Preventing Premature Birth

Center for Prevention and Early Intervention Home Page

Preventing Premature Birth | Johns Hopkins Medicine

The Center for Prevention and Early Intervention is a collaborative effort between the JHU Bloomberg School of Public Health and our community partners in prevention and early intervention (the Baltimore City Public Schools System, Family League of Baltimore City, Baltimore Mental Health Systems and the Maryland Department of Education), and prevention and early intervention researchers at Morgan State University, Pennsylvania State University, the University of California at Los Angeles, the University of Alabama, Columbia University, and Stanford University. The Center is supported by National Institutes of Mental Health and Drug Abuse.

The mission of the Center is (1) to improve school-based preventive and early treatment interventions for children and adolescents by bridging epidemiologic, intervention, services, and dissemination and training research through the development of a research structure and research strategies capable of evaluating the effectiveness and sustainability of promising and evidence based interventions; (2) to identify factors that inhibit or facilitate improved prevention and treatment practices and outcomes; (3) to disseminate the knowledge gained in order to improve prevention and treatment research and dissemination and training practices; and (4) to develop within our collaborating community partners the capacity to carry out and disseminate state of the art prevention and early intervention research and evaluations.

The Center consists of 4 Cores. The Operations Core provides support to Center collaborators in the following areas: administration, biostatistics, economic analysis, clinical trials, assessment/evaluation, and dissemination and training.

The Research Methods Core is focused on advances in biostatistics, economics, and computerized assessment in support of the Center's intervention initiatives.

The Principal Research Core provides the structure and support for pilot and feasibility studies aimed at setting the stage for school-based, effectiveness trials of promising and evidence-based prevention and early interventions and assessments.

The Research Network Development Core focuses on the development of the infrastructure within our community partners for carrying out state of the art prevention and early intervention research and evaluations.

Support over the life of the Center will make it possible: (1) to strengthen and extend research initiatives aimed at evaluating the effectiveness of evidence-based, early preventive and treatment interventions for children and adolescents and (2) to disseminate research on the prevention and treatment of mental disorders in children and adolescents.

The Center for Prevention and Early Intervention builds on the foundation laid by the Johns Hopkins Prevention Intervention Research Center (1985-2001), which provided the basis for two generations of school-based, preventive intervention field trials in Baltimore and their ongoing follow-ups.

Click here to learn more about the 1st generation JHU PIRC trials and their ongoing follow-ups.

Click here to learn more about the 2nd generation JHU PIRC trials and their ongoing follow-ups.

Source: https://www.jhsph.edu/research/centers-and-institutes/johns-hopkins-center-for-prevention-and-early-intervention/

Johns Hopkins Awarded $2 Million Grant to Reduce Preterm Births – 02/25/2013

Preventing Premature Birth | Johns Hopkins Medicine

The federal government has awarded the Department of Gynecology and Obstetrics at the Johns Hopkins University School of Medicine a $2 million grant to advance methods of preventing premature births.

Johns Hopkins is one of only 27 hospitals nationwide awarded this grant by the U.S. Department of Health & Human Services’ Centers for Medicare & Medicaid Services. The grants are part of a $41.

4 million, four-year initiative called the Strong Start for Mothers and Newborns.

“This initiative will help us find new ways to reduce the rate of preterm births, improve the health outcomes of pregnant women and newborns and decrease the anticipated total cost of medical care during pregnancy and delivery and over the first year of life for children,” says Andrew J. Satin, M.D.

, FACOG, director of the Hopkins gyn/ob department and chair of the Medical Board at Johns Hopkins Bayview Medical Center. “These women and their babies require intensive resources, and this initiative will help us create seamless, enhanced prenatal care for those at high risk at all JHM-affiliated sites.

Every year in Maryland alone, the March of Dimes notes, an estimated 13 percent of babies are born premature. Preterm birth, defined as the birth of a baby of less than 37 weeks gestational age, occurs at a time when infants' brains and lungs are at a critical stage of development.

According to HHS, the Strong Start for Mothers and Newborns award is designed to help recipient medical centers improve prenatal care for high-risk pregnant women and newborns in the areas with the highest preterm birth rates in the country.

The Strong Start effort, part of the new Affordable Care Act, is designed to serve 80,000 women enrolled in Medicaid or the Children’s Health Insurance Program (CHIP) over a three-year period in 32 states, the District of Columbia and Puerto Rico.

Satin adds that the Johns Hopkins Coordinated Antenatal Service Enhancement (J-CASE) will lead his department’s efforts among the Medicaid population of East Baltimore.

