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For chronic conditions such as rheumatoid arthritis, treatment often involves lifelong injections. Fear of needles, injection-associated infection and pain are responsible for patients skipping doses, which encourages the development of new delivery strategies that combine efficacy with limited side effects to treat patients adequately.
Researchers at Baylor College of Medicine and collaborating institutions have explored a better way of delivering medications that does not require injections but could be as easy as swallowing a pill. The study appears in the Proceedings of the National Academy of Sciences.
“People don’t like to have injections for the rest of their lives,” said co-corresponding author Dr. Christine Beeton, professor of integrative physiology at Baylor. “In the current work, we explored the possibility of using the probiotic bacteria Lactobacillus reuteri as a novel oral drug delivery platform to treat rheumatoid arthritis in an animal model.”
Previous work from the Beeton lab had shown that a peptide, or short protein, derived from sea anemone toxin effectively and safely reduces disease severity in rat models of rheumatoid arthritis and patients with plaque psoriasis. “However, peptide treatment requires repeated injections, reducing patient compliance, and direct oral delivery of the peptide has low efficacy,” Beeton said.
Beeton joined forces with Dr. Robert A. Britton, professor of molecular virology and microbiology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. The Britton lab has developed the tools and expertise to genetically modify probiotic bacteria to produce and release compounds. In the current study, the team bioengineered the probiotic L. reuteri to secrete peptide ShK-235 derived from sea anemone toxin.
They chose L. reuteri because these bacteria are indigenous to human and other animal guts. It is one of the lactic acid bacteria groups that has long been used as a cell factory in the food industry and is recognized as safe by the U.S. Food and Drug Administration. L. reuteri has an excellent safety profile in infants, children, adults and even in an immunosuppressed population.

“The results are encouraging,” Beeton said. “Daily delivery of these peptide-secreting bacteria, called LrS235, dramatically reduced clinical signs of disease, including joint inflammation, cartilage destruction and bone damage in an animal model of rheumatoid arthritis.”
The researchers followed bacteria LrS235 and the peptide ShK-235 it secretes inside the animal model. They found that after feeding rats live LrS235 that release ShK-235, they could detect ShK-235 into the blood circulation.
“Another reason we chose L. reuteri is that these bacteria do not remain in the gut permanently. They are removed as the gut regularly renews its inner surface layer to which the bacteria attach,” Beeton said. “This opens the possibility for regulating treatment administration.”
More research is needed to bring this novel drug delivery system into the clinic, but the researchers anticipate that it could make treatment easier for patients in the future. “These bacteria could be stored in capsules that can be kept on the kitchen counter,” Beeton said. “A patient could take the capsules when on vacation without the need of refrigeration or carrying needles and continue treatment without the inconvenience of daily injections.”
The findings provide an alternative delivery strategy for peptide-based drugs and suggest that such techniques and principles can be applied to a broader range of drugs and the treatment of chronic inflammatory diseases.
Other contributors to this work include Yuqing Wang, Duolong Zhu, Laura C. Ortiz-Velez, Jacob L. Perry, Michael W. Pennington and Joseph M. Hyser. The authors are affiliated with Baylor College of Medicine, Pana Bio, Inc. or Ambiopharm Inc.
This project was funded in part by a pilot grant from the Alkek Center for Metagenomics and Microbiome Research at Baylor College of Medicine and by Bridge Funding from Baylor College of Medicine. The work also was supported in part by the Cancer Prevention and Research Institute of Texas (RP180672, RP150578 and RP1806721 and RP170719), the National Institutes of Health (DK56338, CA125123, HG006348 and RR024574), the Dan L Duncan Comprehensive Cancer Center and the John S. Dunn Gulf Coast Consortium for Chemical Genomics.

For many people, keeping a healthy body weight can be a challenge. According to the Centers for Disease Control and Prevention, among adults 20 years-old and over, the prevalence of obesity is 42% in the U.S. Obesity-related conditions, including heart disease, stroke, type 2 diabetes and certain types of cancer, are among the leading causes of preventable, premature death.
Looking to find strategies to help people reach and maintain a healthy weight, researchers at Baylor College of Medicine, the Second Xiangya Hospital of Central South University-China and the University of Texas Health Science Center at San Antonio investigated how the activity of the hormone leptin, which is involved in controlling appetite and energy expenditure, is regulated. Working with mouse models, the team discovered that the protein Grb10 promotes leptin activity in the brain, opening the possibility of developing Grb10-based new approaches to treat obesity. The study appears in Nature Metabolism.
The fat tissue-brain connection
One way the body controls its weight is with leptin, which is produced by fat tissue. The more fat tissue the body has, the more leptin it produces. Leptin travels to the brain where it informs specialized neurons of the amount of fat stored in the body. Large amounts of leptin tell the brain there is a large fat storage. In response, the brain triggers behaviors that suppress appetite and increase energy use, which lead to a reduction of fat tissue and weight loss. When all works well, this leptin-mediated feedback loop between the fat tissue and the brain results in sustained healthy body weight.
