Atomic imaging finds root of tooth decay

A collaboration between researchers from Cornell University, Northwestern University and University of Virginia combined complementary imaging techniques to explore the atomic structure of human enamel, exposing tiny chemical flaws in the fundamental building blocks of our teeth. The findings could help scientists prevent or possibly reverse tooth decay.

The team's paper, "Chemical Gradients in Human Enamel Crystallites," published July 1 in Nature. Cornell's contribution was led by Lena Kourkoutis, associate professor in applied and engineering physics. Derk Joester, professor of materials science and engineering at Northwestern, directed the research.

The paper's co-lead authors are Northwestern doctoral student Karen DeRocher and postdoctoral researcher Paul Smeets.

Thanks to its high mineral count, tooth enamel is a sturdy substance that can withstand the rigors of chewing, although excessive acid in the mouth can make it vulnerable to decay. While scientists have previously peeked into the crystallites that compose enamel, nanoscale images of its structure and chemical composition have been harder to come by. In one method, scanning transmission electron microscopy, or STEM, a beam of electrons is shot through a sample. But that process has its limits.

"Enamel is mechanically a very, very strong material, but when you put it in the electron microscope, it's very sensitive to the electron beam," Kourkoutis said. "So compared to the crystalline materials that you find in electronics, for example, you can only put a fraction of the number of electrons into an enamel crystal. Normally, pushing down to the atomic scale means you have to put more electrons into the material. But if it damages the material before you get the information out, then you're lost."

In recent years, Joester's Northwestern group has imaged sensitive biological materials with atom probe tomography, a process that essentially strips atoms off a sample's surface one at a time and reconstructs the structure of the material.

At the same time, Cornell researchers at PARADIM (Platform for the Accelerated Realization, Analysis and Discovery of Interface Materials), a National Science Foundation-supported user facility, have advanced a form of low-temperature electron microscopy that can image the atomic structure of radiation-sensitive samples. The technique can also safely map a sample's chemical composition by measuring how much energy is lost when the electrons interact with the atoms.

"When you operate at low temperature, the material becomes more robust against electron beam damage," said Kourkoutis, who directs PARADIM's electron microscopy facility. "We are now working at the intersection between the developments in the physical sciences which have pushed electron microscopy to the atomic scale and the developments in the life sciences in the cryogenic field."

The two university groups linked up after Smeets, a member of Joester's group, attended PARADIM's summer school on electron microscopy in 2017. There, he learned how PARADIM's cryogenic electron microscopy capabilities could complement Northwestern's human enamel project.

Smeets worked with Kourkoutis' doctoral students Berit Goodge and Michael Zachman, Ph.D. '18, co-authors of the new paper. The group performed cryogenic electron microscopy on enamel samples that were cooled with liquid nitrogen to around 90 kelvins, or minus 298 degrees Fahrenheit.

By combining their complementary techniques, the Cornell and Northwestern researchers were able to image an enamel crystallite and its hydroxylapatite atomic lattice. But all was not crystal clear: The lattice contained dark distortions -- caused by two nanometric layers with magnesium, as well as sodium, fluoride and carbonate ion impurities near the core of the crystal.

Additional modeling confirmed the irregularities are a source of strain in the crystallite. Paradoxically, these irregularities and the enamel's core-shell architecture may also play a role in reinforcing the enamel, making it more resilient.

The researchers say the findings could lead to new treatments for strengthening enamel and combating cavities.

"On the foundation of what we discovered, I believe that atom probe tomography and correlative electron microscopy will also have tremendous impact on our understanding of how enamel forms, and how diseases like molar incisor hypomineralization disrupt this process," Joester said.

And mouths aren't the only beneficiaries of cryogenic electron microscopy. Kourkoutis is also using the process to probe the chemistry in energy systems, such as batteries and fuel cells that contain a mix of soft electrolytes and hard electrode materials.

The research was supported by the National Institutes of Health's National Institute of Dental and Craniofacial Research, the National Science Foundation and the University of Virginia.

Archaeologists use tooth enamel protein to show sex of human remains

A new method for estimating the biological sex of human remains based on reading protein sequences rather than DNA has been used to study an archaeological site in Northern California. The protein-based technique gave superior results to DNA analysis in studying 55 sets of human remains between 300 and 2,300 years old. The work is published July 17 in Scientific Reports.

