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ANN ARBOR--The use of opioids to soothe the pain of a pulled tooth could be drastically reduced or eliminated altogether from dentistry, say University of Michigan researchers.

More than 325 dental patients who had teeth pulled were asked to rate their pain and satisfaction within six months of extraction. Roughly half of the study's patients who had surgical extraction and 39% who had routine extraction were prescribed opioids.

The U-M researchers compared the pain and satisfaction of those who used opioids to those who didn't.

"I feel like the most important finding is that patient satisfaction with pain management was no different between the opioid group and non-opioid group, and it didn't make a difference whether it was surgical or routine extraction," said study co-author Romesh Nalliah, clinical professor and associate dean for patient services at the U-M School of Dentistry.

Surprisingly, patients in the opioid group actually reported worse pain than the non-opioid group for both types of extractions, Nalliah said.

The researchers also found that roughly half of the opioids prescribed remained unused in both surgical and nonsurgical extractions. This could put patients or their loved ones at risk of future misuse of opioids if leftover pills are not disposed of properly.

The findings are scheduled to appear March 13 in JAMA Network Open.

"The real-world data from this study reinforces the previously published randomized-controlled trials showing opioids are no better than acetaminophen and nonsteroidal anti-inflammatory drugs for pain after dental extraction," said study co-author Chad Brummett, director of the Division of Pain Research and of Clinical Research in the Department of Anesthesiology at Michigan Medicine, U-M's academic medical center.

Brummett co-directs the Michigan Opioid Prescribing Engagement Network, or Michigan OPEN, which has developed, tested and shared guidelines for the use of opioids in patients with acute pain from surgery and medical procedures.

"These data support the Michigan OPEN prescribing recommendations calling for no opioids for the majority of patients after dental extractions, including wisdom teeth extraction," he said.

The results have big implications for both patients and dentists, and suggest prescribing practices need an overhaul, Brummett and Nalliah said.

The American Dental Association suggests limiting opioid prescribing to seven days' supply, but Nalliah believes that's too high.

"I think we can almost eliminate opioid prescribing from dental practice. Of course, there are going to be some exceptions, like patients who can't tolerate nonsteroidal anti-inflammatories," he said. "I would estimate we can reduce opioid prescribing to about 10% of what we currently prescribe as a profession."

For dentists, many of whom are sole proprietors, this new information means they needn't worry so much about unhappy patients changing practices if they aren't prescribed strong opioids. Alternatives such as nonsteroidal anti-inflammatory drugs or acetaminophen appear to control pain better, and patient satisfaction remains high.

Nalliah gives two possible reasons for this. First, dentists may have prescribed opioids in only the toughest cases, which would have resulted in more pain regardless.

"Or alternatively, and this is the reason I tend to accept, is that our study concurs with previous studies that suggest opioids are not the most effective analgesic for acute dental pain," Nalliah said.

"Dentists are torn between wanting to satisfy patients and grow business and limiting their opioid prescribing in light of the current crisis. I think it's an extremely liberating finding for dentists who can worry more about the most effective pain relief rather than overprescribing for opioids."

Dentists account for about 6% to 6.5% of U.S. opioid prescriptions--a relatively small amount. But the study notes that dentists are among the most common prescribers for minors, and for many patients, dental opioid prescriptions are their first exposure.

If you've ever played an immersive game using virtual reality (VR) technology, you'll be familiar with the concept of customising an avatar to represent you. Most people design an aspirational, buffed-up version of themselves, but new research from the University of Bath suggests you should temper your vanity when the game is for fitness, as your performance improves when they compete against an avatar that more closely matches your authentic self.

"Idealised avatars increase wishful identification but seem to impact physical performance negatively," said Dr Christof Lutteroth, who led the research from the University's Department of Computer Science.

The Bath study explores the effects of two types of customisation (idealised and realistic) in an immersive bike racing exergame. The findings are presented in a paper that has received a prestigious Best Paper Award from the CHI Conference on Human Factors in Computing Systems, due to take place in Hawaii next month.

For the study, racers wearing VR headsets self-competed against both a generic avatar and an avatar that represented them more accurately. They performed better against their realistic avatar and found the game more motivating. Next, racers self-competed against their realistic versus an idealised avatar. Though they had fun playing against their pumped-up selves, they performed better against their realistic avatar, as measured through power output.

"The game pushed people to their limits for 30 seconds to see how hard they could exert themselves over a short time. When they competed against their realistic avatar, they were 3% faster than when with their idealised avatar - in other words, they exerted themselves 3% more. We believe that over time, as fitness is increased, the gap in effort would grow."

Also involved in the study were Professor Eamonn O'Neill from the Department of Computer Science, PhD student Zoe Jeffery and former students Jordan Koulouris and James Best.

Ms Jeffery said: "This study is the first of its kind, blending both quantitative and qualitative methods to give a deeper understanding of the effects of avatar customisation on motivation within virtual reality exercise games. It has the potential to influence further research in this field, and has given me a well-needed boost for my own PhD study."

Dr Lutteroth said a possible explanation for the positive effect of the realistic avatar is a mechanism known as feedforward. This describes the motivation and performance gains that come from competing against a self-model that you can readily identify with. A generic and idealised self-model are likely to lower the feedforward effect by reducing self-recognition.

"Our results suggest that exergame designers should definitely consider using realistic avatar customisation to improve player experience and performance," said Dr Lutteroth.

