Publisher Health

 Eating disorders are stereotypically associated with adolescents and young adults. Growing evidence, however, suggests that these conditions can occur at any time during a woman’s lifespan, including at midlife. A new study finds that body dissatisfaction is a primary cause of eating disorders, especially during perimenopause. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
Eating disorders are serious mental health conditions characterized by disturbances in eating behavior and body image that occur in approximately 13.1% of women across the lifespan. The prevalence of any eating disorder specifically for women aged older than 40 years is roughly 3.5%, with specific symptoms such as dissatisfaction with eating patterns being documented as high as 29.3%.
Serious complications such as high mortality and morbidity are associated with eating disorders. These adverse health events are likely to be magnified when present at older ages. However, few studies on eating disorders have included participants at midlife, including premenopause, perimenopause, and postmenopause.
There is some evidence that supports the idea that perimenopausal women have the highest rates of dysregulated eating behaviors (eg, weight-control behaviors such as regular counting of calories or consumption of diet foods) of any reproductive stage at midlife and are significantly different from premenopausal women with regard to body dissatisfaction and feelings of fatness. Although findings such as these remain scant; the association between eating disorders and symptoms of perimenopause (eg, negative mood, depression, and fatigue) confirm that perimenopause may be a particularly risky time for eating pathology.
In this new small study, which sought to investigate the structure of eating disorder symptoms specifically during perimenopause and early postmenopause, the researchers used network analysis statistical models to compare the structure and importance of specific eating disorder symptoms across reproductive stages. Although they admit that larger studies are necessary with this underrepresented female population, the researchers believe that the study confirms that dissatisfaction with body image is a key risk factor for eating disorders across the lifespan, especially at midlife.
Study results are published in the article “Network analysis of eating disorder symptoms in women in perimenopause and early postmenopause.”
“This study shows that, similar to studies in young adults, dissatisfaction with body image remains a core feature of eating disorder pathology in midlife women. Specifically, fear of gaining weight and fear of losing control over eating habits are central symptoms of eating disorders in perimenopause and early postmenopause. These findings may help direct more targeted treatment strategies in women during midlife,” says Dr. Stephanie Faubion, NAMS medical director.
For more information about menopause and healthy aging, visit www.menopause.org. Founded in 1989, The North American Menopause Society (NAMS) is North America’s leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field—including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education—makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit www.menopause.org. 

Glioblastoma (GBM) is a WHO grade IV brain tumor with dismal prognosis. Although post-surgical radiation chemotherapy combined with temozolomide is the standard line of treatment, GBM cells surviving radiotherapy contribute to tumor progression and recurrence even more aggressively. Researchers have now unveiled the mechanism of radioresistance in GBM cells, identifying therapeutic targets to overcome radioresistance. Moreover, the team has discovered a clinical drug that sensitizes GBM cells to radiotherapy and could replace temozolomide.
Post-surgical radiotherapy and temozolomide, a chemotherapeutic drug, targeting post-cell division is the current standard of care for glioblastoma (GBM) — the most prevalent and lethal primary tumor of the central nervous system. An aggressive form of brain tumor, GBM is highly resistant to current therapies with high mortality and frequent recurrence. Moreover, GBM cells are highly radioresistant and contribute to tumor progression and recurrence even more aggressively when surviving radiotherapy. Thus, there is an urgent need to revise the standard treatment strategy and develop a new therapy to overcome the radioresistance of GBM cells.
To this end, a team of researchers from Korea and USA led by Professor BuHyun Youn from Pusan National University in Korea has now unveiled a plausible mechanism underlying the radioresistance of GBM cells that involves regulating an internal steady state of lipid within the cells, known as “lipid homeostasis.” “Put simply, radioresistant GBM cells prefer to stock up on fatty acids instead of utilizing them as an energy source in order to reduce mitochondrial reactive oxygen species that may cause damage to their DNA, RNA, and proteins, and, in turn, cell death,” explains Prof. Youn.
In their study published in Cell Reports Medicine, the researchers derived GBM stem cells from patients and established radioresistant cells for investigation. They showed that diacylglycerol kinase B (DGKB), a regulator of the intracellular level of diacylglycerol (DAG), was significantly suppressed in radioresistant GBM cells. This, in turn, increased DAG accumulation and decreased fatty acid oxidation, reducing mitochondrial lipotoxicity (harmful lipid accumulation in non-adipose tissues) in GBM cells and contributing to their radioresistance. Further, the team showed that the ionizing radiation induced an increase in the level of diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the formation of triglycerides from DAG.
Armed with this understanding, the researchers further demonstrated that the genetic inhibition of DGAT1 suppresses radioresistance. In addition, they discovered that cladribine, a clinical drug, activates DGKB and inhibits DGAT1. This action sensitized GBM cells to radiotherapy both in vitro and in vivo ( in mouse models).
“Our research has revealed cladribine as a radiosensitizer for GBM treatment by drug repurposing, which can offer multiple advantages,” says Prof. Youn. “As an FDA-approved oral drug, the side-effects of cladribine are quite manageable and it has been well evaluated for pharmacokinetics. Additionally, the clinical trial period will be considerably shorter than that required for new drug development. In this regard, cladribine could become a standard future treatment for GBM.”
Taken together, this study demonstrates that DGKB and DGAT1 are potential therapeutic targets for overcoming GBM radioresistance. Moreover, drugs like cladribine could potentially replace existing treatment options with a new and more effective strategy.