The method targets amelogenin, a protein found in tooth enamel, said first author Tammy Buonasera, postdoctoral researcher working with Glendon Parker, adjunct associate professor in the Department of Environmental Toxicology at the University of California, Davis. The technique was developed in Parker's laboratory.

Buonasera, Parker, Jelmer Eerkens, professor of anthropology, and colleagues compared three methods for sex determination: the new proteomic method; DNA analysis; and osteology, or analysis of the size, shape and composition of the bones themselves. They applied these methods to remains from two ancestral Ohlone villages near Sunol, California. The site is being excavated by the Far West Anthropological Research Group of Davis in collaboration with the Muwekma Ohlone tribe.

Amelogenin is a protein found in tooth enamel, the hardest and most durable substance in the human body. The gene for amelogenin happens to be located on both the X and Y sex chromosomes, and the amelogenin-Y protein is slightly different from amelogenin-X.

The method works by retrieving a tiny amount of protein from a tooth. All proteins are made up of a chain of amino acids, so the protein is analyzed to give the amino acid sequence, which then defines the protein. Each of the 20 naturally occurring amino acids is specified by a three-letter code in DNA, so it is possible to work backward from the amino acid sequence and figure out the likely DNA code.

Superior to existing methods

The researchers were able to determine the sex of all of the remains using the new protein method and all but five using DNA methods. Results from osteology and proteomics agreed in almost all cases, although examining bones themselves was only effective for about half the skeletons.

The protein method allowed them to estimate sex for children, which is not possible from osteology. It was reliable even when the signal from DNA was weak.

"This is a more sensitive technique for older skeletons where we would expect more DNA degradation," Parker said.

Being able to determine the biological sex of human remains provides a greater window into the persona of each individual. Anthropologists are interested in determining biological sex because sex interacts with health and can have a large impact on how people form an identity and are treated within a society, Eerkens said.

"Almost every human society around the world incorporates sex and gender as a way to classify people, and these can affect your status and who you associate with in society," Eerkens said. While gender and biological sex are not the same thing, they are linked, so the ability to estimate sex gives archaeologists important insight when attempting to understand the cultural aspects of gender, which are not as readily preserved.

For example, in a society based on small villages, people often have to find mates outside their village. Depending on cultural rules, either men or women will leave the village to marry.

Gum disease may raise risk of some cancers

People with history of gum disease appear to have higher risk of developing oesophageal and gastric cancer, suggest researchers

BMJ

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People who have periodontal (gum) disease may have a higher risk of developing some forms of cancer, suggests a letter published in the journal Gut detailing a prospective study.

US researchers found that a history of periodontal disease appeared to be associated with a raised risk of oesophageal (gullet) cancer and gastric (stomach) cancer and this risk was also higher among people who had lost teeth previously.

Previous findings on the relationship of periodontal disease and tooth loss with oesophageal and gastric cancer have been inconsistent.

Therefore, a team of researchers from Harvard T.H. Chan School of Public Health, in Boston, USA, carried out a study of data on patients over decades of follow up.

They examined the association of history of periodontal disease and tooth loss with the risk of oesophageal and gastric cancer in 98,459 women from the Nurses' Health Study (1992-2014) and 49,685 men from the Health Professionals Follow-up Study (1988-2016).

Dental measures, demographics, lifestyle, and diet were assessed using follow-up questionnaires and self-reported cancer diagnosis was confirmed after reviewing medical records.

The results showed that during 22-28 years of follow-up, there were 199 cases of oesophageal cancer and 238 cases of gastric cancer.

A history of periodontal disease was associated with a 43% and 52% increased risk of oesophageal cancer and gastric cancer, respectively.

Compared to people with no tooth loss, the risks of oesophageal and gastric cancer for those who lost two or more teeth were also modestly higher - 42% and 33%, respectively.

In addition, among individuals with a history of periodontal disease, no tooth loss and losing one or more teeth were equally associated with a 59% increased risk of oesophageal cancer compared to those with no history of periodontal disease and no tooth loss.

Similarly, the same group of individuals had 50% and 68% greater risk of gastric cancer, respectively.

