Deep brain stimulation alleviates Alzheimer's symptoms in rodent models

 People with Alzheimer's disease develop defects in cognitive functions like memory as well as problems with noncognitive functions that can lead to anxiety and depression. In a paper published April 6 in the journal Cell Stem Cell, investigators used mice to study a process through which new neurons are generated in adulthood, called adult hippocampus neurogenesis (AHN). The research showed that deep brain stimulation of new neurons helped restore both cognitive and noncognitive functions in mouse models of Alzheimer's disease.

"We were surprised to find that activating only a small population of adult-born new neurons was enough to make a significant contribution to these brain functions," says senior author Juan Song, an associate professor at the University of North Carolina at Chapel Hill. The neurons were modified by deep brain stimulation of the suprammamillary nucleus (SuM), which is located in the hypothalamus. "We are eager to find out the mechanisms that underlie these beneficial effects," Song says.

This research used two distinct mouse models of Alzheimer's. The investigators used optogenetics to stimulate the SuM and enhance AHN in Alzheimer's mice. Their earlier research had shown that stimulation of the SuM could increase the production of new neurons and improve their qualities in normal adult mice. In the new study, the investigators showed that this strategy was also effective in the Alzheimer's mice, leading to the generation of new neurons that made better connections with other parts of the brain.

However, having more improved new neurons is not enough to improve memory and mood. Behavioral improvement in Alzheimer's mice were seen only when these improved new neurons were activated by chemogenetics. The researchers used memory tests as well as established assessments to look for anxiety-like and depression-like behavior to confirm these improvements. The results suggested that multi-level enhancement of new neurons -- enhancement in number, properties, and activity -- is required for behavioral restoration in Alzheimer's brains.

To further understand the mechanism, they also analyzed the protein changes in the hippocampus of Alzheimer's mice in response to activation of SuM-modified adult-born new neurons. They found several well-known protein pathways activated inside cells, including those known to be important for improved memory performance, as well as those that allow clearance of the plaques related to Alzheimer's.

"It was striking that multilevel enhancement of such a small number of adult-born new neurons made such a profound functional contribution to the animals' diseased brains," Song says. "We were also surprised to find that activation of SuM-enhanced neurons promoted the process that can potentially remove plaques."

Future efforts of the team will focus on developing potential therapeutics that mimic the beneficial effects mediated by activation of SuM-modified new neurons. "We are hoping these drugs could exert therapeutic effects in patients with low or no hippocampal neurogenesis," Song says. "Ultimately, the hope is to develop first-in-class, highly targeted therapies to treat Alzheimer's and related dementia."

Journal Reference:

1. Ya-Dong Li, Yan-Jia Luo, Ling Xie, Dalton S. Tart, Ryan N. Sheehy, Libo Zhang, Leon G. Coleman, Xian Chen, Juan Song. Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer’s disease. Cell Stem Cell, 2023; 30 (4): 415 DOI: 10.1016/j.stem.2023.02.006

https://www.sciencedaily.com/releases/2023/04/230406113950.htm

Samsung employees reportedly leaked sensitive info on ChatGPT by accident

 Samsung Electronics employees interacting with artificial intelligence tool ChatGPT accidentally leaked company information, according to an exclusive report by the South Korean outlet The Economist.

Employees in the company's semiconductor division told the news outlet that corporate data was leaked on three separate occasions.

The website said the leaks came within 20 days after the South Korean conglomerate had lifted a ban on the chatbot. 

That ban was reportedly put into place to avoid such leaks.

Information shared with ChatGPT supposedly included "source code related to Samsung Electronics facility measurement."

The Economist said a worker had uncovered an error while executing the source code and inquired about a solution.

Another employee uploaded program code written to identify yield and defective equipment and requested code optimization.

A third employee uploaded recordings of a meeting to generate the meeting minutes.

"It is difficult to confirm because it is an internal matter of the company," a Samsung Electronics official told a reporter, according to The Economist, which noted that the company had applied "emergency" protective measures.

The company may also block ChatGPT on the company network if a similar accident occurs, the report said.

https://www.foxbusiness.com/technology/samsung-employees-reportedly-leaked-sensitive-info-chatgpt-accident

DiCaprio Testifies That CCP-Linked Financier Planned $30 M Donation To Obama 2012 Campaign

 by Zachary Stieber via The Epoch Times (emphasis ours),

Malaysian financier Jho Low planned to donate up to $30 million to help then-U.S. President Barack Obama’s 2012 reelection campaign, according to actor Leonardo DiCaprio.

