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Stress during pregnancy is known to influence health outcomes, but a new study from Mass General Brigham researchers suggests that stress levels before pregnancy are also important to evaluate. Investigators at Massachusetts General Hospital and Brigham and Women’s Hospital analyzed the link between self-reported stress immediately before conception among women seeking fertility care and blood glucose levels, a marker of heart health. The team found that maternal stress during preconception was associated with higher blood glucose levels, especially among women using intrauterine insemination to conceive and women of higher socioeconomic status. Results are published in the Journal of the Endocrine Society.
“Stress prevalence has increased over the years, particularly for couples who are not able to conceive naturally,” said corresponding author Lidia Mínguez-Alarcón, PhD, MPH, Bpharm, a reproductive epidemiologist in the Brigham’s Channing Division of Network Medicine and co-investigator of the Environment and Reproductive Health (EARTH) study. “We wanted to evaluate how this stress affects health during pregnancy, which can affect both the mother and child in the long term.”
Mínguez-Alarcón and colleagues analyzed data from the EARTH study conducted at the Massachusetts General Hospital Fertility Center from 2004 to 2019 for 398 women between 18 and 45 years of age. The women self-reported preconception-perceived stress at study entry. Additional clinical characteristics and sociodemographic information, including family and medical history, consumer products use and smoking history, were either collected by the study staff through medical records or questionnaires.
Women had a median age of 35 years at study entry, and most were of white ethnic background (83 percent), reported never smoking (78 percent), and were at least college educated (64 percent). Three hundred of the women conceived using medically assisted technologies like intrauterine insemination (IUI) or in vitro fertilization (IVF). During IUI, sperm is injected directly into the uterus while IVF is a multi-step technology that involves retrieving an egg for fertilization in a lab before transfer back to the uterus. Glucose testing was done at a median of 26 weeks into pregnancy and taken one hour after the women drank a 50 gram glucose solution. A blood sugar that was equal to or less than 140 mg/dL was considered normal.
Researchers found that blood sugar levels, a measure of cardiovascular health, were abnormally high in 82 of the women involved. Previous studies have shown that women with a history of gestational diabetes (GD) during pregnancy are at increased risk of developing type 2 diabetes as well as cardiovascular problems later in life, including heart artery calcification.
The team found that women who experienced higher preconception stress had higher mean glucose levels. In addition, women who conceived through IUI had both higher stress and blood sugar levels than those who conceived through IVF. The study also found that women of higher socioeconomic status had higher levels of preconception stress and blood glucose levels during their pregnancy. Median family income was used to measure socioeconomic status.
“Professional women with higher incomes and attained education levels may be employed in demanding, time-intensive jobs and are often also responsible for balancing demands in the workplace with household duties and childcare,” Mínguez-Alarcón said. “It has previously been shown that women with a higher education level experience greater levels of job stress. Given that education level is positively associated with salary, it is possible that this explanation applies to women with higher incomes as well.”
Still, findings are limited since the study comprises a group of mostly white women of high socioeconomic status seeking fertility care. Self-reporting perceived stress may also result in participant bias. Future research can investigate additional variables like sleep quality or neighborhood safety as well as the effect of preconception stress on the baby’s health.
“Our results are of public health importance given the increasing rates of stress over the years and its effect on cardiovascular health,” Mínguez-Alarcón said. “Women can try to lower their stress levels through a variety of strategies like being more active, avoiding alcohol and drugs, eating healthy and avoiding isolation. Given the scarce literature in this field, our study has the potential to start important discussions.”
Authorship: The other authors of this study are Olivia Chagnon, Aya Tanaka, Paige Williams, Tamarra James Todd and Jennifer Ford of Harvard T.H. Chan School of Public Health; Irene Souter of Massachusetts General Hospital and Harvard Medical School in Boston, Mass.; Kathryn Rexrode of Brigham and Women’s Hospital and Harvard Medical School; and Russ Hauser of Harvard T.H. Chan School of Public Health and Harvard Medical School.

A team of researchers from UC San Francisco has found that Paxlovid (Nirmatrelvir-ritonavir) did not reduce the risk of developing long COVID for vaccinated, non-hospitalized individuals during their first COVID-19 infection. They also found a higher proportion of individuals with acute symptoms rebound and test-positivity than previously reported.
The study appears Jan. 4, 2024, in the Journal of Medical Virology.
Paxlovid treatment for acute COVID-19 has been shown to be effective for high-risk unvaccinated individuals. But the effect of the treatment on long COVID risk, including whether it protects vaccinated people from getting long COVID, has been less clear.
