Publisher Health

Learning to navigate social relationships is a skill that is critical for surviving in human societies. For babies and young children, that means learning who they can count on to take care of them.
MIT neuroscientists have now identified a specific signal that young children and even babies use to determine whether two people have a strong relationship and a mutual obligation to help each other: whether those two people kiss, share food, or have other interactions that involve sharing saliva.
In a new study, the researchers showed that babies expect people who share saliva to come to one another’s aid when one person is in distress, much more so than when people share toys or interact in other ways that do not involve saliva exchange. The findings suggest that babies can use these cues to try to figure out who around them is most likely to offer help, the researchers say.
“Babies don’t know in advance which relationships are the close and morally obligating ones, so they have to have some way of learning this by looking at what happens around them,” says Rebecca Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences, a member of MIT’s McGovern Institute for Brain Research, and the senior author of the new study.
MIT postdoc Ashley Thomas is the lead author of the study, which appears today in Science. Brandon Woo, a Harvard University graduate student; Daniel Nettle, a professor of behavioral science at Newcastle University; and Elizabeth Spelke, a professor of psychology at Harvard, are also authors of the paper.
Sharing saliva
In human societies, people typically distinguish between “thick” and “thin” relationships. Thick relationships, usually found between family members, feature strong levels of attachment, obligation, and mutual responsiveness. Anthropologists have also observed that people in thick relationships are more willing to share bodily fluids such as saliva.

An artificial pancreas developed by a team of Cambridge researchers is helping protect very young children with type 1 diabetes at a particularly vulnerable time of their lives. A study published today found that it is both safe to use and more effective at managing their blood sugar levels than current technology.
Writing in the New England Journal of Medicine, researchers compared the performance of the artificial pancreas, which uses an algorithm to determine the amount of insulin administered by a device worn by the child, against ‘sensor-augmented pump therapy’.
Management of type 1 diabetes is challenging in very young children, because of a number of factors including the high variability in levels of insulin required and in how individual children respond to treatment, and their unpredictable eating and activity patterns. Children are particularly at risk of dangerously low blood sugar levels (hypoglycaemia) and high blood sugar levels (hyperglycaemia). Previous studies have linked prolonged hyperglycaemia in children with type 1 diabetes with lower IQ scores and slower brain growth.
To manage children’s glucose levels, doctors increasingly turn to devices that continuously monitor glucose levels and deliver insulin via a pump, which administers insulin through a cannula inserted into the skin. These devices have proved successful to an extent in older children, but not in very young children.
Current technology — sensor-augmented pump therapy — requires parents to review their child’s glucose levels using a monitor and then manually adjust the amount of insulin administered by the pump.
Professor Roman Hovorka from the Wellcome-MRC Institute of Metabolic Science at the University of Cambridge has developed an app — CamAPS FX — which, combined with a glucose monitor and insulin pump, acts as an artificial pancreas, automatically adjusting the amount of insulin it delivers based on predicted or real-time glucose levels. It is a ‘hybrid closed loop system’, meaning that the child’s carer will have to administer insulin at mealtimes, but at all other times the algorithm works by itself. There are no commercially available versions of fully closed loop systems yet.

Testis development is a complex process that starts even before birth. Normally, the developing testes progressively migrate to reach the scrotum during the fetal stage. However, any abnormality in this developmental cascade — orchestrated by many physiological processes and interactions of various cell types — may manifest as a disorder of sex development and subsequent male infertility.
In one of the most prevalent abnormalities observed in pediatric urology, one or both testicles fail to descend into the proper scrotal position by birth, a condition known as cryptorchidism. As boys with undescended testis run a high risk of being infertile later in life, predicting an association between cryptorchidism and the chance of infertility can be useful while treating the condition and studying male infertility. However, as far as the current medical knowledge is concerned, there is very limited means for such prediction, mainly because of the lack of suitable biomarkers.
