Day: March 30, 2021

Categories : Ageing Immune SystemTags :

Study Shows That Viral Infections Affect Immune System like Ageing

On By ModernMedia


A study from the Buck Institute and Stanford University suggests that chronic viral infections leave an impact on the human immune system, similar to those seen during ageing.

Using systems immunology and artificial intelligence, researchers profiled and compared immune responses in a cohort of aging individuals, people with HIV on long-term antiretroviral therapy, and people infected with hepatitis C (HCV) before and after the virus was treated with sofosbuvir, a drug with a 97% cure rate. Shared immune system alterations include T cell memory inflation, upregulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells.

“Chronic inflammation stemming from immune system dysfunction is associated with many of the diseases of ageing,” said senior author David Furman, PhD, Buck Institute associate professor. “Whether chronic viral infection contributes to age-associated immune dysfunction is still an open question, but studies of this type provide a way to start getting answers. At this point it’s clear that both ageing and chronic viral infections leave profound and indelible marks on immunity.”

The body is normally able to clean out acute viral infections, such as the common cold. But some viruses besides just HIV and HCV can remain alive, setting up ‘host-parasite housekeeping’ in the body, without people’s awareness. Dr Furman said that, depending on geographic location, 70 to 90% of the population is infected with cytomegalovirus. In healthy people, this is harmless and problematic only for pregnant women or those with compromised immune systems. Various herpes viruses can also lead to chronic infections.

“Each of us has our own virome; it’s the collection of the viral infections you have during your lifespan,” Furman said. “You probably have been infected by 12 or 15, or even more viruses that you never knew you had. Fortunately technology now exists that allows us to profile these infections in the human population; it is helping us move these types of inquiries forward.” Dr He said this study is the first to fully incorporate the concept of systems immunology, holistically analysing the immune system with the same technological platforms across different cohorts of patients.

The study demonstrated that in patients with HIV, immune system dysregulations were evident despite having been on antiretrovirals for over ten years. However, clearing the HCV virus partially restored cellular sensitivity to interferon-a, which inhibits viral replication. “This plasticity means there is room for intervention in both chronic viral infections and in ageing,” said Dr Furman. “It’s just a matter of identifying and understanding the molecular pathways and networks involved.” The study also identified changes in STAT1, the primary transcription factor activated by interferons. STAT1 plays a major role in normal immune responses, particularly to viral, mycobacterial and fungal pathogens.

As for COVID, Dr Furman said that we are in the midst of an ongoing “living” experiment. Future studies are needed to determine whether the functional imprinting of the immune system is hardwired to only involve the chronic nature of specific infections, or whether short but vigorous ones such as COVID also leave a lasting mark on the immune system. “Has the immune system of those infected with the coronavirus taken a big hit? That’s a theory, but we don’t know what will happen,” says Furman, who is collaborating with Stanford University and the University of California, San Francisco on projects involving COVID-19 and immunity.

Source: Medical Xpress

Journal information: Cesar J. Lopez Angel et al., “Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination,” PNAS (2021). www.pnas.org/cgi/doi/10.1073/pnas.2022928118

Categories : Diseases, Syndromes and Conditions NeurologyTags :

Mystery Brain Disease Baffles Canadian Doctors

On By ModernMedia

Doctors in Canada are struggling to explain a spate of cases involving memory loss, hallucinations and muscle atrophy.

For more than a year public health officials in New Brunswick province have been tracking a “cluster” of 43 cases of suspected neurological disease with no known cause.

A leaked memo from the province’s public health agency asking physicians to be on the lookout for symptoms similar to Creutzfeldt-Jakob disease (CJD), a rare, fatal and largely sporadic disease caused by prion proteins. Symptoms such as memory loss, vision problems and abnormal jerking movements were similar enough to trigger an alert with Canada’s CJD surveillance network. However, it was confirmed that this disease was not CJD.

“We don’t have evidence to suggest it’s a prion disease,” said Dr Alier Marrero, the neurologist leading New Brunswick’s investigation.
Patients initially reported unexplained pains, spasms and behavioural changes, easily misdiagnosed as anxiety or depression.

