Categories : Pain ManagementTags :

Transcranial Focused Ultrasound for Chronic Pain Relief

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A rodent study has demonstrated the potential for transcranial focused ultrasound (tFUS) to relieve chronic pain and other symptoms.

Neuromodulation, or therapeutic stimulation of neurons with electrical energy. chemicals or potentially with acoustic waves, can amplify or dampen neuronal impulses in the brain or body to relieve symptoms such as pain or tremor.

Ultrasound is a promising non-invasive, non-surgical type of neuromodulation. It offers a temporary modulation that can be tuned for a desired effect. In this study, researchers have shown that it can be targeted at neurons with specific functions.

A team led by Bin He, PhD, professor of biomedical engineering at Carnegie Mellon University, and funded in part by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), has demonstrated the potential of a neuromodulation approach that uses low-intensity ultrasound energy, called transcranial focused ultrasound-;or tFUS. In a paper published in Nature Communications, the authors describe the use of tFUS in rodent experiments, demonstrating the non-invasive neuromodulation alternative.

Moria Bittmann, PhD, Director of the Program in Biorobotic Systems, National Institute of Biomedical Imaging and Bioengineering, said: “Transcranial focused ultrasound is a promising approach that could be used to treat forms of chronic pain, among other applications. In conditions where symptoms include debilitating pain, externally generated impulses of ultrasound at controlled frequencies and intensity could inhibit pain signals.”

The researchers designed an assembly that included an ultrasound transducer and a multi-electrode array, which records neuronal data. During experiments with anaesthetised rodents, the researchers sent acoustic pulses into the brain cortex, targeting specific neurons, while recording change in electrophysiological signals from different neuron types.

When neurons transmit signals, whether engaging the senses or controlling movement, the firing of that signal across the synapse is termed a spike. The researchers observed two types of neurons: excitatory and inhibitory neurons.

When using tFUS to emit repeated bursts of ultrasound stimulation directly at excitatory neurons, the researchers saw an elevated impulse rate, or spike. Inhibitory neurons subjected to the same tFUS energy however did not display a significant spike rate disturbance. This showed that the ultrasound signal can be transmitted through the skull to selectively activate specific neuron sub-populations, in effect targeting neurons with different functions.

“Our research addresses an unmet need to develop non-toxic, non-addictive, non-pharmacologic therapies for human use,” said Prof He. “We hope to further develop the tFUS approach with variation in ultrasound frequencies and to pursue insights into neuronal activity so that this technology has the optimal chance for benefiting brain health.”

There are many broad applications for this research. Prof He believes non-invasive tFUS neuromodulation could be used to facilitate treatment for many people suffering from pain, depression and addiction. “If we can localise and target areas of the brain using acoustic, ultrasound energy, I believe we can potentially treat a myriad of neurological and psychiatric diseases and conditions,” Prof He said.

Source: National Institute of Biomedical Imaging and Bioengineering

Categories : Medical Research & TechnologyTags :

Improvement of Cell Culture Reporting Needed

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Photo by CDC on Unsplash
Photo by CDC on Unsplash

There is an urgent need for more standardised and detailed reporting of research on mammalian cells, and for greater control over and measurement of the environmental conditions of cell cultures, according to a recent study. This will improve the precision of human physiology models and contribute to the reproducibility of research.

Researchers analysed 810 randomly selected papers on mammalian cell lines. Fewer than 700 of those, involving 1749 individual cell culture experiments, included relevant data on the environmental conditions of the media in which the cells were cultured. The analysis suggests that the relevance and reproducibility of this type of research needs significant improvement.

“Mammalian cell cultures are fundamental to manufacturing viral vaccines and other biotechnologies,” explained marine scientist, Shannon Klein. “They are used to study basic cell biology, replicate disease mechanisms and investigate the toxicity of novel drug compounds before they are tested on animals and humans.”

Though cells are cultured in controlled incubators in line with standard protocols, cells grow and ‘breathe’ over time and exchange gases with their surrounding environment. This impacts their immediate environment, and even these small changes can affect parameters like culture acidity and dissolved oxygen and carbon dioxide. These changes in turn can affect cell function, causing different conditions to that found in a living human body.

