Pump up the Volume: Killing Cancer with Ultrasound

Sound waves
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University of Michigan scientists have developed an ultrasound technology that uses high-powered pulses to break down liver tumours in rats, kill cancer cells and stimulate the immune system to destroy the remaining tumour and prevent metastasis.

The researchers reported in Cancers that, by destroying just 50% to 75% of liver tumour volume, the rats’ immune systems were able to clear away the rest, with no evidence of recurrence or metastases in more than 80% of animals.

“Even if we don’t target the entire tumour, we can still cause the tumour to regress and also reduce the risk of future metastasis,” said Professor Zhen Xu, corresponding author of the study.

The treatment was also found to spur the rats’ immune responses, possibly contributing to the eventual regression of the untargeted portion of the tumour and preventing further spread of the cancer.

The noninvasive technique, called histotripsy, focuses ultrasound waves to mechanically destroy target tissue with high precision. The relatively new technique is currently being used in a human liver cancer trial in the US and Europe.

Often, a tumour cannot be directly targeted for certain treatments due to the mass’ size, location or stage. To investigate the effects of partially destroying tumours with sound, this latest study targeted only a portion of each mass, leaving behind a viable intact tumour. It also allowed the team to demonstrate the technique in less ideal conditions.

“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective noninvasive liver tumour ablation,” said Tejaswi Worlikar, a doctoral student in biomedical engineering.

Liver cancer ranks among the top 10 causes of cancer related deaths worldwide, with poor prognosis despite multiple treatment options. Tumour recurrence and metastasis after initial treatment is common, demanding improved treatments.

The ultrasound approach comes without the side effects from present treatments such as radiation and chemotherapy.

“Our transducer, designed and built at U-M, delivers high amplitude microsecond-length ultrasound pulses – acoustic cavitation – to focus on the tumour specifically to break it up,” Prof Xu said. “Traditional ultrasound devices use lower amplitude pulses for imaging.”

The microsecond pulses create microbubbles within targeted tissues that rapidly expand and collapse, tearing up cancer cells and disrupting the tumour’s structure.

Source: University of Michigan

Report Finds One in Four Preschool Children in SA Malnourished

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One in four preschool children (aged four to five years) shows signs of long-term malnutrition, according to a new survey.

The Thrive by Five Index, released on 8 April, was produced by First National Bank and Innovation Edge in collaboration with the Department of Basic Education (DBE). The study surveyed more than 5000 children enrolled in early learning programmes across the country.

The study found about 25% of children were physically stunted, as a result of malnutrition in pregnancy and the early years of life. About 65% of children are either cognitively delayed, physically stunted, or both. This means they are not meeting the learning or growth standards expected of a child their age, and will start school at a disadvantage.

“Children from poorer households tended to perform worse,” said Sonja Giese, the lead researcher in the study. Giese is the founder of Innovation Edge, which was set up to support innovation in early childhood development. The rates of stunting were highest among the poorest children.

She said each child was assessed for about an hour. Children were assessed for things such as early mathematical skills, literacy and communication, motor development and coordination, among other things.

But Giese also drew attention to the positive outcomes of the study, saying that even within the poorest group of children there were some children who performed very well, causing a kind of “positive deviance”.

“I think there are some really interesting lessons we can learn from these outliers …Some children just thrive in difficult circumstances,” said Giese. She said more research could help to figure out how and why these children are thriving.

Giese said as the DBE had just taken over responsibility for early childhood education from the Department of Social Development, the study could show where attention should be focused.

In a statement about the survey, the DBE said that the first five years of the child’s life are the most important and stressed the importance of physical development during this stage.

Data for the survey was collected in late 2021 from a nationally representative sample of children aged 50-59 months enrolled in early learning programmes. The final weighted sample used for analysis included 5,139 children from 1,247 programmes across the country. The school quintile system was used to measure the probable socio-economic background of the children who were assessed. School quintiles are based on the income, education and unemployment levels of households in the school catchment area and for the purposes of the Thrive by Five study, the researchers assumed that the income level of children attending early learning programmes within each school cluster matched the income level of children attending the nearest school.

