Probiotic markedly reduces S. Aureus colonization in phase 2 trial

 A promising approach to control Staphylococcus aureus bacterial colonization in people—using a probiotic instead of antibiotics—was safe and highly effective in a Phase 2 clinical trial. The new study, reported in The Lancet Microbe, found that the probiotic Bacillus subtilis markedly reduced S. aureus colonization in trial participants without harming the gut microbiota, which includes bacteria that can benefit people. The research was conducted by researchers at the National Institutes of Health led by Michael Otto, Ph.D., an NIH senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID).

Methicillin-resistant S. aureus, or MRSA, is familiar to many people as a cause of serious disease. Less well known is that S. aureus often lives in the nose, on the body and in the gut without causing any harm. However, if the skin barrier is broken, or the immune system compromised, these colonizing bacteria can cause serious skin, bone, lung, and blood infections.

The prevention of S. aureus infections using approaches to "decolonize" the body has gained increased attention as the spread of antibiotic resistance limits treatment options. Some decolonization strategies are controversial because they also require large amounts of antibiotics, raising concerns about damage to the microbiota and the development of antibiotic resistance. So far, it appears that only nasal S. aureus colonization can be targeted with topical antibiotics without doing too much harm, but bacteria quickly can recolonize in the nose from the gut.

Probiotics, digestive supplements containing live microorganisms, may be a way to complement or replace antibiotics. Probiotic Bacillus is especially promising because it is administered orally as spores that can survive passage through the stomach and then temporarily grow in the intestine.

In prior studies, Dr. Otto's group discovered an S. aureus sensing system needed for S. aureus to grow in the gut. They also found that fengycins, Bacillus lipopeptides that are part peptide and part lipid, prevent the S. aureus sensing system from functioning, thereby eliminating the bacteria.

In the clinical trial, conducted in Thailand, the research team tested whether this approach works in people. They enrolled 115 healthy participants, all of whom were colonized naturally with S. aureus. A group of 55 people received B. subtilis probiotic once daily for four weeks; a control group of 60 people received a placebo.

After four weeks researchers evaluated the participants' S. aureus levels in the gut and nose. They found no changes in the control group, but in the probiotic group they observed a 96.8% S. aureus reduction in the stool and a 65.4% reduction in the nose.

"The probiotic we use does not 'kill' S. aureus, but it specifically and strongly diminishes its capacity to colonize," Dr. Otto said. "We think we can target the 'bad' S. aureus while leaving the composition of the microbiota intact."

The researchers also found that levels of S. aureus bacteria in the gut far exceeded S. aureus in the nose, which for decades has been the focus of staph infection prevention research. This finding adds to the potential importance of S. aureus reduction in the gut.

"Intestinal S. aureus colonization has been evident for decades, but mostly neglected by researchers because it was not a viable target for antibiotics," Dr. Otto said. "Our results suggest a way to safely and effectively reduce the total number of colonizing S. aureus and also call for a categorical rethinking of what we learned in textbooks about S. aureus colonization of the human body."

More information: Pipat Piewngam et al, Probiotic for pathogen-specific Staphylococcus aureus decolonisation in Thailand: a phase 2, double-blind, randomised, placebo-controlled trial, The Lancet Microbe (2023). DOI: 10.1016/S2666-5247(22)00322-6

Pipat Piewngam et al, Pathogen elimination by probiotic Bacillus via signalling interference, Nature (2018). DOI: 10.1038/s41586-018-0616-y

https://medicalxpress.com/news/2023-01-probiotic-aureus-colonization-phase-trial.html

Smartphone app can significantly improve memory recall

 Researchers at the University of Toronto have demonstrated that a new smartphone application helps to significantly improve memory recall, which could prove beneficial for individuals in the early stages of Alzheimer's disease or other forms of memory impairment.

Dubbed HippoCamera for its ability to mimic the function of the brain's hippocampus in memory construction and retention, the app enhances the encoding of memories stored in the brain by boosting attention to daily events and consolidating them more distinctly—thus later enabling richer, more comprehensive recall.

