular vesicles or EVs. Think of these like molecular telephones that let cells talk to each other. We wanted to know if some of those messages included information related to immune response," said Hui, who graduated from the UF/IFAS College of Agricultural and Life Sciences in 2019 and is now a postdoctoral researcher in the UF College of Medicine, division of rheumatology and clinical immunology.

"Host EVs have not been previously studied in the context of fighting enteric bacterial infections, so that is part of what makes our approach new and adds to the field," said Edelmann, senior author on the study, Hui's dissertation director and an assistant professor of microbiology and cell science.

Edelmann hypothesized that a specific type of EVs called exosomes were part of the immune response against salmonella and may one day hold the key to developing a vaccine.

To test their idea, the research team took exosomes from white blood cells infected with salmonella. Inside those exosomes, which measure just a few dozen nanometers across, they found salmonella antigens, which are bits of salmonella protein known to trigger an immune response.

Next, the researchers wanted to know if these exosomes might function as a vaccine, helping the body build up its defenses against salmonella, said Lisa Emerson, one of the study's co-authors and a doctoral student in Edelmann's laboratory.

"We put the exosomes in 'nanobubbles' that the mice inhaled. Later, we ran tests to see how their immune systems responded," said Emerson, who is in the UF/IFAS College of Agricultural and Life Sciences.

The researchers found that after they introduced the exosomes containing salmonella antigens, the exosomes localized to tissues that produce mucous, activating specific cells at these sites. Weeks later, mice developed antibodies against salmonella and specific cellular immune responses, which typically target this bacterium for elimination. For the researchers, this is a promising result.

"There are two types of immune responses generated when our bodies encounter a pathogen. The first one is called innate immunity, which is an immediate response to an infection, but it is also less specific. The other response is called adaptive immunity, and this protective response is specifically tailored to a given pathogen, but it also takes longer to develop. Exosomes generated by infected white blood cells stimulated both of these responses in animals," said Hui.

While these results show promise, more research will be needed before we have a salmonella vaccine that works in humans, Hui said.

"Our study has identified a novel role of exosomes in the protective responses against salmonella, but we also think that exosomes can find broader applications for other intestinal infections and beyond," Edelmann said.

"Exosomes have this unique capability to encapsulate precious cargo while enabling its targeted delivery to tissue of interest. For many conditions and infections, this precise delivery of therapeutic payload is what makes a difference, and we are currently also evaluating exosomes in delivering cargo to other tissues of choice," said Edelmannn whose work is supported by several federal funds focused on the roles of extracellular vesicles in bacterial infections and disease and host-directed therapies against intestinal infections.

Credit: 
University of Florida

New study examines social network's relation to binge drinking among adults

image: Hank Green

Image: 
Indiana University

For some people, social gatherings can be a time to imbibe. And for some, that can turn into a time to overindulge. But how do your neighborhood and your social network affect binge drinking?

Along with colleagues at the RAND corporation in Santa Monica, Indiana University researcher Hank Green examined how neighborhood and social network characteristics were related to adult binge drinking. He and his co-authors found that both factors play a role in how much someone drinks, information that can help us better understand binge drinking among adults.

The study was published in the journal Health and Place, indexed in Science Direct and PubMed.

"Adults living in cohesive neighborhoods where people get along, help and look out for one another had a lower likelihood of any binge drinking at all compared to those living in less cohesive neighborhoods," the co-authors point out.

"Living in a highly cohesive neighborhood may impact social norms and constrain behavior in such a way that binge drinking is very unlikely, even if the opportunity to drink arises," Green said.

The researchers also found that, for those who live in neighborhoods they consider safe and orderly, and who have a more interconnected social network, the likelihood of social drinking increases, and drinking heavily might occur in those social drinking situations, regardless of how cohesive they find their neighborhood to be. However, the study also found that those neighborhood and network factors also restrict how often someone binge-drinks, probably through social control processes such as friends and neighbors looking out for each other or commenting on someone's drinking, etc.

"We also found that binge drinking was more likely among adults who lived in orderly neighborhoods and who had denser social networks, but reported lower neighborhood cohesion," said Green, associate professor at the IU School of Public Health-Bloomington.

In neighborhoods ranked by study participants as disordered, unsafe, and lacking cohesion, neighborhood factors lose their overall impact. Social networks tend to take over the role of social control, according to the study. In these types of neighborhoods, it's people with more interconnected social networks who binge less often.

Researchers utilized online surveys from adults ages 30-80 drawn randomly from the RAND American Life Panel. The main predictor variables were neighborhood cohesion (do neighbors help neighbors, do neighbors get along); neighborhood order (my neighborhood is clean, safe); and social network density. Associations of these measures with past month binge drinking (any, number of days) were examined, controlling for demographic characteristics.