Explaining the significance of his research, he added: "Many people struggle to meet the recommended levels of physical activity, with 40-65% of those who begin exercise regimes dropping out within three to six months. Combining exergames with VR has revolutionised the possibilities for health interventions, creating an immersive experience with possible attentional distraction from physical exertion. If we can persuade people to stick with their exercise programmes through self-identification with their avatar, that will be a move in the right direction."

March 13, 2020 - As outbreaks of COVID-19 disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue worldwide, there's reassuring evidence that children have fewer symptoms and less severe disease. That's among the insights provided by an expert review in The Pediatric Infectious Disease Journal, the official journal of The European Society for Paediatric Infectious Diseases. The journal is published in the Lippincott portfolio by Wolters Kluwer.

Like previous epidemic coronaviruses, "SARS-CoV-2 [seems] to cause fewer symptoms and less severe disease in children compared with adults," according to the review by Petra Zimmerman, MD, PhD, of the University of Fribourg, Switzerland and Nigel Curtis, FRCPCH, PhD, of The University of Melbourne, Australia. They summarize available evidence on coronavirus infections in children, including COVID-19.

"There is some suggestion that children are just as likely as adults to become infected with the virus but are less likely to be unwell or develop severe symptoms," Drs. Zimmerman and Curtis write. "However, the importance of children in transmitting the virus remains uncertain."

The Evidence on SARS-CoV-2 - Focusing on Risks to Children

Coronaviruses are a large family of viruses that can cause infection and disease in animals. "Coronaviruses are capable of rapid mutation and recombination, leading to novel coronaviruses that can spread from animals to humans," Drs. Zimmerman and Curtis write. There are four coronaviruses that circulate in humans, mostly causing respiratory and gastrointestinal symptoms - ranging from the common cold to severe disease.

Over the past two decades, there have been three major disease outbreaks due to novel coronaviruses: SARS-CoV in 2002, MERS-CoV in 2012, and now SARS-CoV-2 in 2019. Arising in the Chinese city of Wuhan, SARS-Cov-2 spread rapidly around the world and has been declared a pandemic by the World Health Organization. "The term COVID-19 is used for the clinical disease caused by SARS-CoV-2," according to the authors. Transmission of SARS-CoV-2 appears similar to that of the related SARS and MERS coronaviruses, but with a lower fatality rate. SARS-CoV-2 can still cause serious and life-threatening infections - particularly in older people and those with pre-existing health conditions.

What are the risks for children from SARS-CoV-2? It's a pressing question for pediatric infectious disease specialists and concerned parents alike. Children appear to have milder clinical symptoms than adults and to be at substantially lower risk of severe disease - which was also true in the SARS and MERS epidemics.

In Chinese data from February 2020, children and adolescents accounted for only two percent of SARS-CoV-2 hospitalizations, Drs. Zimmerman and Curtis write. However, as children are less frequently symptomatic and have less severe symptoms they are less often tested, which might lead to an underestimate of the true numbers infected. Also, children are less frequently exposed to the main sources of transmission.

Again based on Chinese data, "Most infected children recover one to two weeks after the onset of symptoms, and no deaths had been reported by February 2020," the researchers add. Most reported infections with SARS-CoV-2 have occurred in children with a documented household contact. Children with COVID-19 may be more likely to develop gastrointestinal symptoms.

The experts also review the diagnostic findings (laboratory tests and imaging studies) of children with COVID-19 laboratory and imaging findings in children. Whole genome sequencing approaches have enabled rapid development of molecular diagnostic tests for SARS-CoV-2. For now, treatment is supportive; no specific antiviral medications are available.

Several approaches are being considered for development of new drugs and vaccines - some targeting a "spike glycoprotein" involved in interactions between coronaviruses and cells. Until such treatment and preventive measures are available, the researchers emphasize the importance of the full range of strategies for controlling SARS-CoV-2 - as for the "highly effective global public health response" that led to containment of the SARS epidemic.

In the first study of its kind, University of Miami researchers have found a strong behavioral signal to indicate which infants who have an older sibling with an autism spectrum disorder (ASD) will themselves be diagnosed with ASD as they grow older.

The researchers found that such high-risk infants who exhibit an early social difficulty, specifically an insecure-resistant attachment to a parent, are more than nine times more likely to receive an ASD diagnosis by age 3 than high-risk infants with secure attachments.

Early recognition of an insecure-resistant attachment--measured by how 15-month-old babies react when they are briefly separated then reunited with a parent--won't prevent a future ASD diagnosis. But, the researchers said, it could lead to interventions that help infants who will develop an ASD form more secure social relationships, which is often difficult for people with the neurodevelopmental disorder.

"Insecure attachment patterns are generally associated with less optimal behavioral and emotional developmental outcomes later in life than secure attachments. And, there are critical interventions designed around attachment security--but not for infants at high risk for ASD," said Katherine Martin, the lead author, who initiated the research as a Ph.D. candidate under the guidance of psychology professor Daniel Messinger.

"This new study," Martin continued, "suggests the need for interventions for high-risk infants that specifically focus on sensitizing parents to social and emotional communication behaviors in infants identified as having insecure-resistant attachments. This would hopefully be a means to decreasing resistant attachment behaviors and lowering the obstacles to acquiring social competencies, which are already impaired in children with autism."

Many babies cry or show other signs of distress when a parent departs and they are left behind with a stranger. But secure babies are soothed when the parent returns. That, however, is not the case with babies classified with insecure-resistant attachments.

"They not only cry when the parent leaves, but they never really settle down when the parent returns, which indicates that the infants are not confident in their ability to be calmed," said Messinger, who has been studying the infant siblings of older children diagnosed with ASD for 15 years.

