Tag: 9/4/25

Categories : Cardiovascular DiseaseTags :

CVD and Obesity: When Protective Lipids Decline, Health Risks Increase

On By ModernMedia
The mesenteric arteries from obese and lean mice, pictured above, supply oxygen and nutrients to the intestines. Immunofluorescence staining revealed that the NOGO-B protein increases in the vascular walls of mice fed a high fat diet compared to mice fed a standard diet. As a result, ceramides decrease in the mesenteric arteries of the obese mice, damaging endothelial cells lining blood vessels. Credit: Annarita Di Lorenzo/Weill Cornell Medicine

New research from Weill Cornell Medicine has uncovered a surprising culprit underlying cardiovascular diseases in obesity and diabetes—not the presence of certain fats, but their suppression. The study, published in Nature Communications, challenges the conventional belief that a type of fat called ceramides accumulates in blood vessels causing inflammation and health risks. Instead, their findings reveal that when ceramides decrease in endothelial cells lining blood vessels, it can be damaging and cause chronic illnesses. Ironically, the findings could ultimately lead to therapies that maintain high levels of these protective lipids in patients with obesity.

Ceramides are found throughout the body and in the endothelium, the thin lining inside blood vessels. These waxy lipids regulate blood vessel tone, dilating or contracting vessels to modulate blood pressure. They also help prevent blood clots, keeping blood flowing easily through the body’s extensive highway of arteries and veins.

“The common assumption in the field was that high levels of ceramides in the endothelium of blood vessels contributed to cardiovascular disease, but this conclusion was extrapolated from in vitro data in cells,” said Dr Annarita Di Lorenzo, professor of pathology and laboratory medicine at Weill Cornell Medicine. “Ours is the first in vivo study that measures the levels of the lipids in the endothelial cells of an animal model. In obese mice fed a high-fat diet, ceramides do not build up—they decrease compared to lean mice.” Also working on this research are co-first authors Dr Onorina L. Manzo, postdoctoral associate and Luisa Rubinelli, both in Dr Di Lorenzo’s lab.

Ceramide to the Rescue

Dr Di Lorenzo and her team discovered the importance of ceramides in blood vessels two years ago. Together with Dr Giuseppe Faraco, assistant professor of neuroscience at Weill Cornell Medicine, they found that decreased levels of ceramides in otherwise healthy mice causes severe blood vessel inflammation in the brain, clot formation and death. Last year, the team reported that ceramide production increases as a protective response in a mouse model of coronary artery disease. Ultimately, when ceramide is broken down by the body it produces a compound called sphingosine-1-phosphate (S1P), which builds up and protects mice against cardiovascular disease. But when this process doesn’t work the mice are left vulnerable.

The researchers also found that two proteins, Nogo-B and ORMDL, decreased the production of ceramides and S1P in obesity. This decrease leads to increased blood pressure, impaired vascular regulation and higher glucose levels—all of which contribute to cardiometabolic conditions that affect the heart (cardiovascular system) and energy processing (metabolism), like diabetes like diabetes, hypertension, coronary artery disease and stroke.

Maintaining Balance

To understand how these different molecules interact, the researchers tested what happens in animal models. Mice with obesity fed a high-fat diet had low levels of ceramides and S1P, but high levels of Nogo-B. These mice showed signs of inflammation, diabetes and high blood pressure.

But what happens if the Nogo-B inhibitor wasn’t present? The researchers knocked out Nogo-B only in the endothelium of blood vessels in a mouse model to find out. “These mice have the same body weight and diabetes as controls, but their blood vessel health is much better,” said Dr. Di Lorenzo. “By knocking out this inhibitor, we preserved vascular health. This also showed that the regulation of ceramide metabolism causes vascular dysfunction and inflammation in obesity.”

The paper suggests that targeting this metabolic pathway could have multiple beneficial effects in the treatment of cardiometabolic diseases related to obesity. “Nogo suppresses biosynthesis of ceramides, so if we can identify a drug that can block Nogo-B, we could restore ceramide levels to a healthy balance and this would fight not only obesity and diabetes, but would directly keep blood vessels functioning properly,” she said.

Source: Weill Cornell Medicine

Categories : IT in HealthcareTags :

Is AI in Medicine Playing Fair?

On By ModernMedia
Photo by Christina Morillo

As artificial intelligence (AI) rapidly integrates into health care, a new study by researchers at the Icahn School of Medicine at Mount Sinai reveals that all generative AI models may recommend different treatments for the same medical condition based solely on a patient’s socioeconomic and demographic background.  

Their findings, which are detailed in the April 7, 2025 online issue of Nature Medicine, highlight the importance of early detection and intervention to ensure that AI-driven care is safe, effective, and appropriate for all.