The research team selected a group of vaccinated people from the UCSF Covid-19 Citizen Science study who had reported their first positive test for COVID-19 between March and August of 2022 and who were not hospitalized. Some of these participants reported taking oral Paxlovid treatment during the acute phase of their COVID infection, while others did not. In December of 2022, they were invited to answer a follow-up survey with questions about long COVID, COVID rebound symptoms and how long they continued to test positive.
Researchers found the two groups were similar. About 16% of those treated with Paxlovid had long COVID symptoms compared to 14% of those who were not treated with the medication. Commonly reported symptoms included fatigue, shortness of breath, confusion, headache, and altered taste and smell. Those who took Paxlovid and then went on to develop long COVID reported as many long COVID symptoms as those who were not treated with Paxlovid. A small percentage of people developed severe long COVID, and those who had received Paxlovid were just as likely to have severe Long COVID symptoms as those who did not.
Among individuals who experienced symptomatic improvement during Paxlovid treatment, 21% reported rebound symptoms. And among those with rebound symptoms, 10.8% reported one or more Long COVID symptom compared to 8.3% without rebound symptoms. For participants who repeated antigen testing after testing negative and completing treatment, 25.7% reported rebound test positivity. In total, 26.1% reported rebound symptoms or test positivity.
“We found a higher proportion with clinical rebound than previously reported but did not identify an effect of post-treatment rebound on long COVID symptoms,” said study first author Matthew Durstenfeld, MD, MAS, a cardiologist and UCSF assistant professor of Medicine. “Our finding that Paxlovid treatment during acute infection is not associated with lower odds of long COVID surprised us, but it is consistent with two other rigorously conducted studies finding no difference in post-COVID conditions between 4 and 6 months after infection.”
The authors note that the study may have been impacted by limitations arising from its observational nature with researchers relying on patient self-reporting of treatment and Long COVID symptoms.
Authors: Other UCSF authors include Michael J. Peluso, Feng Lin, Noah D. Peyser, Carmen Isasi, Thomas W. Carton, Timothy J. Henrich, Steven G. Deeks, Jeffrey E. Olgin, Mark J. Pletcher, Alexis L. Beatty, Gregory M. Marcus, Priscilla Y. Hsue
Funding: This work (Eureka Research Platform) was supported by NIH/NIBIB 3U2CEB021881-05S1. The COVID-19 Citizen Science Study is supported by Patient-Centered Outcomes Research Institute (PCORI) contract COVID-2020C2-10761 and Bill and Melinda Gates Foundation contract INV-017206. Dr. Durstenfeld is supported by NIH/NHLBI grant K12HL143961.

In a first for USC Stem Cell scientists, the laboratory of Giorgia Quadrato, an assistant professor of stem cell biology and regenerative medicine, has pioneered a novel human brain organoid model that generates all the major cell types of the cerebellum, a hindbrain region predominantly made up of two cell types necessary for movement, cognition, and emotion: granule cells and Purkinje neurons. This marks the first time that scientists have succeeded in growing Purkinje cells that possess the molecular and electrophysiological features of functional neurons in an all-human system. These breakthroughs in organoid-directed brain modeling have been published recently in the journal Cell Stem Cell.
“The reproducible co-development and maturation of the main cell types of the developing cerebellum in a human organoid model provide a new way to explore the underlying biology of cerebellar development and disorders and advance therapeutic interventions,” explained Quadrato, an assistant professor in the Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research at the Keck School of Medicine of USC.
The cerebellum controls movement and plays important roles in cognitive functions, including language, spatial processing, working memory, executive functions, and emotional processing.
Degeneration of Purkinje cells is associated with various neurodevelopmental and neurodegenerative disorders, including autism spectrum disorder and cerebellar ataxia, a condition that affects muscle movement.
Other neurons within the organoids — both excitatory neurons that share information, and inhibitory neurons that inhibit the sharing of information — formed circuits and showed coordinated network activity, demonstrating that they were also functional nerve cells. In addition, organoids formed human-specific progenitor cells, which are associated with medulloblastoma, the most prevalent metastatic brain tumor in children. This makes the organoids a potentially useful model for studying and finding treatments for this pediatric cancer.
Given the right external cues, the organoids could also be coaxed into forming anatomical features such as layers, mirroring normal embryonic brain development.
The organoid model creates a platform for discovering new treatments for variety of diseases.
“This study provides a physiologically relevant, all-human model system to elucidate the cell type-specific mechanisms governing cerebellar development and disease,” said Alexander Atamian, a PhD candidate in the Quadrato Lab and first author of the Cell Stem Cell study.
