Year: 2021

Categories : Cancer Medical Research & TechnologyTags :

Plant Virus-based Treatment Protects Against Lung Tumours

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Image source: CDC/Unsplash

Using a virus that grows in black-eyed pea plants, nanoengineers developed a new treatment that could keep metastatic cancers at bay from the lungs. 

Not only did the treatment slow tumour growth in the lungs of mice with either metastatic breast cancer or melanoma, it also prevented or drastically minimised the spread of these cancers to the lungs of healthy mice that were challenged with the disease. The research was published in Advanced Science.

Researchers developed an experimental treatment that combats metastatic spread. This involves a plant virus called the cowpea mosaic virus, harmless to animals and humans, but which the body still registers as a foreign invader, thus triggering an immune response that could also boost the body’s cancer-fighting ability.

The idea is to use the plant virus to help the body’s immune system recognise and destroy cancer cells in the lungs. The virus itself is not infectious in our bodies, but it has all these danger signals that alarm immune cells to go into attack mode and search for a pathogen, said Nicole Steinmetz, professor of nanoengineering at the University of California San Diego.

To draw this immune response to lung tumours, Prof Steinmetz’s lab engineered nanoparticles made from the cowpea mosaic virus to target a protein in the lungs. The protein, called S100A9, is expressed and secreted by immune cells that help fight infection in the lungs. Overexpression of S100A9 has been observed to play a role in tumour growth and spread.

“For our immunotherapy to work in the setting of lung metastasis, we need to target our nanoparticles to the lung,” said Prof Steinmetz. “Therefore, we created these plant virus nanoparticles to home in on the lungs by making use of S100A9 as the target protein. Within the lung, the nanoparticles recruit immune cells so that the tumors don’t take.”

“Because these nanoparticles tend to localise in the lungs, they can change the tumor microenvironment there to become more adept at fighting off cancer — not just established tumors, but future tumors as well,” said Eric Chung, a bioengineering PhD student in Steinmetz’s lab who is one of the co-first authors on the paper.

To make the nanoparticles, the researchers infected black-eyed pea plants with cowpea mosaic virus, and harvested the virus in the form of ball-shaped nanoparticles. They then fixed S100A9-targeting molecules to the particles’ surfaces.

The researchers performed both prevention and treatment studies. In the prevention studies, they first injected the plant virus nanoparticles into the bloodstreams of healthy mice, and then later injected either triple negative breast cancer or melanoma cells into these mice. Treated mice showed a dramatic reduction in the cancers spreading to their lungs compared to untreated mice.

In the treatment studies, the researchers administered the nanoparticles to mice with metastatic tumours in their lungs. The treated mice exhibited smaller lung tumours and survived longer than untreated mice.

Prof Steinmetz envisions that the treatment could be useful after tumourectomy. “It wouldn’t be meant as an injection that’s given to everyone to prevent lung tumours. Rather, it would be given to patients who are at high risk of their tumors growing back as a metastatic disease, which often manifests in the lung. This would offer their lungs protection against cancer metastasis,” she said.

More detailed immunotoxicity and pharmacology studies are needed before this can progress to a treatment. Future studies will also explore combining this with standard cancer therapies such as chemotherapy.

Source: University of California – San Diego

Categories : Diseases, Syndromes and ConditionsTags :

Immune System Mutation Found in Tree-man Syndrome

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Cryo-electron microscopy structure of the human papillomavirus. Source: Wikimedia Commons CC0

A new study explores why some extremely rare cases of human papilloma virus (HPV) infections cause horn-like growths on the skin, a condition known as tree-man syndrome. 

Infection with HPV is extremely common, with most people catching it at some point and not even being aware of it due to a robust immune response, though some may experience skin or genital warts. Why only a handful of individuals react to it by developing tree-man syndrome was not well understood.

To find out why this strikes a handful and not others, Rockefeller’s Jean-Laurent Casanova examines the genetics of an otherwise healthy patient who contracted a severe case of tree-man syndrome and several family members who exhibited milder reactions to HPV. Casanova’s team identified a mutation that affects one’s reaction to HPV by decreasing the production of CD28, a molecule within the immune system that plays an important role in activating pathogen-fighting T cells.

