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UNIVERSITY PARK, Pa. -- When protesters use social media to attract attention and unify, people in power may respond with tweeting tactics designed to distract and confuse, according to a team of political scientists.

In a study of Twitter interactions during Venezuela's 2014 protests, in which citizens voiced opposition to government leaders and called for improvements to their standard of living, the tweets of the protesters focused mainly on the protest itself, while the tweets issued by the ruling regime covered more diverse topics. The team added that this could mean that regimes are growing more savvy in their use of social media to help suppress mass movements.

"When we started doing this study there had been a lot of optimism about the capacity of social media to produce revolutions throughout the world, like Arab Spring and the Color Revolutions in Europe," said Kevin Munger, assistant professor of political science and social data analytics, Penn State. "But it seems like, in hindsight, this was the result of short-term disequilibrium between the capacity of the masses to use this technology and the limited capacity of these elites to use it. A lot of these elites may have not been keeping up with modern communication technology and got caught unawares. So, for that short period of time, social media did produce better outcomes for revolutions and mass movements."

The researchers, who published their findings in a recent issue of Political Science Research and Methods, specifically examined social media from both the Venezuela regime and its opposition. Following the death of Venezuelan President Hugo Chavez in early 2013, Nicolas Maduro, Chavez's vice-president, won a special election. After his election, mass protests erupted related to economic decline and increased crime.

In their analysis, the researchers noted that the regime abruptly shifted its Twitter strategy after protests swept across the country. The topics of the regime's tweets became even more diverse than usual -- including such topics as a tree-planting event -- and often did not address the protests at all, according to Munger, who is an associate of Penn State's Institute for Computational Data Sciences, which connects Penn State faculty with advanced and supercomputing resources.

As the protests continued, however, the researchers said that the opposition also became less focused, which the researchers suggest may have been a reaction to the regime's social media strategy.

The way that attention works on social networks offers a glimpse into why the strategy to distract citizens might be effective, added Munger, who worked on the study while a doctoral student in politics at New York University.

"To have effective protests, you need to have a ton of people coordinated on a single message, so spreading other narratives disrupts that process of coordination," said Munger. "Being able to spread doubt is effective. You don't have to get people to love your regime, you just need people to less convinced of the single narrative."

The regime also seemed to develop a more sophisticated approach to using hashtags, which are words or phrases that begin with a hash sign -- # -- that are often used by social media sites to help users better identify and follow conversations about certain subjects. The regime used long hashtags, as opposed to the shorter hashtags that are more commonly used, to promote distraction among the protest groups.

For example, the regime added the hashtag -- #RodillaEnTierraConNicolásMaduro -- to their tweets, which translates, in English, to "knees on the ground with Nicolás Maduro." This represents a more top-down approach at using Twitter to galvanize support, compared to the grassroots bottom-up strategy of the protesters.

"That's not a hashtag that individual protesters would come up with, and not just because it mentions the opposition leader, but because it is more of a focus-group tested way of specifically promoting a narrative," said Munger. "The opposition was using short hashtags to coordinate different groups on a single message. But, we see the regime's lengthy hashtags as an explicit attempt by them to generate a new topic of discussion."

The researchers used a computer application to help them examine the Twitter accounts of 65 legislators aligned with the regime, and accounts of 56 opposition leaders. They examined the tweets from Dec. 19, 2013, to May 29, 2014, when the protests had significantly waned.

Venezuela presented a unique research opportunity to study the use of Twitter in protests, said Munger. The country had one of the highest Twitter adoption rates in the world at the time. The country also had a large opposition party in government so the researchers were able to identify the two distinct groups and their different messaging strategies.

Damage to energy-producing mitochondria may underlie prolonged muscle weakness following a sepsis-like condition in mice, according to a new study published today in eLife.

The findings may explain why humans struggle to regain strength after sepsis recovery, and suggest the need for antioxidant or other alternative treatments to restore muscle health.

Sepsis is the result of an infection that moves into the bloodstream and causes an exaggerated immune response, including harmful inflammation and organ damage. With intensive care and prolonged hospitalisation, some people can survive the condition. But survivors may face chronic weakness and fatigue and find it difficult to return to work and other normal activities.

"Researchers had not previously been able to study the causes of long-term weakness because animal models which capture the long-term effects of sepsis did not exist," explains lead author Allison Owen, PhD, who conducted the research as a PhD student at the University of Kentucky in Lexington, US, and is now a postdoctoral research fellow at Vanderbilt University Medical Center in Nashville, Tennessee, US.

To address this, Owen and her colleagues developed and studied a mouse model of muscle weakness after sepsis recovery. They confirmed that reduced muscle strength in the mice was not caused by a loss of muscle. They also looked for signs of ongoing inflammation in the muscles that might contribute to weakness and found that this did not appear to be the cause.

Instead, they discovered that energy-producing mitochondria in the animals' muscle cells were abnormal and showed signs of ongoing oxidative damage. "This suggests that chronic muscle weakness among sepsis survivors is not due to muscle wasting, but rather caused by the loss of muscle quality," Owen says.

While current treatments for post-sepsis weakness aim to help patients rebuild muscle mass, these results hint at the need for antioxidant therapies or other treatments to restore mitochondrial health in muscles.

"This work may eventually benefit the millions of sepsis survivors who are discharged from the hospital every year and experience prolonged physical weakness and fatigue," says senior author Hiroshi Saito, PhD, Professor in the Department of Surgery at the University of Kentucky. "It provides evidence that therapeutic strategies aimed at restoring mitochondrial health, in addition to restoring muscle mass, may allow survivors to regain strength and improve their quality of life after sepsis."

Neuroblastoma can grow and spread in the body very aggressively, making it very difficult to treat. New research has shed important light on the factors at play in the metastasis of neuroblastoma, which could potentially lead to new treatment strategies.