Additional co-authors are Macella Birtele, Negar Hosseini, Tuan Nguyen, Anoothi Seth, Ashley Del Dosso, and Marcelo P. Coba from USC; Sandeep Paul, Neil Tedeschi, and Ryan Taylor from Spatial Genomics; Ranmal Samarasinghe from UCLA; and Carlos Lois from the California Institute of Technology.
This project was funded by the Robert E. and May R. Wright Foundation, The Eli and Edythe Broad Foundation, and the Edward Mallinckdot, Jr. Foundation.

New research indicates that the eating disorder anorexia nervosa is associated with being an early riser, unlike many other disorders that tend to be evening-based such as depression, binge eating disorder and schizophrenia.
The study, which is published in JAMA Network Open and led by investigators at Massachusetts General Hospital (MGH), in collaboration with University College London and the University of the Republic in Uruguay, also revealed a link between anorexia nervosa and insomnia risk.
Previous research has suggested a possible connection between eating disorders and the body’s internal clock, or circadian clock, which controls a wide range of biological functions such as sleep and affects nearly every organ in the body.
This study aimed to further understand this relationship by assessing genes associated with anorexia nervosa, the circadian clock and several sleep traits including insomnia.
The investigators used a statistical method called Mendelian Randomization to see how genes that are associated with a certain trait affect other traits of interest. For example, examining the sleep patterns of people with genetic differences that makes them more likely to have anorexia nervosa, this provides evidence on the relationship between anorexia nervosa and sleep.
They found a two-way association between genes associated with anorexia nervosa and genes associated with morning chronotype (waking early and going to bed early).
In other words, the findings suggest that being an early riser could increase the risk for having anorexia nervosa, and having anorexia nervosa could lead to an earlier wake time. The team also found an association between anorexia nervosa and insomnia.

When they further assessed the insomnia connection using the Mass General Brigham Biobank by developing a “genetic risk score” for anorexia nervosa, the scientists found that the genetic risk score was indeed associated with higher insomnia risk.
“Our findings implicate anorexia nervosa as a morning disorder in contrast to most other evening-based psychiatric diseases and support the association between anorexia nervosa and insomnia as seen in earlier studies,” says senior author Hassan S Dashti, PhD, RD, an assistant investigator in the Department of Anesthesia, Critical Care and Pain Medicine at MGH and an assistant professor of anesthesia at Harvard Medical School.
Treatments for anorexia nervosa are limited and current treatments have relapse rates of up to 52%. In addition, the cause of the disease is still unclear.
With anorexia nervosa having the second highest mortality rate of psychiatric diseases, more research is desperately needed into new prevention strategies and treatments.
“The clinical implications of our new findings are currently unclear; however, our results could direct future investigations into circadian-based therapies for anorexia nervosa prevention and treatment,” says Hannah Wilcox, lead author of the study and researcher at MGH.
Additional authors include Valentina Paz, MSc, Richa Saxena, PhD, John W. Winkelman, MD, PhD, and Victoria Garfield, PhD.
This research was supported by the National Institutes of Health.

A research team has detected various substances that have a dual effect against tuberculosis: They make the bacteria causing the disease less pathogenic for human immune cells and boost the activity of conventional antibiotics.
In cooperation with research partners in Germany and France, the infectious disease specialist Dr Jan Rybniker and his team at University Hospital Cologne and the University of Cologne’s Faculty of Medicine have identified new, antibiotic molecules that target Mycobacterium tuberculosis and make it less pathogenic for humans. In addition, some of the discovered substances may allow for a renewed treatment of tuberculosis with available medications — including strains of the bacterium that have already developed drug resistance. The research has been published in the article ‘Discovery of dual-active ethionamide boosters inhibiting the Mycobacterium tuberculosis ESX-1 secretion system’ in Cell Chemical Biology.
Tuberculosis (TB) — or ‘consumption’, as it used to be called — mainly affects the lungs, but can also damage other organs. If diagnosed early and treated with antibiotics, it is curable. Although the disease is relatively rare in most western European countries, it still ranks among the infectious diseases that claim the most lives worldwide: According to the World Health Organization (WHO), only Covid-19 was deadlier than TB in 2022. The disease also caused almost twice as many deaths as HIV/AIDS. More than 10 million people continue to contract TB every year. This is mainly due to insufficient access to medical treatment in many countries.