DiCaprio recounted a discussion he had with Low, whose given name is Low Taek Jho, while testifying during a federal trial in Washington.

“It was a casual conversation about what party he was in support of,” DiCaprio said, telling jurors that Low said he planned on giving “a significant donation” to the Democratic Party that was “somewhere to the tune of $20 to 30 million.”

“I basically said, ‘Wow, that’s a lot of money.'”

DiCaprio took the witness stand during the trial of Prakazrel “Pras” Michel of the Fugees hip-hop group, who, according to an indictment, conspired with Low to funnel money from the foreigner to Obama’s 2012 campaign.

Prosecutors say Michel received $21 million from Low and funneled the money to political committees through a series of straw donors, including various companies and people associated with the musician.

Low and Michel enacted the conspiracy “to gain access to, and influence with” Obama, the U.S. Department of Justice stated. In one instance, an associate of Michel forwarded an email from Michel asking for financial contributions to Obama and told Low that funding would “guarantee you a maximum 15 minutes audience” with Obama.

Low’s father met and took pictures with Obama at an event in Washington but Low didn’t meet with the president, according to charging documents.

Michel also allegedly attempted to conceal the funding, which ran afoul of a U.S. law that makes it illegal for foreigners to donate directly or indirectly to U.S. campaigns, and he allegedly conspired with others to pressure the Trump administration to drop its probe of Low.

Michel has denied the allegations.

According to prosecutors, China’s vice minister of public security, a member of the Chinese Communist Party (CCP), was also involved in the scheme, which included pushing to send a Chinese dissident back to China.

DiCaprio is one of several prominent figures linked to Low, a fugitive who’s facing separate federal criminal charges for allegedly embezzling $4.5 billion from 1MDB, a wealth fund created by the Malaysian government to increase economic development through reaching agreements with other countries and foreign individuals.

The financier, who was known to pay Hollywood celebrities to party with him, supported DiCaprio’s charitable foundation and helped fund “The Wolf of Wall Street,” the 2013 movie in which DiCaprio starred and was nominated for an Oscar.

https://www.zerohedge.com/political/leonardo-dicaprio-testifies-ccp-linked-financier-planned-30-million-donation-obamas-2012

Fasting diet reduces risk markers of type 2 diabetes

 A fasting diet which focuses on eating early in the day could be the key to reducing the risk of developing type 2 diabetes.

Researchers from the University of Adelaide and South Australian Health and Medical Research Institute (SAHMRI) compared two different diets: a time restricted, intermittent fasting diet and a reduced calorie diet to see which one was more beneficial for people who were prone to developing type 2 diabetes.

"Following a time restricted, intermittent fasting diet could help lower the chances of developing type 2 diabetes," said senior author the University of Adelaide's Professor Leonie Heilbronn, Adelaide Medical School.

"People who fasted for three days during the week, only eating between 8am and 12pm on those days, showed a greater tolerance to glucose after 6 months than those on a daily, low-calorie diet.

"Participants who followed the intermittent fasting diet were more sensitive to insulin and also experienced a greater reduction in blood lipids than those on the low-calorie diet."

Type 2 diabetes occurs when the body's cells don't respond effectively to insulin and it loses its ability to produce the hormone, which is responsible for controlling glucose in blood.

It's estimated that nearly 60 percent of type 2 diabetes cases could be delayed or prevented with changes to diet and lifestyle.

Almost 1.3 million Australians are currently living with the condition, for which there is no cure.

There were more than 200 participants recruited from South Australia in the 18-month study, which was published in the journal Nature Medicine.

Participants on both the time restricted, intermittent fasting diet and the low-calorie diet experienced similar amounts of weight loss.

"This is the largest study in the world to date and the first powered to assess how the body processes and uses glucose after eating a meal, which is a better indicator of diabetes risk than a fasting test," said first author Xiao Tong Teong, a Ph.D. student at the University of Adelaide.

"The results of this study add to the growing body of evidence to indicate that meal timing and fasting advice extends the health benefits of a restricted calorie diet, independently from weight loss, and this may be influential in clinical practice."

Further research is needed to investigate if the same benefits are experienced with a slightly longer eating window, which could make the diet more sustainable in the long term.

