Category: Science

LJI scientists identify potential targets for immune responses to novel coronavirus

LA JOLLA, CA—Within two months, SARS-CoV-2, a previously unknown coronavirus, has raced around globe, infecting over a 100,000 people with numbers continuing to rise quickly. Effective countermeasures require helpful tools to monitor viral spread and understand how the immune system responds to the virus.

Publishing in the March 16, 2020, online issue of Host, Cell and Microbe, a team of researchers at La Jolla Institute for Immunology, in collaboration with researchers at the J. Craig Venter Institute, provides the first analysis of potential targets for effective immune responses against the novel coronavirus. The researchers used existing data from known coronaviruses to predict which parts of SARS-CoV-2 are capable of activating the human immune system.

When the immune system encounters a bacterium or a virus, it zeroes in on tiny molecular features, so called epitopes, which allow cells of the immune system to distinguish between closely related foreign invaders and focus their attack. Having a complete map of viral epitopes and their immunogenicity is critical to researchers attempting to design new or improved vaccines to protect against COVID-19, the disease caused by SARS-CoV-2.  

“Right now, we have limited information about which pieces of the virus elicit a solid human response,” says the study’s lead author Alessandro Sette, Dr. Biol.Sci, a professor in the Center for Infectious Disease and Vaccine Research at LJI. “Knowing the immunogenicity of certain viral regions, or in other words, which parts of the virus the immune system reacts to and how strongly, is of immediate relevance for the design of promising vaccine candidates and their evaluation.”

While scientists currently know very little about how the human immune system responds to SARS-CoV-2, the immune response to other coronaviruses has been studied and a significant amount of epitope data is available.

Four other coronaviruses are currently circulating in the human population. They cause generally mild symptoms and together they are responsible for an estimated one quarter of all seasonal colds. But every few years, a new coronavirus emerges that causes severe disease as was the case with SARS-CoV in 2003 and MERS-CoV in 2008, and now SARS-CoV-2.

“SARS-CoV-2 is most closely related to SARS-CoV, which also happens to be the best characterized coronavirus in terms of epitopes,” explains first author Alba Grifoni, Ph.D, a postdoctoral researcher in the Sette lab

For their study, the authors used available data from the LJI-based Immune Epitope Database (IEDB), which contains over 600,000 known epitopes from some 3,600 different species, and the Virus Pathogen Resource (ViPR), a complementary repository of information about pathogenic viruses. The team compiled known epitopes from SARS-CoV and mapped the corresponding regions to SARS-CoV-2.

“We were able to map back 10 B cell epitopes to the new coronavirus and because of the overall high sequence similarity between SARS-CoV and SARS-CoV-2, there is a high likelihood that the same regions that are immunodominant in SARS-CoV are also dominant in SARS-CoV-2 is,” says Grifoni. 

Five of these regions were found in the spike glycoprotein, which forms the “crown” on the surface of the virus that gave coronaviruses their name; two in the membrane protein, which is embedded in the membrane that envelopes the protective protein shell around the viral genome and three in the nucleoprotein, which forms the shell. 

In a similar analysis, T cell epitopes were also mostly associated with the spike glycoprotein and nucleoprotein.

In a completely different approach, Grifoni used the epitope prediction algorithm hosted by the IEDB to predict linear B cell epitopes. A recent study by scientists at the University of Texas Austin determined the three-dimensional structure of the spike proteins, which allowed the LJI team to take the protein’s spatial architecture into account when predicting epitopes. This approach confirmed two of the likely epitope regions they had predicted earlier.

To substantiate the SARS-CoV-2 T cell epitopes identified based on their homology to SARS-CoV, Grifoni compared them with epitopes pinpointed by the Tepitool resource in the IEDB. Using this approach, she was able verify 12 out of 17 SARS-CoV-2 T cell epitopes identified based on sequence similarities to SARS-CoV. 

“The fact that we found that many B and T cell epitopes are highly conserved between SARS-CoV and SARS-CoV-2 provides a great starting point for vaccine development,” says Sette. “Vaccine strategies that specifically target these regions could generate immunity that’s not only cross-protective but also relatively resistant to ongoing virus evolution.”

The work was funded in part by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health through contracts 75N9301900065, 75N93019C00001 and 75N93019C00076.

Full citation: Alba Grifoni, John Sidney, Yun Zhang, Richard H Scheuermann, Bjoern Peters and Alessandro Sette. A Sequence Homology and Bioinformatic Approach Can Predict Candidate Targets for Immune Responses to SARS-CoV-2. Cell, Host and Microbe, 2020.

A pre-proof is available here.

About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

Does smoking increase your risk for dementia and cognitive decline?

Photo by Abhishek Koli on Unsplash

Scientists from the Uniformed Services University (USU), Emory University and the University of Vermont have found that cigarette smoking is linked to increased lesions in the brain’s white matter, called white matter hyperintensities.  White matter hyperintensities, detected by MRI scan, are associated with cognitive decline and Alzheimer’s disease. These findings may help explain the link between smoking and increased rates of dementia and other forms of cognitive decline.

