Older women who suffer tooth loss more likely to develop high blood pressure

A new study in the American Journal of Hypertension indicates that postmenopausal women who have experienced tooth loss are at higher risk of developing high blood pressure. Multiple studies have suggested an association between periodontal disease and tooth loss with hypertension, but the relationship remains unclear.

Study participants were 36,692 postmenopausal women in the Women's Health Initiative-Observational Study, in the US, who were followed annually from initial periodontal assessment in 1998 through 2015 for newly diagnosed hypertension.

The study observed a positive association between tooth loss and hypertension risk among postmenopausal women. Specifically, these women had approximately 20% higher risk of developing hypertension during follow-up compared to other women. The association was stronger among younger women and those with lower BMI.

There are several possible reasons for the observed association. One possible explanation is that as people lose teeth, they may change their diets to softer and more processed foods. These changes in dietary patterns could be associated with higher risk of hypertension. There was no association found between periodontal disease and hypertension.

The study suggests that older postmenopausal women who are losing their teeth may represent a group with higher risk for developing hypertension. As such, the researchers involved in the study believe that improved dental hygiene among those at risk for tooth loss as well as preventive measures such as closer blood pressure monitoring, dietary modification, physical activity, and weight loss may reduce the risk of hypertension. The findings also suggest that tooth loss may serve as a clinical warning sign for increased hypertension risk.
"These findings suggest tooth loss may be an important factor in the development of hypertension," said the paper's senior author, Jean Wactawski-Wende. "Further research may help us to determine the underlying mechanisms by which these two common diseases are associated."

Opioid prescriptions from dentists linked to youth addiction risk

Teens and young adults who receive their initial opioid prescriptions from their dentists or oral surgeons are at increased risk for opioid addiction in the following year, a study from the Stanford University School of Medicine has found.
The study, which will be published Dec. 3 in JAMA Internal Medicine, examined opioid use and abuse in a large group of privately insured patients from across the United States. Among nearly 15,000 young people who received initial opioid prescriptions from their dentists in 2015, 6.8 percent had additional opioids prescribed between 90 and 365 days later, and 5.8 percent were diagnosed with opioid abuse during the year after the initial prescription. In a comparison group that did not receive an opioid prescription from their dentists, 0.1 percent got another opioid prescription and 0.4 percent were diagnosed with opioid abuse over the same period.
The researchers began the study to explore the risks of wisdom tooth extraction, a common elective dental surgery in teenagers and young adults. Many patients are prescribed opioids to manage pain after wisdom tooth removal.
"This work raises two really important related but separate questions: Do we need opioids, and do we need the procedure?" said the study's lead author, Alan Schroeder, MD, clinical professor of pediatrics at Stanford.
Beneficial procedure?
Though extremely common, wisdom tooth extractions are not well-studied, and the balance of risks and benefits is not clear, Schroeder said. His overall research focus is "safely doing less" -- trying to identify common interventions in pediatrics that may have unfavorable risk-benefit profiles and asking if they could be simplified or eliminated for patient safety. Removal of disease-free wisdom teeth has not been studied thoroughly enough to determine whether it benefits patients, according to a 2016 Cochrane review of the subject.
The research team used a database that contains de-identified information on millions of privately insured patients from across the United States. The researchers focused on patients who were 16 to 25 years old in 2015, the age group in which wisdom tooth extractions are typically performed. The database included 754,002 people of these ages who were enrolled in health insurance for the entire year. Of those, 97,462 (13 percent) received at least one opioid prescription; 30 percent of the opioid prescriptions came from dental practitioners.
To zero in on patients who had probably not had prior opioid exposure and who were probably receiving the drugs for elective dental procedures, the researchers excluded patients who had been hospitalized during the week before they were prescribed dental opioids, as well as all patients who had received other opioid prescriptions or been diagnosed with opioid abuse in the year before getting a prescription from a dentist. This left 14,888 young people who got an initial opioid prescription in 2015 from a dental practitioner. The median number of pills prescribed was 20.
Each person in the group was matched with two control individuals who did not receive dental opioid prescriptions that year. Each control patient was randomly assigned a start date, which the researchers referred to as their phantom prescription date, during 2015 for the study's one-year follow-up period.
The researchers checked whether patients in either group got subsequent opioid prescriptions 90 to 365 days after the initial or phantom prescription date. They also examined whether patients' records during the year included diagnostic codes for opioid abuse.
Tracking the opioid use
Seventy-five percent of the opioid prescriptions were for hydrocodone-acetaminophen, commonly known by the brand names Lortab, Norco or Vicodin. In the 12 months prior to the real or phantom opioid prescription date, about 3 percent of subjects in each group had been diagnosed with substance abuse of nonopioid substances.
Compared with patients in the control group, the group that received dental opioids had significantly greater rates of continuing opioid use and abuse.
"Almost 7 percent of these patients had new, persistent use at least three months after the initial prescription and almost 6 percent had an opioid abuse diagnosis," Schroeder said. "That's pretty alarming."
The youngest patients, ages 16 to 18, were significantly more likely to have persistent opioid use than the oldest patients, ages 22 to 25. Female patients were more likely to have persistent opioid use, while patients of Asian race/ethnicity were less likely to have persistent use.
Follow-up research is needed to determine whether opioids are the safest method of treating pain from wisdom tooth extractions, and whether the extractions themselves are always necessary, Schroeder said. "I think we should ask, No. 1, Why are we prescribing such a high quantity of opioids so frequently? And No. 2, Are all the procedures that are driving these opioid prescriptions necessary?" he said.

Prescribing of antibiotic prophylaxis (AP) to prevent a life-threatening heart condition infective endocarditis (IE) in patients before undergoing invasive dental treatment.

New research has revealed the impact a change in US guidelines had on the prescribing of antibiotic prophylaxis (AP) to prevent a life-threatening heart condition infective endocarditis (IE) in patients before undergoing invasive dental treatment.
The findings of the international research provide further evidence that the UK's National Institute of Health and Care Excellence (NICE) were wrong to call for a complete ban on the use of AP before invasive dental procedures - even for those considered to be at high-risk of IE such as patients with artificial or repaired heart valves or a previous history of IE.
The study is the largest and most comprehensive research into the 2007 American Heart Association's (AHA) recommendations that AP should continue to be given to patients at high-risk of developing IE, but not to those at moderate-risk.
The research showed a large fall in AP prescribing for those at moderate-risk of IE (64 per cent). However, it also identified a concerning fall in AP prescribing to those at high-risk (20 per cent) - despite the AHA's recommendation that high-risk individuals should continue to receive AP before invasive dental treatment.
In parallel, the study also identified a significant increase in IE (177 per cent) in those at high-risk but only a barely significant increase in those at moderate-risk.
Lead author, Professor Martin Thornhill from the University of Sheffield's School of Clinical Dentistry, said: "Although the data do not prove a cause-effect relationship between AP reduction and IE increase, they are very supportive of the AHA recommendation to give AP to those at high-risk but not to those at moderate-risk of endocarditis."
"It also provides further evidence that the 2008 NICE recommendation that AP should cease completely in the UK, was probably wrong and should be changed."
Professor Thornhill added: "Current NICE guidance on the use of AP to prevent IE is confusing and unhelpful for clinicians and patients, and probably wrong."
"In the absence of clear and sensible advice from NICE, the recent attempt by the Scottish Dental Clinical Effectiveness Program (SDCEP) to provide advice for dentists about how to implement the NICE guidelines - effectively suggesting they follow the AHA recommendations, is very welcome."
IE is a serious infection of the heart valves with high morbidity and mortality - 30 per cent of people die within a year of being diagnosed. Previous studies have shown that approximately 40 per cent of cases are likely to have been caused by bacteria from the mouth.
A large number of people with pre-disposing cardiac conditions are at increased risk of IE and some patients, for example those with prosthetic or repaired heart valves, previous history IE or certain congenital heart conditions, are at high-risk of developing IE.
Consultant Cardiologist and co-author of the study, Mark Dayer from Taunton and Somerset NHS Trust, said: "The recent implementation advice by SDCEP is a timely recognition that the patient has the right to be told the arguments both for and against prophylaxis and decide whether or not they wish to take it. To my mind, the data in this study further supports the use of prophylaxis in patients at high risk of endocarditis, as recommended in America and across the rest of Europe."
Since the 1950s, the main method for preventing IE world-wide has been to give those at increased risk AP before invasive dental and medical procedures.
A lack of evidence for the efficacy of AP, concerns about the risk of adverse reactions and the development of antibiotic resistance has led guideline committees to gradually reduce the number of situations where AP is recommended.
In 2008, however, NICE recommended the complete cessation of AP in the UK, despite a lack of evidence for or against AP efficacy.
In contrast the majority of guidelines committees across the world, including the American Heart Association (AHA), recommended that individuals at high-risk of IE should continue to receive AP but it should stop for those at moderate-risk.
In 2015, research conducted by Professor Thornhill and his team published in The Lancet , found that the 2008 change in NICE guidelines had led to an 89 per cent fall in AP prescribing in the UK.
This pioneering research also showed there had been an increase of 35 IE cases per month since the guideline change. As a result, NICE reviewed their guidance but continued to recommend against AP.
The new study provides further evidence to support the advice given by the AHA, and most other guideline committees around the world, that those at high-risk of IE undergoing invasive dental procedures should receive AP. It also supports the advice recently published by the Scottish Dental Clinical Effectiveness Program (SDCEP), about how to implement the NICE guidelines - which tells dentists to discuss and offer AP to patients at high-risk of IE, just like the AHA guidelines.
The results of the study will be published online in the Journal of the American College of Cardiology (JACC) today (5 November 2018), and in hard copy on the 27 November.