As part of their investigation, the researchers stress-tested nine large language models (LLMs) on 1,000 emergency department cases, each replicated with 32 different patient backgrounds, generating more than 1.7 million AI-generated medical recommendations. Despite identical clinical details, the AI models occasionally altered their decisions based on a patient’s socioeconomic and demographic profile, affecting key areas such as triage priority, diagnostic testing, treatment approach, and mental health evaluation. 

“Our research provides a framework for AI assurance, helping developers and health care institutions design fair and reliable AI tools,” says co-senior author Eyal Klang, MD, Chief of Generative-AI in the Windreich Department of Artificial Intelligence and Human Health at the Icahn School of Medicine at Mount Sinai. “By identifying when AI shifts its recommendations based on background rather than medical need, we inform better model training, prompt design, and oversight. Our rigorous validation process tests AI outputs against clinical standards, incorporating expert feedback to refine performance. This proactive approach not only enhances trust in AI-driven care but also helps shape policies for better health care for all.” 

One of the study’s most striking findings was the tendency of some AI models to escalate care recommendations—particularly for mental health evaluations—based on patient demographics rather than medical necessity. In addition, high-income patients were more often recommended advanced diagnostic tests such as CT scans or MRI, while low-income patients were more frequently advised to undergo no further testing. The scale of these inconsistencies underscores the need for stronger oversight, say the researchers. 

While the study provides critical insights, researchers caution that it represents only a snapshot of AI behavior.  Future research will continue to include assurance testing to evaluate how AI models perform in real-world clinical settings and whether different prompting techniques can reduce bias. The team also aims to work with other health care institutions to refine AI tools, ensuring they uphold the highest ethical standards and treat all patients fairly. 

“I am delighted to partner with Mount Sinai on this critical research to ensure AI-driven medicine benefits patients across the globe,” says physician-scientist and first author of the study, Mahmud Omar, MD, who consults with the research team. “As AI becomes more integrated into clinical care, it’s essential to thoroughly evaluate its safety, reliability, and fairness. By identifying where these models may introduce bias, we can work to refine their design, strengthen oversight, and build systems that ensure patients remain at the heart of safe, effective care. This collaboration is an important step toward establishing global best practices for AI assurance in health care.” 

“AI has the power to revolutionize health care, but only if it’s developed and used responsibly,” says co-senior author Girish N. Nadkarni, MD, MPH, Chair of the Windreich Department of Artificial Intelligence and Human Health Director of the Hasso Plattner Institute for Digital Health, and the Irene and Dr. Arthur M. Fishberg Professor of Medicine, at the Icahn School of Medicine at Mount Sinai. “Through collaboration and rigorous validation, we are refining AI tools to uphold the highest ethical standards and ensure appropriate, patient-centered care. By implementing robust assurance protocols, we not only advance technology but also build the trust essential for transformative health care. With proper testing and safeguards, we can ensure these technologies improve care for everyone—not just certain groups.” 

Next, the investigators plan to expand their work by simulating multistep clinical conversations and piloting AI models in hospital settings to measure their real-world impact. They hope their findings will guide the development of policies and best practices for AI assurance in health care, fostering trust in these powerful new tools. 

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : Metabolic DisordersTags :

High Muscle Strength Linked to Lower Risk of Type 2 Diabetes

On By ModernMedia
Photo by Jonathan Borba on Unsplash

Researchers from the School of Public Health, LKS Faculty of Medicine of the University of Hong Kong (HKUMed) conducted a large-scale epidemiological study to explore the potential health benefits of high muscle strength in preventing type 2 diabetes (T2D) across varying levels of genetic risk. The study found that higher muscle strength was associated with over 40% lower risk of T2D, regardless of genetic susceptibility to T2D. The study highlights the importance of maintaining or improving muscle strength as a key strategy for preventing T2D. The findings were published in BMC Medicine.

T2D is one of the most common chronic metabolic disorders, and it is associated with an increased risk of various complications, including heart disease, stroke, high blood pressure, and narrowing of blood vessels. It is characterised by hyperglycaemia, due to insulin resistance and impaired insulin secretion. Evidence suggests that around 10% of the global population is affected by T2D, therefore, preventing T2D is a significant global public health concern. T2D can be caused by the interplay between non-modifiable genetic traits and modifiable lifestyle factors. Muscle strength is an important aspect of muscular fitness, and it has been found to be associated with lower risk of various cardiometabolic diseases including T2D. However, it remains unclear whether improving muscle strength should be considered a T2D prevention strategy in individuals with varying levels of genetic susceptibility to T2D, particularly those with high genetic susceptibility to T2D.

The research utilised data of 141 848 white British individuals without baseline T2D from the UK Biobank, an ongoing prospective cohort of over 500 000 UK adults which includes extensive genotype and phenotype information. Muscle strength was assessed in the form of grip strength. Genetic risk of T2D was estimated based on 138 known genetic variants for T2D.