The findings, recently published in the British Journal of Cancer, were discovered by Professor Maria Kavallaris and her team, through scientific research funded by The Kids Cancer Project.

The aggressive nature of neuroblastoma

Neuroblastoma is the most common solid tumour found in young children and is renowned for its aggressive nature - its ability to quickly grow and spread (metastasise) throughout the body. Sadly, children with neuroblastoma that has metastasised have a less than 50% chance of survival. There is an urgent need to better understand metastasis, so we might learn how to improve the treatment of metastatic neuroblastoma.

Understanding metastasis

Cancer spreads when cells become detached from the original tumour (the primary tumour), move to the surrounding tissue (migration), then get into the blood or lymphatic vessels where they can end up in different parts of the body (invasion). Metastasis is a complex process that involves many different steps and molecules in the body. In the study just published, Professor Kavallaris and her team have shown that a protein called stathmin may be a very important player in this process.

The role of stathmin

Stathmin is known to be overexpressed in neuroblastoma cells; that is, it occurs at higher levels in neuroblastoma cells than healthy cells. In earlier research, the team found that stathmin appears to help control the migration and invasion of neuroblastoma cells. In the new study, they tried to work out exactly how it does this, and how the process might be exploited to provide a therapeutic advantage. After all, if we can understand the factors that control metastasis, we may be able to inhibit these factors.

How stathmin does its work... and the significance

When they investigated stathmin's role in metastasis, the team found that it has a direct effect on a number of genes and other molecules called 'micro RNAs' (miRNAs) that are directly involved in the migration and invasion of neuroblastoma cells. In particular, stathmin appears to affect a protein called PTPN14, which has recently been identified as a tumour-suppressor.

"Our results showed that stathmin can regulate PTPN14 expression, which in turn affects neuroblastoma cell migration and invasion," explains Professor Kavallaris.

"This study has highlighted that both stathmin and PTPN14 appear to be important factors in metastasis of neuroblastoma. This raises the exciting possibility that targeting one or both of these molecules could be a potential new treatment strategy against this devastating disease."

"A substantial part of the initial project was supported by funding from The Kids' Cancer Project, which was invaluable in allowing this work to progress," said Professor Kavallaris.

One-third of Americans rely on news platforms they acknowledge are less reliable, mainly social media and peers. The other two-thirds of the public consider their primary news sources trustworthy, mainly print news and broadcast television, according to a new RAND Corporation report.

The report draws from a national survey of 2,543 Americans to examine how reliability, demographics and political partisanship factor into news choices and how often people seek out differing viewpoints in the news. It is the latest in a series of RAND-funded reports into Truth Decay, the phenomenon defined as diminishing reliance on facts, data and analysis in American public life.

"A lack of time and competing demands may explain why a third of Americans turn to news sources they deem less reliable, which suggests improving the quality of news content or teaching people how to 'better consume' news isn't enough to address Truth Decay," said Jennifer Kavanagh, senior political scientist and co-author of the report. "Media companies and other news providers may need to provide more easily accessible and digestible ways for individuals to consume high quality investigative journalism."

About 44 percent of respondents reported that news is as reliable now as in the past, while 41 percent said it has become less reliable and 15 percent - mostly women, racial and ethnic minorities and those without college degrees - said it is more reliable.

Respondents who lean on print and broadcast platforms were more likely to deem them reliable. Those who rely on social media and peers for news, on the other hand, don't see those platforms as reliable yet still choose to get their news from these sources.

"Our findings suggest that perceived reliability is not the only factor that drives what Americans choose as their go-to news sources," said Michael Pollard, a sociologist and lead author of the report. "Despite acknowledging that there are more reliable sources for news, people with demands on their time may be limited to using less reliable platforms."

Asked whether they ever seek out alternate viewpoints when catching up on the news, 54 percent said they "sometimes" do, 20 percent said, "always or almost always," 17 percent said "infrequently," and 9 percent said, "never or almost never."

"Political partisanship was linked to whether or not individuals were willing to seek out different viewpoints," Pollard said. "For example, those who self-identified as more liberal were more likely than conservatives to report that they 'never or almost never' seek differing views."

The report also identified the four most common combinations of news media types consumed by Americans: print publications and broadcast television; online; radio; and social media and peers.

The survey was conducted via the RAND American Life Panel, a nationally representative, probability-based panel of more than 6,000 participants who are regularly interviewed over the internet. Age was an important predictor of how respondents obtain news. Perhaps unsurprisingly, those who are younger were more likely to get news from social media and peers, while older individuals were more likely to get their news from print publications and broadcast television.

Those who are college-educated were less likely to get their news from social media and peers, instead opting for radio and online sources. Those with less than a college education were more likely to report "never or almost never" seeking out news with alternate viewpoints.

Those who are married were three times more likely than singles to rate their peers as the most reliable source for news. Unmarried people were more likely than married people to report they "always or almost always" seek out sources with differing views.

Past reports in the Truth Decay series have looked at different aspects of the changed media and information landscape, including a linguistic analysis that found increasing subjectivity in "new media" sources compared to more traditional forms of news, as well as an examination of media literacy initiatives in the United States. Future reports will include research into Americans' trust in public institutions and the prevalence of Truth Decay in Europe.

Labelling food and drink with the amount and type of exercise needed to burn off the calories in it might be a more effective way of encouraging people to make 'healthier' dietary choices, indicates research published online in the Journal of Epidemiology & Community Health.

Given that the current system of food labelling by calorie and nutrient content is poorly understood, and there's little evidence that it is altering purchasing decisions or having any impact on obesity levels, it may be worth trying, suggest the researchers.

If widely applied, it might, on average, shave off up to 195 calories per person per day, they calculate.

