Tag: 12/8/21

Tiny Generators Tap Body Motion for Medical Applications

Researchers have created biocompatible generators which harvest body motion to produce electrical impulses for medical applications such as wound healing.

Piezoelectric materials such as ceramics and crystals can generate an electrical charge when mechanically stressed, and are used in many devices such as ultrasound transducers, vibration sensors, and cell phones. In medicine, electrostimulation using piezoelectric devices has been shown to be beneficial for accelerating wound and bone fracture healing, maintaining muscle tone in stroke victims, and chronic pain reduction. However, lack of biocompatibility has stalled progress in the field.

Now bioengineers at the University of Wisconsin’s Department of Materials Science and Engineering, led by Professor Xudong Wang, have developed implantable piezoelectric therapeutic devices. These thin, flexible devices make use of the piezoelectric properties of non-rigid, nontoxic biological materials such as silk, collagen, and amino acids.
The team came up with a method for self-assembly of small patch-like constructs that use the amino acid lysine as the piezoelectric generator. The self-assembly process incorporates a biocompatible polymer shell that surrounds the lysine as the polymer/lysine solution evaporates. Chemical interactions between the inner layer of lysine and the polymer coating orient the lysine into the crystal structure necessary for it to produce electric current when flexed.

“This work is an outstanding example of using the chemical properties of the materials to create a self-assembling product,” explained David Rampulla, director of the Division of Discovery Science and Technology at the National Institute of Biomedical Imaging and Bioengineering. “The process used is rapid and inexpensive, making production of such wafers for therapeutic applications feasible. That the wafers are biodegradable opens the possibility for creating electrotherapies that could be used to accelerate healing of an injured bone or muscle, for example, and then degrade and disappear from the body.”

In one of a number of tests, wafers were placed in the leg and chest of rats, movements of which compressed the piezoelectric wafers enough to create an electrical output. Blood tests performed after the transplanted wafer dissolved showed normal levels of blood cells and other metabolites, indicating no harmful effects from the dissolved device.

Prof Wang emphasises the simplicity of the elegant work. “We believe the technology opens a vast array of possibilities including real-time sensing, accelerated healing of wounds and other types of injuries, and electrical stimulation to treat pain and other neurological disorders. Importantly, our rapid self-assembling technology dramatically reduces the cost of such devices, which has the potential to greatly expand the use of this very promising form of medical intervention.”

The results were reported in the journal Science.

Source: Medical Xpress

Cervical Cancer Rates Falling Worldwide

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Cervical cancer incidence and mortality rates are holding steady or falling in most countries across the globe, according to a new analysis. Each country’s socioeconomic development level, cervical cancer screening use, and human papillomavirus (HPV) vaccination rates affect the rates. The findings are published online in CANCER.

Cervical cancer can be potentially prevented through screening for and treatment of precancerous lesions and through HPV vaccination. A team led by Mingjuan Jin, PhD, of the Zhejiang University School of Medicine in China, examined information on 31 countries released by the International Agency for Research on Cancer.

The analysis found that cervical cancer incidence and mortality rates were lower in more socioeconomically developed countries. Also, both past and predicted trends appear to be stable or decreasing in most countries, especially in those with effective cervical cancer screening and HPV vaccination programs.

Over the past decade, 12 countries had stable cervical cancer incidence rates, while rates fell in 14 and rose in five. Twelve countries had stable mortality rates from cervical cancer, with falling rates in 18 and only one had an increased rate.

The researchers predicted that for 27 countries, most are expected to have stable or decreasing trends over the next 15 years. Ten of the 27 countries are predicted to have stable incidence rates, nine to have decreasing rates, and eight to have increasing rates. Mortality rates are predicted to be stable in 16, decreasing in 10 and one to have an increasing rate.

“Effective cervical cancer screening programs and HPV vaccination should be further popularized to increase their coverage and ultimately decrease cervical cancer’s short-, mid-, and long-term burden,” said Dr Jin.

Source: Wiley Online

Joint Statement Says Prior Radiation Should not Affect Decisions to Image

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Previous radiation exposure should not be considered when assessing the clinical benefit of radiological exams, according to a statement by three scientific groups representing medical physicists, radiologists, and health physicists.

Medical radiation exposure is a hot topic. People receive average annual background radiation levels of around 3 mSv; exposure from a chest X-ray is about 0.1 mSv, and exposure from a whole-body CT scan is about 10 mSv. The annual radiation limit for nuclear workers is 20mSv.

The American Association of Physicists in Medicine, along with the American College of Radiology and the Health Physics Society, issued a joint statement opposing cumulative radiation dose limits for patient imaging, saying that there could be negative impacts on patient care. The statement opposes the position taken by several organisations and recently published papers.

“It is the position of the American Association of Physicists in Medicine (AAPM), the American College of Radiology (ACR), and the Health Physics Society (HPS) that the decision to perform a medical imaging exam should be based on clinical grounds, including the information available from prior imaging results, and not on the dose from prior imaging-related radiation exposures,” the statement reads.