Tooth loss can indicate malnutrition, Rutgers study says

Older adults are at risk for both impaired oral health and malnutrition, according to a study by Rutgers University researchers.

The study, recently published in the Journal of Aging Research and Clinical Practice, analyzed the health records of 107 community-dwelling senior citizens treated at the Rutgers School of Dental Medicine clinic between 2015 to 2016.

The results showed that more than 25 percent of the patients had malnutrition or were at risk for malnutrition. The researchers saw a trend in which patients with 10 to 19 teeth were more likely to be at risk for malnutrition. Those patients classified as having malnutrition had higher rates of weight loss, ate less and more frequently reported that they suffered with dementia and/or depression and severe illnesses than those who had a normal nutrition status.

"The mouth is the entry way for food and fluid intake," said lead author Rena Zelig, director of the Master of Science in Clinical Nutrition Program at Rutgers School of Health Professions. "If its integrity is impaired, the functional ability of an individual to consume an adequate diet may be adversely impacted."

Although further studies need to examine the relationships between tooth loss and malnutrition risk, Zelig said the findings show that dental clinics are ideal locations to perform nutritional status screenings as they can identify patients who may not regularly visit a primary care provider and who may be at risk for malnutrition. "Clinicians also can provide patients with referrals to Registered Dietitians and community assistance programs such as Meals on Wheels to prevent further decline in nutritional status," she said.
This was the first part of a mixed-methods grant to research the associations between tooth loss and nutritional status in older adults. The second part of the grant built on these results and qualitatively studied the eating experience and eating-related quality of life of community-dwelling older adults using qualitative interviews.
The study sets the stage for further research to examine the relationships between tooth loss and malnutrition risk and the impact of tooth loss on the eating experience and eating-related quality of life.

Loss of first baby tooth a positive experience for children

Scared, ashamed, happy or proud - how do children feel when they lose their first baby tooth? An interdisciplinary research group at the University of Zurich has now found that children's feelings are predominantly positive. The study also reveals that previous visits to the dentist's as well as parental background and level of education affect how children experience the loss of their first tooth.

Deciduous teeth, more commonly known as milk or baby teeth, are the first set of teeth that develop in children. These teeth usually fall out and are replaced by permanent teeth. Children generally lose their first baby tooth when they're about six years old: The tooth comes loose and eventually falls out, leaving a gap which is then permanently filled by its replacement tooth. This gradual process is probably one of the first biological changes to their own bodies that children experience consciously. The emotions that accompany this milestone are extremely varied, ranging from joy at having finally joined the world of grown-ups to fear about the loss of a body part.

Parents report positive reactions

An interdisciplinary team of dental researchers and developmental and health psychologists at the University of Zurich, in cooperation with the City of Zurich's School Dental Services, has now examined the feelings that children experience when they lose their first baby tooth, and which factors are at play. The scientists surveyed parents of children who had already lost at least one of their milk teeth. Of the nearly 1,300 responses received for the study, around 80 percent of parents reported positive feelings, while only 20 percent told of negative emotions. Raphael Patcas, first author of the study, is happy with the findings: "The fact that four out of five children experience the loss of a baby tooth as something positive is reassuring, for parents and dentists alike."

The longer it's loose, the better the feelings

The researchers found that previous visits to dentists played a role when it comes to children's feelings. Children whose previous visits were cavity-related and thus perhaps associated with shame or guilt experienced fewer positive emotions when they later lost their first baby tooth. If, however, previous dental appointments were the result of an accident, and thus an abrupt, unexpected and painful event, then the loss of the first milk tooth was more likely to be associated with positive emotions. According to dental researcher Raphael Patcas, one possible explanation for this is that baby teeth loosen gradually before falling out - a process that, unlike an accident, unfolds slowly and predictably. This is also supported by the fact that children who experience the loosening of their tooth over an extended period of time tend to have more positive feelings: The longer the preparation and waiting time, the greater the relief and pride when the tooth finally falls out.

Parental education and background matter

Moreover, the study also found that sociodemographic factors are related to children's feelings: For example, children were more likely to have positive feelings such as pride or joy if the parents had a higher level of education and came from non-Western countries. The researchers indicate that cultural differences could be at play here: These include education style and norms that parents pass on to their children, as well as transitioning rituals that accompany the loss of the first baby tooth.
"Our findings suggest that children deliberately process previous experiences concerning their teeth and integrate them in their emotional development," says Moritz Daum, UZH professor of developmental psychology. This finding is important for dentists and parents alike: "Especially where cavities are concerned, it's worth communicating with children prudently", says Daum. "This way, emotions in connection with teeth and dentists can be put on the most positive trajectory possible."

New dental adhesive prevents tooth decay around orthodontic brackets

Researchers at Queen Mary University of London have produced a new orthodontic bracket bonding adhesive that protects the tooth surfaces around the brackets from decay. This decay is often referred to as white spot lesions which affects, according to a 2015 meta-analysis, nearly 70 per cent of people fitted with orthodontic braces*.

The problem areas are around the edges of the retaining brackets where plaque accumulates. Because of the wires and brackets it is difficult to keep the teeth clean. This results in many patients ending up with straight teeth after orthodontics but with blotchy marks that can affect their willingness to smile and reduce their self-confidence. This discolouration takes many months or even years to disappear.

The new bioactive bonding adhesive differs from the currently used materials by continuously releasing fluoride, calcium and phosphate to form fluorapatite. Fluorapatite will remineralise adjacent tooth surfaces and also reduce plaque formation around the orthodontic bracket, reducing the risk of initial decay seen as a chalky surface on the tooth enamel.

Professor Robert Hill at Queen Mary University of London said: “This is a significant breakthrough which will benefit all those wearing orthodontic braces” explained. The research we undertook is an extension of the technology we developed with BioMin Technologies when developing BioMin F toothpaste and this adhesive prevents the development of unsightly white spot lesions around the brackets.”

Braces are very popular, with more than 200,000 children and adults in England and Wales starting orthodontic treatment last year. They allow the wearer to have an attractive, confident smile, bite correctly, eat more comfortably, and to care for their teeth and gums more effectively. In the USA, over four million people are wearing braces, of which 25 percent are adults.

Professor Robert Hill added: “This new special adhesive includes a much lower sodium content than that used in BioMin F toothpastes so it reacts, rather than dissolves. Our latest research shows the adhesive forms protective fluorapatite - the fluoride analog of tooth mineral – around the brackets. We hope to see the first commercially available product within two years.”

The research is published in the journal Dental Materials.

Full bibliographic information

• Research paper: Fluoride containing bioactive glass composite for orthodontic adhesives — Apatite formation properties. N.A.Al-eesa, A.Johal, R.G.Hill, F.S.L.Wong. Dental Materials. Doi: 10.1016/j.dental.2018.04.009.