The researchers found that around half of the papers analysed failed to report the temperature and carbon dioxide settings of their cell cultures. Less than 10 percent reported the atmospheric oxygen levels in the incubator and less than 0.01 percent reported the medium’s acidity. No papers reported the dissolved oxygen or carbon dioxide in their media.

“We were very surprised that researchers largely overlooked the maintenance of environmental factors, like culture acidity, at levels relevant to the physiological body over the full course of the cell cultures, despite it being well known that this is important for cell function,” said Ph.D. student Samhan Alsolami.

The team, led by KAUST’s marine ecologist Carlos Duarte and stem cell biologist Mo Li in collaboration with developmental biologist Juan Carlos Izpisua Belmonte from the Salk Institute, who is currently a visiting professor at KAUST, recommends that biomedical scientists develop standard reporting and control and measuring procedures, in addition to employing specialised instruments for controlling the culture environments of different cell types. Additionally, scientific journals should establish reporting standards and require adequate monitoring and control of culture medium acidity and dissolved oxygen and carbon dioxide.

“Better reporting, measurement and control of the environmental conditions of cell cultures should improve how well scientists can repeat and reproduce experimental results,” said Alsolami. “More careful attention could drive new discoveries and increase the relevance of preclinical research to the human body.”

The study is published in Nature Biomedical Engineering.

Source: Medical Xpress

Categories : Cardiovascular DiseaseTags :

Lung Fibrosis Drug Pirfenidone Shines in Heart Failure Trial

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Pirfenidone, a drug to treat lung fibrosis, has shown in early trial phases that it could also help patients who suffer from a common form of heart failure.

Trialed by University of Manchester and Manchester University NHS Foundation Trust doctors and scientists, in conjunction with Liverpool Clinical Trials Centre, pirfenidone could offer a much-needed viable treatment for heart failure with preserved ejection fraction (HFpEF). The study was published in Nature Medicine.

Just under a third of 55-year-olds will develop heart failure, and 2 to 3 of every 10 people diagnosed die within a year. In about half of patients with heart failure, the forward pumping function of the heart is normal, referred to as heart failure with preserved ejection fraction (HFpEF).

While a number of processes lead to heart failure, fibrosis of the heart muscle is thought to be an important mechanism in around half to two-thirds of patients with HFpEF and is associated with adverse outcomes.

Study leader Dr Chris Miller, National Institute for Health Research Clinician Scientist at The University of Manchester, said: “Heart failure is as devastating an illness as some of the most common cancers, however its profile is much lower and treatment options for HFpEF are very limited.

“Using cardiac MRI, we were able to select patients in whom heart scarring is important. Pirfenidone then reduced that scarring.”

Pirfenidone inhibits the biological processes involved in scar formation.

The study enrolled 94 patients with heart failure, normal forward pumping function of the heart and evidence of fluid retention, randomising half to a pirfenidone treatment group and half to placebo.

Eligible patients had cardiac MRI scanning, and those who had evidence of heart scarring, as indicated by a measurement called ‘extracellular volume’. 

A second cardiac MRI was conducted a year later to measure change in heart scarring, and researchers found that extracellular volume fell by 1.21% on average in patients who took pirfenidone compared with those receiving placebo.

“Based on data from previous studies, this amount of reduction in heart scarring could translate into a substantial reduction in rates of death and admission to hospital for heart failure, however larger trials are needed to determine this,” said Dr Miller.

Additionally, fluid retention also improved in patients taking pirfenidone compared to those receiving placebo, measured using a blood test called NT-proBNP.

Dr Miller added: “Though further investigation is required, the associated improvement in fluid retention provides support for heart scarring having a causal role in heart failure and being an effective treatment target”.

The most common side effects were nausea, insomnia and rash, which are similar to that which lung patients can experience taking the drug. The results are “exciting”, Dr Miller said, but added that further trials are needed.

Source: University of Manchester

Categories : Cancer Mental HealthTags :

How do Patients Who Exit Clinical Trials Early Feel?