The study, “Associations of cigarette smoking with gray and white matter in the UK Biobank” was published online in the journal, Neuropsychopharmacology, https://rdcu.be/b1jPS

In June 2019, the Surgeons General of the Army, Navy, Air Force, and United States, released an open letter stating that tobacco use is a threat to the health and fitness of U.S. military forces and compromises readiness. This burden also extends to care provided by the Veterans Health Administration, which spends more than $2.5 billion annually on smoking-related care.  In response, Dr. Joshua Gray, assistant professor of Medical and Clinical Psychology and Neuroscience at USU, and colleagues, examined the association between cigarette smoking and brain structure. Cigarette smoking is associated with increased risk for myriad health consequences including increased risk for neuropsychiatric conditions, but research on the link between smoking and brain structure is limited.

Their study was the largest of its kind, including MRI brain scans from more than 17,000 individuals from the UK Biobank, a large cohort of volunteers from across the United Kingdom. They found that smoking was associated with smaller total gray and white matter volume, increased white matter lesions, and variation in specific gray matter regions and white matter tracts. By controlling for important variables that often co-occur with smoking, such as alcohol use, this study identified distinct associations between smoking and brain structure, highlighting potential mechanisms of risk for common neuropsychiatric consequences of smoking such as depression and dementia.

“Cigarette smoking is known to elevate risk for neuropsychiatric conditions such as depression and dementia. We found that smoking is associated with multiple aspects of brain structure, in particular with increased white matter lesions. White matter lesions are linked to many of the same neuropsychiatric diseases as smoking,” said Gray.  “Although further research is needed to understand to what extent smoking is a cause or consequence of these aspects of brain structure, our findings suggest a mechanism that links smoking to increased risk for dementia, depression, and other brain diseases.”

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How to prepare in the event of a pandemic

As COVID-19, also known as coronavirus, becomes more prevalent around the world, University of Alabama at Birmingham experts share tips to help you prepare yourself, your family and your home should the virus continue to gain momentum.

Photo by Pixabay on Pexels.com

What is COVID-19?

Human coronaviruses are the second most common cause of colds and generally cause mild to moderate symptoms. Sometimes, coronaviruses that infect animals can evolve and become a new human coronavirus, as in the case of Severe Acute Respiratory Syndrome (SARS) in 2003 or the novel coronavirus, COVID-19, which first appeared in late 2019.

“This has become dangerous because this is a first-of-its-kind type of coronavirus, and all humans do not have immunity built up to fight it,” said Rachael Lee, M.D., UAB Medicine’s health care epidemiologist and assistant professor in the Division of Infectious Diseases

The Centers for Disease Control and Prevention (CDC) is closely monitoring the evolving epidemic of respiratory illness caused by the novel coronavirus, which was first identified in Wuhan, Hubei Province, China. To date, Chinese health officials have reported thousands of infections with the virus in China, as well as community spread in other locations such as South Korea, Italy and Iran.  To date, the United States has had a minimal number of cases. The CDC anticipates that the virus could spread and affect countries worldwide, including the United States. 

Based on early reports of COVID-19, symptoms typically include fever, runny nose, headache, cough and a general feeling of being unwell; these are the same symptoms of the common flu virus.

If you begin to experience flu-like symptoms, UAB doctors recommend seeking medical care as soon as possible.

Wash your hands

Caroline Cartledge, a nurse practitioner with UAB Student Health Services, details the right way to make sure your hands are as clean as possible. 

 “Wash your hands as much as you can,” she said. “We always recommend handwashing before you eat anything, before you make food for other people and after you use the restroom. I wash my hands anytime I touch a doorknob; if there is hand-sanitizer around, I always use it.

People touch their faces more often than they realize. Every time you touch a door handle and then scratch your nose, you are susceptible to contracting viruses.” 

Cartledge recommends lathering your hands with soap and water for at least 20 seconds. 

“A good rule of thumb is to sing or hum ‘Happy Birthday’ to yourself twice,” she said. 

Traveling and more

Lee says to follow the CDC and local health care authorities’ guidance regarding travel to areas with active disease. She recommends using common sense to be safe and careful in traveling. 

“As with any respiratory virus, the main recommendations hold true with the novel coronavirus,” Lee said. “Wash your hands, cover your cough with your arm, and stay home if you feel sick. Wearing surgical masks out in public is not recommended, as brief exposure to the virus in public is unlikely to make a person sick. Most cases have occurred when there has been prolonged contact, such as with health care professionals or family members serving as a caregiver. Use of masks is recommended for health care professionals, caregivers and those with disease symptoms.” 

Lee adds that, in the United States, we have seen very few cases of COVID-19. However, we are still seeing a large number of influenza cases that are causing many hospitalizations across the United States. 

