Posted on Rheumatoid arthritis

Rheumatoid arthritis: Signals from the gut could transform treatment

Genetic link between diabetes and gut health could offer treatment solutions
Link between RA and gut health could offer treatment solutions

Research suggests that alterations in the gut microbiome before the onset of rheumatoid arthritis may present an opportunity for preventive treatments.

According to a longitudinal study conducted by researchers in Leeds, bacteria linked to inflammation are found in the gut in higher amounts about ten months before patients develop clinical rheumatoid arthritis.

Rheumatoid arthritis, which affects over half a million people in the UK, is a chronic disease that causes swelling, pain, and stiffness in the joints. The immune system mistakenly attacks the body’s healthy cells, causing the disease.

Previous research has connected rheumatoid arthritis to the gut microbiome, the community of microbes in the intestines. However, this recent study, published in the Annals of the Rheumatic Diseases, reveals a potential intervention point.

Lead researcher Dr. Christopher Rooney stated: “Patients at risk for rheumatoid arthritis often experience symptoms like fatigue and joint pain. They may also have a family member who has developed the disease. Since there is currently no cure, at-risk patients frequently feel a sense of hopelessness and may even avoid getting tested.”

“This new research might allow us to act sooner to prevent rheumatoid arthritis.” 

A major opportunity for treatment 

Versus Arthritis funded the longitudinal study involving 19 patients at risk of rheumatoid arthritis. Samples were taken five times over 15 months.  

Five of these patients progressed to clinical arthritis, and the research showed they had gut instability with higher amounts of bacteria, including Prevotella, which is associated with rheumatoid arthritis, about ten months before progression. The remaining 14, whose disease didn’t progress, had largely stable bacteria in their gut. 

Potential treatments that the researchers want to test during the ten-month window include changes to diet, such as eating more fibre, taking prebiotics or probiotics, and improving dental hygiene to keep harmful bacteria from periodontal disease away from the gut. 

The exact relationship between gut inflammation and rheumatoid arthritis development remains unclear. In a small number of patients within the study, the gut changes occurred before a rheumatologist observed any joint changes. Still, more research is needed to determine whether these influence each other. 

Although bacteria is associated with rheumatoid arthritis, the researchers want to emphasize that there is no evidence that it is contagious. 

Lucy Donaldson, director for research and health intelligence at Versus Arthritis, said: “At Versus Arthritis, we welcome the findings of this study, which could give the clinicians of the future a crucial window of opportunity to delay – or even prevent – the onset of rheumatoid arthritis. This success is a testament to UK researchers’ dedication to personalising treatment and preventing chronic conditions that significantly impact a person’s ability to work, raise families and live independently.” 

Years in the making 

The study initially collected data from 124 individuals with high levels of CCP+, an antibody that attacks healthy cells in the blood and indicates a risk of developing rheumatoid arthritis. The researchers compared their samples to 22 healthy individuals and seven people with a new rheumatoid arthritis diagnosis.  

The findings from this larger group showed that the gut microbiome was less diverse in the at-risk group compared to the healthy control group. 

The longitudinal study, which took samples from 19 patients over 15 months, revealed the changes in bacteria at ten months before progression to rheumatoid arthritis. 

Posted on Multiple Sclerosis

Multiple Sclerosis is Becoming Milder [Data Presented by Neurologist]

On average, the rates of relapses, accumulation of disability, and even mortality are decreasing in people with multiple sclerosis. This video presents historical and modern studies that demonstrate this clear trend. But what is causing this improvement? Is it due to better diagnoses, changes in diagnostic criteria, or the effectiveness of disease-modifying therapies?

Posted on Cardiovascular disease, Exercise

5 minutes of exercise each day could lower blood pressure

Findings show importance of activities that raise heart rate for blood pressure control
Findings show the importance of activities that raise heart rate for blood pressure control.

Recent research indicates that incorporating small amounts of physical activity, such as walking uphill or climbing stairs, can help reduce blood pressure.

Research suggests that just five minutes of activity each day could potentially lower blood pressure. Additionally, replacing sedentary behaviour with 20 to 27 minutes of exercise daily—such as uphill walking, stair climbing, running, or cycling—can significantly reduce blood pressure clinically.

Joint senior author Professor Emmanuel Stamatakis, Director of the ProPASS Consortium at the Charles Perkins Centre, stated, “High blood pressure is one of the most significant health issues globally. Unlike some major causes of cardiovascular mortality, there are potentially accessible methods to address this problem beyond just medication.”

Finding that just five extra minutes of exercise daily can lead to significantly lower blood pressure readings highlights the effectiveness of short, intense bouts of physical activity for managing blood pressure.

Hypertension, or consistently high blood pressure, is one of the leading causes of premature death worldwide. It affects 1.28 billion adults and can lead to serious health issues such as stroke, heart attack, heart failure, and kidney damage. Often referred to as the “silent killer,” hypertension typically presents no symptoms, making it especially dangerous.

