We’re celebrating Dentistry Today’s 40th anniversary by interviewing 40 of the profession’s top leaders. Today we’re speaking with Dr. Wenyuan Shi, CEO and chief scientific officer of the Forsyth Institute, about the role his organization has played in pioneering oral health research, its community outreach efforts, and how it facilitates innovation by partnering with key entrepreneurs.

Drashty Mody, a second year student at the Indiana University School of Dentistry (IUSD), will participate in the National Institutes of Health (NIH) Medical Research Scholars Program (MRSP).

Mody will spend the 2021-2022 academic year at NIH in a comprehensive, residential research enrichment program for medical, dental, and veterinary students at the NIH Intramural Research Program in Bethesda, Maryland, according to IUSD.

MRSP scholars engage in a mentored research project in an area that matches their interests and career and research goals. Mody is the first IUSD student to be accepted into the MRSP.

“Drashty has shown a passion for research throughout dental school, and her acceptance into this highly competitive NIH training program is well deserved,” said Dr. Angela Bruzzaniti, associate professor and director of dental student research at IUSD.

“Not only will she be given a world-class research experience, she will be a great ambassador for our school and a role model for other dental students who have an interest in advancing evidence-based dentistry,” said Bruzzaniti.

At IUSD, Mody has been researching the dental disease process on multispecies biofilm models under the mentorship of Dr. Simone Duarte and postdoctoral research fellow Dr. Beatriz Panariello in the Department of Cariology, Operative Dentistry, and Dental Public Health.

“I was seven when my grandfather gifted me a microscope to help me visualize the finer structures of the plants that we were growing that summer. He was my first science teacher and made me appreciate the big impact of little things,” Mody said.

“Since then, it has been my passion to integrate theoretical research to understand real-world processes and problems. I am beyond honored to continue this research immersion and represent IUSD at the NIH Medical Research Scholars Program,” she said.

The NIH MRSP is an immersive residential experience where student scholars share in the excitement of new discovery with like-minded scholars from multiple academic institutions, IUSD said. They receive mentorship within and across disciplines, advising, independent research time, team science, peer collaboration, and professional networking, IUSD said.

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Yuyin Lin, DDS, a third-year resident in pediatric dentistry at the University of Alabama at Birmingham School of Dentistry, has won the 2021 American Academy of Pediatric Dentistry (AAPD) Graduate Student Research Award (GSRA).

Lin’s research, “Chemical, Physical and Antibacterial Properties of Contemporary Pulp Capping Materials,” compared the calcium-releasing, pH changes, water sorption and solubility, and antibacterial effects against Streptococcus mutans and Enterococcus faecalis of eight contemporary direct pulp capping materials.

“A better understanding of the clinical relevant properties of different pulp capping materials will help clinical decision making in choosing a pulp capping material for achieving the best clinical outcome,” Lin said.

Lin’s mentors included Nate Lawson, DMD, Ping Zhang, DDS, PhD, Kyounga Cheon, DMD, MS, and Janice Jackson, DMD.

The AAPD established the GSRA in 1989 for pediatric dentistry residents and recent graduates for completed research projects with significant findings. Awardees present their research during the AAPD Annual Session.

Also, awardees receive complimentary registration to the Annual Session as well as a cash award and plaque presented during the event’s General Assembly. A matching cash award is presented to each finalist’s training program as well.

Lin is one of eight residents from more than 90 pediatric dentistry residency programs across the United States and Canada to receive the award this year.

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Poor oral hygiene has a negative impact on athletic training and performance, according to Sunstar, which notes that maintaining a healthy mouth should be an essential part of athletes’ training programs and has partnered with the FDI World Dental Federation to launch Sports Dentistry Guidelines.

In a study of 302 athletes, 40% said they were bothered by their oral health, while 28% reported an impact on their quality of life, and 18% reported an effect on their training and performance. Also, 55% of the athletes had cavities, 45% had dental erosion, and 76% had periodontal disease.