Physical activity calorie equivalent or expenditure (PACE) food labelling aims to show how many minutes or miles of physical activity are needed to burn off the calories in a particular food or drink.

For example, eating 229 calories in a small bar of milk chocolate would require about 42 minutes of walking or 22 minutes of running to burn these off.

The UK Royal Society for Public Health has already called for PACE labelling to replace the current system, but to date, there's been little strong evidence to back this stance.

The researchers trawled research databases and other relevant online resources for studies that compared PACE labelling with other types of food labelling or none for potential impact on the selection, purchase, or consumption of food and drinks (excluding alcohol).

They found 15 relevant randomised controlled trials, and pooled the data from 14 of them. The results showed that when PACE labelling was displayed on food and drink items and on menus, on average, significantly fewer calories--65 fewer per meal--were selected.

PACE labelling was also associated with the consumption of 80 to 100 fewer calories than no food labelling, or other types of labelling.

Based on their findings, and average consumption of three meals a day plus two snacks, the researchers suggest that PACE labelling might potentially slice around 200 calories off daily intake.

But they caution, the number of included studies was small, and the design of each varied considerably. Most weren't carried out in real life settings, such as restaurants and supermarkets.

Nevertheless, they suggest: "PACE labelling shows some promise in reducing the number of kilocalories (calories) selected from menus, as well as the number of calories and the amount of food (grams) consumed."

The evidence shows that even a relatively small reduction in daily calorie intake (100) combined with a sustained increase in physical activity is likely to be good for health and could help curb obesity at the population level: PACE labelling may help people achieve this, they say.

"PACE labelling is a simple strategy that could be easily included on food/beverage packaging by manufacturers, on shelving price labels in supermarkets, and/or in menus in restaurants/fast-food outlets," they write.

"Public health agencies may want to consider the possibility of including policies to promote [it] as a strategy that contributes to the prevention and treatment of obesity and related diseases," they conclude.

A lack of physical activity, a poor diet and too much stress are taking their toll on the health of Canadians, says a new UBC study.

Researchers from UBC's Faculty of Medicine caution that too many Canadians live with a number of health issues that impact their ability to lead healthy lifestyles.

Brodie Sakakibara is an assistant professor with the Centre for Chronic Disease Prevention and Management based at UBC Okanagan. He, along with colleagues Adebimpe Obembe and Janice Eng from UBC's department of physical therapy, recently published a study examining how common it is for Canadians to have multiple--and serious--health conditions.

"Inactivity, poor diet and more than optimal amounts of stress combined with an aging population are resulting in increasing numbers of Canadians with cardiometabolic conditions, and thus increasing their risk of poor health," says Sakakibara.

Stroke, heart disease and diabetes are three of the most prevalent chronic diseases worldwide, he says and they have a substantial social and economic burden. They are cardiometabolic diseases--affecting the heart and blood vessels--mostly caused by lifestyle behaviours and are the leading causes of health resource use, hospitalizations, morbidity and mortality in Canada.

Cardiometabolic multimorbidity (CM) is having a diagnosis of at least two of those conditions. Using data from a 2016 Canadian Community Health Survey with 689,300 respondents, the researchers investigated CM and its connection to physical activity, diet and stress.

The study reports that the number of Canadians with CM or at risk of CM is high, and an increasing onset of cardiometabolic conditions is associated with higher chances of physical inactivity and stress.

"We found that people with all three diseases had four times the chance of reporting zero minutes of physical activity per week than people with none of the conditions. And similarly, they had four times the chance of reporting high levels of stress," says Sakakibara. "These lifestyle behaviours are clearly associated with bad or even dangerous health outcomes."

The issue, he adds, is that healthcare management for people with multiple chronic diseases is traditionally based on disease-specific strategies often independent of one another--a person with diabetes is treated for that chronic illness and not others. This leads to fragmented care with multiple care providers and systems.

"Often most patients with multiple chronic conditions develop complications that are clinically complex and become unique healthcare challenges. These complexities are often poorly understood, which means these patients have unmet health care needs," says Eng.

While getting more active, lowering stress and eating well won't cure all ailments, Sakakibara says it would certainly be a step in the right direction. The study suggests the time has come for greater efforts to prevent CM in individuals at high risk (i.e., those with one cardiometabolic condition), as well as efforts to help people with CM better manage their health and well-being.

"Lifestyle behaviour modification is an important strategy for the management and prevention of future heart or stroke events," he says. "Physical activity several times a week, combined with a healthier diet, can manage risk and complications, while at the same time helping to lower stress."

Worcester, Mass. - Dec. 10, 2019 - A study by researchers in the United States and India has shown that probiotic yeasts derived from food are able to reduce the virulence of, and even prevent infections by, several types of fungi that are responsible for life-threatening infections in hospitalized and immune-compromised individuals, including the multi-drug resistant Candida auris, which was recently listed as an urgent threat by the U.S. Centers for Disease Control in its 2019 Antibiotic Resistance Threats report.

While Candida albicans is the leading cause of hospital-acquired fungal infections, the study focuses on a number of non-albicans species that are of increasing concern to public health officials as they can cause similar infections and as many of these strains are developing resistance to available antifungal medications.

Reeta Rao, professor of biology and biotechnology and associate dean of graduate studies at Worcester Polytechnic Institute (WPI) and one of the lead authors of the study, explained, "Candida auris, for example, which can cause severe, often fatal infections in hospitalized patients, frequently does not respond at all to commonly used antifungal drugs, making infections almost impossible to treat."

In immune-compromised patients or even healthy individuals with implanted medical devices, Candida can penetrate the submucosal tissue of the gastrointestinal tract and reach the internal organs, where it can cause life-threatening systemic infections. The microbes' drug resistance stems, in part, from their ability to adhere to surfaces and form biofilms. "A biofilm is a complex ecosystem that can become a physical barrier against drugs," Rao said. "Biofilms can form on medical devices, catheters and IV lines, and even contact lenses. They can also penetrate epithelial tissue in the body, leading to a variety of infections, including the deadly bloodstream infections we can see with Candida auris."

