Publisher Health

Although human skin heals from injuries and wounds, many of us have scars that are left behind. Scar formation happens in adult mammals because skin regeneration does not fully occur. This poses a challenge to physicians who wish to conduct surgeries without scars appearing afterwards. In a newly published article in Biomedicines, a team led by researchers at the University of Tsukuba investigated the use of the adult newt, Cynops pyrrhogaster, as a model system for studying scarless wound healing for technology development in surgical and cosmetic medicine.
After an injury occurs, the epidermis, which is the outer layer of the skin, can grow and migrate to fill in the wound. This is known as re-epithelialization. Although this takes place, the original skin color and texture is sometimes not retained, leading to the appearance of what we know as a scar. Processes called granulation and dermal fibrosis underpin scar formation, making them a focus for scientists aiming to minimize scarring following clinical procedures. Amphibians have been used as animal models for studying this, because they do not scar prior to metamorphosis. However, it is not clear what happens to fully mature amphibian skin.
“We chose to examine the adult Japanese fire-bellied newt, which is a type of salamander that is well understood on the genetic level,” explains Dr. Tatsuyuki Ishii, lead author of the study. “We know adult newts are capable of complicated tissue, organ, and limb regeneration. Despite that, their ability to regenerate skin has not been scientifically demonstrated.”
The team excised a small piece of skin from various body parts of adult newts, including the head, trunk, limbs, and abdomen. They periodically observed the skin healing and regeneration progression for up to two years, making note of re-epithelialization and dermal fibrosis, as well as recovery of texture, appendage, and color.
“Interestingly, we found that the adult newts could successfully and fully regenerate their skin at each part of the body that we examined,” describes Professor Chikafumi Chiba, senior author. “Re-epithelialization occurred at all locations, while no dermal fibrosis was observed at all.”
However, the original color pattern of the dorsal-lateral and ventral skin was not restored. Because humans do not have such color patterns, the researchers believed this to be a newt-specific issue. Thus, they concluded that Cynops pyrrhogaster could be a perfect model system for investigating skin regeneration and scar formation in humans.
The team also further studied skin regeneration in these newts at the morphological and molecular level. The wounds tended to heal within only a few days, while skin regeneration took up to two years to complete. Inflammatory gene markers were only briefly expressed during wound healing.
“Dermal fibrosis is often characterized by prolonged inflammation at the wound site,” explains Dr. Ishii. “Scar-free skin occurred in the newts through rapid re-epithelialization and skipping of granulation and dermal fibrosis.”
Overall, these findings will be crucial for future studies in humans focusing on efforts to prevent scarring in human skin following various medical procedures.
Story Source:
Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

