Publisher Health

Moles and melanomas are both skin tumors that come from the same cell called melanocytes. The difference is that moles are usually harmless, while melanomas are cancerous and often deadly without treatment. In a study published today in eLife Magazine, Robert Judson-Torres, PhD, Huntsman Cancer Institute (HCI) researcher and University of Utah (U of U) assistant professor of dermatology and oncological sciences, explains how common moles and melanomas form and why moles can change into melanoma.
Melanocytes are cells that give color to the skin to protect it from the sun’s rays. Specific changes to the DNA sequence of melanocytes, called BRAF gene mutations, are found in over 75% of moles. The same change is also found in 50% of melanomas and is common in cancers like colon and lung. It was thought that when melanocytes only have the BRAFV600E mutation the cell stops dividing, resulting in a mole. When melanocytes have other mutations with BRAFV600E, they divide uncontrollably, turning into melanoma. This model is called “oncogene-induced senescence.”
“A number of studies have challenged this model in recent years,” says Judson-Torres. “These studies have provided excellent data to suggest that the oncogene-induced senescence model does not explain mole formation but what they have all lacked is an alternative explanation — which has remained elusive.”
With help from collaborators across HCI and the University of California San Francisco, the study team took moles and melanomas donated by patients and used transcriptomic profiling and digital holographic cytometry. Transcriptomic profiling lets researchers determine molecular differences between moles and melanomas. Digital holographic cytometry helps researchers track changes in human cells.
“We discovered a new molecular mechanism that explains how moles form, how melanomas form, and why moles sometimes become melanomas,” says Judson-Torres.
The study shows melanocytes that turn into melanoma do not need to have additional mutations but are actually affected by environmental signaling, when cells receive signals from the environment in the skin around them that give them direction. Melanocytes express genes in different environments, telling them to either divide uncontrollably or stop dividing altogether.
“Origins of melanoma being dependent on environmental signals gives a new outlook in prevention and treatment,” says Judson-Torres. “It also plays a role in trying to combat melanoma by preventing and targeting genetic mutations. We might also be able to combat melanoma by changing the environment.”
These findings create a foundation for researching potential melanoma biomarkers, allowing doctors to detect cancerous changes in the blood at earlier stages. The researchers are also interested in using these data to better understand potential topical agents to reduce the risk of melanoma, delay development, or stop recurrence, and to detect melanoma early.
The study was funded by National Institutes of Health/National Cancer Institute including P30 CA042014, 5 For The Fight, and Huntsman Cancer Foundation. Judson-Torres recognizes critical contributions by other HCI scientists, including Rachel Belote, PhD; Sheri Holmen, PhD; Matthew VanBrocklin, PhD; David Lum, PhD; Doug Grossman, MD, PhD; and University of California San Francisco scientists Andrew McNeal, PhD; Maria Wei, MD, PhD; and Ursula Lang, MD, PhD.
Story Source:
Materials provided by Huntsman Cancer Institute. Note: Content may be edited for style and length.

One in five individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms, according to a new study publishing Nov. 23 in PLOS Medicine by Silvan Licher of Erasmus University Medical Center Rotterdam, the Netherlands, and colleagues.
During the COVID-19 pandemic, consultations in both primary and specialist care declined compared to pre-pandemic levels. It is unclear to what extent healthcare avoidance by the general population contributed to these declines. In the new study, researchers sent out a paper questionnaire to 8,732 participants of the Rotterdam Study, a cohort study designed to investigate chronic diseases in mid to late-life, covering several COVID-19 related topics, including healthcare avoidance. 73% of participants responded between April and July 2020 and the final population for the study was 5,656 individuals residing in the same district in Rotterdam, the Netherlands.
About one in five (20.2%) of participants reported having avoided healthcare during the pandemic. Of those, 414 participants (36.3% of avoiders) reported symptoms that potentially warranted urgent medical attention, including limb weakness (13.6%), palpitations (10.8%) and chest pain (10.2%). However, there was no data available on the severity of symptoms. Groups most likely to have avoided healthcare included females (adjusted odds ratio (OR) 1.58, 95% confidence interval (CI) 1.38-1.82), those with poor self-appreciated health (per level decrease 2.00, 95% CI 1.80?2.22), and those with high levels of depression (per point increase 1.13, 95% CI 1.11-1.14) and anxiety (per point increase 1.16, 95% CI 1.14-1.18). Lower educational level, older age, unemployment, smoking and concern about contracting COVID-19 were also associated with healthcare avoidance.
“Findings of our study suggest that healthcare avoidance during COVID-19 may be prevalent amongst those who are in greater need of it in the population, such as older individuals, those with low perceived health and those who report symptoms of poor mental health,” the authors say. “These findings call for population-wide campaigns urging individuals who are most prone to avoid healthcare to reach out to their primary care physician or medical specialist to report both alarming and seemingly insignificant symptoms.”
“One in five avoided healthcare during COVID-19 lockdown, often with alarming symptoms like chest pain or limb weakness,” Licher adds. “Vulnerable citizens were mainly affected, emphasising the urgent need for targeted public education.”
Story Source:
Materials provided by PLOS. Note: Content may be edited for style and length.