However, over 18 to 36 months they began to develop cognitive decline, muscle wasting, drooling and teeth chattering. Some also began experiencing frightening hallucinations, including the sensation of crawling insects on their skin.  

Each time a possible case arises, a battery of tests is administered to determine if they match the cluster. Cases have risen from only one in 2015 to 24 in 2020, and so far five people are believed to have died from the illness.

“We have not seen over the last 20-plus years a cluster of diagnosis-resistant neurological disease like this one,” said Michael Coulthart, head of Canada’s CJD surveillance network.

The majority of cases are linked a sparsely populated region of the province, with the overall number of cases in the cluster remaining low. However, New Brunswick has a population of fewer than 800 000 people.

Dr Marrero and his team have consulted experts in neurology, environmental health, field epidemiology, zoonotics and toxicology to better understand the possible cause of the mysterious illness.

A growing team of researchers are trying to pin down a common cause or perhaps environmental effect.

“We don’t know what is causing it,” said Dr Marrero. “At this time we only have more patients appearing to have this syndrome.”

Valerie Sim, a researcher of neurodegenerative diseases at the University of Alberta cautioned against jumping to conclusions. “I don’t really know if we even have a defined syndrome. There just isn’t enough information yet,” she said.

She observed that key markers for degenerative neurological illnesses had not been identified, with the cluster’s wide range of symptoms being “atypical” for most brain diseases. Conversely, the scope of symptoms could be explained by certain cancers, dementia or even misdiagnoses.

Frustratingly, when the ailment is unclear a number of tools can be deployed, “and then the patient somehow recovers. You come away never knowing what they actually had,” said Sim.

“We see odd neurological syndromes from time to time. Sometimes we figure them out. Sometimes we don’t.”

Source: The Guardian

Categories : Cardiovascular DiseaseTags :

Study Reveals Additional Pathway From Brain to Cardiovascular System

On By ModernMedia

Researchers at  University of Tsukuba in Japan have uncovered a previously unknown pathway from the brain to the cardiovascular system.

Though the cardiovascular system has a degree of autonomy to allow their independent functioning from the brain, the brain still has some control over it in order to respond to life-threatening situations. This control is exerted through the sympathetic and parasympathetic systems of the autonomic nervous system.

“From an evolutionary standpoint, the brain has had an incredibly important function in protecting the individual from predators,” says the lead author of the study Professor Tadachika Koganezawa. “But even in the absence of predators, our bodies react to stressful situations. In this study, we wanted to determine how the brain regulated the cardiovascular system via the autonomic nervous system.”

Located deep within the brain, the lateral habenula (LHb) has been known to elicit strong behavioural and cardiovascular responses to stressful events. But how it did so was still unclear. so to find out the researchers electrically stimulated the LHb in rats. This resulted in bradycardia and increased mean arterial pressure (MAP). The researchers then turned off the parasympathetic system by means of cutting the main parasympathetic nerve, the vagal nerve, or using a drug to antagonise it. 
Though this suppressed the LHb’s effect on the heart rate, the MAP was unchanged. Antagonising the sympathetic system had the opposite effect—decreasing the MAP but there was no effect on the heart rate.

To understand the mechanism by which the LHb elicits these cardiovascular responses, the researchers focused on the neurotransmitter serotonin, which plays an important role in the brain in modulating mood, cognition, and memory, among other functions.

While blocking all serotonin receptors significantly reduced the LHb’s effect on both the MAP and heart rate, the researchers found that specific subtypes of serotonin receptors were particularly involved in the process.

“These are striking results that show how the lateral habenula controls the cardiovascular system,” said study author Professor Masayuki Matsumoto , University of Tsukuba. “Our results demonstrate the mechanism of a neural circuit that plays an important role in stress-induced behavioral responses.”

Source: News-Medical.Net

Journal information: Doan, T. H., et al. (2021) Lateral Habenula Regulates Cardiovascular Autonomic Responses via the Serotonergic System in Rats. Frontiers in Neuroscience. doi.org/10.3389/fnins.2021.655617.

