Publisher Health

Old, obese flies get healthier and live longer if put on a diet, University of Connecticut researchers report on Dec. 8 in PNAS. If the effect holds true for humans, it would mean it’s never too late for obese people to improve their health with diet.
For way too many of us,eating too much goes along with getting old and a tendency to be obese.Different health organizations define obesity differently, but all agree it means having too much body fat, and is associated with a host of diseases related to metabolism including heart disease and diabetes. Many animal studies have shown that eating less — meaning sharply restricting calories without malnutrition — lengthens lifespan. While human trials have shown evidence of beneficial effects of eating less on health, especially in healthy obese individuals, studies examining effects on lifespan have been unrealistic for humans.
Now, UConn School of Medicine researchers have shown that fruit flies fed a high sugar, high protein, high calorie diet that mimics the processed modern diet have metabolic changes similar to obese humans. Switching these obese flies to a low calorie diet, even very late in life, can dramatically change their metabolisms and extend their lives.
Fruit flies live short and fast — the lifespan of flies raised on a high calorie diet is less than 80 days, while the longest lived on a low calorie diet can reach 120 days. To test whether changes in diet late in life can change a fly’s lifespan, researchers led by geneticist Blanka Rogina from UConn’s Department of Genetics and Genome Sciences and the Institute for Systems Genomics raised several batches of fruit flies. Some of the flies were raised on a low calorie diet that provided just half the energy of a regular diet, while the others were raised on a high calorie diet that provided three times the usual number of calories.
In this study, they looked specifically at male flies. Young flies switched from a high calorie to a low-calorie diet at 20 days old lived very long lives, similar to the flies fed a low-calorie diet from day one.
What surprised the researchers was that switching the flies’ diet to a low calorie one remained a reliable way to extend lifespan even for old flies in ill health. The older insects raised on the high calorie diet had more lipids in their bodies, and they expended more energy defending their bodies from reactive oxygen species. They also had a higher death rate than flies raised on the low-calorie diet. But when the surviving high calorie flies were switched to a low-calorie diet at 50 or even 60 days (when most of the high calorie flies had already died) their metabolisms changed, their death rate plummeted, and their lifespans lengthened.
“Our studies were performed in flies aged on a high calorie diet, akin to obese individuals, suggesting that late-life diet shift in obese humans might have remarkable beneficial impact on health,” Rogina says.
UConn School of Medicine Genetics and Genome Sciences Chair Brent Graveley and other researchers on the team looked at the genes expressed by the high calorie flies and contrasted them with the low calorie flies. Genes that control physiological and metabolic adaptation are different between the groups.
“The remarkable finding of this study is that even after living a significant portion of their lives on a high calorie diet, flies can gain the benefits of life span extension by simply switching to a low calorie diet,” Graveley says.
The team’s results show that flies’ metabolisms can adapt to a change in diet even in old age. Since many basic metabolic pathways in fruit flies are shared with humans, this study suggests that human metabolism may respond the same way, and individuals eating a high calorie diet could benefit from reducing their calorie intake in old age. The researchers are currently analyzing data from female fruit flies to see if there are any sex-related differences in response to diet shifting.

Self-propelled nanoparticles could potentially advance drug delivery and lab-on-a-chip systems — but they are prone to go rogue with random, directionless movements. Now, an international team of researchers has developed an approach to rein in the synthetic particles.
Led by Igor Aronson, the Dorothy Foehr Huck and J. Lloyd Huck Chair Professor of Biomedical Engineering, Chemistry and Mathematics at Penn State, the team redesigned the nanoparticles into a propeller shape to better control their movements and increase their functionality. They published their results in the journal Small.
Due to fabrication challenges, the shape of nanoparticles has previously been limited to rods and donuts, according to Ashlee McGovern, doctoral student in chemistry at Penn State and first author on the paper. With a nanoscribe machine that can 3D print at the nanoscale in Penn State’s Materials Research Institute, McGovern experimented to optimize the nanoparticle shape. She redesigned the shape of the particles to a propeller, which can spin efficiently when triggered by a chemical reaction or magnetic field.
The propeller shape employs chirality, akin to a screw or spiral staircase, where the top face is mirrored by the bottom face.
“Shape predetermines how a particle is going to move,” McGovern said. “Chirality, or handedness, as a design feature has not been utilized enough in nanoparticle research and is a way to make the particles move in more and more complex ways.”
The chiral shape allows the particles to move in a prescribed direction, and, depending on the tilt of the blades, spin clockwise or counterclockwise in place, fueled by a chemical reaction between the metals in the nanoparticles and hydrogen peroxide.
After experimenting with different numbers and angles of fins, as well as different thicknesses, researchers found that using four or more fins at a 20-degree tilt and 3.3-micron thickness allowed for the greatest amount of stability. With three or fewer fins, the propellers exhibit uncontrolled movement.