Athletes are at high risk of developing oral diseases for several reasons, Sunstar said. For example, they require a lot of calories, which often are consumed via sugary protein sports bars. Also, athletes consumer a lot of sports drinks, which are mostly acidic and have high sugar content. Training leads to increased mouth breathing and reduced saliva flow, causing dry mouth and creating ideal conditions for bacteria to grow as well.

Sports-related stress is another risk factor that can cause gum disease, tooth erosion, cavities, and teeth grinding. In aquatic sports, low pH in swimming pool water can cause tooth erosion.

Just as athletics can impact oral health, oral health can impact athletic performance, Sunstar said. Poor oral health overall affects quality of life and well-being, which are key for optimal athletic performance, the company said.

Also, tooth decay and gum disease can cause and maintain inflammation in the body, which can negatively impact athletic performance. And athletes who have an infected tooth, mouth abscess, or some other painful condition could possibly perform badly or even withdraw from competition or training.

Sunstar offers advice for athletes:

• Make your oral health a priority, just like other parts of your training program, and include it as part of your daily routine like training, nutrition, and physio.
• Brush your teeth twice a day for at least two minutes with a fluoride toothpaste, ideally 30 minutes after eating, and clean between your teeth using interdental brushes, picks, or floss.
• Chew sugar-free gum or rinse with water after meals and snacks when brushing isn’t an option.
• Ensure you visit your dentist at least twice a year for a complete oral health checkup.

“We are striving to raise awareness of the importance of good oral hygiene to athletes and to their overall performance,” said Dr. Marzia Massignani, PhD, senior manager of scientific affairs at Sunstar. 

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Oral health during pregnancy can greatly impact the mother and the fetus. While the physiological changes during pregnancy can certainly cause oral health issues, pre-existing oral health conditions can have an effect on the well-being of the mother and her unborn child.¹

Dental practitioners can help their patients by educating them about the potential impact of pre-existing dental conditions, as well as diagnose and treat dental conditions that can develop with or during pregnancy.

Pre-Existing Disease

Several pre-existing conditions can negatively impact pregnancy. When examining oral health, studies support that pregnant women with pre-existing periodontal disease are at higher risk for compromised pregnancy outcomes including preterm birth, delivery of low-birth-weight babies, and development of pre-eclampsia.²

In fact, women with periodontitis have double the risk of pre-term birth.³ Complications of pre-term birth may include developmental delays, growth reduction, and hearing impairment.⁴ But why does periodontitis cause this to happen?

The gram-negative bacteria in the gingival biofilm leads to inflammatory markers in the bloodstream. These inflammatory markers cause an immune inflammatory response in the fetal-placental unit as well as suppression of local growth factors. This response can generate uterine contractions that may result in pre-term labor and/or babies with low birth weight.^3,5

Oral Health Issues During Pregnancy

During pregnancy, the placenta produces higher levels of estrogen and progesterone. These hormonal changes may lead to increased gingivitis, gingival sensitivity to irritants, and pyogenic granulomas. This is partially due to progesterone increasing the vascular permeability.⁶

Pregnant and/or postpartum women also may neglect their own oral care to focus on the health and well-being of their baby.⁶ This leads to toxic plaque remaining on the teeth and gums long term. Not surprisingly, approximately 60% to 75% of pregnant women have gingivitis.¹

In addition, the vomiting that may occur during pregnancy causes an acidic environment in the oral cavity. The acidity may lead to erosion and decay of the tooth structure.