Given the purported importance of CD28 to the immune system, the scientists were surprised that this CD28-deficient individual was healthy prior to contracting tree-man syndrome. “CD28 is thought of as a pillar of T cell immunity,” says Casanova. “The fact that this patient was otherwise healthy suggests that CD28 is largely redundant in human health. Something else is able to step up to provide protection against other infections.”

The findings, published in Cell, form a small part of Casanova’s larger work, which continues to demonstrate that the severity of  influenza, tuberculosis, COVID, and other diseases, is not solely dependent on the pathogen itself, but on genetics of the host, too.

Source: Rockerfeller University

Categories : Cardiovascular DiseaseTags :

Study Links Poor Sleep to Arrhythmias

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Photo by Cottonbro on Pexels

A large observational study linked poor sleep to arrhythmias, although genetic risk factors for rhythm problems appeared to lessen the association.

The results, published in the American College of Cardiology, show that best self-reported sleeps (getting 7-8 hours etc) had a 29% lower risk of developing atrial fibrillation or flutter and a 35% lower risk of bradyarrhythmia compared with those with the worst sleep patterns (eg, being a night owl, sleeping too little, snoring, and having insomnia or daytime drowsiness).

The ventricular arrhythmia risk fell away after demographic, lifestyle, and genetic risk factors were accounted for.

Together with previous research linking a healthy sleep pattern to reduced cardiovascular disease and heart failure risks, the findings, according to the researchers, “emphasise the importance of improving the overall sleep behaviours in the prevention of cardiovascular disease at an early stage among the high-risk populations”.

Being reversible, the findings support the idea of better sleep for arrhythmia prevention.

“However, rest assured, we must not yet lose sleep over their findings,” cautioned Alan Kadish, MD, and Jason Jacobson, MD, in an accompanying editorial. They drew attention to a number of limitations, making the findings more theoretical than currently practicable.

Despite the study’s more sophisticated approach, “a major limitation is that arrhythmia diagnoses were obtained from diagnostic codes,” they noted. Furthermore, arrhythmias are subject to significant variability.
Arrhythmia prevention doesn’t mean cardiovascular disease prevention, they added. “[N]ot all arrhythmias have the same significance, and many are the consequence (not cause) of cardiovascular disease,” they wrote. “Alternatively, sleep disorders and arrhythmias may both simply be indicators of declining health overall and not causally linked.”

The researchers proposed potential mechanisms of action including disrupted autonomic nervous balance of sympathetic nervous and vagal outflows and metabolic changes.

The editorialists pointed out the interesting finding that genetic predisposition to atrial fibrillation significantly modified the associations. Good self-reported sleep and low genetic risk together presented a 46% lower risk of atrial fibrillation than a poor sleep pattern plus high genetic risk.

Progressively poorer sleep health scores were associated with higher incidences of atrial fibrillation and bradyarrhythmias.

Sleeping 7 to 8 hours per day, infrequent or no insomnia, and no frequent daytime sleepiness were each linked to lower arrhythmia risk.

Source: MedPage Today

Categories : CancerTags :

Second or Third-degree Relatives Still Share Colon Cancer Risk

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Colon cancer cells. Source: National Cancer Institute on Unsplash

A new study has found that having second- or third-degree relatives with colorectal cancer increases a person’s risk of developing the disease.

Early colonoscopy screening is often recommended for first-degree relatives of someone diagnosed with early-onset (before age 50) colorectal cancer, cases of which have been increasing significantly over the past few decades. But the study suggests that early screening may be beneficial for second- and third-degree relatives as well.

The study reviewed more than 1500 early-onset colon cancer cases in the Utah Cancer Registry,found that first-degree relatives of someone diagnosed with early-onset colorectal cancer are 6 times more likely to be diagnosed with colorectal cancer before age 50, while second-degree relatives (aunts, grandparents etc) are 3 times likelier and third-degree relatives (first cousins etc) 1.56 times likelier.