Drugs absorbed into the body are metabolized and thus removed by enzymes from several organs like the liver. The how fast the drug is cleared out of the system can be increased by other drugs that increase the amount of enzyme secretion in the body. This dramatically decreases the concentration of a drug, reducing its efficacy, often leading to the failure of having any effect at all. Therefore, accurately predicting the clearance rate in the presence of drug-drug interaction* is critical in the process of drug prescription and development of a new drug.
*Drug-drug interaction: In terms of metabolism, drug-drug interaction is a phenomenon in which one drug changes the metabolism of another drug to promote or inhibit its excretion from the body when two or more drugs are taken together. As a result, it increases the toxicity of medicines or causes loss of efficacy.
Since it is practically impossible to evaluate all interactions between new drug candidates and all marketed drugs during the development process, the FDA recommends indirect evaluation of drug interactions using a formula suggested in their guidance first published in 1997, revised in January of 2020, in order to evaluate drug interactions and minimize side effects of having to use more than one type of drugs at once.
The formula relies on the 110-year-old Michaelis-Menten (MM) model which has a fundamental limit of making a very broad and groundless assumption on the part of the presence of the enzymes that metabolizes the drug. While MM equation has been one of the most widely known equations in biochemistry used in more than 220,000 published papers, the MM equation is accurate only when the concentration of the enzyme that metabolizes the drug is almost non-existent, causing the accuracy of the equation highly unsatisfactory — only 38 percent of the predictions had less than two-fold errors.
“To make up for the gap, researcher resorted to plugging in scientifically unjustified constants into the equation,” Professor Jung-woo Chae of Chungnam National Univeristy College of Pharmacy said. “This is comparable to having to have the epicyclic orbits introduced to explain the motion of the planets back in the days in order to explain the now-defunct Ptolemaic theory, because it was THE theory back then.”
A joint research team composed of mathematicians from the Biomedical Mathematics Group within the Institute for Basic Science (IBS) and the Korea Advanced Institute of Science and Technology (KAIST) and pharmacological scientists from the Chungnam National University reported that they identified the major causes of the FDA-recommended equation’s inaccuracies and presented a solution.
When estimating the gut bioavailability (Fg), which is the key parameter of the equation, the fraction absorbed from the gut lumen (Fa) is usually assumed to be 1. However, many experiments have shown that Fa is less than 1, obviously since it can’t be expected that all of the orally taken drugs to be completely absorbed by the intestines. To solve this problem, the research team used an “estimated Fa” value based on factors such as the drug’s transit time, intestine radius, and permeability values and used it to re-calculate Fg.
Also, taking a different approach from the MM equation, the team used an alternative model they derived in a previous study back in 2020, which can more accurately predict the drug metabolism rate regardless of the enzyme concentration. Combining these changes, the modified equation with re-calculated Fg had a dramatically increased accuracy of the resulting estimate. The existing FDA formula predicted drug interactions within a 2-fold margin of error at the rate of 38%, whereas the accuracy rate of the revised formula reached 80%.
“Such drastic improvement in drug-drug interaction prediction accuracy is expected to make great contribution to increasing the success rate of new drug development and drug efficacy in clinical trials. As the results of this study were published in one of the top clinical pharmacology journal, it is expected that the FDA guidance will be revised according to the results of this study.” said Professor Sang Kyum Kim from Chungnam National University College of Pharmacy.
Furthermore, this study highlights the importance of collaborative research between research groups in vastly different disciplines, in a field that is as dynamic as drug interactions.
“Thanks to the collaborative research between mathematics and pharmacy, we were able to recify the formula that we have accepted to be the right answer for so long to finally grasp on the leads toward healthier life for mankind.,” said Professor Jae Kyung Kim. He continued, “I hope seeing a ‘K-formula’ entered into the US FDA guidance one day.”

The frequency and size of meals was a stronger determinant of weight loss or gain than the time between first and last meal, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.
According to the senior study author Wendy L. Bennett, M.D., M.P.H., an associate professor of medicine at Johns Hopkins University School of Medicine in Baltimore, although ‘time-restricted eating patterns’ — known as intermittent fasting — are popular, rigorously designed studies have not yet determined whether limiting the total eating window during the day helps to control weight.
This study evaluated the association between time from the first meal to last meal with weight change. Nearly 550 adults (18 years old or older) from three health systems in Maryland and Pennsylvania with electronic health records were enrolled in the study. Participants had at least one weight and height measurement registered in the two years prior to the study’s enrollment period (Feb.-July 2019).
Overall, most participants (80%) reported they were white adults; 12% self-reported as Black adults; and about 3% self-identified as Asian adults. Most participants reported having a college education or higher; the average age was 51 years; and the average body mass index was 30.8, which is considered obese. The average follow-up time for weight recorded in the electronic health record was 6.3 years.
Participants with a higher body mass index at enrollment were more likely to be Black adults, older, have Type 2 diabetes or high blood pressure, have a lower education level, exercise less, eat fewer fruits and vegetables, have a longer duration from last mealtime to sleep and a shorter duration from first to last meal, compared to the adults who had a lower body mass index.
The research team created a mobile application, Daily24, for participants to catalog sleeping, eating and wake up time for each 24-hour window in real time. Emails, text messages and in-app notifications encouraged participants to use the app as much as possible during the first month and again during “power weeks” — one week per month for the six-month intervention portion of the study.