The researchers included more children from quintile 1 – the poorest – in order for the study to be representative of the country and each province. “That’s how we tried to make sure that it really provides a window into the world of children today in South Africa, exactly where they are and how they’re living,” said Giese.

Giese said that some of the data had not yet been analysed and further findings would be released over the next year.

This story was written by Liezl Human for GroundUp and is reproduced under a Creative Commons 4.0 Licence.

Source: GroundUp

Low Sex Hormone Levels Linked to Rotator Cuff Tears

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Patients with lower levels of sex hormones are more likely to need to undergo surgery for rotator cuff tears, suggests a study in The Journal of Bone & Joint Surgery

Sex hormone deficiencies “was associated with a significantly increased incidence of RCR within [two] independent databases,” according to the new research by Peter N. Chalmers, MD, and colleagues at University of Utah. These findings add to previous evidence that hormone levels may be a systemic factor contributing to the development of rotator cuff tears, a common condition that is a major cause of shoulder pain.

The study used health insurance data for nearly 230 000 adults under age 65 who underwent surgery to repair a torn rotator cuff from 2008 through 2017. Patients were matched for age, sex, and type of insurance to patients who did not undergo rotator cuff surgery.

Patients undergoing rotator cuff repair had an average age of 54 years, and 58% were men. Most patient characteristics were similar between those who underwent rotator cuff repair and those who did not, except tobacco use, which was more common in the surgical cohort.

Dr Chalmers and colleagues found that 27% of women and 7% of men undergoing rotator cuff surgery had diagnosed sex hormone deficiency, compared with 20% and 4% respectively in the control group. Controlling for other factors, rotator cuff repair likelihood was 48% higher in women with oestrogen deficiency and 89% higher in men with testosterone deficiency.

To confirm their findings, the researchers then accessed the Veterans Administration Genealogy database which has data on millions of individuals. Here, they found that rotator cuff repair was about 2.5 times more likely for women with oestrogen deficiency and three times more likely for men with testosterone deficiency.

This study builds on a prior study by the same research group, which demonstrated that women with mutations in an oestrogen receptor gene were more likely to develop rotator cuff disease, with higher rates of failed rotator cuff surgery.

Despite limitations such as not accounting for hormone replacement therapy, the observed association between sex hormone deficiency and rotator cuff repair strongly supports the theory that low oestrogen and testosterone levels may contribute to the development of rotator cuff tears. The researchers concluded that “Future prospective studies will be necessary to understand the relationship of sex hormones to the pathophysiology of rotator cuff disease.”

Source: EurekAlert!

Kids are a Significant Source of COVID Spread in Households

COVID spreads extensively in households, with children being a significant source of that spread. These are the findings from an antibody surveillance study published in CMAJ Open, which also shows that about 50% of household members were infected from the first-infected individual during the study period.

Although kids were less likely to spread the virus compared to adults, children and adults were equally likely to become infected from the first-infected individual.

The antibody surveillance study included 695 participants from 180 households in the Canadian city of Ottawa in Ontario, between September 2020 and March 2021. Included households had at least one member having had a confirmed COVID infection and at least one child within their household.

“Our study was conducted when we were dealing with a less transmissible virus and pandemic restrictions were strongly in place, and we still had a 50% transmission rate within households. Flash forward to where we are today with an extremely transmissible variant of COVID and the majority of pandemic restrictions lifted; it’s safe to say transmission rates will be higher even though we have a high vaccination rate amongst those who are eligible,” said Dr Maala Bhatt, the study’s lead author. 

“I know many want to ‘live with COVID’ and abandon the layers of protection that were previously mandated, but it’s important to be aware of the high transmissibility of this virus in closed, indoor settings, such as schools,” she cautioned.  “Our most vulnerable and our youngest children who are not yet able to be vaccinated are still at risk for COVID infection.”