The increased control allowed researchers to manipulate the particles to capture and transport polymer cargo particles.
“Using a magnetic field, we can steer the micropropellers to hunt down and collect cargo particles,” McGovern said. “Our lab’s rod- and donut-shaped nanoparticles would accidentally pick up cargo, but not in any controlled fashion.”
To further control the movements of the particles, researchers manipulated the rotational direction of the micropropellers.
“With the built-in flows that the particles create, we can control the particle-to-particle interactions between the two propellers,” McGovern said. “Switching the rotational direction from counterclockwise to clockwise and vice versa allows two propellers to attract or repel each other.”
Aronson, who heads the Active Biomaterials Lab in which McGovern works, emphasized the future reach of this research.
“Using tailored mechanical, magnetic and chemical responses, we can exert more control than ever before on these nanoparticles,” Aronson said. “In the future, we can leverage this control to apply this technology to design concepts for microscale devices or microrobotics.”
In addition to McGovern and Aronson, the co-authors include Mu-Jie Huang and Raymond Kapral from the University of Toronto and Jiyuan Wang from the Heilongjiang University of Science and Technology, who contributed simulation work to support the experimental research. The U.S. Department of Energy and the Natural Sciences and Engineering Research Council of Canada partially funded this work.
Video URL: https://vimeo.com/892258599

Research from Tokyo Medical and Dental University (TDMU) warns that rates of urgent dialysis and death are on the rise over the last decade in people hospitalized for acute high blood pressure.
High blood pressure is called the silent killer because symptoms can remain hidden until a medical crisis strikes. You might think hypertension is no longer serious because blood pressure medication is widely available, but newly reported trends in people with dangerously high blood pressure might change your mind.
In a study recently published in Hypertension, researchers from Tokyo Medical and Dental University (TDMU) found that people admitted to the hospital over the last decade with spiking blood pressure — also known as acute hypertension — are increasingly likely to need urgent kidney dialysis or to die in the hospital.
The researchers examined the medical records of more than 50,000 patients admitted to the hospital for acute hypertension between 2010 and 2019. Over the study’s 10 years, urgent dialysis rates rose significantly, from 1.52% to 2.6%.
“Of note, the rising trend in urgent dialysis was similar in patients who were younger, male, or overweight, and those with hypertensive heart failure. People with these traits are a high-risk group,” says the study’s lead author, Hisazumi Matsuki. “Unfortunately, the urgent dialysis procedure can cause complications like infection or bleeding, which in turn may increase the patient’s risk of dying.”
Mortality rates also increased over the 10 years from 1.83% to 2.88%, but not only because of the risks associated with urgent dialysis. “We saw a trend towards rising in-hospital mortality rates since 2010, particularly in patients who were elderly, male, and underweight, and in patients with hypertensive heart failure,” says senior author Shintaro Mandai.
However, mortality rates were lower in patients who were overweight. “We observed the obesity paradox, which is an unexpected decrease in mortality that sometimes accompanies an increased body mass index,” notes senior author Shinichi Uchida. “Underweight patients tend to have poor nutritional status and low physical activity and may have underlying conditions causing weight loss. Additionally, it can be difficult to find hidden heart congestion if the patient has no overt rise in blood pressure.”
Despite advances in hypertension treatment, the authors note that there has been no decrease in the number of acute hypertension cases. High blood pressure leads to serious organ damage by altering the structure of blood vessels, which run through every part of the body. People with hypertension need appropriate outpatient care and intensive blood pressure control, such as blood pressure medication, exercise, and healthy diets.
The research also highlights the importance of detecting hidden congestion early and providing underweight patients with nutritional support. Measures must be taken to avoid as many unplanned hospital admissions due to acute hypertension as possible.