Based on the timing of sleeping and eating each day recorded in the mobile app, researchers were able to measure: the time from the first meal to the last meal each day; the time lapse from waking to first meal; and the interval from the last meal to sleep.They calculated an average for all data from completed days for each participant.
The data analysis found: Meal timing was not associated with weight change during the six-year follow-up period. This includes the interval from first to last meal, from waking up to eating a first meal, from eating the last meal to going to sleep and total sleep duration. Total daily number of large meals (estimated at more than 1,000 calories) and medium meals (estimated at 500-1,000 calories) were each associated with increased weight over the six-year follow up, while fewer small meals (estimated at less than 500 calories) was associated with decreasing weight. The average time from first to last meal was 11.5 hours; average time from wake up to first meal measured 1.6 hours; average time from last meal to sleep was 4 hours; and average sleep duration was calculated at 7.5 hours. The study did not detect an association meal timing and weight change in a population with a wide range of body weight.As reported by Bennett, even though prior studies have suggested intermittent fasting may improve the body’s rhythms and regulate metabolism, this study in a large group with a wide range of body weights did not detect this link. Large-scale, rigorous clinical trials of intermittent fasting on long-term weight change are extremely difficult to conduct; however, even short-term intervention studies may be valuable to help guide future recommendations.
Although the study found that meal frequency and total calorie intake were stronger risk factors for weight change than meal timing, the findings could not prove direct cause and effect, according to lead study author Di Zhao, Ph.D., an associate scientist in the division of cardiovascular and clinical epidemiology at Johns Hopkins Bloomberg School of Public Health.
Researchers note there are limitations to the study since they did not evaluate the complex interactions of timing and frequency of eating. Additionally, since the study is observational in nature, the authors were unable to conclude cause and effect. Future studies should work toward including a more diverse population, since the majority of the study’s participants were well-educated white women in the mid-Atlantic region of the U.S., the authors noted author.
Researchers also were not able to determine the intentionality of weight loss among study participants prior to their enrollment and could not rule out the additional variable of any preexisting health conditions.
According to the American Heart Association’s 2022 statistics, 40% of adults in the U.S. are obese; and the Association’s current diet and lifestyle recommendations to reduce cardiovascular disease risk include limiting overall calorie intake, eating healthy foods and increasing physical activity.
The 2017 American Heart Association scientific statement: Meal Timing and Frequency: Implications for Cardiovascular Disease Prevention did not offer clear preference for frequent small meals or intermittent fasting. It noted that irregular patterns of total caloric intake appear to be less favorable for the maintenance of body weight and optimal cardiovascular health. And, altering meal frequency may not be useful for decreasing body weight or improving traditional cardiometabolic risk factors.

Raphidocystis contractilis belongs to Heliozoa, a group of eukaryotes commonly found in fresh, brackish, and sea water. The organisms of this group have finger-like arms — axopodia — which radiate out from their body, giving them a sun-like appearance. Hence, they are also known as “solar worms.” Each axopodium is composed of the proteins, alpha-beta tubulin heterodimers, which form filaments called microtubules. R. contractilis can withdraw its axopodia extremely fast in response to external stimuli. However, the mechanism underlying this rapid arm shortening remains a mystery.
To this end, a team of researchers including Professor Motonori Ando, Dr. Risa Ikeda (both from the Laboratory of Cell Physiology) and Associate Professor Mayuko Hamada (from the Ushimado Marine Institute), of Okayama University, Japan, explored the mechanism involved in one of the fastest cell movements in the living world.
So, where did it all begin? Sharing the motivation behind their study, Professor Ando says, “Recently, a wide variety of heliozoans have been discovered in various hydrospheres in the Okayama Prefecture, making it clear that several species of sun worms inhabit the same environment. We are trying to unravel the mysteries around these protozoans and gradually expand the horizons of our knowledge.”
The authors started their investigation by immunolabelling the tubulin protein and observing its movement before and after axopodial contraction. They found that before shortening, tubulins were arranged systematically all along the length of the axopodia, but after axopodial withdrawal, those swiftly accumulated at the cell surface. This led them to believe that during the rapid axopodial withdrawal, the microtubules broke down into tubulin instantly. However, microtubule degradation is generally not a rapid phenomenon; it progresses rather slowly.
How then, could R. contractilis achieve this change so quickly?
The researchers hypothesized that this was possible if the microtubules split at multiple sites simultaneously. To validate their hypothesis, the authors set out to find the proteins and genes involved in the instant cleavage of microtubules in R. contractilis. Their findings were published online in TheJournal of Eukaryotic Microbiology on 21 November 2022.
The researchers performed de novo transcriptome sequencing (analysis of the genes expressed at a particular time in a cell) and identified close to 32,000 genes in R. contractilis. This gene set was most similar to that found in protozoans (which are single-celled organisms), followed by metazoans (multicellular organisms with well-differentiated cells; this includes humans, and other animals).
Homology and phylogenetic analysis of the obtained gene set revealed several genes (and their corresponding proteins) involved in microtubule disruption. Among these, the most important ones were katanin p60, kinesin, and calcium signaling proteins. Katanin p60 was involved in controlling the axopodial arm length. Several duplicates of kinesin genes were found. Among the identified kinesins, kinesin-13, a major microtubule destabilizing protein, was found to play an important role in the rapid contraction of axopodia. Calcium signaling genes regulate the entry of calcium ions into the cell from its surroundings and the induction of axopodial withdrawal.
The researchers also noticed a lack of genes linked with flagellar formation and motility, indicating that the axopodia of R. contractilis have not evolved from flagella. Although many genes remain unclassified, the newly established gene set will serve as a reference for future studies aiming to understand the axopodial motility of R. contractilis.
Heliozoan axopodia can function as a sensitive sensor. They can detect minute changes in their environment, e.g., the presence of heavy metal ions and anticancer drugs. Discussing their vision for the future, Professor Ando shares, “We believe that the axopodial response of heliozoa can be used as an index to develop temporary detection and monitoring devices for environmental and tap water pollution. It can also be used as a novel bioassay system for the primary screening of novel anticancer drugs. In the future, we plan to continue to work together as a team to enhance basic and applied research on these organisms.”

