Publisher Health

You and your dentist have a lot of tools and techniques for stopping cavities, but detecting the specific chemical conditions that can lead to cavities and then preventing them from ever getting started is much harder. Now, in a new study, University of Washington researchers have shown that a dental tool they created can measure the acidity built up by the bacteria in plaque that leads to cavities.
The O-pH system is a prototype optical device that emits an LED light and measures the reactions of that light, the fluorescence, with an FDA-approved chemical dye applied to teeth. The O-pH then produces a numerical reading of the pH, or acidity, of the plaque covering those teeth. Knowing how acidic the plaque is can tell dentists and patients what area of a tooth is most at risk of developing a cavity.
“Plaque has a lot of bacteria that produce acid when they interact with the sugar in our food,” said Manuja Sharma, lead author and a doctoral student in the UW Department of Electrical and Computer Engineering. “This acid is what causes the corrosion of the tooth surface and eventually cavities. So, if we can capture information about the acidic activity, we can get an idea of how bacteria are growing in the dental biofilm, or plaque.”
Sharma explained that not all bacteria in that biofilm are bad or will lead to cavities, so measuring the acidity of the environment can tell a dentist what they need to know about the threat of developing problems. That can limit the need to test for specific harmful bacteria, of which there can be a multitude.
To test their device, the researchers recruited 30 patients between the ages of 10 and 18, with a median age of 15, in the UW School of Dentistry’s Center for Pediatric Dentistry. The researchers chose kids for their study in large part because the enamel on kids’ teeth is much thinner than that of adults, so getting early warning of acid erosion is even more important. To perform the measurements with the O-pH device, the researchers also recruited second- and third-year students in the dentistry school, who were supervised by a faculty member.
The test is non-invasive. While the dye is applied to the teeth, at the end of a length of cord is the probe that transmits and collects light while hovering over the surface of a tooth (see photos). The collected light travels back to a central box that provides a pH reading. The conditions on the patients’ teeth were read several times before and after sugar rinses and other condition changes, such as pre- and post-professional dental cleaning.
Eric Seibel, senior author and research professor of mechanical engineering in the UW College of Engineering, said the idea for adding the acidity test as a new clinical procedure came from envisioning that when a patient first sits in the dental chair, before their teeth get cleaned, “a dentist would rinse them with the tasteless fluorescent dye solution and then get their teeth optically scanned to look for high acid production areas where the enamel is getting demineralized.”
The study was published in February in IEEE Transactions on Biomedical Engineering. The research team reported that one limitation to their study was being unable to consistently measure the same location on each tooth during each phase of testing. To address this limitation, in particular, the researchers are evolving their device to a version that produces images for dentists that instantly show the exact location of high acidity, where the next cavity may occur.
“We do need more results to show how effective it is for diagnosis, but it can definitely help us understand some of your oral health quantitatively,” said Sharma. “It can also help educate patients about the effects of sugar on the chemistry of plaque. We can show them, live, what happens, and that is an experience they’ll remember and say, OK, fine, I need to cut down on sugar!”
Co-authors include Lauren Lee, UW Department of Microbiology; Matthew Carson, UW Human Photonics Laboratory; David Park, Se An, Micah Bovenkamp, Jess Cayetano, Ian Berude, Zheng Xu, Alireza Sadr, UW School of Dentistry; and Shwetak Patel, UW Electrical and Computer Engineering, Paul. G. Allen School of Computer Science. This research was funded by the National Science Foundation, Oral Health Monitor, Institute of Translational Health Sciences; and the National Center for Advancing Translational Sciences of the National Institutes of Health.
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Materials provided by University of Washington. Original written by Jake Ellison. Note: Content may be edited for style and length.

A Florida State University College of Medicine researcher has made a discovery that alters our understanding of how the body’s DNA repair process works and may lead to new chemotherapy treatments for cancer and other disorders.