“Our study provides new insight into the magnitude of risk for more distant relatives of colorectal cancer cases, and in particular, for relatives of cases who were diagnosed before age 50,” said first author Heather Ochs-Balcom, associate professor of epidemiology and environmental health, UB School of Public Health and Health Professions. “This work is important given the rising rates of early-onset colorectal cancer.”

There was also 2.6-fold higher risk of colorectal cancer at any age if they have a first-degree relative with early-onset colon cancer. The risk is 1.96 and 1.3 times greater for second- and third-degree relatives, respectively. In addition, the risk for all degrees of relatives for early-onset colon cancer is higher than the risk for colon cancer at any age.

The findings, published in Cancer Epidemiology, suggest that early colonoscopy screening may be beneficial for second-degree relatives and possibly third-degree relatives, in addition to first-degree relatives of individuals diagnosed with colorectal cancer before age 50.

The researchers also point out that relatives may benefit from being more aware of their extended family history and sharing this information with their physician when making cancer-screening decisions.

Source: University at Buffalo

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

Is Heart Pump Development Dead in the Water?

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Photo by Robina Weermeijer on Unsplash

At an annual meeting of the Heart Failure Society of America (HFSA), heart failure specialists agreed that recalling the HeartWare heart pump was good but debated whether its departure leaves the field of mechanical circulatory support (MCS) dead in the water.

In June, Medtronic stopped sales of its HeartWare Ventricular Assist Device (HVAD), citing excess neurological events and mortality with the device. As a result, Abbott’s HeartMate 3 became the only FDA-approved, durable left ventricular assist device (LVAD) on the market.

“Competition breeds innovation. When competition is absent or minimal, there is little incentive for corporations to innovate,” said Jennifer Cowger, MD, MS, of Henry Ford Hospital in Detroit, during the annual scientific meeting.

“While I believe the removal of the HVAD from the market was the ethical thing to do, unless we as a field start embracing MCS technology and change our messaging to the general cardiology community, our field is going to be viewed as niche to referring cardiologists and we’re going to face irrelevance and we’re going to have bad times ahead,” she added.

However Nancy Sweitzer MD, PhD, of the University of Arizona in Tucson, disagreed, pointing out that there are plenty of advances on the horizon.

Nine companies worldwide are developing heart pumps for this $3-4 billion market, Dr Sweitzer noted. Several devices under investigation — implantable ones with no external component — will probably proceed to first-in-man trials in the next year, she said. “There’s a lot of money if you do this well,” she added

Internal competition alone may be enough to advance the field, Sweitzer argued, citing Thoratec’s HeartMate II superseding their old HeartMate XVE.

“They put their own device up against their own device. So I would argue that corporate competition isn’t necessary when the stakeholders realize that we need to get better at this. I think the companies in this space realize there’s a huge unmet need here if we develop a really good MCS that was truly portable, gave people excellent quality of life, and had lower complications,” she said.

Yet given the pace of LVAD research, “in the next decade, we have cause for concern in the MCS field,” Dr Cowger countered.

Both debaters suggested that MCS technology shouldn’t stop at HeartMate 3, even with its relatively impressive performance.

“Outcomes on HeartMate 3 are not the outcomes we really want for these patients. There are still innumerable complications. Hospitalization rates are extraordinarily high in these patients post-implant even if they’re successful implants. They bleed, they get infected, they get strokes. That still happens,” noted Dr Sweitzer.

Innovation issues aside, Dr Cowger pointed out that HeartMate 3 is also much larger than the HVAD, and the smaller device’s loss leaves a gap for patients. She said negative media views had not helped the recent “sense of apathy and loss of enthusiasm for MCS”.

“Physicians don’t want to use technology that will harm or be perceived to harm patients,” she said, noting that sentiment has shifted from “VADs are sexy, cool” to “we would not choose LVADs over [heart] transplant.”

Source: MedPage Today

Categories : Neurodegenerative DiseasesTags :

Antioxidant Trial for Parkinson’s Disease Flops

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Source: Pixabay

Raising brain levels of the natural antioxidant urate through ionosine administration failed to slow the progression of Parkinson’s disease (PD), reported researchers at Massachusetts General Hospital (MGH).