“It’s important at this time to get to your flu shot if you have not already done so,” Lee said. 

She also suggests that, if you have symptoms and need to see a health care professional, call ahead to your health care provider, so that they can take appropriate precautions to treat you and safeguard themselves and others in the clinic or hospital when you arrive. 

Building immunity

While washing your hands is always recommended, Jessica Grayson, M.D., assistant professor with the UAB Department of Otolaryngology, says certain foods and supplements can help boost your immune system, potentially protecting your body from germs. 

“Foods that contain indole-3-carbinols have been found to reduce the number of viral infections — while this hasn’t been specifically tested in coronaviruses, the prevention of any viral illnesses that may weaken your immune system is and will be important,” Grayson said. “These foods include leafy greens like kale, spinach, collard greens, turnip greens, mustard greens, etc. They can be cooked or raw.”

Grayson adds that elderberry has certain compounds that have been approved by the FDA for use in flavoring of food. 

“There are many studies on the antiviral and antimicrobial activity of elderberry,” Grayson said. “It has been shown in some studies to bind to some subtypes of the flu virus to prevent cell entry. However, there are still more studies needed to confirm whether this is true substantial benefit.” 

You can also boost your immune system by maintaining a healthy lifestyle, says Lee. Eat a balanced diet, get plenty of rest, and avoid stress. 

Grayson also says there is no data to support that increased Vitamin C helps prevent or shorten viral illnesses. In fact, studies looking at this have shown no benefit. Utilizing the leafy greens above in a smoothie can be an easy way to increase intake, but strictly drinking orange or pineapple juice does not have proof of benefit. 

Protect your home and loved ones

Ian McKeag, M.D., a family and community medicine physician at UAB, says now is the time to disinfect and clean your home. Use isopropyl alcohol, or disinfecting wipes, to wipe down countertops and common areas. 

“Keep the surfaces of your home clean, especially areas where you eat and spend the most time,” McKeag said. “Use soap and water to wash your hands after you touch contaminated areas, such as doorknobs, toilet and faucet handles, and any cooking items. If you do not have access to soap and water, use hand-sanitizer.” 

McKeag adds that it is also a good idea to avoid shaking hands with others right now. If you do, wash your hands or use sanitizer right away, especially before touching your face. 

Grayson says you should limit the amount of time spent in public places and avoid people who are sick, including those who are coughing or presenting symptoms. 

“If you have a fever or other symptoms, stay home,” Grayson said. “If your children have a fever, do not send them to school. Consider working from home if your workplace allows it.” 

Finally, she recommends planning ahead for your daily medications.

“Be sure that you have plenty of the medicines that you routinely take so that if ill you can avoid going out in public to retrieve these things,” Grayson said. “In the case of a pandemic or major outbreak in the U.S., it is a good idea to stock up on non-perishable foods should your community be quarantined.” 

Pretrial publicity for high profile cases like Harvey Weinstein

If you see something in the news, can you unsee it or forget it?

When it comes to pretrial publicity, conventional wisdom says “no.” That is why defense attorneys for high-profile clients like Harvey Weinstein or Lori Loughlin, in order to ensure a fair trial, argue for moving a trial’s location or reject potential jurors who have been exposed to news reports about their clients.

Jon Bruschke, chair and professor of human communications at Cal State Fullerton, however, believes that this so-called “strong publicity effect” is massively overstated. He argues that the genesis of this line of thought — a 1997 literature review by Studebaker and Penrod — is flawed, and his own research suggests a more limited effect, mostly on the length of sentencing. 

Challenging the ‘Strong Publicity Effect’
Bruschke disputes Studebaker and Penrod’s case on human biology, communications theory and the study’s methodology.  

“People can’t remember things,” he says. “In a 2002 study by Neil Vidmar at Duke University School of Law, respondents were given three front-page stories about a notorious drug dealer and murderer who was named 17 times in the articles. Two weeks later, only one person could recall the name.”

Furthermore, the elaboration likelihood model suggests that the intense spotlight on trial evidence would override any publicity seen previously. “The O.J. Simpson trial might be one of the best examples of this,” says Bruschke.

He also questions the choice of studies included in the 1997 literature review; if the publicity effect is as prevalent as claimed; and whether such an effect is augmented by bias in the study design. For example, there are often long delays (six months to two years) in real-life cases between the arraignment and trial. Delays in research studies are much shorter (weeks), so people are less likely to forget pretrial publicity.

“None of these methodological issues are a problem in isolation,” Bruschke notes. “But they all put upward pressure on the size of the effect.”

Weinstein should have no problem with publicity … it is largely negative, but this should not compromise his trial being fair.

Support for the ‘Weak Publicity Effect’
Bruschke and his colleagues are the leading proponents of a weak pretrial publicity effect. His 1999 study of all federal murder trials in a three-year period showed that high publicity and no publicity cases had equal conviction rates, and low levels of publicity resulted in the highest conviction rates. For those convicted, more publicity resulted in a longer sentence.