Available here: https://www.sciencedirect.com/science/article/pii/S0109564117311867?via%3Dihub

Poor oral health linked to higher blood pressure, worse blood pressure control

People with high blood pressure taking medication for their condition are more likely to benefit from the therapy if they have good oral health, according to new research in the American Heart Association's journal Hypertension. 

Findings of the analysis, based on a review of medical and dental exam records of more than 3,600 people with high blood pressure, reveal that those with healthier gums have lower blood pressure and responded better to blood pressure-lowering medications, compared with individuals who have gum disease, a condition known as periodontitis. Specifically, people with periodontal disease were 20 percent less likely to reach healthy blood pressure ranges, compared with patients in good oral health.

Considering the findings, the researchers say patients with periodontal disease may warrant closer blood pressure monitoring, while those diagnosed with hypertension, or persistently elevated blood pressure, might benefit from a referral to a dentist.

"Physicians should pay close attention to patients' oral health, particularly those receiving treatment for hypertension, and urge those with signs of periodontal disease to seek dental care," Pietropaoli said. "Likewise, dental health professionals should be aware that oral health is indispensable to overall physiological health, including cardiovascular status," said study lead investigator Davide Pietropaoli, D.D.S., Ph.D., of the University of L'Aquila in Italy.

The target blood pressure range for people with hypertension is less than 130/80 mmHg according to the latest recommendations from the American Heart Association/American College of Cardiology. In the study, patients with severe periodontitis had systolic pressure that was, on average, 3 mmHg higher than those with good oral health. Systolic pressure, the upper number in a blood pressure reading, indicates the pressure of blood against the walls of the arteries. 

While seemingly small, the 3mmHg difference is similar to the reduction in blood pressure that can be achieved by reducing salt intake by 6 grams per day (equal to a teaspoon of salt, or 2.4 grams of sodium), the researchers said.

The presence of periodontal disease widened the gap even farther, up to 7 mmHg, among people with untreated hypertension, the study found. Blood-pressure medication narrowed the gap, down to 3 mmHg, but did not completely eliminate it, suggesting that periodontal disease may interfere with the effectiveness of blood pressure therapy.

"Patients with high blood pressure and the clinicians who care for them should be aware that good oral health may be just as important in controlling the condition as are several lifestyle interventions known to help control blood pressure, such as a low-salt diet, regular exercise and weight control," Pietropaoli said.

While the study was not designed to clarify exactly how periodontal disease interferes with blood pressure treatment, the researchers say their results are consistent with previous research that links low-grade oral inflammation with blood vessel damage and cardiovascular risk.

Hypertension is estimated to affect up to 40 percent of people over age 25 worldwide.

Untreated or poorly controlled hypertension can lead to heart attacks, strokes and heart failure, as well as kidney disease. Hypertension is estimated to claim 7.5 million lives worldwide.

Red, swollen, tender gums or gums that bleed with brushing and flossing are tell-tale signs of inflammation and periodontal disease. So are teeth that look longer than before, a sign of receding gums, and teeth that are loose or separating from the gum line.

Researchers identify immune culprits linked to inflammation and bone loss in gum disease

Microbiome-triggered Th17 cells switch from protective to destructive; may be potential treatment targets

NIH/National Institute of Dental and Craniofacial Research

IMAGE: A new study led by NIDCR clinical investigator Dr. Niki Moutsopoulos suggests that periodontal disease is driven by Th17 immune cells, which are triggered by an unhealthy bacterial community. view more 

Credit: National Institute of Dental and Craniofacial Research, NIH

An unhealthy population of microbes in the mouth triggers specialized immune cells that inflame and destroy tissues, leading to the type of bone loss associated with a severe form of gum disease, according to a new study in mice and humans. The research, led by scientists from the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health and the University of Pennsylvania School of Dental Medicine, Philadelphia, could have implications for new treatment approaches for the condition. The findings appear online Oct. 17, 2018, in Science Translational Medicine.
Periodontal disease is a common disorder that affects nearly half of American adults over age 30, and 70 percent of adults 65 and older. In those affected, bacteria trigger inflammation of the tissues that surround the teeth, which can lead to loss of bone and teeth in an advanced stage of the disease called periodontitis.
"We've known for years that microbes stimulate inflammation. Removing bacteria by tooth-brushing and dental care controls inflammation, but not permanently, suggesting there are other factors at play," said study senior author Niki Moutsopoulos, D.D.S., Ph.D., a clinical investigator at NIDCR. "Our results suggest that immune cells known as T helper 17 cells are drivers of this process, providing the link between oral bacteria and inflammation."
Moutsopoulos and colleagues observed that T helper (Th) 17 cells were much more prevalent in the gum tissue of humans with periodontitis than in the gums of their healthy counterparts, and that the amount of Th17 cells correlated with disease severity.
Th17 cells normally live in so-called barrier sites--such as the mouth, skin, and digestive tract--where germs make first contact with the body. Th17 cells are known to protect against oral thrush, a fungal infection of the mouth, but they are also linked to inflammatory diseases such as psoriasis and colitis, suggesting that they play dual roles in health and disease.
To better understand this dynamic, the NIDCR scientists teamed up with an NIDCR-funded research group led by study senior author George Hajishengallis, D.D.S., Ph.D., at the University of Pennsylvania School of Dental Medicine and colleagues from NIH's National Institute of Allergy and Infectious Diseases (NIAID) and National Cancer Institute (NCI).
The scientists found that similar to humans, more Th17 cells accumulated in the gums of mice with periodontitis compared to healthy mice, which served as a control group.
To see if the oral microbiome might be the trigger for Th17 cell accumulation, the researchers placed mice on a broad-spectrum antibiotic cocktail. They found that eliminating oral microbes prevented expansion of Th17 cells in the gums of mice with periodontitis while leaving other immune cells unaffected, suggesting an unhealthy bacterial population triggers Th17 cell accumulation.
Next, the group wanted to know if blocking Th17 cells could lessen periodontal disease. When the scientists genetically engineered mice to lack Th17 cells, or gave the animals a small-molecule drug that prevents Th17 cell development, they saw similar outcomes: reduced bone loss from periodontitis. RNA analysis showed the Th17-blocking drug led to reduced expression of genes involved in inflammation, tissue destruction, and bone loss, suggesting that Th17 cells may mediate these processes in periodontitis.
Finally, the researchers studied a group of 35 patients at the NIH Clinical Center with a gene defect causing them to lack Th17 cells. The scientists reasoned that if Th17 cells are as important to periodontitis as the animal studies suggested, not having Th17 cells should protect against gum disease. This is indeed what the group found--the patients were less susceptible to the condition and had less inflammation and bone loss compared to age- and gender-matched volunteers.
"Our clinical observations point to the relevance of our animal studies to humans and provide further evidence that Th17 cells are drivers of periodontitis," said NIDCR researcher Nicolas Dutzan, Ph.D., first author of the paper.
"These results provide key insights into the mechanisms that underlie development of periodontal disease," said NIDCR Director Martha J. Somerman, D.D.S., Ph.D. "Importantly, they also offer compelling evidence for therapeutic targeting of specific cells, which might eventually help us provide better treatment and more relief to patients with this common disease."