Still, the rigor of the clinical study and some of its novel investigative approaches are seen as improving the prospects for future clinical trials to demonstrate the benefits of disease-modifying therapies for people with Parkinson’s disease. The results were published in JAMA.

“The convergence of epidemiological, biological, and clinical data from past research made a compelling argument that elevating urate, the main antioxidant circulating in the blood, could protect against the oxidative damage thought to play a role in Parkinson’s disease,” explained senior author Michael Schwarzschild, MD, PhD, a neurologist at MGH. “While our study did not rule out a protective effect of urate in Parkinson’s, it clearly showed that increasing urate did not slow disease progression based on clinical assessments and serial bran scan biomarkers of neurodegeneration.”

So far, no treatment has been shown to prevent or forestall progression of Parkinson’s disease, which affects the body’s motor system. The Phase III trial, SURE-PD3, enrolled 298 individuals recently diagnosed with early Parkinson’s disease based on MRI scans indicating loss of dopamine-producing brain cells characteristic of PD. In participants who received the metabolite inosine — which raises levels of urate in the brain and blood and has shown neuroprotective properties in preclinical models — there was no significant difference in the rate of disease progression compared to placebo. Additionally, there was an increased rate of kidney stones among those randomised to inosine treatment.

Despite the lack of evidence to support urate elevation, Dr Schwarzschild found the study successful in other ways. “The findings were very helpful in providing a reality check that now allows the field to move on to other therapeutic approaches,” he explained. “We also learned a lot in terms of clinical trials science for Parkinson’s, and ways to conduct future studies that will increase their chance of success.” One of those ways is to tailor treatment to subsets of patients who are most likely to benefit – a hallmark of the move to precision medicine in Parkinson’s research. In SURE-PD3, for example, only patients who had lower levels of urate were enrolled to increase the chance of benefit and reduce the chance of side effects.

Another innovative feature of the trial is that many participants gave blood samples for genotyping – a valuable source of genetic information that could figure in the hunt for clinical solutions in smaller subpopulations of PD patients. A significant number also volunteered for an extension of the study to help determine how monitoring at home could provide more efficient ways to conduct future clinical trials. “There were many positive results from SURE-PD3 which we believe will improve the prospects of researchers discovering a disease-modifying therapy which people with Parkinson’s have been desperately seeking,” Dr Schwarzschild concluded.

Source: Massachusetts General Hospital

Categories : Injury & Trauma VaccinesTags :

The Nagging Pain of Vaccination Shoulder Injuries

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Image source: NCI on Unsplash

Shoulder injury related to vaccine administration (SIRVA) has been documented long before COVID, and most commonly reported after influenza vaccination. The cause is often due to poor administration. 

However, the medical community cautions that currently it’s more of a medicolegal determination rather than a distinct diagnosis. The condition is also plagued by the lack of a solid evidence base, and causality is difficult to pin down.

However, most physicians that MedPage Today interviewed put shoulder injury down to improper injection technique, and that these problems should be taken seriously and treated appropriately. One recent overview noted that SIRVA is a “rare yet increasingly recognised complication of immunisation.”

“We’re certainly not seeing a pandemic of SIRVA” from COVID vaccines, said Dr DJ Kennedy, chair of physical medicine & rehabilitation at Vanderbilt University Medical Center. “It’s really rare and the literature to date is mostly case reports. But I do think it’s possible, absolutely” for vaccine-related shoulder injury to occur.

Dr Laura Keeling, orthopedic surgeon at MedStar Georgetown University Hospital, told MedPage Today that part of the reason SIRVA remains in the medicolegal realm is that it’s “more of a constellation of symptoms and findings” as opposed to a specific diagnosis.

Symptoms can vary depending on where the stray shot landed, resulting in various manifestations such as bursitis, tendonitis, or adhesive capsulitis (aka ‘frozen shoulder’).

Generally, it’s characterised as a “constellation of shoulder pain and reduced range of motion that occurs within 48 hours of vaccination and does not resolve within 1 week,” according to a recent paper co-authored by Dr Keeling. It’s also different from typical post-injection soreness, as the pain is more severe and it can impact mobility and function.