Recently published in the journal Developmental Science, the new study on how attachment security differs in babies who are later diagnosed with an ASD builds on Messinger's previous research. In one prior study, he and his collaborators found that about one in five infants of siblings with an ASD also will be diagnosed with an ASD, which is why they are considered high risk.

But with the goal of understanding the relationship between infant attachment security--the preeminent measure of the infant-parent relationship--and later ASD outcomes, Messinger and his students also investigated whether high-risk infants were more likely to be classified as insecurely attached to a parent than infant siblings of typically developing children.

And, they were not. "Although children may demonstrate resistant attachment patterns, that does not necessarily indicate they are headed towards autism," said John D. Haltigan, a former student of Messinger's and an author on both the previous and the current study. "However, if you're at high risk for autism and you have a resistant attachment, then you are more likely to have an ASD outcome."

Although difficulties with social relationships are key to autism spectrum disorder, no previous study had assessed security attachments in infants with a familial risk for ASD prior to their later ASD diagnosis, which typically occurs after age 3. When Martin, who now works for a psychology-related company, joined Messinger's lab in 2014 to pursue her Ph.D., she set out to change that.

"We know that one of the cornerstone impairments of ASD is this difficulty in forming and maintaining social relationships, and attachment security is the key measure of the infant-parent relationship, so it made sense to look at how attachment security relates to ASD diagnoses," she explained. "That hadn't been looked at prospectively, so this is the first time we looked at it prior to ASD diagnoses."

For the new study, Martin, Messinger, Haltigan, and two other students analyzed the attachment security of 95 infants who were classified by trained coders into four different attachment classifications when they were 15 months old. Then the researchers looked for a correlation between each infant's attachment classification and their ASD diagnosis, or absence of one, when the child turned 3 years old.

As it turned out, 16 of the 95 infants were high-risk infants who eventually developed ASD; 40 were high-risk infants who did not develop ASD; and 39 were low-risk infants who likewise didn't develop ASD.

Recruited from one of Messinger's larger, long-term studies, all 95 infants and one of their parents were initially assessed with the Strange Situation Procedure. Long considered the gold-standard, laboratory-based approach for measuring attachment security in infants, the procedure involves briefly separating infants from their mother or father on two occasions and assessing how they react during their parent's absence and upon their return.

Secure babies typically explore their surroundings in their parent's presence, and then seek to be close to the parent after an absence. Those classified with insecure resistant attachments explore less and are not often comforted by the parent's return or soothing overtures. By matching the classification for each of the 95 children with their diagnoses at age 3, the researchers determined that high-risk infants with insecure-resistant attachments were more than nine times more likely to receive an ASD diagnosis than high-risk infants with secure attachments.

"There are a lot of questions about when early indications of autism emerge, and this is a pretty strong risk signal at 15 months among infants who have an older sibling with ASD," Messinger said. "And while we can't stop a future ASD diagnoses, this suggests we should also consider attachment-related interventions for high-risk infants who show insecurity. We don't do that at all right now."

In addition to Messinger, Martin, and Haltigan, who is now at the University of Toronto, co-authors of the study included Messinger's former post-doctoral student, Naomi Ekas, now at Texas Christian University, and Emily Prince, his current graduate student.

The cover for issue 10 of Oncotarget features Figure 3, "Overall survival (OS) for high (red) versus low (black) risk groups in the (A) OSU, (B) TCGA, and (C) SNU resected cohorts," by Wolfe, et al.

Digital mi RNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated mi RNAs and dichotomized about the median to detect correlations between risk group, LRR and overall survival.

On multivariable analysis, the risk score remained significantly associated with LRR.

They have developed a 4-mi RNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts.

Dr. Terence M. Williams from The Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute, Columbus, OH, USA said, "In the United States, there are an estimated 56,770 new cases of pancreatic carcinoma (PC) and 45,750 estimated deaths."

"In the United States, there are an estimated 56,770 new cases of pancreatic carcinoma (PC) and 45,750 estimated deaths"

- Dr. Terence M. Williams, Ohio State University Medical Center, Arthur G. James Comprehensive Cancer Center and Richard J. Solove Research Institute

Interestingly, a National Cancer Database study and retrospective studies from Mayo Clinic and Johns Hopkins have reported superior local-regional control and OS in patients receiving adjuvant chemoradiation versus observation or chemotherapy alone.

The ongoing phase III RTOG 0848, a randomized trial between adjuvant CRT versus chemotherapy alone should provide more clarity on whether adjuvant chemoradiation can improve outcomes.

Past efforts have focused on using clinical and pathologic features to predict patterns of failure and prognosis after surgery, in hopes that improved patient selection for adjuvant therapy may improve outcomes.

To that end, the researchers carefully characterized patterns of recurrence in patients treated with surgery and postoperative chemotherapy alone at our institution using patterns of failure radiologic analysis.

Their aim is to identify a mi RNA expression profile that correlates with LRR and OS after surgical resection which might be used to better select patients who could benefit most from adjuvant chemoradiation in the future.