He found similar results in a 2004 study of all federal murder or bank robbery cases in Atlanta, Los Angeles and Detroit between 1993-95.

In his 2016 study, Bruschke found an effect for positive publicity but not for negative publicity. Jurors exposed to negative publicity were more prone to convict than those exposed to positive publicity.

Jon Bruschke, chair and professor of human communication studies at Cal State Fullerton, says the ‘strong publicity effect’ is massively overstated.

“So the evidence is still a little equivocal, and you can’t say it always matters, and you can’t say it never matters,” says Bruschke. “The next big step is to find out when it does matter, and I don’t think social science is quite there yet.

“To me, the bigger question is: What does bias even mean? If you get charged with a felony, you have a 99% chance of being found guilty. The judicial system is replete with bias on the lines of class, race, sex and intersections between them. Paradoxically, the bias introduced by publicity might help defendants gain more resources for their case, which matters more.” 

Publicity for Weinstein and Loughlin
So what does this all mean for the 2020 trials of Weinstein and Loughlin?

“Weinstein should have no problem with publicity,” says Bruschke. “All research on pretrial publicity specific to sexual misconduct suggests that, if anything, even negative publicity favors defendants with male jurors. There is publicity, and it is largely negative, but this should not compromise his trial being fair.

“For Loughlin, I know of no research that is specific to celebrities in civil cases, but celebrities do tend to fare better than typical defendants, probably because they have access to better lawyers by and large.”

Music May Be an Effective Guide For Understanding Human Brain Activity

NSF grant supports research to develop new models to better understand the brain

TROY, N.Y. — When Sergio Pequito thinks about the brain, he visualizes a piano. The keys represent different parts of the brain, and the pressure applied by the pianist’s fingers represents the outside stimuli that promote brain functions. 

Just as notes and harmonies can be mapped onto sheet music, Pequito, an assistant professor of industrial and systems engineering at Rensselaer Polytechnic Institute, is looking to transcribe the brain’s complex dynamics into new data models that can help researchers better understand how the brain and human cognition work. This composition effort, of sorts, is being supported by a new grant from the National Science Foundation

“We have showed that, by thinking like this, there was a lot of activity in the brain that we were able to mimic and capture,” Pequito said. “We believe that we can use the math and models we have developed to capture intrinsic features that justify how the brain behaves over space and time.” 

Pequito’s team, which includes a collaborator from the University of Southern California, will use publicly available brain signal data from the National Institutes of Health to improve the models they have built. The data has been collected using functional magnetic resonance imaging (fMRI) technology, which tracks blood and oxygen flow as they increase in active parts of the brain. 

Pequito and his team are trying to provide insight into how a healthy brain functions, as well as how one with a neurological disease may behave. Continuing this analogy, Pequito explained that just as a pianist who hits the wrong key may create a dissonant noise, the models developed by his research team will show when something is a bit off in the brain’s activity. 

Industrial and systems engineers develop tools to analyze how complex systems interact. Pequito believes that this type of approach to humanity’s long-standing questions about the brain can provide new understanding about the relationships between functions like attention, learning, memory, decision-making, and language. These insights may prove useful in improving current technology by reverse-engineering the brain, which is one of the National Academy of Engineering’s Grand Challenges for Engineering

“We have all sorts of tools that we, as industrial engineers, can use,” Pequito said. “Now, we are working to improve them so we can provide new insights for the neuroscience and medical community.”

Saving Mother and Child

Oncologist Dr. Rita Mehta, whose research over the past 15 years has led to many advances in treating some of the most aggressive forms of breast cancer – with lifesaving results, stands in front of an inspirational quilt that hangs on display at the UCI Breast Health Center in Orange.
Credit: Photo: Steve Zylius / UCI

Multidisciplinary teams of UCI oncologists and maternal-fetal specialists utilize scientific advances to treat patients with high-risk pregnancies

Five-year-old Emlee jumps high, runs fast and likes to pirouette around the living room in her white ballet slippers.

Her mom, Karalayne Maglinte, calls her a miracle. Indeed, Emlee is the embodiment of the word: She’s one of the reasons Maglinte is alive today. Another reason: High-risk pregnancy physicians and cancer specialists at UCI Health were able to help the Fontana woman when no one else could.

Cancer during pregnancy is a rare event, occurring approximately once per 1,000 pregnancies annually, according to the National Institutes of Health’s World Journal of Oncology. Fortunately, “we have plenty of experience treating patients who need a multidisciplinary approach,” says Dr. Rita Mehta, a UCI Health oncologist.

Mehta has cared for several pregnant women with cancer, including Michelle Clark-Salib, who was just 28 when diagnosed with breast cancer. Her son Caleb is now 7, and Clark-Salib is cancer-free.