The authors point to possible reasons for an association between oral bacteria (oral microbiota) and oesophageal and gastric cancer, with evidence from other studies suggesting that tannerella forsythia and porphyromonas gingivalis - members of the 'red complex' of periodontal pathogens - were associated with the presence or risk of oesophageal cancer.

Another possible reason is that poor oral hygiene and periodontal disease could promote the formation of endogenous nitrosamines known to cause gastric cancer through nitrate-reducing bacteria.

This was an observational study, so no firm conclusions can be drawn about cause and effect, and the researchers cannot rule out the possibility that some of the observed risk may be due to other unmeasured (confounding) factors.

However, they conclude: "Together, these data support the importance of oral microbiome in oesophageal and gastric cancer. Further prospective studies that directly assess oral microbiome are warranted to identify specific oral bacteria responsible for this relationship. The additional findings may serve as readily accessible, non-invasive biomarkers and help identify individuals at high risk for these cancers."

Materials scientists drill down to vulnerabilities involved in human tooth decay

Enamel formation study could lead to new interventions to prevent and treat disease and defects

NORTHWESTERN UNIVERSITY

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Volume 90%

 

VIDEO: A ROTATING VIEW OF THE "WORLD'S TINIEST SANDWICH. " MAGNESIUM IONS (MAGENTA) FORM TWO LAYERS ON EITHER SIDE OF THE ENAMEL CRYSTALLITE'S CORE, JUST 6 BILLIONTHS OF A METER ACROSS. SODIUM... view more 

CREDIT: NORTHWESTERN UNIVERSITY

Northwestern University researchers have cracked one of the secrets of tooth decay. In a new study of human enamel, the materials scientists are the first to identify a small number of impurity atoms that may contribute to the enamel's strength but also make the material more soluble. They also are the first to determine the spatial distribution of the impurities with atomic-scale resolution.

Dental caries -- better known as tooth decay -- is the breakdown of teeth due to bacteria. ("Caries" is Latin for "rottenness.") It is one of the most common chronic diseases and a major public health problem, especially as the average life expectancy of humans increases.

The Northwestern discovery in the building blocks of enamel -- with detail down to the nanoscale -- could lead to a better understanding of human tooth decay as well as genetic conditions that affect enamel formation, which can lead to highly compromised or completely absent enamel.

Enamel, the human tooth's protective outer layer, covers the entire crown. Its hardness comes from its high mineral content.

"Enamel has evolved to be hard and wear-resistant enough to withstand the forces associated with chewing for decades," said Derk Joester, who led the research. "However, enamel has very limited potential to regenerate. Our fundamental research helps us understand how enamel may form, which should aid in the development of new interventions and materials to prevent and treat caries. The knowledge also might help prevent or ameliorate the suffering of patients with congenital enamel defects."

The study will be published on July 1 by the journal Nature.

Joester, the corresponding author, is an associate professor of materials science and engineering in the McCormick School of Engineering. Karen A. DeRocher and Paul J.M. Smeets, a Ph.D. student and a postdoctoral fellow, respectively, in Joester's lab, are co-first authors.

One major obstacle hindering enamel research is its complex structure, with features across multiple length scales. Enamel, which can reach a thickness of several millimeters, is a three-dimensional weave of rods. Each rod, approximately 5 microns wide, is made up of thousands of individual hydroxylapatite crystallites that are very long and thin. The width of a crystallite is on the order of tens of nanometers. These nanoscale crystallites are the fundamental building blocks of enamel.

Perhaps unique to human enamel, the center of the crystallite seems to be more soluble, Joester said, and his team wanted to understand why. The researchers set out to test if the composition of minor enamel constitutents varies in single crystallites.

Using cutting-edge quantitative atomic-scale techniques, the team discovered that human enamel crystallites have a core-shell structure. Each crystallite has a continuous crystal structure with calcium, phosphate and hydroxyl ions arranged periodically (the shell). However, at the crystallite's center, a greater number of these ions is replaced with magnesium, sodium, carbonate and fluoride (the core). Within the core, two magnesium-rich layers flank a mix of sodium, fluoride and carbonate ions.

"Surprisingly, the magnesium ions form two layers on either side of the core, like the world's tiniest sandwich, just 6 billionths of a meter across," DeRocher said.