Lastly, many women are hesitant to visit the dentist during pregnancy. This may be because there is a lack of perceived need, or they may mistakenly believe it is unsafe to visit the dentist during pregnancy.¹

However, research supports that professional dental care during pregnancy is integral to improving oral health.⁶ Additionally, when appropriate pregnancy guidelines are followed, dental care is safe during pregnancy.¹ If possible, a full oral examination is recommended prior to pregnancy to achieve optimum oral health and encourage proper oral care habits at home.⁶

Patient Communication

Dental professionals must effectively communicate the risks of pre-existing disease, such as periodontitis, to their patients who are pregnant or wish to become pregnant. Recommended conversation starters may include:

• The bacteria in your mouth impacts the rest of your body and can actually lead to pre-term labor. Let’s work together to treat your periodontal disease so you can have a healthier pregnancy and baby.
• I know you are planning to have children soon. Did you know that the bacteria that causes your periodontal disease can negatively impact your pregnancy? With proper treatment and home care, we can work together to manage your periodontal disease

For pregnancy gingivitis, dental professionals may say something like:

• During pregnancy, your hormones may cause your gums to be more susceptible to swelling and irritation. It’s really important that you keep plaque under control. Try by brushing with an oscillating-rotating toothbrush such as the Oral-B iO and an antimicrobial paste like Crest Gum Detoxify.

The patient and dental professional must work together to stop this cycle before it begins with diligent daily oral hygiene: brushing and interdental cleaning, getting regular oral health checkups, and properly treating periodontal disease early. Oral hygiene in pregnant women can be improved by amplifying their oral care routine at home with the proper oral care products.

The primary factor for gingivitis in pregnant women, toxic plaque, can likely be ameliorated by improved hygiene including the use of antimicrobial pastes such as Crest Gum Detoxify, antimicrobial rinse like Crest Pro-Health Multi-Protection Clean Mint, and optimal mechanical plaque control via an electric rechargeable toothbrush with a round head, like the Oral-B iO.

Moreover, pastes that include stannous fluoride such as Crest Gum Detoxify can prevent the erosion that may be caused by the acidic oral environment during pregnancy. Helping your patients to take good care of their mouth, teeth, and gums during pregnancy can help them to have a healthy pregnancy and a healthy baby.

References

1. Hartnett E, Haber J, Krainovich-Miller B, Bella A, Vasilyeva A, Lange Kessler J. Oral Health in Pregnancy. J Obstet Gynecol Neonatal Nurs. 2016 Jul-Aug;45(4):565-73. doi: 10.1016/j.jogn.2016.04.005. Epub 2016 Jun 6. PMID: 27281467.
2. Daalderop LD,Wieland BV, Tomsin K, Reyes L, Kramer BW, Vanterpool SF. Periodontal disease and pregnancy outcomes: Overview of systematic reviews. JDR Clinical & Translational Research 3:10-27.
3. Manrique-Corredor EJ, Orozco-Beltran D, Lopez-Pineda A, Quesada JA, Gil-Guillen VF, Carratala-Munuera C. Maternal periodontitis and preterm birth: Systematic review and meta-analysis. Community Dent Oral Epidemiol 2019; 47:243-251.
4. Ward RM, Beachy JC. Neonatal complications following preterm birth. BJOG. 2003 Apr;110 Suppl 20:8-16. doi: 10.1016/s1470-0328(03)00012-0. PMID: 12763105.
5. Puertas A, Magan-Fernandez A, Blanc V, Revelles L, O’Valle F, Pozo E, León R, Mesa F. Association of periodontitis with preterm birth and low birth weight: a comprehensive review. J Matern Fetal Neonatal Med. 2018 Mar;31(5):597-602. doi: 10.1080/14767058.2017.1293023. Epub 2017 Feb 28. PMID: 28282773.
6. Yenen Z, Ataçağ T. Oral care in pregnancy. J Turk Ger Gynecol Assoc. 2019;20(4):264-268. doi:10.4274/jtgga.galenos.2018.2018.0139

Ms. Jordan is a graduate of Westbrook College, UNE, dental hygiene, where she worked as adjunct clinical faculty for nearly 10 years and now serves on the advisory committee. She holds a master’s degree in organizational leadership and worked in private practice until 2001, when she became an employee of Procter & Gamble (Crest + Oral-B). She has held several positions for the company and currently holds the role of global professional & scientific relations. She has contributed to the Darby Walsh dental hygiene textbooks and has lectured locally to dental professionals, as well as students and faculty. She can be reached at jordan.ba.1@pg.com.