A tendency for one or both spouses to avoid or withdraw from tough conversations could set up married couples for emotional distress, bad feelings about their relationship, chronic inflammation and lowered immune function, new research suggests.
The analysis revisits data from a 2005 Ohio State University study that showed the stress couples feel during a brief argument could slow their bodies’ ability to heal from wounds by at least a day — a landmark finding at the time showing how psychological stress affects immunity.
A fresh look at the data shows that when married couples typically communicate with each other in negative ways, both spouses — and women in particular — suffer emotionally and their immune function wanes, in the form of having wounds that take longer to heal. The analysis revealed that the health consequences of negative communication patterns were evident even before the 2005 study began: These couples arrived at the lab with higher blood markers for inflammation.
The initial trial showed that one stressful argument — in a lab, recorded and analyzed by researchers — could harm immune function. This new study suggests that the more combative arguments in the lab were linked to more negative typical marital communication for these couples — and those daily patterns are a likely culprit behind persistent negative emotions and biological markers that can lead to poorer health outcomes.
“Marriage is associated with better health, but chronically distressed marriages can worsen health,” said first author Rosie Shrout, who completed this work as a postdoctoral researcher in Ohio State’s Institute for Behavioral Medicine Research (IBMR). “It’s important to understand what is going on behind the scenes that contributes to these effects.
“What we’re seeing is that both chronic daily negativity and acute negativity, and their combination — experiencing both of those — is particularly bad for couples’ emotions, relationships and immune functioning,” said Shrout, now an assistant professor of human development and family science at Purdue University.

The new study was published recently in the journal Psychoneuroendocrinology.
The 2005 research was co-led by Jan Kiecolt-Glaser, senior author of the new study and professor emerita of psychiatry and psychology at Ohio State, whose decades of discoveries as a leader of the IBMR have shown the many ways in which stressful life events are detrimental to health.
The 2005 work involved 42 married heterosexual couples who had been together for an average of 12 years. Researchers tested the baseline level of a proinflammatory protein in their blood and used a device to raise small blisters on each partner’s forearm — the wounds’ healing progress was monitored as an indicator of how well each participant’s immune system was functioning.
Participants completed questionnaires assessing their typical communication patterns when problems arise — mutual constructive or symmetrical positive communication, or variations of negative communication patterns that involved either mutual avoidance or instances where one partner made demands and the other withdrew from the discussion in response.
Couples were recorded having discussions in two separate lab visits: The first focused on social support and the second was an attempt to resolve a known source of tension in the marriage, such as finances or in-laws. Researchers coded negative and positive behaviors during these talks.

In follow-ups, couples evaluated the discussions — whether they were satisfied with the conversation, and the degree to which they felt supported and understood by their partner, and in control and working productively while sorting out a problem. Their blister wound healing was assessed daily for eight days and then again on day 12.
In the new study, statistical modeling of the qualitative and biological data showed that couples’ negative communication patterns — specifically mutual avoidance or demand/withdrawal — had cascading effects on how they felt after the lab conversations, and on their inflammation and immune function measures.
“If they were more negative typically on a day-to-day basis, and were negative in those specific interactions, they rated the discussion more negatively and less positively, they felt fewer positive emotions, and their wounds healed more slowly,” Shrout said. “That chronic negativity and acute negativity had emotional, relational and immune effects — most notably for women.”
In contrast, couples who reported more mutual constructive communication patterns rated the lab conversations more favorably.
A few specific findings suggested how insidious the effects of poor communication patterns could be: Wounds healed more slowly in couples who mutually avoided talking about tough topics and also showed fewer positive behaviors during lab discussions. Even when mutual avoiders were more positive while trying to resolve conflict, that positivity didn’t help their wounds heal more quickly.
Kiecolt-Glaser, who has led a number of marriage and health studies, said it doesn’t take long for married couples to have expectations of what the marriage is like that can override any evidence to the contrary. In a bad marriage, a negative behavior is perceived as reinforcement of this expectation, while in a good marriage, a negative behavior is taken as a sign one’s partner is in distress.
“This study provides a window into relationships: What couples say about their relationship really did translate not only into how they behaved, but also what they said about the behavior, and their biology,” she said. “They walked into this study situation, and the way they’re responding may in part be because that’s what they’re expecting. They have such well-worn tracks in terms of interactions that it’s hard to derail the train.”
That doesn’t mean all is lost, Shrout noted — couples have lots of options to pursue education or therapy to help them learn better communication skills.
This work was supported by an Ohio State Presidential Postdoctoral Scholars Fellowship and the National Institutes of Health.
Additional co-authors include Megan Renna of the University of Southern Mississippi, and Annelise Madison and William Malarkey of Ohio State.

Last fall, the university’s law school joined other top programs in dropping out of the magazine’s annual list. The medical school’s dean said the rankings “cannot meaningfully reflect” the school’s goals.Harvard Medical School will no longer submit data to U.S. News & World Report for the magazine’s annual “best medical schools” rankings, becoming the university’s second graduate school to boycott the list in recent months, the school’s dean said on Tuesday.In a letter, Dr. George Daley, dean of the faculty of medicine, said he had been debating the decision since becoming dean six years ago and was inspired by a group of top of law schools that withdrew from the rankings last fall.“My concerns and the perspectives I have heard from others are more philosophical than methodological, and rest on the principled belief that rankings cannot meaningfully reflect the high aspirations for educational excellence, graduate preparedness, and compassionate and equitable patient care that we strive to foster in our medical education programs,” Dr. Daley said.U.S. News has published the rankings for decades, and while they have come under growing criticism, they continue to be an influential guide for students and their parents during the college selection process.Dr. Daley said the rankings create what he called “perverse incentives” for institutions to report misleading information and set policies that boost rankings. Although Harvard’s medical school will no longer share key data with the magazine, it will continue to share some of the data on its admissions website.More on America’s College CampusesAffirmative Action: With the Supreme Court widely expected to overturn or roll back affirmative action in college admissions, schools may need to rethink everything about the process.Hamline University Controversy: After an outcry among Muslim students, a professor who showed a painting of the Prophet Muhammad in class lost her job. Some scholars take issue with the idea that the incident was Islamophobic.Columbia’s Business School: On the developing Manhattanville campus, the architecture reinforces a social movement in business education to do good as well as make money.U.S. News & World Report: Under pressure amid a boycott by top law schools, the magazine said that it would make several changes in the next edition of its influential ratings.Harvard Medical School was ranked first in the magazine’s 2023 best medical school for research list, released last spring, and the Grossman School of Medicine at New York University was ranked second. Tying for third were the College of Physicians and Surgeons at Columbia University, the School of Medicine at Johns Hopkins University and the School of Medicine at the University of California, San Francisco.Medical schools are evaluated on faculty resources, the academic achievements of entering students and qualitative assessments by schools and residency directors, according to U.S. News. More than 190 medical and osteopathic schools were surveyed by the magazine. That information, coupled with the results from peer-assessment surveys, was used to calculate the overall rankings.“What matters most to me as dean, alumnus, and faculty member is not a #1 ranking, but the quality and richness of the educational experience we provide at Harvard Medical School that encourages personal growth and lifelong learning,” Dr. Daley said.U.S. News did not immediately return a request of comment on Wednesday, and it was unclear if the magazine planned to make adjustments to how it ranks medical schools.It was also unclear what effect Harvard’s decision would have on other medical schools’ participation. Last fall, many of the country’s top law schools announced that they would no longer participate in the rankings after the ones at Harvard and Yale said they were pulling out.In response, the magazine said this month that it would make several changes in the next edition of the law school rankings, including giving more weight to those whose graduates pursue advanced degrees, or school-funded fellowships to work in public-service jobs that pay lower wages. Factors including indicators of student debt or the schools’ spending per student would no longer be considered. The magazine said its rankings would also rely less on surveys of law schools’ reputations submitted by academics, lawyers and judges.While top-tier schools can weather potential fallout from dropping out of the rankings, there is a sense of hesitation among lesser known schools, which depend on the ratings to attract students.Angela Onwuachi-Willig, the dean of Boston University, which was ranked 17th among law schools, said lower-ranked schools, applicants and employers get some benefit out of the “free marketing” of rankings.

