Can smartphones predict mortality risk?

 Passive smartphone monitoring of people's walking activity can be used to construct population-level models of health and mortality risk, according to a new study publishing October 20thin the open access journal PLOS Digital Health by Bruce Schatz of University of Illinois at Urbana-Champaign, USA, and colleagues.

Previous studies have used measures of physical fitness, including walk tests and self-reported walk pace, to predict individual mortality risk. These metrics focus on quality rather than quantity of movement; measuring an individual's gait speed has become a standard practice for certain clinical settings, for example. The rise of passive smartphone activity monitoring opens the possibility for population-level analyses using similar metrics.

In the new study, researchers studied 100,000 participants in the UK Biobank national cohort who wore activity monitors with motion sensors for 1 week. While the wrist sensor is worn differently than how smartphone sensors are carried, their motion sensors can both be used to extract information on walking intensity from short bursts of walking -- a daily living version of a walk test.

The team was able to successfully validate predictive models of mortality risk using only 6 minutes per day of steady walking collected by the sensor, combined with traditional demographic characteristics. The equivalent of gait speed calculated from this passively collected data was a predictor of 5-year mortality independent of age and sex (pooled C-index 0.72). The predictive models used only walking intensity to simulate smartphone monitors.

"Our results show passive measures with motion sensors can achieve similar accuracy to active measures of gait speed and walk pace," the authors say. "Our scalable methods offer a feasible pathway towards national screening for health risk."

Schatz adds, "I have spent a decade using cheap phones for clinical models of health status. These have now been tested on the largest national cohort to predict life expectancy at population scale."

Story Source:

Materials provided by PLOS. Note: Content may be edited for style and length.

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Journal Reference:

1. Haowen Zhou, Ruoqing Zhu, Anita Ung, Bruce Schatz. Population analysis of mortality risk: Predictive models from passive monitors using motion sensors for 100,000 UK Biobank participants. PLOS Digital Health, 2022; 1 (10): e0000045 DOI: 10.1371/journal.pdig.0000045

https://www.sciencedaily.com/releases/2022/10/221020140626.htm

Cytoskeleton acts as cells' bouncer for bacteria

 Pseudomonas aeruginosa (P.a.) are resistant to most antibiotics and cause life-threatening infections of wounds or the lungs. The P.a. bacteria species has an entire arsenal of strategies for evading the immune system and infecting tissue. Researchers working with Prof. Dr. Winfried Römer and Dr. Carsten Schwan of the University of Freiburg and the Excellence Cluster CIBSS -- Centre for Integrative Biological Signalling Studies -- have identified a previously unknown, natural, defense mechanism that protects cells from Pseudomonas infection. The study has been published in Cell Reports.

Pseudomonas aeruginosa also enter cells in a targeted way

Surrounded by nutrients and undetected by the immune system, the interior of a cell is the ideal place for pathogenic bacteria to reproduce. Nevertheless, it was long thought that they existed outside of cells for the most part. "In the meantime, it's clear that the picture is more complex and the bacteria target the cells they penetrate," explains Römer. With the aid of live cell imaging microscopy, this can be observed in the laboratory. The bacteria take up close contact to the cell and make indentations in its membrane until they are completely engulfed by it.

Pseudomonas triggers the denting of the cell's membrane by binding the virulence factor LecA to sugar molecules on the membrane's surface. Proteins that bind with sugars are common in the natural world and are also observed on other bacteria and viruses. The strong binding of the bacteria and host cells leads to the cell membrane closing itself like a zipper around the bacteria -- a process that Römer's working group has been examining for quite some time.

"Now we've intentionally focused on the role septins play in Pseudomonas infection," says Schwan, describing the objective of the current study. "It's known of other bacteria that they manipulate host cell septins and can exploit them to ease penetration. Yet at the same time, septins can also encapsulate bacteria that have already penetrated and induce their liquidation, so they have an ambivalent function in infections," Schwan continues. Septins are part of the cytoskeleton and serve as a key structural element similar to a modular scaffold that can be flexibly put together and taken apart. They also frequently play a role precisely when curved membranes are involved.