A trial by the University of Eastern Finland found that taking a much higher dose of vitamin D than recommended for five years did not affect total mortality or the incidence of cardiovascular disease or cancer in older men and women.
In population studies, low levels of vitamin D in the body have been linked to an increased risk of many chronic diseases as well as premature death. However, it cannot be directly deduced from such observational studies whether the use of vitamin D supplementation can reduce the risk of disease or death. The early 2010s saw the commencement of large-scale vitamin D trials in several countries examining the effects of higher than recommended doses of vitamin D on the risk of developing diseases. One of these was the Finnish Vitamin D Trial (FIND) conducted at the University of Eastern Finland in 2012-2018.
In the FIND trial, 2,495 participants (men 60 years or older and women 65 years or older) were randomised for five years to either the placebo group or the groups that received either 40 or 80 micrograms (1600 or 3200 IU) of vitamin D3 per day. All participants were free of cardiovascular disease and cancer at the start of the trial and were allowed to use their own vitamin D supplement of up to 20 micrograms (800 IU) per day (the recommended intake for this age group at the time when the trial was started). At the beginning and during the trial, research forms were used to collect comprehensive information from the subjects on lifestyle, nutrition, risk factors for and the incidence of diseases. Information on the incidence of diseases and on deaths was also obtained from national health registers. Approximately one fifth of the randomly selected subjects underwent more detailed examinations and provided blood samples.
Majority were not deficient in vitamin D at the start of the trial
During the five years of the trial, 119 participants developed cardiovascular disease, 129 subjects were diagnosed with cancer and 19 died. There was no statistically significant difference in the number of events between the groups. The vitamin D doses proved to be safe as no differences in side effects were observed between the groups. In the sub-sample examined in more detail, the mean blood vitamin D (calcidiol) concentration, was 75 nmol/L (30 ng/mL) at baseline. After one year, the mean calcidiol concentration was 100 nmol/L (40 ng/mL) in the group taking 40 micrograms of vitamin D per day and 120 nmol/L (48 ng/mL) in the group taking 80 micrograms of vitamin D per day. There was no significant change in the calcidiol concentrations in the placebo group. Only 9% of subjects had low vitamin D levels at baseline, i.e., they had a blood calcidiol concentration of less than 50 nmol/L (20 ng/mL).
The findings of the FIND trial are well in line with other similar studies that have shown that taking higher doses of vitamin D than recommended for many years does not have a significant effect on the risk of developing cardiovascular disease or cancer if the body’s vitamin D status is already adequate. In Finland, the average vitamin D intake of the population has increased since the early 2000s due to, among other things, the vitamin D supplementation of vegetable oil spreads and liquid dairy products as well as the increased use of vitamin D supplements. Securing one’s vitamin D intake with vitamin D supplements is still recommended, especially during the winter, if the diet is low in sources of vitamin D, such as fish or vitamin D-fortified foods. In Finland, vitamin D supplementation of 10 micrograms per day (400 IU) is recommended for the adult population; the recommendation is 20 micrograms per day (800 IU) for those aged 75 and over. However, the study does not support the use of large vitamin D doses for prevention of cardiovascular diseases or cancer.
In addition to these main findings, the FIND trial will provide comprehensive reports on the effects of vitamin D supplementation on, among other things, type 2 diabetes, fractures and falls, mood changes, infections, pain conditions, and other outcomes.
Story Source:
Materials provided by University of Eastern Finland. Note: Content may be edited for style and length.

Scientists have found evidence that a type of the antibiotic resistant superbug MRSA arose in nature long before the use of antibiotics in humans and livestock, which has traditionally been blamed for its emergence.
Hedgehogs carry a fungus and a bacteria on their skin, and the two are locked in a battle for survival. The fungus secretes antibiotics to kill the bacteria, but in response the bacteria has evolved antibiotic resistance — becoming Methicillin-resistant Staphylococcus aureus, or MRSA. Up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA, which causes 1 in 200 of all MRSA infections in humans. Natural biological processes, not antibiotic use, drove the initial emergence of this superbug on hedgehogs around 200 years ago.
Staphylococcus aureus first developed resistance to the antibiotic methicillin around 200 years ago, according to a large international collaboration including the University of Cambridge, the Wellcome Sanger Institute, Denmark’s Serum Statens Institut and the Royal Botanic Gardens, Kew, which has traced the genetic history of the bacteria.
They were investigating the surprising discovery — from hedgehog surveys from Denmark and Sweden — that up to 60% of hedgehogs carry a type of MRSA called mecC-MRSA. The new study also found high levels of MRSA in swabs taken from hedgehogs across their range in Europe and New Zealand.
The study is published today in the journal Nature.
The researchers believe that antibiotic resistance evolved in Staphylococcus aureus as an adaptation to having to exist side-by-side on the skin of hedgehogs with the fungus Trichophyton erinacei, which produces its own antibiotics.