The initiative will focus on improved communication among Hopkins entities that provide care and services to pregnant women, and will coordinate all prenatal care through care coordinators embedded in each of the prenatal clinics at Johns Hopkins Bayview Medical Center, the Johns Hopkins Outpatient Center and the Johns Hopkins Community Physicians (JHCP) East Baltimore Medical Center.

The grants will also provide for prenatal group visits, expand access to care and provide psychosocial support to expectant mothers.

“The role of case managers will be expanded so that all patients, even those without traditional high-risk factors for preterm birth, will have a designated case manager available at their prenatal visits to facilitate procurement of any needed community resources,” says Satin. “The goal is to avoid gaps in care, reduce redundancies and improve the quality and experience of prenatal care.”

HHS says some 500,000 infants are born prematurely in the United States annually, a public health issue with significant long-term consequences for both families and children.

Children born preterm require costly medical attention, often require early intervention services and special education and can develop conditions that may affect their health and productivity as adults.

The estimated total cost of preterm birth in the United States annually is approximately $26 billion dollars. 

Source: https://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_awarded_2_million_grant_to_reduce_preterm_births_

Preterm birth prevention drug proves ineffective

Preventing Premature Birth | Johns Hopkins Medicine

Makena is the only drug to date that has been approved by the U.S. Food and Drug Administration (FDA) for preventing recurrent preterm births. Makena’s chemical compund name is 17-alpha-hydroxyprogesterone caproate (17P) and it was approved by the FDA in 2011.

Since then, the drug was endorsed for widespread use by both the American Congress of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine.

More recently, in January 2017, the Society for Maternal-Fetal Medicine repeated its recommendation of 17P in light of the under-utilization of what is deemed an effective drug.

However, a study conducted by researchers at the University of Texas Southwestern Medical Center, has found that the use of 17P had hardly any benefit for expecting mothers with prior preterm births.

Published in the March 2017 issue of the American Journal of Obstetrics and Gynecology, the study details the results of a four year trial from January 2012 to March 2016, during which 430 women with prior preterm births were injected with 17P.

Beginning from 16 to 20 weeks of gestation, pregnant women involved in the study received weekly injections at the Parkland Memorial Hospital in Dallas, Texas.

Having noted the typical rate of 16.8 percent recurrent preterm births at the Parkland Hospital, the researchers evaluated the clinical effectiveness of 17P in reducing the recurrence of premature births.

To compare the premature birth rates, the preterm birth profiles of the study’s participants were matched to similar profiles in the historical cohort.

the mother’s race, body mass index and pregnancy history, 1,290 mothers in the historical control were matched to 430 research participants.

Even after controlling for these demographic factors, 17P did not significantly reduce the rate of recurrent preterm births. In fact, the overall rate of recurrence was higher for the study group treated with 17P at 25 percent.

Researchers observed higher or similar recurrence rates in the 17P study group compared to the historical control for all of the specific pregnancy histories.

For instance, for mothers with one prior preterm birth, the recurrence rate was 31 percent in the 17P study group compared to 18 percent in the historical control.

Moreover, recurrence rates among mothers with three or more preterm births were not statistically different for the 17P group and the historical cohort, which were at 44 percent and 45 percent respectively.

Upon the analysis of blood draws, researchers also discovered that 13.4 percent of the pregnant women treated with 17P were diagnosed with gestational diabetes in contrast to the eight percent of women in the historical control. Researchers found 17P is ineffective at best and at worst, linked to a higher probability of birth complications.

According to the researchers, Makena (17P) was able to receive an accelerated approval from the FDA mostly on the basis of a 2003 study led by Paul J. Meis, a retired professor of obstetrics and gynecology-maternal/fetal medicine at Wake Forest University.

However, questions have been raised following the paper’s publication.

The 2003 study, though completed in two phases, did not include the results of the first phase, which were later reported to have a 36 percent preterm birth recurrence rate in the control group.

On the other hand, the recurrence rate in the control group for the second phase of the study was much higher at 55 percent, leading to speculation that 17P only appeared to be effective because it was compared to an unexpectedly high rate in the control group.

Furthermore, the mechanisms of progestogens, such as 17P, are not well understood. According to the researchers, progestogens were once believed to prevent inflammation in the uterine cervix; however, it was recently discovered that they are not related to reducing the probability of uterine contraction.

On the basis of the 2003 study, pharmaceutical company Lumara Health, formerly KV Pharmaceutical, bought the rights to manufacture 17P and market it under the brand name Makena.

Facing no other competitors, Lumara Health announced the increase of the drug’s cost from $20 to $1,500 per injection in February 2011.

Later that year, Lumara Health lowered the price to $690 per injection, and now, according to Drugs.com, the price is $767.98. In spite of its price gouging, 17P can be found at lower prices ranging from $10 to $25 in the America, albeit in compounded forms at certain pharmacies.