The fact that DNA can be repaired after it has been damaged is one of the great mysteries of medical science, but pathways involved in the repair process vary during different stages of the cell life cycle. In one of the repair pathways known as base excision repair (BER), the damaged material is removed, and a combination of proteins and enzymes work together to create DNA to fill in and then seal the gaps.
Led by Eminent Professor Zucai Suo, FSU researchers discovered that BER has a built-in mechanism to increase its effectiveness — it just needs to be captured at a very precise point in the cell life cycle.
The study appears in the current issue of Proceedings of the National Academy of Sciences.
In BER, an enzyme called polymerase beta (PolyB) fulfills two functions: It creates DNA, and it initiates a reaction to clean up the leftover “chemical junk.” Through five years of study, Suo’s team learned that by capturing PolyB when it is naturally cross-linked with DNA, the enzyme will create new genetic material at a speed 17 times faster than when the two are not cross-linked. This suggests that the two functions of PolyB are interlocked, not independent, during BER.
The research improves the understanding of cellular genomic stability, drug efficacy and resistance associated with chemotherapy.

A medium-chain fatty acid found in energy drinks might one day help protect against heart attack injuries.
“Heart attacks are still a leading cause of death worldwide, that often come with devastating complications,” said Zhong Wang, Ph.D., an associate professor of cardiac surgery at the University of Michigan Frankel Cardiovascular Center, who is the senior author on a recent preclinical study in eLife. “Better options are needed to reduce injury to the heart after a heart attack, and even improve heart function. In this publication, we target the interplay between energy metabolism and epigenetics mediated by the medium chain fatty acid 8C.”
Wang and colleagues were able to protect against heart attack injury in rat models with octanoic acid, an eight carbon (8C) medium chain fatty acid, as well as a few other metabolites. Those fatty acids produced acetyl-CoA, a building block for energy metabolism, which a stressed heart desperately needs.
The idea is that a physician would administer this therapy to a person once they arrive at the hospital after having a heart attack, to reduce further injury and improve heart function during recovery, he says.
“Understanding the crosstalk between energy metabolism and epigenetics may not only provide an effective target for myocardial infarction, but also have broad implications in other ischemic injury-caused organ damage beyond cardiac diseases,” said Ienglam Lei, Ph.D., from the Frankel CVC’s Department of Cardiac Surgery and the University of Macau in China, who conducted the study’s key experiments.
Wang says the next step would be to test this molecule in large animal models, followed by clinical trials. The research team has been studying the epigenetic regulation of heart attack for more than 10 years.
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Materials provided by Michigan Medicine – University of Michigan. Original written by Haley Otman. Note: Content may be edited for style and length.

Leptomeningeal disease is a rare complication of several different types of cancer, including melanoma. It occurs when tumor cells migrate to the cerebrospinal fluid and the tissue that surrounds the brain and spinal column known as the meninges. Patients who develop leptomeningeal disease have a very poor prognosis and typically survive only three to six months after diagnosis. These poor outcomes are partly due to the lack of model systems to study the disease in a laboratory. In a new article published in Neuro-Oncology, Moffitt Cancer Center researchers showed for the first time that patient-derived circulating tumor cells can be cultured from the cerebrospinal fluid of patients with leptomeningeal disease, and that those cells could be used to identify potential drug targets.
Leptomeningeal disease occurs in less than 8% of cancer patients and often presents during the very late stages of the disease. Patients who develop leptomeningeal disease have no effective treatment options, and physicians’ primary goals are to alleviate symptoms and improve quality of life while limiting toxicity as much as possible. Due to these poor outcomes, there is a great unmet need for improved therapies. However, until now scientists have been unable to culture leptomeningeal disease cells from patients to assist with their studies.
A team of Moffitt researchers led by Peter Forsyth, M.D., chair of the Department of Neuro-Oncology, and Keiran Smalley, Ph.D., director of the Donald A. Adam Melanoma and Skin Cancer Center of Excellence, has been able to add an important resource to study leptomeningeal disease by successfully growing and culturing circulating tumor cells derived from the cerebrospinal fluid of patients with melanoma leptomeningeal disease. Importantly, the researchers showed that the culturing process did not significantly change the gene expression pattern of the cultured cells compared to the original patient cells.