The binding of LecA is sufficient to induce septin accumulation

In their latest study, the researchers used human lung cells that they infected with Pseudomonas aeruginosa in the lab. They found the attachment of the bacteria led to septins gathering at the site within a few seconds or minutes. If the bacteria failed to penetrate, the accumulation then dissolved again quickly. The researchers could also observe this effect when instead of bacteria small polymer beads coated with LecA were given to the cells. This showed that binding via LecA was enough to induce septin accumulation.

"We expected that Pseudomonas wanted this accumulation of septins, and that it helped them during infection, just as with other types of bacteria," adds Schwan. Instead, they found that twice as many bacteria could penetrate when the researchers knocked down some of the septins. "We were surprised by the results at first, but now we're thinking it's not just an isolated case. It could be that septins also play a protective role with many other pathogens," he concludes.

A basis for developing drugs to treat antibiotic-resistant bacteria

The researchers were able to measure the strength of the septin barrier in further experiments. To do this, they attached the minimal bacterial model to the cantilever of an atomic force microscope (AFM), which allows the tiniest of indentations and resistances on surfaces to be measured as force. The researchers discovered that the cell membrane was clearly more rigid locally when the polymer beads were coated with LecA and septin accumulated.

"That's an enormous effect when you consider that during the infection process, many different molecules are involved. For an intervention to have such great impact, you often have to inhibit several factors, because otherwise, compensations are made," says Römer. He continues, "That speaks strongly for septins really playing a significant role in warding off infections here." The researchers now intend to further their investigations of lectins and septins. Better understanding of these proteins could aid in finding points of attack for drugs designed to prevent infection by antibiotic resistant bacteria.

About the Cluster of Excellence CIBSS

The Cluster of Excellence CIBSS -- Centre for Integrative Biological Signalling Studies has the goal of gaining a comprehensive understanding of biological signaling processes across scales -- from interactions between individual molecules and cells to processes in organs and entire organisms. Researchers use the knowledge thus gained to develop strategies for controlling signals in a targeted manner. These technologies enable them not only to gain insights in research but also to develop innovations in medicine and plant sciences.

Story Source:

Materials provided by University of Freiburg. Note: Content may be edited for style and length.

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Journal Reference:

1. Sahaja Aigal, Ramin Omidvar, Kai Stober, Jessica Ziegelbauer, Thorsten Eierhoff, Janik Niklas Schampera, Winfried Römer, Carsten Schwan. Septin barriers protect mammalian host cells against Pseudomonas aeruginosa invasion. Cell Reports, 2022; 41 (3): 111510 DOI: 10.1016/j.celrep.2022.111510

https://www.sciencedaily.com/releases/2022/10/221020201443.htm

Oral Microbiome Therapy for Recurrent C. Diff Mostly Holds Up at 6 Months

 Extended follow-up of a phase III trial demonstrated continued benefit for an investigational microbiome therapeutic for patients with recurrent Clostridioides difficile infections.

Of the 182 patients in the randomized ECOSPOR III trial, C. difficile recurrence at 24 weeks occurred in 21.3% of patients who were treated with the oral therapy, SER-109, versus 47.3% of those given placebo (RR 0.46, 95% CI 0.30-0.73, P<0.001), reported Barbara McGovern, MD, of developer Seres in Cambridge, Massachusetts.

"Patients with recurrent C. difficile have a decimated microbiome, usually from multiple exposures to antibiotics," said McGovern at the annual IDWeek meeting here.

The updated analysis, which was published simultaneously in JAMA, builds on previously reported 8-week findings -- the multicenter study's primary endpoint -- which showed a significantly lower recurrence rate with the microbiome therapy versus placebo (12% vs 40%, respectively) for patients who had been treated with standard antibiotics for three or more episodes of C. difficile infection.

SER-109's benefit was evident as early as week 2, according to the new findings, with significantly lower rates of recurrence also seen at weeks 4 and 12.

The sustained responses may be due to changes that the drug initiates in the patient microbiome, McGovern explained. "Microbiome data suggest that these clinical outcomes are due to changes in the microbiome structure and function."

