Publisher Health

A federal appeals court had signed off on the agreement, which would shield members of the wealthy Sackler family from opioid-related lawsuits in exchange for $6 billion for victims.The Supreme Court agreed on Thursday to consider the government’s challenge of a bankruptcy settlement involving Purdue Pharma, putting on pause a deal that would have shielded members of the wealthy Sackler family from civil opioid lawsuits in exchange for payments of up to $6 billion to thousands of plaintiffs.In doing so, the court sided with the Justice Department, which had requested the court put the settlement plan on hold while it considered reviewing the agreement. The government has argued that the family behind Purdue Pharma, maker of the prescription painkiller OxyContin, should not be able to take advantage of legal protections meant for debtors in “financial distress.”The court’s order, which was unsigned, gave no reasons and included no public dissents, adds to the uncertainty around the plan to compensate states, local governments, tribes and individuals harmed by the opioid crisis while offering protection for the Sackler family. The order specified that the justices would hear arguments in the case in December.The court’s decision to take up the challenge to the bankruptcy agreement is the latest twist in the yearslong legal battle over compensation for victims of the prescription drug crisis.In May, the U.S. Court of Appeals for the Second Circuit approved the settlement plan as part of a court review of bankruptcy restructuring for Purdue Pharma. The company had filed for bankruptcy protections in September 2019. At the time, both the company and members of the Sackler family were facing lawsuits connected with the opioid crisis.Although it is routine for companies who seek bankruptcy protection to be shielded from legal claims, the unusual part of this agreement was that it extended that liability protection to the company’s owners. Sackler family members have said they would not sign onto a settlement without an agreement protecting them from lawsuits.The U.S. Trustee Program, an office in the Justice Department that oversees the administration of bankruptcy cases, has long argued that bankruptcy judges do not have the power to permanently block lawsuits against company owners if those owners haven’t sought personal bankruptcy protection.The government has argued that federal appeals courts are split on this issue and that the settlement agreement may set a troubling precedent.“Allowing the court of appeals’ decision to stand would leave in place a road map for wealthy corporations and individuals to misuse the bankruptcy system to avoid mass tort liability,” the solicitor general, Elizabeth B. Prelogar, wrote in a brief for the government.The appeals court, Ms. Prelogar wrote, had “pinned itself firmly on one side of a widely acknowledged circuit split about an important and recurring question of bankruptcy law.”Ms. Prelogar called the agreement “a release from liability that is of exceptional and unprecedented breadth.” She argued that the deal “applies to an untold number of claimants who did not specifically consent to the release’s terms,” a deal that “constitutes an abuse of the bankruptcy system, and raises serious constitutional questions.”In a statement released after Thursday’s decision, a spokeswoman for Purdue Pharma said the company was “confident in the legality” of the bankruptcy plan. Members of the Sackler family are no longer on the board of the pharmaceutical company. When the bankruptcy is finalized, they will no longer be owners of the company, which would be renamed Knoa Pharma and owned by its creditors. However, the family still remains wealthy. Some estimates put their fortune at $11 billion, much of it in offshore holdings.Victims’ groups have expressed frustration at the government’s position, raising concerns that it would further delay payments to those harmed.“Regardless of how one feels about the role of the Sackler family in the creation and escalation of the opioid crisis, the fact remains that the billions of dollars in abatement and victim compensation funds hinge on confirmation and consummation of the existing plan,” a brief filed on behalf of a victims’ group said. “These funds, which the Sackler family members are providing in exchange for releases, are critically needed now.”Jan Hoffman