“Leptin’s ability to prevent excessive body weight gain by inhibiting appetite and simultaneously enhancing energy expenditure made it a promising therapeutic approach to treat obesity,” said co-corresponding author Dr. Yong Xu, professor of pediatrics- nutrition and molecular and cellular biology at Baylor. “Unfortunately, leptin supplementation strategies often turned out to be ineffective in most cases of diet-induced obesity, partly due to the development of leptin resistance, a state in which circulating leptin level remains high but it fails to suppress food intake and body weight gain.”
In the current study, Xu and his colleagues looked for molecules that would regulate leptin activity and could potentially be used to overcome leptin resistance. The team discovered that the protein Grb10 is a new regulator of leptin activity.
“We found that Grb10 promotes leptin activity,” Xu said. “One feature of Grb10 that separates it from previously discovered leptin regulators is its mode of action. Grb10 binds directly to the leptin receptor on neurons, forming a complex. The binding enhances leptin signaling and helps decrease food intake and increase energy expenditure. Other regulators do not bind to the leptin receptor but to other molecules downstream.”
After eliminating Grb10 in leptin-responsive neurons in the brain of mice, the animals ate more or reduced energy expenditure and gained weight. Increasing Grb10, on the other hand, had beneficial effects — it helped animals decrease food intake, increase energy expenditure and lose weight. “These results suggest that enhancing Grb10 activity may provide a means to increase leptin signaling and help lose weight,” Xu said. “Our findings support further investigations into the possibility of developing a Grb10-based treatment for obesity.”
Going forward, the team is interested in further investigating Grb10’s mechanism of action in the brain. “Leptin also can regulate mood and other emotional states,” Xu said. “We want to know whether Grb10 is involved in regulating mood via interaction with leptin receptor.”
Other contributors to this work include Hailan Liu, Yang He, Juli Bai, Chuanhai Zhang, Feng Zhang, Yongjie Yang, Hairong Luo, Meng Yu, Hesong Liu, Longlong Tu, Nan Zhang, Na Yin, Junying Han, Zili Yan, Nikolas Anthony Scarcelli, Kristine Marie Conde, Mengjie Wang, Jonathan Carter Bean, Camille Hollan Sidell Potts, Chunmei Wan, Fang Hu and co-corresponding author Feng Liu. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Second Xiangya Hospital of Central South University-China and the University of Texas Health Science Center at San Antonio.
Investigators involved in this work were supported by grants from the USDA/ARS (51000-064-01S and a fellowship award), National Nature Science Foundation of China (8173022, 31871180), National Key R&D Program of China (2020YFA0803604) and the American Heart Association.
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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

A clinical research team from the Department of Paediatrics and Adolescent Medicine and the Department of Obstetrics and Gynaecology, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKUMed) leads the discovery of applying amniotic fluid cells obtained during 16-24 weeks of pregnancy as a novel sample type for RNA-sequencing in prenatal diagnosis to help more families with tailored clinical management. It is the first proof-of-concept study to demonstrate the potential clinical utility of amniotic fluid cells RNA-sequencing in the literature. The ground-breaking findings have been published in the academic journal, npj Genomic Medicine.
Rare diseases are usually genetic in origin. Although individually rare, collectively rare diseases were found to be 1 in 67 in the Hong Kong population, based on the team’s previous study.The identification of genetic cause in rare diseases can provide accurate counselling for better clinical management and future pregnancy planning, which is essential to support the patients. Current technologies for prenatal diagnosis are largely DNA-based, with a large proportion (60-70%) remains undiagnosed, leading to clinical uncertainty and parental anxiety. Recently, RNA-sequencing has been found to increase diagnostic yield by 10% to 36%, however, none of these studies focused on prenatal diagnosis. In addition, in spite of the availability of well-established large database cataloging the gene expression profile of different tissues for adult, similar publicly-available dataset for amniotic fluid cells reflecting the embryological and fetal stage is lacking. Further study and research on RNA-sequencing in prenatal setting is thus necessary.
The research team demonstrated the potential clinical utility of amniotic fluid cells RNA-sequencing. A baseline for gene expression profile of amniotic fluid cells is established by performing RNA-sequencing on over 50 amniotic fluid samples. Establishment of gene expression profile is an essential step in applying RNA-sequencing to the current selected clinical diagnosis workflow. They found that the number of well-expressed genes in amniotic fluid cells was comparable to other clinically accessible tissues commonly used for genetic diagnosis across different disease categories. The research team also compared RNA-sequencing data of four affected fetuses with structural congenital anomalies with the established baseline to detect potential outliers. In collaboration with the Technical University of Munich in Germany, a bioinformatics pipeline was adapted to enhance the detection of outliers for subsequent analysis. Further in-depth curation showed that outliers can be identified in genes associated with the corresponding structural congenital anomalies in all four affected fetuses. Identifying the outliers provide more evidence at the RNA level to help diagnosis.
The findings of this study have significant implications in solving undiagnosed rare diseases in Hong Kong. It is the first time that amniotic fluid cells RNA-sequencing is reported to provide potential clinical utility in prenatal diagnosis in literature. With the identification of the genetic cause, precision medicine such as tailored clinical management and preimplantation genetic diagnosis for families with family history is possible.
