Tag: biomarkers

Categories : Lab Tests and Imaging Obstetrics & GynaecologyTags : 1 Comment

Researchers Discover a Lipid Biomarker that can Identify Preeclampsia Risk

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University of Virginia School of Medicine researchers have discovered a lipid biomarker to identify pregnant women at risk of preeclampsia, complications from which are the second-leading cause of maternal death around the world. Their findings are published in the Journal of Lipid Research.

The UVA scientists, led by Charles E. Chalfant, PhD, say that their finding opens the door to simple blood tests to screen patients. Further, the approach worked regardless of whether the women were on aspirin therapy, which is commonly prescribed to women thought to be at risk.

“Clinicians have been seeking simple tests to predict risk of preeclampsia before symptoms appear. Although alterations in some blood lipid levels have been known to occur in preeclampsia, they have not been endorsed as useful biomarkers. Our study presents the first comprehensive analysis of lipid species, yielding a distinctive profile associated with the development of preeclampsia,” said Chalfant. “The lipid ‘signature’ we described could significantly improve the ability to identify patients needing preventative treatment, like aspirin, or more careful monitoring for early signs of disease so that treatment could be initiated in a timely fashion.”

Preeclampsia affects up to 7% of all pregnancies. Symptoms typically appear after 20 weeks and include high blood pressure, kidney problems and abnormalties in blood clotting. The condition is associated with dangerous complications such as kidney and liver dysfunction and seizures, as well as a lifelong increased risk of heart disease for the mothers. An estimated 70 000 women around the world die from preeclampsia and its complications each year.

Doctors commonly recommend low-dose aspirin for at-risk women, but it works for only about half of patients, and it needs to be started within the first 16 weeks of pregnancy – well before symptoms appear. That makes it all the more important to identify women at risk early on, and to better understand preeclampsia in general.

Chalfant and his team wanted to find ‘biomarkers’ in the blood of pregnant women that could reveal their risk of developing preeclampsia. They examined blood plasma samples collected from 57 women in their first 24 weeks of pregnancy, then looked at whether the women went on to develop preeclampsia. The researchers found significant differences in ‘bioactive’ lipids in the blood of women who developed preeclampsia and those who did not.

This, the researchers say, should allow doctors to stratify women’s risk of developing preeclampsia by measuring lipid changes in their blood. The changes represent an important ‘lipid fingerprint’, the scientists say, that could be a useful tool for identifying, preventing and better treating preeclampsia.

“The application of our comprehensive lipid profiling method to routine obstetrical care could significantly reduce maternal and neonatal morbidity and mortality,” Chalfant said. “It represents an example of how personalised medicine could address a significant public health challenge.”

Source: University of Virginia Health System

Categories : Mental Health NeurologyTags :

Neuroimaging can’t Identify Psychiatric Disorders – Yet

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Neuroimaging technologies hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new study published in the American Journal of Psychiatry shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).

Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.

“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.

For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at US emergency departments following traumatic events. Specifically, when researchers measured patients’ brain activity during the performance of simple tasks such as mapping responses to threats and rewards, they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.

However, when Yale researchers analysed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.

“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalise across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.

In fact, Yale researchers are currently working with the investigators of the original study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.

“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”

Source: Yale University

Categories : Diseases, Syndromes and Conditions Lab Tests and ImagingTags :

Low Serum Urate Increases Sarcopenia Risk

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Adults with low blood levels of urate, the end-product of the purine metabolism in humans, may be at higher risk of sarcopenia and may face a higher risk of early death, according to a new study published in Arthritis & Rheumatology.

Whether or nor low serum urate (SU) levels contribute to adverse outcomes has been the subject of controversy.  The study involved 13 979 participants aged 20 years and older, sourced from the National Health and Nutrition Examination Survey from 1999–2006.

Low serum urate concentrations (<2.5 mg/dL in women; <3.5 mg/dL in men) were associated with low lean mass, underweight BMI (<18.5 kg/m2), and higher rates of weight loss. While low SU was associated with increased mortality (61%) before adjusting for body composition, its effect was reduced and non-significant after adjustment for body composition and weight loss.