Now, in a pioneering study, a research team from Japan, including Dr. Taiki Kato of Nagoya City University East Medical Center; and Dr. Kentaro Mizuno, Dr. Hidenori Nishio, and Dr. Yutaro Hayashi of Nagoya City University Graduate School of Medical Sciences, has found that the ratio of a few sex hormones in serum can serve as important clues to predict future infertility in cryptorchid boys. The study was recently published in The Journal of Urology.
Conventionally, to diagnose male infertility, testicular biopsy is the most widely used method. Germ cells are the source of sperm cells in males and therefore directly linked with fertility.Some cryptorchid boys have a reduced number of germ cells in their testes.So, the mean number of germ cells per tubular transverse section (G/T) found in the small portion of the testis that is removed during “orchidopexy” or surgical intervention to move the undescended testicle into the scrotum is used to predict future infertility in cryptorchid boys. However, the surgical nature of biopsy also introduces the risk of complications like injury, infection, or hypogonadism, highlighting the need for an alternative method for diagnosing male infertility.
The researchers, determined to address this gap, focused their search on suitable biomarkers that can easily be detected in the serum of cryptorchid boys. Dr. Kato, the senior author of the study explains their approach, stating “The state of testes dramatically changes during puberty. Therefore, we identified 145 prepubertal boys, aged between 7-91 months, who underwent orchidopexy due to unilateral or bilateral cryptorchidism between 2014 and 2019, at our hospital. From the available clinical records, we evaluated the pretreatment testicular position and size; serum hormone levels; and the mean number of germ cells per tubule transverse section (G/T) of these boys.”
Among various serum hormones, inhibin B and anti-Mullerian hormone (AMH) act as direct markers of spermatogenesis and the function of Sertoli cells that are important for proper testicular development. The researchers found that serum inhibin B levels and G/T were significantly lower in boys suffering from bilateral cryptorchidism than those with unilateral cryptorchidism. In bilateral cryptorchid boys no more than 24 months of age, the inhibin B/follicle-stimulation hormone (FSH) ratio and AMH/FSH ratio positively correlated with G/T, the standard infertility marker. However, the serum hormones levels and G/T did not differ in boys with unilateral undescended testis.
From a patient care perspective, the results of the study are highly meaningful, suggests Dr. Kato. He emphasizes, “Based on the ratios of sex hormones in serum, we can now predict the extent of impaired germ cells and the high risk of infertility without performing a testicular biopsy. Further, the hormonal assessment may guide decisions regarding additional hormonal therapy after orchiopexy for a closer and longer follow-up of patients after the surgery.” In a nutshell, the findings might change clinical practice scenarios for patients with cryptorchidism. This may mean a change in the clinical guidelines for these patients, or even the counseling strategy of families of boys with bilateral undescended testes based on the preoperative hormonal evaluation.
In the future, it indeed might be useful to prioritize the order of patients requiring orchidopexy based on the predicted chance of infertility.
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Materials provided by Nagoya City University. Note: Content may be edited for style and length.

