Many people bothered by skin blemishes might turn to laser treatment. To improve efficacy and reduce complications from such laser treatment, an Osaka Metropolitan University-led research group has developed an index of the threshold energy density, known as fluence, and the dependent wavelength for picosecond lasers.
Picosecond lasers have in recent years been used to remove pigmented lesions. These lasers deliver energy beams in pulses that last for about a trillionth of a second. The lasers target melanosomes, which produce, store, and transport the melanin responsible for pigment.
Postdoctoral Fellow Yu Shimojo of OMU’s Graduate School of Medicine and Specially Appointed Professor Toshiyuki Ozawa and Professor Daisuke Tsuruta of the school’s Department of Dermatology were among the researchers who developed this first picosecond laser index for each of the wavelengths used in clinical practice in treating pigmented lesions.
Comparing previously reported clinical studies, the researchers confirmed that clinical results showing low complication rates and high efficacy can be explained based on these wavelength-dependent indicators.
“The use of this indicator is expected to play an important part in setting irradiation conditions in clinical practice,” Postdoc Fellow Shimojo said. “In addition, the implementation of picosecond laser therapy based on scientific evidence, rather than relying solely on physicians’ experience, is expected to improve the safety and effectiveness of the treatment.”

Feeling sleepy can make you feel ten years older. Researchers at Stockholm University have discovered that sleep affects how old you feel. The study is published in the scientific journal Proceedings of the Royal Society B.
Do you ever find yourself longing for the energy and vitality of your younger years? Feeling young is not just a matter of perception — it is actually related to objective health outcomes. Previous studies have shown that feeling younger than one’s actual age is associated with longer, healthier lives. There is even support for subjective age to predict actual brain age, with those feeling younger having younger brains.
“Given that sleep is essential for brain function and overall well-being, we decided to test whether sleep holds any secrets to preserving a youthful sense of age,” says Leonie Balter, researcher at the Department of Psychology, Stockholm University.
In the first study, 429 individuals aged 18 to 70 were asked how old they felt, how many days in the past month they had not gotten enough sleep, and how sleepy they were. It turned out that for each night with insufficient sleep in the past month, participants felt on average 0.23 years older.
In a second study, the researchers tested whether it was indeed the lack of sleep causing participants to feel older. Therefore, they conducted an experimental sleep restriction study involving 186 participants aged 18 to 46. Participants restricted their sleep for two nights -only four hours in bed each night — and another time slept sufficiently for two nights, with nine hours in bed each night.
After sleep restriction, participants felt on average 4.4 years older compared to when having enjoyed sufficient sleep. The effects of sleep on subjective age appeared to be related to how sleepy they felt. Feeling extremely alert was related to feeling 4 years younger than one’s actual age, while extreme sleepiness was related to feeling 6 years older than one’s actual age.
“This means that going from feeling alert to sleepy added a striking 10 years to how old one felt,” says Leonie Balter, and states that the implications for our daily lives are clear:
“Safeguarding our sleep is crucial for maintaining a youthful feeling. This, in turn, may promote a more active lifestyle and encourage behaviours that promote health, as both feeling young and alert are important for our motivation to be active.”