The Williams Research Team concluded, in their Oncotarget Research Article, "we have developed a four miRNA risk score that provides prognostic information for clinical outcomes after surgical resection for pancreatic cancer. Based on the ability of our four miRNA risk score to predict local-regional control, as well as overall survival in three cohorts, such molecular profiles have the potential to help guide clinical decision-making for pancreatic cancer patients after surgical resection. We further intend to apply our risk stratification miRNA score to patients treated on prospective clinical trials with surgery followed by chemotherapy with and without chemoradiation to validate its ability to predict LRR and OS. In addition, this risk score warrants testing on patients who have received neoadjuvant (preoperative) chemotherapy for locally-advanced or borderline resectable PC in order to determine if this miRNA signature can risk-stratify patients in the neoadjuvant setting who would benefit from escalated local-regional therapy (such as radiation or chemoradiation). Such a risk score in the neoadjuvant setting could help decide the need to employ radiation therapy to improve margin negative resection rates and lymph node clearance rates, thereby likely improving local-regional recurrence. Thus, we feel that further validation studies with larger patient numbers and with rigorous patterns of failure data are warranted."

ROCHESTER, Minn. -- Mayo Clinic researchers have uncovered stem cell-activated mechanisms of healing after a heart attack. Stem cells restored cardiac muscle back to its condition before the heart attack, in turn providing a blueprint of how stem cells may work.

The study, published in NPJ Regenerative Medicine, finds that human cardiopoietic cells zero in on damaged proteins to reverse complex changes caused by a heart attack. Cardiopoietic cells are derived from adult stem cell sources of bone marrow.

"The extent of change caused by a heart attack is too great for the heart to repair itself or to prevent further damage from occurring. Notably, however, cardiopoietic stem cell therapy reversed, either fully or partially, two-thirds of these disease-induced changes, such that 85% of all cellular functional categories affected by disease responded favorably to treatment," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine. Dr. Terzic is the senior author of the study.

This new understanding of how stem cells restore heart health could provide the framework for broader applications of stem cell therapy across various conditions.

"The actual mode of action of stem cells in repairing a diseased organ has until now been poorly understood, limiting adoption in clinical care. This study sheds light on the most intimate, yet comprehensive, regenerative mechanisms ? paving a road map for responsible and increasingly informed stem cell application," says Dr. Terzic.

Heart disease is a leading cause of death in the U.S. Every 40 seconds, someone in the U.S. has a heart attack, according to the Centers for Disease Control and Prevention. During a heart attack, cardiac tissue dies, weakening the heart.

"The response of the diseased heart to cardiopoietic stem cell treatment revealed development and growth of new blood vessels, along with new heart tissue," adds Kent Arrell, Ph.D., a Mayo Clinic cardiovascular researcher and first author of the study.

The research

Researchers compared the diseased hearts of mice that did not receive human cardiopoietic stem cell therapy with those that did. Using a data science approach to map all the proteins in the heart muscle, researchers identified 4,000 cardiac proteins, more than 10% of which suffered damage by a heart attack.

"While we anticipated that the stem cell treatment would produce a beneficial outcome, we were surprised how far it shifted the state of diseased hearts away from disease and back toward a healthy, pre-disease state," says Dr. Arrell.

Cardiopoietic stem cells are being tested in advanced clinical trials in heart patients.

"The current findings will enrich the base of knowledge pertinent to stem cell therapies and may have the potential to guide therapeutic regimens in the future," says Dr. Terzic.

STONY BROOK, NY, March 12, 2020 - A new study published in Scientific Reports reveals that the language people use on Facebook subtly changes before they make a visit to the emergency department (ED). A team of researchers in part led by H. Andrew Schwartz, PhD, Assistant Professor of Computer Science at Stony Brook University along with Sharath Chandra Guntuku, PhD, a research scientist in Penn Medicine's Center for Digital Health, compared patients' Facebook posts to their medical records, which showed that a shift to more formal language and/or descriptions of physical pain, among other changes, reliably preceded hospital visits. The study provides more evidence that social media is often an unseen signal of medical distress and could be used to better understand the contexts in which patients seek care, such as during the current COVID-19 pandemic.

The study's researchers recruited 2,915 patients at an urban hospital who consented to sharing their Facebook posts and electronic health records (EHRs). Of those patients, 419 had a recent emergency department (ED) visit, ranging from chest pain to pregnancy-related issues. Posts from as early as two-and-a-half months before the date of the patients' ED visit were analyzed using a machine learning model that processed their language to find changes over time.

As patients got closer to their eventual ED visit, the researchers found that Facebook posts increasingly discussed family and health more. They also used more anxious, worrisome, and depressed language and less informal language such as "lol" "?" or swearing.

"The decrease in informal language seems to go hand-in-hand with an increase in anxiety-related language," said Schwartz, who collaborated with the Penn Medicine Center for Digital Health, part of the Perelman School of Medicine at the University of Pennsylvania. "While it is hard to say right now if this would be the same result across multiple social media platforms, people live a lot of their lives online and Facebook is that dominant platform right now."

"The better we understand the context in which people are seeking care, the better they can be attended to," said lead author Guntuku. "While this research is in a very early stage, it could potentially be used to both identify at-risk patients for immediate follow-up or facilitate more proactive messaging for patients reporting doubts about what to do before a specific procedure." Guntuku and Schwartz designed and conducted the analyses along with Stony Brook University graduate student, Adarsh Kashyap, MS CS.

Ultimately, it was found that most patients underwent a significant change in language before they went to the ED. Before their visit, patients were less likely to post about leisure (not using words like "play," "fun," and "nap") or use internet slang and informal language (such as using "u" instead of "you").

When the researchers looked more closely at the context of some posts, they noticed there might be some clues to patients' health behaviors related directly to their hospital visit. One post, for example, talked about the patient eating a cheeseburger and fries less than a month before they were admitted for chest pain related to having heart failure. Another patient confirmed that they were following directions from their care team, posting about fasting 24 hours before they had a scheduled surgery.