Categories : Genetics Medical Research & TechnologyTags :

New Bioluminescent System Illuminates Biological Processes

On By ModernMedia

Scientists at the Federal University of São Carlos (UFSCar) have developed a new bioluminescent system that can enable greatly improved imaging of biological and pathological processes in organisms.

Luciferases are enzymes that catalyse the oxidation of luciferins present in organisms such as fireflies, which results in bioluminescence in the visible light spectrum. Images of cell cultures and live animal models are made using the luciferin-luciferase system found in fireflies. For example, this can show the structure and activity of tumours, or follow the viral process in cells, helping physicians develop treatments.

“We obtained a novel luciferin-luciferase system that produces far-red light at the wavelength of 650 nanometres and emits the brightest bioluminescence ever reported in this part of the spectrum,” said principal investigator Professor Vadim Viviani, biochemist at UFSCar. “It’s a highly promising result for bioluminescence imaging of biological and pathological processes in mammalian tissues.”

“Red bioluminescence is preferred when imaging biological or pathological processes in mammalian tissues because haemoglobin, myoglobin and melanin absorb little long-wavelength light. Detection is best of all in the far red and near-infrared bands, but bioluminescent systems that naturally emit far red light don’t exist,” Prof Viviani added.

“Some genetically modified forms of luciferase and synthetic analogs of natural luciferins are produced commercially. In conjunction, they produce light at wavelengths as long as 700 nanometers, but the light produced by these artificial systems is generally much weaker and more short-lived than light from natural bioluminescent systems.”

Prof Viviani and collaborators genetically modified luciferase from the Railroad worm Phrixothrix hirtus, the only luciferase that naturally emits red light, and combined with luciferin analogues synthesised by colleagues at the University of Electro-Communications in Tokyo. The resulting luciferin-luciferase generates a much more efficient far-red bioluminescence.

“Our best combination produces far-red at 650 nanometres, three times brighter than natural luciferin and luciferase, and roughly 1000 times brighter than the same luciferase with a commercial analog,” Viviani said.

“Besides the long-wavelength and intense brightness, our combination has better thermal stability and cell membrane penetrability. Above all, it produces more lasting continuous bioluminescence, taking at least an hour to decay and significantly facilitating the real-time imaging of biological and pathological processes.”

Source: News-Medical.Net

Journal information: Viviani, R. V, et al. (2021) A Very Bright Far-Red Bioluminescence Emitting Combination Based on Engineered Railroad Worm Luciferase and 6′-Amino-Analogs for Bioimaging Purposes. International Journal of Molecular Sciences. doi.org/10.3390/ijms22010303.

Categories : Cardiovascular DiseaseTags :

Recurrence Risk of Heart Attack is Increased by Long Hours

On By ModernMedia
Photo of neon-lit heart by Leon Collett, via Unsplash.

For heart attack survivors, the risk of recurrent coronary heart disease is increased by working long hours.

Heart attack survivors who working 55+ hours per week were at higher risk of recurrent coronary heart disease (CHD) events (ie, myocardial infarction [MI] or unstable angina) over 6 years compared with people working a more standard 35-40 hours a week (adjusted HR 1.67). This included adjustment for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors.

“These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain,” wrote Xavier Trudel, PhD, of CHU de Québec-Laval University Research Centre in Quebec City, and colleagues. 
The researchers suggested secondary interventions in curbing working hours among patients at risk of CHD recurrence.

In an accompanying editorial, Jian Li, MD, PhD, of UCLA, and Johannes Siegrist, PhD, of Heinrich-Heine-University, concurred: A “short standardized assessment of working time and stressful working conditions among economically active cardiac patients would enrich physicians’ awareness of patients’ needs and inform medical decision making.”

“With the transformation of the modern work due to technological advances and economic globalisation, an increase in work load and an extension of irregular, nonstandard forms of employment, including working from home, were reported, aggravating the control and prevention of long working hours,” Drs Li and Siegrist wrote.

They urged cardiac rehabilitation programmes to offer “training skills of coping with stressful demands and of strengthening resilience and relaxation” and involving occupational health services to develop return-to-work plans.