This study was selected as the ‘Reviewers’ Choice Abstract’ (top 10% of poster abstract) at the American Society of Human Genetics (ASHG) Annual Meeting 2022, one of the largest conferences of its kind, in which scientists from around the world are selected to present their cutting-edge research findings collaboratively . ‘It is an honour for HKUMed poster to be selected and scored as the top 10% of poster abstracts in this international conference. RNA-sequencing has great potential in solving unexplained genetic disorders. We will continue to strengthen ties and collaborations with institutions in Hong Kong and abroad, contribute to international scientific research and bring benefits back to our local patients,’ said Dr Brian Chung Hon-yin, Clinical Geneticist, Clinical Associate Professor, Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, HKUMed.
Dr Anita Kan Sik-yau, Honorary Clinical Associate Professor, Department of Obstetrics and Gynaecology, School of Clinical Medicine, HKUMed cum Deputy Laboratory Director of the Prenatal Diagnostic Laboratory at Tsan Yuk Hospital added, ‘On the memorable occasion of Tsan Yuk Hospital (TYH)’s 100th Anniversary, this study demonstrated TYH’s exceptional service for Hong Kong over the past century, and continuous effort to contribute to all those in need, alongside innovative research.’
Research team
This research was led by Dr Brian Chung Hon-yin, Clinical Associate Professor, Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, HKUMed; Dr Anita Kan Sik-yau, Honorary Clinical Associate Professor, Department of Obstetrics and Gynaecology, School of Clinical Medicine, HKUMed. Mianne Lee, MPhil candidate, and Dr Anna Kwong Ka-yee, Assistant Research Officer, Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, HKUMed are the first authors.
Other contributors included Dr Christopher Mak Chun-yu, Martin Chui Man-chun, Jeffrey Chau Fong-ting, Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, HKUMed; Dr Kelvin Chan Yuen-kwong, Dr Sandy Au Leung-kuen and Lo Hei-man, Department of Obstetrics and Gynaecology, School of Clinical Medicine, HKUMed. International collaborators were Professor Julien Gagneur and Dr Vicente A Yépez from Department of Informatics, Technical University of Munich, Garching, Germany.
This study was supported by The Society for the Relief of Disabled Children, Health and Medical Research Fund of the Health Bureau, the Government of the Hong Kong Special Administrative Region and the Mr and Mrs Edward CM Wong Foundation.

Myocarditis, a condition in which the heart muscle becomes inflamed, is a rare complication that can occur after mRNA COVID vaccination. It’s estimated that roughly 18 cases occur in every 1 million vaccine doses administered, making it so rare that it is challenging to find cases to investigate. In a new study by researchers from Mass General Brigham’s founding members, Brigham and Women’s Hospital and Massachusetts General Hospital, a team extensively investigated the immune response of 16 adolescents and young adults who developed myocarditis after receipt of the COVID mRNA vaccine. The researchers found no differences in antibody production, auto-antibodies, T cell profiles, or prior viral exposures, but found elevated levels of spike protein along with increased cytokines (consistent with innate inflammation) and increased troponin (indicating cardiac injury). Their results are published in Circulation.
“The risk of developing severe disease from acute infection significantly outweighs this rare risk,” said co-corresponding author Lael Yonker, MD, a pediatric pulmonary medicine specialist at Mass General for Children. “While this finding helps us better understand this potential complication, it does not alter the risk benefit ratio of receiving the COVID vaccines. The incidence of myocarditis and other heart-related complications among children infected with SARS-CoV-2 is much higher than the risk of post-vaccination myocarditis.”
Patients with myocarditis can be treated with steroids to reduce inflammation, and there are largely favorable early outcomes for young adults and adolescents who develop this condition after vaccination. The new study may point to additional ways to treat and improve outcomes for patients with post-vaccination myocarditis.
“Understanding the mechanisms that drive post-vaccine myocarditis could guide vaccine development in the future and give us important insights about the immune response,” said co-corresponding author David Walt, PhD, a professor in the Brigham’s Department of Pathology. “This was a precious sample set because these cases are so rare. We studied them in great depth, which led to an interesting finding that could guide treatment strategies to reverse post-vaccine myocarditis.”
Yonker, Walt and colleagues examined blood samples collected from 61 adolescents and young adults, including 16 who developed myocarditis and 45 who had no complications following vaccination with either the Pfizer BNT162b2 or Moderna mRNA-1273 COVID-19 mRNA vaccines. The team performed antibody profiling, including testing for SARS-CoV-2 specific humoral responses and assessment for autoantibodies or antibodies against the human relevant virome, SARS-CoV-2-specific T cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Antibody responses and T cell responses were essentially indistinguishable between cases and controls. Using Simoa, an ultrasensitive test for detecting single molecules, the team found that adolescents who developed myocarditis had markedly higher levels of full-length Spike protein in their blood. Adolescents in the asymptomatic, vaccinated control group had no detectable Spike protein. The team also looked for anti-N IgG, an immunological marker of recent SARS-CoV-2 infection, which was undetectable, suggesting that natural infection was unlikely a contributing factor.