Using a “liquid biopsy” to study genetic material from tumors shed into the bloodstream together with immune cells could help clinicians predict which patients with advanced lung cancers are responding to immunotherapies and which patients may develop immune-related side effects several months later, according to research directed by investigators at the Johns Hopkins Kimmel Cancer Center, the Bloomberg~Kimmel Institute for Cancer Immunotherapy and Allegheny Health Network Cancer Institute in Pittsburgh.
By monitoring changes in circulating tumor DNA (ctDNA) among 30 patients treated with immunotherapies for metastatic non-small cell lung cancers, the researchers were able to determine molecular response — the clearance of tumor genetic material in the bloodstream — which was significantly associated with progression-free and overall survival. Serial blood testing was also able to detect an expansion of T cells — immune cells that typically recognize and target foreign or non-self molecules on tumor cells — in patients with immune-related adverse events such as lung tissue inflammation as early as five months ahead of the emergence of clinical symptoms. Similar results were seen in an independent cohort of 49 patients with advanced lung cancers enrolled at the Allegheny Health Network Cancer Institute.
These results were published in the journal Clinical Cancer Research on Nov. 8, 2023.
“Immunotherapy has revolutionized how we take care of patients with lung cancer, but it’s been challenging to determine how to assess response,” says lead study author Joseph Murray, M.D., Ph.D., an assistant professor of oncology and co-director of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins. “We don’t have reliable biomarkers, so we rely a lot on imaging and patient symptoms to see how patients are clinically responding. Now, we can potentially use noninvasive tests like this to study response and predict side effects very early on, and change therapy regimens if necessary.”
The test also was able to help understand the clinical outcomes of patients with stable disease on imaging, says senior study author Valsamo “Elsa” Anagnostou, M.D., Ph.D., associate progressor of oncology, director of the thoracic oncology biorepository at Johns Hopkins, leader of Precision Oncology Analytics, co-leader of the Johns Hopkins Molecular Tumor Board and co-director of the Lung Cancer Precision Medicine Center of Excellence at Johns Hopkins.
“All of the patients who appeared to have stable disease on imaging tests had very different DNA molecular response patterns that helped predict their overall clinical outcomes,” Anagnostou says. “This is a particular subset of patients for whom we may want to intervene, and use liquid biopsies to guide therapeutic decision-making, as ctDNA can rapidly and accurately capture the amount of cancer present.” This work ties in the ongoing efforts of the thoracic oncology group at Johns Hopkins to implement liquid biopsies in clinical decision-making, through a ctDNA-adaptive clinical trial of chemo-immunotherapy for patients with metastatic lung cancer (NCT04093167).

While the lithium-ion batteries in disposable electronic cigarettes are discarded after a single use, they can continue to perform at high capacity for hundreds of cycles, according to a study published December 12 in the journal Joule. The analysis, conducted by scientists from University College London (UCL) and the University of Oxford and supported by The Faraday Institution, highlights a growing environmental threat from these increasingly popular vape pens, which are not designed to be recharged.
“The surprise for us were the results that pointed toward just how long these batteries could potentially cycle,” says Paul Shearing, Professor of Sustainable Energy Engineering at the Department of Engineering Science at the University of Oxford and UCL.
“If you use a low charge and discharge rate, you can see that for over 700 cycles, you still have more than 90% capacity retention. That’s a pretty good battery, actually. And these are just being discarded. They’re being chucked on the side of the road.”
Disposable e-cigarettes have skyrocketed in popularity in the UK since 2021, with a survey finding an 18-fold increase recorded between January 2021 and April 2022. Within 15 months, their popularity among 18-year-olds rose from 0.4% to 54.8%. The speedy rise of single-use e-cigarettes has led to pressing new waste problems, with about 1.3 million of the devices thrown away in the nation each week. As a result, about 10,000 kilograms (over 22,000 lbs) of lithium from e-cigarette batteries wind up in UK landfills each year, threatening nearby waterways with toxic nickel, cobalt, and organic solvents.
“Early on, we got the notion that the batteries going into these e-cigs were likely to be rechargeable batteries,” says Shearing, noting that, to his team’s knowledge, previous studies had not assessed how long the lithium-ion batteries in these products are capable of lasting.
To test their hunch, Shearing and colleagues harvested batteries from disposable e-cigarettes under controlled conditions and assessed them using the same tools and techniques that they use to study batteries in electric vehicles and other devices. They examined the batteries under microscopes and used X-ray tomography to map their internal structure and understand the constituent materials. By repeatedly charging and discharging the batteries, they determined how well the batteries maintained their electrochemical performance over time, finding that they could be recharged “sometimes many hundreds of times,” says Shearing.
“As a bare minimum, the general public needs to be aware of the types of batteries going into these devices and the need to properly dispose of them,” he said. “Manufacturers should provide the ecosystem for reuse and recycling of e-cigarette batteries, and also should be moving towards rechargeable devices as the default.”
Shearing and his team are also researching new, more selective ways to recycle batteries that allow individual components to be recovered without cross-contamination, as well as more sustainable battery chemistries, including post-lithium ion, lithium sulfur, and sodium ion batteries.