People who live in areas with social and environmental adversities may have up to twice the increased risk for developing heart disease and stroke, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.
In this study, environmental adversities included air and water pollution, potentially hazardous or toxic sites, few recreational parks, and high traffic roads, railways or airports. Social vulnerabilities were defined as racial and ethnic minority status; socioeconomic factors such as income, education and employment levels; housing status; and access to internet and health care.
“Our study is one of the first to examine the impact of both social and environmental factors in combination and looked at the complex interplay between them,” said the study’s senior author Sarju Ganatra, M.D., a cardiologist and vice chair in the department of medicine for research and director of the Cardio-Oncology Program and South Asian Cardio-Metabolic Program at Lahey Hospital and Medical Center in Burlington, Massachusetts.
This study used the Environmental Justice Index — developed with data from the U.S. Census Bureau, the U.S. Environmental Protection Agency, U.S. Mine Safety and Health Administration and the U.S. Centers for Disease Control and Prevention — to rate environmental disadvantages across all U.S. census tracts.
The analysis found: People living in the most environmentally vulnerable neighborhoods had 1.6 times the rate of blocked arteries and more than twice the rate of stroke compared to people living in the least environmentally vulnerable neighborhoods. Cardiovascular disease risk factors were higher in the most vulnerable areas with twice the rate of Type 2 diabetes, 1.8 times higher rates of chronic kidney disease, and 1.5 times higher incidence of high blood pressure and obesity. About 30% of all U.S. residents aged 18-44, 21% of Black adults and most Hispanic adults resided in places with alarmingly high environmental burdens.”I was amazed to see the tight links and complex interplay between social and environmental factors on health outcomes. We were able to demonstrate their ‘dual hit’ on health outcomes. And beyond that, we were more amazed by the fact that even after adjusting for socioeconomic factors, environmental factors played a crucial and independent role in determining various heart disease and other related health outcomes,” Ganatra said.
According to researchers, reversing the impact of social and environmental disadvantages will require a multi-pronged approach with interventions to reduce pollution exposure and policies that address the causes of poverty, urban revitalization, high quality public education, job creation programs and affordable housing, along with steps to ensure universal access to quality health care.
“Our aim is to empower the health care community to better inform patients about environmental factors they encounter daily. Patients, in turn, gain the ability to reduce their exposure to harmful environmental conditions, such as exposure to harmful chemicals and air pollutants to minimize health hazards and mitigate health risks,” Ganatra said.

This unusual, subterranean mammal with extreme longevity shows genetic adaptations to low oxygen environments which could offer opportunities for advancing other areas of physiological and medical research in humans, including the development of novel therapeutic approaches.
New research from Queen Mary University of London led by Dr Dunja Aksentijevic in the Faculty of Medicine and Dentistry has revealed that that the genome of the naked mole-rat contains specific adaptations that allow them to survive in low-oxygen, and even no oxygen environments in their natural habitat. The findings also show the mammals’ distinct cardiometabolic profile helps to avoid damage to their hearts caused by cardiovascular events.
Dr Aksentijevic led the team of scientists from London, Pretoria and Cambridge to sample heart tissue from the naked mole-rat and compared it to samples from other African mole-rat species (Cape, Cape dune, common, Natal, Mahali, highveld and Damaraland mole-rats), as well as evolutionarily divergent mammals (Hottentot golden mole and C57/BL6 mouse).
In this study, they found that the naked mole-rat has a unique expression of genes in heart cells controlling energy generation from sugars resulting in a metabolic profile that is distinct from any of the other mole-rats as well as the other species studied. These unique cardiac metabolic and genetic features of the naked mole-rat heart led to enhanced energy reserves even during blood occlusion and return of blood flow after in vitro simulated heart attack. Collectively, these adaptations result in the naked mole-rat ‘s tolerance to reduced oxygen and negligible damage to their heart tissue.
Dr Chris Faulkes, Reader (Associate Professor) in Evolutionary Ecology at Queen Mary and Lead Author, said: “Naked mole-rats live in a unique hypoxic and social environment, and we believe these factors have driven the evolution of special adaptations in their hearts that contribute to their exceptional longevity and health span,”
Dr Dunja Aksentijevic, Wellcome Trust Career Re-Entry Fellow, Reader (Associate Professor) in Cardiovascular Physiology and Metabolism at Queen Mary, said: “Unlike humans, who are prone to heart injury by hypoxia and anoxia caused by blood occlusion during heart attacks, NMR hearts have adapted to evade such damage. Thanks to our research, we are now able to understand the metabolic and genetic mechanisms underpinning this unique level of protection.”

