Publisher Health

To put the COVID-19 pandemic in the rearview mirror and prevent other coronaviruses from causing havoc, the world needs an arsenal of measures to prevent and treat these infections. To develop new medications, researchers are working to target one protein, nsp13, that these viruses need to replicate. In a study in ACS Infectious Diseases, one team describes a new approach to identifying molecules that interfere with this protein, a step toward development of pan-coronavirus antivirals.
While vaccines prepare the immune system to fight off the virus, antiviral medications treat infections that have already begun by interfering with an essential part of the viral machinery. Some antivirals, including remdesivir, molnupiravir and nirmatrelvir, are already available for COVID-19 patients; however, health authorities want additional options that disrupt infection in different ways. Researchers have identified a promising new target within SARS-CoV-2 and other coronaviruses, a protein called nsp13. It is an enzyme that works with other viral proteins to help copy the pathogen’s genetic code by unwinding its double-stranded viral RNA. Nsp13 fuels this work by breaking bonds between phosphate groups, including those in the energy-storing molecule known as adenosine triphosphate (ATP). Nsp13 is also involved in capping the viral RNA, which protects it from the human immune system. To speed up the search for drugs that block nsp13, Masoud Vedadi and colleagues developed a new way to screen large numbers of molecules to identify those with the most potent activity.
Because nsp13’s energy-releasing activity increases in the presence of single-stranded nucleic acids, the team devised tests that focus on this activity in the presence and absence of single-stranded DNA. In both cases, the tests glow more brightly when less ATP is broken down, which occurs when something is interfering with nsp13. They used one of these tests to screen a library of 5,000 small molecules, turning up 17 promising results. Additional work, including performing the second test, narrowed the field to only six compounds — potential starting points for the development of future, more-potent nsp13 inhibitors, according to the researchers. The new tests, meanwhile, could be used to efficiently screen large numbers of small molecules for activity against nsp13, or to confirm results from other approaches, they say.
The authors acknowledge funding from the University of Toronto (Toronto COVID-19 Action Initiative-2020) and support of the Structural Genomics Consortium, University of Toronto site.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

Researchers at the University of California, Davis, have been able to produce antibodies to the SARS-CoV-2 spike protein in hen eggs. Antibodies harvested from eggs might be used to treat COVID-19 or as a preventative measure for people exposed to the disease. The work was published July 9 in the journal Viruses.
“The beauty of the system is that you can produce a lot of antibodies in birds,” said Rodrigo Gallardo, professor in poultry medicine, Department of Population Health and Reproduction at the UC Davis School of Veterinary Medicine. “In addition to a low cost to produce these antibodies in hens, they can be updated very fast by using updated antigens to hyperimmunize hens, allowing protection against current variant strains.”
Birds produce a type of antibody called IgY, comparable to IgG in humans and other mammals. IgY does not cause allergy or set off immune reactions when injected into humans. IgY appears both in birds’ serum and in their eggs. As a hen lays about 300 eggs a year, you can get a lot of IgY, Gallardo said.
Gallardo and colleagues immunized hens with two doses of three different vaccines based on the SARS-CoV-2 spike protein or receptor binding domain. They measured antibodies in blood samples from the hens and in egg yolks three and six weeks after the last immunization.
Purified antibodies were tested for their ability to block coronavirus from infecting human cells at the National Center for Biodefense and Infectious Diseases at George Mason University in Virginia.
Both eggs and sera from immunized hens contained antibodies that recognized SARS-CoV-2. Antibodies from serum were more effective in neutralizing the virus, probably because there is more antibody in blood overall, Gallardo said.
Gallardo is working with colleagues Daria Mochly-Rosen at Stanford University and Michael Wallach, University of Technology, Sydney, to develop the egg-based antibody technology. The team hopes to deploy these antibodies in a preventative treatment such as a spray, that could be used by people at high risk of exposure to coronavirus.
