Neurons that track and regulate blood sugar levels

 New research has discovered neurons within the brain that detect and respond to changes in the level of sugar within the bloodstream.

Understanding how this blood sugar detection system works and how these neurocircuits operate would give researchers and doctors greater insights into how our brains regulate our blood sugar, and perhaps, how to target them therapeutically to treat metabolic diseases like diabetes and obesity, according to the study authors.

The study was published June 22 online in Diabetes.

"We've known for a long time that many neurons can detect sugar locally within the brain," said Dr. Michael Schwartz, an endocrinologist with the University of Washington School of Medicine and co-director of the UW Medicine Diabetes Institute. "What is new, however, is the evidence that a subset of neurons located in the hypothalamus can sense and respond to sugar in the bloodstream itself, analogous to the cells in the pancreas that secrete insulin."

In this study, researchers were able to monitor both blood sugar levels and the activity of neurons within the hypothalamus of conscious mice in real time. They found that when blood sugar levels rise, the activity of this subset of neurons decreases rapidly. Researchers speculate that these neurons detect and respond to variation in blood sugar transmitted by sensory neurons that supply the vasculature (rather than sugar levels in the brain, which change much more slowly), Schwartz noted. This sensory information is then transmitted to one or more neurocircuits that control the blood sugar level in conjunction with the pancreas, which produces insulin for the body.

Clinically, this is important because when treating patients with diabetes, clinicians often find that the patients' system is actively maintaining an elevated blood sugar level, presumably "because that's where the brain thinks the blood sugar level is supposed to be," Schwartz said.

"For example, if a normal blood sugar is 100, a patient with diabetes may well have a blood sugar above 300," he said. "If it's been at that elevated level for days or weeks, and if you suddenly lower it back to 100, the brain will think that's too low, and will try to increase blood sugar level again."

This evidence that diabetes is associated with an impaired ability of the brain to sense the blood sugar level suggests that in the future, reversing this type of sensing defect may allow the brain to control blood sugar in a more appropriate way, Schwartz concluded.

More information: Jennifer D. Deem et al, Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia, Diabetes (2023). DOI: 10.2337/db23-0139

https://medicalxpress.com/news/2023-07-neurons-track-blood-sugar.html

Brisk Walking: No-Cost Option for Patients to Improve Cancer Outcomes

I 'm Dr Maurie Markman from Cancer Treatment Centers of America. I wanted to discuss very briefly a highly provocative paper that I think deserves attention. It was published in the Journal of Clinical Oncology, entitled Physical Activity in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

This is an incredibly important paper that highlights something that has not been emphasized enough in oncology practice. What are the things that we can recommend to our patients that are not expensive, but which they can do for themselves to impact a potential for adding to a positive outcome? In this case, we're talking about physical activity.

This was an extremely well-conducted study. It was a prospective cohort study that was built into an ongoing phase 3 randomized, multicenter study looking at adjuvant therapy of stage III colon cancer. The median follow-up in this population was almost 6 years. We're talking about 1696 patients.

The investigators did a survey, asking patients when they started treatment and then a short time after that, and measured the level of recreational physical activity. They didn't do a design. They asked the individuals how much activity they had.

There were a number of analyses done in terms of looking at this that were reported in the paper. I want to highlight one because it's so simple. The investigators looked at brisk walking. For brisk walking, the 3-year disease-free survival was 81.7% for individuals who had less than 1 hour per week of brisk walking vs 88.4% for individuals who walked briskly more than 3 hours per week.

Walking an additional 2 hours or more per week, prospectively viewed in individuals who had the same baseline characteristics otherwise, impacted disease-free survival in stage III colon cancer. There is no additional expense. It's walking. There were other activities that were looked at here, including aerobic activities.

The bottom line is that physical activity is positive, not expensive, and focuses on what the individual patient can do for themselves. It's something I believe that, in the oncology community, we need to emphasize more.

I encourage you to review this paper and use your own opinion as to what you want to do with this information, but I strongly urge you to look at this — and other types of activities — that we can recommend that individuals do themselves to impact their outcomes related to cancer.

Thank you for your attention.

Maurie Markman, MD, is president of medicine and science at Cancer Treatment Centers of America in Philadelphia. He has more than 20 years of experience in cancer treatment and gynecologic oncology research.

https://www.medscape.com/viewarticle/987177

Stem Cell Medical Tourism Leads to Meningitis in MS Patient

 A woman with multiple sclerosis (MS) who had intrathecal injections of umbilical cord stem cells in Mexico ended up with a severe Mycobacterium abscessus infection that took weeks to identify and treat, according to a case study.

In October 2022, the woman in her 30s traveled to Baja California, Mexico, and received two lumbar punctures of the stem cell product as a "treatment" for MS after researching the clinic online, Daniel Pastula, MD, of the University of Colorado and the Colorado School of Public Health, and colleagues reported in Emerging Infectious Diseasesopens in a new tab or window.