SER-109 is a consortium of highly purified Firmicutes spores that "normally live in a healthy microbiome," said McGovern. "You may ask, why enrich for spore-forming Firmicutes? Well, they have a key role in preventing C. difficile spore germination and growth."

The spores are also resistant to gastric acid, she added, "allowing it to be put into oral capsules so the spores can germinate and replicate into the GI tract." Moreover, she said, the manufacturing processes inactivate vegetative bacteria, fungi, parasites, and viruses.

Patients in the study were randomized to receive SER-109 (n=89) or placebo (n=93) capsules four times a day for 3 days. Mean patient age was 65.5 years, and 59.9% were women. Most of the patients were white (93%), and 99% were outpatients.

Patients in both arms of the study had comorbidities, with a mean Charlson Comorbidity Index score of 4.1 in the SER-109 group and 4.2 in the placebo group. The most common treatment-related adverse events were flatulence, abdominal distention, abdominal pain, fatigue, and constipation. There were three deaths in the treatment group, and none in the placebo group; McGovern said the deaths were reported by a blinded investigator as unrelated to treatment.

Researchers counted patients who left the study early, were lost to follow-up, or died as recurrences. Patients who were missing components for recurrent C. difficile infection criteria (for example, having a positive toxin test result) were also counted as reinfected.

Limitations included that the study excluded patients in first recurrence, a subgroup with similar microbiome disruption.

In her presentation, McGovern also included limited data on a subsequent single-arm open-label study (ECOSPOR IV) that enrolled 263 patients. The trial was conducted to provide sufficient safety data to the FDA following a breakthrough therapy and orphan drug designation, and included patients with one or more episodes of C. difficile.

Seres announced last month that it is seeking approval for SER-109 in recurrent C. difficile.

Disclosures

The study was supported by Seres Therapeutics.

Several of the authors are employed by or have other relationships with the company, including McGovern, who is a vice president; co-authors reported financial relationships with Finch Therapeutics, Summit, Rebiotix/Ferring, Vedanta, MGB, Janssen, Genentech, Diasorin, Shire, Kinevant, Regeneron, OpGen, Epigenomics, Merck, Prenosis, Leonard-Meron, AstraZeneca, Contrafect, QIAGEN, Crestone, and Alkermes.

Primary Source

IDWeek

Source Reference: McGovern B, et al "SER-109, an oral investigational microbiome therapy for the prevention of recurrent Clostridioides difficile infection" IDWeek 2022; Presentation 50.

Secondary Source

JAMA

Source Reference: Cohen SH, et al "Extended follow-up of microbiome therapeutic SER-109 through 24 weeks for recurrent Clostridioides difficile infection in a randomized clinical trial" JAMA 2022; DOI: 10.1001/jama.2022.16476.

https://www.medpagetoday.com/meetingcoverage/idweek/101358

Viridian: Positive Interim Data in Phase 1/2 Thyroid Eye Disease Trial

 Clinial and in vitro data presented in three late-breaking presentations at ATA provide emerging evidence of VRDN-001 efficacy and differentiation -

- Full 10 mg/kg cohort data presented at ATA, 20 mg/kg and 3 mg/kg cohort data on track for 4Q22 -

- Pivotal program for VRDN-001 in TED patients set to begin this quarter -

Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biotechnology company advancing new treatments for patients suffering from serious diseases underserved by current therapies, presented positive proof-of-concept data from the 10 mg/kg cohort in its ongoing Phase 1/2 clinical trial of VRDN-001, an anti-IGF-1R antibody, in patients with active thyroid eye disease (TED). These data, as well as new in vitro data further characterizing and differentiating the pharmacological profile of VRDN-001, were included as part of three late-breaking poster presentations at the American Thyroid Association (ATA) 91st Annual Meeting. The abstract describing new in vitro data on the distinct anti-IGF-1R profile of VRDN-001 was also selected as an oral highlighted late breaking presentation. The three posters are available on the Viridian website (click here).

https://finance.yahoo.com/news/viridian-presents-positive-clinical-data-180400445.html

Parents struggle to afford baby supplies, nonprofits stepping up to help

 The baby formula shortage that had parents scrambling earlier this year has eased up, but families are still struggling because inflation is hitting other baby supplies.