While the study adds new insights about post-vaccination myocarditis, the authors note it is limited by a small sample size and cannot distinguish between cause and consequence; that is, it’s unknown whether the Spike protein itself is causing inflammation to the heart muscle or is a biomarker of immune dysregulation that leads to myocarditis.
“In most cases, post-vaccination myocarditis is mild and self-resolving,” said Yonker. “But new insights about its cause could further help us to improve patients’ symptoms or prevent this complication from occurring.”
Disclosures: David Walt has a financial interest in Quanterix Corporation, a company that develops an ultrasensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company, and also serves on its Board of Directors. Galit Alter has been employed by Moderna since Oct 2022; her contributions to this manuscript preceded her employment by Moderna. Alter is also a founder and equity holder of Seromyx Systems, a company developing a platform technology to profile antibody immunity. Boris Juelg and Alter are employees and equity holders of Leyden Labs, a company developing pandemic prevention therapeutics. Adrienne Randolph received funding (to Boston Children’s Hospital) from the US Center for Disease Control and Prevention to study COVID-19 complications in children outside of this work.
Funding: This research was supported by the National Institutes of Health: National Heart, Lung, and Blood Institute (5K08HL143183), the National Institute of Diabetes and Digestive and Kidney Diseases (DK104344), National Institute of Child Health and Human Development (R01HD100022-02S2), National Institute of Allergy and Infectious Diseases (3R01AI072726-10S1, 3R37AI080289-11S1, R01AI146785, U19AI42790-01,U19AI135995-02, 1U01CA260476-01, CIVIC75N93019C00052), The Chleck Family Foundation and Barbara and Amos Hostetter.
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Published18 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Sam CabralBBC NewsRetail pharmacies in the US can dispense the abortion pill mifepristone for the first time, under a new rule change by the Biden administration.Patients currently obtain mifepristone – part of a two-drug regimen that is safe and effective in inducing abortion – in person from a health provider.A prescription is still required under the new rule, but patients can now pick up the pill in-store or by mail order.The move could significantly expand access to abortion through medication.Abortion pills have become more sought after in the wake of last year’s Supreme Court decision overturning the federal right to abortion, with several states banning or sharply restricting access to abortion. More than half of US abortions are already done with pills rather than by surgery, according to the pro-choice Guttmacher Institute.In December 2021, the US Food and Drug Administration (FDA) had said it would permanently lift the requirement for patients to obtain a prescription in person via a healthcare provider, as part of its pandemic-driven move toward telemedicine.On Tuesday, the FDA updated its website with the new requirements, saying the drug “can be dispensed by certified pharmacies or by or under the supervision of a certified prescriber”.Danco Laboratories and GenBioPro, the two US companies who make the drug, confirmed in separate statements that the agency had informed them of its decision.The move has been hailed as “an important step” forward by the American College of Obstetricians and Gynecologists.”Although the FDA’s announcement today will not solve access issues for every person seeking abortion care, it will allow more patients who need mifepristone for medication abortion additional options to secure this vital drug,” the organisation said in a statement.Mifepristone is taken in combination with a second drug called misoprostol, typically taken within 10 to 12 weeks of pregnancy to induce what is known as medication abortion. Misoprostol, which is commonly used for miscarriage management, is not a restricted drug and can easily be obtained at pharmacies via prescription. Pharmacies – from large chains to corner drugstores – can now apply for certification to distribute mifepristone, which will allow them to directly service customers with a prescription from a certified prescriber. Drug chains CVS and Walgreens have both said they are reviewing the new requirements.But the political landmines surrounding abortion are likely to influence whether or not, and where, pharmacies will offer the pill.Women in the more than dozen states where abortion has been banned will also likely need to travel to other states to obtain medication abortion.