In the Canadian province of Eastern Ontario, where the study was done, COVID is on the rise once again. Three-quarters of all children admitted to CHEO with COVID have come during the Omicron wave. Since the beginning of January this year a third of the roughly 4900 monthly visits to the Emergency Department were for COVID-related symptoms.

The study hypothesised that children would act as “an even greater source of spread within households with the emergence of more infectious variants.” Children also have “considerable potential to spread” in settings such as school and daycare, where they congregate indoors for long periods, especially now when masking is not required in many jurisdictions.

“While we’re lucky hospitals aren’t currently overloaded, emergency departments are and positivity rates are on the rise, even amongst children,” said Dr Bhatt, paediatric emergency physician and Director of Emergency Medicine Research at CHEO and an Investigator at the CHEO Research Institute.

“We continue to learn more about COVID and its potential long-term health impacts, and we still aren’t clear about how long immunity lasts; these are all things researchers continue to study.”

Source: University of Ottawa

Thoracic Aorta Diameter Can Predict Cardiovascular Risk

Anatomical model of a human heart
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A new study in the journal Radiology has found that the diameter of the thoracic aorta can be a biomarker for heart attacks and other adverse cardiovascular events in women and men, and has the advantage of being simple to add on to existing screening.

The thoracic aorta is divided into an ascending aorta that rises from the left ventricle of the heart and a descending aorta in the back of the chest.

While the thoracic aorta grows with age, but changes of vessel size and structure, a phenomenon known as vascular remodelling, have a systemic nature involving haemodynamic and biological processes that are also linked to cardiovascular disease.

“While enlargement of the thoracic aorta is a frequent finding in clinical practice, few longitudinal data regarding its long-term prognosis for major cardiovascular disease outcomes at the population level exist,” said study senior author Maryam Kavousi MD, PhD, from University Medical Center Rotterdam.

Dr Kavousi and colleagues assessed these associations in 2178 participants from the population-based Rotterdam Study. Participants underwent multi-detector CT scans between 2003 and 2006 and were followed for an average of 9 years. Thoracic aorta diameters were indexed for body mass index (BMI).

Larger BMI-indexed ascending and descending thoracic aortic diameters were significantly associated with increased risk of adverse cardiovascular outcomes like stroke and death in both women and men.

“Our results suggest that imaging-based assessment of diameter of thoracic aorta can be considered as a risk marker for future cardiovascular disease,” Dr Kavousi said.

In women, greater ascending aortic diameter was associated with 33% higher cardiovascular mortality risk. There seems to be a sex difference in remodelling of the ageing aorta, with faster deterioration in women.

“Ageing could affect aortic health and structure more adversely in women than in men,” Dr Kavousi said.

The study findings suggest that cardiovascular risk assessment associated with thoracic aortic size among asymptomatic women and men could lead to effective, sex-specific prevention strategies.

“As the aortic diameter is significantly related to body size, use of aortic diameters indexed for body measurements could improve its prognostic value for cardiovascular outcomes,” Dr Kavousi said.

Measurement of thoracic aorta size is an easy addition to current screening, the researchers said. The study made use of cardiac CT scans that are already commonly used to assess coronary calcium. Thoracic aortic diameter could also be measured routinely, for example as part of CT-based lung cancer screening.

The current study was based on a single CT-based assessment of thoracic aorta among a large group of participants from the general population, followed up for nine years for incidence of cardiovascular outcomes and mortality. The researchers have recently repeated the CT-based assessment of thoracic aorta among these participants after a median of 14 years.

“This provides an exciting and unique opportunity to study sex-specific risk profiles and patterns of growth in thoracic aorta in the general population,” Dr Kavousi said.

Source: Radiological Society of North America

Greater Concussion Risk in Fighters Who Cut Weight for a Bout

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There is more risk of suffering concussions or being misdiagnosed with head trauma is greater among fighters who rapidly cut weight before bouts, usually by dehydrating, researchers have revealed for the first time.

More than 60% of athletes in combat sports such as boxing and mixed martial arts (MMA) reported that their symptoms worsened after they dehydrated to make strict weight classes.