Still, the FDA recommends using the approved Makena  except in cases in which the patient  has an allergy or medical condition that prevents consumption.

However, as shown by the researchers at the UT Southwestern Medical Center, 17P may not be potent with regard to preventing premature births and may introduce additional complications.

Correction: The drug Makena was originally misspelled as Maketna in an earlier version of this article. The News-Letter regrets this error. 

Source: https://www.jhunewsletter.com/article/2017/05/preterm-birth-prevention-drug-proves-ineffective

Johns Hopkins Opens New Center for Psychedelic Research

Preventing Premature Birth | Johns Hopkins Medicine
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Since childhood, Rachael Petersen had lived with an unexplainable sense of grief that no drug or talk therapy could entirely ease. So in 2017 she volunteered for a small clinical trial at Johns Hopkins University that was testing psilocybin, the active ingredient in magic mushrooms, for chronic depression.

“I was so depressed,” Ms. Petersen, 29, said recently. “I felt that the world had abandoned me, that I’d lost the right to exist on this planet. Really, it was my thoughts were so stuck, I felt isolated.”

The prospect of tripping for hours on a heavy dose of psychedelics was scary, she said, but the reality was profoundly different: “I experienced this kind of unity, of resonant love, the sense that I’m not alone anymore, that there was this thing holding me that was bigger than my grief. I felt welcomed back to the world.”

On Wednesday, Johns Hopkins Medicine announced the launch of the Center for Psychedelic and Consciousness Research, to study compounds LSD and psilocybin for a range of mental health problems, including anorexia, addiction and depression.

The center is the first of its kind in the country, established with $17 million in commitments from wealthy private donors and a foundation. Imperial College London launched what is thought to be the world’s first such center in April, with some $3.

5 million from private sources.

“This is an exciting initiative that brings new focus to efforts to learn about mind, brain and psychiatric disorders by studying the effects of psychedelic drugs,” Dr. John Krystal, chair of psychiatry at Yale University, said in an email about the Johns Hopkins center.

The centers at Johns Hopkins and Imperial College give “psychedelic medicine,” as some call it, a long-sought foothold in the scientific establishment.

Since the early 2000s, several scientists have been exploring the potential of psychedelics and other recreational drugs for psychiatric problems, and their early reports have been tantalizing enough to generate a stream of positive headlines and at least two popular books.

The emergence of depression treatment with the anesthetic and club drug ketamine and related compounds, which cause out-of-body sensations, also has piqued interest in mind-altering agents as aids to therapy.

But the drugs’ history of abuse and the still thin evidence base have kept the field largely on the fringes, and many experts are still wary. Psychedelic trials cannot be “blinded” in the same way most drug trials are: participants know when they have been dosed, and reports of improvement aren’t yet standardized.

“It raises the caution that the investigation of hallucinogens as treatments may be endangered by grandiose descriptions of their effects and unquestioning acceptance of their value,” Dr.

Guy Goodwin, a professor of psychiatry at Oxford wrote, in a recent commentary, in the Journal of Psychopharmacology. “Timothy Leary was a research psychologist before he decided the whole world should ‘Turn on, tune in, and drop out.

’ It is best if some steps are not retraced.”

The scientists doing the work, at Hopkins, Imperial College and elsewhere, acknowledge as much, and say the new infusion of funding will help clarify which drugs help which patients, and when the altered states are ineffectual, or potentially dangerous.

“It’s been hand-to-mouth in this field, and now we have the core funding and infrastructure to really advance psychedelic science in a way that hasn’t been done before,” said Roland Griffiths, a neuroscientist at Johns Hopkins who will direct the new center. Dr.

Griffiths said the new funds will cover six full-time faculty, five postdoctoral scientists and the costs of running trials.

Among the first of those trials are a test of psilocybin for anorexia nervosa and of psilocybin for psychological distress and cognitive impairment in early Alzheimer’s disease.

“The one that’s crying out to be done is for opiate-use disorder, and we also plan to look at that,” Dr. Griffiths said.

Trials using psychedelics or other mind-altering drugs tend to have a similar structure.

Participants, whether they have a diagnosis of PTSD, depression or substance abuse, do extensive preparation with a therapist, which includes a complete medical history and advice and information about the study drug.

People with a history of psychosis are typically excluded, as psychedelics can exacerbate their condition. And those on psychiatric medications usually taper off beforehand.

On treatment day, the person comes into the clinic, takes the drug and sits or lies down, under continuous observation by a therapist, who provides support and occasional guidance as the drug’s effects become felt. In the Johns Hopkins trial that Ms. Petersen joined, participants wore eyeshades and headphones, lay down and listened to music.

