Tag: 4/8/21

Cancer Survivors Experience Accelerated Ageing

Source: JD Mason on Unsplash

A new study published in Journal of the American Geriatrics Society indicates that cancer survivors, especially older ones, are more likely to experience faster functional decline as they age, compared with those without a history of cancer.

For the study, 1728 men and women (aged 22 to 100 years) were evaluated from 2006 to 2019, with 359 of these adults reporting a history of cancer. Among all participants, a history of cancer was associated with a 1.42 greater odds of weak grip strength. Those with a history of cancer and over 65 had a 1.61 greater odds of slow gait speed than those with no cancer history, and also had lower physical performance scores. Additionally, compared with those with no history of cancer, older individuals with a history of cancer experienced steeper declines in grip strength and gait speed. Reduced prefrontal cortex area is one of the factors thought to contribute to slow gait.

“Findings from our study add to the evidence that cancer and its treatment may have adverse effects on aging-related processes, putting cancer survivors at risk for accelerated functional decline,” said senior author Lisa Gallicchio, PhD, of the National Cancer Institute. “Understanding which cancer survivors are at highest risk, and when the accelerated decline in physical functioning is most likely to begin, is important in developing interventions to prevent, mitigate, or reverse the adverse aging-related effects of cancer and its treatment.”

Source: EurekAlert!

Helping People With Depression Quit Smoking can Save Lives

Source: Sabine R on Unsplash
Source: Sabine R on Unsplash

Giving the means to quit smoking to patients with depression could save as many as 125 000 lives over the next 80 years, researchers estimate. This number could be as high as 203 000 if people with depression who are not yet in mental health care settings are included.

The study, led by the Yale School of Public Health, shows the potential benefits that smoking cessation could have in a population suffering disproportionately from tobacco-related disease and death. Smokers with depression already find it harder to quit, and experience more negative withdrawal symptoms if they do, including increased depression. The study is also the first to estimate the population health effects of integrating smoking cessation treatments with standard mental health care.
Using more than a decade of data from the National Survey on Drug Use and Health, the researchers made a model to project the effectiveness of smoking-cessation treatments into the future. They assessed how the benefits varied based on different rates of treatment adoption over the next 80 years.

Simulating the health benefits reveals that, at least 32 000 deaths could be prevented by 2100 if a significant number of patients with depression adopted any kind of cessation treatment. Assuming 100% mental health service utilisation and pharmacological cessation treatment, the number of potential lives saved could rise to 203 000.

“We’ve known for a long time that people with depression smoke more than the general population, and that mental health care settings often don’t have cessation treatment as part of standard care. Our study asks: what is that missed opportunity? What do we have to gain when mental health care and smoking cessation treatment are fully integrated,” said lead author and assistant professor Jamie Tam, PhD. The findings are published in the American Journal of Preventive Medicine.

Such high benefits would be a best-case scenario, the researchers cautioned. Even so, the model’s results match public health experts’ long-standing predictions of the results of smoking-cessation treatment becoming a routine part of mental health care. The findings show that even less-optimal cessation treatments would greatly impact both quality and length of life for patients living with depression.

“Beyond reducing the risk of early death, smoking cessation improves quality of life and increases productivity,” Tam added. “Decision makers should remove barriers to mental health care and smoking cessation treatments for people with mental health conditions.”

The researchers concluded that while existing treatments, such as nicotine replacement therapy, varenicline, and bupropion, can raise cessation rates by nearly 60%, in the future there would be even larger health gains if there were better cessation treatments.

Source: Yale University

Exact Location of Body’s Blood Pressure Sensors Finally Revealed

Credit: CC0

After 60 years of fruitless searches by scientists, researchers from the University of Virginia have finally determined the location of our bodies’ natural blood-pressure sensors.

These cellular sensors monitor blood pressure and adjust hormone levels to keep it in check. Scientists have long suspected that these ‘baroreceptors’, may exist in or around specialised kidney cells called renin cells, but no one has been able to locate the baroreceptors within the cell until now.

The new findings, from UVA Health’s Dr Maria Luisa S Sequeira-Lopez and colleagues, finally reveal where the barometers are located, how they work and how they help prevent hypertension or hypotension. The study was published in Circulation Research.

“It was exhilarating to find that the elusive pressure-sensing mechanism, the baroreceptor, was intrinsic to the renin cell, which has the ability to sense and react, both within the same cell,” said Dr Sequeira-Lopez. “So the renin cells are sensors and responders.”

Back in 1957, it was first proposed that a pressure sensor existed inside renin cells because the cells had to know when to release renin, a hormone that helps regulate blood pressure. Though the baroreceptors had to exist, scientists couldn’t tell what it was and whether it was located in renin cells or surrounding cells.

To tackle this decades-old mystery, the study’s researchers used a combination of innovative lab models and determined that the baroreceptor was a ‘mechanotransducer’ inside renin cells. This mechanotransducer detects pressure changes outside the cell, then transmits these mechanical signals to the cell nucleus, akin to how the cochlea turns sound vibrations into nerve impulses.

Through in vitro tests, the researchers found that applying pressure to renin cells triggered changes within the cells and decreased activity of the renin gene, Ren1. The scientists also compared differences in gene activity in kidneys exposed to lower pressure and those exposed to higher pressure.

Ultimately, when the baroreceptors detect excess pressure outside the renin cell, renin production is cut back, while low blood pressure prompts more renin production.