Dr. Gans graduated from the Ohio State University’s College of Dentistry in 2013 and completed a general practice residency at Saint Vincent Charity Hospital. She practiced dentistry in her hometown of Cleveland, Ohio, prior to joining Procter & Gamble in 2018. She is currently a P&G Professional and Scientific Relations Manager for Crest + Oral-B. Her goal is to teach dental professionals about the recent advances in paste and power brush technology to help improve oral health. In her free time, she enjoys spending time with her friends and family. She has five siblings including an identical twin who is also a dentist.

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Fungi and bacteria can activate genes associated with head and neck tumors, according to an in vitro study at São Paulo State University (UNESP) in Araraquara, Brazil. The metabolism of biofilms stimulates tumor cells by favoring the cell signaling pathways required for tumor development and resistance to treatment, the UNESP researchers said.

These findings include entirely novel information about the links between microbial biofilms and cell behavior in head and neck cancer, said the researchers, who discovered that metabolites secreted by biofilms known as the secretome can modulate the expression of proto-oncogenes and cell cycle genes associated with tumor cell growth and survival.

The researchers’ analysis of gene expression focused on two signaling pathways, EGFR/RAS/RAF/MEK/ERK and EGFR/PI3K/AKT/mTOR, that play a key role in tumor cell proliferation, differentiation, and survival. Alterations to gene expression in these pathways are highly prevalent in various types of tumors.

The researchers analyzed head and neck and oral cavity squamous carcinoma cells. Squamous cell carcinoma is the most common type of mouth cancer, which produces functional and aesthetic changes that degrade the patient’s quality of life, the researchers said.

The cells were challenged via stimulation by metabolites from biofilms of Candida albicans fungi and Staphylococcus aureus bacteria. These microorganisms are very frequent in denture users, the researchers said, as prior research has found both in 30% to 40% of subjects examined.

Oral microbiota play an important role in cancer development, the researchers said. Genetic markets associated with the presence of microorganisms have been identified for some types, such as stomach cancer, but there is no consensus regarding the most prevalent genes linked to head and neck cancer. Also, no molecular markers had been found yet for this disease, especially HPV-negative cancer, which has a worse prognosis.

Metabolites from C albicans and S aureus biofilms can endanger the homeostasis of normal and neoplastic oral epithelial cells, altering the expression of important genes such as CDKN1A, Bcl-2, PI3K, BRAF, hRAS, and mTOR, the researchers said, impairing cell viability and survival and disrupting the cell cycle profile.

Understanding the cell cycle is important because cancer entails unchecked cell division and growth, the researchers said, with tumor cells potentially invading tissues and organs throughout the body. Failure of the inhibitors of this cycle and excessive signaling by cell division regulators can lead to tumor progression.

The oral microbiome is a diversified community of microorganisms with as many as 700 species of viruses, protozoans, bacteria, and fungi, the researchers said. When biofilms develop, they produce metabolites that alter the immune response and can lead to chronic inflammation and even production of cancerous substances.

According to study co-leader professor Paula Aboud Barbugli, the findings show that “molecules secreted by these microorganisms in biofilms may modulate host cell activities even far away from the primary infection site.”

For principal investigator professor Carlos Eduardo Vergani, the results serve as a warning about the treatment of cancer patients who have dentures.

“Control of biofilms, including denture and oral cavity hygiene, is extremely important to minimize inflammatory processes, as shown by our prior research and the study just published, which points to interference with the expression of genes associated with tumor progression,” Vergani said.

A 2017 study by Vergani showed that soluble factors in methicillin-sensitive C albicans and S aureus biofilm promoted cell death and inflammatory responses. Also, according to Brazil’s National Cancer Institute, about 22,800 new cases of laryngeal and oral cavity cancer are reported each year, mostly in male patients.

The COVID-19 pandemic forced the group to interrupt the clinical trial they had planned to conduct on the basis of their research. Barbugli said a PhD project supervised by another member of the group will investigate the prevalence of C albicans and S auereus biofilms in the dentures and oral cavities of head and neck cancer patients to understand how they influence prognosis in these cases.

