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Stroke symptoms that disappear in under an hour, known as a transient ischemic attack (TIA), need emergency assessment to help prevent a full-blown stroke, according to a new American Heart Association scientific statement published today in the Association’s journal Stroke. The statement offers a standardized approach to evaluating people with suspected TIA, with guidance specifically for hospitals in rural areas that may not have access to advanced imaging or an on-site neurologist.
TIA is a temporary blockage of blood flow to the brain. Each year, about 240,000 people in the U.S. experience a TIA, although this estimate may represent underreporting of TIA because symptoms tend to go away within an hour. While the TIA itself doesn’t cause permanent damage, nearly 1 in 5 of those who have a TIA will have a full-blown stroke within three months after the TIA, almost half of which will happen within two days. For this reason, a TIA is more accurately described as a warning stroke rather than a “mini-stroke,” as it’s often called.
TIA symptoms are the same as stroke symptoms, only temporary. They begin suddenly and may have any or all of these characteristics: Symptoms begin strong then fade; Symptoms typically last less than an hour; Facial droop; Weakness on one side of the body; Numbness on one side of the body; Trouble finding the right words/slurred speech; or Dizziness, vision loss or trouble walking.The F.A.S.T. acronym for stroke symptoms can be used to identify a TIA:
F Face drooping or numbness;
A Arm weakness;
S Speech difficulty;

T Time to call 9-1-1, even if the symptoms go away.
“Confidently diagnosing a TIA is difficult since most patients are back to normal function by the time they arrive at the emergency room,” said Hardik P. Amin, M.D., chair of the scientific statement writing committee and associate professor of neurology and medical stroke director at Yale New Haven Hospital, St. Raphael Campus in New Haven, Connecticut. “There also is variability across the country in the workup that TIA patients may receive. This may be due to geographic factors, limited resources at health care centers or varying levels of comfort and experience among medical professionals.”
For example, Amin said, “Someone with a TIA who goes to an emergency room with limited resources may not get the same evaluation that they would at a certified stroke center. This statement was written with those emergency room physicians or internists in mind — professionals in resource-limited areas who may not have immediate access to a vascular neurologist and must make challenging evaluation and treatment decisions.”
The statement also includes guidance to help health care professionals tell the difference between a TIA and a “TIA mimic” — a condition that shares some signs with TIA but is due to other medical conditions such as low blood sugar, a seizure or a migraine. Symptoms of a TIA mimic tend to spread to other parts of the body and build in intensity over time.
Who is at risk for a TIA?
People with cardiovascular risk factors, such as high blood pressure, diabetes, obesity, high cholesterol and smoking, are at high risk for stroke and TIA. Other conditions that increase risk of a TIA include peripheral artery disease, atrial fibrillation, obstructive sleep apnea and coronary artery disease. In addition, a person who has had a prior stroke is at high risk for TIA.

Which tests come first once in the emergency room?
After assessing for symptoms and medical history, imaging of the blood vessels in the head and neck is an important first assessment. A non-contrast head CT should be done initially in the emergency department to rule out intracerebral hemorrhage and TIA mimics. CT angiography may be done as well to look for signs of narrowing in the arteries leading to the brain. Nearly half of people with TIA symptoms have narrowing of the large arteries that lead to the brain.
A magnetic resonance imaging (MRI) scan is the preferred way to rule out brain injury (i.e., a stroke), ideally done within 24 hours of when symptoms began. About 40% of patients presenting in the ER with TIA symptoms will actually be diagnosed with a stroke based on MRI results. Some emergency rooms may not have access to an MRI scanner, and they may admit the patient to the hospital for MRI or transfer them to a center with rapid access to one.
Blood work should be completed in the emergency department to rule out other conditions that may cause TIA-like symptoms, such as low blood sugar or infection, and to check for cardiovascular risk factors like diabetes and high cholesterol.
Once TIA is diagnosed, a cardiac work-up is advised due to the potential for heart-related factors to cause a TIA. Ideally, this assessment is done in the emergency department, however, it could be coordinated as a follow-up visit with the appropriate specialist, preferably within a week of having a TIA. An electrocardiogram to assess heart rhythm is suggested to screen for atrial fibrillation, which is detected in up to 7% of people with a stroke or TIA. The American Heart Association recommends that long-term heart monitoring within six months of a TIA is reasonable if the initial evaluation suggests a heart rhythm-related issue as the cause of a TIA or stroke.
Early neurology consultation, either in-person or via telemedicine, is associated with lower death rates after a TIA. If consultation isn’t possible during the emergency visit, the statement suggests following up with a neurologist ideally within 48 hours but not longer than one week after a TIA, given the high risk of stroke in the days after a TIA. The statement cites research that about 43% of people who had an ischemic stroke (caused by a blood clot) had a TIA within the week before their stroke.
Assessing stroke risk after TIA
A rapid way to assess a patient’s risk of future stroke after TIA is the 7-point ABCD2 score, which stratifies patients into low, medium and high risk based on Age, Blood pressure, Clinical features (symptoms), Duration of symptoms (less than or greater than 60 minutes) and Diabetes. A score of 0-3 indicates low risk, 4-5 is moderate risk and 6-7 is high risk. Patients with moderate to high ABCD2 scores may be considered for hospitalization.
Collaboration among emergency room professionals, neurologists and primary care professionals is critical to ensure the patient receives a comprehensive evaluation and a well-communicated outpatient plan for future stroke prevention at discharge.
“Incorporating these steps for people with suspected TIA may help identify which patients would benefit from hospital admission, versus those who might be safely discharged from the emergency room with close follow-up,” Amin said. “This guidance empowers physicians at both rural and urban academic settings with information to help reduce the risk of future stroke.”
This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association’s Emergency Neurovascular Care Committee of the Stroke Council and the Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists, and it is endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS).
American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association’s official clinical practice recommendations.
Co-authors are Vice Chair Tracy E. Madsen, M.D., Ph.D.; Dawn M. Bravata, M.D.; Charles R. Wira, M.D.; S. Claiborne Johnston, M.D., Ph.D.; Susan Ashcraft, D.N.P.; Tamika Marquitta Burrus, M.D.; Peter David Panagos, M.D.; Max Wintermark, M.D., M.A.S.; and