When a person experiences a trauma that leads to significant bleeding, the first few minutes are critical. It’s important that they receive intravenous medication quickly to control the bleeding, but delivering the medication at the right rate can prove challenging. Slower infusions can cause fewer negative reactions, but the medication might not work fast enough, particularly in the case of a serious trauma.
Four UMBC researchers have developed a unique way of modifying the surfaces of nanoparticles within these life-saving medications to provide infusions that can be delivered more quickly, but with a reduced risk of negative reactions. Infusion reactions can cause a range of symptoms, such as rashes and inflammatory responses. This can include anaphylaxis, a life-threatening respiratory failure. Up until this point, the seriousness of these reactions has limited the use of promising nanomedicines, and reducing the likelihood of adverse reactions could be game-changing.
The core of the issue
In a paper recently published in Nano Letters, Erin Lavik, professor of chemical, biochemical, and environmental engineering; Chuck Bieberich, professor of biological sciences; Nuzhat Maisha, Ph.D. ’21, chemical engineering; and Michael Rubenstein, M.S. ’14, Ph.D. ’22, biological sciences, discuss their novel approach to the research. They focused on the core material of the nanoparticles delivered to patients.
“We found that using a polyurethane core reduced the markers associated with infusion reactions,” explains Lavik, who is also the associate dean for research and faculty development in UMBC’s College of Engineering and Information Technology.
Currently, 7% of people experience infusion reactions, the authors note in their paper. “These reactions…limit the treatments available in a substantial portion of patients,” they explain.
“We, like most of the field, have spent a lot of time trying to modify the surfaces of nanoparticles to modulate the reaction,” says Lavik. She shares that while that approach does help to a degree, going a step further by changing the core material appears to have a greater impact.
The research conducted by Lavik, Bieberich, and their colleagues lays the groundwork for future testing of preclinical models using nanocapsules to stop internal bleeding. Lavik explains that collaboration was an important element of this work.
Story Source:
Materials provided by University of Maryland Baltimore County. Original written by Megan Hanks. Note: Content may be edited for style and length.