Omicron was probably present in New York City’s wastewater more than a week before the first case of the new variant was detected in the United States, according to a new report from the Centers for Disease Control and Prevention and researchers across the country.The samples suggest that someone in New York City may have had the Omicron variant as early as Nov. 21, four days before South African scientists first announced cases of the variant and ten days before the first U.S. case was reported. Researchers in California and Texas also found evidence of Omicron in wastewater samples from late November.The findings suggest that at the time, the Omicron variant was more widespread in the United States than the case data alone would indicate, and provide more evidence that wastewater surveillance can serve as an early warning system about the spread of new variants.“At first it was uncertain whether this variant was going to come to the United States,” said Alexandria Boehm, an environmental engineer at Stanford and an author of the paper. “The wastewater answered that question way before the clinical samples could, and the answer was yes.”The research does not provide conclusive evidence that Omicron was present in these cities. The virus present in wastewater is fragmented, and while the researchers detected many of Omicron’s telltale mutations, the findings do not prove that they were all present on the same genome.Still, the results are highly suggestive, and are consistent with what scientists have learned about how quickly Omicron spreads and where it was likely to pop up first, said Amy Kirby, the program lead for the C.D.C.’s National Wastewater Surveillance System and an author of the paper.“I don’t think anyone is surprised to see a new variant show up in a major city like New York first,” she said.A team of scientists from several institutions — John Dennehy at Queens College, Monica Trujillo at Queensborough Community College, Davida Smyth at Texas A&M University and Marc Johnson at the University of Missouri — have been tracking the coronavirus in New York City’s wastewater since the summer of 2020. The team typically collects samples weekly and then sequences the virus they find.The scientists collected one of their routine samples on Nov. 21 and sent it for sequencing two days later. By the time they got the results, in early December, the Omicron news had broken, and they “immediately recognized” the new variant’s distinct mutations, Dr. Dennehy said.Dr. Boehm’s team took a different approach in California, using P.C.R. tests capable of detecting some of Omicron’s specific mutations. They got their first hit on Nov. 26, from a sample collected in Merced the previous day, Dr. Boehm said. They got another on a sample collected in Sacramento on Nov. 30.The first confirmed case of Omicron in the U.S. was announced on Dec. 1.“We have really rapid turnaround and really frequent sampling,” Dr. Boehm said. She added, “This just gives information way earlier than clinical sequencing can.”

COVID-19 vaccination in either partner does not appear to affect fertility, according to new research led by Boston University School of Public Health (BUSPH) investigators.
Published in the American Journal of Epidemiology, the prospective study of couples trying to conceive found no association between COVID-19 vaccination and fecundability — the probability of conception per menstrual cycle — in female or male partners who received the Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines.
In contrast, the findings indicate that COVID-19 infection among males may temporarily reduce fertility — an outcome that could be avoidable through vaccination.
“Many reproductive-aged individuals have cited concerns about fertility as a reason for remaining unvaccinated,” says study lead author Dr. Amelia Wesselink, research assistant professor of epidemiology at BUSPH. “Our study shows for the first time that COVID-19 vaccination in either partner is unrelated to fertility among couples trying to conceive through intercourse. Time-to-pregnancy was very similar regardless of vaccination status.”
Wesselink and colleagues analyzed survey data on COVID-19 vaccination and infection, and fecundability, among female and male participants in the BUSPH-based Pregnancy Study Online (PRESTO), an ongoing NIH-funded study that enrolls women trying to conceive, and follows them from preconception through six months after delivery. Participants included 2,126 women in the US and Canada who provided information on sociodemographics, lifestyle, medical factors, and characteristics of their partners from December 2020 to September 2021, and the participants were followed in the study through November 2021.
The researchers calculated the per menstrual cycle probability of conception using self-reported dates of participants’ last menstrual period, typical menstrual cycle length, and pregnancy status. Fertility rates among female participants who received at least one dose of a vaccine were nearly identical to unvaccinated female participants. Fecundability was also similar for male partners who had received at least one dose of a COVID-19 vaccine compared with unvaccinated male participants. Additional analyses that considered the number of vaccine doses, brand of vaccine, infertility history, occupation, and geographic region also indicated no effect of vaccination on fertility.
While COVID-19 infection was not strongly associated with fertility, men who tested positive for COVID within 60 days of a given cycle had reduced fertility compared to men who never tested positive, or men who tested positive at least 60 days prior. This data supports previous research that has linked COVID-19 infection in men with poor sperm quality and other reproductive dysfunction.
“These data provide reassuring evidence that COVID vaccination in either partner does not affect fertility among couples trying to conceive,” says study senior author Dr. Lauren Wise, professor of epidemiology at BUSPH. “The prospective study design, large sample size, and geographically heterogeneous study population are study strengths, as was our control for many variables such as age, socioeconomic status, preexisting health conditions, occupation, and stress levels.”