Understanding the structure of proteins is critical for demystifying their functions and developing drugs that target them. To that end, a team of researchers at Brown University has developed a way of using machine learning to rapidly predict multiple protein configurations to advance understanding of protein dynamics and functions.
A study describing the approach was published in Nature Communications on Wednesday, March 27.
The authors say the technique is accurate, fast, cost-effective and has the potential to revolutionize drug discovery by uncovering many more targets for new treatments.
In targeted cancer therapy, for example, treatments are designed to zero in on proteins that control how cancer cells grow, divide and spread. One of the challenges for structural biologists has been understanding cell proteins thoroughly enough to identify targets, said study author Gabriel Monteiro da Silva, a Ph.D. candidate in molecular biology, cell biology and biochemistry at Brown.
Monteiro da Silva uses computational methods to model protein dynamics and looks for ways to improve methods or find new methods that work best for different situations. For this study, he partnered with Brenda Rubenstein, an associate professor of chemistry and physics, and other Brown researchers to experiment with an existing A.I.-powered computational method called AlphaFold 2.
While Monteiro da Silva said that the accuracy of AlphaFold 2 has revolutionized protein structure prediction, the method has limitations: It allows scientists to model proteins only in a static state at a specific point in time.
“During most cellular processes, proteins will change shape dynamically,” Monteiro da Silva said. “In order to match protein targets to drugs to treat cancer and other diseases, we need a more accurate understanding of these physiological changes. We need to go beyond 3D shapes to understanding 4D shapes, with the fourth dimension being time. That’s what we did with this approach.”
Monteiro da Silva used the analogy of a horse to explain protein models. The arrangement of the horse’s muscles and limbs create different shapes depending on whether the horse is standing or galloping; protein molecules conform into different shapes due to the bonding arrangements of their constituent atoms. Imagine that the protein is a horse, Monteiro da Silva said. Previous methods were used to predict a model of a standing horse. It was accurate, but it didn’t tell much about how the horse behaved or how it looked when it wasn’t standing.

In this study, the researchers were able to manipulate the evolutionary signals from the protein to use AlphaFold 2 to rapidly predict multiple protein conformations, as well as how often those structures are populated. Using the horse analogy, the new method allows researchers to quickly predict multiple snapshots of a horse galloping, which means they can see how the muscular structure of the horse would change as it moved, and then compare those structural differences.
“If you understand the multiple snapshots that make up the dynamics of what’s going on with the protein, then you can find multiple different ways of targeting the proteins with drugs and treating diseases,” said Rubenstein, whose research focuses whose research focuses on electronic structure and biophysics.
Rubenstein explained that the protein on which the team focused in this study was one that had different drugs developed for it. Yet for many years, no one could understand why some of the drugs succeeded or failed, she said.
“It all came down to the fact that these specific proteins have multiple conformations, as well as to understanding how the drugs bind to the different conformations, instead of to the one static structure that these techniques previously predicted; knowing the set of conformations was incredibly important to understanding how these drugs actually functioned in the body,” Rubenstein said.
Accelerating discovery time
The researchers noted that existing computational methods are cost- and time-intensive.

“They’re expensive in terms of materials, in terms of infrastructure; they take a lot of time, and you can’t really do these computations in a high throughput kind of way — I’m sure I was one of the top users of GPUs in Brown’s computer cluster,” Monteiro da Silva said. “On a larger scale, this is a problem because there’s a lot to explore in the protein world: how protein dynamics and structure are involved in poorly understood diseases, in drug resistance and in emerging pathogens.”
The researchers described how Monteiro da Silva previously spent three years using physics to understand protein dynamics and conformations. Using their new A.I.-powered approach, the discovery time decreased to mere hours.
“So you can imagine what a difference that would make in a person’s life: three years versus three hours,” Rubenstein said. “And that’s why it was very important that the method we developed should be high-throughput and highly efficient.”
As for next steps, the research team is refining their machine learning approach, making it more accurate as well as generalizable, and more useful for a range of applications.

Researchers from the Nuffield Department of Clinical Neurosciences at the University of Oxford have used data from UK Biobank participants to reveal that diabetes, traffic-related air pollution and alcohol intake are the most harmful out of 15 modifiable risk factors for dementia.
The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age. They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.
In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40,000 UK Biobank participants aged over 45.
The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age. They classified these so-called ‘modifiable’ risk factors — as they can potentially be changed throughout life to reduce the risk of dementia — into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialisation, diet, physical activity, and education.
Prof. Gwenaëlle Douaud, who led this study, said: ‘We know that a constellation of brain regions degenerates earlier in aging, and in this new study we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution — increasingly a major player in dementia — and alcohol, of all the common risk factors for dementia.’
‘We have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.’
Prof. Lloyd Elliott, a co-author from Simon Fraser University in Canada, concurs: ‘In fact, two of our seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes. This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.’
Importantly, as Prof. Anderson Winkler, a co-author from the National Institutes of Health and The University of Texas Rio Grande Valley in the US, points out: ‘What makes this study special is that we examined the unique contribution of each modifiable risk factor by looking at all of them together to assess the resulting degeneration of this particular brain ‘weak spot’. It is with this kind of comprehensive, holistic approach — and once we had taken into account the effects of age and sex — that three emerged as the most harmful: diabetes, air pollution, and alcohol.’
This research sheds light on some of the most critical risk factors for dementia, and provides novel information that can contribute to prevention and future strategies for targeted intervention.