A team of scientists have identified coronaviruses closely related to SARS-CoV-2 from two bats sampled in Cambodia more than a decade ago. The discovery described in the journal Nature Communications, along with the recent detection of the closest ancestors of SARS-CoV-2 known to date in cave-dwelling bats in Laos, indicates that SARS-CoV-2-related viruses that cause COVID-19 have a much wider geographic distribution than previously reported and further supports the hypothesis that the pandemic originated via spillover of a bat-borne virus.
Scientists used metagenomic sequencing to identify the nearly identical viruses in two Shamel’s horseshoe bats (Rhinolophus shameli) originally sampled in 2010. The finding suggests that SARS-CoV-2 related viruses likely circulate via multiple Rhinolophus species.
The authors state that the current understanding of the geographic distribution of the SARS-CoV and SARS-CoV-2 lineages possibly reflects a lack of sampling in Southeast Asia, or at least across the Greater Mekong Subregion, which encompasses Myanmar, Laos, Thailand, Cambodia and Vietnam, as well as the Yunnan and Guanxi provinces of China.
Along with bats, the authors note that pangolins, as well as certain species of cat, civet, and weasels found in this region are readily susceptible to SARS-CoV-2 infection, and might represent intermediary hosts for transmission to humans. In 2020, viruses of the SARS-CoV-2 sublineage, one exhibiting strong sequence similarity to SARS-CoV-2 in the receptor biding domain, were detected in distinct groups of pangolins seized during anti-smuggling operations in southeast China. While it is not possible to know where these animals became infected, it is important to note that the natural geographic range of the pangolin species involved (Manis javanica) also corresponds to Southeast Asia and not China.
Said Dr. Lucy Keatts of the Wildlife Conservation Society’s (WCS) Health Program and a co-author of the study: “These findings underscore the importance of increased region-wide investment in bridging capacity for sustainable surveillance of pathogens in wildlife, through initiatives such as WildHealthNet. Southeast Asia hosts a high diversity of wildlife and an extensive wildlife trade that puts humans in direct contact with wild hosts of SARS-like coronaviruses. The region is undergoing dramatic land-use changes such as infrastructure development, urban development, and agricultural expansion that can increase contacts between bats, other wildlife, domestic animals and humans. Continued and expanded surveillance of bats and other key wild animals in Southeast Asia is a crucial component of future pandemic preparedness and prevention.”
Story Source:
Materials provided by Wildlife Conservation Society. Note: Content may be edited for style and length.

In new research, Aric N. Rogers, Ph.D., who studies the cellular and molecular mechanisms of aging at the MDI Biological Laboratory in Bar Harbor, Maine, has discovered that muscle may be a protected tissue under conditions of dietary restriction, or DR.
Dietary restriction, in which calories are restricted without malnutrition, is one of the most robust anti-aging interventions. When confronted with a scarcity of nutrients, an organism conserves resources by lowering the translation, or production, of proteins, which is one of the most energetically expensive processes in the cell. Proteins serve as the building blocks for tissues and organs and perform vital physiological functions.
The conservation of cellular resources through reduced protein translation confers an evolutionary benefit by allowing the organism to survive so that it can reproduce when food becomes plentiful. But it comes at the cost of a reduction in anabolic function, or growth and reproduction.
Working in the tiny nematode worm, C. elegans, Rogers sought to identify the effects of genetically suppressing protein translation in various tissues. While skin, nerve and reproductive tissue responded as expected with enhanced survival and decreased growth and reproduction, the effect was the opposite in muscle: instead of being suppressed, growth and reproduction were accelerated.
C. elegans is a popular model in aging research because it shares many of its genes with humans, including those governing nutrient-sensing pathways, and because its short lifespan allows scientists to rapidly assess the effects of anti-aging interventions.
The role of foraging
Rogers theorizes that muscle may be protected under conditions of nutrient scarcity in order to support the ability of an organism to forage for food.