Even when they do work, antifungal drugs often have serious side effects. Fungal cells are similar to the eukaryotic cells that make up human bodies, so the drugs can attack and damage the very tissues they are designed to protect. "This has led to a growing recognition of the need for alternative therapies," Rao said. "We chose to look at food-derived probiotic yeast, which could present a safe and cost-effective method to keep Candida in check."

In the study, published in the journal mBio ("Probiotic Yeasts Inhibit Virulence of Non-albicans Candida Species") and recommended by F1000Prime, an online service that highlights scientific articles of critical interest to the research community, the researchers examined the ability of two food-derived yeasts, Saccharomyces cerevisiae and Issatchenkia occidentalis, which grow naturally on fruits and other foods, to combat adhesion and biofilm formation in non-albicans species of Candida.

They found that applying these yeasts to non-biological surfaces reduced the ability of non-albicans fungi, including Candida auris, to adhere to these surfaces by as much as 53 percent. The yeasts also reduced the formation of biofilms by as much as 70 percent. Similar results were obtained with mixed cultures containing non-albicans and albicans fungal species. Applying the food-derived yeasts to surfaces also inhibited a process known as filamentation in a number of non-albicans fungi. Filamentation is a mechanism used by virulent fungi to evade the body's immune response and is believed to be important to adhesion and biofilm formation.

In another set of experiments, the researchers examined the effect of the presence of the food-derived yeasts on the ability of non-albicans fungi to adhere to human epithelial cells. They found that the yeasts were highly effective in reducing adhesion, particularly when they were present before the fungal microbes were introduced. To test whether the yeasts would have a similar effect in a living organism, the researchers infected Caenorhabditis elegans, a nematode that mimics key aspects of human intestinal physiology, with non-albicans fungi. They found that the nematodes lived longer and the fungi recovered from infected nematodes were less active when they were treated with the food-derived yeasts.

The researchers also showed that extracts from the yeast cells were able inhibit adhesion by non-albicans fungi, suggesting that the effect might be due by secondary metabolites produced by the yeasts. "As the rate of deadly infections by Candida auris and other non-albican fungi species increases, there is a pressing need for more effective and safer medications to both prevent and treat these intractable illnesses," Rao said. "This study has shown that probiotic yeast may be the alternative we have been looking for, and certainly warrants further investigation."

Rao, a fellow of the American Academy of Microbiology, is currently focused on understanding the molecular mechanism of action, as well as computational modeling of the microbial interactions in silicon.

Bethesda, MD (Dec. 6, 2019) -- Gastric intestinal metaplasia (GIM), which is linked to non-cardia gastric cancer, is often detected during routine endoscopy, leading to questions about how patient care should be managed. A new clinical guideline1 from the American Gastroenterological Association, published in Gastroenterology, the official journal of the AGA Institute, provides recommendations for the management of patients with GIM detected as part of routine upper endoscopy for reasons including work up of endoscopically identified gastropathy/presumed gastritis, dyspepsia or exclusion of Helicobacter pylori (H. pylori).

"There is wide variation in practice patterns for the management of gastric intestinal metaplasia among endoscopists in the U.S., even those caring for populations at increased risk based on their race, ethnicity or immigration status," according to Samir Gupta, MD, MSCS, AGAF, lead author of the guideline, and associate professor of clinical medicine and staff physician at the University of San Diego, CA, and Veterans Affairs San Diego Healthcare System. "AGA developed this evidence-based guideline, the first supported by a comprehensive literature review in the U.S., for the management of patients with GIM incidentally detected on gastric biopsies in to help standardize clinical practice."

Screening for gastric cancer (either population-wide or in select populations), management of patients with dysplasia of the gastric mucosa, gastric adenocarcinoma, and/or autoimmune gastritis are beyond the scope of this guideline.

The guideline recommends:

1. In patients with GIM, AGA recommends testing for H. pylori followed by eradication over no testing and eradication. (strong recommendation: moderate quality evidence)

2. In patients with GIM, AGA suggests against routine use of endoscopic surveillance. (conditional recommendation: very low-quality evidence)

* Comments: Patients with GIM at higher risk for gastric cancer who put a high value on potential but uncertain reduction in gastric cancer mortality, and who put a low value on potential risks of surveillance endoscopies, may reasonably elect for surveillance.

3. In patients with GIM, AGA suggests against routine repeat short interval endoscopy with biopsies for the purpose of risk stratification (conditional recommendation: very low-quality evidence)

* Comments: Based on shared decision making, patients with GIM and high risk stigmata, concerns about completeness of baseline endoscopy, and/or who are at overall increased risk for gastric cancer (racial/ethnic minorities, immigrants from regions with high gastric cancer incidence, or individuals with family history of first-degree relative with gastric cancer) may reasonably elect for repeat endoscopy within 1 year for risk stratification.

AGA recognizes that new evidence may emerge in the future that may more strongly support short-interval repeat endoscopy with biopsies for risk stratification, and/or endoscopic surveillance for gastric cancer risk reduction.

Read the AGA Institute guidelines for management of gastric intestinal metaplasia to review the complete recommendations.

What is gastric intestinal metaplasia?

