Publisher Health

Classrooms are opening their doors to a different pandemic. Here is how to think about risk.Last week, in what was intended to be an internal document, the Centers for Disease Control and Prevention made a stark admission: The highly contagious Delta variant had redrawn the battle lines of the coronavirus pandemic, necessitating new public health measures like universal mask mandates. Or, as the agency put it in the document, which was obtained by The New York Times, “the war has changed.”The news came just as the first school districts were preparing to reopen; children in Atlanta and some of its suburbs head back to the classroom this week.Over the past year, there has been contentious debate over how much schools contribute to the spread of the virus and whether, and when, they should close. For some parents, teachers and officials, keeping schools open when a new, poorly understood virus was circulating seemed like an unacceptable risk. For others, however, it was school closures that posed the bigger danger — of learning loss, widening educational disparities and worsening mental health, not to mention the hardships for parents.As the new school year begins, however, the C.D.C., the American Academy of Pediatrics and many other experts agree that reopening schools should be a priority.“We are in a very different place than we were a year ago,” said Elizabeth Stuart, an epidemiologist at Johns Hopkins Bloomberg School of Public Health. “We have very effective vaccines, we know a lot more about how to open schools safely, and we, I think, have a heightened awareness of some of the challenges that kids face when they’re not in in-person school.”Signs encouraging social distancing are commonplace at schools across the country.James Estrin/The New York TimesJust a few months ago, with vaccinations for those 12 and older proceeding at a steady clip and new cases declining, the stage seemed set for at least a partial return to normal.Delta has thrown that into question. Much remains unknown about the variant, including whether it affects children more seriously than earlier forms of the virus. And with vaccination rates highly uneven, and most decision-making left up to local officials, the variant adds new uncertainty to the coming school year — and makes it even more critical for schools to take safety precautions as they reopen, scientists said.“Delta, because it’s so contagious, has raised the ante,” said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases and a vaccine expert at Vanderbilt University. “It makes all these details all the more important.”Here are answers to some common questions.What have we learned about the risk of transmission in schools?Overall, studies suggest that — last year at least — in-school transmission was generally low when schools took basic precautions..css-1xzcza9{list-style-type:disc;padding-inline-start:1em;}.css-3btd0c{font-family:nyt-franklin,helvetica,arial,sans-serif;font-size:1rem;line-height:1.375rem;color:#333;margin-bottom:0.78125rem;}@media (min-width:740px){.css-3btd0c{font-size:1.0625rem;line-height:1.5rem;margin-bottom:0.9375rem;}}.css-3btd0c strong{font-weight:600;}.css-3btd0c em{font-style:italic;}.css-w739ur{margin:0 auto 5px;font-family:nyt-franklin,helvetica,arial,sans-serif;font-weight:700;font-size:1.125rem;line-height:1.3125rem;color:#121212;}#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-family:nyt-cheltenham,georgia,’times new roman’,times,serif;font-weight:700;font-size:1.375rem;line-height:1.625rem;}@media (min-width:740px){#NYT_BELOW_MAIN_CONTENT_REGION .css-w739ur{font-size:1.6875rem;line-height:1.875rem;}}@media (min-width:740px){.css-w739ur{font-size:1.25rem;line-height:1.4375rem;}}.css-9s9ecg{margin-bottom:15px;}.css-uf1ume{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-box-pack:justify;-webkit-justify-content:space-between;-ms-flex-pack:justify;justify-content:space-between;}.css-wxi1cx{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;-webkit-flex-direction:column;-ms-flex-direction:column;flex-direction:column;-webkit-align-self:flex-end;-ms-flex-item-align:end;align-self:flex-end;}.css-12vbvwq{background-color:white;border:1px solid #e2e2e2;width:calc(100% – 40px);max-width:600px;margin:1.5rem auto 1.9rem;padding:15px;box-sizing:border-box;}@media (min-width:740px){.css-12vbvwq{padding:20px;width:100%;}}.css-12vbvwq:focus{outline:1px solid #e2e2e2;}#NYT_BELOW_MAIN_CONTENT_REGION .css-12vbvwq{border:none;padding:10px 0 0;border-top:2px solid #121212;}.css-12vbvwq[data-truncated] .css-rdoyk0{-webkit-transform:rotate(0deg);-ms-transform:rotate(0deg);transform:rotate(0deg);}.css-12vbvwq[data-truncated] .css-eb027h{max-height:300px;overflow:hidden;-webkit-transition:none;transition:none;}.css-12vbvwq[data-truncated] .css-5gimkt:after{content:’See more’;}.css-12vbvwq[data-truncated] .css-6mllg9{opacity:1;}.css-qjk116{margin:0 auto;overflow:hidden;}.css-qjk116 strong{font-weight:700;}.css-qjk116 em{font-style:italic;}.css-qjk116 a{color:#326891;-webkit-text-decoration:underline;text-decoration:underline;text-underline-offset:1px;-webkit-text-decoration-thickness:1px;text-decoration-thickness:1px;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:visited{color:#326891;-webkit-text-decoration-color:#326891;text-decoration-color:#326891;}.css-qjk116 a:hover{-webkit-text-decoration:none;text-decoration:none;}“When you have masks and even three-foot distancing, you are not going to see major outbreaks in schools,” said Dr. Yvonne Maldonado, a pediatric infectious-disease specialist at Stanford Medicine and chair of the American Academy of Pediatrics Committee on Infectious Diseases. “There may be some transmissions, but they’re going to be pretty relatively infrequent.”Studies in North Carolina, Utah, Missouri and elsewhere revealed that when schools layered several kinds of safety measures — some combination of masking, symptom screening, distancing, improved ventilation, virus testing, handwashing and dividing students into smaller groups — transmission rates in schools were even lower than they were in the surrounding community.