Month: March 2021

Categories : AgeingTags :

‘Feed-forward’ Loop in Cartilage Cells Worsens Osteoarthritis

On By ModernMedia


An unfortunate ‘feed-forward’ loop in cartilage cells appears to exacerbate arthritis, according to researchers Duke University and Washington University in Saint Louis.

Cartilage resists compressive forces, enhances bone resilience, and provides support on bony areas where there is a need for flexibility. In osteoarthritis, the most common form of arthritis,  the cartilage breaks down, allowing painful bone-on-bone contact. Osteoarthritis is the and affects millions of people worldwide with joint pain and stiffness. It is most commonly found in the knees, hips and spine.  

Chondrocytes build and maintain cartilage, with force-sensitive ion channels on their surface, which are called Piezo1 and Piezo2. Piezo channels respond to mechanical loads on the joint by sending signals into the cell that can change gene activity.

In osteoarthritis, degeneration and malfunction of chondrocytes, which are unable to repair themselves by division, contributes to the progressive breakdown of cartilage. Osteoarthritis is als marked by chronic, low-grade inflammation, driven by interleukin-1 alpha, a signalling molecule. Taking cartilage cells from pigs and from human joints removed for replacement surgeries, the researchers investigated the way inflammation affects chondrocytes.

The researchers found that interleukin signaling causes the chondrocytes to produce more Piezo channels, in turn increasing their sensitivity to pressure and resulting in what the researchers term a harmful ‘feed-forward’ loop that leads to further cartilage breakdown.

“Interleukin reprograms the chondrocytes so that they’re more sensitive to mechanical trauma,” Liedtke said. “The feed-forward cycle slowly grinds them down and the cell cannot be replaced.”

Liedtke likened healthy chondrocyte to “a tennis ball”, a bouncy sphere which is kept stiff by its internal matrix of actin fibres. But as these cells lose their ability to replace actin fibres, “they get softer, more squishy.”

However, more Piezo channels were created as the chondrocytes became squishier.

“Overexpressed Piezo channels render the inflamed chondrocyte hypersensitive to mechanical microtrauma, thus increasing the risk of mechanically-induced chondrocyte injury and subsequent progression of osteoarthritis,” said  first and co-corresponding author and biomedical engineer, Whasil Lee, who moved from the Liedtke-Lab to open her own laboratory at the University of Rochester

“It’s cartilage reprogramming itself to do more damage,” Liedtke said.

To confirm this relationship, the researchers blocked the activity of the Piezo channels and observed that the ‘squishiness’ of chondrocytes was reverted.

“We have known that mechanical loading of the joint is essential for maintaining cartilage health,” Guilak said. “In this study, we have uncovered a mechanism by which excessive loading under inflammatory conditions can create a situation that can lead to progressive cartilage degeneration.”

“We’re always looking for feed-forward mechanisms as facilitators of chronic disease,” Liedtke said. “Here we found one, which opens the door for us to come up with disease-modifying treatments, currently non-existent for osteoarthritis.”

Source: Duke University

Journal information: “Inflammatory Signaling Sensitizes Piezo1 Mechanotransduction in Articular Chondrocytes as a Pathogenic Feed-Forward Mechanism in Osteoarthritis,” Whasil Lee, et al. PNAS, March 22, 2021, DOI: 10.1073/pnas.2001611118

Categories : Environmental EffectsTags :

Edible Food Film Packaging Developed as Alternative to Plastic

On By ModernMedia

Researchers from India and Russia have created edible food films for packaging fruits, vegetables, poultry, meat, and seafood. 

These films are made up of natural ingredients, and as such are safe for health and the environment. In addition, these films are water-soluble and dissolve by almost 90% over 24 hours. A description of their research and the results of their experiments are published in the Journal of Food Engineering.