“The first trip lasted six and half hours, and I didn’t move,” she recalled. A week later, she returned for another dose; each dose was about twice what recreational users take. Therapy using psychedelics or other mind-altering compounds typically involves just one or two sessions on the drug.

“I would be lying if I said aspects of my experience weren’t deeply challenging and upsetting,” Ms. Petersen said. “The therapist would grab my hand — would save me in a moment — and encourage me to adopt a posture of welcoming everything, a meditation.”

The literature so far, from trials these, suggests that psilocybin is promising for chronic depression and addiction, and that M.D.M.A., or ecstasy, can help people with post-traumatic stress, including veterans. Cannabis and LSD also have been tried, for addiction and other problems, with mixed results.

One finding many drug studies share is that any positive effects are far more ly to last if the participant has an especially intense trip. The intensity is subjectively graded using a variety of measures, including what scientists call the MEQ, for “mystical experience, questionnaire,” although Dr. Griffiths allowed that the term is misleading.

“That was a significant branding mistake, because awe is not fun,” he said. “There’s something existentially shaking about these experiences.”

It is that existential reckoning, the theory goes, that prompts many people to rejigger their identities or priorities in a way that reduces habitual behaviors or lines of thinking that cause distress.

In a continuing trial, Matthew Johnson, an addiction specialist at Johns Hopkins and a member of the new psychedelic center, is investigating how psilocybin treatment compares to use of a nicotine patch in helping people to quit smoking. So far, in the 39 people who have been in the study for at least six months, the abstinence rate in the psilocybin group is 50 percent, compared to 32 percent using the patch.

“The most compelling thing that makes psilocybin different from other addiction drugs is that it’s showing this cross-drug efficacy,” Dr. Johnson said. “It appears to have a similar effect, regardless of what drug the person is addicted to.”

That great potential, across many different diagnoses, is what attracted a small group of donors to Johns Hopkins, said Tim Ferriss, who brought in half the donated amount from investors, including more than $2 million from himself. Mr.

Ferriss, an investor and author, said that depression and addiction ran in his own family, and that available treatments were often inadequate. His investment in the center, he said, “was a chance to have a large output from a small input — a real Archimedes lever.

” The Steven & Alexandra Cohen Foundation provided the balance of the commitments.

Ms. Petersen is convinced that her psilocybin trip made a lasting difference. She has had one relapse since the trial, she said, and continued on antidepressant drugs. As a result of the trial, she also reordered her life, committing more time to things that are emotionally sustaining, and letting go of those there weren’t.

“I think that trial was the single most effective thing I’ve done to manage my mental health, and I had tried almost everything,” she said. “And it leads me to believe that we need to radically change how we think about mental health.”

“,”author”:”Benedict Carey”,”date_published”:”2019-09-04T16:17:11.000Z”,”lead_image_url”:”https://static01.nyt.com/images/2019/09/10/science/04PSYCHEDELICS1/04PSYCHEDELICS1-Jumbo.jpg”,”dek”:null,”next_page_url”:null,”url”:”https://www.nytimes.com/2019/09/04/science/psychedelic-drugs-hopkins-depression.html”,”domain”:”www.nytimes.com”,”excerpt”:”The research center, with $17 million from donors, aims to give “psychedelic medicine” a long-sought foothold in the scientific establishment.”,”word_count”:1360,”direction”:”ltr”,”total_pages”:1,”rendered_pages”:1}

Source: https://www.nytimes.com/2019/09/04/science/psychedelic-drugs-hopkins-depression.html

Preterm Birth Interventions Reviewed

Preventing Premature Birth | Johns Hopkins Medicine

The prevalence of preterm births has dropped in recent years, but more than 11 percent of U.S. infants are delivered before 37 weeks of gestation. More than 450,000 babies were born preterm in 2012, one in every nine deliveries.

Rita Driggers, MD, FACOG

“Preterm birth is the largest single cause of infant death in this country,” said Rita Driggers, MD, FACOG, associate professor of gynecology and obstetrics at The Johns Hopkins School of Medicine. “It is also the leading cause of neurological defects in infants. Our goal is simple: prevent preterm birth.”

Dr. Driggers discussed the variety of interventions available to deal with preterm birth during a clinical seminar on “Preterm Birth: Cerclage, 17-OH-P, Vaginal Progesterone, Tocolyze, or Cross Your Fingers?” Crossing your fingers is never a good option, she said, but the others have a place in reducing preterm birth.

The mechanisms of preterm birth remain a mystery. Contributing factors include uterine overextension, cervical insufficiency, low maternal weight, nutritional insufficiency, stress, tobacco use, recreational and illicit drug use, allergic disorders, hormonal changes and vascular factors.