The results obtained so far pave the way for future metabolomics and proteomics research into oral biofilms, Vergani said.

The study, “Proto-Oncogenes and Cell Cycle Gene Expression in Normal and Neoplastic Oral Epithelial Cells Stimulated with Soluble Factors from Single and Dual Biofilms of Candida Albicans and Staphylococcus Aureus,” was published by Frontiers in Cellular and Infection Microbiology.

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The Forsyth Institute has entered into a strategic collaboration with Sherlock Biosciences, an engineering biology company dedicated to making diagnostic testing better, faster, and more affordable, according to the organizations. The partnership will focus on research, development, and commercialization of products and services for the detection of human biomarkers in the oral cavity and other oral health applications.

The oral cavity provides unique insights into overall health, Forsyth said. For example, microbial communities in the mouth are linked to a variety of systemic diseases such as cardiovascular disease, Alzheimer’s disease, and diabetes.

Saliva includes virtually all of the same medical information as blood, including peptides, proteins, DNA, and RNA, but it is much easier to collect as a biological sample, Forsyth said. Forsyth and Sherlock Biosciences said they see the oral cavity as a clinically valuable yet largely unexplored frontier that has the potential to revolutionize human health.

“As the world’s leading research organization in oral health, Forsyth brings a wealth of expertise that can rapidly advance applications of Sherlock’s technology to improve both oral health as well as diagnostic testing that relies on oral sampling,” said Rahul Dhanda, cofounder, chief executive officer, president, and director of Sherlock Biosciences.

“Forsyth’s leadership is built on its long and successful history of discovery in the oral health space, and we are thrilled to partner around our leading diagnostics solutions to enable the institute to deliver the next generation of oral health-focused technologies,” Dhanda said.

Forsyth said that its scientists have been exploring the oral cavity for decades. Since its founding in 1910, it said, it has contributed some of the most fundamental advances in oral health.

From the discovery of fluoride for tooth protection and the microbial pathogens that cause dental decay and gum disease, to creating the widely used Human Oral Microbiome Database and characterizing more than 700 microbial species that colonize the human oral cavity, Forsyth said, it continues to shed new light on oral and overall health.

“The mouth is the gateway to the rest of the body and in many ways holds the keys to better health outcomes,” said Dr. Wenyuan Shi, chief executive officer and chief scientific officer at Forsyth. “Forsyth’s expertise in this field, combined with Sherlock’s impressive technological capabilities and culture of creative ingenuity, will create a powerful force in oral health innovation.”

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The combination of a carb-heavy diet and poor oral hygiene can leave children with early childhood caries (ECC), a severe form of dental decay that can have a lasting impact on their oral and overall health.

A few years ago, researchers from Penn Dental Medicine found that the dental plaque that gives rise to ECC is composed of both a bacterial species, Streptococcus mutans, and a fungus, Candida albicans. The two form a sticky symbiosis, known as a biofilm, that becomes extremely virulent and difficult to displace from the tooth surface.

Now, the researchers offer a strategy for disrupting this biofilm by targeting the yeast-bacterial interactions that make ECC plaques so intractable. In contrast to some current treatments for ECC, which use antimicrobial agents that can have off-target effects, potentially harming healthy tissues, this treatment uses an enzyme specific to the bonds that exist between microbes.

“We thought this could be a new way of approaching the problem of ECCs that would intervene in the synergistic interaction between bacteria and yeast,” said Geelsu Hwang, an assistant professor and senior author of the study. “This offers us another tool for disrupting this virulent biofilm.”

The work builds on the findings of a 2017 study by Hwang and colleagues including Hyun (Michel) Koo that found that molecules called mannans on the Candida cell wall bound tightly to an enzyme secreted by S mutans, glycosyltransferases (Gftb). In addition to facilitating the cross-kingdom binding, Gftb contributes to the stubbornness of dental biofilms by manufacturing gluelike polymers called glucans in the presence of sugars.