In order to address challenges across the entire battery supply chain, scientists should consider batteries’ life cycles when thinking about any of their applications, he said.
“That permeates all the work we do, really, whether it’s a vape battery or whether it’s a battery going into an electric helicopter,” says Shearing. “It’s the same kind of thought process where we need to fully understand the life cycle of a battery device.”
This work was supported by the EPSRC CASE Award; the Faraday Institution; the Department of Science, Innovation and Technology (DSIT); and the Royal Academy of Engineering for the Chair in Emerging Technologies; and the National Physical Laboratory (NPL).

In the past ten years, the percentage of Americans who use medical marijuana has more than doubled as state-level legalization becomes increasingly common. But despite its prevalence as a medication, the full health effects of cannabis remain unknown, especially for specific populations — such as pregnant people — that might be especially at risk of health complications.
Now, in a large study of more than 9,000 pregnant people from across the U.S., researchers at University of Utah Health have found that cannabis exposure during pregnancy is associated with a composite measure of unhealthy pregnancy outcomes, especially low birth weight, and that higher exposure is associated with higher risks.
Compared to most prior studies, this study was larger and measured cannabis exposure more accurately, which allowed researchers to distinguish the effects of cannabis itself from those caused by other correlated health conditions. The research publishes online on December 12 in JAMA.
“Cannabis use is not safe,” says Robert Silver, M.D., professor of obstetrics and gynecology at U of U Health and last author on the study. “It increases the risk of pregnancy complications. If possible, you shouldn’t use cannabis during pregnancy.”
The researchers were driven to answer this question in part by the contradictory answers that many people encounter when trying to learn about the health impacts of cannabis use. “There’s so much information out there — discussion and social media channels and on the Internet — about cannabis use and pregnancy,” explains Torri Metz, M.D., vice chair of research of obstetrics and gynecology at U of U Health and lead author on the study. “I think it’s hard for patients to understand what they should be worried about, if anything.”
Uncovering new risks
Indeed, some previous studies on the topic found no association between cannabis use and pregnancy complications. One hurdle facing such research, Metz says, is that there are “so many differences between baseline characteristics of people who use and don’t use cannabis during pregnancy. There’s different rates of anxiety and depression.” These differences can also impact pregnancy risks, which makes it challenging to figure out the consequences related specifically to cannabis use.

The large study population, including participants from eight medical centers across the U.S., allowed the researchers to address this issue. Being able to compare pregnancy outcomes for so many participants, 610 of which had detectable levels of cannabis exposure, meant that the researchers could statistically untangle the impacts of cannabis use from many other factors, including pre-existing health conditions, nicotine exposure, and socioeconomic status.
The scientists found that cannabis exposure was associated with a 1.5-fold increase in risk: 26% of cannabis-exposed pregnant people experienced an unhealthy pregnancy outcome, versus 17% of non-exposed pregnant people. Higher levels of cannabis exposure over the course of pregnancy were associated with higher risks.
A distinguishing feature of the study was how the researchers measured cannabis exposure. While other studies had asked participants to report their own cannabis use (which has been shown to underestimate the actual rate of use by two or three times), the scientists measured the levels of a metabolic byproduct of cannabis in participants’ urine samples, which gave more accurate measurements of cannabis exposure.
Open questions
To gauge impacts on pregnancy, the researchers looked at an aggregate measure of negative health outcomes, including low birth weight, pregnancy-related high blood pressure, stillbirth, and medically indicated preterm birth. Of these, the association between cannabis use and low birth weight was the strongest. All of these conditions have been linked to reduced function of the placenta, which supplies the growing baby with oxygen and nutrients.
While this type of study can’t determine why cannabis is associated with negative pregnancy outcomes, previous studies in non-human primates have found that long-term cannabis exposure can interfere with blood supply to the placenta. The correlation Metz and her colleagues observed suggests that cannabis may disrupt the human placenta in a similar way.