When cardiac disease patients return to work, their workplaces will need to adopt tailored, programs to retain the workers and manage disease, Drs Li and Siegrist added.

The prospective cohort study included 967 MI survivors under age 60, of whom 205 had a recurrent CHD event over follow-up averaging 5.9 years.Men and people in their 40s and 50s were most likely to be working long hours after an MI. Job strain, defined as a combination of high psychological demands and low decision latitude at work, was measured with a questionnaire.

Work hours for each participant were assessed only once, at about 6 weeks after returning to work. “Some patients could have changed exposure during follow-up, leading to potential nondifferential misclassification and to an underestimation of the true effect,” Trudel’s group acknowledged.

The observational study was limited by only one tenth of participants being women, limiting generalisability, and by unknown confounding variables.

“In conclusion, the study by Trudel et al. provides a new piece of research evidence that work-related factors play an important role in CHD prognosis,” Drs Li and Siegrist wrote. “Occupational health services are urgently needed to be incorporated into cardiac rehabilitation programs and secondary prevention of CHD.”

Source: MedPage Today

Journal article information: Trudel X, et al “Long working hours and risk of recurrent coronary events” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.012.

Editorial information: Li J, Siegrist J “Occupational risks of recurrent coronary heart disease” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.020.

Categories : COVID General InterestTags :

CDC Director Fears ‘Impending Doom’ as COVID Cases Rise Again

On By ModernMedia

Rochelle Walensky, MD, the Centers for Disease Control (CDC) Director, says that she fears “impending doom” as COVID deaths in the US edge upwards as people increasingly ignore health restrictions and start to travel.

Beginning her usual COVID status update,  Dr Walensky spoke as she often did of “concerning trends in the data.”

Dr Walensky spoke about the country surpassing 30 million COVID cases; of a 10% increase in the 7-day average of COVID-19 cases over the past week, to slightly below 60 000 cases; and of an uptick in hospitalisations, from a 7-day average of around 4600 per day to around 4800 per day.

“And deaths, which typically lag behind cases and hospitalizations, have now started to rise,” she said, pointing to a nearly 3% increase to a 7-day average of “approximately 1000 deaths per day.”

“I’m going to pause here,” she said. “I’m going to lose the script and I’m going to reflect on the recurring feeling I have of impending doom.”  

At the start of her tenure, Walensky said she had pledged to always tell the truth even if it wasn’t something Americans wanted to hear.

“We have so much to look forward to, so much promise and potential of where we are, and so much reason for hope. But right now I’m scared,” she said.

She recalled her time caring for COVID patients, saying: “I know what it’s like as a physician to stand in that patient room, gowned, gloved, masked, shielded and to be the last person to touch someone else’s loved one because their loved one couldn’t be there.

“I know what it’s like when you’re the physician, when you’re the healthcare provider, and you’re worried that you don’t have the resources to care for the patients in front of you.” 

She also recalled “that feeling of nausea, when you read the ‘Crisis Standards of Care’ and you wonder whether there are going to be enough ventilators to go around and who’s going to make that choice.”

She emphasised that she was speaking “not only as your CDC director, but as a wife, as a mother, as a daughter, to ask you to just please hold on a little while longer.”

She sympathised, she said, with those “wanting to be done” with the pandemic.

“We are just almost there, but not quite yet. And so I’m asking you to just hold on a little longer, to get vaccinated when you can. So that all of those people that we all love will still be here when this pandemic ends.”

Dr Walensky warned that the US pandemic trajectory was looking dangerously similar to that of European countries like Germany that were still struggling to contain the virus.

“We are not powerless. We can change this trajectory of the pandemic,” she said.

“But it will take all of us recommitting to following the public health prevention strategies consistently while we work to get the American public vaccinated.”

According to the New York Times’  COVID vaccination tracker, 146 million vaccinations have been administered in the US to date, with 2.76 million doses being given daily. At this rate, 70% of the adult population will have been vaccinated by June 16.

She urged community and religious leaders, officials, and other influencers to help support the vaccination programme.

“For the health of our country, we must work together now to prevent a fourth surge.”

Source: MedPage Today