“It’s actually safer for the kids in school than it is for them to be home,” said Dr. Daniel Benjamin Jr., a specialist in pediatric infectious diseases at Duke University.Susan Elsamna taught her students in Edison, N.J., how to socially distance last fall.Victor J. Blue for The New York TimesThese low rates may stem, in part, from the fact that children under 10 seem to be less likely to transmit the virus than older children and adults are. But another contributing factor is that schools are — or can be — controlled environments and may have stricter safety measures than the surrounding community, Dr. Benjamin said.Outbreaks, however, have occurred in schools that reopened without good mitigation measures. Israel’s first big school-based outbreak, which ultimately infected 260 people, came during a heat wave, when officials temporarily lifted a mask mandate and students were crowded into air-conditioned classrooms.How does Delta complicate the equation?Roughly twice as transmissible as the original version of the virus, Delta has fueled a rise in infections and hospitalizations, especially in areas of the country where vaccination rates are low. Recent data suggests that people who are infected with Delta may carry a thousand times as much virus — which could make them more contagious and for longer — as those who catch the original version of the virus.But many questions about the variant remain unanswered, including the precise risk it poses in a school setting. What is clear, however, is that Delta is already driving outbreaks in many American communities, which raises the risks for local schools.“Schools are not islands and so if there’s a lot of community spread some of that spread is going to spill over into schools,” said Dr. Westyn Branch-Elliman, an infectious-disease specialist at Harvard Medical School.In a study conducted before Delta was widespread, British researchers found that for every five additional cases per 100,000 people in a community at large, the risk of a school outbreak increased 72 percent.The good news is that since the last school year started, the United States has authorized three highly effective vaccines for emergency use, and they are widely available to those 12 and older.The vaccines are not flawless. Some fully vaccinated people will get breakthrough infections, which are generally mild and rare. And those vaccinated people who are infected with Delta can carry high levels of the virus in their noses and throats, which means they may be able to readily transmit it.But vaccines provide strong protection against the Delta variant. They reduce the odds of being infected with the virus and guard against the worst outcomes, including hospitalization and death.Loida Hill, 13, receiving a dose of the Pfizer-BioNTech vaccine in New York in May.James Estrin/The New York TimesSchools with high vaccination rates are likely to have far fewer people who are infected with the virus and carry or spread it in the classroom.“It’s our best tool for controlling the virus,” said Justin Lessler, an epidemiologist at the University of North Carolina. “Even when it’s imperfect, it has huge impacts on reducing transmission and protecting people’s health.”What does the C.D.C. recommend?Initially, the C.D.C.’s guidelines recommended that unvaccinated people who were 2 or older wear masks in schools. And they strongly implied that vaccinated students did not need to be masked in the classroom.But last week, because of concerns about Delta, the C.D.C. revised its guidelines, recommending that everyone, regardless of vaccination status, wear masks in schools this fall.A face mask in a school parking lot in Odessa, Texas.Tamir Kalifa for The New York TimesThe agency recommends a layered approach to Covid precautions, suggesting that schools combine several mitigation measures and encourage everyone who is eligible for vaccination to get vaccinated.But the guidelines also leave many decisions up to local officials, who are told to make decisions about when to tighten or loosen restrictions based on data about local case and vaccination rates.What about states that ban mask mandates?Some states, including some currently experiencing major surges — including Florida, South Carolina and Texas — are making it harder for schools to put protective measures into place. Those three states, as well as a handful of others, have either banned or sharply curtailed universal mask mandates.That does not necessarily mean that schools in these states will all have huge outbreaks, and even schools that do may see mostly mild or asymptomatic cases. But districts that open without safety measures in place are taking a real risk, Dr. Benjamin said.“Here’s another way to put it,” he said. “When I grew up, I got away with riding in the back of a pickup truck all the time. But that does not make children riding in the back of pickup trucks good national policy.”Families protesting potential mask mandates ahead of a Hillsborough County School Board meeting in Tampa, Fla., last month.Octavio Jones/Getty ImagesGiven the patchwork of policies and uneven vaccination rates across the country, experts said they would not be surprised if school safety varies widely this fall. “I do think that there will be risks of infections when school districts decide to not follow any recommendations,” Dr. Maldonado said.As the pandemic continues to evolve, schools and officials will need to make complicated decisions based on local conditions, including when to insist on certain precautions and when it is safe to lift them.