Link between periodontitis and cardiovascular disease in individuals with rheumatoid arthritis

Rates of both periodontal disease and cardiovascular disease are elevated in individuals with rheumatoid arthritis. New research published in Arthritis & Rheumatology suggests that immune responses to certain bacteria that cause periodontal disease may play a role in patients' higher cardiovascular disease risk.

Among 197 patients with rheumatoid arthritis, those with antibody responses to common periodontal pathogens were more likely to also show signs of atherosclerosis.

"Evidence of exposure to a particular periodontal pathogen called Aggregatibacter actinomycetemcomitans had the strongest associations with atherosclerosis in the patients with rheumatoid arthritis that we studied," said lead author Jon T. Giles, MD MPH, of Columbia University. "Moreover, it was associated with measures of coronary, carotid, and peripheral atherosclerosis, over and above other risk factors for atherosclerosis. Further studies are needed to determine if eliminating exposure to this pathogen might modify the increase in cardiovascular disease known to be part of rheumatoid arthritis."

A reason for early deterioration of dental implants

 

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IMAGE: A TEAM OF DENTISTS FROM RUDN UNIVERSITY CONFIRMED THAT A CHANGE IN THE DOMINANT SIDE OF CHEWING IS A REASON FOR THE EARLY DETERIORATION OF DENTAL IMPLANTS. SUCH A CHANGE... view more 

CREDIT: RUDN UNIVERSITY

A team of dentists from RUDN University confirmed that a change in the dominant side of chewing is a reason for the early deterioration of dental implants. Such a change makes it more difficult for a patient to get accustomed to an implant and can lead to bone tissue abnormalities. The discovery can help dentists plan the recovery process after implantation surgeries. The results of the study were published in the European Journal of Dentistry.

Every year, around 2 mln dental implants with fixed dentures attached to them are installed all over the world. An implant is an effective way to restore a deformed or lost tooth without negatively affecting a patient's quality of life. Modern-day dental implants, usually made of titanium, are durable and quick to take in the bone tissue of a jaw. The only issue with them is their early deterioration in 4-5% of patients. Such deterioration is caused by microdamage that occurs when the load on the implant is calculated incorrectly before the surgery. Excessive load affects the junction between the metal and the bone, letting the bacteria in under the implant and causing inflammation. A team of dentists from RUDN University suggested that additional load on the implant might occur when a patient changes the dominant side of chewing in the first months after the surgery.

Most people don't chew symmetrically on both sides of the jaw but have a dominant side that accounts for up to 75% of chewing movements. However, such a side can be changed, for example, because of a sore tooth. It usually takes a patient 3 to 4 months to get accustomed to a dental implant and during this time the type of chewing and the load on the teeth can change. As a result, after the surgery, a patient can switch to a different side of chewing, and load calculations from before the surgery can become invalid. Until recently, the effect of this dramatic change in chewing habits on the state of dential implants remained understudied.

The team monitored the course of rehabilitation of 64 patients with dental implants. The participants of the study were adults with implants installed only on one side of the jaw. Surgeries on both sides of the jaw were not included in the study as they would not allow for measuring the effect of dominant chewing side change. The team took X-ray images of the participants' teeth, measured the strength of their chewing muscles, and in some cases took CT images of the jaws. All these operations were conducted once before the surgery and twice within a year after it. To analyze the results of the treatment, the team asked the participants to fill in questionnaires.

40 patients (62.5%) reported changes in the dominant side of chewing after the surgery. According to the dentists, this might have happened because the patients returned to the chewing patterns they had been used to earlier, before losing a tooth. Having compared this group with the rest of the patients that reported no changes in their chewing habits, the team found out that a change of the dominant side of chewing leads to more bone tissue formation pathologies. In 4 patients with changed chewing habits, the first signs of issue deterioration around the implant were visible in X-ray images. As for the second group, these signs were identified in only one participant. Six months after the surgery the patients that changed their dominant side of chewing felt 22% less adapted to the implants than the patients with no changes in their chewing patterns.