Gastric cancer is the third-leading cause of cancer death worldwide.2 Each year, 1,033,701 incident cases are diagnosed globally2, including 26,240 in the U.S.3 The majority of gastric cancers in the U.S. are non-cardia gastric cancers, arising from the antrum, incisura, body and/or fundus.4 Chronic infection with H. pylori is the primary risk factor for (intestinal-type) non-cardia gastric cancer, with at least 80% of the global gastric cancer burden attributable to this pathogen. Gastric intestinal metaplasia (GIM) may represent the histologic step just prior to development of dysplasia. GIM has been considered as one specific marker to identify patients who might benefit from surveillance because it has been associated with increased risk for gastric cancer and is routinely encountered in clinical practice.5

Resources for health care providers

Guideline

Technical review: Natural history and clinical outcomes

Technical review: Epidemiology and risk factors

References

1 Gupta S, Li, D, El Serag, HB, et al. American Gastroenterological Association Institute Guidelines for Management of Gastric Intestinal Metaplasia. Gastro. https://doi.org/10.1053/j.gastro.2019.12.003.

2 Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.32.

3 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin 2018;68:7-30.

4 Gupta S, Tao L, Murphy JD, et al. Race/Ethnicity-, Socioeconomic Status-, and Anatomic Subsite-Specific Risks for Gastric Cancer. Gastroenterology 2019;156:59-62.e4.

5 Plummer M, Franceschi S, Vignat J, et al. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer 2014;136:487-90.

Media contact: Rachel Shubert, media@gastro.org, 301-272-1603

About the AGA Institute

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. http://www.gastro.org.

About Gastroenterology

Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, Current Awareness in Biological Sciences, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visit http://www.gastrojournal.org.

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Journal

GASTROENTEROLOGY

DOI

10.1053/j.gastro.2019.12.003

Amsterdam, NL, December 10, 2019 - For patients with Huntington's disease (HD), clinical trials can offer hope when there are no treatments available despite unknowns about whether the therapy will work or is safe. A new study in the Journal of Huntington's Disease found that although the HD community appears highly optimistic about HD research, patients are at risk for therapeutic misconception. In order to allay patients' misgivings, investigators recommend improvements to patient-doctor communication to better convey trial goals, risks and benefits.

New therapies to modify the course of HD are currently entering clinical trials. "This is a very exciting time for the HD community," explained lead investigator Kristina Cotter, PhD, CGC, Department of Genetics, Stanford University School of Medicine, Stanford, CA. "Currently, there are no therapies that slow down the progression of HD; existing treatments only help manage some of the disease symptoms. There are several therapies being studied in trials that could potentially slow down the disease. However, there is a risk inherent in clinical trial participation because the trial is studying whether or not these new therapies are safe. Potential participants should be able to discuss their hopes and fears associated with the clinical trial."

In order to assess clinical trial attitudes and expectations investigators administered a questionnaire that rated participant attitudes towards a hypothetical HD clinical trial and how well participants understood the clinical research process. They also asked participants whether the way a therapy is administered (such as a pill or injection) changes their willingness to participate in a trial. The questionnaire was distributed through HD-related organizations. There were 73 responses from individuals who self-reported as clinically diagnosed with HD (20 patients) or who have the HD gene mutation but who are not yet symptomatic (22 patients), and 31 primary caregivers.

The study found that patients and families affected by HD believe that individuals with HD should participate in research. They viewed clinical trials positively and generally safe. They were able to appraise risks and benefits of research and were usually optimistic a new therapy would work. Individuals with prior HD-related research experience were less likely to have negative expectations about trials than those without research experience. Respondents also wanted as much information about a study as possible, with women exhibiting higher information needs than men. Investigators also learned that willingness to participate was highest when the route of administration was minimally invasive and that invasive therapies (such as those injected into the spinal column, brain, or eye) might decrease the likelihood that an individual would participate in research.

Interestingly, investigators found that patients with HD were less likely to recognize the difference between clinical trials and the typical care received in an HD clinic. Finally, they found that patients with HD are more likely to believe that research participation is for personal benefit and that care they receive in a clinical trial is similar to that received in an HD clinic.

"It is possible that this belief is linked to the cognitive decline that occurs in HD," noted Dr. Cotter. "This tells us that as we recruit for clinical trials, we should take extra care to share detailed information about trial goals, risks and benefits, how a new therapy is administered, and how the trial is different from clinical care."

Regardless of the disease, participating in clinical trials is a big decision for patients and their families. This study provides clinicians with information about how to discuss research with the HD community:

Emphasize the distinction between research and clinical standard of care and consider a patient's past experiences with clinical research when discussing trial opportunities

Evaluate patients and caregivers for misunderstandings around the clinical research process

Anticipate questions and concerns surrounding more invasive routes of administration

Provide patients and caregivers with both written and verbal information about the trial, bearing in mind that women may require more details than men

"It is very exciting to be able to offer possible disease-modifying therapies to patients with HD in clinical trials," commented co-investigator Sharon J. Sha, MD, MS, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA. "However, we need to make sure everyone involved - patients and families - can ask questions and receive all of the information they need to make informed decisions. This research is important because it reminds us, as clinicians, to provide better informed consent and to be wary of both the investigators' and participants' biases towards research participation."

The investigators hope that the findings from this study will help guide conversations among clinicians, researchers, and patients to help patients make the best decision for themselves and their families. "The better clinicians and researchers understand HD patients' and families' beliefs and values, the better equipped we will be to help them decide whether participation in clinical trials is appropriate for them," added co-investigator Andrea Hanson-Kahn, MS, LCGC, Department of Genetics, Stanford University School of Medicine and Department of Pediatrics, and Division of Medical Genetics, Stanford University Medical Center, Stanford, CA.

HD is a fatal genetic neurodegenerative disease characterized by atrophy of certain regions of the brain. It causes the progressive breakdown of nerve cells in the brain. HD patients experience behavioral changes and uncontrolled movements. Symptoms include personality changes, mood swings and depression, forgetfulness and impaired judgment, and unsteady gait and involuntary movements (chorea). Every child of an HD parent has a 50% chance of inheriting the gene. Patients usually survive 10-20 years after diagnosis.