Silver adds that the greater risk seen at higher levels of exposure is especially concerning given the high amount of THC found in newer cannabis products — products that were barely starting to become available from 2010 to 2014, when the study data was collected. The health impacts of these more concentrated products remain largely unknown.
The researchers urge people who are considering using cannabis while pregnant to have an open conversation with their doctor. While pregnant people may turn to cannabis to alleviate nausea or anxiety, other remedies have been proven to be safe. “There are many, many reasons people use cannabis,” Silver says. “But there may be alternative therapies that can help mitigate the symptoms.”
Silver emphasizes that continued research on the health impacts of cannabis is urgently needed so that patients can make informed decisions about their health. “As long as humans are interested in using this product,” he says, “we ought to assess health effects both good and bad, as accurately as we can, and provide that information for folks.”
The research published as “Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function” and was carried out in collaboration with researchers from ARUP Laboratories, University of California, Irvine, The Ohio State University, Indiana University, Case Western Reserve University, University of Pennsylvania, Columbia University, Eastern Virginia Medical School, and University of Pittsburgh.
Support was provided by the National Institutes of Health and the Center for Clinical and Translational Sciences.

The problem of foodborne metal contamination has taken on new urgency, thanks in part to a 2021 US Congressional Report detailing high levels of metals found in infant food pulled off grocery shelves.?(More recently, high levels of lead were discovered in children’s fruit puree pouches.) Now, two new studies provide information on the correlation between exposure to heavy metals in food and the risk of cancers and other serious health risks. The findings will be presented at the 2023 Society for Risk Analysis Annual Conference.
Food crops can absorb heavy metals from contaminated soil, air, and water. As a result, traces of dangerous heavy metals — lead, arsenic, and cadmium — are found in common foods from rice and cereals to nuts and spinach. Felicia Wu, Michigan State University food scientist and incoming president of the SRA, is leading several investigations to gain a better understanding of the health risks of heavy metal exposure.
She will present the results of two recent studies at the December SRA meeting. The first is a comprehensive evaluation of the health risks associated with dietary exposure to lead, arsenic, and cadmium. The second is a quantitative assessment of the risk of cancer from inorganic arsenic exposure. “Results from these studies have important implications for food safety regulations, public health policies, and consumer awareness” says Wu.
Health risks of dietary exposure to lead, arsenic, and cadmium
In the first study, Wu, working with postdoctoral research fellow Charitha Gamlath and Ph.D. student Patricia Hsu, gathered data on the dietary intake of each metal from various sources such as food and water samples and existing studies and reports. The researchers analyzed the data to determine the strength of the association between dietary exposure and adverse health effects. Both cancer and non-cancer health effects were considered, and the strengths of the links between heavy metal exposure and each effect using Bradford Hill Criteria scores.
Lead is a toxic metal commonly found in old paint, water pipes, and contaminated soil. Food sources of lead include root vegetables like beets. In the study, lead showed moderate to high risk scores for causing lung, kidney, bladder, stomach, and brain cancers. It also showed moderate to high scores for non-cancer risks (hematopoietic, reproductive, neurological, renal, and respiratory effects).
Arsenic is a naturally occurring toxic element that can contaminate drinking water and food — especially in areas with high levels of arsenic in the soil. It can be found in rice, wheat, and leafy green vegetables, among other foods. Arsenic demonstrated moderate to high scores for skin, bladder, lung, kidney, and liver cancers. It also showed moderate to high scores for non-cancer risks (skin lesions, cardiovascular disease, immunological, neurological, reproductive, developmental, and renal effects).