The participants were followed up for more than seven years. During the follow-up period, 4,743 new T2D cases were identified. The findings indicated that, compared with low muscle strength, individuals with high muscle strength was associated with a 44% lower relative risk of developing T2D, even after taking into account T2D genetic risk as well as other risk factors. Moreover, the research team observed evidence of an interaction between muscle strength and genetic susceptibility to T2D, suggesting that muscle strength may play a role in modifying the impact of genetic risk to T2D onset. The findings further revealed that individuals at high genetic risk of T2D but with high muscle strength could have a lower absolute risk of T2D, compared with those at low or medium genetic risk but with low muscle strength.

This groundbreaking study uncovered the first-ever prospective associations between muscle strength, genetic susceptibility to type 2 diabetes, and the risk of developing the disease. ‘The findings emphasise the crucial role of maintaining or enhancing muscle strength as a key strategy for preventing T2D in middle-aged and older adults, regardless of their genetic risk levels and including those at high genetic risk. We believe that these results offer novel insights into the significant impact of higher muscle strength on metabolic health,’ said Dr Wang Mengyao, from the School of Public Health at HKUMed, the first author of this study.

‘This study highlights the significance of Biobank studies in examining the interaction between exposures and genetics in influencing the risk of T2D. Further research utilising ethnic-specific Biobank studies is needed to determine if these findings are applicable to other populations, such as East Asians,’ expressed Professor Ryan Au Yeung, Assistant Professor from the School of Public Health at HKUMed, a co-author of this study.

‘Individuals in middle-to-late life are at increased risk of type 2 diabetes. However, our study has demonstrated the potential roles of high muscle strength in preventing the future risk of developing type 2 diabetes not only in all individuals, but also in individuals with high genetic predisposition to type 2 diabetes. Our study supports the current public health guidelines which suggest that adults should engage in muscle-strengthening activities for at least two days per week from a disease prevention perspective,’ added Professor Youngwon Kim, from the School of Public Health at HKUMed, the corresponding author of the study.

Source: The University of Hong Kong

Categories : Diet and Nutrition NeurologyTags :

Researchers Discover Natural Compound may Slow ALS and Dementia

On By ModernMedia
Researchers from the University of Missouri have discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS. Photo: Pixabay CC0

A natural compound found in everyday fruits and vegetables may hold the key to protecting nerve cells — and it’s showing promise as a potential treatment for ALS and dementia, according to new research from the University of Missouri.

“It’s exciting to discover a naturally occurring compound that may help people suffering from ALS or dementia,” Smita Saxena, a professor of physical medicine and rehabilitation at the School of Medicine and lead author of the study, said. “We found this compound had a strong impact in terms of maintaining motor and muscle function and reducing muscle atrophy.”

The study, which appears in Acta Neurologica, discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS.

In lab-grown nerve cells from ALS patients, the compound helped the cells produce more energy and eased stress in the protein-processing center of the cell called the endoplasmic reticulum. Additionally, the compound improved overall cell function and slowed nerve cell damage. Researchers found that kaempferol worked by targeting a crucial pathway that helps control energy production and protein management — two functions that are disrupted in individuals with ALS.

“I believe this is one of the first compounds capable of targeting both the endoplasmic reticulum and mitochondria simultaneously,” Saxena said. “By interacting with both of these components within nerve cells, it has the potential to elicit a powerful neuroprotective effect.”

The challenge

The catch? The body doesn’t absorb kaempferol easily, and it could take a large amount to see real benefits in humans. For instance, an individual with ALS would need to consume at least 4.5kg of kale in a day to obtain a beneficial dose.

“Our bodies don’t absorb kaempferol very well from the vegetables we eat,” Saxena said. “Because of this, only a small amount reaches our tissues, limiting how effective it can be. We need to find ways to increase the dose of kaempferol or modify it so it’s absorbed into the bloodstream more easily.”

Another hurdle is getting the compound into the brain. The blood-brain barrier — a tightly locked layer of cells that blocks harmful substances — also makes it harder for larger molecules like kaempferol to pass through.

What’s next?

Despite its challenges, kaempferol remains a promising candidate for treating ALS, especially since it works even after symptoms start. It also shows potential for other neurodegenerative diseases including Alzheimer’s and Parkinson’s.

To make the compound easier for the body to absorb, Saxena’s team at the Roy Blunt NextGen Precision Health building is exploring ways to boost its uptake by neurons. One promising approach involves packaging lipid-based nanoparticles — tiny spherical particles made of fats that are commonly used in drug delivery.

“The idea is to encapsulate kaempferol within lipid-based nanoparticles that are easily absorbed by the neurons,” Saxena said.  “This would target kaempferol to neurons to greatly increase its beneficial effect.”

The team is currently generating the nanoparticles with hopes of testing them by the end of the year.

Source: University of Missouri-Columbia