BOSTON - A new study led by Boston Medical Center uncovered a need to improve testing rates for Hepatitis C Virus (HCV) in young people, specifically those with documented substance use history. In the national data sample, under 30 percent of young patients who reported using opioids, methamphetamine, and/or cocaine were tested for HCV. Given the increased incidence of HCV in the US, especially among young people, fueled by the opioid epidemic, the study highlights the importance of ensuring that clinicians better screen and test younger patients for HCV when they present with risk factors, as well as connect those found to have current infection to treatment.

Published in the Journal of the American Medical Association, this is the first study to analyze national data on how adolescents and emerging adults are both tested and treated for HCV. Data from the Centers for Disease Control and Prevention (CDC) reveal that of all people reported to have chronic HCV infection, the proportion of individuals between the ages of 15 and 24 years increased from 3.8 percent in 2009 to 9.1 percent in 2013-16. In fact, most new infections are in people under age 30 who inject drugs. The major risk factor for HCV in young adults is injection drug use. According to the National Institute on Drug Abuse, 4,235 adolescents and young adults between the ages of 15 and 24 died from a drug-related overdose in 2015 - more than half of which can be attributed to opioids.

"We need to consider and test for hepatitis C in younger age groups when we identify opioid or other injectable substance use," said lead researcher Rachel Epstein, MD, MSc, an infectious diseases physician at Boston Medical Center and the study's corresponding author. "Improving our standards for testing and identifying at-risk populations sooner and treating those with chronic infection, are necessary to ultimately reduce hepatitis C transmission".

Using electronic health record data, the study investigators identified 269,124 patients, age 13-21 years old, seen at a network of federally qualified health centers (FQHCs). The multi-step testing process for HCV involves first testing for HCV antibodies (for which 1.8 percent of those tested in this study had positive results). Among those with documented substance use, who were tested, over 7 percent were positive for HCV antibodies, and 45 percent of patients who had follow-up confirmatory testing had detectable RNA, indicating a current infection.

"These data are cause for concern - and action - to ensure that patients are not only being tested, but are also receiving the treatment necessary to cure the disease," said Sabrina Assoumou, MD, MPH, also an infectious diseases physician at BMC and senior author of the study. "As patients do not always disclose substance use, more universal testing and earlier identification of HCV is critical to prevent transmission and morbidity from disease progression." In fact, the CDC and the US Preventive Services Task Force have recently disseminated draft updates to testing guidance recommending HCV testing for all adults ages 18 and older.

Once a patient has been tested for HCV and found to have detectable antibodies and RNA, genotype testing is done to determine a personalized approach to treatment based on the specific strain of HCV that the patient has contracted. Only 36.6 percent of HCV-infected youth in this study completed genotype testing, and only one individual had documented HCV treatment, representing a gap in care for young people in underserved communities accessing community health center services.

HCV treatment typically takes 2-3 months and involves taking just a few pills each day, with minimal side effects. The FDA recently approved the first direct-acting antiviral treatment for children 3-11 years-old, and multiple regimens are available for youth aged 12-17. Now that treatment is feasible for young children, the discussion between pediatricians and their patients about both substance use and HCV in at-risk patients is even more critical.

"This is now an easily treatable virus, meaning that HCV elimination is possible," said Epstein. "However, to achieve this, we must focus on early detection and on removing barriers to testing and treatment so we can connect patients to treatment early to improve individual care and prevent future transmission."

Tumor volume in a preclinical model of triple negative breast cancer (TNBC) was reduced four times more when an experimental polo-like kinase 1 (PLK1) inhibitor was combined with a standard-of-care chemotherapeutic agent than when the agent was used alone. Hollings Cancer Center scientists at the Medical University of South Carolina reported these findings in PLOS ONE.

TNBC disproportionately affects African American and Hispanic women under the age of 50. It is an aggressive form of breast cancer that lacks the three receptors ¬- estrogen, progesterone and human epidermal growth factor receptor 2 - that many existing breast cancer treatments target. For that reason, patients with TNBC do not respond well to these therapies.

Standard-of-care treatment for these patients has traditionally included surgery, chemotherapy and radiation, individually or in combination. Recently, immunotherapy has been shown to improve survival in eligible patients with breast cancer. However, only about 40% of patients with stage 4 TNBC qualify for immunotherapy.

In hopes of one day helping the remaining 60%, Hollings cancer researcher Antonio Giordano, M.D., Ph.D., and his team studied whether a combination of a PLK1 inhibitor and a standard-of-care chemotherapeutic drug would be more effective against TNBC than the drug alone. The team included Yueying Liu, who carried out most of the laboratory experiments, and Stephen P. Ethier, Ph.D., director of the Center for Genomic Medicine at MUSC, who conceptualized and supervised this work. Their work was funded by the National Institutes of Health.

They thought the PLK1 inhibitors would interfere with cancer cells' ability to divide without check, enabling a chemotherapeutic drug to kill them.

"The PLK1 inhibitors are like traffic light signals that stop the uncontrolled growth of the breast cancer cells, allowing the taxanes to actually catch up with the cancer cells and kill them," explained Giordano. "That's why we thought that combining a drug that blocks PLK1 with a standard chemotherapy drug like a taxane would work well together to kill the cancer cells that have lost total control of division."

The MUSC team studied how PLK1 inhibitors and taxanes, alone and in combination, affected TNBC cell lines known to be resistant to chemotherapy. They found that the combination of a PLK1 inhibitor and a taxane makes the TNBC cells more vulnerable to chemotherapy. It also reduces the number of cancer stem cells, which are associated with metastasis.

"With promising results from the cell line experiments, we decided to try only the combination of the PLK1 inhibitor onvansertib and paclitaxel on animals," explained Giordano. "Onvansertib is already in clinical trial for other diseases as a single agent and has shown a good toxicity profile. Paclitaxel, given weekly, has a much better toxicity profile than docetaxel, with fewer side effects."