Cadmium is a toxic metal found in nuts, potatoes, seeds, cereal grains, leafy green vegetables, and tobacco smoke. Among its sources in the environment are fertilizers and industrial emissions. In the study, cadmium revealed moderate to high risk scores for prostate, renal, bladder, breast, pancreatic, and endometrial cancers. It also showed moderate to high scores for non-cancer risks (renal, developmental, reproductive, immunological, and neurological effects).
Earlier this year, Wu co-authored a study on cadmium in baby food that was published in Food and Chemical Toxicology. In that paper, the researchers found that babies and young children 6 months to 5 years old are the most highly exposed to cadmium in common foodstuffs. American infants and young children of these age groups who regularly consumed rice, spinach, oats, barley, potatoes, and wheat had mean cadmium exposures exceeding the maximum tolerable intake level set by the Agency for Toxic Substances and Disease Registry (ATSDR).
Arsenic exposure and bladder, lung, and skin cancer cases in the U.S.
In the second study to be presented, Wu and Ph.D. student Rubait Rahman conducted a quantitative cancer risk assessment for different food products in the United States containing inorganic arsenic.
Their preliminary estimates suggest that every year, more than 6,000 additional cases of bladder and lung cancers and over 7,000 cases of skin cancers can be attributed to the consumption of inorganic arsenic in the United States. The researchers also found that certain food products can be associated with higher cancer risk than others. These include rice, wheat, and leafy green vegetables.
For this project, a comprehensive review of scientific literature was conducted to identify relevant studies on inorganic arsenic contamination in various food products and associated cancer risks. Data on arsenic levels in food products were obtained from regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the U.S. Department of Agriculture (USDA). Quantitative cancer risk assessment models were applied to estimate the cancer risk attributable to inorganic arsenic exposure through different food products. These models integrated exposure data, dose-response relationships, and population characteristics to quantify the probability of cancer occurrence.
Assessing the Association between Dietary Exposure to Lead, Arsenic, and Cadmium and Adverse Health Effects: A Comprehensive Evaluation Using Bradford Hill Criteria- Tuesday, December 12
Cancer burden from dietary exposure to inorganic arsenic in the United States: Risk assessment and policy implications- Tuesday, December 12

A team from the UCO’s Nursing Department has determined the presence of two pain biomarkers and their levels in saliva as a tool to diagnose pain,effectively and non-invasively, in people with dementia and communication problems
Pain is an underdiagnosed and undertreated problem in people with dementia, especially if they are in an advanced stage of the disease that prevents them from being able to communicate effectively. Taking into account that the prevalence of pain and dementia increases with age, and that alleviating this ‘silent’ pain in people with impaired verbal communication is difficult, the search for an alternative and complementary pain diagnosis method has been an objective pursued by research and health personnel.
The Nursing Department at the University of Cordoba has been studying pain in the context of neurodegenerative diseases, such as Alzheimer’s disease, for years. Now they have published a study carried out by researchers Vanesa Cantón, Pilar Carrera, and Manuel Rich, in collaboration with the University of Jaén, showing how saliva may be used as an effective and non-invasive pain detection method in these patients.
In their latest work they describe the levels of sTNFR2 (Soluble Tumor Necrosis Factor Receptor 2) and SIgA (immunoglobulin A) pain biomarkers in saliva samples from patients over 65 years of age diagnosed with moderate-advanced stage dementia and an inability to communicate, compared to a control group of people over 65 years of age without dementia. This tool makes it possible to complement observational pain scales and assess them in a simple and non-invasive way, which could make it easier for health personnel and caregivers to ascertain the patient’s situation, and employ the use of the corresponding analgesia, if necessary, thus improving patients’ quality of life.
sTNFR2and sIgA are related to pain through inflammation, and that inflammatory process is related to dementia.
“The fact that we can determine these biomarkers in saliva is very auspicious, since most of the people from whom we have been able to obtain the samples were in a very advanced state, bedridden with advanced dementia, so the less irritating and invasive it is for the patient to obtain the sample, the better,” explained researcher María Pilar Carrera.
This first determination of pain biomarkers in saliva (it had previously been done using blood or plasma) “helps treat an unresolved problem in patients with dementia, which we consider the fifth vital sign: pain,” pointed out Vanesa Cantón, the article’s lead author.
The results of the test described the levels of these biomarkers, with a decrease in sTNFR2in patients with dementia compared to the control group, which “indicates how inflammation is modulated,” In the case of sIgA, the team observed “an increase in this immunoglobulin in people with dementia, showing that there is an alteration of the immune system response.” Thus, they establish the usefulness of these biomarkers to evaluate the development of the pain process throughout the evolution of the disease and during its moderate-advanced stage.
Until now the usual way to detect pain in patients with reduced communication was using the PAINAD scale, a methodology of pain observation in patients with advanced dementia, recently validated in Spanish by this same research team and based on five behavioral indicators: breathing, vocalization, facial expression, body language and consolability. The saliva biomarkers proposed can now be corroborated with the data obtained through the scale, thus confirming their efficacy.
“This method is very important from the point of view of the quality of life of patients with a disease that has no cure,” the researchers noted. Testing it with a larger sample and in a specific environment, such as a nursing home, could be the next step on the way to implementing the use of this tool.