The new data also help quell concerns about COVID-19 vaccines and fertility that arose from anecdotal reports of females experiencing menstrual cycle changes following vaccination.
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Materials provided by Boston University School of Medicine. Original written by Jillian McKoy. Note: Content may be edited for style and length.

When the muscles become acidic after doing too many press-ups, squats or cycling to work, it is because of lactic acid.
Strained muscles produce energy fast, and a by-product of that process is lactic acid. However, lactic acid is also abundant in cancer cells, which invest a lot of energy into dividing and forming tumours.
Now a new study from the University of Copenhagen reveals that specific enzymes can remove lactic acid marks from proteins, and the researchers hope this will increase our understanding of the effect of cancer medicine, among others.
“Of course, the ultimate goal is to develop drugs with as few side effects as possible,” says Professor Christian Adam Olsen from the Department of Drug Design and Pharmacology, who is responsible for the new study. He adds:
“The more knowledge we are able to generate about the enzymes that are able to remove lactic acid marks, the easier it will be to design new drug candidates capable of targeting these specific enzymes. So the discovery may affect the development of new cancer medicine using these enzymes as the target.”
The process that leads to lactic acid both helps the body out in connection with e.g. physical exercise and corrupts it in connection with cancer. Therefore, it is interesting to determine how the level of lactic acid affects the human cells.

Before consuming a meal, many people with diabetes need to inject themselves with insulin. This is a time-consuming process that often requires estimating the carbohydrate content of the meal, drawing blood to measure blood glucose levels, and then calculating and delivering the correct insulin dose.
Those steps, which typically must be repeated for every meal, make it difficult for many patients with diabetes to stick with their treatment regimen. A team of MIT researchers has now come up with a new approach to streamline the process and help patients maintain healthy glucose levels.
“Any intervention that makes it easier for patients to receive therapy can have an enormous impact, because there are multiple barriers that have to do with time, inconvenience, dexterity, or learning and training,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital. “If we’re able to overcome those barriers through the implementation of new engineering solutions, it will make it easier for patients to receive that therapy.”
Traverso and his colleagues designed two different devices that can simplify the process of calculating and injecting the correct dose of insulin. One, which combines many of the existing steps into a single device, could be used in patients in the near future. Their second prototype incorporates flexible electronics onto the surface of a needle so that the blood measurement and insulin delivery can happen through the same needle. This could eventually make the process of managing diabetes even more streamlined.
MIT postdocs Hen-Wei Huang and Sean You, and visiting students Luca Di Tizio and Canchen Li, are the lead authors of the paper, which appeared recently in the Journal of Controlled Release.
All-in-one device
Diabetes affects 34 million people in the United States and more than 400 million people worldwide. Patients with diabetes often use two types of insulin to control their blood sugar levels: long-acting insulin, which helps control glucose levels over a 24-hour period, and short-acting insulin, which is injected at mealtimes. Patients first measure their blood glucose levels with a glucose meter, which requires pricking their finger to draw blood and placing a drop of blood onto a test strip. They must also estimate how many carbohydrates are in their meal and combine this information with their blood glucose levels to calculate and inject the proper insulin dose.

By mapping all the protein interactions of a dementia-linked protein in the brain called Tau, a team of Weill Cornell Medicine investigators has created a road map for identifying potential new treatment targets for Alzheimer’s disease and related dementia.
Tau protein has long been implicated in neurodegenerative diseases. Mutations in the gene that encodes the Tau protein result in neurodegenerative conditions like frontotemporal dementia, while in Alzheimer’s disease the protein accumulates and becomes toxic. But the exact role of the Tau protein in these diseases have remained a mystery.