These controversial weight cutting techniques involve stop drinking water and endure long periods in saunas.

MMA athletes reported concussion severity to be 40% higher compared to other sports, particularly boxing – believed to be due to the mix of striking and contact with the ground.

Published in the Clinical Journal of Sports Medicine, the study comes after a series of tragedies associated with weight cuts, with some athletes even dying in the attempt to achieve a perceived competitive edge, by competing in a smaller weight class.

They found that as competitors dramatically dehydrate themselves to meet stringent weight classes, the associated symptoms may ‘muddy the waters’ of baseline concussion testing, due to similar symptoms.

This is because the symptoms of hypohydration – where competitors enter a water deficit – match concussive signs, such as dizziness, headaches, and lethargy.

This study has spurred further probes into the neurological implications of rapid weight loss. The researchers have called on governing bodies to check fighters’ hydration levels before fights.

Researcher Nasir Uddin, from St Mary’s University, said: “This study shows that current concussion testing does not account for the crossover of symptoms from being dehydrated, and is potentially putting fighters at risk.

“Not only is cutting weight through dehydration in and of itself dangerous, but it might actually exacerbate concussion symptoms and, even more concerningly, means medical professionals may actually misdiagnose it.

“Going forward, governing bodies should ensure hydration and baseline concussion symptoms are taken into account before and after bouts.”

The study surveyed more than 130 anonymous athletes representing six combat sports, all aged 18 or above and who had previously cut weight.

It also found that 65% of the fighters had an experience of a weight cut “not going to plan”, suffering a lack of energy, strength, power, coordination or increased susceptibility to being ‘rocked’ during a bout.

This means the dangerous practice may not offer a competitive advantage after all.

Dr Jamie Tallent, from the University of Essex, said: “This is perhaps the most surprising finding that not only are weight cuts dangerous – they leave fighters at a disadvantage more often than not and may exacerbate the risks of being further injured.”

Source: University of Essex

Why Some Lung Cancer Patients Stop Responding to Treatment

Anatomical model of lungs
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Published in Cancer Research, researchers have discovered why some patients with nonsmall cell lung cancer stop responding to treatment with tyrosine kinase inhibitors (TKIs): an epigenetic switch is flipped, reactivating genes that inhibit the effect of these drugs.

TKIs, specifically epidermal growth factor receptor inhibitors, are typically used to treat people with nonsmall cell lung cancer, a prevalent and usually incurable type of cancer that accounts for 80–85% of lung cancers. About 15–20% of these patients will become resistant to these standard treatments, resulting in their eventual death. This is because the cells develop a mutation that leads to resistance. But about half of the remaining resistant patients remain unexplained. 

Cellular biologist Andrea Kasinski and her lab have found that the cause involves epigenetics. When cells lose a histone called methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors. This could open up development of new therapeutics and gives researchers and doctors a deeper insight into the biology and progression of cancers, especially the role that epigenetic-modifying proteins play in drug resistance, a poorly understood phenomenon.

“For the majority of genes that contribute to cancer, we’re not sure how they work yet,” Kasinski said. “And for many, we don’t have a way to therapeutically target them. Research like this, that helps us understand how those genes work to determine cancer outcomes, adds to our understanding of the network. This knowledge will ultimately lead us to better therapeutics.”

Source: Purdue University

For Some, It may be Daydreaming – not ADHD

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Maladaptive daydreaming (MD) may be a better diagnosis for some people than ADHD, researchers argue in a paper in the Journal of Clinical Psychology. MD is a condition whereby people slip into involved highly detailed and realistic daydreams that can last hours at the cost of normal functioning – but it is not yet recognised as a psychiatric disorder.

Dr Nirit Soffer-Dudek of the Consciousness and Psychopathology Laboratory in the Department of Psychology at BGU is one of the leadings experts on the condition and wants to have MD added to the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM VI), by promoting rigorous research into this condition.