Her diagnostic odyssey started the day after her second injection, when she went to an emergency department in the U.S. for a headache and received an epidural blood patch for presumed postlumbar puncture cerebrospinal fluid (CSF) leak.

After two more outpatient blood patches and persistent fevers, she was admitted to a hospital with a fever of 101.3ºF but otherwise normal vital signs and complete blood counts, and nothing remarkable in CSF. A 10-day course of antibiotics helped, but as soon as she stopped them, she had a worsening headache and her fever came back -- which was when she ended up with Pastula's team.

Pastula and colleagues ultimately discovered a rapidly growing nontuberculous mycobacterium after 7 days of incubation.

They started one intensive antibiotic regimen that was intolerable due to gastrointestinal side effects; but once they homed in on M. abscessus, they were able to adjust the regimen to azithromycin (500 mg IV 1x/d), ceftaroline (600 mg IV 3x/d), eravacycline (80 mg IV 1x/d), imipenem (500 mg IV 4x/d), and tedizolid (200 mg orally 1x/d).

Pastula and team reported that the regimen resolved the patient's headaches and fevers, and she's now completed 3 months of treatment without recurrent symptoms. It's not clear how long she will have to remain on the regimen, as the infection can be indolent and antibiotic treatment may be needed for many months, Pastula said.

They noted that it took "8 weeks of evaluations after her initial visit to the outside emergency department to identify and treat M. abscessus."

Pastula said the case is particularly dangerous not only because of the procedure itself, but also the severity of the infection, the challenge in treating it, and potential longterm effects on the patient.

In addition, drugs to treat MS are immunosuppressive, and should not be used during an active chronic infection, Pastula pointed out.

"Not only did the clinic give her something that wasn't effective against MS and cause an infection; now, we have to delay, for some unknown period of time, the treatments that work best for MS," he said. The patient had not previously been on disease-modifying or immunosuppressive drugs for MS.

The case also highlights the problematic nature of medical tourism, particularly when it comes to stem cell therapies, the researchers said.

"Right now, stem cell therapy for various chronic neurologic conditions, chronic progressive [ones], is not proven," Pastula told MedPage Today. "It has not proven to be ... safe, and it is not proven to be effective."

According to the National Multiple Sclerosis Society, stem cell therapy for MS "should only be provided at accredited stem cell centersopens in a new tab or window that meet specific criteria to perform stem cell procedures or within a clinical trialopens in a new tab or window." The organization also notes that there is currently "no evidence that injection of cells in the spine or brain has any benefit in MS." (Hematopoietic stem cell transplant for MS is a different procedure, and while investigational, has been used in severe cases of disease with promising effects.)

Stem cell experts say this case is yet another example of clinics both abroad and in the U.S. using misleading marketing to lure the most desperate patients -- often with chronic progressive diseases -- into risky and unproven treatments. A recent investigationopens in a new tab or window by MedPage Today found a number of patients whose vision was harmed after treatment at a Florida clinic claiming to be able to treat chronic diseases with autologous bone marrow-derived stem cells.

Pastula said the clinic in Mexico claimed in marketing materials that the umbilical cord stem cells were "programmed to treat MS."

Paul Knoepfler, PhD, of the University of California Davis, who tracks dubious stem cell treatments, wrote to MedPage Today in an email, "How were the cells programmed and could such changes put people at risk? A worry is that, especially in immunocompromised individuals, receiving donor cells in the brain could pose a tumor risk long-term. Any kind of changes to stem cells such as by some kind of 'programming' could increase that risk."

It's also difficult to quantify the extent of damage from stem cell medical tourism. "There is not some sort of systematic data collection going on," Leigh Turner, PhD, executive director of the bioethics program at the University of California Irvine, who also studies stem cell companies, told MedPage Today. "We don't know exactly how many people are entering this global marketplace. You don't know how many procedures are being done."

Disclosures

The authors disclosed no financial relationships.

Primary Source

Emerging Infectious Diseases

Source Reference: opens in a new tab or windowWolf AB, et al "Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism" Emerg Infect Dis 2023; DOI: 10.3201/eid2908.230317.

https://www.medpagetoday.com/special-reports/features/105448

Biden's NSA nominee defends collecting data on foreigners and Americans alike

 The Biden administration's nominee to lead the National Security Agency (NSA) says he will champion the mass surveillance power that has been used to collect data from foreigners and Americans alike and which has come under renewed scrutiny from lawmakers.

Efforts to renew the spy power, known as Section 702 of the FISA Act, faces resistance from both parties before its slated expiration date at the end of the year. Lieutenant General Timothy Haugh, Biden's pick to replace outgoing NSA leader General Paul Nakasone, defended it Wednesday as a critical authority that had enabled the intelligence community to gather information on a host of threats.

"In my experience it is absolutely essential," he told lawmakers.