“Culturing these cells was an extremely difficult process. There was a lot of trial and error until we found the precise mix of growth factor supplements and culture conditions to be successful,” said Forsyth.
With their success of growing the cells, the researcher team wanted to confirm their utility in laboratory experiments to study leptomeningeal disease and identify new drug targets. They compared gene expression patterns of the cultured cells to normal nontumorigenic cells from the same patient and discovered that the cultured tumor cells had enriched expression of genes in the insulin-like growth factor signaling pathway, including IGFBP2 and IGF1R, which control many processes involved in cancer development.
The researchers assessed whether the cells could be used as a tool for therapeutic experiments and focused on targeting IGF1R. They reported that treating the cells with the IGF1R inhibitor ceritinib inhibited growth of the tumor cells in cell culture and in mice, and combination treatment with ceritinib and the MEK inhibitor trametinib resulted in greater inhibition than either agent alone.
“Collectively, our results showed that cerebrospinal fluid-circulating tumor cell expansion was possible. These findings also provide support that these patient derived cells are impactful tools for better understanding leptomeningeal disease pathology and testing the efficacy of targeted therapies,” said Vincent Law, lead author and a research associate in Forsyth’s lab.
This study was supported by the National Cancer Institute (P50CA168536, R21CA198550, R21CA216756, K99CA226679), the Department of Defense (W81XWH1810268), the Moffitt Foundation Research Acceleration Fund, the Moffitt Chemical Biology & Molecular Medicine Program and the Moffitt Foundation.
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People with dementia struggle to adapt to changes in their environment because of damage to areas of the brain known as ‘multiple demand networks’, highly-evolved areas of the brain that support general intelligence, say scientists at the University of Cambridge.
There are many different types of dementia, such as Alzheimer’s disease and frontotemporal dementia (FTD), which are characterised by the build-up of different toxic proteins in different parts of the brain. This means that the symptoms of dementia vary, and can include problems with memory, speech, behaviour or vision. But one symptom seen across every type of dementia is a difficulty in responding to unexpected situations.
Dr Thomas Cope from the MRC Cognition and Brain Science Unit and Department of Clinical Neurosciences at the University of Cambridge said: “At the heart of all dementias is one core symptom, which is that when things change or go unexpectedly, people find it very difficult. If people are in their own environment and everything is going to plan, then they are OK. But as soon as the kettle’s broken or they go somewhere new, they can find it very hard to deal with.”
To understand why this happens, Dr Cope and colleagues analysed data from 75 patients, all of whom are affected by one of four types of dementia that affect different areas of the brain. The patients, together with 48 healthy controls, listened to changing sounds while their brain activity was recorded by a magnetoencephalography machine, which measures the tiny magnetic fields produced by electrical currents in the brain. Unlike traditional MRI scanners, these machines allow very precise timing of what is happening in the brain and when. The results of their experiment are published today in the Journal of Neuroscience.
During the scan, the volunteers watched a silent film — David Attenborough’s Planet Earth, but without its soundtrack — while listening to a series of beeps. The beeps occurred at a steady pattern, but occasionally a beep would be different, for example a higher pitch or different volume.
The team found that the unusual beep triggered two responses in the brain: an immediate response followed by a second response around 200 milliseconds — a fifth of a second — a later.

It’s common to say that someone looks either younger or older than their chronological age, but aging is more than skin deep. Our various organs and systems may have different ages, at least from a biological perspective. In a study published March 8 in the journal Cell Reports, an international team of investigators used biomarkers, statistical modeling, and other techniques to develop tools for measuring the biological ages of various organ systems. Based on their findings, the researchers report that there are multiple “clocks” within the body that vary widely based on factors including genetics and lifestyle in each individual.