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A new study has helped researchers understand the experiences of people who withdraw from clinical cancer trials.

Cancer clinical trials (CCTs) provide patients with an opportunity to receive experimental drugs, tests, and/or procedures that may lead to remissions. Such opportunities can be a great benefit for those who took part, but there is little known of the experiences of participants who withdraw from CCTs.

To address this, a first-of-its-kind study from the University of Pennsylvania School of Nursing (Penn Nursing) was conducted to better understand the post-trial needs of these patients and define responsible transitions when patients exit CCTs.

“Understanding the post-trial needs of patients with cancer and their families represents a measure of ethical respect of the many contributions that patients with cancer make to advancing our scientific knowledge and finding treatments that save lives,” said the study’s lead researcher, Connie M Ulrich, the Lillian S Brunner Chair in Medical and Surgical Nursing, professor of nursing, professor of medical ethics and health policy.

The study revealed three important areas:

  • Patients exiting CCTs feel intense symptoms, emotions, and awareness that their life spans are short and options seem limited.
  • The limited discussions with patients who are exiting on their immediate post-trial care needs can result in many feeling that there is no clear path forward.
  • Good communication that deliberately includes attention to post-trial needs throughout the CCT is needed to help scared and disappointed patients navigate their next steps.

The study is set for publication on the JAMA Network.

Source: University of Pennsylvania

Categories : COVIDTags :

WHO Urges Support for New COVID Origin Investigation

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The World Health Organization (WHO) has urged all countries “to put differences aside” in order to speed up investigations into the origins of the SARS-CoV-2 virus – including the unproven suggestion that it was accidentally released from laboratory.

This announcement follows a joint report into the origins of the coronavirus issued in March by the WHO and China. The UN agency, noting “insufficient scientific evidence to rule any of the hypotheses out” about the origins of the new coronavirus, insisted that to address the ‘lab hypothesis’, it needed access “to all data” in order to prevent global health threats in future.
“WHO calls for all governments to depoliticise the situation and cooperate to accelerate the origins studies, and importantly to work together to develop a common framework for future emerging pathogens of pandemic potential,” it said.

“We call on all governments to put differences aside and work together to provide all data and access required so that the next series of studies can be commenced as soon as possible.”

In a detailed statement, WHO explained the need for additional studies into “all hypotheses” about how SARS-CoV-2 made the jump from animals to humans.

Transparency call
A new independent advisory group of experts, the International Scientific Advisory Group for Origins of Novel Pathogens (SAGO), will support the project by coordinating the studies recommended in the March report, it said.

Nominations for the panel would be welcomed from all countries, WHO said, whose task would be similar to previous COVID missions to China and those launched to investigate the origins of avian influenza, Lassa virus and Ebola virus.

“This open call aims to ensure that a broad range of scientific skills and expertise are identified to advise WHO on the studies needed to identify the origins of any future emerging or re-emerging pathogen of pandemic potential,” the UN agency said.

Scientific endeavour
Noting how hard it is to identify the origin of any novel pathogen, the agency insisted that the mission “is not and should not be an exercise in attributing blame, finger-pointing or political point-scoring. It is vitally important to know how the COVID pandemic began, to set an example for establishing the origins of all future animal-human spill-over events.”

Access to sensitive information was needed for the success of the operation with “a further examination of the raw data from the earliest cases”, along with blood serum from potentially infected people in 2019, before the pandemic.

Data sharing
Data from “a number of countries” that reported finding the virus in blood samples taken in 2019 has already been shared with WHO, it noted. This included Italy, where WHO coordinated retesting of pre-pandemic blood samples outside the country.

“Sharing raw data and giving permission for the retesting of samples in labs outside of Italy reflects scientific solidarity at its best and is no different from what we encourage all countries, including China, to support so that we can advance the studies of the origins quickly and effectively,” WHO said, and restated that access to data was “critically important for evolving our understanding of science and should not be politicised in any way”.

Source: UN News

Categories : COVIDTags :

Western Cape Plateaus but Still in Grip of Third Wave

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In a digital media briefing, Western Cape Premiere Alan Winde said that the province had still not exited its third wave of COVID infections.