In a two-step process, HippoCamera users record a short video of up to 24 seconds of a moment they want to remember with a brief eight-second audio description of the event. The app combines the two elements just as the brain's hippocampus would, with the video component sped up to mimic aspects of hippocampal function and to facilitate efficient review. Users then replay cues produced by HippoCamera at later times on a curated and regular basis to reinforce the memory and enable detailed recall.

"We found that memories with an associated HippoCamera cue were long-lasting, and that it worked for everyone in the study—healthy older adults, those starting to show cognitive decline and even one case with severe amnesia due to an acquired brain injury," said study co-author Morgan Barense, a professor in the department of psychology in U of T's Faculty of Arts & Science and Canada Research Chair in Cognitive Neuroscience.

"Many months after the initial part of the study ended, and participants had not watched their HippoCamera cues, they were able to recall these memories in rich detail."

The study, published in the Proceedings of the National Academy of Sciences, shows that regular users of the app were able to recall more than 50% more details about everyday experiences that took place as many as six months earlier than if they had only recorded events and never replayed them. The new research suggests that systematic reactivation of memories for recent real-world experiences can help to maintain a bridge between the present and past in older adults and holds promise for people in the early stages of Alzheimer's disease or other forms of memory impairment.

The study also found that reviewing memory cues with HippoCamera resulted in more positive sentiment during later retrieval.

"There's something about being better able to remember these events that made people feel closer to them and more positive," said Barense, who is leading the development of the app and is adjunct scientist at the Rotman Research Institute at Baycrest. "This is a really important finding given what we know about dementia and the fact that positive reminiscence or focusing on positive life events and positive emotions can improve both memory and well-being in dementia."

For the study, participants recorded unique HippoCamera clips for everyday events that they wanted to remember and subsequently replayed these memory cues approximately eight times over a two-week period in one experiment, and over a 10-week period in a second experiment. The researchers then initiated a cued recall task where they showed the participants their memory cues and asked them to describe everything they could remember about each event.

This was followed by fMRI brain scanning sessions where researchers measured patterns of brain activity while participants saw their cues and completed a memory test. Three months later, after not practicing their HippoCamera memories and not having access to the cues, the participants were asked to recall these events a second time.

"On average, we saw on later recall an increase of more than 50% in the amount of rich, detailed information that someone was able to remember about events that happened as many as 200 days ago, which is significant," said Chris Martin, an assistant professor in the department of psychology at Florida State University and lead author of the study. "Memory is truly self-sustaining —a strong memory cue can bring along another memory, which can feed into another. You just have to focus on the cue in the first place."

The brain scans showed that replaying HippoCamera memory cues changed the way in which these everyday experiences were coded in the hippocampus, which has a well-established role in storing detailed memories for recent experiences. Recall-related activity in the hippocampus was more distinctive, meaning that HippoCamera replay helps to ensure that memories for different events remain separate from one another in the brain.

"The more detailed recollection seen earlier in the study was associated with more differentiated memory signals in the hippocampus," said Martin. "That HippoCamera is aiding the hippocampus in distinctly encoding memories, so they do not become confused with one another, explains why users are able to recall past events in such great detail. It's evidence that rich and detailed memory reactivation promotes memory differentiation at the neural level, and that this allows us to mentally re-experience the past with vivid detail."

One key factor in HippoCamera's effectiveness, the researchers say, is the sense of purpose and intention inherent in its use. By its very design, the intervention prompts users to think about what it is that they want to remember and why a particular moment is important to them—and then regularly re-engage with the memories in a meaningful way.

"Someone who is committed to using HippoCamera is going to go through their lives paying attention to what is happening to them, asking themselves if this is an event they want to capture," said Barense. "If it is, they're going to take the time to stop and describe that event. And that act of approaching events in our lives with more attention is going to be good for memory.

"Then later, there's an intention with how we study those memories, taking the time to review them using optimal learning techniques."

The researchers note that as people begin to lose their existing memories at any point in their lives, as well as their ability to create new ones, they start to lose their sense of self. As a result, they often become disengaged from the people and events in their lives.