“We need to be making nuanced decisions about what to do in schools,” Dr. Branch-Elliman said. “But that’s a much harder public health message then the polarized ‘Schools are safe’ or ‘Schools are unsafe.’”What about unvaccinated elementary school students?Although the exact timeline is unclear, vaccines for some children under 12 could be authorized before the end of the year. Until then, however, elementary schools will open with essentially none of their students vaccinated. (Children who are participating in the trials may have received the shots.)Research shows, however, that the virus is much less likely to cause severe illness in children. They are not entirely protected; a small number of children may develop a rare but serious inflammatory condition, and some children with mild infections may experience long-term symptoms.Masking requirements outside of an elementary school in Austin, Texas, in December.Sergio Flores for The New York TimesThere is not yet good, solid data on how Delta affects young children, but there is no evidence that Delta is specifically targeting them.Still, because a large number of adults have been vaccinated, children may make up an increasing share of Delta cases. The variant’s infectiousness may also mean that more children contract the virus. There is also some emerging evidence that the variant is causing more severe disease in adults.Given these observations, and out of an abundance of caution, it is particularly important for schools with young, unvaccinated students to take other precautions, including universal masking, experts said.In schools or districts that do not have mask mandates, parents can provide some degree of protection by ensuring that their children, at least, wear masks to school, Dr. Maldonado said.And adults can help protect younger children by getting vaccinated themselves. “The single most important thing any community can do in order to reduce the risk in schools is for the entire community to be vaccinated,” Dr. Schaffner said.

SharecloseShare pageCopy linkAbout sharingimage sourceGetty ImagesThe southern Indian state of Kerala accounts for more than half of the country’s new Covid-19 infections. The BBC’s Soutik Biswas and Vikas Pandey report on why cases continue to rise in the state, months after the waning of the deadly second wave.In January 2020, Kerala reported India’s first Covid-19 case in a medical student who returned from Wuhan, in China, where the pandemic began. The number of cases rose steadily and it became a hotspot. By March, however, half a dozen states were reporting more cases than the picturesque southern state.Sticking faithfully to the contagion control playbook of test, trace and isolate and involving grassroots networks, Kerala brought down its case count drastically. There were breathless stories about the state flattening the curve. The first wave was protracted, but Kerala managed to control the spread of infection. The official death count remained low.Infections rose faster during the deadly second wave this summer. And they show no signs of abating even as the pandemic wanes in other parts of the country. With barely 3% of India’s population, Kerala has been accounting for more than half of India’s new cases. The reproduction number of the virus – which explains a disease’s ability to spread and estimates the number of people infected by one already infected person – has crossed one.This indicates a growing number of cases which, in turn, require lockdowns and other measures to stem a tide of infections. The percentage of people who test positive for the virus from the overall numbers being tested has hovered above 10% for a month. Kerala has recorded 3.4 million infections and 16,837 deaths from Covid-19 so far.But these disturbing numbers don’t tell you the whole story, say epidemiologists. Kerala, they say, is testing a lot more people – more than double the people per million compared to the rest of the country. It has kept infection levels in control. How Kerala’s Covid ‘success story’ came undoneHow India’s Kerala state ‘flattened the curve’The state is capturing one out of every two infections compared to other states which are catching one out of 30-odd infections. “Kerala is testing more, and testing smarter. By tracing contacts to find out real cases, testing is also better targeted,” says Dr Gagandeep Kang, one of India’s top virologists. The latest antibody tests survey reveals that only 43% people above the age of six in Kerala have been exposed to the infection, compared to 68% nationwide. This, many believe, proves that Kerala has done an admirable job in controlling the spread of coronavirus unlike the rest of India. Also, despite the rising number of cases, hospitals have not been overwhelmed. Kerala’s case fatality rate is a third of India’s national estimate; half of the Covid-19 beds in hospitals are free; and under-reporting of Covid-19 deaths is possibly the lowest in the state, according to a report.Also, Kerala has fully vaccinated more than 20% of its people and 38% – including 70% of people over 45 years – have received a single jab, much higher than the national average. So the state appears to be testing widely, reporting cases honestly, vaccinating quickly and ensuring that hospitals are not overwhelmed. Future waves of infection will not be “as severe as the second wave, given the pace at which Kerala is vaccinating its population”, reckons Dr Rijo M John, a health economist.Yet, epidemiologists worry that Kerala’s apparent success does not tell us the whole story.For one, a large number of people remain susceptible to the virus. “This is likely to be driving the pandemic in the state now,” says Prof Gautam Menon, a disease modelling expert.There is also risk in “letting people get infected, even while preventing deaths”, says virologist Dr Shahid Jameel. And that risk is of long Covid – long-term problems after recovering from