With an R value of 0.9, this was the first time in the third wave that the value was below 1. However, this could be due to testing delays caused by the long weekend. Indeed, a sharp daily increase in national COVID cases has been recorded as of Thursday’s latest data, with the NICD reporting a 90% jump to 14 271. Overall case positivity still hovers above the 20% mark at 22.52%.

Cases continue to spike
While overall cases in the Western Cape are plateauing, spikes in certain areas are seeing higher case rates than in the peak of the second wave. Oxygen is still being used as fast as it can be produced in the province, being supplemented by an additional 22 tonnes per day by truck deliveries from other provinces. A total of 3665 patients are in acute hospitals, with 99% occupancy in Metro areas. The Metro area is seeing a week-on-week case rise of 7%, which points to a plateau.

Vaccines proving effective – even against beta
The Johnson & Johnson vaccine however is proving effective, with 91-95% protection against death and 65-66% protection against hospitalisation. With regard to variants, the vaccine confers 67% protection against hospitalisation when beta is dominant and 71% where delta is dominant.

The Western Cape’s vaccination programme remains on track, with 287 000 doses of Pfizer and 28 800 J&J doses to arrive today, Friday 13th. 

Elsewhere, with 31.2 new cases per 100 000 people, KwaZulu-Natal may be becoming a COVID hotspot. 

A further 473 people have died from COVID, bringing the official death toll to 76 247.

Source: Western Cape Government

Categories : COVIDTags :

New Study Sheds More Light on AstraZeneca Blood Clots

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Credit: National Institutes of Health

A UK study has furthered the understanding of the novel blood-clotting condition associated with the Oxford/AstraZeneca vaccine.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is characterised by a blockage of veins and a marked platelet reduction. The rare condition was first identified in the UK by Professor Marie Scully (University College of London Institute of Cardiovascular Science), also a Consultant Haematologist at UCLH, and Dr Will Lester from University Hospitals Birmingham NHS Foundation Trust.

In a paper published in the New England Journal of Medicine (NEJM), the first 220 cases of definite and probable VITT in the UK are detailed.

The cases were presented by 182 consultant haematologists, and builds on understanding about the condition outlined in an April 2021 NEJM paper led by Professor Scully.

Meanwhile, a study led by Dr Richard Perry (UCL Queen Square Institute of Neurology and UCLH) published in the Lancet earlier this month provided the most detailed observations so far of cases of cerebral venous thrombosis (CVT). one of the commonest and severest manifestations of VITT.

The overall mortality rate of those presenting to hospitals with definite or probable VITT was 23%, the paper reported. The condition almost entirely manifested between five and 30 days after their first vaccination, with no sex differences seen, and no predisposing prior medical conditions.

The chances of death increased significantly the lower the platelet count and the greater the activation of the blood clotting system, increasing to 73% in patients with a very low platelet count and intracranial haemorrhage following blood clots in the brain.

Overall, 41% of patients had no previous medical diagnoses and 85% were less than 60 years old. Overall incidence in individuals under 50 was estimated to be 1 in 50 000 – in line with reports from other countries.

Though optimal treatment was still uncertain, it was being continually refined in real time, the researchers wrote. For instance, the introduction of the use of plasma exchange in the most severe cases has led to survival rates that were significantly better than would be predicted based on baseline characteristics.

The research adds to evidence for use of non-heparin-based blood thinners to tackle blood clotting in cases of VITT, and that use of intravenous immunoglobin was associated with better outcomes.

Professor Scully said: “As a new condition we are still learning about how best to diagnose and manage VITT, but as time goes on, we have been able to refine our treatment approaches and improve rates of survival and chance of recovery. This continuous learning in real time has been made possible thanks to collaboration between colleagues across the UK.”

Lead author Dr Sue Pavord, at Oxford University Hospitals NHS Foundation Trust, said: “We have worked relentlessly to understand and manage this new condition, so that the hugely successful vaccine roll out can continue, which is the most viable solution to the global pandemic.”