Universal cervical ultrasound screening could help identify women at risk for cervical insufficiency, Dr. Driggers said. Johns Hopkins Medicine has a prenatal screening program that begins with abdominal ultrasound.

If the cervix is 35mm or larger, usual prenatal care is appropriate. Women with a small cervix may be candidates for vaginal ultrasound screening, which provides a more accurate measurement. Women with a short cervix may be candidates for vaginal progesterone starting between 16 and 24 weeks.

While ACOG does not support universal screening, the College advises appropriate quality control measures and sonographers credentialed by either the Fetal Medicine Foundation or the Cervical Length Education and Review Program when screening is used.

Other preventative measures include halting elective deliveries prior to 39 weeks, encouraging women to remain on contraception to extend the time between pregnancies, counseling to aid smoking and drug use cessation, nutritional support, and psychosocial support as needed.

No known treatments are effective in preventing preterm birth for twins, Dr. Driggers said. There are a variety of interventions that can reduce preterm births, delay preterm delivery and reduce morbidity and mortality in preterm babies.

Intramuscular progesterone, or 17-alpha hydroxyprogesterone caproate, better known as 17-OH-P or 17P, can help prevent preterm birth in women with a history of preterm births. Physicians don’t use 17P in women who do not have a history of preterm birth or who are carrying more than one fetus.

For women who have no history of preterm birth but are at risk due to a short cervix, vaginal progesterone is the agent of choice. Vaginal progesterone has shown a 45 percent reduction in preterm births in women who are carrying a singleton. It has shown no benefit for women carrying twins in clinical trials.

Cerclage has been shown to reduce preterm birth in women with a short cervix carrying a singleton. “Short” is either less than 15 cm or less than 25 cm, depending on the trial. But cerclage can more than double the risk of preterm birth in women carrying twins.

Small studies suggest that a pessary can also be effective in preventing preterm birth in women with a short cervix. More data are needed, Dr. Driggers said, and more than 20 clinical trials are under way.

Tocolytics can delay preterm labor up to seven days, she said. There are no data showing differences in effectiveness between beta agonists, calcium channel blockers, or NSADS, the three classes of tocolytics approved in the United States.

Magnesium sulfate given during delivery can reduce the risk and severity of cerebral palsy.

Source: https://annualmeeting.acog.org/news/preterm-birth-interventions-reviewed/

Susan Michaelis, Ph.D

Preventing Premature Birth | Johns Hopkins Medicine

Spear, E.D, Alford, R.F., Babatz, T.D., Wood, K., Mossberg, O.  Shilgardi, K., Odinammadu, K Gray, J., and Michaelis, S. (2019) A Humanized Yeast System to Analyze Cleavage of Prelamin A by ZMPSTE24. Methods 157:47-55

Spear E. D,. Hsu E.-T., Nie L., Carpenter E.P., Hrycyna C.A., and Michaelis S. (2018). ZMPSTE24 Missense mutations that cause progeroid diseases decrease prelamin A cleavage activity and/or  protein stability.  Disease Models and Mechanism 11:1-12 PMID 29794150 

Worman, H. J. and Michaelis, S. (2018). Permanently Farnesylated Prelamin A, Progeria and Atherosclerosis.  Circulation 183:283-6 PMC6056017 

Preston G. M., Guerriero C. J., Metzger M.B., Michaelis S. and Brodsky J.L. 2018. Substrate insolubility dictates Hsp104-dependent endoplasmic reticulum associated degradation.  Mol. Cell 70:242-253 

Ast, T., Michaelis, S., Schuldiner, M.  (2016) The protease Ste24 clears clogged translocons.  Cell 164:103-114

Maurer, M.J., Spear, E.D., Yu, A.T., Lee, E.J., Shahzad, S, and Michaelis, S.  (2016)  Degradation signals for ubiquitin-proteasome dependent cytosolic protein quality control (CytoQC) in yeast. G3:Genes, Genomes, Genetics 6:1853-66, PMC4938640.

Mehmood S., Marcoux J., Gault J., Quigley A., Michaelis S., Young S.G. Carpenter, E.P. and Robinson C.V. 2016. Mass spectrometry captures off-target drug binding and provides mechanistic insights into the human metalloprotease ZMPSTE24. Nature Chem. 8:1152-1158. PMC 512 3592

Kane, M. S., Linsday, M. E., Judge, D. P., Barrowman, J., Ap Rys, C., Simonson, L., Dietz, H.C., Michaelis, S. (2013) LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. American Journal of Medical Genetics A 161:1599-1611 PMCID: PMC3740161

Snider J., Hanif A., Lee M. E., Jin K., Yu A. R., Graham C., Chuk M., Damjanovic D., Wierzbicka M., Tang P., Balderes D., Wong V., Jessulat, M., Darowski, K.D. San Luis, BJ., Shevelev, I. Sturley S. L.

