Tag: 21/7/23

Novel Metal Complex Treatment Kills Antibiotic-resistant Bacteria

Photo by CDC on Unsplash

An innovative treatment paves the way for reducing antimicrobial resistance in the treatment of a deadly infection in chickens, according to a new study in Veterinary Microbiology. The ground-breaking study investigated the effectiveness of a novel metal-derived complex in treating Avian Pathogenic Escherichia coli (APEC), a serious respiratory infection of chickens which has become increasingly more resistant to antibiotics. A growing body of evidence indicates that the APEC could potentially spread to humans.

University of Surrey’s Professor Roberto La Ragione said: “Antimicrobial resistance is one of the biggest threats to human and animal health. Not being able to use antibiotics to treat an infection not only prolongs an illness and associated welfare issues, but also increases the likelihood of it spreading.

“Coronavirus demonstrated how easily a pandemic can happen, and the threat of another is looking more likely as antibiotics to treat simple bacterial infections are no longer working.”

To test the effectiveness of the metal complex, manganese carbonyl, researchers worked with the Greater Wax Moth larvae and APEC. Split into two groups, the first received manganese carbonyl, whilst the second, the controls, received either a phosphate-buffered saline (PBS) or dimethyl sulfoxide (DMSO). After four days, the survival rate for the larvae which received manganese carbonyl was between 56–75%, whereas in the control group, the survival rate was between 25–45% (PBS) and 19-45 per cent (DMSO), demonstrating the protective effect of the complex.

The test was repeated in chickens infected with APEC, who again received either manganese carbonyl or PBS. Bacterial shedding identified in the faeces of the chickens was significantly lower 24 hours post-treatment in those who received manganese carbonyl compared to the PBS control group, indicating bacterial killing induced by the compound. This is supported by caecal samples taken three days post-treatment which again found significantly fewer bacteria in those that received manganese carbonyl. Examination of tissue samples from the livers of the birds indicated no toxic effects from the metal compound, which was observed in the larvae.

Dr Jonathan Betts, a Research Fellow at the University of Surrey School of Veterinary Medicine, said:

“The development of alternatives to antibiotics is vital to safeguard our future health. Metal complexes such as manganese carbonyl could do this, as we have shown not only are they effective, but they are much cheaper to produce than traditional antibiotics.

“Discovering the effectiveness of manganese carbonyl in treating APEC is a monumental step forward in tackling antimicrobial resistance as it shows we don’t necessarily need more antibiotics; we just need to think more innovatively in developing treatments.”

The international research team also included the University of Surrey, the Animal and Plant Health Agency, the University of Connecticut, the University of Sheffield and Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg.

This study was made possible by a BBSRC grant to Professor La Ragione and Professor Poole.

Source: University of Surrey

Black Adults Experience Less Cognitive Decline after Retirement

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A study published in the Journal of the American Geriatrics Society found that immediately after retirement, white adults tended to experience a significant decline in cognitive function, whereas Black adults experienced minimal cognitive decline. White men showed the steepest post-retirement cognitive decline across sex/race combinations, whereas Black women showed the least decline.

White women performed better cognitively at retirement than other race/sex subgroups, and after retirement, their cognitive functioning declined at a rate that was slightly less than the average for this study. Results were adjusted for sociodemographics and physical and mental health indicators.

The study, which included 2226 US participants followed for up to 10 years, revealed greater post-retirement cognitive decline among individuals who attended college compared with those who did not.

“The results seem to point to the possibility that better job opportunities could lead to greater cognitive losses after retirement whereas exposure to lifelong structural inequalities may actually ease transition to retirement with respect to cognitive aging,” said lead author Ross Andel, PhD, of Arizona State University’s Edson College of Nursing and Health Innovation.

Source: Wiley

Microwaving Plastic Baby Food Container Releases Billions of Plastic Nanoparticles

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Experiments have shown that microwaving plastic baby food containers available on the shelves of US stores can release huge numbers of micrometre or smaller-sized plastic particles – in some cases, more than 2 billion nanoplastics and 4 million microplastics for every square centimetre of container.

Though the health effects of consuming micro- and nanoplastics remain unclear, the University of Nebraska-Lincoln researchers further found that three-quarters of cultured embryonic kidney cells had died after two days of being introduced to those same particles. A 2022 report from the World Health Organization recommended limiting exposure to such particles.

“It is really important to know how many micro- and nanoplastics we are taking in,” said Kazi Albab Hussain, the study’s lead author and a doctoral student in civil and environmental engineering at the University of Nebraska-Lincoln. “When we eat specific foods, we are generally informed or have an idea about their caloric content, sugar levels, other nutrients. I believe it’s equally important that we are aware of the number of plastic particles present in our food.

“Just as we understand the impact of calories and nutrients on our health, knowing the extent of plastic particle ingestion is crucial in understanding the potential harm they may cause. Many studies, including ours, are demonstrating that the toxicity of micro- and nanoplastics is highly linked to the level of exposure.”