Detecting and visualizing the sandwich structure required scanning transmission electron microscopy at cryogenic temperatures (cryo-STEM) and atom probe tomography (APT). Cryo-STEM analysis revealed the regular arrangement of atoms in the crystals. APT allowed the researchers to determine the chemical nature and position of small numbers of impurity atoms with sub-nanometer resolution.

The researchers found strong evidence that the core-shell architecture and resulting residual stresses impact the dissolution behavior of human enamel crystallites while also providing a plausible avenue for extrinsic toughening of enamel.

"The ability to visualize chemical gradients down to the nanoscale enhances our understanding of how enamel may form and could lead to new methods to improve the health of enamel," Smeets said.

This study builds on an earlier work, published in 2015, in which the researchers discovered that crystallites are glued together by an extremely thin amorphous film that differs in composition from the crystallites.

Simple oral health steps help improve elite athletes' performance

Elite athletes who adopted simple oral health measures, such as using high fluoride toothpaste and cleaning between their teeth, reported significantly reduced negative effects on performance related to poor oral health, finds a study led by UCL.

The new research, published in BMJ Open Sport & Exercise Medicine, is the latest in a series of studies* led by the UCL Centre for Oral Health and Performance (COHP), based at UCL Eastman Dental Institute, which have found that elite athletes have substantial rates of oral disease**, including tooth decay and gum inflammation, and these symptoms negatively affected their wellbeing and sporting performance.

To help address this, researchers at UCL COHP designed a behavioural change programme aimed at better educating elite athletes about oral health and providing some simple interventions to improve their daily oral health routines.

Explaining the study, lead author, Dr Julie Gallagher (UCL Eastman Dental Institute), said: "Poor oral health of elite athletes is common and is associated with negative performance. However, compared with other health and training pressures, oral health care is not a high priority in elite sport.

"We therefore wanted to develop a programme which was aligned with the existing high-performance culture of the athletes and their teams. Underpinning the study was health behaviour psychology, which included education, self-motivation, goal setting, and an easy to use toolkit, ensuring the athletes had a readily available opportunity to improve."

In total, 62 athletes from two Great Britain Olympic Teams, rowing and cycling, and one Premiership Rugby Club, Gloucester Rugby, were recruited to the study.

Athletes and support teams were asked to watch a 10-minute presentation which focussed on building motivation to improve oral health, and three 90-second information films, featuring GB rower Zak Lee-Green, which focussed on increasing oral health knowledge and skills to perform optimum oral health behaviour.

In addition, each athlete received an oral health screening to check for diseases such as caries (tooth decay) and gingivitis (gum inflammation). They were then given a bespoke follow up report with tailored advice and an oral health toolkit, containing a manual toothbrush, prescription fluoride toothpaste and flosspicks. As a minimum, they were also asked to brush their teeth for two minutes twice a day, to include brushing before training in the morning and before bed in the evening.

In total 89% of athletes completed the four-month study. On completion athletes were asked to fill in an oral health knowledge questionnaire, undergo a follow-up gingival (oral disease) assessment and evaluate the oral health kit.

Results

The study found that the behaviour change model was associated both with reductions in self-reported negative performance impacts and in improvements in oral health behaviours.

Athlete use of prescription strength fluoride toothpaste increased from 8 (12.9%) to 45 (80.4%), use of interdental cleaning aids at least two to three times per week increased from 10 (16.2%) to 21 (34%). Bleeding (gums) score remained unchanged. A desire to avoid inflammation in the body resulting from poor oral health was cited by 93% of athletes as the key motivator to make changes to their oral health routine. ]

Improvements in sporting performance were measured using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire (OSTRC-O), developed to monitor illness and injury in elite athletes. UCL COHP adapted the questionnaire to focus on oral health, asking the extent to which the oral health problem affected 1) sports participation, 2) training volume; 3) sporting performance; and 4) the extent to which the individual has experienced oral pain.

As a result of the behavioural change programme the mean OSTRC score across athletes reduced from 8.73 (out of 100) to 2.73, which while low at the outset, does indicate a statistically significant reduction in problems associated with oral health and sporting performance.

In addition the number (proportion) of athletes who reported a 0 (zero) score, meaning they had no negative sporting impact from oral health conditions, increased from 32 (51.6%) at baseline to 54 (98.2%) at the end of the study

Dr Gallagher added: "Through our previous research and focus group sessions, we established that athletes' motivations for taking part in the study were both appearance and athletic performance, with many keen to avoid gum inflammation affecting other parts of their bodies, which can happen in serious cases.