But the situation was touch-and-go for a long time, just as it was for Karalayne and Emlee Maglinte. Their poignant story began to unfold in 2013 when Maglinte was 15 weeks pregnant. She was 36 years old and had two boys at home: Ian, 6, and Isaac, 18 months.

“Because I was pregnant, I was much more aware of my body’s cues that something wasn’t right, and I was quicker to react than I might have been otherwise,” Maglinte says.

“My hands and feet were itchy,” she says, “so itchy I wanted to tear them off.” She consulted “Dr. Google” and read that it might be a liver issue.

“At first I thought perhaps it was because I was pregnant with a girl, and the other two were boys,” Maglinte recalls. “But it got so intense that I began to worry. I didn’t want to endanger her.” The itchiness began on a Friday. By Monday, she was convinced she needed to call her doctor.

A Challenging Diagnosis

An arduous round of tests, physician appointments and hospitalizations ensued as several Inland Empire doctors tried unsuccessfully to diagnose and treat Maglinte. In addition to the itchiness, she developed jaundice. After four days at a community hospital, she was taken by ambulance in the middle of the night to UCI Douglas Hospital, in Orange.

A team quickly assembled, including high-risk maternal-fetal expert Dr. Julianne Toohey, gastrointestinal endoscopy specialist Dr. John Lee, and pancreatic cancer surgeons Dr. Aram Demirjian and Dr. David Imagawa.

Lee – an authority in diseases of the liver, pancreas, bile ducts and gallbladder – examined Maglinte using endoscopic ultrasound. His findings led to a biopsy of her pancreas. He also implanted a bile duct stent to alleviate her jaundice. Although complex, each procedure was minimally invasive and safe for the baby.

But the diagnosis was daunting: Maglinte had an aggressive form of pancreatic cancer. “It’s strange that she would have had cancer at that age,” Lee notes. Statistically, almost all pancreatic cancer patients are older than 45, with the average age at the time of diagnosis being 70. Maglinte was only about half that.

She was devastated. “I kept walking around the halls of the maternity ward saying: ‘How the heck did I get here? This is crazy.’”

There weren’t many options. Early delivery “meant the baby would not have survived, as I was only 19 weeks pregnant,” Maglinte explains.

But she also had two children at home to consider. She and her husband, Dennis, discussed it. “He said it was my choice,” Maglinte relates. “I wanted to fight for her, but I also needed to fight for myself.”

The physicians worked together to save both mother and child. “Taking care of a high-risk patient with cancer involves careful communication with the whole team and, of course, the patient,” Toohey says. “Karalayne was very involved in decision-making.”

A week after the diagnosis, Demirjian operated, performing a seven-hour Whipple procedure, or pancreaticoduodenectomy, to remove the tumor. But Maglinte didn’t have chemotherapy, which would have jeopardized Emlee’s survival.

“We watched the baby’s growth and ended up with a planned delivery at 39 weeks,” Toohey recalls. “This is rather unusual with cancer patients – we usually deliver several weeks earlier in order for chemo or other treatment to begin as soon as possible.”

Happily, 7-pound, 1-ounce Emlee was born without complications. Her mom says she’s a “little lifesaver” because only 20 percent of pancreatic cancers are diagnosed early, mainly because symptoms – abdominal or mid-back pain, jaundice, weight loss and indigestion – can overlap with those of other conditions. “Without Emlee, I probably wouldn’t have reacted to my symptoms the way I did,” Maglinte says.

She and Emlee received the kind of advanced care that’s usually only available at an academic medical center like UCI.

Applying the Research

Oncologist Mehta, who joined the faculty in 2001 as a clinical professor of medicine, lauds the university, saying, “One of the great things is that not only can you do research here, but you can apply what you learn from that research to treat high-risk pregnancies with cutting-edge techniques. That’s not possible in a community hospital setting.”

That distinction was as important to Michelle Clark-Salib as it was to Maglinte. In 2012, at age 28, she was diagnosed with an aggressive 8-centimeter breast tumor. After undergoing nearly three months of chemotherapy with a community oncologist in Riverside, Clark-Salib found out that she was 23 weeks pregnant with her son Caleb.

The North Fontana woman consulted with an obstetrician, who discovered that her amniotic sac contained almost no fluid, a side effect of one of her chemo drugs that posed a serious threat to the developing fetus. The doctor sent Clark-Salib to the high-risk maternalfetal physicians at UCI Health, where he had trained as a resident.

Mehta, an international expert in metastatic breast cancer, eventually took over the case. “Michelle is an amazing young woman,” Mehta says. “She was at a very critical stage when she came to us but wanted to save her baby’s life and her own life. Abortion wasn’t an option for her.”

The drug that was causing the amniotic fluid problem was discontinued, and Mehta devised a modified cancer treatment plan that avoided the more toxic drug Herceptin until the infant arrived.

“As soon as the baby was delivered, we put her back on a chemotherapy regimen, and her cancer went into complete remission,” Mehta recalls. Caleb was born healthy at 37 weeks’ gestation.