“AAPM has long advised, as recommended by the International Commission on Radiological Protection (ICRP), that justification of potential patient benefit and subsequent optimization of medical imaging exposures are the most appropriate actions to take to protect patients from unnecessary medical exposures. This is consistent with the foundational principles of radiation protection in medicine, namely that patient radiation dose limits are inappropriate for medical imaging exposures.

“Therefore, the AAPM recommends against using dose values, including effective dose, from a patient’s prior imaging exams for the purposes of medical decision-making. Using quantities such as cumulative effective dose may, unintentionally or by institutional or regulatory policy, negatively impact medical decisions and patient care.

“This position statement applies to the use of metrics to longitudinally track a patient’s dose from medical radiation exposures and infer potential stochastic risk from them. It does not apply to the use of organ-specific doses for purposes of evaluating the onset of deterministic effects (e.g., absorbed dose to the eye lens or skin) or performing epidemiological research.”

The Radiological Society of North America also endorses the position.

The AAPM emphasises the importance of patient safety in their position. Radiation usage must be both justified and optimised and benefits should outweigh the risks.

“This statement is an important reminder that patients may receive substantial clinical benefit from imaging exams,” said James Dobbins, AAPM President. “While we want to see prudent use of radiation in medical imaging, and many of our scientific members are working on means of reducing overall patient radiation dose, we believe it is an important matter of patient safety and clinical care that decisions on the use of imaging exams be made solely on the presenting clinical need and not on prior radiation dose.

“AAPM is pleased to partner with our fellow societies—the American College of Radiology and the Health Physics Society—to bring a broadly shared perspective on the important issue of whether previous patient radiation exposure should play a role in future medical decision making.”

The AAPM cites the International Commission on Radiological Protection, which stresses that setting radiation exposure limits to patients is not appropriate. This is partly due to a lack of standardised dose estimates.

The position only addresses stochastic risks from radiation exposure, which are chance effects whose risk for a given imaging exam, like cancer,is unrelated to the amount of prior radiation. Deterministic effects, incremental, direct exposure responses, such as skin damage, result from different biological mechanisms and are not included.

The AAPM compiled a list of answers to frequently asked questions on the topic of medical radiation safety along with references to research papers which support the organisation’s position.

Source: News-Medical.Net

Red Blood Cell Abnormalities May Trigger Lupus

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A new study revealed that lupus may be triggered by a defective process in the development of red blood cells (RBCs) which leaves mitochondria remnants. The study was published in Cell.

The researchers found that in a number of lupus patients, maturing red blood cells fail to get rid of their mitochondria, which are normally excluded from red blood cells. This abnormal retention of mitochondria can trigger the cascade of immune hyperactivity characteristic of this disease.

“Our findings support that red blood cells can play a really important role in driving inflammation in a subgroup of lupus patients. So this adds a new piece to the lupus puzzle, and could now open the door to new possibilities for therapeutic interventions,” said the study’s senior author, Dr Virginia Pascual, the Drukier Director of the Gale and Ira Drukier Institute for Children’s Health and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine

Lupus is a chronic disorder with no cure that features intermittent and sometimes debilitating attacks by the immune system on the body’s own healthy tissues, including skin, joints, hair follicles, heart and kidneys. A common underlying factor in lupus is the abnormally elevated production of immune-activating proteins called type I interferons. Treatments aim to suppress immune activity, including interferon-driven inflammation.

Previous research found defective mitochondria in the immune cells of lupus patients. In the current study, the researchers focussed on red blood cells, which should lack mitochondria. Many lupus patients had red blood cells with detectable levels of mitochondria, and more common in patients with worse symptoms. By contrast, healthy controls had no mitochondria-containing red blood cells.

Lead author of the study, Dr. Simone Caielli, assistant professor of immunology research at the Drukier Institute and the Department of Pediatrics at Weill Cornell Medicine, then studied how human red blood cells normally get rid of mitochondria as they mature, as prior studies had mainly examined this in mice, and why this process could be defective in lupus patients.

Subsequent experiments showed these abnormal red blood cells cause inflammation. Normally, when red blood cells age or display signs of damage they are removed by macrophages, with binding antibodies helping removal. When the macrophages ingest them, the mitochondrial DNA in the red blood cells triggers a powerful inflammatory pathway called the cGAS/STING pathway, in turn driving type I interferon production. These findings show that “those lupus patients with mitochondria-containing red blood cells and evidence of circulating anti-RBC antibodies had higher interferon signatures compared to those who didn’t,” Dr Caielli said.

The researchers are now investigating how the mitochondria is retained in these cells. Identifying lupus patients with these cells could help predict when they are likely to undergo lupus flares and to develop therapies.

Source: Weill Cornell Medicine

Are There Different Symptoms for the Delta Variant?

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MedPage Today investigates whether, according to some reports, there is in fact a difference in Delta symptoms compared to earlier variants.