“These observations support what many have intuited, namely that people with low serum urate levels have higher mortality and worse outcomes not because low urate is bad for health, but rather that low urate levels tend to occur among sicker people, who have lost weight and have adverse body composition,” explained lead author Joshua F. Baker, MD, MSCE, of the University of Pennsylvania. “While this observational study doesn’t disprove a causal association, it does suggest that great care is needed in interpreting epidemiologic associations between urate levels and health outcomes.”

Source: Wiley

Categories : Immune SystemTags :

Airway Immune Risks of Fourth Generation e-Cigarettes

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Fourth-generation e-cigarettes, such as Juul devices, are associated with unique changes in markers of immune responses inside our airways, according to a new peer-reviewed paper in the American Journal of Respiratory and Critical Care Medicine.

Third-generation e-cigarettes include vape pens and box mods. Fourth generation include nicotine-salt-containing e-cigarettes, such as Juul products, and disposable e-cigarettes, which have become increasingly popular, especially after the recent FDA ban on the sale of Juul products.

Researchers in the lab of Professor Ilona Jaspers at the UNC School of Medicine found that users of fourth-generation nicotine-salt-containing devices display a unique mix of cellular biomarkers indicative of immune suppression.

“Our work demonstrates the importance of considering device type in future clinical, epidemiological, and mechanistic studies on the health effects of e-cigarettes,” said Prof Jasper, who led the study. “We also think this research can help regulators determine which products cause the most severe types of biological changes in airway cells important for maintaining proper health.”

E-cigarettes have become popular in the last decade. Some started used them to quit smoking, believing vaping was a safer alternative, both in the short-term and long-term. Also, because electronic cigarettes don’t contain tar, consumers assumed vaping decreased their risk of cancer down the road.

“It’s impossible to know if vaping decreases cancer risk or many other long-term conditions,” Prof Jaspers said. “It took 60 years of research to show that smoking causes cancer.” In contrast, e-cigarettes have only been around for about 15 years. “Still, the research from our lab and many others has shown many of the same acute biological effects in the airways that we have documented in smokers,” she said. “And we’ve seen some changes to cells and immune defences in people who vape that, frankly, we’ve never seen before, which is very concerning.”

A major concern for researchers, doctors, and public health officials is the fact that teenagers who would not have otherwise tried cigarettes began using e-cigarettes, which contain nicotine – with its attendant health implications – and thousands of chemicals, many of which are FDA-approved for eating but not inhaling.

Several studies have documented that inhaling chemical-laden nicotine aerosols suppresses the immune responses in the respiratory tracts of smokers and e-cigarette users. Some studies, including some at UNC, have detailed how different chemicals in various e-cigarettes, including chemicals that make up thousands of different flavours, have adverse effects on airway cells. The Jaspers lab, which has been at the forefront of such research, set out to study the effects of different varieties of e-cigarette devices. For this study, her team collected central airway (sputum) samples from non-smokers, smokers, and users of both third-generation and fourth-generation e-cigarette devices.

They found that users of fourth-generation e-cigarettes had significantly more bronchial epithelial cells in their sputum, suggestive of airway injury because normally, bronchial epithelial cells make up an intact barrier in the airways and are not found in sputum samples. Levels of two proteins, sICAM1 and sVCAM1, were significantly lower in fourth-generation e-cigarette users compared to all other groups. These proteins are important in fighting infections and other disease.

In addition, proteins are important for overall immune defence were significantly lower in fourth versus third generation e-cigarette users. Lower of these proteins – CRP, IFN-g, MCP-1, uteroglobin, MMP-2, and VEGF – indications immune system depression. “Another key finding of the study was that, when examining the mixture of immune markers overall rather than one by one, fourth generation e-cigarette users had the most distinguishable changes out of all of the groups, indicating a shift away from immune homeostasis,” said the study’s lead author, Elise Hickman, PhD.

The study did not demonstrate that e-cigarettes cause cancer, emphysema, COPD, or other long-term diseases associated with long-term cigarette smoking. But researchers think that altering immune responses in the respiratory tract over the course of many years, especially for teens, could play a major role in the development of long-term health conditions and in susceptibility to inhaled pathogens.