"Memory and our sense of identity are very closely linked," said Barense, who is receiving support from U of T startup accelerator UTEST to take the app from lab to market. "We understand who we are as people by remembering the things that we've done. Our hope with HippoCamera is that by helping people feel closer to these people and events in their lives, we can help give them back their sense of self."

More information: Chris B. Martin et al, A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults, Proceedings of the National Academy of Sciences (2022). DOI: 10.1073/pnas.2214285119

https://medicalxpress.com/news/2023-01-smartphone-app-significantly-memory-recall.html

New therapeutic approach to prevent ARDS

 A novel peptide designed by University of California, Irvine researchers has been found to suppress the damaging lung inflammation seen in acute respiratory distress syndrome, or ARDS. The study, which appears in iScience, describes the first specific treatment designed to prevent the deadly disease, which can appear in patients with severe lung injury from infections with bacteria and viruses, like pneumonia, flu, respiratory syncytial virus (RSV) and COVID-19.

The mouse study revealed how the C6 peptide blocks voltage-gated Hv1 proton channels in white blood cells called neutrophils, suppressing the production of damaging reactive oxygen species, proteases and cytokines. This inhibits infiltration of the lung tissue by these cells that trigger uncontrolled inflammation and fluid buildup seen in severely damaged lungs.

The study was led by Dr. Steven A. N. Goldstein, distinguished professor of pediatrics, physiology & biophysics and pharmaceutical sciences at UC Irvine; Ruiming Zhao, assistant project scientist at UC Irvine; and Dr. Andreas Schwingshackl, associate professor of pediatrics at UCLA.

ARDS occurs when the lungs become inflamed following injury or infections. Inflammation and fluid buildup damage the lung tissue, decreasing how much oxygen can reach the bloodstream. People with ARDS have shortness of breath and failure of oxygenation that is so severe that they often require support from a ventilator.

Numerous studies over the past decade show that ARDS affects approximately 200,000 adults and 8,000 children each year in the U.S., causing 75,000 and 1,500 deaths, respectively. ARDS survivors often have long-lasting adverse outcomes, including cognitive dysfunction, mental health issues and physical impairments. In fact, only 50 percent of ARDS patients discharged from the hospital return to their jobs in the first two years.

"Despite five decades of effort, there are no disease-modifying drugs that can treat patients with acute respiratory distress syndrome," said Goldstein, who is also the vice chancellor of health affairs at UC Irvine. "The C6 peptide shows promise as a therapy for this damaging lung disease, giving hope to patients where so little exists now."

In an established mouse model, the researchers administered the C6 peptide in a clinically relevant manner to mice to suppress disease. In addition, they showed that C6 inhibits Hv1 in human neutrophils—the predominant inflammatory cell type accumulating in the lungs of ARDS patients—shutting down the same inflammatory signaling pathways that it did in mice. The absence of apparent toxic side effects in the mice suggests that targeting Hv1 will be tolerated in humans as a therapeutic approach to ARDS, and that C6 may also be useful in treating other inflammatory diseases.

The UC Irvine researchers first created the novel C6 peptide in 2018 and found in 2022 that it could become a more potent therapeutic when linking together two of the peptides.

Peptides are small chains of amino acids and are becoming more widely used as drugs in recent years. They constitute a subset of medications called biologics that are proving desirable for drug discovery. They differ from proteins like antibodies, which are made from longer, more complex amino acid chains.

Goldstein said the next steps include further study of C6, C6 derivatives, and small molecule mimetics his team has isolated to treat inflammatory diseases of the lungs and other tissues, including assessment of how long the peptide stays in the body and how it gets eliminated.

Benjamin Lopez of UCLA was also a crucial contributor to the design and execution of the experiments.

More information: Ruiming Zhao et al, Protection from acute lung injury by a peptide designed to inhibit the voltage-gated proton channel, iScience (2022). DOI: 10.1016/j.isci.2022.105901

https://medicalxpress.com/news/2023-01-therapeutic-approach-ards.html

Aspirin effective as blood thinners to prevent deadly complications in bone fractures

 Patients hospitalized with fractures typically receive an injectable blood thinner, low-molecular-weight heparin, to prevent life-threatening blood clots. A new clinical trial, however, found that inexpensive over-the-counter aspirin is just as effective. The findings, published today in the New England Journal of Medicine, may lead surgeons to change their practice and administer aspirin to these patients.