Drivers of inflammation provide valuable targets for new gum disease therapies

T cells help fight off infection, but they can go overboard. A new study led by researchers at the University of Pennsylvania School of Dental Medicine and the National Institutes of Health (NIH) shows that a subset of T cells contributes to the problematic inflammation and bone loss that is associated with periodontitis, a severe form of gum disease.
The research, conducted with the help of animal models and a group of human patients with a rare genetic mutation, point to a new target for treating periodontitis, as well as other diseases involving the inappropriate response of this group of T cells, known as Th17 cells. These include autoimmune conditions such as rheumatoid arthritis and multiple sclerosis. The work appears in Science Translational Medicine.
"I think this work leaves no doubt that these cells are important mediators of periodontitis," says George Hajishengallis, the Thomas W. Evans Centennial Professor in the Department of Microbiology at Penn Dental Medicine. "The translational aspect of our studies is pinpointing a new approach to blocking the tissue destruction we see in periodontitis, by inhibiting Th17 development."
Hajishengallis collaborated on the work with Niki M. Moutsopoulos of the NIH's National Institute for Dental and Craniofacial Research, with whom he has made previous insights into the molecular drivers of periodontitis.
T cells are broadly considered to fall into two categories: helper T cells, which aid in orchestrating the immune system's response to threats, and cytotoxic T cells, which take a lead role in carrying out an attack. Until about 13 years ago, helper cells were further divided into two groups: Th1 or Th2 cells. Then a new subset, Th17 cells, was identified, and researchers quickly realized Th17 cells played a role in certain human diseases. By 2008, Hajishengallis and other researchers began to suspect that these cells may be implicated in periodontitis. More recent studies have found that people with chronic periodontitis have an unusually high number of Th17 cells in their gum tissue, but these investigations hadn't uncovered the particular role of these cells in the condition or whether they were required for the development of periodontitis.
In the current work, the researchers looked at gum tissue from patients with chronic periodontitis and confirmed that they had higher numbers of Th17 cells compared to healthy controls, with the numbers correlating with the severity of disease. In parallel, they observed that mice in which periodontitis was induced, Th17 cell numbers, along with the IL-17 signaling molecule which they produce, increased with the onset of gum disease. This increase in Th17 cell numbers, the researchers found, was the result of local proliferation rather than recruitment from nearby lymph nodes.
To interrogate possible triggers of the local expansion of Th17 cells, the team decided to see how changes in the community of microbes in the gum tissue, the gingival microbiome, affected the accumulation of Th17 cells. In the mouse model of disease, animals were treated with broad- or narrow-spectrum antibiotics. Only those antibiotics which lowered the numbers of Th17 cells were capable of suppressing the disease, again implicating these cells in disease.
To definitively link the cells to the condition, however, the researchers took advantage of a mouse model missing a key protein required for Th17 cell development, as well as a population of human patients with a mutation in the corresponding gene, Stat3, who are monitored at the NIH. In both cases, they found that the Stat3 mutation, which dramatically cut the number of Th17 cells present in the gum tissue, also protected against the bone loss seen in chronic periodontitis. While people with this Stat3 mutation have other problems, gum disease is not one of them.
"Here we have a unique patient population with the same defect we checked in the mice, and they are similarly not susceptible to the same disease," Hajishengallis says. "This type of rigorous evidence is not easy to come by in medical science."
Though antibiotics could serve to protect against the disease, the side effects of taking such drugs, which can kill both beneficial and disease-causing microbes throughout the body, are too significant to recommend the treatment for broad use. But employing a small-molecule that inhibits Th17 cell development gave the researchers a similar effect, reducing Th17 cell accumulation and associated periodontal bone loss in mice.
"There is no antibiotic that is that targeted, that specific," Hajishengallis says. Such an inhibitor offers promise as a periodontal therapy and perhaps as a target for treating other diseases in which Th17 play a destructive role.

Study suggests vaping does not stain teeth

IMAGE: Top row: The discoloration of enamel exposed to cigarette smoke. Middle row: Minimal discoloration of enamel exposed to the aerosol from a Tobacco Heating Product. Bottom row: Minimal discoloration of... view more 

Credit: British American Tobacco

A study by scientists at British American Tobacco has shown that e-cigarettes and tobacco heating products cause significantly less staining to teeth than conventional cigarettes.
For the first time at BAT, scientists assessed and compared a novel e-cigarette (EC), a tobacco heating product (THP) and a conventional cigarette for their impact on teeth enamel staining. The results are published today in the American Journal of Dentistry.
While cigarette smoke caused significant enamel discoloration, vapour from the EC and aerosol from the THP caused only minimal staining (see Figure 1).
These next generation products (NGPs) do not involve combustion; the vapour and aerosol they produce are less complex and contain significantly lower levels of certain toxicants compared to cigarette smoke.
It is well known that smoking cigarettes causes stains on teeth that cannot easily be removed by regular brushing, but little is known about such effects from NGPs. So scientists at BAT conducted in vitro teeth staining studies to compare the effect of an EC, BAT's THP glo, and a reference cigarette (3R4F).
Tests were carried out on enamel blocks cut from bovine incisors. To mimic conditions in the mouth, the enamel blocks were first incubated with saliva to allow the formation of a pellicle layer, a protective protein film that normally forms on teeth. The enamel blocks were exposed to the particulate matter (isolated from the smoke/vapour) for 14 days and then whole smoke/vapour (equivalent to one pack of cigarettes per day) for 5 days.
The enamel samples were assessed before, during and after treatment; colour readings were determined by an independent laboratory using an established method involving a commercially available spectrophotometer and trained scientists.
Discoloration of enamel blocks exposed to cigarette smoke was apparent in as little as one day and continued to increase as the concentration of cigarette smoke increased. In contrast, exposure to vapour from the EC or THP resulted in little or no colour change that was comparable to the untreated controls.
"Many studies have postulated that it is the tar in cigarette smoke that stains teeth. We now have a method where we can rapidly assess in the laboratory the level of enamel discoloration by cigarette smoke and vapour from our ECs and THPs," explains Annette Dalrymple, a senior scientist at BAT R&D.
"The data generated from this study clearly shows that the EC and THP assessed caused minimal discoloration--very promising for consumers of our NGPs. However, further studies are required to understand the long-term effect on teeth staining and oral health when smokers switch to using NGPs."

Periodontal disease bacteria may kick-start Alzheimer's

Long-term exposure to periodontal disease bacteria causes inflammation and degeneration of brain neurons in mice that is similar to the effects of Alzheimer's disease in humans, according to a new study from researchers at the University of Illinois at Chicago.
The findings, which are published in PLOS ONE, suggest that periodontal disease, a common but preventable gum infection, may be an initiator of Alzheimer's, which currently has no treatment or cure.
"Other studies have demonstrated a close association between periodontitis and cognitive impairment, but this is the first study to show that exposure to the periodontal bacteria results in the formation of senile plaques that accelerate the development of neuropathology found in Alzheimer's patients," said Dr. Keiko Watanabe, professor of periodontics at the UIC College of Dentistry and corresponding author on the study.
"This was a big surprise," Watanabe said. "We did not expect that the periodontal pathogen would have this much influence on the brain, or that the effects would so thoroughly resemble Alzheimer's disease."
To study the impact of the bacteria on brain health, the Watanabe and her colleagues -- including Dr. Vladimir Ilievski, UIC research assistant professor and co-author on the paper -- established chronic periodontitis, which is characterized by soft tissue damage and bone loss in the oral cavity, in 10 wild-type mice. Another 10 mice served as the control group. After 22 weeks of repeated oral application of the bacteria to the study group, the researchers studied the brain tissue of the mice and compared brain health.
The researchers found that the mice chronically exposed to the bacteria had significantly higher amounts of accumulated amyloid beta -- a senile plaque found in the brain tissue of Alzheimer's patients. The study group also had more brain inflammation and fewer intact neurons due to degeneration.
These findings were further supported by amyloid beta protein analysis, and RNA analysis that showed greater expression of genes associated with inflammation and degeneration in the study group. DNA from the periodontal bacteria was also found in the brain tissue of mice in the study group, and a bacterial protein was observed inside their neurons.
"Our data not only demonstrate the movement of bacteria from the mouth to the brain, but also that chronic infection leads to neural effects similar to Alzheimer's," Watanabe said.
The researchers say these findings are powerful in part because they used a wild-type mouse model; most model systems used to study Alzheimer's rely on transgenic mice, which have been genetically altered to more strongly express genes associated with the senile plaque and enable Alzheimer's development.
"Using a wild-type mouse model added strength to our study because these mice were not primed to develop the disease, and use of this model gives additional weight to our findings that periodontal bacteria may kick-start the development of the Alzheimer's," Watanabe said.
The researchers say that understanding causality and risk factors for the development of Alzheimer's is critical to the development of treatments, particularly when it comes to sporadic, or late-onset disease, which constitutes more than 95 percent of cases and has largely unknown causes and mechanisms.
While the findings are significant for the scientific community, Watanabe said there are lessons for everyone.
"Oral hygiene is an important predictor of disease, including diseases that happen outside the mouth," she said. "People can do so much for their personal health by taking oral health seriously."