“Our study used approaches that can help improve our understanding of aging and — more importantly — could be used some day in real healthcare practice,” says co-corresponding author Xun Xu of the Beijing Genomics Institute (BGI) and China National GeneBank (CNGB) in Shenzhen, China. “We used biomarkers that could be identified from blood and stool samples plus some measurements from a routine body checkup.”
The concept of evaluating people’s biological aging rates has been around since the 1970s, but earlier studies were focused either on developing methods for estimating one centralized aging index or studying the molecular aging biomarkers using tissues and cell cultures outside the body.
“There has been a lack of practical applications in a population-based sample for precisely estimating the aging rates of live people’s organs and systems,” says co-corresponding author Xiuqing Zhang, also of BGI and CNGB. “So we decided to design one.”
To do this research, the investigators recruited 4,066 volunteers living in the Shenzhen area to supply blood and stool samples and facial skin images and to undergo physical fitness examinations. The volunteers were between the ages of 20 and 45 years; 52% were female and 48% were male. “Most human aging studies have been conducted on older populations and in cohorts with a high incidence of chronic diseases,” says co-corresponding author Brian Kennedy of the National University of Singapore. “Because the aging process in young healthy adults is largely unknown and some studies have suggested that age-related changes could be detected in people as young as their 20s, we decided to focus on this age range.”
In total, 403 features were measured, including 74 metabolomic features, 34 clinical biochemistry features, 36 immune repertoire features, 15 body composition features, 8 physical fitness features, 10 electroencephalography features, 16 facial skin features, and 210 gut microbiome features. These features were then classified into nine categories, including cardiovascular-related, renal-related, liver-related, sex hormone, facial skin, nutrition/metabolism, immune-related, physical fitness-related, and gut microbiome features.
Because of the difference in sex-specific effects, the groups were divided into male and female. The investigators then developed an aging-rate index that could be used to correlate different bodily systems with each other. Based on their findings, they classified the volunteers either as aging faster or aging slower than their chronological age.
Overall, they discovered that biological ages of different organs and systems had diverse correlations, and not all were expected. Although healthy weight and high physical fitness levels were expected to have a positive impact, the investigators were surprised by other findings. For example, having a more diverse gut microbiota indicated a younger gut while at the same time having a negative impact on the aging of the kidneys, possibly because the diversity of species causes the kidneys to do more work.
The investigators also used their approach to look at other datasets, including the National Health and Nutrition Examination Survey from the US Center for Disease Control and Prevention and the Chinese Longitudinal Healthy Longevity Survey, which includes data on more than 2,000 centenarians with matched middle-aged controls. In addition, they looked at single nucleotide polymorphisms (SNPs) to determine whether differences could be explained by genetic factors. There, they did find certain pathways that could be associated with aging rates.
The researchers plan to regularly follow up with the study participants to track the development of aging and validate their findings. Future studies will use additional approaches for classifying features of aging and studying the interactions between organ systems.
They also plan to use single-cell technology to look at programmed aging in more detail. “It’s important to capture the cell-to-cell variation in an aging individual, as this will tell us important information about the heterogeneity within cell types and tissues and provide important insights into aging mechanisms,” says co-corresponding author Claudio Franceschi of Lobachevsky State University in Russia.
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Scientists have shed new light on the role of the placenta in managing the relationships between maternal vitamin D and fetal development, according to a study published today in eLife.
The findings demonstrate a complex interplay between vitamin D and the placenta, and could help inform future interventions using vitamin D to support fetal development and maternal adaptations to pregnancy.
As vitamin D is unable to be produced by a fetus, it must be transferred across the placenta. This is important for both fetal and lifelong health. Maternal vitamin D concentrations are positively associated with fetal bone growth and birth weight, and these associations continue into postnatal life.
Previous work has suggested that maternal vitamin D transfers passively across the placenta, but the current study challenges this idea.