A St. Louis doula program, part of a nonprofit that received funding in the $1.7 trillion federal budget bill, looks for solutions in a benefit largely associated with affluent white women.ST. LOUIS, Mo. — Tara Ervin will never forget the week her sister Kelly died.It was July 1996 and Kelly, 34 weeks pregnant, was in the emergency room with swollen feet and what the doctors said was likely a bladder infection. She was sent home with antibiotics but returned less than 48 hours later in worse shape, vomiting profusely. A blood test confirmed the worst as Kelly’s doctors rushed to deliver her son by emergency cesarean. They told her family they were sorry, they had done everything they could to save her.An otherwise healthy 28-year-old had died from toxemia poisoning caused by pre-eclampsia, a serious complication of pregnancy that went untreated. Friends showed up at Kelly’s baby shower the next day, only to learn she was gone. Kelly’s family put photos of her newborn in her coffin.“I thought that was something that only happened in the movies,” Ms. Ervin said in a recent interview, vowing that her sister’s death would not be in vain. “I don’t want any other family to endure the trauma we endured.”Today Ms. Ervin is a certified doula at a St. Louis-based childhood development nonprofit that is part of a movement fighting a growing maternal mortality health crisis among Black women, who suffer and die at a higher rate — as a result of substandard maternal care and racial biases — than their white counterparts.The nonprofit, Parents as Teachers, is in a network of more than one dozen “home visiting” programs that won a large funding increase in the $1.7 trillion spending bill that Congress passed late last year.By providing the doulas, who offer nonmedical support to mothers before, during and after delivery, the program is extending a benefit largely associated with white and affluent women to predominantly Black, low-income mothers in St. Louis who would not otherwise know about it or be able to afford it. Unlike certified nurse midwives who deliver babies, doulas offer guidance on pain or complications ahead of delivery and help clients navigate hospitals and doctors — exactly the problems that Kelly experienced. Continuous guidance from a doula has been cited as one of the most effective interventions in easing pregnancy.“I don’t want any other family to endure the trauma we endured,” said Ms. Ervin, whose sister died from a serious pregnancy complication.Akilah Townsend for The New York TimesThe goal of the doulas is to go beyond the standard mission of supporting America’s most vulnerable children from “cradle to career.” Instead they start in mothers’ wombs.“Doula support for a Black mother is like giving them a cape,” said Constance Gully, the president and chief executive officer of the Parents as Teachers National Center. The program, she said, teaches mothers to “advocate for their babies beyond the hospital.”The doula program began in St. Louis about four years ago when a group of Black women working at Parents as Teachers noticed a familiar refrain from clients fearful of the health care system.“I don’t want to die,” Aminah Williams, one of the first of the group to be certified as a doula, recalled more than one Black expectant mother telling her.“That shouldn’t be the thing that comes to Black women’s minds,” Ms. Williams said. “And it breaks my heart that it is.”The concerns are not hyperbole. Nationally, Black women are nearly three times more likely to die from a maternal cause than white women: The National Center for Health Statistics reports that in 2020, the maternal mortality rate for Black women was 55.3 deaths per 100,000 live births. The 2020 rate for white women was 19.1 deaths per 100,000 live births.Black women are also more likely to have C-sections, have their pain minimized or ignored, report mistreatment, and have stillbirths than white women.Over the years, mounting research and high-profile cases of fatal or near-fatal experiences — from that of the tennis superstar Serena Williams to an epidemiologist at the Centers for Disease Control and Prevention — have shown that the grim statistics are often a result of a health care system that leaves Black mothers to fend for themselves.“Racial and ethnic inequities in obstetrics and gynecology cannot be reversed without addressing all aspects of racism and racial bias, including sociopolitical forces that perpetuate racism,” the American College of Obstetricians and Gynecologists said in a statement last year. “We have an obligation to work to overhaul currently unjust systems that perpetuate unacceptable racial inequities in health outcomes.’’Women who look like usThe five certified doulas at the organization in St. Louis are a rarity — roughly 10 percent of the nation’s doulas are Black women — and see themselves as crucial to their Black patients, including newborns, who some research has shown fare better when treated by Black health care professionals.“I’m Black and I matter to those moms because of it,” said Robin Lloyd, one of the doulas, who almost bled to death after giving birth nearly 20 years ago when she said her concerns were disregarded. “We always matter a little more to those who look like us, who go through what we go through.”“We’re here to make sure they have a good experience when no one else is interested in that,” said Donna Givens, the manager of community partnerships and groups for Parents as Teachers, who was the first certified doula in the St. Louis program.Donna Givens was the first certified doula in the Parents as Teachers program in St. Louis.Akilah Townsend for The New York TimesOn a recent day, Ms. Givens was at a St. Louis maternal homeless shelter, Our Lady’s Inn, leading a support group session with a half-dozen new and expectant mothers.“I wasn’t thinking of myself pregnant in a maternal shelter,” said Kaneisha, 22, who began to cry, and who asked to be identified only by her first name. “But I shouldn’t be judged for having somewhere to lay my head.”One of the other mothers, Diamond, who also asked that only her first name be used, said Kaneisha would not have to worry about that with a doula. Diamond, 21, said she had recently had a vaginal birth after an earlier cesarean, even though her doctors had pressured her against it.“When I said I had a doula, they flipped the script,’’ Diamond said. “They looked at me like, ‘How do you know about that?’ I felt famous.”That same day, Ms. Lloyd hauled a backpack with a doll, a prosthetic breast and a bag of diapers up to an apartment to check on another mother, Alaila Jordan, who had delivered the day before Thanksgiving. Ms. Jordan told Ms. Lloyd that her baby girl was finally gaining weight, but she was still on edge. She worried about where to store her milk supply and had been researching some storage strategies on TikTok.“Please don’t stress yourself out,” Ms. Lloyd said. “And please, please stay off TikTok.”Alaila Jordan said there was a marked difference between talking to Ms. Lloyd and her obstetrician. “It’s nice to have somebody asking about me,” she said. Akilah Townsend for The New York TimesMs. Lloyd pulled out a postpartum depression screening and handed it to Ms. Jordan. The 22-year-old filled it out and handed it back, prompting Ms. Lloyd to lean over to her and ask softly, “So tell me, what can we do to make you feel better?”Ms. Jordan admitted that she was frustrated with her partner and felt unsupported. “I try to hide it and say it’s the breastfeeding, but it’s really that,” she said.Ms. Lloyd promised she would be back to work with the young couple, and that she’d also bring a thermometer after noticing the apartment was too warm for safe sleeping.Ms. Jordan said there was a marked difference between talking to Ms. Lloyd and her obstetrician. “It’s nice to have somebody asking about me,” she said.A birth plan, deliveredImoni Cooper was in the early stages of labor at Barnes-Jewish Hospital in St. Louis last October and frustrated. The nurses, she recalled, kept asking her to sign paperwork she did not understand, and would not look at her birth plan, which included directions on everything from her epidural to the music she wanted during labor and delivery, that she and Ms. Ervin, her doula, had drawn up.“We all know that as African Americans, they paint us in a different picture — drug addicts, father not there — and treat us accordingly,” Ms. Cooper, 27, said. “So I wasn’t signing nothing, doing nothing.”From the hospital Ms. Cooper was in phone contact with Ms. Ervin, who was not planning to get there until Ms. Cooper was further along in her labor, as was standard practice. But there was something in Ms. Cooper’s voice that made her uneasy.“I’m not doing anything until Ms. Tara gets here,” Ms. Ervin could hear Ms. Cooper tell her medical team.Ms. Ervin, who had conferenced in this reporter on the phone as she raced to Ms. Cooper, said she heard the kind of strain in those words that she knew all too well could lead to fatal outcomes.“Not today,” Ms. Ervin said, part declaration and part prayer, as she started to race toward Barnes-Jewish. “By the time I leave the hospital, I’m going to have a beautiful baby. And a living mama.”Minutes later, Ms. Ervin was at the hospital with Ms. Cooper, where she said the attentiveness of the medical team changed as the nurses took the birthing plan in hand. In a statement, a representative for the health care center said it has collaborated with doulas in the community and has sought to “thoughtfully focus on how to close gaps in maternal health outcomes.”Ms. Cooper with her two daughters at home.Akilah Townsend for The New York TimesMs. Ervin dimmed the lights, walked Ms. Cooper around the hospital three times, then had her bouncing on a birthing ball and inhaling peppermint essential oil fragrances from a towel.When Ms. Cooper was five centimeters dilated, her mother prayed for the baby via FaceTime, as requested. Ms. Cooper held on as long as she could before shouting the code word she and Ms. Ervin had come up with, “cookies,” to ask for an epidural.Then it came time to push. Ms. Ervin was rubbing the back of Dushawn Blakely, Ms. Cooper’s partner and the father of her children, while holding Ms. Cooper’s leg. A baby girl, Denim, was born on Oct. 10 at 9:49 p.m., weighing 7 pounds, to the soundtrack of Ms. Cooper’s favorite gospel song, Kirk Franklin’s “Melodies From Heaven,” just as planned.A close call with pre-eclampsiaSince the doula program started in St. Louis, the women have helped expectant mothers through more than 50 births. The program so far reports that 88 percent of the births have been without complications, 56 percent of mothers participated in two prenatal doula visits, and 88 percent of them began breastfeeding. All reported reduced stress.At least one credits the doula program with saving her life.Kodi Washington, 30, experienced intense swelling in her feet after the birth of her second child last March. The doctors told her that it was normal and should subside in 10 days, and that she should drink water, elevate her feet, and avoid fried food. When it hurt for her to stand up, she sent a picture to her doula, Ms. Givens, who was alarmed and urged her to go to the hospital.Ms. Givens’s fears were confirmed. Ms. Washington was admitted with postpartum pre-eclampsia and dangerously high blood pressure and spent three days in treatment.“If it wasn’t for you, I wouldn’t have ever even gone to the hospital,” she told Ms. Givens in tears on a recent day. “I would have just spent 10 days — dying.”“Wasn’t going to happen,” Ms. Givens replied. “Not on my watch.”Kodi Washington, right, with her daughter and Ms. Givens.Akilah Townsend for The New York Times