, Boone C., Greenblatt J. F., Zhang Z., Paumi C. M., Babu M., Park H.-O., Michaelis S., and I. Stagljar. (2013) Mapping the functional yeast ABC interactome. Nature Chem. Biol.

9:565-72 PMID: 23831759

Michaelis, S. and Hrycyna, C.A. (2013) A protease for the ages. Science 339:1529-30. PMID: 23539586

Barrowman, J., and Michaelis, S. (2013) The Ste24p Protease. In “Handbook of Proteolytic Enzymes,3nd Edition” (N. Rawlings, and G. S. Salvesen, eds.) Academic Press, Oxford, pp.668-676

Michaelis, S. and Hrycyna, C.A. (2013) A protease for the ages. Science 339:1529-30

Kane, M. S., Lindsay, M. E., Judge, D. P., Barrowman, J., Ap Rys, C., Simonson, L., Dietz, H.C., Michaelis, S. (2013) LMNA-associated cardiocutaneous progeria: an inherited autosomal dominant premature aging syndrome with late onset. American Journal of Medical Genetics, Part A (In Press).

Michaelis, S. and Barrowman, J. Biogenesis of the Saccharomyces cerevisiae pheromome a-factor; from yeast mating to human disease. (2012) Microbiology and Molecular Biology Reviews 76: 626-651.

Barrowman J., Wiley, P.A., Hudon, S., Hrycyna, C.A. Michaelis, S. (2012) Human ZMPSTE24 disease mutations: residual enzymatic activity correlates with disease severity. Human Molecular Genetics 21:4084-4093.

Barrowman, J., Hamblet, C., Kane M.S., Michaelis, S. (2012) Requirements for efficient proteolytic cleavage of prelamin A by ZMPSTE24. PLoS ONE 7: e32120.

Metzger MB, and Michaelis S. (2009) Analysis of Quality Control Substrates in Distinct Cellular Compartments Reveals a Unique Role for Rpn4p in Tolerating Misfolded Membrane Proteins Mol. Biol. Cell 20:1006-1019.

Barrowman, J., and Michaelis, S. (2009) ZMPSTE24, an integral membrane zinc metalloprotease with a connection to progeroid disorders. Biological Chemistry 390: 761-773.

Nakatsukasa, K., Huyer, G., Michaelis, S., and Brodsky J. L. (2008) Dissecting the ER-Associated Degradation of a Misfolded Polytopic Membrane Protein. Cell 132: 101-112

Hudon, S. E., Coffinier, C., Michaelis, S., Fong, L. G., Young, S. G., and Hrycyna, C. A. (2008) HIV-Protease inhibitors block the enzymatic activity of purified Ste24p. Biochem Biophys Res Comm. 374:365-368

Barrowman, J., Hamblet, C., George, C.M., and Michaelis, S. (2008) Analysis of prelamin A biogenesis reveals the nucleus to be a CaaX processing compartment. Mol. Biol. Cell 12:5398-5408

Metzger, M. B. Maurer, M. J., Dancy, B. M., and Michaelis, S. (2008) Degradation of a cytosolic protein requires ER-associated degradation (ERAD) machinery. J. Biol. Chem. 283:32302-32316

Paumi, C. M., Menendez, J., Arnoldo, A, Engels, K, Iyer, K. R., Thaminy, S, Georgiev, O., Barral Y., *Michaelis, S, and *Stagljar, I. (2007) Mapping Protein-Protein Interactions for the Yeast ABC Transporter Ycf1p by Integrated Split-Ubiquitin Membrane Yeast Two-Hybrid (iMYTH) Analysis. Molecular Cell 26: 15-25. * Co-corresponding senior authors.

Mallampalli, M. P., Huyer, G., Bendale, P., Gelb, M. H., and Michaelis, S. (2005) Inhibiting Farnesylation Reverses the Nuclear Morphology Defect in a HeLa Cell Model for Hutchinson-Gilford Progeria Syndrome, Proc Natl. Acad Sci. USA 102:14416-14421.

Young, S. G. Fong, L., and Michaelis, S.  (2005) Prelamin A, Zmpste24, misshapen cell nuclei, and progeria- new evidence suggesting that protein farnesylation could be important for disease pathogenesis.  Journal of Lipid Research 46:2531-2558. 

Source: https://cellbio.jhmi.edu/people/faculty/susan-michaelis-phd

Johns Hopkins Co-Leads Research Effort on Child ‘Polio’ Condition

Preventing Premature Birth | Johns Hopkins Medicine

Johns Hopkins Medicine and University of Alabama at Birmingham (UAB) researchers will lead a multicenter, multinational study of acute flaccid myelitis (AFM), the “polio” condition affecting children that causes loss of muscle control.