Mifepristone, the first of two drugs in medication abortions, previously had to be dispensed only by clinics, doctors or a few mail-order pharmacies. Now, if local drugstores or chains like CVS agree to certain rules, they can provide it.For the first time, retail pharmacies, from corner drugstores to major chains like CVS and Walgreens, will be allowed to offer abortion pills in the United States under a regulatory change made Tuesday by the Food and Drug Administration. The action could significantly expand access to abortion through medication.Until now, mifepristone — the first pill used in the two-drug medication abortion regimen — could be dispensed only by a few mail-order pharmacies or by specially certified doctors or clinics. Under the new F.D.A. rules, patients will still need a prescription from a certified health care provider, but any pharmacy that agrees to accept those prescriptions and abide by certain other criteria can dispense the pills in its stores and by mail order.The change comes as abortion pills, already used in more than half of pregnancy terminations in the U.S., are becoming even more sought after in the aftermath of last year’s Supreme Court decision overturning the federal right to abortion. With conservative states banning or sharply restricting abortion, the pills have increasingly become the focus of political and legal battles, which may influence a pharmacy’s decision about whether or not to dispense the medication.The F.D.A. did not issue an announcement but updated its website to reflect the decision and added to a series of questions and answers. The two makers of the pill, Danco Laboratories and GenBioPro, released statements saying the agency had informed them of the action.The action is the latest step taken by the federal government to expand access to abortion pills by easing some of the restrictions that have applied to mifepristone since it was approved in 2000.In December 2021, the F.D.A. said it would permanently lift the requirement that patients obtain mifepristone in person from a health provider, a step that paved the way for telemedicine abortion services which conduct medical consultations with patients by video, phone or online questionnaires and then arrange for them to receive the prescribed pills by mail.On Tuesday, the F.D.A. officially removed the in-person requirement from its regulatory rule book for mifepristone, leaving in place the remaining two requirements: that health providers be certified to show they have the knowledge and ability to treat abortion patients and that patients complete a consent form.More on Abortion Issues in AmericaWhen Does Life Begin?: We explore the question at the heart of America’s abortion debate, one that pushes the limits of politics, science, religion and philosophy.Morning-After Pills: The Food and Drug Administration revised its guidance on the most commonly used emergency contraceptives, making clear they are not abortion pills.Abortion Pills: In a move that could significantly expand access to medication abortions, the F.D.A. moved to allow retail pharmacies to offer abortion pills in the United States.‘Parental Involvement’ Laws: As abortion access dwindles in America, these laws weigh heavily on teenagers — who may need a court’s permission to end their pregnancies.Mifepristone, which blocks a hormone necessary for pregnancy development, is authorized by the F.D.A. to be taken in the first 10 weeks of pregnancy, although many clinics and telemedicine providers have begun offering it up to 12 or 13 weeks into pregnancy, a step they can legally take because there is scientific evidence that the pills are safe and effective in that time frame.The second drug in the regimen, misoprostol, has never been as tightly restricted as mifepristone and is used for many different medical conditions; it is easily obtained at pharmacies through a typical prescription process. Misoprostol, which causes contractions that expel pregnancy tissue, is taken 24 to 48 hours after mifepristone.Tuesday’s action is a result of an agreement between the F.D.A. and the companies that make the pills. The agreement was worked out in negotiations that took about a year and considered issues such as whether to allow pharmacies to offer the pills in stores or only via mail order and how to keep the identity of prescribing doctors confidential to protect their privacy and safety, according to people familiar with the discussions.Whether large pharmacy chains and local drugstores would opt to make the pills available was not immediately clear Tuesday. A spokesman for Walgreens, Fraser Engerman, said the company would review the F.D.A.’s decision and would “continue to enable our pharmacists to dispense medications consistent with federal and state law.”.css-1v2n82w{max-width:600px;width:calc(100% – 40px);margin-top:20px;margin-bottom:25px;height:auto;margin-left:auto;margin-right:auto;font-family:nyt-franklin;color:var(–color-content-secondary,#363636);}@media only screen and (max-width:480px){.css-1v2n82w{margin-left:20px;margin-right:20px;}}@media only screen and (min-width:1024px){.css-1v2n82w{width:600px;}}.css-161d8zr{width:40px;margin-bottom:18px;text-align:left;margin-left:0;color:var(–color-content-primary,#121212);border:1px solid var(–color-content-primary,#121212);}@media only screen and (max-width:480px){.css-161d8zr{width:30px;margin-bottom:15px;}}.css-tjtq43{line-height:25px;}@media only screen and (max-width:480px){.css-tjtq43{line-height:24px;}}.css-x1k33h{font-family:nyt-cheltenham;font-size:19px;font-weight:700;line-height:25px;}.css-1hvpcve{font-size:17px;font-weight:300;line-height:25px;}.css-1hvpcve em{font-style:italic;}.css-1hvpcve strong{font-weight:bold;}.css-1hvpcve a{font-weight:500;color:var(–color-content-secondary,#363636);}.css-1c013uz{margin-top:18px;margin-bottom:22px;}@media only screen and (max-width:480px){.css-1c013uz{font-size:14px;margin-top:15px;margin-bottom:20px;}}.css-1c013uz a{color:var(–color-signal-editorial,#326891);-webkit-text-decoration:underline;text-decoration:underline;font-weight:500;font-size:16px;}@media only screen and (max-width:480px){.css-1c013uz a{font-size:13px;}}.css-1c013uz a:hover{-webkit-text-decoration:none;text-decoration:none;}What we consider before using anonymous sources. Do the sources know the information? What’s their motivation for telling us? Have they proved reliable in the past? Can we corroborate the information? Even with these questions satisfied, The Times uses anonymous sources as a last resort. The reporter