Published1 day agocommentsCommentsShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Philippa RoxbyHealth reporterPeople of all ages are being encouraged to do more to look after their brains to try to reduce their dementia risk.A new brain check-up tool from Alzheimer’s Research UK offers tips on staying sharp, keeping active and connecting with others.Getting regular hearing checks in your 40s and 50s is one way to prevent social isolation, it says.But most cases of dementia cannot be prevented, so early detection and better treatments are still vital.Research suggests there are 12 risk factors for dementia which, if modified, could stop four in 10 people developing memory loss, confusion and communication problems.Advice based on these risk factors is to stop smoking, do regular exercise, cut back on alcohol and challenge your brain – and it is never to early or too late to start doing it, experts say.Anyone can take the brain check, which has been based on the latest research, to find out how to lower their individual chances of dementia.But it is particularly aimed at adults aged 40-50 because this is seen to be an important window for taking action to look after brain health.Prof Jonathan Schott, chief medical officer at the charity, said it would “provide a practical and easy means to allow people to take action to reduce their risk of dementia”.But he said only a third of people realised that was possible, which needed changing.Image source, Alzheimer’s Research UKAlzheimer’s is the most common cause of dementia, which affects nearly one million people in the UK and 55 million worldwide.Numbers are forecast to rise sharply over the coming decades as more people live longer and their risk of dementia goes up with age.Dr Sarah Bauermeister, senior scientist at Dementia Platforms UK, said several studies had found a link between hearing loss and dementia risk.”Why is not clear,” she said, “but a probable factor is they are working harder to hear conversations rather than focusing on cognitive tasks – and their world shrinks.”She said it was a good idea to get your hearing checked and corrected with a hearing aid if needed.No blameOur individual risk of developing dementia is linked to a combination of our age, the genes we inherit and the lifestyle we lead. Many of those things cannot be changed, which is why there is no foolproof way of preventing dementia in 60% of cases.”It’s important not to blame people for getting dementia,” said Dr Charles Marshall, clinical senior lecturer in dementia at Queen Mary University of London.Some groups, such as those from poorer background and those with less education, are at higher risk.But he said the NHS Health Check, a service for those aged 40-74, could be used to test brain health and give people advice on how to improve it, while also identifying those with early signs of dementia.At present it takes an average of three years to get a diagnosis of dementia and there are very few treatments for symptoms.”We need the same diagnostic process for dementia as for cancer, and that means redesigning services,” Dr Marshall said.”We need to prepare now for delivering new treatments when they come.”A drug called lecanemab has recently shown promise at slowing the decline of the brain in people with Alzheimer’s. Hilary Evans, chief executive of Alzheimer’s Research UK, said: “With 40% of dementia cases potentially being preventable, there’s an enormous opportunity to reduce the personal and societal impact of this heart-breaking condition.”It’s time for the nation to wake up to the idea of brain health and how looking after our brains can reduce the risk of dementia.” More on this storyHRT might cut Alzheimer’s risk in some women – study4 days agoAlzheimer’s drug hailed as momentous breakthrough30 November 2022’Just like that – the woman I love changed’16 October 2022Lifestyle changes that could lower your dementia risk14 July 2019Related Internet LinksThink Brain Health Check-in – Think Brain Health – Alzheimer’s Research UKThe BBC is not responsible for the content of external sites.