Generally, treatments include anti-inflammatory drugs, corticosteroid injections, and physical therapy. Occasionally surgery is necessary to treat an underlying pathology such as an exacerbated rotator cuff injury. Patients with SIRVA often land in their GP’s office first, and then may be referred to a specialist such as a physiatrist or an orthopedic surgeon.

“It’s the patients who have persistent symptoms who are referred to orthopedic surgeons,” Dr Keeling said. “If physical therapy and injection don’t work, then primary care refers to us.”

Physical medicine & rehabilitation physicians, or physiatrists, also play a large role in treating SIRVA.

“We treat based on a full evaluation including history and physical findings, and imaging if needed,” Dr Kennedy said. “Then we develop a comprehensive rehabilitation plan … that usually involves doing range of motion and strengthening exercises on a daily basis.”

Scott Noren, DDS, an oral surgeon in Ithaca, New York, said after his second COVID shot in early February, he developed shoulder pain: “It went in pretty deep and pretty high,” he told MedPage Today.

An MRI revealed fluid collecting in his joint, as well as adhesive capsulitis, he said. Physical therapy helped improve his range of motion to an extent, but he has lingering pain. It’s difficult to take x-rays and do long procedures as an oral surgeon: “I have pretty good pain even with just normal function now,” he said.

Source: MedPage Today

Categories : COVIDTags :

2-Metre Social Distancing May be Insufficient Indoors

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Photo by Paul Wong on Unsplash

A new study found that the two-metre physical distance required to avoid the viral shedding from a person infected with COVID caused by speaking or breathing may be insufficient indoors.

Researchers from the Penn State Department of Architectural Engineering found that indoor distances of two metres may not be enough to sufficiently prevent transmission of airborne aerosols. Their results were published online in Sustainable Cities and Society.

“We set out to explore the airborne transport of virus-laden particles released from infected people in buildings,” said first author Gen Pei, a doctoral student in architectural engineering at Penn State. “We investigated the effects of building ventilation and physical distancing as control strategies for indoor exposure to airborne viruses.”

The researchers looked at three factors: the amount and rate of air ventilated through a space, the indoor airflow pattern associated with different ventilation strategies and the aerosol emission mode of breathing versus talking. They also compared transport of tracer gas, usually used to test leaks in air-tight systems, and human respiratory aerosols ranging in size from one to 10 micrometres, a size that can still carry SARS-CoV-2.

“Our study results reveal that virus-laden particles from an infected person’s talking — without a mask — can quickly travel to another person’s breathing zone within one minute, even with a distance of two meters,” said corresponding author Donghyun Rim, associate professor of architectural engineering. “This trend is pronounced in rooms without sufficient ventilation. The results suggest that physical distance alone is not enough to prevent human exposure to exhaled aerosols and should be implemented with other control strategies such as masking and adequate ventilation.”

Aerosols were found to travel farther and more quickly in rooms with displacement ventilation, where fresh air continuously flows from the floor and pushes old air to an exhaust vent near the ceiling. This is the type of ventilation system installed in most residential homes, and it can result in a human breathing zone concentration of viral aerosols seven times higher than mixed-mode ventilation systems. Many commercial buildings have mixed-mode systems, which bring in outside air to dilute the indoor air and result in better air integration as well as tempered aerosol concentrations, according to the researchers.

“This is one of the surprising results: Airborne infection probability could be much higher for residential environments than office environments,” Prof Rim said. “However, in residential environments, operating mechanical fans and stand-alone air cleaners can help reduce infection probability.”

According to Rim, increasing the ventilation and air mixing rates can effectively reduce the transmission distance and potential accumulation of exhaled aerosols, but ventilation and distance are only two options in an arsenal of protective techniques.

“Airborne infection control strategies such as physical distancing, ventilation and mask wearing should be considered together for a layered control,” Prof Rim said.

The researchers are now applying this analysis technique to other kinds of occupied spaces, such as classrooms and transportation environments. 