The multi-center randomized clinical trial, which included more than 12,000 patients at 21 trauma centers in the U.S. and Canada, is the largest trial ever conducted on orthopedic trauma patients. This multidisciplinary collaboration between orthopedic surgeons and trauma surgeons points to the importance of evaluating techniques used to prevent post-surgical complications, like blood clots and infections, through high-quality, head-to-head comparison studies.

The trial was co-led by the Department of Orthopaedics at the University of Maryland School of Medicine (UMSOM) and the Major Extremity Trauma Research Consortium (METRC) based at the Johns Hopkins Bloomberg School of Public Health.

"Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots," said the study's principal investigator Robert V. O'Toole, MD, the Hansjörg Wyss Medical Foundation Endowed Professor in Orthopaedic Trauma at UMSOM and Chief of Orthopaedics at the R Adams Cowley Shock Trauma Center at the University of Maryland Medical Center (UMMC). "We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care."

Blood clots cause as many as 100,000 deaths in the U.S. each year, according to the U.S. Centers for Disease Control (CDC). Patients who experience fractures that require surgery are at increased risk of developing blood clots in the lungs and limbs. Large clots in the lungs even can be life-threatening. Current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin) to prevent these clots, although smaller clinical trials in total joint replacement surgery suggested a potential benefit of aspirin as a less-expensive, widely available option.

The study enrolled 12,211 patients with leg or arm fractures that necessitated surgery or pelvic fractures regardless of the treatment. Half were randomly assigned to receive 30 mg. of injectable low molecular-weight heparin twice daily. The other half received 81 mg. of aspirin twice daily. Patients were followed for 90 days to measure health outcomes from the two treatments.

The main finding of the study was that aspirin was "non-inferior," or no worse than low molecular-weight heparin in preventing death from any cause—47 patients in the aspirin group died, compared with 45 patients in the heparin group. For other important complications, the researchers also found no differences between the two groups in clots in the lungs (pulmonary embolisms). The incidence of bleeding complications, infection, wound problems, and other adverse events from the treatments was also similar in both groups.

Of all the outcomes studied, the only potential difference noted was in blood clots in the legs, called deep vein thrombosis. This condition was relatively uncommon in both groups as it occurred in 2.5 percent of patients in the aspirin group, and in 1.7 percent of patients in the heparin group.

"This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment," said study co-principal investigator Deborah Stein, MD, MPH, Professor of Surgery at UMSOM and Director of Adult Critical Care Services at UMMC.

The $11.7 million study was funded by the Patient-Centered Outcomes Research Institute (PCORI), (PCS-1511-32745), an independent, non-profit organization that funds comparative clinical effectiveness research to help patients and clinicians make better-informed healthcare decisions.

"This large multicenter study was needed to adequately measure the impact of prophylaxis on the infrequent, but important, outcome of death that is of utmost importance to patients," said study methods center principal investigator Renan Castillo, Ph.D., Professor of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health.

The trial was called PREVENTion of CLots in Orthopaedic Trauma, or PREVENT CLOT. Patients enrolled in the trial were treated at the R Adams Cowley Shock Trauma Center at UMMC and 20 other trauma centers in 15 other states, as well as two in Canada. Recruitment started in April 2017 and continued through 2021.

"Many patients don't like giving themselves injections. It's not fun in terms of giving the actual injection because it burns, and your stomach tends to bruise more easily compared to aspirin," said Debra Marvel, a 53-year-old from Columbia, MD, who served as a patient advisor on the study. She received Lovenox (low-molecular-weight heparin) after her legs were crushed in a 2015 pedestrian accident, requiring multiple surgeries at the University of Maryland Shock Trauma Center. "Patients also prefer aspirin because Lovenox can be expensive based on insurance."

"An estimated one million Americans are hospitalized each year with extremity fractures, and this new finding could help prevent potentially fatal blood clots in these patients using a medication that is cheaper and far easier to administer," said Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. "Given these important results, we can expect the guidelines for the prevention of blood clots to be revised to include the option of aspirin for patients with traumatic bone fractures."