the original infection – which afflicts up to a third of those infected, including asymptomatic patients.image sourcePTIKerala is at an “early [stage] in runaway exponential growth” in infections, believes Dr Swapneil Parikh, a physician. The highly infectious Delta variant has a much higher viral load and spreads faster, making it difficult to stamp out the infection, he says.”The hospitalisations and deaths now represent infections from sometime before, so I would not necessarily take solace in the fact that they are low right now,” says Dr Parikh. The consistently high test positive rate of infections is “still a cause for worry”.How India volunteers ‘exposed’ hidden Covid deathsWill a deadlier third Covid wave hit India?Prof Menon says a prolonged pandemic could mean the possibility of more mutations of the virus, leading to the emergence of new and dangerous variants which could spread the disease to the unvaccinated and uninfected people. “This is a time for caution. Kerala’s main focus should be to bring down case numbers.” Many say Kerala needs to be wiser and more forceful while enforcing rolling lockdowns – the state has allowed festivals to go ahead, leading to mass gatherings and risks of increased infections. Virologists say Kerala also requires a more granular data on targeted testing and increased genome sequencing to find out where the infections are rising the most and to track new variants. “If there is one thing which we should have learnt from India’s pandemic by now, it is to treat narratives of exceptionalism with caution,” says Dr Murad Banaji, a mathematician at London’s Middlesex University, who has been tracking the pandemic closely. Clearly, Kerala might not turn out to be an exception. Charts by Shadab NazmiYou may also be interested in:

David Peace has motor neurone disease, a terminal illness which gradually affects the brain and nerves.He says he intends to travel to a Swiss clinic to end his life before his condition prevents him from making the journey.David, who lives in central London, is one of a number of people behind renewed calls to update England and Wales assisted dying laws to allow terminally ill people, with six months to live, the right to end their life, subject to strict criteria.A second reading of the assisted dying bill is due to take place in the House of Lords this autumn.But opponents say there should be better focus on helping people to live more comfortable lives, rather than assisting them to die.Reporter and video producer: Paul Murphy-KaspIf you have been affected by issues highlighted in this video, help and support is available via the BBC Action Line website

She argued that categorizing premenstrual syndrome or feelings of guilt as disorders resulted from sexism in a field dominated by men.Paula Caplan, a pioneering psychologist who exposed how her profession had pathologized a wide range of female traits and social responsibilities, including motherhood, menstruation and even shopping, died on July 21 at her home in Rockville, Md. She was 74.Her daughter, Emily Stephenson, said the cause was metastatic melanoma.Starting in the late 1970s, Dr. Caplan merged a rigorous clinical analysis with a fierce feminist perspective to show how many of the problems that psychologists said were innate to women — and especially mothers — had in fact resulted from social structures and discrimination that forced them into difficult situations, then medicalized their inevitably negative responses.For example, in a 1984 article, “The Myth of Women’s Masochism” (and in a subsequent book by the same title), she took aim at Sigmund Freud and his acolytes, who said women suffered from “moral masochism” — that is, that they took pleasure in the frustrations and guilt that often arose from their roles as mothers and spouses.Dr. Caplan demolished Freud’s claim, first by pointing out that most women get no joy out of such pain, and then by showing how such frustration and guilt were often the results of unfair expectations placed on them by a patriarchal society.“She was a great defender of women’s honor,” said Phyllis Chesler, who is also a feminist psychologist and the author of “Women and Madness” (1972). “The image of women as vicious and cruel, she sought to repair that.”Dr. Caplan, the author of 11 books, was perhaps best known for her seven-year battle with the American Psychiatric Association as it planned the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, the encyclopedic guide used by millions of doctors to make diagnoses and by insurers to pay for them.She took particular issue with the decision by the manual’s editors to include “premenstrual dysphoric disorder,” in effect a lengthy or intense instance of premenstrual syndrome. Dr. Caplan argued that because P.M.S. was the natural result of a woman’s fluctuating hormone levels, it stood to reason that some women would experience it more strongly than others, in the same way that varying levels of testosterone made some men more aggressive than others.“If they had made a decision suddenly pathologizing a half million men, there would be a public outcry,” she told The New York Times in 1994. “I was so deeply disturbed by the lack of concern with scientific support for what they were including or rejecting, and the low level of apparent concern for the effects on patients who might get these diagnoses.”Half in jest, she proposed that the manual include “delusional dominating personality disorder” for men with high testosterone levels. The editors rejected her proposal, which, she said, just proved her point — and showed that they had no sense of humor.Still, she continued to attack the way her profession treated women, especially as the proliferation of antidepressants in the 1990s made diagnosis lucrative for medical professionals and insurers.