Source: University College London

Categories : AgeingTags :

Metabolism Through Life Varies in Unexpected Ways

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A new study published in Science suggests that falls in metabolism occur much later in life, with a peak at a much younger age than anticipated.

“There are lots of physiological changes that come with growing up and getting older,” said study co-author Herman Pontzer, associate professor of evolutionary anthropology at Duke University. “Think puberty, menopause, other phases of life. What’s weird is that the timing of our ‘metabolic life stages’ doesn’t seem to match those typical milestones.”

Together with an international team of scientists, Prof Pontzer analysed the average energy expenditure of more than 6,600 people ranging from one week old to age 95 as they went about their daily lives in 29 countries.

Previously, most large-scale studies measured how much energy the body uses to perform basic vital functions. But that amounts to only 50% to 70% of the calories we burn each day. It doesn’t take into account the energy we spend doing everything else.

To come up with a number for total daily energy expenditure, the researchers relied on the “doubly labeled water” method, a urine test that involves having a person drink water with isotopes of hydrogen and oxygen and measuring how quickly these were flushed. This gold standard technique for measuring energy expenditure in humans outside the lab since the 1980s, but studies have been limited in size and scope due to cost. To overcome this, multiple labs pooled their data.

The research into energy expenditures revealed some surprises: compared to body weight, infants had the highest metabolic rates of all, rather than people in their teens or 20s as might be expected.

Energy needs shoot up during the first 12 months of life, and by their first birthday, a one-year-old burns calories 50% faster for their body size than an adult.

This comes from more than just tripling their birth weight in the first year. “Of course they’re growing, but even once you control for that, their energy expenditures are rocketing up higher than you’d expect for their body size and composition,” said Pontzer, author of the book, “Burn,” on the science of metabolism. “Something is happening inside a baby’s cells to make them more active, and we don’t know what those processes are yet,” Pontzer said.

After this initial surge in infancy, the data show that metabolism slows by about 3% each year until we reach our 20s, when it stabilises.

Teenagers, despite their growth spurt, did not result in an uptick in energy intake once weight was accounted for. “We really thought puberty would be different and it’s not,” Pontzer said.

Midlife was another surprise, with a thickening waistline from the 30s often ascribed to a changing metabolism, but the results show other factors are responsible.

In fact, the researchers discovered that energy expenditures from the 20s to 50s were the most stable. Even during pregnancy, a woman’s calorie needs were no more or less than expected given her added bulk as the baby grows. Metabolism only declines after age 60, and only by 0.7% a year. A person in their 90s needs 26% fewer calories than one in midlife.

Lost muscle mass explains part but not all of the picture. “We controlled for muscle mass,” Pontzer said. “It’s because their cells are slowing down.”

The patterns held even when differing activity levels were taken into account.

Energy expenditure changes have been difficult to analyse because so much else is going on, Prof Pontzer said. But the research supports the idea that it’s more than age-related changes in lifestyle or body composition.

“All of this points to the conclusion that tissue metabolism, the work that the cells are doing, is changing over the course of the lifespan in ways we haven’t fully appreciated before,” Prof Pontzer said. “You really need a big data set like this to get at those questions.”

Source: Duke University

Categories : VaccinesTags :

The Promise of Plant-based Vaccines

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Recent advances in the development and testing of plant-made vaccines has rekindled interest in plant-produced pharmaceuticals, including edible drugs, for human use. Technology and manufacturing advances could boost the uptake of such therapeutics, wrote Hugues Fausther-Bovendo and Gary Kobinger in an article published in Science. 

Currently, therapeutic proteins such as antibodies, hormones, cytokines, and proteins in vaccines are mostly produced in bacteria or eukaryotic systems, including chicken eggs and mammalian or insect cell cultures. In 1986, scientists proposed the use of plants for the production of these proteins in what is termed ‘molecular farming’. Such a production process can be less costly and produce fewer contaminants. 