Fox News stopped by a store to see how much it would cost to buy a few of the basics for a baby. A week’s worth of diapers, three packs of wipes and a 12-ounce jar of baby formula would cost around $60.

To help ease the financial burden for families, Baby’s Bounty in Las Vegas has given out nearly 2 million free diapers to families in southern Nevada since 2008.

"Diapers right now are really, really expensive," said Angie Melgar, a new mom receiving free diapers from Baby’s Bounty. "Everything right now for babies, anything in general is expensive. So this is just a big help.

Inflation is hitting all sorts of baby supplies, such as diapers, which have seen a cost increase of about 20% since last year, according to Nielsen IQ. (Fox News / Fox News)

The cost of diapers has increased 20% over the past year, while baby food has increased 11.8% and car seats 41%.

In addition to its diaper bank, held twice a month at two of its locations, Baby’s Bounty gives bundles of baby items.

The bundles include an infant regulation car seat, blankets, a play mat, 25 items of clothing and more.

"This is what someone might receive at a baby shower," said Kelly Maxwell, the executive director. "We hear from our bundle clients that without these items, they would have nothing to care for their newborn."

Baby Center, a digital parenting resource, found parents would spend at least $16,000 on basic items for a baby in the first year.

It's especially tough on low-income families.

"We see monthly incomes in the $500 range quite often so that they can absolutely not afford to buy all of these items," Maxwell said.

Inflation is also hitting nonprofits like Baby’s Bounty.

They buy about 75 car seats each month.

"It's one thing if you're buying one car seat, right. But when you buy 75 and distribute those, it's a big number, too big a strain on smaller nonprofits that are doing nearly all of the heavy lifting in our communities," Maxwell said.

They also became a "de facto formula bank," as Maxwell described the situation during the height of the baby formula shortage, helping 700 families.

"My employees were emotionally drained. We were all exhausted from the frantic calls from our clients saying things like, I haven't fed my baby in 12 hours because I can't find any formula," Maxwell said. 

The team of four was "operating basically a match service for formula," she said.

Baby’s Bounty, a member of the National Diaper Bank Network, will launch its mobile diaper bank next month, with a van traveling across southern Nevada three times a week to help those with limited or no transportation.

The National Diaper Bank Network has locations nationwide.

https://www.foxbusiness.com/economy/inflation-hits-baby-supplies-industry

Passengers in fatal Boeing 737 MAX crashes are ‘crime victims,’ US judge says

 A US judge in Texas ruled on Friday that people killed in two Boeing (BA) 737 MAX crashes are legally considered “crime victims,” a designation that will determine what remedies should be imposed.

In December, some crash victims’ relatives said the US Justice Department violated their legal rights when it struck a January 2021 deferred prosecution agreement with the planemaker over two crashes that killed 346 people.

The families argued the government “lied and violated their rights through a secret process” and asked US District Judge Reed O’Connor to rescind Boeing’s immunity from criminal prosecution – which was part of the $2.5 billion agreement – and order the planemaker publicly arraigned on felony charges.

O’Connor ruled on Friday that “in sum, but for Boeing’s criminal conspiracy to defraud the (Federal Aviation Administration), 346 people would not have lost their lives in the crashes.”

Paul Cassell, a lawyer for the families, said the ruling “is a tremendous victory” and “sets the stage for a pivotal hearing, where we will present proposed remedies that will allow criminal prosecution to hold Boeing fully accountable.”

Boeing did not immediately comment.

After the families filed the legal challenge saying their rights were violated under the Crime Victims’ Rights Act, Attorney General Merrick Garland met with some of them but stood by the plea deal, which included a $244 million fine, $1.77 billion compensation to airlines and a $500 million crash-victim fund.

The deal capped a 21-month investigation into the design and development of the 737 MAX following the deadly crashes in Indonesia and Ethiopia in 2018 and 2019.