"How does life affect personal decisions to seek care? How does care affect life? These are the things I would hope that we could fully describe, how people's everyday lives intermix with health care," Schwartz added.

The study primarily looked at the change in language before a hospital visit, but a previous study involving Schwartz and the paper's senior author, Raina Merchant, MD, the director of the Center for Digital Health, showed that a person's depression could be predicted through the language of Facebook posts as far ahead as three months before official diagnosis.

Guntuku said that there is tremendous potential in user generated content (on Facebook, Twitter, and now on smartphones) to study the behaviors and mental states that lead to a healthcare visit. "Any research in this domain must give patient privacy and agency utmost priority and transparency about where, how and by whom these digital markers are being used to understand health is critical," he added.

The researchers plan to study broader populations in subsequent studies in an attempt to understand what actionable and interpretable insights can be provided to patients who opted to share their data.

Between 2015 and 2016, Brazil suffered from an epidemic outbreak of the Zika virus, whose infections occurred throughout the country states. Despite the concentration of cases in other regions of Brazil, it was the Northeast that registered the highest incidence of microcephaly associated with the Zika virus. The concentration of this clinical outcome drew the attention of scientists, who raised the hypothesis that this aggravation could result from the association between the epidemic and some preventable environmental factors in the region. The research was a joint action of the D'Or Institute for Research and Education (IDOR), the Federal University of Rio de Janeiro (UFRJ), Federal Rural University of Pernambuco (UFRPE) and the Oswaldo Cruz Foundation (Fiocruz).

More than a coincidence

The Northeast of Brazil has the drier weather of its 5 regions. The northeastern backlands, locally known as "Sertão" and "Agreste", are areas characterized by its semi-arid climate and the lowest rainfall in the country. Stricken frequently by dry seasons, the region faced an unforgiving drought from 2012 to 2017: the worst on record, according to data from the Brazilian National Institute of Meteorology. Nevertheless, the country suffered in the same period the greatest Zika epidemic in Latin America, which reached its most critical point in the years of 2015 and 2016.

Due to a lack of drinking water distribution in the Brazilian semi-arid, its poorer population often resort to consuming water with inadequate treatment, obtained from unsanitized water trucks and reservoirs. The water ingested under these conditions tends to contain microorganisms, which in the case of the Zika epidemic may have intensified the action of the virus in infected people at the Brazilian northeast. Data provided by SisAgua, a water quality data bank integrated with the Brazilian Ministry of Health, showed that, between 2014 and 2018, about a third of the water consumed in the region had more than 20,000 cyanobacteria per milliliter. Then, the researchers revealed that half of the water reservoirs in the Northeast had a high incidence of saxitoxin, a substance produced by cyanobacteria and potentially harmful to human and animal nervous systems. In the other regions of Brazil, this incidence was much less expressive, reaching less than 5% in some states and a maximum of 25% in the Southeast, the second region on rank.

Considering this information, scientists tested the effects of saxitoxin when combined with the Zika virus. The experiments were carried out on mice and on human brain organoids. In both cases, it was observed that the combination of the toxin and the virus results in the worsening of the Zika neurotoxicity, tripling cell mortality in brain organoids and causing malformations similar to microcephaly in the young mice, whose mothers were infected during pregnancy while consuming water with saxitoxin.

These results confirmed that the toxin exacerbates cell death caused by Zika, both in human brain organoids and animals. This fact could help to explain the higher incidence of brain malformations in the Northeast even when comparing to data from regions with greater occurrence of infections but notably fewer records of microcephaly.

The neuroscientist Stevens Rehen, a researcher at IDOR and UFRJ and corresponding author of the study, argues that this research highlights a public health problem in the Northeast region of the country. Rehen -- who also participated in the multi-institutional effort that correlated, for the first time, the Zika virus with the occurrence of microcephaly-- warns that, in addition to its aggravating factors regarding arbovirus diseases (viruses transmitted by insects such as mosquitoes), the low water quality consumed in the region is an extremely harmful factor for the local population, causing other health problems and greater vulnerability to various diseases.

`Below please find links to new coronavirus-related content published today in Annals of Internal Medicine. All coronavirus-related content published in Annals of Internal Medicine is free to the public. A compete collection is available at https://annals.org/aim/pages/coronavirus-content.

Histopathologic Changes and SARS-CoV-2 Immunostaining in the Lung of a Patient With COVID-19

Huilan Zhang, PhD; Peng Zhou, PhD*; Yanqiu Wei, MD*; Huihui Yue, MD*; Yi Wang, PhD*; Ming Hu, MD*; Shu Zhang, PhD; Tanze Cao, MD; Chengqing Yang, MD; Ming Li, MD; Guangyun Guo, MD; Xianxiang Chen, MD; Ying Chen, MD; Mei Lei, MD; Huiguo Liu, PhD; Jianping Zhao, PhD; Peng Peng, MD; Cong-Yi Wang, PhD; and Ronghui Du, MD

Brief Research Report

FREE full text: http://annals.org/aim/article/doi/10.7326/M20-0533

BOSTON - Among adults at high risk of liver cancer, those who took low-dose aspirin were less likely to develop the disease or to die from liver-related causes. The findings come from an analysis published in the New England Journal of Medicine and conducted by a team led by investigators at the Karolinska Institutet, in Sweden, and Massachusetts General Hospital (MGH).