To help solve this mystery, senior author Dr. Li Gan, director of the Helen and Robert Appel Alzheimer’s Disease Research Institute, and her colleagues created a comprehensive atlas, called Tau interactome, that maps all the Tau protein’s interactions with other proteins in human neurons grown in the laboratory. The results, published Jan. 20 in the journal Cell, reveal that mutations that diminish the interactions between Tau and mitochondrial proteins may hamper energy production in the brain, the most energy-intensive organ in the body. Additionally, they found that Tau interacts with proteins in the synaptic sites that send electric signals to other neurons, which may provide clues on how toxic Tau protein spreads in brains with Tau pathology.
“Tau is at the center of neurodegeneration, and understanding how it causes toxicity and cognitive decline has the potential to lead to new therapies to treat dementia,” said Dr. Gan, who is also the Burton P. and Judith B. Resnick Distinguished Professor in Neurodegenerative Diseases in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine.
In normal and diseased neurons, Tau protein forms physical interactions with specific proteins to participate in diverse neuronal functions. To develop an atlas that maps the interactions modified by disease-causing mutations and neuronal activity, Dr. Gan and her colleagues grew human neurons from induced pluripotent stem cells that carry normal Tau gene or Tau gene with mutations that cause frontotemporal dementia. They used a technique called quantitative affinity purification mass spectrometry (AP-MS), which enables the study of protein interactions, to compare how normal and disease-causing mutants of Tau behave. To capture how neuronal activity alters the Tau interactome, they used a cutting-edge technology called engineered ascorbic acid peroxidase (APEX) to label proteins in close proximity to Tau within milliseconds.
“The combination of two highly quantitative proteomic technologies has allowed us to establish Tau interactions with unprecedented spatial and time resolution in human neurons,” said Dr. Gan, who is a co-founder with equity and consultant for Aeton Therapeutics, Inc.
Unexpectedly, the team discovered that Tau interacts with proteins that are released into the synapses that send signals to neighboring neurons. This may allow disease-causing versions of Tau to spread from one region of the brain to another and help explain the phenomena that neurons fire together often die together, Dr. Gan said.
Another surprise finding is that they found Tau proteins have strong interactions with many proteins in the energy-producing mitochondria of neurons.
“More and more studies link dysregulated energy metabolism with neurodegeneration, but the mechanism remains elusive,” she said. “We found disease-causing mutations reduce Tau-mitochondrial protein interaction and impair mitochondrial function.”
When they analyzed patient data from the Accelerating Medicines Partnership — Alzheimer’s Disease (AMP-AD), Dr. Gan and her team found that patients with Alzheimer’s disease had lower levels of Tau-interacting proteins, including mitochondria proteins. Patients with the most severe disease had the lowest levels of Tau-interacting proteins, suggesting that the discovery they made in neurons is relevant to human patients.
Dr. Gan and her team will next investigate if strategies elevating the mitochondria Tau interactions could enhance energy metabolism to counteract the effects of disease-causing Tau protein. They are also studying which cellular processes allow toxic versions of Tau to spread throughout the brain via the synapses to see if they can be stopped. Dr. Gan also thinks her team’s research may help scientists develop novel biomarkers to detect the early signs of mitochondrial dysfunction, allowing clinicians to intervene earlier in the course disease.
“The Tau interactome atlas provides an exciting roadmap for scientific community to explore new therapeutic targets and biomarkers for Alzheimer disease and related dementia,” Dr. Gan said.
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Materials provided by Weill Cornell Medicine. Note: Content may be edited for style and length.

Iowa State University scientists may have uncovered an important clue that sheds light on why pigs don’t get sick when exposed to the coronavirus.
Studies since the start of the pandemic have noted that pigs can be infected by the virus if exposed to high doses, but the infection is self-limited and pigs don’t show clinical signs of disease nor do they transmit the virus to other animals. So Rahul Nelli, a research assistant professor of veterinary diagnostic and production animal medicine, and Luis Gimenez-Lirola, an associate professor of veterinary diagnostic and production animal medicine, set out to find out why in a newly published study in the academic journal Cell Death Discovery. What they found could lead to new ways to treat humans who contract COVID-19, the disease that results from infection by the virus SARS-CoV-2, said Nelli and Gimenez-Lirola.