Most patients with Type 2 diabetes will end up needing to add a second-line medication after metformin — the go-to primary drug for glucose management — to control their blood sugar levels. But adherence to these second-line drugs can be hit or miss, reports a new Northwestern Medicine study.
When patients discontinue their medication, switch to a different drug or intensify their treatment (either via an increased dose, adding a third medication or starting insulin), it wastes the doctor and patient’s time, costs the health system unnecessary expense and, in the case of discontinuation, can result in a patient not fully treating their Type 2 diabetes.
The study will be published Dec. 12 in the American Journal of Managed Care.
The study of more than 82,000 patients between 2014 and 2017 found that within one year of their initial prescription, nearly two-thirds of patients either discontinued their medication, switched to a different medication class or intensified their treatment.
The scientists analyzed five non-insulin classes of diabetes medications. In four of the five classes, 38% of patients discontinued their medication. But among patients prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs), half (50%) discontinued treatment.
“Discontinuation is bad. It is common in all five types of medications, but we see significantly more in those prescribed the GLP-1 RAs,” said corresponding author David Liss, research associate professor of general internal medicine at Northwestern University Feinberg School of Medicine.
“Presumably, the doctor is saying, ‘You need to start a new medication to control your Type 2 diabetes,’ and then within a year, half of them just stop and don’t start another one, and that’s not a good thing.”
Prior studies have shown that treatment discontinuation is common for Type 2 diabetes medications, but this is the first large American study to show such high discontinuation rates in second-line medications, Liss said.

“Our findings highlight the need for new prescribing approaches and to better understand the barriers patients face when taking these medications, to ultimately reduce wasting patients’ time, clinicians’ time and the health system’s money,” Liss said.
Association with gastrointestinal side effects
While the scientists did not have data on reasons why patients discontinued treatment, the particularly high discontinuation rate for GLP-1 RAs may have been due to adverse gastrointestinal side effects — such as nausea, vomiting and diarrhea — which have been observed in patients who take these medications for diabetes control and for weight loss, Liss said.
Originally approved by the U.S. Food and Drug Administration (FDA) for treating Type 2 diabetes, GLP-1 RAs (with brand names like Ozempic and Wegovy) are now used for weight loss, too. “We know there are gastrointestinal side effects for these drugs that are currently in the news, both for patients with diabetes and patients attempting to lose weight,” Liss said.
What happens after discontinuation?
For many patients in this study, discontinuing a second-line diabetes medication wouldn’t immediately lead to hyperglycemia (high blood sugar) symptoms or medical emergencies, Liss said.

“But discontinuation still puts these patients at greater risk for downstream hospitalizations related to diabetes,” Liss added.
Endocrinologist versus internal medicine prescribers
Discontinuation risk was lower and intensification risk was higher when an endocrinologist prescribed the medication, compared to when a family medicine or internal medicine physician prescribed the second-line drugs, the study found. Liss said this difference could be because endocrinologists had particular expertise in the newer classes of diabetes drugs, enhancing their ability to discuss the pros and cons of medications when making prescribing decisions with patients.
Importance of follow-ups on new drugs
The study retrospectively analyzed patients’ health insurance claims data, meaning the scientists could identify when a patient had been prescribed a medication; if the care provider switched their medication to a new class; or if they increased their dose.
The scientists assumed that patients who experienced a treatment switch or intensification did so after talking with their doctor. But the scientists suspect that many patients made the decision to discontinue their medication without having talked to a doctor.
“Our results may represent a ‘wake-up call’ for clinicians that many of their patients were not taking the medicines that were prescribed,” Liss said. “While we don’t know if providers were aware of the discontinuation events observed in this study, our results highlight the need for ongoing communication between patients and prescribers over time — around medication benefits, side effects and costs — not just at the time of prescribing.”
Other Northwestern study authors include Dr. Matthew O’Brien, Cassandra Aikman, Dr. Amisha Wallia, Andrew Cooper and Dr. Ronald Ackermann.
Funding for the study was provided by a grant from the UnitedHealth Group, which also gave the researchers access to the claims data analyzed in the study.