The National Institutes of Health’s National Institute of Allergy and Infectious Diseases awarded an approximate $10 million contract to UAB that will fund at least 38 research sites across the United States, Canada, the United Kingdom and Peru.

AFM is a rare condition that causes inflammation and damage to the spinal cord in children, resulting in a sudden paralysis of arms and/or legs and loss of muscle strength and reflexes. Other symptoms can include facial drooping, difficulty swallowing, slurred speech and trouble breathing.

“The major problem with AFM as a public health threat is not only the emergence of hundreds of cases around the U.S. and the world, but the fact that AFM produces devastating and long-standing neurological problems for children affected,” says Carlos Pardo-Villamizar, M.D.

, director of the Johns Hopkins Hospital Transverse Myelitis Center and co-principal investigator of the study.

“Thus, there is an urgent need for a concerted collaborative effort around the country to tackle the problem with our best research tools and come up with better options for diagnosis and treatment, to help children and families affected.”

The condition can be severely debilitating, and although many children recover fully, it may take many months of physical therapy to regain strength and movement.

AFM’s cause is unknown, though it is thought that a virus brings on the condition. Outbreaks tend to cluster in the late summer and through the fall. According to the Centers for Disease Control and Prevention (CDC), there were 233 confirmed cases in 2018 — the largest outbreak yet.

The investigators will document the clinical course of the disease, including the number and location of cases and variation in symptoms and severity, and they will assess the outcomes from the illness.

The researchers will isolate serious and life-threatening viruses that are believed to be connected to AFM cases.

The goal is to collect data that can inform how to design clinical trials on treatment of the condition, strategies for management, and establishment of a repository of specimens and data from AFM patients that will be used for future research.

“Since at least 2014, children have been at risk of developing a polio syndrome ly due to enteroviruses, and this study will provide the basis for understanding the cause of those children’s paralyses.

Knowledge gained from this study hopefully will provide the foundation for future treatment studies of antiviral drugs,” says David Kimberlin, MD, co-director of the Division of Pediatric Infectious Diseases at UAB and co-principal investigator of the study.

“We hope to better understand why acute flaccid myelitis occurs, which children are most at risk, and to develop the biorepository and associated clinical database to understand what we can do about it in the future.”

This new, five-year study will take advantage of the expertise of clinicians and researchers in the AFM Working Group — a network of neurologists and researchers established in 2018 in response to the AFM outbreak — and the Collaborative Antiviral Study Group, an NIH-funded network of academic medical centers established in the 1970s to study rare viral diseases. Study enrollment is expected to begin in August.

Johns Hopkins and UAB will continue to work closely with the National Institutes of Health, the CDC, investigators at the study sites, and parents and families of AFM patients to ensure that the medical community is making the most informed decisions to direct the national responses to this public health situation.

Source: Johns Hopkins Medicine

Source: http://www.infectioncontroltoday.com/infectious-diseases-conditions/johns-hopkins-co-leads-research-effort-child-poliolike-condition

Students Design Early Labor Detector to Help Prevent Premature Births

Preventing Premature Birth | Johns Hopkins Medicine

The birth of a baby is usually a joyous event, but when a child is born too early, worrisome complications can occur, including serious health problems for the baby and steep medical bills for the family. To address this, Johns Hopkins graduate students and their faculty adviser have invented a new system to pick up very early signs that a woman is going into labor too soon.

The normal length of a pregnancy is 40 weeks, while babies born before 37 weeks gestation are considered to be preterm. By detecting preterm contractions with greater accuracy and sensitivity than existing tools, the new system could allow doctors to take steps at an earlier stage to prevent premature births, its inventors say.

The health concerns and costs associated with premature births have received increasing attention in recent years, due in part to a rise in the number of multiple births, the use of fertility treatments, which can cause multiple births, and to an increase in women who are having babies later in life. These trends are all associated with a higher risk of preterm labor.

This computer graphic depicts the cervical ring and sensors used by the student-designed preterm labor detector. In the actual prototype, the extended ring is about 50 millimeters in diameter.

The scope of the problem is significant: The National Center for Health Statistics has reported that about 500,000 premature live births occur annually in the United States alone.

In a 2006 report, the Institute of Medicine described the high rate of premature births in the United States as “a public health concern that costs society at least $26 billion a year.

” Preterm births are widely linked to neonatal deaths or serious health problems such as breathing difficulties and brain development issues.

To help reduce these statistics, the Johns Hopkins biomedical engineering students wanted to improve the way doctors detect preterm labor.

They designed and built a prototype that is now undergoing testing in animals.