"We believe that bringing behaviour change science together with an understanding of the athletes' and teams' priorities is key to making changes stick." There are a number of reasons athletes are more likely to have poor oral health: physical activity causes a dry mouth, which in the long-term increases risk of tooth decay and gum diseases, along with frequent sugar intakes from normal diet and energy supplements.

Co-author and UCL Centre for Oral Health and Performance lead, Professor Ian Needleman, said: "To compete at the top level elite athletes need to make the most of marginal gains and maintaining good oral health has been proven to have real performance benefits.

"With so many other competing interests, such as training, nutrition, sleep and mental health, it is remarkable to see such great rates of adherence to the new routines in a high-performance environment."

Zak Lee-Green, a member of the GB Rowing Team and a dentist who took part in the study, said: "As athletes we are acutely aware of the marginal gains required to achieve peak performance and maintaining good oral health is a prime example of an area often overlooked.

"This programme has gone a step further than showing the positive effect of excellent oral health on everyday life and has shown the potential benefits for improved performance, helping us reach the highest levels of sport. It can only be a step in the right direction if the sporting role models of the present and future are managing their oral health in the same way that they do their elite training."

Dr Nigel Jones, Head of Medical Services at British Cycling, said: "The topic of oral health amongst athletes is an important one, especially as it can be linked to performance. My role with the Great Britain Cycling Team is to ensure the holistic well-being of our cyclists, and as oral health can have a big impact on immune function as well as being important in its own right, I wanted to support this project. The learnings which the riders took from the study have been invaluable and will be deployed across the whole team as we ramp up our preparations for the Tokyo Olympic and Paralympic Games next year."

This behavioural change study was based on the COM-B model, which identifies sources of behaviour that could provide opportunities for intervention.

Capability (C) that is, the person having the physical skills and knowledge to perform the behaviour, Opportunity (O), that is, access to the necessary materials and social environment such that the person feels able to undertake the new behaviour, while Motivation (M) refers to a person deciding to adopt the behaviour

Researchers believe the bespoke model they have developed could be used for other health promotion needs in elite sport.

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*Previous UCL studies

* Elite athletes have poor oral health despite brushing twice daily, published August 2019.

* High levels of oral disease among elite athletes affecting performance, published June 2018

* Better oral health for footballers is needed: https://www.ucl.ac.uk/eastman/news/2015/nov/new-research-better-oral-health-footballers-needed, published November 2015

* London 2012 athletes had 'bad teeth' https://www.ucl.ac.uk/news/headlines/2013/sep/london-2012-athletes-had-bad-teeth, published September 2013

** In 2018 researchers at UCL COHP found nearly half (49.1%) of the athletes had untreated tooth decay, 77% had gingivitis, an early indicator of gum disease, and 39% self-reported having bleeding gums while cleaning their teeth, a sign of gum inflammation. Only 1.1% of the participants had 'excellent' periodontal health. In addition, more than a third (32%) reported that these conditions had impacted negatively on their sporting performance, along with their ability to eat (34.6%), relax and sleep (15.1%) and smiling and self-confidence (17.2%).

A probiotic derived from Chinese pickles prevents cavities

Can a probiotic derived from Chinese pickles prevent cavities? That seems to be the case, according to a study by researchers at Ben-Gurion University of the Negev and Chengdu University in China.

Pickles are an integral part of the diet in the southwest of China. When fruits and vegetables are fermented, healthy bacteria break down the natural sugars. These bacteria, also known as probiotics, not only preserve foods but offer numerous benefits, including immune system regulation, stabilization of the intestinal microbiota, reducing cholesterol levels, and now inhibiting tooth decay.

According to the study published in Frontiers in Microbiology, a strain of Lactobacilli (L. plantarum K41) found in Sichuan pickles reduced S. mutans by 98.4%. Dental caries (cavities) are caused by Streptococcus mutans, (S. mutans) commonly found in the human oral cavity as plaque and is a significant contributor to tooth decay.