The team embarked on its study in 2021, the same year that Hussain became a father. While prior research had investigated the release of plastic particles from baby bottles, the team realised that no studies had examined the sorts of plastic containers and pouches that Hussain found himself shopping for, and that millions of other parents regularly do, too.

Hussain and his colleagues decided to conduct experiments with two baby food containers made from polypropylene and a reusable pouch made of polyethylene, both FDA-approved plastics. In one experiment, the researchers filled the containers with either deionised water or 3% acetic acid (the latter intended to simulate dairy products, fruits, vegetables and other relatively acidic consumables) then heated them at full power for three minutes in a 1000-watt microwave. Afterward, they analysed the liquids for evidence of micro- and nanoplastics: the micro- being particles at least a micrometre in diameter, the nano- any particles smaller.

The actual number of each particle released by the microwaving depended on multiple factors, including the plastic container and the liquid within it. But based on a model that factored in particle release, body weight, and per-capita ingestion of various food and drink, the team estimated that infants drinking products with microwaved water and toddlers consuming microwaved dairy products are taking in the greatest relative concentrations of plastic. Experiments designed to simulate the refrigeration and room-temperature storage of food or drink over a six-month span also suggested that both could lead to the release of micro- and nanoplastics.

“For my baby, I was unable to completely avoid the use of plastic,” Hussain said. “But I was able to avoid those (scenarios) which were causing more of the release of micro- and nanoplastics. People also deserve to know those, and they should choose wisely.”

With the help of Svetlana Romanova from the University of Nebraska Medical Center, the team then cultured and exposed embryonic kidney cells to the actual plastic particles released from the containers – a first, as far as Hussain can tell. Rather than introduce just the number of particles released by one container, the researchers instead exposed the cells to particle concentrations that infants and toddlers might accumulate over days or from multiple sources.

After two days, just 23% of kidney cells exposed to the highest concentrations had managed to survive – a much higher mortality rate than that observed in earlier studies of micro- and nanoplastic toxicity. The team suspects that kidney cells might be more susceptible to the particles than are other cell types examined in prior research. But those earlier studies also tended to examine the effects of larger polypropylene particles, some of them potentially too large to penetrate cells. If so, the Hussain-led study could prove especially sobering: Regardless of its experimental conditions, the Husker team found that polypropylene containers and polyethylene pouches generally release about 1000 times more nanoplastics than microplastics.

The question of cell infiltration is just one among many that will require answers, Hussain said, before determining the true risks of consuming micro- and nanoplastics. But to the extent that they do pose a health threat – and that plastics remain a go-to for baby food storage – parents would have a vested interest in seeing that the companies manufacturing plastic containers seek out viable alternatives, he said.

“We need to find the polymers which release fewer (particles),” Hussain said. “Probably, researchers will be able to develop plastics that do not release any micro- or nanoplastics – or, if they do, the release would be negligible.

“I am hopeful that a day will come when these products display labels that read ‘microplastics-free’ or ‘nanoplastics-free.'”

Source: University of Nebraska-Lincoln

Going Viral: Dr Chivaugn Gordon on Medical School with a Difference

Dr Chivaugn Gordon, head of undergraduate education at UCT’s Department of Obstetrics and Gynaecology, reflects on her love of teaching future doctors about women’s health issues. PHOTO: Nasief Manie/Spotlight

By Biénne Huisman for Spotlight

With humour and wearing an occasional wig, Dr Chivaugn Gordon teaches medical students about serious women’s health issues. During hard lockdown she delighted students at the University of Cape Town (UCT) with educational videos using household items as props. For example, she created an endometrium (the inner lining of the uterus) from hair gel and red glitter, performed a biopsy on a potato, and showed a chicken hand puppet go into labour.

One video features a patient named Zoya Lockdownikoff – who is a spy – consulting with her doctor about abnormal menstrual bleeding. Gordon, in a blonde wig with round sunglasses, plays Lockdownikoff; and Gordon’s husband, Dr Adalbert Ernst, plays her doctor.

Lockdownikoff explains that the bleeding started when she “did a very complicated backflip to escape a very compromising situation” and that it’s ruining her expensive super-spy coats.

Gordon is head of undergraduate education at UCT’s Department of Obstetrics and Gynaecology, while Ernst is with the university’s Department of Anaesthesia and Perioperative Medicine.

Speaking from her yellow-walled lounge in Cape Town’s Bergvliet, Gordon says: “I became a doctor because I love working with patients. And then I realised, oh cool, I love teaching too. And now I can do these two things together.”

Interest in IPV

For Gordon a driving interest has been intimate partner violence (IPV) which she introduced into her undergraduate curriculum in 2015.

“The aim is to have graduating doctors who are able to recognise intimate partner violence. Everybody thinks that you can’t possibly be abused unless you have a black eye or a fractured arm. But actually, IPV is often more psychological. It’s often psychological abuse. So the challenge is to teach young doctors what are the red flags in someone’s behaviour, or in their clinical presentation, that might indicate IPV.”

Published online in April, Gordon delivered a talk for TEDxUCT called “Tackling IPV, one awkward dad conversation at a time”, in which she notes IPV is “a global pandemic that has been ongoing since time began”. The title refers to Gordon’s father who raised her.