Additional authors on the paper are Emily Aston, UC Davis Department of Animal Science; Aarthi Narayanan, National Center for Biodefense and Infectious Diseases; and Sofia Egaña-Labrin, UC Davis School of Veterinary Medicine. The work was supported by the School of Veterinary Medicine at UC Davis, Stanford University and poultry producers in the state of California.
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Materials provided by University of California – Davis. Original written by Andy Fell. Note: Content may be edited for style and length.

Lehigh University and Bentley University health economics researchers have published the first study to confirm a causal relationship between lead-in-water and adverse fetal health outcomes. Although many studies have found a correlation between lead exposure and health, a causal link had been lacking in the literature — until now.
The study has recently been published in the Journal of Health Economics in an article titled: Lead in Drinking Water and Birth Outcomes: A Tale of Two Water Treatment Plants.
The researchers,Muzhe Yang, professor of economics at Lehigh University and Dhaval M. Dave of Bentley University, used data on the exact home addresses of pregnant women living in the City of Newark together with information on the spatial boundary separating areas within the city serviced by two water treatment plants. Their study exploits an exogenous, or external, change in the water’s pH level that caused lead to leach into the drinking water of one plant’s service area, but not the other’s, to identify the causal effect of prenatal lead exposure on fetal health.
Yang and his colleague found robust evidence of adverse health impacts. Among the findings: prenatal lead exposure increased the chance of low-birth-weight by 18% and increased the probability of preterm birth by 19%.
“These findings have important policy implications,” says Yang, “especially in light of the substantial number of lead water pipes that remain in use as part of the aging infrastructure and the cost-benefit calculus of lead abatement interventions.”
Yang notes that the crisis in Newark is not singular, but rather emblematic of the nation’s aging water infrastructure.
According to the American Academy of Pediatrics, there is no safe threshold for lead exposure that has been identified for children. Lead collects over time in the human body through repeated exposure and is stored in the bones alongside calcium. In utero exposure is of particular concern as lead in the mother’s bones can be mobilized during pregnancy and released as a calcium substitute to aid in the formation of the bones of the fetus, and lead in a mother’s blood can also cross the placenta, exposing the fetus to lead poisoning. Prenatal lead exposure has been associated with impaired neural development putting children at risk for cognitive impairment later.
The Environmental Protection Agency (EPA) estimates that drinking water may account for more than 20 percent of total lead exposure for adults and 40 to 60 percent for infants.
In the introduction to their paper, Yang and Dave write: “Drinking water contamination is becoming an increasingly important and widespread source of prenatal exposure to environmental pollution. Between 2018 and 2020, nearly 30 million people received their drinking water from community water systems that were in violation of the EPA’s Lead and Copper Rule, which sets maximum enforceable levels of these metals in drinking water…”
“We are glad that the urgency of the problem was finally recognized in the infrastructure bill passed by the Congress that includes funding of $15 billion for lead pipe replacement,” said Yang.
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Materials provided by Lehigh University. Original written by Lori Friedman. Note: Content may be edited for style and length.

Of all the fungi that live in the human body, the most infamous is probably the yeast Candida. This distant cousin of baker’s yeast is notorious for causing various types of thrush that can be a major nuisance, but it can also lead to an invasive infection that may, on occasion, prove fatal. In a study published today in Nature Immunology, a Weizmann Institute of Science research team headed by Prof. Jakub Abramson uncovered a previously unknown defense mechanism employed by the immune system in fighting Candida infections.
Candida is present at low levels in the bodies of most healthy people, forming part of the microbiome — a diverse spectrum of microbes that reside peacefully in our gut and on our skin. Under normal circumstances, Candida is held in check by the immune system, but it can occasionally grow excessively, invading the lining of the mouth, the vagina, the skin or other parts of the body. In severe cases, it can spread to the bloodstream and from there to the kidneys. Such life-threating infections may occur when a person’s immune system has been weakened, for example, by AIDS or by immunosuppressive drugs such as cancer chemotherapy or steroids. Antibiotics, which wipe out many of the beneficial bacteria within our microbiome, can also unleash local or invasive Candida eruptions by providing this yeast with an unfair advantage vis-à-vis other microorganisms. That’s why, for instance, women sometimes develop a vaginal yeast infection after taking antibiotics.