Using such films would help to reduce the problem of microplastics, micrometre-scale fragments of plastic which have been detected in human stools as well as inhaled through the lungs.Chemicals such BPAs, phthalates and flame retardants, as well as heavy metals included in plastics are of concern to human health. The increased surface area/volume ratio of microplastics in combination with their hydrophobicity, results in a high affinity with a broad range of hydrophobic and persistent organic pollutants, antibiotics, and heavy metals that could be introduced into the human body through the uptake of microplastics.

“We have created three types of food films based on the well-known naturally occurring seaweed biopolymer sodium alginate. Its molecules have film-forming properties. Sodium alginate is an auspicious carbohydrate macromolecule that has the potential film-forming properties upon hydrolysis and abundantly existed in cell walls as a mixture of various salts. The greatest advantage of sodium alginate is that it performs as liquid-gel in an aqueous medium.”

Rammohan Aluru, Study Co-Author and Senior Researcher of Organic Synthesis Laboratory, Ural Federal University

The researchers cross-linked alginate molecules with a natural antioxidant ferulic acid, resulting in a strong and homogeneous film that is more rigid and prolongs the life of the products. However, being able to produce edible, naturally sourced films also has other benefits.

“Food stays fresh longer due to the antioxidant components that slow down the oxidation processes,” said Grigory Zyryanov, professor of the Department of Organic and Biomolecular Chemistry at Ural Federal University. “In addition, we can add to the films natural antiviral agents that will also extend the shelf life of food. Garlic, turmeric, and ginger contain compounds that may prevent the spread of the viruses.”

No special equipment for the production of films is required, the authors claim, and can be scaled up to an industrial scale by manufacturers of  food products and films.

“It can also be produced at a polymer production plant. The only condition is that it must meet the standards that apply to food production. And if an inexhaustible source of algae the ocean is nearby it will be quite simple to create such films,” said Prof Zyryanov.

Source: News-Medical.Net

Journal information: Yerramathia, B. B., et al. (2021) Structural studies and bioactivity of sodium alginate edible films fabricated through ferulic acid crosslinking mechanism. Journal of Food Engineering. doi.org/10.1016/j.jfoodeng.2021.110566.

Categories : Cardiovascular DiseaseTags :

Patients Might Benefit From Thrombectomy in Basilar Strokes

On By ModernMedia

Despite the disappointing results of the BEST and BASICS trials for basilar artery occlusion strokes, in some cases, patients might benefit from endovascular therapy (EVT) after all, according to a closer look at the data.

Raul Nogueira, MD, of Grady Memorial Hospital and Emory University School of Medicine in Atlanta, and colleagues in the VERITAS group, presented their findings at the American Stroke Association virtual International Stroke Conference.

On adjusted intention-to-treat analysis, among the 351 stroke patients with baseline NIH Stroke Scale (NIHSS) scores of ≥ 10, having EVT showed a 38.7% chance of zero-to-moderate disability modified Rankin Scale [mRS] 0-3) at 90 days compared to 26.5% with best medical management (adjusted OR 1.94).

EVT also offered a mortality reduction benefit over controls (40.3% vs 48.2%), although at the risk of increased risk of symptomatic intracranial hemorrhage (5.0% vs 0.6%). Subgroup analysis suggested that older patients tended to have especially good outcomes with EVT.

Based on the study’s results, it does appear “that some patients with basilar artery occlusion strokes benefit from mechanical thrombectomy,” commented Steven Hetts, MD, of UCSF Mission Bay Hospitals in San Francisco.

“The trends do appear to be toward favoring EVT in selected patients, which is consistent with our earlier experience in anterior circulation large vessel occlusion [LVO] strokes,” he noted.

Given how rare they are, posterior circulation LVO strokes are challenging to study, and are also characterised by complex symptoms and severity.