"A change in the dominant side of chewing is an important factor in one's adaptation to dental implants. According to our study, it can also be the reason for pathological processes, eventually leading to the loss of an implant. Dentists need to be aware of the prevalence of such changes, consider them when developing postsurgical rehabilitation plants, and look for their signs during regular checkups," said Prof. Igor Voronov, MD, from the Department of Orthopedic Dentistry, RUDN University.

Most dentists have experienced aggression from patients

NYU study is first to describe rates of physical, verbal, and reputational aggression by patients toward practicing dentists

Roughly half of U.S. dentists experienced verbal or reputational aggression by patients in the past year, and nearly one in four endured physical aggression, according to a new study led by researchers at NYU College of Dentistry.

The study, published in the October issue of the Journal of the American Dental Association, is the first to document aggression toward dentists in the United States.

Workplace aggression toward health care professionals is common, with health care settings second only to law enforcement in the rate of violent incidents. However, there are no studies of aggression toward dentists in the U.S.--a workforce of 200,000--and only four studies have been conducted in other countries.

"Workplace violence toward health care professionals is both widespread and widely overlooked," said Kimberly Rhoades, a research scientist in the Family Translational Research Group at NYU College of Dentistry and the study's lead author. "The purpose of this study was to provide an initial estimate of rates of patient aggression in dental practices in the United States."

Rhoades and her colleagues surveyed 98 dentists practicing in the New York City metropolitan area; the dentists had been working an average of 17 years. Participants completed a confidential online survey assessing whether they had experienced any of 21 specific types of aggressive behaviors from their patients, including types of physical (e.g. being pushed or kicked), verbal (e.g. being insulted or sworn at), and reputational (e.g. threats of lawsuits or posting nasty comments on social media) aggression.

A substantial proportion of dentists reported experiencing aggression from patients in the past year, including physical (22.2%), verbal (55%), and reputational (44.4%) aggression. An even larger proportion of dentists surveyed were subjected to physical (45.5%), verbal (74%), and reputational (68.7%) aggression at some point during their career. These rates of patient aggression toward dentists are high and comparable with those reported in other health care settings.

Rates of aggression did not differ by dentists' sex, race, ethnicity, specialty, age, years practicing, or average number of patients treated per day.

The rates of physical and reputational aggression toward dentists were similar to those from a parallel study by NYU researchers of aggression toward dental students published earlier this year in the Journal of Dental Education. However, practicing dentists experienced less verbal aggression from patients than dental students (55% versus 86%), suggesting that additional experience may reduce the risk of verbal aggression.

"Dentistry is rife with situations that can elicit strong negative emotions, such as fear, pain, distrust, and anger. Many patients also experience high levels of anxiety and vulnerability, which may increase negative responses or aggression," said Rhoades. "Establishing that aggression toward dentists is a problem and how often it occurs can help us develop interventions to prevent aggression in dental practices."

The researchers note that, while a larger, national study is needed to determine the true prevalence of aggression in U.S. dental settings, dental practices should consider implementing training that incorporates strategies for handling workplace violence. Training could address how to prevent patient aggression, and manage or de-escalate aggression when it does occur.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered

Researchers at the University of Toronto have found first evidence that neutrophil immune cell activity is the missing link connecting periodontal disease with heart disease, cancer, and other inflammatory conditions

UNIVERSITY OF TORONTO - FACULTY OF DENTISTRY

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IMAGE: NEUTROPHIL ACTIVATION IS NOW BELIEVED TO BE AT THE ROOT OF OVERACTIVE INFLAMMATORY RESPONSES, AND LINKS CONDITIONS SUCH AS PERIODONTAL DISEASE AND HEART DISEASE view more 

CREDIT: NOAH FINE

(TORONTO, ON) Oct. 20, 2020 -- The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery. This month, a team of scientists and clinicians led by the University of Toronto's Faculty of Dentistry say they've found the reason why -- and it's related to the body's own hyperactive immune response. The findings were published in October in the Journal of Dental Research.