Thus far, just one therapeutic protein derived from plants for human use has been approved (in 2012, for Gaucher disease). More recently in 2019, a plant-produced influenza virus vaccine completed phase III clinical trials with promising results, and phase III trials for a plant-made vaccine COVID vaccine started in early 2021. Plant-produced proteins have a number of advantages for vaccine development, according to Fausther-Bovendo and Kobinger, in particular the strong immune response the plant components of virus-like particles in vaccines can generate, which may reduce the need for adjuvants. 

Also interesting to consider are oral, plant-made therapeutics, said Fausther-Bovendo and Kobinger. Possibly needing minimal processing, they could avoid expensive, lengthy manufacturing. 

Edible vaccines – still predominantly in the preclinical stage of development – are also currently under development, the authors note. Compared to the proof-of-concept edible vaccines first tested decades ago, which generated weak immune responses, newly developed edible plant-made vaccines are now capable of provoking stronger immune responses, thanks to improved technology. 

Because doses for therapeutics are much higher than for vaccines, investment in manufacturing infrastructure must increase to achieve large-scale manufacturing of plant therapeutic products, Fausther-Bovendo and Kobinger said.

Source: EurekAlert!

Categories : PaediatricsTags :

Only 10% of Children Completely ‘Outgrow’ ADHD

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In contrast to popular belief, most children diagnosed with attention deficit hyperactive disorder (ADHD) do not in fact outgrow the disorder according to a new study in the American Journal of Psychiatry. Instead, it manifests itself in adulthood in different ways over a lifetime, increasing and decreasing.

“It’s important for people diagnosed with ADHD to understand that it’s normal to have times in your life where things maybe more unmanageable and other times when things feel more under control,” said lead researcher Margaret Sibley, associate professor of psychiatry and behavioral sciences at the University of Washington School of Medicine and a researcher at Seattle Children’s Research Institute.

Decades of research characterise ADHD as a neurobiological disorder typically first detected in childhood that persists into adulthood in approximately 50% of cases, but this study found that only 10% of children completely outgrow it.

“Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in the Multimodal Treatment Study of ADHD continued to experience residual symptoms into young adulthood,” they wrote.

ADHD is characterised by two main clusters of symptoms: inattentive symptoms which look like disorganisation and forgetfulness, and also the hyperactive, impulsive symptoms. In children, those symptoms look like having a lot of energy, such as running around and climbing on things. In adults, it manifests more as verbal impulsivity, difficulty with decision-making, and not thinking before acting. The disorder affects people differently and looks different depending on the phase of life.

Some people with ADHD also report a unique ability to hyper-focus, as in some Olympic athletes. While many people may experience symptoms similar to ADHD, it is estimated the disorder roughly affects 5% to 10% of the population, said Sibley.

This study followed a group of 558 children with ADHD from 8-years old to 25 years-old. Every two years, the cohort had assessments to determine whether they had symptoms of ADHD. Family members and teachers were also asked about their symptoms.

According to Prof Sibley, the belief that 50% of children outgrow ADHD was first put forward in the mid-1990s. Most studies, she said, only re-connected once when the kids reached adulthood and weren’t able to see if the ADHD had really gone away.

Coping with ADHD
Researchers have yet to find what causes ADHD to flare. Prof Sibley said it could be stress, the wrong environment, and not having a healthy lifestyle of proper sleep, healthy eating, and regular exercise. Also, if a person is not taking the time to manage symptoms and really understand what works best for them, then the symptoms are probably going to get more out of control, she said.

The two main treatments for ADHD are medication and therapy, though people can pursue their own healthy coping skills as well, said Prof Sibley.

Researchers found that most people who technically no longer meet criteria for ADHD in adulthood still retained traces though they were coping well.

“The key is finding a job or a life passion that ADHD does not interfere with,” Prof Sibley said. “You are going to see a lot of creative people have ADHD because they’re able to be successful in their creative endeavors despite having ADHD, whereas people who might be required to do very detail-oriented work at a computer all day—that could be a really hard combination for a person with ADHD.”

Prof Sibley said the time to seek professional help is when the symptoms cause problems in life, including not performing at one’s best, interpersonal problems, and inability to complete basic daily tasks.

Source: Medical Xpress