Choline, an essential nutrient produced in small amounts in the liver and found in foods including eggs, broccoli, beans, meat and poultry, is a vital ingredient for human health. A new study explores deficiency in dietary choline adversely affects the body and may be a missing piece in the puzzle of Alzheimer’s disease.
It’s estimated that more than 90% of Americans are not meeting the recommended daily intake of choline. The current research, conducted in mice, suggests that dietary choline deficiency can have profound negative effects on the heart, liver and other organs.
Lack of adequate choline is also linked with profound changes in the brain associated with Alzheimer’s disease. These include pathologies implicated in the development of two classic hallmarks of the illness, amyloid plaques, which aggregate in the intercellular spaces between neurons, and tau tangles, which condense within the bodies of neurons.
The new research, led by scientists at Arizona State University, describes pathologies in normal mice deprived of dietary choline as well as choline deficient transgenic mice, which already exhibit symptoms associated with the disease. In both cases, dietary choline deficiency results in liver damage, enlargement of the heart and neurologic alterations in the AD mice typically accompanying Alzheimer’s disease, including increased levels of plaque-forming amyloid-beta protein and disease-linked alterations in tau protein.
Further, the study illustrates that choline deficiency in mice causes significant weight gain, and alterations in glucose metabolism, (which are tied to conditions such as diabetes), and deficits in motor skills.
In the case of humans, “it’s a twofold problem,” according to Ramon Velazquez, senior author of the study and Assistant professor with the ASU-Banner Neurodegenerative Disease Research Center. “First, people don’t reach the adequate daily intake of choline established by the Institute of Medicine in 1998. And secondly, there is vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions.”
Ramon Velazquez led the new study on the importance of dietary choline for the brain and other organs. He is a researcher in the ASU-Banner Neurodegereative Disease Research Center.

The research highlights a constellation of physical and neurological changes linked to choline deficiency. Sufficient choline in the diet reduces levels of the amino acid homocysteine, which has been recognized as a neurotoxin contributing to neurodegeneration and is important for mediating functions such as learning and memory, through the production of acetylcholine.
The growing awareness of choline’s importance should encourage all adults to ensure proper choline intake. This is particularly true for those on plant-based diets, which may be low in naturally occurring choline, given that foods high in choline are eggs, meats, and poultry.
Plant-based, choline-rich foods, including soybeans, Brussel sprouts and toast can help boost choline in these cases. Further, inexpensive, over-the-counter choline supplements are encouraged to ensure system-wide health and guard the brain from the effects of neurodegeneration.
Brain-boosting nutrient
Choline is needed to produce acetylcholine, a neurotransmitter that plays an essential role in memory, muscle control and mood. Choline also builds cell membranes and helps regulate gene expression. The established recommendations set forth by the Institute of Medicine were based on evidence preventing fatty liver disease in men. New lines of evidence imply that the established recommended daily intake of dietary choline for adult women (425mg/day) and adult men (550mg/day) may not be optimal for proper brain health and cognition. Additionally, ~90% of Americans are not meeting the recommendation levels and may not even be aware that dietary choline is required on a daily basis.

