Medical Bulletin 24/ September/ 2024
Here are the top medical news for the day:
Having PTSD Symptoms? Tetris Video Game May help: A BMC Study on healthcare workers Reveals
A single treatment session, which includes the video game Tetris, may help reducing the symptoms of post-traumatic stress disorder (PTSD). This has been shown in a new study carried out with healthcare professionals working during the COVID-19 pandemic. The study led by researchers at Uppsala University is published in BMC Medicine.
“It is possible to reduce the frequency of unpleasant and intrusive memories of trauma, and thereby also alleviate other PTSD symptoms. With just one guided treatment session, we saw positive effects that persisted after five weeks and even six months after treatment. Trauma can affect anyone. If this effect can be achieved with an everyday tool that includes video gaming, it could be an accessible way to help many people,” explains Emily Holmes, Professor at Uppsala University who led the study.
In the current study, the researchers focused on getting rid of flashbacks. By replacing intrusive memories using a visual task, other PTSD symptoms can also be reduced.
The treatment is based on what is known as mental rotation, which lies at the heart of Tetris. When you look at an object from one angle, you can imagine what it would look like if it were rotated to a different position and could be seen from a different angle.
The study involved 164 participants. All participants monitored their intrusive memories of trauma for a week. After that they were randomized to one of the two conditions. Half the group were asked to play Tetris with mental rotation. The other half, the control group, was given a non-visual task: listening to the radio. All participants kept a diary about their flashbacks. At the start of the study, participants were experiencing an average of 15 flashbacks a week. At a five-week follow-up, participants in the control group had an average of five episodes a week, but those in the gaming group had an average of just one.
At a follow-up six months after treatment, participants in the gaming group had less severe symptoms of PTSD. In an assessment using a recognized questionnaire (PCL-5) often used to assess all PTSD symptoms, the gaming group experienced around half as many as problems as the control group.
“It was surprising to us that the treatment method was so effective and that the improvement in symptoms lasted for six months. I realize that it may seem unlikely that such a short intervention, which includes video games but doesn’t include an in-depth discussion of trauma with a therapist, could help. But the study provides scientifically controlled evidence that a single guided digital treatment session can reduce the number of intrusive memories, and that it can be used safely by participants,” said Emily Holmes.
“My vision is that one day we will be able to provide a tool for people such as healthcare professionals after traumatic events to help prevent and treat early PTSD symptoms, that is a 'cognitive vaccine', in a similar way that we currently vaccinate against some infectious physical diseases” explains Holmes.
Reference: Kanstrup, M., Singh, L., Leehr, E.J. et al. A guided single session intervention to reduce intrusive memories of work-related trauma: a randomised controlled trial with healthcare workers in the COVID-19 pandemic. BMC Med 22, 403 (2024). https://doi.org/10.1186/s12916-024-03569-8
Science of Aging: Stanford Researchers find Major Biomolecular Shifts in Our 40s and 60s
Researchers assessed many thousands of different molecules in people from age 25 to 75, as well as their microbiomes the bacteria, viruses and fungi that live inside us and on our skin and found that the abundance of most molecules and microbes do not shift in a gradual, chronological fashion. Rather, we undergo two periods of rapid change during our life span, averaging around age 44 and age 60. The paper was published in the journal Nature Aging
“We’re not just changing gradually over time; there are some really dramatic changes,” said Michael Snyder, PhD, professor of genetics and the study’s senior author. “It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that’s true no matter what class of molecules you look at.”
These big changes likely impact our health the number of molecules related to cardiovascular disease showed significant changes at both time points, and those related to immune function changed in people in their early 60s.
Snyder, the Stanford W. Ascherman, MD, FACS Professor in Genetics, and his colleagues were inspired to look at the rate of molecular and microbial shifts by the observation that the risk of developing many age-linked diseases does not rise incrementally along with years. For example, risks for Alzheimer’s disease and cardiovascular disease rise sharply in older age, compared with a gradual increase in risk for those under 60.
The researchers used data from 108 people they’ve been following to better understand the biology of aging. Past insights from this same group of study volunteers include the discovery of four distinct “ageotypes,” showing that people’s kidneys, livers, metabolism and immune system age at different rates in different people.
The new study analyzed participants who donated blood and other biological samples every few months over the span of several years; the scientists tracked many different kinds of molecules in these samples, including RNA, proteins and metabolites, as well as shifts in the participants’ microbiomes. The researchers tracked age-related changes in more than 135,000 different molecules and microbes, for a total of nearly 250 billion distinct data points.
They found that thousands of molecules and microbes undergo shifts in their abundance, either increasing or decreasing — around 81% of all the molecules they studied showed non-linear fluctuations in number, meaning that they changed more at certain ages than other times. When they looked for clusters of molecules with the largest changes in amount, they found these transformations occurred the most in two time periods: when people were in their mid-40s, and when they were in their early 60s.