Nogueira noted that the BEST and BASICS were underpowered as they had suffered from poor recruitment, crossovers, and selection issues. Additionally, the BASICS trial had undergone a protocol modification to allow recruitment of people with milder strokes (NIHSS <10), which had potentially diluted the treatment effect. An important point which had been missed was that underlying atrial fibrillation was more prevalent at baseline among the EVT arm than controls.

This implies “that their basilar occlusions may more likely have been from embolization of a clot from the heart to an otherwise normal basilar artery,” according to Dr Hetts. “I would expect that those patients would do better clinically than patients with underlying atherosclerotic disease in the basilar artery itself that leads to basilar artery occlusion.”

Source: MedPage Today

Presentation information: Nogueira RG, et al “Vertebrobasilar occlusion randomization to endovascular reperfusion versus intravenous thrombolysis or medical treatment alone systematic evaluation (VERITAS) collaboration” ISC 2021; Abstract LB 11.

Categories : COVIDTags :

Brazil’s ICU Beds Full Amidst ‘Catastrophe’

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Brazilian doctors say the situation is “well beyond chaos” even as the country’s COVID-sceptic president refuses to take decisive action against the pandemic.  

An article in The Guardian reports that Brazil is facing the worst medical crisis in its history, as researchers from its leading healthcare institute, Fiocruz, have said the country is entering into a “catastrophe”.

COVID intensive care units in virtually all of the country’s hospitals are either full or almost full, with Fiocruz warning that “The situation is absolutely critical.”

Ricardo Barros, Bolsonaro’s leader in the lower house said on Wednesday: “Our situation isn’t all that critical. Compared to other countries, it’s actually quite comfortable.” This was said on a day in which 2798 fatalities and a record 90 830 new cases were reported.

However, intensive care physicians interviewed by The Guardian tell a different story.

“Things are desperate,” said Dr Hermeto Paschoalick, the head of the critical care unit in the midwestern state of Mato Grosso do Sul, where ICUs are currently 93% full.

Things were worse elsewhere, especially in the state’s capital. “I was told yesterday that there’s a health clinic there with 20 ambulances parked outside. The patients are arriving from small towns in the interior and there’s nowhere to put them – so they just keep them in the ambulances,” said Dr Paschoalick.

Although most in his care were over 60s, Dr Paschoalick said there were young people as well. “Right now, I’ve got three people on ventilators including a 22-year-old woman and another who is 25. Both were pregnant when they arrived. One lost the baby, the other managed to give birth. Both are intubated and in a really bad state,” he said.

Many doctors are forced to choose which patients can receive a bed in ICU.

“People are going around saying Brazil is going to collapse,” said critical care doctor Pedro Carvalho at a university hospital in the riverside town of Petrolina. “But we’ve collapsed already – completely collapsed.” 

Brazil’s President Jair Bolsonaro meanwhile, shows no sign of changing his stance, claiming that there is a “war” against him. 

Source: The Guardian

Categories : Pain ManagementTags :

Dopamine Affects Pain Differently in Female and Male Mice

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Researchers have found that dopamine affects the neurons of male and female mice in different ways, a discovery which could have great potential in pain management for women, who suffer pain disproportionately throughout their lives.

Dopamine, popularly known as the brain’s ‘pleasure chemical’, is implicated in many functions, including the reward pathways and also the pain-relieving pathways associated with heroin that the researchers were focussing on. Dopamine is also suggested to be involved in attention, suggesting a link between substance abuse, pain and attention.

“We focused on this neural pathway because our previous work and that of others show that specific neurons release dopamine to regulate pain responses,” explained Thomas Kash, PhD, the John R Andrews Distinguished Professor of Pharmacology, School of Medicine lab, University of North Carolina. “Unfortunately, that research was done only in male mice. So we decided to look at both male and female mice, and what we found was very surprising.”

Previous research from Dr Kash’s lab using male mice showed that dopaminergic neurons were key in how opiates dampen pain, likely through dopamine and glutamate release. The new experiments focussed on a neural pathway starting at the midbrain region called the periaqueductal grey, including part of the dorsal raphe.