In a crucial step towards understanding the mechanisms involved in cardiovascular disease and certain cancers, a Canadian led research team has succeeded in a world first: they’ve found the molecular mechanism by which the protein PCSK9 degrades the receptor of low density lipoproteins, the richest cholesterol particles in the bloodstream.
The discovery by Nabil G. Seidah, director of the biochemical neuroendocrinology research unit at the Montreal Clinical Research Institute and a medical professor at Université de Montréal, is published in the January issue of Molecular Metabolism.
His work was done in collaboration with Carole Fruchart Gaillard and colleagues at the Université de Paris-Saclay’s Department of Drugs and Technologies for Health, as well as with scientists in the pharmacy department of the University of Pisa, in Italy.
Low density lipoproteins, or LDL, can accumulate in the blood and lead to atherosclerosis and heart disease. The level of LDL and the cholesterol associated with it (LDLc), is directly modulated by the ability of LDL receptors (LDLR) to collect LDL from the bloodstream and internalize it, mainly into the cells of the liver. The surface LDLR drives LDL into the cell where it is captured, and the LDLR returns to the surface for another round of capture.
Rare cases linked to the PCSK9 protein
Most cases of familial hypercholesterolemia are related to LDLR dysfunction. But rarer cases have been linked to the PCSK9 protein, which Seidah’s laboratory’s discovered in 2003. PCSK9 is also present in the bloodstream where it associates with LDLR and promotes its degradation by liver cells, preventing it from returning to the surface to capture LDL. Some hypercholesterolemic patients have a “super PCSK9” that enhances the degradation of the LDLR.

In recent years, highly effective treatments have been available to patients that inhibit the function (called monoclonal antibody) or reduce the level (called RNAi) of PCSK9 in the bloodstream, resulting in larger amounts of LDLR that ensure a decrease in LDLc of more than 60 per cent compared to conventional statins.
Now the work of Seidah and his team lifts the veil on the previously misunderstood mechanism by which PCSK9 drags the LDLR towards the lysosomes, where cells degrade the PCSK9-LDLR complex.
A complex of three partner proteins
In their lab, Seidah and his team conducted structural analyses that revealed the formation of a complex of three PCSK9 partner proteins, including the LDLR, CAP1 and HLA-C.
A key protein in the immune system, HLA-C was found to play a critical role: it directs the entire complex to the lysosomes. HLA-C allows the recognition of the “self,” and also stimulates the anti-tumor activity of T lymphocytes.
PCSK9, for its part, helps protect against the growth of tumours and associated metastasis by increasing the level of HLA-C on the cell surface.
Ultimately, the hope is that inhibitors can be developed that would prevent the interaction of PCSK9 and HLA-C and block the function of PCSK9 on LDLR and HLA-C.
That breakthrough could then be applied in clinical practice to treat cardiovascular pathologies as well various types of cancer and metastases in patients.