Although much research has focused on how different molecules increase or decrease as we age and how biological age may differ from chronological age, very few have looked at the rate of biological aging. That so many dramatic changes happen in the early 60s is perhaps not surprising, Snyder said, as many age-related disease risks and other age-related phenomena are known to increase at that point in life.
The large cluster of changes in the mid-40s was somewhat surprising to the scientists.
“This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women. Identifying and studying these factors should be a priority for future research,” Xiaotao Shen, PhD, a former Stanford Medicine postdoctoral scholar, the first author of the study said.
In people in their 40s, significant changes were seen in the number of molecules related to alcohol, caffeine and lipid metabolism; cardiovascular disease; and skin and muscle. In those in their 60s, changes were related to carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle.
It’s possible some of these changes could be tied to lifestyle or behavioral factors that cluster at these age groups, rather than being driven by biological factors, Snyder said. For example, dysfunction in alcohol metabolism could result from an uptick in alcohol consumption in people’s mid-40s, often a stressful period of life.
“I’m a big believer that we should try to adjust our lifestyles while we’re still healthy,” Snyder said.
Reference: Shen, X., Wang, C., Zhou, X. et al. Nonlinear dynamics of multi-omics profiles during human aging. Nat Aging (2024). https://doi.org/10.1038/s43587-024-00692-2
Bariatric Surgery Surpasses GLP-1 Diabetes Medication in Progression of Chronic Kidney Disease, shows Cleveland Clinic Study
Bariatric surgery was shown to protect kidney function and reduce the risk of kidney failure in study participants when compared to GLP-1 medications.
A Cleveland Clinic study showed that in patients with type 2 diabetes, obesity, and chronic kidney disease, bariatric surgery was associated with a significant decrease in the progression of chronic kidney disease compared to those who received GLP-1 diabetes medications. The paper was published in Annals of Surgery.
Ali Aminian, M.D., lead author of the study and director of Cleveland Clinic’s Bariatric & Metabolic Institute, said, “Our study shows that bariatric surgery can protect the kidneys and prevent the worsening of kidney function. In patients with obesity and type 2 diabetes who already have established chronic kidney disease, bariatric surgery can change the trajectory of the disease.”
The study included 425 adult patients (aged 18 to 75) with type 2 diabetes, obesity, and stage 3 or 4 chronic kidney disease. Among the study participants, 183 patients underwent bariatric surgery while 242 patients were treated with GLP-1 receptor agonist medications.
Patients involved in the study underwent bariatric surgery between 2010 and 2017 or continuously received GLP-1 medications that were FDA-approved and available during the time frame of the study. In the nonsurgical group, the most common GLP-1 medications were liraglutide and exenatide. During follow-up, 20% of patients in the nonsurgical group received newer GLP-1 medications such as semaglutide (Ozempic) or tirzepatide (Mounjaro) at some point.
Researchers found that bariatric surgery could protect kidney function and reduce the risk of kidney failure or death in patients. Specifically, study findings showed that bariatric surgery was associated with a 60% lower risk of progression of kidney disease and a 44% lower risk of developing kidney failure or death in comparison to the nonsurgical group.
Over the length of the eight-year study, researchers also found that 22% of the participants in the surgical group experienced progression of kidney disease compared to 45% in the non-surgical group. In addition, 24% in the surgical group developed kidney failure or died over the seven-year span of the study, compared to 44% in the non-surgical group.
The study participants who underwent bariatric surgery experienced more weight loss and better control of their diabetes. They also required less medication to control their diabetes, high blood pressure and high cholesterol.
“Despite its kidney-protective benefits, bariatric surgery is underutilized in clinical practice,” said Dr. Aminian. “In the current management guidelines of chronic kidney disease, while maintaining a healthy weight through lifestyle changes is advised, the option of bariatric surgery has not been considered.”
Jonathan Taliercio, D.O., a nephrologist at Cleveland Clinic and co-author of the study, added: “These numbers are promising and show bariatric surgery should be considered as a treatment option for patients with chronic kidney disease and obesity.”
Dr. Aminian said that GLP-1 receptor agonist medications are quickly evolving, and the role they have in combination with bariatric surgery needs further investigation.
Reference: Aminian, A., Gasoyan, H., Zajichek, A., Alavi, M. H., Casacchia, N. J., Wilson, R., Feng, X., Corcelles, R., Brethauer, S. A., Schauer, P. R., Kroh, M., Rosenthal, R. J., Taliercio, J. J., Poggio, E. D., Nissen, S. E., & Rothberg, M. B. (2024). Renoprotective effects of metabolic surgery versus GLP-1 receptor agonists on progression of kidney impairment in patients with established kidney disease. Annals of Surgery, 280(3), 414-423. https://doi.org/10.1097/SLA.0000000000006379
MIT Study Shows That Two Dose Schedule May Make HIV Vaccine More Effective
In a new study, the researchers have now found that they can achieve an immune response similar to multidose regimen, with just two doses, given one week apart. The first dose, which is much smaller, prepares the immune system to respond more powerfully to the second, larger dose.