Young children's oral bacteria may predict obesity

---

The composition of oral microbiota -- the collection of microorganisms, including beneficial bacteria, residing in the mouth -- in two-year-old children may predict their weight gain, according to a new study of over 226 children and their mothers.

Credit: Penn State

Weight gain trajectories in early childhood are related to the composition of oral bacteria of two-year-old children, suggesting that this understudied aspect of a child's microbiota -- the collection of microorganisms, including beneficial bacteria, residing in the mouth -- could serve as an early indicator for childhood obesity. A study describing the results appears September 19 in the journal Scientific Reports.

"One in three children in the United States is overweight or obese," said Kateryna Makova, Pentz Professor of Biology and senior author of the paper. "If we can find early indicators of obesity in young children, we can help parents and physicians take preventive measures."
The study is part of a larger project with researchers and clinicians at the Penn State Milton S. Hershey Medical Center called INSIGHT, led by Ian Paul, professor of pediatrics at the Medical Center, and Leann Birch, professor of foods and nutrition at the University of Georgia. The INSIGHT trial includes nearly 300 children and tests whether a responsive parenting intervention during a child's early life can prevent the development of obesity. It is also designed to identify biological and social risk factors for obesity.
"In this study, we show that a child's oral microbiota at two years of age is related to their weight gain over their first two years after birth," said Makova.
The human digestive tract is filled with a diverse array of microorganisms, including beneficial bacteria, that help ensure proper digestion and support the immune system. This "microbiota" shifts as a person's diet changes and can vary greatly among individuals. Variation in gut microbiota has been linked to obesity in some adults and adolescents, but the potential relationship between oral microbiota and weight gain in children had not been explored prior to this study.
"The oral microbiota is usually studied in relation to periodontal disease, and periodontal disease has in some cases been linked to obesity," said Sarah Craig, a postdoctoral scholar in biology at Penn State and first author of the paper. "Here, we explored any potential direct associations between the oral microbiota and child weight gain. Rather than simply noting whether a child was overweight at the age of two, we used growth curves from their first two years after birth, which provides a more complete picture of how the child is growing. This approach is highly innovative for a study of this kind, and gives greater statistical power to detect relationships."
Among 226 children from central Pennsylvania, the oral microbiota of those with rapid infant weight gain -- a strong risk factor for childhood obesity -- was less diverse, meaning it contained fewer groups of bacteria. These children also had a higher ratio of Firmicutes to Bacteroidetes, two of the most common bacteria groups found in the human microbiota.
"A healthy person usually has a lot of different bacteria within their gut microbiota," said Craig. "This high diversity helps protect against inflammation or harmful bacteria and is important for the stability of digestion in the face of changes to diet or environment. There's also a certain balance of these two common bacteria groups, Firmicutes and Bacteroidetes, that tends to work best under normal healthy conditions, and disruptions to that balance could lead to dysregulation in digestion."
Lower diversity and higher Firmicutes to Bacteroidetes (F:B) ratio in gut microbiota are sometimes observed as a characteristic of adults and adolescents with obesity. However, the researchers did not see a relationship of weight gain with either of these measures in gut microbiota of two-year-olds, suggesting that the gut microbiota may not be completely established at two years of age and may still be undergoing many changes.
"There are usually dramatic changes to an individual's microbiota as they develop during early childhood," said Makova. "Our results suggest that signatures of obesity may be established earlier in oral microbiota than in gut microbiota. If we can confirm this in other groups of children outside of Pennsylvania, we may be able to develop a test of oral microbiota that could be used in clinical care to identify children who are at risk for developing obesity. This is particularly exciting because oral samples are easier to obtain than those from the gut, which require fecal samples."
Interestingly, weight gain in children was also related to diversity of their mother's oral microbiota. This could reflect a genetic predisposition of the mother and child to having a similar microbiota, or the mother and child having a similar diet and environment.
"It could be a simple explanation like a shared diet or genetics, but it might also be related to obesity," said Makova. "We don't know for sure yet, but if there is an oral microbiome signature linked to the dynamics of weight gain in early childhood, there is a particular urgency to understand it. Now we are using additional techniques to look at specific species of bacteria -- rather than larger taxonomic groups of bacteria -- in both the mothers and children to see whether specific bacteria species influence weight gain and the risk of obesity."

Study: Antibiotics destroy immune cells and worsen oral infection

New research shows that the body's own microbes are effective in maintaining immune cells and killing certain oral infections.
A team of Case Western Reserve University researchers found that antibiotics actually kill the "good" bacteria keeping infection and inflammation at bay.
Scientists have long known that overuse of antibiotics can do more harm than good. For example, overuse can cause antibiotic resistance. But research into this phenomenon in oral health was uncharted territory.
Pushpa Pandiyan, an assistant professor of biological sciences in the School of Dental Medicine, led a team of researchers to examine "resident" bacteria, their fatty acids and their effect on certain types of white blood cells that combat infections in the mouth.
Specifically, researchers looked at the "short-term maintenance" of Tregs and Th-17 cells in fighting fungal infections, such as Candida, in a laboratory setting.
They found that those natural defenses were very effective in reducing infection and unwanted inflammation-- and antibiotics can prevent such natural defenses. Their work was recently published in Frontiers in Microbiology.
"We set out to find out what happens when you don't have bacteria to fight a fungal infection," Pandiyan said. "What we found was that antibiotics can kill short-chain fatty acids produced by body's own good bacteria."
"We have good bacteria doing good work every day, why kill them?" Pandiyan added. "As is the case with many infections, if you leave them alone, they will leave on their own."
"Of course, antibiotics are still needed for life threatening infections. No question about that. Our bodies have many natural defenses that we shouldn't meddle with," she said. However, needless overuse of antibiotics is not helpful, she said.
"Also, we know there is a definite link between oral health and overall health," she added.
Pandiyan said the study could have broader implications on protective effects of "resident microbiota" in other types of infections.
Pandiyan is concurrently working on a National Institutes of Health research project examining HIV patients who have developed oral-health conditions as a result of weakened immune systems.
She was joined in the study by dental school research staff Natarajan Bhaskaran, Cheriese Quigley, and Elizabeth Schneider, and students Clarissa Paw and Shivani Butala.

Smoking weakens the ability for pulp in teeth to fight illness and disease.

As if lung cancer, emphysema and heart disease weren't enough, there's more bad news for cigarette smokers.

Researchers at the Case Western Reserve University School of Dental Medicine found that smoking also weakens the ability for pulp in teeth to fight illness and disease.

In other words, smokers have fewer defense mechanisms on the inside of their teeth.

"That might explain why smokers have poorer endodontic outcomes and delayed healing than non-smokers," said Anita Aminoshariae, associate professor of endodontics and director of predoctoral endodontics. "Imagine TNF-α and hBD-2 are among the soldiers in a last line of defense fortifying a castle. Smoking kills these soldiers before they even have a chance at mounting a solid defense."
The results of the study were published in the Journal of Endodontics.

Aminoshariae said that, previously, there was little research into the endodontic effects of smoking--the inside of teeth. Smokers had worse outcomes than nonsmokers, with greater chances of developing gum disease and nearly two times more likely to require a root canal.

This new preliminary research set out to explain the possible contributing factors.

Thirty-two smokers and 37 nonsmokers with endodontic pulpitis--more commonly known as dental-tissue inflammation--were included in the study.

"We began with a look at the dental pulp of smokers compared with nonsmokers," she said. "We hypothesized that the natural defenses would be reduced in smokers; we didn't expect them to have them completely depleted."
One interesting find, Aminoshariae noted, was that for two patients who quit smoking, those defenses returned.
Joining Aminoshariae in the study were former students Caroline Ghattas Ayoub and Mohammed Bakkar; faculty members Tracey Bonfield, Catherine Demko, Thomas A. Montagnese and Andre K. Mickel; and research Santosh Ghosh--all from the School of Dental Medicine.

