The oral microbiomes of 25 otherwise healthy participants who use e-cigarettes daily closely match those seen in patients with gum disease, a new study shows. The results suggest that e-cigarettes trigger a proinflammatory response, coating commensal bacteria in the mouth with a layer of slime that makes them unrecognizable to the body and prevents the sequential colonization of other bacteria that form a healthy community. Sukirth Ganesan and colleagues conclude that the glycerol/glycol vehicle in e-cigarettes appears to drive these changes.
E-cigarettes have grown wildly popular among Americans, with six percent of the country's population - including 2.5 million high schoolers - puffing on the products nine years after their introduction to the United States. But while these e-cigarettes contain potentially toxic substances, including volatile organic compounds and metals, much remains unknown their long-term effects on human health.
To gain insight into how e-cigarettes affect the oral microbiome, Ganesan et al. recruited 123 otherwise healthy individuals, including 25 smokers, 25 nonsmokers, 20 e-cigarette users, 25 former smokers currently using e-cigarettes, and 28 smokers who also use e-cigarettes. They created a catalog of bacterial genes in the microbial communities of e-cigarette users based on plaque samples collected from their teeth, finding that variations arose based on the duration of e-cigarette use, but were not tied to variations in the concentration of nicotine or the type of flavoring.
The researchers also observed that while both smoking and e-cigarette use cause inflammation, they do so through different molecular pathways.
"I am hoping this research will drive some level of policymaking about the harm we are seeing," said Purnima Kumar, a coauthor of the study, in an interview, challenging the popular perception that e-cigarettes provide a safer alternative to smoking. "If we can see changes in people who are otherwise healthy and have nothing wrong with them, then we should start seriously considering why would you put their lives and their wellbeing at risk."
Though non-opioid painkillers can be just as effective, patients having dental procedures just before weekends and holidays are more likely to fill prescriptions for opioids
IMAGE: KEY FINDINGS FROM A STUDY OF MORE THAN 2 MILLION AMERICANS WHO HAD DENTAL PROCEDURES IN THE PRE-COVID19 ERA view more
CREDIT: UNIVERSITY OF MICHIGAN/JADA
As dentists and their teams across America get back to their regular schedules after a sharp COVID-19-related reduction, a new study shows a key opportunity to reduce the use of opioid painkillers by their patients.
The analysis of four years' worth of datafrom two million patients show that those who had dental procedures on a Friday or a day before a holiday were much more likely to fill a prescription for an opioid than other patients.
Teens and young adults were the most likely to get opioids, which were likely prescribed in order to get them through the weekend or holiday break without needing to contact the dentist for pain care.
One in five of the patients, all between the ages of 13 and 64, filled a prescription for an opioid, even though non-opioid pain medications are equally effective at controlling pain and have lower risks.
Those who had pre-weekend or pre-holiday procedures were 27% more likely to pick up an opioid prescription. If they were teens or young adults, they were 43% more likely than older patients to do so.
The new findings, reported in the Journal of the American Dental Association by a team from the University of Michigan, build on prior work showing overprescribing of opioids by dentists with no increase in pain relief or patient satisfaction .
The rate of weekend and holiday opioid prescription-filling by young people is especially troubling because of previous work showing that those who get opioids after getting their wisdom teeth out are nearly three times as likely to keep refilling the prescription long after their mouths should have healed.
"Variation in opioid prescription fills may put some patients at increased risk," says Caitlin Priest, the U-M Medical School student who led the analysis as part of the Michigan Opioid Prescribing Engagement Network team. "Now that we understand that dental opioid prescription fills were increased on Fridays and before holidays, we can create and disseminate best practices to avoid unnecessary prescribing."
Just over half of the patients whose records were analyzed had their dental procedure on an emergency basis. But the rest were scheduled - one-fifth of them on Fridays and the days before holidays.
Half of the patients who filled an opioid prescription had had scheduled surgical tooth extractions, but the pre-weekend and pre-holiday increase was seen across all 11 dental procedures studied.