In mice, the combination of onvansertib and paclitaxel reduced TNBC tumor volume more than four times as much as paclitaxel alone after 21 days of treatment. And it achieved the impressive reduction despite using much less of each individual drug than when it was given alone. Lower doses reduce the likelihood of toxic side effects, making the combination regimen more attractive as a potential therapy for patients with TNBC.

These promising results have prompted the researchers to plan a phase 1 clinical trial. They hope to begin recruiting patients for the trial sometime in 2020.

"Scientists are working hard every day to develop new drugs for triple negative breast cancer treatment, and the most important thing is for patients to participate and support clinical trials," said Giordano. "That is the only way drugs can advance in clinical experimentation and get approved for patients. It is also the only way patients can receive drug therapies earlier in the course of the disease."

Sometimes, the medications needed to function and live a quality life cause side effects that can make life quite uncomfortable.

Dr. Jeffrey Strawn, associate professor in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati College of Medicine, and Jeffrey Mills, associate professor in the Department of Economics at the UC Lindner College of Business, published a study in the Journal of the American Academy of Child & Adolescent Psychiatry looking specifically at side effects that impact children and adolescents being treated for anxiety disorders and obsessive-compulsive disorder (OCD).

Strawn says this is one of the first studies examining side effects of these medications in youth that doesn't just focus on suicidal thinking or discontinuation of medication.

"For youth with anxiety disorders and OCD, these medications improve symptoms and functional outcomes," he says. "Over the past two decades, selective serotonin reuptake inhibitors, known as SSRIs, and serotonin-norepinephrine reuptake inhibitors, known as SNRIs, have become the standard medication treatments for pediatric patients with these conditions."

The UC study assessed quality-of-life issues.

"Evaluations of antidepressant tolerability focus almost entirely on discontinuation of the medicine or suicidality. We wanted to examine side effects commonly reported in pediatric patients treated with antidepressants, including agitation, nausea, abdominal pain, insomnia, headache and fatigue, in addition to suicidality and discontinuation of medication."

SSRIs increase levels of serotonin in the brain. SNRIs block the reabsorption of the neurotransmitters serotonin and norepinephrine in the brain.

In this study, Mills and Strawn looked at academic peer-reviewed articles through March 1, 2019, and identified SSRI and SNRI studies in patients under 18 with OCD and anxiety disorders, specifically noting side effect rates.

They used statistical tools known as Bayesian hierarchical models created by Mills that enable results from different studies to be combined while taking into account variations across patients and those studies.

"Out of 18 trials, which included more than 2,500 patients who were treated and then compared to patients taking a placebo, SSRIs produced more side effects; agitation was more common with SSRI use," Mills says.

"SSRIs and SNRIs were not associated with suicidal thoughts. This finding is consistent with earlier studies that suggest that suicidality relates to the condition being treated," Strawn adds. "Medication side effects are important for clinicians to consider, particularly in light of data suggesting these medications also differ in terms of how effective they are. SSRIs are a better option compared to SNRIs and are the treatment of choice for children and adolescents with anxiety."

Preventable deaths are those that can be stymied by public health intervention, and deaths related to tobacco use are at the top of that list in the United States as well as globally.

And while rates of adolescent smoking have declined over the years, 4.9 million middle and high school students reported using tobacco in 2018, according to the U.S. Department of Health and Human Services.

The primary focus of smoking cessation research in the past has always been adults, but a new study in JAMA Pediatrics zeroed in on adolescents. "Too often, we make the assumption that adolescents are just little adults," said Kevin Gray, M.D., a psychiatry and behavioral sciences professor and physician at the Medical University of South Carolina. "And so, we treat them the same way as we do our adult patients. But it's much more complicated than that."

One of the key differences in treating adolescents is the pressure surrounding their smoking habit. Adolescents are more likely than adults to start using addictive substances, and they are more likely to do something risky without considering the long-term consequences. "Most people who decide it's time to quit are well into adulthood," said Gray. "Oftentimes, their health consequences are becoming quite real for them." Adolescents don't usually experience health issues related to smoking until much later.

Gray also points to peer influence. Adolescents are more likely to be influenced by and pressured by their peers, and they're more likely to try new things.

Varenicline tartrate, more commonly recognized under the brand name Chantix, is a popular pharmacotherapy for smokers looking to quit. It has proven effective in adults but has not been examined as a smoking cessation tool for adolescents. By adhering closely to the protocol used when treating adults, Gray and his research team at MUSC can compare past research to their current results.

Participants were treated with varenicline in conjunction with therapy over the course of 12 weeks to determine the drug's efficacy. But what Gray and his team found was that at the end of 12 weeks, there was no significant difference between the placebo group and the treatment group in terms of end-of-treatment smoking abstinence. A similar number of participants in the two groups had quit by the end of the trial, but when Gray looked at posttreatment abstinence -- that is, the number of participants who remained smoke-free even after treatment had ended -- he saw that those in the varenicline group were less likely to relapse.

"The group differences at the end of treatment, considered in isolation, may not always be the most important marker of efficacy," said Gray. "The nuanced piece of it is quitting smoking earlier on in treatment, which in our study occurred in the varenicline group compared to the placebo group, is a better indicator of a participant's long-term success."

This study showed that varenicline affects smoking cessation in adolescents differently than in adults and may not be an effective treatment on its own. Overall rates of quitting were lower in these trials than in previous adult varenicline trials, a common finding when comparing studies between the two age groups. Gray suggests that participant motivation plays a role. The desire to quit waxes and wanes over time, especially in adolescence. Gray compares it to a dimmer switch as opposed to an on-off switch and says that motivation can depend on timing as well as life situations. He embraces the idea that medication alone likely won't work as well for adolescents as pairing a medication like varenicline with therapy and behavioral treatments.