The research team analysed health data from 14,761 volunteers in five countries to see how replacing one type of movement behaviour with another across the day is associated with blood pressure.  

Each participant used a wearable accelerometer device on their thigh to measure their activity and blood pressure day and night.  

Daily activity was split into six categories: sleep, sedentary behaviour (such as sitting), slow walking, fast walking, standing, and vigorous exercise such as running, cycling or stair climbing. 

The team statistically modelled what would happen if an individual changed various amounts of one behaviour for another to estimate the effect on blood pressure for each scenario and found that replacing sedentary behaviour with 20-27 minutes of exercise per day could potentially reduce cardiovascular disease by up to 28 per cent at a population level.  

Dr. Jo Blodgett, the lead author from the Division of Surgery and Interventional Science at UCL and the Institute of Sport, Exercise, and Health, stated, “Our findings suggest that for most people, engaging in exercise is more effective for reducing blood pressure than opting for less strenuous forms of movement, like walking.”

“The good news is that whatever your physical ability, it doesn’t take long to have a positive effect on blood pressure. What’s unique about our exercise variable is that it includes all exercise-like activities, from running for a bus or a short cycling errand, many of which can be integrated into daily routines.  

“For those who don’t do a lot of exercise, walking still has some positive benefits for blood pressure. But if you want to change your blood pressure, putting more demand on the cardiovascular system through exercise will have the greatest effect.” 

Posted on Cardiovascular disease, Diabetes

Study shows how high blood sugar increases risk of thrombosis

Discoveries by Brazilian researchers belonging to a FAPESP-supported research center could lead to strategies to prevent cardiovascular disease associated with diabetes
Discoveries could lead to strategies to prevent cardiovascular disease associated with diabetes.

A study conducted at the Center for Research on Redox Processes in Biomedicine (Redoxoma) has enhanced our understanding of how high blood sugar levels (hyperglycemia), a common symptom of diabetes, can lead to thrombosis. The findings, published in the Journal of Thrombosis and Haemostasis, could inform the development of strategies to prevent cardiovascular issues in individuals with diabetes.

“The primary causes of death in Brazil and many other Latin American countries are ischemic events, including heart attacks and strokes, where arterial thrombosis plays a significant role. These cardiovascular disorders can result from various risk factors such as high blood sugar (hyperglycemia), abnormal lipid levels (dyslipidemia), and high blood pressure (hypertension). Among these factors, hyperglycemia is notably associated with an increased risk of cardiovascular disease,” stated Renato Simões Gaspar, the article’s lead author.

The investigation was conducted with support from FAPESP during Gaspar’s postdoctoral research and led by Francisco Laurindo, the last author of the article. Laurindo is a professor at the University of São Paulo’s Medical School (FM-USP) in Brazil and is also a member of Redoxoma, a Research, Innovation, and Dissemination Center (RIDC) established by FAPESP at the Institute of Chemistry (IQ-USP). Gaspar currently teaches at the State University of Campinas (UNICAMP).

The authors state that prolonged hyperglycemia and diabetic ketoacidosis increase the risk of thrombosis. This is due to their effects on endothelial dysfunction, which refers to changes in the inner lining of blood vessels. These changes can lead to the binding of platelets to the endothelial cells, triggering the formation of blood clots.

The study showed that peri/epicellular protein disulfide isomerase A1 (pecPDI) regulates platelet-endothelium interaction in hyperglycemia through adhesion-related proteins and alterations in endothelial membrane biophysics.

“We found that a pathway for this PDI in endothelial cells mediates thrombosis in diabetes when hyperglycemia is present, involving a specific molecular mechanism, which we identified,” Laurindo said.

PDI is an enzyme that resides in the endoplasmic reticulum and has the classic function of catalyzing the insertion of disulfide bridges into nascent proteins so that they merge in the correct shape, i.e. so that the amino acid chain folds to form the three-dimensional structure that makes the molecule functional. It is also found in the extracellular space as pecPDI, a pool secreted or bound to the cell surface, in various cell types including platelets and endothelial cells. Studies have shown that pecPDI regulates thrombosis in several models. 

Biochemical and biophysical modifications

To investigate platelet-endothelium interaction in hyperglycemia, the researchers created a model with human umbilical vein endothelial cells cultured in different glucose concentrations to produce normoglycemic and hyperglycemic cells. They assessed PDI’s contribution using whole-cell PDI or pecPDI inhibitors.

The cells were incubated with platelets derived from healthy donors. The platelets adhered almost three times more in hyperglycemic than normoglycemic cells. PDI inhibition reversed this effect, and the researchers concluded that the process is regulated by endothelial pecPDI.

To better understand the result, they investigated biophysical processes such as endothelial cell cytoskeleton remodelling and found that hyperglycemic cells had more well-structured actin filament fibres than normoglycemic cells. They also measured the production of hydrogen peroxide, an oxidizing compound, because reactive oxygen species are mediators of cytoskeleton reorganization and cell adhesion—hyperglycemic cells produced twice as much hydrogen peroxide as normoglycemic cells.