Published6 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, South Gloucestershire Trading StandardsBy Philippa Roxby and Elena BaileyHealth reportersShops selling illegal vapes and the sale of vaping products to children are the top threats on the UK’s High Streets, according to Trading Standards officials.Hundreds of thousands of vapes which flout current laws have been seized.And there is concern that cheap, brightly-coloured vapes are ending up in the hands of 12 and 13-year-olds.The government said it was considering what more could be done to protect children from vaping.Child health experts said they were already “deeply disturbed” by the rise of children and young people picking up e-cigarettes.To hear that these products could also be illegal and unregulated was “terrifying”, they added.Shops selling to kids In a survey of more than 400 Trading Standards officers, 60% said their main worries were shops selling illegal vapes which are potentially unsafe, and the sale of any vaping products to under-18s, which is also illegal.”When Trading Standards teams do spot checks on the sale of vaping products to kids, we find around one in three businesses break the law,” says Duncan Stephenson, director of external affairs at the Chartered Trading Standards Institute.Image source, North East Trading Standards Association Mobile phone shops, gift shops and convenience stores are among the shops found to be selling the devices to children.Mr Stephenson wants to see tougher penalties for these businesses and a review of how vaping products are promoted – particularly when it comes to flavourings, colours and branding which appeal to children.UK laws limit how much nicotine and e-liquid is contained in vapes, and which health warnings are required on packaging.In recent years, vapes and e-cigarettes have been a successful way of helping many people give up smoking.But some shops are selling vapes containing 12,000 puffs of e-liquid, when the law permits only about 600. Others contain illegally high levels of nicotine.In the north-east of England alone, more than 1.4 tonnes of illegal vapes was seized from shops in the second half of last year, while in Kent there was a dramatic rise in counterfeit vaping products seized at Channel ports in December, with more than 300,000 removed.’My 15-year-old daughter wasn’t asked for ID once’One mother in Scotland, who wants to be anonymous, told the BBC that her 15-year-old daughter was sold disposable vapes illegally for months by her local corner shop.”They sold her 31 disposable vapes and never once asked her for ID,” she said.”There would be certain points of the day where she could go in and buy them. She would have to wait for the shopkeeper to give her the nod.”The woman said she was “angry” that corner shops would sell the devices to children “who are clearly under-age and in their school uniform”.”I couldn’t work out why my daughter was getting nosebleeds, headaches and mood swings, and when I came across the vapes hidden in her bedroom I was shocked,” she said.The girl told her mother she started vaping because all of her friends at school were doing it, and it got to the point where she was being picked on because she was not doing it.She has now stopped vaping and feels much better for it, the mother said.Vapes or e-cigarettes are far safer than normal cigarettes because they do not contain harmful tobacco, or produce dangerous tar or carbon monoxide from tobacco smoke.However, health experts say they are not risk-free, and more research is needed to find out about their potential effects over many years.They do contain nicotine – the substance which makes people addicted to smoking. A spokesperson for the Department of Health and Social Care in England said: “We have introduced tough regulations to deter the appeal of vaping to children, including restrictions on product advertising, setting limits on nicotine strength, labelling and safety requirements, and making it illegal to sell nicotine vapes to those aged under 18 years old. “We are carefully considering the recommendations from the Khan review: making smoking obsolete, including what more can be done to protect children from vaping.”Plain packaging pleaDr Helen Stewart, officer for health improvement from the Royal College for Paediatrics and Child Health, said she was “deeply disturbed” by the rise of children and young people picking up e-cigarettes.”We strongly advise children and young people against using illegal and unregulated e-cigarettes, and call on government and regulators to stop the sale of these products.”She said plain packaging of e-cigarettes and nicotine and non-nicotine e-liquids should be introduced, as well as tighter restrictions on advertising of vaping products so they are only used as an aid to stopping smoking.”If action is not taken soon, we run the risk of having generations of children addicted to nicotine,” Dr Stewart said.What are UK rules on vaping?only those aged 18 and over can buy vapes or e-cigarettescertain ingredients, such a caffeine and taurine, are bannednicotine ingredient warnings must appear on packagingpackaging should be childproofall e-cigarette and e-liquids containing nicotine have to be certified by the Medicines and Healthcare Products Regulatory Agency (MHRA) before they can be sold in the UK. Search for brands on the MHRA websiteany product that is not listed should be returned to the shop where it was bought, or to your local Trading Standards officeanyone’s experience of suspected side effects from using vapes can be sent to the MHRA via the Yellow Card schemenicotine-free e-cigarettes do not have to be certified by the MHRA – they are subject to product safety regulations by Trading Standards More on this storyMarket flooded by unsafe vapes aimed at children13 July 2022Sharp rise in counterfeit vapes at Channel ports27 December 2022Related Internet LinksHow safe is vaping? – FRANKThe BBC is not responsible for the content of external sites.