Source: University of North Carolina

Categories : Cardiovascular DiseaseTags :

Two Biomarkers Predict CVD Risk in Psoriatic Disease

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In a new study published in Arthritis & Rheumatology, scientists have found that two biomarkers predict cardiovascular disease (CVD) risk in people with psoriatic disease. People with psoriatic disease, which includes psoriasis and psoriatic arthritis, are more likely to develop CVD than the general population.

The study, which included 1000 adults with psoriatic disease, found that elevated blood levels of two indicators of cardiovascular health, namely, cardiac high-sensitivity troponin I (cTnI) and N-terminal pro-brain-type natriuretic peptide (NT-proBNP), were associated with higher risks of experiencing cardiovascular problems independent of traditional risk factors such as hypertension and high cholesterol.

These findings pave the way for further studies exploring the clinical potential of measuring cTnI and NT-proBNP levels in helping assess the heart health of individual patients with psoriatic disease.

“Our study provides new insights regarding the pathophysiology of cardiovascular diseases in psoriasis and psoriatic arthritis. However, at this time, ordering tests of cardiac biomarkers is not recommended for risk stratification of asymptomatic patients with psoriatic disease,” said senior Lihi Eder, MD, PhD, associate professor of medicine at Women’s College Hospital and University of Toronto.

Source: Wiley

Categories : COVIDTags :

Viral RNA Levels Can Predict COVID Mortality

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Viral RNA levels in the blood is a reliable indicator in predicting COVID mortality, according to a study published in Science Advances.

“In our study, we were able to determine which biomarkers are predictors of mortality in the 60 days following the onset of symptoms,” said Université de Montréal medical professor Dr. Daniel Kaufmann, the study’s co-lead author alongside colleagues Nicolas Chomont and Andrés Finzi.

“Thanks to our data, we have successfully developed and validated a statistical model based on one blood biomarker,” viral RNA, Prof Kaufmann said.

Despite advances in COVID management, identifying patients at greater risk of dying of the disease has been difficult. Other studies identified various biomarkers, but assessing so many parameters is not possible in a clinical setting and gets in the way of doctors’ quick clinical decision-making ability.

Using blood samples from 279 patients hospitalised for COVID of differing severity, Kaufmann’s team measured amounts of inflammatory proteins, looking for any that stood out.

At the same time, Chomont’s team measured the amounts of viral RNA and in Finzi’s the levels of antibodies targeting the virus. Samples were collected 11 days after the onset of symptoms and patients were monitored for a minimum of 60 days after that.

The goal: to test the hypothesis that immunological indicators were associated with increased mortality.

“Among all of the biomarkers we evaluated, we showed that the amount of viral RNA in the blood was directly associated with mortality and provided the best predictive response, once our model was adjusted for the age and sex of the patient,” said Elsa Brunet-Ratnasingham, a doctoral student in Kaufmann’s lab and co-first author of the study.

“We even found that including additional biomarkers did not improve predictive quality,” she added.

Prof Kaufmann and Brunet-Ratnasingham tested the model on two independent cohorts of infected patients from Montreal’s Jewish General Hospital (recruited during the first wave of the pandemic) and the CHUM (recruited during the second and third waves).

No matter which hospital the patients were treated at, nor which period of the pandemic they fell into: in all cases, the predictive model worked. Now Prof Kaufmann and his colleagues want to put it to practical use.

“It would be interesting to use the model to monitor patients,” he said, “with the following question in mind: when you administer new treatments that have proven effective, is viral load still a predictive marker of mortality?” 

Source: University of Montreal

Categories : LungTags :

A New Biomarker for Chronic Lung Diseases

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Scientists have discovered that people with asthma and chronic obstructive pulmonary disease (COPD) have a protein in their lungs that leaks a molecule into their bloodstream that leads to restricted breathing instead of relaxing their airways.

The findings of their study, appearing in the American Journal of Respiratory Cell and Molecular Biology, will help clinicians diagnose and determine the severity of chronic lung diseases and make bronchodilators more effective.