“Research in kidneys has questioned the role of passive diffusion in the uptake of vitamin D. It has instead shown that this uptake is driven primarily by endocytosis of vitamin D, where the vitamin is bound to the binding protein albumin and introduced into the organ tissue cells,” explains Dr Claire Simner, Research Assistant at the University of Southampton, UK. Simner is a co-first author of the study alongside Dr Brogan Ashley, who was also at the University of Southampton at the time the work was carried out. “We proposed that a similar endocytic mechanism exists in the placenta, suggesting that this organ plays an active role in the delivery of vitamin D to the fetus.”
To explore this idea further, the team designed a study to find out how maternal vitamin D is taken up, metabolised and mediates gene expression within the human placenta. They used a perfusion model — involving the use of human placental samples collected from term pregnancies immediately after delivery — and placental fragment cultures to study the behaviour of the organ tissue. These methods contrast with cell-model approaches of previous research into how vitamin D transfers across the placenta.
To determine the mechanisms of placental vitamin D uptake, the team incubated fresh term human placental fragments with vitamin D alongside albumin for eight hours. They then analysed the gene expression of the fragments using a technique called quantitative rtPCR. Their analysis revealed a significant increase in the expression of the CYP24A1 gene — which is involved in controlling the amount of vitamin D in the body — in the fragments following incubation, compared to fragments that were incubated with vitamin D only. This suggests that albumin might enable vitamin D uptake.
“These findings show that endocytosis may play an important role in the uptake of vitamin D into the human placenta, as previously seen in the kidneys,” says Dr Jane Cleal, Lecturer in Epigenetics at the University of Southampton, and a co-senior author of the study alongside Professor Nicholas Harvey, Professor of Rheumatology and Clinical Epidemiology at the MRC Lifecourse Epidemiology Centre, University of Southampton.
Additionally, the team demonstrated that vitamin D exposure leads to rapid effects on the full set of messenger RNA molecules (the transcriptome) and of proteins (the proteome) expressed by the placenta. Their results revealed that the underlying epigenetic landscape of the placenta — the interaction between the genes and the environment — helps to dictate this transcriptional response to vitamin D treatment.
“This is the first quantitative study demonstrating the active transfer and metabolism of vitamin D by the human placenta, with widespread effects on the placenta itself,” Dr Cleal concludes. “As our data are generated from term placenta only, additional studies are needed to determine how our findings relate to earlier stages of gestation. Together, the insights from our work and future research will be helpful for identifying potential new options for targeted interventions to improve pregnancy outcomes.”
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Have you ever felt uncomfortable when asked about depression or any other sensitive personal issue when checking in for a medical visit?
You’re not alone.
Doctors at Wake Forest School of Medicine wondered if patients might be more forthcoming with honest information by completing a self-administered questionnaire on a tablet computer instead of responding verbally to nursing staff.
Seems they were right.
In a recent study, the tablet screening detected twice as many people with depression, fall risk or intimate partner violence compared to usual in-person screening by nursing staff, according to the study’s principal investigator, David Miller, M.D., professor of internal medicine at Wake Forest School of Medicine. The study is published in the March 8 issue of JAMA Network Open.
“We think using an iPad provides more privacy for patients and gives us more accurate health information than when nurses verbally do the screening as part of the check-in process for clinic visits,” Miller said. “It also saves nursing staff time since they don’t have to ask the questions while checking a patient’s vitals and updating their medical information.”
For this non-randomized controlled trial, the screening questions for depression, fall risk and intimate partner violence that are asked at every primary care visit were programmed into the mPATH app, which was developed by Miller’s team in 2018 to assist patients with colorectal cancer screening.

Squeezing through tight spaces makes cancer cells more aggressive and helps them evade cell death, shows a study published today in eLife.
The findings reveal how mechanical stress makes cancer cells more likely to spread, or metastasise. While metastasis is the cause of most cancer deaths, there are currently no available cures. However, the new results may help scientists develop novel approaches to treat or prevent metastasis.
It can be a tight squeeze for cancer cells to escape their tumour or enter tiny blood vessels, called capillaries, to spread through the body. The cells must collapse and change their shape to do this, in a process called confined migration. As they spread, the cells must also avoid detection and destruction by the immune system.