Green said the study could help inform intervention practices such as cognitive behavioral therapy because those approaches already focus on identifying people and places that trigger binge drinking and addressing those triggers with behavioral changes. Indirectly, Green said, the study suggests that those interventions could also focus on people and places that discourage binge drinking or facilitate less frequent binge drinking and better drinking choices. Those interventions could also consider a broader definition of "place" that moves beyond a specific location to consider how larger areas like neighborhoods might impact drinking.

"Because neighborhood and social network factors work in tandem to affect the likelihood of binge drinking and the frequency of binge drinking, interventions for problem drinking should incorporate both of these aspects to make them more effective," Green said.

Credit: 
Indiana University

Stop the genetic presses!

image: Model of NusA-dependent and NusG-dependent intrinsic termination of transcription of DNA into RNA. A new study shows that NusA and NusG together facilitate termination at about 88% of the intrinsic terminators in the bacteria Bacillus subtilis, helping to prevent unwanted transcription. (1) During transcription elongation, NusA and NusG bind RNA polymerase (blue). (2) NusA assists with RNA hairpin formation required for intrinsic termination and NusG helps to pause transcription allowing time for hairpin formation. (3) The RNA transcript is released.

Image: 
Babitzke Laboratory and Dani Zemba, Penn State

The protein, known as NusG, pauses the transcription machinery at specific DNA sequences to facilitate what is called "intrinsic termination" and prevent unwanted transcription that could disrupt cellular function.

A new study, led by Penn State researchers, shows that NusG and the related protein, NusA, together facilitate termination at about 88% of the intrinsic terminators in the bacteria Bacillus subtilis. Understanding this process expands our basic knowledge of this key cellular function and could eventually aid in the development of antibiotics that target and disrupt gene regulation in bacteria. A paper describing the research appears online in the journal eLife.

"For a cell to access the genetic information stored in DNA, it first must be transcribed into RNA by an enzyme called RNA polymerase," said Zachary F. Mandell, a graduate student at Penn State and first author of the paper. "This process is highly coordinated to ensure that the right genes are expressed at the right times and at appropriate levels for the cell to function properly. We are interested in understanding the mechanisms that allow the cell to stop transcription at precise locations along the genome."

Proper regulation of gene expression occurs in three basic stages. First, transcription is initiated by RNA polymerase that binds to the DNA at the beginning of the sequence that is being transcribed. NusA and NusG then bind to RNA polymerase during the elongation process to make an RNA copy of the DNA sequence. Finally, the transcription must be terminated at the appropriate spots in the genome.

"Termination of transcription is especially important in bacteria because the genes are packed tightly together along the genome, such that failure to terminate transcription at the right locations could lead to inappropriate gene expression," said Paul Babitzke, professor of biochemistry and molecular biology at Penn State and the leader of the research team.

The mechanisms for termination in bacteria traditionally have been classified as either "factor-dependent," which relies on a protein called Rho, or intrinsic termination, which was thought to be "factor-independent." Intrinsic termination relies on an RNA hairpin structure that forms in the RNA molecule being produced, which causes the RNA to be released from the transcription machinery.

NusG and NusA are both proteins classified as transcription factor that help regulate gene expression and are part of the complex of proteins that read and transcribe DNA during elongation. NusA interacts with the RNA molecule being produced and NusG can bind to the DNA to pause elongation. Based on previous research, NusA is thought to play a role in intrinsic termination by aiding in the formation of the RNA hairpin, but the role of NusG in termination had not been established.

To further explore the role of these two proteins in intrinsic termination, the research team produced strains of bacteria that lacked NusA, lacked NusG, and lacked both NusA and NusG. They then used a technique that they invented called "Term-Seq," in which they can preserve and identify the ends of all the RNA molecules produced in their bacterial strains. The RNA ends from the mutant strains could then be compared to RNA molecules from bacteria with normally functioning NusA and NusG.

"We found that some intrinsic termination sites were dependent on NusA, some on NusG, some on either NusA or NusG, and some required both," said Mandell. "We were somewhat surprised by how big of a role these two proteins play in intrinsic termination. A total of 88% of all intrinsic termination sites relied on NusA or NusG in some capacity. Intrinsic termination is clearly not completely 'factor-independent.'"

The researchers are still investigating the precise role that the Nus proteins play in transcription termination.

"We think that NusA helps directly in the formation of the hairpins required for intrinsic termination and that NusG is pausing elongation at termination sites to give the hairpin additional time to form," said Babitzke.

Credit: 
Penn State