“This protein has been recognised as important in some diseases, but it has never been defined before in airway diseases, such as asthma and COPD, until now,” explained co-author Reynold Panettieri, vice chancellor of translational medicine at Rutgers. “In addition to identifying this protein, we demonstrated that if you decrease the leakage, the smooth muscles in the airways relax, which could be potentially very important in improving asthma and COPD management. In addition, the presence of too much cAMP in a patient’s blood is a new biomarker that can help characterize specific types of asthma and COPD.”

The researchers found that a protein in smooth muscle cell membranes in the lungs of patients with chronic airway disease can leak cyclic adenosine monophosphate (cAMP), which signals to help relax muscles in the lungs and widen the airways. The leakage causes the airways to become constricted and cAMP can be found in the bloodstream, which can improve diagnosis of chronic airway diseases.

Researchers working together discovered the leak of cAMP from human airway smooth muscle cells from patients with and without asthma.  These cells control airway constriction in asthma, and by losing cAMP, the cells are more apt to constrict and worsen asthma. By analysing blood samples from a well-defined cohort of asthma patients, they defined cAMP in the bloodstream as a biomarker.

“We determined that cAMP blood levels are higher in asthma patients,” Panettieri said. “This knowledge allows for better diagnostics of the illness and forms the basis for new therapeutics that will plug the leak of cAMP in the protein.”

Source: Rutgers University

Categories : CancerTags :

Less than Half of Community Oncologists Use Biomarker Testing

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A survey found that less than half of community oncologists surveyed indicated using biomarker testing to guide patient discussions, compared to 73% of academic clinicians.

Recent advances have substantially altered the management of lung cancer but, there is a concern these new methods, which include biomarker testing, will not be used equally throughout the health care system and worsen disparities that may already be entrenched.

To determine this, the Association of Community Cancer Centers (ACCC), led by Leigh Boehmer, Pharm.D., chief medical officer, developed a US oncology clinician-facing survey instrument.

To help guide clinicians in the use of biomarker testing, the College of American Pathologists, the IASLC, and the Association for Molecular Pathology published the 2018 CAP/IASLC/AMP Molecular Testing Guidelines for Lung Cancer. Dr. Boehmer reported that of the 99 responses collected, only 40 percent indicated they were “very” or “extremely familiar” with the 2018 Guidelines.

The researchers found that clinicians were most confident in selecting appropriate tests to use, interpreting test results, and prognosticating based on test results, but less confident in determining when to order testing and coordination of care. This lack of communication was echoed in focus groups, Dr Boehmer reported.

Clinicians are most likely to order biomarker testing to make more accurate treatment decisions and inform patient discussions, but only 48% of community clinicians indicated that they use biomarker testing to guide patient discussions compared to 73% of academic clinicians.

Asked about preferences when making a final testing decision, 41% of clinicians prefer that they share responsibility with the patient while 52% prefer to make the final decision themselves. Only 6% prefer that the patient make the final decision. Focus groups suggested that clinicians perceive that patients rarely understand what testing entails and how it affects treatment options.

To make more informed decisions about biomarker testing, clinicians indicated that they need more information on financial resources, as well as education around both published guidelines and practical implications of clinical data. Sixty-seven percent of clinicians provide printed educational materials to their patients. When asked what resources their patients need most, 27% said their patients need handouts or educational resources, followed by psychosocial support (23%) and financial assistance (22%).

“This study identifies key areas of ongoing clinician need related to biomarker testing, including increased guideline familiarity, practical applications of guideline-concordant testing, and how to optimally help coordinate multidisciplinary care,” said Dr. Leigh Boehmer, Pharm.D. “Professional organisations and advocacy groups should focus on developing impactful education materials and tools for improving patient-clinician discussions about biomarker testing.”

Source: International Association for the Study of Lung Cancer

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

Study Uncovers Assortment of New Biomarkers for Dementia

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An international study identified 15 novel biomarkers that are linked to late-onset dementias. These protein biomarkers predict cognitive decline and subsequent increased risk of dementia 20 years before the disease onset. 

The proteins identified by the study are involved with immune system dysfunction, blood-brain-barrier dysfunction, vascular pathologies, and central insulin resistance. Six of these proteins can be modified with currently available medications.  