While this study specifically looked at adolescent smoking cessation, it is part of a larger team at the hospital. The MUSC Youth Collaborative works together to further advance the education, clinical care and research surrounding substance use treatment outcomes for both adolescents and their families through studies like this one.

Next, Gray's team will be working on "outside-the-box" treatment opportunities for their patients. Having to schedule clinic time around participants' school hours as well as factoring in transportation has inspired the team to look into mobile technology as a way of enhancing treatment options. "We want to match our treatments to the needs of adolescents," said Gray. "And part of that is truly understanding where adolescents are with smoking and designing treatments around that."

A new study suggests that specialized immune cells that dampen inflammation and help repair the gut could be used as a potential therapy for children dealing with the painful symptoms of inflammatory bowel disease (IBD).

The research from BC Children's Hospital and the University of British Columbia shows that a specific type of T cell, called a Tr1 cell, produces a chemical signal that helps repair the barrier formed by cells lining the gut and encourages the production of protective mucus. This study was published in the December issue of Gastroenterology.

"This study offers new hope for kids with IBD who urgently need new treatments by showing that Tr1 cells have the potential to reverse the damage caused by IBD," said senior author Dr. Megan Levings, an investigator and head of the Childhood Disease Research Theme at BC Children's and a professor in UBC's department of surgery and school of biomedical engineering. "As a new therapy, Tr1 cells could both suppress the inflammation that is ravaging the lining of the gut and help heal the tissue lining that keeps out harmful bacteria."

Inflammatory bowel disease occurs when the body's immune system mistakenly triggers inflammation in the digestive tract. Inflammation is part of the body's normal response to illness and injury, but in conditions like Crohn's and colitis it can severely damage healthy tissue.

More than 7,000 Canadian children have been diagnosed with IBD and deal with constant belly pain, cramps, diarrhea and vomiting. These symptoms can lead to malnutrition, weight loss and a lack of energy which can result in missed school days and less time for sports and hobbies. The incidence of two main kinds of IBD -- Crohn's disease and ulcerative colitis -- is increasing and diagnoses of Crohn's in Canadian kids under 10 have doubled since 1995.

The most common frontline therapy for IBD is the use of antibodies to block inflammation. However, as many as a third of IBD patients do not respond to this treatment -- and even if treatment is initially successful, the disease can flare up again later.

"Kids with IBD develop abnormal immune responses to normal gut bacteria," said study co-author Dr. Ted Steiner, an infectious disease specialist, investigator at BC Children's and professor in UBC's department of medicine. "Training our immune system to fight off infections and bad gut bacteria while maintaining normal relationships with the good bacteria is critical for the health of children with these diseases."

"We created self-organized, three-dimensional mini-guts in the lab that we could use to test how Tr1 cells interact with other cells in a more life-like setting," says study co-author Dr. Bruce Vallance, an investigator at BC Children's, the CH.I.L.D. Foundation Chair in Pediatric Gastroenterology and professor in UBC's department of pediatrics. "What we found was unexpected, that Tr1 cells can promote the mini-guts to release protective mucus and improve the local gut environment. No other types of T cell that we've studied can do this."

Importantly, the researchers found that Tr1 cells isolated from patients with IBD are just as capable of reducing inflammation as those derived from healthy individuals.

"It's not yet clear why people with IBD develop disease if their Tr1 cells are intact, but it could be there are simply too few of these cells to stave off the inflammation," says the study's lead author Dr. Laura Cook, a UBC postdoctoral fellow. "By isolating and boosting the number of these cells in the lab we could one day offer this as a new personalized treatment strategy for children with colitis or Crohn's disease."

Further work is needed to see how these cells can be best nurtured in the lab to ensure that when they are given to children with IBD they will have the best possible chance of relieving the condition. In the future, growing these cells from a patient and then reintroducing them to the gut could be a new cell-based therapy for inflammatory bowel disease.

London, UK: Cephalalgia, the official journal of the International Headache Society, published the article entitled "Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial", by Man Amanat, and Mahmoud Reza Ashrafi from the Tehran University of Medical Sciences, Tehran, Iran.

Migraine affects about 8% of children and adolescents. About half of them continue to experience it into adulthood, leading to remarkable disability and a substantial social and financial burden to the patient and society. Early diagnosis and interventions can diminish the burden of the condition. Preventive pharmacologic treatment should be recommended when the frequency of headaches is more than 4 attacks per month or when the quality of life, school attendance or daily activities are restricted. Studies show that migraine preventive treatment can decrease the global burden of migraine. Although various preventive medications have been used for migraine in adults, few have been suggested in a pediatric population.

This paper studied the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in 149 children and adolescents (49 in the cinnarizine, 51 in the sodium valproate, and 49 in the placebo group).

Cinnarizine is a medicine that belongs to the category of antihistaminic medications. It is used to treat problems associated with the inner ear and the brain, dizziness, and sickness associated with motion sickness. Cinnarizine is used to relieve symptoms of motion sickness and balance (vestibular) disorders such as tinnitus (ringing in the ears), vertigo, nausea, and vomiting, as well as Ménières disease (a disorder of the inner ear).

Sodium valproate is a medication primarily used to treat epilepsy and bipolar disorder and to prevent migraine headaches. It is an anticonvulsant drug that is approved for use in epilepsy and bipolar disorder. It has also been used for neuropathic pain and migraine prophylaxis.

The medications were considered effective in reducing (more than 50%) the (frequency) number of migraine attacks and intensity, compared to the placebo group.

"Cinnarizine and sodium valproate may be useful for migraine preventive treatment for children and adolescents. Both medications are safe and well-tolerated in terms of adverse events, but cinnarizine could be considered as a new preventive option for pediatric migraine", explained the authors. Long term safety regarding weight gain should be studied in future trials.