A new analysis shows that infectious bacteria exposed to the antibiotic albicidin rapidly develop up to a 1,000-fold increase in resistance via a gene amplification mechanism. Mareike Saathoff of Freie Universität Berlin, Germany, and colleagues present these findings August 10 in the open access journal PLOS Biology.
Bacterial resistance to antibiotics is a growing problem associated with millions of deaths around the world every year. Understanding how bacteria evolve resistance is key to developing more effective antibiotics and strategies for using them.
In recent years, albicidin has emerged as a promising antibiotic capable of killing a wide range of bacterial species by disrupting their DNA replication. Researchers are working to develop new albicidin-based medications; yet, despite its promise, some bacteria are able to develop resistance to albicidin.
To further investigate albicidin resistance mechanisms, Saathoff and colleagues conducted a suite of experiments employing a broad set of tools, including RNA sequencing, protein analysis, X-ray crystallography, and molecular modeling. They found that two bacteria often associated with human infection — Salmonella typhimurium and Escherichia coli — develop resistance to albicidin when exposed to increasingly higher concentrations of the compound. Their analysis narrowed down the source of this resistance to an increase in the number of copies of a gene known as STM3175 (YgiV) in the bacterial cells, which is amplified in each new generation of cells as they multiply. STM3175 encodes a protein that interacts with albicidin in such a way that protects the bacteria from it.
Further experiments showed that the same albicidin-resistance mechanism is widespread among both pathogenic and harmless bacteria, including the microbes Vibrio vulnificus, which can infect wounds, and Pseudomonas aeruginosa, which can cause pneumonia and other infections. These findings could help inform the ongoing development of albicidin-based antibiotic strategies.
The authors add, “Our study reveals a gene duplication and amplification-based mechanism of a transcriptional regulator in Gram-negative bacteria, that mediates resistance to the peptide antibiotic albicidin.”

Cancer cells can evade the body’s immune defenses by exploiting a normally helpful and ubiquitous group of molecules known as mucins. Now, Stanford researchers have engineered a biomolecule that removes mucins specifically from cancer cells — a discovery that could play a significant role in future therapies for cancer.
Mucins are sugar-coated proteins whose primary function is to defend the body against physical insults and pathogens. But cancer cells can co-opt mucins to aid their survival. Cutting mucins off cancer cells is a plausible therapy, but mucins exist in various forms on every cell in mammalian bodies, so targeting mucins indiscriminately could have unforeseen side effects.
The solution devised by the Stanford-led research team is essentially an enzyme-based scissors composed of a mucinase — a protein-cutting enzyme (called a protease) that specifically cuts mucins — fused to a cancer-cell-targeting nanobody (an antibody fragment). This two-part biomolecule selectively targets and prunes only mucins associated with specific cancer cells.
This study, carried out in lab-grown human cancer cells and in mouse studies that simulated human breast and lung cancer, found the biomolecule treatment significantly reduced tumor growth and increased survival. Their findings, published Aug. 3 in Nature Biotechnology, have broad applications as mucins are associated with many diseases, including cystic fibrosis, respiratory diseases, and viruses.
“We found that we could target this mucinase to cancer cells, use it to remove mucins from those cancer cells, and there was a therapeutic benefit,” said senior author Carolyn Bertozzi, the Anne T. and Robert M. Bass professor in Stanford’s School of Humanities and Sciences.
Graduate scholar Gabrielle “Gabby” Tender is co-lead author on the study with two former Bertozzi lab researchers — Kayvon Pedram, a group leader at HHMI’s Janelia Research Campus, and D. Judy Shon, a postdoctoral scholar at Caltech.
When good mucins go bad
Although cancer cells use mucins for nefarious purposes, mucins are generally good. But when mucins go bad, they’re awful.