“These findings provide novel avenues for further studies to examine whether drugs targeting these proteins could prevent or delay the development of dementia,” explained lead author Joni Lindbohm MD, PhD from the University College London and University of Helsinki.

The study findings have been published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

Pathophysiological research on dementia aetiology has focused on amyloid beta and tau proteins, but thus far prevention and treatment trials targeting these biomarkers have been unsuccessful. This has spurred the search for other potential mechanisms that could predispose to dementia. Recent development of scalable platforms has made it possible to analyse a wide range of circulating proteins, which may reveal novel dementia-linked biological processes.

In this study, the researchers analysed proteins with a novel large-scale protein panel from stored blood samples of the British Whitehall II and US Atherosclerosis Risk in Communities (ARIC) study collected 20 years ago. Using a panel of 5000 proteins, the researchers identified proteins in plasma that predicted cognitive decline in 5-yearly screenings and subsequent onset of clinical dementia. The 15 proteins that were identified were predictive of dementia in both the British and US cohorts.

“This new study is the first step in our 5-year Wellcome Trust funded research programme. We will next examine whether the identified proteins have a causal association with dementia, and whether they are likely to be modifiable, and druggable”, said study author Professor Mika Kivimäki, Director of the Whitehall II study at University College London.

The research programme ultimately aims to identify novel drug targets for dementia prevention.

Source: EurekAlert!

Categories : Mental HealthTags :

Researchers Hit upon a Possible Biomarker for Schizophrenia

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Investigators at Sanford Burnham Prebys have discovered that a certain protein circulating in blood could be a potential biomarker for schizophrenia. The activity of this protein, present in both the brain and blood, affects neural connections in human brains and is uniquely imbalanced in people with schizophrenia. 

The study, an international collaboration among groups at Yokohama City University Graduate School of Medicine in Japan and the Department of Psychiatry at Harvard Medical School in Belmont, Massachusetts, was recently published in PNAS.

“This study examined the activity of CRMP2, a protein found in the brain (called a ‘cytoskeletal protein’) that regulates how neurons make connections with each other,” said co-senior author of the study Evan Y Snyder, MD, PhD, director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys. “CRMP2 also happens to be expressed in lymphocytes in the blood and can therefore be readily sampled in people by doing nothing more than a simple venipuncture.

“There was an abundance of CRMP2 levels in samples from people with schizophrenia compared to people without the disorder. We also saw structural abnormalities in the dendrites of neurons that could potentially be disabling because dendrites play an important role in receiving impulses from other nerve cells in the brain.”

In previous research, most people were found to maintain an even proportion of the two forms of CRMP2: its active, non-phosphorylated form and its inactive, phosphorylated form. Postmortem brain tissue and then blood samples from people with schizophrenia were examined and compared these levels to those in people without the disorder.

The findings indicated that the amount of active CRMP2 was too high in people with schizophrenia and, at least in young people with schizophrenia, was not balanced by an appropriate amount of increased inactive CRMP2. That imbalance between active and inactive CRMP2 could account for some dysfunctions in neural connections.

Testing blood for high levels of active CRMP2, along with low levels of inactive CRMP2, could support schizophrenia diagnosis.

“Schizophrenia can be challenging to diagnose early on or in young patients for a number of reasons,” explained Dr Snyder. “Pairing a blood test with psychiatric and neurobehavioral exams could help doctors distinguish schizophrenia from other conditions that have somewhat similar symptomologies, such as the manic phase of bipolar disorder or other behavioral, personality, or thought disorders.

“Our results were most striking in people under the age of 40, and even more so in people under the age of 30. An early diagnosis could improve the clinical management of affected individuals as well as accelerate the development of new therapeutic options,” Dr Snyder added.

As a next step, the researchers want to delve into the molecular biology of the disease to discover the ‘regulator’  that balances most people’s CRMP2 levels. They also want to conduct a larger, multi-centre clinical study that compares schizophrenia with other psychiatric disorders, which would include participants from more ethnicities and age groups.

Source: Sanford Burnham Prebys Medical Discovery Institute

Journal information: Munetaka Nomoto el al., “Clinical evidence that a dysregulated neural network modulator may aid in diagnosing schizophrenia,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2100032118