Prof. Ariel Kushmaro of the BGU Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and the Chinese research team evaluated 14 different types of Sichuan pickles from southwest China. They extracted 54 different strains of Lactobacilli and found that one, L. plantarum K41, significantly reduced the incidence and severity of cavities. K41 was also highly tolerant of acids and salts, an additional benefit as a probiotic for harsh oral conditions. It also could have potential commercial value when added to dairy products.

According to Doug Seserman, chief executive officer of American Associates, Ben-Gurion University of the Negev based in New York City, "the researchers currently have no plans to evaluate Jewish deli pickles."

Largest study to date of electronic dental records reviews understudied populations

Data is from solo and small practice dentists where most Americans receive dental care

REGENSTRIEF INSTITUTE

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IMAGE: THE LARGEST STUDY TO DATE OF ELECTRONIC DENTAL RECORDS (EDRS) DELVES INTO BOTH PREVIOUSLY INACCESSIBLE DATA AND DATA FROM UNDERSTUDIED POPULATIONS WITH THE ULTIMATE GOAL OF IMPROVING ORAL TREATMENT OUTCOMES.... view more 

CREDIT: REGENSTRIEF INSTITUTE

INDIANAPOLIS - The largest study to date of electronic dental records delves into both previously inaccessible data and data from understudied populations with the ultimate goal of improving oral treatment outcomes. The work presents a learning health system - a mechanism for dentists to learn from their own experience and the experiences of fellow practitioners.

Researchers led by Regenstrief Institute Research Scientist Thankam Thyvalikakath, DMD, PhD, associate professor and director of the Dental Informatics Core at Indiana University School of Dentistry, evaluated de-identified data from the electronic dental records (EDRs) of 217,887 patients of 99 solo or small dental practices across the United States. These EDRs contained more than 11 million observations, with observation periods as long as 37 years.

The study determined that it is feasible to mine and utilize enormous amounts of EDR data to learn which dental therapies work and which do not, empowering quality improvement by individual dentists. EDR data is sufficiently reliable for purposes beyond the clinical care of individual patients.

Learning from aggregating data across practices gives each dental practitioner the opportunity to acquire knowledge not only from his or her own patient data but also the opportunity to compare their practice with their peers. Information obtained during each patient's visit thus contributes to improved care for all, creating a true learning health system.

Now that the they have completed the proof of concept; the researchers will use the data to evaluate of the long-term effectiveness of two common dental procedures performed on permanent teeth -- root canal therapy and tooth-colored fillings in rear teeth. Data analysis for that portion of the study, which will determine how well and how long root canal treated teeth and back teeth filled with tooth-colored fillings continue to function, will help both dentists and the patients make evidence-based care decisions. Data analysis is currently nearing completion and the findings will be published in the future.

"Here in the real world of the dentist's office we are seeing patients with all kinds of real-world conditions - pain, underlying medical conditions, lack of adequate past oral health care -- so this large data set provides a unique insight into the treatments offered in the type of dental offices where most Americans receive care," said Dr. Thyvalikakath, the founding director of Regenstrief-IU School of Dentistry dental informatics program.

Information on demographics, reason for visit, medical and dental history, social history, tooth characteristics and treatment, as well as practice and practitioner characteristics was collected for each patient visit.

Dr. Thyvalikakath describes the work as groundbreaking in four areas:

1. Dentists were able to share their data for research in an anonymized process with their EDR vendors' help, because a typical solo dentist or even small practice does not have dedicated IT staff.
2. Data from two electronic dental record systems with varying formats and operating systems were combined. Interoperability has proved difficult with data from electronic medical record systems.
3. It is the largest study to evaluate data quality in a regular patient setting.
4. It looked at the oral health and treatment options of both insured and uninsured patients. Past studies have relied on insurance records and thus have provided no information on uninsured patients.

"Findings derived from patient data in real-world conditions is typically less difficult for clinicians to translate at the point of care than studies performed in large health systems which often represent a patient population that does not mirror the community dentists see in their practices," said Dr. Thyvalikakath. "We are presenting a mechanism for dentists, many of whom practice by themselves or with only one or two others, to learn from their own experience and from the experiences of their peers to assist in improving skills and facing problems."

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"Leveraging Electronic Dental Record Data for Clinical Research in the National Dental PBRN Practices" is published in the peer-reviewed journal, Applied Clinical Informatics