Chalky teeth

Depending on symptomatic and phenotypic severity the condition of chalky teeth is categorised into three levels. The symptoms of chalky teeth were first described in 1978, with the term molar-incisor hypomineralisation (MIH) introduced in 2001. The condition is the consequence of a deline-ated defect in tooth enamel development which affects at least one of the permanent back teeth (molars) and, under certain circumstances, will also comprise the incisors. According to recent media coverage such tooth defects are claimed to be attributable to the uptake of Bisphenol A (BPA).
Amongst a wide range of various products BPA can also occur in food contact materials. Its use in the manufacture of baby bottles has been banned since 2011. Reports of a possible connection between MIH and BPA-exposure are based on a study by Jedeon et al. (2013) which examined the connection between BPA exposure and mineralisation defects of tooth enamel in rats. In subsequent publications the authors reported that the mineralisation dis-turbances occurred mainly in male (up to 71%) and less frequently in female rats (only up to 31%) (Jedeon et al., 2016a; Jedeon et al., 2014), and identified selected hormone-controlled signalling pathway as potential molecular targets (Houari et al., 2016).
The German Federal Institute for Risk Assessment (BfR) has evaluated the study (Jedeon et al., 2013) and concludes that there is currently no scientific reason to assume a connection between the uptake of BPA the occurrence of MIH in children. According to recent data from the Netherlands, oral uptake of BPA in highly-exposed children amounts to 0.14 micrograms (μg) per kilogram (kg) body weight and day. This is is 35 times lower than the dose used by Jedeon et al. (2013). In conjunction with the different toxicokinetic behaviour of BPA in hu-mans a direct connection between BPA and MIH therefore appears unlikely in humans under conditions of expectable real-life exposure.
It should be noted that the study of Jedeon et al. is subject to several limitations, which limit its transferability. The examination in 2013 was conducted exclusively on male rats with only one dose of BPA being used. Later studies showed that the respective findings were considerably weaker or non-existent in females (Jedeon et al., 2014). It also appears that missing effects on day 100 of postnatal development were not put sufficiently into context. The findings of other groups from multigenerational studies on rats and mice, some of which used very high BPA doses with no reported tooth damage, were not taken into consideration.
The condition of MIH occurs in Europe with a frequency of 3-22 %, with a worldwide occurrence of 2-40 % (Elhennawy et al., 2017). Various reasons are assumed to contribute to this occurrence. Epidemiological studies point for example to maternal diseases during the last quarter of pregnancy, complications during birth or frequent illness in the first year of the born child (possibly also connected too high fever). Other reasons discussed are low blood levels of vitamin D as well as early intake of the antibiotic amoxicilli. Other studies report on a possible connection between MIH and increased exposure to dioxin, for under 5-year olds with high serum levels of tetrachlorodibenzo dioxin (TCDD) in Seveso later showed an in-creased prevalence of MIH.
Altogether it appears that MIH is caused by a variety of factors and thus has to be considered a multifactorial condition (Schneider and Silva, 2018).

New findings re chronic oral pain condition known as Burning Mouth Syndrome

The picture is becoming clearer regarding the chronic oral pain condition known as Burning Mouth Syndrome, or BMS, which mainly affects women who are middle-aged and older. In a dissertation at Sahlgrenska Academy, additional steps are being taken toward better diagnosis and treatment.

"Our hope is that the new findings will contribute to the development of objective diagnostic criteria and effective individualized treatment both that are currently lacking," says Shikha Acharya, who has a PhD in oral microbiology and immunology at the Institute of Odontology.

Burning Mouth Syndrome (BMS) is a chronic pain syndrome in the oral cavity that affects approximately 4% of the Swedish population. This chronic condition mainly affects middle-aged and elderly women.

The pain is experienced as burning or stinging. The tongue is most often afflicted, but the palate, lips and gums also may be affected. Other common symptoms include dry mouth and altered taste sensation, such as a bitter or metallic taste in the mouth.

BMS is a challenge for health care providers, particularly in dental care, and a debilitating condition for many of the patients. When they estimate their problem on a visual analogue scale (VAS) where 0 is "not at all difficult" and 100 is "unbearable," the average response is 66, the dissertation indicates. The findings came from 56 women with BMS.

In her work Shikha Acharya also connected clinical findings and self-reported reported findings from questionnaires from patients with BMS about their symptoms and background (other diseases, use of medications, etc.) along with saliva-related factors. The results have been compared with a gender- and age-matched control group.

It turns out that 45 percent of the BMS patients reported to have altered taste sensations. A total of 73 percent experienced pain that was burning or stinging or a combination of the two, but stinging and numbness also occurred.

In addition to BMS, they have a higher incidence of other types of diseases, use more medications, are more prone to grinding their teeth and report more allergies than the control group. However, more advanced analyses show that BMS was strongly associated to self-reported skin diseases and subjective oral dryness.

The fact that the BMS patients, compared with people in the control group, report that they suffer considerably more from skin diseases and skin problems is a new discovery. Similarly, that the mucin proteins in BMS patients' saliva are altered and contain lower amounts of carbohydrate structures that affect the oral cavity's immune system.

Analysis of inflammatory constituents in saliva shows complex relationship between BMS and background inflammation, with some of the BMS patients having higher levels of inflammation than the control group while others had lower.

The dissertation work is part of a larger project aimed at finding a model for BMS that can facilitate diagnosis and treatment in the future. The new pieces of the puzzle are helping to characterize the disease and the persistent mouth pain associated with it.

"It's important because the afflicted patients often feel that their surroundings and health care professionals doubt their ailment," says Shikha.

###

Title: On Characteristics of Burning Mouth Syndrome Patients; http://hdl.handle.net/2077/55387

Regrowing dental tissue with stem cells from baby teeth

Sometimes kids trip and fall, and their teeth take the hit. Nearly half of children suffer some injury to a tooth during childhood. When that trauma affects an immature permanent tooth, it can hinder blood supply and root development, resulting in what is essentially a "dead" tooth.
Until now, the standard of care has entailed a procedure called apexification that encourages further root development, but it does not replace the lost tissue from the injury and, even in a best-case scenario, causes root development to proceed abnormally.
New results of a clinical trial, jointly led by Songtao Shi of the University of Pennsylvania and Yan Jin, Kun Xuan, and Bei Li of the Fourth Military Medicine University in Xi'an, China, suggest that there is a more promising path for children with these types of injuries: Using stem cells extracted from the patient's baby teeth. The work was published in the journal Science Translational Medicine.
"This treatment gives patients sensation back in their teeth. If you give them a warm or cold stimulation, they can feel it; they have living teeth again," says Shi, professor and chair in the Department of Anatomy and Cell Biology in Penn's School of Dental Medicine. "So far we have follow-up data for two, two and a half, even three years and have shown it's a safe and effective therapy."
Shi has been working for a decade to test the possibilities of dental stem cells after discovering them in his daughter's baby tooth. He and colleagues have learned more about how these dental stem cells, officially called human deciduous pulp stem cells (hDPSC), work and how they could be safely employed to regrow dental tissue, known as pulp.
The Phase I trial, conducted in China, which has a research track for clinical trials, enrolled 40 children who had each injured one of their permanent incisors and still had baby teeth. Thirty were assigned to hDPSC treatment and 10 to the control treatment, apexification.
Those that received hDPSC treatment had tissue extracted from a healthy baby tooth. The stem cells from this pulp were allowed to reproduce in a laboratory culture, and the resulting cells were implanted into the injured tooth.
Upon follow-up, the researchers found that patients who received hDPSCs had more signs than the control group of healthy root development and thicker dentin, the hard part of a tooth beneath the enamel. Blood flow increased as well.
At the time the patients were initially seen, all had little sensation in the tissue of their injured teeth. A year following the procedure, only those who received hDPSCs had regained some sensation. Examining a variety of immune-system components, the team found no evidence of safety concerns.
As further support of the treatment's efficacy, the researchers had the opportunity to directly examine the tissue of a treated tooth when the patient reinjured it and had to have it extracted. They found that the implanted stem cells regenerated different components of dental pulp, including the cells that produce dentin, connective tissue, and blood vessels.
"For me the results are very exciting," Shi says. "To see something we discovered take a step forward to potentially become a routine therapy in the clinic is gratifying."
It is, however, just a first step. While using a patient's own stem cells reduces the chances of immune rejection, it's not possible in adult patients who have lost all of their baby teeth. Shi and colleagues are beginning to test the use of allogenic stem cells, or cells donated from another person, to regenerate dental tissue in adults. They are also hoping to secure FDA approval to conduct clinical trials using hDPSCs in the United States.
Eventually, they see even broader applications of hDPSCs for treating systemic disease, such as lupus, which Shi has worked on before.
"We're really eager to see what we can do in the dental field," Shi says, "and then building on that to open up channels for systemic disease therapy."

