They conducted the study with colleagues at the Maryland Department of Health and presented their findings at this week’s Infectious Disease Society of America annual meeting in Boston.

“We found patients in long-term care facilities, like skilled nursing homes, were more likely to be colonized with these pathogens than those getting treated in hospitals,” said study leader Anthony Harris, MD, MPH, Professor of Epidemiology & Public Health at UMSOM and infectious disease specialist at University of Maryland Medical Center. “We were the first in the nation to get a statewide survey of all ventilated patients, and I think it points to the stringency of the infection control programs in place in the state of Maryland and the excellent collaboration between the University of Maryland and the State Health Department.”

Both A. baumannii and C. auris have been highlighted by the federal Centers for Disease Control and Prevention (CDC) as emerging pathogens that present a global health threat. C. auris is a fungus that spreads within and among local healthcare facilities — usually in those hospitalized and on breathing machines (ventilators). Older people with weakened immune systems are particularly susceptible to this infection, which resists treatment with common anti-fungal medications. A. baumannii, a bacteria, also poses a threat to these same types of patients and has become very resistant through the years to treatment with most antibiotics.

To conduct the study, Dr. Harris and his colleagues obtained culture swabs from all 482 patients receiving mechanical ventilation in Maryland healthcare facilities between March and June of this year. All eligible healthcare facilities, 51 in total, participated in the survey. They identified A. baumannii from at least one patient in one-third of the acute care hospitals and from 94 percent of the long-term care facilities. They identified C. auris in nearly 5 percent of hospitalized patients and in 9 percent of patients in long-term care facilities.

“Testing positive, however, does not mean that patients have symptoms or active infections that are potentially life-threatening,” said study co-author J. Kristie Johnson, PhD, Professor of Pathology at UMSOM whose lab did the A. baumannii testing for the study. “But knowing which patients are colonized with these pathogens can help contain their spread to other patients.”

Over the course of 2022, state and local health departments around the country reported 2,377 clinical cases, according to the CDC, nearly five times the number infections in 2019, which was less than 500 cases. Maryland alone had 46 cases in 2022. While these infections don’t normally pose much of health risk to hospital workers, they pose a significant risk of death in patients with weakened immune systems. Often the infections can be spread from patient to patient by health care workers carrying the germs on their hands, equipment or clothing.

“There is a need for more health care facilities nationwide to be aware of the extent of the problem through surveillance testing,” Dr. Harris said.Certain measures can be implemented to help reduce spread of these pathogens includingmore stringent use of disposable gloves and gowns between patients and the use of chlorhexidine bathing of the critically ill to disinfect their skin.

“Emerging pathogens that are resistant to available therapeutics present a growing challenge in our country, especially with a projected increased growth in our aging population entering long term care facilities,” said UMSOM Dean Mark Gladwin, MD, who is also Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor at UMSOM. “Nearly half of patients who contract C. auris infections die within 90 days, according to the CDC, and this pathogen is now found in nearly 50 states. This is why it is critical for these surveillance studies to be conducted nationwide, not just in Maryland.”

UMSOM faculty members Lisa Pineles, MA, Lyndsay O’Hara, PhD, Leigh Smith, MD, and Indira French, MS, were co-authors on this study. The study was funded by a grant from the CDC (1U54CK000450-01).

Scientists at UC San Francisco are getting close to an answer. In a breakthrough that could transform how doctors treat conditions from eczema to allergies, they have discovered a feedback loop centered on a single immune protein called IL-31 that both causes the urge to itch and dials back nearby inflammation.

The findings, published on October 13th in Science Immunology, lay the groundwork for a new generation of drugs that interact more intelligently with the body’s innate ability to self-regulate.

Previous approaches suggested that IL-31 signals itch and promotes skin inflammation. But the UCSF team discovered that nerve cells, or neurons, that respond to IL-31, triggering a scratch, also prevent immune cells from overreacting and causing more widespread irritation.

“We tend to think that immune proteins like IL-31 help immune cells talk to one another, but here, when IL-31 talks to neurons, the neurons talk right back,” said Marlys Fassett, M.D., Ph.D., UCSF professor of dermatology and lead author of the study. “It’s the first time we’ve seen the nervous system directly tamp down an allergic response.”

The discovery could eventually change how asthma, Crohn’s and other inflammatory diseases are treated, due to IL-31’s presence throughout the body.

“IL-31 causes itch in the skin, but it’s also in the lung and in the gut,” said Mark Ansel, Ph.D., UCSF professor of immunology and senior author of the study. “We now have a new lead for fighting the many diseases involving both the immune and nervous systems.”

More than an itch

IL-31 is one of several “itch cytokines” because of its ability to instigate itch in animals and people. Fassett, a dermatologist and a researcher, has wanted to know why since she arrived at UCSF in 2012, a few years after its discovery. She reached out to Ansel, a former colleague and asthma expert who welcomed her into his lab.