Dr Sequeira-Lopez said she is looking forward to the work to “unravel the signaling and controlling mechanisms of this mechanotransducer and how we can use the information to develop therapies for hypertension.”

Source: University of Virginia

Lipid Shield Protects Both Immune and Cancer Cells

Colourised scanning electron microscope image of a natural killer cell. Credit: National Institutes of Health

A newly discovered lipid ‘shield’ that prevents natural killer cells from being destroyed by their own deadly biological weapons also allows some cancer cells to evade an immune system attack, a study at Columbia University has found.

The findings, which may lead to new treatments for aggressive cancers, were published in the journal PLoS Biology.

Natural killer cells are efficient assassins that can eliminate up to six infected or cancer cells each day. The deadly immune cells grab onto their target and blast it with toxic proteins and enzymes that punch holes in the cell’s membrane. But these substances are also capable of destroying the natural killer cell’s membrane during the attack.

But how do natural killer cells survive releasing this blast of deadly substances? “I’ve been working on natural killer cells since the early 1990s, and every time I gave a talk about these cells, someone always asked that question,” said study leader and immunology expert Jordan Orange, MD, PhD, a professor at Columbia University Vagelos College of Physicians and Surgeons. “And nobody really knew until now.”

Avoiding self-destruction

Yu Li, a graduate student working with Prof Orange to understand how natural killer cells work and co-author of the study, thought the answer might lie in the double layer of lipids that makes up the outer membranes of all cells. Compared with other cells, Li noticed, the membranes of natural killer cells looked more orderly and more densely packed with lipids when viewed under a microscope.

“There were a lot of hypotheses about why natural killer cells don’t kill themselves during their attack on other cells, but they all proposed there might be a magic, unknown protein protecting these cells,” Li says. But Li had doubts. “Based on biophysical considerations, I didn’t think a protein would be strong enough to protect the cells. When I looked at the cells, I thought of lipids.”

To test out his idea, he exposed the membranes to a compound that weakens the structure of the lipid layer. With less dense and less orderly membranes, the natural killer cells were unprotected from their own toxic blast—and perished along with their targets.

Shields up

To survive their own toxic blast natural killer cells reinforce their membranes immediately beforehand, Li found. The small granules holding the deadly substances move to the outer edge of the natural killer cell. As the granule unleashes its cargo into the space between the killer and target cells, its own unusually dense lipid membrane merges with and reinforces the natural killer cell membrane.

“In essence, Li found that the membrane turns into a blast shield,” Prof Orange says. “And the protection comes from the way the membrane’s lipids are arranged. When the lipids are arranged in a more orderly fashion, more lipids can be packed into the membrane. The toxic substances simply can’t find a way into the membrane,” Orange says.

Cancer cells steal the idea

Besides natural killer cells, some cancer cells have adopted this defence against natural killer cells’ attacks, Li and Prof Orange found. They may also use this as a defence from cytotoxic T cells, another immune cell that uses lipids for self-protection.

Li found that cells from an aggressive breast cancer known to be impervious to natural killer cells fortify their membranes during the attack. The reinforcement was vital for the cancer cells, Li discovered, because when he added a membrane compound that disrupts lipid packing, the cancer cells were rendered vulnerable.

“We don’t know yet if this is a general mechanism by which cancer cells resist natural killer cells,” Li said. “If it is generalisable, we can start to think of therapies that disrupt the tumor cell membrane and make it more susceptible to attack by the immune system.” 

Source: Medical Xpress

New Guidelines for Venous Thromboembolism Released

Source: Marcelo Leal on Unsplash

The American College of Chest Physicians (CHEST) have released new clinical guidelines for venous thromboembolism (VTE) management, which provide 29 recommendations on 17 Patients, Interventions, Comparators, Outcomes (PICO) questions, four of which have not been addressed previously.

The last full edition of the guideline, “Antithrombotic Therapy and Prevention of Thrombosis 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines,” was published in 2012, with an update in 2016. This guideline is the first addressing this topic, which will have regular updates as new evidence emerges according to the Living Guidelines Model of the American College of Chest Physicians.

Within the updated recommendations, the panel generated 29 guidance statements, 13 of which are graded as strong recommendations. These include:

  • In patients with acute isolated distal deep vein thrombosis (DVT) of the leg who are managed with anticoagulation, we recommend using the same anticoagulant regimen as for patients with acute proximal DVT.
  • In patients with cerebral venous sinus thrombosis, we recommend anticoagulation therapy for at least the treatment phase (first 3 months) over no anticoagulant therapy.
  • In patients with acute DVT of the leg, we recommend against the use of an inferior vena cava (IVC) filter in addition to anticoagulants.
  • In patients with thrombosis and antiphospholipid syndrome being treated with anticoagulant therapy, we suggest adjusted-dose vitamin K antagonists over direct oral anticoagulant therapy.

“These guidelines help to clarify for providers the intricacies of managing patients with VTE,” said expert panel member, Scott C Woller, MD, FCCP. “Serving as a comprehensive reference for any stage, the recommendations cover aspects from initial management through secondary prevention and risk reduction of post-thrombotic syndrome.”

The order in which PICOs and guidance statements are presented in the manuscript is intended to follow the chronology of VTE management:

  • Whether to treat
  • Interventional and adjunctive treatments
  • Initiation phase
  • Treatment phase
  • Extended phase
  • Complications of VTE

The guidance statements are mainly intended for clinicians who manage patients with VTE but could also inform researchers selecting topics for future studies. Patients and policy makers may also be informed by the guideline content.

Source: EurekAlert!