Limited targets
Multidrug-resistant tuberculosis is emerging especially in eastern Europe and Asia. That is of particular concern to researchers because like all bacteria that infect humans, Mycobacterium tuberculosis possesses only a limited number of targets for conventional antibiotics. That makes it increasingly difficult to discover new antibiotic substances in research laboratories.
Working together with colleagues from the Institute Pasteur in Lille, France, and the German Center for Infection Research (DZIF), the researchers at University Hospital Cologne have now identified an alternative treatment strategy for the bacterium. The team utilized host-cell-based high-throughput methods to test the ability of molecules to stem the multiplication of bacteria in human immune cells: From a total of 10,000 molecules, this procedure allowed them to isolate a handful whose properties they scrutinized more closely in the course of the study.
Double attack
Ultimately, the researchers identified virulence blockers that utilize target structures that are fundamentally distinct from those targeted by classical antibiotics. “These molecules probably lead to significantly less selective pressure on the bacterium, and thus to less resistance,” said Jan Rybniker, who heads the Translational Research Unit for Infectious Diseases at the Center for Molecular Medicine Cologne (CMMC) and initiated the study.

In deciphering the exact mechanism of action, the researchers also discovered that some of the newly identified chemical substances are dual-active molecules. Thus, they not only attack the pathogen’s virulence factors, but also enhance the activity of monooxygenases — enzymes required for the activation of the conventional antibiotic ethionamide. Ethionamide is a drug that has been used for many decades to treat TB. It is a so-called prodrug, a substance that needs to be enzymatically activated in the bacterium to kill it. Therefore, the discovered molecules act as prodrug boosters, providing another alternative approach to the development of conventional antibiotics. In cooperation with the research team led by Professor Alain Baulard at Lille, the precise molecular mechanism of this booster effect was deciphered.
Thus, in combination with these new active substances, drugs that are already in use against tuberculosis might continue to be employed effectively in the future. The discovery offers several attractive starting points for the development of novel and urgently needed agents against tuberculosis. “Moreover, our work is an interesting example of the diversity of pharmacologically active substances. The activity spectrum of these molecules can be modified by the smallest chemical modifications,” Rybniker added. However, according to the scientists it is still a long way to the application of the findings in humans, requiring numerous adjustments of the substances in the laboratory.
This research was made possible with the support of the German Center for Infection Research (DZIF) and other funding institutions.

With Covid deaths rising to about 1,500 per week, researchers question why Paxlovid use has remained low among high-risk patients.As Covid rises again, killing about 1,500 Americans each week, medical researchers are trying to understand why so few people are taking Paxlovid, a medicine that is stunningly effective in preventing severe illness and death from the disease.A study of a million high-risk people with Covid found that only about 15 percent who were eligible for the drug took it. If half of the eligible patients had gotten Paxlovid, 48,000 deaths could have been prevented, authors of the study, conducted by the National Institutes of Health, concluded.It’s not because people don’t know about the drug — most do — but the reluctance seems to come from doctors worried about interactions with other drugs and people wary of a possible rebound case or the metallic aftertaste.Regional differences offer a clue, with uptake highest in the Democratic strongholds of the Northeast and Pacific Northwest regions of the United States and lowest in deep red areas including Florida and Indiana. Yet no careful study has clarified why so few people used the medication, which cut the risk of death by 73 percent for high-risk patients in the N.I.H. study.“I don’t know why there is such variability and why uptake isn’t higher across the board,” said Dr. Josh Fessel, a senior clinical adviser on the National Institutes of Health team that studied the drug’s use. “If you can take Paxlovid and you do take Paxlovid within the recommended time frame, the likelihood of death or hospitalization are significantly reduced. That’s a big deal.”Covid deaths have been elevated since September at about 1,200 to 1,300 deaths per week, inching up to about 1,500 per week in December. Researchers say they will most likely continue to rise unless more people get the updated Covid vaccines and antiviral treatments.Dr. Fessel said that over the course of the entire million-person N.I.H. study, about 10 percent of high-risk patients eligible for Paxlovid took it, though the rate rose to about 15 percent toward the end of the study period in early 2023. All told, the N.I.H. authors estimated that about 135,000 