Aspirin use is associated with a 26% raised risk of heart failure in people with at least one predisposing factor for the condition. That’s the finding of a study published today in ESC Heart Failure, a journal of the European Society of Cardiology (ESC).1 Predisposing factors included smoking, obesity, high blood pressure, high cholesterol, diabetes, and cardiovascular disease.
“This is the first study to report that among individuals with a least one risk factor for heart failure, those taking aspirin were more likely to subsequently develop the condition than those not using the medication,” said study author Dr. Blerim Mujaj of the University of Freiburg, Germany. “While the findings require confirmation, they do indicate that the potential link between aspirin and heart failure needs to be clarified.”
The influence of aspirin on heart failure is controversial. This study aimed to evaluate its relationship with heart failure incidence in people with and without heart disease and assess whether using the drug is related to a new heart failure diagnosis in those at risk.
The analysis included 30,827 individuals at risk for developing heart failure who were enrolled from Western Europe and the US into the HOMAGE study. “At risk” was defined as one or more of the following: smoking, obesity, high blood pressure, high cholesterol, diabetes and cardiovascular disease. Participants were aged 40 years and above and free of heart failure at baseline. Aspirin use was recorded at enrolment and participants were classified as users or non-users. Participants were followed-up for the first incidence of fatal or non-fatal heart failure requiring hospitalisation.
The average age of participants was 67 years and 34% were women. At baseline, a total of 7,698 participants (25%) were taking aspirin. During the 5.3-year follow-up, 1,330 participants developed heart failure.
The investigators assessed the association between aspirin use and incident heart failure after adjusting for sex, age, body mass index, smoking, alcohol use, blood pressure, heart rate, blood cholesterol, creatinine, hypertension, diabetes, cardiovascular disease, and treatment with renin-angiotensin-aldosterone-system inhibitors, calcium channel blockers, diuretics, beta-blockers and lipid-lowering drugs. Taking aspirin was independently associated with a 26% raised risk of a new heart failure diagnosis.
To check the consistency of the results, the researchers repeated the analysis after matching aspirin users and non-users for heart failure risk factors. In this matched analysis, aspirin was associated with a 26% raised risk of a new heart failure diagnosis. To check the results further, the analysis was repeated after excluding patients with a history of cardiovascular disease. In 22,690 participants (74%) free of cardiovascular disease, aspirin use was associated with a 27% increased risk of incident heart failure.
Dr. Mujaj said: “This was the first large study to investigate the relationship between aspirin use and incident heart failure in individuals with and without heart disease and at least one risk factor. Aspirin is commonly used — in our study one in four participants were taking the medication. In this population, aspirin use was associated with incident heart failure, independent of other risk factors.”
He concluded: “Large multinational randomised trials in adults at risk for heart failure are needed to verify these results. Until then, our observations suggest that aspirin should be prescribed with caution in those with heart failure or with risk factors for the condition.”
Story Source:
Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.

Good news for those of us who can’t face the day without their morning flat white: a long-term study has revealed drinking higher amounts of coffee may make you less likely to develop Alzheimer’s disease.
As part of the Australian Imaging, Biomarkers and Lifestyle Study of ageing, researchers from Edith Cowan University (ECU) investigated whether coffee intake affected the rate of cognitive decline of more than 200 Australians over a decade.
Lead investigator Dr Samantha Gardener said results showed an association between coffee and several important markers related to Alzheimer’s disease.
“We found participants with no memory impairments and with higher coffee consumption at the start of the study had lower risk of transitioning to mild cognitive impairment — which often precedes Alzheimer’s disease — or developing Alzheimer’s disease over the course of the study,” she said.
Drinking more coffee gave positive results in relation to certain domains of cognitive function, specifically executive function which includes planning, self-control, and attention.
Higher coffee intake also seemed to be linked to slowing the accumulation of the amyloid protein in the brain, a key factor in the development of Alzheimer’s disease.

A new “image analysis pipeline” is giving scientists rapid new insight into how disease or injury have changed the body, down to the individual cell.
It’s called TDAExplore, which takes the detailed imaging provided by microscopy, pairs it with a hot area of mathematics called topology, which provides insight on how things are arranged, and the analytical power of artificial intelligence to give, for example, a new perspective on changes in a cell resulting from ALS and where in the cell they happen, says Dr. Eric Vitriol, cell biologist and neuroscientist at the Medical College of Georgia.
It is an “accessible, powerful option” for using a personal computer to generate quantitative — measurable and consequently objective — information from microscopic images that likely could be applied as well to other standard imaging techniques like X-rays and PET scans, they report in the journal Patterns.
“We think this is exciting progress into using computers to give us new information about how image sets are different from each other,” Vitriol says. “What are the actual biological changes that are happening, including ones that I might not be able to see, because they are too minute, or because I have some kind of bias about where I should be looking.”
At least in the analyzing data department, computers have our brains beat, the neuroscientist says, not just in their objectivity but in the amount of data they can assess. Computer vision, which enables computers to pull information from digital images, is a type of machine learning that has been around for decades, so he and his colleague and fellow corresponding author Dr. Peter Bubenik, a mathematician at the University of Florida and an expert on topological data analysis, decided to partner the detail of microscopy with the science of topology and the analytical might of AI. Topology and Bubenik were key, Vitriol says.
Topology is “perfect” for image analysis because images consist of patterns, of objects arranged in space, he says, and topological data analysis (the TDA in TDAExplore) helps the computer also recognize the lay of the land, in this case where actin — a protein and essential building block of the fibers, or filaments, that help give cells shape and movement — has moved or changed density. It’s an efficient system, that instead of taking literally hundreds of images to train the computer how to recognize and classify them, it can learn on 20 to 25 images.