A commonly used questionnaire adopted by GPs to monitor the treatment of depression does not provide any immediate benefits to patients, a new study has found.
Primary care researchers testing the PHQ-9 assessment, which measures the severity of depression, found it did nothing to improve people’s symptoms after 12 weeks.
Doctors use the forms to assess depression and recommend appropriate treatments.
The study by the University of Southampton did, however, reveal that patients reported a better quality of life at six months if they completed the PHQ-9 consistently.
Findings from the four-year investigation, conducted with the University of Liverpool and University College London, are published in the British Journal of General Practice.
Professor of Primary Care Tony Kendrick, from Southampton, said current evidence that PHQ-9s improve the management of depression for patients in primary care is inconsistent.
He added: “Our study shows that people who tracked their PHQ-9 scores reported significantly improved overall wellbeing across a longer period of about six months.

“It also showed that a benefit for depression at six months could not be ruled out.
“Despite this, asking GPs to use these tools more regularly in primary care remains a challenge — particularly as patients struggle to book appointments at their surgeries.”
Monitoring with patient-reported outcome measures, or PROMS, is recommended by NICE and they are used regularly by psychologists in NHS Talking Therapies as well doctors in Europe and the USA.
The Southampton study enrolled more than 500 adults with depression treated in GP practices — half the patients received the PHQ-9 questionnaire twice.
After 12 weeks, there was no significant difference in depression scores between the groups.
But, after 26 weeks, those who received the questionnaire reported a better quality of life and improved on some measures of anxiety and depression.

Those with GP-recorded follow up PHQ-9 scores were also more likely to be prescribed antidepressants and to see a mental health professional.
Prof Kendrick added: “More research into PROMs is needed but clearly patients who were monitored using PHQ-9s showed some improvements at six months.
“Self-assessment tools like the PHQ-9 are still well valued by many GPs and patients for monitoring depression treatment.
“We would like to see future studies test PROMs which are automatically administered and integrated into patients’ records, and which create more specific recommendations for treatment, possibly using artificial intelligence.”

New research from Cedars-Sinai suggests people who are scheduled for certain medical procedures should stop taking popular weight loss drugs in the days or weeks prior to avoid complications.
Investigatorsfound glucagon-like peptide-1 receptor agonists (GLP-1RAs) — medications like Ozempic and Wegovy that are used to treat diabetes and obesity — are associated with an increased risk of aspiration pneumonia following endoscopy. The large, population-based study is published in the leading peer-reviewed journal Gastroenterology.
Aspiration pneumonia is caused by inhaling foreign materials — including food in the stomach, or secretions from the mouth and nose — into the lungs. Endoscopy is a medical procedure in which a physician puts a tube-like scope down a patient’s throat and into the body to look inside.
One way the new obesity medications work is by slowing digestion, so people feel full longer, causing them to eat less. This also means that food sits in the stomach longer. As a result, the stomach may not empty completely during the usual duration of fasting that is recommended ahead of a surgical procedure to decrease risk of aspiration, explained the study’s corresponding author, Ali Rezaie, MD, medical director of the GI Motility Program and director of bioinformatics at the MAST Program at Cedars-Sinai.
“Aspiration during or after endoscopy can be devastating,” Rezaie said. “If significant, it can lead to respiratory failure, ICU admission and even death. Even mild cases may require close monitoring, respiratory support and medications including antibiotics. It is important we take all possible precautions to prevent aspiration from occurring.”
The study analyzed data from nearly 1 million de-identified U.S. patients who underwent upper or lower endoscopy procedures between January 2018 and December 2020. Patients who were prescribed GLP-1RA medications had a 33% higher chance of experiencing aspiration pneumonia than those who did not take these medications before the procedure. This comparison also considered other variables that could influence the outcome to ensure a fair comparison between the two groups.
“When we apply this risk to the more than 20 million endoscopies that are performed in the U.S. each year, there may actually be a large number of cases where aspiration could be avoided if the patient safely stops their GLP-1RA medication in advance,” Rezaie said.
“The results of this study could change clinical practice,” said Yee Hui Yeo, MD, first author of the study and a clinical fellow in the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. “Patients taking these medications who are scheduled to undergo a procedure should communicate with their healthcare team well in advance to avoid unnecessary and unwanted complications.”