This brain region is involved in behavioural adaptation, which is the way animals respond to their environment. The dopamine-producing neurons in this region form a neural pathway with a structure known as the bed nucleus of the stria terminalis (BNST). 

“We found that activating this pathway reduced pain sensitivity in male mice, but made female mice move more, especially in the presence of something capturing their attention,” said first author Waylin Yu, PhD, a former graduate student in the Kash lab and current postdoctoral researcher at UC San Francisco. “We think this is because of the different ways males and females respond to pain.”

This seems to indicate that dopamine helps male mice simply not feel as much pain, while female mice are able to focus their attention elsewhere while experiencing pain.

While further investigation is needed, the results appear to show that the activation of specific neural projections to the BNST reduces acute and persistent inflammatory pain. This adds to the evidence that dopamine signaling can enhance the blocking of pain stimuli, counteracting severe pain.

“We hope to investigate how this pathway can regulate more emotional behaviours associated with chronic pain, and then also look at the dynamics of the system, such as how this pathway works in real time during behaviour measurements,” Dr Kash said. “These neurons are also implicated in the actions of opioids such as morphine, so we plan to investigate that domain, as well.”

Source: News-Medical.Net

Categories : CancerTags :

Colorectal Cancer Risk Is Not Reduced by Maintaining Weight

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A new study shows that, contrary to conventional wisdom, significant weight changes before treatment do not by themselves increase the mortality risk from colorectal cancer, rather it is changes in body composition.

In a population-based cohort study, for every 5% loss of body weight after colorectal cancer diagnosis had a 41% increased mortality risk.

“The conventional wisdom has been that colorectal cancer patients should avoid losing or gaining weight during treatment,”  explained Dr Justin C Brown, Assistant Professor and Director of Cancer Metabolism Program, Pennington Biomedical Research Center. “But maintaining your weight does not mean your body composition remains the same. Muscle can change quite dramatically, and those changes are associated with a much higher risk of death.”

“This study highlights how body composition can have a powerful impact on long-term health. We at Pennington Biomedical are committed to conducting innovative research to enable cancer survivors around the world to achieve their best possible health,” said Dr John Kirwan, Executive Director.

The study enrolled 1921 patients with stage I-III colorectal cancer, measuring skeletal muscle and body weight at diagnosis and then an average of 15 months later. The definition of stable body weight was a change of less than 5% of weight at diagnosis.

Researchers found having a stable body weight hides changes in skeletal muscle loss. Women were particularly vulnerable to losing muscle. One in five women with stable body weight lost muscle, while less than one in 10 men did.

“More research is needed to determine whether physical activity offers the best solution to prevent muscle loss or fatty deposits in muscle,” Dr Brown said. “But the findings provide colorectal cancer patients with more incentive to engage in physical activity programs that maintain and build muscle.”

Source: News-Medical.Net

Categories : Pain ManagementTags :

Electroacupuncture Tops Standard Care for Cancer Pain

On By ModernMedia
Image by wei zhu from Pixabay

A study found that electroacupuncture was superior to both auricular acupuncture and standard care for skeletal muscle pain management in cancer survivors.

Electroacupuncture reduced pain by 1.9 points on the 0-10 scale of the Brief Pain Inventory (BPI), compared to standard care. Auricular acupuncture, which was developed by the US military, reduced pain by 1.6 points compared to standard care, and was associated with more adverse effects (AE). Standard care consisted of analgesics, physical therapy, and steroid injections.

“The magnitude of effect of electroacupuncture was clinically important and durable,” the authors wrote. “This finding is consistent with evidence from other large acupuncture trials for chronic pain in the general population. Electroacupuncture has been shown to influence endogenous opioid release, which provides a mechanistic basis for chronic pain management.”

“The present trial includes a large and diverse group of cancer survivors and provides evidence that electroacupuncture provides additional benefits beyond usual care, including not only reduction in pain severity, but also improvements in physical function and quality of life and reductions in analgesic use.”