"Rates of liver cancer and of mortality from liver disease are rising at an alarming pace in U.S. and European countries. Despite this, there remain no established treatments to prevent the development of liver cancer, or to reduce the risk of liver-related death," said lead author Tracey Simon, MD, MPH, investigator in the Division of Gastroenterology and Hepatology at MGH.

For the analysis, investigators examined information from Swedish registries on 50,275 adults who had chronic viral hepatitis, a type of liver infection that is caused by the hepatitis B or C virus and is the most common risk factor for liver cancer. Over a median follow-up of nearly 8 years, 4.0% of patients who took low-dose aspirin (less than 163mg/day) and 8.3% of nonusers of aspirin developed liver cancer. Aspirin users had a 31% lower relative risk of developing liver cancer.

Importantly, the study showed that the longer a person took low-dose aspirin, the greater the benefit. Compared with short-term use (3 months to 1 year), the risk of liver cancer was 10% lower for 1-3 years of use, 34% lower for 3-5 years of use, and 43% lower for 5 or more years of use.

Also, liver-related deaths occurred in 11.0% of aspirin users compared with 17.9% of nonusers over 10 years, for a 27% lower risk.

The benefits were seen regardless of sex, severity of hepatitis, or type of hepatitis virus (B or C). The risk of internal bleeding--a concern when taking aspirin long-term--was not significantly elevated among aspirin users.

"This is the first large-scale, nationwide study to demonstrate that the use of aspirin is associated with a significantly reduced long-term risk of liver cancer and liver-related mortality," said senior author Jonas F. Ludvigsson, MD, PhD, of the Department of Medical Epidemiology and Biostatistics at the Karolinska Institutet.?

The investigators noted that prospective randomized controlled trials are needed to test the benefits of aspirin for patients affected by liver disease.

The human papillomavirus (HPV) causes, amongst other diseases, cancer of the cervix and oropharynx. A Swedish-Finnish study published in The Journal of Infectious Diseases now shows that the most oncogenic HPV types can be eliminated, but only if both girls and boys are vaccinated. Both genders will be offered vaccination in Sweden as of 2020.

The researchers began a randomised study in 2007, inviting 80,000 young people between the ages of 12 and 15 from 250 schools in 33 towns to take part. In 11 towns, both boys and girls were given HPV vaccination, in another 11 towns only girls were vaccinated, and in 11 towns the participants were vaccinated against a totally different virus (control).

General HPV screening at the age of 19 showed that the vaccination of both genders prevented HPV infections in society much more effectively than the vaccination of girls only. A gender-neutral strategy was also effective at preventing HPV infections in unvaccinated girls.

HPV was included in the Swedish vaccination programme in 2012. To date, the vaccine has only been offered to girls, but in 2019 the government decided to offer it to both genders as of autumn 2020.

"Our study is unique because the entire population of the communities included in the study was invited to take part, and the choice of vaccination strategy was randomised by community," says Matti Lehtinen, researcher at the Department of Laboratory Medicine, Karolinska Institutet, who led the study. "The results have definitely influenced the decision about offering HPV vaccination to boys, which more and more countries are also deciding."

Mathematical modelling was used to calculate what the results of the randomised HPV vaccination study would mean for programs with different vaccination coverage. The improved effectiveness of vaccinating both boys and girls is particularly important if only 80 per cent or fewer of girls are vaccinated.

"If only girls are offered HPV vaccination not even a school-based vaccination programme will be able to eliminate the most oncogenic HPV type 16, ever," says Simopekka Vänskä, docent at the Finnish Institute for Health and Welfare and the study's first author. "Vaccination of both boys and girls with a 75-per cent participation rate can, however, eliminate HPV 16 even in people under 30, which is the segment of the population that is mainly spreading the infection. The elimination will take place only in a few years after the vaccinated cohorts achieve these ages."

The World Health Organisation (WHO) has established the elimination of cervical cancer as a priority objective.

"The results of the randomised study of different vaccination strategies now published gives us information about how this objective could be achieved at the earliest possible time," says Lehtinen.

HPV causes a variety of cancers, above all cervical cancer in women and cancer of the oropharynx in women and men. Almost everyone has had at least one sexually transmitted HPV infection in his or her life.

The study was financed by the Academy of Finland and the Cancer Society of Finland. GlaxoSmithKline Biologicals SA financed the constituent study (data to be published separately) and was given an opportunity to check that baseline data from that study were accurately reproduced in the paper in The Journal of Infectious Diseases. The international team of co-authors has received research grants from the Swedish Cancer Society, the Ministry of Health, Government of Catalonia, and the EU's 6th and 7th Framework Programmes in the context of this study.

The language people use on Facebook subtly changes before they make a visit to the emergency department (ED), a new study found. Researchers from the Perelman School of Medicine at the University of Pennsylvania and Stony Brook University's Computer Science Department compared patients' Facebook posts to their medical records, which showed that a shift to more formal language and/or descriptions of physical pain, among other changes, reliably preceded hospital visits. Published today in Nature Scientific Reports, the study provides more evidence that social media is often an unseen signal of medical distress and could potentially be used to trigger health care interventions.

"The better we understand the context in which people are seeking care, the better they can be attended to," said lead author Sharath Chandra Guntuku, PhD, a research scientist in Penn Medicine's Center for Digital Health. "While this research is in a very early stage, it could potentially be used to both identify at-risk patients for immediate follow-up or facilitate more proactive messaging for patients reporting doubts about what to do before a specific procedure."

The study's researchers recruited 2,915 patients at an urban hospital who consented to sharing their Facebook posts and electronic health records (EHRs). Of those patients, 419 had a recent emergency department (ED) visit, ranging from chest pain to pregnancy-related issues. Posts from as early as two-and-a-half months before the date of the patients' ED visit were analyzed using a machine learning model that processed their language to find changes over time.