More information: Aspirin or Low-Molecular-Weight Heparin for Thromboprophylaxis after a Fracture, New England Journal of Medicine (2023). DOI: 10.1056/NEJMoa2205973

https://medicalxpress.com/news/2023-01-aspirin-effective-blood-thinner-deadly.html

CT bill would let children as young as 12 get vaccines without parental consent

 A bill introduced to the Connecticut state legislature on Tuesday would allow children ages 12 and older to receive vaccines without a parent’s approval.

The bill, proposed by state Rep. Kevin Ryan (D), would amend Connecticut’s general statute and allow a child 12 years or older to get a vaccine without the consent of their parent or guardian, if passed. The bill was referred back to the state legislature’s Joint Committee on Public Health on Tuesday.

In Connecticut, a child under the age of 18 needs verbal or written consent of a parent or guardian to receive general medical care, including vaccines.

Washington D.C., passed a similar law in 2021 that allowed a child who is at least 11 years old receive a vaccine without a parent or guardian’s consent. Other states have varying minor health care consent laws; for example, a child in Oregon who is at least 15 years can consent to medical care, including immunizations.

The Centers for Disease Control and Prevention reported earlier this month that childhood vaccinations fell in the 2021-2022 school year again, saying that coverage for the measles, mumps and rubella vaccine was the lowest in a decade, and that coverage for other vaccines, including chickenpox and polio, was also on the decline.

https://thehill.com/homenews/state-watch/3818347-connecticut-bill-would-let-children-as-young-as-12-get-vaccines-without-parental-consent/

Department of Labor fueling our labor shortage

 Days before the midterm elections, Labor Secretary Marty Walsh issued a stark warning regarding an imminent economic catastrophe should Congress fail to introduce and implement a comprehensive immigration reform package.

“We need a bipartisan fix here,” Walsh told CNBC. “I’ll tell you right now, if we don’t solve immigration … we’re talking about worrying about recessions, we’re talking about inflation. I think we’re going to have a bigger catastrophe if we don’t get more workers into our society, and we do that by immigration.”

While this statement is true, from an immigration perspective, Walsh should look closer to home — his own Department of Labor. When most think of immigration, they think about the border. But immigration is so much more. Beyond the well-known agencies and departments that we know, such as border patrol agencies, tens of thousands of bureaucrats across the government handle immigration. One of those agencies is Labor and their ability, or lack thereof, to process legal immigration, is in turn, fueling the border crisis.   

Even though there are concerns propagated by the media that immigrants take jobs from Americans, this is a myth. For an immigrant to be sponsored for employment, the Department of Labor has extensive processes in place to ensure that Americans are not denied work in favor of immigrants. Before employers are allowed to sponsor an immigrant for employment, they must first offer those jobs to Americans. It’s not simply a rubber stamp process and it takes years to document it all. Employers must record who applies and who is hired. If American workers are not pursuing the position, then the Department of Labor works to ensure fair wages are being offered to immigrant workers that will work in that role.   

Labor’s immigration component though, due to COVID-19, backlogs, and delays at other government agencies, is broken. Just over a year ago, immigrant workers seeking visas for entry-level positions took only 10 months for the total Department of Labor process. In 2020 the application processing time took as little as four months. In October 2022, the total process now takes 18-24 months with the application alone taking up to 18 months to process, leaving multitudes of willing and able workers waiting while American businesses suffer. Currently, there are over 10 million job openings in the United States, but only 6 million unemployed workers. In manufacturing alone, an industry heavily impacted by the labor crisis, current statistics point to a shortage of 8 million people by 2030, with a potential revenue loss of $607 billion.

At a time when our government should be working at all cylinders to lessen our labor shortages, the Biden administration has let Labor slide farther and farther into backlogs and delays. There are many common sense and easily implementable changes that the Department of Labor can make to improve the immigration process. It can change the fee structure to raise additional funds, it can change how it receives documents, or even collaborate more with state agencies to lessen its own backlog. Finally, Labor could prioritize cases of employers providing essential services to the American economy. Right now, Labor does far too much with too little resources and expectations.   