hospitalizations and 48,000 deaths could have been avoided if half of the patients eligible for the antiviral got it.Paxlovid, made by Pfizer, is a two-medication treatment meant to be taken within five days of the onset of Covid symptoms to quash viral spread within the body. It was approved for adults who are at high risk for severe Covid, which tends to include those 65 and older and people with diabetes, obesity, asthma and other conditions.Federal officials still have more than one million free doses out to pharmacies, but officials have handed distribution of the drug off to Pfizer, which has priced it at $1,400 per course.Pfizer, via ReutersReasons for not prescribing or taking it have varied: Doctors balk at the long list of medications not to be mixed with Paxlovid, including common drugs meant to lower blood pressure or prevent blood clots. Patients tend to complain about the drug’s metallic aftertaste. Many wave off the drug in the early days of Covid, when symptoms tend to be mildest, bypassing the chance to limit early viral growth.“They want to wait and see if things get worse, but if you wait and see it’s not effective,” said Dr. David Gifford, chief medical officer of the American Health Care Association, which represents nursing homes. People think, “‘It’s just a cold and I’ll tough it out,’” he said. “And that needs to change.”Price has also become a factor. The federal government provided the five-day course of the medications at no cost in the months since its initial emergency authorization in December 2021. (The Food and Drug Administration fully approved the drug in May.) Federal officials still have more than one million free doses out to pharmacies, and the medication will be free through 2024 for Medicaid and Medicare patients. But in recent weeks, officials have handed distribution of the drug off to Pfizer, which has priced it at about $1,400 per course, though private insurers are expected to cover some portion of the price and Pfizer is offering co-payment assistance.No study has looked at the effect of the handoff. The N.I.H. study period ended early last year. It found wide regional variation in Paxlovid use, with as many as 50 percent of eligible patients getting the medication in Utah and in the Northeast and Northwest regions of the United States. However, rates dipped close to zero in states in the Southeast and in parts of the lower Midwest.Dr. Fessel, of the N.I.H., said he would be curious to see if concerns about so-called Paxlovid rebound contributed. The misgiving has been that the medication dampens symptoms initially and then leads to a second stage of illness.In a recent review of studies, the Centers for Disease Control and Prevention found “no consistent association” with Paxlovid use and Covid rebound. Studies show rebound can also happen without treatment.Denis Nash, a professor of epidemiology at the City University of New York, has also been studying Paxlovid use. In a far smaller study, his team also found uptake of the medication at nearly 14 percent, though lower among some, including 7 percent among people who are Black and nearly 11 percent among those with the lowest income levels.He said his team worked on a nationally representative survey of 4,000 people to dig deeper (results have not yet been published or peer reviewed). One interesting finding, he said, was that awareness of Paxlovid was high — with about 80 percent of respondents saying they knew that it was available.Yet respondents showed a lack of recognition about their own risk: Only about one-third of people older than 65 considered themselves to be at high risk for severe Covid, even though the C.D.C. considers all in that age group high risk. The finding was similar for patients with asthma or diabetes, though half of patients who were overweight or obese recognized their risk.“People don’t necessarily perceive themselves to be at risk,” Dr. Nash said.Another recent study found that starting Paxlovid very early, or on the first day of symptoms, improved odds of survival or avoiding hospitalization, compared with starting the drug a day or two later.Studies have also looked at the use of another antiviral drug, molnupiravir, made by Merck, which was less effective and is used less frequently. Gilead, which makes the antiviral infusion remdesivir, is also studying a Covid antiviral pill called obeldesivir and plans to seek F.D.A. approval. The N.I.H. is studying yet another antiviral option, ensitrelvir, by the company Shinogi that also appears to reduce duration of the illness.Researchers have also reported low Paxlovid use in nursing homes, given the risk patients face of serious illness or death. About one in four nursing home residents got an antiviral prescription to treat Covid by the end of 2022, a study found. The data showed that the rate rose to closer to one-third of nursing home residents by May 2023, said one study author, Brian McGarry, a University of Rochester assistant professor of medicine.After that, federal officials stopped asking about Paxlovid use in their weekly nursing home Covid questionnaire.“I think things are a little bit better,” Dr. McGarry said, “but at the same time, facilities are now dealing with Covid, plus R.S.V., plus flu.”