A new study published in the journal Science by an international team finds that past changes in atmospheric CO2 and corresponding shifts in climate and vegetation played a key role in determining when and where early human species interbred.
Modern-day people carry in their cells a small quantity of DNA deriving from other human species, namely the Neanderthals and the elusive Denisovans. Back in 2018, scientists announced to the world the discovery of an individual, later nicknamed Denny, who lived 90,000 years ago and who was identified as a daughter to a Denisovan father and a Neanderthal mother[Slon et al. 2018]. Denny, along with fellow mixed-ancestry individuals found at Denisova cave, testifies that interbreeding was probably common among hominins, and not limited to our own species Homo sapiens.
To unravel when and where human hybridization took place, scientists usually rely on paleo-genomic analysis of extremely rare fossil specimens and their even scarcer ancient DNA content. In the new Science paper, the team of climate experts and paleo-biologists from South Korea and Italy pursued a different approach. Using existing paleo-anthropological evidence, genetic data and supercomputer simulations of past climate, the team found that Neanderthals and Denisovans had different environmental preferences. More specifically, Denisovans were much more adapted to cold environments, characterized by boreal forests and even tundra, compared to their Neanderthal cousins who preferred temperate forests and grassland. “This means that their habitats of choice were separated geographically, with Neanderthals typically preferring southwestern Eurasia and Denisovans the northeast,” says Dr. Jiaoyang Ruan, postdoctoral researcher at the IBS Center for Climate Physics (ICCP), South Korea and lead author of the study.
However, according to their realistic computer simulations the scientists found that in warm interglacial periods, when Earth’s orbit around the Sun was more elliptic and northern hemisphere summer occurred closer to the Sun, the hominin habitats began to overlap geographically. “When Neanderthals and Denisovans shared a common habitat, there were more encounters and interactions among the groups, which would have increased the chance of interbreeding,” adds Prof. Axel Timmermann, corresponding author of the study and director of the ICCP and professor at Pusan National University.
The simulation of past habitat overlaps does not only put the first generation Neanderthal/Denisovan hybrid Denny into a climatic context, but it also agrees with other known episodes of interbreeding ~78, 120 thousand years ago. Future paleo-genetic reconstructions can be used to test the robustness of the new supercomputer model-based predictions of potential interbreeding intervals around 210 and 320 thousand years ago.
To further determine the climate drivers of the east-west interbreeding seesaw, the scientists looked more closely at how vegetation patterns changed over Eurasia during the past 400 thousand years. They discovered that elevated atmospheric CO2 concentrations and mild interglacial conditions caused an eastward expansion of temperate forest into central Eurasia which created dispersal corridors for Neanderthals into Denisovan lands. “It is as if glacial-interglacial shifts in climate created the stage for a unique and long-lasting human love story, whose genetic traces are still visible today,” comments Dr. Ruan.
One of the key challenges the researchers faced in their study was to estimate the preferred climatic conditions for Denisovans. “To deal with the very sparse Denisovan dataset, we had to devise new statistical tools, which could also account for known ancestral relationships amongst human species,” says Prof. Pasquale Raia from University of Naples, Federico II in Italy, co-author of the study. “This allowed us for the first time to estimate where Denisovans could have lived. To our surprise, we found that, apart from areas in Russia and China, also northern Europe would have been a suitable environment for them,” he adds.
Whether Denisovans ever lived west of the Altai mountains is unknown; but it can be tested using large-sample genetic analyses of Denisovan ancestry in European populations. Such analysis is expected to shed new light on the relationship between early dispersal, habitat encroachment and human genetic diversification.

Scientists can finally hunt down a harmful kind of human T cell, thanks to new research led by scientists at La Jolla Institute for Immunology (LJI) and the Medical College of Georgia (MCG) at Augusta University.
Immune cells called ex-T regulatory cells (exTregs) tend to be rare in the body and, so far, impossible to detect in human samples. The new study gives scientists a reliable way to find human exTregs and provides a window into how exTregs contribute to inflammation and cardiovascular disease.
The researchers used fluorescent tags to track down exTregs in mice prone to atherosclerosis. They then identified specific markers that made these exTregs special. They transposed these findings to humans to detect exTregs in human blood.
“These cells are likely causing damage,” says LJI Postdoctoral Researcher Payel Roy, Ph.D., co-first author of the new Nature Immunology study. “Now we have the potential to use these biomarkers and screen for these cells in human blood.”
“Identifying exTregs in humans opens up more opportunities for research since patient material — like blood samples — are readily available,” adds study senior author Klaus Ley, M.D., co-director of MCG’s Immunology Center of Georgia.
Crazy ex-T regulatory cells
T cells do many jobs in the body. Some T cells have the job of alerting other immune cells to danger or destroying infected host cells. These T cells are the fighters, the offensive lineup. T regulatory cells (Tregs) have the important job of stopping the other T cells from releasing too many inflammatory, or cytotoxic, molecules as they fight infection. The Tregs are like the referees.

Long COVID can persist for at least a year after the acute illness has passed, or appear months later, according to the most comprehensive look yet at how symptoms play out over a year.
The multicenter study, a collaboration between UC San Francisco, the Centers for Disease Control and Prevention (CDC) and seven other sites, expands knowledge of post-COVID-19 conditions, describing trends in more detail than previous research and highlighting significant impacts the epidemic has had on the U.S. health care system.
The study appears Aug. 10, 2023, in Morbidity and Mortality Weekly Report (MMWR), a publication of the CDC.
For about 16% of the COVID-positive people in the study, symptoms lasted for at least a year; but for others, they came and went. The study assessed symptoms every three months, enabling researchers to differentiate between symptoms that improve and those that emerge months after the initial infection.
“It was common for symptoms to resolve then re-emerge months later,” said lead author Juan Carlos Montoy, MD, PhD, associate professor at UCSF’s Department of Emergency Medicine. “A lot of prior research has focused on symptoms at one or two points in time, but we were able to describe symptom trajectory with greater clarity and nuance. It suggests that measurements at a single point in time could underestimate or mischaracterizes the true burden of disease.”
Fluctuating Nature of Disease
Long COVID involves a range of symptoms that persist or develop about a month after initial infection. These symptoms are associated with significant morbidity or reduced quality of life.