Biomaterial could keep tooth alive after root canal (video)

A root canal ranks high on most people's list of dreaded dental procedures. Although the lengthy and sometimes painful surgery relieves the agony of an infection, a root canal results in a dead tooth with no living soft tissue, or dental pulp, inside. Today, scientists report development of a peptide hydrogel designed to stimulate the growth of new blood vessels and dental pulp within a tooth after the procedure. The researchers are presenting their results today at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 10,000 presentations on a wide range of science topics.
A brand-new video on the research is available at http://bit.ly/acsrootcanal.
"What you end up with after a root canal is a dead tooth," Vivek Kumar, Ph.D., the project's principal investigator, says. "It's no longer responsive. There are no nerve endings or vascular supply. So the tooth is very susceptible to subsequent infection and, ultimately, falling out."
During a root canal, the dentist drills off the top of an infected tooth to access the soft tissue inside. The dentist then removes the infected dental pulp and fills the space with tiny rubber rods called gutta percha and caps the repaired tooth with a crown.
Kumar and Peter Nguyen, Ph.D., who is presenting the work at the meeting, wanted to develop a material that could be injected in place of the gutta percha. The material would stimulate both angiogenesis, or new blood vessel growth, and dentinogenesis, or proliferation of dental pulp stem cells, within the tooth. Both Kumar and Nguyen are at the New Jersey Institute of Technology.
Kumar drew on his previous experience developing a hydrogel that stimulates angiogenesis when injected under the skin of rats and mice. The hydrogel, which is liquid during injection, contains peptides that self-assemble into a gel at the injection site. The peptides contain a snippet of a protein called vascular endothelial growth factor, which stimulates the growth of new blood vessels. Kumar, then a postdoctoral researcher at Rice University, and his coworkers showed that the self-assembling peptide hydrogel stimulated angiogenesis and persisted under the rodents' skin for as long as three months.
"We asked the question, if we can stimulate angiogenesis in a limb, can we stimulate angiogenesis in other regions that have low blood flow?" Kumar says. "One of the regions we were really interested in was an organ in and of itself, the tooth." So Kumar and Nguyen added another domain to the self-assembling angiogenic peptide: a piece of a protein that makes dental pulp stem cells proliferate.
When the team added the new peptide to cultured dental pulp stem cells, they found that the peptide not only caused the cells to proliferate, but also activated them to deposit calcium phosphate crystals -- the mineral that makes up tooth enamel. However, when injected under the skin of rats, the peptide degraded within one to three weeks. "This was shorter than we expected, so we went back and redesigned the peptide backbone so that we currently have a much more stable version," says Kumar.
Now, the team is injecting the peptide hydrogel into the teeth of dogs that have undergone root canals to see if it can stimulate dental pulp regeneration in a living animal. If these studies go well, the researchers plan to move the hydrogel into human clinical studies. They have filed a patent for the redesigned peptide.
The hydrogel in its current form likely won't reduce the invasiveness or pain of a root canal, but Kumar and Nguyen are planning future versions of the peptide that contain antimicrobial domains. "Instead of having to rip out everything inside the tooth, the dentist could go in with a smaller drill bit, remove a little bit of the pulp and inject our hydrogel," Kumar says. The antimicrobial portion of the peptide would kill the infection, preserving more of the existing dental pulp, while helping grow new tissue. And the root canal may no longer be such a dreaded procedure.
A press conference on this topic will be held Wednesday, August 22, at 9 a.m. Eastern time in the Boston Convention & Exhibition Center. Reporters may check-in at the press center, Room 102 A, or watch live on YouTube http://bit.ly/ACSLive_Boston2018. To ask questions online, sign in with a Google account.

Bioengineered tooth replacement opens doors to new therapies

Tooth loss is a significant health issue currently affecting millions of people worldwide. While artificial dental implants are the existing standard tooth replacement therapy, they do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Two articles published in the September 2018 issue of the Journal of Dental Research share recent advances in bioengineering teeth.

In the article "Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds" Pamela Yelick, Tufts University School of Dental Medicine, Boston, Mass., USA and co-authors explored new methods to create highly cellularized bioengineered tooth bud constructs that include features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells and mineralized dental tissue formation. The constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats.

This is the first report that describes the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development, pointing to future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.

In the article "Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth" Sabine Kuchler-Bopp, French National Institute of Health and Medical Research and Fédération de Médecine Translationnelle de Strasbourg, France, and co-authors developed a strategy where autologous mesenchymal cells coming from bone marrow can be used to supply nerves to bioengineered teeth without treatment that uses an immunosuppressor. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. This new method provides innervation while avoiding multiple side effects associated with immunosuppressors.

"These exciting studies point to a promising future for bioengineered teeth," said Journal of Dental Research Editor-in-Chief William V. Giannobile. "This cutting-edge research has the potential to advance tooth replacement therapy and the science base to bring such regenerative medicine treatments to improve clinical care."

###

Dental care may benefit patients scheduled for cancer surgery

Preoperative oral care by a dentist may help reduce postoperative complications in patients who undergo cancer surgery, according to a new BJS (British Journal of Surgery) study.

Of 509,179 patients studied, 16% received preoperative oral care from a dentist. When a surgeon requested that a dentist provide preoperative oral care to a patient with cancer, the dentist checked the patient's oral condition, provided professional tooth cleaning, taught the patient self-cleaning methods for the teeth, and provided any treatment needed.

In the study, 15,724 patients (3.09%) developed postoperative pneumonia and 1734 (0.34%) died within 30 days of surgery. After adjustments, preoperative oral care by a dentist was linked with a decrease in postoperative pneumonia (3.28% versus 3.76%) and death within 30 days (0.30% versus 0.42%).

"The findings could help improve strategies for the prevention of postoperative complications," the authors wrote.

Unwise opioids for wisdom teeth: Study shows link to long-term use in teens and young adults

---

Getting wisdom teeth removed may be a rite of passage for many teens and young adults, but the opioid painkiller prescriptions that many of them receive could set them on a path to long-term opioid use, a new study finds.

Young people ages 13 to 30 who filled an opioid prescription immediately before or after they had their wisdom teeth out were nearly 2.7 times as likely as their peers to still be filling opioid prescriptions weeks or months later, according to new research from a University of Michigan team.

Those in their late teens and twenties had the highest odds of persistent opioid use, compared with those of middle school and high school age, the researchers report in a research letter in the new issue of JAMA.

Led by Calista Harbaugh, M.D., a U-M research fellow and surgical resident, the researchers used insurance data to focus on young people who were 'opioid naïve' -- who hadn't had an opioid prescription in the six months before their wisdom teeth came out, and who didn't have any other procedures requiring anesthesia in the following year.

"Wisdom tooth extraction is performed 3.5 million times a year in the United States, and many dentists routinely prescribe opioids in case patients need it for post-procedure pain," says Harbaugh, a National Clinician Scholar at the U-M Institute for Healthcare Policy and Innovation. "Until now, we haven't had data on the long-term risks of opioid use after wisdom tooth extraction. We now see that a sizable number go on to fill opioid prescriptions long after we would expect they would need for recovery, and the main predictor of persistent use is whether or not they fill that initial prescription."

Other factors also predicted risk of long-term opioid use. Teens and young adults who had a history of mental health issues such as depression and anxiety, or chronic pain conditions, were more than others to go on to persistent use after filling their initial wisdom tooth-related prescription.

More about the study

In all, 1.3 percent of 56,686 wisdom tooth patients who filled their opioid prescription between 2009 and 2015 went on to persistent opioid use, defined as two or more prescriptions filled in the next year written by any provider for any reason. That's compared with 0.5 percent of the 14,256 wisdom tooth patients who didn't fill a prescription.

Though those numbers may seem small, the high number of wisdom teeth procedures every year mean a large number of young people are at risk, notes Harbaugh, a research fellow with the Michigan Opioid Prescribing and Engagement Network, or Michigan OPEN.