This study, which was performed by bringing together computational modeling and experiments in mice, used an HIV envelope protein as the vaccine. A single-dose version of this vaccine is now in clinical trials, and the researchers hope to establish another study group that will receive the vaccine on a two-dose schedule.
"By bringing together the physical and life sciences, we shed light on some basic immunological questions that helped develop this two-dose schedule to mimic the multiple-dose regimen," says Arup Chakraborty, the John M. Deutch Institute Professor at MIT and a member of MIT's Institute for Medical Engineering and Science and the Ragon Institute of MIT, MGH and Harvard University.
This approach may also generalize to vaccines for other diseases, Chakraborty notes.
Chakraborty and Darrell Irvine, a former MIT professor of biological engineering and materials science and engineering and member of the Koch Institute for Integrative Cancer Research, who is now a professor of immunology and microbiology at the Scripps Research Institute, are the senior authors of the study, which appears in Science Immunology. The lead authors of the paper are Sachin Bhagchandani PhD and Leerang Yang PhD.
One promising vaccine now in clinical trials consists of an HIV protein called an envelope trimer, along with a nanoparticle called SMNP. The nanoparticle, developed by Irvine's lab, acts as an adjuvant that helps recruit a stronger B cell response to the vaccine.
In clinical trials, this vaccine and other experimental vaccines have been given as just one dose. However, there is growing evidence that a series of doses is more effective at generating broadly neutralizing antibodies. The seven-dose regimen, the researchers believe, works well because it mimics what happens when the body is exposed to a virus: The immune system builds up a strong response as more viral proteins, or antigens, accumulate in the body.
In the new study, the MIT team investigated how this response develops and explored whether they could achieve the same effect using a smaller number of vaccine doses.
"Giving seven doses just isn't feasible for mass vaccination," Bhagchandani says. "We wanted to identify some of the critical elements necessary for the success of this escalating dose, and to explore whether that knowledge could allow us to reduce the number of doses."
The researchers began by comparing the effects of one, two, three, four, five, six, or seven doses, all given over a 12-day period. They initially found that while three or more doses generated strong antibody responses, two doses did not. However, by tweaking the dose intervals and ratios, the researchers discovered that giving 20 percent of the vaccine in the first dose and 80 percent in a second dose, seven days later, achieved just as good a response as the seven-dose schedule.
"It was clear that understanding the mechanisms behind this phenomenon would be crucial for future clinical translation," Yang says. "Even if the ideal dosing ratio and timing may differ for humans, the underlying mechanistic principles will likely remain the same."
Using a computational model, the researchers explored what was happening in each of these dosing scenarios. This work showed that when all of the vaccine is given as one dose, most of the antigen gets chopped into fragments before it reaches the lymph nodes. Lymph nodes are where B cells become activated to target a particular antigen, within structures known as germinal centers.
When only a tiny amount of the intact antigen reaches these germinal centers, B cells can't come up with a strong response against that antigen.
However, a very small number of B cells do arise that produce antibodies targeting the intact antigen. So, giving a small amount in the first dose does not "waste" much antigen but allows some B cells and antibodies to develop. If a second, larger dose is given a week later, those antibodies bind to the antigen before it can be broken down and escort it into the lymph node. This allows more B cells to be exposed to that antigen and eventually leads to a large population of B cells that can target it.
"The early doses generate some small amounts of antibody, and that's enough to then bind to the vaccine of the later doses, protect it, and target it to the lymph node. That's how we realized that we don't need to give seven doses," Bhagchandani says. "A small initial dose will generate this antibody and then when you give the larger dose, it can again be protected because that antibody will bind to it and traffic it to the lymph node."
Those antigens may stay in the germinal centers for weeks or even longer, allowing more B cells to come in and be exposed to them, making it more likely that diverse types of antibodies will develop.
The researchers also found that the two-dose schedule induces a stronger T-cell response. The first dose activates dendritic cells, which promote inflammation and T-cell activation. Then, when the second dose arrives, even more dendritic cells are stimulated, further boosting the T-cell response.
Overall, the two-dose regimen resulted in a fivefold improvement in the T-cell response and a 60-fold improvement in the antibody response, compared to a single vaccine dose.
"Reducing the 'escalating dose' strategy down to two shots makes it much more practical for clinical implementation. Further, a number of technologies are in development that could mimic the two-dose exposure in a single shot, which could become ideal for mass vaccination campaigns," Irvine says.
The researchers are now studying this vaccine strategy in a nonhuman primate model. They are also working on specialized materials that can deliver the second dose over an extended period of time, which could further enhance the immune response.
Reference: Bhagchandani, S. H., Yang, L., Lam, J. H., Maiorino, L., Ben-Akiva, E., Rodrigues, K. A., Romanov, A., Suh, H., Aung, A., Wu, S., Wadhera, A., Chakraborty, A. K., & Irvine, D. J. (2024). Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response. Science Immunology, 9(99). https://doi.org/10.1126/sciimmunol.adl3755
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