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, ReckittBy Sofia Ferreira SantosBBC NewsBatches of two baby formulas have been recalled over the possible presence of a bacteria which can cause fever and diarrhoea. Cronobacter sakazakii can also lead to sepsis or meningitis in severe cases. The recall is for the Nutramigen stage 1 and stage 2 hypoallergenic formula powders. Manufacturer Reckitt took the precaution after finding the bacteria in an “isolated overseas sample”, it said.The UK Health Security Agency (UKHSA) says it is not aware of any cases of illness linked to the formulas.Both of the formula powders are usually medically prescribed, but can also be bought without a prescription, according to the UK Food Standards Agency (FSA).They are often used for infants with a cow’s milk protein allergy, which is estimated to affect around 7% of babies under 1 – though most children grow out of it. One dead following cheese recall over E. coliOver 30,000lb of chicken nuggets recalled in USThe batch codes are ZL3F7D for the stage 1 product and ZL3FAA and ZL3FDM for stage 2.All recalled products have a best before date of 1 July 2025 and the pack size is 400g. In the recall notice, Reckitt said no other batches have been affected and remain safe to use, as do other Nutramigen products.The FSA warned affected customers to not feed the product to their babies and return it to the place of purchase.It said symptoms of meningitis in infants include “poor feeding, irritability, temperature changes, jaundice (yellow skin and whites of the eyes) and abnormal breaths and movements.”Stores and pharmacies have also been made aware of the recall.Reckitt said it is conducting a thorough investigation.The UKHSA told the BBC: “Through our surveillance systems, we are not aware of any cases linked to this product.”Certain batches of the Nutramigen formula have also been recalled in the US, according to the Food and Drug Administration (FDA).The incident comes after it was announced last month that a person in Scotland died from E. coli, following an outbreak of the bacterial infection in the UK linked to cheese. It is unclear if the death was caused by the food.The BBC has contacted Reckitt for comment.What is sepsis?Sepsis is a rare, but life-threatening reaction to an infectionIt is when the body’s immune system attacks the body’s own tissues and organsBabies under 1, particularly those born prematurely or whose mother had an infection during pregnancy, are more likely to get sepsisSymptoms in babies and young children include blotchy skin and difficulty breathingMore information about sepsis is available on the NHS website.What is meningitis? Meningitis is an infection of the protective membranes that surround the brain and spinal cordIt can be caused by a bacterial or viral infection, and can lead to sepsisMeningitis is most common in babies, young children, teenagers and young adultsSymptoms include a high temperature, and a rash that does not fade under a glassMore information about meningitis is available on the NHS website. More on this storyOne dead following cheese recall over E. coliPublished29 December 2023Sepsis: What is it – and how to spot it?Published13 September 2018Sepsis death lessons still not learnt – ombudsmanPublished25 October 2023My freshers’ flu turned out to be meningitisPublished21 September 2023’My girl’s meningitis diagnosed as ear infection’Published14 September 2018Over 30,000lb of chicken nuggets recalled in USPublished6 November 2023

Published31 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Smitha MundasadHealth reporter An expert microbiologist has hailed the discovery of a potential new class of antibiotics that could treat lethal hospital infections as “very exciting”.The new compound, zosurabalpin, worked “extremely well” in test-tubes and mice, Global Antibiotic Research and Development Partnership scientific director Prof Laura Piddock said.The research offered “definite hope” for other hard-to-treat infections, she told BBC Radio 4’s Today programme.It is published in the journal Nature.US researchers focused on finding a new way to treat infections caused by the carbapenem-resistant Acinetobacter baumannii (Crab) bacterium.The organism, classed a “priority-one critical pathogen” by the World Health Organization, can cause very serious invasive blood and chest infections in critically ill hospital patients.It is resistant to many known antibiotics.Drug-resistant infections killing millions – studyWarning of antibiotic-resistant infection pandemicAnd about 40-60% of those infected die.A key reason it is so hard to find new drugs that neutralise it is because of the bacterium’s tricky structure – with a double walled “membrane” surrounding it and protecting it from attack.This configuration “makes it very difficult to get drugs into it and to get drugs to stay inside”, Prof Piddock told BBC News.But zosurabalpin, found after screening about 45,000 small molecules with potential antibiotic properties, appears to destroy the organism’s ability to successfully assemble this key protective membrane.’First-in-man’ studies”What is exciting about this discovery is that one of the building blocks that are part of the outer part of this bacterial cell is disrupted by this new drug,” Prof Piddock said.In laboratory experiments, the compound stopped a critical building block – a lipopolysaccharide – being transported to the outer part of the cell, preventing the protective membrane from forming properly and ultimately leading to cell death. It was “exciting” the researchers had already completed some “first-in-man” studies – on a relatively small number of healthy people – and were “set up now to go on and do full clinical trials in people with the infection”, Prof Piddock said.But “we are a very long way” from it being used in hospitals.’Definite hope’Prof Piddock said: “Full clinical trials… take a lot of time, several years. And indeed, they cost millions of pounds to do. And even if the trial is successful, then the drug has to be approved for use and then made accessible to those that need it – and that is all over the world not just in a few countries that can afford it. “Therein is the big problem – the economics of making antibiotics.” But despite the considerable hurdles, there is “definite hope”.”It is really exciting – and not only is it good for this type of bacteria, but this could be built upon for others as well,” Prof Piddock added.More on this storyDrug-resistant infections killing millions – studyPublished20 January 2022Warning of antibiotic-resistant infection pandemicPublished17 November 2021Related Internet LinksNature.websiteThe BBC is not responsible for the content of external sites.