“Survival rates are so much improved since I began working in oncology. Sometimes the steps are small; sometimes they’re bigger. But overall, each step adds to the next, and rates keep improving.”


Promising Scientific Advances

Mehta finds this an exciting time in her field: “Survival rates are so much improved since I began working in oncology. Sometimes the steps are small; sometimes they’re bigger. But overall, each step adds to the next, and rates keep improving.”

Over the last 15 years, her research has led to many advances in treating the most aggressive breast cancers. In a groundbreaking study published in 2012, Mehta showed that a combination of the drugs anastrozole and fulvestrant was superior in controlling cancer and improving patient survival to anastrozole alone or anastrozole followed by fulvestrant in treating hormone receptor-positive metastatic breast cancer in postmenopausal women. A long-term update of the study, published in March 2019 in The New England Journal of Medicine, confirmed the increase in five-year survival rates for advanced breast cancer patients.

“I don’t know what I would have done without UCI,” says Karalayne Maglinte, sporting hair in solidarity with PurpleStride (which raises pancreatic cancer awareness), with her husband, Dennis, and their children (from left) Ian, 12, Emlee, 5, and Isaac, 7.

Mehta was also one of the first to use chemotherapy combined with Herceptin on women with breast cancer before surgery – rather than only after – to help shrink tumors.

Now, more than seven years after Caleb’s birth, Clark-Salib remains cancer-free. And Maglinte has been cancer-free for more than six years.

“I don’t know what I would have done without UCI,” Maglinte says. “We were at the right place at the right time with the right teams. Everything just fell into line. Everyone we needed to be there was there.”

The “Firewalkers” of Karoo: Dinosaurs and Other Animals Left Tracks in a “Land of Fire”

Several groups of reptiles persisted in Jurassic Africa even as volcanism ruined their habitat

Credit: Bordy et al, 2020
Palaeoenvironmental reconstruction of the Highlands ichnosite at the Pliensbachian–Toarcian boundary.

In southern Africa, dinosaurs and synapsids, a group of animals that includes mammals and their closest fossil relatives, survived in a “land of fire” at the start of an Early Jurassic mass extinction, according to a study published January 29, 2020 in the open-access journal PLOS ONE by Emese M. Bordy of the University of Cape Town and colleagues.

Southern Africa

The Karoo Basin of southern Africa is well-known for its massive deposits of igneous rocks left behind by extensive basaltic lava flows during the Early Jurassic. At this time, intense volcanic activity is thought to have had dramatic impacts on the local environment and global atmosphere, coincident with a worldwide mass extinction recorded in the fossil record. The fossils of the Karoo Basin thus have a lot to tell about how ecosystems responded to these environmental stresses.

Study

In this study, Bordy and colleagues describe and identify footprints preserved in a sandstone layer deposited between lava flows, dated to 183 million years ago. In total, they report five trackways containing a total of 25 footprints, representing three types of animals: 1)  potentially small synapsids, a group of animals that includes mammals and their forerunners; 2) large, bipedal, likely carnivorous dinosaurs; and 3) small, quadrupedal, likely herbivorous dinosaurs represented by a new ichnospecies (trace fossils like footprints receive their own taxonomic designations, known as ichnospecies). 

Fossils

These fossils represent some of the very last animals known to have inhabited the main Karoo Basin before it was overwhelmed by lava. Since the sandstone preserving these footprints was deposited between lava flows, this indicates that a variety of animals survived in the area even after volcanic activity had begun and the region was transformed into a “land of fire.” The authors suggest that further research to uncover more fossils and refine the dating of local rock layers has the potential to provide invaluable data on how local ecosystems responded to intense environmental stress at the onset of a global mass extinction. 

Bordy adds: “The fossil footprints were discovered within a thick pile of ancient basaltic lava flows that are ~183 million years old. The fossil tracks tell a story from our deep past on how continental ecosystems could co-exist with truly giant volcanic events that can only be studied from the geological record, because they do not have modern equivalents, although they can occur in the future of the Earth.”

Sleep Problems in Children

Teens with Autism Are Focus of New AAN Guideline

Photo by Pixabay on Pexels.com

It is not uncommon for children and teens with autism spectrum disorder to struggle with sleep. Trouble falling asleep and staying asleep or refusing to go to bed are just some of the sleep problems they can experience. To help families, neurologists and other healthcare providers make decisions on the best treatments, the American Academy of Neurology (AAN) has issued a new guideline for sleep problems in children and teens with autism, published in the February 12, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

The guideline is endorsed by the American Academy of Sleep Medicine, Autism Speaks, the Child Neurology Society and the Society for Developmental and Behavioral Pediatrics. The American Epilepsy Society has affirmed the value of the guideline to epileptologists.