“In our increasingly psychiatrized world,” she wrote in The Washington Post in 2012, “the first course is often to classify anything but routine happiness as a mental disorder, assume it is based on a broken brain or a chemical imbalance, and prescribe drugs or hospitalization.”Her experience opened the door to a broader critique of her profession — namely, what she saw as an urge to pathologize everyday human emotions. In fact, she argued, doing so could do more harm than good by encouraging healthy people to think they were sick.“She had a major impact that keeps growing on the psychology of women,” Lenore E. Walker, a psychologist and the author of “The Battered Woman” (1979), said in a phone interview. “The body of work she left behind is classic.”Paula Joan Caplan was born on July 7, 1947, in Springfield, Mo., to Jerome and Theda Ann (Karchmer) Caplan. Her mother was a clinical psychologist, her father a businessman.Dr. Caplan attended Radcliffe College, now part of Harvard, where she intended to become a journalist. But she was rejected from the nearly all-male staff of The Harvard Crimson, the student newspaper, an experience she chalked up to sexism. At the same time, in her English classes she found herself more interested in the psychological rather than strictly literary analysis of fictional characters, and she decided to change pursuits.She received her master’s and doctoral degrees in psychology from Duke and moved to Toronto in 1974 after her husband, Marcel Kinsbourne, found a job there.The couple divorced in 1978. A previous marriage also ended in divorce. Along with her daughter, Dr. Caplan is survived by her son, Jeremy; her brother, Bruce; and five grandchildren.After moving to Canada, Dr. Caplan was a psychologist for the Toronto Family Court for three years. Among her first efforts was a study of assertiveness among girls and boys, following on the work of the prominent German American psychologist Erik Erikson, in which he had concluded that boys were innately more assertive than girls.Dr. Caplan showed otherwise. Focusing on very young children and diminishing the presence of adults in the room during the study, she demonstrated that it was gendered socialization, not biology, that made girls act less assertively than boys.Dr. Caplan was a professor at the University of Toronto from 1979 to 1995 and head of its Center for Women’s Studies in Education from 1985 to 1987. She later taught at American University, the University of Rhode Island, Brown University and, most recently, Harvard, where she ran the Voices of Diversity Project at the Hutchins Center for African & African American Research.Dr. Caplan’s work extended beyond academic psychology. An actor since high school, she had small parts in TV shows and commercials, only some of which had anything to do with her intellectual pursuits.She wrote plays and directed documentary films, including “Isaac Pope: The Spirit of an American Century” (2019), about a Black man who had served in the Army under her father in the Battle of the Bulge during World War II.The film was of a piece with her latest interest, veterans and specifically those deemed to be suffering from post-traumatic stress disorder, a diagnosis she largely rejected. There was nothing pathological about having a strong, even debilitating reaction to the horrors of war, she said, and our desire to medicalize those reactions made it possible for nonveterans to ignore just how terrible war could be.“Leaving this work to psychotherapists alone may be not only harmful to the soldiers but also dangerous for us as a nation,” she wrote in The Washington Post in 2004. “It helps hide the consequences of combat, making it easier for us to go to war again the next time.”

Scientists at Children’s Hospital of Philadelphia (CHOP) have identified two proteins that could be used for a potential vaccine against nontypeable Haemophilus influenzae (NTHi). Working in a mouse model, the investigators found that administering two bacterial adhesive proteins that play a key role in helping the bacteria to latch on to respiratory cells and initiate respiratory tract infection stimulated protective immunity against diverse NTHi strains, highlighting the vaccine potential.
The findings were published today in the Proceedings of the National Academy of Sciences.
“Nontypeable Haemophilus influenzae is the most common cause of bacterial respiratory tract infections such as middle ear infections, sinus infections, and exacerbations of chronic obstructive pulmonary disease (COPD) and other underlying lung disease, resulting in significant morbidity in both children and adults. This organism is also an important cause of invasive disease such as sepsis and meningitis. Currently there are no vaccines or other approaches to protect against infection due to this organism,” said senior study author Joseph W. St. Geme, MD, Physician-in-Chief and Chairman of the Department of Pediatrics at Children’s Hospital of Philadelphia. “Our study has identified two proteins that stimulate both an antibody response and a broader cell-medicated immune response that protect against diverse strains of NTHiinfluenzae and thus may be valuable for inclusion in a vaccine to protect against a full range of NTHidisease.”
Because there are numerous strains of NTHi, it has been difficult to develop a vaccine that protects against infection. Surface antigens, which are typically used for immunization, vary from strain to strain, and thus antibodies against one strain of NTHi often do not protect against another strain.
To circumvent this challenge, the investigators focused on HMW1 and HMW2, two high molecular weight adhesive proteins involved in NTHi colonization of the nasopharynx, the first step in the pathogenesis of NTHi disease. These adhesive proteins are exposed on the surface of the bacteria and are present in approximately 75 to 80% of NTHi strains.