Advances in understanding the many different genetic causes of childhood-onset hearing loss indicate that genomic testing could assist in treatment planning, including optimal timing of treatment.
Even if a child with hearing loss did not receive a diagnosis from genetic testing a few years ago, very rapid recent progress in genomics makes re-testing worthwhile, according to scientists in this field.
Hearing loss, usually stemming from sensory problems in the inner ear, affects about 1 in 400 newborns in the United States. About half of these children have a genetic cause for their hearing loss.
More than 120 genes and thousands of different genetic variants can lead to childhood hearing loss. Virtually all children with genetic hearing loss have a mutation or mutations in only one gene.
A recent study, reported Jan. 12 in JAMA Otolaryngology-Head & Neck Surgery, examined a group of more than 400 youngsters with bilateral sensorineural hearing loss affecting both ears.
The researchers from UW Medicine and Seattle Children’s Hospital sought to identify the genetic causes of hearing loss in this group and how each genetic cause relates to a specific type of hearing loss. They also evaluated whether the genetic cause of hearing loss was related to the success of treatment with a cochlear implant, a surgically placed electronic device that enables a person to sense sound through impulses transmitted to the brain.

The findings show that genetic testing is a valuable tool in determining prognosis for a child’s hearing loss and in predicting how useful a cochlear implant could be for that child’s understanding of speech.
“With genetic diagnosis, it is possible to anticipate future hearing loss across sound frequencies and progression with age,” the researchers noted in their paper. “This information can be integrated with current severity of hearing loss to decide on treatment.”
The study was led by Ryan J. Carlson, an M.D./Ph.D. student in the Medical Scientist Training Program at the University of Washington School of Medicine in Seattle.
It was conducted during his training with Mary-Claire King, the senior author and professor of medicine and genome sciences at the UW School of Medicine and with Jay Rubinstein, professor of otolaryngology and head and neck surgery at the UW School of Medicine.
“For more than half of pediatric patients, genomic testing can now identify a genetic cause for their hearing loss and often provide critical information on its clinical characteristics,” explained Carlson.

The study participants included 449 children from 406 families. Genomic analysis resulted in genetic diagnoses for 210 of the 406 families, including 55 of the 82 families with more than one child with hearing loss and 155 of the 324 families with a single child with hearing loss. Rates of genetic diagnosis were similar for all ancestries in the study group.
In this study population, the researchers detected variants responsible for hearing loss in 43 different genes. With one exception, each child’s genetic diagnosis involved only one gene.
The severity of hearing loss, the sound frequencies most affected, and changes in hearing loss over time varied by gene, and, in some cases, by the type of variant within the gene. Children with causative mutations in the genes MYO6, OTOA, SLC2644, TMPRSS3, or the most severe mutations in the GJB2 gene had progressive hearing loss.
All of the children who had cochlear implants had better speech perception than before they received their implants. The degree of success of the cochlear implant varied somewhat based on the participant’s genetic diagnosis.
Taking into account the age of the child at implant and the length of time the implant was in place, speech perception was highest for children whose hearing loss was due to mutations in the MITF or TMPRSS3 genes.
However, the researchers concluded that differences in success of cochlear implants related to the genetic diagnosis was not substantial enough to preclude a cochlear implant for any patient who otherwise met the implant criteria.
Ancestries of the study participants were 17 (4%) African/African American, 32 (8%) East Asian, 219 (54%) European, 53 (13%) Latinx, 16 (4%) South Asian, and 61 (15%) who reported more than one ancestry. Slightly more than half (51%) of the children in the study were female
The study was conducted from 2019 to 2022 at the otolaryngology and audiology clinics at Seattle Children’s Hospital and the University of Washington, including the Center for Human Development and Disability.
DNA from the participants was analyzed by genomic sequencing and structural variant analysis in Mary-Claire King’s genome sciences laboratory at the UW School of Medicine. Severity and progression of their hearing loss was measured through audiological testing, and success of their cochlear implant was evaluated by pediatric or adult speech perception testing.
The research team outlined several key conclusions from their findings:
First, genetic testing for hearing loss can identify a genetic cause in most pediatric patients. Newborn hearing screening misses hearing loss in about one-third of affected children, because the hearing loss is not yet detectable at birth. Genetic testing could resolve that gap.
Second, technologies for genomic analysis are improving rapidly. If a child has already had genetic testing, with negative results, re-testing may find a genetic cause that was previously missed.
Third, genetic testing can identify syndromic forms of hearing loss and lead to necessary referrals of children to key specialists.
Finally, genetic diagnoses can be more effectively used to inform precision treatment for childhood hearing loss. Once the expected clinical characteristics of a certain genetic cause is known, that information can be used to evaluate prognosis and guide treatment.
Overall, the researchers emphasized, “Detection of hearing loss at the earliest possible age is important for cognition and social development, regardless of management approach.”
Carlson noted that the study had a direct positive impact for its participants.
“We were able to provide genetic testing for over 400 families with hearing loss in this one study. Many participants received new genetic diagnoses that were important to their care,” he explained. “I am proud to have directed a project that provided both direct benefits for those involved and indirect benefits for all patients with hearing loss.”
The study was funded by National Institute of Health grants 2R01DC011835, 30DC018702, T32DC005361, T32DC000018, and T32GM007266 as well as grants from the ARCS Foundation, Ben B. Cheney Foundation, and Virginia Merrill Bloedel Hearing Research Center.