The PEACE Study enrolled patients with a history of cancer who had experienced musculoskeletal pain for at least three months and at least 15 of the preceding 30 days, with a worst pain intensity within the past week of ≥ 4 (moderate or greater) on the BPI.

Patients were randomised 2:2:1 to receive either electroacupuncture, auricular acupuncture (which were both delivered by licensed, experienced practitioners) or standard care. 

In electroacupuncture procedure, needles were placed at four sites near the location of pain and four additional sites elsewhere on the body to address comorbid symptoms. The treatments consisted of 10 weekly 30-minute sessions.

The auricular acupuncture, also known as ‘battlefield acupuncture’ had a standardised procedure where a single needle was inserted into the cingulate gyrus of one ear. The patient then walked for one minute, and if pain remained ≥ 1 on the BPI, another needle was inserted into the other ear. The process was repeated for the four remaining ear acupuncture points.

Mean baseline BPI scores ranged from 5.0 to 5.6. At week 12, mean BPI score had declined by 0.48 in the standard care group, 2.39 in the electroacupuncture group (P < 0.001), and 2.03 in the auricular acupuncture group (P < 0.001). The 0.36 difference between the two acupuncture groups exceeded the prespecified noninferiority margin of 0.657 for auricular versus electroacupuncture.

Source: MedPage Today

Journal information: Mao JJ, et al “Effectiveness of electroacupuncture or auricular acupuncture vs usual care for chronic musculoskeletal pain among cancer survivors: the PEACE randomized clinical trial” JAMA Oncol 2021; DOI: 10.1001/jamaoncol.2021.0310.

Categories : Diet and NutritionTags :

Sugar Tax Lacks Teeth in Spanish Study

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A study on the impact of a tax on fizzy drinks and other products with a high sugar content showed that there was little modification of consumer purchasing and consumption habits.

A sugar-sweetened beverage (SSB) tax was introduced in the Spanish region of Catalonia in May 2017.

“In response to rising levels of obesity and the serious and significant negative effects this is having for individuals, their families and wider healthcare systems, over the past five years there has been growing interest in the potential effectiveness of sugar taxes,” said lead researcher Dr Eleonora Fichera at the Department of Economics, University of Bath.

To find out how the sugar tax affected purchasing habits, the researchers used customer store card data from a chain of Spanish supermarkets.

The SSB tax resulted in an increase in the price of a one litre bottle of Fanta, Sprite or Seven Up! from €1.02 to €1.18. The tax also spurred reformulation, whereby drinks producers have created and marketed new products with greatly reduced overall sugar content (such as Coke Zero).

The overall impact was tiny, however – a mere 2.2% reduction in average calories per consumer.

“By analysing the effect of a tiered tax system for sugar-sweetened beverages in Catalonia and by comparing its impact with the rest of Spain (where a tax was not introduced) our results provide important evidence to policymakers keen to explore the potential effectiveness of this approach.

“And whilst our results demonstrate some impact in shifting behaviors towards products lower in sugar, this effect is modest at best. If these taxes are to be more effective, they need to be more visible at the checkout so that consumers become increasingly aware of the added cost of their high-sugar choices. This requires that the tax is more specific too, ensuring producers are forced to pass the tax through to consumers. Although more than 20% of the Catalan tax was passed through to consumers, not all of it was, making the tax less impactful,” concluded Dr Fichera. 

Source: News-Medical.Net

Journal information: Fichera, E., et al. (2021) How do consumers respond to “sin taxes”? New evidence from a tax on sugary drinks. Social Science & Medicine. doi.org/10.1016/j.socscimed.2021.113799.

Categories : COVIDTags :

A Tougher Spike Protein is Behind Transmissibility of Variants

On By ModernMedia

Researchers at Boston Children’s Hospital have analysed the structure of the SARS-CoV-2 variants, and have found that a tougher spike protein is likely responsible for their greater transmissibility.