HYPERACTIVE STATE

Science has already established that state of your oral health is an important indicator of overall health. "There are statistically significant correlations between periodontitis (oral inflammatory disease) and systemic diseases ranging from diabetes to cardiovascular diseases," says Howard Tenenbaum, professor at the University of Toronto's Faculty of Dentistry, and chief dentist at Sinai Health Systems in Toronto, who is one of the authors of the study.

To find what links those conditions, the researchers focused on the behaviours of cells primarily activated by gum disease -- neutrophils, which are cells of the innate immune system. Through in vivo models, the researchers found that the immune system releases an abundance of these neutrophils to tackle the bacterial infections responsible for periodontitis, more commonly known as gum disease.

Activated to fight an oral infection, a systemic effect was noted: once periodontal inflammation was present, an overabundance of neutrophils circulated, 'primed' for attack. The hyper-vigilant immune system then responds with an excess of force to any secondary infection.

"It's almost as if these white blood cells are in second gear when should be in first," says Michael Glogauer, professor at the University of Toronto's Faculty of Dentistry and the study's senior author.

That's when the body becomes susceptible to damage from secondary inflammatory conditions. With the immune system already primed by the neutrophils for attack, a secondary event causes those immune cells to destroy affected tissues and organs.

"The [neutrophils] are much more likely to release cytokines much more quickly, leading to negative outcomes," adds Glogauer, who is also dentist-in-chief at the University Health Network and head of dental oncology at Toronto's Princess Margaret Cancer Centre.

Produced initially in in vivo models, the findings were confirmed through a controlled clinical experiment.

ORAL HEALTH KEY TO OVERALL HEALTH

The study's findings underscore the importance of oral health as a vital indicator of potential complications for other inflammatory conditions, as well as disease model outcomes.

"We believe this is the mechanism by which oral hygiene can impact vulnerability to unrelated secondary health challenges," says lead author Noah Fine, a postdoctoral fellow at the University of Toronto's Faculty of Dentistry. "Neutrophil (immune) priming throughout the body can connect these seemingly distinct conditions," he says.

The study also may have important ramifications for an inflammatory disease at the top of everyone's mind these days: COVID-19.

"There is evidence out there that patients with periodontal disease may be much more likely to have negative outcomes with COVID-19," explains Glogauer. The current study could provide some clues as to why: "Neutrophils are the cells that are at prime risk of causing cytokine storms. That's the exact cell we show is primed with people with periodontal disease," he explains.

Research into the relationship between neutrophils and inflammation is ongoing.

Oral cancer pain predicts likelihood of cancer spreading

Oral cancer is more likely to spread in patients experiencing high levels of pain, according to a team of researchers at New York University (NYU) College of Dentistry that found genetic and cellular clues as to why metastatic oral cancers are so painful.

The findings--which appear in Scientific Reports, a journal published by Nature--may ultimately be used to alleviate oral cancer pain and refine surgical decision making when treating oral cancer.

Oral cancer can cause severe pain during everyday activities, including talking and eating. Previous research by Brian L. Schmidt, DDS, MD, PhD, director of the NYU Oral Cancer Center and one of the study's authors, suggests that patients with metastatic oral cancer--cancer that spreads beyond the mouth--experience more pain than those whose cancer has not spread. The new study helps researchers understand why.

When oral cancer metastasizes, spreading to lymph nodes in the neck, a patient's chance of survival is cut by half. However, it's often unclear through imaging and physical assessment if oral cancer has spread, leaving surgeons struggling with whether to preemptively remove lymph nodes--an invasive procedure termed prophylactic neck dissection--during surgery to remove the oral cancer. While most oral cancer surgeries include a prophylactic neck dissection, research shows that up to 70 percent are unnecessary.

"Clinicians and researchers are keen to define a biomarker that accurately predicts metastasis," said Aditi Bhattacharya, PhD, an assistant professor in the Department of Oral and Maxillofacial Surgery at NYU College of Dentistry, an investigator at NYU Bluestone Center for Clinical Research, and the study's lead author. "Given that patients with metastatic oral cancer experience more pain, we thought that a patient's level of pain might help predict metastasis. A surgeon could then use this knowledge to only remove lymph nodes in patients with cancers that are most likely to metastasize."