Until now, the immune cells that got most of the credit for defending the body against Candida were the small, round lymphocytes of the T cell type, called TH17. These cells were also the ones to take the blame when this defense failed.
In the new study, postdoctoral fellow Dr. Jan Dobeš, working together with colleagues in Abramson’s lab in Weizmann’s Immunology and Regenerative Biology Department, discovered that a powerful commando unit of TH17 cells capable of fighting Candida cannot be generated without crucial early support from an entirely different contingent: a subset of rare lymphoid cells known as type-3 innate lymphoid cells, or ILC3, that express a gene called the autoimmune regulator, or Aire
The two groups of cells belong to the two different arms of the immune system, which, like foot patrols and specialized units, join forces against a common enemy. The Aire-ILC3s — part of the more ancient, innate arm — spring into action almost immediately upon encountering a threat — in this case, a Candida infection. The TH17s belong to the immune system’s more recent, adaptive arm, which takes several days or even weeks to respond, but which launches a much more targeted and potent attack than the innate one.
The scientists found that as soon as Candida starts infecting tissues, the Aire-ILC3s engulf the yeast whole, chop them up and display some of the yeast pieces on their surfaces. That’s how these bits are presented to the TH17s, a few of which are generally on call in the lymph nodes, ready for an infection alert. This kind of presentation instructs the specialized T cells to start dividing rapidly, soaring in number from a few lone commandos to several hundred or even thousands of Candida-specific fighters, capable of destroying the yeast at the sites of infection.

Urban areas with more vegetation, higher density of buildings and facilities, lower population density and without major roads are associated with better health behaviours in children. This is the conclusion of a multicohort study published in Environment International and led by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the “la Caixa” Foundation. Specifically, the study found that children who live surrounded by more natural spaces are more physically active, spend less time doing sedentary activities, get more hours of sleep and are more likely to walk or cycle to school.
Most studies conducted to date have focused on the effect of the urban environment on adults and considered only a single type of exposure, without relating it to other factors. This new study goes a step further by assessing the association between a wide range of urban environmental characteristics and healthy habits in 1,581 children aged 6 to 11 years from six European cohorts. The study reflects the growing interest in investigating how the urban environment contributes to unhealthy behaviours in children and whether a change in urban design could help to promote healthier lifestyles.
To perform the analysis, the researchers estimated exposure to 32 characteristics of the urban environment near the children’s homes and schools, including traffic density on the nearest road and the presence of green spaces or blue spaces (beaches, rivers, lakes, etc.). They also collected information on the children’s healthy habits, including the total amount of time spent doing moderate-to-vigorous physical activity, physical activity outside of school hours, active transport (walking, cycling, etc.) and sedentary activities, as well as sleep duration. A multiple-exposure model was developed using these data.
Urban Design Influences Health
The study found that active transport increased and time spent doing sedentary activities decreased in places where children were exposed to more green space. It also found that proximity to a major road was associated with shorter sleep duration (4.80 fewer minutes per night, on average).
“Our findings have implications for urban planning policies,” commented Martine Vrijheid, head of ISGlobal’s Childhood and Environment programme and last author of the study. “Public health interventions tend to focus on influencing individual behaviours rather than tackling the broader system determinants that drive these behaviours and widen health inequalities. Our evidence reinforces the need to prioritise urban design to improve health-promoting behaviours in children and prevent ill health in adults.” One such strategy should be to increase the number of green spaces and the amount of vegetation in the streets.
Vrijheid added: “We need further research that includes other urban indicators that may be relevant for the behaviour of children and adolescents, such as pedestrian zones and sport facilities (for example, ping-pong tables, volleyball courts, etc.), and which looks at more countries and less-studied areas in order to better assess how changes in the urban environment affect people’s lifestyles.”