The school closures in spring 2020 had a negative effect on the health and well-being of many young people. But homeschooling also had a positive flipside: Thanks to sleeping longer in the morning, many teenagers reported improved health and health-related quality of life. The study authors from the University of Zurich therefore believe school days should begin later in the morning.
The first wave of the Covid-19 pandemic led to the closure of all schools nationwide from 13 March to 6 June 2020. According to multiple studies, symptoms of depression and anxiety among young people increased during this time, while satisfaction and quality of life decreased. The schoolchildren were also less physically active and spent more time sitting in front of screens.
Now, a study by the University of Zurich (UZH) has shown that the homeschooling phase also had a positive effect on the health and well-being of many teenagers. “The students got about 75 minutes more sleep per day during the lockdown. At the same time, their health-related quality of life improved significantly and their consumption of alcohol and caffeine went down,” says the study’s co-leader Oskar Jenni, UZH professor of developmental pediatrics. Because they no longer had to travel to school, they were able to get up later.
More sleep on school days improves young people’s health-related quality of life
The researchers conducted an online survey with 3,664 high school students in the Canton of Zurich during the lockdown, asking about their sleep patterns and quality of life. They then compared the answers with a survey from 2017 with 5,308 young participants. The results showed that during the three months in which the schools were closed, the adolescents got up around 90 minutes later on school days, but went to bed only 15 minutes later on average — meaning their total amount of sleep increased by about 75 minutes a day. On weekends, there was little difference in the sleep times of the two groups.
The students in the lockdown group rated their health-related quality of life higher, and the amount of alcohol and caffeine they reported consuming was less than the pre-pandemic group. “Although the lockdown clearly led to worse health and well-being for many young people, our findings reveal an upside of the school closures which has received little attention until now,” says Jenni.
Unique opportunity to investigate the effect of later school starting times
Sleep deficits in adolescents can lead to general tiredness, anxiety and physical ailments. These in turn have a detrimental effect on cognitive functions such as concentration, memory and attention, making it significantly harder to function in everyday life. The early start of the school day in Switzerland conflicts with the natural, biologically determined sleeping habits of teenagers. Because they have to get up early for school, many young people therefore suffer from chronic lack of sleep. The topic has recently made its way onto the political agenda in several cantons across the country.
“Our findings clearly indicate the benefit of starting school later in the morning so that youngsters can get more sleep,” says Jenni. He speculates that the positive effects on health and health-related quality of life would have been even greater had there not also been the negative effects of the pandemic on mental health.
Story Source:
Materials provided by University of Zurich. Note: Content may be edited for style and length.

For years, public-health experts have been sounding the alarm about the next phase in humanity’s co-existence with bacteria — a dark future where emerging strains have rendered once-powerful antibiotics useless. The United Nations recently projected that, unless new drugs are developed, multidrug-resistant infections will force up to 24 million people into extreme poverty within the next decade and cause 10 million annual deaths by 2050.
Scientists are especially apprehensive about a broad group of bacteria that circulate in hospitals and can dodge not only blockbuster drugs like penicillin and tetracycline, but even colistin, an antibiotic long used as a crucial last option. When colistin fails, there is often no effective antibiotics for patients with multidrug-resistant infections.
Now, Rockefeller scientists report on their discovery of a compound that could potentially outmaneuver colistin resistance. In animal experiments, this prospective antibiotic was highly potent against dangerous opportunistic pathogens like Acinetobacter baumannii, the most common cause of infections in healthcare settings. Published in Nature, the findings could make it possible to develop a new class of antibiotics to combat strains responding to no other treatments.
Evolutionary wars
Colistin has long been abundantly used in the livestock industry, and more recently in the clinic. The overuse is believed to have put a staunch evolutionary pressure on bacteria, compelling them to develop new traits to survive. As a result, some species have acquired a new gene called mcr-1 that evades colistin’s toxicity, making these bacteria resistant to the drug.
Colistin resistance spreads fast, in part because mcr-1 sits on a plasmid, a ring of DNA that isn’t part of the bulk bacterial genome and can transfer easily from cell to cell. “It jumps from one bacterial strain to another, or from one patient’s infection to another’s,” says Zongqiang Wang, a postdoctoral associate in the lab of Sean F. Brady.