The program - which came under widespread scrutiny following the disclosures of former intelligence contractor Edward Snowden a decade ago - is typically framed by its defenders as sweeping up information on non-Americans living outside the United States.

That is how Haugh described it during his confirmation hearing before the Senate Intelligence Committee, saying he wanted to ensure that "American people understand that this is an authority to collect against foreign persons overseas."

That is not the full story, however.

A substantial chunk of the data swept up by the NSA's mass surveillance apparatus belongs to Americans living in the United States. In theory, exploiting this warrantlessly collected data is subject to certain safeguards. But the recent disclosure that the FBI improperly combed through the database more than a quarter million times over several years has only heightened concerns from civil libertarians and lawmakers about Section 702's potential for abuse.

Haugh is unlikely to face too much resistance from the Senate Intelligence Committee on the matter, however.

"We desperately need to get 702 reauthorized," Committee Chairman Mark Warner told him as he kicked off his testimony.

https://www.marketscreener.com/news/latest/Biden-s-NSA-nominee-defends-collecting-data-on-foreigners-and-Americans-alike--44324221/

Biden administration water cybersecurity plan temporarily blocked

 A U.S. appeals court on Wednesday temporarily blocked a Biden administration plan to improve cybersecurity for public water systems, after Republican-led states complained it would thrust burdensome costs on small and rural water suppliers.

The 8th U.S. Circuit Court of Appeals in St. Louis issued a stay temporarily suspending the U.S. Environmental Protection Agency (EPA) cybersecurity plan while a legal challenge filed by the state attorneys general of Missouri, Arkansas and Iowa runs its course.

The EPA's plan announced on March 3, which it called "guidance," meaning it was non-binding, recommended a series of novel rules placing more responsibility for securing water facilities at the state level. The agency issued the plan following several high-profile hacking incidents in recent years.

Arkansas Attorney General Tim Griffin said in a statement on Wednesday that he is pleased with the court's decision and that he believes the EPA doesn't have the authority to impose the rules.

A spokesperson for the National Rural Water Association, which intervened in the lawsuit challenging the EPA plan alongside the American Water Works Association, said in a statement that it supports enhanced cybersecurity, but that the EPA plan would be too burdensome for small water systems.

The EPA did not immediately respond to a request for comment.

Security experts say the water sector has long been seen as vulnerable to cyberattacks, which could cause shortages or dangerously increase the concentration of chemicals normally used to treat drinking water.

In March 2019, a terminated employee at a Kansas-based water facility used his old computer credentials to remotely take systems offline, a Biden administration official said when the plan was announced.

The Republican-led states filed their lawsuit in April, saying the EPA does not have the authority to force cybersecurity assessment responsibilities onto states and local water suppliers.

The lawsuit said the memo creates costly legal obligations, even though the EPA has referred it as only guidance.

https://www.marketscreener.com/quote/stock/AMERICAN-WATER-WORKS-COMP-2989352/news/Biden-administration-water-cybersecurity-plan-temporarily-blocked-44324106/

FDA reviewing concerns over Logan Paul's PRIME energy drink

 The U.S. Food and Drug Administration said on Wednesday it is reviewing concerns raised by Senate Majority Leader Chuck Schumer against a popular influencer-created energy drink.

Schumer said earlier this month that PRIME, a beverage brand started last year by YouTube stars Logan Paul and KSI, should be investigated due to the high caffeine content in the energy drink, adding that it was also being marketed to children.

Prime Energy contains 200 milligrams of caffeine per 12 ounces, equal to six cans of Coca-Cola or nearly two Red Bulls.

Canadian health officials told Reuters on Wednesday the energy drink should not be sold in Canada as the product exceeds the acceptable caffeine limits.

According to Canadian regulations, energy drinks must not contain more than 180 mg of caffeine in a single-serving container and require cautionary statements to protect sensitive subpopulations, including children.

The Canada health agency is aware that some stores in Canada may be selling Prime Energy without approval and it is actively working to address this issue, a spokesperson said.

The company did not immediately respond to Reuters' request for comment.

According to a warning on the company's website, Prime Energy is not recommended for children under the age of 18, women who are pregnant or nursing, and individuals who are sensitive to caffeine.

The company also sells a non-caffeinated hydration drink. Schumer previously said the packaging and marketing of the two drinks were so similar that parents were unknowingly buying the highly caffeinated energy drinks for their children.

The U.S. health regulator said it will respond to Schumer directly regarding his concerns

https://www.marketscreener.com/quote/stock/THE-COCA-COLA-COMPANY-4819/news/US-FDA-reviewing-concerns-over-Logan-Paul-s-PRIME-energy-drink-44324120/

Eli Lilly sees IPR&D charges negatively impacting Q2 EPS

 Eli Lilly said that its Q2 2023 results will include acquired IPR&D charges of approximately $97M, a charge of $0.09 on earnings per share.

https://seekingalpha.com/news/3987245-eli-lilly-sees-iprd-charges-negatively-impacting-q2-eps