Using a mouse model, the researchers found that immunization with HMW1 and HMW2 stimulated the production of antibodies that were protective against the strain of NTHi from which the adhesive proteins were derived. Although the antibodies were specific to the parent strain of NTHi, the investigators found that immunization with HMW1 and HMW2 also provided protection against bacterial colonization by other NTHi strains, stemming from stimulation of cell-mediated immunity and production of interleukin 17.
“These results indicate that mice were protected against infection by heterologous strains, despite an antibody response that was strain specific,” St. Geme said. “Taken together, the findings in this study highlight the vaccine potential of the HMW1 and HMW2 proteins.”
This work was supported by the National Institute of Allergy and Infectious Diseases (NIAID) under the training grant in Microbial Pathogenesis and Genomics (1-T32-AI-141393-01).
Story Source:
Materials provided by Children’s Hospital of Philadelphia. Note: Content may be edited for style and length.

Although visible signs of aging are usually unmistakable, unraveling what triggers them has been quite a challenge. Researchers at Baylor College of Medicine and collaborating institutions have discovered that a cellular phenomenon called cryptic transcription, which had been previously described and linked to aging in yeasts and worms, is elevated in aging mammalian stem cells.
The team reports in the journal Nature Aging that cryptic transcription occurs because a cellular mechanism that keeps it in check falls apart as cells get old. The findings suggest that strategies that control cryptic transcription could have pro-longevity effects.
“In previous work, we showed that cryptic transcription in yeasts and worms is not only a marker of aging but also a cause,” said corresponding author Dr. Weiwei Dang, assistant professor of molecular and human genetics and the Huffington Center on Aging at Baylor. “Reducing the amount of this aberrant transcription in these organisms prolonged their lifespan.”
Cryptic transcription is a phenomenon that interferes with normal cellular processes. Normal gene transcription is a first step in the production of proteins. It begins in a specific location on the DNA called the promoter. This is where the protein coding gene begins to be transcribed into RNA, which is eventually translated into protein. Gene transcription is a well-regulated cellular process, but as cells age, they lose their ability to control it.
“Promoters have a specific DNA sequence that identifies the starting point of the transcription process that is usually located preceding the actual protein coding sequence,” explained Dang. “But promoter look-alike sequences do exist in other locations, including along the actual protein coding sequence, and they could start transcription and generate shorter transcripts, called cryptic transcripts. Here we investigated whether cryptic transcription increased with age in mammals and potential mechanisms involved in this phenomenon.”
The team worked with mammalian stem cells, which have shown to play a significant role in aging. They adapted a method to detect cryptic transcription to determine the level of this transcription in mice and human stem cells and cultured cells. When compared to young stem cells, older ones had increased cryptic transcription. They also looked into other aging cells and found that, in the majority of cells spanning a range of tissues, cryptic transcription was also elevated with age.
“Altogether, our findings indicate that elevated cryptic transcription is a hallmark of mammalian aging,” Dang said.
Young cells have mechanisms in place to prevent cryptic transcription. In aged mammalian cells, the researchers found that one such mechanisms, which involves limiting the access to chromatin, the material that makes up the chromosomes, is failing, facilitating the production of cryptic transcripts.
“It is still not clear how elevated cryptic transcription contributes to aging, but the evidence is accumulating that it is detrimental to mammals as it is for yeast and worms,” Dang said. “Future studies may result in ways of reduce the pro-aging effects of cryptic transcription.”
Other contributors to this work include Brenna S. McCauley, Luyang Sun, Ruofan Yu, Minjung Lee, Haiying Liu, Dena S. Leeman, Yun Huang and Ashley E. Webb. The authors are associated with one or more of the following institutions: Baylor College of Medicine, Texas A&M University, University of Texas MD Anderson Cancer Center, Stanford University, Genentech and Brown University.
This work was funded by NIH grants R01AG052507, R01AG053268, R01HL134780, R01HL146852 and T32AG000183; CPRIT award R1306 and a Ted Nash Long Life Foundation research grant.
Story Source:
Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

Researchers led by City of Hope have developed a powerful miniature brain platform to study the mechanistic causes of Alzheimer’s disease and to test dementia drugs in development, reports a new study published today in Advanced Science.
“Drug development for Alzheimer’s disease has run into challenges due to incomplete understanding of the disease’s pathological mechanisms,” said Yanhong Shi, Ph.D., the Herbert Horvitz Professor in Neuroscience and director of the Division of Stem Cell Biology Research within the Department of Developmental and Stem Cell Biology at Beckman Research Institute of City of Hope.
“Preclinical research in this arena predominantly uses animal models, but there is a huge difference between humans and animals such as rodents, especially when it comes to brain architecture. We, at City of Hope, have created a miniature brain model that uses human stem cell technology to study Alzheimer’s disease and, hopefully, to help find treatments for this devastating illness.”