Some cases of ECC are treated with drugs that kill the microbes directly, potentially reducing the number of pathogens in the mouth. But this doesn’t always effectively break down the biofilm and can have off-target effects on “good” microbes as well as the soft tissues in the oral cavity, the researchers said.

The researchers said they wanted to try a different approach that would directly target the insidious interaction between yeast and bacteria and opted to target the mannans in the Candida cell surface as a point of contact.

Using three different mannan-degrading enzymes, they applied each to a biofilm growing on a tooth-like surface in a human saliva medium and left it for five minutes. Following the treatment, they noted that the overall biofilm volume was reduced.

Using powerful microscopy, the researchers said they also observed drastic reductions in the biofilm thickness and interactions between bacteria and yeast. The pH of the surrounding medium was higher when exposed to the enzymes, indicating an environment that is not as acidic and thus less conducive to tooth decay.

The researchers also measured how easy it was to break up the biofilm after treatment using a device that applies a stress, akin to tooth brushing.

“The biofilm structure was more fragile after the enzyme treatment,” Hwang said. “We were able to see that the biofilms were more easily removed.”

To confirm the mechanism of their approach—that the mannan-degrading enzymes were weakening the binding between yeast and bacteria—the team used atomic-force microscopy to measure the bond between Candida and Gftb. The therapy, the researchers found, reduced this binding by a factor of 15.

Finally, the researchers wanted to get a sense of how well-tolerated these enzymes would be when used in the oral cavity, especially since children would be the patient group targeted.

Applying the enzymes to human gingival cells in culture, the researchers found no harmful impact, even when they used a concentrated form of the enzymes. They also observed that the treatment didn’t kill the bacteria of yeast, which is a sign that it could work even if the microbes developed mutations that would lend them resistance against other types of therapies.

The researchers kept the application time relatively short at five minutes, though they hope to see activity in an even shorter time, like the two minutes recommended for tooth brushing. Hwang said they may consider a non-alcohol-based mouthwash with these enzymes added that could be used by children as a preventive measure against ECC.

The researchers hope to continue pursuing this possibility with additional research, including testing these enzymes in an animal model. With more successes, they aim to add another tool for fighting the public health threat of ECC.

The study, “Intervening in Symbiotic Cross-Kingdom Biofilm Interactions: A Binding Mechanism-Based Nonmicrobicidal Approach,” was published by mBio.

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Sonendo is celebrating National Root Canal Appreciation Day on May 12 as part of the American Association of Endodontists’ Save Your Tooth Month campaign. According to the company, modern endodontics offers advances in treatment like its GentleWave Procedure that are instrumental in saving natural teeth.

“Endodontists are often the unsung heroes in dentistry, as not everyone understands their role or the significance in preserving natural teeth whenever possible,” said Bjarne Bergheim, president and CEO of Sonendo.

“We are proud to have completed over 600,000 GentleWave Procedures, ie, over 600,000 patients whose pain and infection was resolved, and natural teeth saved by endodontists. We want to express our gratitude and celebrate endodontists for the vital services they provide,” said Bergheim.

Hoping to change the negative perceptions that many people have about root canal treatment, endodontist Sonia Chopra of Charlotte, North Carolina, is observing National Root Canal Appreciation Day by highlighting the challenging cases she has been able to resolve for her patients.

The GentleWave System uses patented technology to deliver more thorough cleaning and disinfection to the entire root canal system, according to Sonendo, even in the microscopic places where bacteria can hide, and leaves more of the tooth structure intact.

Most GentleWave Procedures can be performed in one visit, the company continued, and patients generally find them to be comfortable and report minimal to no pain afterward. Also, the system releases virtually no aerosolized material into the air during normal use, potentially reducing the spread of airborne infection, Sonendo said.

Procedure instruments for the GentleWave System also come pre-sterilized and single-use, minimizing the risk of exposure from one patient to the next, the company added.

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