Columbia Engineering neuroscientists identified a specific neural mechanism in the human brain that tags information with emotional associations for enhanced memory. The team demonstrated that high-frequency brain waves in the amygdala, a hub for emotional processes, and the hippocampus, a hub for memory processes, are critical to enhancing memory for emotional stimuli. Disruptions to this neural mechanism, brought on either by electrical brain stimulation or depression, impair memory specifically for emotional stimuli.
Most people remember emotional events, like their wedding day, very clearly, but researchers are not sure how the human brain prioritizes emotional events in memory. In a study published January 16, 2023, by Nature Human Behaviour, Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, and his team identified a specific neural mechanism in the human brain that tags information with emotional associations for enhanced memory. The team demonstrated that high-frequency brain waves in the amygdala, a hub for emotional processes, and the hippocampus, a hub for memory processes, are critical to enhancing memory for emotional stimuli. Disruptions to this neural mechanism, brought on either by electrical brain stimulation or depression, impair memory specifically for emotional stimuli.
Rising prevalence of memory disorders
The rising prevalence of memory disorders such as dementia has highlighted the damaging effects that memory loss has on individuals and society. Disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD) can also feature imbalanced memory processes, and have become increasingly prevalent during the COVID-19 pandemic. Understanding how the brain naturally regulates what information gets prioritized for storage and what fades away could provide critical insight for developing new therapeutic approaches to strengthening memory for those at risk of memory loss, or for normalizing memory processes in those at risk of dysregulation.
“It’s easier to remember emotional events, like the birth of your child, than other events from around the same time,” says Salman E. Qasim, lead author of the study, who started this project during his PhD in Jacobs’ lab at Columbia Engineering. “The brain clearly has a natural mechanism for strengthening certain memories, and we wanted to identify it.”
The difficulty of studying neural mechanisms in humans
Most investigations into neural mechanisms take place in animals such as rats, because such studies require direct access to the brain to record brain activity and perform experiments that demonstrate causality, such as careful disruption of neural circuits. But it is difficult to observe or characterize a complex cognitive phenomenon like emotional memory enhancement in animal studies.

To study this process directly in humans. Qasim and Jacobs analyzed data from memory experiments conducted with epilepsy patients undergoing direct, intracranial brain recording for seizure localization and treatment. During thse recordings, epilepsy patients memorized lists of words while the electrodes placed in their hippocampus and amygdala recorded the brain’s electrical activity.
Studying brain-wave patterns of emotional words
By systematically characterizing the emotional associations of each word using crowd-sourced emotion ratings, Qasim found that participants remembered more emotional words, such as “dog” or “knife,” better than more neutral words, such as “chair.” When looking at the associated brain activity, the researchers noted that whenever participants successfully remembered emotional words, high-frequency neural activity (30-128 Hz) would become more prevalent in the amygdala-hippocampal circuit. When participants remembered more neutral words, or failed to remember a word altogether, this pattern was absent. The researchers analyzed this pattern across a large data set of 147 patients and found a clear link between participants’ enhanced memory for emotional words and the prevalence in their brains of high-frequency brain waves across the amygdala-hippocampal circuit.
“Finding this pattern of brain activity linking emotions and memory was very exciting to us, because prior research has shown how important high-frequency activity in the hippocampus is to non-emotional memory,” said Jacobs. “It immediately cued us to think about the more general, causal implications — if we elicit high-frequency activity in this circuit, using therapeutic interventions, will we be able to strengthen memories at will?”
Electrical stimulation disrupts memory for emotional words
In order to establish whether this high-frequency activity actually reflected a causal mechanism, Jacobs and his team formulated a unique approach to replicate the kind of experimental disruptions typically reserved for animal research. First, they analyzed a subset of these patients who had performed the memory task while direct electrical stimulation was applied to the hippocampus for half of the words that participants had to memorize. They found that electrical stimulation, which has a mixed history of either benefiting or diminishing memory depending on its usage, clearly and consistently impaired memory specifically for emotional words.