With resistance to chemical antibiotics on the rise, the world needs entirely new forms of antibiotics. A new study published in Microbiology Spectrum, a journal of the American Society for Microbiology, shows that an enzymatic cocktail can kill a variety of mycobacterial species of bacteria, including those that cause tuberculosis. The research was carried out by scientists at Colorado State University and Endolytix Technologies.
“We have a mycobacterial drug that works for Nontuberculous Mycobacteria and M. tuberculosis that is biological, not phage therapy, and not small molecule antibiotics,” said Jason Holder, Ph.D., a study coauthor and Founder and Chief Science Officer at Endolytix Technology. “Mycobacterial infections are particularly hard to treat due to poor efficacy with standard of care drugs that are used in multidrug regimens resulting in significant toxicities and treatments lasting 6 months to years. This is often followed up by reemergence of the bacterial infection after a year of testing negative.”
In the new proof of principle study, the researchers took a biological approach instead of a chemical one to develop a cocktail of enzymes that attack the cell envelope of mycobacteria. The cocktail of enzymes contains highly specific biochemical catalysts that target and degrade the mycobacteria cell envelope that is essential for mycobacterial viability. To increase efficacy, the researchers delivered the enzymatic drug inside of host macrophages where mycobacteria grow. In laboratory experiments, the drug was effective against M. tuberculosis and Nontuberculous Mycobacteria (NTMs), both lethal pulmonary lung diseases (PD). TB kills roughly 1.5 million people per year.
“We characterized the mechanism of bactericide as through shredding of the bacterial cells into fragments,” Holder said. “We’ve shown we can design and develop biological antibiotics and deliver them to the sites of infection through liposomal encapsulation. By combining drug delivery science with enzymes that lyse bacteria, we hope to open up treatment options in diseases such as NTM pulmonary disease, tuberculosis pulmonary disease and others.”
According to study coauthor Richard Slayden, Ph.D., a professor in the Department of Microbiology, Immunology and Pathology at Colorado State University, the new therapy complements current standard-of-care drugs and does not have many of the drug-drug interactions that are problematic with many anti-mycobacterial drugs in use. “Endolytix enzymes work powerfully with standard-of-care antibiotics to kill bacteria with lower drug concentrations,” Holder said. “This has the potential to reduce the significant toxicities associated with multi-drug regimens that are the standard for mycobacterial infections and hopefully lead to more rapid cures.”

McGill researchers have discovered a safer and more efficient technique for testing new drugs while they are in development.
“Because this approach is so much more streamlined, it could help accelerate this step in the drug development process and make it less dangerous, since probing the distribution and fate of a drug in the body is required for any pharmaceutical candidate to be approved,” says Bruce A. Arndtsen, a James McGill Professor who teaches in the Department of Chemistry at McGill and is the senior author on the paper describing the new process, published recently in Nature Chemistry.
“This research replaces what can be a days’ long, dangerous and costly process with a simple and safe one requiring only a few hours,” adds José Zgheib, a PhD candidate in the Arndtsen Group at McGill University who worked on the project.
Making sure medication reaches its target
Before a drug makes it to market it is tested to make sure that the molecules reach the appropriate areas of the body. This is typically done by adding a radioactive atom (e.g. carbon-14) to the drug so that its movement through the body can be traced. A bit like a GPS can be used to track the movements of animals.
Improving on a complicated and dangerous process
But to do so currently involves a complicated, multi-step, process whereby the carbon-14 atom is provided in the form of radioactive carbon monoxide or carbon dioxide gases, which are both very difficult and dangerous to work with. The gas is then incorporated into the synthesis of the medication being tested thereby making one of its carbon atoms carbon-14.
A molecular quick switch
McGill researchers have developed a new technique to incorporate the carbon-14 into the drug candidates in a single step. By using a catalyst, they have been able to exchange a carbon already in the drug (in the form of a carboxylic acid) with a carbon-14 from a similar type of donor molecule. More generally, the group’s work in the area highlights a potentially powerful emerging approach to directly modify pharmaceuticals via metal catalyzed exchange reactions.