First, Fassett removed the IL-31 gene from mice and exposed them to the house dust mite, a common, itchy allergen.

“We wanted to mimic what was actually happening in people who are chronically exposed to environmental allergens,” Fassett said. “As we expected, the dust mite didn’t cause itching in the absence of IL-31, but we were surprised to see that inflammation went up.”

Why was there inflammation but no itching? Fassett and Ansel found that a cadre of immune cells had been called into action in the absence of the itch cytokine. Without IL-31, the body was blindly waging an immunological war.

A balance of forces

Ansel and Fassett then homed in on the nerve cells in the skin that received the IL-31 signal. They saw that the same nerve cells that spurred a scratch also dampened any subsequent immune response. These nerve cells were integral to keeping inflammation in check, but without IL-31, they let the immune system run wild.

The findings squared well with what dermatologists were increasingly seeing with a new drug, nemolizumab, which blocked IL-31 and was developed to treat eczema. While clinical trial patients found that the dry, patchy skin of their eczema receded on the drug, other skin irritation, and even inflammation in the lungs, would sometimes flare up.

“When you give a drug that blocks the IL-31 receptor throughout the whole body, now you’re changing that feedback system, releasing the brakes on allergic reactions everywhere,” Ansel said.

Fassett and Ansel also found that these neurons released their own signal, called CGRP, in response to the itch signal, which could be responsible for dampening the immune response.

“The idea that our nerves contribute to allergy in different tissues is game changing,” Fassett said. “If we can develop drugs that work around these systems, we can really help those patients that get worse flares after treatment for itch.”

Fassett recently founded her own lab at UCSF to tease apart these paradoxes in biology that complicate good outcomes in the clinic. And Ansel is now interested in what this itch cytokine is doing beyond the skin.

“You don’t itch in your lungs, so the question is, what is IL-31 doing there, or in the gut?” Ansel asked. “But it does seem to have an effect on allergic inflammation in the lung. There’s a lot of science ahead for us, with immense potential to improve therapies.”

Recurrent C. difficile infections occur after suppressive antibiotic treatments that knock out almost all of the normal gut flora. Patients suffer watery diarrhea, painful abdominal cramps, a feeling of sickness, fevers and weight loss.

In 2021, researchers at the Icahn School of Medicine at Mount Sinai, New York, gave precise quantification of 150 bacterial strains belonging to 42 bacterial species that showed frequent engraftment after fecal microbial transplants. Importantly, they also tested for engraftment soon after transplant — 36 hours to four weeks — as well as later after transplantation, eight weeks to five years.

Now microbiome experts at the University of Alabama at Birmingham have taken that 2021 study, and a similar study for children who had C. difficile infections, a step further. UAB researchers Hyunmin Koo, Ph.D., and Casey D. Morrow, Ph.D., focused on the commensal microbe Bacteroides vulgatus, one of the most common species found in healthy guts. Using DNA sequences from the two studies and powerful bioinformatics analysis, Koo and Morrow searched for genes, out of a total of 4,911 protein-encoding genes in the B. vulgatus strains, that were unique to the three B. vulgatus donors in the two studies that showed early colonization, as opposed to seven other B. vulgatus strains in the studies that did not show early colonization.

“Analysis of the common genes between the three donors revealed that only 19 were in common out of 4,911 genes encoding known and hypothetical proteins,” Morrow and Koo write in the Scientific Reports study. “The result from our analysis supports the screening of donor B. vulgatus for this gene consortium to enhance colonization following a fecal microbe transplant.”

Morrow and Koo identified two of the 19 genes.

One is a putative chitobiase that the UAB researchers found was located next to genes encoding SusD, SusC, putative anti-sigma factor and RNA polymerase ECF-type sigma factor. Others previously have identified these genes as components of a commensal colonization factor complex in Bacteroides fragilis and B. vulgatus. This complex promotes a specific interaction with the host that facilitates stable, resilient colonization in mice.

“Our results, then, provide support that the commensal colonization factor complex might also function in humans to enhance the colonization of B. vulgatus,” Morrow said.

The other identified gene encodes a unique fimbrillin family protein. Fimbrillins are protein polymers, previously identified in Bacteroides, that can form the hair-like structures that protrude from the surfaces of microbes and serve as anchors for microbial adhesion with host cells.

“Based on their known functions, the identification of both the chitobiase — and subsequently a complete commensal colonization factor complex — and fimbrillin proteins supports the involvement of these proteins in B. vulgatus colonization,” Morrow said.

The other 17 genes are hypothetical proteins with no identified function as yet. Interestingly, genes that mapped near the hypothetical proteins involved activities in DNA mobilization and transposition, meaning the ability to move genes into, around or out of the bacterial genome.

Morrow and Koo acknowledge a weakness in their study.