Uma Mohan, another PhD student in Jacobs’ lab at the time and co-author on the paper, noted that this stimulation also diminished high-frequency activity in the hippocampus. This provided causal evidence that — by knocking out the pattern of brain activity that correlated with emotional memory — stimulation was also selectively diminishing emotional memory.
Depression acts similarly to brain stimulation
Qasim further hypothesized that depression, which can involve dysregulated emotional memory, might act similarly to brain stimulation. He analyzed patients’ emotional memory in parallel with mood assessments the patients took to characterize their psychiatric state. And, in fact, in the subset of patients with depression, the team observed a concurrent decrease in emotion-mediated memory and high-frequency activity in the hippocampus and amygdala.
“By combining stimulation, recording, and psychometric assessment, they were able to demonstrate causality to a degree that you don’t always see in studies with human brain recordings,” said Bradley Lega, a neurosurgeon and scientist at the University of Texas Southwestern Medical Center and not an author on the paper. “We know high-frequency activity is associated with neuronal firing, so these findings open new avenues of research in humans and animals about how certain stimuli engage neurons in memory circuits.”
Next steps
Qasim, who is currently a postdoctoral researcher at the Icahn School of Medicine at Mt. Sinai, is now pursuing this avenue of research by investigating how individual neurons in the human brain fire during emotional memory processes. Qasim and Jacobs hope that their work might also inspire animal research exploring how this high-frequency activity is linked to norepinephrine, a neurotransmitter linked to attentional processes that they theorize might be behind the enhanced memory for emotional stimuli. Finally, they hope that future research will target high-frequency activity in the amygdala-hippocampal circuit to strengthen and protect memory — particularly emotional memory.
“Our emotional memories are one of the most critical aspects of the human experience, informing everything from our decisions to our entire personality,” Qasim added. “Any steps we can take to mitigate their loss in memory disorders or prevent their hijacking in psychiatric disorders is hugely exciting.”

New research from the Department of Biomedical Informatics (DBMI) at the University of Colorado School of Medicine has identified 45 genes whose gene expression is associated with body mass index (BMI), many of which have not been explored in obesity research before, after conducting a study using a multiethnic cohort. Their study, “Gene Expression Associations With Body Mass Index in the Multi-Ethnic Study of Atherosclerosis,” published in the International Journal of Obesity, points to potential new biomarkers for obesity. This was accomplished by tapping into data from a large, diverse cohort that was originally gathered in 2000.
“Until now, few genetic studies of BMI have been conducted in ancestrally diverse cohorts,” lead author Luciana Vargas explains. “The novelty of our study is the use of directly measured gene expression data.”
Vargas, a CU School of Medicine PhD student with an interest in personalized medicine, says these known and novel gene associations can provide insights into the biology of obesity, potential biomarkers, and therapeutic targets.
For their study, researchers in the DBMI labs of Ethan Lange, PhD, and Leslie Lange, PhD, leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA). When it was launched, MESA enrolled over 6,000 people, recruited from six field centers across the country, to research risk factors and the early characteristics of cardiovascular disease. Participants continue to report to field centers periodically for collection of health data. Because of the large, ethnically diverse study population, and the amount of health information collected, researchers have used its data for a multitude of studies. The National Heart, Lung, and Blood Institute-funded Trans-Omics for Precision Medicine (TOPMed) consortium, which launched in 2014, began gathering gene expression and other ‘omics* data on a subset of MESA participants, as well as participants from many other cohorts.
“We used the MESA cohort because it’s really difficult to find a well-defined cohort with a lot of good clinical measurements, get the funding, and maintain the contact with study participants to collect blood and do these studies over time,” says Iain Konigsberg, PhD, a biomedical informatics research instructor who works with Vargas in the DBMI Lange Lab.
The researchers analyzed RNA sequencing data from four self-identified race and ethnic groups in the MESA cohort — African American, Chinese American, Hispanic, and White — to assess the association of expression of each gene for an effect on BMI. Many of the characteristics related to cardiovascular risk are also relevant to obesity, making the MESA cohort ideal for obesity research.
The 45 genes they identified had expressions associated with BMI across all four groups. While a small number of these genes have been identified through genetic association studies, the CU authors reported many novel associations.
Konigsberg says their work points to the need for more diversity in obesity research and expects the results of this study to inform additional downstream studies. He expects to continue research using MESA and additional human cohorts. It’s been a valuable lesson in collaborative research for Vargas, who began her studies at CU Anschutz in Fall 2021 as a PhD student in the Human Medical Genetics and Genomics Program. This is her first paper as a graduate student and member of the Leslie Lange Lab.
“Getting involved with the TOPMed consortium that had enrolled thousands of people across the U.S. opened up new opportunities for research,” she says. “I really appreciate the power of collaboration.”
*’Omics refers to measurable differences or changes in biological molecules, such as genes, metabolites, proteins, and RNA.