Using a cryo electron microscope, the researchers imaged the spike protein down to the atomic level and discovered that the D614G mutation (a substitution of in a single amino acid ‘letter’ in the spike protein’s genetic code) produced a sturdier spike protein.

In the original, wild-type SARS-CoV-2, the spike protein would latch onto a cell’s ACE2 receptor and then fold in on itself, allowing the virus’ outer membrane to more easily fuse with the cell’s surface. However, they were susceptible to folding early, rendering those spike proteins useless. Around half of a SARS-CoV-2’s spike proteins would be folded in this way. However, this also made the virus harder for the immune system to lock on to.

“Because the original spike protein would dissociate, it was not good enough to induce a strong neutralising antibody response,” said research leader Bing Chen, PhD  at Boston Children’s Hospital.

When Chen and colleagues imaged the mutated spike protein, fewer are folded early because the D614G mutation blocks the shape change. While the spike protein is sturdier, it comes at the cost of being able to attach less easily to the ACE2 receptor.

“Say the original virus has 100 spikes,” Dr Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that are functional, so even though they don’t bind as well, the chances are greater that you will have infection.”

Dr Chen proposed that vaccines currently being updated should be modified for this new spike protein mutation, which should also have the side benefit of making the vaccines more effective. 

Applying structural biology to the spike protein, the team had come up with a ‘decoy’ molecule that bound to the spike protein 200 times more strongly than to the body’s ACE2 receptors. This was shown to inhibit the virus in the culture, opening up the door to a new type of treatment. 

Source: Medical Xpress

Journal information: Jun Zhang et al. Structural impact on SARS-CoV-2 spike protein by D614G substitution, Science (2021). DOI: 10.1126/science.abf2303

Categories : CancerTags :

Electromagnetic Fields Could Inhibit Breast Cancer Cell Spread

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A new study has shown that electrical fields can slow, and in some cases halt, the spread of breast cancer cells through the body.

The research also found how electromagnetic fields (EMFs) have the ability to hinder the number of cancer cells that can spread. Pulsed EMFs have also been shown to have some effectiveness in pain management, and low level EMFs were shown also to reduce blood glucose in animal models, a possible first step to treating diabetes.

“We think we can hinder metastasis by applying these fields, but we also think it may be possible to even destroy tumours using this approach,” said senior author Vish Subramaniam, former professor of mechanical and aerospace engineering at The Ohio State University. Subramaniam retired from Ohio State in December.

“That is unclear at this stage, but we are working on understanding that – how big should the electromagnetic field be, how close should it be to the tumour? Those are the next questions we hope to answer,” he said.
Subramaniam said that this had the effect of the EMF is to slow down some of the cancer cells. “It makes some of them stop for a little while before they start to move, slowly, again. As a group, they appear to have split up. So how quickly the whole group is moving and for how long they are moving becomes affected.”

The effect was applied to human cancer cells in vitro and has not been applied in humans.

The EMFs seem to selectively slow down the cancer cells’ metabolism by affecting the electrical fields inside the individual cells—completely noninvasively and without side effects like ionising radiation, which would mean a revolutionary form of cancer treatment if it could be made to work in practice. This ability to access a cell’s internal workings is new to the study of how cancer metastasises, said Prof  Subramaniam.

“Now that we know this, we can start to answer other questions, too,” Subramaniam said. “How do we affect the metabolism to the point that we not only make it not move but we choke it, we completely starve it. Or can we slow it down to the point where it will always remain weak?”

Source: News-Medical.Net

Journal information: Jones, T.H., et al. (2021) Directional Migration of Breast Cancer Cells Hindered by Induced Electric Fields May Be Due to Accompanying Alteration of Metabolic Activity. Bioelectricity. doi.org/10.1089/bioe.2020.0048.