Despite decades of research and billions of dollars invested since the discovery of the devastating ailment over a century ago, there remains no therapy capable of slowing the advance of the illness. Yet, new research findings suggest that environmental and lifestyle changes, including adequate choline, may help protect the brain from Alzheimer’s disease as well as improving overall health.
Velazquez is joined on the study by co-lead authors Nikhil Dave and Jessica Judd. The work is highly interdisciplinary, including researchers from the ASU Biosciences Mass spectrometry facility, and the Translational Cardiovascular Research Center at the University of Arizona College of Medicine in Phoenix, AZ.
“This collaborative work, spanning multiple institutions and surveying the molecular processes of aging at the systems level, adds to the body of evidence produced around the importance of dietary choline in healthy aging,” said Nikhil Dave.
“What I found particularly compelling about this project was that multiple organs, whose malfunction can have implications for brain health, were negatively impacted by a choline deficient diet,” said Jessica Judd.
The research appears in the current issue of the journal Aging Cell.
A prolific and mysterious killer
Alzheimer’s disease is the leading cause of dementia and the fifth leading cause of death among Americans aged 65 and older. Today, Alzheimer’s affects 6.5 million in the U.S. alone and is projected to strike close to 14 million Americans by 2060. By this time, the costs of managing Alzheimer’s are expected to exceed a $20 trillion, threatening the healthcare infrastructure while causing immense suffering.
The accumulation of sticky protein fragments outside neurons, (which form amyloid-beta plaques), and the buildup of an abnormal form of the protein tau within the bodies of neurons (tau tangles) have long been recognized signposts of Alzheimer’s disease. These brain alterations are typically followed by neurodegeneration, involving the damage and destruction of neurons. Plaques are believed to damage cell-to-cell communications in the brain while tangles block the transport of vital nutrients essential for proper cell function and survival.
In addition to amyloid-beta plaques and neurofibrillary tangles, the disease causes cell death in the brain and increasing cognitive impairment. The current work also found dysregulation of proteins in the hippocampus, a key structure affected in Alzheimer’s disease, tied to learning and memory. Both normal and AD mice showed dysregulated proteins in the hippocampus with a choline deficient diet, with the AD model showing severe effects.
Gathering storm
The recent, dramatic increase in Alzheimer’s disease incidence is of grave concern. Although deaths from stroke, heart disease and HIV decreased between 2000 and 2019, deaths from Alzheimer’s increased more than 145%. In addition to the toll on patients caused by the disease, Alzheimer’s has placed an immense burden on those caring for the sick. In 2021 alone, 16 billion hours of care were provided by over 11 million family members and other unpaid caregivers.
The first outward symptoms of the disease are usually related to language, memory, and thinking problems, as brain regions associated with these tasks tend to be among the first affected. Yet researchers now know that by the time the disease causes observable symptoms, it has been quietly ravaging the brain for 20 years or more.
Many factors contribute to the development of Alzheimer’s disease, from genetic predisposition to age, lifestyle and environmental influences. For reasons that remain murky, females face an increased risk of developing the disease.
Recent studies have identified diet as a significant factor associated with preventing cognitive decline. In earlier research, Velazquez and his colleagues demonstrated that when mice were fed a high choline diet, their offspring showed improvements in spatial memory, compared with a normal choline regimen in the womb. Intriguingly, the beneficial effects of choline supplementation are transgenerational, not only protecting mice receiving choline supplementation during gestation and lactation, but also the subsequent offspring of these mice, suggesting inherited modifications in their genes.
Subsequent studies in the Velazquez lab showed that choline administered to female mice throughout life yielded improvements in spatial memory, compared with those receiving a normal choline regimen.
Multifaceted effects
The new study examines mice at 3-12 months or early to late adulthood, (roughly equivalent to 20-60 years of age for humans). In the case of both normal and transgenic mice displaying symptoms of Alzheimer’s, those exposed to a deficient choline diet exhibited weight gain and adverse effects to their metabolism. Damage to the liver was observed through tissue analysis, as well as enlargement of the heart. Elevated soluble, oligomeric and insoluble amyloid-beta protein were detected as well as modifications to tau protein characteristic of those leading to neurofibrillary tangles in the brain.
Further, choline deficient mice performed poorly in a test of motor skills, when compared with mice receiving adequate choline in their diet. These adverse effects were heightened in the transgenic mice. Translating these findings to humans, this implies that people who are predisposed to Alzheimer’s disease or in the throes of the illness should ensure they are getting enough choline.
The study also involved a detailed exploration of proteins in the hippocampus, an area of the brain acutely affected by Alzheimer’s disease, as well as proteins detected in blood. Dietary choline deficiency altered important hippocampal networks. These pathologies include disruption of pathways associated with microtubule function and postsynaptic membrane regulation — both essential for proper brain function. In blood, proteins produced in the liver that play a role in metabolic function were particularly dysregulated with the choline deficient diet.
“Our work provides further support that dietary choline should be consumed on a daily basis given the need throughout the body,” Velazquez says.
Ultimately, controlled human clinical trials will be essential for establishing the effectiveness and appropriate dosages of choline, before encouraging lifelong choline supplementation. Nevertheless, the powerful new findings offer hope that choline may be one tool in the arsenal needed to defend the brain from neurodegeneration and age-related cognitive decline.