Biomedical engineers at the University of California, Davis, have created semi-living “cyborg cells.” Retaining the capabilities of living cells, but unable to replicate, the cyborg cells could have a wide range of applications, from producing therapeutic drugs to cleaning up pollution. The work was published Jan. 11 in Advanced Science.
Synthetic biology aims to engineer cells that can carry out novel functions. There are essentially two approaches in use, said Cheemeng Tan, associate professor of biomedical engineering at UC Davis and senior author on the paper. One is to take a living bacterial cell and remodel its DNA with new genes that give it new functions. The other is to create an artificial cell from scratch, with a synthetic membrane and biomolecules.
The first approach, an engineered living cell, has great flexibility but is also able to reproduce itself, which may not be desirable. A completely artificial cell cannot reproduce but is less complex and only capable of a limited range of tasks.
Infused with artificial polymer
Tan and the UC Davis team came up with a third approach. They infused living bacterial cells with the basic units of an artificial polymer. Once inside the cell, polymer was cross-linked into a hydrogel matrix by exposure to ultraviolet light. The cells could maintain their biological activity but could not reproduce.
“The cyborg cells are programmable, do not divide, preserve essential cellular activities, and gain nonnative abilities,” Tan said.
The cyborg cells were more resistant to stressors that would kill normal cells, such as exposure to hydrogen peroxide, antibiotics or high pH, the researchers found.
Finally, they were able to engineer the cells so that they could invade cancer cells grown in the lab.
The group is carrying out further research on how to create and control cyborg cells and on the effects of different matrix materials. They also hope to explore their use in a wide range of applications, from meeting environmental challenges to diagnosing and treating diseases.
“Finally, we are interested in the bioethics of applying cyborg cells as they are cell-derived biomaterials that are neither cells nor materials,” Tan said.
Additional co-authors on the paper are: Luis Contreras-Llano, Conary Meyer, Ofelya Baghdasaryan, Shahid Khan, and Aijun Wang, UC Davis Department of Biomedical Engineering; Tanner Henson, UC Davis Department of Surgery; Yu-Han Liu, Chi-Long Lin, Che-Ming J. Hu, Academia Sinica, Taiwan.
An application has been submitted for a provisional patent on the process. The work was supported in part by grants from the National Institutes of Health.

A newer technique for preparing corneal tissue for transplantation has been shown to be safe and effective, while providing a faster and smoother process than the traditional technique, according to researchers in the Department of Ophthalmology at University of Colorado School of Medicine.
Cornea transplantation has long been an option for patients with vision impairments stemming from cornea problems. In recent years, partial-thickness corneal transplantation, or Descemet’s membrane endothelial keratoplasty (DMEK), has emerged as an effective treatment for patients with Fuchs’ dystrophy, a condition in which endothelial cells — which line the inner layer of the cornea — die off. During DMEK surgery, the surgeon only removes and replaces the damaged inner layer of the cornea, which decreases risks of transplant rejection and offers potential for excellent vision.
“It’s a great procedure because it has wonderful visual outcomes and a much lower risk of transplant problems down the road compared with older transplant techniques,” says Karen Christopher, MD, assistant professor of ophthalmology in the CU School of Medicine and lead author for the study recently published in the journal Cornea. “It can really restore vision-related quality of life for patients who suffer from symptoms of Fuchs’ dystrophy, and our research shows we can do this more successfully now than ever before.”
Christopher notes that it can be a challenge to prepare and transport the corneal transplant tissue, which is as thin as a sheet of plastic wrap, and endothelial cells may die in the process. The procedure has been refined since its advent in 2006, with new tools developed specifically for tissue removal and transport.
Christopher led the CU research team comparing different approaches to preparing cornea tissue for DMEK transplantation — one using a relatively new tool called the DMEK EndoGlide and one using a tool called a Jones tube, modified from a glass tube that had been used in tear drainage surgery. The research was conducted at the Rocky Mountain Lions Eye Bank, which partners with about 120 hospitals in Colorado and Wyoming to recover donated eye tissue for use in transplants, research, and training. The eye bank prepared and then gathered data for 30 DMEK grafts used in the study.
“Most people don’t realize that besides facilitating ocular donation for research and transplant, the eye bank also prepares the grafts for specific transplant procedures, such as DMEK, for the surgeons prior to surgery,” says John Lohmeier, executive director of the eye bank. “The study results confirm that our preparation practices are cutting edge and effective.”
The EndoGlide technique preserves the tissue in a tiny capsule and forceps are later used to pull the tissue into the eye during surgery; it performed comparably to the modified Jones tube technique, which has been used for DMEK surgery for many years.
Christopher says this is the first direct comparison of Jones tube with the EndoGlide technique, which she says provides more control for the surgeon during the transplantation, leading to faster and more regulated tissue implantation — and likely better long-term outcomes.
She credits the team at Rocky Mountain Lions Eye Bank, located at the Sue Anschutz-Rodgers Eye Center, for its role in the research.
“We have a great partnership with the Rocky Mountain Lions Eye Bank,” Christopher says. “Not only do they provide us with excellent quality cornea tissue and meticulously prepare it for DMEK transplantation, they also are on the forefront of developing new techniques such as this one. Without them our surgical successes would not be possible!”
In 2021, the eye bank facilitated the donation of tissue from 2,450 donors, from which 316 corneas were used in DMEK procedures. In its 40-plus year history, this nonprofit organization has facilitated the recovery of more than 58,000 eye tissues for transplant and 15,000 eye tissues for research, training, and education.