We have two copies of each chromosome in every cell in our bodies except in our reproductive cells. Sperm and egg cells contain a single copy of each chromosome with a unique mix of genes from our parents, an evolutionary trick to give our offspring genetic variability. The sperm and egg are made during meiosis, the process by which cells with two chromosome copies reduce their chromosome numbers to one. For meiosis to work, the two chromosomes must align perfectly and exchange the correct amount of genetic information. Any deviation puts fertility at risk.
Enter the synaptonemal complex (SC), a zipper-like protein structure that lines up and anchors the two parental chromosomes together, end-to-end, to facilitate successful genetic exchanges. Failure to regulate this exchange is a leading cause of age-related infertility in humans and could compromise fertility across the tree of life. Humans, fungi, plants, worms and anything that reproduces sexually uses the SC to make reproductive cells, known as gametes. Despite its importance, we don’t understand how proteins within the SC regulate chromosomal interactions because this multi-step process happens in internal organs and has been impossible to recreate in a lab.
In a new study, University of Utah biologists developed a method for illuminating the intricate interactions of the SC in the nematode C. elegans. The authors identified a trio of protein segments that guide chromosomal interactions, and pinpointed the location where they interact with each other. Their novel method uses a technique known as genetic suppressor screening, which can serve as a blueprint for research on large cellular assemblies that resist traditional structural analysis.
“This is a way to lock in on systems in cells that are too ‘loosie-goosey’ to use methods that rely on crystallization,” said Ofer Rog, associate professor of biology at the U and senior author of the study. “A lot of the interactions in cells are loosely bonded together. The problem is that you can’t look at it under an electron microscope because nothing is stable enough — everything is constantly moving. Our approach allows you to study even the interactions that are relatively weak or transient.”
The study published on Dec. 6, 2023, in the journal Proceedings of the National Academy of Sciences (PNAS).
The birds and the bees… and the nematodes
Let’s dig into meiosis. Chromosomes are thread-like structures made of DNA that carry genetic information when cells divide and from generation to generation. Regular cells have a certain number of chromosomes; humans have 46 and C. elegans have 12. Chromosomes come in pairs called homologous chromosomes that carry the genes we inherited from each of our parents — one from our mom, one from our dad. When meiosis begins, homologous chromosomes arrange themselves into elongated structures organized along a backbone called the axis. The axes of homologous pairs are aligned lengthwise to each other while at the same time, the synaptonemal complex (SC) forms between the parallel axes. The homologous pairs have matching genes arranged in the same order, with small variations within the genes — these are the variations that make each individual unique.

“You can think of it like a zipper,” Rog explained. “The axes of the chromosomes are like the two sides of your shirt. The synaptonemal complex is kind of like the teeth of the zippers that lock onto each other and can pull and align the two sides of the shirt correctly.”
Scientist previously knew that the SC of C. elegans formed between homologs, but the U biologists are the first to pinpoint the exact position where the SC interacts with itself to facilitate genetic exchanges.
“When you exchange information between the chromosomes, you want to make sure that at the end you still have two complete chromosomes,” said Rog. “The way the cell does it is that the two chromosomes are perfectly aligned. So, when you exchange segments between them, you’re not losing any information in the process.
How to analyze loosie-goosey structures
The researchers bred 50,000 nematodes that had temperature-sensitive defects in the SC. At high temperatures, the worms were unable to form the SC protein zipper needed to join the chromosomes together. Without the zipper, the gene exchanges during meiosis either didn’t happen at all or didn’t occur at the right number. Lisa Kursel, postdoctoral researcher and lead author of the study ran the experiments.
“We grew the worms at the permissive, cooler temperature, then exposed them to a chemical that caused millions of mutations along their chromosomes and watched to see if any of the mutated worms could reproduce at the warmer temperature,” Kursel said. The chemically induced mutations that corrected the nematode’s infertility are known as suppressor mutations. “Then we’d know if the suppressor mutations restored their fertility.”
To identify the animals with mutations that made them fertile again, the researchers put the nematodes on agar plates filled with yummy bacteria. The agar plates that had fertile nematodes were soon empty as their progeny ate the food. The agar plates with sterile worms died off before they could clean their plate, allowing the bacteria to flourish.