Source: Pennsylvania State University

Categories : Neurodegenerative DiseasesTags :

Brain Cholesterol Production Linked to Alzehimer’s

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Amyloid plaques and neurons. Source: NIAH

Cholesterol manufactured in the brain appears to play a key role in the development of Alzheimer’s disease, new research indicates.

Scientists found that cholesterol produced by cells called astrocytes is required for controlling the production of amyloid beta, a sticky protein which forms the characteristic plaques in patients with Alzheimer’s. These plaques have been the target of efforts to remove or prevent them  in the hopes that this could treat or prevent Alzheimer’s.

The new findings offer important insights into how and why the plaques form and may explain why genes associated with cholesterol have been linked to increased risk for Alzheimer’s. The results also provide scientists with important direction as they seek to prevent Alzheimer’s.

“This study helps us to understand why genes linked to cholesterol are so important to the development of Alzheimer’s disease,” Heather Ferris, MD, PhD, Researcher, UVA’s Division of Endocrinology and Metabolism. “Our data point to the importance of focusing on the production of cholesterol in astrocytes and the transport to neurons as a way to reduce amyloid beta and prevent plaques from ever being formed.”

The work sheds light on the role of astrocytes in Alzheimer’s disease. Scientists have known that these common brain cells undergo dramatic changes in Alzheimer’s, but they have been uncertain if the cells were suffering from the disease or contributing to it. The new results suggest the latter.

The scientists found that astrocytes help drive the progression of Alzheimer’s by making and distributing cholesterol to brain cells called neurons. This cholesterol buildup increases amyloid beta production and, in turn, fuels plaque accumulation.

Normally, the buildup of amyloid beta is limited because cholesterol is kept quite low in neurons. But in Alzheimer’s, the neurons are no longer able to regulate amyloid beta, leading to plaque formation.
Blocking the astrocytes’ cholesterol manufacturing “robustly” decreased amyloid beta production in lab mice, the researchers reported. While it is presently unknown whether this could be applied in people to prevent plaque formation, the researchers believe that further research is likely to yield important insights that will benefit the battle against Alzheimer’s.

The fact that amyloid beta production is normally tightly controlled suggests an important role in brain cells, the researchers said. Doctors may therefore need to be cautious about blockage or removal of amyloid beta. Additional research into the discovery could shed light on how to prevent the over-production of amyloid beta as a strategy against Alzheimer’s, the researchers believe.

“If we can find strategies to prevent astrocytes from over-producing cholesterol, we might make a real impact on the development of Alzheimer’s disease,” Dr Ferris said. “Once people start having memory problems from Alzheimer’s disease, countless neurons have already died. We hope that targeting cholesterol can prevent that death from ever occurring in the first place.”

Source: University of Virginia Health System

Categories : Ageing Skeletal SystemTags :

A ‘Fountain of Youth’ for Bone Marrow Stem Cells

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Source: National Cancer Institute on Unsplash

Scientists have shown that reduced bone marrow stem cell function with ageing is due to changes in their epigenome, and they were able to reverse these changes in isolated stem cells by adding acetate. This ‘fountain of youth’ for the epigenome could become important for the treatment of diseases such as osteoporosis.

One responsible mechanism for age-related osteoporosis and fracture risk involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. 

For a long time, researchers have looked at epigenetics as a cause of ageing. Epigenetics looks at changes that affect the activity of genes. One of these is changes in proteins called histones, which package and thus control access to DNA. In this study, the researchers investigated the epigenome of mesenchymal stem cells, which are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.

“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice,” explained Andromachi Pouikli, first author of the study. “We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”

The researchers then sought to find out if it was possible to rejuvenate the epigenome of stem cells. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. “This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.

To see if this change could also be responsible for increased fracture risk and osteoporosis with age, the researchers studied human mesenchymal stem cells from hip surgery patients. In elderly patients with osteoporosis, the same epigenetic changes seen with mice were also seen in these human cells.

“Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells,” cautioned study leader Peter Tessarz. “However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects.”

The results were published in the journal Nature Aging.

Source: Max Planck Society