The researchers then investigated whether cytoskeleton reorganization affected cell membrane stiffness since substrate stiffness increases platelet adhesion. Using atomic force microscopy, they demonstrated that hyperglycemic cells were stiffer than normoglycemic cells.

The microscope images also showed the formation of cell elongations with extracellular vesicles that appeared to separate from the elongations. This observation led the researchers to investigate the secretome – the set of proteins secreted by an organism into the extracellular space – to find out whether it included proteins that enhanced platelet adhesion. “The purpose of this experiment was to detect proteins exclusively expressed by or present in hyperglycemic cells and not in controls or cells treated with PDI inhibitors,” Gaspar explained.

They found 947 proteins in the secretome, from which they selected eight with a role in cellular adhesion. They then silenced gene expression for three of these proteins using RNA interference and arrived at two proteins, SLC3A2 and LAMC1, as modulators of platelet adhesion. SLC3A2 is a membrane protein, and LAMC1 is the gamma subunit of laminin 1, a key extracellular matrix component.

Posted on Cardiovascular disease, Exercise

Prolonged sitting can sabotage health, even if you’re young and active

Millennials sit more than 60 hour per week, fueling heart disease risk and accelerating aging
Millennials sit more than 60 hours per week, fueling heart disease risk and accelerating ageing.

Recent research from CU Boulder and the University of California, Riverside, reveals that millennials are spending over 60 hours a week sitting due to long commutes, back-to-back Zoom meetings, and evenings spent streaming and scrolling through social media. This sedentary lifestyle could increase their risk of heart disease and accelerate other signs of ageing.

The study of over 1,000 individuals from Colorado, including 730 twins, is one of the first to investigate how prolonged sitting affects health metrics such as cholesterol levels and body mass index (BMI) in young adults.

Research shows that simply meeting the minimum physical activity guidelines—approximately 20 minutes of moderate exercise each day—is insufficient to offset the risks associated with spending most of our waking hours sitting.

“Our research indicates that reducing the sitting time during the day, engaging in more vigorous exercise, or implementing a combination of both may be essential for lowering the risk of premature ageing in early adulthood,” stated the study’s senior author, Chandra Reynolds, a professor in the Department of Psychology and Neuroscience as well as the Institute for Behavioral Genetics.

After the COVID pandemic, Bruellman noticed that he and others his age were sitting more. He set out to learn more about the consequences.

“Young adults often believe they are immune to the effects of aging. They think, ‘My metabolism is excellent, so I don’t need to worry until I reach my 50s or 60s,’” said Bruellman. “However, what you do during this crucial stage of life is important.”

A walk after work isn’t enough.

The authors analyzed data from participants aged 28 to 49, with an average age of 33, from CU’s Colorado Adoption/Twin Study of Lifespan Behavioural Development and Cognitive Ageing (CATSLife), which has followed twins and adopted individuals since Childhood.

Participants reported sitting almost 9 hours daily, with some sitting as much as 16 hours. On average, they reported between 80 and 160 minutes of moderate physical activity weekly and less than 135 minutes of vigorous exercise weekly. The authors note that these results are likely better than national averages due to Colorado’s active lifestyle.

The researchers looked at two key heart and metabolic ageing measures: total cholesterol/high-density lipoprotein and body mass index (BMI). The study found that the more one sat, the older one looked. Adding a little moderate activity on top of a long day of sitting did little to buffer these impacts.

Young adults who sat 8.5 hours per day and performed at or below current exercise recommendations could enter a “moderate to high risk” category for cardiovascular and metabolic disease, the authors said.

“Taking a quick walk after work may not be enough,” said Reynolds. “While this is increasingly apparent with age, we show that associations are already emerging in early adulthood.”

Adding vigorous activity did have a buffering effect.

For instance, those who exercised vigorously (think running or cycling) for 30 minutes daily had cholesterol and BMI measures that looked like those of individuals five to 10 years younger who sat as much as they did but didn’t exercise.

However, even vigorous activity could not fully buffer the negative impacts of prolonged sitting, the study concluded.

Same genes, different lifestyles

Identical twins are handy to study because they share 100% of their genes, making it easier to rule out genetic factors that might contribute to different health outcomes and zero in on lifestyle differences.

When looking at a subset of twins with different sitting and physical activity habits, the researchers found that replacing sitting with exercise seemed to improve cholesterol better than simply adding exercise to a full day of sitting.

The bottom line, the researchers said, is to try to do both.

To reduce sitting time at work, use a standing desk, take breaks, and organize walking meetings. If possible, do something that gets you out of breath for at least 30 minutes per day, or be a “weekend warrior” and get in longer, vigorous workouts when you can, said Bruellman.

He hopes the study will prompt policymakers to revisit physical activity guidelines and specify how much sitting is too much.

Meanwhile, Reynolds encourages young adults to take steps now that could shape their future:

“This is the time to build habits that will benefit health over the long term.”