A large percentage of the children included in the study (63.6%) did not meet the current recommendation of the World Health Organisation (WHO) for moderate-to-vigorous physical activity (at least 60 minutes per day) and 58.6% spent more than two hours per day watching television or playing computer or video games. In addition, active transport was low, with children spending an average of 6.9 minutes per day travelling from home to school.
Cohorts Studied
The study, based on the collaborative Human Early-Life Exposome (HELIX) project, used data from six European birth cohorts: Born in Bradford (BiB, United Kingdom) Étude des Déterminants pré et postnatals précoces du développement et de la santé de l’Enfant (EDEN, France) INfancia y Medio Ambiente (INMA, Spain) Kaunas cohort (KANC, Lithuania) Norwegian Mother, Father and Child Cohort Study (MoBa, Norway) Mother-Child Cohort in Crete, (RHEA, Greece)
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Materials provided by Barcelona Institute for Global Health (ISGlobal). Note: Content may be edited for style and length.

According to ARRS’ American Journal of Roentgenology (AJR), an AI tool for detection of incidental pulmonary embolus (iPE) on conventional contrast-enhanced chest CT examinations had high NPV and moderate PPV for detection, even finding some iPEs missed by radiologists.
“Potential applications of the AI tool include serving as a second reader to help detect additional iPEs or as a worklist triage tool to allow earlier iPE detection and intervention,” wrote lead investigator Kiran Batra from the University of Texas Southwestern Medical Center in Dallas. “Various explanations of misclassifications by the AI tool (both false positives and false negatives) were identified, to provide targets for model improvement.”
Batra and colleagues’ retrospective study included 2,555 patients (1,340 women, 1,215 men; mean age, 53.6 years) who underwent 3,003 conventional contrast-enhanced chest CT examinations between September 2019 and February 2020 at Parkland Health in Dallas, TX. Using an FDA-approved, commercially available AI tool (Aidoc, New York, NY) to detect acute iPE on the images, a vendor-supplied natural language processing algorithm (RepScheme, Tel Aviv, Israel) was then applied to the clinical reports to identify examinations interpreted as positive for iPE.
Ultimately, the commercial AI tool had NPV of 99.8% and PPV of 86.7% for detection of iPE on conventional contrast-enhanced chest CT examinations (i.e., not using CT pulmonary angiography protocols). Of 40 iPEs present in the team’s study sample, 7 were detected only by the clinical reports, and 4 were detected only by AI.
Noting that both the AI tool and clinical reports detected iPEs missed by the other method, “the diagnostic performance of the AI tool did not show significant variation across study subgroups,” the authors of this AJR article added.
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Materials provided by American Roentgen Ray Society. Note: Content may be edited for style and length.

In 2016, Spinraza® became a game-changer for spinal muscular atrophy (SMA) patients. It was the first FDA-approved treatment for the neurodegenerative disease, which is the leading genetic cause of infant death. The drug was conceived and developed by Cold Spring Harbor Laboratory (CSHL) Professor Adrian Krainer and collaborators. But Krainer didn’t stop there. His lab has been investigating whether Spinraza® could be improved, in collaboration with Alberto Kornblihtt at Universidad de Buenos Aires. They discovered pairing Spinraza® with a second FDA-approved drug called valproic acid (VPA) could be a new way to boost its therapeutic effects.
One way to improve the effect of a drug is by increasing its dosage. But as with any drug, increasing the amount of Spinraza® also increases the risk of toxic side effects. Krainer and collaborators took a different approach. They discovered that pairing Spinraza® with VPA may be an alternate way to improve its clinical effect without using more of the drug. Krainer explains:
“Sometimes you don’t want to use a ton of a drug. If you have a condition that allows you to use less drug, then you may have fewer toxicities. So the idea is to combine these two drugs to get maximal effects.”