When Labor initially began its immigration processing, it was designed to be like the IRS’s tax return system where the filings were to be quick, and the government was only to audit bad actors. Instead, Labor reviews all its applications slowly and manually. If we would not tolerate the IRS working this way, we shouldn’t tolerate other government agencies doing so either.   

Foodservice, manufacturing, small businesses or businesses in rural areas should be given priority in processing so that the everyday needs of Americans can be more effectively met. Taking these simple actions could cut down certain parts of the process significantly. Allowing state agencies to take the work of processing parts of this application should be attractive as it would give the state agencies the opportunity to meet the business needs of their own local constituents and give them tools to fight recession within their jurisdictions.  

When employers cannot rely on a functioning, vibrant, immigration system and procedures, they are pressured to work outside of that system. Labor must do all in its power to make sure that does not happen. 

While it’s encouraging that leaders across government are demanding change, we need those leaders to do more. They must not just exhort Congress to act, but they must do what they can in their own backyards to make changes. Our bureaucracy’s stagnation and inability to adapt to the ever-changing needs of the American public not only hurts the “huddled masses” at the border, but harms the global market, consumers and American business leaders nationwide.    

Chris Richardson is a former U.S. diplomat and co-founder of Argo Visa and an expert on immigration policy. Richardson served in Nigeria, Nicaragua, Pakistan and Spain as a U.S. diplomat. 

Ben McEuen serves as a senior immigration specialist at BDV Solutions. He is also a paralegal and Juris Doctor candidate at the University of Dayton School of Law.

https://thehill.com/opinion/immigration/3818356-is-the-department-of-labor-fueling-our-labor-shortage/

UK Royal Mail restarts limited overseas post after cyber-attack

 Royal Mail has restarted the export of parcels from a backlog, and will accept new letters for overseas, as it tries to recover from a cyber-attack.

Parcels that have already been processed will start to be moved in "limited volumes" the firm said.

But no new parcels should be submitted for now, it said.

Royal Mail was the victim of a ransomware attack last week, and it is still working with security authorities "to mitigate the impact".

Ransomware is malicious computer software that encrypts data and locks up systems. Criminals usually demand payment for releasing the data.

Last week, Royal Mail told customers they would not be able to send letters or parcels overseas until the matter was resolved.

On Wednesday Royal Mail said it was trying out "operational workarounds", but it asked customers not to send post yet that needs a customs declaration.

oyal Mail is remaining tight-lipped about what is happening in its depot centres around the country.

As a private company it is required to keep the authorities and regulators informed about the situation, but it has chosen to say very little to the public.

The firm is still referring to the cyber-attack as a "cyber incident" and is refusing to say publicly that it is ransomware, days after reporters confirmed it.

These distinctions matter because ransomware attacks often involve the encryption, destruction or theft of company, and sometimes customer, data.

It also brings up the thorny issue of whether or not the company will pay the cyber-criminals - something police forces the world over discourage.

The company won't say if it is negotiating with the hackers, but their statement says they are "trialling operational workarounds" which implies they are not paying the criminals.

But, as with many cases of ransomware, it won't be easy to know unless they tell us.

Firms that rely on posting items overseas have expressed irritation at the impact on their business.

Sam Cannon, who sells her artwork abroad, said the latest statement would not change exporters in her position.

"Everything needs a customs declaration, so nothing has changed for many small businesses like mine.

"I've had to cancel all overseas sales right now, and have no idea when things will be normal again with so few updates from Royal Mail."

However, she has some items stuck in transit, including original paintings, that may now be delivered.

Royal Mail apologised for the disruption.

"Our initial focus will be to clear mail that has already been processed and is waiting to be despatched," it said in a statement.

It said from 7:00pm on Thursday, customers can start sending international letters which do not need a customs declaration.

It asked customers not to send international parcels.

Letters and parcels coming into the UK were affected by "minor delays" but otherwise were operating normally and domestic postal services had not been affected, it said.

https://www.bbc.com/news/business-64324000