Glioblastoma is one of the most treatment-resistant cancers, with those diagnosed surviving for less than two years.
In a new study in NPJ Genomic Medicine, researchers at the University of Notre Dame have found that a largely understudied cell could offer new insight into how the aggressive, primary brain cancer is able to resist immunotherapy.
“A decade ago, we didn’t even know perivascular fibroblasts existed within the brain, and not just in the lining of the skull,” said Meenal Datta, assistant professor of aerospace and mechanical engineering at Notre Dame and senior author on the study. “My lab’s expertise is examining tumors from an engineering and systems-based approach and looking at the novel mechanical features in rare cancers that may have been understudied or overlooked.”
Using standard bioinformatics and newer AI-based approaches, Datta’s TIME Lab began analyzing different genes expressed in the tumor microenvironment related to the extracellular matrix — or the scaffolding cells create to support future cell adhesion, migration, proliferation and differentiation — and other various cell types. What they found was a surprising, fairly new cell type: perivascular fibroblasts. These fibroblasts are typically found in the blood vessels of a healthy brain and deposit collagen to maintain the structural integrity and functionality of brain vessels.
“It was a serendipitous discovery,” said Maksym Zarodniuk, graduate student in the TIME Lab and the bioengineering doctorate program, and first author on the study. “We started in a completely different direction and stumbled upon this population of cells by using a combination of both bulk and single-cell RNA sequencing analyses of patient tumors.”
In their data, researchers were able to identify two groups of patients: those with a higher proportion of perivascular fibroblasts and those with significantly less. They found that brain cancer patients with more perivascular fibroblasts in their tumors were more likely to respond poorly to immunotherapies and have poor survival outcomes.
When exploring how this is possible, the researchers found that perivascular fibroblasts support the creation of an immunosuppressive tumor microenvironment, allowing the cancer to better evade the immune system. The fibroblasts may also help the cancer resist therapies — such as chemotherapy that targets dividing cells — by promoting stem-like cancer cells that rarely divide, which are believed to be a major source of tumor relapse and metastasis.

“Moving forward, we want to do new experiments to confirm what we found in this paper and provide some good ground to start thinking about how to improve response to immunotherapy,” Zarodniuk said.
Because perivascular fibroblasts are a part of a healthy brain’s vasculature, Datta believes that these cells are breaking off and getting close to or infiltrating the glioblastoma tumor. However, instead of supporting healthy brain function, these fibroblasts are getting reprogrammed and helping the tumor instead.
“Most people think about the brain as being very soft, with soft cells and a soft matrix. But by putting down these fibroblasts and making these very fibrous proteins, it gives us an entirely different perspective on the structure of the brain and how it can be taken advantage of by cancer cells originating in the same organ,” Datta said.
In addition to Datta and Zarodniuk, other Notre Dame collaborators include Jun Li, professor of applied and computational mathematics and statistics, who developed deep learning algorithms in support of this work; Xin Lu, the John M. and Mary Jo Boler Collegiate Associate Professor of Biological Sciences at Notre Dame; and Xander Steele, undergraduate student in the TIME Lab and a Grand Challenges Scholar.
Datta is an affiliated member of Notre Dame’s Berthiaume Institute for Precision Health, Eck Institute for Global Health, Harper Cancer Research Institute, Lucy Family Institute for Data and Society, NDnano and Warren Center for Drug Discovery. Datta is an assistant professor in the following doctorate programs: aerospace and mechancial engineering, bioengineering and materials science and engineering.
This work was funded by the National Cancer Institute.