This suggests multiple opportunities to reduce unneeded opioid prescribing, says Romesh Nalliah, M.H.C.M., D.D.S., the associate dean for patient services at the U-M School of Dentistry and a member of the study team. He notes that patients may seek Friday and pre-holiday appointments for their scheduled procedures to avoid missing work as they recover.
"The significance of our study is that, with the help of big data, it begins to unpack potentially harmful opioid prescribing trends that were not previously understood," he says. "In the event that we have particular concerns about a given case or patient, we can more deliberately book surgeries when we are available to follow-up."
The senior author of the paper, Chad Brummett, M.D., co-directs Michigan OPEN, which has published evidence-based guidelines for opioid prescribing for acute pain caused by many types of procedures and operations. He is also director of pain research in the Department of Anesthesiology at Michigan Medicine, U-M's academic medical center.
The guidelines say that for dental extractions, non-steroidal anti-inflammatory medications and over-the-counter pain relievers should be sufficient for pain control.
Examining bacteria growing on toddlers' teeth, a team from the University of Pennsylvania and Georgia Tech found that the microbes' spatial organization is crucial to how they cause tooth decay
IMAGE: RESEARCHERS FROM THE UNIVERSITY OF PENNSYLVANIA FOUND THAT THE BACTERIA RESPONSIBLE FOR TOOTH DECAY "SHIELDS " ITSELF UNDER BLANKETS OF SUGARS AND OTHER BACTERIA IN A CROWN-LIKE ARRANGEMENT, HELPING IT EVADE... view more
CREDIT: DONGYEOP KIM
Studying bacteria in a petri dish or test tube has yielded insights into how they function and, in some cases, contribute to disease. But this approach leaves out crucial details about how bacteria act in the real world.
Taking a translational approach, researchers at the University of Pennsylvania School of Dental Medicine and the Georgia Institute of Technology imaged the bacteria that cause tooth decay in three dimensions in their natural environment, the sticky biofilm known as dental plaque formed on toddlers' teeth that were affected by cavities.
The work, published in the journal Proceedings of the National Academy of Sciences, found that Streptococcus mutans, a major bacterial species responsible for tooth decay, is encased in a protective multilayered community of other bacteria and polymers forming a unique spatial organization associated with the location of the disease onset.
"We started with these clinical samples, extracted teeth from children with severe tooth decay," says Hyun (Michel) Koo of Penn Dental Medicine, a co-senior author on the work. "The question that popped in our minds was, how these bacteria are organized and whether their specific architecture can tell us about the disease they cause?"
To address this question, the researchers, including lead author Dongyeop Kim of Penn Dental Medicine and co-senior author Marvin Whiteley of Georgia Tech, used a combination of super-resolution confocal and scanning electron microscopy with computational analysis to dissect the arrangement of S. mutans and other microbes of the intact biofilm on the teeth. These techniques allowed the team to examine the biofilm layer by layer, gaining a three-dimensional picture of the specific architectures.
This approach, of understanding the locations and patterns of bacteria, is one that Whiteley has pursued in other diseases.
"It's clear that identifying the constituents of the human microbiome is not enough to understand their impact on human health," Whiteley says. "We also have to know how they are spatially organized. This is largely under studied as obtaining intact samples that maintain spatial structure is difficult."
In the current work, the researchers discovered that S. mutans in dental plaque most often appeared in a particular fashion: arranged in a mound against the tooth's surface. But it wasn't alone. While S. mutans formed the inner core of the rotund architecture, other commensal bacteria, such as S. oralis, formed additional outer layers precisely arranged in a crownlike structure. Supporting and separating these layers was an extracellular scaffold made of sugars produced by S. mutans, effectively encasing and protecting the disease-causing bacteria.
"We found this highly ordered community with a dense accumulation of S. mutans in the middle surrounded by these 'halos' of different bacteria, and wondered how this could cause tooth decay," Koo says. "
To learn more about how structure impacted the function of the biofilm, the research team attempted to recreate the natural plaque formations on a toothlike surface in the lab using S. mutans, S. oralis, and a sugar solution. They successfully grew rotund-shaped architecture and then measured levels of acid and demineralization associated with them.