With further refinement, the students say, their system could eventually help physicians discover early signs of labor and allow the doctors to delay preterm deliveries, giving these babies more time to mature.

“The problem is, the technology now used by most doctors usually detects preterm labor when it’s so far along that medications can only delay some of these births for a few days,” said Karin Hwang of Ontario, Calif., one of the student inventors. “But if labor can be detected earlier, medications can sometimes prolong the pregnancy by as much as six weeks.”

Hwang was one of four Johns Hopkins students who devised and built the system in a yearlong bioengineering innovations and design master’s degree program. The others were Deepika Sagaram of Philadelphia; Rose Huang of Brooklyn, N.Y.

; and Chris Courville of Lafayette, La.

Along with their faculty sponsor, Abimbola Aina-Mumuney, an assistant professor of maternal fetal medicine in the Johns Hopkins School of Medicine, the students have formed CervoCheck, a limited liability corporation, to advance the project.

The students met Aina-Mumuney last year, early in their degree program, when they were asked to follow physicians on their hospital rounds and discover which new instruments and devices the doctors needed most to improve patient care. “I told them it’s really important to know at the earliest possible point when a pregnant patient is contracting,” said Aina-Mumuney. “It’s something I’ve had a strong interest in.”

The Johns Hopkins biomedical engineering students who helped develop the CervoCheck system were, from left, Karin Hwang, Chris Courville, Deepika Sagaram and Rose Huang. Photo courtesy of the University of Louisville Brown-Forman Cardinal Challenge Business Plan Competition.

The students initially proposed a new blood test to find proteins associated with early labor, but Aina-Mumuney steered them toward building a better device to detect physical signals in the expectant mother’s body.

To find signs of preterm labor, physicians have long relied on a tocodynamometer, a belt that is attached to a woman’s abdomen for external monitoring of uterine contractions. But Aina-Mumuney said this device is not effective at picking up preterm labor very early in a pregnancy or in cases where the patient is obese.

“I suggested that the students come up with an internal device,” she said. “I told them that if we could bypass the abdomen, that would be ideal.”

After much research and brainstorming, the students built a prototype ring made of medical grade biocompatible silicone elastomer. The ring is designed to be compressed and inserted into the vaginal canal at a physician’s office or hospital. Embedded within the ring are sensors designed to pick up electrical signals associated with uterine contractions.

“With these sensors, we’re detecting signals directly from the places in the body where they originate, as opposed to trying to pick them up through the abdominal wall,” said Courville, one of the inventors.

The prototype has not yet been used on human patients, but the students say their early animal test results are promising and that improvement of the system is continuing.

Their faculty advisor, Aina-Mumuney, said she is pleased by the great enthusiasm that the biomedical engineering students brought to the project. “They can truly see the impact this could make,” she said.

“If we can detect preterm labor at an earlier point and can delay the delivery by six weeks or more, the risk of the baby being born with serious health problems will go down dramatically.”

The costs of caring for premature babies are significant. A recent article in Managed Care said, “The average cost for infants hospitalized in neonatal intensive care units is around $3,000 per day.

While the average cost to an employer of a healthy baby born at full-term, or 40 weeks of gestation, is $2,830, the average cost for a premature baby is $41,610.

If the baby is born at 26 weeks, the cost can quickly rise to $250,000 or more.”

The inventors of the CervoCheck device say their system may someday help to reduce such expenses. “We estimate that the cost savings could be more than $44,000 per patient for every preterm birth we could prevent,” co-inventor Hwang said.

Working with the Johns Hopkins Technology Transfer office, the students and Aina-Mumuney have obtained a provisional patent covering their invention and established CervoCheck, LLC. The students also have received high marks and prize money in several competitions in which the viability of their device and its sales potential were judged.

The team placed first in the University of California, San Francisco, Business Plan Competition; won second-place honors in business plan contests sponsored by the University of Texas at Arlington and Noetic Technologies, and placed third in the University of Louisville Cardinal Challenge and the Johns Hopkins University Business Plan Competition.

The team’s winnings from these contests totaled $22,000.

All four students recently received their master’s degrees from Johns Hopkins. Sagaram will be entering medical school at Brown University, and Courville has accepted a job at a healthcare software business. Team members Hwang and Huang have opted to work full-time on moving the CervoCheck device toward commercial use. “We’re passionate about seeing this become a reality,” Hwang said.

Digital color images of the student team and the device available; contact Phil Sneiderman.

Related links:

Johns Hopkins Department of Biomedical Engineering: http://www.bme.jhu.edu/

Center for Bioengineering Innovation and Design: http://cbid.bme.jhu.edu/

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Source: https://releases.jhu.edu/2010/07/21/preterm-detector/