and at least one editor know the identity of the source.Learn more about our process.The steps for pharmacies to become certified to dispense mifepristone are not difficult, but they involve some administrative requirements that go beyond the process pharmacies use with most other medications, such as designating an employee to ensure compliance. Given the time and resources required by those steps, some pharmacies may not consider it worthwhile to offer a medication that only a small percentage of their customers may use.But while abortion pills may constitute a small percentage of a pharmacy’s sales, they could have a big impact on its public profile. Calculations about public perception and the highly polarized political landscape are also likely to influence a pharmacy’s decision.In about half the states, abortion bans or restrictions would make it illegal or very difficult for pharmacies to provide abortion pills. In states where abortion remains legal, pharmacies may face customer demand for the medication or public pressure from abortion rights advocates and health providers. National chains could decide to offer the medication in those states while not providing it in their stores in restrictive states.Reaction from advocates on both sides of the abortion debate reflected the country’s deep divisions.“The Biden administration has once again proved that it values abortion industry profits over women’s safety and unborn children’s lives,” said Marjorie Dannenfelser. the president of Susan B. Anthony Pro-life America. “Abortion activists want to turn every post office and pharmacy into an abortion business, and the Biden F.D.A. is a willing participant.” Kirsten Moore, the director of the Expanding Medication Abortion Access project, said: “By allowing brick-and-mortar pharmacies to dispense medication abortion care, the F.D.A. is treating medication abortion like the safe, effective, time-sensitive care that it is.”Mifepristone is currently only approved for abortion. But it is also used in the treatment of some miscarriages, and there may be pressure for pharmacies to dispense it for that purpose as well. Recently, dozens of groups, including the American College of Obstetricians and Gynecologists and the American Medical Association, filed a citizen petition asking the F.D.A. to take action to make it easier for mifepristone to be used for miscarriages.An official with Danco, which for years was the only company to produce the medication, branded as Mifeprex, said the company expected that smaller independent pharmacies might be first to dispense the drug and that it might take the bigger chains longer, partly because of the logistics involved in complying with the requirements.The official, who spoke on the condition of anonymity because of the company’s concerns about threats from abortion opponents, said that one logistically intricate step for big chains would be implementing the companies’ requirement that pharmacies keep confidential the names of health providers who prescribe mifepristone. A chain like CVS would not be able to list a doctor’s name in a companywide database, for example, and would have to keep that information restricted to the store that fills that doctor’s prescriptions, the Danco official said.She predicted that early adopters might include small pharmacies that typically serve university health services or retail pharmacies on hospital campuses, adding that the company wasn’t expecting a boom in sales from the rule change. She said it was also possible that more health care providers would decide to become prescribers if they could now write prescriptions that pharmacies could fill instead of having to stock the medication themselves.“For some people, this is going to be a huge improvement on their ability to access the drug and be able to even consider this as a choice for themselves,” the Danco official said. “For other people, not necessarily. Maybe they don’t want to go into their small mom-and-pop pharmacy. They’d rather receive it from a mail order where there’s just no interaction that way.”Evan Masingill, the chief executive of GenBioPro, which makes the generic version of mifepristone, said in a statement: “Today’s F.D.A. announcement expands access to medications that are essential for reproductive autonomy and is a step in the right direction that is especially needed to increase access to abortion care.”

Cardiac doctors say that blows to the chest causing an erratic heart rhythm are highly unusual, but not unheard-of in sports.A freakish accident may explain the cause of the cardiac arrest that sent Damar Hamlin of the Buffalo Bills to the ground during a football game on Monday night, five cardiac experts said.It is not yet known why Mr. Hamlin’s heart stopped about nine minutes into the game against the Cincinnati Bengals. But his youth, health and other circumstances could mean that a blow to his chest during a collision with a receiver on the opposing team sent his heart into an erratic rhythm known as an arrhythmia.Dr. Aaron Baggish, a sports cardiologist at Harvard Medical School who has worked with the New England Patriots, cautions that, while a blow to the chest “is definitely a front-runner” to explain what occurred on Monday, “it is premature to be definite.” Mr. Hamlin, he said, will most likely undergo extensive testing to be sure there was no other cause.For an arrhythmia to occur, there has to be what Dr. Baggish called “a perfect storm” — the chest must be struck in a precise place at a precise moment while the heart is relaxing after squeezing out blood, and with the right amount of force.