“While up to 40 percent of children and teens in the general population will have sleep problems at some point during their childhood, such problems usually lessen with age,” said lead guideline author Ashura Williams Buckley, MD, of the National Institute of Mental Health in Bethesda, Md., and a member of the American Academy of Neurology. “For children and teens with autism, sleep problems are more common and more likely to persist, resulting in poor health and poor quality of life. Some sleep problems may be directly related to autism, but others are not. Regardless, autism symptoms may make sleep problems worse.”

For the guideline, experts from the American Academy of Neurology carefully reviewed available scientific studies on autism and sleep problems in children and teens.

The guideline addressed four types of sleep problems: refusing to go to bed, stalling, or needing a parent or caregiver present until the child falls asleep; trouble falling asleep and staying asleep; sleeping for only short periods of time or not getting enough total sleep each night; and daytime behavior problems associated with insufficient sleep at night.

The guideline recommends that healthcare providers first identify if the sleep problems are caused by medications or other medical conditions, and if so, that those causes be addressed.

If sleep problems appear to be more behavioral in nature, the guideline recommends a number of behavior treatments that have been shown to be effective in children with autism. These include setting up a consistent sleep routine with regular bedtimes and wake times, choosing a bedtime close to when the child usually gets sleepy, and not allowing use of electronic devices like computers or televisions close to bedtime.

“Behavior-modification strategies are a good place to start because they do not cost anything, there are no side effects and they have been shown to work for some people,” said Williams Buckley.

If behavioral strategies alone do not work, the guideline recommends that healthcare providers also consider adding melatonin.

Melatonin is a hormone that tells the brain when to fall asleep and how long to sleep. Studies suggest that the artificial form of melatonin is safe and effective for children and teens with autism in the short term, for a period of up to three months. More research is needed to determine how safe melatonin is over longer periods of time. Possible side effects include headache, dizziness, diarrhea and rash. The guideline also cautions that over the counter melatonin products may not be reliable in terms of how much melatonin they actually contain. The guideline recommends using products that are labeled “pharmaceutical grade” melatonin.  

The guideline also found that melatonin use alone may be just as helpful in some patients as when melatonin is combined with behavioral strategies.

The guideline did not find that behavior treatments combined with melatonin changed daytime behavior problems or symptoms of autism.

The guideline also found no evidence that routine use of weighted blankets or specialized mattress technologies improve sleep.

“Sleep problems can make behavioral issues in children and teens with autism even worse,” said Williams Buckley. “That’s why it is important for parents and caregivers to work with healthcare providers to find a way to improve a child’s sleep because we know that good quality sleep can improve overall health and quality of life in all children.”

Learn more about autism at BrainandLife.org, home of the American Academy of Neurology’s free patient and caregiver magazine focused on the intersection of neurologic disease and brain health. Follow Brain & Life® on Facebook, Twitter and Instagram.

The American Academy of Neurology is the world’s largest association of neurologists and neuroscience professionals, with over 36,000 members. The AAN is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer’s disease, stroke, migraine, multiple sclerosis, concussion, Parkinson’s disease and epilepsy.

For more information about the American Academy of Neurology, visit AAN.com or find us on Facebook, Twitter, Instagram, LinkedIn and YouTube.

Mutations in Sperm May Reveal Risk for Autism

Credit: Martin Breuss, UC San Diego Health
In this illustration of sperm mosaicism, mutated sperm are depicted in red.

Researchers Use SDSC’s ‘Comet’ Supercomputer to Analyze Genome Sequences

While the causes of autism spectrum disorder (ASD) are not fully understood, researchers believe both genetics and environment play a role. In some cases, the disorder is linked to de novo mutations that appear only in the child and are not inherited from either parent’s DNA.

In a recent study published in Nature Medicine, an international team of scientists led by researchers at University of California San Diego School of Medicine describe a method to measure disease-causing mutations found only in the sperm of the father, providing a more accurate assessment of ASD risk in future children.

“Autism afflicts one in 59 children and we know that a significant portion is caused by these de novo DNA mutations, yet we are still blind to when and where these mutations will occur,” said co-senior author Jonathan Sebat, professor and chief of the Beyster Center for Molecular Genomics of Neuropsychiatric Diseases at UC San Diego School of Medicine. “With our new study, we can trace some of these mutations back to the father, and we can directly assess the risk of these same mutations occurring again in future children.”

The research team used the Comet supercomputer based at the San Diego Supercomputer Center, an Organized Research Unit of UC San Diego, to align the whole genome sequences. “We called variants on the sequences and also detected de novo variants using Comet for these samples,” explained Danny Antaki, a UC San Diego Neurosciences postdoctoral scholar. “In short, Comet provided the foundation for the larger experiment as we were able to find the de novos that we wanted to analyze in sperm with the data generated on the supercomputer.”

Recent studies suggest gene-damaging de novo mutations are involved in at least 10 to 30 percent of ASD cases, with the number of mutations rising with the father’s age at time of conception. De novo mutations occur spontaneously in parents’ sperm or eggs or during fertilization. The mutation is then present in each cell as the fertilized egg divides.