Ultimately, it was found that most patients underwent a significant change in language before they went to the ED. Before their visit, patients were less likely to post about leisure (not using words like "play," "fun," and "nap") or use internet slang and informal language (such as using "u" instead of "you").

As patients got closer to their eventual ED visit, the researchers found that Facebook posts increasingly discussed family and health more. They also used more anxious, worrisome, and depressed language. Study author H. Andrew Schwartz, PhD, an assistant professor of Computer Science at Stony Brook University and a collaborator with the Penn Medicine Center for Digital Health, said that the decrease in informal language "seems to go hand-in-hand" with an increase in anxiety-related language.

"We seem to become more grave and serious when we are unwell," Guntuku said. "And looking beyond the family mentions data, it's possible that, when health is down, the need for belonging increases and shows up in what one posts on social media."

When the researchers looked more closely at the context of some posts, they noticed there might be some clues to patients' health behaviors related directly to their hospital visit. One post, for example, talked about the patient eating a cheeseburger and fries less than a month before they were admitted for chest pain related to having heart failure. Another patient confirmed that they were following directions from their care team, posting about fasting 24 hours before they had a scheduled surgery.

"How does life affect personal decisions to seek care? How does care affect life? These are the things I would hope that we could fully describe, how people's everyday lives intermix with health care," Schwartz said.

This study primarily looked at the change in language before a hospital visit, but a past study involving the paper's senior author, Raina Merchant, MD, the director of the Center for Digital Health and an associate professor of Emergency Medicine, showed that a person's depression could be predicted through the language of Facebook posts as far ahead as three months before an official diagnosis. Guntuku said there is evidence that language changes as far out as a month leading up to an ED visit, but "we need a much better understanding of a person's context" to forecast it accurately. Expressions on social media are just one piece of the puzzle -- albeit a highly telling one -- so context will come into play when determining the applicability of the Facebook findings to other social media platforms.

"It's likely that individuals use different platforms to share varying information and that what is revealed on Facebook to an audience of that person's friend network may be very different from a Twitter or Instagram network," Merchant said.

Moving forward, the researchers plan to study broader populations and attempt to understand what actionable and interpretable insights can be provided to patients who opted to share their data.

ROCHESTER, Minn. -- Older adults who have surgery with general anesthesia may experience a modest acceleration of cognitive decline, even years later. But there's no evidence of a link to Alzheimer's disease, according to new research from Mayo Clinic.

The research, published in the British Journal of Anaesthesia, examined brain scans from 585 patients, ages 70 to 91 ? 493 of whom had at least one surgery with general anesthesia. The analysis found cortical thinning in cerebral areas but no significant evidence of deposits of amyloid protein, a hallmark of Alzheimer's disease. The cortex is the outermost layer of the brain's nerve cell tissue, and thinning of that tissue is associated with diminished cognitive functions.

"This finding suggests that the modest cortical thinning is not related to Alzheimer's disease pathology, but is caused by other processes," says Juraj Sprung, M.D., Ph.D., a Mayo Clinic anesthesiologist and first author of the study. "These results are reassuring and consistent with the conclusion that surgery and anesthesia do not increase the risk for development of Alzheimer's disease."

The potential link between surgery with anesthesia and cognitive decline in older adults has been examined for many years, and concerns have grown as animal studies have indicated that exposure to inhaled anesthetics may be related to brain changes similar to those seen with Alzheimer's disease.

Alzheimer's disease is a progressive disorder that causes brain cells to degenerate and die. It is the most common cause of dementia and the sixth leading cause of death in the U.S. Also, Alzheimer's disease causes a continuous decline in cognition and behavior that disrupts a person's ability to function. While there is no cure, some medications can slow its progression. An estimated 5.8 million Americans are living with the disease, according to the Alzheimer's Association.

One of the key indicators of Alzheimer's disease is a buildup of proteins in the cortical area of the brain, which can be visualized by positron emission tomography (PET) scans. The protein deposits, called "amyloid plaques," have a toxic effect on neurons and can precede any clinical symptoms of the disease by 30 years or more.

The Mayo Clinic study used data from the Mayo Clinic Study of Aging, which started in 2004 and has data on more than 5,000 participants ? all from Olmsted County, Minnesota, where Mayo Clinic in Rochester is located. The study analyzed 585 patients, 493 of whom had at least one surgery with general anesthesia after age 40, and later had PET scans. Of those, the median time between surgery and the PET scan was 25.9 years.

The researchers used two methods to define amyloid deposition in the PET scans. "Regardless of the definition used, no significant associations were detected between exposure to surgery and anesthesia, and increased amyloid deposition," Dr. Sprung says.

Dr. Sprung and Mayo Clinic colleagues published a study last year that also noted the association between surgical anesthesia and cortical thinning in the signature region for Alzheimer's disease. The study cautioned that the pathogenesis and mechanisms driving these changes required more study.

The new study concludes that the cortical thinning was not associated with pathologic changes related to Alzheimer's, but was caused by other undetermined processes.

"Older adults who are considering surgery, and their families, must be properly informed of the risk for slightly accelerated cognitive decline in the years following surgery," says Dr. Sprung. "However, they should also be made aware that this potential impact may be related to preexisting conditions that necessitate the surgery."

"Most important, patients should be reassured by our findings that surgery with anesthesia does not lead to changes associated with Alzheimer's disease," says Dr. Sprung.