More information: Leonie Heilbronn, Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial, Nature Medicine (2023). DOI: 10.1038/s41591-023-02287-7. www.nature.com/articles/s41591-023-02287-7

https://medicalxpress.com/news/2023-04-fasting-diet-markers-diabetes.html

Why viruses like SARS-CoV-2 can reinfect hosts, evade the immune response

 The human body is capable of creating a vast, diverse repertoire of antibodies—the Y-shaped sniffer dogs of the immune system that can find and flag foreign invaders. Despite our ability to create a range of antibodies to target viruses, humans create antibodies that target the same viral regions again and again, according to a new study led by investigators from Brigham and Women's Hospital, a founding member of the Mass General Brigham healthcare system, and Harvard Medical School. These "public epitopes" mean that the generation of new antibodies is far from random and that a virus may be able to mutate a single amino acid to reinfect a population of previously immune hosts. The team's findings, which have implications for our understanding of immunity and public health, are published in Science.

"Our research may help explain a lot of the patterns we've seen during the COVID-19 pandemic, especially in terms of re-infection," said corresponding author Stephen J. Elledge, Ph.D., the Gregor Mendel Professor of Genetics at the Brigham and HMS. "Our findings could help inform immune predictions and may change the way people think about immune strategies."

Before the team's study, there were hints, but no clear evidence, that people's immune systems didn't target sites on a viral protein at random. In isolated examples, investigators had seen recurrent antibody responses across individuals—people recreating antibodies to home in on the same viral protein location (known as an epitope). But the study by Elledge and colleagues helps explain the extent and underlying mechanisms of this phenomenon.

The team used a tool the Elledge lab developed in 2015 called VirScan, which can detect thousands of viral epitopes—sites on viruses that antibodies recognize and bind to—and give a snapshot of a person's immunological history from a single drop of blood. For the new study, the researchers used VirScan to analyze 569 blood samples from participants in the U.S., Peru, and France. They found that recognition of public epitopes—viral regions recurrently targeted by antibodies—was a general feature of the human antibody response. The team mapped 376 of these commonly targeted epitopes, uncovering exactly where antibodies bind their targets. The team found that antibodies recognized public epitopes through germline-encoded amino acid binding (GRAB) motifs—regions of the antibodies that are particularly good at picking out one specific amino acid. So, instead of randomly choosing a target, human antibodies tend to focus on regions where these amino acids are available for binding, and thus repeatedly bind the same spots.

A small number of mutations can help a virus avoid detection by these shared antibodies, allowing the virus to reinfect populations that were previously immune.

"We find an underlying architecture in the immune system that causes people, no matter where in the world they live, to make essentially the same antibodies that give the virus a very small number of targets to evade in order to reinfect people and continue to expand and further evolve," said lead author Ellen L. Shrock, Ph.D., of the Elledge lab.

Interestingly, the team notes that nonhuman species produce antibodies that recognize different public epitopes from those that humans recognize. And, while it is more likely for a person to produce antibodies against a public epitope, some people do produce rarer antibodies, which may more effectively protect them from reinfection. These insights could have important implications for treatments developed against COVID-19, such as monoclonal antibodies, as well as for vaccine design.

"The more unique antibodies may be a lot harder to evade, which is important to consider as we think about the design of better therapies and vaccines," said Elledge.

More information: Ellen L. Shrock et al, Germline-encoded amino acid-binding motifs drive immunodominant public antibody responses, Science (2023). DOI: 10.1126/science.adc9498. www.science.org/doi/10.1126/science.adc9498

https://medicalxpress.com/news/2023-04-reveal-viruses-sars-cov-reinfect-hosts.html

Study could change assumptions about helmet safety

 A new study led by researchers at New York Institute of Technology College of Osteopathic Medicine (NYITCOM) could change public perceptions about helmet safety.

Helmets, which are proven to prevent skull fractures and head wounds, are no doubt critical for safety. However, there is much debate about the extent to which they are capable of mitigating the effects of concussions. The hard-shelled, heavily padded helmets used by many of today's athletes, military personnel, and industrial workers have been much adapted since early helmet models, which lacked inner padding. But do these design enhancements provide additional protection?

That's the question that NYITCOM researchers, led by biomedical engineer and Assistant Professor Milan Toma, Ph.D., address in a new study published in Applied Sciences.

During a concussion, forces from the initial hit cause the brain to move rapidly back and forth (oscillate) within the skull and make contact with skull bones. This brain-skull interaction can damage brain chemicals and tissues, especially if multiple interactions occur. Cerebrospinal fluid (CSF), which is found in the central brain cavities and space surrounding the brain and spinal cord, cushions the brain and protects it from hitting the skull. However, as one of Toma's previous studies indicated, if subsequent hits occur in quick succession, the fluid loses its protective abilities and the brain incurs more stress with each successive skull oscillation.