"What we discovered, and what was exciting for us, is that the rotund areas perfectly matched with the demineralized and high acid levels on the enamel surface," says Koo. "This mirrors what clinicians see when they find dental caries: punctuated areas of decalcification known as 'white spots.' The domelike structure could explain how cavities get their start."
In a final set of experiments, the team put the rotund community to the test, applying an antimicrobial treatment and observing how the bacteria fared. When the rotund structures were intact, the S. mutans in the inner core largely avoided dying from the antimicrobial treatment. Only breaking up the scaffolding material holding the outer layers together enabled the antimicrobial to penetrate and effectively kill the cavity-causing bacteria.
The study's findings may help researcher more effectively target the pathogenic core of dental biofilms but also have implications for other fields.
"It demonstrates that the spatial structure of the microbiome may mediate function and the disease outcome, which could be applicable to other medical fields dealing with polymicrobial infections," says Koo.
"It's not just which pathogens are there but how they're structured that tells you about the disease that they cause," adds Whiteley. "Bacteria are highly social creatures and have friends and enemies that dictate their behaviors."
The field of microbial biogeography is young, the researchers say, but extending this demonstration that links community structure with disease onset opens up a vast array of possibilities for future medically relevant insights.
May 11, 2020, Alexandria, Va., USA--The Journal of Dental Research published today the results of a study that demonstrated that community water fluoridation is not associated with increased risk of osteosarcoma.
More than sixty percent of the U.S. population have access to community water fluoridation, considered to be one of the most important public health policies of the twentieth century due to its reduction of tooth decay at the population level. Fluoride ingestion has been suggested as a possible risk factor for osteosarcoma based on a 1990 animal study. Six of the seven subsequent case-control studies in humans reported that fluoride in drinking water was not associated with osteosarcoma.
This study assessed whether living in a fluoridated community was a risk factor for osteosarcoma by performing a secondary data analysis using data collected from two separate, but linked studies. Patients for both Phase 1 and Phase 2 were selected from U.S. hospitals using a hospital-based matched case-control study design. For both phases, cases were patients diagnosed with osteosarcoma and controls were patients diagnosed with other bone tumors or non-neoplastic conditions.
In Phase 1, cases (N=209) and controls (N=440) were patients of record in the participating orthopedic departments from 1989-1993. In Phase 2, cases (N=108) and controls (N=296) were incident patients who were identified and treated by orthopedic physicians from 1994-2000. This analysis included all patients who met eligibility criteria on whom we had complete data on covariates, exposures, and outcome. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of community water fluoridation with osteosarcoma.
The adjusted OR, for osteosarcoma and ever-having lived in a fluoridated area for non-bottled water drinkers was 0.51(0.31 - 0.84), p=0.008. The same comparison adjusted OR for bottled water drinkers was 1.86 (0.54 - 6.41), p=0.326.
"These results indicate that residence in a fluoridated community is not related to an increase in risk for osteosarcoma after adjusting for race, ethnicity, income, distance from the hospital, urban/rural living status, and drinking bottled water. This should not be surprising given that ingestion of fluoridated water is a common exposure and osteosarcoma remains a rare disease," said Chester Douglass; Harvard School of Dental Medicine, Department of Oral Health Policy and Epidemiology.
IMAGE: COMPARISON OF THE MODEL SEGMENTATION AND THE GROUND TRUTH, FROM THE SECONDARY TEST DATA ANNOTATIONS, FOR A CBCT SCAN. FOR FURTHER EXPLANATION, SEE THE RESEARCH ARTICLE IN SCIENTIFIC REPORTS. view more
CREDIT: THE AUTHORS
In order to plan a dental implant operation and the implant size and position, dentists need to know the exact location of the mandibular canal, a canal located in both sides of the lower jaw that contains the alveolar nerve.