University of Queensland researchers have identified a pathway in cells that could be used to reprogram the body’s immune system to fight back against both chronic inflammatory and infectious diseases.
Dr Kaustav Das Gupta and Professor Matt Sweet from UQ’s Institute for Molecular Bioscience discovered that a molecule derived from glucose in immune cells can both stop bacteria growing and dampen inflammatory responses.
Dr Das Gupta said the finding is a critical step towards future therapeutics that train immune cells.
“The effects of this molecule called ribulose-5-phosphate on bacteria are striking — it can cooperate with other immune factors to stop disease-causing strains of the E. coli bacteria from growing,” Dr Das Gupta said.
“It also reprograms the immune system to switch off destructive inflammation, which contributes to both life-threatening infectious diseases such as sepsis as well as chronic inflammatory diseases like respiratory diseases, chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, heart disease, stroke, diabetes and dementia.”
The research was carried out on a strain of E. coli bacteria that causes approximately 80 per cent of urinary tract infections and is a common cause of sepsis.

Pre-clinical trials were used to confirm the role of this pathway in controlling bacterial infections.
Professor Sweet said human cells were also used to demonstrate that ribulose-5-phosphate reduces the production of molecules that drive chronic inflammatory diseases.
“Host-directed therapies which train our immune systems to fight infections, will become increasingly important as more types of bacteria become resistant to known antibiotics,” Professor Sweet said.
“A bonus is that this strategy also switches off destructive inflammation, which gives it the potential to combat chronic disease.
“By boosting the immune pathway that generates ribulose-5-phosphate, we may be able to give the body the power to fight back against inflammatory and infectious diseases — not one, but two of the major global challenges for human health.”
Many current anti-inflammatory therapies target proteins on the outside of cells but because this pathway occurs inside cells, the researchers devised a new approach to target the pathway using mRNA technology.
Professor Sweet said the technology has shown promising results to deliver the enzyme that generates ribulose-5-phosphate into immune cells and has been filed as a provisional patent by UniQuest, UQ’s commercialisation company.
The work involved international and national cooperation, including UQ researchers Professor David Fairlie and Professor Mark Schembri as key collaborators.
The research was published in the journal, Proceedings of the National Academy of Sciences (PNAS).

A new study suggests that athletes who recover more slowly from concussion may be able to return to play with an additional month of recovery beyond the typical recovery time, according to a new study published in the January 18, 2023, online issue of Neurology®, the medical journal of the American Academy of Neurology. Slow recovery was defined as taking more than 14 days for symptoms to resolve or taking more than 24 days to return to play, both of which are considered the typical recovery times for about 80% of athletes with concussion.
“Although an athlete may experience a slow or delayed recovery, there is reason to believe recovery is achievable with additional time and injury management,” said study author Thomas W. McAllister, MD, of the Indiana University School of Medicine in Indianapolis. “This is an encouraging message that may help to relieve some of the discouragement that athletes can feel when trying to return to their sport. While some athletes took longer than 24 days to return to play, we found that three-quarters of them were able to return to sports if given just one more month to recover.”
The study looked at 1,751 college athletes who had been diagnosed with a concussion by a team physician. Of the athletes, 63% were male and 37% were female. Male athletes participated primarily in football, soccer and basketball. Female athletes participated primarily in soccer, volleyball and basketball.
Participants were evaluated five times: within six hours after their injury, one to two days later, once free of symptoms, once cleared to return to play and at six months.
Participants reported symptoms daily to medical staff, up to 14 days following injury and then weekly if they had not yet returned to play.
A total of 399 athletes, or 23%, had a slow recovery.
Researchers found that of the athletes who took longer than 24 days to return to play, more than three-fourths, or 78%, were able to return to play within 60 days of injury, and four-fifths, or 83%, were able to return to play within 90 days of injury. Only 11% had not returned to play six months after injury.
For the slow recovery group, the average time for returning to play was 35 days after injury, compared to 13 days in the overall group.
“The results of this study provide helpful information for athletes and medical teams to consider in evaluating expectations and making difficult decisions about medical disqualification and the value of continuing in their sport,” McAllister said.
A limitation of the study is that participants were all collegiate varsity athletes and may not be representative of other age groups or levels of sport, and the results may not apply to other types of mild brain injuries.
The study was supported by the Grand Alliance Concussion Assessment, Research, and Education Consortium, National Collegiate Athletic Association, and the Department of Defense.