Studies now point to male sperm as a particularly important source of these mutations, with the chance of the mutation recurring within the same family generally estimated at 1 to 3 percent.

“However, such estimates are not based on actual knowledge of the risk in an individual family, but instead are based on frequencies in the general population,” said co-senior study author Joseph Gleeson, Rady Professor of Neuroscience at UC San Diego School of Medicine and director of neuroscience research at the Rady Children’s Institute for Genomic Medicine. “When a disease-causing mutation occurs for the first time in a family, the probability that it could happen again in future offspring is not known. Thus, families must make a decision with a great deal of uncertainty.”

For their study, Gleeson, Sebat, and colleagues analyzed the sperm of eight fathers who were already parents of children with ASD. The goal was to look for the presence of multiple, genetically different material in cells in the same person, a phenomenon called mosaicism. Using deep whole genome sequencing, they found variants in offspring that were matched only in the fathers’ sperm.

“While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct,” said first author Martin Breuss, an assistant project scientist in Gleeson’s lab. “Mutations occur every time a cell divides, so no two cells in the body are genetically identical. Mosaicism can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body. But if a mutation happens just in sperm, then it can show up in a future child but not cause any disease in the father.”

The researchers determined that disease-causing mutations were present in up to 15 percent of the fathers’ sperm cells, information that could not be determined through other means, such as blood samples.

“My laboratory has a long-standing interest in understanding the origins of pediatric brain disease, and how mutations contribute to disease in a child,” said Gleeson. “We previously showed that mosaicism in a child can lead to diseases like epilepsy. Here, we show that mosaicism in one of parents is at least as important when thinking about genetic counseling.”

If developed into a clinical test, the researchers said fathers could have their sperm studied to determine their precise risk of recurrence in future children. The methods might also be applied to men that haven’t had children yet, but who want to know the risk of having a child with a disease.

About UC San Diego Health

UC San Diego Health, comprising a comprehensive health system throughout San Diego County, UC San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, is one of five academic medical systems within the University of California system. We are committed to improving patient care while also researching new treatments and training tomorrow’s doctors and pharmacists. For more than 50 years, our renowned clinicians and scientists have made advances in numerous fields, including minimally invasive surgeries, personalized cancer therapy, cardiovascular treatment and surgery, transplantation and the early detection of autism.

About SDSC

As an Organized Unit of UC San Diego, SDSC is considered a leader in data-intensive computing and cyberinfrastructure, providing resources, services, and expertise to the national research community, including industry and academia. SDSC supports hundreds of multidisciplinary programs spanning a wide variety of domains, from earth sciences and biology to astrophysics, bioinformatics, and health IT. SDSC’s petascale Comet supercomputer is a key resource within the National Science Foundation’s XSEDE (eXtreme Science and Engineering Discovery Environment) program.

How much is too much caffeine🕉

Photo by bruce mars on Pexels.com

A video of Dr. Ayala discussing caffeine’s impact on the heart is available here:

https://www.wbaltv.com/article/the-woman-s-doctor-how-much-is-too-much-caffeine/30824815

Tomas H. Ayala, M.D., FACC, is a general cardiologist in Baltimore, Maryland. He sees patients at The Heart Center at Reisterstown, a satellite location of The Heart Center at Mercy. Dr. Ayala provides a range of care to diagnose and treat cardiovascular disease. He has an interest in cardiac imaging, valvular heart disease and geriatric cardiology.

Dr. Tomas Ayala has provided adults of all ages comprehensive cardiology care for more than 15 years. With Fellowship training in Cardiology, Dr. Ayala offers personalized care, concentrating on the best treatment plans to improve patient health and quality of life. He treats patients with congestive heart failure, coronary artery diseasearrhythmiashypertension and valvular heart disease, among other heart conditions.

He is Board Certified in Cardiovascular Disease, Nuclear Cardiology and Internal Medicine. Dr. Ayala is a Fellow of the American College of Cardiology as well as a member of the American Society of Echocardiography and the American Society of Nuclear Cardiology.

Dr. Tomas Ayala is committed to providing focused care for his patients. He is currently a Testamur of the ASCeXAM in adult Echocardiology, signifying his achievement in passing the Board exam and progressing to the “Board Eligible” stage. Echocardiography Board Certification will place Dr. Ayala among a group of distinguished experts in cardiovascular ultrasound interpretation and enable him to offer enhanced patient care for cardiovascular disease.

Dr. Ayala works with his patients to help them prevent and manage heart disease and maintain proper heart health. He places emphasis on patient education and understanding of risk factors and medical conditions, encouraging patients to take an active role in their care.

Dr. Tomas Ayala uses comprehensive testing and diagnostic services, including transthoracic echocardiography, transesophageal echocardiogram (TEE) and nuclear myocardial perfusion imaging, to evaluate heart blood flow, pumping function and anatomy in the diagnosis and assessment of cardiac conditions.