Boeing did not disclose key details to the FAA of a safety system called MCAS, which was linked to both fatal crashes and designed to help counter a tendency of the MAX to pitch up. “Had Boeing not committed its crime” pilots in Ethiopia and Indonesia would have “received training adequate to respond to the MCAS activation that occurred on both aircrafts,” O’Connor ruled.

The crashes, which have cost Boeing more than $20 billion in compensation, production costs, and fines, and led to a 20-month grounding for the best-selling plane, prompted Congress to pass legislation reforming FAA airplane certification.

Boeing wants Congress to waive a December deadline imposed by the legislation for the FAA to certify the MAX 7 and MAX 10. After that date, all planes must have modern cockpit alerting systems, which the 737 planes do not have.

Last month, Boeing paid $200 million to settle Securities and Exchange Commission charges it misled investors about the MAX.

https://www.cnn.com/2022/10/22/business/boeing-737-max-crime-victims/index.html

US Is Finally Considering Protections Against Salmonella

 THE AUTUMN OF 2013 was a stressful time for the Craten family, who live outside Phoenix, Arizona. In short order, three family members were diagnosed with the same type of salmonella infection. Salmonella is a foodborne bacteria that can travel on poultry meat and, as they would later find out, was sweeping the US in a nationwide outbreak.

All they knew at the time was that their 18-month-old son, Noah, was the sickest among the relatives: spiking daily fevers, losing the ability to walk straight, and developing a droop on one side of his face. Thanks to a CT scan, doctors discovered the infection had formed a rapidly growing abscess inside his brain. Emergency surgery saved his life, but pressure from the mass left lasting damage, affecting his speech and sensory processing and leaving him with learning disabilities.

Noah Craten is 10 now, a spunky kid who loves playing Minecraft and has an aide to help him through school. And his mother, Amanda, is an activist, a leader in a coalition of consumer groups that may just have compelled the biggest change in federal food-safety regulation in 20 years. Last week, responding to pressure from these groups, the US Department of Agriculture announced that it is considering reforms to the way it regulates the processing and sale of raw poultry, the largest single source of salmonella infections. If the changes go through, they will give that agency the power to monitor salmonella contamination in live birds and slaughterhouses, and the power to force producers to recall contaminated meat from the marketplace.

The agency doesn’t have those powers now, even though salmonella causes more serious illnesses than any other foodborne pathogen. It sickens about 1.35 million people in the US each year; about 26,500 of them end up in the hospital, and 420 die. At its mildest, it causes fever and diarrhea that can last up to a week. But because it can migrate to the bloodstream and invade bones, joints, and the nervous system, it often leaves victims with arthritis and circulatory problems.

Today, the USDA can only ask meat producers to voluntarily recall their products, and companies don’t always move as rapidly as the agency would wish. That leaves consumers vulnerable to threats they do not know exist. “Noah got sick toward the end of an outbreak that lasted for 14 months,” Amanda Craten says. “If there had been some sort of oversight, and there had been a recall early on, my son would not have gotten sick.”

The possible reforms were disclosed October 14 by the USDA’s Food Safety and Inspection Service. They are contained in what the FSIS calls a “proposed framework,” the first steps in a process that might not be resolved until close to the 2024 election. But if that process results in regulation, it will mark a permanent shift in US authority over food safety.

“The exciting thing about this new proposal is that it's going to apply to potentially all raw chicken products, which play a huge role in the number of cases of salmonellosis that we see,” says Sarah Sorscher, an attorney who is deputy director of regulatory affairs at the nonprofit Center for Science in the Public Interest, which has petitioned the USDA four times to declare the most dangerous strains adulterants and regulate them. “If we can bring the risk down in these products, we actually have a chance to bend the curve on foodborne illness.”

It might come as a surprise that the USDA didn’t already have this authority. But that agency (which regulates meat, poultry, and eggs; the US Food and Drug Administration oversees everything else) can force recalls only for contamination with one specific, small group of organisms: E. coli O157:H7 and a few related strains, which make toxins that destroy red blood cells. It got that power during the shocked national reaction to a 1993 outbreak that sickened 732 kids who ate hamburgers from the Jack in the Box fast-food chain. That outbreak killed four and left 178 with kidney and brain damage.