City of Hope researchers were able to model sporadic Alzheimer’s disease, the most common form of the condition, using “brain organoids” derived using human induced pluripotent stem cell (hiPSC) technology. Because Alzheimer’s is a disease of age, the scientists exposed the models to serum to mimic age-associated blood-brain barrier breakdown. Then they ran the organoids through different experiments to test known Alzheimer’s biomarkers, including elevated levels of amyloid plaques and tau tangles as well as synaptic breaks linked to cognitive decline, among other pathological phenotypes brought on by the condition.
More than 6 million people are living with Alzheimer’s disease, which kills more people than breast and prostate cancer combined, reports the Alzheimer’s Association. The heartbreaking degenerative disease affects not only the individual diagnosed with the condition, but also their primary caregiver, family and friends. No cure currently exists, and available treatments merely address symptoms rather than the root cause.
“Other studies using brain organoids to examine Alzheimer’s disease used miniature brain models that are phenotypically young, but to truly understand what happens when Alzheimer’s strikes, we need to use age-associated models, and that’s what we did in this research project when we exposed the miniature brains to serum,” said Xianwei Chen, Ph.D., first author of the study and postdoctoral fellow at City of Hope. “We believe the age-associated brain organoids we generated will provide a powerful platform for us to find effective treatments for disorders affecting the human body’s most complex organ.”
Preclinical research using brain organoids found that exposure to serum from blood could induce multiple Alzheimer’s symptoms, suggesting combination therapies targeting multiple pathological alterations likely would be more effective than single-target therapies currently in development. The researchers studied late-onset or sporadic Alzheimer’s disease, which accounts for most cases (95% sporadic vs. 5% inherited). They found that attempting a single therapy — for example inhibiting only amyloid or tau proteins — did not reduce the levels of tau or amyloid, respectively, suggesting that these two key biomarkers likely cause disease progression independently. Moreover, exposure to serum from blood — which mimics a leaky blood-brain barrier — could cause breaks in synaptic connections that help brains remember things and function properly.
Matt Huentelman, Ph.D., professor of neurogenomics at the Translational Genomics Research Institute (TGen), said the brain model developed by City of Hope provides a new avenue for examining emerging treatments for this memory-robbing disease. Huentelman is a leading expert in the genetic study of Alzheimer’s disease and was not part of this study.
“Using the model developed in this City of Hope-led study could help accelerate the evaluation of potential treatment options, giving a new sense of hope to Alzheimer’s patients and their families,” he said.
This research was supported by the Louise and Herbert Horvitz Charitable Foundation, the Sidell-Kagan Foundation, the Christopher Family Endowed Innovation Fund, the National Institute on Aging of the National Institutes of Health (R01 AG056305, RF1 AG061794, R56 AG061171, P30 AG019610, RF1 DA048813, R01 AG056303, P30 AG066519) and the National Cancer Institute of the National Institutes of Health (P30CA33572).
Story Source:
Materials provided by City of Hope. Note: Content may be edited for style and length.

For people with diabetes who are insulin dependent, glycemic control is a full-time job. But what if their medication could do the work for them — an insulin whose activity in the bloodstream responds to the blood glucose levels and adjusts accordingly? An invention from Indiana University School of Medicine Distinguished Professor Michael A. Weiss, MD, PhD, could lead to just that.
In a breakthrough study published in the peer-reviewed journal PNAS, Weiss and his team describe the use of a synthetic “switch” that can be opened or closed using a simple sugar sensor. The study was in part collaborative with Thermalin, Inc., a small biotech company that Weiss began in 2008.
Their concept exploits a natural mechanism, designated the “protective hinge,” that is built into vertebrate insulins. The protective hinge is a natural structural feature that evolved more than half a billion years ago to keep the hormone stable in its closed state but foldable and functional in its open state.
“The reason a glucose-responsive insulin is important is that the biggest barrier to the effective use of insulin, especially in Type 1 diabetes, is the fear of the consequences of blood sugar going too low,” said Weiss, who is also the Chair of the Department of Biochemistry and Molecular Biology.
Immediate consequences of severely low blood sugar (hypoglycemia) can include delirium, convulsions or loss of consciousness, and repeated episodes of severe hypoglycemia can cause cognitive decline. On the other hand, chronic high blood sugar (hyperglycemia) can lead to blindness, stroke or amputation. Staying in the desired blood glucose range is a delicate balance that insulin-dependent diabetics face every day.
But Weiss said that he envisions a future when people do not have to choose to risk their long-term health to protect themselves from the immediate dangers of severe hypoglycemia.

When we fixate an object, its image does not appear at the place where photoreceptors are packed most densely. Instead, its position is shifted slightly nasally and upwards from the cellular peak. This is shown in a recent study conducted at the University of Bonn (Germany), published in the journal Current Biology. The researchers observed such offsets in both eyes of 20 healthy subjects, and speculate that the underlying fixation behavior improves overall vision.