Cycling to work is associated with a higher risk of admission to hospital for an injury than other modes of commuting, suggests a UK study published in The BMJ today.

But those who cycled to work had a significantly lower risk of cancer, cardiovascular disease and death compared with commuters who did not cycle.

Recent evidence shows that active modes of commuting are linked to potential health benefits such as improved fitness and lower body fat, and a lower risk of cardiovascular disease, cancer, type 2 diabetes, and death. But the number of people cycling to work in the UK and many other countries is low.

Many people are put off by the potential danger linked to cycling in traffic, but there is a lack of individual level data on cycling and injuries in the UK.

So a team of researchers set out to investigate the association between commuter cycling and risk of injury, compared with other modes of commuting. They analysed data from the UK Biobank study, which included 230,390 daily commuters from 22 sites across the UK, half (52%) of which were women, with an average age of 52.

The participants were recruited between 2006-2010 and monitored for an average of 8.9 years. During this time, of the 5,704 people who only cycled to work, 7% were injured. Among people who cycled for part of the commute, 6% were injured. In contrast, 4.3% of the commuters who travelled by car or public transport were injured.

Cycling was associated with a higher risk of injury to arms and legs, the torso, the head or neck, and fracture injuries, as well as injury-related hospital stays of 1, 2-6, and 7 or more days.

Among all commuters using the various modes, those who were injured were slightly older, more likely to be white men and a current smoker, and have a history of cardiovascular disease, diabetes, cancer or longstanding illness.

After taking account of other potentially influential factors, such as age, sex, and physical activity levels, commuting by bicycle was associated with a 45% higher risk of hospital admission for a first injury and a 3.4-fold higher risk of a transport related incident, compared with commuting by car or public transport. And those who cycled greater distances had a higher risk of injury.

But when those who cycled for the whole or part of the journey were compared with all other commuters, the cyclists showed a reduced risk of cardiovascular disease (21%), lower risk of first cancer diagnosis (11%) and lower risk of death (12%).

To put this into context, if 1000 people changed their mode of commuting to include cycling for 10 years, this would mean an estimated 26 additional hospital admissions for a first injury (of which three would require a hospital stay of a week or longer), 15 fewer first cancer diagnoses, four fewer cardiovascular disease events, and three fewer deaths.

This is an observational study, so can't establish cause. The authors point to some limitations, including that UK Biobank is known to be skewed towards better health and affluence, so may not be representative of the general UK population. And assessment centres were located in large cities, so included few people who lived rurally.

They say that the study supports the perception among the general public that cycling poses a greater risk of injury than other modes of commuting, but that the health benefits are considerable.

"The risk of injury associated with cycling commuting needs to be taken seriously and safer infrastructure provided if we are to address cycling dangers (both real and perceived) in the UK. This could help increase the uptake of cycling commuting with resulting benefits to health and the environment," they conclude.

In a linked editorial, Anne Lusk from the Harvard T.H. Chan School of Public Health says that safer cycling infrastructure benefits people and the local economy, and that the study and accelerating climate change indicate it is time to look upstream for transport solutions.

"Enhanced cycle tracks in dedicated space beside pavements (sidewalks) should be as revered and generously funded as historic buildings and trails," she writes.

Lusk calls for an international movement, whereby "business owners, donors, and communities would fund safe and aesthetic cycle tracks and urge governments to support new infrastructure that tackles some of the world's biggest issues--public safety, health, economic development, equity, and climate change."

Researchers from Vanderbilt-Ingram Cancer Center discovered a role for MYCN in triple-negative breast cancer (TNBC), a particularly aggressive form of the disease, and identified a potential intervention for further clinical investigation.

Although there is no way to currently target MYCN directly, investigators from the Pietenpol laboratory determined that experimental drugs called BET inhibitors are effective against TNBCs in model systems that overexpress MYCN, especially when coupled with the inhibition of MEK, another known oncogene. MYCN is a well-known oncogene that plays a role in cancer aggressiveness, but it is typically associated with neuronal and neuroendocrine cancers.

The research, published in Science Translational Medicine, sets the stage for clinical trials and a potential treatment for TNBCs with the MYCN oncogene. The study is the cover story of the March 11 issue of the journal. It's based on the dissertation work of Vanderbilt graduate student and first author Johanna Schafer, PhD, whose brother designed the issue's cover art. Schafer did her graduate research in the lab of Jennifer Pietenpol, PhD, the Benjamin F. Byrd Jr. Professor of Oncology and the study's senior author.

TNBC is a particularly difficult type of breast cancer to treat. Although it represents about 15% of breast cancers, TNBC accounts for about 25% of all breast cancer-related deaths. Treatment options for many patients are still limited to chemotherapy.

"This study provides pre-clinical data for investigation of the potential utility of MEK and BET inhibitors in advanced triple-negative breast cancer," said Pietenpol, Vanderbilt-Ingram director, Executive Vice President for Research at Vanderbilt University Medical Center and holder of the Brock Family Directorship in Career Development. "As a next step, our research team is proposing the further development and clinical trials of this combination therapy."

A number of MEK inhibitors have already been approved by the U.S. Food and Drug Administration. BET inhibitors are a class of compounds currently under clinical development.

Elevated MYCN expression had previously been observed in tumors of the nervous system and non-neuronal tumors, such as neuroendocrine and prostate cancer, hematological malignancies and small cell lung cancers. The study found MYCN is heterogeneously expressed within a substantial fraction of TNBCs and in a higher rate of cases that don't respond to chemotherapy.