“It’s not rare, but it’s pretty unusual,” said Dr. Michael Mack, the chairman of cardiovascular services at Baylor Scott & White Health in Dallas. Most documented incidents have occurred in baseball when a player has been struck in the chest by a ball, and it has also occurred in lacrosse and hockey. Chest protectors did not prevent the incidents in those sports. Dr. Baggish said he would not count on football pads either, saying that to his knowledge, “no commercially marketed pads for any sport guarantee complete protection.”More on Damar Hamlin’s CollapseA ‘True Leader’: As a professional football player and community mentor, Damar Hamlin has reached two of his life goals: making it to the N.F.L. and helping others along the way.N.F.L.’s Violent Spectacle: The appetite for football has never been higher, even as viewers look past the sport’s toll on players’ lives. Mr. Hamlin’s collapse should force a reconsideration, our columnist writes.Football’s Pull: After Mr. Hamlin’s collapse, fans, coaches and players processed what it meant to love a sport that carries the risk of bodily harm for its participants.Faith and Football: The outpouring of public piety from players and fans shows how Christianity is embedded in N.F.L. culture in a way that goes beyond most sports.Dr. Mack added that “the force of a blow can go right through” a pad.There is just a 20-millisecond interval in the heart’s cycle when a strong blow can cause an arrhythmia, said Dr. Javid Moslehi, a cardiologist at the University of California San Francisco School of Medicine.Shortly after Mr. Hamlin, 24, collapsed, medical personnel at the game administered cardiopulmonary resuscitation for nine minutes as they tried to keep blood moving through his body. When his heart rhythm was restored, they took Mr. Hamlin to the University of Cincinnati Medical Center, where he remains in critical condition.Damar HamlinDuane Burleson/Associated PressIt is normal to put patients like Mr. Hamlin on a respirator, Dr. Mack said. But, he added, “if he is still on the respirator today, that means he has not awakened.”The concern is whether, during those long minutes before Mr. Hamlin’s heart rhythm returned, when his heart was not pumping normally, a lack of blood damaged his brain, heart experts said. If a patient in cardiac arrest does not recover right away, doctors will often induce a coma to give the brain a chance to rest, Dr. Mack said. Sometimes doctors also cool the brain to slow its metabolism while it recovers, using cooling blankets — which have coils that circulate chilled water — and headpieces.“The more concern there is about brain injury, the more aggressive doctors are about sedation and hypothermia,” Dr. Mack added. If Mr. Hamlin remains unconscious from 72 to 96 hours after his cardiac arrest, “there is a real concern,” Dr. Mack said.Other athletes, like marathoners, have collapsed and even died when their hearts stopped from heart attacks or from arrhythmias caused by underlying heart abnormalities. Some examples, Dr. Mack said, are hypertrophic cardiomyopathy, in which the heart walls are thickened, or long QT syndrome, a heart-signaling disorder.But, though they can’t rule them out, heart experts doubt that Mr. Hamlin has these conditions. Dr. Rajat Deo, an arrhythmia specialist at the Perelman School of Medicine at the University of Pennsylvania, said the N.F.L. extensively tested its athletes and would be expected to find such problems.Cardiac arrests differ from heart attacks, which are caused when an artery supplying blood to the heart is blocked, depriving the organ of blood. That can trigger an arrhythmia or even sudden death.“Could it have been due to a blockage?” asked Dr. Brahmajee Nallamothu, a professor of internal medicine and cardiology at the University of Michigan. “I guess, but probably unlikely in a young guy.”Ken Belson

Salmonella are food-borne pathogens that infect millions of people a year. To do so, these bacteria depend on a complex network of genes and gene products that allow them to sense environmental conditions. In a new paper, researchers have investigated the role of small RNAs that help Salmonella express their virulence genes.
The bacteria infect humans by first invading the cells of the intestine using a needle-like structure, called a type 3 secretion system. This structure injects proteins directly into the cells, setting off a cascade of changes that cause inflammation, and ultimately cause diarrhea. The genes that encode this system, and other genes that are needed for invasion, are found on a region of DNA known as the Salmonella pathogenicity island 1.
“SPI-1 needs to be well controlled,” said Sabrina Abdulla, a graduate student in the Vanderpool lab, and the first author of the study. “If the type 3 secretion system needle apparatus is not made, Salmonella cannot cause an infection, and if too much of the needle apparatus is made, it makes Salmonella sick.”
SPI-1 is controlled by an extensive regulatory network. First, three transcription factors: HilD, HilC, and RtsA, all control their own and each other’s DNA expression. They also activate another transcription factor, HilA, which activates the rest of the SPI-1 genes. If this isn’t complicated enough, SPI-1 also needs to sense a variety of environmental cues and tune the expression of its genes in order to infect its host.
“We have known for a long time that there are a lot of environmental factors that feed into the gene regulation in Salmonella. However, we didn’t know how. That’s when researchers started looking at small RNAs,” Abdulla said.
Small RNAs play a crucial role in determining how genes function in bacterial cells. Typically, these molecules either interact with proteins, or the mRNA, which carries the instructions for making proteins. As a result, sRNAs affect a variety of bacterial functions, including virulence and responses to the environment.

In this paper, the researchers looked at the sRNAs that regulate the hilD mRNA, specifically a sequence on the mRNA called the 3′ untranslated region, a part of the mRNA not involved in making the HilD protein. In bacteria, the 3′ UTRs are usually 50-100 nucleotides long. However, the 3′ UTR of the hilD mRNA was 300 nucleotides long.
“The starting point for my work was the observation that when we deleted the 3′ UTR, the expression of the hilD gene went up 60-fold,” Abdulla said. “We then decided to look for sRNAs that might be interacting with this region.”
The researchers determined that although the sRNAs Spot 42 and SdsR can both target the 3′ UTR, they do so in different regions. “This result suggests that the entire 3′ UTR is important for regulation,” Abdulla said. “We showed that the sRNAs stabilize the hilD mRNA and protect it from being degraded.”
“Such long 3′ UTRs have not been well studied. With more genomic research, people are realizing more and more that these longer regions exist and that they are important for regulation,” Abdulla said.
Using mice, the researchers also looked at whether Spot 42 and SdsR can affect how Salmonella causes infections. They performed mouse competition assays, where they introduced mutant bacteria that lacked the sRNAs and bacteria that contained the sRNAs, to see which strains survive and cause infection. “We found that when the sRNAs are deleted, the bacteria cannot survive in the host. We also showed that the sRNAs play a role in helping SPI-1 invade the host cells,” Abdulla said.