According to a paper published in the journal Lancet Psychiatry last year, IPV is the most common form of violence worldwide; it is most prevalent in unequal societies, and its victims are mostly women and girls. The paper states that worldwide 27% of women and girls aged 15 and older have experienced physical or sexual IPV, but in South Africa the figure is estimated to be much higher, between 33 and 50%.

Gordon contributed to South Africa’s revised Domestic Violence Amendment Act of 2021, through UCT’s Gender Health and Justice Research Unit.

The new legislation broadens the definition of domestic violence to include (above and beyond physical and sexual abuse) emotional, verbal or psychological abuse, which is described as “a pattern of degrading, manipulating, threatening, offensive, intimidating or humiliating conduct towards a complainant that causes mental or psychological harm…including (repeated) insults, ridicule or name calling; (repeated) threats to cause emotional pain; the (repeated) exhibition of obsessive possessiveness or jealousy…”

Gordon highlights the term coercive control. “Because that underpins most serious intimate partner violence. So, somebody who is extremely controlling; they want their partner to do what they want, when they want, and how they want immediately. They normally start isolating you from friends and family so they can spin a narrative of your reality that can’t be contested by anyone else. And it also makes it more difficult to leave.”

Red flags

Gordon highlights some of the IPV red flags that doctors should look for in their patients.

“Depression, anxiety, PTSD, insomnia, [and] things like self-medicating with substances,” she says. “Because when you are living in absolute, abject terror every day of your life, it’s going to manifest in some kind of psychological manner. So, when people have been broken down and worn down and their self-esteem has been eroded it also affects the way they might interact with the healthcare professional.

“Big red flags come out in body language. Usually when someone goes to a doctor, they tell you everything about all their symptoms, because they want you to make them better. So, if you’ve got a patient who is closed off, they’re not making eye contact, they’re avoiding answering your questions, they’re just very reticent and you can’t get anything out of them…then you’ve got to think.”

Gordon stresses that IPV happens across economic strata and in all walks of life. “Every time I run this workshop, a medical student who comes from a very privileged background, from a very financially stable, loving home, comes to me, saying this is happening to her. It happens everywhere. I’ve got medical colleagues, several, who have experienced intimate partner violence. It doesn’t discriminate.”

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Single Injection of New Anthypertensive Drug Could Reduce BP for Six Months

Pexels Photo by Thirdman

A new drug which interferes with the production of angiotensin could help lower persistent hypertension for up to six months following a single injection, a study suggests. The results were published in the New England Journal of Medicine. If successful, the drug, called zilebesiran, would be more convenient for hypertension management than daily oral antihypertensive drugs.

More than half of patients with hypertension fail to take all of their prescribed medicine, leading to inconsistent blood pressure control. Better management of the condition could reduce the risk of stroke, heart attack and premature death, experts say.

Sustained drop

The international team, including experts from the University of Edinburgh’s Centre for Cardiovascular Science, ran the early stage clinical trials across four UK sites.

Patients who received zilebesiran experienced a substantial reduction in systolic blood pressure which lasted up to six months.

On average, systolic blood pressure lowered by over 10mmHg at a 200mg dose or more of the drug, and more than 20mmHg at the highest dose of 800mg. A drop of this size can take someone with hypertension to within a much safer range.

Blood pressure naturally goes up and down throughout the course of the day, making it difficult to treat – but the study found that the drop in blood pressure seen in patients who were treated with zilebesiran was consistent over 24 hours.

Novel approach

Developed by US-based company Alnylam, zilebesiran works by preventing the production of angiotensin, a hormone in the body that narrows blood vessels, leading to raised blood pressure. A number of existing antihypertensives also target angiotensin.

Zilebesiran uses a novel approach to interfere with the machinery in the liver that makes the protein angiotensinogen, the source of all forms of angiotensin.

Known as small interfering RNA (siRNA), zilebesiran turns off the gene responsible for producing angiotensinogen, preventing it from being made. 

The siRNA approach has already been used to develop treatments for a number of other conditions, with the ability to silence specific genes with high accuracy and effects lasting many months.

Safety data

107 patients with hypertension took part in the trial – 80 received a single injection of zilebesiran under the skin, while 32 received a placebo containing no active ingredients. Five patients who initially received the placebo were later moved to zilebesiran.

Experts caution that further studies involving a larger number of patients are needed to robustly investigate the safety of the drug and provide further insights into its potential to improve clinical outcomes in people with hypertension.

This is a potentially major development in hypertension. There has not been a new class of drug licensed for the treatment of high blood pressure in the last 17 years. This novel approach leads to a substantial reduction in blood pressure, both by day and night, that lasts for around six months after a single injection. This is attractive because it helps avoid the difficulty with adherence to treatment seen with current medicines. The next stage of clinical trials will focus on developing robust safety data, and broader evidence of efficacy, before zilebesiran can be licensed for use.

Professor David WebbChristison Chair of Therapeutics and Clinical Pharmacology at the University of Edinburgh, who led the Edinburgh study site

Source: University of Edinburgh