A surgical treatment commonly used to reduce epileptic seizures in adults also is effective and safe for children, according to a Rutgers study.
The study, published in the journal Neurosurgery, is one of the first to investigate responsive neurostimulation system (RNS) — a device similar to a pacemaker that sends electric charges to the heart, which delivers stimulation directly to the brain when needed to prevent seizures — in children.
Up to 40 percent of people who suffer from epileptic seizures do not respond to medication. RNS, which is implanted in the brain and monitors brain waves, detects seizures and unusual electrical activity that can lead to seizures, then delivers small pulses of stimulation to help the brainwaves return to normal. The system, which has not been well studied in children whose brains are still growing, is being increasingly used in pediatric centers to control seizures.
“As we expand use of RNS to children, it is critical to consider how to determine the lower age limit,” said lead author Yasunori Nagahama, an assistant professor of neurosurgery and director of pediatric epilepsy surgery at Rutgers Robert Wood Johnson Medical School. “Considering this procedure involves removing a portion of the skull to implant the device, the benefits and potential harm based on the variable skull development in individual patients should be considered. Children experience rapid skull growth within the first two years and reach about 90 percent of adult skull volume by around age 8. In this study, there were two patients under 7 years at the time RNS was implanted, including a 3-year-old, who was the youngest reported patient to undergo RNS implantation.”
Researchers looked at 35 children and young adults from age 3 to 25 with drug-resistant epilepsy who were treated with RNS. They found that 84 percent had a reduction in disabling seizures, including 18 percent who had a reduction of more than 90 percent.
“The findings suggest that responsive neurostimulation is an effective off-label surgical treatment of drug-resistant epilepsy in carefully selected pediatric patients,” said Nagahama. “However, more research on long-term efficacy and safety is needed to determine which patients will benefit most.”
Story Source:
Materials provided by Rutgers University. Original written by Patti Verbanas. Note: Content may be edited for style and length.

A folic acid-like drug, L-methylfolate, when administered alongside the standard therapy for patients with recurrent glioblastoma, changed aDNA process within their brain tumors, according to results from a phase 1 clinical trial.
The researchers showed for the first time that the DNA methylome of these brain tumors can be reprogrammed. The study was published on Jan. 5 in Cancer Research Communications. Stephen Clark, MD, PhD, a neuro-oncologist at Vanderbilt-Ingram Cancer Center, who is the study’s corresponding and lead author, said that this is the first time DNA methylome reprogramming has occurred with any solid human tumor.
The DNA methylome is one aspect of the epigenome; the epigenome is a modification of DNA and proteins in a cell that is influenced by the environment. DNA methylation is one such modification, where methyl groups are added to DNA and is a mechanism that controls gene expression, including the silencing or activation of genes related to cancer.
The researchers sought to determine if re-methylation of IDH wild-type tumors, which have a worse prognosis and lower DNA methylation than IDH mutant tumors, could improve survival. They succeeded in showing that the DNA methylome of IDH wild-type, high-grade gliomas could be reprogrammed, but the study group was too small to ascertain the impact on survival.
“This is an important first step in understanding how we can manipulate the epigenome, and hopefully, this study will help design future epigenetic studies in glioblastoma treatment,” said Clark, assistant professor of Neurology in the Division of Neuro-Oncology at Vanderbilt University Medical Center.
Although the study group of 14 patients was not large enough to detect a statistically significant survival advantage, the patients treated with the folic acid supplement L-methylfolate had a median overall survival of 9.5 months, compared to the typical median overall survival of 8.6 months. One of the patients is still alive.

Recent guidelines have restricted aspirin use in the primary prevention of cardiovascular disease to patients under 70, and more recent guidance to patients under 60. Yet, the risks of heart attacks and strokes increase markedly with age.
There has been considerable confusion from recently reported results of four large-scale randomized trials of aspirin in high-risk primary prevention subjects, two of which showed significant benefits of aspirin, but the other two, based possibly on poor adherence and follow-up, did not. As a result, health care providers are understandably confused about whether or not to prescribe aspirin for primary prevention of heart attacks or strokes, and if so, to whom.
Researchers from Florida Atlantic University’s Schmidt College of Medicine and collaborators provide guidance to primary care providers and their patients in their perspective, “Primary Care Providers Should Prescribe Aspirin to Prevent Cardiovascular Disease Based on Benefit to Risk not Age,” published online ahead of print in the journal Family Medicine and Community Health, British Medical Journal.
The authors urge that to do the most good for the most patients in primary prevention of heart attacks and strokes, health care providers should make individual clinical judgements about prescribing aspirin on a case-by-case basis and based on benefit-to-risk not age. They conducted an updated meta-analysis, which adds the results of the four recent trials to the previous comprehensive meta-analysis of six earlier major trials, and aspirin produced a statistically significant 13 percent reduction in cardiovascular disease with similar benefits at older ages in each of the individual trials.
“Any judgments about prescribing long-term aspirin therapy for apparently healthy individuals should be based on individual clinical judgments between the health care provider and each of his or her patients that weighs the absolute benefit on clotting against the absolute risk of bleeding,” said Sarah K. Wood, M.D., senior author and interim dean, FAU Schmidt College of Medicine. “For long-term use of aspirin or any over-the-counter drug, patients should consult their primary care provider.”
FAU collaborated with leading clinical researchers from the University of Wisconsin School of Medicine and Public Health and the Harvard Medical School, Brigham and Women’s Hospital. The authors say that primary care providers have the most insight and knowledge to make appropriate recommendations in collaboration with their patients.