While no helmet can fully prevent a concussion, some researchers, including Toma, hypothesize that helmet design can play a role in limiting concussion severity. The latest advancements in helmet design have shifted away from the conventional hard-shell and extensively padded helmets. Instead, they employ inventive materials and construction methods, with an emphasis on minimizing forces caused by head rotations during and after impacts. Experts believe that these forces are primarily responsible for concussions, as also demonstrated by Toma's earlier studies. Nevertheless, conventional helmets continue to be widely used across various sports disciplines, especially recreational ones like cycling and skateboarding, due to the exorbitant cost of the newer designs.

"Our new study may have implications for future helmet design and calls into question current assumptions regarding the best way to protect soldiers and athletes from concussions," says Toma, whose research largely focuses on how fluids in the human body respond to forces.

Using 3D models, Toma and his fellow researchers, including NYITCOM students Faiz Syed and Elisabeth Frankini, as well as Research Technician Kelsi Hurdle, simulated brain-skull interactions under conditions resembling a low-speed, head-on collision. This force of impact is similar to the collisions experienced by athletes in contact sports and bicycle accidents. The simulation's conditions also accounted for CSF presence and the features found in many of today's helmets: a hard exterior with soft inner padding.

The simulations projected multiple direct brain-skull interactions following the initial hit. In other words, the current helmet design did little to limit concussion severity. The CSF's ability to provide natural protection diminished with each successive skull oscillation, an outcome consistent with Toma's earlier research.

"These smaller back-and-forth motions may seem insignificant compared to the first one, however, we showed that they can still cause serious damage," the researchers write. "As these subsequent head movements occur, they compromise the ability of CSF inside the skull to prevent contact between the brain and skull bones."

Their findings also support a 2020 experimental study by another institution, which compared modern military helmets with the unpadded helmets used during World War I. Surprisingly, that study found that the historical helmets may have had an advantage in protecting from concussions when relying solely on cerebrospinal fluid.

The NYITCOM authors conclude their new research by calling for additional studies aimed at developing advanced helmet designs for better protection against concussions.

However, they make it known that using a helmet—even one with some limitations—is still better than not wearing any head protection at all.

Other co-authors include Jodan Garcia, D.P.T., of Byrdine F. Lewis College of Nursing and Health Professions at Georgia State University, and Rosalyn Chan-Akeley, M.D., of the Lang Research Center at New York-Presbyterian Hospital Queens.

More information: Faiz Syed et al, Cushioning Effect of Conventional Padded Helmets on Interaction between Cerebrospinal Fluid and Brain after a Low-Speed Head Impact, Applied Sciences (2023). DOI: 10.3390/app13074544

https://medicalxpress.com/news/2023-04-assumptions-helmet-safety.html

Improper Charging of FreeStyle Libre Readers Prompts Alert From Abbott

 Abbott has issued a safety notification regarding the readers used as part of the FreeStyle Libre® family of products, specifically the FreeStyle Libre, FreeStyle Libre 14 day, and FreeStyle Libre 2 Flash Glucose Monitoring Systems (all reader serial numbers).

The FreeStyle Libre systems consist of a handheld reader that collects real-time glucose readings directly from the sensor that is inserted just under the skin. The reader uses lithium-ion batteries, which have the potential for battery swelling, leakage or extreme overheating if not properly stored, charged, or used with the Abbott-provided yellow USB cable and power adapter. Though rare, battery issues have been reported worldwide, and in a few instances, have resulted in fires.

In February 2023, Abbott initiated a voluntary medical device correction to emphasize instructions for its readers. At this time, no readers are being recalled; customers should continue to use them with the Abbott-provided USB cable and power adapter.

Abbott’s recommendations to prevent battery-related issues with the readers include:

Using only the Abbott-supplied yellow USB cable and adapter for charging;

Keeping the reader, power adaptor and USB cable away from water or other liquids;

Storing the reader between -4 °F and 140 °F;

Keeping the reader clean by avoiding dust, dirt, blood, control solution, water, bleach or any other substance in the test strip or USB port.

Additional guidance is available at www.FreeStyleBattery.com. The website includes a short survey that can help a user determine whether the reader needs to be replaced.  This safety notification does not affect any of the FreeStyle Libre family of sensors.

https://www.empr.com/home/news/safety-alerts-and-recalls/improper-charging-of-freestyle-libre-readers-prompts-alert-from-abbott/