The lower jaw is an anatomically complex structure and medical experts use X-ray and computer tomography (CT) models to detect and diagnose such structures. Typically, dentists and radiologists define the location of the mandibular canals manually from the X-ray or CT scans, which makes the task laborious and time-consuming. That is why an automatized way to do this could make their work and placement of dental implants much easier.
To bring a solution to this problem, researchers at the Finnish Center for Artificial Intelligence FCAI, Tampere University Hospital, Planmeca and the Alan Turing Institute developed a new model that accurately and automatically shows the exact location of mandibular canals. The model is based on training and using deep neural networks. The researchers trained the model by using a dataset consisting of 3D cone beam CT (CBCT) scans.
The model is based on a fully convolutional architecture, which makes it as fast and data-efficient as possible. Based on the research results, this type of a deep learning model can localise the mandibular canals highly accurately. It surpasses the statistical shape models, which have thus far been the best, automatized method to localise the mandibular canals.
In simple cases - when the patient does not have any special conditions, such as osteoporosis - the model is as accurate as a human specialist. Most patients that visit a dentist fall into this category. 'In more complex cases, one may need to adjust the estimate, so we are not yet talking about a fully stand-alone system,' says Joel Jaskari, Doctoral Candidate and the first author of the research paper.
Using Artificial Intelligence has another clear advantage, namely the fact that the machine performs the job equally fast and accurately every time. 'The aim of this research work is not, however, to replace radiologists but to make their job faster and more efficient so that they will have time to focus on the most complex cases,' adds Professor Kimmo Kaski.
Planmeca, a Finnish company developing, manufacturing and marketing dental equipment, 2D and 3D imaging equipment and software, collaborates with FCAI. The company is currently integrating the presented model into its dedicated software, to be used with Planmeca 3D tomography equipment.
Scientists have long been aware of the virulence potential of this genus of amoebae. The gastrointestinal parasite E. histolytica, for instance, causes a disease known as amebiasis, one of the most common causes of death from parasitic diseases worldwide. "We have shown that an amoeba like E. gingivalis, which colonizes the oral cavity, will invade the oral mucosa and destroy gingival tissue. This enables increased numbers of bacteria to invade the host tissue, which further exacerbates inflammation and tissue destruction," says Prof. Schäfer. The international team of researchers was the first to describe precise roles of E. gingivalis in the pathogenesis of inflammation. During their analysis of inflamed periodontal pockets, the researchers detected evidence of the amoeba in approximately 80 percent of patients with periodontitis, but in only 15 percent of healthy subjects. Their observations revealed that, after invading the gums, the parasites move within the tissue, feeding on and killing host cells. Cell culture experiments showed that infection with E. gingivalis slows the rate at which cells grow, eventually leading to cell death.
The researchers concluded that the amoeba's role in inflammation shows distinct parallels to the pathogenesis of amebiasis. "E. gingivalis actively contributes to cell destruction inside the gingival tissue and stimulates the same host immune response mechanisms as E. histolytica during its invasion of the intestinal mucosa," explains Prof. Schäfer. "This parasite, which is transmitted by simple droplet infection, is one potential cause of severe oral inflammation."
Treatment success is often short-lived in patients with periodontitis. This might be due to the high virulence potential of this previously unnoticed, yet extremely common amoeba. Summing up the results of the research, Prof. Schäfer says: "We identified one infectious parasite whose elimination could improve treatment effectiveness and long-term outcomes in patients with gum disease." He adds: "Current treatment concepts for periodontitis fail to consider the possibility of infection by this parasite or its successful elimination." A clinical trial is underway to determine the extent to which the elimination of this amoeba might improve treatment outcomes in patients with periodontitis.