The team used data from employer-based insurance plans, available through the Truven MarketScan database purchased for researchers' use by IHPI. Chad Brummett, M.D., co-director of Michigan OPEN, is senior author of the new research, and the team includes U-M School of Dentistry professor Romesh Nalliah, D.D.S., MHCM.

The data show opioid prescriptions filled, but not actual use of opioid pills by patients. Leftover opioids pose a risk of their own, because they can be misused by the individual who received the prescription, or by a member of their household or a visitor. The researchers also couldn't tell the reason for the later opioid prescription fills by those who went on to persistent use.

The authors suggest that dentists and oral surgeons should consider prescribing non-opioid painkillers before opioids to their wisdom tooth patients. If pain is acute, they should prescribe less than the seven-day opioid supply recently recommended by the American Dental Association for any acute dental pain.

"There are no prescribing recommendations specifically for wisdom tooth extraction," says Harbaugh. "With evidence that nonsteroidal anti-inflammatories may just as, if not more, effective, a seven-day opioid recommendation may still be too much."

Brummett adds, "These are some of the first data to the show long-term ill effects of routine opioid prescribing after tooth extractions. When taken together with the previous studies showing that opioids are not helpful in these cases, dentists and oral surgeons should stop routinely prescribing opioids for wisdom tooth extractions and likely other common dental procedures."

Importance for patients and parents

Getting a prescription for an opioid painkiller around the time of a wisdom tooth procedure comes with many decision points, Harbaugh says.

"Patients must decide whether to fill the prescription and take the medication, and where to store and dispose of the unused pills. All of these decision points need to be discussed with patients," she says. "Patients should talk to their dentists about how to control pain without opioids first. If needed, opioids should only be used for breakthrough pain, as backup if the pain's not controlled with other medications."

The Michigan-OPEN team is currently studying the wisdom tooth extraction population further, by speaking with patients and parents about their experience and how many opioid pills they actually took. This will allow them to create evidence-based prescribing guidelines just like the ones they've developed for other operations.

The research was funded by the federal Substance Abuse and Mental Health Services Administration, the Michigan Department of Health and Human Services, and the University of Michigan Precision Health Initiative.

Dental plaque is no match for catalytic nanoparticles

Combine a diet high in sugar with poor oral hygiene habits and dental cavities, or caries, will likely result. The sugar triggers the formation of an acidic biofilm, known as plaque, on the teeth, eroding the surface. Early childhood caries is a severe form of tooth decay that affects one in every four children in the United States and hundreds of millions more globally. It's a particularly severe problem in underprivileged populations.

In a study published in Nature Communications this week, researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn's Perelman School of Medicine and School of Engineering and Applied Science used FDA-approved nanoparticles to effectively disrupt biofilms and prevent tooth decay in both an experimental human-plaque-like biofilm and in an animal model that mimics early-childhood caries.

The nanoparticles break apart dental plaque through a unique pH-activated antibiofilm mechanism.

"It displays an intriguing enzyme-like property whereby the catalytic activity is dramatically enhanced at acidic pH but is 'switched off' at neutral pH conditions," says Koo, professor in Penn Dental Medicine's Department of Orthodontics and in the divisions of Pediatric Dentistry and Community Oral Health. "The nanoparticles act as a peroxidase, activating hydrogen peroxide, a commonly used antiseptic, to generate free radicals that potently dismantle and kill biofilms in pathological acidic conditions but not at physiological pH, thus providing a targeted effect."
Because the caries-causing plaque is highly acidic, the new therapy is able to precisely target areas of the teeth harboring pathogenic biofilms without harming the surrounding oral tissues or microbiota.
The particular iron-containing nanoparticle used in the experiments, ferumoxytol, is already FDA-approved to treat iron-deficiency, a promising indication that a topical application of the same nanoparticle, used at several-hundred-fold lower concentration, would also be safe for human use.
Though some scientists have questioned whether coatings used on ferumoxytol and other nanoparticles used for medical applications would render them catalytically inert, Koo, Liu, and Cormode demonstrated that they maintained peroxidase-like activity, activating hydrogen peroxide.
After testing the ferumoxytol-hydrogen peroxide combination on a tooth-enamel-like material, the team moved on to an experimental set-up that more closely replicated the conditions of the human mouth.
"We used plaque samples from caries-active subjects to reconstruct these highly pathogenic biofilms on real human tooth enamel," says Koo. "This simulation showed that our treatment not only disrupts the biofilm but also prevents mineral destruction of the tooth's surface. That offered very strong evidence that this could work in vivo."
Further studies in a rodent model that closely mirrors the stages of caries development in humans showed that twice-a-day rinses of ferumoxytol and hydrogen peroxide greatly reduced the severity of caries on all of the surfaces of the teeth and also completely blocked the formation of cavities in the enamel.
As further evidence of the treatment's targeted effect, the researchers found no significant change in the diversity of microbes in the mouth after therapy and found no signs of tissue damage.
"This therapy isn't killing microorganisms indiscriminately," Koo says, "but rather it is acting only where the pathological biofilm develops. Such a precise therapeutic approach can target the diseased sites without disrupting the ecological balance of the oral microbiota, which is critical for a healthy mouth, while also avoiding infection by opportunistic pathogens."
Incorporating nanoparticles in a mouth rinse or toothpaste could be a cost-effective way to significantly improve their effectiveness, says Koo. Many of these products already contain hydrogen peroxide and would only require the addition of a small amount of relatively inexpensive nanoparticles. With evidence backing this approach in both an animal model and a human-like model of tooth decay, the research team is actively working to test its clinical efficacy.

The effectiveness of chlorhexidine is limited in preventing infections in oral procedures

The human oral cavity is colonised by a huge variety of bacteria. When surgical procedures such as a tooth extraction are carried out, the bacteria can pass into the bloodstream causing bacteraemia that is generally transient. What is not yet clear is how significant this presence of bacteria in the blood is in terms of the origin and evolution of infectious processes such as endocarditis of the heart valves, prosthetic valves, hip and knee joint replacements generally, and in local infection.
Numerous studies have shown that a mouthwash containing chlorhexidine has a powerful antimicrobial effect on saliva microflora and bacterial plaque. "On the basis of this hypothesis we can assume that antimicrobial mouthwashes used before the dental procedure should reduce the number of micro-organisms that pass into the patient's bloodstream, yet this is a hotly debated issue," said the members of the UPV/EHU's research group.
In 1997 the American Heart Association (AHA) suggested that patients at risk of infectious endocarditis should use an antimicrobial mouthwash before a dental procedure. In 2006, the British Society for Antimicrobial Chemotherapy (BSAC) recommended a single mouthwash with 0.2% chlorhexidine (CHX) (10 ml for 1 minute) before the carrying out of dental procedures associated with bacteraemia in patients at risk. Yet in 2007 the AHA recommended against adopting any antiseptic prophylaxis protocol.
In an effort to shed scientific light on this issue, the UPV/EHU research group comprising Iciar Arteagoitia, Carlos Rodriguez-Andrés and Eva Ramos decided to conduct a systematic review and meta-analysis of random controlled trials (RCT), following the PRISMA Statement. The aim was to assess the effectiveness of chlorhexidine in preventing bacteraemia following a tooth extraction. The research was conducted in collaboration with the UPV/EHU's Department of Epidemiology and was published in Plos One, the leading, open-access, global scientific journal which accepts rigorous, innovative papers on scientific research.
In the study that included 8 clinical trials with 523 patients there were 267 in the group treated with chlorhexidine, in which 145 cases of bacteraemia were recorded, and 256 in the control group, in which there were 156 cases of bacteraemia. The results of the research therefore indicate that the percentage of cases of bacteraemia that can be prevented if a population undergoes chlorhexidine-based prevention is 12%. The NNT, the number of patients that need to be treated to prevent bacteraemia, is 16.
The results point to the relative and not particularly significant effectiveness of the use of chlorhexidine when it comes to preventing the bacteria present in the mouth from passing into the bloodstream when dental extraction is carried out. "Yet, given its low cost and the absence of adverse reactions and complications, we would recommend a mouthwash with chlorhexidine before a procedure of this type is carried out," concluded the UPV/EHU's research group.