People with SMA don’t have enough of a protein called SMN. Spinraza® is a type of molecule called an antisense oligonucleotide (ASO) that helps cells make more SMN protein from a gene called SMN2. The team discovered that there were roadblocks on the SMN2 gene when using Spinraza®. This slowed down the cellular machine producing SMN protein. The drug VPA helps remove the roadblocks, allowing Spinraza® to further increase the SMN protein output. When mice with SMA were treated with both VPA and a Spinraza®-like ASO used for research, the mice survived longer and had improved muscle function.
Over 11,000 SMA patients have been treated with Spinraza® in more than 50 countries. Krainer’s latest research shows that there’s always room for improvement. He hopes the team’s findings will help optimize the efficacy of Spinraza® treatments. He also hopes their work will help researchers who are trying to develop therapies for other neurodegenerative diseases.
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Materials provided by Cold Spring Harbor Laboratory. Original written by Luis Sandoval. Note: Content may be edited for style and length.

Surveillance programs for people at high risk of developing pancreatic cancers can help detect precancerous conditions and cancers early, when they are most treatable, according to a new multicenter study directed by experts at the Johns Hopkins Kimmel Cancer Center.
A total of 1,461 individuals at high risk of developing pancreatic cancer were enrolled in the Cancer of Pancreas Screening-5 (CAPS5) study at Johns Hopkins Medicine and seven other medical centers, and underwent annual pancreatic imaging tests. Of these participants, 10 were diagnosed with pancreatic cancer, including one participant who was diagnosed four years after dropping out of recommended surveillance. Seven of the remaining nine patients (77.8%) were diagnosed with stage I disease, and the other two had progressed to higher stage cancer (one had stage IIB, and one had stage III disease). Seven of these patients were alive after a median follow-up of 2.6 years.
These findings were published online in the June 2022 issue of the Journal of Clinical Oncology.
“A clear majority of patients in the CAPS program who were diagnosed with pancreatic cancer were detected at the first stage of the disease if they maintained their surveillance,” says senior study author Michael Goggins, M.B.B.Ch., M.D., Sol Goldman Professor of Pancreatic Cancer Research and director of the Pancreatic Cancer Early Detection Laboratory.
In general, Goggins says, most patients presenting with symptoms already have later-stage pancreatic cancer; very few have their disease detected at stage I. Combining the CAPS5 data with statistics from previous Johns Hopkins Medicine CAPS studies that began in 1998, led by Marcia Canto, M.D., director of clinical research for the gastroenterology division, investigators found that in the entire CAPS cohort of 1,731 patients, 19 of the 26 cases of pancreatic cancer were diagnosed in patients who maintained their pancreas surveillance. Of those, 57.9% had stage I cancers, 15.8% had stage II cancers, 21.1% had stage III cancers and 5.2% had stage IV disease. By contrast, six of the seven pancreatic cancers detected in patients who had stopped their annual surveillance (85.7%) were stage IV. The five-year survival to date of patients with a surveillance-detected pancreatic cancer is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with pancreatic cancer outside surveillance.
“Many of those diagnosed with pancreatic cancer under surveillance can be potentially cured. By contrast, people who dropped off their surveillance had poor survival rates. Our results support the CAPS surveillance recommendation that those who meet the criteria should undergo regular screenings,” says Goggins.
In the CAPS5 study, investigators enrolled individuals between 2014-2021 who had a genetic variant that made them susceptible to pancreatic cancer or who had more than one first-degree relative with pancreatic cancer. Nearly half (48.5%) had a genetic variant predisposing them to cancer, including 18.4% with a mutation in the BRCA2 gene and 6.4% with a variant in the ATM gene. About a third of the group had a personal history of cancer, with breast cancer being the most commonly reported (15.8% affected). Patients received annual screenings with magnetic resonance imaging or endoscopic ultrasound.
Eight other participants had pancreatic surgeries for concerning lesions detected during surveillance. Of these, three were found to have high-grade dysplasia precancerous conditions, and five were found to have low-grade dysplasia. Also, during the study period, 73 patients were diagnosed with other cancers, including 17 cases of breast cancer, 11 cases of prostate cancer and seven cases of melanoma.