“Now that we know that sRNAs play an important role in controlling SPI-1 through their regulatory effects on the hilD 3′ UTR, we want to extend our studies in two directions. We’d like to understand more about how, at a molecular level, the sRNAs influence hilD mRNA levels. We’d also like to better understand how sRNAs participate in regulating expression of other important SPI-1 genes,” said Cari Vanderpool (MME/IGOH), a professor of microbiology.
The work was supported by the National Institutes of Health, the University of Illinois Department of Microbiology Marie Chow Teaching Scholarship, and the Francis M. and Harlie M. Clark Microbiology Fellowship.

Atherosclerosis is a long-term arterial vessel wall disease characterized by the build- up of lipid- rich and inflamed plaques. It often goes undetected, but highly inflamed plaques disrupt and form a blood clot attached to the vessel wall adjacent to the flowing blood. This acute event (atherothrombosis) can lead to heart attack or stroke.
Boston University investigators, working with researchers from Warren Alpert Medical School of Brown University and the Providence VA Medical Center, now have developed and substantiated an advanced magnetic resonance imaging (MRI) tool to reveal new structural insights into atherothrombosis.
Using an experimental model, they combined magnetic resonance imaging (MRI) and mathematical analysis to architecturally define features of fatty material that forms plaques in the arteries not visualized with conventional MRI or histology alone.
“This method uniquely detects regions of arteries at risk of rupture or atherothrombosis, thus increasing the accuracy of diagnosis and assessment of treatment outcomes in individuals with atherosclerotic disease,” explained corresponding author James A. Hamilton, PhD,professor of physiology & biophysics at Boston University Chobanian & Avedisian School of Medicine.
As atherosclerosis progresses, damaged smooth muscle cells (SMC) become inflamed and disorganized. While current bio-imaging techniques focus mainly on plaque features adjacent to the flowing blood, they are unable to capture highly detailed deeper cellular elements and fibrous disorganization across the entire vessel.
In regions with normal vessel wall and low inflammation, researchers observed long-range coherence of SMC and collagen fiber orientation parallel to the vessel wall, whereas in highly inflamed regions, blood clots and underlying vessels were characterized by highly random properties with many short tracts that were perpendicular to the vessel wall.
According to the researchers, this research represents an important step forward by the Hamilton group, in a decade-long collaborative project that has designed MRI methods to identify high risk plaques that are being testing clinically.
Funding for this study was provided by NHLBI T32 HL007224 to ET and Boston University Nanomedicine pilot grant to JH.
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Recent evidence has emerged to suggest that age-related macular degeneration (AMD) is a clinical risk factor for increased risk for infection and mortality. AMD has been reported to confer higher risk of severe complications of SARS-CoV-2 infection, including respiratory failure and death (25 percent), a risk which is higher than Type 2 diabetes (21 percent) and obesity (13 percent).
Considering these observations, researchers from Boston University Chobanian & Avedisian School of Medicine hypothesized that AMD and COVID-19 share common genetic risk factors and designed and executed a study that identified a novel association of the two diseases with variants in the PDGFB gene. This gene encodes a platelet derived growth factor (PDGF) which has a role in the formation of new blood vessels and is involved in the abnormal blood vessel changes that occur in AMD. They also found that more severe COVID-19 outcomes were associated with AMD likely arising from genetic predisposition to dysfunction involving complement proteins, as well as with a higher level of PDGF in blood serum.
“Our findings add to the body of evidence for the increased risk of infection and mortality from COVID-19 among AMD patients. Our analysis lends credence to previously reported clinical studies that found those with AMD have a higher risk for COVID-19 infection and severe disease, and that this increased risk may have a genetic basis,” explained co-corresponding author Lindsay A. Farrer, PhD, chief of biomedical genetics.
The BU research team conducted a genome-wide search for variants that are jointly associated with AMD and each of three COVID-19 outcomes (infection rate, critical illness and hospitalization) using large genetic datasets that contained tens of thousands of individuals. These datasets were previously assembled and studied separately for genetic factors contributing to the risk of AMD and for each of the COVID-19 disease outcomes. Subsequently, the researchers analyzed publicly available data from patients with AMD or COVID-19 and control groups to assess the association of variants in PDGFB with the gene activity. Finally, they employed an analytical technique that allowed them to investigate causal relationships between PDGFB gene variants, PDGFB concentration in blood, AMD, and COVID-19 outcomes.
According to the researchers, these findings suggest that lowering PDGFB gene activity and serum PDGF concentration may reduce the severity of COVID-19, particularly among older people. “Therapeutic strategies combining anti-VEGF therapy (a current treatment for AMD that limits blood vessel growth in the eye that can harm vision) with antagonists (drugs that bind to receptors) for blocking PDGF signaling have been considered even more effective than the single VEGF treatment and are currently under investigation in clinical trials,” added co-corresponding author Manju L. Subramanian, MD, associate professor of ophthalmology.
The researchers believe this discovery of shared genetic risk factors will require a larger sample size for critical illness and hospitalizations to better understand the shared pathology and risk factors that contribute to worsening clinical outcomes in both disease states.
These findings appear online in the Journal of Clinical Medicine.
This work was supported by National Institutes of Health grants RF1 AG057519, R01 AG069453, R01 AG048927, U19 AG068753, and U01 AG062602.
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