Explaining the concept of MD, Dr Soffer-Dudek said: “Some individuals who become addicted to their fanciful daydreams experience great difficulty in concentrating and focusing their attention on academic and vocational tasks, yet they find that an ADHD diagnosis and the subsequent treatment plan does not necessarily help them. Formally classifying MD as a mental disorder would enable psychological practitioners to better assist many of their patients.”

Previous studies had found high levels of ADHD in those also presenting with MD, thereby raising the question of whether MD was separate from ADHD. In the current study, the investigators assessed 83 adults diagnosed with ADHD for inattention symptoms, MD, depression, loneliness, and self-esteem. Of those, about 20% met the proposed diagnostic criteria for MD, with significantly higher rates of depression, loneliness, and lowered self-esteem, compared to those with ADHD that did not meet criteria for MD.

“Our findings suggest that there is a subgroup of those diagnosed with ADHD who would benefit more from a diagnosis of MD,” concluded Dr Soffer-Dudek.

Source: Ben-Gurion University of the Negev

Allergies Linked to Increased Cardiovascular Risk

Runny nose and sneezing symptoms
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A national US health survey has revealed that adults with allergies are at an increased risk of hypertension and coronary heart disease, with the biggest risk increase seen in Black male adults. The study is presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference.

“For patients with allergic disorders, routine evaluation of blood pressure and routine examination for coronary heart disease should be given by clinicians to ensure early treatments are given to those with hypertension or coronary heart disease,” said Yang Guo, PhD, the study’s lead author.

An association between allergic disorders and cardiovascular disease was detected in prior research, findings which remained controversial, Dr Guo explained. The present study sought to determine whether an increased cardiovascular risk exists in adults with allergic disorders.

The study used 2012 data from the National Health Interview Survey (NHIS), a cross-sectional survey of the US population. In the allergic group were adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. The study included a total of 34 417 adults, over half of whom were women, average age 48.5 years. The allergic group included 10 045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors.

Having a history of allergic disorders was found to be associated with increased risk of developing hypertension and coronary heart disease. Further analysis showed that individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of hypertension. An increased risk of coronary heart disease was seen in male Black/African American participants between ages 39-57. Asthma was the largest contributor of risk of hypertension and coronary heart disease.

Dr Guo said that to confirmed these findings, large cohort studies with long-term follow-up are required. Discovering the underlying mechanism could also help with management.

Source: American College of Cardiology

Leukaemia Drug Clofarabine Might Also Treat Bladder Cancer

Woman using lab equipment
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A drug screen on various cancer cell lines revealed hundreds of compounds with inhibitory effects on cancer, and one in particular, the leukaemia drug clofarabine, showed effectiveness in two specific types of bladder cancer. The study was published in the journal European Urology.

A joint study group conducted a drug screen which investigated the effects of over 1700 chemical compounds on 23 cell lines representing different stages and subtypes of bladder cancer. From this, the researchers identified more than 470 substances with inhibitory effects. These included a large number of drugs already used for cancers, but also medications for other diseases, such as malaria, parasitic diseases and various mental disorders.

One of these compounds, clofarabine, an antimetabolite drug currently used to treat childhood leukaemia, was studied in more detail. For this purpose, the researchers developed models from patient material representing different types of bladder cancer. Besides ‘conventional’ urothelial carcinoma, they were also able to establish an animal model for sarcomatoid carcinoma – a rare subtype of bladder cancer, for which there is currently no effective chemotherapy. 

Describing the results, first author Iris Ertl said: “We found that clofarabine induced complete remission in mice with conventional urothelial carcinoma and massive, sustained tumour shrinkage in animals with sarcomatoid carcinoma, while not causing any apparent side effects.” 

Next steps will be clinical trials in which patients with metastatic bladder cancer who cannot receive cisplatin-based therapy, will be treated with clofarabine prior to radical cystectomy. Shahrokh Shariat explains: “Our discovery was made possible by the close interdisciplinary collaboration with CeMM and the Center of Cancer Research. We very much look forward to continuing to work with our partners to incorporate our findings into clinical practice.”

Source: Medical University of Vienna