Pancreatic surveillance is best done at expert centers by multidisciplinary teams, Goggins says, because some abnormalities that show up in pancreatic imaging are of uncertain significance. Researchers are working on blood tests that could be combined with imaging for early detection of cancers, he says.
Study co-authors were Mohamad Dbouk, Alison P. Klein, Ihab Kamel, Ralph H. Hruban, Jin He, Eun Ji Shin, Anne Marie Lennon, and Marcia Canto of Johns Hopkins. Other institutions participating in the study were the University of Pennsylvania Perelman School of Medicine, Philadelphia; University of Pittsburgh Medical Center; University Hospitals Cleveland Medical Center; Dana-Farber Cancer Institute, Boston; Yale Center for Pancreatic Disease, New Haven, Connecticut; Columbia University Irving Medical Center, New York, New York; and the University of Michigan, Ann Arbor.
The work was supported by the National Cancer Institute (grants CA210170, CA176828, CA62924, and P30CA013696); the Pancreatic Cancer Action Network; the V Foundation; Susan Wojcicki and Dennis Troper; the Lustgarten Foundation; the Smith Family Research Fund; the Bowen-Chapman Fund; and a Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Research Grant.
Goggins receives royalties related to licensing as a co-discoverer of PALB2 as a pancreatic cancer susceptibility gene to Myriad Genetics. Klein is a consultant for OptumInsight and Merck, and receives research funding from OptumLabs. Kamel receives research funding from Siemens Healthineers. Hruban receives research funding from Applied Materials Inc. and has the potential to receive royalty payments from Thrive Earlier Detection Corp for the TERT in bladder cancers and GNAS inventions in an arrangement reviewed and approved by The Johns Hopkins University. Shin is a consultant for Boston Scientific. Lennon holds a patent for CancerSEEK. Canto is a consultant for Castle Biosciences and Bluestar Genomics; she receives research funding from Pentax Medical Corp. and Endogastric Solutions; and receives royalties from UpToDate, online. These arrangements are being managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.

Health issues and loss, social isolation and mental health problems — the pandemic has had a drastic effect on our society. But how have the youngest members of society been coping with these changes? Researchers at the University of Zurich have found that the presence of parents and caregivers is enough to mitigate the pandemic’s negative effects on the social development of infants.
The Covid-19 pandemic has had a profound impact on our social lives. Almost overnight, people started to work from home, keep their distance and cover half their face with surgical masks. This affected small children, teenagers and adults alike. And yet, there has been very little research into the effects of pandemic-related changes on infants.
Gaze following fundamental for social development
Researchers at the University of Zurich (UZH) have now studied whether infants born during the pandemic exhibit different social behavior than same-aged infants before the pandemic. The study focused on the children’s ability to follow another person’s gaze. “This ability is fundamental for engaging in social interactions, building relationships and developing language skills,” says Stephanie Wermelinger, who researches developmental psychology in infants and children at the Department of Psychology of UZH. If this ability is impaired, it can hamper a person’s ability to interact with society, as is the case for people with autism.
Eighty infants between the age of 12 and 15 months took part in the study. They were shown different videos in which a person was gazing at one of two objects. By tracking the infants’ eye movements, the researchers recorded how often and how quickly the infants followed the person’s gaze. They then compared their data with eye movement data from 133 children using the same method before the pandemic.
Parents and caregivers soften effects of pandemic
The study revealed no significant behavioral differences between the children born during and before the pandemic. Children born during the pandemic followed the person’s gaze just as often and quickly as the children in the pre-pandemic group. Although the pandemic meant that the children saw fewer people overall and interacted with more people who were wearing masks, they don’t seem to be developing any differently to children who didn’t experience any pandemic-related changes.
“We believe the unchanged social interactions with parents and caregivers at home are enough to mitigate any influence the Covid-19 pandemic might have had on infants,” says author Wermelinger. These contacts could thus be sufficient to provide infants with the social input they need to develop social and emotional skills such as gaze following.
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Materials provided by University of Zurich. Note: Content may be edited for style and length.