Once they had fertile nematodes, they could test if the mutation “fixed” the protein zipper. They then screened every single base pair on the DNA — 100 million base pairs — and identified which mutations restored the worms’ ability to reproduce. They found that all the helpful mutations occurred in short segments of three proteins, SYP-1, SYP-3, SYP-4. Moreover, the mutations carried distinct signatures of interaction. For example, while the original mutations changed the electric charge from positive to negative, the helpful mutations flipped the charge back.
“This was a strong indication that SYP-1, SYP-3 and SYP-4 interact with each other like magnets, with positive and negative regions attracted to each other,” said Rog. Such “sticky” interactions could also help tether the chromosomes together.
Jesus Aguayo Martinez, a senior biology major and co-author of the study, looked at the behavior of the suppressor mutation in nematodes without the original SC-disrupting mutation.
“We thought that since the original mutation alone produced a fertility defect, then the nematodes with the suppressor mutation alone would also have a fertility defect. That wasn’t the case,” said Aguayo Martinez. “Surprisingly, normal worms and worms with only the suppressor mutations produced similar numbers of progeny.”
Next steps
Uncovering the SC’s role in meiosis may help to better understand fertility in humans. The SC has a similar role across all eukaryotes, from nematodes to fungi to plants to humans. Previous research by the Rog Lab at the U showed that the structure itself looks the same and acts similarly to bring in parental chromosomes to facilitate exchanges. However, the actual sequences of the protein components are different between organisms. Such a pattern is unusual: Most cellular structures that carry essential, basic functions like cell division, genome duplication or metabolism are highly conserved, and could in fact be swapped between different organisms.
“A question that we think a lot about is what is special about the SC? Why can it do the same thing and look the same way, but consist of different building blocks?” Rog asked.
Kursel, Aguayo Martinez, Rog and other members of the lab are doing more analysis on the evolution of the SC across species, and of other cellular structures that defy the common wisdom of evolution.
This work was funded by the National Institute for General Medical Sciences grant R35GM128804. Kursel was supported by the Developmental Biology Training Grant from the U.S. National Institute of Child Health and Human Development, and Aguayo Martinez was supported by a University of Utah Biology Research Scholar Award.

Pregnancy weight and biochemical markers measured in blood from women with gestational diabetes mellitus (GDM) were related to increased risk of poor pregnancy outcomes, suggesting a new direction for precision diagnostics, according to researchers.
The study led by Ellen C. Francis, an assistant professor in the Department of Biostatistics and Epidemiology at Rutgers School of Public Health, and published in Communications Medicine, evaluated the diagnostic value of these markers before or at the time of screening for GDM, a type of diabetes that can develop during pregnancy.
“Although we found that obesity is a risk factor for offspring born larger for their gestational age, evidence suggests that the metabolic alterations that accompany obesity increase the risk of adverse outcomes,” said Francis. GDM, characterized by elevated blood sugar (glucose) levels during pregnancy, is the most common metabolic condition among pregnant women and poses risks to both mother and child. While standard treatments are applied, clinical outcomes can differ among individuals.
Francis said the research demonstrates the need for a more nuanced approach to diagnose GDM, which may help improve outcomes. It is the first systematic review of the literature to assess the potential of subtypes in GDM and to examine whether nonglycemic markers could refine risk stratification. Francis said some of the literature suggested insulin profiles and triglyceride levels may serve as promising non-glucose indicators of risk.
“To really assess the clinical implications of precision diagnostics in GDM, we first need to understand if insulin resistance or higher triglycerides are causally linked to adverse outcomes, and whether we can safely target them in pregnancy,” Francis said.
Overall, researchers found a critical gap in the existing literature in which most studies hadn’t focused on comparing clinical, biochemical or sociocultural differences among women who develop GDM.
“In our full text screening of 775 studies, we found that only recently has there been a focus on clinical, biochemical, or sociocultural markers that could improve who is at greatest risk of poor outcomes, and on comparing clinical outcomes between different subtypes of GDM,” said Francis. “The data from these studies indicate that in the future, we may be able to refine how we diagnose GDM by using anthropometric or biochemical information in combination with current diagnostic approaches.”
Future research should delve into mechanistic studies on precision biomarkers, large diverse population studies for replication, and multinational studies focusing on environmental and behavioral factors, Francis said. It should also explore potential insights on casual pathways of heterogeneity within GDM and its outcomes from genetic and multi-omics data using advanced analytical approaches.
Study co-authors include researchers from collaborating institutions in the United States, the United Kingdom, Singapore, South Korea and Australia.