IMAGE: MOST BACTERIAL CELLS ARE COVERED IN TINY, HAIR-LIKE STRUCTURES CALLED PILI. THEIR DIAMETER IS SMALLER THAN 1/10,000TH OF A HUMAN HAIR. view more
CREDIT: S. SHIBATA, OIST
Porphyromonas gingivalis is a major bacterial pathogen which leads to periodontitis also known as gum disease. In Japan, 80% of adults aged 35 and over suffer from this disease. What's more, P. gingivalis has also been linked to rheumatoid arthritis, cardiovascular disease, pancreatic cancer, and even Alzheimer's disease.
Periodontitis is an oral inflammatory disease in response to biofilms - a bacterial plaque that accumulates on surfaces like our teeth. Biofilms are primarily created by bacterial cells attaching themselves to the host, and to each other, by sticky hair-like filaments called pili. In serious cases, periodontitis can result in gum erosion and tooth loss.
A team of researchers from the Molecular Cryo-Electron Microscopy Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), alongside the groups of Professor Koji Nakayama at Nagasaki University and Professor Katsumi Imada at Osaka University, have revealed the structure of these adhesive pili and shed light on how they assemble. Their research, published in Nature Microbiology, has provided new insights into bacteriology and is a crucial step towards combatting the diseases this bacterium is associated with.
"Pili are vital for both the survival of the bacteria, and the creation of the biofilms," said Dr. Satoshi Shibata, first author and staff scientist in OIST's Unit, which is led by Associate Professor Matthias Wolf. "By taking a close look at these pili, our research has provided insights into how we can prevent biofilms from forming."
P. gingivalis is a member of the class Bacteroidia. Previous research, led by Professor Nakayama and colleagues at Nagasaki University, found that most bacteria within this class have unique Type V pili. However, until now, the structure and assembly process of these pili were unknown. "Besides periodontal pathogens, Type V pili are seen in major colon bacteria such as Bacteroides and Prevotella species and their Type V pili may contribute to formation of colon microbiota," said Professor Nakayama.
Pili themselves are made up of smaller protein units, called pilins. In the case of P. gingivalispili, most of these are FimA pilins. Although pilins are only linked by weak interactions, they can assemble into very stable pili.
The first step to determining how this assembly occurred was to take a close look at the structure of individual pilins. "Detailed structural information of FimA is very important because pathogenicity of P. gingivalis strains is closely related with the FimA sub-types," said Professor Imada.
Professor Imada and students from Osaka University crystalized FimA pilins, revealing their unassembled state at atomic resolution.
"Based on findings from earlier experiments by the Nakayama group, we theorized that these pilins assembled themselves via a mechanism of protease-mediated strand-exchange," said Dr. Shibata. "So, our next experiment took a close look at fully assembled pili using cryo-electron microscopy."
Associate Prof. Mikio Shoji from the Nakayama group, and Dr. Shibata prepared a genetically engineered version of the FimA pilins, which successfully assembled into pili, after a protease - a protein that cuts other proteins - was added. Dr. Shibata then collected thousands of images on the high-end cryo-electron microscope at OIST and processed the data on the University's "Sango" supercomputer, resulting in a complete three-dimensional atomic model of the assembled pilus structure.
"When we added the protease, the pilins started to assemble into elongated pili like train cars connecting to form a train. This happened because the protease cut a retaining loop and released a protein strand, known as the donor strand, which triggered the assembly to begin," said Professor Wolf. Once released, the donor strand flipped out of the pilin and inserted itself into a neighboring pilins groove, thus connecting the two pilins.
Finally, in a combined team effort, the three groups took a closer look at the amino acid composition at the end of the donor strand and found that it played a critical role in the assembly mechanism. Using biochemistry, crystallography and cryo-EM, they mutated the protein, which prevented the pili from forming and thus proved how these key amino acids contribute to pilin polymerization.
Ultimately, this research is a step towards new anti-bacterial drugs, not just for the diseases caused by P. gingivalis, but for those caused by any bacteria containing Type V pili. "We're now trying to create an inhibitor that prevents pili from assembling," said Dr. Shibata. "This structure serves as a target to create new drugs, which are desperately needed to counter increasing antibiotic resistance. Finding novel antimicrobial compounds is a critical advantage in fighting these pathogens."