“Mechanical stress can cause cancer cell mutations, as well as an uncontrolled increase in cell numbers and greater tissue invasion,” explains first author Deborah Fanfone, Postdoctoral Fellow at the Cancer Research Center of Lyon, France. “We wanted to know if the mechanical stress of confined migration makes cancer cells more likely to metastasise, and how this happens.”
To answer these questions, Fanfone and colleagues forced human breast cancer cells through a membrane with tiny, three-micrometre-sized holes to simulate a confined migration environment. After just one passage through the membrane, they found that the cells became more mobile and resistant to anoikis — a form of programmed cell death that occurs when cells become detached from the surrounding network of proteins and other molecules that support them (the extracellular matrix). The cells were also able to escape destruction by immune natural killer cells.
Further experiments showed that increased expression of inhibitory-of-apoptosis proteins (IAPs) increased the resistance of cancer cells to anoikis. Treating the cancer cells with a new type of cancer drug called a SMAC mimetic, which degrades IAPs, removed this protection.
The team then studied how breast cancer cells that had undergone confined migration behave when administered to immune-suppressed mice. They found these mice developed more lung metastases than mice that were administered with breast cancer cells that had not been exposed to confined migration.
“By mimicking confined migration, we’ve been able to explore its multifaceted effects on cancer aggressiveness,” says senior author Gabriel Ichim, who leads the Cancer Cell Death team at the Cancer Research Center of Lyon. “We’ve shown how the process boosts survival in cancer cells and makes them more prone to forming deadly metastases.”
The authors add that these results may lead to additional studies of potential metastasis treatments, such as therapies that soften tumours to reduce mechanical stress on cancer cells, or that block IAPs. These include SMAC mimetics, which are currently being tested in clinical trials as a possible new treatment approach.
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Sexual partnerships between individuals from different communities may help explain why some community-based HIV prevention efforts were moderately effective, shows a study published in eLife.
The findings may help explain the results of some community-based prevention studies and help scientists develop better ways to track and prevent the spread of HIV.
Early identification and treatment of HIV can help prevent transmission of the virus. However, large studies of community-based universal HIV testing and treatment in sub-Saharan Africa have not been as effective as mathematical models predicted at curbing new infections.
“To stem the spread of new HIV infections, we need to better understand patterns of HIV transmission in the region,” says first author Lerato Magosi, a postdoctoral research fellow at the Center for Communicable Disease Dynamics at Harvard T. H. Chan School of Public Health, Boston, US.
Magosi and colleagues set out to learn more about HIV transmission patterns in Botswana, Africa. The team genetically sequenced HIV samples collected from 5,114 individuals in 30 communities who participated in an HIV prevention trial. This trial, called the Botswana Combination Prevention Project or Ya Tsie trial, compared HIV transmission in communities that were randomised to receive universal HIV testing and linkage to treatment with communities that did not receive such an intervention.
By identifying samples of HIV that were closely related genetically, the team was able to track how the virus spread within and between these communities. They found that most HIV transmission occurred between individuals who were about the same age and among individuals living in the same community or neighbouring communities, rather than distant communities. Viral spread from communities that did not receive the universal HIV testing and treatment intervention into communities that received the intervention was more likely to occur than vice versa.
“Our results suggest that community-based HIV testing and treatment initiatives are powerful tools to reduce HIV transmission, but will need to be supported by targeted studies aimed at closing age and sex gaps in uptake of testing and treatment,” Magosi explains.
The authors suggest that genetic sequencing may be a valuable tool to help identify geographic HIV transmission patterns. They also recommend widely distributing HIV testing and treatment interventions in communities that are likely to intermingle. “Population mobility patterns are central to understanding HIV transmission dynamics and should be considered when designing and testing HIV control strategies,” concludes senior author Marc Lipsitch, Professor of Epidemiology and Director of the Center for Communicable Disease Dynamics.
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