In their study in Scientific Reports, the researchers first documented the pain experienced by 72 oral cancer patients before surgery, using an oral cancer pain questionnaire developed by the investigators. While most patients reported some pain, those who suffered with the most pain were more likely to have cancer that spread to lymph nodes in the neck. This observation suggests that patients with less pain are at low risk of metastasis, and will rarely benefit from a neck dissection.

To begin to understand why metastatic cancers are more painful, the investigators looked for differences in gene expression between metastatic cancers from patients with high levels of pain compared to non-metastatic cancers from patients not experiencing pain. Cancer pain is attributed to the release of mediators from cancers that sensitize nerves near the cancer. Forty genes were identified that were more highly expressed in painful metastatic cancers, suggesting that they promote metastasis and mediate cancer pain. Many of these genes are found in exosomes, small vesicles that break away from a cell and can be taken up by other cells--revealing a potential mechanism for how cancers communicate with nerves.

"I have been investigating the underlying cause of oral cancer pain for two decades. This is the first time that we have demonstrated a correlation between a patient's pain and the clinical behavior of the cancer," said Schmidt, who is also the director of the NYU Bluestone Center for Clinical Research and professor in the Department of Oral and Maxillofacial Surgery at NYU College of Dentistry.

Next, the team undertook laboratory experiments to study exosomes found in the extracellular fluid of oral cancer cells grown in the lab. When this extracellular fluid was injected into animal models, it produced pain, but when the cancer-derived exosomes in the fluid were removed, it did not cause pain. This suggests that exosomes from cancer may be responsible for oral cancer pain.

Now, with a deeper understanding of why metastatic oral cancers are painful, the researchers point to several potential clinical applications for their research, including a biomarker for oral cancer metastasis to help with surgical decision making and future testing options.

"While we need to undertake a follow-up study, our current data reveal that a patient's pain intensity score works as well as the current method--depth of invasion, or how deeply a tumor has invaded nearby tissue--as an index to predict metastasis," said Bhattacharya.

"The identified genes are targets for therapy aimed at stopping pain and cancer. In addition, exosomes shed from cancers can be detected in saliva, blood, and urine, offering the potential for an objective molecular test to diagnose risk of metastasis," said Donna Albertson, PhD, professor in the Department of Oral and Maxillofacial Surgery at NYU College of Dentistry, an investigator at NYU Bluestone Center for Clinical Research, and the study's corresponding author.

Dentists from RUDN University presented a new classification of root canal shape changes

 

RUDN UNIVERSITY

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IMAGE: INDIVIDUAL CHARACTERISTICS OF THE SHAPE AND CROSS-SECTION OF THE ROOT CANAL ARE ONE OF THE MAIN ISSUES FOR DENTISTS. WHEN TREATING A ROOT CANAL, A DOCTOR NEEDS TO PROPERLY CLEAN... view more 

CREDIT: RUDN UNIVERSITY

Individual characteristics of the shape and cross-section of the root canal are one of the main issues for dentists. When treating a root canal, a doctor needs to properly clean it, fill it, and carry out a rebuilding procedure so that a canal is sealed. The first stage of endodontic treatment requires detailed knowledge of root canal anatomy. A team of dentists from RUDN University studied and classified various changes in root canal shapes. The new classification will help doctors avoid diagnostic errors, better select their tools, and treat patients more efficiently. The results of the work were published in the Applied Sciences journal.

A root canal is a hollow space in a dental root with blood vessels and nerves going through it. Root canals have different shapes and width which makes treating them extremely complicated. Turns and shape changes can occur both in the coronal (visible) part of a tooth and in other parts that are invisible to the eye. Previous studies were focused on the curvatures of root canals in either the upper (coronal) or the lower (apical) part of a tooth. But a team of dentists from RUDN University carried out large scale research and presented the first-ever classification of root canal shape changes along its whole length.