Drugs we take like prednisone can weaken our bones and so can aging, and scientists working to prevent both have some of the first evidence that the best target may not be the logical one.
They are finding that in aging bone, the mineralocorticoid receptor, better known for its role in blood pressure regulation, is a key factor in bone health, says Dr. Meghan E. McGee-Lawrence, biomedical engineer in the Department of Cellular Biology and Anatomy at the Medical College of Georgia.
And drugs that block the receptor, like the hypertension medications spironolactone and eplerenone, may help protect bone cells, says McGee-Lawrence, corresponding author of the study in the Journal of Bone and Mineral Research.
Drugs like prednisone are glucocorticoids, which are better known for their roles in reducing inflammation and suppressing the immune response, which is why they work so well for problems like irritable bowel syndrome and arthritis. But, like aging, they can also disrupt the healthy, ongoing dynamic of bone being made and being destroyed.
Our natural glucocorticoid levels increase with age, and bone, at least when we are young, has more glucocorticoid receptors than mineralocorticoid receptors. Glucocorticoids can actually coax stem cells to make bone-forming osteoblasts, but it also causes those osteoblasts to store more fat, and too much fat in the bone, like anywhere on our body, is probably not good and typically correlates with bone loss, McGee-Lawrence says.
So reducing the impact of glucocorticoid receptors seemed like a logical way to protect bone.

Researchers from the University of Louisville School of Dentistry and their colleagues have discovered details of how proteins produced by oral epithelial cells protect humans against viruses entering the body through the mouth. They also found that oral bacteria can suppress the activity of these cells, increasing vulnerability to infection.
A family of proteins known as interferon lambdas produced by epithelial cells in the mouth serve to protect humans from viral infection, but the oral bacteria Porphyromonas gingivalis reduces the production and effectiveness of those important frontline defenders.
“Our studies identified certain pathogenic bacterial species, P. gingivalis, which cause periodontal disease, can completely suppress interferon production and severely enhance susceptibility to viral infection,” said Juhi Bagaitkar, assistant professor in the UofL Department of Oral Immunology and Infectious Disease. “These resident oral plaque bacteria play a key role in regulating anti-viral responses.”
Bagaitkar and Richard Lamont, professor and chair of the UofL Department of Oral Immunology and Infectious Disease, led the work, with first author Carlos J. Rodriguez-Hernandez and other colleagues at UofL and at Washington University in St. Louis. The findings were published in December in PNAS.
The mouth often is a gateway into the body for viruses that infect the gastrointestinal tract and lungs such as SARS-CoV-2, human immunodeficiency virus (HIV), herpes simplex and cancer-causing viruses such as human papillomavirus (HPV).
P. gingivalis, a common oral bacterium that causes periodontal disease, has been linked to numerous other diseases, including Alzheimer’s disease and rheumatoid arthritis. Recent clinical studies have shown that immune suppression in patients with periodontitis can enhance susceptibility to HIV, herpes simplex and HPV.
Improved understanding of how interferons provide broad antiviral protection and activate antiviral genes to protect people from viruses, as well as how P. gingivalis compromises their protection, may lead researchers to clinical approaches to increase that protection.
Research at UofL has revealed connections between P. gingivalis and multiple other diseases and conditions, including rheumatoid arthritis, Alzheimer’s disease and esophageal cancer.
Bagaitkar was one of the first junior faculty members whose research was supported by the Center of Biomedical Research Excellence (CoBRE) for research in microorganism disease research funded by the National Institute of General Medical Sciences.
Story Source:
Materials provided by University of Louisville. Original written by Betty Coffman. Note: Content may be edited for style and length.