Though hard data are lacking, ZOE study leader Tim Spector, MB, MSc, MD, of King’s College London, said his app’s data suggests the disease is “acting different now. It’s more like a bad cold in this younger population.”

Headache, followed by sore throat, runny nose, and fever were now the most common reported symptoms.

“All those are not the old classic symptoms,” Dr Spector said, adding that cough dropped to fifth place, and “we don’t even see loss of smell coming into the top 10 anymore. This variant seems to be working slightly differently.”

Dr Spector’s data however is only preliminary and comes from self-reports, and has not even been peer reviewed or published. However, other experts also have noticed a change in reported COVID symptoms.

One of those who has heard reports but is cautious about their interpretation is David Kimberlin, MD, a paediatric infectious diseases expert at the University of Alabama at Birmingham.

“I don’t think with what we know right now that we can conclude [Delta] is much different in terms of symptoms,” Dr Kimberlin told MedPage Today. “There have been some reports that it causes more cold-like illness, but so did the original COVID. I think we’ll know more over the next couple of months as we have the opportunity to realise the data.”

Purvi Parikh, MD, of NYU Langone in New York City and a spokesperson for the American College of Allergy, Asthma & Immunology, has also heard of COVID being mistaken for allergies, but allergies do not come with high fever, nausea, vomiting, or diarrhoea.

Other symptoms unlikely in allergy include myalgia and chills, said Alan Goldsobel, MD, of Allergy & Asthma Associates of Northern California, who is also a professor at Stanford University. Allergy indicators include the time of year (for those with seasonal allergy), as well as itching, he added.

Distinguishing COVID from common cold symptoms could be harder, Drs Parikh and Goldsobel noted.

“If you aren’t sure, I do recommend COVID testing,” Dr Parikh said.

Source: MedPage Today

Attaining Herd Immunity for COVID Now Unlikely

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In an article published in the South African Medical Journal, Shabir Madhi, Professor of Vaccinology at Wits, argues that COVID variants have made the initial goal of attaining herd immunity no longer feasible, even for well-resourced countries. However, vaccine protection against severe COVID seems a more realistic path to normalcy.

In low and middle income countries (LMICs), the official COVID case estimates are likely grossly underestimated, Prof Madhi writes, due to a lack of testing coverage. Even in South Africa, the true number of COVID cases is likely in the region of 10 times the 2.39 million recorded through testing. The true number of COVID-related deaths in India is also estimated as 3.4–3.9 million, again 10 times the official count, and in South Africa it is likely three times the official  figure of 70 388 in July 2021.

While New Zealand researchers have suggested that COVID eradication is feasible, it is likely a very long term goal if at all attainable. The herd immunity goal can be considered with the equation (p1 = 1 – 1/R0), where p1 is the proportion of immune individuals who will also no longer transmit the virus, and R0 is the reproduction rate, ie the number of susceptible individuals a single infected person can further infect. However, this ignores key aspects of the virus.

The problem is that the proportion of people that would need to be immunised to achieve herd immunity was initially calculated at 67%, based on an assumed R0 of 3, derived from the Wuhan strain’s R0 of 2.5 to 4. However, the Delta variant has an R0 of 6, meaning that to reach herd immunity, 84% of the population would need to be vaccinated. In South Africa, this would be 100% of the population aged over 12.

The emergence of SARS-CoV-2 variants, especially the Beta variant with the E484K mutation, showed that existing vaccine protection, including the Pfizer variant, can be degraded to an extent.

Studies have strongly suggested that neutralising and antibody titers are associated with mild to moderate COVID protection, while protection from severe COVID may be mediated by T-cell immunity.

Real world data showed that in Israel, with a world best immunisation of 61.6% using the Pfizer vaccine which produces the greatest antibody response, herd immunity appeared to be successful until an outbreak of the more transmissible Delta variant combined with waning vaccine effectiveness. 

However, in the UK, excess death data showed that, even with a resurgence of cases caused by the Delta variant, there was a significant decoupling of deaths from cases. This points to the effectiveness of vaccines in preventing severe illness, as opposed to reaching herd immunity.

Vaccine rollouts have therefore not interrupted COVID transmission. Prof Madhi concludes that, based on an estimated R0 of 6 for the Delta variant, “it is unlikely that any country could have a sustainable strategy for durable high level of protection against infection by the delta variant. Mutations of the SARS-CoV-2 genome are likely to continue resulting in enhanced transmissibility, infectiousness and resistance to neutralising activity.”

He observes that the “UK approach seemingly concedes that the goal of herd immunity, even in a highly resourced setting, is unattainable.”

He adds that aspiring to reach herd immunity by wealthy countries comes at the cost of exacerbating vaccine inequality, which he says “is immoral.”
Antibody dynamics modelling suggests that a booster would be required every 2–3 years to protect against severe COVID, and every 6–9 months to protect against moderate disease. This is a challenging goal, and likely unattainable for most LMICs, especially given the slow rate of vaccination in those settings.

Source: South African Medical Journal