"Earlier researchers tended to study about one-third of the root canal: either its coronal or its apical part. However, its shape changes along its full length, and this is an important factor for therapy. That is why we decided to take a look at the variations of root canal cross-sections in all three thirds and in different age groups of adult patients. Our goal was to develop a new classification of root canal shape changes," said Svetlana Razumova, MD, a Head of the Department of Propaedeutics of Dental Diseases at RUDN University.

The team conducted an experiment that involved 300 patients from 20 to 70 years of age. The medics took CT scans of their healthy teeth in axial projection, i.e. the X-ray from the CT scanner moved along the roll axis of the teeth. This way the images showed the cross-sections of root canals. The team took 4,805 images in total and used them to study the changes in the shape of root canals depending on the part of a tooth. The images were processed using statistical methods.

The most widely spread changes in all age groups affected premolars (the teeth situated between canines and molars). In over 50% of cases, the shape of the root canal in premolars changed from round in the apical third into oval in the coronal third. Another place with frequent changes in root canal shapes was mandibular molars.

Based on the obtained data the team developed a classification of root canal shape changes. The medics suggested dividing all possible changes into four groups: 1 - no changes in the shape, 2 - changes in the middle part of the root canal, 3 - changes in the middle and apical parts of the root canal, and 4 - changes in the apical part only. This classification will help dentists better understand the structure of each particular root canal and select proper tools to work with it.

"Our studies show that the shapes of root canal cross-sections can vary depending on the part of the canal and the age of a patient. All these variations were included in our classification and should be taken into consideration when choosing a method for canal cleaning. The choice of tools and preparation methods determines the efficiency of treatment at this stage and therefore affects the whole prognosis," added Svetlana Razumova.

Breakthrough for tomorrow's dentistry

KAROLINSKA INSTITUTET

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IMAGE: KAJ FRIED, PHD, PROFESSOR, DEPARTMENT OF NEUROSCIENCE (TO THE LEFT). IGOR ADAMEYKO, PROFESSOR, DEPARTMENT OF PHYSIOLOGY AND PHARMACOLOGY. view more 

CREDIT: GUSTAV MARTENSSON

New knowledge on the cellular makeup and growth of teeth can expedite developments in regenerative dentistry - a biological therapy for damaged teeth - as well as the treatment of tooth sensitivity. The study, which was conducted by researchers at Karolinska Institutet, is published in Nature Communications.

Teeth develop through a complex process in which soft tissue, with connective tissue, nerves and blood vessels, are bonded with three different types of hard tissue into a functional body part. As an explanatory model for this process, scientists often use the mouse incisor, which grows continuously and is renewed throughout the animal's life.

Despite the fact that the mouse incisor has often been studied in a developmental context, many fundamental questions about the various tooth cells, stem cells and their differentiation and cellular dynamics remain to be answered.

Using a single-cell RNA sequencing method and genetic tracing, researchers at Karolinska Institutet, the Medical University of Vienna in Austria and Harvard University in the USA have now identified and characterised all cell populations in mouse teeth and in the young growing and adult human teeth.

"From stem cells to the completely differentiated adult cells we were able to decipher the differentiation pathways of odontoblasts, which give rise to dentine - the hard tissue closest to the pulp - and ameloblasts, which give rise to the enamel," say the study's last author Igor Adameyko at the Department of Physiology and Pharmacology, Karolinska Institutet, and co-author Kaj Fried at the Department of Neuroscience, Karolinska Institutet. "We also discovered new cell types and cell layers in teeth that can have a part to play in tooth sensitivity."

Some of the finds can also explain certain complicated aspects of the immune system in teeth, and others shed new light on the formation of tooth enamel, the hardest tissue in our bodies.

"We hope and believe that our work can form the basis of new approaches to tomorrow's dentistry. Specifically, it can expedite the fast expanding field of regenerative dentistry, a biological therapy for replacing damaged or lost tissue."

The results have been made publicly accessible in the form of searchable interactive user-friendly atlases of mouse and human teeth. The researchers believe that they should prove a useful resource not only for dental biologists but also for researchers interested in development and regenerative biology in general.