A change in just one letter in the code that makes up a cancer-causing gene can significantly affect how aggressive a tumor is or how well a patient with cancer responds to a particular therapy. A new, very precise gene-editing tool created by Weill Cornell Medicine investigators will enable scientists to study the impact of these specific genetic changes in preclinical models rather than being limited to more broadly targeted tactics, such as deleting the entire gene.
The tool was described in a study published Aug. 10 in Nature Biotechnology. Dr. Lukas Dow, an associate professor of biochemistry in medicine at Weill Cornell Medicine, and his colleagues genetically engineered mice to carry an enzyme that allows the scientists to change a single base or “letter” in the mouse’s genetic code. The enzyme can be turned on or off by feeding the mice an antibiotic called doxycycline, reducing the prospect of unintended genetic changes occurring over time. Investigator can also grow miniature versions of intestine, lung, and pancreas tissue called organoids from the mice enabling even more molecular and biochemical studies of the impact of these precise genetic changes.
“We are excited about using this technology to try and understand the genetic changes that influence a patient’s response to cancer therapies,” said Dr. Dow, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
Dr. Dow noted that differences in a single base in a gene can have functional consequences. But most gene-editing tools currently available aim at larger targets like whole genes. Scientists can also use viruses to deliver genes with specific mutations, but this technique is limited to targeting specific tissues like the brain and liver, he said.
“We’ve had good tools for a long time now to knock genes out or overexpress genes,” Dr. Dow said. “But we have not had good ways to create the single-base mutations that we see in patient’s tumors.”
The mouse model allows them to study the effects of the changes on tumors and determine which therapies work best for those with a particular mutation. Organoids derived from the mice enable detailed experiments in tissues that scientists could not easily target with virus-based approaches.
“One mouse model allows you to do two things: test the effects of a mutation in cancer initiation, progression, or treatment response in mice and take a closer look at the associated molecular or biochemical changes using organoids,” he said.
Dr. Dow and his team, including co-first authors Dr. Alyna Katti, a former graduate student, and Dr. Adrián Vega-Pérez, a postdoctoral associate, are currently using this new technology to identify the effects of
single-base mutations in lung, colon, and pancreatic cancer. Their genetically engineered mice will be available to other researchers to use, which may help accelerate progress toward personalized cancer treatment.
“We are making the technology available to other people in the field so they can use it to study their mutations of interest,” Dr. Dow said. “If we can learn the genetic underpinnings of what causes tumor formation and why patients have different outcomes, that may help us develop new drugs or select the best drugs for a particular patient.”

A vacuum chamber is never perfectly empty. A small number of atoms or molecules always remain, and measuring the tiny pressures they exert is critical. For instance, semiconductor manufacturers create microchips in vacuum chambers that must be almost entirely devoid of atomic and molecular contaminants, and so they need to monitor the gas pressure in the chamber to ensure that the contaminant levels are acceptably low.
Now, scientists at the National Institute of Standards and Technology (NIST) have validated a new approach to measuring extremely low gas pressures called CAVS, for cold atom vacuum standard. They have established that their technique can serve as a “primary standard” — in other words, it can make intrinsically accurate measurements without first needing to be calibrated to reference pressure readings.
Having developed CAVS over the last seven years, NIST researchers recently put their technique through its most rigorous tests to date. Their new study, in the journal AVS Quantum Science, shows that CAVS results agreed with the traditional “gold standard” method for measuring low pressures, demonstrating that this new technique can make measurements with the same degree of accuracy and reliability.
Not only can CAVS make measurements as good as those in traditional pressure gauges, but it can also reliably measure the much lower vacuum pressures — a trillionth of the Earth’s sea-level atmospheric pressure and below — that will be required for future chip manufacturing and next-generation science. And its operation, based on well-understood quantum physics principles, means that it can make accurate readings “right out of the box,” without requiring any adjustments or calibration to other reference pressure sources or techniques.
“This is the culminating result,” said NIST physicist Julia Scherschligt. “We have had numerous positive developments before. But this validates the fact that our cold atom standard is truly a standard.”
In addition to semiconductor manufacturing, the new method can be useful for other applications that require high-vacuum environments, such as quantum computers, gravitational wave detectors, particle accelerators and many more.
CAVS technology measures vacuum pressures using a cold gas of about a hundred thousand lithium or rubidium atoms trapped in a magnetic field. These atoms fluoresce when illuminated by a laser tuned to just the right frequency. Researchers can count the number of trapped atoms precisely by measuring the intensity of this glow.