We like to think of the eye as a camera, but the analogy falls short if we look at the distribution of light sensitive cells — photoreceptors — in the human retina. In digital cameras, the sensor consists of many millions of photosensitive cells distributed evenly over the sensor surface. These pixels all have the same size and are uniformly packed. In the human retina, on the other hand, there are two types of pixels: rod and cone photoreceptors. While rods help seeing in dim light, cones enable us to see color and fine details. In contrast to their technical counterparts, cones vary greatly in size and spacing. In the fovea, a specialized central area conveying sharpest vision, there are up to 200,000 cones per square millimeter; this number drops to about 5,000 in the periphery. This is comparable to a camera with varying resolution across the field of view, resulting in sharp and less sharp areas in the final image.
Dr. Wolf Harmening, head of the adaptive optics and visual psychophysics group at the Department of Ophthalmology at the University Hospital Bonn explains: “In humans, cone packing varies within the fovea itself, with a sharp peak in its center. When we focus on an object, we align our eyes so that its image falls exactly on that spot — that, at least, was the general assumption so far.”
Gaze is optimized to seeing with two eyes
As part of her doctoral thesis, Harmening’s colleague, Jenny Lorén Reiniger found that this is not quite the case. Her research showed that fixated objects are somewhat shifted nasally and upwards in relation to the location of highest cone density — in a systematic way. “We studied 20 subjects, and found this trend in all of them,” Reiniger says. “The offsets were a little larger for some and smaller for others; yet the direction was always the same, and symmetrically so between the two eyes. We also found that same spot when we repeated the measurement a year later.”
At first glance, this seems paradoxical: Why do we not use the sharpest part of our retina for seeing? Perhaps this ‘trick’ allows us to reserve our eyes’ maximum resolution for areas of the image that need it most. “When we look at horizontal surfaces, such as the floor, objects above fixation are farther away,” Reiniger explains. “This is true for most parts of our natural surrounds. Objects located higher appear a little smaller. Shifting our gaze in that fashion might enlarge the area of the visual field that is sheen sharply.” The researchers speculate that this behavior is an adaptation to seeing with two eyes.
The observed image shift is quite small. “The fact that we were able to detect it at all is based on technical and methodological advances of the last two decades,” says Harmening. The researchers from Bonn use a laser-based adaptive optics ophthalmoscope, enabling them to directly see individual cones in the eyes of their participants. “The method also shows us exactly which cells were used to fixate an object,” says Harmening, who is also a member of the transdisciplinary research area “Life and Health” at the University of Bonn, and part of the Medical Imaging Center Bonn.
In the human retina, there are up to seven million of these tiny color receptors, but when we focus on a point we use only a small fraction of them — probably only a few dozen — and possibly always the same ones throughout our lives. Cell targeted vision testing will likely help to understand which ones are the most important, in health and disease.
Story Source:
Materials provided by University of Bonn. Note: Content may be edited for style and length.

A new treatment for advanced urothelial cancer was effective with tolerable side effects in an international, multi-center phase 2 clinical trial led by investigators at Weill Cornell Medicine and NewYork-Presbyterian.
The trial results prompted a U.S. Food and Drug Administration (FDA) accelerated approval of the treatment on April 13, giving patients with this very aggressive type of cancer a new therapeutic option.
In the study, published online April 30 in the Journal of Clinical Oncology, the researchers gave the treatment, sacituzumab govitecan (SG), previously known as IMMU-132 and now by the trade name Trodelvy, to 113 patients with advanced urothelial carcinoma, the most common type of bladder cancer. The trial population had progressed despite treatment with platinum-based chemotherapy and immune-boosting “checkpoint inhibitors, and overall had a median of 3 prior lines of therapy. Treatment with SG was followed by sustained reductions in tumor size for 31 patients (27 percent), including complete tumor disappearance in six patients. The most common severe side effects included very low white blood cell count in 34 percent (with fever in 10 percent) and severe diarrhea in 9 percent, which were managed with dose adjustment and best supportive care.
“The bottom line is that SG represents another option for patients with this aggressive type and stage of cancer — and it’s also nice that it has a different target and mechanism of action compared to other drugs for this indication,” said lead principal investigator of the global trial Dr. Scott Tagawa, a professor of medicine in the Division of Hematology and Oncology at Weill Cornell Medicine and medical director of the genitourinary oncology program at NewYork-Presbyterian/Weill Cornell Medical Center.
Urothelial carcinoma accounts for about 90 percent of bladder cancers and occurs at a rate of about 70,000 new cases and 17,000 deaths per year in the United States. More than three quarters of these cases are in men, and cigarette smoking increases the risk of this cancer by several times.
Advanced urothelial carcinoma, in which the tumor is inoperable or has metastasized, is normally treated with platinum-based chemotherapy drugs, such as cisplatin or carboplatin, and/or immune checkpoint inhibitor drugs that aim to unleash the immune system’s anticancer capabilities. But in most cases, those treatments work for a limited period of time before the disease progresses again.