Since they hit the market, e-cigarettes have been touted as a safe alternative to tobacco cigarettes for adult smokers. When research began to suggest otherwise, many questioned whether smoking was still to blame for adverse effects, since most vapers are either “dual users” who also smoke cigarettes or have a prior history of smoking.
Now, a team of researchers at the Keck School of Medicine of USC has demonstrated that — independent of the effects of prior smoking — using e-cigarettes is linked to adverse biological changes that can cause disease. The study, published in Scientific Reports, revealed that vapers experience a similar pattern of changes to gene regulation as smokers do, although the changes are more extensive in people who smoke.
“Our study, for the first time, investigates the biological effects of vaping in adult e-cigarette users, while simultaneously accounting for their past smoking exposure,” said Ahmad Besaratinia, PhD, corresponding author and professor of research population and public health sciences at the Keck School of Medicine. “Our data indicate that vaping, much like smoking, is associated with dysregulation of mitochondrial genes and disruption of molecular pathways involved in immunity and the inflammatory response, which govern health versus disease state.”
Isolating the effects of vaping from smoking
The researchers recruited a diverse group of 82 healthy adults and separated them into three categories: current vapers, with and without a prior history of smoking; people who exclusively smoke cigarettes; and a control group of never-smokers and never-vapers. They conducted comprehensive in-person interviews to get a detailed vaping and smoking history from each participant. The team verified the histories by performing biochemical analyses on the participants’ blood to measure the concentration of cotinine, a breakdown product of nicotine.
Using next generation sequencing and bioinformatic data analysis, researchers then conducted a genome-wide search for changes in gene regulation in the blood cells of each of the participants. When the normal regulation of genes is disrupted and genes become dysregulated, that dysregulation can interfere with gene function, leading to disease.

Shigella, a bacterial pathogen that causes dysentery and is the leading cause of childhood diarrheal diseases, inserts a pore called a translocon into an infected person’s intestinal cells and then injects bacterial proteins into the cells. There, the proteins hijack the cells’ machinery to help Shigella multiply. In a study published in mBio, a team at Massachusetts General Hospital (MGH) has uncovered important details about Shigella’s translocon, which may help researchers develop an effective strategy to block this critical component of infection.
“Shigella infects our gut by manipulating our intestinal cells and tricking them into letting the Shigella inside. In fact, there are many bacterial pathogens that use this same, or similar, mechanism to infect us,” says lead author Poyin Chen, PhD, a postdoctoral fellow at MGH. “This translocon pore is essentially the gateway through which bacterial proteins get pumped into our cells. We know that this structure is made of two proteins — IpaB and IpaC — but what we don’t know is how these proteins fit together to make this pore.”
When the investigators used protein mapping techniques to look closely at translocons when they were embedded in cell membranes, they were able to see which of the two proteins — specifically IpaB — makes up the inner ring of the pore. “If you think of the translocon pore as a donut, this would be the walls of the donut hole. This finding is important because this is the part of the translocon pore that directly interacts with bacterial proteins as they are injected into our cells,” explains Chen. “With the findings from this study, we can begin to understand if this pore acts as a slippery tube that bacterial proteins travel through or if the translocon pore can control the flow of bacterial proteins into our cells.”
Such details may help investigators target the translocon and block the entry of Shigella proteins into cells. “For something that is so essential to establishing infection, we know terribly little of how it’s made and how it works,” says Chen. “As we gain a better understanding of its parts, we will be able to approach the structure as a whole and maybe even find ways to neutralize the function of this structure to prevent infection before it can begin.”
Co-authors include Brian C. Russo, Jeffrey K. Duncan-Lowey, Natasha Bitar, Keith Egger and Marcia B. Goldberg.
This work has been supported by the National Institutes of Health, the Massachusetts General Hospital Executive Committee on Research Tosteson Award, and the Charles A. King Trust Postdoctoral Research Fellowship Program.
Story Source:
Materials provided by Massachusetts General Hospital. Note: Content may be edited for style and length.