Salmonella comes from multiple sources: Small turtles sold in pet stores carry it, and so do the varieties of poultry that people keep as pets and backyard egg-layers. But at least one-fourth of the cases recognized in the US each year can reliably be traced back to eating commercially raised chicken. The US Centers for Disease Control and Prevention estimates that salmonella is present in one out of every 25 packages of chicken sold in US grocery stores.

Strains linked to poultry are increasingly likely to be resistant to several common antibiotics, which are used to raise meat animals as well as in human medicine. “One study has shown that poultry raised conventionally with antibiotics is twice as likely to contain multi-drug-resistant salmonella, compared to poultry raised without antibiotics,” says Matt Wellington, the public health campaigns director for the nonprofit US Public Interest Research Group. “And right now, it's really up to consumers to try to navigate that, and that's not fair.” Just last week, US PIRG released a report that documented antibiotic use in the meat supply networks of US grocery chains, finding that suppliers for the companies’ private labels overwhelmingly still use antibiotics.

Salmonella is a tricky organism. There are thousands of strains, and only some cause serious illness. Many of them are common in poultry and can exist in birds’ guts without making them sick, which makes preventing them a low priority for bird growers. The organisms also may be passed down between generations, from breeder birds to the ones that are raised for meat, which potentially implicates the entire production chain. Given all those complications, addressing contamination requires a comprehensive effort, regulating not just tainted meat but also slaughterhouse and farm conditions. The change in USDA leadership installed by the Biden administration may have summoned the political will to create it. A year ago, the FSIS announced it would focus on salmonella and poultry, with the goal of cutting infections by 25 percent.

The framework launched last week lays out the details of that commitment. It calls for testing flocks as they arrive at slaughterhouses, a goal that implies poultry growers would work to control the pathogen on their farms. It proposes specific controls in slaughter and packaging beyond those that currently exist. And it advances the concept of an “enforceable final product standard,” which would consider the presence of salmonella, or certain strains of the pathogen, as reason to prevent meat from being sold.

“We’re really pleased to see this, because it shows that FSIS has been listening to stakeholders, especially consumer advocacy groups,” says Mitzi D. Baum, the CEO of the nonprofit Stop Foodborne Illness, which filed a citizens’ petition with the USDA last year asking it to create salmonella controls. (Stop Foodborne Illness, originally called Safe Tables Our Priority, was founded after the Jack in the Box outbreak; Amanda Craten is on its board.) But it’s not only advocacy groups. Reorganizing salmonella control is backed by four of the largest US poultry producers—Butterball, Perdue Farms, Tyson Foods, and Wayne Farms—which last year established a “coalition for poultry safety reform” with CSPI, Stop Foodborne Illness, Consumer Reports, and the Consumer Federation of America.

Yet industry support is not universal. On the day the framework was announced, the National Chicken Council, the industry group for US poultry products, released a statement objecting to the move, saying the proposal “failed to use science and research.”

A public meeting on November 3 will launch the USDA’s formal process. But the real question is what happens after that. The framework commits the agency to producing an interim rule in 2023 and a final regulation in 2024. That is extraordinarily fast by Washington, DC, standards. The short timeline may signal that the agency feels it needs to make real change—or realizes that change must happen before the 2024 election, if it is to occur at all.

“My worry is that we're going to take till 2023 to propose anything. But then there'll be the elections coming up, and you can't do anything during the election. And then either the same administration, or a new administration, gets new people in,” says Bill Marler, a leading food safety lawyer who filed a USDA petition on salmonella in 2019 and represented one of the original E. coli victims in 1993.

But the consumer advocates who also have been pushing for this change hope the timeline will hold. “The thing that makes it most important for them to move quickly is that there are a million people getting sick from salmonella every year, and those people aren't going to benefit until after this rule has been finalized,” Sorscher says. “It’s very important they move quickly because, yes, we don't know what will happen in 2024—but also because Americans have already waited too long.”

https://www.wired.com/story/the-us-is-finally-considering-protections-against-salmonella/