Nelli and Gimenez-Lirola have studied how coronaviruses affect pigs for years. They’ve developed models that allow them to study in detail how viruses infect pigs and pig cells and how the cells respond to fight the infection. For the latest experiments, they introduced the virus to cultured porcine and human respiratory epithelial cells, which line most of the respiratory tract. They found the pig cells underwent apoptosis, or controlled cell death, in response to infection at a higher rate than human epithelial cells.
“When we looked under the microscope there was an interesting phenomenon going on inside the cells,” Nelli said. “The nuclei of the infected pig cells were starting to shred into fragments but not uninfected pig cells.”
That shredding of the nucleus is a telltale sign of apoptosis, which may be a key in helping pigs avoid symptoms after exposure to SARS-CoV-2. Triggering apoptosis early in the infection essentially causes minimal tissue damage and confines viral replication, thus limiting severe illness. Human cells can undergo apoptosis in response to coronavirus infection as well, but the study found human cells do so much less frequently than porcine cells. Pig cells are roughly 100 times more likely to undergo apoptosis than human cells, according to the study.
Human cells are more likely to go through necrosis, another form of cell death that’s less controlled than apoptosis. During necrosis, the contents of a cell release into the surrounding space, provoking a strong hyperimmune response that isn’t triggered during apoptosis.
The researchers surmise that a wide-scale apoptosis response is helpful for avoiding disease because it disposes of infected cells quickly without the immune system overreacting, while wide-scale necrosis and the resulting hyperimmune response is less favorable to host cells.
“We don’t want to over-conclude, but this response is probably something intrinsic to the pig immune system that is innate and not acquired,” Giminez-Lirola said. “The idea is to kill the virus subtly but fast enough so there’s not an excessive immune response triggered.”
The researchers said further study could lead to therapies designed to trigger apoptosis in human cells, allowing people infected with the coronavirus to avoid severe symptoms.
The next step for the ISU research team is to identify all the genes activated during the infectious process and compare them with other animal species in which those genes are present. That could give them further clues about how and why other animals, such as deer, can carry the virus without suffering symptoms of disease.
In addition to Nelli and Gimenez-Lirola, the research team included Kruttika Phadke, Gino Castillo, Lu Yen and Bryan Bellaire at Iowa State. Amy Saunders, Rolf Rauh and William Nelson of Maryland-based Tetracore, Inc., are also listed as co-authors of the study.
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Materials provided by Iowa State University. Note: Content may be edited for style and length.

A study by researchers at Mayo Clinic Cancer Center has found that patients with cancer who receive chemotherapy — and some targeted therapies, such as CDK4/6 inhibitors and therapies targeted at B cells — may mount an inadequate immune response to COVID-19 vaccination. The findings are published in Mayo Clinic Proceedings: Innovation, Quality & Outcomes.
“It is important for patients with cancer who are receiving chemotherapy to receive a COVID-19 vaccine,” says Saranya Chumsri, M.D., a Mayo Clinic hematologist and oncologist, and author of the paper. Dr. Chumsri says this advice also applies to patients with cancer who are taking a CDK 4/6 inhibitors. These inhibitors are a newer class of medicines used to treat hormone-receptor-positive and HER2-negative breast cancers.
Dr. Chumsri says that while CDK 4/6 inhibitors are not conventionally considered to be as immunosuppressive as chemotherapy, her research on patients with breast cancer who take these drugs found that they exhibited less optimal neutralizing antibody activity. Dr. Chumsri recommends that antibody levels be tested in these patients after vaccination, and they should consider receiving booster vaccinations for COVID-19.
Dr. Chumsri anticipates having additional data later this year regarding broader immune responses to COVID-19 vaccinations, including cellular and antibody responses in patients receiving chemotherapy and targeted therapies with booster vaccinations.
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Materials provided by Mayo Clinic. Original written by Joe Dangor. Note: Content may be edited for style and length.