Pushing into a new chapter of technologically advanced biological sensors, scientists from the University of California San Diego and their colleagues in Australia have engineered bacteria that can detect the presence of tumor DNA in a live organism.
Their innovation, which detected cancer in the colons of mice, could pave the way to new biosensors capable of identifying various infections, cancers and other diseases.
The advancement is described Aug. 11, 2023, in the journal Science. Bacteria previously have been designed to carry out various diagnostic and therapeutic functions, but lacked the ability to identify specific DNA sequences and mutations outside of cells. The new “Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer,” or “CATCH,” was designed to do just that.
“As we started on this project four years ago, we weren’t even sure if using bacteria as a sensor for mammalian DNA was even possible,” said scientific team leader Jeff Hasty, a professor in the UC San Diego School of Biological Sciences and Jacobs School of Engineering. “The detection of gastrointestinal cancers and precancerous lesions is an attractive clinical opportunity to apply this invention.”
Tumors are known to disperse, or shed, their DNA into the environments surrounding them. Many technologies can analyze purified DNA in the lab, but these cannot detect DNA where it is released. Under the CATCH strategy, the researchers engineered bacteria using CRISPR technology to test free-floating DNA sequences on a genomic level and compare those samples with predetermined cancer sequences.
“Many bacteria can take up DNA from their environment, a skill known as natural competence,” said Rob Cooper, the study’s co-first author and a scientist at UC San Diego’s Synthetic Biology Institute. Hasty, Cooper and Australian doctor Dan Worthley collaborated on the idea of natural competence in relation to bacteria and colorectal cancer, the third-leading cause of cancer-related death in the United States.
They began to formulate the possibility of engineering bacteria, which are already prevalent in the colon, as new biosensors that could be deployed inside the gut to detect DNA released from colorectal tumors. They focused on Acinetobacter baylyi, a bacterium in which Cooper identified the elements necessary for both taking up DNA and using CRISPR to analyze it.

Concealed guns significantly impact homicide rates and public safety, according to a Rutgers study that found an increase in homicides based on the number of concealed carry weapons licenses issued.
In a new study published in the Journal of Urban Health, researchers examined the reciprocal county-level relationship between the number of concealed carry weapon licenses issued and gun homicides in 11 states between 2010 and 2019.
“This study takes a close look at the back-and-forth relationship between concealed carry licensing and homicides over a relatively long period of time,” said Daniel Semenza, director of interpersonal research of the New Jersey Gun Violence Research Center and co-author of the study.
“We found no evidence that homicides are reduced where there are more concealed carry licenses,” said Semenza. “On the contrary, we found that more concealed carry permits issued in a given county are linked to a greater number of homicides in that county the following year.”
Semenza, an assistant professor in the Department of Urban-Global Public Health at the Rutgers School of Public Health and in the Department of Sociology, Anthropology, and Criminal Justice at Rutgers University-Camden, studied 832 counties in Colorado, Iowa, Kansas, Michigan, Minnesota, New Mexico, North Carolina, Ohio, Oklahoma, Pennsylvania, and Utah from 2010 through 2019. Researchers analyzed the number of concealed carry licenses in each county alongside the number of firearm homicides per county year.
“We take this all of this to mean that people aren’t using concealed guns in public defensively to thwart potential homicides,” said Semenza. “Rather, having more guns in public through concealed carry appears to be more dangerous and leads to higher homicide numbers. Policy makers need to seriously consider the dangers of allowing more guns in more public places, understanding that an increasingly armed society does not necessarily make us any safer.”