When they analyzed the 42-paired fecal microbe samples from the Human Microbiome Project data set, they found that none had the complete set of the 19 genes that were found in the three early engraftment B. vulgatus strains. Twenty-six of the samples had both the putative chitobiase and the fimbrillin genes, and another 11 had only the fimbrillin gene. There was a varied presence of the other 17 hypothetical genes in the 42 samples.

“Since none of the Human Microbiome Project pairs had the full 19 genes, we do not know whether any of the pairs would have an early colonizing phenotype in fecal microbe transplants,” Morrow said. “Based on our analysis, we would assume that the commensal colonization factor complex and fimbrillin genes would suffice; but to resolve this issue, additional fecal microbe transplants for recurrent C. difficile in humans using early analysis times post-transplant would need to be done.”

The UAB researchers say a further application of their study could be screening following chemotherapy or transplants, which are known to involve medications that can disrupt normal microbial gut flora. “The capacity to rapidly restore the B. vulgatus community in these patients would be important to reduce the risk of infection by pathogens or antibiotic-resistant microbe pathogens that could impact overall health,” Morrow said.

Support for the Scientific Reports study, “Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile,” came from the Marnix E. Heersink School of Medicine at UAB. Morrow is a professor emeritus in the UAB Department of Cell, Developmental and Integrative Biology, and Koo is a bioinformatician in the UAB Department of Genetics.

“Establishing clear ethical guidelines and governance structures for the deployment of AI around the world is the first step to promoting trust and confidence, mitigating its risks, and ensuring that its benefits are fairly distributed,” says social scientist and co-author James William Santos of the Pontifical Catholic University of Rio Grande do Sul.

“Previous work predominantly centered around North American and European documents, which prompted us to actively seek and include perspectives from regions such as Asia, Latin America, Africa, and beyond,” says lead author Nicholas Kluge Corrêa of the Pontifical Catholic University of Rio Grande do Sul and the University of Bonn.

To determine whether a global consensus exists regarding the ethical development and use of AI, and to help guide such a consensus, the researchers conducted a systematic review of policy and ethical guidelines published between 2014 and 2022. From this, they identified 200 documents related to AI ethics and governance from 37 countries and six continents and written or translated into five different languages (English, Portuguese, French, German, and Spanish). These documents included recommendations, practical guides, policy frameworks, legal landmarks, and codes of conduct.

Then, the team conducted a meta-analysis of these documents to identify the most common ethical principles, examine their global distribution, and assess biases in terms of the type of organizations or people producing these documents.

The researchers found that the most common principles were transparency, security, justice, privacy, and accountability, which appeared in 82.5%, 78%, 75.5%, 68.5%, and 67% of the documents, respectively. The least common principles were labor rights, truthfulness, intellectual property, and children/adolescent rights, which appeared in 19.5%, 8.5%, 7%, and 6% of the documents, and the authors emphasize that these principles deserve more attention. For example, truthfulness — the idea that AI should provide truthful information — is becoming increasingly relevant with the release of generative AI technologies like ChatGPT. And since AI has the potential to displace workers and change the way we work, practical measures are to avoid mass unemployment or monopolies.

Most (96%) of the guidelines were “normative” — describing ethical values that should be considered during AI development and use — while only 2% recommended practical methods of implementing AI ethics, and only 4.5% proposed legally binding forms of AI regulation.

“It’s mostly voluntary commitments that say, ‘these are some principles that we hold important,’ but they lack practical implementations and legal requirements,” says Santos. “If you’re trying to build AI systems or if you’re using AI systems in your enterprise, you have to respect things like privacy and user rights, but how you do that is the gray area that does not appear in these guidelines.”

The researchers also identified several biases in terms of where these guidelines were produced and who produced them. The researchers noted a gender disparity in terms of authorship. Though 66% of samples had no authorship information, the authors of the remaining documents more often had male names (549 = 66% male, 281 = 34% female).

Geographically, most of the guidelines came from countries in Western Europe (31.5%), North America (34.5%), and Asia (11.5%), while less than 4.5% of the documents originated in South America, Africa, and Oceania combined. Some of these imbalances in distribution may be due to language and public access limitations, but the team says that these results suggest that many parts of the Global South are underrepresented in the global discourse on AI ethics. In some cases, this includes countries that are heavily involved in AI research and development, such as China, whose output of AI-related research increased by over 120% between 2016 and 2019.

“Our research demonstrates and reinforces our call for the Global South to wake up and a plea for the Global North to be ready to listen and welcome us,” says co-author Camila Galvão of the Pontifical Catholic University of Rio Grande do Sul. “We must not forget that we live in a plural, unequal, and diverse world. We must remember the voices that, until now, haven’t had the opportunity to claim their preferences, explain their contexts, and perhaps tell us something that we still don’t know.”

As well as incorporating more voices, the researchers say that future efforts should focus on how to practically implement principles of AI ethics. “The next step is to build a bridge between abstract principles of ethics and the practical development of AI systems and applications,” says Santos.